H5N1

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H5N1

The H5N1 virus is classified as an influenza A virus. This type of virus is normally found in avian species (birds) and is both highly contagious and highly lethal to bird populations ranging from wild migrating birds to chickens on commercial poultry farms.

Transmission to humans

As of December 2006, H5N1 was not easily transmissible to humans. Most of the cases of human infection with H5N1 involved infections resulting from close contact with infected bird populations. Situations, for example, where people lived in proximity to infected birds (mostly poultry), handled infected birds, or had contact with H5N1-contaminated surfaces. Globally, epidemiologists (scientists who study the origin of disease) had documented only a few cases of human-to-human transmission of H5N1 and all of the documented cases involved close contact (e.g., a family member caring for an infected relative, etc).

The influenza in humans resulting from H5N1 infection is highly lethal. High death rates are not uncommon, including cases where infection resulted in death in more than 75% of persons infected during an outbreak.

Genetic testing of the H5N1 flu virus shows it to be a highly mutable virus. H5N1 has been documented to infected pigs and pigs serve as a host for flu viruses that historically mutate easily into a form that can infect humans. Accordingly, the World Health Organization (WHO) has made the study and containment of H5N1 and other avian flu viruses originating in Asia its top priority. WHO officials fear a potentially devastating global pandemic if H5N1 is able to mutate into a form easier to transmit to humans or a form easier for humans to transmit to other humans.

Mechanism of action

The avian flu viruses attack human cells by first attaching themselves to the outer cell membrane with pointed probelike hemagglutin (HA) molecules that are capable of binding to specific sites on the cell membrane.

Hemagglutinin and neuraminidase (DNA) are glycoproteins (a protein that contains a short chain of sugar as part of its structure). Hemagglutinin and neuraminidase protrude from the outer surface of the influenza virus and neuraminidase is a constituent of the enveloping membrane that surrounds the viral contents. A typical influenza virus particle contains hundreds of molecules of hemagglutinin and neuraminidase studded across the viral surface.

Because the binding must be specific—that is, the HA molecule must be of a certain structure and configuration to bind to the membrane receptor sites—the vast majority of viruses that infect birds are not capable of binding to human cell membranes. Small and subtle changes, driven by the process of mutation, in either the protein structure or in protein configuration (the protein’s shape in three dimensional space) can, however, permit binding to human cell membranes. This allows the virus to infect the human cell, and make the jump from birds to humans.

Researchers and health officials find optimism for containing the current outbreaks of flu in the data obtained from comparative analysis of flu strains that show the structure of the H5N1 HA molecules from the strain responsible for the recent outbreaks in China and Vietnam is actually quite different from the structure of the HA molecules associate with the 1918 flu pandemic.

But scientists remain vigilant—and public health officials remain concerned—because the changes required to make the jump to humans also occurred in the viruses responsible for during global outbreaks of influenza in 1957 and 1968.

Preventative and control measures

Biologically, however, there is little that can be done to stop the virus from spreading and mutating, except to reduce its host environment. Governments of the affected countries (especially Thailand, Vietnam, Laos, Cambodia, Republic of Korea, Indonesia, and in more than a dozen provinces, municipalities and autonomous regions on the Chinese mainland) have often ordered the wholesale slaughter of sick, potentially infected, and exposed birds as a response to avian flu outbreaks (the disease H5N1 causes in avian populations).

Millions of chickens, for example, have been culled in order to attempt to inhibit the spread to other flocks as governments imposed prompt and sometimes severe quarantine restrictions. In other countries chickens have been given vaccines (some with questionable effectiveness) against the disease, in an attempt to minimize the potentially overwhelming negative economic impacts of H5N1 on commercial bird species.

The specific H5N1 virus linked to human deaths is especially dangerous because it is resistant to both amantadine and rimantadine, two commonly used antiviral drugs used to treat influenza. Other antiviral medications, oseltamavir (Tamiflu) and zanamavir, have shown effectiveness but the full extent (or limits of effectiveness) were, as of December 2006, still subject to additional testing. Although research programs (and clinical trials) existed in several countries, as of December 2006, no vaccine against H5N1 was yet formally approved for use in humans.