2009 swine flu pandemic

The World Health Organization reports that the clinical picture in severe cases is strikingly different from the disease pattern seen during epidemics of seasonal influenza. While people with certain underlying medical conditions are known to be at increased risk, many severe cases occur in previously healthy people. In severe cases, patients generally begin to deteriorate around three to five days after symptom onset. Deterioration is rapid, with many patients progressing to respiratory failure within 24 hours, requiring immediate admission to an intensive care unit. Upon admission, most patients need immediate respiratory support with mechanical ventilation.[67]

Most complications have occurred among previously unhealthy individuals, with obesity and respiratory disease as the strongest risk factors. Pulmonary complications are common. Primary influenza pneumonia occurs most commonly in adults and may progress rapidly to acute lung injury requiring mechanical ventilation. Secondary bacterial infection is more common in children. Staphylococcus aureus, including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with a high mortality rate; Streptococcus pneumoniae is the second most important cause of secondary bacterial pneumonia for children and primary for adults. Neuromuscular and cardiac complications are unusual but may occur.[68]

A United Kingdom investigation of risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza looked at 631 patients from 55 hospitals admitted with confirmed infection from May through September 2009. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged <16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically confirmed pneumonia and a raised C-reactive protein (CRP) level (≥100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people.[69]

Fulminant (sudden-onset) myocarditis has been linked to infection with H1N1, with at least four cases of myocarditis confirmed in patients also infected with A/H1N1. Three out of the four cases of H1N1-associated myocarditis were classified as fulminant, and one of the patients died.[70] Also, there appears to be a link between severe A/H1N1 influenza infection and pulmonary embolism. In one report, five out of 14 patients admitted to the intensive care unit with severe A/H1N1 infection were found to have pulmonary emboli.[71]

An article published in JAMA in September 2010[72] challenged previous reports and stated that children infected in the 2009 flu pandemic were no more likely to be hospitalised with complications or get pneumonia than those who catch seasonal strains. Researchers found that about 1.5% of children with the H1N1 swine flu strain were hospitalised within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus.[56]

Spread of the H1N1 virus is thought to occur in the same way that seasonal flu spreads. Flu viruses are spread mainly from person to person through coughing or sneezing by people with influenza. Sometimes people may become infected by touching something—such as a surface or object—with flu viruses on it and then touching their face.[41]

The basic reproduction number (the average number of other individuals whom each infected individual will infect, in a population which has no immunity to the disease) for the 2009 novel H1N1 is estimated to be 1.75.[90] A December 2009 study found that the transmissibility of the H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms.[91]

The H1N1 virus has been transmitted to animals, including swine, turkeys, ferrets, household cats, at least one dog, and a cheetah.[92][93][94][95]

On 27 April 2009, 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.[104] On 6 May 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 had been done.[105] In the U.K., the National Health Service launched a website, the National Pandemic Flu Service,[106] allowing patients to self-assess and get an authorisation number for antiviral medication. The system was expected to reduce the burden on general practitioners.[97]

U.S. officials observed that six years of concern about H5N1 avian flu did much to prepare for the current H1N1 outbreak, noting that after H5N1 emerged in Asia, ultimately killing about 60% of the few hundred people infected over the years, many countries took steps to try to prevent any similar crisis from spreading further.[107] The CDC and other U.S. governmental agencies[108] used the summer lull to take stock of the United States response to H1N1 flu and attempt to patch any gaps in the public health safety net before flu season started in early autumn.[109] Preparations included planning a second influenza vaccination program in addition to the one for seasonal flu, and improving coordination between federal, state, and local governments and private health providers.[109] On 24 October 2009, U.S. President Obama declared swine flu a national emergency, giving Secretary of Health and Human Services Kathleen Sebelius authority to grant waivers to requesting hospitals from usual federal requirements.[110]

President Barack Obama being vaccinated against H1N1 flu on 20 December 2009

By 19 November 2009, doses of vaccine had been administered in over 16 countries. A 2009 review by the U.S. National Institutes of Health (NIH) concluded that the 2009 H1N1 vaccine has a safety profile similar to that of seasonal vaccine.

In 2011, a study from the US Flu Vaccine Effectiveness Network estimated the overall effectiveness of all pandemic H1N1 vaccines at 56%. A CDC study released 28 January 2013, estimated that the Pandemic H1N1 vaccine saved roughly 300 lives and prevented about a million illnesses in the US. The study concluded that had the vaccination program started two weeks earlier, close to 60% more cases could have been prevented. The study was based on an effectiveness in preventing cases, hospitalizations, and deaths of 62% for all subgroups except people over 65, for whom the effectiveness was estimated at 43%. The effectiveness was based on European and Asian studies and expert opinion. The delay in vaccine administration demonstrated the shortcomings of the world's capacity for vaccine-production, as well as problems with international distribution. Some manufacturers and wealthy countries had concerns regarding liability and regulations, as well as the logistics of transporting, storing, and administering vaccines to be donated to poorer countries.[111]

In January 2010, Wolfgang Wodarg, a German deputy who trained as a physician and now chairs the health committee at the Council of Europe, claimed major firms had organized a "campaign of panic" to put pressure on the World Health Organization (WHO) to declare a "false pandemic" to sell vaccines. Wodarg said the WHO's "false pandemic" flu campaign is "one of the greatest medicine scandals of the century". He said that the "false pandemic" campaign began in May 2009 in Mexico City, when a hundred or so "normal" reported influenza cases were declared to be the beginning of a threatening new pandemic, although he said there was little scientific evidence for it. Nevertheless, he argued that the WHO, "in cooperation with some big pharmaceutical companies and their scientists, re-defined pandemics," removing the statement that "an enormous amount of people have contracted the illness or died" from its existing definition and replacing it by stating simply that there has to be a virus, spreading beyond borders and to which people have no immunity.[112]

The WHO responded by stating that they take their duty to provide independent advice seriously and guarded against interference from outside interests. Announcing a review of the WHO's actions, spokeswoman Fadela Chaib stated: "Criticism is part of an outbreak cycle. We expect and indeed welcome criticism and the chance to discuss it".[113][114] In March 2010, the Council of Europe launched an enquiry into "the influence of the pharmaceutical companies on the global swine flu campaign", and a preliminary report is in preparation.[115]

On 12 April 2010, Keiji Fukuda, the WHO's top influenza expert, stated that the system leading to the declaration of a pandemic led to confusion about H1N1 circulating around the world and he expressed concern that there was a failure to communicate in regard to uncertainties about the new virus, which turned out to be not as deadly as feared. WHO Director-General Margaret Chan appointed 29 flu experts from outside the organization to conduct a review of WHO's handling of the H1N1 flu pandemic. She told them, "We want a frank, critical, transparent, credible and independent review of our performance."[116]

In June 2010, Fiona Godlee, editor-in-chief of the BMJ, published an editorial which criticised the WHO, saying that an investigation had disclosed that some of the experts advising WHO on the pandemic had financial ties with drug companies which were producing antivirals and vaccines.[117] Margaret Chan, Director-General of the WHO, replied stating, "Without question, the BMJ feature and editorial will leave many readers with the impression that WHO's decision to declare a pandemic was at least partially influenced by a desire to boost the profits of the pharmaceutical industry. The bottom line, however, is that decisions to raise the level of pandemic alert were based on clearly defined virological and epidemiological criteria. It is hard to bend these criteria, no matter what the motive".[116]

Flu inspection on a flight arriving in China

Thermal imaging camera and screen, photographed in an airport terminal in Greece. Thermal imaging can detect elevated body temperature, one of the signs of swine flu.

On 7 May 2009, the WHO stated that containment was not feasible and that countries should focus on mitigating the effect of the virus. They did not recommend closing borders or restricting travel.[118] On 26 April 2009, the Chinese government announced that visitors returning from flu-affected areas who experienced flu-like symptoms within two weeks would be quarantined.[119]

U.S. airlines had made no major changes as of the beginning of June 2009, but continued standing practices which include looking for passengers with symptoms of flu, measles or other infections, and relying on in-flight air filters to ensure that aircraft were sanitised.[120] Masks were not generally provided by airlines and the CDC did not recommend that airline crews wear them.[120] Some non-U.S. airlines, mostly Asian, including Singapore Airlines, China Eastern Airlines, China Southern Airlines, Cathay Pacific and Aeromexico, took measures such as stepping up cabin cleaning, installing state-of-the-art air filters and allowing in-flight staff to wear face masks.[120]

According to studies conducted in Australia and Japan, screening individuals for influenza symptoms at airports during the 2009 H1N1 outbreak was not an effective method of infection control.[121][122]

U.S. government officials were especially concerned about schools because the H1N1 flu virus appears to disproportionately affect young and school-age people, between six months and 24 years of age.[123] The H1N1 outbreak led to numerous precautionary school closures in some areas. Rather than closing schools, the CDC recommended that students and school workers with flu symptoms should stay home for either seven days total, or until 24 hours after symptoms subsided, whichever was longer.[124] The CDC also recommended that colleges should consider suspending fall 2009 classes if the virus began to cause severe illness in a significantly larger share of students than the previous spring. They also urged schools to suspend rules, such as penalties for late papers or missed classes or requirements for a doctor's note, to enforce "self-isolation" and prevent students from venturing out while ill;[125] schools were advised to set aside a room for people developing flu-like symptoms while they waited to go home and to have ill students or staff and those caring for them use face masks.[126]

In California, school districts and universities were on alert and worked 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 closed.[127] University of California campuses stockpiled supplies, from paper masks and hand sanitizer to food and water.[127] To help prepare for contingencies, University of Maryland School of Medicine professor of pediatrics James C. King Jr. suggested that every county should create an "influenza action team" to be run by the local health department, parents, and school administrators.[128] By 28 October 2009, about 600 schools in the United States had been temporarily closed, affecting over 126,000 students in 19 states.[129]

Fearing a worst-case scenario, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention and the Department of Homeland Security (DHS) developed updated guidance[130] and a video for employers to use as they developed plans to respond to the H1N1 outbreak. The guidance suggested that employers consider and communicate their objectives, such as reducing transmission among staff, protecting people who are at increased risk of influenza-related complications from becoming infected, maintaining business operations, and minimising adverse effects on other entities in their supply chains.[130]

The CDC estimated that as much as 40% of the workforce 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,[131] and advised that individuals should have steps in place should a workplace close down or a situation arise that requires working from home.[132] The CDC further advised 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.[124]

In the UK, the Health and Safety Executive (HSE) also issued general guidance for employers.[133]

Mexico City Metro

Osaka Loop Line, Japan

The U.S. CDC did not recommend the use of face masks or respirators in non-health care settings, such as schools, workplaces, or public places, with a few exceptions: people who were ill with the virus when around other people, and people who were at risk for severe illness while caring for someone with the flu.[134] There was some disagreement about the value of wearing face masks, as some experts feared that masks may have given people a false sense of security and should not have replaced other standard precautions.[135] Yukihiro Nishiyama, professor of virology at Nagoya University's School of Medicine, commented that the masks are "better than nothing, but it's hard to completely block out an airborne virus since it can easily slip through the gaps".[136][137] 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".[135] However, despite the lack of evidence of effectiveness, the use of such masks is common in Asia.[136] [137] [138] They are particularly popular in Japan, where cleanliness and hygiene are highly valued and where etiquette obligates those who are sick to wear masks to avoid spreading disease.[136][137]

During the height of the fear of a pandemic, some countries initiated or threatened to initiate quarantines of foreign visitors suspected of having or being in contact with others who may have been infected. In May 2009, the Chinese government confined 21 U.S. students and three teachers to their hotel rooms.[139] As a result, the US State Department issued a travel alert about China's anti-flu measures and warned travellers against travelling to China if ill.[140] In Hong Kong, an entire hotel was quarantined with 240 guests;[141] Australia ordered a cruise ship with 2,000 passengers to stay at sea because of a swine flu threat.[142] Egyptian Muslims who went on the annual pilgrimage to Mecca risked being quarantined upon their return.[143] Russia and Taiwan said they would quarantine visitors with fevers who come from areas where the flu was present.[144] Japan quarantined 47 airline passengers in a hotel for a week in mid-May,[145] then in mid-June India suggested pre-screening "outbound" passengers from countries thought to have a high rate of infection.[146]

The pandemic virus is a type of swine influenza, derived originally from a strain which lived in pigs, and this origin gave rise to the common name of "swine flu". This term is widely used by mass media, though the Paris-based World Organisation for Animal Health as well as industry groups such as the U.S. National Pork Board, the American Meat Institute, and the Canadian Pork Council objected to widespread media use of the name "swine flu" and suggested it should be called "North American flu" instead, while the World Health Organization switched its designation from "swine influenza" to "influenza A (H1N1)" in late April 2009.[147][148] The virus has been found in U.S. hogs,[149] and Canadian[150] as well as in hogs in Northern Ireland, Argentina, and Norway.[151] Leading health agencies and the United States Secretary of Agriculture have stressed that eating properly cooked pork or other food products derived from pigs will not cause flu.[152][153] Nevertheless, on 27 April Azerbaijan imposed a ban on the importation of animal husbandry products from the entire Americas.[154] The Indonesian government also halted the importation of pigs and initiated the examination of 9 million pigs in Indonesia.[155] The Egyptian government ordered the slaughter of all pigs in Egypt on 29 April.[156]

Both medications mentioned above for treatment, oseltamivir and zanamivir, have known side effects, including lightheadedness, chills, nausea, vomiting, loss of appetite, and trouble breathing. Children were reported to be at increased risk of self-injury and confusion after taking oseltamivir.[157] The WHO warned against buying antiviral medications from online sources and estimated that half the drugs sold by online pharmacies without a physical address were counterfeit.[165]

In December 2012, the World Health Organization (WHO) reported 314 samples of the 2009 pandemic H1N1 flu tested worldwide have shown resistance to oseltamivir (Tamiflu).[166] It is not totally unexpected as 99.6% of the seasonal H1N1 flu strains tested have developed resistance to oseltamivir.[167] No circulating flu has yet shown any resistance to zanamivir (Relenza), the other available anti-viral.[168]

On 8 December 2009, the Cochrane Collaboration, which reviews medical evidence, announced in a review published in BMJ that it had reversed its previous findings that the antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) can ward off pneumonia and other serious conditions linked to influenza. They reported that an analysis of 20 studies showed oseltamivir offered mild benefits for healthy adults if taken within 24 hours of onset of symptoms, but found no clear evidence it prevented lower respiratory tract infections or other complications of influenza.[169][170] Of note, their published finding related only to use in healthy adults with influenza but not in patients judged to be at high risk of complications (pregnant women, children under five and those with underlying medical conditions), and uncertainty over its role in reducing complications in healthy adults still left it as a useful drug for reducing the duration of symptoms. In general, the Cochrane Collaboration concluded "Paucity of good data".[170][171]

The virus was first reported in two U.S. children in March 2009, but health officials have reported that it apparently infected people as early as January 2009 in Mexico.[6] The outbreak was first identified in Mexico City on 18 March 2009;[173] immediately after the outbreak was officially announced, Mexico notified the U.S. and World Health Organization, and within days of the outbreak Mexico City was "effectively shut down".[174] Some countries cancelled flights to Mexico while others halted trade. Calls to close the border to contain the spread were rejected.[174] Mexico already had hundreds of non-lethal cases before the outbreak was officially discovered, and was therefore in the midst of a "silent epidemic". As a result, Mexico was reporting only the most serious cases which showed more severe signs different from those of normal flu, possibly leading to a skewed initial estimate of the case fatality rate.[173]

President Obama at Homeland Security Council meeting in Cabinet Room to discuss the H1N1 flu on May 1, 2009

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 14 April 2009. A second case, from nearby Imperial County, California, was confirmed on 17 April. The patient in the first confirmed case had flu symptoms including fever and cough upon clinical examination on 30 March and the second on 28 March.[175]

The first confirmed H1N1/09 pandemic flu death, which occurred at Texas Children's Hospital in Houston, Texas, was of a toddler from Mexico City who was visiting family in Brownsville, Texas, before being air-lifted to Houston for treatment.[176] The Infectious Diseases Society of America estimated that the total number of deaths in the U.S. was 12,469.[177]

Influenza surveillance information "answers the questions of where, when, and what influenza viruses are circulating. Sharing of such information is especially crucial during an emergent pandemic as in April 2009, when the genetic sequences of the initial viruses were rapidly and openly shared via the GISAID Initiative within days of identification,[178] playing a key role in facilitating an early response to the evolving pandemic.[179][180][181] Surveillance is used to determine if influenza activity is increasing or decreasing, but cannot be used to ascertain how many people have become ill with influenza."[182] For example, as of late June, influenza surveillance information showed the U.S. had nearly 28,000 laboratory-confirmed cases including 3,065 hospitalizations and 127 deaths. But mathematical modelling showed an estimated 1 million Americans had the 2009 pandemic flu at the time, according to Lyn Finelli, a flu surveillance official with the CDC.[183] Estimating deaths from influenza is also a complicated process. In 2005, influenza only appeared on the death certificates of 1,812 people in the US. The average annual US death toll from flu is, however, estimated to be 36,000.[184] The CDC explains:[185] "[I]nfluenza is infrequently listed on death certificates of people who die from flu-related complications" and hence, "Only counting deaths where influenza was included on a death certificate would be a gross underestimation of influenza's true impact."

Influenza surveillance information on the 2009 H1N1 flu pandemic is available, but almost no studies attempted to estimate the total number of deaths attributable to H1N1 flu. Two studies were carried out by the CDC; the later of them estimated that between 7,070 and 13,930 deaths were attributable to H1N1 flu from April to 14 November 2009.[186] During the same period, 1,642 deaths were officially confirmed as caused by H1N1 flu.[187][188] The WHO stated in 2010 that total mortality (including unconfirmed or unreported deaths) from H1N1 flu was "unquestionably higher" than their own confirmed death statistics.[189]

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.[190] "[E]ven in developed countries the [numbers of flu deaths] are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness".[191] Joseph S. Bresee, then CDC flu division's epidemiology chief and Michael Osterholm, director of the Center for Infectious Disease Research and Policy pointed out that millions of people have had H1N1 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.[192]

A Wisconsin study published in the Journal of the American Medical Association in September 2010, reported that findings showed that the 2009 H1N1 flu was no more severe than the seasonal flu. "The risk of most serious complications was not elevated in adults or children", the study's authors wrote. "Children were disproportionately affected by 2009 H1N1 infection, but the perceived severity of symptoms and risk of serious outcomes were not increased." Children infected in the 2009 H1N1 flu pandemic were no more likely to be hospitalized with complications or get pneumonia than those who catch seasonal strains. About 1.5% of children with the H1N1 swine flu strain were hospitalized within 30 days, compared with 3.7% of those sick with a seasonal strain of H1N1 and 3.1% with an H3N2 virus.[193]

CDC illness and death estimates from April 2009 to April 2010, in the US are as follows:

• between 43 million and 89 million cases of 2009 H1N1 occurred between April 2009 and 10 April 2010. The mid-level in this range is about 61 million people infected with 2009 H1N1.
• between about 195,000 and 403,000 H1N1-related hospitalizations occurred between April 2009 and 10 April 2010. The mid-level in this range is about 274,000 2009 H1N1-related hospitalizations.
• between about 8,870 and 18,300 2009 H1N1-related deaths occurred between April 2009 and 10 April 2010. The mid-level in this range is about 12,470 2009 H1N1-related deaths.[194][195][196]

It has been stated that about 36,000 die from the seasonal flu in the U.S. each year,[197] and this is frequently understood as an indication that the H1N1 strain was not as severe as seasonal influenza. The 36,000 estimate was presented in a 2003 study by CDC scientists and refers to a period from 1990 to 1991 through 1998–99. During those years, the number of estimated deaths ranged from 17,000 to 52,000, with an average of about 36,000. Throughout that decade, influenza A (H3N2) was the predominant virus during most of the seasons, and H3N2 influenza viruses are typically associated with higher death rates. The JAMA study also looked at seasonal influenza-associated deaths over a 23-year period, from 1976 to 1977 and 1998–99 with estimates of respiratory and circulatory influenza-associated deaths ranging from about 5,000 to about 52,000, and an average of about 25,000. CDC believes that the range of deaths over the past 31 years (~3,000 to ~49,000) is a more accurate representation of the unpredictability and variability of flu-associated deaths.[198] The annual toll from seasonal influenza in the US between 1979 and 2001 is estimated at 41,400 deaths on average.[199] Therefore, the H1N1 pandemic estimated mortality of 8,870 to 18,300 is just below the mid-range of estimates.[200]

The 2009 pandemic caused US hospitals to make significant preparations in terms of hospital surge capacities, especially within the emergency department and among vulnerable populations. In many cases, hospitals were relatively successful in making sure that those patients most severely affected by the influenza strain were able to be seen, treated, and discharged in an efficient manner. A case-study of the preparation, planning, mitigation, and response efforts during the fall of 2009 is that of the Children's Hospital of Philadelphia (CHOP) which took several steps to increase the emergency department (ED) surge capacity response. CHOP used portions of the main lobby area as an ED waiting room; several of the region's hospital-based outpatient facilities were in use during evening and weekend hours for non-emergency cases; the ED's 24-hour short-stay unit was utilized to care for ED patients in a longer-term capacity; non-board certified physicians (in pediatric emergency medicine) and inpatient-unit medical nurses were utilized for ED patient care; hospital units normally utilized for other medical or therapeutic purposes were transformed into ED patient rooms; and rooms normally used for only one patient were expanded to at least a capacity of 2.[201]