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H5N1 Remains a Pandemic Threat

By Eric Toner, MD, June 5, 2010

Since late April 2009, the world’s attention has been focused on the H1N1 pandemic, which, fortunately, has been less severe than feared. The 2009 H1N1 influenza pandemic has also been much less severe than the H5N1 pandemic scenario that drove pandemic planning for the past 5 years. As a result, some have questioned whether the pandemic threat was exaggerated1 while others are relieved that the pandemic was milder than expected. Before we breathe too easily, though, it is worth noting that the original threat of an H5N1 influenza pandemic has not gone away, even as it has been overshadowed by the actual, albeit mild, 2009 pandemic.

471 Human Cases Since 2003

Since 2003, WHO has confirmed 471 human cases of H5N1 infection, from 15 countries,2 with 282 (60%) deaths.3 To date, the H5N1 panzootic (global outbreak in animals) has caused disease in birds in nearly all of the countries of Asia and Europe and in large parts of Africa.4 Outbreaks among poultry5 and wild birds6 continue to occur in many countries, as do sporadic human cases, especially in Indonesia and Egypt, and the virus remains a pandemic threat to humans.

Number of Human Cases Surges in Egypt and Remains Steady in Indonesia

On January 28, 2009, the World Health Organization (WHO) announced 4 new human cases of H5N1 infection in Egypt.7 The cases are not epidemiologically linked, and all 4 patients had a history of contact with poultry. This brings the total number of laboratory-confirmed human cases in Egypt to 94. Of these, 27 (29%) have been fatal.

While human cases of the disease have been controlled in most of the affected countries, the number of cases in Egypt has increased—43 of the 94 cases in Egypt (46%) have occurred in the last 13 months.8 In contrast, the number of confirmed cases in Indonesia has remained steady at approximately 20 cases per year for the last 4 years.9 China, where the first human cases occurred, has reported approximately 5 cases per year for the last 3 years, and Vietnam, which had been the epicenter of the outbreak in 2004 and 2005, reported no human cases in 2009.

Case Fatality Ratios in Egypt and Indonesia Differ Widely

In 2009, 19 of 20 (95%) of the cases reported in Indonesia were fatal, while in Egypt only 4 of 39 (10%) were. Several possible explanations may account for this difference. It may be an artifact of surveillance if, for instance, only the sickest patients in Indonesia were tested for H5N1 influenza, while those with milder disease went unrecognized. The difference may reflect disparities in treatment and access to care—in Egypt, survivors received medical assistance, on average, in less than 2 days following symptom onset, while those who died did not access care for 6 days.10 There also could be variances in the lethality of the virus. The H5N1 strain circulating in Egypt belongs to clade 2.2, while the strain circulating in Indonesia belongs to clade 2.1.11 Although specimens from the 2 countries have not been reported to show the genetic differences known to be markers of pathogenicity, much is still not known about the factors that determine lethality.

The H5N1 Threat Is Not Diminished

As has been evident with the 2009 H1N1 influenza pandemic, no one can predict where and when a pandemic will arise. In the case of the H5N1 virus, no one can predict whether or when it will become efficiently transmissible from person to person. But the likelihood of that occurrence has not changed in the last year. Given that, it is important to attend to the many persistent vulnerabilities that the experience with the 2009 pandemic brought into sharp focus. They include the time needed to produce and deploy a novel vaccine, the limitations of disease containment strategies, and the inadequacies of medical surge capacity. Rather than inducing complacency or even too strong a sense of relief, the H1N1 experience instead should remind us of the risk posed by novel influenza strains and spur renewed efforts in pandemic preparedness.


  1. Stein R. WHO official denies exaggeration about dangers of swine flu pandemic. Washington Post. January 15, 2010.
    . Accessed February 2, 2010.
  2. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. World Health Organization Website. Accessed February 2, 2010.
  3. Ibid.
  4. H5N1 avian influenza: Timeline of major events 4 January 2010. World Health Organization Website. Accessed February 2, 2010.
  5. Highly pathogenic avian influenza, Vietnam. OIE Website. Accessed February 2, 2010.
  6. Sharshov K, Silko N, Sousloparov I, et al. Avian influenza (H5N1) outbreak among wild birds, Russia, 2009. Emerging Infectious Diseases. 2010;16 (2). Accessed February 2, 2010.
  7. Avian influenza - situation in Egypt - update 27. World Health Organization Website. Accessed February 2, 2010.
  8. Ibid.
  9. Ibid.
  10. Fasina FO, Ajibade AA. Avian influenza A(H5N1) in humans: lessons from Egypt. Eurosurveillance 2010; 15 (4), 28 January 2010 Surveillance and outbreak reports. Accessed February 2, 2010.
  11. Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines. World Health Organization Website. Accessed February 2, 2010.