The years 2003-2004 saw outbreaks of what we now know as H5N1 Avian flu virus in eight East Asian countries: Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand, and Vietnam. It has since spread to Egypt, India, Kazakhstan, Russia and the US, but at much, much lower rates, sometimes with only a few cases per country. This blog will update the reader with some of what has been newly learned, or more strongly confirmed, since then, without “The Pandemic Will Wipe Us Out Tomorrow” hype that has the potential for desensitizing a community that has grown skeptical that Avian flu is much of a threat to anyone, when, in fact it is.
What Birds (“Avians”) Transmit the Virus That Causes the Disease?
Thus far it is pretty clear that two categories of poultry seem to be responsible for most of the outbreaks that spread to humans.
Domestic poultry, basically chickens and ducks grown for home consumption or the marketplace, seem to be the primary carriers from which most humans contract the disease.
These birds can get it from one another, or from migratory waterfowl.
Which Migratory Waterfowl Appear to Be The Culprits?
The family of birds called Anatidae, which consists of ducks, geese and swans are the most likely international vectors. Seagulls have been implicated, but not to as great a degree.
This bit of detective work has primarily used two pieces of evidence: Finding infected migratory birds and then tracking paths of infection along migratory flyways. The match up is good, although trucking of poultry infected by wildlife to cities that are not part of the migratory birds’ flyway can complicate the picture.
The means of transmission from migratory to domestic fowl seems to be through the migratory birds fouling the water and land with their often copious and virus-shedding feces.
The domestic fowl incorporate the viruses through contact or ingestion, and then pass it to on to other members of the domestic flocks through contact and their own virus-laden defecation.
One of the most imaginative studies of risk evaluation from migratory birds comes from Australia, where scientists have co-mapped the locations of poultry farms and the breeding grounds of sea birds and water fowl, and found only a narrow overlap. This will allow them to focus better their preventive efforts.
What about other animals? Rats and pigs can be infected with the virus, but only in experimental settings, and seem not to be likely to become vectors.
Is H5N1 Everywhere Identical?
No, there are at least five different strains, (and a number of related viruses since discovered, like H5N2 ) most of which get named after the location from which they were first isolated, or from where the most cases were reported.
There has already been some rate of mutation among these.
The good news is that most respond to the same drugs.
The bad news is that some of the newer strains appear more virulent.
How Can We Tell the Strains Apart?
Probably the most rapidly progressing area in the field is the differentially diagnostic molecular sequencing of these viruses. Tests are becoming more reliable, faster, more portable, and even cheaper.
False positives remain a problem, but by and large, that is better than false negatives, which would leave patients without any treatment.
What Are The Current Treatments?
By far, the most common treatment is with oseltamivir carboxylate, whose brand name is Tamiflu™. While it is not equally effective against all H5N1 strains, it has been able to be prepared in the multimillions of doses and to have some activity against virtually all of them.
The use of adjuvants (chemicals that seem to boost vaccine performance) and the timing of the injections seem to be more important to current successful treatment than the lack of specificity to all strains at this time of vaccines like Tamiflu™, although the development of cheap, and quickly scalable production of strain-specific vaccines or the development of multivalent vaccines that can inhibit the entire class of H5N1 are ultimately the long term goal.
Curiously, there is a good news/ bad news dichotomy with regard to the longer lasting nature of the drug in waterways. Apparently, it lasts up to two weeks in ponds and rivers. This might seem to suggest that treated humans who wash, void, or defecate nearby could actually decrease the water’s viral load. More likely, however, over-exposure of the drug could induce drug resistance as susceptible strains quickly fall prey, leaving only resistant mutants.
What Are Today’s Mortality Rates?
The most on-point study thus far is Kundun et al. below, from August 14th, 2008 issue of The Lancet . They reported 127 cases in Indonesia, occurring between June 2005 – February 2008.
The mortality was a whopping 81%.
What Are the Common Factors in Exposure to the Virus?
Living in an area where poultry had died with avian flu (30%)
Handling sick or dead poultry (21%)
Being around healthy poultry (15%)
Slaughtering or processing the meat of sick poultry (15%)
H5N1 positive poultry in the home or neighborhood, even if the poultry were apparently healthy at the time (5%).
Visited “wet” market where poultry was slaughtered at point of purchase. (3%)
Handled H5N1 positive poultry feces (perhaps as part of an attempt to clean it out.) (1%)
Symptomatology
Fever (93% of patients), cough (32%), runny nose (17%), nausea/vomiting (7%-13%), vertigo (10%), diarrhea (7%0, headache (6%), muscle aches (1%).
Rates of Admission to Hospital & Effectiveness of Treatment
125 patients were admitted to a hospital. One recovered with treatment at home; the other refused treatment and died. The sooner a patient was admitted to a hospital, the better were his or her chances. Likewise with the onset of treatment with Tamiflu™.
Nonetheless, most patients did die, typically of pneumonia.
The study suggests that the reason for the high death rate was that the hospital admission was too late after the onset of the disease, likewise with the administration of the Tamiflu™.
A curious result was the fact that patients who were part of a group that got ill, had better chances of recovery, than did patients who came down sick with the virus with no apparently sick neighbors, co-workers or family members. This could be because public health workers or primary care physicians were less alert to the possibility that this patient’s cold or flu was in fact, H5N1 based, until it was too late.
Bartels P & von Tumpling W. 2008. The environmental fate of the antiviral drug oseltamivir carboxylate in different waters. The Science Of The Total Environment epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.scitotenv.2008.06.032
Chantratita W, et al. 2008. Qualitative detection of avian influenza A (H5N1) viruses: A comparative evaluation of four real-time nucleic acid amplification methods. Molecular And Cellular Probes epub ahead of print, no volume or pagination yet assigned. DOI: 10.1016/j.mcp.2008.06.005
East IJ, Hamilton S & Garner G. 2008. Identifying areas of Australia at risk of H5N1 avian influenza infection from exposure to migratory birds: a spatial analysis. Geospatial Health 2 (2): 203-213.
Gaidet N, et al. 2008.Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl. PLoS Pathogens 4(8):e1000127.
Gilbert M, et al. 2006. Anatidae migration in the western Palearctic and spread of highly pathogenic avian influenza H5NI virus. Emerging Infectious Diseases 12 (11):1650-1656.
Goji NA, et al. 2008. Immune responses of healthy subjects to a single dose of intramuscular inactivated influenza A/Vietnam/1203/2004 (H5N1) vaccine after priming with an antigenic variant. The Journal Of Infectious Diseases198 (5): 635-641.
Isoda N, et al. 2008. Potency of an inactivated avian influenza vaccine prepared from a non-pathogenic H5N1 reassortant virus generated between isolates from migratory ducks in Asia. Archives of Virology epub ahead of print, no volume or pagination yet assigned.
Kalthoff D, et al. 2008.Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans. Emerging Infectious Diseases 14(8):1267-1270.
Kandun, IN et al. 2008. Factors associated with case fatality of human H5N1 virus infections in Indonesia: A case series. The Lancet epub ahead of print, no volume or pagination yet assigned
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Thanks for your great information, the contents are quiet interesting.I will be waiting for your next post.
life sciences
Posted by: vivek | January 08, 2013 at 12:10 PM
My name is Maura Logan and i would like to show you my personal experience with Tamiflu.
I am 63 years old. Have been on Tamiflu for 5 days now. Formerly had no negative feelings about "Big Pharmaceutical" but this medication has changed my mind. Definitely needed more extensive testing by the FDA.
I have experienced some of these side effects-
Horrible itching started after 8 pills (fourth day) and has lasted for six more days--and counting. Also suffering insomnia, and mood swings--crying and sour temper. Dr. wasn't even sure I had the flu (headache, severe body ache, exhaustion but no cold symptoms). Med seemed to help, but the after-effects are totally miserable. Hugely expensive med and not worth the risk. Absolutely HATE, HATE, HATE this medication!
I hope this information will be useful to others,
Maura Logan
Posted by: Tamiflu Side Effects | December 11, 2008 at 10:54 PM