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NIAID Leads International Collaborative Research Effort Toward Pandemic Influenza Preparedness


Anthony S. Fauci, MD
Director
National Institute of Allergy and Infectious Diseases

Pandemic influenza is a global health threat. International cooperation in research is thus a key component of pandemic preparedness..." (Source: "Pandemic Influenza: The Road to Preparedness", testimony before the Committee on Appropriations Subcommittee on Foreign Operations, Export Financing, and Related Programs, United States House of Representatives, March 2, 2006)

Within the National Institutes of Health (NIH), the National Institute of Allergy and Infectious Diseases (NIAID) is tasked with research to prevent, detect, and treat infectious diseases such as influenza. During the past five years, NIAID influenza research funding grew from $16.8 million to $196.3 million in fiscal year 2006. The NIAID influenza research effort encompasses the spectrum from basic research to clinical trials, leading to the discovery and implementation of influenza vaccines, therapeutics, and diagnostics. Like research on other diseases, influenza research progress hinges upon collaboration and shared resources.

Seasonal influenza presents a fairly predictable annual occurrence. The World Health Organization (WHO) estimates that influenza epidemics result in 250,000-500,000 deaths globally per year. In contrast, the impact of pandemic influenza, an unpredictable but historically proven threat, can range from fairly mild (1968) to catastrophic (1918).

Table 1:


An influenza virus that causes illness in humans, to which the majority of the human population has little or no immunity, and that is easily transmissible among humans, constitutes a pandemic virus. Of the existing potential pandemic viruses, the highly pathogenic avian influenza (HPAI) H5N1 virus that has become endemic in poultry in Southeast Asia, Eastern Europe, and several countries in Africa presents a source of concern to scientists and health officials around the world.

Figure 1:

On the rare occasions that humans have been infected, the H5N1 influenza virus has demonstrated an ability to cause severe illness and death, and since people lack antibodies to this subtype of influenza virus, scientists worry that if the H5N1 influenza virus acquired the characteristic of sustainable human-to-human transmission, it could cause a pandemic. Currently there is no commercially available vaccine against H5N1 and little is known about how effective available antiviral drugs are in treating H5N1 infections. Considerable efforts are underway at NIAID both to support vaccine development and to evaluate antiviral drugs in the prevention and treatment of H5N1 infection.

Not surprisingly, seasonal influenza preparedness and prevention are inherently linked to pandemic influenza preparedness and prevention. Both seasonal influenza research and pandemic influenza research depend on collaboration, especially at the international level. NIAID participates in several international influenza research efforts toward pandemic preparedness. Several international partners identified the need for a clinical research network focused on therapeutics. Thus, in 2005 the NIAID Division of Clinical Research with multilateral partners established the Southeast Asia (SEA) Influenza Clinical Research Network to advance the scientific knowledge and management of human influenza through integrated, collaborative clinical research. Partners include hospitals and institutions in Vietnam, Indonesia, Thailand, the United Kingdom, and the United States.

Figure 2:

The Network is committed to building independent research capacity within the SEA countries involved. NIAID and the Wellcome Trust provide financial support. Initial clinical studies will evaluate appropriate dosage levels of the influenza antiviral, oseltamivir, in patients with severe seasonal or avian influenza. Pharmacokinetics studies of oseltamivir in Asian subjects began in fall 2006 at the Network Pharmacokinetics Unit at Mahidol University. Future studies of intravenous and combination antivirals are in the planning stages.