Influenza Epidemics and Pandemics

Influenza pandemics of the past

Early records of influenza outbreaks

Historic records indicate that influenza pandemics have been among us for many centuries. ²⁹ x CW Potter. Chronicle of influenza pandemics. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, Oxford, 1998) (3 - 18) A report by Hippocrates describes an outbreak as early as 412 BC that could have been due to influenza. Several further accounts are suggestive of influenza outbreaks, but lack sufficient scientific substance to provide certainty. The first convincing report of an influenza pandemic describes an outbreak in 1580, which started in Asia in the summer, and then spread via Africa to Europe and finally to America. ²⁶ x WJ Bean, M Schell, J Katz, et al.. Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts. J Virol 66 (1992) (1129 - 1138) In Britain it came in two waves, a pattern that was also seen in subsequent influenza pandemics. Other convincing accounts of influenza pandemics followed in the 18th and 19th centuries. ²⁹ x CW Potter. Chronicle of influenza pandemics. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, Oxford, 1998) (3 - 18)

Pandemics of the 20th century

Figure 14 gives an overview of the influenza pandemics that occurred in the past century. ^4, x ED Kilbourne. Influenza pandemics of the 20th century. Emerg Inf Dis 12 (2006) (9 - 14) ^29, x CW Potter. Chronicle of influenza pandemics. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, Oxford, 1998) (3 - 18) ³⁰ x WIB Beveridge. The chronicle of influenza epidemics. Hist Phil Life Sci 13 (1991) (223 - 235) The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths, ⁵ x NP Johnson, J Mueller. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76 (2002) (105 - 115) justifying its description as “the last great plague of mankind”.

Figure 14 Influenza A viruses of the 20th century pandemics. The 1918 Spanish flu virus (H1N1) probably originated through direct transmission of an avian virus to man and further adaptation of this virus to the human host. The 1957 Asian (H2N2) and 1968 Hong Kong (H3N2) viruses were reassortants of avian and circulating human viruses (see Figure 13 ). The 1977 Russian flu virus was an old strain, reintroduced into the human population. source: Courtesy of Solvay Pharmaceuticals, Weesp, the Netherlands.

References in context

Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”.
Go to context

1918 – Spanish flu (H1N1)

The Spanish flu first struck in March 1918 in the USA, with reports from Detroit, South Carolina and San Quentin Prison of outbreaks of an unusual respiratory disease that was associated with a disproportionate increase in deaths among young adults. The infection spread rapidly, crossing both the Atlantic and Pacific Oceans in a matter of months, killing many American soldiers during their voyage to Europe in the spring of 1918 ( Figure 15 ). In Europe, initial infections were reported in Madrid in May 1918, hence the name “Spanish” flu. This first wave infected all the armies in Europe during May and June. After the initial wave there was a sharp decline of infections in the summer of 1918, to be followed by a second, more severe, wave that peaked in the autumn of 1918, and a third wave in the spring of 1919, both associated with global spread of the infection. In just 10 months, approximately 50 million people worldwide were killed, ⁵ x NP Johnson, J Mueller. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76 (2002) (105 - 115) more than the total number of victims of the 1914–18 war.

Figure 15 The 1918 Spanish flu pandemic. The origin of the Spanish influenza virus (H1N1) is unclear. First outbreaks were reported in the USA in March 1918. The infection rapidly spread to Europe, where its impact was particularly terrible, and further throughout the world. After the first wave in the spring of 1918, a second, more devastating wave followed in the fall of 1918 and a third wave in the spring of 1919. The pandemic killed an estimated 50 million people. source: Adapted from Potter CW. Chronicle of influenza pandemics. In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of Influenza. Oxford: Blackwell Science, 1998; pp. 3–18 ²⁹ x CW Potter. Chronicle of influenza pandemics. KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, Oxford, 1998) (3 - 18) with permission from Blackwell Publishing.

References in context

The infection spread rapidly, crossing both the Atlantic and Pacific Oceans in a matter of months, killing many American soldiers during their voyage to Europe in the spring of 1918 (Figure 15).
Go to context

The origin of the Spanish influenza is not clear. It may have been imported into the USA by migrant workers from China. It is equally possible that the pandemic originated in the USA. Indeed, the fact that the pandemic started with simultaneous outbreaks at three different locations in the USA supports this hypothesis.

Recently, based on fragments of genetic material isolated from the remains of a victim of the Spanish flu pandemic buried in the permafrost of Alaska, the 1918 virus has been resurrected, ³¹ x TM Tumpey, CF Basler, PV Aguilar, et al.. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310 (2005) (77 - 80) using reverse genetics techniques (see Chapter 9). Challenge studies in mice have confirmed the extreme lethality of the virus.

1957 – Asian flu (H2N2)

The “Asian flu” originated in the Yunan Province of China in March 1957, spreading rapidly to South-East Asia and Japan, and subsequently in May to Australia, Indonesia and India, and during the summer to Europe, Africa, North and South America, and the Caribbean. In just 6 months, the pandemic had spanned the globe. A second wave occurred during the autumn of 1957. Altogether it affected some 40–50% of the population, with 25–30% experiencing clinical disease. Mortality was approximately 1/4000, occurring predominantly among the very young and the very old. The total death rate probably exceeded 1 million.

1968 – Hong Kong flu (H3N2)

This pandemic also originated in China, in July 1968, spreading to Hong Kong, where it peaked after only 2 weeks, causing a major outbreak of 500,000 cases, and receded completely after 6 weeks. By August, the infection had spread to Taiwan, the Philippines, Singapore and Vietnam, and by September to India, Iran and Australia. In that month the infection also entered North America via California, carried by troops returning from Vietnam. In the USA, the epidemic peaked in December. Altogether, 30–40% of the population were infected, causing 56,000 excess deaths. School absenteeism reached 50%. Compared to the earlier pandemics of the century, the Hong Kong flu was relatively mild, possibly as a result of immunity in the population against the N2 subtype neuraminidase which the new pandemic H3N2 virus shared with the circulation H2N2 virus. Worldwide, the total death toll of the 1968 pandemic was between 500,000 and 1 million.

1977 – Russian flu (H1N1)

The outbreak of Russian flu first appeared in northen China in May 1977 and spread throughout Russia by December, and the rest of the world in 1978. As mentioned above, the virus was subsequently found to be virtually identical to one that had caused a human epidemic in 1950. ²⁸ x K Nakajima, U Desselberger, P Palese. Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature 274 (1978) (334 - 339) Consequently, most people over 23 years old possessed antibody to it. Thus, the pandemic was confined almost entirely to children and teenagers. Thankfully, the illness was quite mild and weekly attack rates at peak were about 13% in children 7–14 years old. Unlike the previous two pandemic viruses, this virus failed to replace the previously circulating influenza A virus, such that currently both H1N1 and H3N2 viruses circulate in humans.

References in context

Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”.
Go to context

References in context

The infection spread rapidly, crossing both the Atlantic and Pacific Oceans in a matter of months, killing many American soldiers during their voyage to Europe in the spring of 1918 (Figure 15).
Go to context

References

Label	Authors	Title	Source	Year
4 References in context By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths. Go to context By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths. Go to context Despite their annual seasonal character, influenza epidemics are unpredictable.4,7 When precisely they will start and how long they will last are questions that are difficult to answer in advance. Figure 11 illustrates the variation in the onset and duration of influenza epidemics recorded in the Netherlands in the last three decades of the previous century. Go to context While the bird flu outbreak in 1997 was the first documented example of a purely avian virus causing respiratory disease and deaths among humans,18–20 it has since become apparent that the 1918 Spanish flu virus was also an avian virus.3,22–25 Even though the precise origin of the 1918 virus remains enigmatic,3,11,22 based on characterization of genetic material isolated from victims of the 1918 pandemic, it is clear now that the virus was not a human–avian reassortant, but rather an avian-like virus that was introduced in its entirety into the human population and subsequently adapted to the new host. Go to context As illustrated in Figure 13, the 1957 Asian H2N2 virus subtype obtained its HA, NA, and PB1 genes from an avian virus and the other fives genes from the circulating H1N1 human strain,1,4,7,14–17 the human H1N1 virus in turn being a distant descendent of the 1918 Spanish flu virus.3 Likewise, the 1968 Hong Kong H3N2 virus acquired its HA and PB1 genes from an avian virus, but retained the NA and remaining five other genes from the then circulating H2N2 human virus. Go to context A third way by which an antigenic shift may occur and a pandemic arise is reintroduction of an “old” strain into the human population. Go to context Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”. Go to context	ED Kilbourne.	Influenza pandemics of the 20th century.	Emerg Inf Dis 12 (2006) (9 - 14)	2006
5 References in context By far the most devastating pandemic was the Spanish flu outbreak, which hit at the end of the First World War.3,4 It spread across the globe in three consecutive waves in 1918–19, killing at least 50 million people.5 The subsequent pandemics in 1957 and 1968 were milder,4 but nonetheless also caused a total of approximately 2 million deaths. Go to context Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”. Go to context In just 10 months, approximately 50 million people worldwide were killed,5 more than the total number of victims of the 1914–18 war. Go to context	NP Johnson, J Mueller.	Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic.	Bull Hist Med 76 (2002) (105 - 115)	2002
26 References in context As illustrated in Figure 13, the 1957 Asian H2N2 virus subtype obtained its HA, NA, and PB1 genes from an avian virus and the other fives genes from the circulating H1N1 human strain,1,4,7,14–17 the human H1N1 virus in turn being a distant descendent of the 1918 Spanish flu virus.3 Likewise, the 1968 Hong Kong H3N2 virus acquired its HA and PB1 genes from an avian virus, but retained the NA and remaining five other genes from the then circulating H2N2 human virus. Go to context The first convincing report of an influenza pandemic describes an outbreak in 1580, which started in Asia in the summer, and then spread via Africa to Europe and finally to America.26 In Britain it came in two waves, a pattern that was also seen in subsequent influenza pandemics. Go to context	WJ Bean, M Schell, J Katz, et al..	Evolution of the H3 influenza virus hemagglutinin from human and nonhuman hosts.	J Virol 66 (1992) (1129 - 1138)	1992
28 References in context A third way by which an antigenic shift may occur and a pandemic arise is reintroduction of an “old” strain into the human population. Go to context As mentioned above, the virus was subsequently found to be virtually identical to one that had caused a human epidemic in 1950.28 Consequently, most people over 23 years old possessed antibody to it. Go to context A cyclic theory has been proposed suggesting that pandemics may appear in a specific recurring pattern.28 The interval between the 1889 (H2) and 1900 pandemics (H3) matches that between the 1957 (H2) and 1968 (H3) pandemics. Go to context	K Nakajima, U Desselberger, P Palese.	Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950.	Nature 274 (1978) (334 - 339)	1978
29 References in context Go to context Historic records indicate that influenza pandemics have been among us for many centuries.29 A report by Hippocrates describes an outbreak as early as 412 BC that could have been due to influenza. Go to context Historic records indicate that influenza pandemics have been among us for many centuries.29 A report by Hippocrates describes an outbreak as early as 412 BC that could have been due to influenza. Go to context Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”. Go to context	CW Potter.	Chronicle of influenza pandemics.	KG Nicholson, RG Webster, AJ Hay (Eds.) Textbook of Influenza (Blackwell Science, Oxford, 1998) (3 - 18)	1998
30 References in context Figure 14 gives an overview of the influenza pandemics that occurred in the past century.4,29,30 The most terrible outbreak was the Spanish flu in 1918, with an estimated 50 million deaths,5 justifying its description as “the last great plague of mankind”. Go to context	WIB Beveridge.	The chronicle of influenza epidemics.	Hist Phil Life Sci 13 (1991) (223 - 235)	1991
31 References in context Recently, based on fragments of genetic material isolated from the remains of a victim of the Spanish flu pandemic buried in the permafrost of Alaska, the 1918 virus has been resurrected,31 using reverse genetics techniques (see Chapter 9). Go to context	TM Tumpey, CF Basler, PV Aguilar, et al..	Characterization of the reconstructed 1918 Spanish influenza pandemic virus.	Science 310 (2005) (77 - 80)	2005

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