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Medical lessons from World War I underscore need to keep developing antimicrobial drugs

Wikimedia Commons/UBC Library Digital Collections
British hospital at the Western front.

World War I (1914-1918) occurred at a key transition period in the history of medicine, a time when there was a gap “between knowledge and effective action,” according to a paper published last week in the journal Lancet.

Although many physicians at the start of the war still clung to the old idea that infectious diseases were caused by “bad” air and unpleasant smells (miasma), a growing number — including William Gorgas, who served as surgeon general of the U.S. Army Surgeon General during the war — had come to accept that microorganisms were really the source of such illnesses, writes Dr. G. Dennis Shanks, an infectious-disease epidemiologist at the Australian Army Malaria Institute.

Yet although Gorgas and others knew, at least rudimentarily, what caused diseases like typhoid, tetanus and tuberculosis, their understanding was of limited use, Shanks points out. Antibiotics had not yet been developed, and vaccines were mostly crudely brewed mixtures of killed bacteria. As a result, military doctors had few effective tools on hand to fight any kind of infection.

“Controlled clinical trials had yet to be devised,” says Shanks. “Treatment was by trial and error or dictated by authority.”

Still, he adds, “medical science was progressing, and got drawn into the maelstrom of World War I. Medical laboratories … were deployed with the armies. Top research physicians joined the war as uniformed specialist consultants. … 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 Some of the interventions worked and became part of the medical armamentarium; others did not and were eventually superseded.”

Medical victories — and failures

U.S. Army Surgeon General William C. Gorgas
U.S. Army
U.S. Army Surgeon General Gorgas

In the Lancet article, Shanks focuses on six infectious diseases that were of particular concern to military medical clinicians during World War I and how attitudes toward those diseases were evolving at that time:

  • Typhoid had been a medical disaster for the U.S. Army in the Spanish-American War (1898) and for the British army in the South African Boer War (1899-1902). Typhoid vaccines were available by World War I, and the U.S. Army made getting those shots mandatory for all its enlisted soldiers. The Army’s typhoid rate fell from 142 infections per 1,000 soldiers during the Spanish-American War to less than 1 per 1,000 soldiers during World War I. Typhoid vaccination “was thought to be a genuine medical success story” of the war, says Shanks.
  • The tetanus rate among British soldiers was high on the Western Front in Belgium and France, where battle wounds became “contaminated with spores from the manured farms that were rapidly converted into trench lines,” writes Shanks. To prevent tetanus, wounded soldiers were treated with a primitive anti-toxin made from horse serum, which, unfortunately, often made soldiers sick and sometimes triggered a severe and potentially life-threatening allergic reaction (anaphylaxis). During World War I, the medical community generally believed that the horse-serum tetanus vaccines saved many lives, although some skeptics at the time (and later) pointed out that the rate of tetanus during that war was not that much different from what it had been during previous ones.
  • Malaria, which is transmitted by mosquitoes, was a problem during World War I, but only in the “minor” battle-zone areas of Palestine, Salonika (modern Greece) and Mesopotamia (modern Iraq). Soldiers who developed malaria were treated with quinine, which was extracted from the bark of a tree grown in Southeast Asia. The quinine tended only to suppress the disease, however, rather than cure it. Still, the British army considered the treatment a cure. About 20,000 British soldiers who had developed malaria in Greece or North Africa were put in special camps and forced to undergo 10 weeks of quinine treatment, after which they were sent to fight on the Western Front. Germany eventually became cut off from its supplies of quinine; it tried to develop a synthetic form of the drug, but did not achieve success until after the war was over.
  • Tuberculosis was not much of a factor among soldiers during World War I, says Shanks. Armies simply would reject any recruit infected with the disease, and TB was also one of the few medical conditions that would get a soldier discharged. A huge increase in TB-related deaths did occur during World War I, but among civilians, particularly those living in Eastern Europe.
  • Sexually transmitted infections (STIs) were a big problem for the U.S. Army and other armies during World War I because of the large number of soldiers who developed these infections and because treatment in that pre-antibiotic era required putting the soldiers on inactive duty for long stretches of time. During the 21 months that the U.S. Army fought in the war, it lost 6.8 million “man days” to STIs, Shanks reports. The typical treatment for gonorrhea was six weeks of painful, twice-daily irrigation of the urethra with potassium permanganate, a chemical antiseptic. Syphilis was treated with injections of arsenic or mercury (or both) for 50 days. Soldiers were also given bottles of permangante and tubes of a mercury compound to use immediately after sexual contact, and “disinfection stations” were set up with trained attendants to offer further treatments, including urethral injections of an antiseptic made from silver compounds. “Hundreds of thousands of treatments were given at these disinfection stations,” writes Shanks, “but how this procedure affected the number of soldiers accessing the services of sex workers or the rate of STIs is unclear. Until antibiotics and non-punitive prevention arrived during World War II, little progress was made with the treatment of STIs.”
  • The most significant infectious disease that struck during World War I was influenza. The influenza pandemic of 1918-1919 killed an estimated 50 million people worldwide — more than were killed by the war. About three-quarters of U.S. Navy deaths during World War I, for example, were due not to battle wounds, but to the influenza, Shanks points out. Influenza is a viral infection, but many of the people who died during the 1918-1919 pandemic had developed secondary bacterial pneumonias, for which there were no antibiotic treatments yet available. Despite the massive number of deaths, “medical officers put influenza out of their minds and memories” after the war. “Even though more than 5,000 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,’” writes Shanks. The pandemic was, he adds, “as graphic an example imaginable that scientific medicine had no answer for some infectious diseases.”

Continual progress is not guaranteed

Over the past 100 years we have, of course, greatly improved our knowledge — and treatment — of infectious diseases. Writes Shanks (with British spellings):

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 immunizations 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 I will be adequate to the task remains to be established. Much of the current epidemic of tuberculosis is driven by immuno-compromised people with HIV infection, 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.”

But we must not become complacent, he adds:

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 world’s antibiotic inheritance is dissipated by over-use. 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 I 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.

Shanks’ article is part of a fascinating series of articles that Lancet published Nov. 8 in a special World War I edition of the journal. You can read the article in full at the journal’s website.

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