Avian Influenza: A new global threat?

There are three types of Influenza viruses: A, B, & C. Type A infects a variety of different host species, and consists of 16 subtypes of Hemagglutinin (H) surf protein, and 9 subtypes of Neuraminidase (N) surf protein (eg. H1N1, H2N2, H3N2). The H subtypes are epidemiologically most important, as they control the ability of the virus to bind to and enter cells, where multiplication of the virus then occurs. The N subtypes govern the release of newly formed virus from the cells. Type B is normally found only in humans, and can cause human epidemics but no pandemics. Type C causes mild illness in humans, and does not cause epidemics or pandemics.

The first Influenza Pandemic that occurred in 1918-19, "Spanish flu," was caused by type [H1N1] virus, and caused the highest number of flu deaths, such that 20-50 million people died worldwide, half of them young and healthy adults. The second pandemic occurred in 1957-58, "Asian flu," was first detected in china, and was caused by type [H2N2], appearing as an assortment of Human Virus and Avian Influenza Virus. The third pandemic occurred in 1968-69, "Hong Kong flu," was first detected in Hong Kong, was caused by type [H3N2], and was also an assortment of human virus and avian influenza virus.

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 rare occasions, crossed the species barrier to infect humans.

Domestic poultry are especially vulnerable to infections that can rapidly reach epidemic proportions. In domestic poultry, infection with avian influenza viruses causes two main forms of disease. The "low pathogenic" form commonly causes only mild symptoms, such as ruffled feathers, a drop in egg production, and may easily go undetected. The "highly pathogenic" form causes disease affecting multiple internal organs, and spreads very rapidly through poultry flocks, having a mortality that can approach 100%, within 48 hours.

Migratory waterfowl are the natural reservoir of avian flu viruses, and are known to carry viruses of the H5 and H7 subtypes, usually in the low pathogenic form. These, when introduced to poultry flocks, then mutate to the highly pathogenic form. However, recent evidence suggests that some migratory birds are now directly spreading the H5N1 virus in its highly pathogenic form.

Outbreaks in poultry occurred during 1983-4 in the USA, with H5N2 causing low mortality, which within 6 months became highly pathogenic, leading to a mortality of > 90%, and a decision of destruction of 17 million birds, at a cost of 65 million USD. Another outbreak occurred in Italy during 1999-2000 with H7N1 low pathogenicity, which within 9 months became highly pathogenic, leading to destruction of 13 million birds.

From mid-December 2003 through early February 2004, poultry outbreaks caused by the H5N1 virus were reported in eight Asian countries: Korea, Vietnam, 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. 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. At the same time, 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. The current outbreaks of highly pathogenic avian influenza, are the largest and most severe on record. The causative agent, the H5N1 virus, has proved to be especially tenacious. Control of the disease in poultry is expected to take several years.

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 vi ruses that have crossed the species barrier to infect humans, H5N 1 has caused the largest number of cases of severe disease and death in humans. In the current outbreak, laboratory-confirmed human cases have been reported in five countries: Cambodia, Indonesia, Thailand, Vietnam and Turkey, over half of those infected have died. Most cases have occurred in previously healthy children and young adults. People became infected by direct contact with infected poultry, or surfaces and objects contaminated by their feces. To date, most human cases have occurred in rural or periurban areas where many house-holds keep small poultry flocks, which they depend on for income and food, and are often allowed to roam freely in homes. Infected birds shed large quantities of virus in their faeces, which allows opportunities for exposure to infected droppings.

It has to be mentioned that the virus cannot spread easily from birds to humans. Although more than 100 human cases have occurred in the current outbreak, this is a small number compared with the huge number of birds affected and the numerous associated opportunities for human exposure.

It is of great concern that the virus, if given enough opportunities, may 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 pandemic.

With the H5N1 virus now firmly entrenched in large parts of Asia, the risk that more human cases will occur will persist. Each additional human case will give the virus an opportunity to improve its transmissibility in humans, which can occur via two principal mechanisms. The first is a "reassortment" event, in which genetic material is exchanged between human and avian viruses during co-infection of a human or pig. Reassortment could result in a fully transmissible pandemic virus, announced by a sudden surge of cases with explosive spread. The second is a more gradual process of adaptive mutation, whereby the capability of the virus to bind to human cells increases during scenario would probably give the world some time to take defensive action.

In August 2005, the World Health Organization (WHO) sent all countries a document outlining the recommended strategic actions for responding to the avian influenza pandemic threat, aiming to strengthen national preparedness, reduce opportunities for a pandemic virus to emerge, improve the early warning system, delay initial international spread, and accelerate vaccine development.

Vaccines effective against a pandemic virus are not yet available. Vaccines produced for seasonal influenza but will not protect against pandemic influenza. Although a vaccine against the H5NI 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.

By early 2006, WHO will have a stockpile of antiviral medications, sufficient for 3 million treatment courses. Recent studies suggest that these drugs could be used prophylactically near the start of a pandemic to reduce the risk of emergence of a fully transmissible virus or at least to delay its international spread, thus gaining time to augment vaccine supplies. The neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) known to reduce the severity and duration of illness caused by seasonal influenza may improve prospects of survival if administered early, but clinical data are limited. However, the main constraints for neuraminidase inhibitors involve limited production capacity and its high price.

The WHO has urged all countries to develop preparedness plans, and has urged countries with adequate resources to stockpile antiviral drugs nationally for use at the start of a pandemic.