CREDIT SEMINARTitle: Coccidioidomycosis, A California Fever (Valley Fever)

Student’s Name: Davinder Singh

M.Sc – Molecular Genetics (Semester II)Registration No.: CUPB/MSc-MG/SBAS/BIO/2014-15/06

Centre for BiosciencesSchool of Basic and Applied Sciences

Central University of Punjab, Bathinda

COCCIDIOIDOMYCOSIS INTRODUCTION

• Is a fungal disease of dimorphic saprophytic fungi.

• Coccidioides immitis and Coccidioides posadassi.

• Coccidioides sepp. grows in soil of western hemisphere.

• Storms, Dusty wind, construction, farming and an eartquick disturb soil.

Fig 1: A storm of dust in California.

(Source: http://cmr.asm.org/content/26/3/505/F11.expansion.html)

HISTORY• In 1892 first case was reported by wernick

and posadas.• In 1896, Rixford and Gilchrist identify the

protozoa like structure and named it coccidioides immitis.

• In 1957 intravenous amphotericin B was the first effective therapy for coccidioidomycosis.

• Since the 1980s, various oral antifungal agents, including class of azole drugs are discovered.

• In 1991-1994 the great Coccidioidomycosis outbreak in California.

• In 1995 William Ophuls described the life cycle and pathology of Coccidioides immitis fungus.

Fig 2: Head of Domingo Ezcurra.

(Source: http://botit.botany.wisc.edu/toms_fungi/jan2002.html)

Fig 3: Geographical distribution of coccidioidomycosis.

(Soure: http://theepistlesofpaul.blogspot.in/2012/09/valley-fever-coccidioidomycosis.html)

GEOGRAPHY

ABOUT FUNGIMacroscopic Features:

• The colonies initially seen to be moist,

glabrous, membranous, and grayish,

later producing white and cottony

aerial mycelium. With time, colonies

become tan to brown in color.

Microscopic Features:

1. At 25°C (77 oF)

Hyphae and arthroconidia are produced.

Fig 4: Culture of Coccidioides immitis at 25°C

(Source: http://www.mycology.adelaide.edu.au/gallery/dimorphic_fungi/)

Fig 5: Culture of Cossidioides immitis at 37°C .

(Source: http://www.doctorfungus.org/imageban/index_query.php?&start=825)

2. At 37°C (98.6 oF)

At that human body temperature large, round,

thick-walled spherules filled with endospores

are observed.

Microscopic Features

CELL STRUCTURE AND GENOMECELL WALL

• Chitin

• Mannoproteins

• Glycans ( β 1,6 glycans and β 1,3 glycans)

• Ergosterol

GENOME

• Coccidioides immitis genome is 28,876,84

3 base pairs

• About 29 Mb

• MAT1 -1 or a MAT1 -2

idiomorph, which is 8.1 or 9 kb in length.

Fig 7: Cell wall of Coccidioides Sepp.

(Sorce: http://www.slideshare.net/jstajich/evolution-and-exploration-of-the-transcriptional-landscape-in-two-filamentous-fungi-coccidioides-and-neurospora)

LIFE CYCLE

Fig 6: Life cycle of Coccidioides Sepp.

(Source: http://cmr.asm.org/content/26/3/505/F9.expansion.html)

ABOUT DISEASETypes of coccidioidomycosis:

Acute coccidioidomycosis (Valley Fever)

Symptoms:• Fever • Cough• Chest pain• Chills• Night sweats• Headache• Fatigue• Joint aches• Red, spotty rash

Fig 8: Acute Coccidioidomycosis

(Source: http://jcm.asm.org/content/50/9/3125/F1.expansion.html)

CHRONIC COCCIDIOIDOMYCOSIS

Fig 9: Chronic Coccidioidomycosis.

(Source: http://radiology.casereports.net/index.php/rcr/article/view/237/552)

Symptoms:

• Low grade fever

• Weight loss

• Cough

• Chest pain

• Nodules in the lungs

DISSEMINATED COCCIDIOIDOMYCOSIS

Fig 10: Disseminated Coccidioidomycosis.

(Source: http://www.the-dermatologist.com/content/treating-rare-fungal-infections-coccidioidomycosis)

Symptoms:• Nodules, ulcers and skin lesions

• Painful lesions in the skull, spine or

other bones

• Painful, swollen joints, especially in the

knees or ankles

• Meningitis

Fig 11: Frequency of different manifestations Coccidioidomycosis.

(Source: http://www.life-worldwide.org/fungal-diseases/coccidioidomycosis)

FREQUENCY OF DIFFERENT MANIFESTATIONS OF COCCIDIOIDOMYCOSIS AFTER EXPOSURE

CAUSES• By inhalation of Spores from Air• By organ transplantation

Fig 13: Inhalation of spores.

(Source: http://www.cdc.gov/features/valley-fever-10-things/)

Fig 12: Soil disturbance by farming.

(Source: http://environmenthealth.ucmerced.edu/valley-fever)

It is not transmitted from one person to another

IMMUNOLOGY

Spherules react with complement and promote chemotaxis of neutrophils

and eosinophil's.

Than lymphocytes travel to site of infection, leading to granuloma

formation with the presence of giant cells.

The innate immune response (neutrophil, macrophage and natural killing

cells) contributes to host cell and facilitate killing of organism.

T-helper cytokines promote macrophages killing of endospores.

SEROLOGICAL TESTINGS

• IgM is detected in 50% of patients within first to third week.

• IgG antibodies detected and become positive in 85 -90% of patients

by 3 months after onset of infection.

• Culture grown in laboratory within 3-5 days of incubation.

COCCIDIOIDOMYCOSIS IN HIGH RISK PATIENTS

• Immunocompromised patients

• Pregnant Women

• Age

Fig 14: Distribution of coccidioidomycosiss by Age.

(Source: http://www.mdpi.com/1660-4601/8/4/1150/htm)

Fig 15: Distribution of coccidioidomycosis by Race.

(Source: http://www.mdpi.com/1660-4601/8/4/1150/htm)

COCCIDIOIDOMYCOSIS IN HIGH RISK PATIENTS

• Gender

• Race

• Organ transplantation

• Prisoners

Cont.

PREVENTIONS• Stay inside and keep windows and doors

closed.

• While driving, keep car windows shut and

use “recirculating” air conditioning if

available.

• Wear an N95 mask or respirator.

• Wet down soil before disturbing it to

reduce dust.

• Cover open dirt areas around your home

with grass, plants, or other ground cover.

• After work or play, change out of clothes if

covered with dirt.

Fig 16: N95 Mask.

(Source: http://yourhealth.asiaone.com/content/n95-masks-available-singapore-which-work-and-which-dont)

Treatment

ANTIFUNGAL MEDICATIONS:

• Amphotericin B

AZOLE DRUGS• Fluconazole (Diflucan)

• Ketoconazole:

• Itraconazole (Sporanox):

• Voriconazole (Vfend):

• Posaconazole (Noxafil):

• Caspofungin (Cancidas):

Fig 17: Mechanism action of Azole drugs.

(Source: http://www.slideshare.net/fergua/echinocandins-in-the-icu-presentation)

AFECTED CASES AND DEATHS

Fig 18: Affected cases by coccidioidomycosis during 1998-2013.

(Source: http://www.cdc.gov/fungal/diseases/coccidioidomycosis/statistics.html)

AFECTED CASES AND DEATHS

(Source: http://www.cdc.gov/fungal/diseases/coccidioidomycosis/statistics.html)

• Total 3,089 coccidioidomycosis - associated deaths occurred in the US during 1990 to 2008.

Table 1: Number of reported coccidsioidomycosis cases from 1998 to 2013.

REFERENCES

• Brown, J., Benedict, K., Park, B. J., & Thompson III, G. R. (2013). Coccidioidomycosis: epidemiology. Clinical epidemiology 5: 185-197.

• Spinello, I. M., Munoz, A., & Johnson, R. H. (2008, April). Pulmonary coccidioidomycosis. Respiratory and critical care medicine 29: 166-173.

• Hector, R. F., & Laniado-Laborin, R. (2005). Coccidioidomycosis—a fungal disease of the Americas. PLoS medicine 2(1): 1394–1402.

• Whiston, E., Wise, H. Z., Sharpton, T. J., Jui, G., Cole, G. T., & Taylor, J. W. (2012). Comparative transcriptomics of the saprobic and parasitic growth phases in Coccidioides spp. PloS one 7: 65-75.

• González, A. (2013). Innate Immune Response to the Dimorphic Fungal Pathogen Coccidioides: Molecular and Cellular Mechanisms. J Clinical and Cellular Immunology S 13: 21-27.

• Centers for Disease Control and Prevention (CDC. (2013). Increase in reported coccidioidomycosis--United States, 1998-2011. MMWR. Morbidity and mortality weekly report, 62(12): 215-217.

REFERENCES• Verghese, S., Arjundas, D., Krishnakumar, K. C., Padmaja, P., Elizabeth, D.,

Padhye, A. A., & Warnock, D. W. (2002). Coccidioidomycosis in India: report of a second imported case. Medical mycology, 40(3): 307-309.

• Savio, J., Srinivasa, H., Mathew, J., Chakraborty, A., McNamara, D. R., Hemashettar, B. M., & Padhye, A. A. (2011). Coccidioidomycosis in India: report of a third imported case. Journal de Mycologie Médicale/Journal of Medical Mycology, 21(1): 33-36.

• Nguyen, C., Barker, B. M., Hoover, S., Nix, D. E., Ampel, N. M., Frelinger, J. A., & Galgiani, J. N. (2013). Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis. Clinical microbiology reviews, 26(3): 505-525.