H5N1 influenza virus is a type of influenza A virus which mostly infects birds. H5N1 flu is a concern because its global spread may constitute a pandemic threat. The yardstick for human mortality from H5N1 is the case-fatality rate (CFR); the ratio of the number of confirmed human deaths resulting from infection of H5N1 to the number of those confirmed cases of infection with the virus. For example, if there are 100 confirmed cases of a disease and 50 die as a consequence, then the CFR is 50%. The case fatality rate does not take into account cases of a disease which are unconfirmed or undiagnosed, perhaps because symptoms were mild and unremarkable or because of a lack of diagnostic facilities. The Infection Fatality Rate (IFR) is adjusted to allow for undiagnosed cases.
The IFR is central to pandemic planning. In previous influenza pandemics (not caused by H5N1), IFR estimates have ranged from to 2-3% for the 1918 pandemic, to about 0.6% for the 1957 pandemic, to 0.2% for the 1968 pandemic.
Between 2003 and December 2025, the World Health Organization has recorded 993 cases of confirmed H5N1 influenza, leading to 477 deaths. The true fatality rate is presumably lower because cases with mild symptoms may not have been identified as H5N1.
H5N1 infections in humans are generally caused by bird to human transmission of the virus. Until May 2006, the WHO estimate of the number of human to human transmissions had been "two or three cases". On May 24, 2006, Dr. Julie L. Gerberding, director of the United States Centers for Disease Control and Prevention in Atlanta, estimated that there had been "at least three." On May 30, Maria Cheng, a WHO spokeswoman, said there were "probably about half a dozen," but that no one "has got a solid number." The cases of suspected human to human transmission that continue to be found have been isolated and contained, and include transmission among members of a family in Sumatra, Indonesia in June 2006 as well as earlier and later instances arising in other countries. However, no pandemic strain of H5N1 has yet been found. The key point is that, at present, "the virus is not spreading efficiently or sustainably among humans."
H5N1 vaccines for chickens exist and are sometimes used, although there are many difficulties that make it especially difficult to decide whether vaccination will do more harm than good. In the U.S. H5N1 pre-pandemic vaccines exist in quantities sufficient to inoculate a few million people and might be useful for priming to "boost the immune response to a different H5N1 vaccine tailor-made years later to thwart an emerging pandemic". Japan has inoculated 6,000 health care workers with a pre-pandemic vaccine, and is planning how to proceed with widespread vaccinations, particularly workers who would provide utilities during an outbreak.Pre-pandemic bird flu shots eyed / Health ministry to urge study of potential early vaccination recipients | (Daily Yomiuri Online + AP -- Apr. 25, 2009) http://www.yomiuri.co.jp/dy/national/20090425TDY03103.htmMeasures against flu needed / Govt urged to set up framework to fight new influenza outbreak Apr. 24, 2008 http://www.yomiuri.co.jp/dy/features/science/20080424TDY04302.htm Switzerland is also considering preemptive vaccination to protect the general public.Vaccinations for new flu strains eyed for public (Apr. 17, 2008) http://www.yomiuri.co.jp/dy/national/20080417TDY02301.htm H5N1 pandemic vaccines and the technologies to rapidly create them are in the H5N1 clinical trials stage but cannot be verified as useful until after a pandemic strain emerges. Efforts to identify the changes that might result in a human-communicable strain have resulted in laboratory-generated H5N1 with substantially greater affinity for human cellular receptors after a change of just two of the H5 surface proteins.http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/aug1007mutant.html Researchers create H5N1 mutations to pave way for new vaccines and treatments Aug 10, 2007 (CIDRAP News) "Focusing on genetic changes to one portion of the H5 protein, called the receptor binding domain, [the researchers] found that as few as two mutations could enhance the ability of H5N1 to recognize human cells, according to the press release." Significantly, mouse antibodies were 10 times less potent against the mutants than against the pre-mutated viruses.
H5N1 cases in humans A graphic exhibiting total cases and mortality incidence is kept current by the WHO at https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-a-h5n1-virus and complements the country-specific information shown below.
Country-specific totals of cases and deaths kept current by the WHO may be viewed by clicking through the links provided at Global influenza virological surveillance and the map links provided here Map Gallery Search Results Global influenza virological surveillance (in the Global Health Observatory)
History A strain of H5N1 killed chickens in 1959 in Scotland and turkeys in 1991 in England. This strain was "highly pathogenic" (deadly to birds) but caused neither illness nor death in humans. "The precursor of the H5N1 influenza virus that spread to humans in 1997 was first detected in Guangdong, China, in 1996, when it caused a moderate number of deaths in geese and attracted very little attention." In 1997, in Hong Kong, 18 humans were infected and 6 died in the first known case of H5N1 infecting humans. H5N1 had evolved from a zero mortality rate to a 33% mortality rate.
The first report, in the current wave of HPAI A(H5N1) outbreaks, was of an outbreak that began December 10, 2003 in the Republic of Korea and continued for fourteen weeks. This strain caused asymptomatic infections in humans and may have died out,South Korea raises H5N1 culling target to 5.3 million Lisa Schnirring * Staff Writer Apr 21, 2008 (CIDRAP News)http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/apr2108culling(2).html like the 1959 strain, so that its low mortality level would have little value for predicting the mortality rate of a pandemic evolving from existing HPAI A(H5N1) strains. Contains latest Evolutionary "Tree of Life" for H5N1 The apparently extinct strain that caused human deaths from H5N1 in the Northern part of Vietnam in 2003, 2004 and 2005 also had a much lower case mortality rate than the currently existing strains. Changes are occurring in H5N1 that are increasing its pathogenicity in mammals.http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/oct0507avian.html H5N1 mutation that could help spark pandemic identified "The change promotes better viral replication at the lower temperatures found in the upper airways of mammals..."
Additionally, discussing the same mutation, one of the researchers points out that the mutated strain is in wide circulation: Kawaoka said. But he pointed out that one mutation is not sufficient to turn H5N1 into a major threat to humans.
From inception through 2007, the total number of WHO-confirmed cases was 349, with 216 of those fatalities (as reported by the U.N. on January 15, 2008, confirming earlier deaths) reflecting a 62% fatality rate among WHO-confirmed cases through 2007.Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO / 15 January 2008
For possible later updates by the WHO, see links at These overall figures fail to bring forward fluctuations that have appeared from year to year and in particular geographic areas. In 2005, when a markedly less-lethal strain in Northern Vietnam was responsible for most of the cases reported worldwide, only 42 of 97 people confirmed by the WHO to be infected with H5N1 died — a 43% fatality rate. In 2006, the case fatality ratio was higher among the WHO-confirmed cases, with 79 deaths among 114 confirmed cases.— or 69%. In 2007, 59 of the 86 WHO-confirmed cases ended in death, again a 69% fatality rate.(including cases reported to and confirmed by the WHO up to January 24, 2008)
Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO / 24 January 2008 |
For later updates by the WHO, see And 24 of the first 31 cases of 2008 (to April 30, 2008) have been fatal, Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO 30 April 2008. For later totals as the WHO provides updates, click through links at Epidemic and Pandemic Alert and Response (EPR) Confirmed Human Cases of Avian Influenza A(H5N1) or 77%.
The higher total case fatality ratio after the end of 2005 may reflect the widespread circulation in Vietnam of a less-lethal clade of H5N1 in 2005, which was subsequently brought under control. The change was nonetheless interpreted by some as indicating that the virus itself was becoming more deadly over time. based on the article In fact, when less-virulent strains die off, the surviving strains are the more virulent. Such difficulties in interpretation underscore that the global case fatality ratio can serve as but a crude and imperfect summary of the current complex situation with its many contributing factors, and not a clear or reliable predictive tool. If and when an influenza pandemic arises from one of the currently circulating pre-pandemic strains of Asian lineage HPAI A(H5N1), the mortality rates for the resulting human adapted pandemic strain cannot be predicted with any confidence.
Existing pre-pandemic global case fatality ratio The global case fatality ratio looks only to the official tallyThe tally may be obtained by clicking a link to the most current date shown by the UN on the WHO's web page entitled Epidemic and Pandemic Alert and Response (EPR) of cases confirmed by the WHO. It takes no account of other cases, such as those appearing in press reports. Nor does it reflect any estimate of the global extent of mild, asymptomatic,http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/5964 Options For Influenza Control VI (Conference, Toronto Canada, June 18, 2007) Even those who were in close contact with both infected birds and infected people showed no sign of ever having been infected, Dr. Dejpichai and colleagues found. The study is consistent with findings in Hong Kong, China, and Cambodia, which showed viral seroprevalence of no more than 10% among poultry workers and people living in villages where H5N1 outbreaks occurred, she said. But it contradicts a population-based study in Vietnam, published last year, that concluded that mild cases of the virus were likely to be common. (see Mild Avian Flu Transmission May Be Common) http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/2450
Primary source: Archives of Internal Medicine Source reference:
But note the discussion and critique New Study of Bird Flu Raises Important Issues January 9, 2006 or other cases which are undiagnosed, unreported by national governments to the WHO, or for any reason cannot be confirmed by the WHO. While the WHO's case count is clearly the most authoritative, these unavoidable limitations result in an unknown number of cases being omitted from it. The problem of overlooked but genuine cases is emphasized by occasional reports in which later serology reveals antibodies to the H5N1 infection in the blood of persons who were never known to have bird flu, and who then are confirmed by the WHO only retroactively as "cases." Press reports of such cases, often poultry handlers, have appeared in various countries. The largest number of asymptomatic cases was confirmed in 2006 among Korean workers who had assisted in massive culls of H5N1-infected poultry. This relatively benign Korean strain of H5N1 has died out, and the remaining strains of H5N1 have a higher case fatality rate in humans.