Scrub typhus is a mite-borne rickettsial disease that occurs in southeast Asia and adjacent areas and is characterized by fever, headache, lymphadenopathy, conjunctival injection, a maculopapular rash, and, in most patients, a distinctive es-char or skin lesion.
The typhus disease is caused by Rickettsia tsutsugamushi (R. orientalis), a group of rickettsial agents that produces a single distinctive clinical syndrome in man, but is characterized by extreme variation in antigenic composition of organisms isolated in different geographic areas and even in adjacent foci of the disease within the same country. All strains of R. tsutsugamushi can be propagated in mice and embryonated eggs; some strains will also produce disease in the guinea pig. Because of antigenic variation in the. organisms, complement-fixing antibodies produced in response to infection in man appear to be specific only for the infecting or closely related strains. Nevertheless, all strains of R. tsutsugamushi have the potential of stimulating Weil- Felix Proteus OX-K agglutinins in man.
Distribution and Incidence.
The disease occurs in a roughly triangular area of southeast Asia and adjacent countries approximately 5,000,000 square miles in extent. The western apex of the triangle is located in West Pakistan, the northern in north Japan, and the southern in the north coastal areas of Australia. It is impossible to obtain reliable data on the incidence of the disease among the indigenous populations of the area. However, World War II provided numerous examples of explosive outbreaks of the disease in military units in the Asiatic-Pacific area.
In one such outbreak among British troops in Ceylon, 756 patients were hospitalized with scrub typhus as a result of a four-day jungle training exercise. American forces operating on the islands of Owi and Biak experienced over 1000 cases of the disease in less than two months. During the period from 1942 to 1945, nearly 16,000 cases of the disease occurred in American, British, and Australian troops alone. At present the disease is reported sporadically among the people of southeast Asia and becomes a major medical problem only when development projects or recreational activities bring groups of people into contact with foci of the disease in nature.
Like Rocky Mountain spotted fever, scrub typhus is principally a disease of rodents and their ectoparasites that is propagated in a. “silent” cycle in nature involving man only when he unwittingly comes into contact with the mites that transmit the disease. A variety of rodents, . chiefly rats and feral mice, have been shown to be infected in nature. The disease in these animals is relatively mild but is associated with a rickettsemia that provides an opportunity to infect mites feeding on the animals during their illness. In some areas ground birds have also been implicated in the disease cycle in nature. The vector mite in most areas is a species of the genus Leptotrombiculidium highly adapted to the local ecology, although mites of the genus Schongastia have been shown to transmit the agent in the less important jungle cycle of the disease.
The mite vectors are free-living, feeding upon vegetation and insect eggs, except in their larval stage, during which they must obtain a meal of tissue fluid from a vertebrate host in order to complete their maturation to the adult stage. The mites are not only capable of transmitting R. tsutsugamushi to their vertebrate host during this feeding but are also capable of transmitting the agent to their offspring transovarially. Thus, the mite is both a vector and a reservoir .for scrub typhus, just as is the tick for Rocky Mountain spotted fever.
The highly specific ecologic requirements for propagation of the mite in terms of temperature, humidity, and food sources, coupled with its limited range of locomotion, lead to the formation of “mite islands,” highly localized in terms of both geographic and seasonal distributions. In some exceptional areas, such as Malaysia, the mite population is present throughout the year. More commonly, the mites are highly seasonal in appearance, and are most numerous during the warm, moist months of the year, although one focus of infection in southern Japan is characterized by a winter peak of mite population..
The seasonal distribution of scrub typhus understandably parallels the distribution of the mite vector. Man exposes himself to infection by transferring mites from vegetation to his body; most infections have followed contact with grassy ‘scrub” areas or straw cut from them. The disease may occur elsewhere because infected mites have been found in other habitats.
As with the other rickettsioses, the basic lesion is one of inflammation of the walls of the small blood vessels with perivascular infiltration of mononuclear cells. Pneumonitis and a diffuse myocarditis with mononuclear infiltration of the myocardium are frequently observed at autopsy. Gross pathologic findings are usually limited to enlargement of the spleen, lymphadeno- pathy and the cutaneous eschar of the disease.
The initial symptoms of the disease, frontal headache and temperature of 104 to 105° F., follow the infecting mite bite by 6 to 21 days. Physical examination at onset reveals only generalized lymphadenopathy, conjunctival injection, and, in most Caucasian patients, the developing eschar. This skin lesion, absent in most Asian patients, appears first as a small papule at the site of the mite bite and enlarges during the first few days of fever to approximately 1 cm. in size. On this papular base a multi- locular vesicle develops that evolves into the flat, black eschar characteristic of the disease. Regional lymph nodes draining the area of the eschar may become painful, and may enlarge to
the size of am acorn. About the end of the first week of fever a generalized macular rash appears, which may last only a few hours or may develop to a livid maculc- papular eruption of a week’s duration. In untreated patients complications such as pneumonitis, encephalitis, and cardiac failure occur late in the second week of fever; if the patient survives, defervescence begins about the fifteenth day of fever.
Diagnosis of Scrub Typhus.
Early diagnosis of the disease must be based on the clinical findings and the history of exposure in an endemic area. Laboratory confirmation of the diagnosis is based on isolation from blood of the agent in mice or on a rise in Weil-Felix OX-K agglutinins in serum during the course of illness. If the acute specimen is obtained before the tenth day of fever and the late specimen is obtained during the third week of illness, fourfold or greater rises in Weil-Felix OX-K titers will be observed in almost all untreated patients and in three fourths of those receiving antimicrobial therapy. Because of strain variation inthe etiologic agent, the complement-fixation test is unsatisfactory in the laboratory diagnosis of the disease. Clinical laboratory data are of little assistance in diagnosis; patients usually show only a moderate leukopenia. The differential diagnosis of the disease should include leptospirosis, typhoid fever, dengue, murine typhus, and malaria.
The tetracyclines or chloramphenicol are the therapeutic agents of choice for scrub- typhus at oral dosage levels of 25 and 50 mg. per kilogram per day, respectively. Drug therapy may be discontinued 24 hours after defervescence, which usually occurs within 36 hours after beginning therapy. Relapses have been observed in patients treated during the first week of fever; continuation of therapy through the fourteenth day of disease, or the administration of single 3.0 gram oral doses of drug on the seventh and fourteenth days following cessation of the initial course of antimicrobial therapy will prevent recrudescences of infection. The relapses occur because the antimicrobial drugs are not eradicative.
The choice between the tetracyclines and chloramphenicol is difficult Chloramphenicol may infrequently produce a blood dyscrasia. The tetracyclines may cause severe nausea and vomiting, leading to significant problems of fluid and electrolyte balance in the acutely ill patient. The case for assuming the added risk of chloramphenicol is slightly stronger for scrub typhus than for other rickettsioses because of the severity of the disease and its relatively high fatality rate.
Prognosis and Mortality.
Before effective treatment was available, mortality from scrub typhus was appreciable, varying from 5 to 40 per cent. Early antimicrobial therapy has essentially eliminated deaths from the disease. If the patient is treated in the first week of illness he usually ready to resume full activity in several weeks.
Preventive measures are directed at minimizing contact of man with the —t’tas transmitting the disease. During periods of political stability, the application of residual miticides such as dieldrin or lindane to large areas of terrain will permit safe continuation of operations in rubber plantations and similar industrial activities that bring workers into contact with areas previously known to be the source of numerous infections. When area miticide application is impractfcable, as in military operations, the use of clothing impregnated with mite repellents provides significant protection against infection. Under research conditions the intermittent use of chloramphenicol chemoprophylaxis has been shown to be effective in preventing clinical manifestations of infection. No protective vaccine is available.