Highly pathogenic variant of avian influenza A of the subtype H5N1 is here to stay, at least in the world’s poultry population. While it’s around it continues to cause sporadic but deadly human infections, some 369 of them of whom 234 have died (official WHO figures as of 28 February 2008). So this virus can infect humans and make them seriously or fatally ill. There is truly massive exposure because people live in close contact with infected domestic poultry in many countries. And the human population has not seen this subtype of virus before so there is little natural immunity. All that’s necessary for a really catastrophic pandemic is for this virulent virus to move easily from poultry to humans and then from human to human. These may require different changes in the virus but since it can already move into humans on rare occasions, the human to human feature is the crucial one.

However if it does acquire the ability to move into humans more easily from birds, we could have a lot of bird to human cases, given the exposure, and each of those cases presents the opportunity for the emergence of a human to human transmissible agent because the virus mutates quickly, even in the short span of time it infects a single person. After some days of infection the virus the patient has often changed genetically. So the question of bird to human transmission is of real importance. Lots of poultry workers and cullers of infected poultry flocks are in close contact with diseased birds. Maybe they do get infected only mildly so transmission from birds to humans has been overlooked. As we have noted often here, this would mean the observed case fatality ratio (CFR) is lower than the current dismal 60% plus. Now a new study has been published looking for evidence of infection in poultry farmers in five provinces in Thailand that had large H5N1 outbreaks in late 2003 and 2004. The news is good and bad.

First the good news:

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. From January through March 2004, 12 cases, 8 fatal, in humans resulted from infection with influenza virus (H5N1) in Thailand. In response, the Thailand Department of Livestock Development enlisted government employees to conduct a large-scale cull of poultry in the affected provinces (www.dld.go.th/home/bird_flu/emergency.html). This effort began on January 23, 2004, and resulted in the slaughter of >21 million birds (www.fao.org/ag/againfo/subjects/en/health/diseases-cards/avian_bg.html). Poultry farmers and persons involved in culling are at increased risk for infection. In May 2004, we conducted a seroepidemiologic investigation of Thai poultry farmers to determine the frequency of avian influenza (H5N1) transmission to humans. (Soawapak Hinjoy et al., Emerging Infectious Diseases [cites omitted])

The study involved taking blood from 322 farmers and cullers (92% response rate) and testing to see if there was evidence of past infection with H5N1. The test was to look for specific antibodies to the H5N1 virus. This was definitely an exposed and at risk population (age 5 to 50 years old). 58% of the subjects reported handling sick or dying birds, 33% worked in culling of well birds in outbreak areas while 9% had contact with apparently well birds during routine farming. The level of antibody titer for presumptive infection is set at 80 and no subject had anti-H5N1 antibody levels that high. Seven had antibody levels that were detectable but much lower. They could have been the result of cross-reactivity with other flu viruses, the failure of mild infection to produce high enough levels, the disappearance of antibody levels soon after infection, or an insufficiently sensitive antibody test. In any event, the good news seems to be that there was no evidence of bird to human transmission in a clearly at risk occupationally exposed population.

That’s also the bad news. It means that the hope against hope that there is a lot of mild and inapparent infection with this virus that would mitigate the extraordinary case fatality ratio once again does not seem to have panned out, similar to studies in Cambodia and Nigeria.

As far as we can tell, infection with this virus is unusually virulent. Unlike many infectious diseases, really serious cases are not the tip of the iceberg. They are the whole iceberg. So far it is a small one. If it gets really big, spaceship Earth is going to look more like Titanic Earth.