Influenza pandemics and epidemics have apparently occurred since at least the Middle Ages. When pandemics appear, 50% or more of an affected population can be infected in a single year, and the number of deaths caused by influenza can dramatically exceed what is normally expected. Since 1500, there appear to have been 13 or more influenza pandemics. In the past 120 years there were undoubted pandemics in 1889, 1918, 1957, 1968, and 1977. Although most experts believe we will face another influenza pandemic, it is impossible to predict when it will appear, where it will originate, or how severe it will be. Nor is there agreement about the subtype of influenza virus most likely to cause the next pandemic.
Pandemic 1: 1510
The first recognizable influenza pandemic invaded Europe from Africa in the summer of 1510 and proceeded northward to involve all of Europe and then the Baltic States. Attack rates were extremely high, but fatality was low and said to be restricted to young children. The lack of mention of mortality in the elderly and debilitated is curious, and there is no evidence one way or the other of protection provided by previous illnesses.
Pandemic 2: 1557 to 1558
The pandemic of spring 1557 is the first in which global involvement and westward spread from Asia to Europe was documented. Unlike the pandemic that appeared 47 years previously, this one was highly fatal, with deaths recorded as being due to ‘pleurisy and fatal peripneumony’. High mortality in pregnant women was also recorded. Examination of Parish registries in England showed a high frequency of excess deaths from 1558 to 1560, representing the first documentation of excess influenza deaths in a defined population, and suggesting that the disease prevailed for at least two years, conceivably having exhibited one or more recurrences.
Pandemic 3: 1580
The pandemic that appeared in 1580 again swept over the entire globe, spreading east to west from Asia, and was notable for its extremely quick progression, evolving and disappearing entirely between spring and autumn 1580. Like the 1557 pandemic, it was apparently highly fatal, and was also associated with severe complications. Finkler believes that in England it appeared in two successive waves, in August to September and October to November, but documentation is sparse.
After the 1580 pandemic, pandemics of influenza-like illness were not documented again for almost 150 years, although localised and even non-European epidemics, some of them severe, were seen episodically. Large-scale European outbreaks were documented at relatively short intervals (e.g. 1610, 1658 to 1659, 1675, and 1709 to 1710), but most of these outbreaks had limited, non-directional geographical spread. Among the most interesting feature of this apparently long non-pandemic period is the development of influenza-like epidemic activity in the Americas, which appeared to be independent of European activity. The 1557 pandemic is said to have reached the sparsely populated Americas, which were at that time isolated from Europe by long ocean voyages, but documentation is weak. The 1580 pandemic apparently did not reach the New World. Decades later (in 1617), at a time when there was no major influenza activity in Europe or elsewhere, influenza-like illness broke out in Chile, possibly having been imported from Spain. It quickly spread throughout South and North America and the Caribbean. This epidemic seems to have initiated a period of semi-autonomous American influenza activity, which is discussed separately below.
The pandemic that appeared in 1580 again swept over the entire globe, spreading east to west from Asia, and was notable for its extremely quick progression, evolving and disappearing entirely between spring and autumn 1580. Like the 1557 pandemic, it was apparently highly fatal, and was also associated with severe complications. Finkler believes that in England it appeared in two successive waves, in August to September and October to November, but documentation is sparse.
After the 1580 pandemic, pandemics of influenza-like illness were not documented again for almost 150 years, although localised and even non-European epidemics, some of them severe, were seen episodically. Large-scale European outbreaks were documented at relatively short intervals (e.g. 1610, 1658 to 1659, 1675, and 1709 to 1710), but most of these outbreaks had limited, non-directional geographical spread. Among the most interesting feature of this apparently long non-pandemic period is the development of influenza-like epidemic activity in the Americas, which appeared to be independent of European activity. The 1557 pandemic is said to have reached the sparsely populated Americas, which were at that time isolated from Europe by long ocean voyages, but documentation is weak. The 1580 pandemic apparently did not reach the New World. Decades later (in 1617), at a time when there was no major influenza activity in Europe or elsewhere, influenza-like illness broke out in Chile, possibly having been imported from Spain. It quickly spread throughout South and North America and the Caribbean. This epidemic seems to have initiated a period of semi-autonomous American influenza activity, which is discussed separately below.
Pandemic 4: 1729 to 1730, 1732 to 1733
The pandemic that appeared in 1729 was first detected in Russia and it spread westward and southward into Europe in the winter of 1729. A ‘second invasion’ also began in Russia three years later, in 1732, and it again spread widely, even reaching the Americas. Whether these were two pandemics separated by a very short interval or one pandemic with a long-delayed recurrence is not known. Both occurrences were associated with high attack rates and high mortality, but there are no reliable data to answer the question of whether illness in the first appearance protected against illness in the second. Webster and Finkler both believed that the 1732 pandemic began in America and spread from there to Europe, but this seems questionable. An equine epizootic (featuring lassitude and nasal discharge) was documented before human involvement in 1732. After 1733 there was pronounced global influenza activity for a number of years, especially in 1737 to 1738, when America and Europe were invaded in the same month, and in 1742 to 1744, when European deaths associated with influenza-like illnesses reached extraordinary peaks. Some observers have counted the 1737 to 1738 epidemic as a pandemic rather than a recurrence. Whatever happened, the period 1729 to 1747 remains one of the more remarkable and epidemiologically chaotic eras in the history of pandemic influenza.
The pandemic that appeared in 1729 was first detected in Russia and it spread westward and southward into Europe in the winter of 1729. A ‘second invasion’ also began in Russia three years later, in 1732, and it again spread widely, even reaching the Americas. Whether these were two pandemics separated by a very short interval or one pandemic with a long-delayed recurrence is not known. Both occurrences were associated with high attack rates and high mortality, but there are no reliable data to answer the question of whether illness in the first appearance protected against illness in the second. Webster and Finkler both believed that the 1732 pandemic began in America and spread from there to Europe, but this seems questionable. An equine epizootic (featuring lassitude and nasal discharge) was documented before human involvement in 1732. After 1733 there was pronounced global influenza activity for a number of years, especially in 1737 to 1738, when America and Europe were invaded in the same month, and in 1742 to 1744, when European deaths associated with influenza-like illnesses reached extraordinary peaks. Some observers have counted the 1737 to 1738 epidemic as a pandemic rather than a recurrence. Whatever happened, the period 1729 to 1747 remains one of the more remarkable and epidemiologically chaotic eras in the history of pandemic influenza.
Pandemic 5: 1761 to 1762
The 1761 pandemic is remarkable for the fact that it is said to have begun in the Americas in the spring of 1761 and to have spread from there to Europe and around the globe in 1762. Coming in the midst of Enlightenment fervour, the pandemic of 1762 was the first to be studied by multiple observers who communicated with each other in learned societies and through medical journals and books. Influenza was characterised clinically to a greater degree than it had been previously, as physicians carefully recorded observations on series of patients and attempted to understand what would later be called the pathophysiology of the disease. For example, the sites of inflammation were determined to extend to the larynx and trachea and, in severe cases, to the lungs. Recurrences in subsequent years were sometimes severe; for example, in 1775, an epidemic that spread widely was associated with equine epizootics, and had many features of an actual pandemic.
The 1761 pandemic is remarkable for the fact that it is said to have begun in the Americas in the spring of 1761 and to have spread from there to Europe and around the globe in 1762. Coming in the midst of Enlightenment fervour, the pandemic of 1762 was the first to be studied by multiple observers who communicated with each other in learned societies and through medical journals and books. Influenza was characterised clinically to a greater degree than it had been previously, as physicians carefully recorded observations on series of patients and attempted to understand what would later be called the pathophysiology of the disease. For example, the sites of inflammation were determined to extend to the larynx and trachea and, in severe cases, to the lungs. Recurrences in subsequent years were sometimes severe; for example, in 1775, an epidemic that spread widely was associated with equine epizootics, and had many features of an actual pandemic.
Pandemic 6: 1780 to 1782
The 1780 pandemic, which began in Southeast Asia and spread to Russia and eastward into Europe, was remarkable for extremely high attack rates but negligible mortality, although there were excess deaths in the London bills of mortality, perhaps in part due to excess blood-letting by some physicians. It appears that in this pandemic the concept of influenza as a distinct entity with characteristic epidemiological features was first appreciated.
The 1780 pandemic, which began in Southeast Asia and spread to Russia and eastward into Europe, was remarkable for extremely high attack rates but negligible mortality, although there were excess deaths in the London bills of mortality, perhaps in part due to excess blood-letting by some physicians. It appears that in this pandemic the concept of influenza as a distinct entity with characteristic epidemiological features was first appreciated.
Pandemic 7: 1788 to 1790
Although the 1788 pandemic is generally regarded as being separate from that of 1782 (largely because of its by now typical genesis in Asia, its rapid global and directional dispersion, and its extremely high attack rates), Creighton contends that persons who became ill in the 1782 pandemic were protected not only in 1788 but through 1802. Whatever the case, the 1788 pandemic initiated another pandemic era, in which global influenza activity appears to have been heightened for almost 20 years (1788 to 1806); some observers have postulated additional pandemics in this interval.
Although the 1788 pandemic is generally regarded as being separate from that of 1782 (largely because of its by now typical genesis in Asia, its rapid global and directional dispersion, and its extremely high attack rates), Creighton contends that persons who became ill in the 1782 pandemic were protected not only in 1788 but through 1802. Whatever the case, the 1788 pandemic initiated another pandemic era, in which global influenza activity appears to have been heightened for almost 20 years (1788 to 1806); some observers have postulated additional pandemics in this interval.
Pandemic 8: 1830 to 1831, 1832 to 1833, 1836 to 1837
A similar phenomenon was observed with the next pandemic to appear (1830). It began in Southeast Asia and spread through Russia to Europe and the rest of the globe, causing extremely high attack rates but low mortality. A recrudescence in 1832 and 1833 spread with almost the same directional pattern and was associated with higher mortality. Noting the intense period of global influenza activity that followed the 1830 pandemic, Leichtenstern postulated ‘two or three’ possible successive pandemics separated by short intervals, but it is difficult to determine whether the events of the 1830s represent three separate pandemics or three recurrences of one pandemic virus. Curiously, one observer noted that persons over 45 years old were relatively spared, suggesting the possibility that a virus that circulated before 1782 (e.g. the 1761 pandemic virus) could have been antigenically similar. Such observations on protective immunity have not been systematically sought for influenza pandemics in the pre-virology era, an obvious target for historical research. The 1837 recurrence in Europe led to some of the first attempts to understand pulmonary pathology in influenza.
A so-called pandemic in 1847 is among the more problematic epidemic influenza events to have occurred because of its limited explosivity, progression, and fatality. Beginning in Europe in the winter of 1847, it took several years to spread to the Western Hemisphere (1850 to 1851); this was clearly uncharacteristic behaviour for an influenza pandemic. Moreover, after causing high attack rates in United Kingdom in the first year after its appearance, it promptly disappeared, exhibited a recrudescence in 1857 to 1858 and then vanished almost completely. It is therefore curious that lower than expected mortality in elderly persons in the 1918 pandemic (see below) seems to be associated with birth around 1850. Was the 1847 virus an entirely new pandemic virus that protected against the 1918 virus, or was it a descendant of earlier viruses such as the 1830 virus? The 1847 ‘pandemic-like’ epidemic remains one of the more mysterious events in the history of influenza pandemics.
A similar phenomenon was observed with the next pandemic to appear (1830). It began in Southeast Asia and spread through Russia to Europe and the rest of the globe, causing extremely high attack rates but low mortality. A recrudescence in 1832 and 1833 spread with almost the same directional pattern and was associated with higher mortality. Noting the intense period of global influenza activity that followed the 1830 pandemic, Leichtenstern postulated ‘two or three’ possible successive pandemics separated by short intervals, but it is difficult to determine whether the events of the 1830s represent three separate pandemics or three recurrences of one pandemic virus. Curiously, one observer noted that persons over 45 years old were relatively spared, suggesting the possibility that a virus that circulated before 1782 (e.g. the 1761 pandemic virus) could have been antigenically similar. Such observations on protective immunity have not been systematically sought for influenza pandemics in the pre-virology era, an obvious target for historical research. The 1837 recurrence in Europe led to some of the first attempts to understand pulmonary pathology in influenza.
A so-called pandemic in 1847 is among the more problematic epidemic influenza events to have occurred because of its limited explosivity, progression, and fatality. Beginning in Europe in the winter of 1847, it took several years to spread to the Western Hemisphere (1850 to 1851); this was clearly uncharacteristic behaviour for an influenza pandemic. Moreover, after causing high attack rates in United Kingdom in the first year after its appearance, it promptly disappeared, exhibited a recrudescence in 1857 to 1858 and then vanished almost completely. It is therefore curious that lower than expected mortality in elderly persons in the 1918 pandemic (see below) seems to be associated with birth around 1850. Was the 1847 virus an entirely new pandemic virus that protected against the 1918 virus, or was it a descendant of earlier viruses such as the 1830 virus? The 1847 ‘pandemic-like’ epidemic remains one of the more mysterious events in the history of influenza pandemics.
Pandemic 9: 1889 to 1893
The great pandemic of ‘Russian flu’ was probably the most explosive up to that time and the first to have its progression ‘tracked’ in real time. Like most others before it, it spread east to west from Asia and quickly reached almost every region of the globe. Unlike previous pandemics, it returned in up to five successive and largely seasonal annual recurrences, although some locales had fewer and less substantial recurrences. The pandemic occurred in the very early years of virology, but its cause was at the time attributed by many to a newly characterised bacterium, Bacillus influenzae (now Haemophilus influenzae). Based on epidemiological studies conducted in the 1930s and subsequently, which examined sera obtained from persons born before and after the 1889 pandemic, it has been hypothesised that the virus responsible contained an H3 subtype HA. Specimens from the pandemic and post-pandemic period have not yet been identified and studied to identify the agent further.
The great pandemic of ‘Russian flu’ was probably the most explosive up to that time and the first to have its progression ‘tracked’ in real time. Like most others before it, it spread east to west from Asia and quickly reached almost every region of the globe. Unlike previous pandemics, it returned in up to five successive and largely seasonal annual recurrences, although some locales had fewer and less substantial recurrences. The pandemic occurred in the very early years of virology, but its cause was at the time attributed by many to a newly characterised bacterium, Bacillus influenzae (now Haemophilus influenzae). Based on epidemiological studies conducted in the 1930s and subsequently, which examined sera obtained from persons born before and after the 1889 pandemic, it has been hypothesised that the virus responsible contained an H3 subtype HA. Specimens from the pandemic and post-pandemic period have not yet been identified and studied to identify the agent further.
Pandemic 10: 1918 to 1919
The ‘Spanish influenza’ pandemic, which stands as the single most fatal event in human history, killed an estimated 50 million or more people. Reconstruction of the ribonucleic acid (RNA) genome from the tissues of several victims, conducted in the laboratory of co-author J.K. Taubenberger, has demonstrated that the causative agent was an avian-descended H1N1 virus that appears to be a direct progenitor of all of the influenza A viruses circulating in humans today. The high mortality associated with the 1918 virus appears to have been a result of bacterial pneumonia, but the co-pathogenic mechanisms responsible for such fatal bacterial diseases remain unknown. Epidemiological features of the pandemic were also unprecedented, including its appearance in up to three waves within the first year, and a ‘W-shaped’ (tri-modal) age-specific mortality curve that featured an unexplained peak in healthy young adults. Evidence for a lower than expected mortality elevation in persons over about 65 years old (see above) is consistent with a protective effect that ended around 1855, corresponding to the period of the apparent circulation of the 1847 epidemic virus or perhaps an earlier virus. The place of origin of the 1918 virus is obscure and there is little evidence of directionality of spread other than chaotic multi-directionality during the second of the three major waves. By about 1920 the virus had begun to settle down into a pattern of seasonal endemic recurrences and remained so as it ‘drifted’ for nearly 40 years. When the next pandemic appeared in 1957 (see below), the H1N1 virus disappeared from circulation. However, 20 years later, in 1977, it returned to circulation (possibly after accidental release from a freezer) and caused a (low grade) pandemic that disproportionately affected persons under the age of 20 (see below). The virus continues to co-circulate globally today, along with H3N2 influenza A viruses descended from the 1968 pandemic (see below).
As data have accumulated, evidence has emerged to indicate that the genome of the 1918 H1N1 strain may have had a novel origin that has not been seen in strains responsible for subsequent pandemics. Viral sequence data now suggest that the entire 1918 virus was novel to humans in, or shortly before, 1918, and therefore that it was likely not to have been a reassortant virus produced from previously circulating human influenza strains that acquired one or more new gene segments by reassortment, like those that caused the 1957 and 1968 pandemics. On the contrary, data suggest that the 1918 virus was an avian-like influenza virus that was derived in toto from an unknown source.
Pandemic 11: 1957 to 1958
The pandemic virus that emerged in 1957 was a lineal descendant of the 1918 H1N1 pandemic virus that had somehow acquired three novel gene segments. The gene segments encoding the two surface proteins, HA and neuraminidase (NA), were replaced by an avian-like H2 subtype HA and an N2 subtype NA, respectively. The gene segment encoding the PB1 polymerase was also replaced with an avian-like gene segment. Even though this pandemic occurred in the era of influenza virology, it is not known in what animal host (possibly including humans) the reassortment event(s) occurred. It is also not known how long it took from the initial reassortment event(s) for the virus to evolve into the efficiently transmissible, human-adapted influenza A virus that caused the pandemic.
The pandemic followed the by now typical pattern of appearance in Southeast Asia and subsequent global spread, although its movement and mortality rate were not as impressive as those of the two previous pandemics, in 1889 and 1918. Emergence of the H2N2 ‘Asian’ influenza virus was first detected in April 1957, when it was reported that the strain responsible for epidemic outbreaks throughout Southeast Asia was antigenically distinct from the prevailing H1N1 strain. Predictions that the virus would spread through the Southern Hemisphere during the summer but cause widespread outbreaks in the Northern Hemisphere only in the autumn proved correct. The virus spread through the tropics during May and June, causing outbreaks in the Southern Hemisphere during July and August. While there were limited outbreaks in institutional settings in the United States of America (USA) and Europe as early as June, large-scale epidemics did not begin until September. Japan was the only country in the Northern Hemisphere to experience widespread epidemics during the spring. Contemporary observers noted the easily traceable geographical spread of the epidemics, a characteristic that was shared with the pandemic of 1889 (see above), but was not readily apparent during inter-pandemic influenza epidemics. As the first pandemic to occur in the era of modern virology, the 1957 to 1958 pandemic was studied scientifically with the latest virological and bacteriological methods. Its pathology and clinical appearance were similar or identical to those of the 1918 virus, although the unusual epidemiologic features of the 1918 pandemic noted above were not seen in 1957. As was true for the 1918 pandemic, after about two years the virus became seasonally endemic and sporadic, disappearing entirely within 11 years. To date (2009) it has not returned.
The pandemic virus that emerged in 1957 was a lineal descendant of the 1918 H1N1 pandemic virus that had somehow acquired three novel gene segments. The gene segments encoding the two surface proteins, HA and neuraminidase (NA), were replaced by an avian-like H2 subtype HA and an N2 subtype NA, respectively. The gene segment encoding the PB1 polymerase was also replaced with an avian-like gene segment. Even though this pandemic occurred in the era of influenza virology, it is not known in what animal host (possibly including humans) the reassortment event(s) occurred. It is also not known how long it took from the initial reassortment event(s) for the virus to evolve into the efficiently transmissible, human-adapted influenza A virus that caused the pandemic.
The pandemic followed the by now typical pattern of appearance in Southeast Asia and subsequent global spread, although its movement and mortality rate were not as impressive as those of the two previous pandemics, in 1889 and 1918. Emergence of the H2N2 ‘Asian’ influenza virus was first detected in April 1957, when it was reported that the strain responsible for epidemic outbreaks throughout Southeast Asia was antigenically distinct from the prevailing H1N1 strain. Predictions that the virus would spread through the Southern Hemisphere during the summer but cause widespread outbreaks in the Northern Hemisphere only in the autumn proved correct. The virus spread through the tropics during May and June, causing outbreaks in the Southern Hemisphere during July and August. While there were limited outbreaks in institutional settings in the United States of America (USA) and Europe as early as June, large-scale epidemics did not begin until September. Japan was the only country in the Northern Hemisphere to experience widespread epidemics during the spring. Contemporary observers noted the easily traceable geographical spread of the epidemics, a characteristic that was shared with the pandemic of 1889 (see above), but was not readily apparent during inter-pandemic influenza epidemics. As the first pandemic to occur in the era of modern virology, the 1957 to 1958 pandemic was studied scientifically with the latest virological and bacteriological methods. Its pathology and clinical appearance were similar or identical to those of the 1918 virus, although the unusual epidemiologic features of the 1918 pandemic noted above were not seen in 1957. As was true for the 1918 pandemic, after about two years the virus became seasonally endemic and sporadic, disappearing entirely within 11 years. To date (2009) it has not returned.
Pandemic 12: 1968
Like the pandemic that preceded it, the 1968 pandemic of H3N2, ‘Hong Kong flu’, was caused by a virus that had been ‘updated’ from the previously circulating virus by reassortment of avian genes, in this case two of them, to create yet another new generation of 1918 viral descendants. Spreading again from Southeast Asia, the 1968 pandemic was so mild in its mortality impact that in some locales fewer influenza deaths occurred than in certain non-pandemic years. As had been the case in 1957, the virus quickly became endemic and sporadic in its appearance, and it has now (in 2009) circulated globally for 41 years.
The 1968 H3N2 pandemic virus replaced the H2N2 type virus that had been circulating since the 1957 pandemic. A molecular analysis of the H3N2 virus demonstrated that the H2 HA had been replaced by reassortment with an avian-like H3 HA and that the PB1 polymerase gene segment had also been replaced, again by reassortment with an avian-like PB1. The other six gene segments, including the NA gene segment, were retained from the 1957 H2N2 virus. Antibodies to NA, while not preventing infection, have been shown to reduce the duration and severity of illness. It has been suggested that the relative mildness of the 1968 pandemic in comparison with previous pandemics was the result of the retention of the previously circulating NA.
Like the pandemic that preceded it, the 1968 pandemic of H3N2, ‘Hong Kong flu’, was caused by a virus that had been ‘updated’ from the previously circulating virus by reassortment of avian genes, in this case two of them, to create yet another new generation of 1918 viral descendants. Spreading again from Southeast Asia, the 1968 pandemic was so mild in its mortality impact that in some locales fewer influenza deaths occurred than in certain non-pandemic years. As had been the case in 1957, the virus quickly became endemic and sporadic in its appearance, and it has now (in 2009) circulated globally for 41 years.
The 1968 H3N2 pandemic virus replaced the H2N2 type virus that had been circulating since the 1957 pandemic. A molecular analysis of the H3N2 virus demonstrated that the H2 HA had been replaced by reassortment with an avian-like H3 HA and that the PB1 polymerase gene segment had also been replaced, again by reassortment with an avian-like PB1. The other six gene segments, including the NA gene segment, were retained from the 1957 H2N2 virus. Antibodies to NA, while not preventing infection, have been shown to reduce the duration and severity of illness. It has been suggested that the relative mildness of the 1968 pandemic in comparison with previous pandemics was the result of the retention of the previously circulating NA.
Pandemic 13: 1977 to 1978
The re-emergence in 1977 of a descendant of the 1918 H1N1 virus that had been absent from circulation for 20 years, constitutes a pandemic by definition (see above), but it is usually regarded as a ‘technical’ pandemic that represents an unusual coda to the 1918 pandemic. The issue is partly a semantic one, which nonetheless disarms because it upsets attempts to find patterns in natural pandemic recurrence. It is curious that the same virus that disappeared on its own in 1957 has, after reintroduction, been able to survive for over 30 years in the face of immunity pressures thought to be as great or greater than those associated with its disappearance (i.e. high population immunity from natural infection and additional immunity from annual vaccination, which is much more common now than it was in 1957). The 1968 H3N2 and the 1977/1918 H1N1 pandemic viruses have been co-circulating endemically for over 30 years, in the face of high population immunity, with no evidence of imminent extinction.
The exact place of origin of the 1977 H1N1 virus is uncertain. In May to June 1977 an influenza outbreak occurred in northern China. The epidemic spread rather slowly, in marked contrast to the pandemics of 1957 and 1968. The H1N1 viruses were detected between June and October 1977 in other parts of China. The H1N1 strains did not replace the H3N2 strains then circulating in China, but co-circulated with them during that first year, with more H1N1 circulation in northern China than in the south of the country. By November 1977, H1N1 viruses were causing limited outbreaks in the far eastern Union of Soviet Socialist Republics (USSR), followed by cities in Siberia and the European portions of the USSR. Infection was limited predominantly to young adults (below the age of 25) and school-age children.
During the next winter influenza season (1978 to 1979) H1N1 viruses caused limited outbreaks throughout the world. In the USA, the first H1N1 outbreaks occurred in schools and on military bases in January 1978. Some of these outbreaks were associated with clinical infection rates of up to 70%, but with few cases in individuals over 26 years of age. As in other countries, the H1N1 viruses co-circulated with the H3N2 strains without replacing them, but unlike the H3N2 outbreaks, H1N1 outbreaks were associated with little or no excess mortality.
The H1N1 strains isolated in 1977 and 1978, as represented by the A/USSR/90/77 strain, were antigenically similar to H1N1 viruses that had circulated widely between 1947 and 1956 before being replaced by the H2N2 pandemic strain in 1957. The isolates were also antigenically uniform, which suggests a single source. It is considered unlikely that influenza viruses could have been maintained in nature for 25 years without accumulating mutations, suggesting that the 1977 epidemic resulted from the release of a frozen strain from the 1950s). Molecular genetic techniques confirmed that the USSR/77 strain was very similar to early 1950s H1N1 strains in all eight gene segments. Because the post-1977 H1N1 strains did not replace the previously circulating H3N2 strains, co-circulation of influenza viruses of both subtypes has continued up to the present time (2008), and co-infection with both subtypes has been reported, together with the circulation of reassortant H1N2 viruses.
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The re-emergence in 1977 of a descendant of the 1918 H1N1 virus that had been absent from circulation for 20 years, constitutes a pandemic by definition (see above), but it is usually regarded as a ‘technical’ pandemic that represents an unusual coda to the 1918 pandemic. The issue is partly a semantic one, which nonetheless disarms because it upsets attempts to find patterns in natural pandemic recurrence. It is curious that the same virus that disappeared on its own in 1957 has, after reintroduction, been able to survive for over 30 years in the face of immunity pressures thought to be as great or greater than those associated with its disappearance (i.e. high population immunity from natural infection and additional immunity from annual vaccination, which is much more common now than it was in 1957). The 1968 H3N2 and the 1977/1918 H1N1 pandemic viruses have been co-circulating endemically for over 30 years, in the face of high population immunity, with no evidence of imminent extinction.
The exact place of origin of the 1977 H1N1 virus is uncertain. In May to June 1977 an influenza outbreak occurred in northern China. The epidemic spread rather slowly, in marked contrast to the pandemics of 1957 and 1968. The H1N1 viruses were detected between June and October 1977 in other parts of China. The H1N1 strains did not replace the H3N2 strains then circulating in China, but co-circulated with them during that first year, with more H1N1 circulation in northern China than in the south of the country. By November 1977, H1N1 viruses were causing limited outbreaks in the far eastern Union of Soviet Socialist Republics (USSR), followed by cities in Siberia and the European portions of the USSR. Infection was limited predominantly to young adults (below the age of 25) and school-age children.
During the next winter influenza season (1978 to 1979) H1N1 viruses caused limited outbreaks throughout the world. In the USA, the first H1N1 outbreaks occurred in schools and on military bases in January 1978. Some of these outbreaks were associated with clinical infection rates of up to 70%, but with few cases in individuals over 26 years of age. As in other countries, the H1N1 viruses co-circulated with the H3N2 strains without replacing them, but unlike the H3N2 outbreaks, H1N1 outbreaks were associated with little or no excess mortality.
The H1N1 strains isolated in 1977 and 1978, as represented by the A/USSR/90/77 strain, were antigenically similar to H1N1 viruses that had circulated widely between 1947 and 1956 before being replaced by the H2N2 pandemic strain in 1957. The isolates were also antigenically uniform, which suggests a single source. It is considered unlikely that influenza viruses could have been maintained in nature for 25 years without accumulating mutations, suggesting that the 1977 epidemic resulted from the release of a frozen strain from the 1950s). Molecular genetic techniques confirmed that the USSR/77 strain was very similar to early 1950s H1N1 strains in all eight gene segments. Because the post-1977 H1N1 strains did not replace the previously circulating H3N2 strains, co-circulation of influenza viruses of both subtypes has continued up to the present time (2008), and co-infection with both subtypes has been reported, together with the circulation of reassortant H1N2 viruses.
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