Opinion - News Analysis   

The spread and spread of H5N1

— Photo: AFP

Precarious existence: A chicken sits on a cage on a delivery van near a village market at Gharisha, some 210 km north of Kolkata. Officials in West Bengal are culling poultry in a bid to battle India’s worst-ever outbreak of bird flu.

It was 10 years ago that the highly virulent bird flu virus known as H5N1 came to public attention. It was first isolated from sick geese at a farm in southern China in 1996. The next year, 18 people in Hong Kong caught the virus and six of them died. The Hong Kong government responded with a massive cull of all poultry in the territory and halted its spread.

But the virus was still circulating among poultry in mainland China. In early 2003, a family of five from Hong Kong visited China’s Fujian province. Their seven-year-old daughter died of severe respiratory disease there. Her father died after returning to Hong Kong but her brother, who was also infected by the virus, recovered.

Despite efforts to stamp it out, the H5N1 virus has spread out of China to countries across Asia and to Europe and Africa as well. Since 2003, at least 48 countries have reported outbreaks of the virus in domestic poultry and another dozen or so countries have found it in wild birds, according to the World Organisation for Animal Health. The virus appears to have become endemic in several of these countries.

The H5N1 virus has hitherto largely been a disease affecting birds and is a lethal killer when it infects chicken. According to the U.N. Food and Agriculture Organisation (FAO), over 250 million chicken have died of the disease or been killed to stop the spread of the virus.

While circulating among chicken and other domestic birds, the virus does at times infect humans too. World Health Organisation statistics show that since 2003, some 350 people in 14 countries have been confirmed as having got H5N1 infections, and 218 of whom died.

“The spread of avian influenza typifies the potential emergence of major health crises, with an increased risk of pathogens travelling over large distances in very short time periods, favoured by globalisation and climate change,” remarked Jacques Diouf, FAO Director-General, at a recent international ministerial conference on avian and pandemic influenza in New Delhi.

In a review paper published recently in the New England Journal of Medicine, a WHO panel of experts observed that despite widespread exposure to H5N1-infected poultry, human cases of the disease “remain very rare.” Direct bird-to-human transmission was the predominant means of human infection. However, the exact manner in which the virus managed to infect the human respiratory tract was incompletely understood. “Handling of sick or dead poultry during the week before the onset of illness is the most commonly recognised risk factor,” it added.

But in one quarter or more of the human cases, the source of exposure to the virus was unclear. With respect to some patients, the only identified risk factor was visiting a live-poultry market. Plausible transmission routes included contact with virus-contaminated objects, fertilizer containing poultry faeces or inhalation of aerosolised infectious excreta.

Clusters of human H5N1 illness, involving between two and eight persons, had been identified in 10 countries and accounted for approximately one quarter of the cases. “More than 90 per cent of the case clusters have occurred among blood-related family members, suggesting possible genetic susceptibility, although one statistical model indicated that these clusters might have occurred because of chance alone,” the panel noted.

Most persons in such clusters probably acquired the infection by common exposure to poultry, according to the experts. They added, however, that “limited, non-sustained human-to-human transmission had probably occurred during very close, unprotected contact with a severely ill patient.”

The big worry, the WHO said, “is the risk that the H5N1 virus — if given enough opportunities — will develop the characteristics it needs to start another influenza pandemic. The virus has met all prerequisites for the start of a pandemic save one: an ability to spread efficiently and sustainably among humans.” The H5N1 virus could acquire that ability either through mutation or by swapping genes with a human-adapted flu virus. Such gene swapping can occur when a human or a pig is infected with both the H5N1 virus and human flu virus.

In recent years, scientists have been working feverishly to try and understand what genetic changes might turn a bird flu virus, such as the H5N1, into a dangerous pandemic strain. An important target for such study has been the differences in receptor molecules on cells, which bird and human-adapted flu viruses bind to. Only after latching on to the receptor can the virus enter the cell and hijack the cellular machinery in order to reproduce itself.

The hemagglutinin protein of human-adapted flu viruses are able to bind to receptors where sialic acid and a sugar are joined by an “alpha-2,6” linkage. Cells with such receptors are present along the human respiratory tract. The hemagglutinin of bird flu viruses, on the other hand, attach to receptors with an “alpha-2,3” linkage.

But research by Ram Sasisekharan of the Massachusetts Institute of Technology and his colleagues, published recently in the journal Nature Biotechnology, showed that the differences in the receptors for bird and human flu viruses go beyond just the type of chemical linkage between sialic acid and sugar. They found that the human-adapted viruses attached to long alpha-2,6-linked receptors that had an umbrella-like shape.

Such umbrella-shaped alpha-2,6-linked receptors are found predominantly on cells in the human upper respiratory tract, including the nose and throat.

Thus, a flu virus that successfully colonises such cells is able to spread easily from human to human when the infected person sneezes or coughs.

By contrast, the alpha-2,3-linked receptors found in birds have a conical shape. So do the short alpha-2,6-linked receptors that are also found on cells along the human respiratory tract but in much smaller numbers. As a result, flu viruses that bind to the cone-shaped alpha-2,6-linked receptors do not infect humans very well.

So for a bird flu virus to become adapted for efficient human-to-human transmission, its hemagglutinin protein must change and be able to bind to the umbrella-shaped receptors. But, worryingly, just a few mutations might suffice to produce the changeover. In the case of both the H1N1 flu virus that caused the pandemic of 1918 and the H3N2 virus responsible for the flu pandemic of 1968, “it took 2 to 3 mutations for the [hemagglutinin] of these viruses to be able to bind to human receptors effectively,” Dr. Sasisekharan said in an e-mail. “We do not have any reasons to suspect H5N1 to be any different.”

Printer friendly page  
Send this article to Friends by E-Mail

Stories in this Section

Beyond the Bilkis Bano case
Building on the positives
A new journey in search of the Taliban
The spread and spread of H5N1
Republicans lack consensus, Democrats lack content
Corrections and clarifications
Teach reading
War and peace
Red-letter day
Welcome verdict

Copyright © 2008, The Hindu. Republication or redissemination of the contents of this screen are expressly prohibited without the written consent of The Hindu