When people write about the Spanish Influenza pandemic of 1918-19, they usually start with the staggering global death toll, the immense number of people infected with the virus, and the medical field's inability to do much to help the afflicted. While those factors were hallmarks of the devastating episode, researchers and health workers in the United States and Europe were confidently devising vaccines and immunizing hundreds of thousands of people. This amounted to a medical experiment on a grand scale. What were the vaccines they developed? Did they do anything to protect the immunized and halt the spread of the disease?
First, the numbers. In 1918, the U.S. population was 103.2 million. During the three waves of the Spanish Influenza pandemic between spring 1918 and spring 1919, about 200 of every 1,000 people contracted influenza (approximately 20.6 million). Between 0.8% (164,800) and 3.1% (638,000) of those infected died from influenza or secondary pneumonia.
A few vaccines to prevent other diseases were available at the time—smallpox vaccine had, of course, been used for more than 100 years; Louis Pasteur had developed a rabies vaccine for post-exposure prophylaxis; and typhoid fever vaccines had been developed. Diphtheria antitoxin—a medication made from the blood of previously infected animals—had been used for treatment since the late 1800s, an early form of a diphtheria vaccine had been used, and experimental cholera vaccines had been developed. Almroth Wright had tested a whole-cell pneumococcal vaccine in South African gold miners in 1911. Manufacturers had also developed and sold various mixed heat-killed bacterial stock vaccines of dubious usefulness.
In terms of knowledge of influenza as an infectious disease, not much was understood at the time. Many medical professionals thought that influenza was a specific communicable disease that appeared seasonally, usually in the winter. However, without specific diagnostic tools, mild cases of influenza were difficult to distinguish from other acute respiratory illnesses. The tools of the time could detect bacteria, but not smaller pathogens.
Physicians and scientists struggled to understand whether the annual influenza to which they were accustomed was related to the occasional widespread and highly epidemic illness that we now know were pandemic influenza events (such as those in 1848-49 and 1889-90).
German scientist Richard Pfeiffer (1858-1945) claimed to have identified the causative agent of influenza in a publication in 1892. He described rod-shaped bacilli present in every case of influenza he examined but was unable to demonstrate Koch's postulates by causing the illness in experimental animals. Many professionals accepted his findings and believed Pfeiffer's influenza bacillus, as it was called, was responsible for seasonal influenza.
However, as the 1910s progressed and bacteriological methods matured, other researchers presented results that conflicted with Pfeiffer's findings. They found his organism in healthy individuals and in those suffering from illnesses that clearly were not influenza. Additionally, they looked for Pfeiffer's bacillus in influenza cases and often did not find it at all. Though many physicians still believed that Pfeiffer had correctly identified the culprit, a growing number of others had begun to doubt his findings.
Those true believers had some reason to be hopeful that a vaccine could prevent influenza, as the disease began its second appearance in the United States in early fall 1918. By October 2, 1918, William H. Park, MD, head bacteriologist of the New York City Health Department, was working on a Pfeiffer’s bacillus influenza vaccine. The New York Times reported that Royal S. Copeland, Health Commissioner of New York City, described the vaccine as an influenza preventive and an “application of an old idea to a new disease.” Park was making his vaccine from heat-killed Pfeiffer's bacilli isolated from ill individuals and testing it on volunteers from the Health Department staff (New York Times, October 2, 1918). Three doses were given 48 hours apart. By October 12, he wrote in the New York Medical Journal that he was vaccinating employees from large companies and soldiers in army camps. He hoped to have evidence demonstrating the effectiveness of the vaccine in a few weeks (Park WH, 1918).
In November, the Newark Evening News reported that 39,000 doses of Leary-Park influenza vaccine had been prepared, and that most doses were used. Though it was too soon to tell if the vaccine was effective, “…the average person need have no fear of the results of the vaccine. Neurotic and rheumatic individuals, however, appear to be sensitive to the vaccine, while children take it with less disturbance than adults” (Newark Evening News, 1918).
By December 13, 1918, Copeland was no longer confident about his department's vaccine. He told the Times that vaccines made from Pfeiffer’s bacilli appeared to have no effect on influenza prevention. Instead, he was confident that a mixed bacterial vaccine (streptococcal, pneumococcal, staphylococcal, and Pfeiffer's bacilli) developed by E.C. Rosenow at the Mayo Foundation was an effective preventive. He mentioned that he would have Park prepare some Rosenow vaccines to immunize people in New York throughout the winter (New York Times, December 13, 1918). More than 500,000 doses of Rosenow vaccine were produced (Eyler, 2009).
Universities such as the University of Pittsburgh and Tulane University, as well as private physicians, were making their own vaccines. Convalescent serum was also used (Boston Post, January 6, 1919; Robertson & Koehler, 1918). The Deseret Evening News noted on December 14, 1918, that free vaccine was available in communities around the state.
Based on a survey of newspaper and medical journal articles from the time, it is clear that many hundreds of thousands, if not a million or more, doses of vaccines were produced during the pandemic years.
The Editorial Committee of the American Journal of Public Health tried to temper expectations about the vaccines. In January 1919, they wrote that the causative organism of the current influenza was still unknown, and therefore, the vaccines being produced had only a chance of targeting the right pathogen. They noted that vaccines for secondary infections made some sense but that all vaccines being produced must be viewed as experimental. They urged that control groups be used with all vaccines and that differences between control and experimental groups be minimized in terms of exposure risk, time of exposure during the epidemic, and other factors (Editorial Committee of the American Journal of Public Health, 1919).
Certainly, none of the vaccines described above prevented viral influenza infection—we now know that influenza is caused by a virus, and none of the vaccines protected against it. But were any of them protective against bacterial infections that developed secondary to influenza? Vaccinologist Stanley A. Plotkin, MD, thinks they were not. He told us, “The bacterial vaccines developed for Spanish influenza were probably ineffective because, at the time, it was not known that pneumococcal bacteria come in many, many serotypes and that of the bacterial group they called B. influenzae, only one type is a major pathogen.”
A 2010 article describes a meta-analysis of bacterial vaccine studies from 1918-19 and suggests a more favorable interpretation. Based on the 13 studies that met inclusion criteria, the authors conclude that some vaccines could have reduced the attack rate of pneumonia after viral influenza infection (Chien, 2010).
It was not until the 1930s that researchers established that influenza was caused by a virus, not a bacterium. Pfeiffer’s influenza bacillus would eventually be named Haemophilus influenzae, retaining the legacy of its long-standing yet inaccurate association with influenza. Today, influenza vaccines—as well as H. influenzae type b vaccines—are widely available to prevent illness.
Sources
- Cecil RL. . AJPH. 1919;9(8):593-594.
- Chien Y, Klugman KP, Morens DM. Efficacy of whole-cell killed bacterial vaccines in preventing pneumonia and death during the 1918 influenza pandemic. JID. 2010;202(11):1639-1648.
- Convalescent sera used. Boston Post. January 6, 1919.
- Editorial committee of the American Public Health Association. . AJPH. 1919;9(1)1-12.
- Eyler JM. The state of science, microbiology, and vaccines circa 1918. Public Health Reports. 2010;125(3_suppl):27-36.
- Eyler JM. The fog of research: influenza vaccine trials during the 1918–19 pandemic. Journal of the History of Medicine and Allied Sciences. 2009;64(4):401-428.
- Influenza epidemic not expected here. New York Times. December 13, 1918.
- Park WH. Bacteriology and possibility of anti influenza vaccine as a prophylactic. New York Medical Journal. 1918;108:15:621.
- Plotkin SA. Personal correspondence. November 23, 2011.
- Robertson JD, Koehler G. . AJPH. 1918;8(11)849-856.
- . Newark Evening News. November 30, 1918.
- Tells of vaccine to stop influenza. New York Times. October 2, 1918.
- Free vaccine for communities of state. Deseret Evening News. December 14, 1918.
- . Kansas City Star, September 29, 1918.