A (H1N1) influenza A (H1N1)

A412Hippocrates1933: [Smith et al., 1933] 1933

1Oxford JS. Rev Med Virol 2000;10:11933(Influenza pandemics)

Initial Genetic Characterization of the 1918 Spanish Influenza VirusJeffery K. Taubenberger,* Ann H. Reid, Amy E. Krafft, Karen E. Bijwaard, Thomas G. FanningSCIENCE 1997:275;1793-1796

28% of the U.S. population is estimated to have been infected. The disease was also exceptionally severe, with mortality rates among the infected of over 2.5%, as compared with less than 0.1% in other influenza epidemics. 28%, 2.5%SCIENCE 1997:275;1793-1796

1918 Vs. average annual mortality of 19131917

1957 Vs, 19521956

1968 Vs. 19631967

Source: CID 2001:33:1375-8 (15 October)

Gustau Klimt1862-1918The kiss

Images from the 1918 Influenza Epidemic

(Jeffery K. Taubenberger ) 1995319 PCR19973

DNA1918Eric Haase

1918

(Johan V. Hultin) 1951 1997 -(Lucy) Teller Lutheran missionBrevig

1918 ()

Dr. Terrence Tumpey, a U.S. Centers for Disease Control microbiologist for the National Center for Infectious Diseases, examines specimens of the 1918 pandemic influenza virus, a virus that he reconstructed to identify and research the characteristics that made it so harmful in this 2005 handout photo acquired from the CDC on April 24, 2009.

ABCABC RNARNA (hemagglutinin, H) (neuraminidase, N)

A (H1N1)

Typing and Sub-typing of Influenza Virus MAN PIG HORSE BIRDH typesH1 H2 H3 H4 H5 H6 H7 H8 H9 H10-H15

N typesN1 N2 N3 N4 N5 N6 N7 N8 N9

1. (antigenic drift)labileRNAproof-reading

2. antigenic shift

Antigenic Drift

Antigenic Shift

: : 1~3:

Emergence of a Novel Swine-Origin Influenza A (H1N1)Virus in HumansNovel Swine-Origin Influenza A (H1N1) Virus Investigation Team*N Engl J Med 2009;361

RESULTSFrom April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. 25% of patients had diarrhea, 36 (9%) required hospitalization. 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously.

N Engl J Med 2009;361

N Engl J Med 2009;361

N Engl J Med 2009;361

CONCLUSIONSA novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred.A N Engl J Med 2009;361

PATIENTS IN OUTBREAKOn March 30, 2009, in San Diego County, California, a 10-year-old boy with asthma (Patient 1) had an onset of fever, cough, and vomiting. On April 1, he was evaluated in an urgent care clinic. He recovered from the illness within approximately 1 week. An influenza A virus that could not be sub-typed was identified from a nasopharyngeal specimen that was collected from Patient 1 as part of a clinical trial to evaluate an experimental diagnostic test. As specified by the study protocol, the specimen was then sent to a reference laboratory for further testing and was found to be positive for influenza A virus but negative for both human H1 and H3 subtypes.N Engl J Med 2009;361

On April 15, the CDC received the clinical specimen and identified a novel influenza A (H1N1) virus of swine origin. A viral isolate was found to contain genes from triple-reassortant swine influenza viruses that were known to circulate among swine herds in North America and two genes encoding the neuraminidase and matrix proteins that were most closely related to genes of viruses obtained from ill pigs in Eurasia, according to results available in GenBank.N Engl J Med 2009;361PATIENTS IN OUTBREAK

Viral Gene Sequences to Assist Update Diagnostics for SwineInfluenza A(H1N1) - GenBank Accession Numbers28 April 2009

The WHO Collaborating Centre for influenza in CDC Atlanta USA has posted the full genome sequences of swine influenza A/California/04/2009 (H1N1) influenza virus on the GenBank sequence database.

To access, go to: http://www.ncbi.nlm.nih.gov/sites/entrez?db=nuccore&itool=toolbar,then enter the accession number as shown below: PB2 gene accession number is: FJ966079 PB1 gene accession number is: FJ966080 PA gene accession number is: FJ966081 HA gene accession number is: FJ966082 NP gene accession number is: FJ966083 NA gene accession number is: FJ966084 M gene accession number is: FJ966085 NS gene accession number is: FJ966086

Science 8 May 2009;342;700-703

Comparison of H1N1 Swine Genotypes in Recent Cases in the United States. N Engl J Med 2009;361

All S-OIVs that have been examined are susceptible to both oseltamivir and zanamivir, two antiviral medications approved for the prevention and treatment of influenza in the United States.N Engl J Med 2009;361

The modes of transmission of influenza viruses in humans, including S-OIV, are not known but are thought to occur mainly through the dissemination of large droplets and possibly small-particle droplet nuclei expelled when an infected person coughs. There is also potential for transmission through contact with fomites that are contaminated with respiratory or gastrointestinal material. Since many patients with S-OIV infection have had diarrhea, the potential for fecal viral shedding and subsequent fecaloral transmission should be considered and investigated.N Engl J Med 2009;361Transmission modes

The incubation period for S-OIV infection appears to range from 2 to 7 days; however, additional information is needed.N Engl J Med 2009;361Incubation period

As of May 5, 2009, the CDC has recommended that health care workers who provide direct care for patients with known or suspected S-OIV infection should observe contact and droplet precautions, including the use of gowns, gloves, eye protection, face masks, and fit-tested, disposable N95 respirators.N95N Engl J Med 2009;361

Patients with confirmed or suspected S-OIV infection should be placed in a single-patient room with the door kept closed, and airborne-infection isolation rooms with negative-pressure handling should be used whenever an aerosol-generating procedure is being performed. Frequent hand washing with soap and water may reduce the risk of infection and transmission.N Engl J Med 2009;361

Science 8 May 2009;342;700-703

MMWR Dispatch Vol.58/April 30, 2009

Persons with mild (uncomplicated) ILI are being advised to stay home for 7 days after symptom onset or 2448 hours after symptom resolution, whichever is longer, and to cover their coughs and sneezes and wash their hands frequently48NYC Department of Health and Mental Hygiene (DOHMH) House QuarantineMMWR Dispatch 2009;58:April 30.

Our estimates suggest that 23,000 (range 6,000-32,000) individuals had been infected in Mexico by late April, giving an estimated case fatality ratio (CFR) of 0.4% (range 0.3% to 1.5%) based on confirmed and suspect deaths reported to that time.Clinical severity appears less than that seen in 1918 but comparable with that seen in 1957.0.4%Science 11 May 2009Case fatality ratio

30 April 2009 -- From today, WHO will refer to the new influenza virus as influenza A (H1N1)

H1N1 Flu (Swine Flu)

Medical staff work near a quarantine area where a man is held for having the H1N1 flu at Taoyuan General Hospital, northern Taiwan, May 20, 2009.

A nurse works inside a quarantine area where a man is held for having the H1N1 flu at Taoyuan General Hospital, northern Taiwan, May 20, 2009. Taiwan on Wednesday reported its first case of H1N1 flu case, a foreign national who entered Taiwan from the U.S. The man is a 52-year-old doctor who arrived by air in Taipei on Tuesday night

World now at the start of 2009 influenza pandemicDr Margaret Chan Director-General of the World Health Organization11 June 2009

Two glycoproteins jut out from the surface of the influenza virus: hemagglutinin (HA) and neuraminidase (NA). Both of these antigenic surface proteins play key roles in viral infection and dissemination.Slide 11Lecture NotesSlide 15Repeated influenza epidemics persist because the type A and type B viruses undergo constant and rapid change due to antigenic drift.Antigenic drift refers to a gradual change in the virus that occurs through a slow series of mutations, substitutions or deletions in amino acids constituting the hemagglutinin or neuraminidase surface antigens. Occurring only after a particular viral strain has become established in humans, antigenic drift represents an adaptation to the development of host antibodies. Newly developed antigenic strains of influenza then prevail for a period of 2 to 5 years, only to be replaced by the next emerging strain.15This new strain can then trigger a new epidemic, since it is now unfamiliar to the antibody repertoire of the population. The development of yet another set of host antibodies eventually protects the populationat the same time it puts pressure on the virus to drift yet again. Ongoing change caused by antigenic drift requires ongoing reformulation of influenza vaccines.16 The World Health Organization and the Centers for Disease Control and Prevention continually track these changes.Lecture NotesIn contrast to the gradual evolution of strains subject to antigenic drift, antigenic shift occurs as soon as a type A influenza virus with a completely novel hemagglutinin or neuraminidase formation moves into humans from other host species. The primary source is birds, certain species of which carry a reservoir of 15 influenza A subtypes.16 These subtypes either genetically reassort themselves with circulating human influenza virus or are transmitted directly into humans, typically via intermediate hosts such as swine.15Antigenic shift of type A influenza viruses occurs less frequently than antigenic drift, but with more dramatic impact. The result of global immunologic susceptibility to a new influenza virus is often pandemic. The influenza pandemics of both 1957 and 1968, for example, were caused by genetic reassortment between human and avian influenza A virus.16To date, influenza type B viruses have not been subject to antigenic shift.15Slide 16Lecture Notes**