Bird Flu: Disease takes off around the world, remains primarily an avian threat

Avian influenza: It seems to be everywhere these days — on the news, in magazines, at the bookstores. Avian influenza even has been used on television for sweeps week!

Avian influenza continues its flight path around the world. The H5N1 strain has been the culprit to 200 human infections and counting.

With such notoriety, are you prepared to answer questions from clients regarding this disease du jour?

This article is intended to offer a kind of primer about avian influenza — the ABC's of the bird flu. I've thrown in a few other letters to help address the questions you will likely receive from clients.

A = Influenza A

The influenza viruses are divided into three large categories — A, B and C, based on two proteins found in their inner cores. Influenza B and C viruses infect humans only. The influenza A viruses, which can be found in numerous species, are further divided according to the surface characteristics, in particular two different molecules, called hemagglutinin (16 different kinds of this molecule exist) and neuraminidase (nine different kinds of this molecule exist). As a result, every influenza A virus has a designation H#N#. The bad human influenza viruses are all of the H1, H2 and H3 varieties. To date, all serious avian influenza viruses are H5 or H7. Influenza A viruses are supposed to be restricted to their own species, so, in 1997, when a boy in Hong Kong died of influenza A and the authorities discovered that it was an H5 virus, public health communities around the world sat up and took notice.

B = Birds

As the name indicates, avian influenza (AI) is a disease of birds! Avian influenza viruses are widely distributed in nature. Wild waterfowl, in particular, harbor many AI viruses because the intestinal epithelium of wild waterfowl has receptors that welcome AI viruses and help them proliferate. Even though the AI viruses are replicating quite happily in the guts, the water birds don't usually get sick. The infected birds continue to move around and as they fly overhead, spread plenty of virus their manner of indiscrete defecation. When avian influenza viruses infect poultry, they can cause disease and if the disease is severe, it is referred to as "highly pathogenic avian influenza" (HPAI).

C = Crossing species boundary

In the last nine years, there have been numerous, but sporadic, instances of HPAI viruses causing sickness and sometimes death in humans. The H5N1 strain has proven to be particularly worrisome, with more than 200 human infections, each of which has been associated with contact with poultry. Why is it that bird flu spreads readily bird to bird and human flu spreads readily human to human, but bird flu does not spread readily to humans?

The receptor that allows the avian virus entry into people is present only in the deepest recesses of the human's pulmonary alveoli. This explains why the number of humans infected to date with H5N1 is relatively low, as successful infection requires that virus make its way deep into the respiratory tract to the alveolar structures. It also explains why the virus is not spread readily from human to human. It could happen, but it would require a massive paroxysmal sneeze or productive coughing from a heavily infected person followed by deep inspirations from nearby susceptible recipients.

We have seen some clusters of human infection, each with attendant concerns that the virus has mutated to allow easier person-to-person spread, but in each instance, the infections have been due to very close contact without any pandemic-presaging mutations occurring.

In addition to the relatively small number of people infected with the avian influenza H5N1 virus, there have also been documented infections in large cats, domestic cats, a dog and a stone marten. All have contracted the disease from infected birds.

D is for disease

In poultry, morbidity and mortality with HPAI are both very high. Once within the body, the virus replicates in endothelium in many organs, often spilling over to affect parenchymal cells as well. Death occurs due to multi-organ failure within two to three days of infection. Post-mortem lesions include edema in the subcutaneous tissues anywhere, but especially neck, and foci of hemorrhage in many locations, most prominently trachea and shanks.

Pathologic examination of humans who have died of disease due to H5N1 demonstrates similar pathologic changes as to what is seen in birds experimentally infected with H5N1. Also, experimental infection of cats yields the same clinical course and pathologic picture.

E for eradication

Outbreaks of HPAI are usually approached through a stamping out policy. The virus spreads readily from bird to bird through any kind of body secretion so an entire house will be affected in short order. Poultry mortality with strains of HPAI approaches 100 percent. It is important to eliminate all infected birds and their contacts in order to keep the disease from spreading.

A vaccine exists for avian influenza and is used in some areas to help with control. Unfortunately, a vaccinated bird could still be infected with the virulent form of HPAI, might not appear sick, but could still shed virus. Consequently, any poultry vaccination campaign needs to be accompanied by strict surveillance and continued biosecurity.

F is for the future

Most scientists believe that it will be difficult to avoid an incursion of the H5N1 virus into North America. Either through illegal movement of poultry or through migratory birds, the virus will undoubtedly hitchhike a ride to enter our 50 states. Within the United States, we have well-developed mechanisms to respond to outbreaks in poultry, and it is likely that these response plans would be implemented immediately and help confine the outbreak.

The greater concern is about the occurrence of a pandemic (that is, an influenza virus that causes disease in people on multiple continents). There is a possibility that the bird flu virus may mutate so that it becomes capable of human-to-human spread. Specifically, it would have to mutate in such a way that the virus could use receptors that are present in the upper respiratory tract of humans (as the human influenza A viruses do currently). It is not possible to quantify such a risk, and estimates vary widely.

If the virus does mutate to allow for human-to-human spread, control is far less certain. In the recent ABC made-for-TV movie, "Fatal Contact: Bird Flu in America", this mutation and spread scenario plays out. The first new cases occur in China, and human-to-human transmission is recognized as reality. When an alarmed American epidemiologist asks the Chinese physician if it is too late for containment, the physician responds, "What do you mean, we lost our chances at containment? We never had any chance of containment." This statement is chilling but accurate. The extensive nature of commerce and international travel dictates there will be rapid and global spread.

G means global

The H5N1 strain of avian influenza has now been diagnosed in birds in at least 50 countries of the world. In each new focus, there is an attempt to control the disease through slaughtering of infected poultry. There is little doubt that any country will be able to escape incursion of this avian virus.

To date, there have been more than 200 laboratory-confirmed human infections in nine countries. More than half of the infected people have died. If there is a mutation to allow for easy transmission among people, every country in the world will definitely be affected.

Hope, with a capital H

The good news is that as a result of aggressive campaigns to destroy affected poultry and undertake effective vaccination campaigns, Southeast Asia, the place where the disease first surfaced, is now reporting that large areas are free of the scourge. Also, recent reports that birds returning to Europe after a winter in Africa are not bringing any virus back with them brings hope that Europe does not face massive reinfection through migratory birds. There is a general acknowledgment that wild birds are not playing a major role in spread and that if illegal poultry movement is better controlled, spread can be minimized further.

Veterinarians also should take pride in international efforts to control this disease. Experts from human medicine, veterinary medicine and the wildlife community, representing multiple countries, all came together in a global and team-oriented approach. This template, with its well-integrated veterinary expertise, will serve us well for the next disease threat. Based on recent history of emerging disease threats, e.g., BSE, Ebola, SARS, the next threat will probably be a zoonotic disease. In each of these cases as well as with avian influenza, a problem surfaced first in animal populations before spreading to humans. There is growing recognition that disease in animals can serve as a harbinger of human infection.

Avian flu in birds might just be the canary in the coal mine and our effective response to the danger hopefully has kept and will continue to keep that threat from spreading into a major human pandemic. Veterinarians provide an absolutely vital link to the health of all populations.

Dr. Brown is professor and coordinator of international activities for the University of Georgia's College of Veterinary Medicine.