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Avian Flu: Primer & Update, Part 1

Written by pharmacist  |  23. October 2005

Dear Readers, I have been getting many questions regarding the avian (bird) flu reporting. I would like to share with you some information that is currently known about this latest virus compliments of the World Health Organization (WHO). One must also keep in mind that avian flu is not brand new (reported since the mid part of 2003) and its reports of confirmed human cases have been reported to the World Health Organization. Since January 29, 2004 to present, WHO has reported a cumulative number of confirmed human cases of Avian influenza A (HN51) to be 118 with 61 deaths. All these cases occurred exclusively in Vietnam, Indonesia, Thailand and Cambodia; the majority of cases and deaths reported in Vietnam. WHO reports only laboratory-confirmed cases. What is avian influenza? Avian influenza, or "bird flu", is a contagious disease of animals caused by viruses that normally infect only birds and, less commonly, pigs. Avian influenza viruses are highly species-specific, but have, on infrequent occasions, crossed the species barrier to infect humans. In domestic poultry, infection with avian influenza viruses causes two main forms of disease, distinguished by low and high degrees of virulence. The so-called "low pathogenic" form commonly causes only mild symptoms (ruffled feathers, a drop in egg production) and may easily go undetected. The highly pathogenic form is far more dramatic. It spreads very rapidly through poultry flocks, causes disease affecting multiple internal organs, and has a mortality that can approach 100%, often within 48 hours. Which viruses cause highly pathogenic disease? Influenza A viruses have 16 H subtypes and 9 N subtypes. Only viruses of the H5 and H7 subtypes are known to cause the highly pathogenic form of the disease. However, not all viruses of the H5 and H7 subtypes are highly pathogenic and not all will cause severe disease in poultry. It is presently known that H5 and H7 viruses are introduced to poultry flocks in their low pathogenic form. When allowed to circulate in poultry populations, the viruses can mutate, usually within a few months, into the highly pathogenic form. This is why the presence of an H5 or H7 virus in poultry is always cause for concern, even when the first signs of infection are mild. The contributing agent, the H5N1 virus, has proved to be especially stubborn. Despite the death or destruction of an estimated 150 million birds, the virus is now considered endemic in many parts of Indonesia and Viet Nam and in some parts of Cambodia, China, Thailand, and possibly also the Lao People's Democratic Republic. Control of the disease in poultry is expected to take several years. What has happened, to date, concerning Avian Flu? The Ministry of Public Health in Thailand has, on October 20 2005, confirmed its first case of human infection with H5N1 avian influenza since October 8 2004. The patient, a 48-year old man from Kanchanaburi Province, developed symptoms on 13 October, was hospitalized on 17 October, and died on 19 October. Experts have linked his infection to close contact with diseased poultry during slaughter. Poultry outbreaks in several Kanchanaburi villages were reported earlier this month. Presently the man's, seven year old son, who assisted him in defeathering of diseased birds, has shown respiratory symptoms and is currently hospitalized. Since the start of the outbreaks in Asia, Thailand has confirmed 18 cases, of which 13 have been fatal. As of October 13 2005, tests conducted by the World Organization for Animal Health (OIE) have today confirmed the presence of highly pathogenic H5N1 avian influenza in samples taken from domestic birds in Turkey. In Romania, investigations of recent poultry deaths have, to date, identified the H5 subtype of avian influenza virus. Further testing is under way to determine the strain and whether the virus is highly pathogenic. The World Health Organization (WHO) level of pandemic alert remains unchanged at phase 3: a virus new to humans is causing infections, but does not spread easily from one person to another. WHO continues to recommend that travelers to areas experiencing outbreaks of highly pathogenic H5N1 in poultry should avoid contact with live animal markets and poultry farms. Large amounts of the virus are known to be excreted in the droppings from infected birds. Populations in affected countries are advised to avoid contact with dead migratory birds or wild birds showing signs of disease. Direct contact with infected poultry, or surfaces and objects contaminated by their droppings, is considered the main route of human infection. Exposure risk is considered highest during slaughter, defeathering, butchering, and preparation of poultry for cooking. There is no evidence that properly cooked poultry or poultry products can be a source of infection. What drugs are available for treatment? Two drugs (in the neuraminidase inhibitors class), oseltamivir (commercially known as Tamiflu) and zanamivir (commercially known as Relenza) can reduce the severity and duration of illness caused by seasonal influenza. The efficacy of the neuraminidase inhibitors depends on their administration within 48 hours after symptom onset. For cases of human infection with H5N1, the drugs may improve prospects of survival, if administered early, but clinical data are limited. The H5N1 virus is expected to be susceptible to the neuraminidase inhibitors. An older class of antiviral drugs, the M2 inhibitors amantadine and rimantadine, could potentially be used against pandemic influenza, but resistance to these drugs can develop rapidly and this could significantly limit their effectiveness against pandemic influenza. Some currently circulating H5N1 strains are fully resistant to these the M2 inhibitors. However, should a new virus emerge through reassortment, the M2 inhibitors might be effective. For the neuraminidase inhibitors, the main constraints - which are substantial - involve limited production capacity and a price that is prohibitively high for many countries. At present manufacturing capacity, which has recently quadrupled, it will take a decade to produce enough oseltamivir to treat 20% of the world's population. The manufacturing process for oseltamivir is complex and time-consuming, and is not easily transferred to other facilities. Vaccines effective against a pandemic virus are not yet available. Vaccines are produced each year for seasonal influenza but will not protect against pandemic influenza. Although a vaccine against the H5N1 virus is under development in several countries, no vaccine is ready for commercial production and no vaccines are expected to be widely available until several months after the start of a pandemic. So far, most fatal pneumonia seen in cases of H5N1 infection has resulted from the effects of the virus, and cannot be treated with antibiotics. Nonetheless, since influenza is often complicated by secondary bacterial infection of the lungs, antibiotics could be life-saving in the case of late-onset pneumonia. WHO regards it as prudent for countries to ensure adequate supplies of antibiotics in advance.

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