An epidemic that occurs worldwide, involving many countries and affecting a large population is called as a pandemic. There are various factors which can lead to epidemics of infectious diseases. These include a change in ecology of host population and mutation in reservoir of pathogen. Disease outbreaks may also occur when a new, emerging pathogen is introduced to a host population. When these epidemics become widespread, involving many people mostly due to effective transmission of disease amongst humans, they are classified as pandemics. The wide geographical occurrence of these pandemics is usually by pathogens that are novel to human beings, having a high attack rate, are highly infectious and are able to mutate fast, so as to evade host immunity. Of all pathogens, viruses are particularly common in causation of pandemics due to their vast species occurrence, involvement of non-human hosts, rapid routes of transmission and higher rates of infectivity.
Aim of the present study is to collate data on previous similar pandemics, so that it can be utilized for better knowledge sharing, and learning from past experiences, to combat the present pandemic and to prepare for such pandemics in future.
Major viral pandemics in the last 2 decades mostly involved respiratory viruses like corona, causing 3 major pandemics earlier: severe acute respiratory syndrome (SARS CoV-1), Middle eastern respiratory syndrome (MERS) and ongoing SARS CoV-2 (COVID -19), followed by influenza viruses causing Influenza A H1N1 pdm 2009 (swine flu), Ebola and Zika virus infections.
Pandemic 1: Severe Acute Respiratory Syndrome Corona Virus Infection (SARS- CoV-1)
SARS is a respiratory illness caused by virus SARS CoV-1 belonging to Coronaviridae family, and is first strain to be discovered from severe acute respiratory syndrome–related coronavirus (SARS CoV) species. The virus caused the 2002-2004 SARS pandemic in which 30 countries were affected. A total number of 8,422 cases were reported, with 11% case fatality ratio (CFR). CFR varied from case to case depending on age-group of patients. CFR was <1% in people below age of 24, while it was >55% in those above age of 65 years. The first case was reported in November 2002 from Guangdong, China. The virus was said to have originated from cave-dwelling horseshoe bats found in Yunnan province of south-western China, pointing to zoonotic origin. The transmission was through respiratory route from droplets or fomites. Management was majorly focused on reduction and control of symptoms. There is currently no proven antiviral therapy to treat SARS. Preventive measures such as immediate isolation of confirmed cases, wearing protective gears, barriers by medical practitioners during handling of patients helped to control further spread of disease. Since 2004, no more cases of SARS CoV-1 have been reported. However, till date there is no success in making effective vaccine against virus. This could be due to successful control over disease, led to lack of interest and delayed all ongoing efforts.
Pandemic 2: Influenza A H1N1 2009 (Swine Flu) Pandemic
Influenza A group of viruses had caused 2 major pandemics, first was the 1918 Spanish flu and other was the swine flu in the year 2009. In 2009, the virus originated as a result of triple re-assortment between avian, swine, and human viruses leading to term “swine flu” which is a misnomer as it was actually a human virus. The infection was a typical lung infection known as acute respiratory distress syndrome (ARDS). All symptoms were that of conventional flu or pneumonia.
It was speculated that H1N1 virus that was responsible for the 2009 outbreak also initially circulated for several months before being recognized and identified as a novel strain of influenza virus. It first originated from Mexico. The pandemic lasted for about 19 months and finally was declared over in August 2010. Worldwide, more than 214 countries were affected. Total cases that were reported were close to 700 million to 1.4 billion. The number of deaths reported to WHO were approximately more than 18,000. This flu virus demonstrated a high morbidity but low mortality rate of approximately 1-4%. The pandemic was successfully controlled due to availability of an effective vaccine that incorporated this strain. Moreover, an effective antiviral treatment was also available. The immunity provided by these vaccines lasts for 1 year therefore, the vaccine has to be taken annually and yearly; circulating strains of virus are included in vaccine. Human beings have got adapted to the 2009 strain of the virus and now H1N1 2009 pdm strain is the local circulating strain.
Pandemic 3: Middle East Respiratory Syndrome (MERS) CoV Infection
Middle East respiratory syndrome (MERS), is a type of viral infection involving the respiratory tract which is caused by a corona virus. The virus originated from camels, therefore it is also known as the camel flu. The virus belonged to genus Betacoronavirus and subgenus Merbecovirus and its receptors were identified as dipeptidyl peptidase-4 (DPP4). It was first seen in a patient from Saudi Arabia in 2012. It was not very clear how the transmission of the virus took place from camels to humans. The WHO advised to avoid eating un-cooked or under cooked camel meat, drinking of unpasteurized milk and urine from camels and avoid close proximity with camels. There was minimal human to human transmission. The transmission mostly occurred due to close contact with severely ill patients and transmission from asymptomatic cases was never established.
A total number of 2519 laboratory confirmed cases, with 866 deaths having a case fatality of 34.3% was reported till this year. Most of cases were reported from Saudi Arabia and around 26 countries were affected with pandemic. No specific antivirals or vaccine could be developed for this disease. The studies done on various treatment modalities like use of antivirals like Ribavirin and Interferons did not show much success in management of cases infected with MERS-CoV. The virus got contained by isolation of cases and local containment measures eventually controlling the pandemic.
Pandemic 4: The Ebola Virus Pandemic
The Ebola virus pandemic that lasted from 2013 till 2016 is by far most widespread Ebola virus disease (EVD) epidemic reported so far. The disease was first reported from Guinea in late 2013 and then it spread to Liberia and Sierra Leone.
EVD or Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever. It is caused by Ebolaviruses belonging to family Filoviridae in the order Mononegavirales. Zaire Ebola virus was the cause of EVD in the year 2013–2016 in western Africa. It caused significant mortality. The main route of transmission was direct contact with blood or infected body fluids. The source of initial infection from animals to humans was in fact contact with the infected bat body fluids.
The initial case was an 18-month-old boy, in Guinea, who got infected from bats in December 2013. Following this by March 2014, there were 49 confirmed cases and 29 deaths, reported to the WHO. In 2015 it spread across countries in Africa and outside Africa to Spain, USA, UK, Italy, etc., In Africa itself there were approximately 30,000 cases with 12,000 deaths. The pandemic finally got contained by strict containment measures that were taken; very efficient contact tracing and community surveillance. All the cases were registered and immediately all contacts were traced and contained. An efficient community awareness of risk factors and encouraging people to use protective measures like avoiding contact with infected people and adopting hand hygiene, reduced large scale spread of infection. There was no specific antiviral treatment. However, in July 2015, a vaccine, rVSV-ZEBOV, was launched that showed high efficacy in individuals. The pandemic was called over in 2016 and finally, rVSV-ZEBOV received regulatory approval in 2019.
Pandemic 5: Zika Virus Epidemic
Zika virus (ZIKV) is a virus that spreads through the bite of the Aedes mosquitoes: A. aegypti and A. albopictus. These mosquitoes have a typical day-biting tendency. The virus was named after the Zika forest of Uganda, from where it was first reported in the year 1947.
The disease caused by this virus is called Zika virus disease or simply Zika fever, a minor illness with fever and rash. The virus also demonstrates vertical transmission from infected pregnant female to her fetus, and can cause microcephaly and other major brain abnormalities. The virus belonged to family Flaviviridae and genus Flavivirus. The virus normally infects monkeys and is maintained in circulation in the enzootic cycle of mosquito-monkey-mosquito. Like other flaviviruses, human beings are accidental hosts to the virus. The most important transmission in the Zika virus disease is vertical transmission, at the time of delivery or during antenatal period causing neuronal abnormalities ranging from microcephaly to development of neurocognitive disorders in adulthood.
The pandemic started in 2015 and a total number of 87 countries were affected. The control of the pandemic was done by case identification, controlling mosquito spread and other preventive measures. There is no specific antiviral treatment however trials are going on for development of a successful ZIKV vaccine. Three vaccine designs have reached the stage of human trials but still an effective vaccine is yet to come.
Pandemic 6: SARS-CoV2 Pandemic
The SARS CoV-2 pandemic, is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV2) virus and the disease is caused by it is corona virus infective diseases (COVID-19). The virus belongs to the Coronaviridae family and the virus is an enveloped, positive-sense, single-stranded RNA virus. Corona viruses are known to cause infections in amphibians, birds, and mammals. Coronaviruses have initially originated from bats and rodents. The primary route of transmission is respiratory and is transmitted from droplets through coughs and sneezes up to a range of approximately 6 feet. Some studies have pointed towards a possibility of the virus being airborne as well. Another mode of transmission is by indirect contact with contaminated surfaces. The major and common clinical features include fever, cough, weakness, loss of sense of smell and taste. Further complications of the disease include acute respiratory disease with pneumonia. Preventive measures aimed at decreasing the chances of infection include hand hygiene, surface disinfection, wearing face masks, and avoiding close contact with those showing flu-like symptoms. Many countries have adopted social distancing strategies such as cancelling large public gatherings, shutting down schools, colleges, offices, and putting restrictions on travel.
It was first reported from Wuhan, Hubei province of Central China in month of December in 2019. The outbreak was further declared a public health emergency of international concern on 30th January and declared as a pandemic on 11th March 2020. As of 27th Dec 2020, COVID19 pandemic has affected more than 188 countries across the world, with 79,232,555 confirmed cases and 1,754,493 deaths. The pandemic has led to massive disruption of both social and economic infrastructure, affecting millions of people. At present there is no established treatment for the management of COVID-19 and patients are managed symptomatically. Apart from antiviral drugs a new modality of treatment has been tried with success against COVID-19 which is known as convalescent plasma therapy. Blood of previously COVID-19 infected patients contains neutralizing antibodies against SARS CoV-2 virus. Thus, the plasma from these patients containing antibodies is given to neutralize the virus.
Success with the effective vaccine has come. There are 3 major candidates of vaccine that are being tried, inactivated virus vaccine, vaccine using messenger RNA of virus (mRNA based) and vaccines utilizing recombinant protein of SARS CoV-2 on other viral vector. Hopefully with these efforts very soon control over this pandemic is also done.
The ongoing Covid-19 pandemic has not only impacted global healthcare infrastructure, but has also affected world economy and socio-political framework, effectively bringing the entire world to a standstill. Hence, there was a need to conduct a review of the various viral pandemics that have occurred in the past to understand their origin, transmission and measures that were taken to prevent and control them.
The first observation made during the course of this study was that the frequency of occurrence of pandemics is increasing with time. Earlier, large-scale epidemics spanning various continents were a twice or thrice a century phenomenon, but we have experienced 6 major pandemics in the last 20 years itself. This is due to enhanced globalization, air travel, increasing population and entering into animal habitats; thereby increased close association with them. There has also been a change in socializing behavior of people, with mass gatherings becoming more and more common, contributing to rapid spread of diseases.
Another observation made in this study was that viruses responsible for major pandemics in last 2 decades were air-borne and of animal origin. Growing urbanization has led to the encroachment of forest areas by humans, thus increasing animal to human contact and in turn, the chances of acquiring viruses. Hence, lack of regulation of handling of animals and animal products, rising animal-human contact (especially in case of wild areas), lack of basic hygiene practices, cough etiquettes and a general lack of awareness about spread of viruses and air-borne diseases has contributed significantly to widespread rise in occurrence of these pandemics.
Owing to experiences in handling of previous pandemics, it has been observed that the global healthcare community is much better prepared and equipped for handling and management of pandemics now, than it was before. Table 1 describes the various steps taken to curb outbreaks in the past two decades. This is evident from the fact that the time taken from identification of the first case of the virus, to its complete genome sequencing, making several diagnostic tests and now the development and licensing of vaccines are much faster than the previous pandemics. Within a few weeks of its identification, clinical trials for the vaccine and other therapeutic interventions were initiated within a month.
Despite this knowledge, the ongoing COVID-19 pandemic has emerged as one of the most fatal disease outbreaks known to mankind. This can be attributed to extremely high transmissibility of the virus, human to human transmission at a very early stage of the pandemic, more prominent community spread, and transmission from asymptomatic cases, which has led to an extremely huge surge of infection.
Therefore, the following steps must be followed to slow down the spread of viruses and prevent such outbreaks in future years:
First, all countries must make laws to regulate handling of animals and animal products, (especially exotic/wild species) and wet markets with stringent adherence and enforcement. Second, basic hygiene practices like hand washing, and use of sanitizers and disinfectants must be promoted. Social distancing, following air-borne infection control practices and cough etiquettes like, using a handkerchief while coughing/sneezing, wearing a mask when experiencing even mild flu-like symptoms etc., should be made a norm, especially during mass gatherings and air travel.
Finally, there is a need to increase information and education (IEC) about the origin of viral infections, their mode of transmission and preventive strategies to promote awareness among the general population and curb rising incidences of disease outbreaks.
Viral pandemics are increasing in frequency and infectivity. Great caution should be taken against airborne viral infections especially due to inter species transmission. Such pandemics have affected large populations and have caused considerable havoc on healthcare systems, especially those in developing countries. The recent SARS CoV-2 pandemic has brought the whole world to a virtual standstill severely affecting the world economy. Lessons must be learnt from such pandemics so that adequate strengthening of the healthcare infrastructure and systems can be done in order to prevent or mitigate the long-term effects of such pandemics especially in low and middle-income countries, which are as such struggling with poor health infrastructure. Primary healthcare physicians are important vehicles to bring these practices to more and more people, hence educating them is important.
The current review article focuses on the various viral pandemics that have occurred in the past and how they were controlled. Lessons must be learnt from such pandemics so that adequate strengthening of the healthcare infrastructure and systems can be done in order to prevent or mitigate the long-term effects of such pandemics. Primary healthcare physicians are the first contact with health services hence their knowledge is of utmost importance if we want to strengthen our public health care infrastructure.
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1. Last JMSpasoff RA, Harris SS, Thuriaux MC. Epidemic: The encyclopaedia of ecology and environmental management A Dictionary of Epidemiology. 19984th ed Oxford Newyork Blackwell
2. Tong JW, Zheng YS. Citizen lawsuits against the government in China: Twenty court cases, 2013–2019 Chin Law Gov. 2019;51:49–53
3. Monaghan KJKnobler S, Mahmoud A, Lemon S, et al SARS: DOWN BUT STILL A THREAT. In: Institute of Medicine (US) Forum on Microbial Threats Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. 2004 Washington (DC) National Academies Press (US) Available from: https://www.ncbi.nlm.nih.gov/books/NBK92458/
4. Chan-Yeung M, Xu RH. SARS: Epidemiology Respirology. 2003;8(Suppl 1):S9–14
5. Hu B, Zeng L-P, Yang X-L, Ge XY, Zhang W, Li B, et al Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus PLoS Pathog. 2017;13:e1006698
6. Stockman LJ, Bellamy R, Garner P. SARS: Systematic review of treatment effects PLoS Med. 2006;3:e343
7. Jiang S, Lu L, Du L. Development of SARS vaccines and therapeutics is still needed Future Virol. 2012;8:1–2
8. Trifonov V, Khiabanian H, Rabadan R. Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus N Engl J Med. 2009;361:115–9
9. Butler D. How severe will the flu outbreak be? Epidemiologists race to pin numbers on the global H1N1 spread Nature. 2009;459:14–5
10. Dawood FS, Iuliano D, Reed C, Meltzer MI, Shay DK, Cheng PY, et al Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: A modelling study Lancet. 2012;12:687–95
11. Rha B, Rudd J, Feikin D, Watson J, Curns AT, Swerdlow DL, et al Middle East respiratory syndrome coronavirus (MERS-CoV) MMWR Morb Mortal Wkly Rep. 2015;64:61–2
12. Fehr AR, Perlman SMaier HJ, Bickerton E, Britton P. Coronaviruses: An overview of their replication and pathogenesis Methods in Molecular Biology. 2015;1282:1–23 Springer
13. World Health Organization. Rapid advice note on home care for patients with Middle East respiratory syndrome coronavirus (MERS.CoV) infection presenting with mild symptoms and management of contacts. 2013Last accessed on 2020 Sep 14 Available from: http://www.who.int
14. European Centre for Disease Prevention and Control. Rapid Risk Assessment: Middle East respiratory syndrome coronavirus (MERS.CoV). 17th update. Stockholm: ECDC. 2015
15. World Health Organization. . Ebola virus disease in West Africa – the first 9 months of the epidemic and forward projections N Engl J Med. 2014;371:1481–95
16. Kuhn JH, Becker S, Ebihara H, Geisbert TW, Johnson KM, Kawaoka Y, et al Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations Arch Virol. 2010;155:2083–103
17. Centers for Disease Control and Prevention (CDC). Ebola (Ebola Virus Disease) Transmission [Internet]. 2019Last accessed on 2020 Sep 14 Available from: http://www.cdc.gov./vhf/ebola/index.html
18. Gonzalez JP, Pourrut X, Leroy E. Ebolavirus and other filoviruses Curr Top Microbiol Immunol. 2007;315:363–87
19. Centers for Disease Control and Prevention (CDC). 2014-2016 Ebola outbreak in West Africa [Internet]. 2019Last accessed on 2020 Sep 14 Available from: https://www.cdc.gov/vhf/ebola/history/2014-2016-outbreak/index.html
20. Centers for Disease Control and Prevention (CDC). Treatment [Internet]. 2019Last accessed on 2020 Sep 14 Available from: https://www.cdc.gov/vhf/ebola/treatment/index.html
21. Busta ER, Mancher M, Cuff PA, McAdam K, Keusch G Integrating Clinical Research into Epidemic Responce: The Ebola Experience. 2017 Washington (DC) National Academies
22. World Health Organization. Zika Virus
Microcephaly and Guillain-Barré Syndrome Situation Report [Internet]. 2016Last accessed on 2020 Sep 14 Available from: https://apps.who.int
23. Knipe DM, Howley PM. Fields Virology Lippincott Williams and Wilkins. 20075th ed:1156–1199
24. Ayres CFJ. Identification of Zika virus
vectors and implications for control Lancet Infect Dis. 2016;16:278–9
25. World Heal th Organization. Zika epidemilogy update [Internet]. 2019Last accessed on 2020 Sep 14 Available from: https://www.who.int/emergencies/diseases/zika/zika-epidemiology-update-july-2019.pdf?ua=1
26. Hamzelou J Zika vaccine trials begin – but fears remain over virus's impact [Internet] Wikipedia. 2016 Available from: https://en.wikipedia.org/wiki/2015%E2%80%932016_Zika_virus_epidemic
27. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Lancet. 2019;395:497–506
28. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster Lancet. 2020;395:514–23
29. U.S. Centers for Disease Control and Prevention (CDC). Symptoms of Coronavirus [Internet]. 2020 Available from: https://www.cdc.gov/coronavirus/2019.ncov/symptoms.testing/symptoms.html
30. U.S. Centers for Disease Control and Prevention (CDC). How to protect yourself and others [Internet] CDC. 2019 Available from: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html
31. World Health Organization. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV) [Internet]. 2020Last accessed on 2020 Sep 14 Available from: https://www.who.int
32. UNESCO. Education: From disruption to recovery [Internet] UNESCO. 2019 Available from: https://en.unesco.org/covid19/educationresponse
33. Kupferschmidt K, Cohen J. WHO launches global mega trial of the four most promising coronavirus treatments Science. 2020 New York AAAS
34. London School of Hygiene and Tropical Medicine. COVID-19 vaccine development pipeline [Internet]. Vaccine centre. 2020Last accessed on 2020 Sep 14 Available from: https://www.lshtm.ac.uk/research/centres/vaccine-centre/covid-19
35. World Health Organization. Draft landscape of COVID 19 candidate vaccines [Internet]. WHO. 2020Last accessed on 2020 Sep 14 Available from: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
36. Madhav N, Oppenheim B, Gallivan M, Mulembakani P, Rubin E, Wolfe NJamison DT, Gelband H, Horton S, Jha P, Laxminarayan R, Mock CN, Nugent R. Pandemics: Risks, Impacts, and Mitigation Disease Control Priorities: Improving Health and Reducing Poverty. 20173rd ed(Chapter 17) Washington (DC) The International Bank for Reconstruction and Development/The World Bank PMID: 30212163
37. Figueroa A, Gulati RK, Rainey JJ. Estimating the frequency and characteristics of respiratory disease outbreaks at mass gatherings in the United States: Findings from a state and local health department assessment PLoS One. 2017;12:e0186730
38. Pike BL, Saylors KE, Fair JN, Lebreton M, Tamoufe U, Djoko CF, et al The origin and prevention of pandemics Clin Infect Dis. 2010;50:1636–40
39. Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, et al Global trends in emerging infectious diseases Nature. 2008;451:990–3
40. McCloskey B, Heymann D. SARS to novel coronavirus-old lessons and new lessons Epidemiol Infect. 2020;148:e22
41. Smith AW, Chiew CJ, Lee VJ. Can we contain the COVID-19 outbreak with the same measures as for SARS? Lancet. 2020;20:102–7
42. World Health Organization (WHO). Influenza A (H1N1)–Travel [Internet]. WHO. 2009Last accessed on 2020 Sep 14 Available from: https://www.who.int/csr/don/2009_05_07/en
43. Oh M-D, Park WB, Park S-W, Choe PG, Bang JH, Song KH, et al Middle East respiratory syndrome: What we learned from the 2015 outbreak in the Republic of Korea Korean J Intern Med. 2018;33:233–46
44. Lee J, Kim WJRapid Response Team. . Collaborative intervention of Middle East Respiratory syndrome: Rapid Response Team Infect Chemother. 2016;48:71–4
45. Golding J Ebola: How a killer disease was stopped in its track [Internet]. BBC News. 2018Last accessed on 2020 Sep 14 Available from: https://www.bbc.com/news/health-44872418
46. Carvalho DO, McKemey AR, Garziera L, Lacroix R, Donnelly CA, Alphey L, et al Suppression of a field population of Aedes aegypti in Brazil by sustained release of transgenic male mosquitoes PLoS Negl Trop Dis. 2015;9:e0003864
47. Ferguson NM, Leydon D, Gilani GN, Nedjati-Gilani G, Imai N, Ainslie K, Baguelin M, et al Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand [Internet]. Imperial College COVID-19 Response Team. 2020[Last accessed on 2020 Sep 14] Available from: https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf
48. Srivastava N, Saxena SKSaxena S. Prevention and Control Strategies for SARS-CoV-2 Infection Coronavirus Disease 2019 (COVID-19). Medical Virology: From Pathogenesis to Disease Control. Springer, Singapore. 2020 https://doi.org/10.1007/978-981-15-4814-7_11