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Asymptomatic H5N1 Avian Influenza Infections

Amesh A. Adalja, MD, FACP, FACEP, May 1, 2015

With the continued spread of avian influenza viruses to humans, it is vitally important to understand the pattern of human infections. Spillover of avian influenza viruses, such as H5N1, is generally thought to be a rare event with few to no asymptomatic infections—a major difference from seasonal influenza viruses, which cause a large proportion of asymptomatic infections. To this end, my colleagues and I conducted a review of H5N1 seroprevalence studies, finding little evidence of such infections from well-conducted studies.1

Filling this major gap, Gomaa et al from St. Jude’s Children’s Research Hospital conducted a seroprevalence study of H5N1 and H9N2 influenza viruses, the results of which were published in the Journal of Infectious Diseases.2


Rural Egyptian Study Site

In Egypt, Gomaa et al enrolled 750 poultry-exposed individuals at rural sites and 250 unexposed individuals from Cairo, who served as controls. The study involved micro-neutralization assays followed by horse RBC hemagglutination inhibition assays. Those that tested positive were further tested for cross-reactivity to seasonal human influenza viruses. A titer level of 80 or higher was considered positive. The study involved baseline measurements as well as 2 annual follow-up measurements.


2.1% Positive to H5N1

The results of the serological study revealed, at baseline, that 2.1% of exposed individuals had evidence of H5N1 infection, while 0% of controls were positive. At follow-up, controls remained negative, while the prevalence in the exposed group fell. H9N2 positivity was not detected in either group at baseline but rose to 7.5% by the first follow-up measurement.

Those who were seropositive for H5N1 were all backyard poultry growers with clustering within households (not all were blood relatives). Multivariate analysis revealed chronic lung disease as a risk factor for seropositivity.


Good Study Design Key

Gomaa et al deserve much credit for conducting this important and well-designed study. By using control groups and strict criteria for positivity, 2 important conclusions can be drawn from their work: (1) H5N1 asymptomatic infections are indeed much more rare than what is seen with seasonal variants, and (2) impaired pulmonary function is a risk factor for such infection.

With a symptomatic case fatality rate of approximately 59%, it will be important to follow up these results with further studies of those who were asymptomatically infected to identify distinguishing genetic characteristics of this group.3 Such findings will help us to understand the pathophysiology of this virus and possibly provide clues to its future spread.



  1. Toner ES, Adalja AA, Nuzzo JB, Inglesby TV, Henderson DA, Burke DS. Assessment of serosurveys for H5N1. Clin Infect Dis 2013;56(9):1206-1212.
  2. Gomaa MR, Kayed AS, Elabd MA, et al. Avian influenza A(H5N1) and A(H9N2) seroprevalence and risk factors for infection among Egyptians: a prospective, controlled seroepidemiological study. J Infect Dis 2015;211(9):1399-1407.
  3. Morens DM, Taubenberger JK. How low is the risk of influenza (H5N1) infection? J Infect Dis 2015;211(9):1364-1366.