Few phenomena in the field of infectious diseases have so captured world attention as avian (bird) influenza. From its onset in 2003, until this writing, only 310 cases were reported, resulting in 189 deaths—all limited to 12 countries. Indeed, during the same period, many times that number had died in those same countries of lightning bolts, jellyfish stings, and judicial beheadings. Not a single tourist has contracted the disease, and none of the thousands of health care workers involved in treatment and control has been infected. The few instances in which more than one family member developed avian influenza have been ascribed to common contact with infected birds, rather than human-to-human spread.
The term “avian influenza” is a misnomer, as virtually all strains (types) of the influenza virus pass through ducks or other birds before emerging into the human population. Influenza strains differ from one another according to the nature of two surface proteins: hemagluttinin (H) and neuraminidase (N). There are 15 subtypes of the H antigen (a substance that induces an immune response).
The first recorded outbreak of influenza occurred in 1580, and an additional 31 pandemics (global epidemics) had been documented as of 2003. Twenty-one to 40 million deaths were estimated for the Spanish flu H1N1 pandemic of 1918–1919. The Asian flu (H2N2, 1957) and Hong Kong flu (H3N2, 1968) pandemics each resulted in one to four million deaths. Excess deaths attributable to influenza in the United States numbered 603,600 during the epidemics of 1918–1919, 1957– 1958 and 1968–1969; and an additional 600,000 were estimated to have died in non-pandemic years during 1957 to 1990.
While most human infection is caused by types H1, H2 and H3, types H5 and H7 are known to be more virulent. In fact, before the current outbreak of H5N1 virus, small clusters of human infection by H7N7, H7N3, and even H5N1 had been reported on persons having close exposure to poultry in a variety of countries. Infections were generally mild, often limited to a mild cough and conjunctivitis (inflammation of the membranes of the eye). Nevertheless, prior outbreaks of H5N1 virus in Hong Kong during 1997–1998 resulted in six deaths. Antibody (a protein produced by the immune system in response to the presence of the specific H5N1 antigen) was demonstrated in 17.2 of poultry workers during the outbreak. Approximately 1.5 million chickens and other birds were slaughtered in attempts to control the virus, but the episode generated only passing interest.
H5N1 mutates rapidly and has a propensity to acquire genes from other animal species. Birds may excrete the virus from the mouth and cloaca (the excretory vent of a bird) for up to ten days. H5N1 virus was found to survive in bird feces for at least 35 days at low temperature (39.2°F, 4°C). At a much higher temperature (98.6°F, 37°C), H5N1 viruses have been shown to survive in fecal samples for 6 days.
The current outbreak began in 2003, when one case of human H5N1 (fatal) was reported in China and 3 (fatal) in Vietnam. The following year, 17 cases (12 fatal) were reported in Thailand, and 29 (20 fatal) in Vietnam. Several asymptomatic (without symptoms) infections were subsequently reported in South Korea. In 2005, 20 cases (13 fatal) were reported in Indonesia, 5 (2 fatal) in Thailand, and 61 (19 fatal) in Vietnam. By the end of 2006, cases were being reported in Azerbaijan, Cambodia, China, Indonesia, Iraq, Turkey, and Africa (Djibouti and Egypt). As of 2007, the list of infected countries has expanded to include Laos and Nigeria.
In addition to human cases, numerous outbreaks limited to wild and domestic birds have been reported in Afghanistan, Albania, Austria, Azerbaijan, Bosnia and Herzegovina, Burkina Faso, Croatia, Cyprus, Czech Republic, Denmark, France, Georgia, Germany, Ghana, Greece, Hungary, India, Iran, Israel, Italy, Ivory Coast, Jordan, Kazakhstan, Kuwait, Malaysia, Mongolia, Myanmar, Netherlands, Niger, Nigeria, Pakistan, Poland, Philippines, Romania, Russian Federation, Saudi Arabia, Scotland, Serbia, Slovakia, Slovenia, Spain, Sudan, Sweden, Switzerland, Ukraine, and the United Kingdom. In other words, the principal mode of spread among countries is in the intestines of migrating wild birds—and not in the potential human airplane passenger.
Perhaps more significantly, H5N1 infection has already appeared in a number of non-avian hosts, including pigs, tigers, leopards, dogs, civet cats and domestic cats, Cynomolgus macques, ferrets, New Zealand white rabbits, leopards, rats, mink, and stone marten. Indeed, infected blow flies (Calliphora nigribarbis) have been identified in the vicinity of poultry infected with H5N1 influenza virus in Japan.
A few words concerning the disease itself. Avian influenza is characterized by fever greater than 100.4°F(38°C), shortness of breath, and cough. The incubation period is two to four days. Some persons have reported sore throat, conjunctivitis, muscle pain, rash, and runny nose. Watery diarrhea or loose stools is noted in approximately 50% of the cases, a symptom that is uncommon in the more familiar forms of influenza. All patients reported to date have presented with significant lymphopenia (diminished concentration of lymphocytes, white blood cells, in the blood) and marked chest x-ray abnormalities consisting of diffuse, multifocal or patchy infiltrates (areas of inflammatory cells, foreign organisms, and cellular debris, often indicating pneumonia). Physical examination reveals the patient to be short of breath, with signs of lung inflammation. Myocardial (heart muscle) and hepatic (liver) dysfunction are also reported. Approximately 60% of patients have died, on an average of 10 days after the onset of symptoms.
WORDS TO KNOW
ANTIBODY: Antibodies, or Y-shaped immunoglobulins, are proteins found in the blood that help to fight against foreign substances called antigens. Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).
ANTIGEN: Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body. While antigens can be the source of infections from pathogenic bacteria and viruses, organic molecules detrimental to the body from internal or environmental sources also act as antigens. Genetic engineering and the use of various mutational mechanisms allow the construction of a vast array of antibodies (each with a unique genetic sequence).
CLOACA: The cavity in to which the in testinal, genital, and urinary tracts open in vertebrates such as fish, reptiles, birds, and some primitive mammals.
HOST: Organism that serves as the habitat for a parasite, or possibly for a symbiont. A host may provide nutrition to the parasite or symbiont, or simply a place in which to live.
PANDEMIC: Pandemic, which means all the people, describes an epidemic that occurs in more than one country or population simultaneously.
STRAIN: A subclass or a specific genetic variation of an organism.
Diagnosis depends on demonstration of the virus or serum antibody toward the virus in specialized laboratories. Because of intense media reporting (and misinformation) a given patient may be reported repeatedly; or a case of unrelated respiratory infection may be reported as “avian influenza.” Thus, only reports issued by qualified centralized laboratories should be considered valid. As of 2007, only four anti-viral agents have been used for the treatment of influenza: Amantadine, Rimantadine, Oseltamivir, and Zanamivir. Although some success has been claimed in the use of Oseltamivir for the treatment of Avian Influenza H5N1, a large controlled clinical trial is not feasible. Vaccines against this strain are under development.
So why has this text devoted precious space to a low incidence, non-contagious disease that primarily affects peripheral Asian communities? The answer might be summed up in three words: potential for spread. We all suffer attacks of influenza, most of us repeatedly throughout our lives. Influenza is one of the most contagious of human diseases, and while rarely fatal, impacts on all of us in terms of numbers incapacitated and requiring medical care. The new avian influenza strain, while limited in time and place, is a very severe disease. The chance of dying of the better-known common strains is lower than one tenth of one percent; but the case-fatality rate for avian influenza is 61%. Thus, the fear of all those who deal with this outbreak is that the virus will one day revert to a contagious form, while retaining its high virulence ability to cause disease. At that point, we could be dealing with millions of cases … of a disease that carries a 61% mortality.
Another disturbing feature of the current outbreak is the age of infected persons. The common epidemic forms of influenza to date have had greatest impact among the elderly, with most deaths occurring in persons over age 65 with underlying heart or lung disease. Ninety percent of patients with the new H5N1 Avian influenza virus have been below age 40, with many deaths reported in children.
Primary source connection
The World Health Organization (WHO) publishes Disease Outbreak News reports to provide timely outbreak information and foster communication among various national and international public health organizations. As an example, the following report outlines WHO recommendations for combating the threat of pandemic Highly Pathogenic Avian Influenza H5N1.
Avian Influenza—Necessary precautions to prevent human infection of H5N1, need for virus sharing
WHO continues to be concerned by the simultaneous outbreaks of Highly Pathogenic Avian Influenza H5N1 in several Asian countries.
While these outbreaks thus far remain restricted to poultry populations, they nevertheless increase the chances of virus transmission and human infection of the disease, as well as the possible emergence of a new influenza virus strain capable of sparking a global pandemic.
In this context, WHO re-emphasizes the necessity of protecting individuals involved in the culling of H5N1-infected poultry. Workers who might be exposed to H5N1-infected poultry should have proper personal protective equipment (i.e. protective clothing, masks and goggles) since there is a high risk of exposure during the slaughtering process.
In addition to the use of personal protective equipment, WHO is recommending:
- To avoid the co-infection of avian and human influenza, which could allow for the emergence of a pandemic influenza virus, all persons involved in mass culling operations, transportation and burial/incineration of carcasses should be vaccinated with the current WHO-recommended influenza vaccine.
- All persons exposed to infected poultry or to farms under suspicion should be under close monitoring by local health authorities. National authorities should also increase their surveillance of any reported clusters of influenza or influenza-like illness.
- Antiviral treatment should be available on an ongoing basis for treatment of a suspected human infection with a Highly Pathogenic Avian Influenza virus. If antivirals are available in sufficient quanti-ties, prophylactic use should be considered.
Please see the full list of WHO's interim recommendations for the protection of persons involved in the mass slaughter of animals potentially infected with Highly Pathogenic Avian Influenza viruses.
WHO is also urging countries to work on standardized procedures for immediate sharing of all avian influenza virus strains responsible for outbreaks with WHO's international network of laboratories.
WHO is depending on the continued collaboration of the national health and agricultural services to establish routine procedures for immediate sharing of avian influenza virus samples. Without such virus samples, WHO will not be in a position to provide proper vaccine prototype strains and related guidance for vaccine producers.
IN CONTEXT: REAL-WORLD RISKS
With regard to human transmission, as of May 2007, the Centers for Disease Control and Prevention (CDC) reports stated: “While there has been some human-to-human spread of H5N1, it has been limited, inefficient and unsustained. For example, in 2004 in Thailand, probable human-to-human spread in a family resulting from prolonged and very close contact between an ill child and her mother was reported. Most recently, in June 2006, World Health Organization (WHO) reported evidence of human-to-human spread in Indonesia. In this situation, 8 people in one family were infected. The first family member is thought to have become ill through contact with infected poultry. This person then infected six family members. One of those six people (a child) then infected another family member (his father). No further spread outside of the exposed family was documented or suspected. Nonetheless, because all influenza viruses have the ability to change, scientists are concerned that H5N1 virus one day could be able to infect humans and spread easily from one person to another. Because these viruses do not commonly infect humans, there is little or no immune protection against them in the human population. If H5N1 virus were to gain the capacity to spread easily from person to person, an influenza pandemic (worldwide outbreak of disease) could begin.”
World Health Organization
WORLD HEALTH ORGANIZATION, EPIDEMIC AND PANDEMIC ALERT AND RESPONSE (EPR). “AVIAN INFLUENZA—NECESSARY PRECAUTIONS TO PREVENT HUMAN INFECTION OF H5N1, NEED FOR VIRUS SHARING.” DISEASE OUTBREAK NEWS. JULY 16, 2004.
See AlsoDeveloping Nations and Drug Delivery; Emerging Infectious Diseases; H5N1; Influenza; Influenza, Tracking Seasonal Influences and Virus Mutation; Influenza Pandemic of 1918; Notifiable Diseases; Pandemic Preparedness; Vaccines and Vaccine Development.
Bethe, Marilyn R. Global Spread of the Avian Flu: Issues And Actions. Hauppauge, NY: Nova Science, 2007.
U.S. Department of Health and Human Services 2006 Guide to Surviving Bird Flu: Common Sense Strategies and Preparedness Plans—Avian Flu and H5N1 Threat. Progressive Management, 2006.
Webster, R.G. and E.J. Walker. “The World is Teetering on the Edge of a Pandemic that Could Kill a Large Fraction of the Human Population.” American Scientist 91 (2003): 122.
Centers for Disease Control and Prevention (CDC).“Avian Influenza (Bird Flu).” <http://www.cdc.gov/flu/avian/> (accessed May 10, 2007).
World Health Organization. “Avian Influenza.” <http://www.who.int/csr/disease/avian_influenza/en/index.html> (accessed May 10, 2007).
Stephen A. Berger