Minnesota Medicine

Published monthly by the Minnesota Medical Association
February 2002/Volume 85

The History of Immunization in the U.S. Armed Forces

For centuries, the U.S. military has led the charge against infectious disease.
 

By Ronald R. Blanck, D.O.

The U.S. Army Medical Department has had a long history of developing vaccines and using immunization practices to protect armed forces personnel. With today’s heightened threats of bioterrorism, once again military medical researchers are at the forefront of the battle. 

Conquering Smallpox

The history begins with smallpox, a formidable and widespread illness for centuries until it was eradicated in 1979 by a worldwide World Health Organization immunization program. During the American rebellion, which turned to revolution on Breed’s Hill in Boston in 1775, smallpox was an almost universal accompaniment of war. Even then, there was a preventive measure, which involved an inoculation method called variolation—applying live smallpox to the skin to induce immunity. It produced a rather painful lesion and blisters. This practice was introduced in England in 1719 and was usually done in the face of an epidemic because widespread variolation could itself spread the disease. 

In late 1775, smallpox broke out after the Americans attacked Quebec in an attempt to bring French inhabitants to the American side, and the American forces were decimated. John Morgan, director general of the Army Hospital, had recommended inoculation to Gen. Washington, as did his successor, William Shipper. Fearing the inoculation could also cause an epidemic outbreak, Washington was reluctant to initiate such drastic, untested measures. At Morristown in January 1777, Washington finally conceded, noting: “Should the disorder infect the Army in a natural way and rage with its usual virulence, we should have more to dread from it than from the sword of the enemy.” Washington ordered his troops to be inoculated. 

Thus, the American Army was the first army in the world to be immunized, and the effort was successful. The sick rate fell, and the death rate from smallpox dropped from 16 percent to 0.33 percent.

The next advance in smallpox prevention came when the English physician Edward Jenner noted that milkmaids who got cowpox did not get smallpox. In 1798, he published experimental data that led to the use of his cowpox vaccine. After some early resistance the vaccine was accepted in the United States. In 1812 the Army mandated cowpox vaccination for its personnel, and in 1848 the Navy did the same.

Typhoid Troubles

In 1898, the battleship Maine blew up in the Havana Harbor, leading to the Spanish-American War. Volunteer soldiers, their officers, and physicians marched to the recruit camps, where they began to get sick and die by the thousands. The diagnosis was unclear: typhoid, typho-malaria fever, and typhus were all considered.

Army Surgeon General George Miller Sternberg appointed a board of officers, led by Maj.Walter Reed, to examine the problem. Reed and Victor Vaughn, an epidemiologist and physiologist from the University of Michigan Medical School, produced a model of epidemiological investigation. They constructed maps showing improper siting of latrines and kitchens, and their inspection documented poor sanitation. Spot maps showed that the cases were clustered by unit, which confirmed that the disease was caused by local contamination. By epidemiological study, they were able to rule out typhus, demonstrate the difference between typhoid fever and malaria, and prove that the disease typho-malaria did not exist. Typhoid was the problem.

Based on their study and the work of the Dodge Commission (which was formed after the war to examine the performance of the Army and Navy), courses in sanitation and hygiene began to be taught in military schools.

Even before the Spanish-American War, the new science of bacteriology was marching on. In Paris in 1898, Fernand Widal showed that the serum from a recovered patient would cause typhoid bacteria to clump. From that came the Widal test, the first serodiagnosis.

In Germany in 1896, Richard Pfeiffer demonstrated that cholera bacilli would agglutinate in vivo as well as in guinea pig peritoneum, which suggested to him and Elmo Wright in England that perhaps dead bacilli could produce an antibody response. This understanding led, in 1896, to the development of a typhoid vaccine, which was used by the British during the Boer War. Lt. Col. William Leishman of England continued this research, developing standard methods of production and performing statistically sound epidemiological studies, which by 1908 showed that two shots of typhoid vaccine gave excellent protection.

In 1908, U.S. Army Surgeon General Robert O’Reilly decided that the U.S. Army needed to study Leishman’s vaccine. He sent Capt. Frederick Russell to England to study with Leishman and then to learn Pfeiffer’s methodology in Germany. Russell returned to the Army Medical School laboratories in Washington, D.C., and began to make vaccines with the combination of German and English methods.

In 1911, Army Chief of Staff Maj. Gen. Leonard Wood (who began his army career as a medical officer) ordered that the Army be immunized and that the immunizations be recorded. So from 1911 on, the Army and Navy personnel were immunized against typhoid fever. This made a critical difference in the health of the military personnel. The high rates of morbidity and mortality during the Spanish-American War in 1898 (from typhoid) faded to essentially nothing by World War I.

Yellow Fever Vaccine and Hepatitis B

During the Spanish-American War, yellow fever was also a significant problem for U.S. troops in Cuba. Army Surgeon General Sternberg appointed another board of investigation, and Walter Reed and his colleagues proved Carlos Finlay’s hypothesis of transmission of the disease by mosquito. The follow-up research was done by the newly established Rockefeller Institute, which established a laboratory in Nigeria. There, in 1927, a virus was isolated from a young Nigerian and was attenuated by serial cell culture passage by Max Thieler. The resulting 17-D vaccine became the yellow fever vaccine, which is still used today.

When the United States went to war in December 1941, we knew that yellow fever was a possible biologic weapon, so a yellow fever immunization program was instituted for the U.S. armed forces. By April 1942, seven million doses of the vaccine had been given. But worldwide reports of hepatitis began to come in. Now known to be hepatitis B, the disease outbreak then was thought to be caused by the yellow fever vaccine. This vaccine used human serum in the cell culture manufacturing process, so immunization was stopped and a serum-free vaccine was developed. The epidemic was over by December 1942, but not without some 50,000 cases of hepatitis B and 84 deaths, showing the potential risks involved in inoculating large populations with previously untested vaccines.

Battles Recently Won

Two vaccines of note were developed in the 1970s at the Walter Reed Army Institute of Research, the descendant of the Army Medical School. The first vaccine was developed to deal with acute respiratory disease in recruits. The cause originally was discovered by Maurice Hilleman at the Walter Reed Army Institute of Research. In 1956, he reported the cause of what was then called respiratory infection—a virus isolated from the throat washing of sick recruits.

This virus, hidden in pharyngeal tissue, was named adenovirus. Hilleman developed a bivalent killed vaccine in 1957 for adenovirus types 4 and 7. It worked well but was withdrawn in 1963 when it was shown that the monkey kidney cells in which it was grown had oncogenic simian virus contamination. So Col. Edward Buescher and his colleagues, including Major Franklin Top, perfected an oral bivalent vaccine, which effectively protected U.S. soldiers. With this vaccine, recruits did not get sick, training cycles were not interrupted, and hospitalizations decreased. The armed forces realized a savings of $7.53 million, which more than offset the five-year cost of research, surveillance, and operations, which amounted to $4.83 million.

Next, researchers at the Walter Reed Army Institute of Research looked at meningococcal meningitis—a low-incident, high-mortality disease—which nevertheless occurred with disturbing frequency in military recruits. Antibiotic prophylaxis was used, but the organism became increasingly drug resistant, which led Malcolm Artenstein at the Walter Reed Army Institute of Research to look into the possibility of a vaccine. 

Two young physicians, Capts. Irving Goldschneider and Emil Gotschlich, joined Artenstein in 1967. In 1969, they published five papers defining the humoral responses to the meningococcal organism. Artenstein and his colleagues made a very important new contribution to vaccine development—that of a subunit vaccine—which was not dependent on killed or living organisms or a toxoid. This vaccine protected against meningococcal type C disease and also reduced the carrier rate.

Later refinements added types A,Y and W-135 to make it a quadrivalent vaccine that could attack the organism in four different ways. This work led directly to other subunit vaccines, such as the one for pneumonia, developed at the National Institutes of Health. Cols. Buescher and Artenstein, while working on the surveillance studies for the adenovirus and the meningococcal vaccines with Capt. Paul Parkman, isolated the rubella virus from a recruit at Fort Dix. Parkman and Harry Meyers at the National Institutes of Health used it to make the present-day rubella vaccine. 

Anthrax Anxieties

The anthrax vaccine has been, of course, recently in the news because of the military immunization program but also because of the recent mailings of the anthrax organism. The first anthrax vaccine was developed by Louis Pasteur in 1881. This vaccine was a living, attenuated vaccine similar to that for yellow fever and poliomyelitis. During World War II, when anthrax was considered a serious biologic warfare threat, the need for a better vaccine was established. The U. S. Army laboratories at Fort Dietrick produced a human vaccine in 1955, which was tested by the Public Health Service Centers for Disease Control in 1962 and was found to be both safe and effective. The vaccine was approved by the FDA in 1970 and has been used by several hundred ranchers, research workers, and veterinarians every year.

During the Gulf War, the United States had intelligence data that Iraq had processed anthrax bacteria and botulinum toxin for use as weapons. The United States immunized some of our forces in the Gulf with the limited amount of vaccine available. Postwar inspection verified that Iraq did have a substantial biological warfare capability. In 1997, the joint chiefs of staff and Secretary of Defense William Cohen decided that the threat of anthrax was sufficient to begin immunizing the U. S. military forces. The immunization program began in 1998. 

Since then, more than 400,000 military personnel have received more than 1.4 million doses of vaccine. Objective side effects have included redness and swelling at the site of injection as well as fever. Subjective reactions reported included headache, myalgias, and fatigue. Hospitalizations and lost duty time greater than 24 hours following the immunization occurred in fewer than 1,000 individuals as of the end of 2001.These adverse effects were reviewed by a civilian committee from Health and Human Services, which concluded the vaccine was safe. Nevertheless, the vaccine program was controversial, and approximately 400 military personnel resigned rather than be immunized.

The anthrax vaccine controversy has diminished since the mailing of anthrax-laden letters. The immunization program, although limited because of vaccine supply, continues. The anthrax vaccine now joins the list of many other vaccines that have kept U.S. troops in fighting form. 

The U.S. Army Medical Department continues to protect today’s military from disease. Its immunization programs are but a few examples of public health measures developed or used by the military. From water purification to sanitation and vaccine development and use, military medicine has influenced the health of this nation and the world. 

Ronald Blanck, D.O., is the president of the University of North Texas Health Science Center at Fort Worth and a retired lieutenant general in the U.S. Army Medical Corps. He served as surgeon general for the U.S. Army from 1996 through 2000.