Human to human transmission As of 2005, the
WHO believed that another influenza pandemic is as likely to occur at any time since 1968, when the last century's third of three pandemics took place. The WHO describes a series of six phases, starting with the inter-pandemic period, where there are no new influenza virus subtypes detected in humans, and progressing numerically to the pandemic period, where there is efficient and sustained human-to-human transmission of the virus in the general population. According to WHO, the world has been at phase 3 on the scale, meaning a new influenza virus subtype is causing disease in humans, but has not yet spread efficiently and sustainably among humans. A few isolated cases of suspected human to human transmission exist. with the latest such case in June 2006 (among members of a family in Sumatra).
Prevention Notwithstanding possible mutation of the virus, the probability of a "humanized" form of H5N1 emerging through
genetic recombination in the body of a human co-infected with
H5N1 and another influenza virus type (a process called
reassortment) could be reduced by widespread seasonal
influenza vaccination in the general population. It is not clear at this point whether vaccine production and immunization 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 avian H5N1 varieties. H5N1 continually mutates rendering them, so far for humans, of little use. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain.
Daniel R. Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic.
Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain. It is not likely that use of
antiviral drugs could prevent the evolution of a pandemic flu virus.
Symptoms The human incubation period of avian influenza A (H5N1) is 2 to 17 days. Once infected, the virus can spread by cell-to-cell contact, bypassing receptors. So even if a strain is very hard to initially catch, once infected, it spreads rapidly within a body. For highly pathogenic H5N1
avian influenza in a human, "the time from the onset to presentation (median, 4 days) or to death (median, 9 to 10 days) has remained unchanged from 2003 through 2006." Avian influenza HA preferentially binds to alpha-2,3
sialic acid receptors, while human influenza HA preferentially binds to alpha-2,6 sialic acid receptors. Usually other differences also exist. Currently, there is no human-adapted form of H5N1 influenza, so all humans who have caught it so far have caught avian H5N1.
Human flu symptoms usually include
fever,
cough,
sore throat,
muscle aches,
conjunctivitis and, in severe cases, severe breathing problems and
pneumonia that may be fatal. The severity of the infection will depend to a large part on the state of the infected person's
immune system and if the victim has been exposed to the strain before, and is therefore partially immune. No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu. Highly pathogenic H5N1 avian influenza in a human appears to be far worse, killing over 50% of humans reported infected with the virus, although it is unknown how many cases (with milder symptoms) go unreported. In one case, a boy with H5N1 experienced
diarrhea followed rapidly by a
coma without developing respiratory or flu-like symptoms. As of February 2008, the "median age of patients with influenza A (H5N1) virus infection is approximately 18 years [...] The overall case fatality proportion is 61% [...] Handling of sick or dead poultry during the week before the onset of illness is the most commonly recognized risk factor [...] The primary pathologic process that causes death is fulminant viral pneumonia." The
inflammatory cascade triggered by H5N1 has been called a '
cytokine storm' by some, because of what seems to be a
positive feedback process of damage to the body resulting from immune system stimulation. H5N1 type flu virus induces higher levels of cytokines than the more common flu virus types such as H1N1. Other important mechanisms also exist "in the acquisition of virulence in
avian influenza viruses" according to the CDC. The NS1 protein of the highly pathogenic avian H5N1 viruses circulating in
poultry and
waterfowl in Southeast Asia is currently believed to be responsible for the enhanced proinflammatory cytokine response. H5N1 NS1 is characterized by a single
amino acid change at position 92. By changing the amino acid from
glutamic acid to
aspartic acid, researchers were able to abrogate the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the
pathogenicity of the H5N1 influenza virus. In short, this one amino acid difference in the NS1 protein produced by the NS
RNA molecule of the H5N1 virus is believed to be largely responsible for an increased pathogenicity (on top of the already increased pathogenicity of its hemagglutinin type which allows it to grow in organs other than lungs) that can manifest itself by causing a cytokine storm in a patient's body, often causing pneumonia and
death.
Treatment Neuraminidase inhibitors are a class of drugs that includes
zanamivir and
oseltamivir, the latter being licensed for
prophylaxis treatment in the
United Kingdom. Oseltamivir inhibits the influenza virus from spreading inside the user's body. However, recent data suggest that some strains of H5N1 are susceptible to the older drugs, which are inexpensive and widely available. Research indicates that therapy to block one cytokine to lessen a cytokine storm in a patient may not be clinically beneficial.
Mortality rate ==See also==