Avian Influenza: The Next Pandemic?

In recent decades, Americans have been subjected to various news reports warning of potential threats to public health due to the emergence of a new “killer flu”. These illnesses always seem to have exotic names and appear to affect only foreign people in distant and far off lands. Through the years we’ve watched as reports of Hong Kong flu, Swine flu, West Nile virus and SARS have flashed across our television screens. Americans viewed with collective horror the epidemiological effects of the dreaded Ebola virus as its story was played to light by Hollywood movie actors in the 1995 thriller “Outbreak”. While these diseases can be devastating, they are typically limited in their spread to either localized regions or certain at risk populations. This is not in a small part due to the prudent reactions of local, national and international healthcare officials who have taken the situations at hand and implemented precautionary health measures to the benefit of all.                                                                                    Source: Centers for Disease Control

What is it, then, that makes Avian Influenza, not even circulating among humans, so different from other potential epidemics? What would prompt entire countries to close their borders to effected countries, like several countries have, or cause the deaths of over 200 million birds due to disease or culling to prevent the disease? What would cause President George Bush to approach Congress with a 7.1 billion dollar plan to prepare for possible outbreaks of an epidemic that doesn’t even exist in a human-to-human mode? There are currently no reports of any humans who have contracted the disease other than direct contact with infected birds. And scientists have known about this H5N1 strain for eight years. Why all the publicity now? The answer may best be explained by analyzing the nature and evolution of the familiar seasonal influenza virus, or what we know as the common flu.

Seasonal Influenza - A Flu Primer. Each year most Americans are content in taking routine precautions against garden variety flu strains which plague us during flu season, one which often begins in October and ends as late as April. This time of year thousands of us stock up on supplies of vitamins and flu medicines, try to exercise, eat well and get plenty of rest to support our immune systems, and otherwise make ready for the inevitable spread of “the bug”.

 And each season despite our best efforts, anywhere from five to twenty percent of the population will eventually succumb to the achy, feverish, laying-in-bed-with-chills type experience of uncomplicated influenza. In spite of their best efforts, over 200,000 Americans are hospitalized each year from the illness and over 36,000 will die from the disease, mostly from complications like pneumonia, striking mainly elderly individuals and those with underlying health conditions.  

Flu symptoms are caused by viruses that infect the respiratory tract. Two main types of influenza viruses -- influenza type A and influenza type B -- cause the outbreaks and epidemics of respiratory illness that occur almost every winter. Types A and B are constantly changing, each with numerous subtypes reoccurring regularly. Hence the reason we need to get our flu shots updated each year.  

The influenza virus is spread from person to person primarily through coughing and sneezing. Less often, it is spread by touching a surface that has live virus on it, like shaking a hand or touching a phone or faucet handle contaminated with the virus, then touching the nose, mouth or eyes. Droplets of infected airborne pathogens are breathed in and the virus is passed through the nasal passages, throat, bronchial tubes, and lungs.

The typical incubation period is one to four days, (two being the average). Symptoms of the common flu can be quite abrupt, often beginning with fever lasting a day or two. Somewhere between day 2 and day 4 of the illness, the achiness subsides and respiratory symptoms begin to increase. Since influenza is a virus, it can’t be treated with antibiotics.The virus can settle anywhere in the respiratory tract, producing symptoms of a cold, croup, sore throat, bronchitis, sinus or ear infections, or pneumonia. Nasal discharge (runny nose) and sneezing are common.

Type A Influenza               
Source: Centers for Disease Control

These symptoms (except the cough) usually disappear within 4-7 days. Sometimes, the fever returns. Cough and tiredness can last for weeks after the rest of the illness is over. Doctors can perform tests to see if you have the flu if you are in the first few days of your illness.  

Influenza viruses are highly contagious and adults are typically infectious one to five days from onset. Children can shed virus for several days and can remain infectious for over ten days beyond, while severely immunocompromised persons can shed the virus for weeks or months. Because the flu is airborne, is highly communicable and has a short incubation period, it often strikes a community all at once, creating a cluster of school or work absences. That’s why within 2 or 3 weeks of its arrival in a school, much of the classroom has had it.

Quick Change Artist: Influenza’s Antigenic Drift & Shift. Influenza has been described by science as the classic emerging and reemerging infectious disease. That’s because the virus replicates as it enters a host cell then infects by reproducing its own genetic material, using the host cell’s resources to produce hundreds of copies of its own hereditary matter, or Ribonucleic Acid (RNA). In this way, the virus takes over the cell's productivity. Now, instead of producing only new cellular material, the cell produces hundreds of new virus particles; ones which are eventually released from the cell and drift off in search of their own host cell to pirate.

If the virus would make a perfect copy of itself as it reproduced, there’d be no problem for science to determine the RNA and manufacture a potent vaccine. However, influenza viruses are constantly making small and permanent mutations as they replicate, a process known as “antigenic drift”. This can produce new strains that may not be recognized by the body’s immune system and can even cause re-infection.

Hence the reason you need a new flu vaccine every year, and the reason that despite a vaccination, you can still come down with the flu. Each year, the flu vaccine companies make their best estimate as to which strains already circulating will be the ones that will predominant during the flu season.

Human beings are not the only species susceptible to influenza. Birds, dogs, pigs, horses, seals - even tigers and whales - are among the animals prone to infections from influenza. And normally, animal viruses do not infect humans.

 But what would happen if there were a more abrupt mutation in a Type A influenza virus, known as “antigenic shift”, which would allow genetic materials from two different animal species to swap or re-assort? The result would be a novel, never-before-seen subtype from both parent viruses. One to which no person alive today has a pre-existing immunological protection against.

 According to the World Health Organization, pandemics arise when such a novel influenza virus emerges, infects humans, and spreads efficiently and sustainably among them. This type of mutation is a rare but recurrent event, occurring naturally two to three times a century. Once such an event starts and reaches a certain level of local or regional spread, continued worldwide spread is considered inevitable Influenza pandemics (worldwide epidemics) have been responsible for the deaths of millions of people throughout history.

Avian Influenza. Usually, “avian influenza virus” refers to influenza A viruses found chiefly in birds. Migratory waterfowl – most notably wild ducks – are the natural reservoir of all fifteen subtypes of influenza viruses known to infect birds. They are also the most resistant to infection. Contact with wild migratory waterfowl, whether indirect or direct, has been implicated as a frequent cause of epidemics in domestic flocks.

Avian influenza viruses can be classified into two forms: "low pathogenic" and "highly pathogenic" - based on the severity of the illness they cause in poultry. The low pathogenic form usually causes only mild symptoms (such as ruffled feathers and a drop in egg production) and may even go undetected. However, the highly pathogenic form spreads more rapidly through flocks of poultry.

Among birds, this form may cause disease that affects multiple internal organs and has a mortality rate that can reach 90-100%, often within 48 hours. Influenza viruses of the highly pathogenic form are caused by viruses of the subtype H5 or H7.

Domestic poultry, including chickens and turkeys, are particularly susceptible to epidemics of rapidly fatal influenza. Apart from being highly contagious, avian influenza viruses are readily transmitted from farm to farm by mechanical means, such as contaminated equipment, vehicles, feed, cages, or clothing. Infected birds shed flu virus in their saliva, nasal secretions and feces. These highly pathogenic viruses can survive for long periods in the environment, especially when temperatures are low.

Colorized Transmission Electron Micrograph of Avian Influenza A H5N1
Viruses Grown in MDCK Cells The viruses are gold, and the MDCK cells
are green. (Photo: CDC/C. Goldsmith, J. Katz, and S. Zaki)

Subtype H5N1 – A Novel Mutation. In 1997 epidemiologists and public health officials from around the world got their first glimpse of an entirely new variety of influenza which caused the deaths of six people in Hong Kong . Known simply as subtype H5N1 for the surface proteins which the virus carries, the new strain had only ever previously been observed in birds.

This was the first documented case of an influenza virus jumping directly from chickens to people. Public health authorities responded by ordering the slaughter of more than 1.4 million live poultry – every duck, goose and chicken in Hong Kong - to prevent further spread to humans.

Since then, the H5N1 strain of the bird flu has slowly spread through bird populations in Asia , Europe and now parts of the Middle East and Africa causing the largest and most severe outbreaks in poultry on record. With its spread, there have been over 169 confirmed cases of H5N1 virus in humans from seven different countries ( Vietnam , Thailand , Indonesia , China , Cambodia , and within the past two months, Turkey and Iraq ). Over half of these victims have died (53%). In most instances, the influenza struck people who had direct or close contact with infected poultry or contaminated surfaces; however, in a few instances human-to-human spread of H5N1 has occurred.

Samples obtained from the most recent victims in Turkey analyzed at the National Institute of Medical Research in London show that H5N1 has undergone a slight mutation which makes it more likely to attach to human cells as well as chicken cells. Latest cases in northern Iraq have officials concerned that the virus may also now be spreading undetected among domestic fowl, as there were no confirmed reports of sick birds before the human cases.

In chickens, H5N1 seems to spread to all internal organs, but in humans it appears to devastate the lungs in particular. Researchers at the University of Hong Kong have found that a victim’s own immune system may be part of the problem. It reacts to the virus with a flood of chemical messengers that draw white-blood cells into the lungs, where they trigger a massive inflammatory reaction. This may explain why most of the disease fatalities were previously healthy children or young adults.

To date, H5N1 viruses have not been associated with the type of community-wide outbreaks that are characteristic of human influenza. Among scientists who feel a pandemic is inevitable is Dr. Jai P. Narain, Director of WHO's communicable diseases department, who states "We may be at almost the last stage before the pandemic virus may emerge. Whether the avian influenza pandemic will occur, that is not the question any more, [but] as to when the pandemic will occur."

Experts fear the virus, which mostly affects birds, could mutate to a form that can be easily transmitted between people — sparking a pandemic that could kill millions. Theoretically, many different avian influenza viruses have the potential to evolve into a pandemic virus. But H5N1 is of particular concern for several reasons. First, the subtype has already inherited several ugly characteristics that make it quite similar to a virus that triggered the worst influenza pandemic in human history which occurred early last century.  

Known as the Spanish Flu, the virus struck in late winter 1918; it quickly spread around the globe, infecting nearly one third of the world’s population with a mortality rate of 2.5%, and killed 20 to 40 million people by the spring of 1919. Only American Samoa and parts of Iceland were spared an outbreak.

Although this pandemic was considered exceptional, in October 2005, two teams of scientists were able to determine that four of the eight genes in the H5N1 strain contain mutations seen  in the deadly Spanish flu virus 88 years ago.
The researchers analyzed autopsy tissue from US Army soldiers who died from the flu in 1918, and removed lung tissue from the frozen body of an exhumed flu victim from an Alaskan village wherein 85 percent of the adult population died in just five days and were buried in the ice the same year. Analysis of all eight genes showed the Spanish flu came directly from a bird virus and moved into humans after slowly mutating. The H5N1 has adapted itself to jump from birds to people in at least 169 documented cases.  

1918: Flu victims crowd into an emergency hospital in Kansas
National Museum of Health & Medicine

Historic Chart Showing Mortality Rates in America and Europe during 1918 and 1919

(Photo: Image “Reeve 3143,” National Museum of Health and Medicine, Armed Forces Institute of Pathology , Washington , D.C. )

Second, H5N1 is particularly virulent, killing close to 100 percent of susceptible birds and more than half the people who have been infected. The virus appears to be spreading, including most recently from Asia to Europe to the Middle East and now to Africa ; it has killed tens of millions of birds in the countries it infects. Although the bird flu virus is extremely deadly to humans, it's likely that it would become less virulent if it adapted for human-to-human spread. But no will no for certain until it does.

Third, H5N1 mutates rapidly and has a documented propensity to acquire genes from viruses infecting other animal species. It seems to be affecting more and more species, including cats, which usually aren't susceptible to bird flu, and pigs, which traditionally have been a species that acts as a "mixing bowl" for viruses transmitted between birds and people.

Pandemic Planning. Experts from around the world are watching the H5N1 situation very closely and are preparing for the possibility that the virus may begin to spread more easily and widely from person to person. While neither the timing nor the severity of the next pandemic can be predicted, evidence that the virus is now endemic in bird populations means that the present level of risk will not be easily diminished. In a recent statement, Dr. David Nabarro, who heads the UN drive to contain the virus admits, "Every 30 years, we do get massive pandemics of human influenza. It's likely that the next pandemic will be caused by a version of bird flu."

Theoretically, the H5N1 bird flu virus could become a pandemic flu virus overnight. Per Nabarro, only two more mutations are needed for it to become easily transmissible among humans. These mutations could occur either at random or if the virus mixes its DNA with a human flu virus inside a pig or a human. “"I wake up every morning thinking that today could be the day that I will see a report about a strange case of bird flu among humans." Nabarro has been warning governments around the world to prepare for a pandemic “…as if it were going to start tomorrow.”

 According to the World Health Organization (WHO), once a fully contagious virus emerges, its global spread is considered inevitable, especially if it coincides with a seasonal outbreak of influenza. The WHO lists six stages leading from the detection of a new flu virus in animals to a global human flu pandemic. So far, the H5N1 bird flu has been at stage 4: small, highly localized clusters of human infections. At this stage, the virus cannot spread easily from person to person. The plan for containment involves a rapid deployment of epidemiologists and trained medical investigators to the scene of the first reports of the virus spreading between humans, and the use of anti-virals and antibiotics. Quarantine would be part of the plan.

 The WHO believes a new strain will probably emerge in a rural area and spread from its first human victim into a family and a community. Past pandemics have spread globally in two and sometimes three waves. Not all parts of the world or a single country are expected to be severely affected at the same time. Countries might, through measures such as border closures and travel restrictions, delay arrival of the virus, but cannot stop it. The pandemics of the previous century encircled the globe in 6 to 9 months, even when most international travel was by ship. With the speed and volume of international air travel today, experts fear the virus could spread more rapidly, possibly reaching all continents in less than 3 months.

Should Floridians be concerned? Since there have been no cases of the H5N1 virus anywhere in the United States , the current risk for outbreak is low. Florida has a very strong and robust surveillance system on the alert to potential bird flu, including the use of “sentinel physicians” assigned to report any unusual occurrences of avian flu to the CDC and to the Florida Department of Health. The CDC has increased its personnel at the Miami Quarantine Station to provide services to the international ports of entry in Florida . And while there is no commercially available vaccine to protect humans against the H5N1 virus that is being seen in Asia , Europe , parts of the Middle East and Africa , development efforts are currently taking place. The state has tested its ability to provide mass inoculations should the need arise, and those tests have been very successful.

The Florida Department of Agriculture and Consumer Services and The Fish and Wildlife Conservation Commission have been working together to provide bird surveillance services both in domestic poultry and in the wild. On a national level, the US is currently stockpiling anti-viral medications and in Atlanta, the CDC recently published an 18 page pandemic planning guide (January 2006) for individuals and families in anticipation of a global pandemic which may be helpful to you and your family in the event of a pandemic. For copies of this article and a link to the CDC’s Pandemic Planning Guide, visit our website at http://www.MyMDNow.com/bird.

Dr. Peter Lamelas is Residency trained in Internal Medicine and Board Certified in Emergency Medicine (ABPS). He was Medical Director of the Emergency Department of Columbia Hospital in   West Palm Beach   for 17 years and is a long standing member of the    American   College   of Emergency Physicians. In 2001, he received a gubernatorial appointment to serve on the State of   Florida   ’s Board of Medicine. In 1993 he earned his Masters Degree in Business Administration from   Nova   Southeastern   University   , and on  February 5, 2005 realized a long term dream of building, owning and operating his own highest quality urgent care center in suburban Lake Worth ,  Florida .