2009 swine flu outbreak

The 2009 outbreak of influenza A (H1N1) virus is an epidemic of a new strain of influenza virus identified in April 2009, and is commonly referred to as "swine flu." The source of the outbreak in humans is still unknown but cases were first discovered in the U.S. and officials soon suspected a link between this and an earlier outbreak of late-season flu cases in Mexico. Within days, hundreds more suspected cases, many resulting in death, were discovered in Mexico, with more cases found in the U.S. and several other countries. Soon after, the U.N.'s World Health Organization (WHO), along with the U.S. Centers for Disease Control and Prevention (CDC), became concerned that it could become a worldwide flu pandemic, and WHO then raised its pandemic alert level to "Phase 5" out of 6 maximum, as a "signal that a pandemic is imminent".

Although virologists have noted that the outbreak is so far relatively mild and less fatal than previous pandemics, other health officials, including Director Richard Besser, worry about what might happen later in the year, saying that "we are not seeing any sign of this petering out. We are still on the upswing of the epidemic curve. The number of cases is expected to rise as the new flu spreads across the country."

The new strain is an apparent reassortment of four strains of influenza A virus subtype H1N1.Analysis by the CDC identified the four component strains as one endemic in humans, one endemic in birds, and two endemic in pigs (swine). However, other scientists have stated that analysis of the 2009 swine flu (A/H1N1) viral genome suggests that all RNA segments are of swine origin, and "this preliminary analysis suggests at least two swine ancestors to the current H1N1, one of them related to the triple reassortant viruses isolated in North America in 1998." One swine influenza strain was widespread in the United States, the other in Eurasia.In a step towards understanding the outbreak, and developing a vaccine, Canadian scientists have completed the full genetic sequencing of H1N1 swine flu virus.

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.

In addition to these annual epidemics, the influenza A virus has 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, due to which the population did not possess significant immunity to the virus. .

(est.) Case fatality rate Data sources Spanish flu 1918–19 H1N1500 million 50 million >2.5%[Globalsecurity.org Asian flu 1957 H2N2 2 million <0.1% Globalsecurity.org Hong Kong flu 1968–69 H3N2 1 million <0.1% Globalsecurity.org 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. The world has been at an increased level of alert since the SARS epidemic in Southeast Asia (caused by the SARS coronavirus). 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 capability, or epidemicity.

Initial outbreaks
Source of the virus Both the place and the species in which the virus originated are unknown. Analysis of the virus by an international team of researchers 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. Interviewed in the 1 May issue of the journal Science about the origins and pandemic potential of the virus, Francis Plummer, the head of the National Microbiology Laboratory in Canada stated that "Right now, there's more unknown than there is known".

First diagnosis The new strain was first diagnosed as such when the CDC received a sample on April 14 from a ten-year-old boy who fell ill on March 30 in San Diego County, California and recovered after an illness lasting about one week. A second case was confirmed on April 17, in a nine-year-old girl who had fallen ill on March 28 in Imperial County, California and later made an "uneventful recovery". No person linking these patients was identified, and neither child had recently been in contact with pigs.

Spread within Mexico Further information: 2009 swine flu outbreak in Mexico The outbreak was first detected in Mexico City, where surveillance began picking up a surge in cases of influenza-like illness (ILI) starting March 18. The surge was assumed by Mexican authorities to be "late-season flu" (which usually coincides with a mild Influenzavirus B peak until April 21. when a U.S. Centers for Disease Control and Prevention alert concerning two isolated cases of a novel swine flu was reported in the media. Some samples were sent to the U.S.-based CDC on April 18. The Mexican cases were confirmed by the CDC and the World Health Organization to be a new strain of H1N1

Cases were also reported in the states of San Luis Potosí, Hidalgo, Querétaro and Mexico State. Mexican Health Minister José Ángel Córdova on April 24, said "We’re dealing with a new flu virus that constitutes a respiratory epidemic that so far is controllable."Mexican news media speculate that the outbreak may have started in February near a Smithfield Foods pig plant amid complaints about its intensive farming practices, although no pigs in Mexico have tested positive for the virus.

The first death from swine flu occurred on April 13, when a diabetic woman from Oaxaca died from respiratory complications.The Mexican fatalities are alleged to be mainly young adults of 25 to 45, a common trait of pandemic flu. Although by late April there had been reports of 152 "probable deaths" in Mexico, the WHO had received reports of only 7 confirmed deaths as of April 29 and explicitly denied the larger figure. Later, Mexico's Health Secretary declared that around 100 early suspected deaths from swine flu could not be confirmed because samples were not taken.

Seasonal variation The high humidity of summer and the increase in exposure to ultraviolet light typically leads to the end of the flu season as the virus becomes less likely to spread. In Mexico City, May marks the end of the dry season, and experts speculate that the spread of the swine flu may slow
On April 30, Mexican Health Secretary Jose Angel Cordova voiced cautious optimism that the spread of the swine flu might be slowing in that country. However, the outbreak comes at the beginning of the flu season for Southern Hemisphere countries such as New Zealand, Australia, South Africa, and parts of South America.

International cases and responses

The new strain has spread widely beyond Mexico and the U.S., with confirmed cases in eighteen countries and suspected cases in forty-two. Many countries have advised their inhabitants not to travel to infected areas. Areas including Australia, Hong Kong, Iceland, India, Indonesia, Malaysia, Philippines, Singapore, South Korea and Thailand are monitoring visitors returning from flu-affected areas to identify people with fever and respiratory symptoms. Many countries have also issued warnings to visitors of flu-affected areas to contact a doctor immediately if they had flu-like symptoms.

Mexico's schools, universities, and all public events were closed from April 24 to May 6, 2009. By May 3, 2009, more than 400 school closures in the U.S., which included entire school districts in Texas, affected 250,000 students due to confirmed or probable cases in students or staff

Government actions against pigs and pork Main article: 2009 swine flu outbreak action against pigs Although the FAO, WHO, and OIE have reaffirmed that "Influenza viruses are not known to be transmissible to people through eating processed pork or other food products derived from pigs," and although influenza A viruses are inactivated by heating, nevertheless some countries banned import and sale of pork products "as a precaution against swine flu".

Several countries, including Serbia, China and Russia banned the import of pork products from North America in general as a response to the outbreak, despite assurances from the WHO that the disease is not spread through pork. On April 29, the Egyptian Government decided 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. This led to clashes between pig owners and the police in Cairo.On May 5, Afghanistan's only pig, which resides at the Kabul zoo, was quarantined amid flu fears.

Zoonosis In Alberta, Canada, provincial and federal officials announced on May 2 that a 2,200-head pig herd in central Alberta was under quarantine after preliminary findings indicated some of the animals were infected with swine flu in a case of reverse zoonosis; it was presumed that a man who had recently visited Mexico infected the swine. Alberta agriculture minister George Groeneveld said that health officials expected no problems with export of pork from Canada to the United States, and that there was "absolutely no evidence" that the flu virus can be transmitted through eating pork.

Initial concerns regarding H1N1's pandemic potential See also: Pandemic Severity Index WHO and CDC officials remain concerned that this outbreak may yet become a pandemic. While tracking the progression of the H1N1 epidemic, public health organizations announced a Pandemic Alert Level, describing the degree to which the virus has been able to spread among humans, and a Pandemic Severity Index, which predicts the number of fatalities if 30% of the human population were infected. The criteria for these anouncements included:

The novelty of the strain The virus is a new strain of influenza, from which human populations have not been vaccinated or naturally immunized. In the United States, cases of the new strain infected 25% of family members, in contrast, seasonal influenza usually tends to sicken 5% to 20% of family members in the United States. The epidemicity of the strain The virus infects by human-to-human transmission. Investigations of infected patients indicated no direct contact with swine, such as at a farm or agricultural fair.The strain was later confirmed to have been transmitted between humans. In contrast, for example, disease transmission in the last severe human outbreak of influenza, the bird flu that peaked in 2006, was determined to be almost entirely from direct contact between humans and birds.[citation needed] A preliminary estimate places the basic reproduction number (R0) at 1.4 persons infected per case, slightly below the normal range of 1.5 to 3.0 for seasonal influenza. The generation time (the time until an infected person begins infecting others) is probably at the low end of a range between three to five days.The virulence of the strain All but three of the fatalities to date have been in Mexico where, according to the New York Times, the deaths from the illness have primarily been young, healthy adults. Most influenza strains produce the worst symptoms in young children, the elderly, and others with weaker immune systems. However, the CDC has indicated that symptoms reported from this strain so far are similar to those of normal seasonal flu. While some media outlets have speculated that this virus could cause a cytokine storm in patients, there is presently no evidence for this hypothesis, with the CDC stating that there is "insufficient information to date about clinical complications of this variant of swine-origin influenza A (H1N1) virus infection." A second flu strain, a variant of the seasonal H3N2 virus, has been observed by Canadian researchers and tentatively linked to a case returning from Mexico in mid-March, raising the possibility that this strain may account for some of the unusual patterns of illness observed in Mexico. Lack of contingent epidemiological data That other crucial factors were still largely unknown, such as the effectiveness of influenza vaccine stocks on hand, combined with the innate unpredictability of influenza strains, meant that reliable forecasts could not be made. To an uncertain extent, the risks which H1N1 presents still cannot be fully quantified. Predicting the size and severity of influenza outbreaks is a very inexact science. In 1976 the U.S. government incorrectly predicted a swine flu pandemic that never materialized.

That said, WHO officials observed that because there are "human cases associated with an animal influenza virus, and because of the geographical spread of multiple community outbreaks, plus the somewhat unusual age groups affected, these events are of high concern".

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.

WHO alert phases [show]WHO pandemic influenza phases (2009)Phase Description Phase 1 No animal influenza virus circulating among animals have been reported to cause infection in humans. Phase 2 An animal influenza virus circulating in domesticated or wild animals is known to have caused infection in humans and is therefore considered a specific potential pandemic threat. Phase 3 An animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Phase 4 Human to human transmission of an animal or human-animal influenza reassortant virus able to sustain community-level outbreaks has been verified. Phase 5 The same identified virus has caused sustained community level outbreaks in two or more countries in one WHO region. Phase 6 In addition to the criteria defined in Phase 5, the same virus has caused sustained community level outbreaks in at least one other country in another WHO region. Post peak period Levels of pandemic influenza in most countries with adequate surveillance have dropped below peak levels. Post pandemic period Levels of influenza activity have returned to the levels seen for seasonal influenza in most countries with adequate surveillance.

Phase 3 Prior to the swine flu outbreak, the WHO worldwide pandemic alert was set at Phase 3 due to H5N1 avian flu, which spread widely in birds with occasional cases in humans. A Phase 3 alert means that a new virus has been confirmed but there is no or limited evidence of human-to-human transmission - insufficient to sustain community-level outbreaks. The WHO decided not to raise the level of the worldwide pandemic alert after its first meeting, on April 25

Genetics and effects Genetic origins of the 2009 swine flu virus HA Hemagglutinin swine (H1) North America NA Neuraminidase swine (N1) Europe PA RNA polymerase subunit PA avian North America PB1 RNA polymerase subunit PB1human 1993 H3N2 strain PB2 RNA polymerase subunit PB2avian North America NP Nucleoprotein swine North America M Matrix protein M1, M2 swine Eurasia NS/NEP Non-structural proteins NS1,
NEP (Nuclear Export Protein) swine North America

Genetics On April 24, the CDC determined that seven samples from suspected cases in Mexico matched the strain that had infected patients in Texas and California with no known linkages to animals or one another; the strain appeared to be spreading from human to human. The CDC determined that the strain contained genes from four different flu viruses – North American swine influenza, North American avian influenza, human influenza, and swine influenza virus typically found in Asia and Europe – "an unusually mongrelised mix of genetic sequences."A CDC investigative team arrived in Mexico City on April 25 to work with Mexican counterparts to study the virus.

Pigs are susceptible to influenza viruses that can also infect both humans and birds, so they may act as a "mixing vessel" in which reassortment can occur between flu viruses of several species.Reassortment is a process that happens if two different types of influenza virus infect a single cell and it can produce a new strain of influenza. This is because the virus genome is split between eight independent pieces of RNA, which allows pieces of RNA from different viruses to mix together and form a novel type of virus as new virus particles are being assembled.This new strain appears to be a result of the reassortment of two swine influenza viruses, one from North America and one from Europe.But the North American pig strain was itself the product of previous reassortments, and has carried an avian PB2 gene for at least ten years and a human PB1 gene since 1993. These genes were passed on to the new virus.

Gene sequences for every viral gene were made available through the Global Initiative on Sharing Avian Influenza Data (GISAID). A preliminary analysis found that the hemagglutinin (HA) gene was similar to that of swine flu viruses present in U.S. pigs since 1999, but the neuraminidase (NA) and matrix protein (M) genes resembled versions present in European swine flu isolates. While viruses with this genetic makeup had not previously been found to be circulating in humans or pigs, there is no formal national surveillance system to determine what viruses are circulating in pigs in the U.S.So far, little is known about the spread of the virus in any pig population. A preliminary analysis has also shown that several of the proteins involved in the pathophysiology of the virus are most similar to strains that cause mild symptoms in humans. This suggests that the virus is unlikely to cause severe infections similar to those caused by the 1918 pandemic flu virus or the H5N1 avian influenza.

The seasonal influenza strain H1N1 vaccine is thought to be unlikely to provide protection.The virus is also resistant to amantadine and rimantadine, but sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza).

Symptoms and severity See also: Swine influenza#In humans, for symptoms in previous cases. The symptoms seen in U.S. cases resemble those normally seen in influenza, with fever, cough, sore throat, runny nose, headache, and muscle soreness. However, about 38% of patients had vomiting or diarrhea, which is unusual in infections with other strains of influenza. The incubation period between infection and the appearance of symptoms is about two to seven days

CDC's Dr. Joe Bresee describes symptoms. Watch video The CDC does not fully understand why the U.S. cases' symptoms were primarily mild while the Mexican cases had led to multiple deaths. However, research on previous pandemic strains has suggested that mortality can vary widely between different countries, with mortality being concentrated in the developing world.[161] Differences in the viruses or co-infection are also being considered as possible causes. In 1918, influenza weakened the infected, and it was then lung infections such as pneumonia which killed 3% of them. In the current outbreak, the first deaths (13 and 21 April) were diagnosed as 'atypical pneumonias', a pneumonia which, helped by the flu, becomes more dangerous. The CDC's flu chief Nancy Cox said that genetic analysis of the swine flu strain did not reveal the markers for virulence found in the 1918 flu virus.

At a press briefing on April 27, acting CDC director Richard Besser stated that out of 40 confirmed cases in the United States at that point, only one individual was hospitalized. He also revealed that the median age was 16 years "with a range in age of 7 to 54 years". By May 5, with 642 confirmed cases in the U.S., the age of the patients ranged from 3 months to 81 years, with 60% of cases occurred in people less than eighteen years old. In all, 36 patients (9%) required hospitalization and two people died.
Whereas most influenza strains affect the elderly and young children worst, most early deaths from this strain were in people aged 25–50 and the WHO expressed some concern over the unusual age profile of the deaths. However, more recent cases have a younger age profile, with more than half of Mexico's confirmed cases being in people aged under 20. By May 6, almost half of Mexico's confirmed swine flu deaths were in people aged under 30

Prevention and treatment

Personal hygiene Further information: Influenza: Prevention and Influenza treatment Recommendations to prevent infection by the virus consist of the standard personal precautions against influenza. This includes frequent washing of hands with soap and water or with alcohol-based hand sanitizers, especially after being out in public. The CDC advises not touching the mouth, nose or eyes, as these are primary modes of transmission. When coughing, they recommend coughing into a tissue and disposing of the tissue, then immediately washing the hands.

Transmission

Air There is so far little data available on the risk of airborne transmission of this particular virus. Mexican authorities are distributing surgical masks to the general public. The UK Health Protection Agency considers facial masks unnecessary for the general public. Many authorities recommend the use of respirators by health-care workers in the vicinity of pandemic flu patients, in particular during aerosol generating procedures (e.g. intubation, chest physiotherapy, bronchoscopy).

Food Although some pigs in Canada were recently found to be infected with the new strain of H1N1, the leading international health agencies have stressed that the "influenza viruses are not known to be transmissible to people through eating processed pork or other food products derived from pigs."

Antiviral drugs Of the available antiviral treatments for influenza, the WHO stated that the viruses obtained from the human cases with swine influenza in the United States were sensitive to oseltamivir (Tamiflu)and zanamivir (Relenza) but resistant to amantadine and rimantadine. Tamiflu and Relenza also have a preventative effect against Influenzavirus A in general. On April 27, the CDC recommended the use of Tamiflu and Relenza for both treatment and prevention of the new strain Roche Applied Science and the U.S. government had already extended the shelf life of federally stockpiled Tamiflu from the original five years to seven years because studies indicated that the medication continues to maintain its effectiveness.

Treatment with oseltamivir is typically preferred, because it is more easily administered, but in H3N2 flu treatment leads to resistance in 0.4% of adult cases and 5.5% of children. The resistant strains are typically less transmissible, and resistant human H1N1 viruses have become widely established. Fortunately, simulations reveal that using a second effective antiviral such as zanamivir (Relenza) to treat even 1% of cases will delay the spread of resistant strains. Even a drug such as amantadine (Symmetrel) for which resistance frequently emerges may be useful in combination therapy.

When buying these medications, some agencies such as the MHRA in the UK have recommended not using online souces, as the WHO estimates that half the drugs sold by online pharmacies without a physical address are counterfeit.

Vaccines Influenza vaccines are typically developed to cope with seasonal flu to minimize infection rates, yet it still kills around 500,000 people a year around the world. Currently, most of the world's flu vaccines use an injection of "killed virus," a vaccine method made famous by Jonas Salk when he developed the first vaccine against the polio virus in 1955. As The Economist magazine summarizes the problem today, however, "if a global pandemic is declared and manufacturers are asked to produce a vaccine for H1N1, they are unlikely to be able to respond quickly enough." Furthermore, vaccine producers can produce about a billion doses of any one vaccine each year, so that even if all the capacity was switched to fight the a pandemic flu, as opposed to a seasonal flu, "there would still be a huge global shortfall." Keiji Fukuda of the WHO said, "There’s much greater vaccine capacity than there was a few years ago, but there is not enough vaccine capacity to instantly make vaccines for the entire world’s population for influenza."

There is also concern that should a second, deadlier wave of a new H1N1 strain reappear this fall, producing pandemic vaccines now as a precaution may turn out to be a huge waste of resources with serious results, as the vaccine may not be as effective, and there would also be a shortage of seasonal flu vaccine available.William Schaffner, an infectious disease researcher at Vanderbilt University in Tennessee says that "for now, there is no way to tell whether the swine flu will die out this spring, or tarry through the summer and reappear as a stronger, meaner virus in the fall."As of early May, only a few more weeks were needed for the WHO and CDC to develop a "seed strain" of the pandemic virus, but producers would then need four to six months before they could create large volumes of vaccine.

The costs of producing a vaccine have also become an issue, with some U.S. lawmakers questioning whether a vaccine is worth the unknown benefits. Representatives Phil Gingrey and Paul Broun, for instance, are not convinced that the U.S. should spend up to $2 billion to produce one, with Gingrey stating "We can’t let all of our spending and our reaction be media-driven in responding to a panic so that we don’t get Katrina-ed. ... It’s important because what we are talking about as we discuss the appropriateness of spending $2 billion to produce a vaccine that may never be used — that is a very important decision that our country has to make."

Moreover, should a pandemic be declared and a vaccine produced, the WHO will attempt to make sure that a substantial amount is available for the benefit of developing countries. Vaccine makers and countries with standing orders, such as the U.S. and a number of European countries, will be asked, according to WHO officials, "to share with developing countries from the moment the first batches are ready if an H1N1 vaccine is made."

Previous influenza vaccines for the southern and northern hemispheres, including that for the 2009/2010 flu season, are ineffective against the new strain. The WHO claims that two separate immunizations will be required for seasonal and swine flu, but no decision would be made on whether to begin producing a swine flu vaccine until an advisory board meets on May 14. The board will receive input from manufacturers regarding when they are able to finish manufacturing the seasonal shot and begin production of the swine flu vaccine. Manufacturers at Sanofi-Aventis, GlaxoSmithKline, Baxter International and Novartis stated that they will wait for recommendations and "seed virus" from the WHO, and some may be ready to proceed with production at that time.

Containment On April 28, Dr. Keiji Fukuda, the Assistant Director-General for Health Security and Environment of WHO, pointed out that it is too late to contain the swine flu. "Containment is not a feasible operation. Countries should now focus on mitigating the effect of the virus," he said. He also stressed that the experts did not recommend closing borders or restricting travel. "With the virus being widespread... closing borders or restricting travel really has very little effects in stopping the movement of this virus." However, on April 28, the U.S. CDC began "recommending that people avoid non-essential travel to Mexico."The WHO's early reaction was that it saw no need at this point to issue travel advisories warning travellers not to go to parts of Mexico or the United States. The spokesperson said that the situation might change "depending on what the situation in the field is". WHO Director-General Dr. Margaret Chan also said that it was too premature to issue such recommendations without better analysis and understanding of the situation at this stage. Many countries confirmed that inbound international passengers will be screened. Typical airport health screening involves asking passengers which countries they have visited and checking whether they feel or appear particularly unwell. Thermographic equipment was put into use at a number of airports to screen passengers. In the U.S.A., two confirmed cases were detected through their border infectious disease surveillance.A number of countries advised against travel to known affected regions.

Dr. Ira Longini, a specialist in the mathematical and statistical theory of epidemics, suggests that if those infected stay at home or seek medical care, public meeting places are closed, and anti-flu medications are made widely available, then in simulations the sickness is reduced by nearly two-thirds. "The name of the game is to slow transmission until a well-matched vaccine can be made and distributed. I am fairly optimistic we can do that".

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1918 flu pandemic

1976 swine flu outbreak

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