June 19, 2015

“Spanish flu”: The Infamous Pandemic of the 20th Century

An advert for Formamint to be taken during the Flu Epidemic. 1918
An advert for Formamint to be taken during the Flu Epidemic. 1918

Influenza Pandemics

Influenza, commonly known as “the flu”, is an infectious disease caused by the influenza virus. Influenza is caused by a variety of species and strains of virus, which can cause epidemics and pandemics. The Influenza virus belongs to the orthomyxoviridae family and the “Influenza Virus A” species and its strains are the most virulent human pathogens which can cause severe disease. In general, wild aquatic birds are the natural hosts of the virus, but sometimes the viruses are transmitted to other species and may cause devastating outbreaks in domestic poultry and/or give rise to human influenza pandemics.1
According to Cox et al. (2003),2 an influenza pandemic begins with an abrupt and major change in the surface proteins, haemagglutinin and neuraminidase, of the Influenza A virus. This change is termed as “antigenic shift”, which enables the formation of a new mutant virus, distinct from the earlier. A pandemic is considered likely if the novel virus is readily transmissible from person to person and causes disease, and if there are large populations worldwide that lack immunity to the virus.2 However, it is difficult to predict the occurrence of pandemics, with the exception of a clue from historical analysis that pandemics occur in periodic cycles.
The 20th century witnessed three such influenza pandemics: in 1918 (Spanish flu), 1951 (“Asian flu”) and 1968 (“Hong Kong flu”). Of these, the 1918 Spanish flu pandemic was considered the most devastating in modern history.

Historical Overview of the 1918 Spanish Flu Pandemic

The 1918 flu pandemic, also known as “La Grippe”, was caused by H1N1 influenza A virus3 and infected 500 million people across the world, including remote Pacific islands and the Arctic.4 Among those infected, an estimated 50 to 100 million were killed—3%–5% of the world’s population at that time, making it one of the deadliest natural disasters in human history.5 The pandemic had two unusual aspects. First, the disease killed between 2% and 20% of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1%.6 Second, the pandemic mostly killed young adults, with 99% of deaths occurring in people under 65, and more than half in young adults 20 to 40 years old.7 This is unusual since influenza is normally most deadly to the very young (under the age of two) and the very old (over 70 years).
Historians and biomedical researchers argue that two major contemporary issues contributed to the gravity of the flu pandemic—the effects of World War I, and limited scientific knowledge. In 1918, little was known about influenza virus biology and antiviral therapies. There were mixed theories on the origin of the H1N1 influenza virus and its outbreak into pandemic. Some researchers believe it might have originated in China, while others theorise that it was already in existence before 1918, with minor outbreaks in France in 1916 and England in 1917. Some also argue that the first wave of pandemic started in the United States in early 1918.
Disease Spreads in Three Waves
The 1918 pandemic occurred in three waves over an 18-month period and spread around the world. The first wave, or “spring” wave, began in 1918 and spread unevenly through the United States, Europe and parts of Asia over the following six months. During this wave, high illness rates and above-normal mortality rates were reported. The second, or “autumn”, wave—from September to November 1918—was highly fatal and swept across the globe, leaving no major inhabited region untouched. The focal point of the epidemic in terms of mortality was India, with an estimated death toll in the range of 10–20 million, and an estimated population loss of 13.8 million for the British-controlled provinces.8 This was followed by the third wave in 1919, which lasted for a few months in Australia, Spain and many other countries. The rapid succession of these waves limited preparedness and response, eventually claiming millions of lives.
A Wartime Outbreak
The influenza pandemic of 1918–9 coincided with the end of World War I, but scientific enquiry into the relationship between the flu pandemic and world war started much later. War conditions facilitated the trans-border transmission of Influenza virus and optimised the conditions for the spread of influenza in high-density population pockets such as military barracks, troopships, troop trains, prisoner-of-war camps, labour compounds, factories, mineshafts, schools, mass meetings and processions.9 According to Kolata (1999),10 the Spanish flu pandemic occurred simultaneously with the United States’ involvement in World War I. By the autumn of 1918, the US had been fighting in Europe for more than a year. There were many deaths due to war, and flu increased the number of American deaths. It has been estimated that the 1918 influenza pandemic killed 675,000 Americans, including 43,000 servicemen mobilised for the war.11 The impact was so profound as to depress average life expectancy in the United States by more than ten years,12 and may have played a significant role in ending World War I.11
The 1918 Pandemic as “Spanish Flu”
There are varying opinions on why the Influenza pandemic was also known as “Spanish flu”. During World War I, press censorship in countries such as Britain and the US halted the distribution of information considered detrimental to the war effort, including the influenza outbreak. The press in Spain was not subject to wartime censorship due to the country’s neutrality, and was the first country to report the pandemic; ever since, it has been popularly known as Spanish flu. Another reason to emerge from historical research was that the most accurate information about the flu came from Spain as its king at the time, Alfonso XIII, contracted the illness and became its most high-profile victim. News organisations in Spain frequently released reports on the state of the king’s health.13

Public Health Response to Spanish Flu

The 1918 flu pandemic that swept the globe was perhaps the greatest ever public health challenge as public health measures were minimal to non-existent, and no antibiotics or anti-retroviral drugs for influenza were available. There was no certainty over the causative factors of flu, and the lack of scientific knowledge over viral pathogenicity and limited medical advances posed challenges to public-health responses to the Spanish flu pandemic. In addition, World War I had left many countries with a shortage of physicians and healthcare workers who could respond to the health crisis caused by the pandemic.
Although there were many limitations, public-health practitioners were active in finding means to minimise the impact of the influenza. In many countries, the activities of practitioners on the ground were all employed—quarantine, isolation, public propaganda, warnings, campaigns against spitting, legal restrictions on commercial activities, inspection, surveillance, and compulsory (often public) identification and (perhaps) stigmatisation. With no ability to see the virus and no vaccines available to prevent its spread, the public-health community’s ability to fight the pandemic depended on its moral, political and legal authority.14

Policy and Scientific Progress Against Influenza Pandemics Since Spanish Flu

Influenza prevention and mitigation are key strategies for public health. However, in 1918, lack of scientific knowledge was a major limitation on the strategic public-health approach. It was only in 1940s that the successful development of an influenza vaccine began. The first licensed flu vaccine appeared in the US during World War II; by the 1950s, pharmaceutical manufacturers could routinely produce vaccines that would help control and prevent future pandemics.15
The devastating effects of the flu pandemic led the global community to rethink pandemic preparedness, which eventually helped the development of preparedness and response for the 20th century and beyond. In 1947, following a request by a respected group of scientists, the Interim Commission of the WHO agreed to establish the World Influenza Centre (WIC) to collect and distribute information, conduct and coordinate laboratory work on the virus, and train new laboratory personnel.16 Established in London in 1947, the WIC marked the start of the broader WHO influenza programme to plan against future pandemics, develop control methods to limit the impact when a pandemic did appear, and limit as much as possible the economic impacts of influenza epidemics and pandemics. Brady (1957)17 stated that all these efforts towards influenza pandemic preparedness were the outcome of the 1918 pandemic. Ever since the start of the programme to combat influenza, it has evolved to serve the global good.
Two approaches are currently available for the prevention and control of influenza:18vaccines and antiviral agents.
· Vaccines: The haemagglutinin and neuraminidase proteins are the primary targets of the protective antibody response; antibodies against haemagglutinin neutralise virus infectivity, and antibodies against neuraminidase can modify the severity of disease.
· Antiviral drugs: Two anti-Influenza A drugs are currently licensed in some countries. These are the chemically related adamantane compounds, amantadine and rimantadine—both of which are 70–90% effective in preventing illness caused by naturally occurring influenza A viruses when administered prophylactically to healthy adults or children during the period of exposure in a normal epidemic or outbreak situation. When used therapeutically within 48 hours of the onset of symptoms, these two compounds can also reduce the severity and duration of signs and symptoms of illness caused by Influenza A viruses.

Global Governance for Influenza Pandemics

Globalisation has enabled and intensified the trans-border transmission of influenza viral pathogens, and with it the potential occurrence of pandemics. In order to prevent and mitigate influenza pandemics, effective governance is critical. Lee and Fidler (2007)19 emphasised that effective governance to prepare for, and respond to, a pandemic depends on four key functions:
· Surveillance: Knowledge of what influenza strains are circulating enables the planning and implementation of interventions, such as vaccines
· Protection: A second key function of influenza governance is to protect populations against influenza-related morbidity and mortality
· Response: When influenza breaks through protection efforts, effective governance requires timely and appropriate responses to its impact on populations
· Public communication: A key function in influenza governance is to provide accurate and timely information, essential for ensuring an appropriate perception of risk among the public. However, access to vaccines and virus-sharing issues have challenged influenza pandemic governance and helped the creation of new governing frameworks.
The governing system for influenza began with the creation of the World Health Organization. The core component of this system has been the Global Influenza Surveillance Network (GISN), established in 1948. The GISN, also known as FluNet, a network of 112 national Influenza centres in 83 countries, recommends the formulation of the influenza vaccine for the approaching season, and serves as an early-warning mechanism for the emergence of a virus with pandemic potential.20 In 2011, GISN was renamed the WHO Global Influenza Surveillance and Response System (GISRS) with the adoption of the Pandemic Influenza Preparedness (PIP) Framework. The PIP framework brought together member states, industry, other stakeholders and the WHO to implement a global approach to pandemic influenza preparedness and response, which includes the sharing of influenza viruses with human pandemic potential, and aims to increase the access of developing countries to vaccines and other pandemic-related supplies.


Influenza pandemics date from the 9th century, and occur roughly every few decades. The occurrence of three pandemics during the 19th century and another three during the 20th has led experts to conclude that pandemics occur in cycles. According to historical patterns, the 21st century will also see at least three influenza pandemics (one occurred in 2009). Pandemic cycles may occur in the coming decades, although speculation about the timing of the occurrence and the influenza virus subtype causing it remains inconclusive. In 2018, the world will be commemorating the centenary of the Spanish flu outbreak and its devastating effects, the scientific progress made in vaccine and drug discoveries, and the establishment of governing frameworks for pandemics including the International Health Regulations (IHR). However, “governance” remains the key factor for preparedness and response to influenza and many other emerging pandemics.
1 Klenk, H.D., Matrosovich, M. and Jürgen, S. “Avian Influenza: Molecular Mechanisms of Pathogenesis and Host Range” in Mettenleiter, T.C. and Sobrino, F. (eds) Animal Viruses: Molecular Biology. Caister Academic Press (2008).
2 Cox, N.J., Tamblyn, S.E. and Tam, T. “Influenza Pandemic Planning”. Vaccine 21 (2003) pp. 1801–3.
3 Anhlan, D., Grundmann, N., Makalowski, W., Ludwig, S. and Scholtissek, C. “Origin of the 1918 pandemic H1N1 influenza A virus as studied by codon usage patterns and phylogenetic analysis”. RNA; 17(1) (2011) pp. 64–73. doi:10.1261/rna.2395211
4 Taubenberger, J.K. and Morens, D.M. “1918 Influenza: the Mother of All Pandemics”. Emerging Infectious Diseases 12(1) (2006) pp. 15–22. doi:10.3201/eid1201.050979.
5 “Historical Estimates of World Population”. en.wikipedia.org/wiki/1918_flu_pandemic. Accessed 25 May 2015.
6 Knobler, S., Mack, A., Mahmoud, A. and Lemon, S. (eds). “The Story of Influenza”. The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005). Washington, D.C.: The National Academies Press. pp. 60–1.
7 Simonsen, L., Clarke, M., Schonberger, L., Arden, N., Cox, N. and Fukuda, K. “Pandemic versus epidemic influenza mortality: a pattern of changing age distribution”. The Journal of Infectious Diseases 178(1) (1998) pp. 53–60. doi: 10.1086/515616
8 Johnson, N.P. and Mueller, J. “Updating the accounts: global mortality of the 1918–1920 ‘Spanish’ influenza pandemic”. Bulletin of the History of Medicine 76 (2002) pp. 105–15.
9 Phillips, H. “Influenza Pandemic” in Daniel, U., Gatrel, P., Janz, O., Jones, H., Keene, J., Kramer, A. and Nasson, B. (eds) 1914-1918-online. International Encyclopedia of the First World War.Issued by Freie Universität Berlin, 8 October 2014. doi: dx.doi.org/10.15463/ie1418.10148
10 Kolata, G. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus that Caused It. New York: Farrar, Straus, Giroux; 1999.
11 Crosby, A. America’s Forgotten Pandemic. Cambridge: Cambridge University Press; 1989.
12 Grove, R.D. and Hetzel, A.M. Vital statistics rates in the United States: 1940–1960. Washington, DC: US Government Printing Office; 1968.
13 Harries, S. “Top 10 Facts About the 1918 Flu Pandemic”. www.toptenz.net/top-10-facts-about-the-1918-flu-pa…. Accessed 25 May 2015.
14 Rosner, D. “‘Spanish Flu, or Whatever It Is …’: The Paradox of Public Health in a Time of Crisis”. Public Health Reports 125(Supp. 3) (2010) pp. 38–47.
15 History.com. “1918 Flu Pandemic”.
www.history.com/topics/1918-flu-pandemic. Accessed 21 May 2015.
16 Payne, A.M.-M. “The influenza programme of WHO”. Bulletin of the World Health Organization 8(5–6) (1953) pp. 755–92.
17 Brady, F.J. “Central Technical Services of the World Health Organization”. Public Health Reports 72(2) (1957) pp. 101–4.
18 Cox, N.J. and Subbarao K. “Influenza”. The Lancet 354(9186) (1999) pp. 1277–82.
19 Lee, K. and Fidler, D. “Avian and pandemic influenza: Progress and problems with global health governance”. Global Public Health: An International Journal for Research, Policy and Practice 2(3) (2007) pp. 215–34. doi: 10.1080/17441690601136947
20 Hampson, A.W. “Surveillance for Pandemic Influenza”. Journal of Infectious Diseases 176(Supp. 1) (1997) pp. S8–S13.

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