[Facts] [Symptoms] [In Humans] [Transmission] [Vaccine] [Pandemic]

How do Pandemics Start & Spread and What's
the Potential Impact

Symptoms of Avian Influenza in Humans
 The reported symptoms of avian influenza in humans have ranged from typical influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections (conjunctivitis), pneumonia, acute respiratory distress, viral pneumonia, and other severe and life-threatening complications.

Antiviral Agents for Influenza
 Four different influenza antiviral drugs (amantadine, rimantadine, oseltamivir, and zanamivir) are approved by the U.S. Food and Drug Administration (FDA) for the treatment and/or prophylaxis of influenza. All four have activity against influenza A viruses. However, sometimes influenza strains can become resistant to these drugs, and therefore the drugs may not always be effective. For example, analyses of some of the 2004 H5N1 viruses isolated from poultry and humans in Asia have shown that the viruses are resistant to two of the medications (amantadine and rimantadine). Monitoring of avian viruses for resistance to influenza antiviral medications is ongoing.

Recent Avian Influenza Outbreaks in Asia

Background

Outbreaks of highly pathogenic avian influenza A (H5N1) occurred among poultry in 8 countries in Asia (Cambodia, China, Indonesia, Japan, Lao, South Korea, Thailand and Vietnam) during late 2003 and early 2004. At that time, more than 100 million birds either died from the disease or were culled.

From December 30, 2003 to March 17, 2004, 12 confirmed human cases of avian influenza A (H5N1) were reported in Thailand and 23 in Vietnam, resulting in a total of 23 deaths.

By late February, however, the number of new human H5 cases being reported in Thailand and Vietnam slowed and then stopped. Within a month, countries in Asia were reporting that the avian influenza outbreak among poultry had been contained. No conclusive evidence of sustained human-to-human transmission was found.

Recent Developments

Beginning in late June 2004, however, new lethal outbreaks of avian influenza A (H5N1) infection among poultry were reported by several countries in Asia : Cambodia , China , Indonesia , Malaysia (first-time reports), Thailand , and Vietnam . In late March 2005, state media in the Democratic People’s Republic of Korea ( North Korea ) officially reported the country’s first outbreak of avian influenza A H7 in poultry. It is unknown to what extent H5N1 outbreaks in the other countries may be ongoing.

During August to October 2004, sporadic human cases of H5N1 were reported in Vietnam and Thailand . Of particular note is one isolated instance of probable limited human-to-human transmission occurring in Thailand in September 2004. Since December 2004, a resurgence of poultry outbreaks and human cases have been reported in Vietnam . On February 2, 2005 , the first human case of avian influenza A (H5 N1) infection from Cambodia was reported. On July 21, 2005 , the first laboratory-confirmed human case of avian influenza A (H5N1) in Indonesia was reported.

As of August 5, 2005 , there have been 112 human cases of avian influenza A (H5N1) in Vietnam (90), Thailand (17), Cambodia (4), and Indonesia (1), resulting in 57 deaths reported since January 2004.

Assessment of Current Situation

The avian influenza A (H5N1) epizootic outbreak in Asia is not expected to diminish significantly in the short term. It is likely that H5N1 infection among birds has become endemic to the region and that human infections will continue to occur. So far, no sustained human-to-human transmission of the H5N1 virus has been identified, and no evidence for genetic reassortment between human and avian influenza virus genes has been found; however, the epizootic outbreak in Asia poses an important public health threat.

If these H5N1 viruses gain the ability for efficient and sustained transmission between humans, there is little preexisting natural immunity to H5N1 infection in the human population, and an influenza pandemic could result, with high rates of illness and death. In addition, genetic sequencing of influenza A (H5N1) virus samples from human cases in Vietnam and Thailand shows resistance to the antiviral medications amantadine and rimantadine, two of the medications commonly used for treatment of influenza. This would leave two remaining antiviral medications (oseltamivir and zanamivir) that should still be effective against currently circulating strains of H5N1 virus. Efforts to produce a vaccine that would be effective against this strain of influenza A (H5N1) virus are under way. Vaccine reference virus strains already have been made and provided to manufacturers to produce pilot lots for human clinical trials as well as to produce a larger quantity of H5N1 vaccine, but mass production and availability of such a vaccine is some time off.

Recent research findings give further cause for concern. New research suggests that currently circulating strains of H5 viruses are becoming more capable of causing disease (pathogenic) for mammals than earlier H5 viruses and are becoming more widespread in birds in the region. One study found that ducks infected with H5N1 are now shedding more virus for longer periods of time without showing any symptoms of illness. This has implications for the role of ducks in transmitting disease to other birds and possibly to humans as well. Additionally, other findings have documented H5 infection among pigs in China and H5 infection in felines (experimental infection in housecats in the Netherlands and isolation of H5N1 viruses from infected tigers and leopards in Thailand ), suggesting that cats could host or transmit the infection. These finding are particularly worrisome in light of the fact that reassortment of avian influenza genomes is most likely to occur when these viruses demonstrate a capacity to infect multiple species, as is now the case in Asia.

Notable findings of epidemiological investigations of human H5N1 cases in Vietnam during 2005 have suggested transmission of H5N1 viruses to two persons through consumption of uncooked duck blood. Possible person-to-person transmission of H5N1 viruses is being investigated in several clusters of cases in Vietnam.

One atypical fatal case of encephalitis in a child in southern Vietnam in 2004 was identified retrospectively as H5N1 influenza through testing of cerebrospinal fluid, fecal matter, and throat and serum samples. Further research is needed to ascertain the implications of such findings.

CDC Response to Outbreaks

Domestic Activities:

  • 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, CDC issued a follow-up Health Alert Network (HAN) message on August 12 reiterating criteria for domestic surveillance, diagnostic evaluation, and infection control precautions for avian influenza A (H5N1). The HAN also detailed laboratory testing procedures for H5N1.
     
  • CDC collaborated with Association of Public Health Laboratories on 2 training workshops for state laboratories on the use of molecular techniques to identify H5 viruses. Planning for a third training workshop is under way.
     
  • CDC is working collaboratively with Council of State and Territorial Epidemiologists and others to assist states with pandemic planning efforts.
     
  • CDC is working with other agencies such as the Department of Defense and the Veterans Administration on antiviral stockpile issues.

International Activities:

  • CDC worked collaboratively with WHO to conduct investigations of H5N1 in Vietnam and to provide laboratory diagnostic and training assistance.
     
  • CDC has performed laboratory testing of H5N1 viruses from Thailand and Vietnam.
     
  • CDC has implemented a $5.5 million initiative to improve influenza surveillance in Asia.
     
  • CDC has conducted or taken part in 9 training sessions to enhance local capacities to conduct surveillance for possible human cases of H5 and to detect influenza A H5 viruses by using laboratory techniques.
     
  • CDC has developed and distributed a reagents kit for the detection of the currently circulating influenza A H5 viruses.
     
  • CDC is monitoring the situation and remains in close contact with WHO and other international partners.

In addition, CDC continues to work collaboratively with WHO and the National Institutes of Health (NIH) on safety testing vaccine seed candidates and the development of additional vaccine virus seed candidates for influenza A (H5N1).

Bird Import Ban

On February 4, 2004, CDC and USDA issued an order for a ban on the import of all birds (Class: Aves) from affected areas in Southeast Asia. On March 10, 2004, CDC, in coordination with USDA, lifted the embargo of birds and bird products from Hong Kong. On September 28, 2004, the list of countries affected by the embargo of birds and bird products was expanded to include Malaysia.