Most of Asia and parts of Europe, the Middle East, and Africa, are currently experiencing expanding outbreaks of an avian influenza that is decimating domestic fowl populations, infecting and killing people that have unprotected contact with the infected birds, and causing genuine concern in the medical and scientific communities throughout the world. The reason for the multi-national concern is that a possible mutation of this avian virus will result in an influenza pandemic that could result in millions of deaths worldwide!
Although no outbreaks of this particular avian flu virus have been reported on the North or South American continents as yet, this persistent and deadly virus, commonly called “Bird Flu”, has already spread across much of the globe. This latest ‘Type A’ flu virus, identified by science labs as H5N1, is carried by migratory wild birds that have built-up immunity to its effects. Domestic birds (chickens, turkeys, ducks & geese) contract the virus from the feces and infected secretions of the wild fowl and usually die within days. Well over 100 million birds either died or were destroyed in Asia alone by preventative culling of flocks in the outbreak areas. So far 39 countries have experienced bird flu outbreaks since December 2003 and there have been over 3,000 separate H5N1 outbreaks. The economic impact has been staggering for many countries, devastating for thousands of commercial poultry farms and destroyed hundreds of thousands of family ‘back-yard’ poultry flocks.
H5N1 is not considered a severe threat to humans in its present form. However, people can contract the bird flu virus and, from the 186 confirmed cases to date, 105 have died! Eight of those 39 countries with H5N1 avian flu outbreaks have reported laboratory confirmed human infections. [That number will unfortunately rise before this course is published. Many other severe respiratory infections are suspected to be H5N1 but have not been confirmed by laboratory testing.] The United Nation’s World Health Organization (WHO) maintains an online cumulative data chart of all confirmed cases of infection and fatalities.
As alarming and regrettable as those statistics are, the real fear is that the H5N1 virus will mutate into a deadly human-to-human type and cause another pandemic that could rival the catastrophic 40-50 million deaths in 1918.
H5N1 was first identified in Hong Kong during an outbreak of bird influenza in 1997. At that time it was thought that avian flu virus was only a danger to domestic poultry. But, as soon as human infection began occurring (18 contracted the bird flu and 6 have died), the health authorities there were wise enough to recognize the imminent danger and convince government officials to implement drastic preventative measures. Chickens, ducks, and other edible poultry were banned from export. Travel advisories were issued. Anyone exhibiting signs of the flu was quarantined until a health check was performed. All domestic poultry on the island was culled and destroyed. An estimated 1.5 million birds were destroyed in three days. Those measures were very costly to the economy of Hong Kong and instilled a near-panic among its residents, but the H5N1 virus was stopped. For a time…
Avian Influenza Viral Types, Subtypes and Strains
Three types of viruses are known to cause influenza and are identified as Type A, Type B, and Type C. Influenza A viruses are additionally classified as a subtype which is determined by the two main surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). All flu viruses can infect humans but types B and C are less life-threatening to humans and do not have any subtype identification. Type A subtypes and B viruses are also classified by strains. Influenza Type A
Avian influenza A virus strains are additionally identified as “high pathogenic” (HPAI) or “low pathogenic” (LPAI). This is determined by molecular genetic and pathogenesis criteria that requires specific laboratory testing. Most Type A viruses are LPAI and generally cause only minor disease in domestic poultry. HPAI viruses, however, usually cause acute illness and death in large numbers of domestic birds. Those are the general ‘rules’ but A viruses continue to make surprising changes. Some LPAI avian infections have evolved into HPAI viruses and, in some recent testing, the HPAI H5N1 strain did not infect or cause any illness in some domestic poultry. Subtypes H5 and H7 are usually HPAI and human infection can range from mild flu symptoms (H7N3, H7N7) to severe symptoms and death (H5N1, H7N7). Human infection by LPAI viruses (H7N2, H7N7, H9N2) can occur but with relatively mild symptoms. You may note that H7N7 is a ‘swing’ strain; usually a mild-to-moderate LPAI, but one that can mutate to a fatal HPAI.
Another factor that complicates avian viral classification and control is its ability to change genetic coding via antigenic drift and antigenic shift. Antigenic ‘drift’ are small, gradual changes by point mutations in the main surface proteins hemagglutinin and neuraminidase. These minor drifts occur continuously in Type A and B viruses. That factor negates the possibility of developing a vaccine that remains effective for more than one flu season.
Antigenic ‘shift’ occurs only with Type A viruses. Such a shift in the genetic coding is not commonplace but causes major problems when it does occur. The result is a sudden, drastic change to a new influenza A subtype that is largely unaffected by current vaccines or antiviral medications. This can happen by direct animal-to-human transmission or, more likely, by a mixing of human influenza A with avian influenza A viral genes in the same host to create a new human influenza A subtype. This is a process known as genetic reassortment. This type of mutation is the main concern of health officials around the world for it ushers in the possibility of an influenza pandemic. Modern research indicates that it was a ‘new’ avian influenza A virus that caused the flu pandemic of 1918 which killed 40+ million humans worldwide. The flu type that year was H1N1, which is now one of our regular ‘seasonal’ flu types.3 Seasonal influenza deaths still number in the thousands each year but, due to tailored vaccines and antiviral medications, they no longer become pandemic. Seasonal flu outbreaks usually infect 5-10% of the population, whereas pandemics can infect 25% or more and are considerably more virulent.
For a pandemic to occur, three conditions must be met:
- A new influenza A subtype is introduced into the human community.
- The viral infection results in severe illness or death to the human host.
- The new flu subtype passes easily from person to person.
Other influenza pandemics in the 20th century were H2N2 in 1957, which killed a million people worldwide, and H3N2 infections in 1968, which also resulted in a million human fatalities.
In a recent interview with health reporter Caroline Ryan for BBC News, England’s Chief Medical Officer, Sir Liam Donaldson, echoed the feelings of many health officials around the world by stating that H5N1 was the most likely culprit for creating a pandemic strain but that it was not the only candidate.5 The possibility that any of the current avian type A ‘H’ strains could undergo genetic reassortment into a deadly human-to-human flu pandemic is certainly cause for concern. That is why the World Health Organization (WHO) and national health agencies worldwide are trying to closely monitor any new bird flu outbreaks and carefully examine the type of transmission of any human infections. Subtypes Migratory wild birds are the natural carriers of the influenza type A viruses. They can infect poultry, pigs, horses, cats (large & small), dogs, other birds, humans, and other mammals.2 It is the subtype and strain that identifies which grouping is more likely for infection and its consequences. The two surface proteins hemagglutinin (HA) and neuraminidase (NA) are used in combination with numbers to name the various subtypes. There are 16 known HA subtypes and 9 known NA subtypes. Only a few flu subtypes (such as H1N1, H1N2, and H3N2) are human ‘seasonal’ flu types currently in circulation.
Birds are only infected by influenza type A viruses (no types B or C) but are susceptible to infection by all of the subtypes. The influenza A subtypes that normally infect birds are considerably different genetically from those that infect both humans and birds.
Several subtypes that are known to infect both birds and humans are the H5, H7, and H9 strains.
Influenza A H5 – Nine possible subtypes of H5 are known. The HPAI (high pathogenic) H5N1 that is presently causing such concern has an unusually high mortality rate of about 50% of the infection cases to date. For several reasons (discussed later), it is considered the most likely avian influenza virus that could undergo genetic reassortment and become a new human-to-human subtype that could cause an influenza pandemic.
Influenza A H7 – Nine possible subtypes of H7 are also known. Human infection by H7 is very unusual but can occur by direct contact with infected fowl. The H7 virus can range from LPAI, with symptoms of upper respiratory infection and/or conjunctivitis (eye infection), to HPAI with possible severe and fatal illness.
Influenza A H9 – Again there are nine possible subtypes but H9 has only been reported as a low pathogenic and rarely infects humans. Influenza Type B
Normally Type B flu viruses are only found in humans and are not classified into subtypes. B viruses can cause severe illness and death but are typically associated with less severe epidemics than the type A viruses. No type B virus has caused a pandemic. Flu types B and C are primarily childhood infections.
Influenza Type C
Type C flu viruses only cause mild sickness in people, mostly children, and do not cause widespread outbreaks such as an epidemic or pandemic. There are no subtype classifications.
Both influenza B viruses and subtypes of influenza A virus are classified further by strains when antigenic drift makes a notable change in the original viral structure. Antibody protection developed by vaccination or infection against an older strain may not ward off infection from the new strain. For this reason, influenza vaccine has to be updated as the change occurs. Last year’s vaccine is likely to prove ineffective so the pharmaceutical industry and viral health experts have to keep monitoring the antigenic drift of the influenza viruses and adjust each year’s flu shot to meet the changing demand. It is a ‘best guess’ situation that is based on extensive research, testing, and evaluation of reports and samples from various countries and labs around the world.
North American Avian Influenza Outbreaks
As yet the highly pathogenic H5N1 virus has not spread to North or South America but there have been outbreaks of other, less deadly, avian influenza viral infections among poultry flocks in Canada and the US. Transmission to Humans
H7N3 in Canada – 2004
In February 2004, an outbreak of avian influenza A (H7N3) in poultry occurred in the Fraser Valley region of British Columbia. Culling operations and other measures were performed in an effort to control the spread of the virus. Health Canada reported two cases of laboratory-confirmed influenza A (H7): one in a person involved in culling operations and the other in a poultry worker who had close contact with the infected birds. Both patients developed conjunctivitis (eye infection) and other flu-like symptoms but recovered after treatment with the antiviral medication oseltamivir.
Those were the only laboratory-confirmed cases of avian influenza A (H7) in humans during this outbreak in Canada but several other poultry workers exhibited conjunctivitis and/or upper respiratory symptoms after having contact with poultry. Use of personal protective equipment (PPEs) is mandatory for all persons involved in culling activities, and compliance with prescribed safety measures is monitored. There was no evidence of person-to-person transmission of avian influenza from this outbreak.
H7N2 in New York – 2003
In November 2003, a patient with other serious medical conditions was admitted to a hospital in New York with respiratory symptoms. One of the initial laboratory tests identified an influenza A virus that was thought to be H1N1. Following treatment for multiple complications, the patient recovered and went home after a few weeks. Subsequent testing conducted in March showed that the patient had been infected with an H7N2 avian influenza A virus. Recent Poultry Outbreaks in the US With No Transmission to Humans
H5N2 in Texas – 2004
In February 2004, an outbreak of highly pathogenic avian influenza (HPAI) A (H5N2) was detected and reported in a flock of 7,000 chickens in south-central Texas. This was the first outbreak of a high pathogenic A virus in the United States in 20 years.
H7N2 in Delaware, New Jersey and Maryland – 2004
Also in February 2004, an outbreak of low pathogenic avian influenza (LPAI) A (H7N2) was reported on two chicken farms in Delaware and in four live bird markets in New Jersey that had been supplied by the farms. In March 2004, surveillance samples from a flock of chickens in Maryland tested positive for LPAI H7N2. It is likely that this was the same strain.
Those limited avian influenza poultry infections and minor transmissions to humans pale into insignificance when compared with what is currently taking place in Asia, much of Europe, and just beginning in Africa.
The Ongoing Global Spread of H5N1
Human cases: laboratory confirmed since December 2003
Most of the world is now on alert for potential outbreaks of the lethal strain of bird flu that has become the major avian killer in South East Asia. Adding in the 2005-2006 spread into parts of Europe, the Middle East, and Africa, an estimated 140 million birds have died or had to be destroyed.
There have now been outbreaks in 39 countries since the H5N1 strain began to take hold in Asia in 2003, spread into Europe during the second half of 2005, and then was discovered in 22 new countries in Jan-Mar 2006. It moved into Turkey and Iraq in January, 2006 and by mid-February, 2006 had been confirmed in Nigeria, Italy, Greece, Azerbaijan, Bulgaria, Slovakia, Austria, and Germany. Poultry deaths in Niger are suspected H5N1 incidents but have not been confirmed and it is likely that other African nations as well as other Middle Eastern and European Union countries will soon be victims of this rapidly spreading epizootic. It is by far the most prolific killer of poultry in recorded history. And, as already noted, it is also believed to be the most likely subtype H virus to mutate or evolve into a human-to-human influenza strain that could cause the next pandemic.
*Note: Laos, Japan, and South Korea had isolated outbreaks in the 2003/2004 “flu season” but have reported no reoccurrences and are thought to be disease free in early 2006.
H5N1 is a subtype of avian influenza Type A viruses. Migratory wild birds, primarily waterfowl, are the natural hosts of the virus, thus the name avian influenza or “bird flu”. Infected wild birds generally exhibit little or no ill effects from H5N1 but spread the virus to domesticated flocks via saliva, nasal secretions, and feces. Domesticated birds become infected when they have contact with contaminated excretions. Many other avian influenza subtypes also cause infection in domesticated fowl but are low pathogenic with resulting mild symptoms, such as ruffled feathers and low egg production. H5N1 viruses, however, have caused severe and fatal disease among domesticated poultry and have even begun to kill other species of wild birds.
Highly pathogenic avian flu virus was first identified in Italy in 1878 and later became known as the “chicken Ebola” due to the massive internal hemorrhaging of organs and tissue, other than the respiratory tract. Nearly all H5N1 outbreaks show a rapid progression of severe illness, are highly contagious to the rest of the flock, and can have a mortality rate of 90-100% in 48 hours.
When H5N1 is established in domestic poultry, it is a highly contagious disease and wild birds are no longer an essential ingredient for spread. Infected poultry excrete virus in high concentration in their feces and also in nasal and ocular discharges. Once introduced into a flock, the virus is spread from flock to flock by normal poultry enterprise involving the movement of infected birds, contaminated equipment, egg flats, feed trucks, and boots & clothing of service crews.
All outbreaks of the highly pathogenic forms of avian influenza have been identified as viruses of the H5 and H7 subtypes. These HPAI viruses have a unique genetic composition, a distinctive set of basic amino acids in the cleavage site of the HA. This distinguishes them from all other avian influenza viruses and is associated with their exceptional virulence. Not all viral strains of the H5 and H7 subtypes are highly pathogenic, but most are thought to have the potential to become so. Recent studies have shown that LPAI H5 & H7 viruses can mutate to HPAI after the initial infection as a low pathogenic.
The H5N1 virus is basically a bird disease and does not typically infect humans. But, in 1997, the first instance of direct bird-to-human infection was documented during the outbreak of avian influenza among poultry in Hong Kong. Health authorities there reacted quickly and aggressively but six of the 18 cases of human infection resulted in fatalities. No further outbreaks of H5N1 infection, in poultry or humans, were reported until 2003.
In February 2003, two Hong Kong family members that had recently returned from a visit to mainland China were diagnosed with H5N1 infection. One recovered but the other died. Another relative where they had visited died of a respiratory illness but was not tested. An unreported poultry outbreak in that area is suspected but the Chinese health authorities either didn’t know of it or were reluctant, at that time, to make it public. There was no further spread of the H5N1 infection and the mode of transmission is still unknown. Currently, China appears to be making full disclosure of H5N1 infections in wild birds, domestic flocks, and people. Chinese health authorities have reported to the WHO, in October 2005, that they have an emergency plan with four levels of alert in place, have developed a vaccine to prevent human infection, have begun stockpiling anti-viral drugs, and have established closer links between health & agriculture ministries to fight bird flu outbreaks.
H5N1 Poultry Outbreaks and Human Infections
First Wave — 2003-2004
During late 2003 and early 2004, outbreaks of highly pathogenic bird flu (H5N1) occurred among poultry in eight countries in Asia: Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand, and Viet Nam. At that time, an estimated 100 million birds either died from the infection or were destroyed in an attempt to prevent further spread of the disease.
From December 30, 2003 to March 17, 2004, 12 confirmed human cases of avian influenza A (H5N1) were reported in Thailand (8 deaths) and 23 in Viet Nam (16 deaths). By late February 2004, however, the number of new human H5N1 cases being reported in Thailand and Vietnam slowed and then stopped. By late March, with the flu ‘season’ nearing an end and no new outbreaks, several Asian countries were eager to report that the H5N1 outbreaks among poultry had been contained and human infections were no longer a threat. Second Wave — 2004 – Outbreak Spreads
However, in late June 2004, new outbreaks of the deadly H5N1 infection among poultry were again being reported by many of the countries in Asia: Cambodia, China, Indonesia, Malaysia, Thailand, and Vietnam. From July-October 2004, Thailand suffered four fatalities from five cases of H5N1 infection and Viet Nam had four cases, all fatal. In addition to large poultry losses throughout Asia, it was discovered that H5N1 can infect pigs (China), domestic ducks and cats (Thailand), zoo tigers and leopards (Thailand; the big cats were fed chicken carcasses), and H5N1 was becoming more lethal to many of its wild bird hosts.
Third Wave — December 2004 – February 2006
Poultry outbreaks begin anew in December 2004 in Indonesia, Thailand, and Viet Nam with unconfirmed but possible infections in Cambodia and Laos. Viet Nam reported a new human infection on 30 December and two additional cases on January 6, 2005. A little over a week later that number was up to six and sporadic cases of human infection in Viet Nam continued in 2005 making it the hardest hit (61 cases/19 fatalities) of all the Asian countries.
H5N1 Human Infection Spread
On February 2, 2005, the first of four human cases of H5N1 infection from Cambodia was reported. All four proved fatal but there have been no additional human cases since then.
Of particular concern was the unprecedented demise of over 6,000 wild birds, of different species, at the Qinghai Lake nature reserve in central China in late April 2005. Wild birds rarely die from H5N1 infection and usually are discovered in the vicinity of a severe poultry outbreak. Subsequent research showed that transmission of this highly pathogenic strain of H5N1 was from migratory geese which are now spreading it along their established flight routes. (The virus causing the two recent human deaths in Turkey were almost identical to the virus examined from the dead migratory birds at Qinghai Lake.2)
By June 2005, additional H5N1 poultry outbreaks began occurring in China, Kazakhstan, Romania, Russia, Turkey, and Ukraine. China, Croatia, Mongolia, and Romania also reported fatal outbreaks of H5N1 in wild, migratory birds during this period.
On July 21, 2005, the first human case of H5N1 in Indonesia was reported. Indonesia continued to report human cases in August, September, October, November, and December 2005; a total of 17 in less than six months and 11 resulted in death.
Thailand reported new human cases of H5N1 in October, November, and December 2005, and Viet Nam reported new human cases in November 2005.
China reported that country’s first confirmed human cases in November 2005 (excluding the 1997 Hong Kong outbreak) and has continued to report human cases in December 2005 and January 2006. Turkey reported their first confirmed human cases on January 5, 2006 and reported two additional confirmed human cases two days later. An additional 10 cases of the H5 subtype of avian flu in Turkey have now been tested and confirmed as the H5N1 strain.
Iraq became the seventh nation to suffer poultry and human H5N1 cases when two fatalities were confirmed on January 30th by a CDC Clinician Communication Update with information from the WHO.1 The first case was a 15-year-old girl who died on 17 January of severe respiratory infection. Her 39-year-old uncle, who cared for the girl, became ill on January 24th and died on January 27th. The young girl reportedly had frequent direct contact with the family’s chicken flock but the source of the uncle’s infection is still unknown, although it could have been a limited human-to-human transmission. A 54-year-old woman from the same area of northern Iraq (Sulaimaniyah) is also hospitalized with similar symptoms but the H5N1 viral strain has not been confirmed as yet.
Cumulative Number of Human Cases / Deaths Reported to the World Health Organization by Date
When this beginning development of this course in early January 2006, there were only 17 countries with confirmed H5N1 outbreaks. New outbreaks in an additional 22 countries in less than three months is extremely alarming. Such a rapid spread and the increasing virulence of H5N1 seem to be confirming the fears of the world’s health authorities and disease experts that this “bird flu” epizootic might evolve into the next human pandemic. H5N1 already meets two of the three requirements of a pandemic. And, as human infections increase, so does the possibility of a genetic shift or genetic reassortment into a new human-to-human viral strain with effective and sustained human infection.
On February 8, 2006, a new country and continent (Africa), was included in the listing of confirmed cases of H5N1 infection in domestic poultry. The WHO announced that samples from sick and dead poultry at a large commercial bird market in Kaduna State, northern Nigeria, have been identified with HPAI H5N1. No cases of human infection have been reported yet but there have been untested cases of poultry deaths in other markets and farms, plus some in the neighboring province of Kana. One commercial egg producing chicken farm reported the death of 20,000 birds (80% of the stock) within five days from the first signs of infection. Recent poultry deaths in neighboring Niger are also suspected to be from H5N1 infection.
One troubling report stated that untrained and blood-splattered workers were culling the infected birds with machetes and tossing the carcasses with bare hands into the fire. Their only viral protection was a surgical mask, so it is very likely that human infection reports will be forthcoming. (CNN onsite field report, February 10, 2006.) Even more alarming were televised reports from that area showing neighborhood youths climbing into the culling pits of infected chickens and emerging with their hands full of dead birds to take home for consumption. A WHO Advisory Team has been dispatched to evaluate the situation and assist the local authorities. The cause of this latest outbreak is still unknown but that area of Nigeria is in the proximity of a migratory route of several species of wild birds from central Asia.
Then, on February 11, 2006, news reports by CNN, BBC, and AFP announced that confirmed H5N1 wild bird infections (swans) were being reported by authorities in Azerbaijan, Bulgaria, Greece, and Italy. The World Health Organization has now confirmed those reports and infected swans have now been identified in Slovakia (February 12), plus Iran, Austria, and Germany (February 14). Meanwhile, on February 13th, China reported its 12th human infection and 8th fatality and Indonesia reported its 25th human case and 18th fatality.
On February 17, 2006, Egypt confirms outbreaks of H5N1 in domestic poultry and Iraq reports a second human case. On the 18th India confirms an outbreak in domestic poultry and the next day a wild duck is confirmed to have died from H5N1 in France.
On February 21st, Hungary reports confirmed H5N1 in wild swans and Malaysia suffers an outbreak in free-range poultry, signaling a return of the virus to that country which had been free of bird flu reports since January, 2005. On February 25th, Slovakia and Bosnia-Herzegovina confirm H5N1 in wild swans and France becomes the first European Union country to confirm an outbreak in domestic turkeys. On the 27th, Georgia confirms an outbreak in wild swans and Niger confirms the H5N1 in domestic poultry. Germany confirms the virus in a dead domestic cat on the final day of the month.
The first week of March is equally as busy and alarming. Switzerland, Serbia-Montenegro and Poland confirm cases in wild birds and Albania confirms a poultry infection; plus, Austria reports finding H5N1 in three cats.
On March 8, 2006, Germany reports fatal H5N1 in two more domestic cats and on the 9th, confirms the first infection of this avian influenza virus in a new species, a stone marten. On the 12th Cameroon confirms H5N1 in a domestic duck and Myanmar confirms the virus in poultry. On March 15th, Denmark and Sweden confirm H5N1 in wild birds, followed by poultry infections in Afghanistan and Israel over the next two days. On the 21st, Pakistan confirms H5N1 in poultry and Azerbaijan confirms its first seven cases of human H5N1 infection. Finally, on March 24th, Jordan reports its first confirmed outbreak in poultry and Cambodia reports its first human infection since April 2005.
Bird Flu Symptoms in Humans
Reported symptoms of avian influenza A, subtype H5N1, in humans range from the typical flu-like discomforts (e.g., cough, fever, sore throat, and body aches) to eye infections, acute respiratory distress, viral pneumonia, and other life-threatening complications. Diarrhea, vomiting, abdominal pain, chest pain, and bleeding from the nose and gums have also been reported as early symptoms in some patients. Two atypical fatal cases of encephalitis (brain inflammation) in southern Vietnam were identified retrospectively as H5N1 influenza infection; neither patient showed respiratory illness when first hospitalized. In a case from Thailand, the patient had a high fever and diarrhea, but no respiratory symptoms. The boy died before proper diagnosis could be made and antiviral medication administered.
Most patients have symptoms in the lower respiratory tract when they first seek treatment. Clinical reports show that difficulty in breathing develops around five days following the first symptoms. Respiratory distress, a hoarse voice, and a crackling sound when inhaling are commonly seen. Sputum production is variable and sometimes bloody. Most recently, blood-tinted respiratory secretions have been observed in Turkey. Almost all patients develop viral pneumonia. Home caregivers, healthcare personnel, and funeral service professionals have been urged to use full infectious disease protections and exercise extreme caution around infected patients or when disposing of those who do not survive.
Clinical findings are also suggesting that the H5N1 strain of the 2005/2006 flu season is more virulent than most of the infections of 2003/2004 and 2004/2005. Clinical deterioration appears more rapid. In Thailand, the time between onset of illness to the development of acute respiratory distress was around 6 days, with a range of 4 to 13 days. In severe cases in Turkey, clinicians have observed respiratory failure in only 3 to 5 days after symptoms begin. Another common feature is multi-organ dysfunction, notably involving kidney and heart hemorrhaging and intravascular coagulation.
There are four FDA approved antiviral drugs currently in use around the world for treatment of influenza: amantadine, rimantadine, oseltamivir, and zanamivir. All four have exhibited activity against various influenza A viral subtypes in previous flu seasons but recent genetic sequencing of influenza A (H5N1) viruses from human cases in Vietnam and Thailand shows resistance to the antiviral medications amantadine and rimantadine.
Antiviral testing in the U.S. has also shown increased resistance to these medications by influenza A (H3N2) viruses isolated from patients in 23 states. Of the 120 case samples tested at CDC through January 12, 2006, 90% have shown a marked increase of viral resistance to amantadine and a lesser increase with rimantadine. CDC issued a health advisory on January 14, 2006 to medical practitioners and health departments recommending that amantadine and rimantadine not be used for the remainder of the 2006 flu season. This leaves two remaining antiviral medications, oseltamivir (Tamiflu®) and zanamivir (Relenza ®), which should still be effective against currently circulating strains of H5N1 virus.
One report by two researchers from Oxford University cited resistance in two patients in Viet Nam that died after failure to respond to treatments of oseltamivir. Both patients received Tamiflu but it is believed that the H5N1 infections were too advanced for the antiviral to be effective. (BBC News, December 15, 2005)
Since the hosts of the H5N1 virus are migratory wild birds, there is currently no practical way to totally prevent some spread to domesticated fowl. Some poultry vaccines are being tested in Indonesia, Pakistan, and China. Early indications of efficacy are encouraging but the full effectiveness of those efforts has yet to be compiled and reported. Indonesia elected to try poultry vaccination after losses totaling at least 9 million domestic birds in early 2004. According to Dr. Tri Satya Putri Naipospos, Director of Animal Health in Indonesia, the results of the vaccination program are “very promising” with only a few bird flu cases reported in the early 2005 flu season. Vaccination is used together with selective culling, movement control, and other recommended health & hygiene measures.
Concerted efforts to produce vaccine candidates that would be effective for humans against avian influenza A (H5N1) viruses are under way in several countries. However, a truly effective vaccine has to match the viral structure of the new strain, which isn’t known until (or if) human-to-human transmission begins. Then it will likely require many months before such vaccines could be mass produced in sufficient quantities and made available.
With limited treatment options and inadequate vaccines to prevent the spreading outbreaks of H5N1, it appears the world’s best option for now is to improve our efforts to control this dangerous epizootic (animal outbreak). There will have to be two steps to any effective control: 1) stop the wild bird-to-domestic bird contacts and, 2) take all the precautions necessary to prevent transmission from infected birds (wild or domestic) to humans. Both will be difficult and involve behavioral changes as well as capital investment.
Poultry producers around the world are classified by health officials into four different groups, know as “sectors”:
Sector 1: Industrial integrated system with high level biosecurity and birds / products marketed commercially (e.g., farms that are part of an integrated broiler production enterprise with clearly defined and implemented standard operating procedures for biosecurity).
Sector 2: Commercial poultry production system with moderate to high biosecurity and birds / products usually marketed commercially (e.g., farms with birds kept indoors continuously; strictly preventing contact with other poultry or wildlife).
Sector 3: Commercial poultry production system with low to minimal biosecurity and birds/products usually entering live bird markets (e.g., a caged layer farm with birds in open sheds; a farm with poultry spending time outside the shed; a farm producing chickens and waterfowl).
Sector 4: Village or backyard production with minimal biosecurity and birds/products consumed locally.
Sector 1 & 2 poultry farms, whether egg or meat producers, should have no problem with H5N1 infections but must be inspected periodically to insure that safety & health standards are being maintained.
It is sectors 3 & 4 that are causing the H5N1 poultry outbreaks and infecting humans. The vast majority of human infection cases are directly attributable to direct and/or frequent contact with birds from the sector 4 environments. A smaller number have been traced to contact with or consumption of infected birds or products from “live” or “wet” markets. (A “wet” market is a place either fixed or temporary, where the public goes to buy small animals and birds that are: (a) live and slaughtered there, (b) live and taken home to be slaughtered, or © already slaughtered and sold as meat.
High Risk Production Techniques
- Raising multiple species of animals on one farm unit
- Keeping chickens over fish ponds
- Using untreated chickens feces as fertilizer or livestock feed
- Inappropriate disposal of dying and dead birds
- Using surrogate birds to incubate eggs of different species
- Lack of adopting an “all-in, all-out” husbandry system
Part of the back-yard poultry practices is attributable to behavioral practices, or long standing “custom”, and part is simply due to the economic status of many of the families. Many farming families do not have the time or money to feed and care for their poultry properly. The birds are purposefully allowed “free range”, which often includes the home, the children’s playing areas, and any nearby fields. The poultry is mostly for the family’s personal consumption or egg production, with only a few going to a local live market when the flock multiplies.
Also, it is common practice to slaughter and consume any birds that stop laying eggs or otherwise exhibit signs of being “unwell”. This is regarded as “home culling” and, even though cooking temperatures destroy avian viruses, it is a dangerous practice and should be discouraged. Yet, the risk of infection would be greater in the slaughter, de-feathering, and “dressing out” of the bird than in eating the properly cooked meat.
This is a major problem with the live animal/wet markets. Stall attendants seldom have any protective gear (gloves, mask, goggles, etc) and there is usually a lot of blood and feathers flying around. In 1992 live poultry markets in America were considered the “missing link in the epidemiology of influenza”. Live markets were the source of the lethal H5N1 outbreak in Hong Kong in 1997, which killed six people and resulted in the eradication of the island’s entire poultry population—-an estimated 1.5 million birds.
In Viet Nam, the existence of H5N1 in geese tested in live bird markets in Hanoi had been documented three years before the devastating 2004 viral outbreaks on chicken farms with many subsequent human deaths.8 The latest H5N1 outbreak in Nigeria (February 2006) was also at a live animal market in the northern state of Kaduna. Over 40,000 birds died in live markets in a matter of days.
High Risk Wet Market Practices in Asia
- An apparent regional preference for fresh or “warm” meat
- A limited application of good hygiene, cleaning and disinfection
- Keeping multiple species together and in confined spaces
- Stacking cages on top of one another and poor ventilation
- A lack of pre-marketing health checks
- A lack of personal protective equipment for stall owners
- A lack of training and education for poultry vendors and suppliers
- Returning unsold “market exposed” birds back to the farm
Another facet of the Asian bird markets is that they are “social” occasions as well as shopping trips. Outdoor food markets are similar to the all-purpose “flea markets” throughout the world—-and are often just another part of a large market offering anything and everything, including food & beverage stalls and entertainment, such as rides and musical presentations. The larger, once-a-week rural markets have the atmosphere (and crowds) of a weekly “county fair” in the U.S.A.
So the live animal markets of S.E. Asia are not likely to go away, nor should they have to. It will simply take a good mass education program for the public, training and proper equipment for stall owners, inspection and proper hygiene for all market animals, and probably some form of enforcement to curb violations of good health and safety practices.
Back-yard poultry production can also be improved by educating the owners and making some low-cost improvements to facilities. Governments might offer low-interest loans to farming families for improvements, as well as assurances of reimbursement for any infected poultry losses that are reported promptly to health officials. (This could be a vital tactic in the “rapid response and containment” plans of international health organizations such as the WHO, OIE, and FAO.) An FAO study conducted in Viet Nam concluded that H5N1 infections resulting in dead birds and subsequent culling of small domestic flocks have adversely affected 34,000 people living on the edge of poverty…and 88,000 that were already poor.7 Families with little more than their poultry flock will be much less reluctant to report dead birds if they know that they will be reimbursed for the loss of their stock.
Improving Asian Poultry Production Systems
All Asian countries are diligently trying to cope with the reoccurring bird flu epidemics. The governments know that they must protect their citizens and the health authorities are well aware that conditions could easily get much worse if timely and proper procedures to reduce “high risk” practices are not fully supported; by the public as well as the law makers. Any food distribution system should have appropriate guidelines and effective regulations to insure the safety and wellbeing of everyone involved, including the end consumer.
From a meeting of the U.N.’s World Health Organization (WHO), the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (OIE), held in Kuala Lumpur, Malaysia in July 2005, a report was issued that addressed the pertinent actions needed to effectively combat this persistent “micro killer”. The report did suggest that more legislation be enacted to regulate the poultry production systems and that each of the affected countries should tailor such regulations to best fit their own specific needs. Detailed guidelines were enumerated by the experts in attendance to help diverse cultures choose the best methods of dealing with many currently unsafe practices and high risk behaviors.
The report also noted that many countries already had enacted more restrictive poultry marketing regulations but that there was often a “gap” between legislation and enforcement. The most stringent and effective regulatory controls to address high risk practices in the production, distribution and sale of live birds or poultry products are those in use today by Hong Kong, China—-site of the original H5N1 outbreak in 1997. Prominent control features include:
- Required vaccinations of all chickens raised on the island or imported from mainland China (Hong Kong’s main supplier)
- Requiring health certificates verifying quarantine, inspection, sampling and testing for all consignments of imported poultry
- Mandatory installation of poultry housing that prevents any contact between wild birds and domestic flocks
- The use of “sentinel” (unvaccinated) chickens in each vaccinated flock
- Holding all birds for observation in a wholesale market before being sold by retailers; any sick or dead birds must be surrendered for analysis and the flock quarantined until health authorities permit retail distribution
- Prohibiting any mixing of poultry types to avoid interspecies transmission and minimize the opportunity for reassortment of the viral genes
- Requiring all processed waterfowl be slaughtered in a central facility and the carcasses and edible internal organs be packaged separately to prevent any cross contamination
- Prohibiting sale of live quail in retail poultry markets
- Requiring mandatory “rest days” when retailers must slaughter all remaining live poultry by a designated time and suspend business until a thorough cleaning and disinfection of the premises is completed
- Mandatory inspection for compliance of the rest day requirements and removal of licenses and/or tenancies of any market individuals or individual retailers contravening the requirements
All of the major health agencies of the world are trying to prepare for the worst case scenario, a pandemic. WHO, OIE, and FAO have formulated plans for a “rapid response and containment” policy involving two main strategies. The first strategy, aiming to reduce opportunities for a pandemic virus to emerge, emphasizes efforts to contain outbreaks of highly pathogenic H5N1 avian influenza in poultry, prevent the spread of this disease to new countries, and reduce opportunities for human infections to occur. The prevention of high-risk behaviors is part of this strategy, as well as strengthening the early warning system.
The second strategy is to improve the world’s ability to cope with a pandemic, both nationally and internationally. This will involve: formulation of national preparedness plans, increasing the quantity and access to antiviral drugs, development of pandemic vaccines and plans for increasing their accessibility and affordability, planning for implementation of public health measures to reduce morbidity and mortality, and the development of communication plans to improve compliance with recommended measures and reduce social and economic disruption.
Possible Pandemic Consequences
Rapid Worldwide Spread
- When a pandemic influenza virus emerges, its global spread is considered inevitable.
- Preparedness activities should assume that the entire world population would be susceptible.
- Countries might, through measures such as border closures and travel restrictions, delay arrival of the virus, but cannot stop it.
Healthcare Systems Overloaded
- Most people have little or no immunity to a pandemic virus. Infection and illness rates soar. A substantial percentage of the world’s population will require some form of medical care.
- Nations unlikely to have the staff, facilities, equipment and hospital beds needed to cope with large numbers of people who suddenly become ill.
- Death rates are high, largely determined by four factors: the number of people who become infected, the virulence of the virus, the underlying characteristics and vulnerability of affected populations, and the effectiveness of preventive measures.
- Past pandemics have spread globally in two or three waves.
Medical Supplies Inadequate
- The need for vaccine is likely to outstrip supply
- The need for antiviral drugs is also likely to be inadequate early in a pandemic.
- A pandemic can create a shortage of hospital beds, ventilators and other supplies. Surge capacity at non-traditional sites, such as schools, may be created to cope with demand.
- Difficult decisions will need to be made regarding who gets antiviral drugs and vaccines.
Economic and Social Disruption
- Travel bans, closing of schools and businesses and cancellations of events could have major impact on communities and citizens.
- Care for sick family members and fear of exposure can result in severe worker absenteeism.10
CDC Response to H5N1 Outbreaks and Pandemic Threat
- In May 2005, CDC joined a new, inter-agency National Influenza Pandemic Preparedness Task Force organized by the U.S. Secretary of Health and Human Services. This task force is developing and refining preparedness efforts with international, state, local, and private organizational partners to help ensure the most effective response possible when the next influenza pandemic occurs. For more information about the Pandemic Influenza Preparedness Plan of the U.S. Health and Human Services Department and other aspects of this coordinated federal initiative, please visit www.pandemicflu.gov.
- In February 2004, CDC issued recommendations for enhanced domestic surveillance of avian influenza A (H5N1). Following the reports of human deaths in Vietnam in August 2004 and additional human cases in the following months, CDC issued follow-up Health Alert Network (HAN) notices on August 12 and February 4, 2005, reiterating criteria for domestic surveillance, diagnostic evaluation, and infection control precautions for avian influenza A (H5N1). The HAN notice also detailed laboratory testing procedures for H5N1.
- CDC has collaborated with the Association of Public Health Laboratories to conduct training workshops for state laboratories on the use of molecular techniques to rapidly identify H5 viruses.
- CDC is working collaboratively with the Council of State and Territorial Epidemiologists and other partners to assist states with pandemic planning efforts.
- CDC is working with other agencies, such as the Department of Defense and the Department of Veterans Affairs, on antiviral stockpile issues.
- CDC is one of four WHO Collaborating Centers and in this capacity provides ongoing support for the global WHO surveillance network, laboratory testing, training, and other actions.
- CDC has worked collaboratively with WHO to conduct investigations of human H5N1 infections in China, Indonesia, Thailand, and Vietnam and to provide laboratory diagnostic and training assistance.
- CDC has performed laboratory testing of H5N1 viruses from Vietnam, Thailand, and Indonesia.
- CDC is implementing a multi-million dollar initiative to improve influenza surveillance in Asia.
- CDC has led or taken part in 9 training sessions to enhance local capacities in Asia to conduct surveillance for possible human cases of H5 and to detect avian influenza A H5 viruses using laboratory techniques.
- CDC has developed and distributed a reagent kit for the detection of the currently circulating influenza A H5 viruses.
- CDC has worked with other international and national agencies in Asia to develop a training course for rapid response teams that will be used to help prepare the region to respond to outbreaks when they occur.
- CDC is monitoring the situation closely, along with WHO and other international partners. In addition, CDC continues to work collaboratively with WHO and the National Institutes of Health (NIH) on the development and testing of vaccine seed candidates for influenza A (H5N1).
Food Safety Recommendations
1. Conventional cooking (temperatures at or above 70°C/158°F in all parts of a food item) will destroy the H5N1 virus. Properly cooked poultry is safe to consume.
2. The H5N1 virus, if present in poultry, is not killed by refrigeration or freezing.
3. Home slaughtering and preparation of sick or dead poultry for food is hazardous: this practice must be stopped.
4. Eggs can contain H5N1 virus both on the outside (shell) and the inside (whites and yolk). Eggs from areas with H5N1 outbreaks in poultry should not be consumed raw or partially cooked (runny yolk); uncooked eggs should not be used in foods that will not be cooked, baked or heat-treated in other ways.
5. There is no epidemiological evidence to indicate that people have been infected with the H5N1 virus following consumption of properly cooked poultry or eggs.
6. The greatest risk of exposure to the virus is through the handling and slaughter of live infected poultry. Good hygiene practices are essential during slaughter and post-slaughter handling to prevent exposure via raw poultry meat or cross contamination from poultry to other foods, food preparation surfaces or equipment.
CDC and the U.S. Department of Agriculture (USDA) are currently enforcing a ban on the importation of all birds and bird products from all countries affected by the H5N1 virus. The CDC order applies to all birds (including poultry), whether dead or alive, as well as products derived from birds, such as hatching eggs. The USDA rule restricts entry of poultry, commercial birds, pet birds, and unprocessed bird products from countries with confirmed H5N1 infections.
Travel to countries with H5N1 outbreaks has not been restricted but there are advisories and travel guidelines available on the CDC website, www.cdc.gov./flu/avian/index.htm as well as suggestions for Americans living abroad.
The prevailing view among the world’s health and disease control experts is that we are now closer to another influenza pandemic than any time since the global disease outbreak of 1968. That was the mildest of the three 20th Century pandemics and it still killed about 34,000 people in the U.S. and approximately one million worldwide. It is believed that a genetic shift or reassortment of the highly virulent H5N1 bird flu strain would cause much more illness and death and possibly rival the catastrophic pandemic of 1918. Also, due to modern transportation and increased world trade, a modern pandemic will likely be more widespread, will overload our health care systems, find our medical supplies inadequate, and cause unprecedented social and economic disruption.
The avian influenza A (H5N1) epizootic in Asia, Europe and Africa is not expected to diminish significantly in the next year or two. H5N1 infection among birds has become endemic in some areas of Asia and human infections from direct contact with infected poultry will continue. Fortunately the spread of H5N1 virus from person-to-person has been rare and has not continued beyond one person. No proof of genetic reassortment between human and avian influenza A virus genes has been documented; however, the continued outbreaks in countries around the world pose a very serious public health threat.
Encouragingly, two recent research reports have shown that H5N1 is not as likely to spread from human-to-human as easily as other seasonal influenza virus due to lower respiratory tract infection. Seasonal flu viruses are upper tract infections that spread easily by coughing, sneezing, and hand contact.