February 23, 2012 — The World Health Organization's H5N1 diagnostic criteria only identify the sickest patients, which has resulted in alarming fatality rates that are inaccurate, according to an article published online February 23 in Science by researchers at Mt. Sinai School of Medicine in New York City.
As of December 2011, the WHO has documented 573 cases of human H5N1 infection since 2003 in 15 countries, 58.6% of which have been fatal. Lead author Taia T. Wang, PhD, and colleagues believe the actual fatality rate is much lower, so they conducted 2 different meta-analyses of 27 studies that examined the seroprevalence of H5N1 influenza virus in humans. Of those studies, 19 used modified WHO diagnostic guidelines or presented the data in a way that enabled WHO criteria to be applied. WHO guidelines require the patient to have a documented respiratory illness and fever, known H5N1 virus exposure within the previous 7 days, and molecular confirmation of H5 virus infection conducted in a laboratory.
The second meta-analysis was conducted on 10 studies that used the authors' diagnostic criteria. Two of the studies used both WHO guidelines and other criteria.
Most participants reported no recent respiratory illness of fever. Participants with confirmed H5N1 diagnosis were excluded from the study so seroprevalence in patients without WHO-documented infection could be analyzed. Patients exposed to poultry or humans with suspected or confirmed H5N1 infection were not excluded from the study.
A total of 7304 study participants were involved in the primary analysis that used WHO criteria. Seropositivity rates ranged from 0% to 5.3% in all except 1 study. That study found 11.7% seropositivity in people living with infected individuals. The overall seropositivity rate in this group was 1.2% (95% confidence interval, 0.6% - 2.1%).
The second meta-analysis included 6774 individuals and found a seropositivity rate of 1.9% (95% confidence interval, 0.5% - 3.4%).
The human H5N1 infection rate was approximately 1% to 2% when the investigators used either criterion.
The researchers also conducted subanalyses of individuals who were poultry workers, using the WHO criteria (n = 2729), and found a seropositivity rate of about 1.4%. When they analyzed reports from the 1997 Hong Kong outbreak separately, the seropositivity rate was 3.2%. Studies using WHO guidelines that were conducted after 1997 indicate an overall seropositivity rate of about 0.5%.
These studies "show that avian H5N1 viruses can cause a rate of mild or subclinical infections in humans that is not currently accounted for and thus, the true fatality rate for H5N1 influenza viruses is likely to be less than the frequently reported rate of more than 50%," write the authors.
"Although it is not possible to determine an accurate fatality rate for H5N1 infections based on the data presented here, if one assumes a 1-2% infection rate in exposed populations, this would likely translate into millions of people who have been infected, worldwide. It is possible that deaths caused by H5N1 infection, as documented by the WHO, are also underestimated," they write.
The authors point out that many H5N1 infections occur in areas where healthcare is too expensive or too difficult to be obtained by infected individuals, making these cases unlikely to be identified by the WHO.
The authors explain that larger, standardized studies are needed to accurately calculate the true number of human H5N1 infections that have occurred, as well as to determine fatality rates that are not based only on hospitalized patients.
This study was partially supported by the National Institutes of Health. Dr. Wang was supported by the National Institutes of Health and a Mount Sinai Medical Scientists Training Grant. The other authors have disclosed no relevant financial relationships.
Science. Published online February 23, 2012. Abstract
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