MEASLES VACCINATION:
OLD AND NEW
In 1824, King Kamehameha II of Hawaii and his queen embarked on a near-six-month journey to England. The British host arrangements included a visit to the Royal Military Asylum, a home for orphans of fallen soldiers known for outbreaks of contagious
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| Kamehamaha II (Wikipedia) |
diseases. Several days later, measles struck he entire Hawaiian royal party and, despite efforts of London’s leading physicians, the king and queen succumbed to the disease. Twenty-four years later, a measles epidemic swept away an estimated 10% to 30% of the population in their home country.
A similar outbreak devastated the Fiji Islands in 1874, after the return of a royal visit to Australia. And measles, along with smallpox, were the principal diseases that devastated the native populations of the New World after the arrival of the Spanish in the 16th century.
Europe was not spared. The measles death rate in Edinburgh of the mid-18th century was about 10% and in Glasgow it ranged from about 4% to 20%. Young children faced the highest mortality rates. Americans suffered equally. The Fairfield, New Jersey, farmer, Ephraim Harris, wrote, “That fatal and never-to-be-forgotten year, 1759, when the Lord sent the destroying angel to pass through this place, and removed many of our friends into eternity in a short space of time; not a house exempt, not a family spared from the calamity. So dreadful was it, that it made every ear tingle, every heart bleed; in which time I and my family was exercised with that dreadful disorder, the measles.”
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| Child with measles (CDC Public Health Image Library) |
During WWI, the military assembled thousands of recruits from all over America in training camps, where measles circulated freely among the many unexposed recruits. The lungs are a target in measles, and combined with spreading streptococcal infections (the cause of “strep throat”), widespread pneumonia claimed the lives of over 3200 young soldiers.
Scientific study of measles began in the nineteenth century. During an epidemic in the 1840s in the Faroe Islands, 26-year-old Dr. Peter Panum, sent by the Danish government, investigated the scattered, chronically undernourished population. He determined the incubation period, documented the rapid transmission of infection, and noted that all ages up to age 65 were susceptible. Older residents were still immune after surviving a 1781 epidemic.
The long-lasting immunity after measles stimulated attempts at deliberate immunization. Adopting a procedure known as variolation, introduced into England in the early 1700s to prevent smallpox, in
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| francis Home (Wikipedia) |
1758 a Scottish physician, Dr. Frances Home, took a small amount of blood from a measles patient during the early stage of rash and placed it in a small cut in the arm of another child, producing a mild case of measles. Using similar techniques in subsequent years, several trials, large and small, induced generally mild disease in young children after injecting blood, serum, or oral secretions. The largest trial, in Hungary, in 1841, involved 1122 children and claimed a 79% success rate preventing measles. Administering immune serum to exposed children was also tried.
But measles persisted, and the investigators were operating in the dark. The trials lacked control groups to assess rates of naturally acquired infection, lacked ability to measure the immune status of mothers or children, and had no method to titrate the inoculum. No one had isolated the virus, and parents were reluctant to infect their children with a potentially dangerous agent.
Scientific progress eventually filled the voids. Techniques for culturing virus in eggs, chick embryos, and eventually in tissue culture had advanced quickly. In the laboratory of John Enders,
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| John Enders (Wikipedia) |
recipient of the 1954 Nobel Prize (with Thomas Weller and Frederick Robbins) for growing polio virus in tissue culture, Thomas Peebles grew measles virus in human kidney cells. The blood of an eleven-year-old boarding school student with measles, David Edmonston, provided the “Edmonston strain” of virus from which the first modern measles vaccine emerged. After multiple passages in human and animal cells to weaken the virus and extensive testing, it was released for use in 1963, along with a killed vaccine made from the same strain. However, the killed vaccine was later withdrawn because of a short-lived immune response, and the live vaccine frequently evoked a fever over 103 degrees. There was room for improvement.
Maurice Hillerman, a scientist at Merk Laboratories, stepped in. Obtaining samples from Enders’ lab, he passed the virus forty more times through chick embryo cells, using virus-free chickens he raised on Merk property (chicken leukemia virus had unknowingly contaminated the eggs in Enders’ lab, though it proved to be
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| Maurice Hilleman (Wikipedia) |
harmless). The resulting vaccine, released in 1968, had few side effects and is the one in use today. Hillerman, raised on a Montana farm, worked at Merk for years and, in addition to measles, created the current mumps vaccine, two Hepatitis B vaccines, vaccines for hepatitis A, rubella, chickenpox, meningococcus, pneumococcus, Japanese encephalitis, the 1957 flu vaccine, and the MMR combination. He discovered the SV40 monkey virus that induced cancer when injected into rodents, a finding that drove future vaccines to be derived from virus-free fetal cells rather than animal tissue. His work has saved millions of lives. Though the recipient of many awards, he never received a Nobel Prize.
According to the CDC, in the decade before the first measles vaccine there were an estimated 3 to 4 million cases of measles in the U.S. annually. Of the reported cases each year, approximately 400-500 people died, 48,000 were hospitalized, and 1800 suffered from encephalitis (brain infection). After introduction of the measles vaccines and the addition of a booster dose, the incidence fell drastically, both in the U.S. and abroad. Eventually, measles elimination became a realistic goal, since there is no animal reservoir.
In recent times that goal is proving elusive, though still achievable. Meanwhile, much of the world is, thankfully, measles-free.
SOURCES:
Berche, P, “History of Measles.” Presse Med 2022; 51 (3), September, special issue. Available at: https://www.sciencedirect.com/science/article/pii/S0755498222000422?via=ihubP
Duffy, J, Epidemics in Colonial America. 1972 (2nd ed.) Kennikat Press, pp 164-79.
Plotkin, S A, “Vaccination against Measles in the 18th Century.” Clin Pediatrics 1967; 6 (5): 312-15.
Enders, J F, “Francis Home and his Experimental Approach to Medicine.” Bull Hist Med 1964; 38 (2):101-112.
Morens, D M, Taubenberger, J K, “A Forgotten Epidemic that Changed Medicine: Measles in the U S Army, 191-18.” Lancet Infect Dis 2015; 15 (7): 852-861.
Shulman, S, et al, “The Tragic 1824 Journey of the Hawaiian King and Queen to London.” Pediatric Infect Dis J 2009; 28 (8): 728-33.
Offitt, P A, Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases. 2007; Smithsonian Books, Harper Collins.
CDC website: “History of Measles.” Available at: https://www.cdc.gov/measles/about/history.html
Baker, J P, “The First Measles Vaccine.” Pediatrics 2011; 128 (3): 435-7.
Tulchinsky, T H, “Maurice Hilleman: Creator of Vaccines that Changed the World.” Case Studies in Public Health, 2018; Academic Press, pp 443-470. Available at: https://www.sciencedirect.com/science/article/pii/B9780128045718000032?via=ihub
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