Tidbits from the WHO Report
#199


The recently released WHO (World Health Organization) working group report entitled Influenza Research at the Human and Animal Interface (Sept. 21, 2006) is chock full of information, and presents new problems for scientists to consider. It is well worth reading, and can be downloaded in .pdf form from:

http://tinyurl.com/yypcer

The news media has concentrated on the emergence of the Fujian-like strain in china, but has all but ignored some of the other findings. I detailed in my last blog the differences between the severity and presentation of the H5N1 virus, and seasonal flu, and thought I’d briefly cover some of the other highlights of the report. Quotes from the report are in blue text.


Testing Procedures

The technology for diagnosing human H5N1 infections is mature, but many tests are complex, some are liable to error, and some can be performed safely only in biosafety level 3 facilities. A simple, rapid, robust and reliable test, suitable for use in the field or at the patient’s bedside, is urgently needed.


This is of course, an ongoing problem. Many initial tests for the H5N1 virus come back negative, even when the patient is infected with the Avian or Bird Flu virus. In Thailand last month it was revealed one patient had to be tested 9 times before a positive test was returned.


Officially, we have slightly more than 250 human infections. The real number is unknown. Often, once a single negative test is conducted, no further testing is done. If the patient dies, they are quickly buried, and some other cause of death is assigned.


Medical tests have always had some margin of error. The testing for the H5N1 virus seems particularly prone to inaccurate results. In many cases, this is due more to the methods of sample collection, and shipping to the labs, than it is the test. But the bottom line is, we desperately need a reliable test.


Vaccine Prospects

The development of a pandemic vaccine has become more difficult following the divergence of circulating viruses into distinct genetic and antigenic groups. To date, results from clinical trials of candidate pandemic vaccines have not been promising, as these vaccines confer little protection across the different genetic groups.


A vaccine, of course, is the great hope for averting a pandemic. And while we’ve been repeatedly warned not to expect one for at least 6 months after the pandemic begins, many scientists believe it will take 3 to 5 years to produce in significant quantities. Both statements are true, of course. Five years is at least 6 months.


The problem is that the virus continues to mutate, and as it does, vaccines based on an earlier strain loose much of their effectiveness. The human vaccine we now have is based on a 2 year old strain, and there is much doubt as to how much immunity, if any, it would confer. Nevertheless, nations around the world are considering the purchase of this older vaccine. Switzerland has already ordered enough to inoculate their entire country. The UK and the US are considering large orders. The scientists in this working group, however, are not so sure this is wise.


. . . . concern was expressed that national policy decisions about which vaccines to stockpile may be premature, despite the understandable desire of governments to invest now in some means of protecting their populations in the event of an influenza pandemic.


Antiviral Resistance


For amantadine, which is the second-choice antiviral drug, clade 2 viruses are more sensitive than clade 1 viruses. In Indonesia, however, (where clade 2 viruses are circulating) the prevalence of resistance to amantadine is approximately 50%.

. . . .

Resistance to the neuraminidase inhibitor, oseltamivir – presently the first-choice antiviral drug – has been observed in a few patients, and that finding is of concern. Further, surveillance studies also indicate a low prevalence of resistance mutations to oseltamivir in avian isolates, especially in 2005 and 2006.


Oseltamivir (Tamiflu) remains the primary weapon in are pharmacological arsenal against the Avian Flu, but there are concerns that as it is used to treat patients, and more importantly, as a prophylactic measure to stop the spread of an outbreak, resistance to this drug could develop.


Tamiflu is not a vaccine (despite misleading newspaper articles to the contrary), and it is not a cure for Avian Flu. At best, it is hoped that the early administration of Tamiflu may lessen the severity and duration of an H5N1 infection. It is also hoped that when given prophylactically, it can help prevent the spread of the disease.


For now, Tamiflu, and possibly Amantadine, are still considered viable treatment options. How long that will last is anybody’s guess.


Infection Demographics.

Several participants sought explanations for the strong propensity of the H5N1 virus to infect children and young adults, causing severe disease with high case-fatality. In persons older than 50 years, infections were much less common. Exposure history might be one explanation, as children tend to treat birds as pets or play in areas frequented by poultry. That hypothesis was not, however, considered adequate to explain all cases.


One of the big mysteries surrounding Avian Flu: Why does it attack young adults and children in far greater numbers than older adults and the elderly?


Scientists have theories as to why older adults tend to survive infection in greater numbers than younger, healthier patients. Older patients are believed to have a weaker immune system, and therefore mount a less dramatic immune response to infection. But it would follow then that older patients should be infected at a higher rate than young ones, because of their lower immunity.


Perhaps older patients have had enough influenza exposures in their lifetime to pick up some form of immunity. While the H5 virus is a novel virus for humans, most of us have been exposed to the H1N1 virus, and it may be the N1 portion (neuraminidase) portion of the H1N1 virus that provides some immunity. We simply don’t know.


Mortality Rate

And last but not least, the bombshell. The admission that the current high mortality rate of the virus need not necessarily fall to the hoped for single digit numbers that most governments are planning for.


Should the virus improve its transmissibility by acquiring, through a reassortment event, internal human genes, then the lethality of the virus would most likely be reduced. However, should the virus improve its transmissibility through adaptation as a wholly avian virus, then the present high lethality could be maintained during a pandemic.

For years we have been told the virus would have to give up its lethality for ease of transmission. Many flubies, and a few scientists, have disputed that `fact’. Now, for the first time, the WHO admits that the 60% mortality rate is a possibility, even during a pandemic.



While this report leaves many questions unanswered, it is a sobering look at our current state of understanding of the H5N1 threat.

I highly recommend everyone read it.