The Spanish Influenza Pandemic of 1918-1919

New Perspectives

David Killingray, Howard Phillips, David Killingray, Howard Phillips

• Publisher: Routledge
• Year: 2003
• Topic: History
• eBook ISBN:
  9781134566402
• Subtopic: World History
• Index: History

The Spanish Influenza pandemic of 1918-19 was the worst pandemic of modern times, claiming over 30 million lives in less than six months. In the hardest hit societies, everything else was put aside in a bid to cope with its ravages. It left millions orphaned and medical science desperate to find its cause. Despite the magnitude of its impact, few scholarly attempts have been made to examine this calamity in its many-sided complexity. On a global, multidisciplinary scale, the book seeks to apply the insights of a wide range of social and medical sciences to an investigation of the pandemic. Topics covered include the historiography of the pandemic, its virology, the enormous demographic impact, the medical and governmental responses it elicited, and its long-term effects, particularly the recent attempts to identify the precise causative virus from specimens taken from flu victims in 1918, or victims buried in the Arctic permafrost at that time.

Part I Virological and pathological perspectives

1 A virologist's perspective on the 1918–19 pandemic

Edwin D. Kilbourne

DOI: 10.4324/9780203468371-2

Introduction

Although lacking the clear-cut pathognomic stigmata of such plagues as poliomyelitis and smallpox, influenza pandemics of the past can be identified with reasonable certainty as the manifestations of an acute, prostrating respiratory tract disease with a high attack rate. In a careful examination of both primary and secondary sources, Patterson has postulated the occurrence of nine pandemics during the period 1700–1900. These presumed pandemics occurred at irregular intervals and no common factor seemed to be involved in their precipitation.¹ The causative virus of human influenza was first identified in 1933. In the subsequent modern virological period, pandemics have occurred in 1957 and 1968, associated with the introduction, probably from animal or avian sources, of markedly different strains of the influenza A virus, known by their surface antigens as H2N2 and H3N2. The likelihood that the pandemic of 1918 was caused by a similar infectious agent is strengthened by seroarchaeologic evidence that persons exposed to and presumably infected by the 1918 virus have antibodies to the virus of swine influenza — which appeared as a new disease in the American middle west in 1918. Very recently, it has been reported that fragments of the genome of a virus similar to the swine (H1N1) virus have been demonstrated in the preserved lung tissue of human victims of the pandemic.² Because influenza pandemics have occurred at intervals of 11 to 39 years, and it is now (2003) 35 years since the last pandemic in 1968, there is increasing concern about the prospect of another pandemic and about its potential severity. This concern is heightened by the recognition that the effective vaccines now available have never been sufficiently utilised to affect significantly the course of any pandemic, and by the increasing number of antibiotic-resistant bacterial pathogens which, as secondary invaders, account for most of the deaths in pandemic periods.³

Virus changes that account for pandemics are of two sorts:

1. the principal and essential change is a major change in one or both of the surface viral antigens to create a virus which differs so markedly from those previously encountered in human experience that people of all ages become susceptible;
2. other changes that influence the intrinsic virulence of the virus are suspected, but as yet unproven, although it has been found in animal influenza that virulence⁴ or host range affinity⁵ can be greatly enhanced by mutation of a single viral nucleo tide.

It is also true that a dramatic vaccine failure and world-wide dissemination of a virus occurred in 1947 without subtype changes in the surface antigens of the human virus.⁶ This chapter will address the implications of these findings for putting the 1918 pandemic into perspective and assessing realistically expectations for the dangers of future pandemics.

The literal and figurative exhumation of 1918 influenza by serologic and virologic archaeology

Because the science of virology was in its infancy in 1918, no virus was recovered from victims of the epidemic. Bacteriology at the time was well advanced, and the prevalence of secondary bacterial infections in influenza victims led to the mistaken identification of various bacterial pathogens — notably Pfeiffer's ‘influenza bacillus’ (Haemophilus influenzae) — as causative agents. After influenza viruses were first isolated from mammals, first from swine by Shope in 1931 and later from humans by Smith, Andrewes and Laidlaw in 1933, a retrospective connection was made of these viruses with the virus of 1918 by examining the sera of persons old enough to have been exposed to the 1918 virus. It was found that this cohort of the population carried antibodies reactive with the swine influenza virus, while others did not.⁷ When this evidence was coupled with records of swine influenza appearing as a new disease in the north central United States in 1918,⁸ it appeared that the primary host for the 1918 virus may have been human.⁹ The direction of migration of the virus across species barriers remains moot, however,¹⁰ because the infection can be virtually asymptomatic in swine, and may have escaped recognition prior to 1918.

The previously cited recovery by Taubenberger and his colleagues of remnants of swine influenza virus genes in the lungs of soldiers who died of influenza in 1918 and from the lung of an Inuit woman frozen in the Alaskan tundra, has provided even stronger evidence that a virus resembling contemporary swine influenza viruses was in fact the aetiologic agent of that disaster.

Deductions on the probable virology of the 1918 pandemic from the more recent pandemics occurring within the period of modern virology

Although the clinical picture and epidemiology of the yearly influenza epidemics after the isolation of the influenza virus in 1933 resembled the milder cases of influenza in 1918, no modern epidemics of flu have had the dramatic and lethal impact of that event. Therefore, it has been questioned whether, in fact, the causative agents of ‘Spanish’ influenza and the modern disease are related. There were, however, hints from the study of serum specimens from people exposed to the 1918 virus that suggested that the 1918 virus (if such it was) was antigenically related to the virus now indigenous to American swine.¹¹

No true pandemics of influenza occurred in the interval 1918–57, and therefore there was no opportunity to apply post-1933 technology and science to the study of a pandemic until 1957 when the ‘Asian’ influenza epidemic moved swiftly from the Far East to encompass the world in a matter of months. This, and a second pandemic following close behind in 1968 — as well as pandemic threats in 1976 and 1997 — are worth examining for the light they shed, retrospectively, on the pandemic of 1918. (See Box 1.1 for a chronology of major epidemics.)

The ‘mild' or ‘pseudo-pandemic' of 1947

Although vaccine-induced immunity to influenza A virus is continually challenged by progressively selected mutations in the virus's major antigens, (antigenic drift), virus strains within a subtype (e.g. H₁N₁) are antigenically cross-reactive. Cross-immunity diminishes as further mutations accumulate, necessitating frequent changes in vaccine strains, although older vaccines are usually partially protective. The post-war epidemic of 1947 is notable for the total failure of a vaccine previously effective in the 1943–4 and 1944–5 seasons. We have combined extensive antigenic characterization of the hemagglutinin (HA) and neuraminidase (NA) antigens of the 1943 and 1947 viruses with analysis of their nucleotide and amino acid sequences and have found marked antigenic and amino acid differences in viruses of the two periods. Furthermore, in a mouse model, vaccination with the 1943 vaccine had no effect on infection with the 1947 strain. These findings are important because complete lack of cross-immunogenicity has previously been found only with antigenic shift, in which antigenically novel surface antigens have been captured by réassortaient of human and animal strains, sometimes leading to pandemics. Although the 1947 epidemic lacked the usual hallmarks of pandemic disease, including an extensive increase in mortaliity, it warns of the possibility that extreme intra-subtypic antigenic variation — if coupled with an increase in disease severity — could produce pandemic disease without the introduction of animal virus antigens.¹³

Box 1.1 Major influenza epidemics or pandemic threats since 1918 — every pandemic is different

Early chronology

1929 — last evidence (serologic) of circulation in humans of a ‘swine’-like influenza virus

1930 — isolation by Shope of an influenza virus from swine

1933 — first isolation of an influenza virus from humans by Smith, Andrews and Laidlaw

Pandemics, pseudo-pandemics and pandemic threats

1947 — influenza ‘A Prime’ — a global, relatively non-lethal epidemic of a variant virus of the same A subtype that had circulated since 1929. Vaccines made from antecedent (H1N1) strains failed to protect.

1957 — the first true pandemic since 1918. The H2N2 ‘Asian’ influenza virus differed from its antecedents in both major antigens, thus confronting the world's population with an essentially novel virus to which it had no immunity. This epidemic was important in demonstrating that a ‘modern’ influenza virus could cause pandemic disease and fatal viral pneumonia reminiscent of 1918. Completely replaced all H1N1 subtype viruses.

1968 — in the ‘Hong Kong’ pandemic only the major haemagglutinin (HA) antigen changed, but change was sufficient to induce a pandemic, modified in severity by population immunity against the minor neuraminidase (NA) antigen. Completely replaced all H2N2 viruses.

1976 – at least 250 recruits at Fort Dix, New Jersey were infected with swine influenza virus. A controversial mass immunisation programme was initiated in the USA for fear of ‘another 1918’. With no further cases of disease and complications attributed to the vaccine, programme was cancelled after vaccination of 43 million people.

1977 — the ‘Russian’ flu (actually originating in China) which produced a global pandemic affecting initially those less than 25 years of age. An early return of a virus (H1N1) last seen two decades before. Unprecedented co-circulation of H1N1 and H3N2 (Hong Kong) subtypes continues to this day.

1997 — H5N1 avian influenza in Hong Kong with sixteen proved infections of humans and six fatalities. Perhaps due to mass destruction of chickens suspected to be the source, the epidemic ceased.

1999 — H9N2 avian virus appeared early in the year, also in Hong Kong, as a brief zoonotic infection without evidence of human to human transmission. As with H5N1 virus, apparent origin in chickens. Apparent cessation of cases without mass slaughter of fowl.

The ‘Asian' pandemic of 1957 — the first modern pandemic

The Asian virus was readily isolated from patients by methods that had become standard in the study of contemporary influenza viruses and it proved to be similar in its biological and chemical properties to modern influenza viruses. However, the surface proteins of the virus — the haemag-glutinin (HA) and neuraminidase (NA) antigens — were very different from those of human viruses previously encountered. Most of the population, immunised only by exposure to the H1N1 group of viruses, had no immunity to the new H2N2 ‘Asian’ virus. For this reason, pandemic spread occurred with lethal outcome in some patients, amongst whom the disease was indistinguishable from that seen in 1918.

Three remarkable observations were made during this first modern pandemic and its successor in 1968:

1. the new virus completely and suddenly replaced its predecessor, which was not to reappear until decades later;
2. the magnitude of antigenic change in the virus proteins was unprecedented and differed fundamentally from the gradual and cumulative ‘point’ mutations that had explained the yearly ‘drift’ of the virus to partially escape vaccines and rising levels of population antibodies; and
3. antigenic proteins similar to those in the 1957 and 1968 human viruses had been identified previously in nature in avian species.¹⁴ This third observation suggested the possible derivation of perhaps all human influenza pandemics from animal sources.

The ‘Hong Kong' pandemic of 1968 — a periodicity of pandemics appeared to be emerging

Taken togethe...

Table of contents

• Cover
• Half-Title Page
• Series Page
• Title Page
• Copyright Page
• Table of Contents
• List of illustrations
• List of tables
• Notes on contributors
• A virologist's foreword
• A historian's foreword
• Acknowledgements
• Introduction
• PART I Virological and pathological perspectives
• PART II Contemporary medical and nursing perspectives
• PART III Official responses to the pandemic
• PART IV The demographic impact
• PART V Long-term consequences and memories
• PART VI Epidemiological lessons of the pandemic
• Notes
• Bibliography
• Index