Rocky Mountain spotted fever is a relatively severe, self-limited rickettsial infection transmitted to man by various species of hard ticks. The disease is characterized by fever, headache, bone and muscle pains, and a generalized- rash that frequently may become petechial or hemorrhagic.
The disease is caused by Rickettsia rickettsi (Dermacentroxenus rickettsi), the prototype rickettsia of the spotted fever group of organisms. These include, in addition to R. rickettsi, the agents of rickettsialpox, north Asian tick-borne rickettsiosis, and African and Queensland tick typhus, all of which are distinctive among rickettsiae in their ability to multiply in the nucleus as well as in the cytoplasm of mammalian and tick cells. All these agents share an antigen common to the group, and each .possesses an individual species-specific antigen as well. Serologic differentiation among members of the group has been complicated by the shared antigen; specific antisera, prepared in mice, are useful in laboratory identification of the individual members of the group. All the tick-borne rickettsioses of the Western Hemisphere have proved, to date, to be caused by R. rickettsi, regardless of the country of origin or the local name given the disease. The incubation period of the disease may vary from 2 to 14 days; severe illnesses appear to be associated with short incubation periods.
Distribution and Incidence.
Rocky Mountain spotted fever is limited in distribution to North and South America* The disease was first described in the United States in Montana at the turn of the century, and for some time was thought to be . limited to that area. Beginning in the 1930’s, the disease was recognized in the eastern United
States, Canada, Mexico, Brazil, and Colombia. Incidence and mortality data are difficult to obtain outside the United States, but in this country an average of 300 cases has been reported annually for the ten-year period from 1950 to 1959, with an average mortality rate of 6 per cent. During the 1960’s about 300 cases have been reported annually in the United States, approximately half occurring in the Atlantic seaboard states from Delaware to Florida.*
Rocky Mountain spotted fever is widely disseminated in nature and is principally a disease of ticks and small mammals. Man is rarely involved except when he intrudes into the “silent” wild cycle of disease. The hard ticks involved in transmission, the Ixodidae, feed on small mammals during their development through the larval and nymphal stages to tick adulthood. Once infected with R. rickettsi the tick may transmit the rickettsiae to its progeny transovarially or to man and other animals by feeding upon them. Thus the tick is both a vector and a reservoir of infection. The species of tick involved in the disease cycle varies according to geographic area. In the northern United States, the rabbit tick, Haema- physalis leporis-palustris, rarely bites man, but appears to be responsible for maintaining the disease among rabbits and small mammals.
Human infection in the United States is most commonly acquired in the West from Dermacentor andersoni (the wood tick), in the East from Dermacentor variabilis (the dog tick), and in the South from Amblyomma americanum (the Lone Star tick). Many other species of hard ticks have been implicated in transmission of the disease in Central and South America. Under laboratory conditions soft ticks of the genus Omithodorus are also capable of transmitting the agent, but appear to be unimportant as vectors in nature. Among the animals believed to be involved in the natural cycle of disease are squirrels, rabbits, porcupines, chipmunks, weasels, several species of feral rats and mice, and, perhaps most important from the human viewpoint, dogs.
Pathology and Physiologic Responses.
Histopatho- logically, the disease is an endangitis, starting in the endothelial cells and extending into the smooth muscle of the vessel walls. Rickettsiae may be demonstrated in the lesions by appropriate stains.
Thrombi are formed at the points of inflammation and lead to areas of focal necrosis and hemorrhage. Th6 major organ systems involved are the skin, subcutaneous tissues, and the central nervous system, although mononuclear cell infiltration may also be found in the lungs, heart, liver, and spleen. Except for the rash, gross findings at autopsy are minimal.
Clinical laboratory findings in the milder cases are usually limited to a moderate leukocytosis. Peripheral vascular collapse, the most serious consequence of the disease, may result from the pooling of blood in the damaged capillaries and from loss of water, electrolytes, and proteins into the extravascular space. Patients having this complication will show a decrease in hematocrit, blood chloride, and serum protein levels, and an increase in serum nonprotein nitrogen levels. Thrombocytopenia has also been observed in severe illnesses.
Clinical Manifestations of Rocky Mountain Spotted.
Headache and fever, frequently accompanied by mild chills, appear as initial symptoms of infection 2 to 14 days following contact with ticks. Within the first day of fever the patient usually complains of pains in the bones, joints, and muscles, photophobia, and increasing prostration. Initial physical examination usually reveals only flushing of the skin, conjunctival-injection, and minor respiratory signs referable to a dry cough. By the second day the fever usually rises to 104° to 105° F. and stays at that level until the end of the second week.
Between the second and sixth days of fever a generalized macular rash develops that resembles the eruption of measles. Initially the rash blanches with pressure, but after 24 to 48 hours the eruption frequently becomes petechial or, in the more severe cases, hemorrhagic. In mild illnesses, or in previously vaccinated persons, the rash may be minimal. Central nervous system symptoms in the form of agitation, insomnia, delirium, or Coda Usual’s appear by the end of this first week of fever It is during the second week of fever that the most critical circulatory and Pulmonary complications Of the disease occur.
The symptoms, physical findings, and history of exposure in an area known to harbor ticks must be weighed carefully by the physician, and, if the diagnosis is considered probable, treatment should be initiated. Two other rickettsial diseases, rickettsialpox and murine typhus, may mimic mild cases of Rocky Mountain spotted fever. Fortunately, both respond equally well to treatment appropriate for Rocky Mountain spotted fever.
Laboratory confirmation of the clinical diagnosis may be obtained by isolation of R. rickettsi from the blood during the first week of illness. Isolation studies in guinea pigs or embryonated eggs should be attempted only by laboratories equipped for such work because of the danger of infection of laboratory personnel. More commonly, laboratory diagnosis depends upon serologic tests with paired serum samples, the first obtained as early as possible during illness and the second about the fifteenth to twenty-fifth day of disease. These tests utilize either the Weil-Felix Proteus OX-19 and OX-2 agglutination reactions or the complement-fixation test with yolk sac antigen. In the agglutination test, positive results may be obtained with either or both of the OX-19 or OX-2 antigens; approximately 15 per cent of patients may show no rise in Weil-Felix titers even though complement-fixation tests are positive.* A fourfold or greater rise in titer with the complement- fixation test is considered confirmatory.
Rocky Mountain Spotted Treatment and Prognosis.
Until 1945 treatment of Rocky Mountain spotted fever was limited to supportive therapy; mortality rates were 20 per cent or greater. In 1945, para-aminobenzoic acid (PABA) was shown to be effective in treatment, producing defervescence in approximately three days and reducing mortality virtually to zero. By the early 1950’s, chloramphenicol and the tetracyclines replaced PABA in the treatment of this disease because the newer antimicrobial drugs were equally effective as PABA and far better tolerated. In the majority of patients, headache and other symptoms abate within 24 to 48 hours, and fever disappears within three to four days after beginning therapy with 25 mg. per kilogram per day of the tetracyclines or 50 mg. per kilogram per day of chloramphenicol, given in four divided doses by mouth.
With either regimen, treatment should be continued for 24 to 48 hours after the patient becomes afebrile. The physician must weigh the disadvantages of gastric irritation with the tetracyclines against the risks of blood dys- crasias with chloramphenicol. In general, because of the greater seriousness of the toxicity to chloramphenicol, tetracycline is the preferred therapy. For patients too ill to take oral medication.
The most important step in treatment is early diagnosis; no amount of drug therapy can modify the course of the disease in the patient who is admitted in extremis. Heroic measures such as corticosteroid therapy and parenteral administration of antimicrobials are completely unnecessary if the diagnosis is made and treatment begun early in the course of the disease. Early treatment will also prevent sequelae such as brain or heart damage, which have been observed in patients who have been treated late in their illness.
Although protective vaccine is available, its use has decreased markedly in recent years, presumably because effective antimicrobial therapy is now available for treatment. Nevertheless, use of the vaccine is appropriate for selected persons who may be exposed to the danger of infection in remote areas in which medical treatment may be difficult or impossible to obtain.
Because ticks cannot transmit infection to man without having been attached for several hours, a degree of protection can be achieved by careful examination of one’s person and careful removal of attached ticks on a twice daily schedule. Considerable difference of opinion exists regarding the safest method of removal. The use of a lighted cigarette or the application of kerosene, both highly regarded in some circles, appear to have the disadvantage that agonal responses of the tick may cause actual expression of rickettsiae into the wound. Another method appears to be preferable: the tick is grasped by the head and thorax with a pair of fine forceps and pulled gently but firmly until the mouth parts are extracted from the skin. The third category- of control measures is directed against the tick vector of the disease. The use of clothing impregnated with tick repellents provides significant protection, to those who must travelthrough tick-infested areas. When groups of people may be exposed to ticks in summer camps or recreational areas, the selective use of residual insecticides, such as DDT, dieldrin, or lindane, has proved effective in limited areas in reducing tick populations.