in humans, possibly after it was released from a freezer in a laboratory accident, and caused a pseudo-pandemic. whether the 1977 "pandemic" deserves to be included in the natural history of flu pandemics is debatable. this h1n1 strain was antigenically similar to the h1n1 strains that circulated prior to 1957. since 1977, both h1n1 and h3n2 have circulated in humans as part of seasonal influenza. in 1980, the classification system used to subtype influenza viruses was introduced. thermal imaging camera and screen, photographed in an airport terminal in greece during the 2009 flu pandemic. thermal imaging can detect elevated body temperature, one of the signs of swine flu. at some point, ibv diverged into two strains, named the b/victoria-like and b/yamagata-like lineages, both of which have been circulating in humans since 1983. in 1996, hpai h5n1 was detected in guangdong, china and a year later emerged in poultry in hong kong, gradually spreading worldwide from there. a small h5n1 outbreak in humans in hong kong occurred then, and sporadic human cases have occurred since 1997, carrying a high case fatality rate. the most recent flu pandemic was the 2009 swine flu pandemic, which originated in mexico and resulted in hundreds of thousands of deaths. it was caused by a novel h1n1 strain that was a reassortment of human, swine, and avian influenza viruses. the 2009 pandemic had the effect of replacing prior h1n1 strains in circulation with the novel strain but not any other influenza viruses. consequently, h1n1, h3n2, and both ibv lineages have been in circulation in seasonal form since the 2009 pandemic. in 2011, idv was discovered in pigs in oklahoma, usa, and cattle were later identified as the primary reservoir of idv. in the same year, avian h7n9 was detected in china and began to cause human infections in 2013, starting in shanghai and anhui and remaining mostly in china. hpai h7n9 emerged sometime in 2016 and has occasionally infected humans incidentally. other aivs have less commonly infected humans since the 1990s, including h5n6, h6n1, h7n2-4, h7n7, and h10n7-8, and hpai h subtypes such as h5n1-3, h5n5-6, and h5n8 have begun to spread throughout much of the world since the 2010s. future flu pandemics, which may be caused by an influenza virus of avian origin, are viewed as almost inevitable, and increased globalization has made it easier for novel viruses to spread, so there are continual efforts to prepare for future pandemics and improve the prevention and treatment of influenza. etymology the word influenza comes from the italian word influenza, from medieval latin influentia, originally meaning "visitation" or "influence". terms such as influenza di freddo, meaning "influence of the cold", and influenza di stelle, meaning "influence of the stars" are attested from the 14th century. the latter referred to the disease's cause, which at the time was ascribed by some to unfavorable astrological conditions. as early as 1504, influenza began to mean a "visitation" or "outbreak" of any disease affecting many people in a single place at once. during an outbreak of influenza in 1743 that started in italy and spread throughout europe, the word reached the english language and was anglicized in pronunciation. since the mid-1800s, influenza has also been used to refer to severe colds. the shortened form of the word, "(the) flu", is first attested in 1839 as flue with the spelling flu confirmed in 1893. other names that have been used for influenza include epidemic catarrh, la grippe from french, sweating sickness, and, especially when referring to the 1918 pandemic strain, spanish fever. research professional examining a laboratory-grown reconstruction of the 1918 spanish flu virus in a biosafety level 3 environment influenza research is wide-ranging and includes efforts to understand how influenza viruses enter hosts, the relationship between influenza viruses and bacteria, how influenza symptoms progress, and what make some influenza viruses deadlier than others. non-structural proteins encoded by influenza viruses are periodically discovered and their functions are continually under research. past pandemics, and especially the 1918 pandemic, are the subject of much research to understand flu pandemics. as part of pandemic preparedness, the global influenza surveillance and response system is a global network of laboratories that monitors influenza transmission and epidemiology. additional areas of research include ways to improve the diagnosis, treatment, and prevention of influenza. existing diagnostic methods have a variety of limitations coupled with their advantages. for example, nats have high sensitivity and specificity but are impractical in under-resourced regions due to their high cost, complexity, maintenance, and training required. low-cost, portable ridts can rapidly diagnose influenza but have highly variable sensitivity and are unable to subtype iav. as a result of these limitations and others, research into new diagnostic methods revolves around producing new methods that are cost-effective, less labor-intensive, and less complex than existing methods while also being able to differentiate influenza species and iav subtypes. one approach in development are lab-on-a-chips, which are diagnostic devices that make use of a variety of diagnostic tests, such as rt-pcr and serological assays, in microchip form. these chips have many potential advantages, including high reaction efficiency, low energy consumption, and low waste generation. new antiviral drugs are also in development due to the elimination of adamantines as viable drugs and concerns over oseltamivir resistance. these include: na inhibitors that can be injected intravenously, such as intravenous formulations of zanamivir; favipiravir, which is a polymerase inhibitor used against several rna viruses; pimodivir, which prevents cap-binding required during viral transcription; and nitazoxanide, which inhibits ha maturation. reducing excess inflammation in the respiratory tract is also subject to much research since this is one of the primary mechanisms of influenza pathology. other forms of therapy in development include monoclonal and polyclonal antibodies that target viral proteins, convalescent plasma, different approaches to modify the host antiviral response, and stem cell-based therapies to repair lung damage. much research on laivs focuses on identifying genome sequences that can be deleted to create harmless influenza viruses in vaccines that still confer immunity. the high variability and rapid evolution of influenza virus antigens, however, is a major obstacle in developing effective vaccines. furthermore, it is hard to predict which strains will be in circulation during the next flu season, manufacturing a sufficient quantity of flu vaccines for the next season is difficult, laivs have limited efficacy, and repeated annual vaccination potentially has diminished efficacy. for these reasons, "broadly-reactive" or "universal" flu vaccines are being researched that can provide protection against many or all influenza viruses. approaches to develop such a vaccine include ha stalk-based methods such as chimeras that have the same stalk but different heads, ha head-based methods such as computationally optimized broadly neutralizing antigens, anti-idiotypic antibodies, and vaccines to elicit immune responses to highly conserved viral proteins. mrna vaccines to provide protection against influenza are also under research. in animals birds aquatic birds such as ducks, geese, shorebirds, and gulls are the primary reservoir of iavs. in birds, aivs may be either low pathogenic avian influenza (lpai) viruses that produce little to no symptoms or highly pathogenic avian influenza (hpai) viruses that cause severe illness. symptoms of hpai infection include lack of energy and appetite, decreased egg production, soft-shelled or misshapen eggs, swelling of the head, comb, wattles, and hocks, purple discoloration of wattles, combs, and legs, nasal discharge, coughing, sneezing, incoordination, and diarrhea. birds infected with an hpai virus may also die suddenly without any signs of infection. the distinction between lpai and hpai can generally be made based on how lethal an aiv is to chickens. at the genetic level, an aiv can be usually be identified as an hpai virus if it has a multibasic cleavage site in the ha protein, which contains additional residues in the ha gene. most aivs are lpai. notable hpai viruses include hpai h5n1 and hpai h7n9. hpai viruses have been a major disease burden in the 21st century, resulting in the death of large numbers of birds. in h7n9's case, some circulating strains were originally lpai but became hpai by acquiring the ha multibasic cleavage site. avian h9n2 is also of concern because although it is lpai, it is a common donor of genes to h5n1 and h7n9 during reassortment. migratory birds can spread influenza across long distances. an example of this was when an h5n1 strain in 2005 infected birds at qinghai lake, china, which is a stopover and breeding site for many migratory birds, subsequently spreading the virus to more than 20 countries across asia, europe, and the middle east. aivs can be transmitted from wild birds to domestic free-range ducks and in turn to poultry through contaminated water, aerosols, and fomites. ducks therefore act as key intermediates between wild and domestic birds. transmission to poultry typically occurs in backyard farming and live animal markets where multiple species interact with each other. from there, aivs can spread to poultry farms in the absence of adequate biosecurity. among poultry, hpai transmission occurs through aerosols and contaminated feces, cages, feed, and dead animals. back-transmission of hpai viruses from poultry to wild birds has occurred and is implicated in mass die-offs and intercontinental spread. aivs have occasionally infected humans through aerosols, fomites, and contaminated water. direction transmission from wild birds is rare. instead, most transmission involves domestic poultry, mainly chickens, ducks, and geese but also a variety of other birds such as guinea fowl, partridge, pheasants, and quails. the primary risk factor for infection with aivs is exposure to birds in farms and live poultry markets. typically, infection with an aiv has an incubation period of 3–5 days but can be up to 9 days. h5n1 and h7n9 cause severe lower respiratory tract illness, whereas other aivs such as h9n2 cause a more mild upper respiratory tract illness, commonly with conjunctivitis. limited transmission of avian h2, h5-7, h9, and h10 subtypes from one person to another through respiratory droplets, aerosols, and fomites has occurred, but sustained human-to-human transmission of aivs has not occurred. before 2013, h5n1 was the most common aiv to infect humans. since then, h7n9 has been responsible for most human cases. pigs chinese inspectors checking airline passengers for fevers, a common symptom of swine flu influenza in pigs is a respiratory disease similar to influenza in humans and is found worldwide. asymptomatic infections are common. symptoms typically appear 1–3 days after infection and include fever, lethargy, anorexia, weight loss, labored breathing, coughing, sneezing, and nasal discharge. in sows, pregnancy may be aborted. complications include secondary infections and potentially fatal bronchopneumonia. pigs become contagious within a day of infection and typically spread the virus for 7–10 days, which can spread rapidly within a herd. pigs usually recover from infection within 3–7 days after symptoms appear. prevention and control measures include inactivated vaccines and culling infected herds. the influenza viruses usually responsible for swine flu are iav subtypes h1n1, h1n2, and h3n2. some iavs can be transmitted via aerosols from pigs to humans and vice versa. furthermore, pigs, along with bats and quails, are recognized as a mixing vessel of influenza viruses because they have both α-2,3 and α-2,6 sialic acid receptors in their respiratory tract. because of that, both avian and mammalian influenza viruses can infect pigs. if co-infection occurs, then reassortment is possible. a notable example of this was the reassortment of a swine, avian, and human influenza virus in 2009, resulting in a novel h1n1 strain that caused the 2009 flu pandemic. spillover events from humans to pigs, however, appear to be more common than from pigs to humans. other animals influenza viruses have been found in many other animals, including cattle, horses, dogs, cats, and marine mammals. nearly all iavs are apparently descended from ancestral viruses in birds. the exception are bat influenza-like viruses, which have an uncertain origin. these bat viruses have ha and na subtypes h17, h18, n10, and n11. h17n10 and h18n11 are unable to reassort with other iavs, but they are still able to replicate in other mammals. aivs sometimes crossover into mammals. for example, in late 2016 to early 2017, an avian h7n2 strain was found to be infecting cats in new york. equine iavs include h7n7 and two lineages of h3n8. h7n7, however, has not been detected in horses since the late 1970s, so it may have become extinct in horses. h3n8 in equines spreads