In Search of an Enigma: The “Spanish Lady”

This essay was written by Rod Daniels and was first published in the 1998 Mill Hill Essays.

Not the “Spanish Lady” of sea-shanty fame but influenza, which may be older than mankind. Through written records we can trace outbreaks of influenza-like disease back to 412 BC. More precise descriptions of the disease date from an epidemic in 1173, since which time there have been numerous outbreaks that have varied in severity. The most intense, to date, occurred in the last year of World War 1: the so-called “Spanish Lady” or “Spanish Flu” pandemic of 1918-19 which infected one billion people, half the world’s population at that time, and killed between forty and fifty million. This makes it the most devastating disease of man known, surpassing even the bubonic plague of the fourteenth century, smallpox in the sixteenth century and the human immunodeficiency virus/AIDS pandemic that is happening now.

The given name “Spanish” is a twist of history that occurred because Spain, not being involved in the war, had a free Press which could report on the ravages of the pandemic in their country. In turn, when Russia reported on the situation in Moscow, Pravda printed “Ispanka (The Spanish Lady) is in town” and the name has stuck. In fact, the first case can be traced to Camp Funston, Kansas, USA on 8 March 1918. This heralded the start of the pandemic which spread around the world in three waves. The first wave, in March to July of 1918, was relatively mild causing only a small increase in the death rate, this was followed by the most devastating wave between September and December 1918, the virus having changed its character perhaps in the trenches of France, and the final wave of February to April 1919 which produced intermediate death rates.

In 1918-19 the enormity of the pandemic was not uppermost in most peoples’ minds, due partly to the tendency of human nature to shut out bad experiences, and the fact that most were more concerned with the concepts of the war. Indeed, influenza may have played a role in ending the conflict as soldiers were too sick to fight and more men, on both sides, died of influenza than were killed by weapons. In spite of resource commitment to the war, there is a huge volume of literature on the pandemic in terms of clinical descriptions of cases, autopsy reports, microbiologic studies, attempts to develop an animal model for the disease and social history.

The usual symptoms of influenza, rapid onset with high fever, chills, headache, muscle ache in back and legs, and dry cough, were reported and the vast majority of those infected recovered within a week following bed rest, though many experienced a “depression” which took months to overcome. Some individuals showed signs of infection and were dead within twenty-four hours, and there were reports of people who literally dropped dead; others died within two to three days, essentially by drowning as their lungs filled with blood and fluid due to haemorrhage; the majority of those who died did so as a result of pneumonia often caused by secondary infection with bacteria. Many of those who were to die showed outward signs of blueing of the lips, ears, face generally, finger tips and toes, a condition called cyanosis which results from oxygen deprivation. At autopsy, lung and heart damage was common with frequent occurrence of bleeding. Other organs, such as liver, spleen and kidney often showed abnormalities and a few cases showed swelling of the brain.

In 1892, following an influenza outbreak in 1890, a microbiologist called Pfeiffer isolated the bacterium Bacillus influenzae which was proposed to be the cause of influenza. However, in subsequent outbreaks and in particular that of 1918-19, where extensive bacterial culture from lung specimens was successful, a wide selection of bacteria were isolated which led to the proposal that influenza was caused by an undiscovered virus, whilst bacteria were responsible for the gravity of the secondary complications of pneumonia. In spite of this proposal, an anti-influenza vaccine composed of a lethal cocktail of bacteria was prepared but, fortunately, it was not widely administered as the influenza pandemic ended abruptly, perhaps as a result of exhausting the supply of individuals that it could infect in the human population. This abrupt end to the pandemic also brought experiments in animals, which may have led to the isolation of the virus, to a stop.

One of the major unusual features of the 1918-19 pandemic was the age-distribution of those who died. The majority were between twenty and forty tears old whilst in preceding and subsequent influenza outbreaks it was young children and the elderly who were most likely to die. It is possible that in 1918 the elderly may have benefited from an immunity, having survived attacks by less deadly influenza viruses in previous epidemics. Less likely is the idea that the 1918-19 virus was more infectious towards adolescent and young adult tissues than those of the young and elderly. The gathering of twenty to forty year olds for the purposes of war, and declining standards of hygiene and nutrition often associated with crowding, may have enhanced spread of the virus. However, this explanation is perhaps too simplistic since similar age-distributions of death were seen in all countries, not just those involved in the war, and across all social classes. Maybe the young adult population were taking a more active part in the preparations for and fighting of the war and their bodies would have been more stressed than other members of the community. This may have made them more susceptible to infection and disease development. Indeed, many of the changes in body chemistry associated with stress have been shown to match those which give increased probability of infection by human immunodeficiency virus in the present-day AIDS pandemic.

The conditions prevailing in 1918, with an unprecedented movement of people around the world, gave the “Spanish Lady” the best possible chance of spreading. Too late, many governments and local councils imposed public health measures such as bans on public meetings, closure of places of mass entertainment, the compulsory wearing of masks in public and quarantine of ports. The “Lady” had established herself and spread like wild-fire. Disease spread could be traced to routes of individual ships, along railway lines and even to the postman delivering mail to isolated communities. Reports of whole families dying, up to ninety percent of individual communities, and sixty percent of the total Eskimo population, can be found. Many cities and towns ground to a halt as there were insufficient healthy people to run services; medical facilities were overwhelmed with sick people and the number of deaths led to a shortage of coffins and introduction of mass burial in some areas, to remove the chance of further public health problems.

So what did cause this outbreak? Viruses had been described, as early as 1898, as infectious disease-producing agents of small size as shown by their ability to pass through filters which would hold back ordinary bacteria, but attempts to isolate and characterise the agent of the 1918-19 pandemic were unsuccessful. Indeed, influenza was not isolated from humans until 1933, but since that time we have learned a great deal about influenza viruses through tracking studies and basic laboratory research. We know that there are three different types, A, B and C all of which can infect man. They all cause disease of a more or less serious nature, although modern day vaccines, made from inactivated virus or virus fragments, offer a degree of protection. Type A viruses are often associated with the most severe disease, and show great variation in their properties from year to year. Type A viruses are also found in birds and there have been outbreaks of influenza in other species, such as whales, seals and mink. Horses and pigs are also frequently infected and some researchers have suggested that the pig holds an important position as a mixing-pot for bird and human influenza strains resulting in new combinations which may infect man.

In response to infection with influenza our defence mechanism, the immune system, produces antibodies which circulate in the bloodstream and neutralise the virus. Screening of blood samples for the presence of such antibodies to known influenza viruses, gives us an idea of the influenza-infection history of any particular individual. Results of these tests show that, in this century, there have been three major pandemics the 1918-19 pandemic, the Asian influenza in 1957 which killed over a million people and the Hong Kong influenza of 1968 which claimed nearly three quarters of a million victims.

Armed with the ability to isolate influenza viruses, detect them by antibody testing, to produce them in hens eggs and cells in tissue culture for research purposes and vaccine production, there was new interest in the 1950s in the cause of the 1918-19 pandemic. Two expeditions were made to the Alaskan Arctic to retrieve tissue samples from victims of the “Spanish Lady” who had been buried in permafrost. The United States Army expedition to Nome in Alaska, called Project-George, proved unsuccessful as the bodies had been buried in the active layer of the permafrost and decomposed as a result of successive freezing and thawing over the intervening years. Iowa State University mounted an expedition to Teller, also in Alaska, and retrieved tissue specimens from preserved bodies. However, whilst they were able to recover Bacillus influenzae and pneumococci from the samples, attempts to revive the “Spanish Lady” were unsuccessful. More recently, using molecular biological techniques developed since the 1970’s, there have been attempts to rescue the genetic information of 1918-19 influenza from autopsy samples taken and preserved shortly after the victims’ deaths. This approach has yielded information which confirms that the 1918-19 influenza was like the virus isolated first from humans in 1933 but it gives no indication as to why the virus was so harmful. Similar results are emerging from tissue recovered recently, from a corpse in Teller.

We continue to look for further samples from the 1918-19 pandemic. A study of death records for the winter of 1918, from Alaska, northern Canada and northern Europe, has identified sites where the grave locations of victims of the “Spanish Lady” are known and permafrost conditions provide a good probability of body preservation. Such a site was in Longyearbyen, on the island of Spitsbergen, in the Norwegian Arctic archipelago of Svalbard. Seven Norwegian miners aged between nineteen and twenty eight, typical of those afflicted by the Spanish Flu, became ill en route to Longyearbyen, died of influenza between September and October 1918 and were buried in permafrost. The resident community at Longyearbyen was probably protected as they had already experienced the first wave of the pandemic as indicated by a newspaper entry of August 21, 1918: “Things have looked very grim here recently, especially the last few days. The Spanish influenza has gained territory. Only six or seven out of eighty men have been working for the last fortnight. The others have all been attacked by the flu.”

Ground Penetrating Radar was used to identify a mass grave, coinciding with grave markers of the seven victims. This survey indicated ground disturbance to a depth of one-and-a-half to two-and-a-half metres with the permafrost active layer extending to a depth of no more than one metre. This information suggested that the bodies were probably below the active layer such that they would have remained in a frozen state since interment. However, exhumation carried out this summer showed that the bodies had been buried in the active layer and that the quality of samples available was not as good as hoped for. Nevertheless, samples have been taken and transported to a special containment laboratory, which provides the highest level of biological safety. There, attempts are being made to generate more information on the 1918 virus and a general microbiological analysis of the samples is being undertaken. With some luck, and a lot of hard work, the “Spanish Lady” may drop her veil further and give up secrets held for eighty years.

From written records and ongoing surveillance studies in the twentieth century, periodicities of influenza outbreaks of thirty to forty and eleven years have been proposed and many scientists predict that we are overdue another pandemic influenza outbreak. In some ways, conditions prevail as they did in 1918: there is a huge volume of international travel due to the development of transport, there are a number of war-zones with their inherent problems of malnutrition and poor hygiene, the world population has grown to six and a half billion and a greater proportion of this population is living in urban situations many of which have decaying infrastructures in terms of waste disposal. There have been three scares in the last twenty-five years. In 1976, a soldier died at Fort Dix, New Jersey, USA and the virus recovered was identified as a descendant of the influenza virus 1918-19 pandemic; a massive vaccine production and administration campaign was initiated but fortunately the virus did not spread. In 1977 the Russian influenza appeared and was shown to be a virus closely related to viruses circulating in the 1950’s; escape from a laboratory has been suggested as the cause of its reintroduction. In 1997 a new Hong Kong influenza emerged to become the first documented case of direct transmission between birds and man. The implications of this event were potentially catastrophic as there was no established immunity to this virus in the human population. Fortunately, only eighteen cases of infection have been confirmed with six deaths and there is no evidence for human to human transmission. In order to contain the outbreak the Hong Kong authorities ordered the destruction of over a million chickens. Their prompt action may have saved the lives of many millions of human beings. The surveillance programme in humans and chickens continues and steps towards preparing a vaccine have been taken in case this limited outbreak represents the opening shot in the development of a full pandemic.

It was written in 1927: “In the face of the almost certain recurrence some day of another world-wide pandemic, we remain nearly as helpless to institute effective measures of control as we were before 1918.” Today we are in a much better position and many national authorities are formulating contingency plans for a new pandemic of influenza. We have anti-influenza drugs which prevent or delay infections to allow production of the required vaccine, and there is an arsenal of antibiotics to deal with secondary bacterial infections. Continued research on the “Spanish Lady” and the recent Hong Kong virus will hopefully give new insights into what determines the severity of an influenza outbreak and allow testing of our defence strategies on viruses that have such devastating potential.

 

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