The Fatal Strain (52 page)

68 this disquieting pattern:
“Epidemiology of WHO-Confirmed Human Cases of Avian Influenza A (H5N1) Infection,”
Weekly Epidemiological Record
81, no. 26 (June 30, 2006): 249-57; and “Update: WHO-Confirmed Human Cases of Avian Influenza A (H5N1) Infection, 25 November 2003-24 November 2006,”
Weekly Epidemiological Record
, 82, no. 6 (Feb. 9, 2007): 41-47.

68 “most important unsolved mystery”:
David M. Morens and Anthony S. Fauci, “The 1918 Influenza Pandemic: Insights for the 21st Century,”
Journal of Infectious Diseases
195 (2007): 1018-28.

69 tremendous cytokine storms:
See, for example, John C. Kash, et al., “Genomic Analysis of Increased Host Immune and Cell Death Responses Induced by 1918 Influenza Virus,”
Nature
443 (Oct. 5, 2006): 578-81; Darwyn Kobasa et al., “Enhanced Virulence of Influenza A Viruses with the Hemagglutinin of the 1918 Pandemic Virus,”
Nature
431, no. 7009 (Oct. 7, 2004): 703-7; and Darwyn Kobasa et al., “Aberrant Innate Immune Response in Lethal Infection of Ma caques with the 1918 Influenza Virus,”
Nature
445 (Jan. 18, 2007): 319-23. A study in 2008 comparing the immune response to H5N1 and the 1918 virus in mice showed “considerable similarities” but found that the H5N1 strain actually elicited significantly higher levels of cytokines and macrophages. See Lucy A. Perrone et al., “H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice,”
PLoS Pathogens
4, no. 8 (2008): e1000115.

69 “kissing cousin”:
Remarks at Business Preparedness for Pandemic Influenza, Second Annual Summit, University of Minnesota Center for Infectious Disease Research and Policy, Feb. 5, 2007.

69 a wholly avian virus:
Jeffrey K. Taubenberger et al., “Characterization of the 1918 Influenza Virus Polymerase Genes,”
Nature
437 (Oct. 6, 2005): 889-93; and Terrence M. Tumpey et al., “Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus,”
Science
310, no. 5745 (Oct. 7, 2005): 77-80.

69 “a number of the same changes”:
Jeffrey K. Taubenberger et al., “Characterization of the 1918 Influenza Virus Polymerase Genes,”
Nature
437 (Oct. 6, 2005): 889-93.

69 more like the Spanish flu strain:
For example, see James Stevens et al., “Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus,”
Science
312, no. 5772 (Apr. 21, 2006): 404-10.

69 A series of studies:
H. Chen et al., “The Evolution of H5N1 Influenza Viruses in Ducks in Southern China,”
PNAS
101, no. 28 (July 13, 2004): 10452-57; Taronna R. Maines et al., “Avian Influenza (H5N1) Viruses Isolated from Humans in Asia in 2004 Exhibit Increased Virulence in Mammals,”
Journal of Virology
79, no. 18 (Sept. 2005): 11788-11800; Hui-Ling Yen et al., “Virulence May Determine the Necessary Duration and Dosage of Oseltamivir Treatment for Highly Pathogenic A/Vietnam/1203/04 Influenza Virus in Mice,”
Journal of Infectious Diseases
192 (2005): 665-72; and Adrianus C. M. Boon et al., “Role of Terrestrial
Wild Birds in Ecology of Influenza A Virus (H5N1),”
Emerging Infectious Diseases
13, no. 11 (Nov. 2007): 1720-24.

69 “a process of rapid evolution”:
“Mouse Studies of Oseltamivir Show Promise Against H5N1 Influenza Virus,”
NIH News
, July 18, 2005.

69 already become more ferocious:
Carole R. Baskin et al., “Early and Sustained Innate Immune Response Defines Pathology and Death in Nonhuman Primates Infected by Highly Pathogenic Influenza Virus,”
PNAS
, Published online before print February 13, 2009, doi 10.1073/pnas.0813234106.

70 If the virus continued to develop:
J. S. Malik Peiris, “H5N1 Pathogenesis in Humans: An Update,” Power Point presentation to the WHO working group, Sept. 21-22, 2006.

70 though later reported :
WHO, “Influenza Research at the Human and Animal Interface: Report of a WHO Working Group,” Geneva, September 21-22, 2006.

70 62 million:
Christopher J. L. Murray et al., “Estimation of Potential Global Pandemic Influenza Mortality on the Basis of Vital Registry Data from the 1918- 1920 Pandemic: A Quantitative Analysis,”
Lancet
368, no. 9554 (Dec. 23, 2006): 2211-18.

70 $3.13 trillion during the first year:
The figures for severe, mild, and moderate pandemics are based on numbers included in Andrew Burns, Dominique van der Mensbrugghe, and Hans Timmer, “Evaluating the Economic Consequences of Avian Influenza,” updated in September 2008. An earlier version of this report, which had calculated the costs using a lower figure for global GDP, put the toll of a severe pandemic at $2.38 trillion. The study was originally published in a slightly different form in the World Bank’s June 2006 edition of
Global Development Finance.
For further discussion, see Milan Brahmbatt, “Economic Impacts of Avian Influenza Propagation,” speech at the First International Conference on Avian Influenza in Humans, June 29, 2006.

71 “It’s a possibility in this case”:
Jane Moir, “Cousins of Child Victim in Flu Alert: Human Transmission Suspected,”
South China Morning Post,
Dec. 17, 1997.

71 “They live together at Grandma’s”:
Edward A. Gargan, “Chicken-Borne Flu Virus Puts Hong Kong on Alert,”
New York Times,
Dec. 17, 1997.

71 “working at breakneck pace”:
Jane Moir, “Cousins of Child Victim in Flu Alert: Human Transmission Suspected,”
South China Morning Post,
Dec. 17, 1997.

71 barely three hundred square feet:
Rhonda Lam Wan, “Bird Flu Cousins’ Flat Behind Pile of Rubbish,”
South China Morning Post,
Dec. 19, 1997.

71 they were rebuffed:
Ibid.

72 a city under siege:
See, for example, the following accounts, all from the
South China Morning Post:
Rhonda Lam Wan and Billy Wong Wai-Yuk, “Doctors Scramble for Special Drug,” Dec. 13, 1997; Andrea Li and Alex Lo, “Fears Force Changes to Menus,” Dec. 16, 1997; Stella Lee, “18 Private Doctors to Join Bird Flu Probe,” Dec. 18, 1997; Rhonda Lam Wan, “Flood of Requests Prompts Promise of A-Strain Testing,” Dec. 20, 1997; and Ng Kang-Chung, “Rush for Bird Flu Tests As Seven More Suspected Victims Found,” Dec. 26, 1997.

73 Fukuda had never before missed:
Patricia Guthrie, “Focus on Hong Kong Flu,”
Atlanta Journal and Constitution,
Dec. 25, 1997.

73 “will stop or spread”:
“Hong Kong Tests Show Human-to-Human Transmission of Bird Flu Difficult,” Agence France Presse, Dec. 27, 1997.

73 “measures are sufficient”:
Keith B. Richburg, “Hong Kong Killing All Chickens in Fight Against ‘Bird Flu’ Virus,”
Washington Post,
Dec. 29, 1997.

73 more bad news:
For discussion of the poultry outbreaks in late December 1997, see L. D. Sims et al., “Avian Influenza in Hong Kong 1997-2002,”
Avian Diseases
47, no. s3 (2003): 832-38; and Kennedy F. Shortridge, “Poultry and the Influenza H5N1 Outbreak in Hong Kong, 1997: Abridged Chronology and Virus Isolation,”
Vaccine
17 (1999): s26-s29.

75 would kill every last chicken:
For an overview of the 1997 poultry outbreaks and government response, see Kennedy F. Shortridge et al., “Interspecies Transmission of Influenza Viruses: H5N1 Virus and a Hong Kong SAR Perspective,”
Veterinary Microbiology
74 (2000): 141-47.

75 The government pressed:
Robin Ajello and Catherine Shepherd, “The Flu Fighters,”
Asiaweek,
Jan. 2008.

75 bloody chaos:
Billy Wong Wai-Yuk, “Tears of Anger, Rivers of Blood,”
South China Morning Post,
Dec. 30, 1997; Stella Lee, “Slaughter Held Up by Inexperience,”
South China Morning Post,
Dec. 31, 1997; Keith B. Richburg, “Chicken Sightings Frighten Hong Kong,
Washington Post,
Jan. 3, 1998; and Keith B. Richburg, “Hong Kong Faulted on Handling of ‘Bird Flu’ Crisis,
Washington Post,
Jan. 4, 1998.

76 On the third day of the slaughter:
“Tung Handling of Flu Crisis Attacked,”
South China Morning Post,
Jan. 1, 1998.

76 In a front-page editorial:
“Only Time Will Prove Wisdom of Dramatic Move,”
South China Morning Post,
Dec. 29, 1997.

76 the “botched” operation:
“Taking Charge,”
South China Morning Post,
Jan. 3, 1998.

76 nearly 350 chickens:
Kennedy F. Shortridge, “Poultry and the Influenza H5N1 Outbreak in Hong Kong, 1997: Abridged Chronology and Virus Isolation,”
Vaccine
17 (1999): s26-s29.

76 more widespread than expected:
Kennedy F. Shortridge et al., “Characterization of Avian H5N1 Influenza Viruses from Poultry in Hong Kong,”
Virology
252, no. 2 (Dec. 20, 1998): 331-42.

77 a pandemic had been averted:
Kennedy F. Shortridge, J. S. Malik Peiris, and Yi Guan, “The Next Influenza Pandemic: Lessons from Hong Kong,”
Journal of Applied Microbiology
94 (2003): 70S-79S.

77 its most successful:
Several researchers have held up Hong Kong as the model. See, for example, Robert Webster and Diane Hulse, “Controlling Avian Flu at the Source,”
Nature
435 (May 26, 2005): 415-16. Yet the model may be hard to apply elsewhere. See Les Sims, “Achievements, Issues and Options on Strategies for HPAI Control and Prevention,” Background Paper at the Technical Meeting on Highly Pathogenic Avian Influenza and Human H5N1 Infection, June 27-29, 2007, Rome.

78 Their main exposure:
Anthony W. Mounts et al., “Case-Control Study of Risk Factors for Avian Influenza A (H5N1) Disease, Hong Kong, 1997,”
Journal of Infectious Diseases
180 (1999): 505-8.

78 would resurface in 2001:
On this outbreak and Hong Kong’s response, see Yi Guan et al., “Emergence of Multiple Genotypes of H5N1 Avian Influenza Viruses in Hong Kong SAR,”
PNAS
99, no. 13 (June 25, 2002): 8950-55; and N. Y. Kung et al., “The Impact of a Monthly Rest Day on Avian Influenza Virus Isolation Rates in Retail Live Poultry Markets in Hong Kong,”
Avian Diseases
47 (2003): 1037-41.

78 the virus struck yet again:
For an overview of the poultry outbreaks in 2001- 2002, see L. D. Sims et al., “Avian Influenza in Hong Kong 1997-2002,”
Avian Diseases
47, no. s3: 832-38; L. D. Sims et al., “An Update on Avian Influenza in Hong Kong 2002,”
Avian Diseases
47 (2003): 1083-86; and Kennedy F.
Shortridge, J. S. Malik Peiris, and Yi Guan, “The Next Influenza Pandemic: Lessons from Hong Kong,”
Journal of Applied Microbiology
94 (2003): 70S-79S.

81 “Influenza has been an epidemic illness”:
Prasert Thongcharoen,
Influenza
(Bangkok: Mahidol University, 1998).

82 blame the spiraling death toll on the weather:
Newin Chidchob, deputy agriculture minister, is quoted in “Thailand Declared Free of Bird Flu,”
Nation
(Thailand), Jan. 15, 2004. Yukol Limlamthong, director-general of the Livestock Department, is quoted in “Bird Flu: Govt to Sue over ‘False Report,’”
Nation
(Thailand), Jan. 17, 2004.

85 researchers had confirmed:
Arthit Khwankhom and Sirinart Sirisunthorn, “Govt Ignored Chula Warning,”
Nation
(Thailand), Jan. 30, 2004.

86 “We were fighting”:
“What Happened When the H5N1 Virus Visited Thailand,” lecture at the Asia Medical Forum, Lancet 2006, Singapore, May 4, 2006.

87 “Irresponsible media”:
Tini Tran, “WHO Says SARS Helped Asia Prepare for Bird Flu; Poultry Culls Continue,” Associated Press, Jan. 16, 2004.

87 “There’s absolutely no evidence”:
Alisa Tang, “Thai Cabinet Seeks to Boost Confidence of Chicken-Wary Public,” Associated Press, Jan. 19, 2004.

88 a confidential tip:
Internal WHO report, Jan. 20, 2004.

90 broader resurgence of infectious disease:
For an excellent exploration of what was optimistically called the Health Transition and subsequent setbacks, see Laurie Garrett,
The Coming Plague
(Penguin: New York, 1995).

91 Storm clouds were gathering:
See, for example, David L. Heymann and Guenael R. Rodier, “Hot Spots in a Wired World: WHO Surveillance of Emerging and Re-emerging Infectious Diseases.”

91 WHO’s rapid response:
David L. Heymann and Guenael Rodier, “Global Surveillance, National Surveillance and SARS: Commentary,”
Emerging Infectious Diseases
10, No. 2 (Feb. 1, 2004); and David L. Heymann, Mary Kay Kindhauser, and Guenael Rodier, “Coordinating the Global Response,” in
SARS: How a Global Epidemic Was Stopped
(Manila: WHO Western Pacific Regional Office, 2006).

93 Subsequent study:
Kulkanya Chokephaibulkit et al., “A Child with Avian Influenza A (H5N1) Infection,”
Pediatric Infectious Disease Journal
24, no. 2 (Feb. 2005): 162-66; and Mongkol Uipprasertkul et al., “Influenza A H5N1 Replication Sites in Humans,”
Emerging Infectious Diseases
11, no. 7 (July 2005): 1036-41.

94 followed right behind:
For a synopsis of Thailand’s experience with avian flu in 2004, see Thanawat Tiensin, et al., “Highly Pathogenic Avian Influenza H5N1, Thailand, 2004,”
Emerging Infectious Diseases
11, no. 11 (Nov. 2005): 1664-72.

95 “It’s not a big deal”:
Sutin Wannabovorn, “Thailand Confirms Two Human Cases of Bird Flu as Infection spreads Through Asia,” Associated Press, Jan 23, 2004.

97 teams were running short:
Tipawayan Kwankhauw, “Anger and Tears as Thailand’s Farmers Cull Millions of Chickens,” Agence France Presse, Jan. 25, 2004.

100 mixing vessel:
See, for instance, S. Scholtissek et al., “The Nucleoprotein as a Possible Major Factor in Determining Host Specificity of Influenza H3N2 Viruses,”
Virology
147 (1985) 287-94; H. Kida et al., “Potential for Transmission of Avian Influenza Viruses to Pigs,”
Journal of General Virology
75, no. 9 (Sept. 1994): 2183-88; and Ian H. Brown, “The Epidemiology and Evolution of Influenza Viruses in Pigs,”
Veterinary Microbiology
74, nos. 1-2 (May 22, 2000): 29-46.

101 “Are the doctor and the media”:
“PM Derides Doctor over Pig Comments,”
Nation
(Thailand), Jan. 28, 2004.