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Global Avian influenza Panzootic Continues; Some Preparedness Gains Made, but Hospitals Remain Vulnerable

By Eric Toner, M.D., February 6, 2009

New Outbreaks of H5N1 in Birds and Humans

Although “bird flu” has not been featured prominently on the evening news of late, the influenza A/H5N1 panzootic continues. And, as has been true since this global outbreak erupted in Thailand and Vietnam almost exactly 5 years ago, it remains distinctly seasonal in nature. Following a relatively quiescent period from May to October, outbreaks in poultry and people have occurred in a number of countries over the last several months. Since November 2008, poultry outbreaks have occurred in China, Hong Kong, Vietnam, Indonesia, India, Bangladesh, Nepal, Laos, Thailand, and Cambodia. Human cases have occurred in Cambodia, China, Indonesia, Egypt, and Vietnam.1

Since this panzootic began in late 2003, 67 countries on 3 continents have been affected (see Figures 1 and 2, below). There have been 404 human cases of H5N1. With 254 deaths, the case fatality rate is 63%,4 as it has been for 5 years. (Figure 3, below, shows the cumulative human deaths due to H5N1 since 2003).

In most patients, the clinical syndrome remains one of fulminant viral pneumonia. Case studies indicate that oseltamivir is effective in reducing viral load; however, reduction in mortality has been harder to demonstrate. This is likely due to the fact that antiviral therapy has been started late in most patients.5

Figure 1

Graph of countries with H5N1 in animals
Source: HHS3

Figure 2: Bird (red) and human (green) outbreaks of H5N1 since 2003

Map of bird and human H5N1 outbreaks since 2003
Source: Center for Biosecurity

Figure 3

Graph of confirmed H5N1 human deaths
Source: HHS3

H5N1 Has Evolved and Limited Antiviral Resistance Has Emerged

Like all influenza viruses, the H5N1 lineage continues to evolve. There are now 8 recognized clades and many subclades. Different clades predominate in different geographic regions; Clade 2.1 in Indonesia, Clade 2.2 in Northern China, Africa and Europe, and Clade 2.3 in Southern China. Clade 2.3 has replaced Clade 1 in Thailand and Vietnam. Most Clade 1 and Clade 2.1 viruses are resistant to the amantadine; while most Clade 2.2 viruses are sensitive to amantadine.

To date, nearly all H5N1 isolates have been sensitive to oseltamivir. However, there have been several isolated cases of oseltamivir resistance that emerged during oseltamivir treatment, and at least 2 girls in Egypt seem to have been infected with a resistant virus.5 The sudden, as yet unexplained, global emergence of oseltamivir resistance among H1N1 viruses6 has heightened fears of widespread oseltamivir resistance among H5N1 viruses. 

The Pandemic Threat Posed by H5N1 Remains

In summary, the global outbreak of H5N1 has not abated, and the virus appears to be endemic in much of the world. Human cases continue to occur in people exposed to infected birds; however, in some cases the exact nature of the exposure is unclear. Isolated and limited human-to-human transmission has occurred, but there is no evidence of efficient or sustained person-to-person spread.5 While much has been learned about influenza in general and H5N1 in particular in the past few years, researchers have yet to identify the precise changes that would produce a human pathogen with tremendous destructive potential. Nonetheless, the threat posed by H5N1 remains, and the likelihood of an influenza pandemic, whether due to H5N1 or another strain, remains essentially certain.

Progress Has Been Made in Pandemic Preparedness

Pandemic preparedness continues improve in the U.S. and many other countries. The U.S. federal government has stockpiled more than 12 million courses of H5N1 vaccines in the Strategic National Stockpile (SNS).3 While these vaccines will not be a perfect match for a pandemic strain of H5N1 should one evolve, recent evidence suggests that some degree of cross protection is possible.5 Federal and state governments have stockpiled more than 70 million treatment courses of neuraminidase inhibitors, mostly oseltamivir.3 However, concerns about potential oseltamivir resistance have raised questions about both the ultimate utility of these stockpiles and the best strategy for their use. Some influenza experts now believe that multidrug therapy may be needed during a pandemic.

The Healthcare System Remains Especially Vulnerable

Despite much progress in pandemic preparedness, there is still much work to be done. This is especially true of our overtaxed healthcare system. While all states and nearly all hospitals have pandemic plans, surge capacity continues to decline, and staffing shortages continue to worsen. In addition, the number of chronically and severally ill patients being cared for at home or in outpatient centers has dramatically increased in recent years. This is a population that is very likely to need hospitalization during a pandemic, and few plans have addressed this issue. Since hospitals are already overcrowded and understaffed, even a moderate pandemic is likely to severely disrupt our ability to deliver normal medical care. Therefore, continued progress in healthcare preparedness will require serious planning for alternative approaches to medical care, such as the rational use of non-hospital facilities and the ethical, legal, and coordinated adjustment of patient care standards during a pandemic. This kind of planning cannot be accomplished by any individual hospital working alone and will require close collaboration among healthcare organizations, public health agencies, and other community-based groups.


  1. WHO Avian influenza website. H5N1 Avian Influenza: Timeline of Major Events. Accessed February 4, 2009.

  2. Department of Health and Human Services, Pandemic Planning Update VI. Accessed February 4, 2009.

  3. WHO Avian influenza website. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO.
    . Accessed February 4, 2009.

  4. WHO Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza A (H5N1) virus infection in humans. N Eng J Med 2008;358(3):261-73.

  5. CDC Health Alert Network, December 19, 2008. CDC Issues Interim Recommendations for the Use of Influenza Antiviral Medications in the Setting of Oseltamivir Resistance among Circulating Influenza A (H1N1) Viruses, 2008-09 Influenza Season. Accessed February 5, 2009.