Viral Pandemics

From Smallpox to COVID-19

Rae-Ellen Kavey, Allison Kavey

• Éditeur: Routledge
• Année: 2020
• ISBN:
  9781000174915
• Édition: 1
• Sujet: Medizin
• Sous-sujet: Infektiologie

Written by a public health practitioner and a medical historian, Viral Pandemics explores the terrifying world of viruses as the cause of all acute pandemics since 1900, including the COVID-19 pandemic. The book illuminates the critical dual roles of viral biology and increasing global interconnectedness that have resulted in an escalating pandemic spiral.

Viral Pandemics is the first book to focus exclusively on pandemics caused by viruses and the first to report the COVID-19 pandemic. In each chapter, the historiographic narrative follows the path of the virus from its original detection through its first appearance as the cause of disease, to its emergence as an explosive pandemic. Scientific information is presented in an accessible, straightforward style in compelling narratives that introduce the extraordinary universe of diverse, opportunistic viruses whose remarkable capacities make them formidable adversaries. The book makes it clear that global viral disease challenges are a persistent reality with the potential to cause catastrophic loss of life and major social and economic damage. A summary chapter draws together lessons learned and develops a proposed multidisciplinary global response.

Viral Pandemics is the only book that provides a complete historical narrative focused on viral pandemics. This comprehensive survey is designed for students and scholars in biology, epidemiology, public health, global history and the history of medicine, as well as general readers interested in the science of pandemics.

1

A Brief Introduction to Virology

Preventing the Unknown

Global health in the twenty-first century faces unprecedented challenges from powerful, highly pathogenic viruses. These invisible but enormously powerful agents have already caused a series of terrifying disease outbreaks; since just the turn of the century, we have faced the continuing global spread of HIV/AIDS, SARS (Severe Acute Respiratory Syndrome), a global influenza pandemic with a newly emerged H1N1 strain, the global spread of Zika with its devastating pre-natal consequences, overwhelming and ongoing Ebola pandemics, and now a growing pandemic due to the newly recognized coronavirus shown in Figure 1.1. In each case, the unique abilities of the causative virus were critical elements in determining the outcome of the pandemic. To understand the intrinsic factors that determine viral pathogenicity, we begin by tracing the history of virus discovery.

Figure 1.1Transmission electron micrograph of coronavirus particles found near the periphery of an infected cell.

Source: Image captured at the US National Institute for Allergy and Infectious Disease (NIAID) Integrated Research Facility in Fort Detrick, Maryland. NIAID.gov.

The story begins in the sixteenth century with Girolamo Fracastoro, a Renaissance scholar of philosophy, poetry and medicine who studied with Copernicus at the University of Padua. At the tender age of 19, he was appointed as a professor at the University and elected the official physician of the ecumenical council of the Roman Catholic Church. From his earliest days, he adopted a scientific approach to the study of nature and this may have led to his absorption in understanding the causes of disease. In his 1546 work, De Contagione et Contagiosis Morbis (On Contagion and Contagious Diseases), he described his theory that infection results from “tiny, self-multiplying bodies that can be spread by direct or indirect contact, through infected objects, or even through the air over long distances.”¹ This idea of infectious “contagion” had been suggested by others since antiquity, but Fracastoro’s explanation was the first clear articulation of the concept. At the time, his views were completely ignored in favor of the erroneous “miasma theory”: that lethal disease-causing agents arose spontaneously from decomposing material in the earth that traveled by air as a poisonous, foul-smelling vapor. Given the ghastly stench that arose above communities in the Middle Ages without any form of sewage management, it is easy to understand how this theory persisted. It was the mid-1800s before the French microbiologist, Louis Pasteur, determined that it was microscopic bacteria that caused disease and Robert Koch defined the procedure for proving that specific diseases are caused by specific bacteria, essentially formalizing Fracastoro’s theory as the germ theory of disease.²

Bacteria are the smallest microbes which can survive independently because they carry all the necessary cellular machinery and genetic material to produce energy and reproduce within a single cell. Confirmation of bacteria as the cause of disease transformed the practice of medicine, and by early in the twentieth century, practical extension of the germ theory led to many improved public health sanitation practices like water treatment and sewage disposal. Public education increased awareness of the ways in which bacteria thrive and this supported improved personal hygiene practices like handwashing and safe food preparation. While antibiotics as specific treatments for bacterial infections did not appear until much later in the twentieth century, public health improvements reinforced by comprehension of the germ theory of disease significantly decreased deaths from infectious diseases in the early 1900s.

Within this context of increasing scientific knowledge and improving public health, viruses were virtually unknown. Bacteria which could be recognized and identified with a light microscope were established as the “germs” of the germ theory. However, despite all the progress linking pathogenic bacteria with disease, a significant number of clearly infectious diseases remained for which no causative bacteria could be identified. It was the late nineteenth century before any progress was made with this dilemma. Scientists who were unable to identify a bacterial cause for a well-recognized disease of tobacco plants called tobacco mosaic disease (TMD) found that an extract of crushed leaves from infected plants passed through a filter that removed all bacteria still caused the disease: they theorized that the filtrate must contain a submicroscopic infectious agent.³ The filterable agent was found to multiply only in an environment that included tobacco leaf cells, not in a cell-free environment. This demonstration, confirmed subsequently for all these tiny submicroscopic agents, led ultimately to the conclusion that they were parasites, obligate intracellular organisms which could replicate only in a plant, animal or human host. The term virus comes from the Latin word for poison and during the eighteenth and nineteenth centuries, it was used to describe all forms of infectious agents. Over time, virus became the specific term for these submicroscopic infectious agents. When the 1918 influenza pandemic occurred, viruses were known only as a mysterious group of tiny microbes that were infectious, filterable and required living cells for replication, but their structure and function remained unknown.³

While not specifically identified, viruses had caused disease as long as there had been life on earth, and outbreaks of viral disease were recorded for centuries, ever since humans began living together in communities. Smallpox was first reported in approximately 10,000 bc and it is still considered to be among the most lethal viral infections. At around that same time, mumps, measles and polio, all caused by viral pathogens, were first described in ancient Egypt. While not necessarily identified as influenza, major flu outbreaks occurred throughout recorded history, beginning as early as 412 bc and extending right through the nineteenth century. The yellow fever virus – the first virus specifically recognized as causing human disease – was identified in 1900. In 1909, poliomyelitis was definitively shown to be caused by a virus. By the early twentieth century, viruses had a long and tragic record of causing serious pandemic disease.

It was at this time that the effort to understand viruses became inextricably linked with the devastating 1918 influenza pandemic (more to follow on this pandemic in Chapter 4). Faced with a terrifying disease outbreak for which they had no treatment, doctors and scientists struggled to find a comprehensible bacterial cause, a search which continued long after the pandemic ended. At that time, a viral etiology could only be identified indirectly, by using an ultrafiltrate from a diseased subject to induce disease in a susceptible plant or animal host, or by detecting the presence of antibodies against the disease in survivors of the illness in question. Using these indirect methods, viruses had been confirmed as the cause of a number of important human and animal diseases including smallpox, yellow fever, rabies and measles. In 1919, a year after the primary 1918 pandemic ended, scientists from Japan and from France reported separately that a bacteria-free emulsion of mucous or blood from influenza patients produced classical flu symptoms of varying severity when given to monkeys and to human medical volunteers.^4,5 These results strongly suggested that influenza was caused by a virus but scientists were unconvinced, perhaps because at the time, so little was known about the basic nature of viruses.

It was not until 10 years after the influenza epidemic that a young American scientist named Richard Shope began studying swine flu, an influenza-like illness that had sickened millions of pigs in the Midwest in the fall of 1918, just as the lethal stage of the influenza pandemic began, and had continued as a seasonal illness in pigs since that time. Shope found that a filtrate of mucous from a pig with swine flu would produce a similar flu-like illness in a healthy pig – conclusion: the cause of swine flu was a virus.⁶ By this time, Wilson Smith, Christopher Andrewes and Patrick Laidlaw, three young British researchers, had identified the ferret as a good model for influenza, because the animals developed a classic flu-like illness described by the researchers as “fever, sneezing, mucopurulent nasal discharge and sticky encrustation around the nose” within 48 hours after instillation of nasal washings from human volunteers with the flu (I cannot help but picture cages full of miserable, congested ferrets!). Nasal washings from these infected ferrets were then shown to transmit the disease to other ferrets. In addition, injection of serum from ferrets who had recovered from the flu blocked development of the clinical disease. In 1933, these scientists published their work in The Lancet, confirming for all that human influenza was caused by a virus.⁷ Shope and the British team then collaborated and showed that ferrets inoculated with swine flu filtrate developed an illness indistinguishable from the experimental flu caused by the human flu virus. Did humans give influenza to pigs? Was the swine flu virus actually the human flu virus? Using serum from survivors of the 1918 pandemic, the team showed incomplete blocking of swine flu virus infection, suggesting that the swine flu virus and the human influenza virus were closely related but not identical.⁸ As there was no virus from the 1918 pandemic available for investigation, this swine flu connection could not be further evaluated at the time.

The next important discovery – and this was very important – occurred with attempts to develop an effective influenza vaccine: recognition of the capacity of the influenza virus for spontaneous mutation. Originally, all influenza disease was thought to be caused by the single virus identified in 1933, so vaccines were developed to prevent infection with this specific virus. The concept of immunity was well-established by the early 1900s, based on the historic observation that for many diseases, a single episode conferred lifelong resistance to recurrent infection. With the dawn of bacteriology, antitoxins and vaccines against several important bacterial pathogens including smallpox, diphtheria, tetanus, anthrax, cholera, plague and typhoid had already been developed. In Britain, Smith and Fellowes developed an experimental influenza vaccine using the 1933 virus strain in a mouse lung model with the virus inactivated by formaldehyde. Tests with the vaccine in ferrets showed that it prevented influenza symptoms with an associated increase in neutralizing antibody levels. On this basis, they conducted a small trial in 30 soldiers in 1936; there was no flu outbreak for clinical comparison that ye...