AVIAN INFLUENZA A (H5N1) - OVERVIEW

Saturday, July 18, 2009

bird-flu

INTRODUCTION

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential.

Influenza A virus subtype H5N1, also known as "bird flu," A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu, commonly known as "avian influenza" or "bird flu". It is enzootic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Most references to "bird flu" and H5N1 in the popular media refer to this strain.

The H5N1 flu virus has affected hundreds of thousands of birds, and more than 200 humans worldwide. Health officials are concerned that it will become the next pandemic influenza strain in humans. However, it’s very hard for people to get H5N1 bird flu from each other. Most people get it from direct contact with birds or their droppings. That’s why there have been so few human cases.

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Control of avian influenza A(H5N1): public health concerns

The current outbreaks of highly pathogenic H5N1 avian influenza in poultry in parts of Asia have had immediate and severe consequences for the agricultural sector.1 Human cases, with a high fatality, have been reported in two countries, Viet Nam and Thailand, with very widespread outbreaks in poultry.

It can be anticipated that human cases will also be detected in other countries where outbreaks in poultry are rapidly spreading.

The number of human cases presently detected is very small compared with the large number of infected birds distributed over a wide geographical area. This suggests that the H5N1 virus strain may not easily infect humans.

To date, no human-to-human transmission is known to have occurred. However, the continuing presence of infection in poultry may also create opportunities for the emergence of a new influenza virus subtype with a capacity to spread easily among humans, thus marking the start of an influenza pandemic. Should this rare event occur (three pandemics occurred during the previous century), it would immediately have serious consequences for human health throughout the world.

For this reason, public health concerns about the present H5N1 situation must be given the highest priority when weighing the immediate and measurable economic losses in animals against possible yet unpredictable consequences for humans.

Several other diseases in animals can be transmitted to humans. Experience with such diseases, known as “zoonoses”, has shown that strict measures on animal health, imposed by the need to protect human health, helped rebuild consumer confidence.2

Recent experience has also shown that measures for the control of zoonotic diseases, aimed at halting further spread in animals and minimizing economic losses, need to be closely coordinated with measures that minimize the longer-term risks to human health. In the present situation, measures aimed at eliminating the disease in poultry will also reduce the presence of the virus in the environment and thus reduce opportunities for human exposures and infections. These measures must be carried out urgently, giving highest priority to the protection of human health. Previous outbreaks of highly pathogenic avian influenza associated with human infections occurred in areas, such as Hong Kong and the Netherlands, with industrial poultry production and well developed health and agricultural infrastructures. Even so, elimination of infection in poultry was a complex, difficult, and costly undertaking. Both outbreaks were eventually controlled through immediate culling of infected flocks, quarantine and disinfection of farms, strict biosecurity, restrictions on the movement of animals, and compensation for farmers.

The present situation is different. Control of outbreaks of highly pathogenic avian influenza is known to be especially difficult in areas where poultry range freely. In several affected countries, up to 80% of the total poultry population is raised in small backyard farms. Most rural families keep a small free-range flock.

Given these features of the present situation there is potential that the H5N1 virus could become established in bird populations in this geographical region and possibly spread to other parts of the world. This was one of several conclusions reached during a joint FAO/OIE/WHO technical consultation on the control of avian influenza, held in Rome from 3–4 February.

No single blueprint for control in animals, and thus reduction of risks for humans, is available. Over the past four decades, only 18 outbreaks of highly pathogenic avian influenza, most caused by strains other than H5N1, have occurred throughout the world. Existing evidence will not suffice to provide universally applicable recommendations for a rapid and effective response in affected countries.

Control measures must be tailored to each country’s unique epidemiological situation and unique capacity, with health and agricultural sectors working hand-in-hand. Agricultural authorities face the immediate challenge of rapidly eliminating the H5N1 reservoir in poultry. Authorities in all affected countries need to work together in a coordinated way

Transparency in reporting of human and animal disease is absolutely essential.

Despite the uncertainties, experts fully agree that immediate culling of infected and exposed birds is the first line of defence for both the protection of human health and the reduction of further losses in the agricultural sector. Other measures, such as the vaccination of healthy flocks, may play a supportive role in some cases when undertaken in conjunction with measures for preventing further spread of infection. WHO has repeatedly stressed the need to ensure that culling is carried out in a way that does not fuel more human cases. and that vaccination of poultry should not lead to the dropping of vigilance or compromise other necessary control measures.

In responding to the situation, WHO emphasises three strategic goals: to avert an influenza pandemic, to control the present human outbreaks and prevent further spread, and to conduct the research needed for better preparedness and response, including the immediate development of a new vaccine for humans against H5N1. WHO has issued a series of technical guidelines aimed at minimizing the risk of further human cases and facilitating a coordinated international response.

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Inexpensive Test Detects H5N1 Infections Quickly and Accurately

Scientists from the University of Colorado at Boulder and the Centers for Disease Control and Prevention (CDC) have developed an inexpensive “gene chip” test based on a single influenza virus gene that could allow scientists to quickly identify flu viruses, including avian influenza H5N1. The researchers used the MChip to detect H5N1 in samples collected over a three-year period from people and animals in geographically diverse locales. In tests on 24 H5N1 viral isolates, the chip provided complete information about virus type and subtype in 21 cases and gave no false positive results, report the scientists. They say the MChip could provide a significant advantage over available tests because it is based on a single gene segment that mutates less often than the flu genes typically used in diagnostic tests. As a result, the MChip may not need to be updated as frequently to keep up with the changing virus.

The research was led by University of Colorado scientist Kathy L. Rowlen, Ph.D., and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. A paper describing the work, now available online, is scheduled to appear in the December 15 issue of the American Chemical Society’s journal Analytical Chemistry.

“Concerns about a possible influenza pandemic make it imperative that we continue to devise reliable and easy-to-use diagnostic tests for H5N1 that can be employed on-site where outbreaks are suspected,” says NIAID Director Anthony S. Fauci, M.D. “The MChip developed by Dr. Rowlen and her colleagues performed extremely well in initial tests and has the potential to be a valuable tool in global influenza surveillance efforts.”

The MChip has several advantages over the FluChip, a flu diagnostic previously developed by the same research team, says Dr. Rowlen. While the FluChip is based on three influenza genes — hemagglutinin (HA), neuraminidase (NA) and matrix (M) — the MChip is based on one gene segment. Unlike HA and NA, which mutate constantly and thus are technically difficult to use to develop gene chip diagnostic tests, the M gene segment mutates much less rapidly, Dr. Rowlen explains. “The M gene segment is much less of a moving target than the HA or NA gene. We believe that a test based on this relatively unchanging gene segment will be more robust because it will continue to provide accurate results even as the HA and NA genes mutate over time. The work summarized in our paper strongly supports that idea,” she says.

Another potential advantage is that the MChip would, for the first time, create a way to simultaneously screen large numbers of flu samples to learn both the type and subtype of virus present. Current real-time tests provide information about the type of virus (type A or B) in a sample, but additional tests must be run to determine the virus subtype (for example, H5N1 subtype.)

Working in biosafety-level-3-enhanced labs in Atlanta, CDC scientists, including Catherine B. Smith, M.S., extracted H5N1 genetic material from virus samples derived from human, feline and multiple avian hosts, including geese, chickens and ducks. The samples represented infections that had occurred between 2003 and 2006 over a vast geographic area, including Vietnam, Nigeria, Indonesia and Kazakhstan. Six of the human viral isolates were taken from an Indonesian family in which human-to-human H5N1 virus transmission was suspected. The virus diversity in the samples is important, explains Dr. Rowlen, because any diagnostic tool designed for eventual use on a rapidly changing virus, such as H5N1, must be able to detect as many variants as possible.

Dr. Rowlen and her colleagues tested the ability of the MChip to correctly identify 24 different H5N1 viral isolates, and distinguish those from seven non-H5N1 isolates. The MChip accurately identified and gave complete subtype information (identifying the samples as H5N1) for the 21 out of 24 strains of H5N1. Importantly, notes Dr. Rowlen, the test gave no false positives, meaning that the chip never indicated the presence of H5N1 when none was present. Following exposure to a viral isolate, the MChip displays results as a pattern of fluorescent spots. To automate the process of interpreting this pattern — thus eliminating the possibility of human error — the researchers developed an artificial neural network trained to recognize the distinctive pattern indicative of H5N1. Automating the interpretation of MChip results could allow it to be used more readily by health workers at the site of possible flu outbreaks, notes Dr. Rowlen.

“This new technology, once manufactured and distributed, could have the potential to revolutionize the way laboratories test for influenza,” says Nancy J. Cox, Ph.D., director of the CDC’s influenza division. “The MChip could enable more scientists and physicians, possibly even those working in remote places, to more quickly test for H5N1 and to accurately identify the specific strain and its features. This would greatly increase our ability to learn more about the viruses causing illness and take the best steps to respond.”

The raw materials for the MChip cost less than 10 dollars, Dr. Rowlen says, and discussions are under way to commercialize its manufacture.

For more information on influenza see http://www3.niaid.nih.gov/news/focuson/flu. Also visit http://www.PandemicFlu.gov for one-stop access to U.S. Government information on avian and pandemic flu.

NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies. News releases, fact sheets and other NIAID materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Since it was founded in 1946 to help control malaria, CDC has remained at the forefront of public health efforts to prevent and control infectious and chronic diseases, injuries, workplace hazards, disabilities, and environmental health threats. Today, CDC is globally recognized for conducting research and investigations and for its action oriented approach. For more information on CDC and its programs, visit www.cdc.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Avian Influenza Health Advice

Winter to spring is the seasonal high risk period for avian influenza. The detection of H5N1 among wild birds and carcasses of poultry recently is a cause of concern. In this regard, members of the public are advised to pay extra attention to stay away from the disease by refraining from contacting live poultry, especially dead or sick poultry.
Though our genetic analysis shows that the virus has no mutation for the time being and there is no sign of human-to-human transmission, we should not be off guard against the disease.
While the Government is highly vigilant and will continue to strictly enforce preventive measures against avian influenza, members of the public also have a role to play.
Members of the public should remain vigilant against avian influenza infection and observe the following measures:
* Avoid direct contact with poultry and birds or their droppings; if contacts have been made, they should wash hands thoroughly with soap and water;
* Poultry and eggs should be thoroughly cooked before eating;
* Wash hands frequently;
* Cover nose and mouth while sneezing or coughing, hold the spit with tissue and put it into covered dustbins;
* Avoid crowded places and contact with sick people with fever;
* Wear a mask when you have respiratory symptoms or need to take care of patients with fever;
* When you have fever and influenza-like illnesses during a trip or when coming back to Hong Kong, you should consult doctors promptly and reveal your travel history.
People working in poultry farms, wholesale and retail markets should strictly adhere to the following biosecurity measures:
* Take precautions to prevent any contact between poultry and other birds.
* Use enclosed caging to prevent poultry from leaving/entering livestock premises.
* Feeders and drinking water containers should be properly placed to avoid contact with wild birds and contaminants.
* Newly acquired birds must be isolated for observation. Immediately report any abnormal health condition of the flock.
* Wear suitable protective clothing when touching birds.
* Clean and disinfect thoroughly after touching birds or handling their droppings.
* Seek medical treatment immediately when feeling unwell.

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