History of Medicine

DANGER IN THE BITTERROOT VALLEY:

EARLY STRUGGLES WITH SPOTTED FEVER

     One of America’s most idyllic spots, the Bitterroot Valley, nestled between two mountain ranges in southwest Montana, seemed a healthy place. Lewis and Clark, passing through the Valley, and native-American peoples living there did not

Bitterroot Valley today (Wikipedia)

manifest unusual illness. After the Civil War settlers moved in, felling thousands of trees in the western side of the Valley to feed a burgeoning lumber industry. Scrub vegetation, populated with small mammals, replaced the trees. By the 1880s scattered cases of a “spotted fever” were reported, usually fatal, most coming from the west side of the Valley, and most showing recent tick bites. Between 1895 and 1902 64 people died out of 88 with the disease.    

     In 1902 two investigators from the University of Minnesota, Louis Wilson and William Chowning, suggested the wood tick as a vector and found organisms in the blood of victims they believed were a type of Pyroplasma, similar to that causing Texas cattle fever, another tick-transmitted disease. The notion of insects transmitting disease was popular. In the previous 25 years mosquito transmission of filaria, malaria, and yellow fever, and tick transmission of Texas cattle fever had all been discovered.

     Getting rid of ticks, though, by burning brush and killing animal hosts didn’t reduce the disease incidence. Other

Howard Ricketts,
martyr to typhus (Wikipedia)

investigators cast doubt on the tick theory, adding confusion, until the arrival of Howard Ricketts and William King. They were able in 1906 to infect guinea pigs and to prove that ticks transmitted the disease. Ricketts also thought he saw tiny microorganisms he believed were the disease agents but could not culture them. Stymied by an interruption of funding, Ricketts left for Mexico to study typhus (another spotted fever). He perished in Mexico, tragically, from that very disease.

     Ricketts had recommended learning more about wood tick habits, enticing Robert Cooley, Montana State entomologist, to step in. Cooley employed Willard King and Clarence Birdseye (who later founded the frozen food industry), both field biologists, to collect ticks and wild animals for study. The work was hazardous. Their lab was set up in an old two-room log cabin in which one man had died of

Cabin and tent of Cooley's team, Bitterroot Valley
(National Library of Medicine)

spotted fever. The yard, full of ticks, was burned, then sprayed with kerosene (a tick repellant), and the team slept in tents around the cabin. As they worked collecting animals and ticks they wore high shoes, with tight kerosene-soaked khaki leggings above them, and doused their outer clothing with kerosene. They stripped and inspected each other for ticks every two hours. Somehow they remained healthy.

     The team demonstrated a 2-year cycle from egg to adult tick and showed that adults fed primarily on large domesticated animals. As a result dipping centers were set up to “de-tick” farm and domestic animals. But, related to poor dipping agents and bureaucratic infighting, the program foundered and spotted fever (now called Rocky Mountain spotted fever) claimed more victims.

     What about the supposed causative agent, Pyroplasma? No one else could find it. S. Burt Wolbach, a young Harvard pathologist, saw tiny intracellular organisms, particularly in vascular endothelial cells, that he could not grow and which he named Dermatocentroxenus rickettsii, in honor of Ricketts (later renamed Rickettsia rickettsii). They were a new type of organism that grew only in cells, the details of which had to await further developments in technology.

     In the era before antibiotics the main strategy against infectious diseases was vaccination, and so it was with the spotted fever.

Roscoe Spencer (National Library
of Medicine)

Roscoe Spencer, a US Public Health Service physician, and Ralph Parker, a Montana entomologist, working in an abandoned two-story brick schoolhouse in Hamilton (in the Valley) in the 1920s, discovered that injecting material into guinea pigs from ground-up infected ticks, sterilized with formalin and phenol, could produce an imperfect but substantial immunity. Spencer developed this into a commercial vaccine.

     Vaccine production was a cumbersome process. Each year’s supply required collection of 30-40,000 adult ticks to feed on 4 to 6,000 rabbits and 20-30,000 guinea pigs. The adult ticks were fed on rabbits, then collected for egg laying. The hatched larvae were fed on newly infected rabbits, dropped off, and molted into nymphs. The nymphs fed on more rabbits (400/rabbit), were

Brick schoolhouse where original vaccine work
was done (National Library of Medicine)

collected, dried with hair dryers, and kept at 22 degrees C to molt into adults. The adults were stored at near freezing levels for 6-12 months (to enhance vaccine efficiency), after which they were warmed up and fed on guinea pigs. Swollen with blood, they were emulsified in a Waring blender with formalin, phenol, and saline. Finally, after storage, further dilution, and purification, the vaccine was ready, and was accepted by residents.

      The toll was heavy. In the process three laboratory workers died of spotted fever. Others, including Spencer, Parker, and a third all developed tularemia, a tick-born disease originally discovered in Tulare County, California (they survived). Spencer, depressed, was transferred back east. The head of the tick-rearing room resigned, and Parker carried on as chief in a new, safer laboratory building.

     The tick-based vaccine continued to be produced by the Rocky Mountain laboratory until 1948 when it was replaced by an egg yolk-derived vaccine and the advent of antibiotics. There is no vaccine available today. The laboratory continues as a part of the National Institute of Allergy and Infectious Diseases/NIH.

     Once considered a localized disease, Rocky Mountain spotted fever has been found throughout much of the U.S., primarily in the central eastern and mid-western states. Its history could be said to have had a “rocky” beginning, with false starts and at least three martyrs.

SOURCES:

Harden, Victoria. Rocky Mountain Spotted Fever: History of a Twentieth Century Disease. 1990; J Hopkins Univ. Press.

Price, Ester. Fighting Spotted Fever in the Rockies. 1948; Naegele Printing Co. Helena.

Ricketts, H. “The Transmission of Rocky Mountain Spotted Fever by the bite of the Wood Tick (Dermacentor occidentalis). 1906; JAMA 47: 358.

Spencer, R and Parker, R. “Rocky Mountain Spotted Fever: Vaccination of Monkeys and Man. 1925; Public Health Reps 41: 2159-67.

Wolbach, S B. “Studies on Rocky Mountain Spotted Fever”. 1919; J Med Research 41:3.