The influenza viruses

There are three types of influenza viruses: A, B & C. Humans can be infected by all the three types whereas wild birds are the natural hosts for influenza A.

Influenza A viruses are further classified by subtype on the basis of the two main surface glycoproteins: haemaglutinin (HA) and neuraminidase (NA).

Influenza viruses are normally highly species-specific - which means viruses that infect an individual species (humans, certain species of birds, pigs, or horses) stay "true" to that species, and only rarely spill over to cause infection in other species. Of the hundreds of strains of avian influenza A viruses, only four are known to have caused human infections: H5Nl, H7N3, H7N7, and H9N2. In general, human infection with these viruses has resulted in mild symptoms and very rarely severe illness, with one notable exception: the highly pathogenic H5Nl virus.

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What is Avian Influenza or Bird Flu?

Avian influenza or Bird Flu is an infectious disease of birds caused by type A strains of the influenza virus. The disease occurs worldwide. While all birds are thought to be susceptible to infection by avian influenza viruses, many wild bird species carry these viruses with no apparent signs of harm.

All 16 HA (haemaglutinin) and 9 NA (neuraminidase) subtypes of influenza A viruses are known to infect wild waterfowl, thus providing an extensive reservoir of such viruses perpetually circulating in bird populations. In wild birds, routine testing will nearly always find some influenza viruses. The vast majority of these viruses cause no harm. To date, all outbreaks of the highly pathogenic form of avian influenza have been caused by viruses of the H5 and H7 subtypes. Not all virus strains of the H5 and H7 subtypes are highly pathogenic, but most are thought to have the potential to become so.

The current outbreaks of highly pathogenic avian influenza, which began in poultry populations 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 H5N 1 virus, has proved to be especially tenacious. The H5 N 1 virus is also of particular concern for human health.

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What are the implications for human health?

The widespread persistence of H5Nl in poultry populations poses two main risks for human health.

1. 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, H5Nl 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 H5Nl follows an unusually aggressive clinical course, with rapid deterioration and high fatality. Primary viral pneumonia and multi-organ failure are common. 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.

2. A second risk, of even greater concern, is that the virus if given enough opportunities will change into a form that is higWy infectious for humans and spread  easily from person to person. Such a change could mark the start of a global outbreak (a pandemic).

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How do people become infected?

Direct contact with infected poultry, or surfaces and objects contaminated by their faeces, is presently considered the main route of human infection. To date, most human cases have occurred in rural or peri urban areas where many households keep small poultry flocks, which often roam freely, sometimes entering homes or sharing outdoor areas where children play. As infected birds shed large quantities of virus in their faeces, opportunities for exposure to infected droppings or to environments contaminated by the virus are abundant under such conditions. Moreover, because many households in Asia depend on poultry for income and food, many families sell or slaughter and consume birds when signs of illness appear in a flock, and this practice has proved difficult to change. Exposure is considered most likely during slaughter, defeathering, butchering, and preparation of poultry for cooking.

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Does the virus spread easily from birds to humans?

No. Though more than 100 human cases of infection 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, especially in areas where backyard flocks are common. It is not presently understood why some people, and not others, become infected following similar exposures

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What about the pandemic risk?

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 H5N 1 virus amply meets the first two conditions: it is a new virus for humans (H5N 1 viruses have never circulated widely among people),  it has infected more than 150 humans, killing over half of them. No one will have immunity should an H5Nl-like pandemic virus emerge.  All prerequisites for the start of a pandemic have therefore been met save one: the establishment of efficient and sustained human-to­human transmission of the virus. The risk that the H5Nl 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.

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How serious is the current pandemic risk?

The risk of pandemic influenza is serious. With the H5N 1 virus now firmly entrenched in large parts of Asia, the risk that more human cases will occur will persist. Each additional human case gives the virus an opportunity to improve its transmissibility in humans, and thus develop into a pandemic strain. The recent spread of the virus to poultry and wild birds in new areas further broadens opportunities for human cases to occur. While neither the timing nor the severity of the next pandemic can be predicted, the probability that a pandemic will occur has increased.

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Clinical features and pathology of H5NI in humans

In many patients, the disease caused by the H5Nl virus follows an unusually aggressive clinical course, with rapid deterioration and high fatality. Like most emerging diseases, H5Nl influenza in humans is poorly understood. Clinical data from cases in 1997 and the current outbreak are beginning to provide a picture of the clinical features of the disease, but much remains to be learnt. Moreover, the current picture could change given the propensity of this virus to mutate rapidly and  unpredictably.

The incubation period for H5NI avian influenza is 2-8 days. possibly as long as 17 days.

The main clinical manifestations of avian influenza infections depend on the viral subtype causing the disease. In the H5NI outbreak:

• An influenza-like illness typically appears early in the course of the disease.

• Conjunctivitis may be seen in some patients.

• Some patients may have prominent gastrointestinal (GI) symptoms with abdominal pain, diarrhoea and vomiting.

• Patients may progress to pneumonia or eventually die due to acute respiratory distress syndrome (ARDS) or mulriorgan failure.

• All patients had abnormal chest radiographic findings with features of interstitial infiltration, lobar infiltration, collapse/ consolidation and air bronchograms.

• Reye's syndrome and pulmonary haemorrhage are the likely complications.   Advanced age, a longer symptomatic period before admission, pneumonia, leucopaenia and lymphopaenia are the risk factors associated with severe disease.

Onset of disease occurs at a median of 3 to 4 days after exposure. In H5NI infection reports from Vietnam, the main presenting syndrome was community-acquired pneumonia, and fever was universally present.

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Clinical findings

• Lymphopaenia and thrombocycopaenia were common findings in all patients; these were prognostic indicators for ARDS and death.

• Pneumothorax occurred in patients who received mechanical ventilation.

• Post-mortem findings in 2 patients in Hong Kong due to H5Nl infection showed multiorgan damage, disseminated intravascular coagulation, lymphoid tissue necrosis and atrophy and the expected pulmonary pathology of diffuse alveolar damage.

• Haemophagocycic syndrome was a prominent feature.

• Viral RNA has been detected in the lungs, intestine and spleen but active viral replication was limited to the lungs and the intestine. Intestinal involvement by H5Nl   virus may explain the common occurrence of diarrhoea.

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