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Avian Flu of Death By Amit Sen Gupta

IN the last two years about 60 deaths in four countries (Indonesia, Vietnam, Thailand and Cambodia) have been reported due to the dreaded “avian flu”.  On the face of it, not something that would appear to be a cause for major concern. Yet there is widespread panic across the world. Is this mere scare-mongering or do we really stand on the precipice of the next global “pandemic” of influenza?
Avian flu is influenza caused by varieties of the virus that primarily cause infection in birds. Pandemics of influenza are different from seasonal outbreaks or “epidemics” of influenza. Seasonal outbreaks are caused by subtypes of influenza viruses that already circulate among people, whereas pandemic outbreaks are caused by new subtypes, by subtypes that have never circulated among people, or by subtypes that have not circulated among people for a long time.

DEVASTATION BY PREVIOUS PANDEMICS

To understand the genesis of the panicky reaction we need to go back almost ninety years in time. The First World War was in its last stages and the world would soon start rebuilding. The War was to end in the destruction of an estimated 15 million human lives – including both military and civilian deaths. Very few people realised then that the globe was on the edge of another disaster – one that in two years would kill more than three times the number of people who died in the First World War. Between 1918-1919 an estimated 50 million people died due to an infection caused by a tiny virus which can be seen only with the help of very powerful microscopes. Named the "Spanish flu” this pandemic which raged across the globe was caused by a strain of the Influenza A virus. Many people died within the first few days after infection, and others died of secondary complications. Nearly half of those who died were young, healthy adults. The devastation in terms of number of deaths would be matched only twenty years later by the Second World War. Though the 1918-19 pandemic was the worst ever, there have been very several serious outbreaks of influenza pandemics in the twentieth century, including in1957-58 (called the “Asian flu") and in 1968-69 (called the Hong Kong flu).

INFLUENZA A DEADLY KILLER

It might still be puzzling for many people how an influenza epidemic can be so deadly. Most people have had one or more episodes of influenza in their lifetime, usually without major consequences. The answer lies in something that is common to all the three great pandemics of influenza in the twentieth century. All three pandemics were caused by types of influenza virus that had genetic material derived from influenza viruses that primarily affect birds – also called avian influenza viruses.

Pandemic viruses which cause the worst devastation emerge as a result of a process called "antigenic shift,” which causes an abrupt or sudden, major change in influenza A viruses. Changes results in a new influenza A virus subtype. The appearance of a new influenza A virus subtype is the first step toward a pandemic; however, to cause a pandemic, the new virus subtype also must have the capacity to spread easily from person to person. Once a new pandemic influenza virus emerges and spreads, it usually becomes established among people and moves around or “circulates” for many years as seasonal epidemics of influenza. The bird flu virus in some cases can suddenly become capable of infecting human populations (that is it “jumps” species) -- for whom it becomes an entirely new and deadly virus.

When a new subtype of the virus establishes itself in the human population it causes very severe infection because the human body has no immunity to the virus. After a few years the population develops complete or partial immunity and the virus causes only sporadic epidemics in low or non-immune population pockets. Gradually the sporadic outbreaks too die down, but may resurface decades later as immunity levels to the virus go down in the population. For example, we still see today cases of influenza caused by the subtype that was responsible for the 1918-19 pandemic.

RAGING PANDEMIC IN BIRD POPULATION

So the primary attention today is naturally focused on the epidemic that has been raging in the avian (bird) population across the world. In domestic poultry, infection with avian influenza viruses causes two main forms of disease, distinguished by low and high extremes of virulence. The so-called “low pathogenic” form commonly causes only mild symptoms (ruffled feathers, a drop in egg production) and may even 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 per cent, often within 48 hours.

The current outbreaks in the bird population, of avian influenza, which began in South-east Asia in mid-2003, are the largest and most severe on record. Never before in the history of this disease have so many countries been simultaneously affected, resulting in the loss of so many birds.

The causative agent, the H5N1 virus, has proved to be especially tenacious. 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.

From mid-December 2003 through early February 2004, poultry outbreaks caused by the H5N1 virus were reported in eight Asian nations (listed in order of reporting): the Republic of Korea, Viet Nam, Japan, Thailand, Cambodia, Lao People’s Democratic Republic, Indonesia, and China. Most of these countries had never before experienced an outbreak of highly pathogenic avian influenza in their histories.

In early August 2004, Malaysia reported its first outbreak of H5N1 in poultry, becoming the ninth Asian nation affected. Russia reported its first H5N1 outbreak in poultry in late July 2005, followed by reports of disease in adjacent parts of Kazakhstan in early August. Deaths of wild birds from highly pathogenic H5N1 were reported in both countries. Almost simultaneously, Mongolia reported the detection of H5N1 in dead migratory birds. In October 2005, H5N1 was confirmed in poultry in Turkey and Romania. Outbreaks in wild and domestic birds are under investigation elsewhere.

Japan, the Republic of Korea, and Malaysia have announced control of their poultry outbreaks and are now considered free of the disease. In the other affected areas, outbreaks are continuing with varying degrees of severity.

The role of migratory birds in the spread of highly pathogenic avian influenza is not fully understood. Wild waterfowl are considered the natural reservoir of all influenza A viruses. They have probably carried influenza viruses, with no apparent harm, for centuries and it is believed that wild waterfowl are not agents for the onward transmission of these viruses. Recent events however make it likely that some migratory birds are now directly spreading the new avian flu virus in its highly pathogenic form to other birds. Further spread to new areas is expected.

THREAT TO HUMANS

The widespread persistence of H5N1 in poultry populations poses two main risks for human health. The first is the risk of direct infection when the virus passes from poultry to humans, resulting in very severe disease. Of the few avian influenza viruses that have crossed the species barrier to infect humans, H5N1 has caused the largest number of cases of severe disease and death in humans. Unlike normal seasonal influenza, where infection causes only mild respiratory symptoms in most people, the disease caused by H5N1 follows an unusually aggressive clinical course, with rapid deterioration and high fatality. In the present outbreak, more than half of those infected with the virus have died. Most cases have occurred in previously healthy children and young adults. However, only about 100 human cases have occurred in the current outbreak -- a very small number compared with the huge number of birds affected and the numerous opportunities for human exposure. Direct contact with infected poultry, or surfaces and objects contaminated by their faeces, is presently considered the main route of human infection. The other good news is that human-to-human transmission of the H5N1 virus is still rare and in no instance has the virus spread beyond a first generation of close contacts or caused illness in the general community.

But the real danger lies in the possibility that given enough opportunities – the virus may (probably will) change into a form that is highly infectious for humans and spreads easily from person to person. Such a change could mark the start of a global outbreak (a pandemic). A pandemic can start when three conditions have been met: a new influenza virus subtype emerges; it infects humans, causing serious illness; and it spreads easily and sustainably among humans. The H5N1 virus meets the first two conditions -- the prerequisites for the start of a pandemic have therefore been met save one: the establishment of efficient and sustained human-to-human transmission of the virus. The risk that the H5N1 virus will acquire this ability will persist as long as opportunities for human infections occur. These opportunities, in turn, will persist as long as the virus continues to circulate in birds, and this situation could endure for some years to come.

ROCHE TRIES TO CASH IN

Though there is a substantial amount of research on developing a vaccine, it is unlikely to be available soon. There are anti-viral drugs which do not prevent the infection but can mitigate the severity of infection. The most effective is a new drug called oseltamivir (commercially known as Tamiflu). Tamiflu is marketed at present by Roche, who hold the Patent for this drug till 2016. Roche has till now refused to voluntarily license the drug to other companies to manufacture. Clearly the damocles sword of millions of deaths are not what Corporations are really concerned about. Recently the Indian company Cipla announced that it was ready to put the generic version of the drug on the market anywhere in the world where it would be allowed to market it. Roche countered by saying that it would take years to develop the manufacturing process for any new company, but soon backtracked from this statement. Clearly, if Roche doesn’t give in, this is an open and shut case for issuing of compulsory licenses to produce the drug. Recently the Indian government has said that it wouldn’t hesitate to issue a license, and one hopes it will follow up its promise with actions.

Meanwhile the world waits with bated breath. The scientific community has long held that a new influenza pandemic is round the corner. What we still do not know is if this is the one.