Thursday, February 28, 2008

The Thailand Serological Study


# 1727




One of the ongoing debates surrounding the H5N1 virus centers on the CFR, or case fatality ratio, among reported cases.  More than 60% of known cases have succumbed to the virus.


For years some scientists have suggested that there must be many mild, unreported cases of H5N1 infection, and that we only detect the sickest of the sick.   The true CFR would be much lower, if that were true.  It would also indicate that the virus is more easily transmitted than we believe, as well.


While there was precious little science to support the idea, it wasn't an  unreasonable assumption.   We've never seen an influenza virus with anywhere near a 60% mortality rate.  The idea that we were only seeing the most serious cases made some sense.


In order to determine the actual incidence of human infection, the gold standard is serological testing for H5N1 specific antibodies.  These antibodies show up 2 to 4 weeks post exposure, and should remain detectable for years.



The March, 2008 issue of The Journal of Emerging Infectious Diseases is carrying the following study, conducted in Thailand in 2004, where poultry workers in areas where bird flu outbreaks had occurred were tested for antibodies to the virus.



Hinjoy S, Puthavathana P, Laosiritaworn Y, Limpakarnjanarat K, Pooruk P, Chuxnum T, et al. Low frequency of infection with avian influenza virus (H5N1) among poultry farmers, Thailand, 2004. Emerg Infect Dis [serial on the Internet]. 2008 March [date cited]. 




In Thai provinces where avian influenza outbreaks in poultry had been confirmed in the preceding 6 months, serum from 322 poultry farmers was tested for antibodies to avian influenza virus subtype H5N1 by microneutralization assay.


No study participant met the World Health Organization serologic criteria for confirmed infection.



During late 2003 and 2004, highly pathogenic avian influenza virus (H5N1) caused extensive outbreaks and die-offs in poultry flocks in Thailand and several other countries in Southeast Asia (1). From January through March 2004, 12 cases, 8 fatal, in humans resulted from infection with influenza virus (H5N1) in Thailand (2). In response, the Thailand Department of Livestock Development enlisted government employees to conduct a large-scale cull of poultry in the affected provinces

( This effort began on January 23, 2004, and resulted in the slaughter of >21 million birds



Poultry farmers and persons involved in culling are at increased risk for infection (3). In May 2004, we conducted a seroepidemiologic investigation of Thai poultry farmers to determine the frequency of avian influenza (H5N1) transmission to humans.



Of the 322 people tested, they found that "no poultry workers had microneutralization titers >80, whereas 7 (2%) had lower titers that did not meet the WHO definition for seropositivity".


The author's conclusions are that "growing evidence indicates that this virus is not easily transmitted from poultry to humans and that mild or asymptomatic infections in humans are not common"



Does this definitively answer the question about the true number of human H5N1 infections and the CFR of the H5N1 virus?



Well, not exactly.  


This study gives us a snapshot of the situation 4 years ago, when this research was conducted.  The H5N1 virus circulating today, and in other regions of the world, may have different qualities than the one circulating in Thailand in 2004.


There are also questions about the sensitivity of the serological testing.  The Micro-NT assay is a highly specific and strain sensitive test and probably would not have picked up another strain of the virus. 


It may not conclusively answer the question, but it does strongly suggest that human H5N1 infections are probably rare, and that we aren't missing a lot of mild cases.


More research of this kind is obviously needed.


Why it has taken nearly 4 years since the study was conducted for it to be published, however, mystifies me.





(A hat top to Anne on Flutrackers for posting this study)