TRANSMISSION AND INFECTION

Infected birds pass on H5N1

Infected birds pass on H5N1 through their saliva, nasal secretions, and feces. Other birds may pick up the virus through direct contact with these excretions or when they have contact with surfaces contaminated with this material. Because migratory birds are among the carriers of the H5N1 virus it may spread to all parts of the world. Past outbreaks of avian flu have often originated in crowded conditions in southeast and east Asia, where humans, pigs, and poultry live in close quarters. In these conditions a virus can mutate into a form that more easily infects humans.

The majority of H5N1 flu cases have been reported in southeast and east Asia. Once an outbreak is detected, local authorities often order a mass slaughter of birds or animals affected. If this is done promptly, an outbreak of avian flu may be prevented. However, the United Nations (UN) World Health Organization (WHO) has expressed concern that not all countries are reporting outbreaks as completely as they should. China, for example, is known to have officially denied past outbreaks of severe acute respiratory syndrome (SARS) and HIV.

H5N1 infections in humans are generally caused by bird to human transmission of the virus. A few isolated cases of suspected human to human transmission exist, but there is no proof either way in those cases.

Prevention

The current method of prevention in animal populations is to destroy infected animals as well as animals suspected of being infected. In southeast Asia, millions of domestic birds have been slaughtered to prevent the spread of the virus.

The probability of a "humanized" form of H5N1 emerging through recombination in the body of a human co-infected with H5N1 and another influenza could be reduced by influenza vaccination of at-risk workers. It is not clear at this point whether vaccine production could be stepped up sufficiently to meet this demand.

If an outbreak of pandemic flu does occur, its spread might be slowed by increasing hygiene in aircraft, and by examining airline cabin air filters for presence of H5N1 virus.

The American Centers for Disease Control and Prevention advises travelers to areas of Asia where outbreaks of H5N1 have occurred to avoid poultry farms and animals in live food markets. Travelers should also avoid surfaces that appear to be contaminated by feces from any kind of animal, especially poultry.

There are several H5N1 vaccines for several of the H5N1 varieties. H5N1 continually mutates rendering them, so far for humans, of little use.

Symptoms

Since H5N1 is an influenza virus, symptoms similar to those of the common flu, such as fever, cough, sore throat, and sore muscles, can develop in infected humans. However, in more severe cases, pneumonia and respiratory failure can develop and eventually cause death. Patients with H5N1 avian influenza have rarely had conjunctivitis, unlike human cases of infection by the H7 virus.

"The H5N1 virus causes an exaggerated response of cytokines (such as TNF-a), and this could result in a toxic-shock-like syndrome (including fever, chills, vomiting and headache), which ultimately results in death "In many diseases (including H5N1 in humans), a 'cytokine storm' [also called hypercytokinemia (sometimes spelled hypercytokinaemia)] is triggered by the infection. Cytokines are hormones that regulate the immune sytem. When released at the right time in the proper amounts, cytokines can help fight infections and regulate processes through out the body. But many cytokines are inflammatory and are damaging to the body if present in too high levels, or for too long. But whatever it is called, this phenomenon is a type of inflammatory cascade.  Many inflammatory cascades have self limiting components - the release of an inflammatory agent often leads to the production of both anti-inflammatory and inflammatory compounds. But as microbes evolve, they sometimes begin producing a mix of toxins that interfere with the control mechanisms of the immune system. This seems to be the case for the deadly strains of avian influenza. The H5N1 virus is not only partially resistant to the cytokines that are involved in fighting viruses, but it also reduces the production of anti-inflammatory cytokines - in essence, it enhances the accelerator while impairing the brakes, and the immune system goes out of control and crashes."

Treatment

"The 3 viral envelope proteins of influenza A virus are most medically relevant. The hemagglutinin (HA), neuraminidase (NA), and M2 are essential viral proteins targeted by host antibodies or antiviral drugs such as oseltamivir and rimantadine. The HA glycoprotein forms spikes at the surface of virions, mediating attachment to host cell sialoside receptors and subsequent entry by membrane fusion. The NA forms knoblike structures on the surface of virus particles and catalyzes their release from infected cells, allowing virus spread. The M2 is a transmembrane protein that forms an ion channel required for the uncoating process that precedes viral gene expression."

Neuraminidase inhibitors are a class of drugs which act on a protein conserved in all influenza A viruses. Drugs of this type include zanamivir and oseltamivir, the latter being licensed for prophylaxis treatment in the United Kingdom. Oseltamivir, which "attacks the influenza virus and stops it from spreading" inside the user's body, is marketed by Roche as Tamiflu, and this brand has become the drug of choice for governments and organizations in their preparations for a possible H5N1 pandemic. In August 2005, Roche agreed to donate three million courses of Tamiflu to the World Health Organization, to be deployed by the WHO to contain a pandemic in its region of origin. Although Tamiflu is patented, international law gives governments wide freedom to issue compulsory licenses for life-saving drugs.

A further class of drugs, which include amantadine and rimantadine, target M2 protein, a proton channel found in the viral membrane. Unlike zanamivir and oseltamivir, these drugs are inexpensive and widely available and the WHO had initially planned to use them in efforts to combat a H5N1 pandemic. However, the potential of these drugs was considerably lessened when it was discovered that farmers in China has been administering amantadine to poultry with government encouragement and support since the early 1990s, against international livestock regulations; the result has been that the strain of the virus now circulating in South East Asia is largely resistant to the medication and hence significantly more dangerous to humans. However, the strain of H5N1 spread throughout Northern China, Mongolia, Kazakhstan, Russia and Europe by wild birds in the summer of 2005 is not amantadine resistant.