Influenza A virus subtype H1N1.

Influenza A (H1N1) virus is a subtype of influenzavirus A and the most common cause of influenza (flu) in humans. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a large fraction of all seasonal influenza. H1N1 strains caused roughly half of all human flu infections in 2006. Other strains of H1N1 are endemic in pigs (swine influenza) and in birds (avian influenza).
In June 2009, World Health Organization declared that flu due to a new strain of swine-origin H1N1 was responsible for the 2009 flu pandemic. This strain is often called "swine flu" by the public media.
Nomenclature
Influenza A virus strains are categorized according to two proteins found on the surface of the virus: hemagglutinin (H) and neuraminidase (N). All influenza A viruses contain hemagglutinin and neuraminidase, but the structures of these proteins differ from strain to strain, due to rapid genetic mutation in the viral genome.
Influenza A virus strains are assigned an H number and an N number based on which forms of these two proteins the strain contains. There are 16 H and 9 N subtypes known in birds, but only H 1, 2 and 3, and N 1 and 2 are commonly found in humans.
Spanish flu
The Spanish flu, also known as La Gripe Española, or La Pesadilla, was an unusually severe and deadly strain of avian influenza, a viral infectious disease, that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919. It is thought to be one of the most deadly pandemics in human history. It was caused by the H1N1 type of influenza virus.
The 1918 flu caused an unusual number of deaths, possibly due to it causing a cytokine storm in the body. (The current H5N1 bird flu, also an Influenza A virus, has a similar effect.) The Spanish flu virus infected lung cells, leading to overstimulation of the immune system via release of cytokines into the lung tissue. This leads to extensive leukocyte migration towards the lungs, causing destruction of lung tissue and secretion of liquid into the organ. This makes it difficult for the patient to breathe. In contrast to other pandemics, which mostly kill the old and the very young, the 1918 pandemic killed unusual numbers of young adults, which may have been due to their healthy immune systems mounting a too-strong and damaging response to the infection.
The term "Spanish" flu was coined because Spain was at the time the only European country where the press were printing reports of the outbreak, which had killed thousands in the armies fighting World War I. Other countries suppressed the news in order to protect morale.[8]
Russian flu
The more recent Russian flu was a 1977–1978 flu epidemic caused by strain Influenza A/USSR/90/77 (H1N1). It infected mostly children and young adults under 23 because a similar strain was prevalent in 1947–57, causing most adults to have substantial immunity. Some have called it a flu pandemic, but because it only affected the young it is not considered a true pandemic. The virus was included in the 1978–1979 influenza vaccine.
2009 A(H1N1) pandemic
In the 2009 flu pandemic, the virus isolated from patients in the United States was found to be made up of genetic elements 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." This new strain appears to be a result of reassortment of human influenza and swine influenza viruses, in all four different strains of subtype H1N1.
Preliminary genetic characterization 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. The six genes from American swine flu are themselves mixtures of swine flu, bird flu, and human flu viruses. 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.
On June 11, 2009, the WHO declared an H1N1 pandemic, moving the alert level to phase 6, marking the first global pandemic since the 1968 Hong Kong flu

The 2009 flu pandemic is a global outbreak of a new strain of influenza A virus subtype H1N1, officially referred to as novel H1N1, first identified in April 2009 and commonly called swine flu. The virus is a mixing (reassortment) of four known strains of influenza A virus: one endemic in humans, one endemic in birds, and two endemic in pigs (swine). Transmission of the new strain is human-to-human, and eating cooked pork products will not transmit the virus.
The outbreak began in Mexico, with evidence that there had been an ongoing epidemic for months before it was officially recognized as such. The Mexican government soon closed most of Mexico City's public and private offices and facilities to contain the spread of the virus. As the virus quickly spread globally, clinics were overwhelmed by testing and treating patients, and the WHO and the U. S. Centers for Disease Control and Prevention (CDC) eventually stopped counting all cases and focused instead on tracking major outbreaks. In early June 2009, the World Health Organization (WHO) declared the outbreak to be a pandemic, but also noted that most of the illnesses were of moderate severity.
The illness is generally mild, except in some cases for people in higher risk groups, such as those with asthma, diabetes, obesity, heart disease, or who are pregnant or have a weakened immune system. In addition, even in people who were previously healthy, secondary infections, such as those caused by bacterial pneumonia or a relapse of the illness with worse symptoms, are considered very serious and require medical treatment.
Like other influenza viruses, novel H1N1 influenza is spread by coughing, sneezing, or touching contaminated surfaces and then touching the nose or mouth. Symptoms, which last up to a week, are similar to those of seasonal flu, and can include fever, sneezing, sore throat, cough, headache, and muscle or joint pains. To avoid spreading the infection, the CDC recommended that those with symptoms stay home from school, work, and crowded settings; in general, wearing facial masks was not recommended, except in healthcare settings.
Historical context
Annual influenza epidemics are estimated to affect 5–15% of the global population. Although most cases are mild, these epidemics still cause severe illness in 3–5 million people and 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,[6] although the swine flu outbreak (as well as the 1918 Spanish flu) differs in its tendency to affect younger, healthier people.
In addition to these annual epidemics, Influenza A virus strains caused three global pandemics during the 20th century: the Spanish flu in 1918, Asian flu in 1957, and Hong Kong flu in 1968–69. These virus strains had undergone major genetic changes for which the population did not possess significant immunity.[6][8] Recent genetic analysis has revealed that three-quarters, or six out of the eight genetic segments of the 2009 flu pandemic strain arose from the North American swine flu strains circulating since 1998, when a new strain was first identified on a factory farm in North Carolina, and which was the first-ever reported triple-hybrid flu virus.
The great majority of deaths in the 1918 flu pandemic were the result of secondary bacterial pneumonia. The influenza virus damaged the lining of the bronchial tubes and lungs of victims, allowing common bacteria from the nose and throat to infect their lungs. Subsequent pandemics have had many fewer fatalities due to the development of antibiotic medicines that can treat pneumonia.
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.[8] 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 (anthroponotic) capability, or epidemicity.
People who contracted flu before 1957 appeared to have some immunity to H1N1. Dr. Daniel Jernigan of the CDC has stated: "Tests on blood serum from older people showed that they had antibodies that attacked the new virus [...] That does not mean that everyone over 52 is immune, since Americans and Mexicans older than that have died of the new flu."
Initial outbreaks
It is not known where the virus originated. Analyses in scientific journals have suggested that the H1N1 strain responsible for the current outbreak first evolved in September 2008, and circulated among humans for several months before being identified as a new strain of flu.
Mexico
The virus was first reported in two US children in March 2009, but health officials have reported that it apparently infected people as early as January 2008 in Mexico. The outbreak was first detected in Mexico City on March 18, 2009; immediately after the outbreak was officially announced, Mexico requested material support from the US, and within days of the outbreak Mexico City was "effectively shut down". Some countries canceled flights to Mexico while others halted trade. Calls to close the border to contain the spread were rejected. Mexico already had hundreds of cases before the outbreak was officially recognized, and was therefore in the midst of a "silent epidemic". As a result, Mexico was reporting only the most serious cases, possibly leading to a skewed initial estimate of the case fatality rate."
United States
The new strain was first identified by the CDC in two children, neither of whom had been in contact with pigs. The first case, from San Diego County, California, was confirmed from clinical specimens (nasopharyngeal swab) examined by the CDC on April 14, 2009. A second case, from nearby Imperial County, California, was confirmed on April 17. The patient in the first confirmed case had flu symptoms including fever and cough on clinical exam on March 30, and the second on March 28. It was not identified as a new strain in Mexico until April 24.[32]
Response
On April 27, the European Union health commissioner advised Europeans to postpone nonessential travel to the United States or Mexico. This followed the discovery of the first confirmed case in Spain. On May 6, 2009, the Public Health Agency of Canada announced that their National Microbiology Laboratory (NML) had mapped the genetic code of the swine flu virus, the first time that was done. In England, the National Health Service launched a website, the National Pandemic Flu Service, allowing patients to self-assess and get an authorization number for antiviral medication. The system was expected to reduce the burden on general practitioners.
US officials observed that six years of worrying about H5N1 avian flu did much to prepare for the current swine flu outbreak, noting that after H5N1 emerged in Asia, ultimately killing about 60% of the few hundred people infected by it over the years, many countries took steps to try to prevent any similar crisis from spreading further. The CDC and other American governmental agencies[39] used the summer lull to take stock of the United States's response to the new H1N1 flu and attempt to patch any gaps in the public health safety net before flu season started in early autumn. Preparations included planning a second influenza vaccination program in addition to the one for seasonal influenza, and improving coordination between federal, state, and local governments and private health providers.
Pigs and food safety
The novel H1N1 virus is a type of swine influenza, derived originally from a strain that lived in pigs and this origin gave rise to the common name of "swine flu", widely used by mass media. Despite this origin, however, the strain was transmitted between people and not from swine. The United States Secretary of Agriculture made clear that despite its common name being "swine flu", there is no risk of contracting flu from eating cooked pork products and the virus has not been found in American hogs. On April 27, Azerbaijan imposed a ban on import of animal husbandry products from America. The Indonesian government halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia. The Egyptian government ordered the slaughter of all pigs in Egypt on April 29, 2009.
Nomenclature
The initial outbreak was called the "H1N1 influenza". The CDC began also referring to it as "Novel Influenza A (H1N1)". In the Netherlands, it was originally called "pig flu", but is now called "Mexican flu" by the national health institute and in the media. South Korea and Israel briefly considered calling it the "Mexican virus". Later, the South Korean press used "SI", short for "swine influenza". Taiwan suggested the names "H1N1 flu" or "new flu", which most local media adopted. The World Organization for Animal Health proposed the name "North American influenza". The European Commission adopted the term "novel flu virus".
Virus characteristics
The virus is a novel strain of influenza, and existing vaccines against seasonal flu provide no protection. A study at the US Centers for Disease Control and Prevention, published in May 2009, found that children had no preexisting immunity to the new strain but that adults, particularly those over 60, had some degree of immunity. Children showed no cross-reactive antibody reaction to the new strain, adults aged 18 to 64 had 6–9%, and older adults 33%. It was also determined that the strain contained genes from five 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 proteins of the virus are most similar to strains that cause mild symptoms in humans, leading virologist Wendy Barclay to suggest on 1 May 2009 that the initial indications are that the virus was unlikely to cause severe symptoms for most people.
In July 2009, the CDC noted that most infections were mild, similar to seasonal flu, recovery tended to be fairly quick, and deaths to date had been only a fraction of the number of people who die every year from seasonal flu. The 1918 flu epidemic began with a wave of mild cases in the spring, followed by more deadly waves in the autumn, eventually killing hundreds of thousands in the United States. Researchers from the University of Maryland mixed swine flu and seasonal flu and concluded that the swine flu was unlikely to get more lethal.
Symptoms and severity
CDC's CAPT Dr. Joe Bresee describes symptoms.The symptoms of swine flu are similar to other influenzas, and may include a fever, coughing (typically a "dry cough"), headaches, pain in the muscles or joints, sore throat, chills, fatigue, and runny nose. Diarrhea, vomiting, and neurological problems were also reported in some cases. People at higher risk of serious complications include people age 65 and older, children younger than 5 years old, children with neurodevelopmental conditions, pregnant women, and people of any age with underlying medical conditions, such as asthma, diabetes, obesity, heart disease, or a weakened immune system (e.g., taking immunosuppressive medications or infected with HIV).
Most hospitalizations in the US were people with such underlying conditions, according to the CDC.
In adults
In adults, shortness of breath, pain in the chest or abdomen, sudden dizziness, or confusion may require emergency care. In both children and adults, persistent vomiting or the return of flu-like symptoms that include a fever and cough may require medical attention. Dr. Thomas R. Frieden, Director of the CDC, suggests that people with "underlying conditions" who come down with flu symptoms should consult their doctors first before visiting an "emergency room full of sick people," since it "may actually put them in more danger." This was especially true of pregnant women.
In children
As with the seasonal flu, certain symptoms may require emergency medical attention. In children, signs of respiratory distress include blue lips and skin, dehydration, rapid breathing, excessive sleeping, seizures, and significant irritability including a lack of desire to be held. Although "too early" to tell for certain, Dr. Frieden has noted that so far the swine flu "seems to be taking a heavier toll among chronically ill children than the seasonal flu usually does." Of the children who have died so far, nearly two-thirds had pre-existing nervous system disorders, such as cerebral palsy, muscular dystrophy, or developmental delays. "Children with nerve and muscle problems may be at especially high risk for complications," the CDC report stated. In children without chronic health problems, it is a warning sign if they seem to recover from the flu but then relapse with a high fever, Dr. Frieden added. The relapse may be bacterial pneumonia, which must be treated with antibiotics.
Vaccination and prevention
The pandemic is expected to peak by mid-winter in the Northern hemisphere. The CDC recommended that initial vaccine doses should go to priority groups such as pregnant women, people who live with or care for babies under six months old, children six months to four years old and health-care workers. In the UK, the NHS recommended vaccine priority go to people over six months old who were clinically at risk for seasonal flu, pregnant women, and households of people with compromised immunity.
Although it was initially thought that two injections would be required, clinical trials showed that the new vaccine protects "with only one dose instead of two", and so the limited vaccine supplies would go twice as far as had been predicted. Costs would also be lowered by having a "more efficient vaccine". For children under the age of 10, two administrations of the vaccine, spaced 21 days apart, are recommended. The seasonal flu will still require a separate vaccination.
Health officials worldwide were also concerned because the virus was new and could easily mutate and become more virulent, even though most flu symptoms were mild and lasted only a few days without treatment. Officials also urged communities, businesses and individuals to make contingency plans for possible school closures, multiple employee absences for illness, surges of patients in hospitals and other effects of potentially widespread outbreaks.
To combat the virus, the WHO and the US government geared up for a massive vaccination campaign in late 2009, one not seen since Jonas Salk discovered the polio vaccine in 1955, despite the questionable benefits of the H1N1 vaccines available to date.
The Mayo Clinic suggested personal measures to avoid seasonal flu infection were applicable to the 2009 pandemic: vaccination when available, thorough and frequent hand-washing, a balanced diet with fresh fruits and vegetables, whole grains, and lean protein, sufficient sleep, regular exercise, and avoiding crowds. The leading health agencies stressed that eating properly cooked pork or other food products derived from pigs would not cause flu.
Travel precautions.
The WHO stated that containment was not a feasible option and that countries should focus on mitigating the effect of the virus. It did not recommend closing borders or restricting travel. On April 26, 2009, the Chinese government announced that that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined. On May 2, 2009, China suspended flights from Tijuana to Shanghai.
The president of the Association of Flight Attendants told members of a US Congressional subcommittee that all flight attendants should be given training in how to handle a person with flu and help in communicating to passengers the importance of keeping clean hands. She also said that flight attendants need to be provided gloves and facemasks to deal with flu-stricken passengers. Lahey Clinic vice chairman of emergency medicine and Tufts University assistant professor of emergency medicine Mark Gendreau adds that airlines should also ensure that passenger cabins are always properly ventilated, including during flight delays in which passengers are kept aboard the plane. But he also adds that although the aviation industry in the US, along with the CDC, have tried to reassure passengers that air travel is safe, they have so far done too little to try to limit infection risks.
US airlines had made no major changes as of the beginning of June 2009, but continued standing practices that included looking for passengers with symptoms of flu, measles, or other infections, and relying on in-flight air filters to ensure that aircraft were sanitized. Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them. Some non-US airlines, mostly Asian ones, including Singapore Airlines, China Eastern Airlines, China Southern Airlines, Cathay Pacific, and Mexicana Airlines, took measures such as stepping up cabin cleaning, installing state-of-the-art air filters, and allowing in-flight staff to wear face masks.
Schools
The early days of the swine flu outbreak led to numerous precautionary school closures in several countries. However, as the virus eventually proved to be milder than had been initially feared, schools reopened and the closures stopped. Among countries that reported school closures were the United States, India, Australia, New Zealand, Hong Kong, Mexico, Guatemala, Argentina, Brazil, Canada, and Costa Rica. Rather than closing schools, the CDC recommends that students and school workers with flu symptoms should stay home for either seven days, or until 24 hours after symptoms subside—whichever is longer. If the outbreak suddenly turns severe, additional measures such as school closings would then be considered.
In California, school districts and universities are on alert and working with health officials to launch education campaigns. Many planned to stockpile medical supplies and discuss worst-case scenarios, including plans to provide lessons and meals for low-income children in case elementary and secondary schools close.[83] University of California campuses were stockpiling supplies, from paper masks and hand sanitizer to food and water, and were considering screening students for fever when they check into dorms, though it appears they did not end up doing so. The CDC has also advised that schools set aside a room for people developing flu-like symptoms while they wait to go home and that surgical masks be used for ill students or staff and those caring for them. To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggests that every county should create an "influenza action team" to be run by the local health department, parents, and school administrators.
In the US, the Department of Health and Human Services (HHS), Department of Education (ED), and the Centers for Disease Control and Prevention (CDC) have published new guidelines along with a toolkit for Institutions of Higher Education (IHE) to plan for and respond to the upcoming flu season. Government officials are especially concerned because the virus appears to disproportionately affect young people between ages 6 months to 24 years of age, making them one of the top priority groups when it comes to the new H1N1 vaccine. The new guidelines provide a list of strategies to keep learning facilities open while reducing exposure of students, faculty, and staff. They state that the most important actions are to encourage and facilitate good hand washing and covering coughs and sneezes, flu vaccinations for people at risk; and to separate sick people from healthy people as soon as possible.
The CDC recommends that colleges should consider suspending fall 2009 classes if the virus begins to cause severe illness in a significantly larger share of students than last spring. They have also urged schools to suspend any rules, including penalizing late papers or missed classes, or requiring a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill.
Workplace
The US Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC), with input from the US Department of Homeland Security (DHS), has developed updated guidance[88] and a video for employers to use as they develop or review and update plans to respond to 2009 H1N1 influenza now and during the upcoming fall and winter influenza season. The guidance states that employers should consider and communicate their objectives, which may include reducing transmission among staff, protecting people who are at increased risk of influenza related complications from getting infected with influenza, maintaining business operations, and minimizing adverse effects on other entities in their supply chains.
The CDC estimates that as much as 40% of the workforce, in a worst-case scenario, might be unable to work at the peak of the pandemic due to the need for many healthy adults to stay home and care for an ill family member, and advising that individuals should have have steps in place should a workplace close down or a situation arise that requires working from home. The CDC further advises that persons in the workplace should stay home sick for seven days after getting the flu, or 24 hours after symptoms end, whichever is longer. In the UK, the Health and Safety Executive (HSE) has also issued general guidance for employers.
Warnings
In Tasmania, Australia swine flu notices such as "Wash your Hands" and "Cover your Cough" have been placed in numerous schools, offices, shops, clinics, businesses and even in residential homes to remind Tasmanians of the importance of staying clean and proper hygienic habits.
Facial masks
The CDC does not recommend use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who are ill with the virus should consider wearing one when around other people, and people who are at risk for severe illness while caring for someone with the flu. There is general uncertainty among health professionals about the value of wearing either facial masks or more expensive respirators to prevent infection. Dr. Laurene Mascola, Los Angeles County Department of Public Health's director of acute communicable disease control, stated that "masks may give people a false sense of security," and associate professor of medicine at the USC Keck School of Medicine Dr. Paul Holtom stressed that masks should not replace other standard precautions. Masks may benefit people in close contact with infected persons but it was unknown whether they prevented swine flu infection. According to mask manufacturer 3M, masks will filter out particles in industrial settings, but "there are no established exposure limits for biological agents such as swine flu virus."
Quarantines
Countries have begun quarantining or have threatened to quarantine foreign visitors suspected of having or being in contact with others who may have been infected. In May, the Chinese government confined 21 US students and three teachers to their hotel rooms. As a result, the US State Department issued a travel alert about China's anti-flu measures and was warning travelers about traveling to China if ill. In Hong Kong, an entire hotel was quarantined with 240 guests; Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat. Egyptians who went on the annual Muslim pilgrimage to Mecca risked being quarantined upon their return. Russia and Taiwan said they would quarantine visitors from areas where the flu is present who have fevers. Japan quarantined 47 airline passengers in a hotel for a week. India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection.
Treatment
The Mayo Clinic and Medline listed ways to help ease symptoms, including adequate liquid intake and rest, soup to ease congestion, and over-the-counter drugs to relieve pain. Aspirin was a very effective way to treat fever in adults, although in children and adolescents, aspirin is advised against due to the risk of Reye's syndrome. While over-the-counter drugs relieve symptoms, they do not kill the virus. Most patients were expected to recover without medical attention, although those with pre-existing or underlying medical conditions were more prone to complications.
According to the CDC, antiviral drugs could be given to treat those who become severely ill, two of which were recommended for swine flu symptoms: oseltamivir (Tamiflu) and zanamivir (Relenza). To be most useful, they were to be given within two days of showing symptoms and "may shorten the illness by a day or so," according to the Mayo Clinic. To help avoid shortages of these drugs, the CDC recommended Tamiflu treatment primarily for people hospitalized with swine flu; people at risk of serious flu complications due to underlying medical conditions; and patients at risk of serious flu complications. The WHO likewise recommended that Tamiflu only be given to particularly vulnerable people and noted that healthy people who catch mild to moderate cases of swine flu did not need the drug at all. The CDC warned that the indiscriminate use of antiviral medications to prevent and treat influenza could ease the way for drug-resistant strains to emerge which would make the fight against the pandemic that much harder. In addition, a British report found that people often failed to complete a full course of the drug, a behavior which encouraged resistance.
Both medications could have caused side effects, including lightheadedness, nausea, vomiting, loss of appetite, and trouble breathing, and it was recommended that patients discuss possible side effects with their doctor before starting antiviral medication. Children were reported to be at increased risk of self-injury and confusion after taking Tamiflu. The WHO warned against buying antiviral medications from online sources, estimating that half the drugs sold by online pharmacies without a physical address are counterfeit
Data reporting and accuracy
The initial outbreak received a week of near-constant media attention. 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. Inaccuracies could also be caused by authorities in different countries looking at differing population groups. Furthermore, countries with poor health care systems and older laboratory facilities may take longer to identify or report cases.[108] Dr. Joseph S. Bresee (the CDC flu division's epidemiology chief) and Dr. Michael T. Osterholm (director of the Center for Infectious Disease Research) have pointed out that millions of people have had swine flu, usually in a mild form, so the numbers of laboratory-confirmed cases were actually meaningless, and in July 2009 the WHO stopped keeping count of individual cases and focused more on major outbreaks.

Fuentes:
http://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H1N1
http://en.wikipedia.org/wiki/2009_flu_pandemic