The 2009 outbreak of Influenza A virus subtype H1N1 is an epidemic of a new strain of influenza virus identified in April 2009, commonly referred to as swine flu. It is thought to be a mutation (reassortment) of four known strains of influenza A virus subtype H1N1: one endemic in humans, one endemic in birds, and two endemic in pigs (swine).^[73] The outbreak began in Mexico, where early reports indicated a surge of cases that had already killed at least 81 people by April 26. As a result, the U.N.'s World Health Organization (WHO), along with the U.S. Centers for Disease Control and Prevention (CDC), expressed concern that this could become a worldwide flu pandemic, with WHO raising its alert level to Phase 5 out of the six maximum, indicating that a pandemic was "imminent".

According to the CDC, it's not yet clear how serious this new virus actually is compared with other influenza viruses, although on May 26 they stated that new cases in the U.S. have probably peaked, and most cases throughout the world have so far been mild relative to "seasonal flus." But because this is a new virus, most people will not have immunity to it, and illness may eventually become more severe and widespread in different demographic and population groups as a result. The H1N1 flu mainly spreads in the same way that regular "seasonal influenza" spreads, which is through the air from coughs and sneezes or touching those infected. It cannot be transmitted from eating cooked pork or by being in close contact with pigs. ^[74]

As yet there is no vaccine available to prevent infection although companies are in the planning stages for having one available later this year. But there is concern that the virus could mutate again over the coming months, leading to a new and potentially more dangerous flu outbreak later in the year, and a vaccine that will be less effective in preventing its spread. Health officials in the U.S. point out that the "terrible experience" of the 1918 flu pandemic, which killed approximately 600,000 in the United States alone, was preceded by a mild "herald" wave of cases in the spring. ^[75]

As of June 1, the virus had spread to more than 66 countries, however over 80% of reported deaths have taken place in Mexico. This has led to speculation that Mexico may have been in the midst of an unrecognized epidemic for many months prior to the current outbreak, thereby showing a fatality rate that was much higher than it would have been if earlier cases had been counted. According to the CDC, the fact that the flu's infection activity is now monitored more closely may also help explain why more flu cases than normal are being recorded in many countries. With the southern hemisphere soon entering its winter flu season, the CDC, as part of WHO's global surveillance network, will help monitor cases in that region. It has supplied test kits to laboratories in more than 100 countries, and will be providing technical assitance to governments during the coming months.^[75]

[edit] Historical context

Annual influenza epidemics are estimated to affect 5–15% of the global population, resulting in severe illness in 3–5 million patients and causing 250,000–500,000 deaths worldwide. In industrialized countries severe illness and deaths occur mainly in the high-risk populations of infants, the elderly, and chronically ill patients.^[76]

In addition to these annual epidemics, the Influenza A virus caused three major global pandemics during the 20th century: the Spanish flu in 1918, Asian flu in 1957 and Hong Kong flu in 1968–69. These pandemics were caused by an Influenza A virus that had undergone major genetic changes and for which the population did not possess significant immunity.^[76][77] The overall effects of these pandemics are summarized in the table below.

The influenza virus has also caused several pandemic threats over the past century, including the pseudo-pandemic of 1947, the 1976 swine flu outbreak and the 1977 Russian flu, all caused by the H1N1 subtype.^[77] The world has been at an increased level of alert since the SARS epidemic in Southeast Asia (caused by the SARS coronavirus).^[81] The level of preparedness was further increased and sustained with the advent of the H5N1 bird flu outbreaks because of H5N1's high fatality rate, although the strains currently prevalent have limited human-to-human transmission (anthroponotic) capability, or epidemicity.^[78][82]

People who contracted flu prior to 1957 may have some immunity. A May 20 New York Times article stated: “Tests on blood serum from older people showed that they had antibodies that attacked the new virus, Dr. Daniel Jernigan, chief flu epidemiologist at the Centers for Disease Control and Prevention, said in a telephone news conference. That does not mean that everyone over 52 is immune, since some Americans and Mexicans older than that have died of the new flu.”^[83]

[edit] Initial outbreaks

A semi-logarithmic chart of laboratory-confirmed A(H1N1) influenza cases by date according to WHO reports.^[69]

[edit] Mexico

The outbreak was first detected in Mexico City on March 18, where surveillance began picking up a surge in cases of influenza-like illness. The surge was initially assumed by Mexican authorities to be "late-season flu" outbreak and not a new virus strain.^[84] Health Secretary Jose Angel Cordova confirmed that a 4-year-old boy was part of an outbreak in Veracruz state that began in February. Residents of the town of Perote worried at the time that they had a contracted a new and aggressive flu, and publicly demonstrated against the pig farm they initially blamed for their illness. It was only after U.S. labs confirmed a swine flu outbreak that Mexican officials sent the boy's sample in for testing, and it tested positive for swine flu.^[85] While there was speculation that the outbreak may have started at the pig plant in Veracruz,^[86] the plant owners said that no pigs had tested positive for the virus.^[87]

As the outbreak spread throughout Mexico and into the U.S., scientists were trying to understand why there were so many deaths in Mexico while infections in the United States and Canada were relatively mild and not unusually dangerous compared to seasonal flus. "If that continues to be true," wrote the Washington Post, "then it may help explain the mysteriously high mortality in Mexico." The newspaper noted that "it may be that Mexico already has had hundreds of thousands, and possibly millions, of cases -- all but the most serious hidden in the 'noise' of background illness in a crowded population."^[88] They added, "the fact that most people infected in other countries had recently been to Mexico -- or were in direct contact with someone who had been -- is indirect evidence that the country may have been experiencing a silent epidemic for months." ^[88][89] A study published May 11 in the journal Science estimated Mexico alone may have already had 23,000 cases of swine flu by April 23, the day it announced the epidemic.^[90]

As experts struggled to explain why so many deaths had initially occurred in Mexico and nowhere else, the CDC on May 1, suggested a simple explanation: "there are many cases in Mexico, most are mild, and just the bad ones have been seen so far."^[91] It noted that recent severe cases had focused on patients seeking care in hospitals and acknowledged that there could in fact be a large number of undetected cases of illness, which would explain the much higher mortality rate. Other experts agreed: "The central question every flu expert in the world would like answered, is how many mild cases Mexico has had," said Dr. Martin Cetron, director of global migration and quarantine for the Centers for Disease Control, in an interview. "We may just be looking at the tip of the iceberg, which would give you a skewed initial estimate of the case fatality rate," as he also speculated that there may have been tens of thousands of unreported mild infections, which would then make the number of deaths seemingly low, and as the flu spreads, the number of people who become seriously ill would remain relatively small.^[84]

[edit] U.S.

Both the place and the species in which the virus originated are unknown.^[92][93] Analysis has suggested that the H1N1 strain responsible for the current outbreak first evolved around September 2008 and circulated in the human population for several months before the first cases were detected.^[92][94][95] The new strain was first diagnosed in two children by the CDC, first on April 14 in San Diego County, California and a few days later in nearby Imperial County, California.^[96] Neither child had been in contact with pigs. ^{[96] [97]}

[edit] International cases and media responses

     Confirmed cases followed by death     Confirmed cases     Unconfirmed or suspected cases See also: H1N1 live map, WHO updates

[edit] Data accuracy

The initial outbreak received a week of near-constant media attention. ^[98] Epidemiologists cautioned that the number of cases reported in the early days of an outbreak can be very inaccurate and deceptive due to several causes, among them selection bias, media bias, and incorrect reporting by governments.^[99] This could also be due to authorities in different countries looking at different population groups, many poor, which may in part explain higher mortality rates in countries such as Mexico.^[99] Furthermore, countries with poor health care systems and older laboratory facilities may take longer to identify or report cases.^[100]

In late April, experts had predicted there would be 2,000 to 2,500 U.S. cases by the end of May. However, by May 15, the Centers for Disease Control and Prevention estimated that there were "upwards of 100,000" cases in the country, even though only 7,415 had been confirmed at that point. There have been no new estimates. Tim Germann, a computational scientist who worked on a 2006 flu forecast model at Los Alamos National Laboratory, has estimated there were now "a few hundred thousand" cases.^[101] The C.D.C. and state health departments have reportedly stopped confirming most cases in laboratories.^[101]

In some instances, governments have accused other countries of intentionally underreporting cases. Moscow, for instance, has hinted that the Caribbean island of The Dominican Republic was underreporting its number of swine flu cases to "boost tourism," and on May 30 advised its citizens not to travel there.^[102] In early May, Cuba's Fidel Castro accused Mexico of hiding the scope of the epidemic until after President Obama visited the country last month, and a study published in the journal Science on May 11, estimated Mexico alone may have had 23,000 cases of swine flu by April 23, the day it announced the epidemic.^[103]

On a local level the accuracy of data has also become an issue, with some U.S. school districts deciding to keep the names of students and schools that have reported infections confidential, one stating that "it would not be fair to single out one school," since doing so would likely trigger requests by parents to have their children tested despite their health not being in danger, and the schools lack the ability to test everyone.^[104]

[edit] Travel advisories

The new strain has spread widely beyond Mexico and the U.S., with confirmed cases in fifty-four countries and suspected cases in fifty-nine. Many countries had earlier advised citizens to avoid travelling to infected areas, especially Mexico, and were monitoring visitors returning from flu-affected areas for possible flu symptoms. In late April Mexico closed all of its schools and public places for a week to control its spread.^[105]

At first, most cases outside North America were recent travellers to Mexico or the U.S. However, intra-national infections have now also been reported from Canada, Japan, Panama, the UK, Spain, Germany, Australia, Italy, and Belgium.^[106]

On May 15, CDC’s "Travel Health Warning" recommending against non-essential travel to Mexico, in effect since April 27., was downgraded to a "Travel Health Precaution for Mexico." In lifting its warning, the CDC said, "There is evidence that the Mexican outbreak is slowing down in many cities though not all.” It also said that the “risk of severe disease” from the H1N1 virus "now appears to be less than originally thought."^[107]

Government actions against pigs and pork

Although the FAO, WHO, and OIE have reaffirmed that the H1N1 virus is not known to be transmissible from eating cooked pork or pork products,^[108] countries including Serbia, China, and Russia, have nevertheless banned the import and sale of pork products "as a precaution against swine flu".^[109][110] And in late April, the Egyptian Government had begun to kill all 300,000 pigs in Egypt, despite a lack of evidence that the pigs had, or were even suspected of having, the virus.^[111] This led to clashes between pig owners and the police in Cairo. Egypt's 80-million population consists mainly of Muslims, whose religion forbids them from eating pork, but also has an estimated six to ten percent of its population being native Christians (Copts), who eat pork as part of their diet.^{[112] [113]}

On May 10, in Alberta, Canada, officials quarantined 500 pigs at a pig farm which had caught the H1N1 virus, with evidence that some of the animals may have caught the virus from a person who had recently visited Mexico.^[114][115] Alberta's chief veterinarian says just under 500 hogs have been culled on the pig farm where the new swine flu virus was detected, but not because the animals were sick.^[116]

[edit] Virus characteristics

The virus is a novel strain of influenza from which human populations have been neither vaccinated nor naturally immunized.^[117] The CDC, after examining virus samples from suspected cases in Mexico, matched the strain with those from cases in Texas and California, and found no known linkages to either to animals or one another. It was also determined that the strain contained genes from four different flu viruses: North American swine influenza; North American avian influenza; human influenza; and two swine influenza viruses typically found in Asia and Europe. Further analysis showed that several of the proteins of the virus are most similar to strains that cause mild symptoms in humans, leading some to suggest that the virus is unlikely to cause severe symptoms for most people.^[118]

[edit] Rate of Infection

According to the World Health Organization, as of May 27, 2009, 54 countries have officially reported 12,954 cases of infection, including 92 deaths.^[119] But according to CDC experts, however, the flu outbreak in the U.S. is dying down in the country as a whole.^[120] As of May 30, Wisconsin had more cases than any other state: 1,430. However, Wisconsin officials said this was "nothing to worry about," pointing out that the higher numbers largely reflected the state's efficiency in testing suspected cases, and spokesman Seth Boffeli adding that the Wisconsin cases have been relatively mild.^[121]

But some news reports indicate that the swine flu is spreading more widely than official figures indicate, with outbreaks in Europe and Asia following those of North and South America. According to the CDC, about one in 20 cases is being officially reported in the U.S.^[122] In the U.K., according to virologist professor John Oxford, the virus may be 300 times more widespread than health authorities have said, with total infections estimated at 30,000. ^[123] Oxford's estimate comes as leading scientists are warning that estimates by the U.K. and other governments on the spread of the disease are "meaningless" and hiding its true extent. He also estimates that Japan may have approximately 30,000 cases. Professor Michael Osterholm, one of the world's top flu experts and an adviser to the U.S. government, also called the official figures "meaningless," claiming that officials were not hiding cases, but were not hunting very hard to find them.^[123] Oxford also believes that thousands of people have caught the virus and "suffered only the most minor symptoms," or none at all, over the past weeks.

Although the United States is past its flu season, the Southern Hemisphere, where the virus has also spread, is entering the cold months when influenza cases increase. Jeffery Taubenberger, a National Institutes of Health researcher, states that "I am loath to make predictions about what an influenza virus that mutates so rapidly will do," but he believes it will spread across the planet. Other experts concur, adding that "the new swine flu virus is almost certain to eventually infect every continent and country, although that may take years."^[88]

[edit] Virulence

Most fatalities have been in Mexico (87%, as of May 24, 2009) where, according to the New York Times, the deaths from the illness have primarily been young, healthy adults.^[124] The WHO Rapid Pandemic Assessment Collaboration estimated the case fatality ratio in Mexico prior to mid-April to be 0.4%. This is comparable to that of the 1957 Asian flu,^[125][126] a category 2 pandemic that killed approximately 1 to 4 million people.^[127]

By May 27, the CDC was reporting 6764 U.S. cases in 47 states resulting in fourteen deaths, but noted that for the most part, the infections continue to be mild—similar to seasonal flu—and recovery is fairly quick.^[128] Furthermore, analysis hasn't turned up any of the markers which scientists associate with the virulence of the 1918 "Spanish flu" virus, said Nancy Cox, head of the CDC's flu lab.

[edit] Mutation potential

On May 22, WHO chief Dr. Margaret Chan said that the virus must be closely monitored in the southern hemisphere, as it could mix with ordinary seasonal influenza and change in unpredictable ways. "In cases where the H1N1 virus is widespread and circulating within the general community, countries must expect to see more cases of severe and fatal infections," she said. "This is a subtle, sneaky virus."^[129]

This led other experts to become concerned that the new virus strain could mutate over the coming months. Guan Yi, a leading virologist from the University of Hong Kong, for instance, described the new H1N1 influenza virus as "very unstable", meaning it could mix and swap genetic material when exposed to other viruses. During an interview he said "Both H1N1 and H5N1 are unstable so the chances of them exchanging genetic material are higher, whereas a stable (seasonal flu) virus is less likely to take on genetic material." The H5N1 virus is mostly limited to birds, but in rare cases when it infects humans it has a mortality rate of between 60% to 70%.^[130] Experts worry about the emergence of a hybrid of the more virulent Asian-lineage HPAI (highly pathogenic avian influenza) A/H5N1 strain (media labeled "bird flu") with more human-transmissible Influenza A strains such as this novel 2009 swine-origin A/H1N1 strain (media labeled "swine flu"), especially since the H5N1 strain is and has been for years endemic in a variety of wild bird species in countries like China, Indonesia, Vietnam and Egypt.^[130] (See the suite of H5N1 articles for details.)

Nor had federal health officials in the U.S. dismissed the possibility that the worst was yet to come. "Far from it," Ann Schuchat of the CDC says, noting that the horrific 1918 flu epidemic, which killed millions in the United States alone, was preceded by a mild "herald" wave of cases in the spring, followed by devastating waves of illness in the fall. "That 1918 experience is in our minds," she said.^[120]

[edit] Pandemic potential

The WHO and CDC officials remain concerned that this outbreak may yet become a pandemic. WHO declared a Pandemic Alert Level of five, out of a maximum six, which describes the degree to which the virus has been able to spread among humans, and uses a Pandemic Severity Index, which predicts the number of fatalities if 30% of the human population were infected. By the end of April, however, some scientists believed that this strain was unlikely to cause as many fatalities as earlier pandemics, and may not even be as damaging as a typical flu season.^[132] WHO Director General Margaret Chan, on May 22, continued to stop short of declaring the outbreak a "pandemic," by moving to alert level six, because of recent doubts fostered by its mild symptoms to date^[133] along with fear that a pandemic "declaration would trigger mass panic" and be economically and politically damaging to many countries.^[134]

According to some experts, however, the current outbreak is already a pandemic. Michael Osterholm, director of the Center for Infectious Disease Research and Policy of the University of Minneapolis, feels that WHO’s criteria for a pandemic has been met.^[122] While Britain’s Health Secretary Alan Johnson has requested that the disease's severity and other determinants, besides its geographic spread, need to be considered before the pandemic alert is raised to the highest of WHO’s 6-level scale, since a move to phase 6 means that "emergency plans are instantly triggered around the globe." In addition, at phase 6, many pharmaceutical companies would switch from making seasonal flu shots to pandemic-specific vaccine, "potentially creating shortages of an immunization to counter the normal winter flu season."^[122] Keiji Fukuda, WHO's assistant director general of health security and environment, states that a move to phase 6 would "signify a really substantial increase in risk of harm to people."

Osterholm feels that the primary concern should be "scientific integrity," stating, "If they want to change the definition, then go ahead. But don’t say that we are not in phase 6 right now because we don’t want to go there." Rather than redefine what constitutes a pandemic, he suggests that health officials should help people understand that the current threat may resemble the 1957 or 1968 pandemics, in which fewer than 4 million people died, rather than the 1918 Spanish flu, blamed for killing about 50 million.^[122]

[edit] Symptoms and expected severity

CDC's CAPT Dr. Joe Bresee describes symptoms.