1818,1918,2018: Two Centuries of Pandemics

Driving Forces

The cholera pandemic of 1817 to 1824 and the influenza pandemic of 1918-19 shocked the world in their respective eras. In hindsight, they appear hardly unexpected. In many ways, these pandemics were the natural consequence of dramatic social, political, economic, military, and technological changes to human society, which contributed to favorable conditions for the global spread of infectious diseases.

Globalization was an overarching driver behind the rise of both pandemic cholera and pandemic influenza, represented most starkly by the transcontinental movement of military forces by ascendant global powers. In the 19th century, the British Empire employed its army and navy extensively to advance its colonial interests. The colonization of large swaths of the globe by the British Crown or its commercial proxies, including the East India Company, facilitated the spread of cholera outside its origins in Bengal, where it had remained for centuries. British historians of the era “represented cholera as an enemy force advancing to attack a defenceless army”;^3(p127) accordingly, 764 British soldiers stationed in Bundelkhand, in central India, died of the disease in a single week in 1817. ³ Thousands more Indians perished during the outbreak. British troops deployed to the Gulf in 1820-21 to quell an uprising unknowingly brought cholera from India and infected the local population of Muscat, from which it spread to Zanzibar and Basra. ¹ Then, as now, the introduction of cholera to the Arabian Peninsula proved particularly dangerous for Muslim pilgrims completing the Hajj. ⁴

Arguably, nowhere is the military's role in precipitating the spread of disease more evident than during World War I. America's entry into the Great War contributed to one of the largest mobilizations of troops in history, cramming together tens of thousands of young men as they trained in military cantonments in Kansas, Texas, Massachusetts, and other states. Historian John Barry writes that “[e]ven at the front in Europe … the concentration and throwing together of men with different [disease] vulnerabilities may not have been as explosive a mix [for the spread of influenza] as that in American training camps.”^5(p145) Many, including Barry, believe that the fateful flu strain hitched a ride with army recruits from Haskell County, Kansas, to other parts of the world. He concludes that the virus “might well have died [in Kansas]”^5(p95) were it not for the war.

Others trace the disease's origin to a mysterious “winter sickness” that broke out at the sprawling military camp at Étaples in northern France, only miles from the Western front. Journalist Laura Spinney writes that if the origin were indeed French, then the pandemic can “truly be described as an outcome of the conflict, because in that case it was brewed in a camp where men were brought together (with some women) for the express purpose of killing other men.”^6(p165) A third rival theory locates the index case to China's inland provinces. According to the China origin theory, the Chinese Labour Corps, which sent hundreds of thousands of Chinese men to support the Allied war effort by digging trenches and repairing railways in France, Belgium, and Russia, was key to influenza's spread from remote China to the other side of the globe. ⁶

This massive military mobilization was part of the larger trend toward globalization occurring at the time. Historian George Dehner observes that while the Great War did not directly bring about globalization, “the demands of the war [in men and materiel] accelerated the rate and volume of global connections,” such that influenza “exploited chains of infection to quickly expose virtually the entire planet's population.” ^{7 (p44)} By 1921, approximately a quarter of the world's population fell under British rule—or about 500 million people—with another 10% of the world's land area under French sovereignty.^8,9 This colonial world was a remarkably fluid one, within which imperial subjects, including millions of horses, pigs, cattle, and other zoonotic disease vectors, moved relatively freely with few border controls.

This unprecedented movement was enabled by a transportation and industrial revolution that began about a century earlier, linking the colonial periphery with the center. Railroads and steamships enabled Vibrio cholerae—the causative agent of cholera that had been confined to South Asia for most of its existence—to escape from the subregion. Dehner writes that “technological advances in the speed and volume of transportation from India combined with the colonial concerns of imperial Britain to facilitate cholera's emergence from its traditional limits,” until eventually reaching the center of global capital, London, in 1831-32.^5(p33) This marked an uncanny reversal of the estimated trajectory of the Spanish flu, which may have begun in the industrialized world and later spread to the global south, with India among the last nations affected. As journalist Steven Johnson remarked of this new, interconnected world, “the sanitary conditions of Delhi could directly affect the conditions of London and Paris.”^10(p42) He attributes cholera's unchecked growth to “sprawling new metropolitan spaces … overwhelmed with their human filth … increasingly connected by the shipping routes of the grand empires and corporations of the day.”^10(pp41-42) Some 15,000 Londoners died during the 1848-49 cholera outbreak, demonstrating how population density without adequate sanitation infrastructure could act as a powerful driver of pandemic disease. ¹⁰

Compared to today, authorities possessed an insufficient understanding of and limited countermeasures against the diseases they were tasked with controlling. Nonpharmaceutical interventions, including hygiene and social distancing measures, that might have mitigated the highly transmissible, airborne influenza virus were often implemented too late, after many had already fallen ill. ¹¹ In 1918, despite warning by the scientific community, including the dean of the Johns Hopkins School of Public Health William Henry Welch, US military leaders did little to improve the conditions in overcrowded training camps. ⁵ Echoing the role of traditional burial practices in fueling the 2014-16 epidemic of Ebola virus disease in West Africa, spiritual leaders in northern Spain disregarded the directives of local health authorities by organizing mass funerals, evening prayers, and religious processions that led to some of the highest rates of infection in the country. ⁶ While social distancing, hygiene campaigns, and other preventative measures were eventually instituted in many regions of the globe, Australia, by imposing a strict maritime quarantine, was the only continent that did not record a single case of the Spanish flu during the first and second waves. ⁶

Global Impacts

The Spanish flu led to an estimated 50 to 100 million deaths globally, exceeding all expectations of its destructive potential. ¹² It is believed that more American soldiers died of disease than in battle—a recurrent theme throughout history. Historian Alfred Crosby estimates that approximately 675,000 Americans of all backgrounds, including military and civilian, died from influenza and pneumonia between September 1918 and June 1919. ¹³ Yet, when one considers that about a quarter of the US population, or about 25 million Americans, may have been infected, the case fatality rate may not have been greater than 3%. ¹³

The global south—crippled by weak public health systems, poverty, and malnutrition—bore the brunt of the pandemic. ¹⁴ In Sierra Leone, an estimated 3% to 6% of the population of black Africans died following influenza exposure from foreign navy vessels. ⁵ This number dwarfs the proportion of Sierra Leoneans killed in the 2014-16 epidemic of Ebola virus disease, estimated at a fraction of 1% of the population. ¹⁵ In the Indian subcontinent alone, between 13 and 17 million people died from influenza, comprising approximately 6% of its population. ¹⁶ The reason for this high mortality compared to epidemics of seasonal influenza is subject to debate, but one prominent explanation considers a so-called “cytokine storm”—the result of an overactive immune response—leading to acute respiratory distress syndrome. ¹⁷ This may help to explain why, unlike outbreaks of seasonal influenza, which primarily target infants and the elderly, more than half of the deaths occurred in young adults aged 18 to 40 with healthy immune systems. ¹⁷

While pandemic influenza led to widespread morbidity, pandemic cholera was typically localized but quite deadly. Case fatality ratios for cholera were recorded to be higher than 60% in the worst affected European cities in the mid-1800s (although adjusted estimates place this significantly lower). ¹⁸ These waves of cholera emerged as a near-permanent fixture in human society, with profound social, economic, and health effects. Upon spreading from rural South Asia in the 19th century, cholera devastated both the West and global south, as each suffered from the dismal hygiene and sanitation practices prevalent at the time. When it reached densely populated New York City in 1832, cholera killed 3,515 residents among a population of 250,000. ¹⁹ In contrast to influenza, which infected paupers and presidents alike, vulnerable populations were the hardest hit, including dirty and overcrowded neighborhoods of African Americans and Irish Catholic immigrants. The urban poor were quickly stigmatized, exemplifying how infectious disease often exacerbates existing social disparities.

Though difficult to quantify because of the many confounding factors that contribute to political and economic crises, these pandemics arguably have caused significant geopolitical disruptions and may have altered, or at least accelerated, the course of history. German commander Erich Ludendorff blamed the Spanish flu as the decisive blow that doomed his 1918 spring offensive along the Western front, a loss that sealed Germany's defeat in World War I. ⁵ (In actuality, opposing Allied forces may have been equally decimated by the wave of influenza. ⁶ ) Thousands of miles away, influenza may have catalyzed nascent efforts in India to become an independent nation. Though Mahatma Gandhi, the stalwart leader of the Quit India Movement, would eventually recover from his bout with flu, broader mismanagement of India's public health system in the face of massive loss of life, combined with a climate of post-war repression and scarcity, stoked anti-colonial sentiments across the country, including a fateful protest at Amritsar in 1919. ²⁰

Scientific, not geopolitical, disruption would arguably be the defining legacies of both pandemics. Crosby argues that while the Spanish flu, due to its propensity to affect all sides equally, had limited influence on military and political events, it spurred great innovation among the medical and scientific community. ¹³ In the 1930s, the viral, not bacterial, origin of influenza was established, with the subsequent development of medical countermeasures, such as viral vaccines and antivirals. Similarly, London's cholera epidemic in 1854 set the stage for British doctor John Snow's famous discovery on Broad Street, which demonstrated the bacteria's water-borne transmission. Subsequently, Snow's discovery and methodology based on detecting and mapping broader patterns in disease transmission helped to inaugurate a data-driven approach to modern epidemiology, promote the germ (as oppose to miasma) theory of disease, and spur sanitary reform across many Western cities. ¹⁰ Civic engineer Joseph Bazalgette's elaborate sewer network, opened in 1865, kept contaminated waste out of London's water supply and, once completed, ensured the metropolis would never experience another outbreak of cholera again. From Chicago to Hamburg, replicating his engineering marvel “became the central infrastructure project of every industrialized city on the planet.”^10(p214)

Other Progress Made Since 1818

Since the first Asiatic cholera pandemic and the Spanish flu pandemic, countries have made enormous strides in science, medicine, public health, and urban development, resulting in broad improvements to standards of living and health outcomes across the world. Still, increasing rates of globalization and varying levels of access to health care, clean water, and sanitation have ensured that both influenza and cholera remain perennial threats, particularly in the developing world.

In 2017, for example, the World Health Organization (WHO) underscored the severity of both endemic and epidemic cholera in sub-Saharan Africa, southern Asia, and Haiti, noting that these regions report an estimated 2.86 million cases of cholera and 95,000 deaths per year, leaving some 1.3 billion persons at risk of contracting the disease in endemic countries. ²¹ With regards to influenza, a simulation by the Institute for Disease Modeling presented by Bill Gates predicted that were a pandemic strain with the same virulence and pathogenicity of the Spanish flu to emerge today, it would kill 30 million people within 6 months. ²² This does not consider the disease burden of seasonal influenza, which is estimated to kill between 291,000 and 646,000 people worldwide annually from associated respiratory illness. ²³

Fortunately, new tools for detection and treatment—including PCR tests, rapid diagnostic tests, oral rehydration therapy, administration of intravenous fluids, and antibiotic therapy—have bolstered public health arsenals against cholera. Similarly, new rapid tests for influenza have elevated clinical diagnostic capabilities beyond conventional cell culture, immunofluorescence, and PCR methods.^24,25 Advances in vaccinology have also played critically important roles in mitigating the pandemic threats posed by cholera and influenza. In 2013, WHO established the Global Oral Cholera Vaccine (OCV) stockpile, which consists of 2 oral, killed, whole-cell vaccines: Shanchol™ and Dukoral^®. ²⁶ WHO's Global Task Force on Cholera Control has overseen international efforts to integrate targeted oral cholera vaccine delivery in both endemic and epidemic settings; as of May 2018, more than 25 million doses of oral cholera vaccine have been administered via mass vaccination campaigns across 19 countries. ²⁷

Though vaccines against seasonal influenza have generally proven effective against their intended targets, long discovery and production times and poor vaccine uptake nevertheless continue to contribute to high rates of infection. In light of these longstanding challenges, the US National Institute of Allergy and Infectious Diseases recently unveiled a strategic plan for developing a universal influenza vaccine that would provide recipients with lasting protection against multiple strains of influenza, including those with pandemic potential. ²⁸ WHO has also added both influenza and cholera vaccine to its list of essential medicines, further signifying their importance in global pandemic preparedness efforts.

While novel diagnostic tools and medical countermeasures have enhanced pandemic preparedness at the frontlines of public health and clinical care, new legal mechanisms and policy frameworks have similarly strengthened national and international health systems' capacities. International health cooperation formally began in response to the threat of cholera in Europe with the International Sanitary Conventions of 1851-52, the predecessor to the International Health Regulations of 1969 (IHR). ²⁹ The revised IHR (2005) and the Global Health Security Agenda have further revitalized global efforts to both counter emergent infectious disease threats and address underlying socioeconomic, political, and infrastructural factors contributing to the persistence of such threats. Additionally, the One Health paradigm encourages cross-disciplinary, integrative approaches to infectious disease threats emerging at the fulcrum of human, animal, and environmental health. Such approaches could prove particularly effective in combating the threats of cholera and influenza, which are often closely connected to clean water availability and livestock health, respectively.

2018 and Beyond

Though vaccines, diagnostics, and new policy approaches have saved countless lives since the pandemics of cholera and flu active in 1818 and 1918, respectively, the world still struggles to contain pandemic threats amid persistent conflict, disasters, and ever-increasing globalization. For example, in a striking historical parallel, a Nepali military contingent of United Nations peacekeepers sparked a devastating cholera outbreak in Haiti while responding to a major earthquake in 2010—echoing both the British military's role in carrying cholera to the Gulf in 1820-21, as well as the Allied war engine's role in spreading the Spanish flu during World War I. Though Haiti's cholera epidemic began from an international humanitarian response effort, as opposed to emerging under military or imperial pretexts, it nevertheless illustrates the ease with which rapid global movement of humans and pathogens can ignite catastrophe, especially in volatile settings saddled with weak health systems.

Between 2010 and 2012, the cholera outbreak in Haiti infected approximately 600,000 people and killed 7,500. ³⁰ Now, in 2018, the Gulf nation of Yemen is experiencing an unprecedentedly severe cholera outbreak following the destruction of its water, sanitation, and health systems during Saudi-led airstrikes; in fact, the outbreak has escalated into one of the most complex humanitarian emergencies in recent times. In 2017, Yemen experienced more than a million cases of cholera. Health authorities have also reported on the unusual severity of the 2017-18 flu season in the United States—which, despite available vaccines, was the deadliest since the 2009 H1N1 pandemic. ³¹ Therefore, medical countermeasures and policy reform alone are necessary but insufficient tools for mitigating pandemics, which remain perennial challenges on a global scale—and thus, will require complementary solutions of a similar scale.

The specter of pandemic catastrophe is unlikely to subside unless public health practitioners, clinicians, and policymakers consider infectious disease outbreaks in the broader context of relevant sustainable development issues: namely, ensuring access to clean water and sanitation, providing universal health coverage, increasing access to essential medicines, addressing climate change, and eliminating poverty. Decision makers need not consider investing in human development at the expense of continued investment in bolstering pandemic response capabilities, such as novel vaccines, clinical and humanitarian responders, and medical supplies. However, compared to prioritizing response assets, a preventive approach to pandemic mitigation that emphasizes sustainable development may prove to be more cost-effective in the long run by alleviating some of the health security risks stemming from globalization, urbanization, and industrialization—upstream factors that history has shown to function as critical accelerants of pandemic threats. For example, more than half of the world's population currently lives in cities, with the United Nations projecting that number to rise to 66% by the year 2050. ³² Slum dwellers suffer from increased health risks, including infectious diseases, and face greater exposure to environmental hazards.

The UN Sustainable Development Goals articulate a critical framework for reducing infectious disease threats. Unlike the IHR, the Sustainable Development Goals do not explicitly mention the goal of preventing pandemics, but they do address upstream factors that often catalyze their emergence, underscoring the ways in which socioeconomic and political disparities, urban infrastructure, environmental conditions, and other factors outside the purview of host-pathogen interactions nevertheless modulate countries' vulnerability to pandemic threats. However, the Sustainable Development Goals themselves must be coupled with appropriate incentives—funding, political commitments, and programmatic support—to transform their ambitious targets into reality and, in doing so, bolster defenses against infectious disease threats with pandemic potential.

Conclusion

This year marks an apt occasion to reflect on both the centennial of the 1918-19 Spanish flu epidemic and the bicentennial of the 1817 to 1824 Asiatic cholera pandemic. History has demonstrated the ability of these diseases to overwhelm health systems, destabilize economies and livelihoods, and inflict suffering and death, which have contributed to their unique longevity as major global public health threats. Modern approaches to combating these perennial threats should therefore account for the ways in which hallmarks of modern life, such as globalization, urbanization, and military conflict, exacerbate pandemic risks. As such, countries should ensure that in addition to investments in defense and emergency response capabilities, tools of soft power—namely, diplomacy and development—also remain at the forefront of national security policymaking and global public health efforts. In addition to fully investing in the Sustainable Development Goals, leveraging the international partnerships forged through soft power will strengthen preparedness for infectious disease threats that do not respect national borders. Continued participation and investment in international health alliances and institutions—such as the Coalition for Epidemic Preparedness Innovations, the Global Health Security Agenda, and WHO—is sure to hasten progress toward a safer, healthier world.