– IS THE AVIAN INFLUENZA AN END TIME PLAGUE?

Why we should be afraid of bird flu?
By: Dr. I. Ibopishak Singh

H5N1, a highly pathogenic avian influenza virus (HPAIV), is one of the several bird flu viruses that could infect many species of birds and is very contagious and lethal to poultry fowls. Wild migratory birds-ducks, geese, gulls, & cormorants- are the natural hosts (reservoirs) of this virus. They carry the viruses in their intestine without any apparent harm for centuries. The viruses remain in an evolutionary stasis. Host and virus seem to exist in a state of a meticulously balanced mutual tolerance. The birds do not develop any overt disease and the virus do not replicate inside the carries (host). The viruses are maintained in a low pathogenic mode (LPAIV) as long as they remain inside the host.
 

However, once they cross over to the domestic poultry (chickens, turkeys,) they get adapted to the poultry and could switch by insertional mutations, statutorily into a highly pathogenic from (HPAIV) and thereby inducing overwhelming systemic and rapidly fatal disease. Such HPAI viruses may arise unpredictable de novo in poultry infected with LPAI progenitors of H5 and H7 subtypes. Avian influenza is verily the ultimate master of disguise. However, strains of the subtypes H5 and H7 carry the potential to mutate to a highly pathogenic form after transmission and adaptation to the new domestic poultry hosts. Nascency of highly pathogenic form of H5 and H7 or of other subtypes has never been observed in wild birds. Wild birds have never infected to date human directly.

Morphologically, this virus is very delicate. Like any other virus, it is caught between the world of the living and non - living. The primordial RNA virus mutate fast generating many new variants each time they invade a cell. The high mutation rate enables the virus to keep changing and stay one step ahead of the immune system of birds, pigs or humans. This virus measures just about 100 manometers (one thousand-millionth of a meter) and resemble a spiky pin cushion. The spikes are glycoproteins known H (haemaglutinin) and N (neuraminidase). There are 16 different H subtypes and 9 different N subtypes. Many different combination strains of H and N are possible. There are therefore 144 (16 X 9) possible strains. All subtypes of flu A virus can be found in a birds. Avian flu subtypes are H5,H7,H9,H6,H4, etc H5 and H7 are most virulent. The glycoprotein H & N are the most lethal weapons in the virus arsenals. The H protein helps the virus invade the cells in the respiratory tract ( in birds, it is the digestive tract ), while the N protein allows the viral progeny to chop their way out of the infected cells. Oseltamivir (Tamiflu), Zanamivir (Relenza) prevent the activity of N protein. However drugs become ineffective when a virus like H5N1 changes its genetic make up. The changeable nature is also the reason we cannot produce a vaccine (that long last) as we don’t know exactly what form the virus will take. In addition, it is proved recently that there are 2 variants of H5N1. So we may have to innovate more than one candidate vaccine. Unlike a sophisticated DNA virus, it makes small mistakes when it makes copies of its own genes. Influenza has its genetic information in 8 segment rather than in a continuous strain. This allows different influenza viruses from different species to rearrange, recombine a swap genes among themselves.

H5N1 virus swept across Asia from mid-December 2003 to early February 2004. The affected countries are South Korea, Vietnam, Japan, Thailand, Cambodia, Laos, Indonesia and China (listed in order of reporting). As estimated 150 million domestic fowls were killed and culled. In early August 2004, Malaysia reported its first outbreak of H5N1 in poultry. The outbreak reached Russia in late July 2005 and Kazakhastan in early August. Death of wild birds from HPAIV (H5N1) were reported in both countries. Almost simultaneously, Mongolia reported the detection of H5N1 in dead migratory birds. In October 2005, H5N1 was confirmed in poultry in Turkey and Romania. 4 humans died in Turkey. Japan, Korea & Malaysia are now considered free from the disease. Vietnam & Indonesia are the endemic zones. The virus penetrated deep into Europe. Germany, Croatia, Italy & Austria reported H5N1 in domestic poultry and wild ducks. The death of 5 persons was confirmed in Azerbaijan in March 2006. The virus had sneaked into Africa affecting domestic poultry in Egypt & Nigeria. 6 persons died in Egypt. The H5N1 virus that hit Gujarat and Maharashtra in Feb 2005 is similar to the strain found in infected barheaded goose at Qinghai (Central and Western China) lake reserve in late April and early May 2005 and Jiangxi (South China). The Indian strain is found to have 6 basic amino acids at the cleavage site of HA gene. The higher the amino acid, the more lethal the virus, Any virus having over 2 basic amino acids are pathogenic. Amino acids helps the virus in entering the bird’s system, killing it in no time. The death of above 6,000 bar-headed geese along with ducks, cormorants etc at Qinghai lake reserve raises great concern among health experts throughout the World. It is speculated that HPAIV(H5N1) is reintroduced to the wild migratory water fowls by domestic ducks and poultry while sharing common water source. The total number of human death out of 218 infected is 124 as on 23 May 2006 giving mortality rate of almost 50%.Vietnam records highest infection of 93 with 42 deaths.

Prior to the Qinghai lake event, the highly pathogenic H5N1 virus was known to cause occasional sporadic deaths in migratory waterfowl, but not to kill them in large numbers or be carried by them over long distances. If the reintroduction theory is scientifically proved, the migratory water fowls would, no doubt, be increasingly infected with HPAIV. This would disturb interaction of the host and the virus. The dropping of wild birds would be saturated with HPAIV. In the near future, HPAIV would virtually rain down from the sky with bird droppings infecting humans, animals and birds. This would be the most frightening and worrisome trend. The recent Chinese study also found that house sparrow is also the carrier of H5N1 virus. Rodents can also act as mechanical carrier.

In the early part of the epidemic, almost all the countries except Japan and South Korea handled the crisis ineptly. Tendency to denial and cover - up due to ignorance about the disease, official stonewalling, lack of money and manpower to implement preventive measures cause much delay and this, in turn, provided ample opportunity to the virus to roll through the chicken population and mutate, and become more pathogenic. H5N1 virus does not typically infect humans. In 1997, however, the first instance of direct bird to human transmission of bird flu virus was documented during an outbreak of avian influenza among poultry in Hongkong. The virus crossed the species barrier (transpecies infection). The virus caused severe respiratory illness in 18 people, of whom 6 died. On the advice of WHO experts, the local authority of Hongkong culled the entire poultry populations (1.4 millions) - chickens, ducks & turkeys - in 3 days (29,30 & 31 Dec) and possible pandemic was averted.

The Hongkong epidemic was caused by a reassortant virus of 3 viral strains coming from 3 different species including a H5N1 virus from domestic goose donating the HA, a H6N1virus probably from teal contributing the NA and segments of the internal proteins which underwent many more cycles of reassortation with other unknown influenza viruses. The avian influenza virus loves to have promiscuous affairs with different viruses, be it from birds, humans or mammals. The Hongkong outbreak, as such, had the pandemic potential.

The currently circulating Asian lineage H5N1 virus is different from 1997 (Hongkong epidemic) and 2004 one in a number of ways. The present strain in more lethal in experimentally infected mice and ferrets. They are hardier, surviving several days longer in the environment. They share the same genetic make - up of the Spanish influenza pandemic of 1918 - 19. Domestic ducks have acquired an ability to resist the disease caused by some strains, and are now capable of excreting large quantities of HPAIV without showing the warning signs of illness and subtly acting as a “Trojan horse” of the virus, and verily would contribute to perpetuate transmission cycle in the endemic SE Asian regions.

H5N1 has expanded its host range, infecting and killing mammalian species previously considered resistant to infection with this virus. In Dec 2003, two tigers and two leopards fed on chicken carcasses infected with H5N1 died at a zoo in Thailand. A clouded leopard and a white tiger also died in the same zoo of H5N1 infection. At least, some tiger to tiger transmission, reportedly, took place in the same zoo. Bird flu is feared to have jumped to some exotic species, killing herons in Cambodian, pheasants in Taiwan and cat in Tibet and Germany.

The geographical range of H5N1 invasion is historically unprecedented. About 40 countries in 3 continents are affected. Each additional human case gives the virus and opportunity to improve its transmissibility in humans, and thus develop into a pandemic strain. The SE Asian countries particularly Vietnam and Indonesia may likely be the epicenter of the impending pandemic.

How Serious is the pandemic risk ?
when an epidemic goes global, then it becomes a pandemic. In a pandemic virtually all the countries of the world are involved. It is a rare but recurrent event. One an average 3/4 pandemic occur in one 100 years. In the last century 3 pandemics took place. They are :-

1918-19 “Spanish Flu” [A(H1N1)], the worst pandemic which killed 40-50 million people worldwide. It was caused by mutation of swine flu virus that evolved in pigs in USA, and spread around the globe by sikduers mobilizing for WW1. 50% of the people including young healthy Persons died within the first 4-5 days after being introduced to human population in the 1970s.

1957-58 “Asian Flu”[A(H2N2)] started in southern China. The virus remained dormant in ducks, and passed on to pigs (mixing bewl) where it mutated and then migrated to humans. About 1 million worldwide died.
1968-69 “Hongkong Flu” [A(H3N2)] killed 2 million people globally while Hongkong shared 60% of the causality. A(H3N2) virus still circulate today in humans.