Global spread of H5N1

The global spread of H5N1 (an avian virus) is a pandemicthreat.

"Since 1997, studies of H5N1indicate that these viruses continue to evolve, with changes in antigenicity and internal geneconstellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability." [1] Image:BirdFluWorld.png

Tens of millions of birds have died of H5N1 influenza and hundreds of millions of birds have been culled (slaughtered and disposed of) to protect humans from H5N1. Countries that have reported one or more H5N1 outbreaks include (in order of first outbreak occurrence): Korea, Vietnam, Japan, Thailand, Cambodia, Laos, Indonesia, China, Malaysia, Russia, Kazakhstan, Mongolia, Turkey, Romania, Croatia, Ukraine, Cyprus, and Iraq.

Human and bird cases

1996-2003

"The precursor of the H5N1influenza virus that spread to humansin 1997was first detected in Guangdong, China, in 1996, when it caused a moderate number of deaths in geeseand attracted very little attention." [4]

In 1997, in Hong Kong, 18 humans were infected and 6 died in the first known case of H5N1infecting humans. [5]

"Human disease associated with influenza A subtype H5N1re-emerged in January2003, for the first time since an outbreak in Hong Kongin 1997." [6]

In 2003three humans were confirmed infected with H5N1 (in Vietnam). All three died. [7]

H5N1in Chinaand Hong Kongin this and later periods is less than fully reported. For example WHO records an H5N1 death in Hong Kong in 2003 hereand herebut not here. "An outbreak of atypical pneumoniaoccurred between November 2002and February 2003in Guandongprovince, China. Health authorities in Chinainvestigated the outbreak and identified Chlamydiapneumoniae as the causitive agent. The Ministry of Health in Beijinghas informed WHOthat the outbreak in Guandong is over and that there is no evidence of a link between the outbreak in Guandong and the H5N1 cases in Hong Kong SAR." [8]Blogs have reported many discrepancies between official China government anouncements concerning H5N1 and what people in China see with their own eyes. Many reports of total H5N1 cases exclude China due to widespread unbelief in China's official numbers.

2004

January 2004: A major new outbreak of H5N1surfaced in Vietnamand Thailand's poultryindustry, and within weeks spread to ten countries and regions in Asia, including Indonesia, South Korea, Japanand China. Intensive efforts were undertaken to slaughter chickens, ducksand geese(over forty million chickens alone were slaughtered in high-infection areas), and the outbreak was contained by March, but the total human death toll in Vietnam and Thailand was twenty three people.

February 2004: "The Ministry of Public Health in Thailand has confirmed the country?s tenth case of H5N1 infection." [9]

July 2004: Fresh outbreaks in poultry were confirmed in Ayutthayaand Pathumthaniprovinces of Thailand, and Chaohucity in Anhui, China.

August 2004: Avian flu was confirmed in Kampung Pasir, Kelantan, Malaysia. Two chickens were confirmed to be carrying H5N1. As a result Singaporehas imposed a ban on the importation of chickens and poultry products. Similarly the EUhas imposed a ban on Malaysian poultry products. A cull of all poultry has been ordered by the Malaysian government within a 10km radius of the location of this outbreak. These moves appear to have been successful and since then, Singapore has lifted the ban and Malaysia has requested the OIEdeclare Malaysian poultry bird flu free [10].

September 2004: More cases of H5N1in humans in Thailand. [11]

October 2004: Researchers discover H5N1is far more dangerous than previously believed. "In the past, outbreaks of highly pathogenic avian influenza in poultry began following the primary introduction of a virus, of low pathogenicity, probably carried by a wild bird. The virus then required several months of circulation in domestic poultry in order to mutate from a form causing very mild disease to a form causing highly pathogenic disease, with a mortality approaching 100%. Only viruses of the H5 and H7 subtypes are capable of mutating to cause highly pathogenic disease. In the present outbreaks, however, asymptomatic domestic ducks can directly introduce the virus, in its highly pathogenic form, to poultry flocks." [12]Limiting this conclusion to domestic waterfowlproved to be wishful thinking, as in later months it became clear that nondomestic waterfowlwere also directly spreading the highly pathogenic strain of H5N1to chickens, crows, pigeons, and other birds and that it was increasing its ability to infect mammals as well. From this point on, avian fluexperts increasingly refer to containment as a strategy that can delay but not prevent a future avian flu pandemic.

November 2004: The US's National Institutes of Health's (NIH) National Institute of Allergy and Infectious Diseases's (NIAID) Influenza Genome Sequencing Projectto provide complete sequence data for selected human and avian influenza isolates begins. Nature article: "Race against time"

December 2004: "[F]irst human case of H5N1 [is] detected in Viet Nam since early September" [13].

2005

January 2005: An outbreak of avian influenza affected thirty three out of sixty four cities and provinces in Vietnam, leading to the forced killing of nearly 1.2 million poultry. Up to 140 million birds are believed to have died or been killed because of the outbreak.

February 2005: "Surveillance stepped up in province where Cambodia's first human avian influenza case was detected" [14].

March 2005: Vietnamand Thailandhave seen several isolated cases where human-to-human transmission of the virus has been suspected in care-givers of H5N1 patients, including a mother of a girl who died from H5N1 and two nurses.

April 2005: "The Ministry of Health in Viet Nam has provided WHO with official confirmation of an additional eight human cases of H5N1 avian influenza. Two of the cases were recently detected, between 2 and 8 April, in Hung Yen and Ha Tay Provinces, respectively. Both patients are alive. The other six cases are thought to have been detected prior to 2 April. WHO is seeking further details from the authorities on this six cases." [15]

May 2005: "Since January 2004, when human cases of H5N1 avian influenza were first reported in the current outbreak, 97 cases and 53 deaths have been reported in Viet Nam, Thailand and Cambodia. Viet Nam, with 76 cases and 37 deaths, has been the most severely affected country, followed by Thailand, with 17 cases and 12 deaths, and Cambodia, with 4 cases and 4 deaths." [16]

June 2005: "[T]esting of clinical specimens by international experts working in Viet Nam provided further suggestive evidence of more widespread infection with the virus, raising the possibility of community-acquired infection" but "the detection of H5N1 in clinical specimens is technically challenging and prone to errors" so team members and supplies from "institutes in Australia, Canada, Hong Kong SAR, Japan, the United Kingdom, and the United States of America having extensive experience in the testing of avian influenza viruses in human clinical specimens" investigated and concluded that "no laboratory evidence suggesting that human infections are occurring with greater frequency or that the virus is spreading readily among humans." [17]

July 2005: A death in Jakartawas the first confirmed human fatality in Indonesia. On July 28, avian influenza was reported to have killed two more people in Vietnam, raising the death toll to sixty [18].

August 2005: On August 32005, WHOsaid it was following closely reports from Chinathat at least 38 people have died and more than 200 others have been made ill by a swine-borne virus in Sichuan Province. Sichuan Province, where infections with Streptococcus suis have been detected in pigs in a concurrent outbreak, has one of the largest pig populations in China. The outbreak in humans has some unusual features and is being closely followed by the WHO. [19]In early August, an avian outbreak of H5N1flu was confirmed in Kazakhstanand Mongolia, suggesting further spread of the virus [20]. Later in August, the virus was found in western Russia, marking its appearance in Europe. As a result, Dutchauthorities ordered that free-range chickens would have to be kept indoors. [21]EUofficials chose not to impose a similar policy on member countries.

September 2005: On September 292005, David Nabarro, the newly appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill 5 to 150 million people. Also, due to a bipartisan effort of the United States Senate, $4 billion dollars was appropriated to develop vaccines and treatments for Avian influenza. [22] David Nabarrostated that as the virus had spread to migratory birds, an outbreak could start in Africaor the Middle East. Agricultural ministers of Association of South East Asian Nationsannounced a three-year plan to counter the spread of the disease. [23]

October 2005: On 13 October2005the EU Health Commissioner Markos Kyprianouconfirmed that tests on the dead turkeysfound on farms in Kiziksa, Turkey, showed that they had died from the H5N1strain. Even before the test results were available, some 5,000 birds and poultry have been culled in the area. It is believed that the disease had spread from migratory birds that land at the Manyasbird sanctuary (a few miles from the infected farm) on their way to Africa. On 15 October2005, the British Veterinary Laboratory in Weybridge confirmed that the virus detected in Ciamurlia, Romaniais H5N1. On 19 October2005, Chinaannounced a fresh outbreak of bird flu, saying 2,600 birds have died from the disease in Inner Mongolia. The deaths, at a farm near the region's capital of Hohhot, were due to the H5N1strain, the Xinhua news agency said. On 26 October2005, Croatiaannounced H5N1 strain was found in dead swans[24]. On 31 October2005, Russiaconfirmed previously suspected H5N1bird flu in ten rural communities across Russia. The confirmed outbreak sites are in the central areas of Tula and Tambov, as well as in the Urals province of Chelyabinsk and in Omsk and Altai, in Siberia. [25]

November 2005: Kuwaithas reported positive testing of two birds, one infected with H5N1, and the other with the H5N2 virus, making them the first cases of infection in the Middle East. A flamingoholding the H5N1 virus was found dead by the sea, as the sourcereports, it was killed by authorities and did not die from the virus.

December 2005: "China confirms its third human death from bird flu. That brings the death toll [...] to 74, comprising 14 victims in Thailand, four in Cambodia, 11 in Indonesia, 42 in Vietnam and three in China." [26]

2006

January

January 52006

• Second Turkish child dies from bird flu. A second Turkish child from the same family died from bird flu on Thursday at a hospital in eastern Turkey where she was being treated, a regional governor said. Her brother, 14-year-old Mehmet Ali Kocyigit, had already died of the H5N1strain of bird flu, officials said on Wednesday, confirming the first human death from the disease outside China and southeast Asia. "We lost Fatma Kocyigit this morning," Niyazi Tanilir, governor in the eastern province of Van, said on the CNN Turk news channel. Newspapers said Fatma was 15-years-old. She died around 6:30 a.m. (0430 GMT). [27]

January 62006

• A third Turkish child dies of suspected bird flu. The third from the same family. A fourth remained in critical condition.

January 72006

• Two more children are hospitalized after contracting bird flu like symptoms then later test postive for H5N1. They are both from the same area as the three children that succomb to the disease bringing the total amount of cases in Turkey to 5, with 2 of them fatal. 76 people have died since the outbreak began in 2003.

January 82006

• Three people are hospitalized after developing suspected H5N1 in the Turkish capital.

January 102006

• A woman is diagnosed with bird flu, as Turkey struggles to contain the outbreak.
• China announces that two more people had died of bird flu before 2006 began.
• Indonesia confirms that a 29 year old woman has died from suspected bird flu.

January 162006

• A 15-year-old Indonesiangirl from Indraymayu, Java, dies of bird flu. [28]

January 182006

• China and Turkey each confirm another human death from H5N1. [29]
• A 13-year-old boy dies in Indonesia, he is the brother of the girl who died on January 16.

January 212006

• The WHO confirms that the two Indonesian children died of H5N1. [30]

January 292006

• H5N1 is found in dead birds in northern Cyprus. The European Commissionfreezes transfers of animals and animal products from the island to the European Union. [31]

January 302006

• According to WHO:

The Ministry of Health in Iraq has confirmed the country?s first case of human infection with the H5N1 avian influenza virus. The case occurred in a 15-year-old girl who died on 17 January following a severe respiratory illness. Her symptoms were compatible with a diagnosis of H5N1 avian influenza. Preliminary laboratory confirmation was provided by a US Naval Medical Research Unit located in Cairo, Egypt. The girl?s 39-year-old uncle, who cared for her during her illness, developed symptoms on 24 January and died of a severe respiratory disease on 27 January. Both patients resided in the town of Raniya near Sulaimaniyah in the northern part of the country, close to the border with Turkey. Poultry deaths were recently reported in their neighbourhood, but H5N1 avian influenza has not yet been confirmed in birds in any part of the country. Poultry samples have been sent for testing at an external laboratory. A history of exposure to diseased birds has been found for the girl. The uncle?s source of infection is under investigation. The Ministry of Health has further informed WHO of a third human case of respiratory illness that is under investigation for possible H5N1 infection. The patient is a 54-year-old woman, from the same area, who was hospitalized on 18 January. Specimens are on their way to a WHO collaborating laboratory in the United Kingdom for diagnostic confirmation and further analysis. An international team, including representatives of other UN agencies, is being assembled to assist the Ministry of Health in its investigation of the situation and its planning of an appropriate public health response. WHO staff within Iraq have been directly supporting the government?s operational response, which was launched shortly after the girl?s death. Iraq is the seventh country to report human H5N1 infection in the current outbreak. The first human case occurred in Viet Nam in December 2003. [32]

February

February 42006

• Indonesia confirms three new cases, two of which were fatal.
• A dead swan near the city of Vidin, Bulgariais found to contain the H5 strain. Further testing begins to determine if the bird died from the H5N1 type of the disease. Over 20 dead birds are found along the Danubeand in lakes near the Black Sea.

Pig cases

Avian influenza virus H3N2is endemic in pigs("swine flu") in Chinaand has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. Health experts say pigs can carry human influenzaviruses, which can combine (i.e. exchange homologous genome sub-units by genetic reassortment) with H5N1, swapping genesand mutating into a form which can pass easily among humans.

H3N2evolved from H2N2by antigenic shiftand caused the Hong Kong Flupandemic of 1968and 1969that killed up to 750,000 humans.

The dominant strain of annual fluin humans in January 2006is H3N2. Measured resistance to the standard antiviral drugs amantadineand rimantadinein H3N2 in humans has increased to 91% in 2005.

A combination of these two subtypes of the species known as the avian fluvirus in a country like Chinais a worst case scenerio.

Tigers, leopards, domestic cats

Variants have been found in a number of domestic cats, leopardsand tigersin Thailand, with high lethality. [33][34]

"The Thailand Zoo tiger outbreak killed more than 140 tigers, causing health officials to make the decision to cull all the sick tigers in an effort to stop the zoo from becoming a reservoir for H5N1 influenza (ProMED-mail, 2004i; ProMED-mail, 2004w). A study of domestic cats showed H5N1 virus infection by ingestion of infected poultry and also by contact with other infected cats (Kuiken et al., 2004)." [35]

The spread to more and more types and populations of birds and the ability of cats to catch H5N1from eating this natural prey means the creation of a reservoir for H5N1 in cats where the virus can adopt to mammals is one of the many possible pathways to a pandemic.

Worst case scenario

The worst case scenario for a H5N1pandemic is somewhere around 150,000,000 human deaths directly due to H5N1 infection (or two to three percent of the world's human population). No one knows what the chances are for this worst case scenario.

"Influenza viruses keep changing. They mutate. And they exchange genetic material with other flu viruses, a process called reassortment. All that?s needed is a mutationor reassortment that produces a new variant of H5N1? one that?s as deadly as the current strain but as easily transmitted from human to human as lots of other flu strains. Most virologistsbelieve something like this will happen sooner or later, and many believe it will happen soon. When it does, H5N1 will inevitably spread throughout the world. Worldwide mortality estimates range all the way from 2?7.4 million deaths (the ?conservatively low? pandemic influenza calculation of a flu modeling expert at the U.S. Centers for Disease Control and Prevention) to 1 billion deaths (the bird flu pandemic prediction of one Russian virologist). The estimates of most H5N1 experts range less widely but still widely. In an H5N1 pandemic, the experts guess that somewhere between a quarter of us and half of us would get sick, and somewhere between one percent and five percent of those who got sick would die ? the young and hale as well as the old and frail. If it?s a quarter and one percent, that?s 16 million dead; if it?s a half and five percent, it?s 160 million dead. Either way it?s a big number." Pandemic Influenza Risk

Further reading

General information

• Nature Magazine focus on the global spread of H5N1
• Bird Flu Fears: Is There a Better Way to Develop Drugs? (Center for Economic and Policy Research) October 2005(PDF)
• Nature Magazine: Avian flu special: The flu pandemic: were we ready!?- Fictional account of flu epidemic from Nature magazine
• On line book available herecalled "The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)" by Board on Global Health (BGH) from the INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
• Emergency Measures Avian flu is on the rise in Vietnam and is now endemic in much of Asia. Can heightened vigilance keep it at bay?

News

• Current status (Google news of "H5N1")
• University of Pittsburgh scientists say they've genetically engineered an avian flu vaccine that has proven 100 percent effective in mice and chickens.from physorg.com

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It uses material from the http://en.wikipedia.org/wiki/Global+spread+of+H5N1 Wikipedia article Global spread of H5N1.