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Quality and Relevance of Research and Related Activities at the Gorges Memorial

Laboratory

August 1983

NTIS order #PB87-142238

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Foreword

The Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc. (GMI)and its operating arm, the Gorgas Memorial Laboratory (GML) have been conductingtropical research, training, and public health activities for more than half a century.Questions about GMI’s continued existence were raised this spring when the NationalInstitutes of Health requested no funds for the core support for GML. Gorgas’ existenceis at stake because the core support appropriation by the United States represents about

three-quarters of GMI’s total budget.

The Senate Committee on Appropriations and its Subcommittee on Labor, Healthand Human Services, and Education requested that the Office of Technology Assess-ment (OTA) examine the quality and relevance of research and related activities of GML.Such information is needed in order to adequately judge whether the core support shouldbe terminated. The subcommittee also requested that the General Accounting Officeund ertake a concurrent evaluation of four areas: the peer review process at GMI/ GML,the extent of other federally funded tropical medicine research activities, efforts by Gorgasto broaden its financial base of support, and the possible impacts on U.S. regional rela-tionships if funding was terminated.

This technical memorandum presents the results of OTA’s examination. It reviewsthe quality and relevance of activities at GML, based on Gorgas’ publishing record,an OTA-commissioned survey of GML’s scientific reputation, a critical review of re-cent articles and current manuscripts, a comparison of GML’s areas of effort with healthproblems in tropical America and with scientific opportunity, and a review of past scien-tific evaluations of GML.

OTA finds that GML’s research and related activities are generally of high qualityand relevance to the region and the United States. The United States receives excellentbenefit for its contribution to GMI/ GML. If Gorgas were to close down , the UnitedStates would most likely have to develop a capability to undertake many of the currentactivities of GML. OTA finds that there would be both health-related and internationalrelations repercussions if the United States were to withdraw its support for GML.Although GMI could be improved in several significant respects, GML is producingimportant work of high quality and represents an excellent investment of health funds.

This memorandum benefited from the consultation and review of a large numberof persons in the Federal Government, universities, international health organizations,and private industry. Key OTA staff involved in the analysis and writing were HellenGelband, Clyde J. Behney, Steven S. Bjorge, and John S. Willems.

/j2?- %. “

JOHN H. GIBBONSDirector

. Ill

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OTA Staff—Quality and Relevance of Research atGorgas Memorial Laboratory

H. David Banta, Assistant Director, OTA

Health and Life Sciences Division

Clyde J. Behney, Health Program Managerand Study Co-Director

Hellen Gelband, Study Co-Director

Steven S. Bjorge, Ana ly s t

John S. Willems, Research Assistant

Virginia Cwalina, Administrative Assistant

Jennifer Nelson, Secretary

Mary Walls, Secretary

Gwenn Sewell, Research Assistant

Contractors

Michael B. MacdonaldThe Johns Hopkins University

Richard K. RiegelmanThe George Washington University

OTA Publishing Staff

John C. Holmes, Publishing Officer

John Bergling Kathie S. Boss Debr a M. Datch er Joe Henson

Glen da Law in g Lin da A. Leah y Cheryl Manning

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Contents

Page

CHAPTER 1: INTRODUCTION AND BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . .Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Organization of the Technical Memorandum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Summary of Findings and Conclusions. ..., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

The Tropics and Tropical Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . .

The Value of Laboratories Located in the Tropics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .CHAPTER 2: GORGAS MEMORIAL INSTITUTE AND LABORATORY . . . . . . . . . . . . . . .Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . .Activities of GIL...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 3: QUALITY OF RESEARCH AT THE GORGAS MEMORIAL LABORATORY.Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . . . . . .Site Visits by the Fogarty International Center ...,...,. . . . . . . . . . . . . . . . . . . . . . . .

Review of Research Programs. . . . . . . ..., ..., ..., . . . . . . . . . . . . . . . . . . . ..., ..., ...,Arbovirus Program. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Environmental Assessment Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Diarrheal Diseases Program ., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Sexually Transmitted Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Can cer Regist ry/ Cancer of th e Cervix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Publications . . . . . ..., ..., . . . . . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . ..., . .

Peer Review at the Gorgas Memorial Laboratory, . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . .Grants and Contracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . . . . .

Quality of Research at GML as Seen by Experts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 4: RELEVANCE OF RESEARCH AT GORGAS MEMORIAL LABORATORYTO HEALTH PROBLEMS IN TROPICAL AMERICA . . . . . . . . . . . . . . . . . . . . . . . .

Tropical Diseases: Description and Status ., ..., . . . . . . . . ..., . . ..., ..., ..., . . . . . .Acute Respiratory Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Diarrheal and Enteric Diseases . . . . . . . . . . . . . . . . . ..., . . . . . . . ..., ..., . . . . . .Malnutrition . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., ..., ..., . . .Malaria . . . . . . . . . . . . . . . . . . . ..., . . . . . . ..., ..., ..., . . . . ..., ..., ..., ...,

Chagas’ Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Leishmaniasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . .Anthropod-Borne Viral Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Filariasis ..., . . . . . . . . . . . ..., . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . . . . . . . .Schistosomiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., . . . .Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Relevan ce of Research at Gorgas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CHAPTER 5: FINDINGS AND CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Findings. ..., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...,Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3

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v

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Contents—Continued

Page

Appendixes

A. Acknowledgments; Pan American Health Organization Liaison Group;OTA Health Program Advisory Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

B. Tropical Disease Research Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64C. Bibliography of Publications by the Gorgas Memorial Laboratory Staff . . . . . . . . . . . . . . . . 67D. Summary of the Telephone Survey on Gorgas Memorial Laboratory . . . . . . . . . . . . . . . . . . 77

E. Glossary of Acronyms and Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

Tables

Table No. Page

l. The Gorgas Memorial Laboratory’s Major Accomplishments From 1970 to the Present . . 72. Major Accomplishments of the Gorgas Memorial Laboratory, 1929-69 . . . . . . . . . . . . . . . . 83. A: Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82 15

B: Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82 164. Gorgas Memorial Institute of Tropical and Preventive Medicine, Incorporated:

Operating Budgets Fiscal Years 1982 and 1983 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175. Gorgas Memorial Institute of Tropical and Preventive Medicine, Incorporated:

Projection Fiscal Year 1984 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

6. Gorgas Memorial Laboratory Information on Scientific Staff as of July 1983 . . . . . . . . . . . 207. Recent Activities of Gorgas Memorial Laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228. Total Publications of the Gorgas Memorial Laboratory, 1975-83 . . . . . . . . . . . . . . . . . . . . . . 319. Gorgas Memorial Laboratory: Publication Location for Articles

Written by Staff; 1980 to July 1983 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3110. Articles and Manu scripts Reviewed for the Office of Technology Assessm ent

by Richard K. Riegelman, M.D. Ph. D..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3211. Gorgas Memorial Laboratory: Grants and Contracts as of July 1983 . . . . . . . . . . . . . . . . . . 35

Figures

Figure No. Page

l. Gorgas Memorial Institute Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192. Gorgas Memorial Institute-Proposed Organization Chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

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Chapter 1

Introduction and Background

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Chapter 1

Introduction and Background

The Gorgas Memorial Laboratory (GML) is a

research insti tution concerned with tropicalmedicine and pu blic health, It un dertakes both ap-plied and basic research, and performs laboratory,clinical, and field research activities. GML wasestablished in 1928 in commemoration of the workof Gen. William Gorgas in in controlling yellowfever. The Laboratory is located in Panama City,Republic of Panama. It is the research arm of theGorgas Memorial Institute of Tropical and Pre-ventive Medicine, Inc. (GMI), a (U. S.) domestic,nonprofit corporation headquartered in Washing-ton, D.C.

INTRODUCTION

GML is a specific subject of evaluation becauseof questions concerning its fiscal year 1984 ap-propriation. GMI is authorized by act of Congress(Public Law 70-350, as am end ed) to receive a year-ly appropriation, not to exceed $2 million, fromthe U.S Government. The original fiscal year 1984budget request from the Fogarty InternationalCenter (FIC)—the unit of the National Institutesof Health (NIH) given responsibility for admin-istering the Gorgas budget request—included a

budget request for Gorgas. A subsequent revisionby NIH, of the NIH bud get, led NIH/ FIC to re-quest no funds at all for core support of GMI.Because this core support of close to $2 millionis an extremely large percentage of the total GMLbudget (see ch. 2), this action effectively meantthat GML would have to close down.

In order to evaluate whether this action was justified on the basis of the quality of Gorgas’research and on its success in identifying needsand conducting research relevant to health con-cerns of Panama and tropical America* (especially

Central America and the Caribbean), the re-questing subcommittee and committee asked both

‘The term tropical America here refers to the southern part of North America, all of Central America and the Caribbean, andtropical South America,

This technical memorand um presents the results

of a review of the quality and relevance of re-search and related activities of GML. The evalua-tion was conducted at the request of the SenateCommittee on Appropriations and, especially,its Subcommittee on Labor, Health and HumanServices, and Education. It is part of a broaderOTA assessment of the status of biomedical re-search and related technology for tropical medi-cine, also requested by the committee and sub-commit tee.

the General Accounting Office (GAO) and theOffice of Technology Assessmentvide relevant information.

The related effort by GAOtopics:

1.

2.

3.

4.

the process of peer review

(OTA) to pre-

examines four

used by GMLbefore initiating research projects and aftertheir completion,efforts to broaden the financial base of GML,

other federally funded tropical medicineresearch activities, andthe possible impact of GML’s closing onU.S.-Panamanian relations. That report isscheduled for completion in August 1983.

The OTA effort devotes some attention to thefirst of those four topics, but is primarily ad-dressed to issues of:

1.

2.

the quality of GML’s applied biomedicalresearch projects, epidemiological activities,maintenance of research animal p opulations,and other research-related activities such as

training; andthe relevance of GML’s research and otheractivities to the health needs and problemsof Panama, other tropical American coun-tries, the U.S. interests, and to tropicalmedicine in general.

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Organization of the TechnicalMemorandum

The remainder of this chapter contains a sum-mary of the findings and conclusions of thetechnical memorandum and background informa-tion on the Tropics, tropical diseases, and the roleof research laboratories located in the Tropics.Chapter 2 presents descriptive material on Gorgas,its structure, and past and current research activ-ities. Chapter 3 examines evidence on the quali-ty of GML’s research, public health, and train-ing activities.

The fourth chapter presents descriptions andbrief data on the status of the diseases and healthproblems of critical importance to tropical Amer-ica and of research related to them. Gorgas’s ac-

tivities are then discussed in the context of thesediseases and conditions. The final chapter presentsthe findings and conclusions.

Appendix A presents the acknowledgments,lists the members of the Liaison Group formed

by the Pan American Health Organization to pro-vide advice to OTA on this project, and lists theOTA Health Program Advisory Committee. Ap-pendix B is a brief presentation of other currentresearch activities in tropical health. Appendix Cis a bibliograph y of publications since 1975 byGML staff. Appendix D is a summary of the OTAsurvey of experts’ opinions concerning Gorgas andits research quality and relevance. Appendix Econtains a list of acronyms and a glossary of terms.

SUMMARY OF FINDINGS AND CONCLUSIONS

OTA examined the quality and relevance of tropical medicine research and related activitiesat GML, The evaluation of the quality of an in-stitution such as Gorgas cannot take place with-out explicit recognition of certain premises:

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There is an inherent value in supportingtropical research laboratories in tropicalcountries. Field conditions present opportu-nities that cannot be duplicated by organiza-tions such as NIH.Evaluations of the quality of research are in-evitably, and properly, made partly on thebasis of fairly objective criteria such aspublications record and partly on the basisof subjective judgments by qualified individ-uals.The criteria used to judge quality, althoughsimilar in type, need to be modified andweighted differently for research performedin well-equipped, state-of-the-art laboratoriesthan for field research laboratories.Relevance is directly dependent on the type

and location of institution, and it should beexamined from each of the appropriate view-points (e.g., host country, region, UnitedStates, general advancement of knowledge).

With these premises in mind, OTA examinedthe quality of Gorgas’ research against a range of

objective and subjective criteria. There was veryimpressive agreement among the results of: 1 ) thepast scientific evaluations of GML, 2) the criticalevaluation of the research design and presenta-tion of articles and manuscripts, 3) the survey of expert scientific opinion on Gorgas’ quality, 4) in-terviews with Panamanian health officials andprofessionals, 5) the examination of GML staff’spublications record, and 6) an examination of GML’s record of competing for grants and con-

tracts. All evidence gathered by OTA led to thefinding that the overall scientific quality of GMLis high, especially when considered in the contextof GML’s status as a research laboratory locatedin the Tropics. Quality was, naturally , notuniformly even.

OTA also found that the large majority of GML’s research is highly or adequately relevantto health concerns and problems of Panama, thetropical American region, U.S. interests, and theadvancement of scientific knowledge and the fieldof tropical medicine in general. (Table 1 lists

significant accomplishments of GML in the pastdecade; table 2 shows significant activities dur-ing the previous period of GML’s history. ) Theevidence for this finding lies, for the first two, inthe match between tropical health problems andGML research directed at them, and from strongly

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7

Table 1 .—The Gorgas Memorial Laboratory’s Major

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Accomplishments From 1970 to the Present

Continued yellow fever surveillance and monitoring ofvectorsSt. Louis encephalitis and Venezuelan equineencephalitis vectors and reservoirsInsect genetic studies using isozyme markers

Transovarial transmission of yellow fever virus inmosquitoesUse of Aotus monkey model for testing of therapeuticsSeveral new viral isolates in areaScreening of antimalarial drugs and identification ofpromising therapeutic antimalarial compoundsWHO regional center for bloodmeal analysisImproved identification of insect vectors: sandflies,triatomines, blackflies, etc.Development of cancer registry in the Republic ofPanamaDiscovery of high incidence of cervical and penilecancer in Herrera Province (Republic of Panama)Studies of sexually transmitted diseases in theRepublic of Panama (the first such studies in LatinAmerica)Rapid identification of viral agent in recent epidemics

of conjunctivitis and encephalitis in the Republic ofPanamaDiscovery of high HTLV antibodies in the Republic ofPanamaEnvironmental impact assessment of TabasaraHydroelectric project

SOURCE: Gorgas Memorial Laboratory, Office of the Director August 1983

expressed opinions and examples by various Pan-amanian officials and professionals.

The importance of GML to Panama cannot be judged solely on the basis of Panama’s monetary

contribution. Panama is going through a difficulteconomic period. Even so, the Ministry of Healthhas arranged a loan to keep GML in operationfor the remainder of fiscal year 1983. The valueof the land, buildings, and tax-favored status havenever been adequately assessed. And to put theoften criticized direct financial contribution of $10,000 from Panama in perspective, the researchbudget of the Panamanian medical school is re-portedly only $20,000. As one official of the U.S.Department of State expresses it: Each year, theUnited States sends a message to Panama and theregion by funding GML and supporting activities

related to the health of U.S. and Panamaniancitizens alike (51).

Activities related to the recent Panama CanalTreaty process provide a specific example of theimportance of GML to Panama, As part of the

treaty, a Joint Committee on the Environment wasestablished. Panama turned to GML, as the onlyinstitution in Panama with the necessary skills andexperience, for assistance in relation to environ-mental protection and human and animal health,and additionally named Dr. Pedro Galindo, for-

merly of GML, as the senior Panamanian on theCommittee.

Relevance to U.S. health interests can be foundin th e surveillance activities, the trainin g activities,and the various research activities undertakenunder contract to the U.S. military. There areabout 20,000 U.S. Government employees and de-pendents in Panama; and many thousands morein nearby countries. The work of GML is direct-ly relevant to the health of these people.

Gorgas’s contributions in the areas of malaria,yellow fever, and leishmaniasis illustrate itsrelevance to the general advancement of knowl-edge (see also, tables 1 and 2).

Based on the above evidence, OTA finds thatwith some exceptions that occur almost entirelywithin the core-funded activities, the research con-ducted at Gorgas is relevant to the various par-ties at interest.

Conclusions: OTA concludes that the benefitsof supporting GML justify, on scientific and othergrounds, the relatively small amount of funds re-quired. Quality and relevance are high. With-

drawing core support from Gorgas would prob-ably not even save the amount of the appropria-tion, since other Federal agencies may need toeither conduct or support research now carriedout at GML.

Gorgas is not ideal; improvements could cer-tainly be made. Some of the shortcomings stemfrom its uncerta in funding. The prospect of unstable funding and perhaps closure may havekept individual scientists [rem joining GML orbecoming visiting scientists there and may reducethe desire of U.S. universities to collaborate withGML on research projects.

Another example of the effect of uncertainfunding has been the decision by the U.S. Navyto hold off on the next scheduled training class,because the course would extend a few weeks intofiscal year 1984. It is extraordinarily difficult to

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Table 2.–Major Accomplishments of the Gorgas Memorial Laboratory, 1929-69——.

i. Protozoa/ Diseases of Man and Lower Animals: Malaria: 1933 and subsequently: First long-range, large-scale field

tests of the antimalarial drugs, Atebrine, chloro-quine, and paludrine under controlled conditions in

the New World Tropics,1954: First long-range field tests of DDT house-sprayingto control malaria.

1960: Field demonstration of the effectiveness of weeklydoses of pyrimethamine-primaquine drugs com-bined with the eradication of Plasmodium falciparum malaria from a tropical area.

1966: Demonstration that certain common human malariaparasites could be grown in certain species ofPanamanian monkeys and could be transferred toman and other monkeys by blood inoculation andby bites of mosquitoes.

American Trypanosomiasis: 1931: First report of Chagas’ disease in Panama and

discovery of the vectors.1959: First report of Trypanosoma range/i from man and

wild vertebrates i n Panama and demonstration of the

development of the human strain in the salivaryglands of Rhodnius pallescens.1965: Demonstration that the Panamanian strain of T.

range/i differs from the South and Central Americanstrains in its behavior of development i n the insectvector.

Leishmaniasis: 1965: Incriminate ion of seven wild vertebrates as reservoir

hosts of human Ieishmaniasis.1966: Demonstration that Ieishhmania infection may com-

monly occur i n the apparently normal skin of someferal animals without producing lesions.

1945-68: Recognition of over 70 species of Phlebotomus inPanama, of which 4 or 5 have been found infectedwith Ieishmania.

Animal Trypanosomiasis: 1932: Discovery of the vampire bat transmission of equine

trypanosomiasis.1932: Discovery of bovine trypanosomiasis in Panama.Intestinal Protozoa: 1944: First finding of Isopora hominis in Panama.

Il. Helminthic Diseases of Man and Lower Animals:1934-35: First comprehensive survey of the worm parasites

of equines in Panama.1966: Finding a new human disease entity caused by

Echinococcus oligarthrus, a little known cestodeparasite of pumas and other large felines; descrip-tion of the first known human case that terminatedfatally; and demonstration of the life cycle of theparasite.

—

Ill. Rickettsial Diseases: 1946: First report of Q Fever in Panama.1 947: First report of murine typhus in Panama.1 951: First recognition of Rocky Mountain Spotted Fever

in Panama.

IV. Virus Diseases: 1 949:

1 957:

1958:1960:1961 :

1963:

1964:

1965:

1968:

First demonstration of the mosquito vectors ofyellow fever in Panama and Central America and theinauguration of comprehensive studies on vectorecology and transmission capabilities.First recovery of St. Louis encephalitis virus andrecognition of human cases in Panama.First isolation of Ilheus virus in Central America.First isolation of Changuinola virus from man.Discovery of four new arboviruses: Madrid, Ossa,Patios, and Zegla.First isolation of Wyeomyia subgroup of arbovirusesfrom man.Recognition of the first human case of Ilheusencephalitis.Finding of crab-hole mosquitoes (Deinocerites) ashosts for St. Louis encephalitis virus.

First isolation of Vesicular Stomatitis virus (Indiana)from man in Panama and detection of virus transmis-sion by the use of sentinel monkeys.

V. Medical Entomology:1929: First elucidation of the human botfly, Dermatobia

hominis, in man.1 935: First establishment of a laboratory colony of

anopheles albimanus, the main vector of malaria inCentral America.

1 944: First tests of DDT to control phlebotomine sandflies,1 945: First experimental trials of DDT for the control of

Simulium spp., the vectors of Onchocerca volvulus,the blinding filariid parasite of man.

1 945: First experiments with DDT for the control ofCulicoides sandflies.

1 945: First observ ations in Panama on the habits and lifehistories of chigger mites (Trombiculidae), potential

vectors of disease.1966: First comprehensive survey of the ticks and biting

insects of Panama.

V/. Miscellaneous Projects: 1930-54: Comprehensive survey of the poisonous snakes of

Panama and the incidence of snake bites.

SOURCE Willard H Wright, 40 Years of Tfopcal kfe~iClfw Res=cb (wmhlngton, D C Reese Pre;s, 1970) — — . ——

plan and carry out research related to trop ical dis- q

eases without multiyear budgeting and some as-q

surance of multiyear funding.

Gorgas itself could improve its standing and its Ž

relevance by:

being more aggressive in its publishing,by making better use of its Advisory Scien-tific Board (see ch 5 for examples of possi-bilities),by more actively seeking out associations andcollaborations with a range of universities,

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9

groups from other countries, and internation-al organizations,

Ž by making strategic plans to move more fullyinto the developing areas of modern science(e.g., work with monoclonal antibodies andother immunological diagnostics, and bio-

technology approaches to vaccine-relatedresearch and development), and

Ž by making more of an effort to run vigorousvisiting scientist and fellowship programs.

OTA concludes that the only benefit to theUnited States of defunding Gorgas would be sav-ings of perhaps significantly less than $2 milliona year, The negative consequences would includeloss of one of the few, high-quality, broadly rele-vant, tropical research institutions located in atropical country. The standing of the United Statesin tropical America would inevitably suffer.

BACKGROUND

The Tropics and Tropical Diseases

The Tropics can be roughly considered to in-clude Central America, much of South America,the South Pacific, southern Asia, and most of sub-Saharan Africa. Tropical nations are usuallycharacterized by poverty, substandard drinkingwater and sanitation, hot and humid climates,poor health services, low levels of education, andin some cases swampy or jungle areas. Annualper capita income is often extremely low (as lowas or even less than $100). Ir. tropical America,the average per capita gross domestic prod uct was$1,500 in 1980. However, the variation is wide,ranging from nearly $9,000 in the Bahamas and$2,685 in Barbados (both figures may be decep-tive) to $267 in Haiti and $568 in Bolivia (75).

Of the world’s approximately 4½ billion peo-ple, about three-quarters live in less developedcountries, most of which are tropical. Of the ap-proximately 600 million population (1980 figures)of the Western Hemisphere, about 60 percent live

in Latin America, most of which is tropical.Health status is generally poor, with high rates

of infant m ortality (primarily du e to m alnutrition,lack of prenatal care, and diarrheal and respira-tory infections), widespread infection with debil-

Ironically {GML is ir: danger of extinction atthe very time that U.S. interest in Latin Americais high, and at a time when tropical medicine hasnever been more relevant to U.S. interests.

In summary, OTA concludes that the positiveconsequences of U.S. core support of Gorgasgreatly outweigh the amount of funds involved.Defunding new, followed by an appreciation of the loss later and a subsequent attempt to reinstatesuch a research capability, may result in muchlarger required investments, an inabili ty torecreate successful conditions for quality research,or both. *

‘In fact, it may be imposs ib le to recreate GMI. or a ~imilar ]n -sti t u tion In the current political climate in I.atin America (s 1 )

itating disease, and high mortality and morbidi-ty rates from all diseases except certain chronicones associated with a higher standard of living(such as some cancers).

Any definition of “tropical disease” is arbitrary.In its strictest sense, perhaps, a tropical diseaseis one found—for reasons of physical environmentand climate or the presence of specific diseasevectors—entirely or predominantly in tropical re-

gions.However, a more realistic, and more useful,

definition includes those diseases or conditions—such as acute respiratory infection, tuberculosis,malnutrition, or cholera—that occur or could oc-cur in many regions, but which are considerablymore prevalent in tropical areas because of thesocial and economic conditions that characterizemany tropical countries. In countries with verylow per capita gross domestic products, inade-quate or u nsafe water supp lies and sanitation, lowlevels of health care services, high levels of il-

literacy, and similar conditions, certain diseasesare able to flourish beyond the extent that wouldbe predicted simply on the basis of climate.

The OTA assessment, including this technicalmemorandum, will consider “classic” tropical dis-

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10

eases such as malaria that fit the narrower defini-tion, but it will more generally be guided by thebroader definition. Thus, a more appropriatephrase to describe the subject of the assessmentand the context in which Gorgas will be evaluatedis “medicine and health in the tropics. ”

The direct economic and social impacts of widespread disease are obvious, but the mostsubstantial economic impacts may be indirectones, affecting a country’s human resources andproductivity. For example, a country whose pop-ulation has an extremely high prevalence of debilitating disease loses labor resources, and pro-ductivity inevitably suffers.

In addition to the humanistic concern with thehealth and quality of life of people in tropicalcountries, and in addition to the stake that alldeveloped countries have in the economic health

and development of developing countries, thereis a smaller, yet definite benefit that can accrueto the United States through support of tropicaldisease research and technology development.Tropical countries are no longer—if they everreally were—’’exotic” far off lands seen only byadventurers. A great many people now travel toand live in tropical countries, as tourists, in thediplomatic or military service, or as employeesof U.S. or multinational companies. The numberof such people is most likely increasing. * “Thetropics are coming closer and bringing their dis-eases with them” (69).

In addition, advances in tropical disease re-search can represent valuable knowledge in gen-eral medical science, particularly in the areas of infectious disease control, general preventive med-icine, and environmental health.

The Value of LaboratoriesLocated in the Tropics

Laboratories and field stations located in theTropics have played a vital role in tropical dis-ease research during this century. There is a cer-

tain point at which research taking place in tem-

*The Increasing number of refugees in recent years serves as adramatic example of an additional reason for regarding attentionto tropical medicine as an important priority for the United States

perate countries, even though aimed at eventuallyeliminating or controlling tropical diseases, cango no further, regardless of the quality of re-searchers or institutions. Initially, informationabout the occurrence (incidence, prevalence, case-fatality rates), natural history, and transmission

of diseases is necessary for the rational design of strategies to deal with diseases, and this can onlybe collected in the field. Finally, the fruits of research—e.g., drugs and vaccines, vector con-trol programs—must be tested where the diseasesoccur: in tropical regions. These are the veryminimum involvements for institutions in theTropics.

There is absolutely no substitute for field con-ditions in tropical countries. This point has beenmade to OTA time and again by tropical healthexperts in academia, Government research orga-

nizations, and the U.S. military.Apart from research, tra ining in tropical

medicine can only reasonably take place in theTropics. Training needs and expertise have tradi-tionally been concentrated largely in the military.Additionally, professionals with training in trop-ical medicine are in demand by foreign govern-ments, academic institutions, and voluntary agen-cies (107).

In addition to benefits to the U.S. populationfrom knowledge of the control of tropical diseases,the existing tropical field laboratories benefit the

countries in which they are located. The coun-try’s health science professionals who are involvedin the projects or receiving training raise the levelof sophistication of biomedical research in thesecountries, The disease problems studied are of ob-vious importance to the pop ulations in these coun-tries, and any progress in treatment or control willbenefit them. An additional benefit can be a less-ening of the “brain drain” that occurs in many,especially developing, countries. When a goodquality research institution exists in a country, itsprofessionals have a place and the opportunityto work and develop without emigrating and thus

not depriving the country of their skills.The U.S. Government supports a relatively

small number of laboratories in tropical areas (seeapp. B). The Department of Defense operateseight medical research laboratories in the Tropics.

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11

In Latin America, the Centers for Disease Con-trol (CDC) operates the Medical Entomology Re-search and Training Unit in Guatemala. CDC pre-viously ran a field station in El Salvador, whichhas been closed. The United States also supportstropical health research through contributions to

international development agencies and throughbilateral aid.

Establishing new field laboratories is a difficultand time-consuming task. Building good relations

with the host country and becoming a produc-tive unit may take years. The decision to eliminatean existing laboratory should consider that point.

Thus, any evaluation of GML must not onlyconsider the quality and relevance of its research,

but also its role as a research, training, and publichealth unit actualIy located in the Tropics.

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Chapter 2

Gorgas Memorial Institute

and Laboratory

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. . .\ - & 7=4-- ---

— — --J --Photo credits: Gorgas Memorial Laboratory

Front entrance to the Gorgas Memorial Laboratory, in Panama City, Republic of Panama (bottom photo). Photo at topshows the Laboratory complex in Panama City. At the extreme left is the side of the administrative offices; the lowerconnecting structure houses the Library; to the right rear are the research laboratories. The complex also contains

animal buildings and an insect facility (insectory)

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Chapter 2

Gorgas Memorial Institute and Laboratory

The Gorgas Memorial Institute of Tropical andPreventive Medicine, Incorporated (GMI), a pri-

vate, nonprofit organization, was incorporatedin Delaware and registered in the Republic of Panama in 1921 as a memorial to Major GeneralWilliam Crawford Gorgas (47).

The Gorgas Memorial Laboratory (GML),GMI’s research arm and primary function, wasestablished in 1928 in the Republic of Panama,with resources made available by the Govern-ments of the United States and Panama and byseveral national and international agencies. Theestablishment of GML was made possible by anact of Congress (Public Law 70-350), whichauthorized a permanent annual contribution forthe facility, provided that a site and building weremade available from other sources, and by actionof the National Assembly of the Republic of Pan-ama, which granted land and a building on thecondition that the property be used for a researchlaboratory (47),

The contribution made annually by the U.S.Government to GMI, which constitutes the coresupport for the maintenance and operation of GML, is administered by the Fogarty InternationalCenter (FIC) of the National Institutes of Health

(NIH). Public Law 70-350, as amended, authorizesCongress to provide up to $2 million for GMI.

In fiscal year 1983 GMI received $1.8 millionthrough FIC, an increase from the fiscal year 1982allotment of $1.692 million. Although GMI askedfor $1.9 million in core support for GML in fiscalyear 1984, the latest fiscal year 1984 NIH budgetrequest targets no funds for GMI (47,115).

GML also receives grants and contracts sup-porting specific research projects from a varietyof United States, Panamanian, and internationalorganizations. In fiscal year 1982, total U.S. con-tributions including research grants from the U.S.Army, Navy, NIH, and the Agency for Inter-

national Development tota led approximately$2,225,200, or 96.9 percent of all direct financialsup port for GMI/ GML (see tables 3A and 3B).

Panamanian support for GML, which largelycomes in the indirect form of property grants anda tax-favored status, is more difficult to tabulate.In 1930, the appraised value of the land donatedby the Republic of Panama was $126,750. Esti-mates of the current value of the land and facilitieshave gone as high as $20 million by one seniorPanamanian official, but no exact figure is avail-able. In 1979, FIC estimated the value of the “in-

Table 3A.—Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82(dollars in thousands)

1975-82

1975 1976 1977 1978 1979 1980 1981 1982 total

U.S Appropriation . . . . . . . . . . . . . . . . . . $ 707.5 $1,360 $1,400.0 $1,400.0 $1,700.0 $1,700.0 $1,800.0 $1,692.0 $11,759.0National Institutes of Health ... , . . . . 929.1 174.8 228.1 248.4 333.3 255.9 305.1 219.2 2,693.1Health and Human Service (HEW) . . . . – – – – 4.4 4.7 0.9 – 10.0U.S. Army . . . . . . . . . . . . . . . . . . . . . . . . 223.4 203.5 111.7 130.2 145.2 187.5 257.8 228.6 1,488.0U.S. Navy . . . . . . . . . . . . . . . . . . . . . . . . . 35.0 33.8 25.0 25.0 30.0 35.0 35.0 35.0 235.8AID ., ... . . . . . . . . . . . . . . . . . . . . . . . . 120.0 5.5 – – 8.1 23.3 45.2 — 202.1

Subtotal Federal support . . . . . . . . . $2,015.0 $1,777.6 $1,764.8 $1,803.6 $2,221.0 $2,205.5 $2,444.0 $2,174.9 $16,406.3Other U.S. support ... , . . . . . . . . . . . . . $ 7.3 $ 4.3 $ 2.7 – $ 58.3 $ 89.5 $ 58.6 $ 50.3 $ 271.1

Total U.S. support. . . . . . . . . . . . . . . . $2,022.3 $1,781.9 $1,767.6 $1,803.6 $2.279.2 $2,295.0 $2,502.6 $2,225.2 $16,677.5

Government of Panama . . . . . . . . . . . . . – $ 59.3 $ 17.2 $ 37.1 $

1.0 $ 308.4 $251.0 $22.5$696.5WHO/PAHO . . . . . . . . . . . . . . . . . . . . . . . $ 7.7 4.4 16.0 36.9 118.2 57.0 47.8 49.0 336.9

World Bank . . . . . . . . . . . . . . . . . . . . . . . — — — 6.8Wellcome Laboratories . . . . . . . . . . . . . — — — (a)

6.91.0 - - 1.0

Total non-U.S. Support. . . . . . . . . . . . $ 7.7 $ 63.7 $ 33.2 $ 80.8 $ 120.2 $ 365.4 $ 298.8 $ 71.5 $ 1,041.3Total support . . . . . . . . . . . . . . . . . . $2,030.0 $1,845.6 $1,800.8 $1,884.5 $2,399.5 $2,660.4 $2,801.4 $2,296.7 $17,718.7

aLess than $50

15

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16

Table 3B.—Sources of Financial Support for the Gorgas Institute and Laboratory Fiscal Years 1975-82(as of percent)

U.S Appropriation . . . . . . . . . . . . . . . . . .National Institutes of Health . . . . . . . .

Health and Human Service (HEW) . . . .U.S. Army . . . . . . . . . . . . . . . . . . . . . . . . .U.S. Navy . . . . . . . . . . . . . . . . . . . . . . . . .AID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Subtotal Federal support . . . . . . . . .Other U.S. support . . . . . . . . . . . . . . . . .

Total U.S. support . . . . . . . . . . . . . . . .

Government of Panama. . . . . . . . . . . . .WHO/PAHO . . . . . . . . . . . . . . . . . . . . . . .World Bank . . . . . . . . . . . . . . . . . . . . . . .Wellcome Laboratories . . . . . . . . . . . . .

Total non-U.S. Support . . . . . . . . . . . .

Total suppport. . . . . . . . . . . . . . . . . .

1975-821975 1976 1977 1978 1979 1980 1981 1982 average

34.9 73.7 77.7 74.3 70.8 63.9 64.3 73.7 66.445.8 9.5 12.7 13.2 13.9 9.6 10.9 10.0 16.7

— — — — 0.2 0.2 (a) – 0.111.0 1 1 . 0 6.2 6.9 6.1 7.0 9.2 10.0 8.4

1.7 1.8 1.4 1.3 1.3 1.3 1.2 2.0 1.45.9 0.3 – – 0.3 0.9 1.6 — 1.1

99.3 96.3 98.0 95.7 92.6 82.9 87.2 94.7 92.6

0.4 0.2 0.2 – 2.4 3.4 2.1 2.2 1.5

99.6 96.5 98.2 95.7 95.0 86.3 89.3 96.9 94.1 — 3.2 1.0 2.0 (a) 11.6 9.0 1.0 3.90.4 0.2 0,9 2.0 4.9 2.1 1.7 2.1 — . — 1.9 — — — (a ) (a) - - (a)

0.4 3,5 1.8 4.3 5.0 13.7 10.7 3.1 5.9

100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0a

Less than 0.05 support.

SOURCE: Gorgas Memorial Institute, 1983,

direct services’’ provided each year by the Pana-manian Government to be $175,000.

GMI is required by law to make an annual re-port to Congress on the activities and expendituresof the laboratory, The U.S. General AccountingOffice (GAO) aud ited all GMI/ GML financialstatements until 1980 (47).

GML is currently engaged in an effort to cutcosts and broaden its financial base of support.This issue is being addressed in the related GAO

study, and will not be covered in this technicalmemorandum. Plans call for the the closure of Building 265, which cost an estimated $279,102to maintain in fiscal year 1982 (see table 4);however, modifications to accommodate the re-location of the virology program formerly housedin the building are estimated at a one-time costof $250,000 (table 5 shows this figure, as well asother projected costs for fiscal year 1984).

The Laboratory has just finished terminatingthe employment of some 29 of GML’s employeesand staff. The closing of the entire bacteriology

department eliminated three Panamanian scien-tists with 10 to 22 years tenure at GML (121). GMIsought relief from the Panamanian Minister of Health and Minister of Labor from penaltycharges attributable to early termination of Pan-amanian employees (47), but waivers were not

granted. GMI has established a DevelopmentCommittee to explore fund-raising possibilities inthe private sector. Because of the completion of a number of commissioned projects, revenuesfrom research grants and contracts dropped from$995,641 in fiscal year 1981 to $594,224 in fiscalyear 1982. As a result of this decline, the propor-tion of total funding represented by U.S. core sup-por t rose from 64.3 percent of all revenu es in fiscalyear 1981 to 73.7 percent in fiscal year 1982.

Of the $1,884,824 spent by GMI/ GML over the12-month period ending July 1983 after thereduction-in-force, over half ($928,101) wenttowards salary costs. Utility charges, includingthose for Building 265, came to $413,257. Ad-ministrative costs accounted for $130,732, andanother $163,258 was spent to maintain the GMIoffice in Washington, D.C. The “direct” nonsalaryresearch dollars amount for the laboratory was$209,476 (121).

At its headquarters in Washington. D. C., GMIis governed by a 47-member Board of Directors,

which includes officials of the Governments of theUnited States and Panama, representatives of na-tional and international agencies active in areasof common interest, and U.S. and Latin Americanscientists and professionals. The board meets an-nually to determine the policies of the organiza-

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17

Table 4.—Gorgas Memorial Institute of Tropical and Preventive Medicine, Incorporated:Operating Budgets Fiscal Years 1982 and 1983

Fiscal year 1982 Fiscal year 1983

Budgeted Actual Program Budget

(1/20/82) unaudited Old New

Revenue:Contribution by the United States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Research grants and contracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Other. ....,.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Subtotal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Additional revenue required . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total revenue required . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Expenditures:Core—

Infectious Disease ProgramVirology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Bacteriology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Parasitology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ecology & Epidemiology Program

Ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Vertebrate Zoology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Entomology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

EpidemiologyVector Biology

TotalPrimatology & Laboratory Animals Program

Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Animal Colony . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Education & Technical Support Program

Educational Programs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Library . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Data Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Administration

Washington, D.C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Panama . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Maintenance

Panama . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Building 265. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Seniority Premium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Total core expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

$1,692,000609,407

2,500

$1,692,000594,224

10,442

$1,800,000346,209

10,000

$1,800,000346,209

10,000

2,303,907386,888

2,690,795

275,390105,76578,51521,43071,297

552,397

110,21642,47417,000

494143,839

314,023

46,25473,546

2,296,666

2,296,666

340,752110,82685,05321,58581,809

2,156,209390.930

2,156,209524,011

2,547,139

383,547114,741

79,56535,36460,366

2,680,220

374,146183,05273,92048,16667,688

640,025

95,84039,83115,8016,664

158,478

673,583

105,15541,03918,0299,331

139,477

746,972

106,58641,03918,0299,331

139,477

316,614

47,35081,969

313,031

57,75485,977

314,462

53,95488,427

119,800

5,42557,99163,416

43,712

161,256326,647

129,319

4,34656,82961,175

36,777

146,242256,095

143,731

6,13962,45168,590

39,551

163,258313,609

142,381

5,63971,05676,695

45,738

163,258330,765

487,903

232,992309,693

402,337

269,449279,102

476,867

277,804290,583

494,023

290,539321,011

542,68525,000

548,55121,028

568,38715,000

611,550

2,148,936Direct grant and contract expenditures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541,859

Total expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2,690,795Excess revenue over/(under)

expenditures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $ - o -

2,155,826445,089

2,600,915

$ (304.249)

2,298,740248,399

2,431,821248,399

2,547,139

$ -o-

SOURCE Gorgas Memorial Institute, 1983.

2,680,220

$ -o-

tion, review the managerial and fiscal operation, manship of the President of GMI, Dr. Leonapp rove budgets, and elect officers, Board mem - Jacobs, a Scientist Emeritus of NIH. The 24-mem-bers, and advisors. Between meetings, the Board’s ber Advisory Scientific Board, consisting of scien-functions are delegated to the 9-member Executive tists in various disciplines, is to advise on theCommittee, which meets monthly u nder the chair- development and review of scientific programs

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Table 5.—Gorgas Memorial Institute of Tropicaland Preventive Medicine, Incorporated:

Projection Fiscal Year 1984

Revenue:Contribution by the United States . . . . . . . . . $1,899,000Research grants and contracts . . . . . . . . . . . . 300,000

Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10,000Subtotal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . -2,209,000

Additional revenue required . . . . . . . . . . . . . . 18,000

Total revenue required . . . . . . . . . . . . . . . . . ‘ 2,227,000Expenditures:Core—

Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . 180,509Microbiology . . . . . . . . . . . . . . . . . . . . . . . . . . 276,237Tropical Ecology . . . . . . . . . . . . . . . . . . . . . . . . 326,553Applied Pharmacology . . . . . . . . . . . . . . . . . . . 165,699Administrative Services & Training—

Panama ....., . . . . . . . . . . . . . . . . . . . . . . . . 913,553’Administration—Washington, D.C. . . . . . . . . . 177,000

Total core expenditures . . . . . . . . . . . . . . . . 2,039,551Direct grant and contract expenditures. . . . . 187,449

Total expenditures . . . . . . . . . . . . . . . . . . . . ‘2,227,000

Excess revenue over/(under) expenditures . . . . $ -o-

alnclude~ $250,000 for an~iclpated facilities remv’tlon

SOURCE:Gorgas Memorial Institute, 1983

ORGANIZATIONThe organization of research activities of GML

is currently undergoing change. Previously (andstill officially) GML was divided among four sci-entific programs (see fig. 1). The InfectiousDiseases Program was divided into Virology, Bac-teriology, Parasitology, Immunology, and Clin-

ical sections. The Ecology and Epidemiology Pro-gram was responsible for Vertebrate Zoology,Entomology, Epidemiology, and Vector Biology.Animal Models, Primate Biology, and AnimalColony research were under the Primatology andLaboratory Program. Education and TechnicalSupport programs handled the Library, Photo-Laboratory, and Educational sections. In additon,GML maintained administrative and data process-ing sections.

Tentative plans for departmental reorganiza-tion have been drawn up, but will not be imple-

mented until GML’s financial situation is moresecure (121). The new organization will includedivisions for epidemiology, laboratory sciences(e.g., immunology, parasitology, serum bank),environmental biosciences (e. g., vector bionom-ics, ecology), clinical therapeutics (e.g., animal

and, if plans are fulfilled, to serve as an editorialreview board for GML staff’s scientific manu-scripts. * The officers, members, and advisorsserve without compensation (47).

In 1972, the Middle American Research Unit,

which had been in existence since about 1960 inthe Canal Zone as an offsite laboratory of the Na-tional Institute of Allergy and Infectious Diseases(NIAID), was merged with GML. At the end of fiscal year 1975, NIAID concluded its support forthe work formerly done by this unit with a re-sulting loss of senior personnel and financial sup-port for GML (11 O).**

q See the GAO report for a review of the activities of the AdvisoryScientific Board.

* *Because of a deteriorating political situation, the Centers forDisease Control was forced to close its own Central AmericanResearch Center located in El Salvador in 1981 and relocate to asmaller research and trainin g unit in Guatemala (53).

models, clinical investigation), and support serv-ices (library, administration, etc. ). Figure 2 il-lustrates the proposed organization.

The interdisciplinary scientific staff of sixAmericans, nine Panamanians, and one Peruvianincludes entomologists, arbovirologists, parasit-ologists, and other specialists (see table 6). On eU.S. Navy medical officer and one Navy Ph. D.parasitologist are currently on GML’s scientificstaff. The director of GML, Raymond H. Wat-ten, M. D., previously the commanding officer atthe Navy’s Medical Research Unit in Cairo, over-sees a total of 94 staff members and employees(121).

GML is strategically located for studies of dis-ease transmission and movement in tropicalAmerica. Panama is a crossroad of transporta-tion in the region and GML itself is in close prox-

imity to the field. GML also benefits from anavailable supply of Aotus monkeys, a simianvaluable for the study of human malaria (110).The U.S. Fish and Wildlife Service classifies the

Aotus as an animal which could become en-dangered by international trade.

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19

Figure 1. –Gorgas Memorial Institute Organization (currently official, but in process of being changed)

I Gorgas Memorial Institute

IData Processing Gorgas Memorial Laboratory A d m i n i s t r a t i o n

Biostat ic ian I Director Admi n i s t ra to r(Reeves) Raymond H. Watten Alvaro E Paredes ”

1 1 I1 1 r 1

m IFinance-De La Lastra b

I

Personnel-(Paredes)

L I

i

Assistant Director Maintenance Nelson’

Rolando E, SaenzI

Supplies-( Paredes)

Infectious DiseaseProgram

BacteriologyKourany (Vasquez)

iParasi tology

Sousa”

(Bawden)

1 Immunology

(Johnson’”] (Saenz)

m

Ecology and EpidemlologyProgram

i

EcologyReeves* (1)(Petersen)

Vertebrate Zoologyn Mendez’

Entomology:- (Reeves) (1)(Christensen)

i

Epidemlology, (Reeves)(Saenz)

Primatology & Laboratory

Programs I

G%El

EE!zlF==l

m

Education & Technical ISupport Programs

I

EEl

q Chief** Volunteer( ) Secondary Duty(1) Acting

Adjunct Associates:Ministry of Health:

Dr. Evelia QuirozU.S. Navy:

Dr. Frank S. WignallDr. Monte Bawden

Administrative Assistant:HMC Charles R. Miranda

SOURCE Gorqas Memor, al lnstll~te J ~11 { 1982

24-122 0 - 83 - 4

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2 0

Figure 2.—Gorgas Memorial Institute-Proposed Organization Chart


IGorgas Memorial Laboratory

Laboratory Environmental Clinical supportEpidemiology Sciences Biosciences Therapeutics Services

Data Processing Parasitology Vector Bionomics C. Investigation AdministrationImmunology Ecology Animal Models FinanceVirology zoology Animal Resources MaintenanceTissue Culture EducationSerum Bank Library

Tentative DepartmentalReorganization - July/63

SOURCE Gorgas Memorial Laboratory, 1983

Table 6.—Gorgas Memorial Laboratory Information onScientific Staff as of July 1983

Watten, Raymond H., M.D. (U. S.)Director

Saenz, Rolando E., M.D. (Panamanian)Assistant Director

Adames, Abdiel J., Ph. D. (Panamanian)Ecologist-Entomologist

Christensen, Howard A., Ph. D. (U. S.)Entomologist

Dutary, Bedsy C., Ph. D. (Panamanian)

ArbovirologistEscajadillo, Alfonso, D.V. M. (Peruvian)

Medical VeterinarianJustines, Gustave, Ph. D. (Panamanian)

VirologistKourany, Miguel, M. P. H., Ph. D. (Panamanian)

BacteriologistMendez, Eustorgio, Ph. D. (Panamanian)

Vertebrate EcologistOre, Gladys, M.S. (Panamanian)

MicrobiologistPeralta, Pauline, Ph. D. (U. S.)

VirologistPetersen, John L., Ph. D. (U. S.)

Insect GeneticistReeves, William C., M.D. (U. S.)

Medical Virologist

Rossan, Richard N., Ph. D. (U. S.)Parasitologist-Primatologist

Sousa, Octavio E., Ph. D. (Panamanian)Parasitologist

Vasquez, Manuel A., M.D. (Panamanian)Physician-Microbiologist

SOURCE” Office of the Director, Gorgas Memorial Laboratory, July 1983,

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ACTIVITIES OF GML

The activities at GML can be characterized asbasic and applied biomedical research, publichealth and medical services, and training, Projectsuse the laboratory, the clinic, and the field as

bases. Neither the types of activities nor the areaswhere they are carried out are entirely categoricalor mutually exclusive. The border between basicand applied research, for instance, is not a cleanline. Basic biomedical research, as used in thispaper, refers to work that seeks to advance thestate of knowledge about the vital processes thatunderlie the normal functioning of organisms andtheir malfunctioning in disease. Applied biomed-ical research draws upon basic information todevelop means of prevention, treatment, and cureof disease (4).

At the two ends of the research spectrum, thedistinction is clear. Observing and characterizingthe physical and metabolic behavior of a malarialparasite is basic research. Using the informationgained in th at w ay to d esign an intervention, e.g.,a vaccine or drug therapy, is applied research.Further down the line, e.g., testing the drug orvaccine in nonhuman primates, a major line of research at Gorgas, the work falls farther towardthe applied end of the spectrum. A clinical trialof the intervention in humans is a final step beforeresearch turns to practice. Even during a clinicaltrial, however, observations can be made thatwould fit the definition of basic research, in fur-thering the basic knowledge of normal and ab-normal human functioning. Marking the check-point between basic and applied research in theprocess described is all but impossible, and tospend a great deal of time attempting to do so isunproductive.

Many projects at GML have both research andservice components. About 1,000 patients peryear are treated in the clinic, providing an impor-tant service to the community. Observations of

those patients are an important source for learn-ing about the natural history and treatment of dis-eases, many of which cannot be adequately stud-ied elsewhere.

GML began as a traditional tropical medicineresearch institute concentrating on studies of malaria, trypanosomiasis, and leishmaniasis. Inrecent years, attention has been increasinglydirected to arboviruses and their vectors (110).Currently, GML also is involved in research proj-ects concerning sexually transmitted diseases,specific cancers, and ecological studies (see table7 for a more detailed listing of areas of activity).In the past, GML has been called on to serve asa reference center for the region (76). GMI alsooffers “Med icine in th e Tropics, ” a 6-week trop ical

medicine training program offered primarily tophysicians from the U.S. Navy, intended to pre-pare the medical officers for operational assign-ments in tropical areas. GML also hosts predoc-toral and postdoctoral students and scientists. In1981, students came from Venezuela, Costa Rica,Panama, and the United States; in 1982, fromKenya, Hungary, Argentina, Brazil, Cuba, Pan-ama, and the United States. In the past 12 months,GML lists these training figures (121):

3 0 Students, Medicine in the Tropics (6-week course)25 Visiting scientists

1 Postdoctoral student

2 Predoctoral students3 Bachelor-level stu den ts6 Trainees and graduate students

GML has working relationships with the Med-ical Entomology Research and Training Unit inGuatemala, the Centers for Disease Control, NIH,Louisiana State University (LSU), Johns HopkinsUniversity, and other academic and scientific in-stitutions. Most of these arrangements are “infor-real, ” but GML has a Memorand um of Agreementwith LSU, Yale University, Johns Hopkins, andthe University of Panama (121).

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22

Table 7.—Recent Activities of Gorgas Memorial Laboratory

Area of activity Active/recent Funding

Animal colonies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Care and maintenance of experimental animals

Applied pharmacology:Malaria drug testing (Aotus studies) (also under Malaria) . . . . . . . . . . . . . . . . . .

Rabies, clinical trial to identify best minimaldose of human diploid vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Arboviruses (various):

Arbovirus survey in Tabasara River Basin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Various projects relating to characterization of arboviruses

and investigating outbreaksAseptic meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Blackflies:

Vector competence of S. quadrivittatum for O. volvulus . . . . . . . . . . . . . . . . . . .Blackfly control in Fortuna Hydroelectric project

Species bionics; intervention at breeding sitesBlood meal analysis:

Feeding habits of known and potential vectors . . . . . . . . . . . . . . . . . . . . . . . . . .Campylobacter:

Survey of this important cause of diarrhea in Panama . . . . . . . . . . . . . . . . . . . .Cancer:

Human T-cell Ieukemia virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cervical and penile cancer in Herrera Province. . . . . . . . . . . . . . . . . . . . . . . . . . .Association with HTLV; and with herpes simplexCervical cancer and Herpes simplex . . . . . . . . . . . . . . . . . . . . ... , . . . . . . . . . . . .

Cell culture lines:Culturing of Sloth kidney cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Culturing of haemogogus equinus cells

Chagas’ disease:Study of risk of infection and human manifestations of Chagas’ disease

transmitted by R. pallescens (Central Panama) and T. dimidiata (Western Panama) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Biological and Isozyme characterization ofT. cruzi and T. range/i strains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Clinical diagnosis and treatment (approximately 1,000 cases per year) . . . . . . . .Data Processing:

National Cancer Registry (Panama) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cervical cancer projectNational serologic surveyBayano Lake clinical surveillance projectMalaria chemotherapy projectSTD Project

Environmental Impact Assessment:Tabasara Hydroelectric Project . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Fortuna River . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Influenza and clinical diagnostic virologyservices and surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Leishmaniasis:Identification of vector special; identification of reservoir (porcupine) . . . . . . .Isozyme electrophoresis diagnosis of strain and species of Leishmania

and identification of Ieishmaniasis vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . .Library:

Reference service and collection available to staff andoutside researchers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Malaria:In Vitro cultivation of infectious agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Antimalarial Drug Testing in Aotus monkey. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Phlebotomus fever:Serologic surveys of U.S. troops and Panamanians for Chagres and

Punta Toro Fevers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Comparison of Punto Toro and Rift Valley Fevers . . . . . . . . . . . . . . . . . . . . . . . .Identification of amplifying host vertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Retinochoroiditis due to Toxoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Serum Bank Reference Collection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

A

A

R

R

R

R

A

R

A

A

A

A

A

AA

A

R

R

A

A

A

A

RA

R

R

R

R

A

Core

U.S. Army contract

Core, with MOH

Contract

Core

Core, with JohnsHopkins University

Core

Core

Core

Core

and WHO TDR

and NCI grant

Core, with McMasterUniversity

Core

WHO TDR grant (partial)

CoreCore, with MOH

Core, plus miscellaneous

ContractContract

Core, with MOH

Core and WHO

Core and WHO

Core and grantPanama

AID grant

TDR grant

TDR grant

from

U.S. Army contract

CoreCoreCoreCoreCore

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23

Table 7.— Recent Activities of Gorgas Memorial Laboratory-Continued

Area of activity Active/recent Funding —

Sexually transmitted diseases (STDS):Gonorrhea—survey of prostitutes on prevalence and

penicillin resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Epidemiology of STDS in Panama (prevalence; maternal STD

and effect on pregnancy outcomes) . . . . . . . . . . . . . . . . . . . . . . .Shigellosis:Study of drug resistance in shigella isolates. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

St. Louis encephalitis (SLE):Study of how virus is maintained in the tropics . . . . . . . . . . . . . . . . . . . . . . . . .Studies with olivaceous cormorant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Susceptibility to infection of Panamanian vector with three geographic

isolates of SLE virus . . . . . . . . . . . . . . . . . . .Virulence testing and RNA fingerprinting of Panamanian SLE

virus isolates . . . . . . . . . . . . . . . . . . . . . . .Training:

Medicine and health in the Tropics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Triatoma Colony maintained for xenodiagnosis . . . . . . . . . . . . . . . . . . . . . . . . . .Trypanosomiasis ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Venezuelan equine encephalitis (VEE):

Search for epizootic virions from enzootic strains . . . . . . . . . . . . . . . . . . . . . . .Vertebrate zoology

Survey of Mammalian Fauna of Panama. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Long-term survey of rodents (zoogeography) . . . . . . . . . . . . . . . . . . . . . . . . . . . .Studies of Ectoparasites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Yellow fever:Monitoring of animal reservoirs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Monitoring of epizootics in Spider monkeysMonitoring of variations in vectors’ ability to transmit virus. . . . . . . . . . . . . . . .Genetic studies of jungle vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Longevity and age structure of Sylvan Yellow fever vectors. . . . . . . . . . . . . . . . NIH grant

KEY AID—U S Aqency for International Development, MOH–Panamanian Ministry of Health NC1—National Cancer Institute NIH—National Institutes of health, TDR–

.

R

A

R

R

R

R

R

AAA

A

R

AA

A

AR

R

Core

Core, with MOH

Core

NIH grantNIH grant

NIH grant

NIH grant

U.S. NavyCoreCore and WHO grant

Core

CoreCoreCore

Core

CoreNIH grant

Special Programme for Research and Tralnlng in Tropical Diseases (WHO), WHO—World Health Organizat!on

SOURCE Off Ice of Technology Assessment, 1983 Information provtded by Gorgas Memorial Laboratory WHO and Gorgas Memorial Laboratory flscai year 1981 and1982 reports

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Chapter 3

Quality of Research at the

Gorgas Memorial Laboratory

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Chapter 3

Quality of Research at theGorgas Memorial Laboratory

INTRODUCTIONThe Gorgas Memorial Laboratory (GML) en-

gages in a wide range of public health, research,and training activities. Gorgas scientists work inthe laboratory, in the field, and in the medicalclinic. GML performs applied and basic research,and provides public health services in those set-tings. (See ch. 2 for a description of currentactivities. )

This chapter examines the quality of research,training, and public health activities at GML.

Ideally, assessing the quality of the work at GMLwould be accomplished by a review of each proj-ect in each program. A multidisciplinary team of scientists would visit GML, speak with investi-gators, review research protocols, procedures, andpublications, and evaluate the physical plant. Anoverall rating would then be made, pointing outstrong and weak points. Such a thorough reviewwould serve as the basis for recommendingchanges in current programs, and to point outareas with future potential. OTA was unable totake such an approach.

Another avenue for assessing the quality of GML activities, and one that was suggested to theOffice of Technology Assessment (OTA) by anumber of people, is to compare GML activitiesand its record of productivity with that of asimilar institution. The logical choices for sucha comparison might be, e.g., Institute of Nutri-tion of the Caribbean and Panama, InternationalLaboratory of Research on Animal Diseases, theDepartment of Defense (DOD) medical researchunits, or the Centers for Disease Control’s formerfield station in El Salvador. Even these institu-

tions, however, are very different from GML intheir administrative structures and their researchagendas. While it was possible with the time avail-able and information at hand to make gross com-parisons of GML and DOD budgets, it was notpossible to make adequate comparisons of thequality of scientific activities.

For its review, OTA relied on:

1.

2.

3.

4.

5.

the record of past scientific review of GML’s

programs;a review of recent publications by GMLresearchers, including an in-depth analysisof a selection of active manuscripts andpublished articles;an assessment of peer review at GML;a review of recent grants and contracts heldby GML; andthe results of a telephone survey, commis-sioned by OTA, of experts familiar withGML.

OTA is aware that this type of assessment is

not definitive. It relies heavily on circumstantialevidence about quality (e. g., number of publica-tions), some unsubstantiated opinions about qual-ity (e. g., comments from the telephone survey),and the opinions of site visitors in previous years.As discussed above, other, more detailed methodsof assessment are possible which would both givea better reading of the state of GML activities andserve as a guide for future directions. Such anassessment could be valuable to GML as well asits funding agencies, and might be considered asa GML priority for the near future.

SITE VISITS BY THE FOGARTY INTERNATIONAL CENTER

The Fogarty International Center (FIC) at the other in 1980 (111). In 1978, a review of all pro-National Institutes of Health (NIH) has conducted grams was carried out by a team with represent-two site visits to GML, one in 1976 (110) and the atives from FIC and the Gorgas Memorial Institute

24-122 0 - 83 - 527

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28

(GMI) Executive Committee and Advisory Scien-tific Board. These are the only comprehensive pro-gram reviews that have taken place in recentyears, A scheduled site visit for 1983 has beenpostponed due to the uncertainties surroundingGML’s future (57). Before those site visits, com-

mittees of GMI’s Advisory Scientific Board hadconducted reviews of the virology and parasitol-ogy programs in. 1973 and 1974, respectively.

The FIC site visits were conducted by multidis-ciplinary teams which evaulated the scientific ac-tivities at GML. The charge of the 1980 five-person team was:

. . . an examination of the scientific programs of the Laboratory as to th eir quality, adequ acy, andrelevance in furtherance of the mission of thelaboratory, to provide ad vice and to make recom-mend ations as to any alterations in p riorities and

program or project implementation that seemedindicated, and in the final analysis to arrive atsome composite jud gment as to the v alue of thescientific work relative to the investment by theU.S. Government.

In add ition to reviewing the research p rograms,the site visit report comments on administrativeoperations and GML’s program in tropical medi-cine training.

Both FIC site visit reports were strongly positiveabout the overall operation of GML, while iden-tifying weaknesses and areas of unused potential.

The 1980 report concludes:The core long-range p rogram em pha ses of the

GML on parasitology, arbovirology, and ecologicstud ies continu e to be of scientific imp ortance,relevant to the health concerns of the UnitedStates, Panam a, and the region, and ap prop riate

to the unique location and facilities offered byGML.

The overall quality of research condu cted byGML is of high standard, nationally (UnitedStates) and internationally. As with an y institu-tion und ertaking a broad sp ectrum of projects,there are u nevenn esses that necessitate periodic

review and reevaluation, especially in terms of pr iority relative to available resources. The Teamfelt that, in general, this [review and reevaluation]was being done conscientiously and well. It would

emp hasize, as the p revious FIC review d id, thatGMI actively continue to support the GML Direc-

tor in this respect through regular site visits bymembers of the Executive Committee and / or theAdvisory Scientific Board.

The 1980 report noted a strengthening and con-solidation of research activities since the previous(1976) site visit. A major factor facilitating thatimprovement was the relatively stable fundingthrough the core grant, after several years of “uncertainty and adjustments” associated withGML’s absorption of the former NIH MiddleAmerica Research Unit (MARU). At this time, adjustments are continuing, as described in chapter2. Equilibrium has not yet been reached, and theresearch programs may be affected to some de-gree, particularly in terms of long-range planning,until the reorganization is complete.

Review of Research Programs

The FIC team critiqued each program as to itsquality and relevance, and developed specificrecommendations for each. The findings andrecommendations of the 1980 site visit report aresummarized below.

Parasitic Infections

Programs in leishmaniasis, trypanosomiasis,malaria, and toxoplasmosis are critiqued separate-ly. In general, these diseases are considered to beimportan t in Panama. The site visit report,however, pointed out the need for refocusin g

some of the studies.

The report stressed the unique availability of large numbers of patients with Ieishmaniasis, andthe potential for expanding and redirecting effortsin clinical investigations. Ongoing research witha known major animal reservoir of leishmaniasis,the two-toed sloth, is promising, and could alsobe more carefully focused.

GML has conducted research on Chagas’ dis-ease (American trypanosomiasis) for many years.Although GML is in possession of a large poolof clinical data, little has been published. The sitevisitors suggested that a major contribution to un-derstanding the importance of Chagas’ disease inPanama could result from analysis and publica-tion of clinical observations. GML had made someinteresting observations about treatment of

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29

Chagas’ disease with metronidazole, which the sitevisit team thought worthy of followup by otherlaboratories. Studies of vectors and animal reser-voirs, and longitudinal prevalence studies in onepopulation had provided interesting information,but the goals of those projects required reevalua-

tion.

Malaria

The main activities in malaria research are drugtesting for the U.S. Army, in Aotus monkeys.This work is considered important, but the sitevisitors recomm ended expanding the scope of ma-laria research to make greater use of the exper-tise and resources at GML.

Toxoplasmosis

Toxoplasmosis is a major cause of chorioret-initis (inflammation of parts of the eye) in Pana-ma, and as such is important, although, accord-ing to the site visit report “not of the highest pri-ority. ” While the site visit team thought contribu-tions could be made toward understanding toxo-plasm osis, “the principal focus of the project asdescribed seems somewhat lacking in relevancy.”

Arbovirus Program

Yellow fever, Venezuelan equine encephalomy-elitis, and St. Louis encephalitis are the major ar-

boviral diseases studied at Gorgas, though GMLretains the capability to investigate and evaluateoutbreaks of other diseases.

Yellow Fever

The site visit report deemed the yellow feversurveillance “one of the most important programsof GML. ” Panama is the key location for earlydetection of spreading yellow fever from Colom-bia into Central America. Gorgas has developeda proven method for surveillance of wild howlerand spider monkeys, the animal reservoirs of yel-

low fever. At this time there is no alternativemethod. The report favored continuation of mon-itoring seasonal variations in known mosquitovectors of yellow fever, and expanded efforts instudying transmission of yellow fever.

Venezuelan Equine Encephalomyelitis (VEE)

Past efforts in VEE research have produced use-ful information. The site visit report suggests ex-panding in this area,

St. Louis Encephalitis (SLE)Comments on the SLE research program indi-

cate that they are headed in productive directionsand the work should be continued.

Environmental Assessment Program

Assessments o f two major hydroe lec t r icschemes have been carried out under contract tothe Panamanian power authority. Although verydifferent in nature from most of the activities tak-ing place at GML, these assessments were con-sidered successful and useful by the site visitors.

They concluded:

In add ition to their technical and social impor-tance, such environmental assessment projects canhelp p rovide a m odel for similar studies in otherparts of the developing and d eveloped w orld. Fur-

thermore, they can readily be perceived by thepublic as dealing with actual concerns of thatcountry’s society, We feel that more thananything else in recent years, these projects inPanama have probably helped improve the im-age of the GML in the eyes of Panamanians.

Diarrheal Diseases Program

Several projects in diarrheal diseases were inprogress at the time of the site visit. They wereof variable quality and relevance, according tothe report. For instance, a project demonstratingthe efficacy of oral fluid therapy in the treatmentof dehydration secondary to acute diarrhea du-plicated research done elsewhere, but the projectappeared to be beneficial nonetheless. The reportstates:

Althou gh the m erits of the project as originalresearch are relatively low, the project served as

an edu cational effort of considerable importan ce.

A study of travelers’ diarrhea in Panamanianvisitors to Mexico was considered of only second-ary importance and not central to the mission of GML.

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At the time of the site visit, a collaborative ar-rangement with the Johns Hopkins UniversitySchool of Medicine had produced worthwhile re-sults in studying the incidence of acute diarrhealdisease in the San Bias Islands with respect to theavailability of water. However, the Hopkins unit

was not refunded beyond 1980 and the researchwas terminated.

Sexually Transmitted Diseases

Studies in sexually transmitted diseases (STDS)were carried out in collaboration with the Pana-manian Ministry of Health. They have focusedon the epidemiology and etiology of STDS, andhave led to further studies bearing on the veryhigh rate of cervical cancer in Panama. The sitevisit report commented that STD research was of “secondary importance” to the other major pro-

grams in parasitology, arbovirology, and envi-ronmental impact studies.

Cancer Registry/Cancer of the Cervix

GML has worked with the Panamanian nation-al cancer registry in epidemiologic studies of cer-vical cancer. Analysis of registry data indicatedthat Panama has one of the highest rates of cer-vical cancer in the world, and that geographicclusters in certain provinces have extremely highrates. Though not considered of the highest priori-ty by the site visitors, they rated the work of high

quality and recommended that it be continued.

Training

The site visit team was enthusiastic about theexcellence of training provided in the “Medicinein the Tropics” course. To be more consistent withthe mission of GML, however, it was suggestedthat Panamanians be included in the course ona regular basis* and that GML take over the direc-tion of the course entirely, rather than the direc-tor being a U.S. Navy assignee. They concluded:

. . . it app ears that the training capabilities andopportunities offered by GML, including the Lis-ter Hill fellowship s of GMI itself, warrant w idernotice in the scientific comm un ity.

q According to the Director of GML, only one or two Panamani-ans take the 6-week course each session (121).

Publications

Research and scientists are often judged on theirpublication records. The number of publications,the journals in which they are published, and thenumber of other authors who later cite the papers

are some objective, though indirect, indicators of quality. However, there are no fixed standardsagainst which to make a judgment of excellence.Research activities, in general, are aimed towardpublishing results, while public health service ac-tivities do not have publication as a primary goal.Even in research, each field of study and type of research varies greatly, and may result in a dif-ferent array of publications. Long-term field sur-veillance studies may result in a major publica-tion only after several years. Clinical observationsmay be published as case reports after only a sin-gle visit.

Environmental assessments are performed un-der contract to development agencies or compa-nies, and may result in few external publications,though they may be quite successful. Surveillanceactivities are routine until something is found. InPanama, yellow fever outbreaks have occurredevery 8 or 9 years, but surveillance must go oncontinuously.

Given the above perspective, OTA examinedthe GML publication record by looking at thenumber of publications in recent years and the journals in which they were published, and by

evaluating the quality of a sample of recentpublications and active manuscripts.

Number of Publicationsand Journals of Publication

Over the years of its existence, GML researchershave been authors or coauthors of about 950published scientific papers, about 200 of themsince 1975. (App. C lists publications since 1975. )Though it is impossible to rate the number of publications on a meaningful, objective scale,

GML’s record is indicative of continuous publish-ing activity. Table 8 shows the number of publi-cations by GML staff by year. Whether morepublications should have been expected is asubjective matter. A comparison of GML scien-tists’ publishing record to that of six of the

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31. ——— — . — . - — .— —

Table 8.—Total Publications of the Gorgas MemorialLaboratory, 1975-83

Year Total articles appearing

1975 .., . . . . . . . . . . . ... , . . . . . . . 341976 . . . . . . . . . . . . . . . . . . . . . . . . . 181977 . . . . . . . . . . . . . . . . . . . . . . . . . 14

1978 . . . . . . . . . . . . . . . . . . . . . . . . . 71979 . . . . . . . . . . . . . . . . . . . . . . . . . 161980 . . . . . . . . . . . . . . . . . . . . . . . . 241981 . . . . . . . . . . . . . . . . . . . . . . . . . 101982 . . . . . . . . . . . . . . . . . . . . . . . . . 171983 (to date) ..., . . . . . . . . . . . . . 6

SOURCE Office of Technology Assessment, 1983 Based on data provided byGorgas Memorial Laboratory, Offlce of the Director, Raymond Watten,July 1983

centers supported by the Rockefeller Foundation’sGreat Neglected Diseases program shows GMLto be at an acceptable but rather low level.GML scientists should certainly give more atten-tion to publishing the results of their work, andGMI/ GML management should be aggressive inurging such activity (the Director of GML andthe President of GMI have indicated they sharethis view).

GML researchers publish in a variety of scien-tific journals. Table 9 1ists the journals in whichpapers have appeared since 1980. These are large-ly refereed journals, meaning that p apers are scru-tinized in some formal way before acceptance, andgenerally there is some competition for publica-tion.

In most cases, Gorgas investigators were theprincipal authors (listed first among the authors,and generally taken to mean that the ideas andmost of the work can be attributed to that indi-vidual). Publications appear in both English andSpanish language journals. In general, papers of direct relevance to medical practice in tropicalAmerica appear in Spanish language publications(e.g., Revista Medica de Panama). Those of moreglobal interest have appeared in journals withmore international circulation (e.g., The Ameri-can Journal of Tropical Medicine and Hygiene).

An example of a subject of interest both locally

and internationally is oral dehydration therapy of infantile diarrhea. On the basis of clinical researchcarried ou t at GML, a pap er was pu blished in 1980in Revista Medica de Panama (6). The researchand resulting publication was of great value tolocal physicians in demonstrating the value of oral

Table 9.— Gorgas Memorial Laboratory: PublicationLocation for Articles Written by Staff; 1980 to July 1983

Number ofJournal or other location: publications

American Journal of TropicalMedicine and Hygiene . . . . . . . . . . ... . . .

Revista Medica de Panama . . . . . . . . . . . . . . .Revista Medica de la Cajade Seguro Social . . . . . . . . . . . . ... ...

Applied and Environmental Microbiology . .Infection and Immunity . . . . ... . . . . . .American Museum of Novitates ., . . . . . . . . .Journal of Medical Virology, , . . . . . . . . . . . . .Journal of Medical Entomology . . . . . . . . . .Mosquito News . . . . . . . . . . . . . . . . . . ...Epidemiological Bulletin . . . . . . . . . . . . . . . .Ecological Entomology . . . . . . . . . ... , . . .Bulletin of the WHO . . . . . . . . . . . . . . . . . . . .Revista de Biologica Tropical . . . . . . . . ... .Journal of Pacific Insects . . . . . . . . . . . . . . . .Transactions of the Royal Society of

Tropical Medicine and Hygiene . . . . . . . .Entomological and Ecological Studies ...

International Journal for theStudy of Animal Problems . . . . . . . . . . . . .Journal of Infectious Diseases . . . . . . . . . .Journal of the National Cancer Institute . . .Journal of Wildlife Diseases . . . . . . . . . . . . .New England Journal of Medicine ., . . . . . . .Journal of Economic Entomology . . . . . . .Revista Medico Cientifica . . . . . . . . . . . . . . .Annals of Internal Medicine. . . . . . . . . ... .Mosquito Systematic . . . . . . . . . . . . . . .PAHO Workshop ... , . . . . . . . . . . ... .BOOKS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Bacteria/ Infections of Humans Pediatric Cardiology

Presentations at Symposia/Conferences . . . .

Total articles appearing . . . . . . . . . . . . . . . .

15

13

32

2221

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

2

3

64.SOURCE Off Ice of Technology Assessment, 1983 Data from Office of the Dlrec

tor, Gorgas Memo;ial Laboratory, Raymond Watten, July 1983

rehydration. Subsequently , the same researchserved as a basis for the Panam anian arm of a con-trolled study of oral dehydration therapy of chil-dren in the United States and Panama, which waspu blished in the New England Journal of Medicine

(95). An editorial accompanying the article (12)highlighted the importance of this work, makingthe point that “Western-tra ined pediatricians

have created major impediments . . . to the. . .promulgation of oral-dehydration treatment . . .Indeed, local herb doctors, quick to recognize the

value of oral dehydration, have often been morehelpful than their Western-trained colleagues indisseminating the concept of oral dehydration. ”The contribution of GML in this case was to fa-cilitate a “technology transfer” to medical prac-tice in the developed world.

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Quality of Articles

OTA commissioned a review, * summarizedhere, of five currently active manuscripts and fourrecently published articles written by Gorgas staff members (the articles and manuscripts are listed

in table 10). The articles are not necessarily a rep-resentative sample of the total GML output. Theywere selected by OTA to cover as diverse a groupof topics as possible, subject to the practical con-straint of what was available immediately. Thereview assessed the process of the research, in-cluding the adequacy of study design, extent of data collection, and methods of presenting theresearch findings. Presented below is an examina-tion of the overall features which characterize theresearch reports, and assessment of the methodsof presentation of the data.

q The review was carried out for OTA by Richard K. Riegelman,

M. D., Ph. D., author of Studying a Study; Testing a Test, and amember of OTA's Health Program Advisory Committee. This sec-tion is based entirely on that review.

Table 10.—Articles and Manuscripts Reviewedfor the Office of Technology Assessment

by Richard K. Riegelman, M. D., Ph. D.

Articles 1. Christensen, H., and DeVasquez, A. M., “The Tree-Buttress

Biotope: A Pathobiocenose of Leishmania braziliensis,”American Journal of Tropical Medicine and Hygiene 31(2):243-251, 1982.

2. Dietz, E., Galindo, P., and Johnson, K., “Eastern EquineEncephalomyelitis in Panama: The Epidemiology of the

1973 Epizootic,” American Journal of Tropical Medicine and Hygiene 29(1) :13;1-140, 1980.

3. Dietz, W., Peralta, P., and Johnson, K., “Ten Clinical Casesof Human Infection With Venezuelan Equine Encephalo-myelitis Virus, Subtype l- D,” American Journal of Tropical Medicine and Hygiene 29(2):329-334, 1979.

4 .Young, M., Baerg, D., and Rossan, R., “Studies With in-duced Malarias in Aotus Monkey s,” Institute Animal Sciences 25(6):1 131-1137, 1976.

Manuscripts 5. Petersen, J., “identification of Phlebotomine Sand Flies

(Diptera: Psychodidae) by Cellulose Acetate Electrophor-esis” (in press).

6. Piesman, J., Sherlock, l., and Christensen, H., “TriatomineDensity and Host Availability” (in press).

7. Seymour, C., Kramer, L., and Peralta, P., “Experimental St.Louis Encephalitis Virus Infection of Sloths and Cormo-rants” (in press).

8 .Seymour, C., Peralta, F)., and Montgomery, G., “SerologicEvidence of Natural Togavirus Infections in PanamanianSloths and Other Vertebrates” (in press).

9 .Seymour, C., Peralta, P., and Montgomery, G., “VirusesIsolated From Panamanian Sloths’ ’-(in press).

SOURCE: Office of Technology Assessment, 1983,

Overall Features of the Articles and Manuscripts

The articles and manuscripts reviewed reflecta wide spectrum of scientific activities. These ac-tivities include:

q

q

q

q

q

q

q

q

study of a naturally occurring epidemic with

potential for human transmission;development of new animal models forstudying human disease;investigations of the mechanisms for trans-mission and reservoirs of disease in their na-tural field environment;laboratory investigations designed to assessthe susceptibility of animal hosts as interme-diaries in the transmission of human disease;reporting on a series of human cases of dis-ease collected over more than 15 years;development of a new technique for perform-ing enzymatic studies on disease vectors;field studies of the effect of a human livingenvironment on the transmission of disease;an d

correlation of biochemical genetic character-istics of disease vectors with the epidemiolog y

of disease.

Important features of these investigations in-clude the ability to collect and coordinate datafrom a variety of sources. The ability of the in-vestigators at GMI to bring together data froma variety of sources is demonstrated in these stud-ies in at least the following ways.

q

q

q

correlation of their laboratory investigationswith findings from their field research andknowledge of the epidemiology and naturalhistory of disease;cooperation with other laboratories, in-cluding CDC and a number of U.S. univer-sity, public health, and military programs;ability to respond to a naturally occurringepidemic, collecting data requiring coopera-tion with public health control programs,hospitals, and correlation with laboratory in-vestigations; and

ability to collect and test large numbers of disease vectors from a variety of natural en-vironments.

The majority of the investigations represent un-related studies. Three of the investigations how-

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ever, include coordinated studies using two- andthree-toed sloths found in the Panam anian forests,

These three studies reflect the ability of in-vestigators at the laboratory to:

q

q

q

Ž

q

collect a large spectrum of species of birdsand mammals from a variety of natural en-vironments;track the natural history of disease by plac-ing radio transm itters on selected animals andrecapturing them for sequential testing;perform viral isolation and serological testingneeded to correlate with the epidemiolog y

and natural history of disease found in thePanamanian forests;relate the field and laborator y findings tohuman disease potential; anduse knowledge gained from earlier studies to

improve the design and performance of sub-sequent studies.

Presentations of Data

Background and Hypotheses.—The authorsfrequently introduce their presentations by a suc-cinct discussion of their study’s purpose and itsrelationship to existing knowledge. These intro-du ctions are w ell referenced an d place the studiesin a context which does not require the reader tohave a previous detailed knowledge of the field.

The study hypotheses are usually clearly statedand their relationship to previous studies are, onthe whole, well outlined.

Study Methods.—The authors of the fieldlaboratory studies provide detailed discussions of the location of their collections and the methodsof preservation and preparation of their materials.The experimental studies provide an adequate de-scription of the study methods, including refer-ences to the specific techniques employed. Thesepresentations appear to fulfill the essential criteriathat other investigators are provided adequate in-formation to attempt to reproduce the findings.

When judgments as to technique and criteriafor positive results are required the authors ap-propriately present the justifications for theirchoice. When the methods themselves possess lim-itations in their ability to measure the intendedphenomena, the authors clearly identify these lim-itations,

Results.—The authors present the results of their studies in adequate detail. They consistent-ly present and acknowledge their failures and thelimitations of their results as well as presentingtheir positive findings. This practice should addto the value of these investigations by identify-ing areas for further research, appropriately lim-iting the conclusions, and preventing other inves-tigators from pursuing unproductive approaches.

The statistical methods used in the articles re-

quire only basic methods. However, the methodsused are appropriate and appear to be properlyemployed.

When interpreting the results of their studiesthe authors usually present a variety of potentialexplanations for their findings, including the ex-planation they favor.

In presenting their results, the authors generallyare able to relate their findings to current scien-tific thinking as well as their implications for im-mediate disease prevention or control. The articlesoften suggest areas for further investigations.

Summary

In summary, the articles and manuscripts re-viewed reflect a high level of expertise in design-ing and carrying out scientific research. The in-vestigators demonstrate an ability to collect andcoordinate data from a variety of sources, pre-sent data in an analytical manner, and build onand contribute to the worldwide scientific litera-ture. The authors are able to take advantage of the unique features of their setting and experi-ments to contribute to knowledge of basic and ap-plied biological science.

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PEER REVIEW AT THE GORGAS MEMORIAL LABORATORY

One of the questions being addressed by theGeneral Accounting Office (GAO) is about thepeer review process at GML. Thus, this memoran-dum will not discuss peer review except for some

comments on the relationship of peer review tothe quality of research. By peer review, OTA isconsidering basically the process by which deci-sions are made to fund research projects with in-ternal (core grant) money and the process of evaluating internal research. Research fundedthrough grants and contracts is subject to peerreview by the funding agencies, e.g., NIH and theWorld Health Organization (WHO). In thosecases, GML is competing with other researchorganizations for support. In a sense, GML staff are competing with each other for core funds tosupport their projects that are not under grants

or contracts. A peer review system for researchproposals, and reviews of ongoing and completedwork are mechanisms used to allocate resourcesaccording to merit and to assure that researchquality is acceptable.

It is not uncommon for internal peer reviewsystems to be less rigorous than externally fundedsystems. For instance, at NIH, researchers on thecampus do not submit proposals through the samesystem that funds extramural research. Research-ers within each institute do go through a formalprocess for allocation of intramural research

funds, but review is basically within the instituteitself. Proposals and protocols are not scrutinizedby outside experts, but, at specified intervals out-siders do evaluate the work that goes on withininstitutes.

OTA gained some insight into the peer reviewprocess at GML through the telephone surveyabout Gorgas. There was a general lack of agree-ment about w hether a p eer review process—either

GRANTS AND CONTRACTS

The record of an institution or a researcher canbe measured in the number and dollar value of grants and contracts awarded from externalsources. Externally funded projects are more likely

to review research proposals, protocols, or re-sults—does in fact exist. It is clear that even if aprocess has been set up on pap er, it does not func-tion effectively on a regular basis.

The fact that GML does not seem to have awell-known system for allocating money withinthe organization is something that requires con-sideration in futu re plans. A tru ly internal system,such as NIH uses, may not be the best plan forGML. Institutes in NIH have a large core of in-dividuals with knowledge in a specific field. Forinstance, all researchers at the National CancerInstitute are knowledgeable about some aspect of cancer. There is a large number of people thereto provide adequate review of internal researchproposals,

At GML, investigators are unique in education,training, and research areas. It would probablybe difficult and perhaps not so effective to haveonly GML staff review each other’s proposals andresearch results, though that is also desirable. Themain peer review body could be drawn from theAdvisory Scientific Board, which has good scien-tific representation from the relevant disciplines.A model for how such a group might operate isthe peer review process of the Plum Island (NewYork) Animal Disease Center of the U.S. Depart-ment of Agriculture, In that case, there are fivenon-Government consultants who visit once eachyear (but may be called to visit in the interim if necessary). The consultants are selected by thelaboratory director and are responsible directlyto that person. The consultants produce a reportassessing all programs. The consultants’ expensesfor the visit are paid (98). Paying for travel is evenmore critical for GML, since travel to Panama isrelatively expensive.

to undergo vigorous peer review than are thosefunded internally by an institution. (See “PeerReview at the Gorgas Memorial Laboratory, ”above. ) This is a p articularly app ropriate measure

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for researchers in the United States, where thereis a relatively large amount of money availablefor research, though competition is quite keen.

Most of the research at GML is funded throughthe core grant, rather than through competitive

grants and contracts. Addressing this, the 1980Fogarty Site Visit Report states:

In these times of financial constraint every-wh ere, the Team d oes not feel that too m any ex-

pectations shou ld be held ou t that project grantsand contracts could or even should su pp lant thenecessity for the maintenance of adequate coresupport.

A number of past and current projects have re-ceived grant or contract funding from sourcesother than the core grant, including the WHOSpecial Programme for Research and Training inTropical Diseases (see app. A), the U.S. Army andNavy, NIH, and private foundations, Table 11lists current, completed, newly approved, and

Table 11 .—Gorgas Memorial Laboratory: Grants andContracts as of July 1983

Current grants: U.S. Army Drug Evaluation ContractU.S. Navy Training ProjectWHO/TDR Triatomine Blood Meal ContractWHO Clinical Trial for Evaluation of Leishmaniasis TherapyWHO Isozyme Lutzomyia—Sand FliesNIH/Yale Arbovirus—Yellow FeverWHO/TDR Chagas’ Disease

UNDP/World Bank/WHO Leishmaniasis in HondurasCompleted and or terminated grants/contracts: Tabasara Hydroelectric Environmental Impact StudyNIH/NCl Cervical Cancer StudyNIH/NIAID Epidemiology of St. Louis EncephalitisAID In Vitro Malaria CultureWHO/TDR Control of Simuliids

Approved contracts: Panamanian Ministry of Health/lnteramerican Development

Bank—Malaria and LeishmaniasisNIH/NCl Epidemiology of Human T-Cell Lymphoma VirusWHO/PAHO Epidemiology of Childhood Respiratory Illnesses

in Panama

Pending grants: Rapid Early Serodiagnosis of Leptospirosis by Detection of

Antigen in Body Fluids of Infected Persons

Epidemiologic Assessment of Preventable Illness inHonduran Refugee Camps

Effects of Two Arbovirus in the Development of PanamaRegional Reference Center for Studies on New World

Phlebotomine Sand Fly Host Feeding Patterns

ausually because of lack of funding

SOURCE Gorgas Memor!al Laboratory, Off Ice of the Director, July 1983

pending grants and contracts. There are somegrants and contracts in every GML program.

The fact that GML has competed successfullyfor research money is evidence that the qualityof research is equal to other research projects

funded by those agencies at other institutions.Support for new projects by these funding bodiesis also dependent on successful past performance,giving some assurance that GML is considered de-pendable. An official at the National Cancer In-stitute (32) was very positive about Gorgas’ abilityto carry out a newly approved epidemiologicstudy involving human T-cell lymphoma virus,based on their past work. He also mentioned thatGML is the obvious choice as a coordinatingcenter for a possible future collaborative study of cervical cancer in several countries in the region.

Quality of Research at GMLas Seen by Experts

Several questions in the telephone survey thatwas commissioned for this technical memoran-dum (see app. D for a more detailed discussionof the survey results) addressed the quality of research and training at GML. In response to ageneral question, “How w ould you rate the workof GML?” most of the 23 experts interviewedreacted positively. Some programs were rated ex-cellent, including the work in virology (especial-ly in arboviruses), malaria, medical entomology,trypanosomiasis and leishmaniasis, cancer, STDS,and environmental studies. Other programs, bac-teriology, for instance, were rated lower.

A commonly held sentiment was that the quali-ty of work varies from program to program, withmany strong points and some weak points, butthat such a state of affairs was to be expected inan institution that has been in existence for solong. In some areas the work has become routine,with slow but steady progress. Some work wasdescribed as not very original, but, technicall y

good. Presumably this refers to such activities as

serotyping of viruses, which is of public healthimportance, and is done routinely at GML, butis not necessarily innovative.

Several people made the point that judgmentsabout quality of research must be tempered b y

24–1 2’? () - 83 - 6

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36

consideration of the conditions under which workis done—field conditions make for a much dif-ferent situation than that encountered at NIH.Particularly in light of working conditions in theTropics, GML was rated highly.

The uncertainty of financial support affects thequality of research, according to a number of ex-perts. Lacking a secure future, it is difficult to at-tract top scientists to work at any institution. Inaddition, the researchers already there are ham-pered in planning for all but the most immediateresearch.

There was a diversity of opinion about whetherthe quality of research at GML has changed ap-preciably over the years. Research emphases havechanged and the whole field of scientific researchhas changed so greatly that such a judgment isdifficult to make. Of those who did answer, some

felt there was no change, others a change for thebetter (variously since World War II, to withinthe last 11/ z years). A number n oted a general de-cline in research quality over the years, all of thoserespondents r elating the decline to un certain fund -ing.

The experts contacted were asked about thequality of tropical medicine training offered atGML. Most gave it a high rating. The unique set-ting was considered the most important asset inthe training programs. The opportunities for clin-ical experience were particularly important for the

military. In this regard two respondents referredto a comment of General Douglas MacArthur’sthat in the Philippines he needed three divisionsto do the work of one, since two would be in thehospital with malaria or dengue. The diseaseecology is such in. Panama that similar oppor-tunities for learning about tropical diseases do notexist in many other places. One expert mentionedthat training in Puerto Rico, for instance, wouldnot be as valuable as that at GML. A few people

said that the training had gone downhill duringthe past few years because of financial constraints.

Summary

The research carried out at GML over the years

has been of generally high quality. OTA’s analy-sis, the survey of expert opinion, the criticalreview of articles and manuscripts, and past sitevisits are all in agreement on this general conclu-sion. As is the case in any institution with a longhistory, there are strengths and weaknesses. Re-search emphases have shifted over the years, andthe quality has varied as well. The results of thetelephone survey confirm that most of the majorprograms are strong and of good quality, and thatthere are fewer weak points.

However, mechanisms to assure continued high

quality of research are not in evidence. There isa lack of an effective peer review process forallocating money to research projects funded bythe core grant. While grants and contracts fundedexternally have passed through a competitiveprocess designed to assure high quality, internal-ly generated and funded projects do not n ecessari-ly receive the same degree of scrutiny. Anotherexample of a potential problem area is collabora-tion with other high-quality institutions. GMLmust become more aggressive in seeking and instrengthening interaction and collaboration withscientists and institutions from other countries

(especially the United States). And, as mentioned,GML could make a larger effort to publish studyresults.

OTA finds that GML is carrying out researchof high quality, and that the institution enjoys agenerally solid reputation in the field of tropicalmedicine research. The most serious threat tomaintaining good research is continuing uncer-tainty about future financial support.

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Chapter 4

Relevance of Research at Gorgas

Memorial Laboratory to Health

Problems in Tropical America

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Re

——

Chapter 4

Ievance of Research at GorgasMemorial Laboratory to HealthProblems in Tropical America

This technical memorandum considers the termtropical diseases to refer both to those classicallydefined as tropical diseases, such as schistosomi-asis, and to those in a broader definition of theterm, such as tuberculosis and malnutrition (seech. 1). Socioeconomic status (e. g., malnutrition,poverty) defines the Tropics and, to a very largedegree, tropical diseases, Otherwise life in ur-banized tropical America presents the same haz-ards to health as life in North America or Europe.

The intimate relationship between health statusand economic and social progress means thatsome health problems in tropical America willonly succumb to long-term socioeconomic ad-vancement, yet tropical diseases, by their enor-mous impact on health status, simultaneously andseriously affect the economies of tropical coun-tries. The six tropical diseases singled out by theWorld Health Organization (WHO) for specialprogrammatic research support—malaria, schis-tosomiasis, filariasis, trypanosomiasis, leishma-niasis, and leprosy—together affect between 700million to 80 0 million people. The first three each

affect more than 200 million people worldwide(5).

The resulting amount of human suffering anddisability is enormous. This argues for urgenthumanitarian action where feasible interventionsexist. Significant costs are involved in treatingsuch diseases and in implementing public healthprograms for their prevention and diagnosis, eventhough health services are usually underfundedand inadequate in most of the less developedcountries. However, the most substantial econom-ic impacts may be the indirect ones affecting a

country’s human resources and productivity.Health problems in the region of tropical Amer-

ica cover a broad range because of the great varia-tions in climate, geography, socioeconomic con-ditions, and culture. Modernization, population

growth, and rapid rural-to-urban migration causemany diseases of the developed world to havegrowing significance in tropical and developingAmerica, especially among affluent, middle-aged,and urbanized persons. For example, heart dis-ease, stroke, diabetes, cancers, and accidental in-

juries are all emerging as major causes of mor-bidity and mortality in statistics for the LatinAmerican and Caribbean regions. *

Even as diseases of the developed world acquire

increasing importance as major causes of mortali-ty in tropical America, the nonfatal diseasescaused by parasitic and infectious agents remaina critical drag on developmental progress and thequality of life. Furthermore, in the developingcountries, life expectancy at birth is much lowerthan in th e developed w orld. This is a direct resultof high infant and childhood mortality. The major killers of infants and children are three groupsof diseases: diarrheal and enteric infections (fecal-borne), respiratory infections and measles, andmalnutrition.

This chapter will first describe some of the major tropical diseases and conditions of ill-healthof tropical America. Following that, the GorgasMemorial Laboratory’s (GML) research and re-lated activities will be discussed in light of the in-formation on regional health problems and re-search needs.

Evaluation of research relevance quickly be-comes subjective. Research by its nature is open-ended. If science administrators and researcherscould predetermine all lines of productive re-search, they would do so. The reality is often a

simpler hope—for good judgment and good luck.*Caution is necessary, however, in interpreting these statistics,because they derive from health care systems that are weighted(because of the training of physicians, the availability of health fa-cilities, the logistical problems of data collection, etc. ) towards thediagnosis and recording of acute, traumatic, or degenerative diseasepresentations in urban areas.

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In evaluating the relevance of research at GML, nities, and the relationship of GML’s research toOTA depended on identified health problems and those health problems and research needs.needs, resulting research questions and opportu-

TROPICAL DISEASES: DESCRIPTION AND STATUS

Acute Respiratory Infections

Acute respiratory infections (ARI) area majorcause of mortality in children under 5 and theelderly. The group includes many viral and bac-terial infections: influenza (myxoviruses, type A,B, C), parainfluenza (paramyxoviruses), measles(paramyxovirus), respiratory syncytial viruses,adenoviruses, rhinoviruses, Streptococcus pneu-monia and other bacteria, chlamydia (congenital),and mycoplasma. Influenza and pneumonia areamong the top five causes of death in children

under 5 in every country of the Pan AmericanHealth Organization (PAHO) region (75). In ad-dition to the serious mortality risk for the veryyoung and the very old, these infections are atremendous social burden in terms of work pro-ductivity lost and demands on the health caresystem by all age groups.

These infections are aggravated in conditionsof malnutrition and substandard living conditions,and in combination with other infectious diseases.A principal epidemiological factor of ARI trans-mission is close, overcrowded associations thatpromote inhalation of aerosolized pathogens bycoughs, sneezes, and personal contact.

For most of these diseases there is no treatmentother than symptomatic and supportive relief,though bacterial infection can be effectivelytreated with antibiotics. Vaccinations for measles,whooping cough, and diphtheria are feasible andpromoted under the Expanded Program on Im-munization of WHO. Vaccines against influenzaand pneumococcal pneumonia are available buthave reduced usefulness in developing countries:Pneumococcal vaccine is not very effective inchildren under 2 years old; influenza vaccines

must be renewed periodically according to the cur-rently prevalent strain.

Improved access to health care is a critical fac-tor, but also needed are field-based epidemiolog-ical studies. ARI control is largely ignored in most

developing countries. This is a function of difficultdiagnosis (of the etiologic agent), lack of effec-tive treatment, lack of definition as a tropical dis-ease, and as an entity worthy of focused research.Longitudinal studies on the epidemiology of ARIusing rapid diagnostic techniques are needed.These studies could simplify the prevention andtreatment of ARI by precisely identifying the im-portant etiologic agents in geographic areas andby determining the risk factors which make ARImortality so high. Practical management of ARIdepends on differential diagnosis of viral from

other bacterial, chlamydial, and mycoplasmalagents for which specific treatments are effective.With risk factors defined, intervention againstthem could be initiated. At the same time, suchstudies would produce baseline prevalence datafor subsequent evaluation of intervention meas-ures taken.

Diarrheal and Enteric Diseases

Diarrheal diseases are the leading cause of deathin children under 5 years of age in over half thecountries of Latin America and one of the top five

for all other countries. Data from several coun-tries indicate that the typical child below 5 yearsof age experiences four to eight diarrheal episodesannually. In some countries, up to 45 percent of all hospital visits during the months of highestdiarrhea pr evalence are due to childhood d iarrhea,and case fatality rates as high as 40 percent havebeen recorded (76).

A comparison of death rates in children under1 year of age is startling. For North America(United States and Canada), the mortality rate ininfants in 1979 was 21.9 per 100,000; for Latin

America it was 914.6 per 100,000, 40 times higher,almost 1 in 100 infants dying of diarrheal disease.Because underreporting from rural areas is stilla problem, it is likely that the statistical numberof diarrheal cases will increase as health servicesare extended to rural populations.

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Diarrheal diseases constitute a clinical syn-drome of varied etiology, all of which are trans-mitted by human feces. These include bacilli, vi-ruses, and parasitic and helminthic parasites, suchas shigellae, salmonella, Escherichia coli, Cam-

pylobacter, Yersinia, rotaviruses, amoeba, giar-

dia, ascaris, and ancylostoma. Poliomyelitis isalso a fecal-borne disease.

Rotaviruses, which in recent years have beenfound responsible for almost half of infant diar-rheas in the developing world, were first detectedin humans in 1973. Serologic studies have shownthat by the age of 2 years, nearly all children havehad the infection. A Guatemala communitystudy indicated that rotavirus accounted for 10to 20 percent of all diarrhea there.

Escherichia coli is a second important causeworldwide of diarrheal disease. Only certainstrains which are classified in three groups causedisease: enterotoxigenic E. coli, enteroinvasive E .

coli, and enteropathogenic E. coli. Each group hasa distinctive physiological and pathological symp-tomatology. Serotyping based on bacterial cellwall antigens is a second classification system.

Other important diarrheal pathogens are S h i -

gellae, Salmonellae (both typhoid and nonty-phoid), Campylobacter, Entamoeba histolytica

(amebiasis), and Giardia lamblia (giardiasis).

Although acute diarrheal diseases remain aleading cause of childhood morbidity and mor-tality in most of the Americas, prospects for theircontrol are steadily improving. Intensive researchin recent years into almost all aspects of diarrhealdisease has led to a number of breakthroughs andtechnical innovations, such as oral dehydrationtherapy (ORT), which has become the main strat-egy of the WHO/ PAHO d iarrheal disease con-trol program. Therapeutic studies continue todocument the effectiveness of this simple, safemethod which uses a single specific orally ad-ministered water solution of electrolytes andglucose. An ORT trial project begun in 1978 in

Costa Rica has proved an effective lifesaver inboth bacteria l and rotaviral infant diarrhea(70,72,83). A recent study (95) demonstrated thateven in well-nourished children in developedcountries, ORT is a safe and effective treatmentfor acute diarrhea (regardless of etiologic agent)

and could replace the use of intravenous fluidsin the majority of such children.

In addition to ORT, four other major strategiescomprise the diarrheal disease control program:1) improved child care practices, including pro-

motion of breastfeeding, proper w eaning, and per-sonal hygiene; 2) health education; 3) improvedwater supply, environmental sanitation, and foodhygiene; and 4) epidemiologic surveillance. Amedium- to long-term objective is to integratediarrheal disease activities into existing primaryhealth care systems.

With the growing evidence of rotavirus impor-tance in diarrheal disease, further epidemiologic,clinical, and basic research is needed. A major objective now is to develop a vaccine for humans.Such a vaccine exists for animals. Immunologicaldiagnostic testing exists which can be utilized forfield studies of prevalence and incidence in geo-graphic localities.

Childhood mortality is the highly visible tragicaspect of enteric disease, but the chronic anddebilitating effects of these parasitic and infectiousdiseases (e.g., chronic anemia due to intestinalhookworm) rob a nation of productivity, vitali-ty, and initiative. WHO estimates there are at least650 million people in the world with roundworm(ascariasis), 450 million people with hookworm(ancylostomiasis), 350 million people with amoe-biasis, and 350 million people with whipworm

(trichuriasis) (99). Fecal-oral transmission is thecommon denominator of all these diseases. Lackof safe and adequate water supply and of properexcreta disposal, two of humankind’s most basicneeds, are the critical deficiencies that promotethese diseases. In rural Latin America, 68 percentof the population lack access to water supply serv-ice, and 98 percent lack sewage service of anytype. In urban areas, 22 percent lack access towater su pply service, and 57 percent have no sew-age service.

Malnutrition

Malnutrition is a primary cause of death of children under 5 years of age in Latin America.Though not a disease per se, it is so intimatel y

involved in disease processes and ill-health to war-rant specific mention in this overview. The Inter-

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American Investigation of Mortality in Childhoodshowed that low birth-weight (2,500 g or less) andnutritional deficiency were the direct cause of 6percent of deaths ‘before age 5 and an associatedcause in 57 percent of all deaths (85). Death is thefinal outcome in a chain of events that begins be-

fore birth and then involves the pernicious interac-tion of malnutrition and infectious disease. Mater-nal malnutrition (together with maternal age andparity, two other determinants in infant mortali-ty (86)); prod uces prematur e birth and low w eightat birth, both serious risk factors for the newborn.Infants who survive the neonatal period tend tothrive for the first 6 months of maternal feeding,but then come to risk from varying degrees of kwashiorkor and marasmus, the two poles of pro-tein-energy malnutrition. According to Gueri (48),in a great majority of cases the problem resultsnot from lack of food in the home but rather from

maldistribution of food within the household,from lack of knowledge about child feeding, froman unsanitary physical environment conducive toinfectious diseases (particularly gastroenteritis)that increase the child’s energy requirements whiledecreasing its appetite, from early replacement of breastfeeding with highly diluted and contami-nated m ilk formulas, and in some cases from sheerneglect.

Though malnutrition as a primary cause of morbidity and mortali ty is less prevalent inadolescents and adults, it still must be considered

a major contributing factor in infectious diseases.Immunologic defense mechanisms are seriouslycompromised by malnutrition. The synergistic in-teraction of malnutrition and disease is well doc-umented. For example, Scrimshaw, Taylor andGordon (101) observed that, except where popula-tions are malnourished, or otherwise uncommon-ly susceptible to disease, the incidence of tuber-culosis is significantly lower than would be ex-pected by the widespread presence of the tuber-cule baccilus. Mortality due to measles was 274times higher in Ecuador than in the United Statesin 1960-61, a time before the development of im-munization to the disease (85). Thus in all analysisof tropical health problems, protein-energy mal-nutrition must be considered a contributing causein the disease process, and as a primary cause inchildren under 5 years old.

Important research and intervention experi-ments have been carried out under the auspicesof PAHO. The principal research centers are theInstitute of Nutrition of Central America andPanama (INCAP), the Caribbean Food and Nutri-tion Institute (CFNI), and the Latin American

Center for Perinatology and Human Develop-ment.

Malaria

Malaria is a disease caused by a protozoanblood parasite transmitted by various anophelinespecies of mosquitoes. It is one of the most wide-spread and destructive diseases in the world andhas made a resurgence in the last decade with amore than two-fold increase in world prevalence(127,128). The incidence of malaria in developednations, such as England and the United States,

has also been increasing due to imported cases.Estimated malaria incidence worldwide is 300 mil-lion cases per year. In 1982, 702,000 confirmedcases were reported from the Americas. Thesestatistics are large but undoubtedly underre-ported, because the disease is contracted in ruralareas remote from medical facilities. An estimated64.9 million people live in areas of tropicalAmerica where the risk of contracting malaria per-sists. The countries of worst malaria incidence areHaiti, Guatemala, Honduras, El Salvador, Co-lombia, Bolivia, and Brazil.

The resurgence of malaria in the last decade isa setback due to the failure of the global eradica-tion campaign based on DDT house-spraying andsupplementary mass drug distributions. Early suc-cesses led to overconfidence that ignored the com-plexity of a disease caused by four d ifferent sp eciesof parasite and transm itted by many different spe-cies of mosquito vectors, each with peculiar be-havior patterns in widely varying ecological andsociological settings. The serious consequences of that failure are insecticide-resistant mosquito vec-tors and drug-resistant strains of the parasite.

Malaria research is in a new period of vigorousactivity, like most of parasitology. Molecular biol-ogists, geneticists, and biochemists have begun toapply their research skills to the many importantquestions that were ignored during the eradica-tion era. Metabolic studies can identify parasite-

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specific enzyme pathways that can be exploitedto kill the parasite without harming the humanhost, Membrane research can reveal how theparasite finds, attaches to, and invades red bloodcells yielding important clues for d rug therapy an dvaccine research. Recent clinical studies have sug-

gested better ways of pr eventing and treating cere-bral malaria, an often fatal complication of severemalaria infection.

The spread of drug-resistant malaria (by thespecies Plasmodium falciparum ) is of great con-cern worldwide. Regular monitoring of local para-site strains is necessary to keep abreast of thera-peutic changes that may be needed, both in typeof drug and dose. In Latin America, serious drug-resistance has still not moved north of the PanamaCanal. Renewed effort to develop new drugs isproducing results, but takes years to move from

laboratory screening thr ough animal testing to hu-man trials.

Vector biology studies are critical to any ra-t iona l mosqui to -con tro l e f fo r t . Cytogene t icresearch which analyzes insect chromosomes hasidentified species complexes that were previous-ly unrecognized by conventional taxonomy. Asan example, Anopheles gambiae, the notoriousmalaria vector in Africa, is now known to be acomplex of several distinct species all identical tothe unaided eye. Cytogenetic differentiation of thevarious species has explained the different behav-

ior patterns of the A. gambiae complex and de-fined the important vector species. Research onphysiological resistance mechanisms can aid thedevelopment of better insecticide methods. Behav-ioral resistance, the avoidance of insecticides byinsects, is important for two opposite reasons—the killing effect is reduced, but transmission maystill be interrupted, if vectors avoid humanhabitations.

Field- and comm unity-based stud ies are neededto assess the impact of antimalarial interventions.The ecological impact of vector intervention iscritically important. The selection of insecticide-resistant vectors has seriously handicapped cur-rent control efforts. The effect of antimalarial ac-tivities on population immunity levels still needsclarification. Studies in the past have clearlydocumented the immediate impact of antimalarial

projects on morbidity and mortality, but not thelong-term consequences when projects cease orfail. Other studies need to evaluate the importanceof sociological and human behavioral factors andthe usefulness of health education, communityself-help, and volunteer collaborators.

Significant progress is being made on the de-velopment of a vaccine against malaria, includingthe identification of surface antigens and their pro-duction by bacteria. If animal testing confirms thefeasibility of immunization against this parasite,extensive human and field trials will be required,before there is widespread usage of vaccines inthe control of this disease. The wide usefulnessof a vaccine is also debated considering the manydifficulties associated with implementing otherdisease immunization campaigns.

Chagas’ DiseaseChagas’ disease (American trypanosomiasis) is

caused by a protozoan parasite of the blood andtissues and transmitted by reduviid bugs (“cone-nosed” or “kissing” bugs), common blood-suckinginsects in the Americas. It is a disease of poor ruralareas with substandard housing that provides har-boring sites for the bugs to live and breed. About150 species of mammals have been incriminatedas reservoir hosts, including dogs, cats, guineapigs, rats, opossums, and other rodents and mar-supials. The parasite has two life stages in the

mammalian host, one that circulates in the bloodand another that proliferates intracellularly intissues.

In 1974, WHO estimated that out of 50 millionexposed, a total of 10 million persons were in-fected with the Chagas’ disease parasite Trypa-nosoma cruzi (discovered by Carlos Chagas of Brazil). Studies in Brazil have shown Chagas’ dis-ease to be a significant cause of mortality in thoseunder 45 years of age (84) and a heavy socialburden due to high rates of hospitalization (withunsatisfactory outcome) and disability assistance

(78).After initial infection by the reduviid bug, the

acute phase of the disease varies in severity ac-cording to age. Cardiac arrhythmias, myocardialinsufficiency and collapse, or central nervous

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system damage may result in death. The youngerthe individual, the greater the severity. Mortali-ty is high in children under 2 years of age, whileadults may show no symptoms. The acute stagemay resolve completely in a few weeks or months,or may pass into a subacute or chronic stage.

There is no effective cure. Long-term sequelae arecardiomyopathy leading to heart failure andgrotesque enlargement of the digestive tract (meg-aesophagus and megacolon).

The transmission threat in rural areas is great,but transmission by blood transfusion is also amajor problem for blood banks in Latin America.

The disease is found in every country of theWestern Hemisphere, except Canada and the Car-ibbean. Opossums and other mammals harbor thedisease in the Southern United States, and a smallnumber of indigenous human cases have occurred

in recent years (e.g., two in California in 1982).

Control measures concentrate on insecticidespraying of houses and upgrading of housing con-struction (adobe, mud, cane, thatch, or otherwisepoorly constructed rural homes with cracks in thewalls are the usual harborage of the insect vector).

An effective drug cur e is a critical research need.With a therapeutic drug in hand, a simple effec-tive test for early diagnosis would be essential—the long-term effects once they appear are irre-versible. Vaccine research is underway, but thisdisease has a complicating factor—the long-termpathology seems to result from the body’s imm uneresponse reacting against the parasite and cross-reacting to its own heart and nerve tissue. Vec-tor bionomics remain important research topicsfor defining transmission areas, vector behavioralcharacteristics, and improved control measures.

Leishmaniasis

Leishmaniasis is a disease with three clinicalpresentations depending on the leishamanial para-site species. In each case, the protozoan parasitespecies is transmitted by bloodsucking phleboto-mine sandflies. Cutaneous leishmaniasis is a self-limiting and usually self-resolving sore at the pointof infection. Mucocutaneous leishmaniasis iscaused by a different Leishmania species thatbegins as a sore but commonly metastasizes and

proliferates in the nasal and pharyngeal mucousmembranes. Gross destructive disfigurement of the nasal passages occurs. Visceral leishmaniasis(kala-azar) is a third type of disease in whichspleen, liver, bone marrow, and lymph glands arethe sites of parasite proliferation. Fatal outcome

in children is common.The disease exists in all Latin American coun-

tries except Chile, and in some the number of casesis increasing because of agricultural colonizationin jungle areas, In the late 1970’s, cutaneousleishmaniasis seriously impeded a Bolivian schemeto relocate people outside the overcrowded alti-

piano. Many of the colonists abandoned theirland. More than 60 percent of those who did saidthat leishmaniasis was their reason for returningto the mountains. It has also significantly ham-pered both oil exploration and roadbuilding in

several Andean countries (76).Epidemiologically, most forms of the disease

are transmitted to humans from animals in the jungle (zoonoses), representing a health hazardto anyone working there, and rendering controlunsatisfactory or impracticable.

Specific treatment is now limited to antimonycompounds that are not always effective and oftenhave adverse toxic side-effects. Another disadvan-tage is that they require daily injections over 10to 20 days, which makes them impractical for pa-tients living in remote and inaccessible areas.

Hospitalization for such a period is not only ex-pensive but also a major inconvenience to the pa-tient who cannot afford to leave work or farmfor an extended period. For these reasons, im-proved treatment of the tens of thousands of ex-isting cases is a priority research goal. PAHO/ WHO currently has a structured effort to developnew therapeutic drugs. Allopurinol is a promis-ing compound of current research activity (119).

In other PAHO investigations of leishmaniasisepidemiology, a seroepidemiologic survey inPanama revealed an apparent focus of leishma-

niasis transmission without clinical infection.Completely subclinical leishmaniasis was previ-ously unknown and may be important to vaccinedevelopment. Rapid species diagnosis of leish-manial sores may be soon possible by a recentlypublished technique of DNA hybridization (124).

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This would permit early treatment of the destruc-tive mucocutaneous form of the disease, as wellas facilitate precise epidemiologic field studies.

Arthropod-Borne Viral

Diseases (Arboviruses)This large group of diseases is caused by viruses

(currently about 80 in humans) defined by eco-logical, epidemiological, and clinical parameters.Strictly speaking, arboviruses replicate in and aretransmitted by arthropods (predominantly mos-quitoes, but also ticks, sandflies, midges andgnats). There are some arbovirus- like diseaseswhose vector is still unidentified and some whoseearly epidemiological profile incorrectly suggestedarthropod transmission; their symptoms (e. g.,Argentinean and Bolivian hemorrhagic fevers)must be differentiated from those of true arbovi-ruses. The number of arboviruses is growing ra-pidly as research resolves the etiologic agent of many fevers and brain inflammations (encepha-litis) of unknown origin and elucidates transmis-sion cycles. Examples of arboviruses include:yellow fever, dengue fever, eastern equineencephalitis (EEE), western equine encephalitis(WEE), St. Louis encephalitis (SLE), Venezuelanequine encephalitis (VEE), California encephalitis(CE), Colorado tick fever, Chagres fever, andOropouche fever. (Locality names denote thesource of first isolation; range of each is far

wider. )Clinically these diseases are classed in four

groups (6): I ) acute central nervous system dis-ease usually with inflammation of the brain(encephalitis), ranging in severity from mild ase p-tic meningitis to coma, paralysis, and death (WEE,EEE, CE/ LaCrosse en cephalitis, SLE); 2) acut ebenign fevers of short duration, many resembl-ing dengue with and without a rash (exanthem),although on occasion some may give rise to amore serious illness with central nervous systeminvolvement or hemorrhage (yellow fever, den-gue, VEE, Oropouche); 3) hemorrhagic fevers, in-cluding complications of acute febrile diseases(previous group), with extensive hemorrhagic in-volvement, frequently serious, and associatedwith shock and high-fatality rates. One of them,yellow fever, also causes liver damage and jaun-

dice; 4) polyarthritis and rash, usually withoutfever and of variable duration, benign, or witharthralgic sequelae lasting several weeks tomonths.

Most of these infections are diseases of animals

(zoonoses) accidentally transmitted to man,though epidemics can occur with man; the prin-cipal source of vector infection, In 1981, anepidemic of dengue fever swept through Cubawith 344,208 cases and 158 deaths. The 1977-80

pandemic of dengue in the Caribbean and Cen-tral America caused a half-million cases.

Laboratory diagnosis can identify arbovirusesand define antigenically similar groups, but greatgeographic and climatic diversity is found in eachserologic grouping. This emphasizes the complex-ity and challenge of arbovirus research and con-trol. There is no cure for these diseases, onlysymptomatic and supportive relief. Early diagno-sis of serotype has three important values: to dif-ferentiate ambiguous presenting symptoms; to an-ticipate life-threatening complications, as inyellow fever and dengue fever; and to target thetype of vector which then determines controlstrategies. Current control efforts rely on identi-fying epidemic outbreaks early in order to institutevector-control measures such as insecticide fog-ging. However, disease surveillance is not welldeveloped in many tropical countries of theregion.

Only yellow fever has an effective vaccine.There are experimental vaccines for certain strainsof dengue fever, VEE, and WEE. The general utili-ty of arbovirus vaccination is doubtful, though,because of the complexity involved. The wide va-riety of arboviruses, most occurring only spor-adically in humans, and without inducing cross-immunity, raise many questions about implemen-tation and bring the realization that vaccinationis unlikely to be a panacea. Vector control willremain the primary intervention method. Ento-mologic research on vector bionomics togetherwith surveillance of sentinel populations (animalreservoirs and vectors) are activities for emphasis.Especially important is elucidation of the vector-bridge concept—the factors permitting transmis-sion of these zoonoses to humans when the prin-cipal vector arthropod is not a human-biter.

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Yellow fever was the first arbovirus disease of the Tropics to be recognized and elucidated. It wasWilliam Gorgas who eradicated the disease fromthe Panama Canal Zone and Cuba in the early1900’s. Further success was recorded throughoutLatin America against urban yellow fever, such

that no cases were documented in the Americasfor the past four decades. Jungle yellow fever,however, remains a major threat in tropical Amer-ica. It is the same virus maintained by transmis-sion through a number of jungle mosquitoes withmonkeys and possibly certain marsupials servingas reservoirs. Recent research has demonstratedthat transovarial transmission (passage of thevirus from the female mosquito to the egg) oc-curs in vectors of yellow fever (26) (and other ar-boviruses). Thus, the mosquito may function notonly as a vector, but also as a reservoir. Humancases are associated with man invading the junglehabitat. In recent years, however, an outbreak inColombia appeared where there were no apparentknown vectors or reservoirs and in Trinidadwhere no cases had been detected for almost 20

years. The possibility of unknown reservoirs orvectors is of concern. Aedes aegypti the vectorof urban yellow fever remains abundant through-out the hemisphere (including the United States),posing a persistent threat of epidemic outbreaksin large population centers.

The disease occurs in periodic cycles stretchingover several years which depend on the buildup

of nonimmune individuals in a population whoare then swept by an epizootic of the virus leav-ing an immune population of survivors.

Vaccination of human populations near endem-ic jungle areas is one strategy. Surveillance of monkey populations and jungle mosquitoes bysampling for virus isolation is an important con-trol measure that gives early warning to instituteremedial action.

Dengue fever is a. disease caused by four dif-ferent serotypes of the dengue flavivirus. In re-cent years large epidemics of this virus have sweptthe Caribbean and Central America. In 1981, thefirst indigenous cases in the United States sincethe 1940’s occurred. The virus is endemic in theCaribbean and is transmitted by mosquitoes of the genus Aedes, including the common urban

vector Aedes aegypti which is found as far northas St. Louis, Mo, It breeds in small containers of water such as discarded tires, cans, and jars. Aserious, sometimes fatal, complication of denguefever is dengue hemorrhagic fever (or dengueshock syndrome).

Oropouche fever is emerging as a very impor-tant type of arbovirus disease, because of its de-bilitating symptoms that reduce productivity dueto convalescence. The virus is transmitted by bitingmidges (Culicoides spp. ) in urban and periurbanareas. There is probably also a silent transmis-sion cycle in forested areas.

Filariasis

Several species of filarial nematode worms caninhabit the skin, other tissues, or the lymphatic

system causing disease in humans. These parasitesare transmitted by bloodsucking insects. In LatinAmerica only two worms are considered publichealth problems, Wuchereria bancrofti and On-chocerca volvulus.

The bancroftian filariasis was introduced fromAfrica. It is transmitted by several species of mos-quitoes including common household pest species.The adult worm s live in the lymp hatic system andcause pathology depending on the immune re-sponse of the host. Inflammation and gross ob-struction results in varying degrees of swelling of the lymph glands up to frank elephantiasis of thelegs, breasts, or scrotum. Adult worms release im-mature forms (microfilariae) that circulate in theblood which then infect feeding mosquitoes tocomplete the transmission cycle. Chemotherapyand vector control are currently imperfect andneed more research.

Onchocerciasis is also known as river blindness,because th e blackflies (Simulium spp. ) that trans-mit it live and breed in or near waterways. Thedisease occurs in well-defined parts of Africa andin the Americas, in discrete foci in Guatemala,Brazil f Colombia, Ecuador, Mexico, and Vene-zuela. Ecuador’s onchocerciasis focus was onlydiscovered in 1980. A Panamanian blackfly hasrecently been shown to be a potential vector of O. volvulu s .

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The adult worm lives in the tissues of the bodyand often forms large nodules where an inter-twined clump of worms localizes. Microfilariaereleased by the adults migrate through the bodyin the subcutaneous tissues where they can bepicked up by feeding black flies. If microfilariae

reach the eye, lesions and blindness can result.Control measures focus on vector control andblindness prevention (imperfectly achieved bychemotherapy and nodule removal),

Schistosomiasis

This debilitating disease is caused by a fluke.The worm-like adult parasite lives in the humanhost’s bloodstream, Eggs are deposited in t h eblood vessels and escape into the bowel or blad-der, or lodge in other organs, where they produceinflammation and scars. The complex lifecycle in-

volves excretion of the eggs into water sources,an intermediate snail host in which proliferationoccurs, and an immature stage that can penetratethe unbroken skin of persons who enter infectedwater. Three major species of the fluke occurworldwide, only one in the Americas, Schistoso-ma mansoni, which was introduced from Africa.

S. mansoni is now established in suitable snailhosts in more than half the States of Brazil, where10 million people are believed infected, in Suri-nam, where 10,000 people are probably infected,and in parts of Venezuela, where 10,000 more

people are thought to have the infection. Foci inthe Caribbean occur in the Dominican Republic,Guadaloupe, Martinique, and St. Martin. A fewcases have been detected in Montserrat. The dis-ease is declining in Puerto Rico and Saint Luciadue to intervention measures (76).

Chemotherapy against the disease is effectiveand relatively safe. Total and complete coveragein endemic areas can be difficult to achieve re-quiring other measures to complement control ef-forts, particularly attention to water and excretasanitation and anti-snail treatment of breeding

sites (mollusciciding against the snail host).Schistosomiasis is spreading worldwide due to

water impoundment and irrigation projects whichcreate and expand suitable environmental condi-tions for snail hosts and increase human-snail con-

tact. Areas where large hydroelectric dams arebeing built especially in South America deservespecial surveillance and assessment.

Leprosy

Leprosy is a chronic bacterial disease that con-tinues to be an important public health problemin the Caribbean and Latin America. A quarter-million cases are registered in the region, perhapstwice that number are prevalent. As case-findingand notification improved, reported incidence in-creased with extension of anti-leprosy efforts. De-pending on the host’s immunologic response, lep-rosy can range from the benign tuberculoid formwith localized skin lesions and some nerve in-volvement to the malign lepromatous form thatcauses spreading lesions which become nodularand disfiguring, destruction of the nose, involve-ment of the vocal cords and eyes, and severe nervedamage. Over half the cases in Latin America arethe lepromatous form.

Research on the epidemiology of leprosy is stillneeded. A number of useful drugs are now avail-able for treatment. Drug-resistant stra ins of

Mycobacterium leprae have resulted in recom-mendations for combination chemotherapy whichwill shorten the treatment period. If organized andadministered well, this will lighten the workloadof health services, improve patient compliance,and result in better prognosis. Vaccination against

the disease is in human trials but still years fromroutine use. The PAHO-associated Pan AmericanCenter for Research and Training in Leprosy andTropical Diseases (CEPIALET) in Caracas, Ven-ezuela, carries out a full research agenda onleprosy, as does the U.S. Public Health Servicein Carville, La. Other philanthropic institutionsprovide support to leprosy control either direct-ly to the countries or through PAHO.

Tuberculosis

Tuberculosis is a mycobacterial disease trans-

mitted mainly by airborne droplets. The lungs ar efirst involved, after which infection can spreadto all parts of the body. Though the disease isdecreasing slowly in the Americas, it is still aserious problem in most countries of the region.

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Even countries such as Canada and the UnitedStates, with highly developed coverage for diag-nosis and treatment, have significant numbers dueto immigrants from tuberculosis-prevalent areas.

Control methods based on BCG (bacille Cal-

mette-Guerin) vaccination, diagnosis from thosewith productive cough and treatment for thosewith sputum positive, is the policy of PAHO andthe health ministries of Latin America.

BCG vaccination of uninfected persons can pro-duce high resistance to tubercule bacilli, none-theless, the p rotection conferred has v aried greatlyin field trials. Because some trials have shown highprotection, BCG is still recommended in areas of high-transmission risk. The resolution of the ques-tion of BCG effectiveness needs further evidence.

Cancers

Cancers deserve mention in the context of thistechnical memorandum. They are already one of the leading causes of death in Latin America. Thisis an unhappy indicator of progress against other

causes of mortality, because to die of most can-cers, one must survive past middle age.

Epidemiologic research has identified varyingpatterns of site-specific prevalence in the region.This points out areas for research on risk factorsas possible causes. Extremely high rates of cervi-cal cancer and penile cancer, compared to the restof the world, occur in several of the Latin Amer-ican countries, including Panama.

RELEVANCE OF RESEARCH AT GORGASThe relevance of GML research maybe evalu-

ated in comparison to the health problems of Panama, the tropical Americas, the United States,and to biomedical research in general. The broadrange of pressing health problems in Latin Amer-ica and the modest amounts of research supportavailable dictate that careful stewardship and ra-tional integration of resources and activities takeplace so that research programs do not overlapunproductively and that the restricted resourcesare used efficiently.

Historically, GML has concentrated on vector-borne parasitic and infectious diseases. Conse-quently, it is not surprising to note that GML hasno active research program on malnutrition, lep-rosy, or tuberculosis. These health problems,however, are under active research and study byother institutions in the region. For example, mal-nutrition is the focus of a longstanding agenda of research and intervention studies by INCAP inGuatemala, by CFNI in Jamaica, and others.Leprosy research is carried out by CEPIALET inVenezuela, and the U.S. Public Health Service in

Carville, La., while PAHO and philanthropic in-stitutions also provide other support for researchand intervention in several coun tries of the region.Tuberculosis research and training is also fundedby PAHO. Thus, a lack of GML activities in theseareas, by itself, does not indicate low relevance.

On diarrheal disease, GML has researchedCampylobacter-caused diarrhea in Panama whichwas found to be very prevalent in hospitalizedcases. Another recent study examined epidemi-ologic features of Norwalk virus and Escherichia

coli. This work complements other diarrheadisease work in the region, such as rotavirusresearch by INCAP and the Caribbean Epidemi-ology Center.

A recent GML collaborative clinical study of

oral dehydration therapy (95), published in theNew England Journal of Medicine and also inSpanish in the Revista Medica de Panama, docu-mented the wide applicability of this techniquethat was highlighted by an accompanying edito-rial (12). Thus, GML exploited the availability of a health problem to expand basic scientific un-derstanding, to test clinical therapy, and to dis-seminate the knowledge in Latin America and theUnited States.

Malaria research utilizes the GML monkey col-ony to test experimental drugs. The spread and

multiplication of drug-resistant malaria is a causefor concern throughout the world emphasizing theneed for discovery and testing of new therapeuticdrugs. GML research has identified several prom-ising compounds. This work is not only relevantto the countries with high-malaria prevalence, but

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also to the U.S. military, which in fact supportsmuch of this research.

The Aotus monkey also appears to be a goodanimal model for leishmaniasis, which has beenused at GML to test therapeutic treatment with

allopurinol (119) of this disfiguring, sometimesfatal, disease. The GML monkey colony consti-tutes a resource to conduct screening of promis-ing anti-leishmanial drugs.

Cancer is a growing concern in Panama, as wellas the rest of Latin America, to which GML hasresponded by assisting in the development of acancer registry utilizing the computer facility atGML. One result is the identification of a focusof strikingly high prevalence of cervical and penilecancers. Continuing research has since examinedvarious epidemiological parameters, and has alsoshown a very high prevalence of a cancer-associ-ated virus (HTLV) in this population. This isbeing investigated u nder a gr ant from the N ationalInstitutes of Health (NIH) and the National Can-cer Institute (NCI). This work appears to be highlyrelevant to the region and especially to Panama.This finding was corroborated by the Minister of Health of Panama (34).

Epidemiological capability at GML is availableto assist in epidemic outbreaks, such as occurredin 1981, with aseptic viral meningitis and withacute hemorrhagic conjunctivitis. GML’s labora-tory expertise for diagnosis of viruses comple-

mented these investigations. GML maintains oneof the few viral diagnostic capabilities in thetropical Americas. This type of activity is veryimportant to Panama and the region.

Current research on Chagas’ disease is survey-ing the human populations in two geographicalareas of Panama in which different vector speciestransmit the T. cruzi parasite to determine epi-demiological differences in the transmissioncycles, This is under a grant from WHO.

Arbovirus research, especially on the vectorsand reservoirs, is a major GML activity. A largeeffort is expended to monitor jungle yellow fever,using a system developed by GML, in the belief that surveil lance can give early warning of epidemic potential. Urban yellow fever has notoccurred for several decades in Latin America, but

the vector Aedes aegypti is abundant throughoutthe region, including the United States. When anepizootic of jungle yellow fever flares, there is aprobability of spillover transmission to humans,but, worst of all, would be involvement of A .

aegypti in the transmission. Furthermore, there

still remain questions about reservoirs and vec-tors of this disease. For Panama and Latin Amer-ica, the relevance is obvious. For the UnitedStates, too, the relevance is not just theoreticalor abstract. There are 20,000 U.S. Governmentemployees and dependents in Panama, another20,000 U.S. citizens in neighboring Costa Rica(51).

St. Louis encephalitis is another focus of arbo-viral research. GML is attempting to elucidatehow the virus is maintained in tropical areas, thevectors and reservoirs, in order to expand know-

ledge of this arboviral disease that is prevalentthroughout Latin America and the United States.

Research on insect vectors and animal reser-voirs of other diseases is carried out as well atGML. Two important functions of entomologicfield studies are discrimination of vector andnonvector species in various localities of actualand potential transmission (different species havevarying transmission capabilities in different hab-itats), and elucidation of vector behavior and bio-nomics (e. g., biting times, resting h abits, insec-ticide susceptibilities) in order to develop interven-tion strategies and to understand the interactionof host, parasite, and vector. Work at GML hasrecently demonstrated that a common blackfly of Panama, Simulium quadrivittatum, can functionas a vector of onchocerciasis, though the diseaseis currently unknown there, Endemic foci of thisdisease occur in neighboring countries, thus thedisease could spread. Recent work at GML dem-onstrated that transovarial transmission of yellowfever occurs in one of the mosquito vectors. Thus,the vector may also function as a reservoir of thevirus, that may explain the persistence of the virusin the absence of disease in animal hosts. Identi-fication of reservoir hosts is an important adjunctactivity. Reduction of disease is sometimes feasi-ble through control of animal hosts (e.g., Chinaclaims to have reduced leishmaniasis through con-trol of dogs that harbor the parasite. ) These ac-tivities have relevance to possible intervention in

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5 0

Panama and the region, as well as to basic un-derstanding of disease processes.

GML maintains a reference capability (avail-able to the region as a WHO CollaborativeResearch Center) for the identification of bloodmeals in suspected insect vectors. This is used todetermine host-preference from field-collectedspecimens throughout the region.

Investigation by isozyme electrophoresis’ of disease vectors is carried out by GML. Identifica-tion of these biochemical markers improves thedifferentiation of vectorial status, especially wherespecies complexes are involved. GML is examin-ing sandfly vectors of leishmaniasis. Isozyme iden-tification was also developed to differentiate the

Leishmania species isolated from cutaneous sores.This can diagnose the mucocutaneous type beforethe destructive pathology develops.

Recently, ecological studies on the effects of im-poun dm ent of the Bayano River on insect p opula-tions and arbovirus activity have been carried outon contract. Also, environmental and disease im-pact assessments were carried out in connectionwith the Tabasara Hydroelectric Project. Rele-vance seems obvious given that the work w as car-ried out under contract with a third party (theGovernment of Panama), but the relevance isseveral-fold:

1.

2.

the scientific merit and addition to scientificknowledge;that environmental concern is being ad-dressed and promoted in a developing coun-try;

*Isozyme electrophoresis is a method of separating and identify-ing variant proteins in apparently similar organisms which then per-mits differentiation and classification. This is most useful when itcorrelates with geographic, pathogenic, or other varying charac-teristics of the organisms.

3.

4.

related to the development of environmen-tal concern in Panama is the significant rolethat environmental preservation plays in thecontinued function and maintenance of thePanama Canal, a gravity-flow, natural wa-tershed-fed navigational waterway; and

that GML was contracted, recognizing it asa body of expertise, within Panama, compe-tent to do the work,

GML’s work in sexually transmitted diseases(STDS) has focused on forms of STD that are of high prevalence in Panama, as well as surround-ing countries of the region. STDS are epidemic intropical America, as they are in the rest of theworld, but very little public health activity is cur-rently underway in Latin America or the Carib-bean:

With the exception of the four nations men-

tioned above [Canad a, United States, Costa Rica,Cuba], few coun tries have been able to carry outwell-organized STD control efforts. Althoughmost countries have d eveloped guidelines andstandards for diagnosis and treatment, few pro-grams to carry them out exist, especially outsidelarge cities (76).

GML research on STDS in tropical America isan early and unique effort. For a problem of largemagnitude with very little current information orother research underway, relevance to the needsof Panama and the region seems to be very high.

GML physicians see about 1,000 patients eachyear. These are people suffering from a varietyof tropical diseases for which GML can provideexpert and specialized services lacking amonglocal physicians and clinics. This clinical servicenot only adds to the research effort at GML butalso supplies a superb and unique teaching facili-ty, and evidently creates much good will amongthe general, and health professional, populationin Panama.

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SUMMARY

Overall, the work of GML appears to have highrelevance to tropical Latin America, especially toPanama, to tropical disease research in general,and to the United States’ interests. Not every ac-tivity of GML has obvious relevance. * Nonethe-less, the Office of Technology Assessment findsthat there is no major problem relating to therelevance of GML’s areas of research. This find-ing is supported by the information presentedabove, by the personal statements of officials of

*Clearly stated objectives and goals for the institution, as wellas individual projects, together with regular, at least annual, for-malized intramural review procedures could improve this situation.

Panama’s Ministry of Health and other health pro-fessionals in Panama, by award of grant and con-tract funding of research projects by NIH, theDepartment of Defense, WHO, and the Govern-ment of Panama, by Fogarty International Center(FIC) site visit reports, and by N IH/ FIC testimonybefore congressional committee. *

*House of Representatives, Committee on Appropriations, 98thCongress: Subcommittee on the Departments of Labor, Health andHuman Services, Education, and Related Agencies, Appropriationsfor 1984, National Insti tu tes of Health , Part 4B, April 1983,

pp. 1635-37, 1641-43.

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Chapter 5

Findings and Conclusions

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Chapter 5

Findings and Conclusions.—— ———— .—— —— .—.———-——— . —-. ——-.

FINDINGS

Previous chapters have presented informationon the quality and relevance of tropical medicineresearch at the Gorgas Memorial Laboratory(GML). At the same time, they were designed toprovide enough information about tropical dis-eases, tropical disease research, and researchcriteria so that research policy makers could placeGML’s quality and relevance in the context of thegoals and capabilities of any comparable organi-zation.

Gorgas cannot be compared to the National In-stitutes of Health (NIH). Neither can Panama’smedical research system be compared to that of the United States. The differences depend on morethan simply size. For example, the disease patternsdiffer, the level and organization of health caredelivery differ, and availability of equipment andcollaborating scientists differ. Field conditionsboth create obstacles and present opportunitiesthat cannot be d up licated by an organization suchas NIH.

OTA thus finds that th e evaluation of the quali-ty of an institution such as Gorgas cannot take

place without explicit recognition of certain prem-

ises. The following are the premises assumed byOTA during this evaluation:

q

q

q

There is an inherent value in supp orting trop-ical research laboratories in tropical coun-tries. These benefits (see the last section of ch. 1) extend to the tropical country, tropicalregions in general, and to the country sup-porting the activities.Evaluations of the quality of research are in-evitably, and properly, made partly on thebasis of fairly objective criteria such aspublications record and partly on the basisof subjective judgments by qualified individ-

uals.The criteria used to judge quality, althoughsimilar in type, need to be modified andweighted differently for basic research or re-search performed in well-equipped, state-of-

the-art laboratories than for field researchlaboratories.Relevance is directly dependent on the typeand location of institution, and it should beexamined from each of the appropriate view-points (e.g., host country, region, UnitedStates, general advancement of knowledge).

With these premises in mind, OTA examinedthe quality of GML’s research against a range of objective and subjective criteria. There was veryimpressive agreement among the results of: 1) thepast scientific evaluations of GML, 2) the criticalevaluation of the research design and presenta-

tion of articles and manuscripts, 3) the surve y of expert scientific opinion on GML’s quality, 4) in -terviews with Panamanian health officials andprofessionals, 5) the examination of the GMLstaff’s publications record, and 6) an examinationof GML’s record of competing for grants and con-tracts. All evidence gathered by OTA led to thefinding that the overall scientific quality of G M Lis high, especially when considered in the context

of its status as a research laboratory located in

the Tropics. Quality was, naturally, not uniform-ly even, but it also appears that the Gorgas Me-morial Institute’s and GML’s management isaware of unevenness and is attempting to makeimprovements.

Relevance is more difficult to judge, but in gen-eral OTA found that the large majority of GML’sresearch is highly or adequately relevant to healthconcerns and problems of Panama, the tropicalAmerican region, U.S. interests, and the advance-ment of scientific knowledge and the field of trop-ical medicine in general (see tables 1 and 2 in ch.1). The evidence for this finding lies, for the firsttwo, in the match up between tropical healthproblems and GML research d irected at them, and

from strongly expressed opinions and examplesby the Panamanian Minister of Health (who is aformer Dean of the Panamanian School of Med-icine), his Deputy Minister, the medical directorof Panama’s Childrens’ Hospital (a former Min-

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ister of Health and former head of Social Securi-ty in Panama), and numerous officials of the PanAmerican Health Organization.

The importance of GML to Panama cannot be judged solely on the basis of Panama’s monetary

contribution. Panama is going through a difficulteconomic period. Even so, the Ministry of Healthhas arranged a loan to keep GML in operationfor the remainder of fiscal year 1983. The valueof the land, buildings, and tax-favored status havenever been adequately assessed. And to put theoften criticized direct financial contribution of $10,000 from Panama in perspective, the researchbudget of the Panamanian medical school is re-portedly only $20,000 (34).

As one official of the U.S. Department of Stateexpresses it: Each year, the United States sendsa message to Panama and the region by funding

GML and supporting activities related to thehealth of U.S. and Panamanian citizens alike (51).

Activities related to the recent Panama Canaltreaty process provide a specific example of the

CONCLUSIONS

OTA concludes that the benefits of supportingGML justify, on scientific and other grounds, therelatively small amount of funds required. Qualityand relevance are high. Withdrawing core sup-

port from GML would probably not even savethe amount of the appropriation, since otherFederal agencies, such as the Department of De-fense, may need to either develop their own ca-pabilities to conduct research now carried out atGML or to fund similar research at other tropicalmedicine research centers.

Gorgas is not ideal; improvements could cer-tainly be made. Some of the shortcomings stemfrom its uncertain funding. As mentioned earlier,the prospect of unstable funding and perhaps clo-sure m ay hav e kept individual scientists from join-

ing GML or becoming visiting scientists there andmay reduce the desire of U.S. universities to col-laborate with GML, on research projects, As anexample, two highly qualified entomologists fromthe United States discussed with GML the possi-bility of their coming to GML for a period. Uncer-

importance of GML to Panama. As part of thetreaty, a Joint Committee on the Environment wasestablished. Panama turned to GML, as the onlyinstitution in Pan ama with the necessary skills andexperience, for assistance in relation to environ-mental protection and human and animal health,

and additionally named Dr. Pedro Galindo, for-merly of GML, as the senior Panamanian on theCommittee.

Relevance to U.S. health interests can be foundin the surveillance activities, the training activities,and the various research activities undertaken un-der contract to the U.S. military. Gorgas’ contri-butions in the areas of malaria, yellow fever, andleishmaniasis illustrate its relevance to the generaladvancement of knowledge.

Based on the above evidence, OTA finds thatwith some exceptions that occur almost e n t i r e l y

within the core-funded activities, the research con-

ducted at GML is relevant to the various parties

at in te res t .

tainties over the budget and the very future of GML have resulted in not being able to join GML,although one is still considering doing so.

The point about uncertainty should be placed

in perspective: most research scientists operateunder some degree of uncertainty about futurefunding. In GML’s case, the uncertainty appliesto the very existence of the entire institution.Thus, the uncertainty is a matter of degree(though perhaps a significant one), and not asituation unique to GML.

Another example of the effect of uncertainfunding has been the decision by the U.S. Navyto hold off on the next scheduled training class,because the course w ould extend a few w eeks intofiscal year 1984.

Gorgas itself could improve its standing and itsrelevance by:

• being more aggressive in its pu blishing;q by making better use of its Advisory Scien-

tific Board (e.g., in planning for research di-

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5 7

rections, as part of a more formal and effec-tive peer review process and as visiting con-sultants);by more actively seeking out associationswith universities and collaborations with arange of groups from other countries and in-

ternational organizations;by making strategic plans to move more fullyinto the developing areas of modern science(e.g., work with monoclinal antibodies andother immunological diagnostics, and bio-technology approaches to vaccine-relatedresearch and development*);by making more of an effort to run vigorousvisiting scientist and fellowship programs;an d

similar types of actions that should be con-sidered by GMI/ GML at a very near date.

Gorgas has also done a rather poor job of let-ting Congress, Panama, and the public know howmuch it is doing and what its capabilities are. Itsfinancial base should be broadened. Alternately,or in combination with broadening, some changein the structure (e. g., an international arr ange-ment of sup port) of GMI/ GML might be under-taken. Any such step should be taken carefully,in view of the importance of GML and its activi-ties (e.g., its disease surveillance work) to theUnited States.

OTA concludes that the only benefit to theUnited States of defunding Gorgas would be sav-ing of perhaps significantly less than $2 million.The negative consequences would include loss of one of the few, high-quality, broadly relevant,

q The contributions of the International Laboratory of Researchon Animal Diseases in Kenya to the molecular biology of Africantrypanosomes is an example where a field unit has done importantwork at the forefront of science (68). Other good examples are thecenters supported by the Rockefeller Foundation’s Great NeglectedDiseases Program.

tropical research institutions located in a tropicalcountry. The Army’s malaria research would behurt, as would disease surveillance in the CentralAmerican region. The U.S. ’S standing in Panama,and perhaps more broadly in tropical America,would inevitably suffer. For example, the lead

editorial on July 7, 1983, in Panama City’s leadingnewspaper spoke emotionally of the “incompre-hensible budget policies” of the United States inregard to defunding Gorgas.

Ironically, GML is in danger of extinction atthe very time that U.S. interest in Latin Americais high, and at a time when tropical medicine hasnever been more relevant to the United States.Health aspects of the increased numbers of refugees in the United States, an increased amountof international travel, and the growth of multina-tional corporations located in tropical regions are

examples of this heightened relevance.Loss of the training activities at Gorgas would

not only hurt the U.S. Navy but would alsopreclude the desirable possibility of expandingsuch training in tropical medicine to include morevisiting physicians and students in health sciences*from the United States and to increase the nu mberof Panamanians and others attending.

In summary, OTA concludes that the positiveconsequences of U.S. core support of Gorgasgreatly outweigh the amount of funds involved.Defunding now, followed by an appreciation of

the loss later and a subsequent attemp t to reinstatesuch a research capability, may result in muchlarger required investments, an inability to re-create successful conditions for quality research,or both.

*For example, GML and Yale University have an ongoing pro-gram whereby students of Yale’s School of Medicine go to GMLfor 2- to 3-month periods for experience in research and clinicalaspects of tropical medicine.

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Appendixes

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Appendix A

Acknowledgments;Pan American Health

Organization Liaison Group;OTA Health Program Advisory Committee

ACKNOWLEDGMENTS

The development of this technical memorandum was greatly aided by the advice and review of a numberof people in addition to the Pan American Health Organization Liaison Group, and the Health Program Ad-visory Committee. OTA staff would like to express their appreciation especially to the following individuals:

Thomas AitkenYale University

Maj. Richard G. Allen

United States Army MedicalResearch Command

Karen BellNational Academy of Sciences

Mark S. BeaubienFogarty International Center

Mark BoyerHarvard University

Louise Brinton

National Cancer Institute

Gloriella CalvoThe Gorgas Memorial Institute

Cdr. Patrick CarneyNavy Research &

Development CommandRichard Cash

Harvard University

Barnett Cline

Tulane University School of Medicine

William CollinsCenters for Disease Control

Joseph A. CookThe Edna McConnell Clark Foundation

Gustave DamminHarvard University

William Dietz

Clinical Research Center

Col. Carter Diggs

Walter Reed ArmyInstitute of Research

Jose Renan Esquivel

Medical DirectorChildren’s HospitalPanama City

Phyllis Eveleth

Fogarty International Center

Allan Fleener

General Accounting OfficeGaspar Garcia de Paredes

Minister of HealthRepublic of Panama

Robert J. A. GoodlandThe World Bank

Co], Michael GrovesWalter Reed Army

Institute of Research

Sherman HinsonU.S. Department of State

Rod Hoff Harvard University

Donald Hopkins

Centers for Disease ControlAbraham Horowitz

Pan American Health Organization

Lee HowardPan American Health Organization

Leon Jacobs

The Gorgas Memorial Institute

Geoffrey Jeffries

Centers for Disease Control

Karl M. JohnsonFort Detrick

William Jordan

National Institute of Allergy

and Infectious Diseases

Irving KaganCenters for Disease Control

Robert Kaiser

Centers for Disease Control

Cpt. James F. KellyCommanding OfficerNaval Medical Command

Dieter Koch-WeserHarvard University

Richard KreutzerYoungstown State University

Austin J. MacInnisEditor, the Journal of Parasitolog y

University of California, Los Angeles

Arnold Monto

University of Michigan

Russell Morgan

Nation al Council forInternational Health

Ladene NewtonCenters for Disease Control

Clifford PeaseAgency for International Development

Martha G. PeckExecutive Director

Bourroughs-Wellcome Fund

CO]. C. J. PetersUSAMRIIDMedical Division

William C. Reeves


D. S. RoweThe World Health OrganizationSpecial Programme for Research and

Training in Tropical Diseases

Ira Rubinoff Smithsonian Tropical

Research Institute

Col. Phillip K. RussellDirectorWalter Reed Army Institute

of Research

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Rolando E. SaenzGorgas Memorial Laboratory

Warren R. SanbornPortable Rapid Diagnostic

Technology, Inc.John E. Scanlon

American Society of TropicalMedicine and Hygeine

Robert E. ShopeYale Arboviral Research Unit

Reuel A. StallonesUniversity of Texas

Ronald St. JohnPan American Health Organization

Jose Teruel

Pan American Health Organization

Paul Tiggert


Ronald Vogel

University of Arizona

Kenneth WarrenThe Rockefeller Foundation

Raymond H. WattenDirector


Thomas WellerHarvard University

Karl A. WesternNational Institute of Allergy

and Infectious Diseases

Kerr L. WhiteThe Rockefeller Foundation

Roy WiddusNational Academy of Sciences

Frank S. WignallUnited States Navy

Phillip WinterWalter Reed Army Instituteof Research

Martin Wolfe

U.S. Department of StateMartin Young

University of Florida

PAN AMERICAN HEALTH ORGANIZATION LIAISON GROUP

OTA would like to thank the m embers of the group formed by th e Pan American H ealth Organization toprovide a dvice on OTA’s stud y of the Gorgas Memorial Laboratory and the main project on the status of research

for

Dr .Dr .Dr .Dr .

tropical medicine in tropical America.

Gloria Coe, Ph. D.Liaison Group Coordinator

Francisco J. Lopez-Antunano Dr. Gabriel SchmunisFernando A. Beltram Hernandez Dr. Juan Cesar GarciaGeorge Alleyne Dr. Rafael CedillosPedro Acha Mr. Jorge Pena Mohr

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Appendix B

Tropical Disease Research Activities —

This appendix is a brief profile of tropical medicineresearch support, concentrating primarily on activitieswith which the United States is involved, either

through direct research activities or by block contribu-tions, but also containing several examples of othersupporting organizations. Table B-1, at the end of thisappendix, summarizes the tropical medicine researchfunding levels of the organizations covered. This dis-cussion should not be regarded as a comprehensive re-view. For example, many U.S. universities maintaintropical biomedical research programs. In addition,most developed and some developing countries havenational agencies or institutes which in some way fundtropical disease research. These are not covered. Formore detail on the range of support for tropical medi-cine research, see the General Accounting Office reporton Gorgas, to be completed in August 1983.

Multinational Programs

The United Nations Development Program/World

Bank/World Health Organization Special Programme

for Research and Training in Tropical Disease (TDR)has targetted six specific diseases for biomedicalresearch: malaria, schistosomiasis, filariasis, Africanand American trypanosomiasis, leishmaniasis, and lep-rosy. Essentially a grant institution, TDR also fundsprojects on vector biology and control, biomedical sci-ences, epidemiology, and social and economic research(126). Of the more than $30 million spent by TDR in1981, approximately $5.6 million went to researchactivities in the Americas (77). Total U.S contributionsto the TDR in 1982 were more than $5 million, ap-proximately 22 percent of all TDR fundings (105).

The Pan American Health Organization (PAHO),

regional office of the World Health Organization,

sponsored 131 research projects during 1980-81 for atotal of $5.2 million. Direct monetary contributionsfrom PAHO/ WHO comprised 32 percent of that sum,the remainder coming from the 30 institutions, inter-national organizations, agencies, and governments thatcollaborate with PAHO. Research efforts were primar-ily directed towards the diarrheal diseases, a reflectionof the Special Programme for the Control of DiarrhealDisease. PAHO-funded programs also researchedother infectious diseases, parasitic diseases, foot andmouth diseases and vesicular stomatitis, zoonoses,nutrition, and other areas (77), In 1982-83, U.S. con-tributions to PAHO of $57.1 million constituted 61.3percent of the organization’s funding (18).

PAHO maintains nine centers, including the Car-ibbean Epidemiology Center (CAREC) located in Port-of-Spain, Trinidad, the Institute of Nutrition of Cen-

tral America and Panama (INCAP) in Guatemala City,the Caribbean Food and Nutrition Institute in Kings-ton, Jamaica, and the Pan American Center for Re-search and Training in Leprosy and Tropical Diseases,in Caracas, Venezuela (76), PAHO provides scientistsand researchers to each of the centers, and with theexceptions of INCAP, which is semi-independent, andCAREC, which receives moneys from 19 differentcountries and institutions, the centers are primarilyPAHO- funded. It is important to note that the centersare by no means exclusively devoted to research.CAREC, for example, provides extensive training, epi-demiological surveillance, and laboratory services formuch of the English-speaking Caribbean (100).

United States Agencies

The majority of Agency for International Develop-

ment (AID) funding for tropical diseases research

comes from its Office of Health. In fiscal year 1982the office allotted $5.8 million for research in malariaimmunology and vaccine development, $5 million tothe TDR, and $1.9 million as part of the core supportfor the International Center for Diarrheal Diseases Re-search/ Bangladesh, The AID Africa Bureau spent ap-proximately $1.3 million on the biomedical researchcomponents of three projects—onchocerciasis control,combatting communicable childhood diseases, andschistosomiasis activities in the Cameroons and theSudan. The remainder of AID’s tropical diseases ac-tivities, some $1 million, was channeled through theOffice of the Science Advisor for collaborative researchbetween U.S. universities and developing countries.All AID funding may be considered “extramu ral,” withmoneys given out on a competitive basis to univer-sities, profit, and nonprofit institutions (79).

Nearly all tropical diseases research a t the National

Institutes of H ealth (NIH) is carried out at the National

Institute of Allergy and Infectious Diseases (NIAID).

NIAID spent more than $9.5 million in fiscal year 1982for research on trypanosomiasis, schistosomiasis, leish-maniasis, malaria, filariasis, and leprosy. The GeneralTropical Medicine Program spent $7.7 million for re-search involving virology, bacteriology, vector path-ogens, and other disciplines; NIAID’s General Para-sitology Program expended an additional $3.5 million.The NIAID International Collaboration in Infectious

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th e Trust’s Tropical Units in Ind ia, Brazil, Thailand, Burroughs Wellcome Fund, an entirely separate enti-Kenya

Jand Jamaica. Approximately 20 percent of the ty supported by profits from the U.S. branch of the

allocations were used for special lectures and fellow- company, awarded $406,000 in supp ort of molecularships with the remaining sO percent awarded to re- parasitology research in fiscal year 1982. This sumsearchers and research institutions around the world represented 18 percent of the Fund’s awarded grantson an individual project basis (122). In addition, the during that period (80).

Table B-1 .—A Profile of Funding for Tropical Medical Research

MillionsOrganization of dollars Year Reference

World Health Organization:Special Programme for Research and Trainingin Tropical Diseases (TDR) . . . . . . . . . . . . . . . . . . . . . . 23.832 81 102

Pan American Health Organization . . . . . . . . . . . . . . . . . 5.2 80-81 77Agency for International Development. . . . . . . . . . . . . . 15.0 FY82 79National Institutes of Health:

NIAID . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.856 FY82 111, 112Fogarty International Center . . . . . . . . . . . . . . . . . . . . 1.8 FY83 114

Department of Defense. . . . . . . . . . . . . . . . . . . . . . . . . . . 31.246 FY83 2Centers for Disease Control . . . . . . . . . . . . . . . . . . . . . . 5.5 FY83 53Edna McConnell Clark Foundation . . . . . . . . . . . . . . . . . 2.573 82 27

Great Neglected Diseases Program . . . . . . . . . . . . . . . . 1.9 82 89International Development Research Centre. . . . . . . . . 4.2a

82 56Burroughs-Wellcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6b 80-82 80, 122a Approximately equal to 4.9 million Canadian dollars.b Approximately equal to $600,000 U.S plus 3.6 million pounds Sterling.

NOTE: The definitions of tropical diseases and tropical disease research activity used in compiling these data are not uniform.For example, CDC totals include activity in research which is not covered by the Department of Defense. TDR//WHO totalsare for research and development and research capability strengthening only. The DOD data are only restricted to those diseaseswhich are of concern to American troops stationed in tropical countries, As part of the Department of State, AID contributesfunds for tropical disease research to both the TDR/WHO and the PAHO; these funds then lose their “American” label, Inaddition, more than $1 million was given by AID to NIAID. Only 32 percent of PAHO activities came directly from PAHO/WHO,the remainder coming from matching contributions from local governments.

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Appendix C

Bibliography ofPublications by the Gorgas

Memorial Laboratory Staff—— ——. - ——

LISTA DE LAS PUBLICACIONES DEL

LABOR ATORIO CONMEMORATIVO GORGAS

DE 1975 A 1979‘

( E N L O S 5 0 A N O S D E S U F U N D A C I O N )

CON ADICIONES PARA 1980

Prof. Manuel Victor De Las Casas ++

753*

754

755*

756*

757*

Blandón R, Edgcomb JH, Guevara JF, Johnson CM: Elect-

cardiographic Changes in Panamanian Ruttus rattus N a t u -

rally Infected by Trypanosoma cruzi. Am Heart J 88 (6):

758-764, 1974

Kourany M, Martinez R: La Situacion de la Shigelosis en Pa-

nama” (Parte B, pp. 7 1-73). En: Simposio Sobre Disenteria

Shiqa en Centroamerica (Ciudad de Guatemala, 27 y 28 de

ju l io de 1971) , Washington, D.C: OPS, 1974 (Publicacion

Cientifica No. 283)

Bacrg D.C: Boreham MM: Experimental Rearing of Chagasia

bathana (Dyar) Using Induced Mating, and Description of

the Egg Stage (Diptera: Culicidae). J Med Entomol 11(5):

631-632, 1974

Bacrg DC, Boreham MM: Anopheies neivai Howward Dyar &Knab: Laboratory observations on the Life Cycle and Des-

cription of the Egg Stage (Diptera: Culicidae). J Med En-

tomol 11(5): 629-630, 1974

Boreham MM, Baerg DC: Description of the Larva, Pupa and

Egg of Anopheles (Lophopodomyia) squamifemur A n t u n e s

with Notes on Development (Dipterea: Culicidae). J Med

Entomol 11 (5): 564-569, 1974

+

++

+

Segundo Suplemento. La presentation de esta bibliografia (Nos. 753 at 846) difiere denuestra Bibliografia Basica y sus Suplementos en que, para ahorrar espacio, se supri-

mio la sangria y se usaron tanto has abreviaturas como el estilo de la Seccion de Mate-ria del CIM, normas adoptadas por la Revista Medica de Panama.

Bibliotecologo Medico del Laboratorio Conmemorativo Gorgas y Profesor de Biblio-tecologia en la Facultad de Filosofia, Letras y Educacion, de la Universidad de Pana-ma.

El asterisco que sigue al numero de una pubticacion indica que, al memento de preparar esta bibliografia, hay disponibles reimpresos de la misma

67

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Peter s, C. J ., John son, K. M., Reeves, W. C. (1982). ‘ ‘Hepat itis

B in Families. ” Ann Int Med 97(5):787.

K o u r a n y , M . , Mart inez , R. , Vasquez , M. A. (1983) . “ Indices

de Ente roba c t i e r i a s Pa toge na s y Pa ra s i t i sm In te s t ina l e n

Poblaciones de la Region del Rio Bayano antes del Embalse.

Rev Med Panama 8(1) :32-43.

Sousa , O. E. , Wolda , H. , Batis ta , F. (1983) . “Tria tominos En-

contrados en el Ambiente Selvatico de la Isla Barro Golorado.

Rev Me d Pa na ma 8(1) :50-55 .

Mendez , E. (1983) . ‘‘Estado Actual de la Fauna de Mamiferos de

Panama. ” Rev Med Pa na ma 8(1) :72-79 .

Kourany, M. (1983) . ‘‘A Medium for the Isolation and Differen-

tiation of Vibrio parahaemolyticus and Vibro a lginolyt icus

From Seawater and the Marine Environment, Appl Environ

Microbiol 45(1):310-312.

Peter son , J. L. (1983). ‘ ‘Book Review: Cytogenetics and Genetics

o f V e c t o r s , ed. by R. Pal, J. B. Kitzmiller and T. Kanda.

Am J Trop Med H yg 32(l): 198-199.

Walton, B. C., Harper III, J., Neal, R. A. (1983). “Effectiveness

of Allopurinol Against Lesihmania braziliensis panamensis

in Ao tu s t r i v i rg a tu s . Am J T rop M ed Hyg 32 (1 ):4 6 -5 0 .

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Appendix D

Summary of the Telephone Surveyon Gorgas Memorial Laboratory

Conducted July 13-17, 1983

.— ——

— ——— —.

— — —————

Michael B. Macdonald, under contract to OTA,conducted a telephone survey of experts knowledge-able about the Gorgas Memorial Laboratory (GML).OTA supplied Mr. Macdonald with a list of approxi-mately 70 potential interviewees. He attempted to con-tact each of them, and was able to complete 23 inter-

views. (The individuals contacted are among those in-cluded in the Acknowledgments for this memoran-alum. )

The original list of potential interviewees was com-piled by OTA staff. It included the names of individ-

uals known to have specific knowledge of GMI/ GML.The names were gathered during the previous 2months of preliminary work on this technical mem-orandum. During that process, solicitations were con-tinually made for additional people who would haveuseful information on this subject. Names were addedto the list regardless of whether biases of the in-dividuals were known or unknown to OTA, and re-gardless of the nature of those biases. The wide rangeof responses, positive and negative, gives some assur-ance that a spectrum of viewpoints was expressed,though OTA does not claim the survey to be globalor entirely representative of opinion about Gorgas.

Most of those contacted by Mr. Macdonald had

some firsthand knowledge of Gorgas. They had eitherworked there, collaborated with Gorgas investigators,participated in site visits, or had experience withGorgas grants or contracts. Nearly all those who par-ticipated in the survey are technical specialists intropical diseases, including experts in infectious dis-eases (mainly arboviruses and other viruses); malaria,leishmaniasis, helminthic, and other parasitic diseases;traditional tropical disease and cancer epidemiology;vector biology; microbiology; nutrition; and the gen-eral fields of clinical research, tropical medicine, pre-ventive medicine, and international health.

Ten of the participants hold positions in U.S. aca-demic institutions, five are in the military, six areemployed by other U.S. Government departments(Department of Health and Human Services and De-partment of State), and two are with an internationalhealth organization.

The results of the survey are summarized in the re-mainder of this appendix. Opinions and quotes are notattributed to specific individuals.

1. How would you rate the work ofGML?

The respondents generally rated the quality of workat GML high. Most felt that some programs were ex-cellent, especially the work on arboviruses, malaria,and medical entomology, while other programs, suchas the bacteriology, were of lower quality. Threerespondents said that GML has done excellent work.The most solid endorsement came from one who saidthat it was “outstanding, the best in the world. ” Twoothers who have spent many years in tropical medicinestressed that the location of GML makes it an excellentsite for training, as a place for visiting scientific groups,and for field situations that are not available elsewhere.

Other responses were less enthusiastic but still gen-erally positive, Some programs were considered ex-cellent, others less so. One person commented, “Likeany large institution which has existed for many years,it has its weak p oints, but on a scale of 1 to 5, I would

give it a 4 (high). ” Another offered a similar rating.

He felt tha t while some of the resear ch may not be ori-

ginal, it is technically very good.

Certain programs, including the entomology, virol-

ogy, and malaria work got high marks. Other pro-

grams th at were r ated as excellent were the cancer and

sexually transmit ted diseases programs, trypanosomi-

asis and leishmaniasis studies, and the ecology and en-

vironmental studies.

One respondent said that while the arbovirus andecology studies were excellent, some of the other pro-grams were “mediocre. ” Another individual com-mented, “some of the work was excellent, some rou-tine, but you can expect that in any institution thathas existed for so many years. ”

The bacteriology and some parasitology programswere sometimes said to be the weakest points. Tworespondents characterized some of the parasitologystudies as slow but steady.

77

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78

Many chose to qualify their answ er and said thatone must consider the setting when rating the workof GML. The field conditions make it a much differentsituation than that of the National Institutes of Health(NIH), for instance. One person commented, “I wouldrate the work as high. As a person who has worked

in the field for many years, I know what tropicalmedicine work is like. Its only weak point is thedecrease in support which makes it difficult to attracttop scientists. ” Another also rated the work as “un-dersupported.”

2. How should GML be judged?

The quality of publications and GML’s impact onthe pu blic health oft he region were th e most frequentlyoffered criteria for evaluation. Other responses in-cluded judging how GML fared in grant competition;on the productivity of researchers; on the reputationof the staff; on the training provided at GML; and by

the contributions to progress against specific diseases.Those respondents with the most experience in the

field stressed that one should not make a direct com-parison between an institution such as GML and uni-versity or NIH laboratories. Some felt that it shouldbe judged on a regional basis, in comparison to lab-oratories in other countries in the region. One in-dividual pointed out that because many of the pro-grams are involved in vector control, it is inap-propriate to look simply at short-term output. Thebenefits of surveillance accrue in the long term.

3. Has the quality of research

changed over the years?Most of the participants agreed that this was a dif-

ficult question, since the emphasis of the research haschanged. Many chose not to answer. Three thoughtthat there was no change. Two said there had beena p ositive change. Four oth ers said that th ere were fluc-tuations in the quality of research, but through all of the fluctuations, some programs, such as entomology,continued to meet a very high standard.

A number of people responded that there has beena general decline in the quality of the research overthe years. All of those who said that there has beena decline blamed the uncertain funding, citing an in-

ability to buy sophisticated equipment or attract top-notch scientists.

4. Are you aware of the Peer ReviewProcess at GML?

Few had any knowledge of the peer review processat GML. There was a general lack of consensus aboutwhether such a process exists. It seems that respond-

ents felt that sometimes the peer review process wasoperating, while at other times it was not, possiblydepending on who was in charge. One person com-mented that a process exists, but it needs strengthening.

5. What is the relevance of GMLto research in: Panama, Latin America,

the United States, and BiomedicalResearch in general?

In various ways, GML research is perceived to berelevant to Panama, the region, and the United States.A number of individuals noted that Panama benefits

from activities such as the surveillance field studies andthe environmental impact assessments of hydroproj-ects.

Another respondent, familiar with the cancer re-search, noted that GML has been a great help in in-creasing the sophistication of Panamanian cancerresearchers.

In terms of the region, GML served as a serum anddata bank during the recent dengue epidemic. It wasalso the only laboratory in the region that was capableof looking into the resurgence of yellow fever.

Another aspect of its importance as a regional centeris that it is a place where researchers in Central andSouth America can call and receive answers in Span-

ish.Everyone contacted mentioned that GML is partic-ularly important to the United States, specifically forthe military. Since NIH no longer has its own labora-tory in Central America, it is the only place for themilitary to commission work in the region.

One respondent said that if GML did not exist, thenthe military would have to build its own tropical lab-oratory.

Many respondents stressed the potential impact of GML work. Some said it should be more closely linkedto the Panamanian Ministry of Health, that it shouldbe a leader in the region and that it could be more pro-ductive. One respondent, however, felt that political

barriers presently limit its importance as a regionalcenter.

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79

6. What is the value of the training intropical medicine carried out at GML?

Most of those who commented gave GML traininga high rating. They felt that it was a unique settingand very important to maintain, since there are so few

other places available for training in tropical medicine.One person said that a training center in a place suchas Puerto Rico, for example, would not be as valuablebecause of a different disease ecology. Two respond-ents offered the same quote by General Douglas Mac-Arthur that in the Philippines he needed three divi-sions to do the work of one, since two would alwaysbe in the hospital with malaria or dengue.

Not all of the responses to this question were posi-tive. Two felt that the level of training had gone dow n-hill over the past few years because of financial con-straints. Another felt that the trainers were not sophis-ticated enough. He noted that there were more Pana-manians involved in the training now and that the pro-

gram was hurt when NIH cut back on funding foryoung American scientists to go to GML. A third neg-ative opinion w as offered by a u niversity scientist whofelt that there should be more civilians involved intraining programs at GML.

7. What is the value to research of theanimal population kept at GML?

Nearly all of the responses to this question were verypositive about the animal populations. This questionevoked the most immediate and strongest reactions of any on the survey. The colonies were variously termed

“Crucial, Critical and Unique, cannot be duplicatedelsewhere. ” One noted that this function is becomingeven more important with the increasing prevalenceof malaria strains resistant to current drugs. A numberof respondents noted that it was much more cost ef-fective to keep the colonies in Panama than in theUnited States. Besides malaria, the colonies are veryimportant in the study of diseases such as trachomaand hepatitis.

One person stressed that the work on antimalarialmust be carried out. He said that if GML cannot doit then the Army would have to build its own lab toscreen the antimalarial drugs. Others concurred thatthis was one of the most important functions of GML.

“The screening of antimalarial must continue. ” “Themonkey colonies are invaluable to our study of humanmalaria. ” It was mentioned that to an outsider the col-onies seem to be dull and routine work, but they pro-vide a very important service.

One who is quite knowledgeable about malaria felt

th e value of th e Aotus population had declined overthe years and that there w as some difficulty in m eshingthe colony to current research needs. He felt that thecolony was not reaching its potential.

In addition to the monkey colony, it was menioned

that the wild animals in the area also provide a veryvaluable resource for the study of disease ecology of such diseases as leishmaniasis, the arboviruses, andChagas’ disease.

8. Do you have any suggestions forchange?

Nearly all respondents had suggestions for change:stabilization of fund ing and increased fund ing were themost common answers.

It was felt that the constant budget problems erodedthe confidence of the staff and GML’s attraction to topscientists. One respondent who had worked there for

many years said that it was demoralizing to hear atevery weekly meeting that, “Funding might be cut nextweek. ” He said that u ncertain fund ing was a m ajor rea-son for failing to attract top university scientists. Onesaid that GML cannot continue in such a precariousfinancial position and that it should either be fundedproperly or closed. Others felt that GML/ GMI shouldlook for more international support and operate morelike the cholera research institution in Dacca or theInternational Laboratory of Research on Animal Dis-eases in Kenya.

Another respondent suggested that GML should col-laborate more with labs in the United States, butbureaucratic changes would be needed for travel

money and arrangements for cooperative agreementswith other institutions.

Some felt that major changes should be made in themanagem ent structure of GML/ GMI, expressing theopinion that even with solid core support, they wouldnot be able to compete with other tropical medicineunits. “The current direction must change” noted oneindividual. The need for a strong executive was rec-ognized by many other respondents. One felt that theyshould pay the high salary needed to get a good direc-tor in the United States and in Panama. Two other sci-entists with many years of experience in tropical med-icine felt also that it was important to develop closerties to the region.

Other suggestions were for more long-range plan-

ning, a firmer peer review process and pruning thedead wood. Two felt that there should be closer linksto basic science and a greater use of more sophisticatedimmunologic and diagnostic techniques.

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80

9. What do you think is the overall valueof GML?

All the respondents, without exception, felt that it

would be a terrible mistake to lose GML. “For better

or worse, it is the only one we have, and we are bet-ter off with something than nothing, If it did n ot exist

[the military] would have to build one there.” It is a

resource that cannot be duplicated. “It is irreplaceable

in the panorama of tropical disease research related

to Latin America and the United States. ” A numberof other respondents noted the unique setting of GML.“While it does have its weaknesses, it w ould be a terri-ble mistake to let it go. “ “The relative cost is peanutscompared to the benefits, and it would be insane toreduce our limited involvement in the area. ” “If lostnow, we would never get it back. ”

Many spoke in terms of GML’s potential. One feltthat GML’s value now was only marginal but that it

could be great, if it had stable funding.

GML is also viewed as a front line defense againstcertain diseases that could spread to the United States.Panama Canal forms a barrier to many diseases at thispoint. But now that the Pan American Highway isopening up it is even more essential that diseases suchas foot and mouth disease, swine fever, yellow fever,Venezuelan and eastern equine encephalitis be confinedat this point.

Besides its importance in traditional tropical medi-cine, GML is very important in cancer research in theregion. It is unique in that it is capable of doingsophisticated cancer research in a place which is in theprocess of modernization.

GML was also felt to be very important politically.It would be an affront to Panama if we pulled out asit is a very important indicator of U.S. concern withnonpolitical problems in the region. The general feel-ing was that with the current direction of events in theregion, GML is becoming more important than ever,if constructive changes are made.

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Appendix E

Glossary of Acronyms and Terms — — — — r

Glossary of Acronyms

AFRIMS —Armed Forces Research Institute of

Medical SciencesAID —Agency for In ternational

Development (U.S. Department of State)

A RI —acu te resp iratory in fectionsBC G —b acille Ca lm et te-Gu er in Va ccin at io nCAREC —Caribbean Epidemiology Research

Center (PAHO)CCCD —Combatting Communicable

Childhood Diseases (AID)CDC –Centers for Disease Control (PHS)CE/ LAS —California Encephalitis/ LaCrosse

EncephalitisCEPIALET —Pan-American Center for Research

CFNI

D O DDRGEE E

EPI

FICG A O

GM I

GM L

GN D

HH S

HTLV

and Training in Leprosy and TropicalDiseases (PAHO)

—Caribbean Food and NutritionInstitute (PAHO)

—U.S. Department of Defense–Division of Research Grants (NIH)—eastern equine encephalitis—Expanded Program on Immunization

(WHO)–Fogarty International Center (NIH)–General Accounting Office (U.S.

Congress)—Gorgas Memorial Institute of

Tropical and Preventive Medicine,Inc.

—Gorgas Memorial Laboratory (of GMI)

—Great Neglected Diseases of Mankind(Rockefeller Foundation)

–U.S. Department of Health andHuman Services

—human T-cell leukemia virusICDDRB —International Center for Diarrheal

Disease Research/ Bangladesh

IC ID R —In ter na tio na l Co lla bo ra tio n inInfectious Diseases (NIAID)

ID RC —In te rn at io na l De ve lo pm en t Rese ar ch

Centre (Canadian)ILRA D —Interna tiona l Labora to ry o f Research

on Animal DiseasesIN CA P —Inst itute o f N u tr it ion o f the

Caribbean and Panama (PAHO)IRG –Internal Review Group (NIH)M ARU —Mid d le Am er ica n Resea rch U nit

(NIAID)MERTU/ G—Medical Entomology Research and

Training Unit in Guatemala (CDC)NAMRU —Naval Medical Research UnitN CI –N ational Cancer In stitu te (N IH )NIAID —National Institute of Allergy and

Infectious Diseases (NIH)

NIH –National Institutes of Health (PHS)O RT —oral d ehyd ration therapyO T A —Office of Technology Assessment

(U.S. Congress)P A H O —Pa n Am er ica n H ea lt h O rg an iz ationPH S –U.S. Public Health Service (HHS)SLE —St. Louis encephalitisSTD —sexu ally tran sm itted diseasesTD R —United Nations Develop ment

Program/ World Bank/ World H ealthOrganization Special Programme forResearch and Training in TropicalDiseases

UNDP —United Nations DevelopmentProgramme

USAMRU —United States Army Medical ResearchUnit

VEE —Venezuelan equine encephalitisWEE —western equine encephalitisWH O —World Health OrganizationWRAIR —Walter Reed Army Institute of

ResearchYARU —Yale Arboviral Research Unit (Yale

University)

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82

Glossary of Terms*

acute: Having a sudden onset, sharp rise, and short

course; not chronic.

Aedes (ah-ee’dez): A genus of mosquitoes. A. aegyp-ti , the tiger mosquito, is a common urban speciesthat breeds near houses and transmits urban yellow

fever and dengue fever.amebiasis (am-ee-bi’ah-sis): Infection by amebae, es-

pecially, infection with Entamoeba histolytica, anintestinal p arasite, characterized by diarrhea withblood and mucous and also causing abcesses in theintestine and liver (sometimes called amebic dysen-tery). See AMEBA.

am eb a (ah-me’bah), also, amoeba: A protozoan; aminu te single-celled life form. One species, Entamoe-ba histolytica, is a parasitic pathogen producing

amebiasis in man. See AMEBIASIS.ancylostomiasis (an-ki’los-to-mi’ ah-sis): Infection with

Ancylostoma duodenale, th e human intestinal hook-worm. Causes chronic anemia.

Anopheles gambiae (a-nof’a-leez gam -bee’ee): A sp e-cies of mosquito in Africa that transmits malaria;also, a group of closely related species of mosqui-toes. See SPECIES COMPLEX.

antigen (an’ti-jen): Any substance that stimulates theproduction of antibodies.

Aotus (ay-oftus): A g en u s o f m o n k ey ; t h e o wlmonkey.

arbovirus (ar’bo-vi-rus): An abbreviation for arthro-pod-borne virus, virus transmitted by arthropods.

Argentinean hemorrhagic fever: An acute, sometimesfatal disease caused by a virus, transmitted throughcontamination by urine or feces of infected rats.Characterized by chills, fever, severe headache,

hemorrhagic symptoms, shock, kidney involve-ment, and necrologic involvement.arthropods (ar’thro-podz): Invertebrate animals of the

phylum Arthropoda that includes insects, ticks,

spiders, and crustaceans.

arthropod-borne: Transmitted by arthropods.

ascariasis (as-kah--ri’ah-sis): An infection with wormsof the genus Ascaris, especially, Ascaris lumbri-coides, the human intestinal round worm, charac-terized by intestinal pain and diarrhea.

*SOURCES:

1. The American Heritage Dictionary of the English Language, W. Morse

(cd. ) (Boston, Mass.: Houghton Mifflin Co., 1976).2. Control of Communicable Diseases in Man, Mth ed , A. S. Benensen (ed )(Washington, DC.: American Public Health Association, 1981).

3. Dorland’s Illustrated Medical Dictionary, 25th ed. (Philadelphia: W. B.S aunders , 1974).

4. Office of Technology ,4ssessment, U.S. Congres s , Was hington , D.C.

s Roper, N., Pocket ,tfedical D~c t i ona r y , 13th ed, (Edinburgh , S cot l and:

Churchill Livingstone, 1978).

asepti c menin gitis (a-sep’tik m en-in-ji’tis): Viral-caused

inflammation of the membranes surrounding the

brain and spinal cord.

bacille Calmette-Guerin, abbr. BCG: An attenuated(weakened) strain of tuberculosis bacteria used tovaccinate against virulent tuberculosis.

bacillus (ba-sil’us), pl. bacilli: Any of various rod-

shaped, aerobic bacteria of the genus Bacillus.bacteriology (bak-tir’ee-ol’o-ji): The scientific study of

bacteria.bacterium (bak-tir’ee-um), pl. bacteria: Any of numer-

ous unicellular micro-organisms (class Schizomy-

cetes), occurring in a wide variety of forms, existingeither as free-living organisms or as parasites, andhaving a wide range of biochemical, often patho-genic, properties.

bilharzia (bil-har’zi-ah): See SCHISTOSOMIASIS.bilirubin (bi-li-roo’bin): A pigment largely derived

from the breakdown in the spleen of hemoglobinfrom red blood cells.

Bolivian h emorrhagic fever: An acute, sometimes fatal

disease caused by a virus, transmitted through con-tamination by urine or feces of infected rats, occur-

ring in Bolivia. Characterized by chills, fever, severeheadache, hemorrhagic symptoms, shock, kidneyinvolvement, and necrologic involvement.

California encephalitis: An acute encephalitis caused

by an arbovirus, transmitted by mosquitoes.

Campylobacter (kam’p i l -o -bak’ te r ) : A genus o f

bacteria, one of which, C. jejuni, causes an acutediarrheal disease.

cellulose acetate electrophoresis: A type of isozymeelectrophoresis. See ISOZYME; ISOZYME ELEC-TROPHORESIS.

cervical cancer (ser’vi-kal): Cancer of the cervix (the

neck of the uterus).Chagas’ disease (sha’gus): Infection by Trypanosoma

cruzi, transmitted by reduviid bugs. Discovered anddescribed by Carlos Chagas of Brazil, Characterizedby an acute course in children with fever, encepha-litis, and inflammation of the heart muscle (oftenlife-threatening or fatal), and a chronic course inadults leading to heart disease and heart failure.Widely distributed in Central and South America.Also called American trypanosomiasis. See TRYP-ANOSOMIASIS.

Chagres fever: A febrile disease caused by an arbovi-

rus, transmitted by phlebotomine sandflies. Also

called “Panama fever. ”

chemotherapy (kee-mo-ther’a-pi): The use of specificchemical agents to arrest the progress of, or eradi-cate, disease in the body without causing irreversi-ble injury to healthy tissues.

chorioretinitis (kawr-i-o-ret-in-it’ is): Inflammation of the choroid and retina of the eye.

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chronic: Lingering, lasting, as opposed to acute.

Colorado tick fever: A febrile disease without rash

caused by an arbovirus, transmitted by a tick, oc-

curring in the Rocky Mountain region of the UnitedStates.

cytogenetics (si’to-je-net’iks): Laboratory examination,

usually microscopic, of chromosomes.dengue fever (deng’gee): An acute febrile disease

caused by an arbovirus, transmitted by mosquitoesof the genus Aedes, characterized by fever, severepains in the head, eyes, muscles, and joints, and askin eruption. Occurring in Japan, Southeast Asia,the South Pacific, India, the Caribbean, Middle andSouth America. Sometimes called “breakbone fe-ver. ”

dengue hemorrhagic fever: Life-threatening complica-

tions of dengue infection; syn. DENGUE SHOCK

SYNDROME. See DENGUE FEVER.

dengue shock syndrome: Life-threatening complica-tions of dengue infection; syn. DENGUE HEMOR-

RHAGIC FEVER. See DENGUE FEVER.diarrh ea (dy-a-ree’a): Pathologically excessive freq uen -

cy and fluidity of fecal discharges. Adj., diarrheal.

diphtheria (dif-theer’ee-a): An acute infectious diseasecaused by the bacterium Corynebacterium diphther-

ia . Characterized by grey, adherent, false mem-brane growing on mucous surface of the upper res-piratory tract. Locally there is pain, swelling, andmay be suffocation. Systemically the toxins attackthe heart muscle and nerves.

DNA hybridization: Laboratory method for species

and strain identification based on m atching of DN A

from an unknown organism with DNA from known

organisms.

eastern equine encephalitis, abbr. EEE: An arbovirusdisease of horses and mules, possibly other verte-brates, with a reservoir of infection in birds, trans-mitted by mosquitoes. Can be transmitted to hu-mans and cause death. Occurring in the UnitedStates in a region extending from New Hampshireto Texas to Wisconsin, in Canada, Mexico, the Car-ibbean, and parts of Central and South America.Characterized by encephalomyelitis.

elephantiasis (el-ef-an-ti’a-sis): The swelling of a limb,usually a leg, as a result of lymphatic obstruction,followed by thickening of the skin and subcutaneoustissues. A complication of filariasis in tropical coun-tries. See FILARIASIS.

encephalitis (en-sef-a-li’tis): Inflammation of the brain.encephalomyelitis (en-sef’-al-o-mi-e-li’ tis): Inflamma-

tion of the brain and spinal cord.endemic (en-dem’ik): The constant presence or persist-

ence of a human disease or infectious agent withina given geographic area. Cf. EPIDEMIC; ENZOOT-IC.

enteric (en-ter’ik): Pertaining to the intestine.entomology (en-to-mol’o-ji): The science dealing with

insects.enzootic (en-zo-ot’ik): The constant presence or per-

sistence of an animal disease or infectious agentwithin a given geographic area. Cf. ENDEMIC; EPI-

ZOOTIC.epidemic (ep-i-dem’ik): The occurrence of a human ill-

ness in excess of usual frequency in a particular area.Cf. ENDEMIC; EPIZOOTIC.

epidemiology (ep-i-de-mi-ol’ o-ji): The scientific studyof the distribution and occurrence of diseases andhealth conditions.

epizootic (ep-i-zo-ot’ik): The occurrence of an animaldisease in excess of usual frequency in a particulararea. Cf. EPIDEMIC; ENZOOTIC.

Escher ichia col i (esh-er-ik’i-a ko’ii): A species of bac-teria; motile, rod-shaped bacterium which is ubiq-uitous in the intestinal tract of vertebrates. Somestrains are pathogenic to humans, causing intestinal

disease and diarrhea.etiology (ee-ti-ol’o-ji): The scientific study of disease

causation; the causation of a disease.

filariasis (fil-a-ri’a-sis): Infection with Filaria, parasiticthread-like worms, found mainly in the tropics andsubtropics, transmitted by mosquitoes. Adults of Wuchereria bancrofti an d Brugia m alayi live in thelymphatic system and connective tissues, where th eymay cause obstruction, but the embryos (microfil-ariae) migrate to the blood stream. Completion of the lifecycle is dependent on passage throu gh a m os-quito. See ELEPHANTIASIS.

genus (jen’us): The taxonomic category next greaterthan species.

granulomatous (gran-u-lom’ah-tus): Composed of tumor-like mass or nodule of tissue, due to inflam-matory process associated with an infectious disease,such as tuberculosis.

helminth (hel’minth): Parasitic worm. Adj. helminthic.hemorrhage: The escape of blood from a blood vessel.hemorrhagic fever: Severe complication of some viral

diseases involving internal or external bleeding.host: Human or other living animal, including birds

and arthropods, that affords subsistence or lodg-ment to an infectious agent under natural condi-tions.

human T-cell leukemia virus, abbr. HTLV: A recent-

ly identified virus that induces a specific type of can-cer of the blood-forming organs.immunity (i-my oo’ne-ti): Nonsusceptibility, or relative

resistance, to a specific infection, due to antibodiesproduced against that specific antigen.

immunology (im’yoo-nol’o-ji): The scientific study of immu nity. Adj., immun ologic, immu nological.

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incidence (in’se-dens): The frequency of new occur-rences of disease within a defined time interval. In-cidence rate is the quotient of new cases of a speci-fied disease divided by the number of people in apopulation in a defined period of time.

inflammation (in-flam-ma’shun): The reaction of liv-

ing tissues to injury, infection, or irritation; char-acterized by pain, swelling, redness, and heat.influenza (in-floo-en’za): An acute viral infection of

the nasopharynx and upper respiratory tract.in v i t ro (vi’tro): In glass, as in a test-tube.in v ivo (vi’vo): In living tissue.isozyme (i’so-zime): Two or more forms of the same

enzyme having, identical chemical function but dif-fering physical structure, which can be separatedand identified,

isozyme electrophoresis (i’so-zime el-ek-tro-for-ee’ sis):Laboratory method of separating isozymes (cf. )based on their migration distance in an electric fieldapplied across a standardized inert material (poly-

acrylamide gel, agarose gel, or cellulose acetate). jaundice (jawn’dis): A condition characterized by

yellow appearance due to raised bilirubin level inthe blood resulting from: 1) obstruction in the biliarytract, 2) excessive rupture of red blood cells, 3) tox-

ic or infective damage of liver cells.

kwashiorkor (kwash-ee-or’kor): A nutritional diseaseprodu ced by persistent deficiency in essential dietaryprotein. Characteristic features are anemia, wasting,edema, potbelly, depigmentation of the skin, lossof hair or change of hair color. Untreated, it pro-gresses to death.

LaCrosse encephalitis: An acute encephalitis caused b y

an arbovirus, transmitted b y mosquitoes. Closely

related to California encephalitis.Leishmania (leesh-may’ni-a): A genus of flagellated

parasitic protozoans causing several clinical diseases.See LEISHMANIASIS.

l e i s hm an ias i s (leesh-man-i’a-sis): I n f e c t i o n b yLeishmania, transmitted by sandflies. Cutaneousleishmaniasis is a skin ulcer caused by L. mexicana

(New World) or L. tropica (Old World). Mucocu-taneous leishmaniasis is an ulceration of the noseand throat caused by L. braziliensis, occurring intropical America. Visceral leishmaniasis, also calledkala-azar, is a generalized and internal diseasecaused by L. donovani (New and Old World).

leprosy (lep’ra-si): A chronic, infectious, granuloma-

tous disease occurring almost exclusively in tropicaland subtropical regions, caused by the bacillus

Mycobacterium leprae, and ranging in severity fromnoncontagious and spontaneously remitting formsto contagious, malignant forms with progressiveanesthesia, paralysis, ulceration, nutritive disturb-

ances, gangrene, and mutilation. Also called “Han-sen’s disease. ”

leptospirosis (lep-to-spi-ro’ sis): Disease caused by spi-rochete (finely coiled bacterium), commonly trans-mitted in water contaminated by urine of infectedanimals, Characterized by inflammation of the spi-

nal cord, the nervous system, and liver.lifecycle: The progressive stages of development of anorganism.

lymphatic system (lim-fa’tik): The system of vesselsin the body that carry lymph fluid.

lymph glands (limf-glanz): The organs at variouspoints of the lymphatic system that filter the lymphfluid.

malaria: A disease caused by protozoan parasites thatinfect red blood cells, transmitted by mosquitoes of the genus Anopheles. Four species of the parasitecause disease in humans: Plasmodium falciparum,

P. v ivax , P . malariae, and P. ovale. P. vixax a n dP. ovale have a persistent stage in the liver that

causes relapses. Many other species infect monkeys,rodents, birds, and reptiles. Characterized by fever,chills, and sweating that occur at intervals depend-ing on the time required for development of a newgeneration of parasites in the body. See PLASMO-DIUM FALCIPARUM.

marasmus (ma-raz’mus): Wasting away of the bodydue to gross lack of calories in the diet.

measles (meez’lz): An acute infectious disease causedby a virus, Characterized by fever, a blotchy rash,and inflammation of mucous membranes.

metabolic: Pertaining to metabolism, the series of chemical changes in the living body by which lifeis maintained.

metastasize (me-tas’ta-syz): Tranfer of a disease fromone part of the body to another, usually by bloodor lymph, leading to secondary growth or lesions.

molluscicide (mol-lusk’i-side): Any chemical agentused to kill molluscs, especially snails.

morbidity: Disease or illness.mortality: Death,onchocerciasis (on-ko-ser-ki’a-sis): An infection of hu-

mans with Onchocerca worms, transmitted by thebite of blood-sucking blackflies (Simuliidae). Adultworms become encapsulated in subcutaneous nod-ules. Immature worms (microfilariae) migrate in thetissues and can cause “river blindness” if reachingthe eye. Occurring in western Africa and discrete

foci in tropical America.oral dehydration therapy: The treatment of fluid-loss

due to diarrhea by a specific water solution of elec-trolytes and glucose taken by mouth,

Oropouche fever (or-o-poosh): An arbovirus diseasetransmitted by biting midges (Culicoides spp. ).

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Characterized by fever, headache, aches and pains,and occasionally encephalitis. Found in Trinidadand Brazil, but recognized range in tropical Americais expanding. Occurrence is primarily rural or forest,but explosive urban and suburban outbreaks occur.

parasitology (par-a-sit-ol’o-ji): The scientific study of

parasites.pathogen (path’o-jen): A disease-producing agent.pathological: Of or pertaining to disease processes.Phlebotomus (fle-bot’o-mus): A genus of sandflies,

many of which are vectors of leishmaniasis. Adj.phlebotomine.

physiological: In accordance with natural processesand normal function of the body.

P l a s m o d i u m f a l c i p a r u m (plaz-mo’de-um fal-sip’ar-um): One of the four species of protozoan parasitescausing malaria in humans. Only P. falciparum

causes life-threatening complications; only specieswith drug-resistant characteristics. See MALARIA.

pneum occoca l (nyoo-mo-kok’al): Referring to the

bacterium, Diplococcus pneumonia, that causespneumococcal pneumonia.pneu monia (nyoo-mon’ya): Inflamm ation of the lun g,

usually the lower respiratory tract.poliomyelitis (po’lee-o-my’a-li’tis): An infectious viral

disease occurring mainly in children an d in its acute,more virulent form attacking the central nervoussystem and producing paralysis, muscular atrophy,and often deformity. Transmitted by the oral-fecalroute.

prevalence (prev’a-lens): The number of existing casesof a disease in a defined population at a particulartime.

protozoa (pro-to-zo’a): Unicellular organisms, the

smallest type of animal life. Adj. protozoan, pro-tozoal.protozoology (pro-to-zo-ol’o-ji): The scientific study

of protozoa. Adj. protozoologic.r eduv i id (r e-du ’v i-id ): Be long ing to the fam i ly

Reduviidae, winged, “true” bugs (Order Hemiptera),including blood-sucking vectors of Chagas’ disease.See CHAGAS’ DISEASE.

reservoir: Any person, animal, arthropod, plant, soilor substance (or combination of these) in which aninfectious agent normally lives and multiplies, onwhich it depends primarily for survival, and whereit reproduces itself in such manner that it can betransmitted to a susceptible host.

rotavirus (ro-ta-vi-rus): Any of a group of v i r us es(round in shape) causing gastroenteritis in infantsand children.

St. Louis encephalitis, abbr. SLE: An arbovirus dis-ease transmitted by mosquitoes, with the reservoirof infection in birds. Can be transmitted to humans

and cause death. First observed in Illinois in 1932.Occurring in most of the United States, Trinidad,Jamaica, Panama, and Brazil. Mild cases character-ized by aseptic meningitis; severe infection usuallymarked by acute onset, headache, high fever, coma,convulsions, and paralysis.

schistosomiasis (shis’to-so-mi’a-sis): An infection of thehuman body by worms of the genus Schistosoma(“blood flukes”), from drinking or bathing in in-fected water. Infected humans pass eggs in urine orfeces (depending on parasite species) into watersource. Immature form (miricidia) hatchs and infectssuitable snail host. After multiplication, interme-diate form (cercariae) is shed from snail into water,where penetration of human skin occurs. Adultworm develops in human, localizing in veins of bladder or intestine. Schistosoma mansoni occurs

in Africa, the Caribbean, and Brazil; S. japonicum

occurs in the Far East; in both, adult worms localizein veins of intestine; deposited eggs cause tissue scar-

ring of intestine and liver; S. haematobium occursin Africa and the Middle East producing the urinaryform as adult worms localize in veins of the blad-der; characterized by obstruction due to scar for-mation, inflammation, and possibly cancer. Alsocalled “bilharzia. ”

sequelae (se-kwel’ee): The pathological consequencesof a disease.

seroepidemiologic: Pertaining to a branch of epidemi-ology that studies antigens from h um ans to delineateepidemiologic patterns of a disease. See EPIDEMI-OLOGY; SEROLOGY.

serology (se-rol’o-ji): The scientific study of sera (thefluid portion of blood). Adj. serologic, serological.

sexually transmitted diseases: A group of infectiousdiseases defined by transmission through intimate

contact, including gonorrhea, syphilis, chancroid,

lymphogranuloma venereum, granuloma inguinale,

chlamydia, herpes simplex, trichomonas, as well as

hepatitis virus and intestinal parasites such as giar-dia, entamoeba, ascaris, and trichuris.

species: A taxonomic subdivision of a genus. A groupof individuals having common characteristics dis-tinguishing them from other categories of individ-uals of the same taxonomic level. Always carries theimplication of reproductive isolation, i.e., membersof a species only reproduce successfully with oneanother,

species complex: A group of two or more closelyrelated insect species that can only be differentiatedby cytogenetic analysis or cross-breeding experi-ments.

strain: A group of organisms of the same species (cf. )

having a distinctive quality or characteristic (bio-

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chemical, pathogenic, or other feature) that can bedifferentiated, but not different enough to constitutea separate species.

subacute: Mild or moderately severe. Often the stagebetween the acute and chronic phases of disease.

symptomatic: Of or per ta in ing to the symptoms,

rather than the causes of a disease.symptomatology: The branch of medicine concernedwith symptoms. The combined symptoms typicalof a particular disease.

therapeutic: Dealing with the treatment of disease.

toxoplasmosis (toks-o-plas-mo’sis): Infection by the

protozoal parasite Toxoplasma gondii. Many mam-

mals can harbor the parasite which encysts in tissueafter ingestion (oral-fecal route), but only in cats isthe lifecycle completed, with the infective form shedin feces. Characterized by lesions of the central ner-vous system, which may lead to chorioretinitis,blindness, brain defects, and death.

trachoma (tra-ko’mah): A chronic, infectious disease

of the eye caused by the bacterium Chlamydia tra-chomatis, characterized by inflammation, pain, wa-tery eye, then scarring, and finally blindness.

triatomine (tri-a-to-meen): Pertaining to the genus Tri-atoma, blood-sucking bugs important as vectors of Chagas’ disease See CHAGAS’ DISEASE.

trichuriasis (trik-u-ri’ah-sis): Infection with the intes-

tinal parasitic whipworrn, Trichuris trichiura.

Trypanosoma (tri-pan-o-so’ma): A genus of parasiticprotozoans . Their l i fecycle a l ternates betweenblood-sucking arthropods and vertebrate hosts. SeeTRYPANOSOMIASIS.

trypanosomiasis (tri-pan’a-so-my’a-sis): Disease pro-

duced by infection with Trypanosoma. In man this

may be with Trypanosoma cruzi, transmitted byblood-sucking reduviid bugs in the Americas (alsocalled Chagas’ disease); or with T. rhodesiense inEast Africa or T. gambiense in West Africa, bothtransmitted by the tsetse fly, causing “sleeping sick-ness.” See CHAGAS’ DISEASE.

tubercle bacillus (tu’ber-kl ba-sil’es): A bacillus caus-ing tuberculosis; usually refers to Mycobacterium

tuberculosis, the principal cause of human tubercu-losis.

tuberculosis (tu-ber-ku-lo’sis): An infectious disease

caused by any of several species of mycobacteria.Usually begins with lesions in the lung, but can me-tastasize to other parts of the body.

vector: A carrier of disease; usage commonly refersto arthropods or rodents.

vector bionomics: The relationship between organisms

and their environment.vector-borne: Transmitted by a vector.vector control: Intervention aimed at disease reduc-

tion by action against vectors.Venezuelan equine encephalitis, abbr. VEE: An ar-

bovirus disease of horses and mules, possibly othervertebrates, with a reservoir of infection in birds,transmitted by mosquitoes. Can be transmitted tohumans and cause death. Endemic in northern SouthAmerica, Trinidad, Middle America, Mexico, andFlorida. Characterized by severe headache, chills,fever, pain in muscles and eyes, nausea and vomit-ing, possibly with severe central nervous systemcomplications leading to convulsions, coma, and

death.western equine encephalitis, abbr. WEE: An arbovirusdisease of horses and mules, possibly other verte-brates, with a reservoir of infection in birds, trans-mitted by mosquitoes. Can be transmitted to hu-mans and cause death. Occurring in Western andCentral United States and Canada and in scatteredareas further east. Characterized by encephalomy -elitis.

whooping cough: Pertussis; an infectious respiratorydisease of children with attacks of coughing whichreach a peak of violence ending in an inspiratorywhoop. Caused by Bordetella pertussis, Prophylac-tic vaccination is responsible for a decrease in case

incidence.yellow fever, abbr. YF: An acute febrile disease causedby an arbovirus, transmitted by mosquitoes. Char-acteristic features are fever, jaundice, black vomit,and a nu ria (absence of urin e excretion). Jun gle/ syl-van yellow fever is maintained in monkey reservoirhosts; urban yellow fever refers to transmission withhuman reservoir hosts.

zoonosis (zo-on-o’sis): An infection or infectious dis-ease transmissible under natural conditions fromvertebrate animals to man,

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