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HOW WORLD WAR 1 CHANGED GLOBAL ATTITUDES TO WAR AND INFECTIOUS DISEASES

Friday, 30th of January 2015 Print

HOW WORLD WAR 1 CHANGED GLOBAL ATTITUDES TO WAR AND INFECTIOUS DISEASES 

Prof G Dennis Shanks, MD

http://dx.doi.org/10.1016/S0140-6736(14)61786-4

Summary

World War 1 was a key transition point towards scientific medicine. Medical officers incorporated the discoveries of Louis Pasteur into their understanding of microorganisms as the cause of infectious diseases, which were therefore susceptible to rational control and treatment measures even in the pre-antibiotic era. Typhoid vaccination led to the successful evasion of the disastrous epidemics of previous wars. The incidence of tetanus was probably decreased by giving millions of doses of horse antitoxin to wounded soldiers. Quinine treated but could not control malaria; its use required mass compulsion. Tuberculosis was not a great military problem during World War 1, although mortality in civilian populations increased substantially. Treatment of sexually transmitted infections remained a matter of aversive conditioning, with invasive antiseptics used in the absence of antibiotics. Pandemic influenza in 1918–19 killed more people than died during the entire war, showing how much remained beyond the capability of the scientists and doctors who fought infectious diseases during World War 1.

This is the first in a Series of three papers about the legacy of the 1914–18 war

Introduction

Human beings coevolution with the microorganisms that infect them often progresses faster than does understanding of the resulting infectious diseases, especially during epidemics and armed conflicts. For most of modern existence, disease was thought to be a product of evil spirits or miasmic forces, constraining approaches to prevention and treatment to traditional means going back to Galen. Science gradually changed these attitudes, as physiological processes came to be thought of no longer as a clash of humours but as the result of chemistry.

The discovery of microorganisms and their causative role in infectious diseases eventually changed nearly everything about how such diseases are considered. Louis Pasteur had died only in 1895, so the medical officers of World War 1 still viewed the idea that diseases were caused by infectious microorganisms as novel, and older physicians still clung to antique concepts of miasma and bad air (mal aria).1 During the building of the Panama Canal (1904–14), the idea that mosquitoes spread the malarial parasites that caused disease was deemed so outrageous that the physician in charge, William Gorgas (who, during World War 1, became the US Army Surgeon General), had to appeal to US President Theodore Roosevelt to get funds released for the essential environmental control measures that made massive engineering projects in the tropics possible.2

The medical officers of World War 1 thus were at a transition between knowledge and effective action. They understood that infectious diseases were caused by microorganisms, which largely meant bacteria because viruses were still undefined other than as agents that would pass through a bacteria-excluding porcelain filter.3 This understanding was of limited use in the pre-antibiotic era. Quinine could be used for malaria and arsenic (Salvarsan or Ehrlich 606) for syphilis; otherwise treatments were restricted to disinfectants and topical application.4, 5, 6 Vaccines other than those for smallpox and typhoid were only being developed—crude killed mixtures of bacteria for injection often brewed up in batches.7, 8 Appendicitis was still a major killer of young adults because nothing could be done if peritonitis developed.9, 10 Typhoid fever killed many people irrespective of social status (two of Louis Pasteurs five children died of typhoid).1 Admission to hospital often meant weeks of confinement with little on offer other than detailed nursing care and long convalescent periods.

Public health was still in its infancy, with campaigns to produce safe food and water not yet completed. The ancient Roman army knew that military camps had to be organised with the messing areas distant from the latrines—an empirical observation that remains the basis of military field sanitation.11 Malaria control during World War 1 comprised draining swamps and mass administration of quinine.12, 13, 14 Nearly everyone from urban populations carried quiescent tubercule bacilli in their lungs; control consisted of excluding those obviously ill from the military.15, 16, 17 Sexually transmitted infections were deemed a moral issue, and management was largely left to chaplains, who would try to persuade the large groups of single men not to access the services of the sex workers waiting outside their camp.18 Respiratory infections were a seasoning process: large numbers of recruits from widely varying urban and rural settings were mixed in huge tented camps to trade various pathogens.19, 20 Measles was still a major military health problem, as a result of the isolated rural upbringing of many soldiers.9

Controlled clinical trials had yet to be devised. Treatment was by trial-and-error or dictated by authority. Yet medical science was progressing, and got drawn into the maelstrom of World War 1. Medical laboratories, some funded by the founder of the Wellcome Trust, were deployed with the armies.21 Top research physicians joined the war as uniformed specialist consultants.22 World War 1 marked a key transition towards scientific medicine incorporating the understanding that infectious diseases are caused by microorganisms and therefore susceptible to rational control and treatment measures even in the pre-antibiotic era. New drugs and vaccines were tried in abundance and reported with remarkable rapidity in medical journals. Some of the interventions worked and became part of the medical armamentarium; others did not and were eventually superseded. In this Series paper, I examine this range of success and failure for six important military diseases during World War 1 to understand better the evolving attitudes towards infectious diseases. I chose these specific infections to show the widest possible differences between infections that were well understood and had effective interventions and those without a defined cause or treatment.

Typhoid

“Typhoid and paratyphoid fevers were of but minor importance as causes of sickness in the US Army during the World War.”

Joseph F Siler23

Armies are known for being prepared to fight the previous war. The US army in the Spanish–American War (1898) and the British army in the South African Boer War (1899–1902) experienced epidemics involving tens of thousands of typhoid cases, which directly led to 2192 and 8227 soldiers dying, respectively.11, 23, 24 The avoidable enormity of these medical disasters caused a public outcry, leading to the reorganisation of both nations military medical organisations.25 For the US army, where most of the disease occurred in recruit camps, Walter Reed led a research team that clearly worked out the epidemiology of typhoid.11 However, the recommended solution of better organisation of recruit camps with improved field sanitation did not appeal to the US army non-medical leadership. A technological solution was sought in further development of typhoid vaccines, which were still investigational at the beginning of the 20th century. In the UK, a phenol-killed, whole-cell vaccine had been developed by Almroth Wright during the Boer War and tested on a voluntary basis.26 Based on returns of named typhoid deaths, the vaccine used during the Boer War seemed effective, but this finding is arguable because no established method of assessment existed.24 An epidemic in a US army barracks in Hawaii, where some of the soldiers were already vaccinated suggested a vaccine efficacy of 75%.23 British army estimates of vaccine efficacy were also around 70%, which was estimated by determination of vaccination status, which was entered in the soldiers pay book with variable consistency.24, 27

Typhoid vaccination was thought to be a genuine medical success story in World War 1 (figure 1).

Figure 1

British soldier being vaccinated, possibly for typhoid, by a Royal Army Medical Corps captain medical officer, Salonika (modern Greece) circa 1917

Photo from the Great War Gallery 02588, originally from The Doctor in War.28

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Rates of typhoid in the US army fell from from 142 infections per 1000 soldiers in 1898, to less than one per 1000 soldiers during World War 1. In the British army, the rate fell from 285 infections per 1000 soldiers during the Boer War to less than one per 1000 during World War 1.23, 24 The French army experienced more than 100 000 cases of typhoid and 14 482 deaths in 1914–15, before their vaccination programme became functional.23

The British army policy was to vaccinate troops on tropical deployment only, which meant that the British Expeditionary Force (BEF) was largely unvaccinated during its emergent deployment to Belgium in 1914.24 Typhoid vaccine supplies became sufficient only in 1915, and, by 1916, triple vaccines including protection against paratyphoid A and B were being used, with an estimated 90% vaccination rate.7 Although the US army ordered that all soldiers receive the typhoid vaccine and compulsion was eventually instituted in the French and Italian armies, the British army never made typhoid vaccination mandatory, and the policy of recommended but not required still applies to vaccines in the British army.23 This reluctance was probably because typhoid vaccine had first been introduced on a voluntary basis during the Boer War, and also as a result of the existence of a strong antivaccination movement in England since the 19th century.26

Typhoid vaccines during World War 1 comprised a large injection of endotoxin and made most soldiers sick. More than 35 000 of roughly 4 million vaccinated US soldiers were admitted to hospital after vaccination.23 In view of the 10% case-fatality rate and the 3–6 month hospital stay associated with typhoid fever, along with the constant exposure to faecal contaminated environments, why vaccination against the disease was not made compulsory, even with known side-effects, is difficult to understand.24, 27 The British army regularly ordered men to charge across no-mans-land to assault heavily defended trenches, but would not order the same men to receive typhoid vaccine—a scenario that shows the degree of disconnection between medical science and military logic during World War 1.

Tetanus

“If a fatal amount [of tetanus toxin] has been absorbed, then no amount of antitoxin will save the mans life.”

David Bruce29

Tetanus is a frighteningly lethal disease, and had been well described during the Napoleonic and Crimean wars.29 Yet the British army was surprised by the incidence of tetanus in soldiers wounded in Belgium and France. New weapons left devitalised tissue contaminated with spores from the manured farms that were rapidly converted into trench lines. The tetanus rate was 8·6 infections per 1000 soldiers in 1914, which initiated one of the largest British army medical research projects of the war, as medical officers sought to both prevent the disease and decrease the high case-fatality rate.29, 30, 31 The only prevention or treatment available was antitetanus toxin horse serum (World War 1 predated widespread immunisation with tetanus toxoid).21

A research committee was formed, a standard treatment policy was formulated, and two Royal Army Medical Corps (RAMC) Surgeons General (Bruce and Leishman) took tetanus as a special interest.29, 31 Despite the unmistakable diagnostic sign of jaw muscle spasms, collection of clinical data was challenging because of the size of the armies and mobility of casualties from wounding to hundreds of separate field hospitals followed by evacuation to Britain. Several revisions of the tetanus pamphlet were issued to all medical officers and tetanus rates fell in 1915 only to rise again during the Somme offensive of 1916.30, 32 Semi-annual research updates were published in The Lancet throughout the war, with a final count of 2529 cases and a case-fatality rate of 38% in 1918.29, 33, 34, 35, 36, 37, 38 Tetanus antitoxin was widely judged a great success of medical technology against a particularly distinctive military infectious disease.39

But whether the tetanus programme was a success depends on how the data are interpreted, because many physicians still doubted the usefulness of tetanus antitoxin. The rate of two infections per 1000 soldiers reported during the US Civil War did not differ substantially from the results achieved on the Western Front.29 A French medical officer reported something resembling a controlled trial when a shortage limited the number of soldiers who could receive antitoxin.40 Of 200 wounded German prisoners of war, half were given antitoxin before the onset of any disease and half were not. The remarkably high tetanus rates reported (one soldier in the antitoxin group vs 18 in the control group) showed a very significant (p<0·0005) difference and raises questions about population selection. Clearly, this trial would not even have been considered under todays standards of clinical research, which shows how differently medical officers of World War 1 thought of prevention and treatment amid thousands of wounded men.

2 million doses of antitoxin in the British army were given to wounded men to prevent tetanus, with instructions that the dose was to be given at the earliest possible moment after wounding (figure 2).29 Horse serum is not a benign product and causes anaphylaxis in people sensitised to the foreign protein.32, 39 When the disease is rare but the intervention common, postevent analysis is necessary to establish if the intervention was actually effective. As late as 1917, Surgeon General Bruce had to admit that there were no returns that would allow such an analysis.29 The RAMC thought that early use of antitoxin was critical to the prevention of tetanus on the basis of improved mortality rates (87% vs 38% during 4 years) and progressively longer incubation times, but the data could be interpreted differently.29 The prevalence of tetanus in the British civilian population was estimated to be about the same (ie, one case per 1000 people) as that reported in British soldiers, and was not substantially different from what was reported during previous wars.41 The successful prevention of tetanus was not unanimously agreed upon: some members of the War Office Committee for the Study of Tetanus wrote dissenting opinions in The Lancet,42, 43 disputing the positive interpretations in view of the fragmentary data.

Figure 2

Wounded Australian soldiers receiving tetanus antitoxin outside a medical dressing station, Villers-Bretonneux, France, 1918

Australian War Memorial E05242.

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Malaria

“The clinical type of the disease was a very severe one, and there were many fatal cases.”

Philip Manson-Bahr44

Colonial-era armies were familiar with malaria and with the ability of this mosquito-borne disease to shut down military operations rapidly, but except for relapses, malaria was not a major problem on the Western Front.14 Thousands of malaria casualties occurred in minor battle zones in Palestine, Salonika (modern Greece), and Mesopotamia (modern Iraq), and at times halted combat operations.10, 45 Falciparum malaria was a major cause of death during military operations in east Africa.10 Quinine, a bitter alkaloid extracted from a tropical tree bark, was the only drug available.6 The allied armies obtained most of their quinine from cinchona plantations in the southeast Asian Dutch colonies, but Germany and Austria-Hungary were cut off from such supplies by naval blockade. To overcome this challenge, the German chemical industry undertook a major scientific research programme to develop synthetic antimalarial drugs, although success with atebrine (mepacrine) and chloroquine was not achieved until after World War 1.6

Quinine killed malaria parasites in the blood, but the quantity necessary to induce this effect also caused adverse events such as tinnitus.45 Common regimens comprised weeks of treatment, which were variably complied with once the soldiers immediate illness abated. In the absence of alternatives, quinine doses were pushed to toxic effects. Various route of administration were tried, including the very painful intramuscular injection, which suggests that many medical officers thought that soldiers would avoid the drug whenever possible.46 Unit formations, in which each man was seen to have ingested powdered quinine, swallowed water from his canteen, and shouted his name while observed by non-commissioned officers, were instituted in Salonika because of particularly crippling malaria casualties (figure 3).47

Figure 3

British soldiers parading to receive their daily quinine dose under supervision of their officers, Salonika, 1916

Photo by Ariel Varges, Imperial War Museum Q32159.

Blackwater fever, a malaria-associated haemolytic syndrome that often leads to renal compromise seemed to be the result of intermittent parasite suppression with quinine.48 When atebrine was introduced during World War 2 blackwater fever immediately disappeared, although how quinine caused massive haemolysis resembling a mismatched transfusion has never been elucidated.49 Ronald Ross, the discoverer of mosquito transmission of malaria, was assigned the task of getting two divisions of soldiers (roughly 20 000) who had been invalided as “useless” from Salonika fit to fight on the Western Front despite debilitating chronic malaria infections.12, 50 He created quinine concentration camps, a term used by Ross, in both England and France for 10 weeks of intensive, enforced drug treatment, which was made as pleasant as possible by providing extra rations and light duties. With such aggressive treatment, blood-stage parasites could be cleared, demonstrating that treatments had suppressed but not cured them of their (largely Plasmodium vivax) parasites, despite having no effect on residual hepatic forms.50

Malaria stopped the last great cavalry operation of the war, when the largely Indian and Australian army units broke through the Turkish lines in Palestine and went on to capture Amman, Beirut, and Damascus.51 Before the offensive began in September, 1918, malaria had been controlled by engineering works that drained mosquito-breeding areas around the Jordan River.13, 52 Once the cavalry charged north, epidemic malaria resulted within a single incubation period, limiting combat operations to 2–3 weeks.53 This threat had been anticipated and small mobile malaria diagnostic units—wagon-drawn medical teams with microscopes—raced after the cavalry.44 This diagnostic capability was quite useful when pandemic influenza struck at the same time as the malaria epidemic. Although not much could be done to treat the influenza, soldiers identified as also having malaria (a particularly lethal combination) could be treated with quinine.54

Tuberculosis

“In a majority of the cases the germ enlists with the soldier. A few, very few, catch the disease in infected billets or barracks.”

William Osler55

Tuberculosis caused remarkably little illness in soldiers during World War 1, although active pulmonary tuberculosis was one of the few diseases that would discharge a soldier from the army.56 The military approach to tuberculosis was not to recruit infected individuals, but physical examination alone was a problematic method of diagnosis.16, 17 Detailed prerecruitment chest examinations led to the exclusion of too many recruits and procedures had to be relaxed. Although radiography was available, the technology of the time did not permit its use as a mass screening method.57 Despite ideal conditions for the spread of respiratory pathogens in trenches and on troopships, epidemic tuberculosis rarely occurred.55 Most soldiers were already carrying quiescent tubercule bacilli, especially those from urban Europe.

World War 1 caused a huge increase in tuberculosis mortality in civilians, particularly those in Eastern Europe. Probably as a result of starvation due to wartime shortages and blockades, many civilians developed active tuberculosis from a previously controlled infection; a large proportion died because no effective chemotherapy was available.58 Tuberculosis was a great military problem only after the war. It was generally accepted as a war-related disease for veterans pension and compensation purposes.10 Because seriously wounded soldiers often did not survive to be repatriated, medical illnesses, especially tuberculosis, rapidly became the main reason for veterans to apply for financial support from governments (figure 4). By World War 2, tuberculosis was the largest single expense for Canadas veterans compensation programme, which was typical of programmes in other Allied countries.59 Although some veterans who developed active tuberculosis between the world wars died of their disease, many survived until effective chemotherapy became generally available in the 1950s.57 Whether they would have developed active tuberculosis had they not been soldiers during World War 1 is unknown.60

Figure 4

Poster soliciting funds for French World War 1 veterans with tuberculosis by Abel Faivre, circa 1919

US National Library of Medicine A026647.

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Sexual transmitted infections

“To many the venereal situation looks dark and hopeless. It is not.”

William Osler61

Sexually transmitted infections (STIs) were of great military importance because of the vast numbers of soldiers who were removed from active service for extended periods (6 weeks) in the preantibiotic era.4 For example, in the US army during the 21 months of the war that they were involved in, 6·8 million man days were lost due to STIs, and more than 10% of all disease admissions were for STIs.62 STIs were concentrated away from the fighting; at its peak in August, 1918, the rate of STIs in the US army in the USA (272 infections per 1000 soldiers) was more than 14 times that in the US army in Europe (19 infections per 1000 soldiers).9 Gonorrhoea was the most common infection (66%), followed by syphilis (24%) and chancroids (6%). However, these statistics are at best an approximation—punitive measures ranging from loss of pay and leave to confinement in prison-like conditions were often used, thus providing tangible incentives to conceal infections.18

Treatment in the absence of antibiotics was crude.4 Gonorrhoea was treated acutely in hospital with 6 weeks of urethral irrigation with potassium permanganate twice daily followed by dilation and prostatic massage for chronic cases (figure 5).4 Patients with syphilis were given intravenous injections of arsenic (salvarsan) or mercury, or both, for 50 days. Adverse events were severe, and a treatment-related mortality of less than one per 1000 soldiers was deemed a success.4, 5 An epidemic of acute yellow atrophy of the liver in a hospital led to the appointment of a special medical research committee of salvarsan and its substitutes, who concluded that efforts to shorten the treatment regimen had resulted in toxic effects.4 An iatrogenic malaria epidemic resulting from contaminated intravenous equipment killed eight soldiers being treated for syphilis.4 Although attempts were made to determine how many syphilitic soldiers relapsed after treatment in military hospitals after demobilisation, there was little confidence that the 1% relapse rate was accurate.

Figure 5

Irrigation arrangements for treatment of gonorrhoea at No 9 Stationary Hospital, circa 1917

From Medical Services Diseases of the War.4

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Stopping of pay, restriction of leave, and antiseptic solutions were the basis of prevention and treatment. Individuals were issued with bottles of permanganate and tubes of calomel (mercury compound) for immediate use after sexual contact.4 Disinfection stations with trained attendants seemed more successful than was depending on the soldier to apply solutions.18 Regimens at disinfection stations varied, but included washes with soap and water, mercury perchloride, and urethral injections of a silver antiseptic. Hundreds of thousands of treatments were given at these disinfection stations, but how this procedure affected the number of soldiers accessing the services of sex workers or the rate of STIs is unclear.18 Until antibiotics and non-punitive prevention arrived during World War 2, little progress was made with the treatment of STIs.

Influenza

“I shall never forget the sight of the mortuary tents. There were rows of corpses, absolutely rows of them, hundreds of them, dying from something quite different. It was a ghastly sight, to see them lying there dead of something I didnt have the treatment for.”

Geoffrey Keynes63

The single greatest human mortality event ever was the influenza pandemic of 1918–19, which killed an estimated 50 million people globally—more than died during World War 1.64 Although heralded by a wave of influenza-like illness in early 1918, the pandemic arrived suddenly, starting in port cities and rapidly moving to the front line through the railroad lines of communication in September. It peaked in October, and then started to wane around the armistice in November, 1918.64, 65 In retrospect, astute clinicians stated that this fulminating respiratory infection leading to secondary bacterial pneumonia had been reported during the winter of 1916–17, when it was called purulent bronchitis.66, 67, 68

Massive amounts of epidemiological data were gathered in 1918, and published within a year.19, 69 Many facets of the pandemic remain unexplained despite the molecular resurrection of the causative influenza A H1N1 virus from US army archived autopsy specimens.70 Why did the 1918 pandemic severely affect military-aged adults (20–40 years) with a particular peak at age 28 years?71 Why could apparently identical army units or naval ships have ten-times differences in mortality?72, 73, 74 What was the protective factor that soldiers acquired within their first year in the military, which meant that new recruits were particularly at risk of death?20, 75 The 2009 pandemic was caused by a closely related influenza virus, suggesting that prediction of future pandemics will be difficult to understand until what happened in 1918 is elucidated.71, 76, 77

Despite the suddenness of the pandemic, heroic research was done to define the causative agent.3, 8, 78, 79, 80 Viruses were as yet undefined, but many bacterial cultures were done, which showed the importance of secondary bacterial pneumonias.20, 81 The Medical Research Council formed another committee and gathered the existing data for influenza, a respiratory infection that previously had not been deemed important enough to be reported separately.69 Case series promoting various treatments were published very quickly,19, 78, 80 but thereafter the awful experiences, such as those described in the Keynes quote, largely seemed to be forgotten (figure 6).82, 83

Figure 6

The Interior of a Hospital Tent, a watercolour by John Singer Sargent, painted while the artist recovered from pandemic influenza in France circa late September, 1918

Imperial War Museum ART 1611.

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The 1918–19 influenza pandemic seemed to be largely ignored until the 21st century, because it represented a throwback to a previous era when epidemic infectious diseases had no known causes or specific treatments.83 It was as if one of the old plagues had returned. Even though more than 5000 British soldiers died from influenza in France, the official casualty statistics did not note this mortality and stated that “little needed to be said about this disease”.10 Three-quarters of US navy deaths during World War 1 were due to influenza.73, 84 Some have suggested that the collective sense of failure induced by the overwhelming casualties made medical officers put influenza out of their minds and memories.82, 83 Perhaps physicians were anticipating another massive mortality wave, which never arrived.

Conclusion

Attitudes evolve with time on the basis of education and experience. Historical reviews serve as a reminder of how differently infectious diseases were perceived a century ago. Vaccines were a pasteurian notion, consisting of the growth, killing, and injection of microorganisms and then waiting hopefully for the desired effect.8, 26 This ad-hoc approach successfully reduced deaths from typhoid, but did not stop the outbreak of pandemic influenza in soldiers recently arrived to the UK from New Zealand because the supposed influenza vaccines given were of so-called mixed respiratory bacteria; the influenza virus was not identified until after the war.8, 23, 80 Borrowing animal immunity by injecting millions of ampules of horse serum was used for tetanus but whether the improved results were from the antitoxin or better surgical techniques to eliminate dead tissue depends on which data are used.39 Malaria was known to be a blood parasite diagnosed by blood smear, but the only drug available was quinine.6, 12 Tuberculosis was a great killer of young adults that was best avoided. So too were STIs, but evasion was dependent on coercion of soldiers not to have sex.4, 16 The great influenza pandemic of 1918–19 was as graphic an example imaginable that scientific medicine had no answer for some infectious diseases. Prisoners of war could be used in lethal clinical investigations, and confinement of thousands of men for enforced drug therapy was accepted practice.40, 50

During the past 100 years, attitudes towards infectious diseases have changed.85 Typhoid is now a disease associated with poor sanitation that mainly occurs in developing countries and rarely occurs in Europe or the USA. Tetanus toxoid immunisations have eliminated tetanus from places with even a rudimentary health system. Malaria elimination is back on the international health agenda, but whether the drugs and insecticides developed since World War 1 will be adequate to the task remains to be established.86 Much of the current epidemic of tuberculosis is driven by immunocompromised people with HIV infection,87 a virus largely transmitted sexually, that no one had even imagined in 1918. Antibiotics treat most other STIs, despite growing resistance. Although the 2009 influenza pandemic was caused by a virus similar enough to the 1918 causative organism to induce cross-immunity by vaccination, mortality in 2009 was subdued, and people more than 60 years of age were apparently protected by previous exposures.76, 76

Many of these positive historical changes were initially possible because the military catalysed medical research. Controlled clinical trials became the accepted means to assess new vaccines and antimicrobial drugs. A creative burst of antibiotic drug discovery and development was initiated by the requirements of World War 2 but then terminated by the absence of commercial incentive to develop further antibiotics for a world no longer in fear of pyogenic infections, particularly those transmitted sexually.88 Influenza vaccines were initially developed because of the need to control respiratory disease epidemics in military recruit camps.20 Antimalarial drug discovery and development were largely sponsored by the military: the public had little interest in diseases of developing countries and the need to keep soldiers healthy in endemic areas of the tropics.

But it would be inaccurate to present this situation as continual progressive improvement. Funding for medical research goes through boom–bust cycles as a result of short political attention spans often focused only in times of armed conflict. Evolution of microbial drug resistance is clearly a growing threat, as the worlds antibiotic inheritance is dissipated by over-use.88 Untreatable gonorrhoea, tuberculosis, influenza, and perhaps even falciparum malaria are not just potential worst-case scenarios but rapidly evolving clinical problems. What the medical officers of World War 1 were able to achieve with few resources other than their ability to think should command respect. To avoid experiencing the same helplessness that they felt in 1918 in the face of untreatable infectious diseases, more attention should be paid to the evolution of drug-resistant organisms and the pressing need to develop new antimicrobial drugs.

Search strategy and selection criteria

The search for historical information concerning infectious diseases of World War 1 was done using libraries at Oxford University, UK and The Wellcome Library, UK, and intra-library loans from various Australian university libraries. The Official War Histories of the United Kingdom and the United States were the starting point following with their various bibliographies. The criteria used for selection was to locate illustrative examples of infectious diseases across a broad spectrum of clinical success and failure as perceived by medical officers of the Great War. Although some French and German sources were consulted, the search was largely limited to English language sources January, 1897 to December, 2013. The author admits that the sources used are incomplete due to the mass of material available and the physical need to consult original printed reports.

Declaration of interests

I declare no competing interests.

Acknowledgments

The Australian Defence Force and the Global Emerging Infections Surveillance and Response System (GEIS) at the Armed Forces Health Surveillance Center of the US Department of Defense provided support for this project. I thank Peter Dennis at the University of New South Wales for assistance with military history, Ian Howie-Willis for commenting on an early version of the paper, and Odette Hopwood and other medical librarians at Australian Defence Force Library Services, Gallipoli Barracks, for help in locating references. The opinions expressed are my own, and do not necessarily reflect those of the Australian Defence Force or the US Department of Defense.

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