The Topic of This Month Vol.22 No.9(No.259)
Scrub typhus (tsutsugamushi disease) is an infectious disease transmitted by attaching of the larval trombiculid mites of a particular colony infected transovarially with a Rickettsia species, Orientia tsutsugamushi . The disease occurs mainly in Southeast Asia and also in Indian subcontinent and Australia. In Japan, it was known in the early 1800s as an endemic disease occurring in summer on riversides along the coast of the Sea of Japan in northern Honshu. It was known that this disease (classical type of tsutsugamushi disease) has been transmitted mainly by Leptotrombidium akamushi . A new type of tsutsugamushi disease transmitted by L. pallidum or L. scutellare was discovered after World War II and its incidents have been reported all over Japan except a few prefectures such as Hokkaido and Okinawa.
L. pallidum is distributed widely from southern Hokkaido all the way to Kagoshima Prefecture. Its eggs hatch into larvae in autumn, and the larvae seek a host to attach and feed. However, the larvae that have failed to develop to adults hibernate during the snowy season and seek a host again next spring. L. scutellare is distributed mainly in southwestern Japan throughout the central part of Tohoku District, its eggs hatch into larvae in autumn, and the larvae are active in host seeking until winter. The serotypes of O. tsutsugamushi comprise several subtypes; L. akamushi is infected with Kato type, L. pallidum with Karp or Gilliam type, and L. scutellare with Kawasaki or Kuroki type.
The reporting of tsutsugamushi disease began in 1950 in compliance with the Communicable Diseases Prevention Law. Later, the disease was classified into the category IV notifiable infectious diseases in the National Epidemiological Surveillance of Infectious Diseases (NESID) under the Law concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted in April 1999. In 1950, with the beginning of the reporting, the disease was classical type at the most and the cases used to count at about 100 per year, thereafter showed a rapid decrease (Fig. 1). After 1980, patients of new type of tsutsugamushi disease were on the rapid increase. Although they tended to decrease after 1991 (see IASR, Vol. 18, No. 9), they increased from 423 in 1996 up to 794 in 2000 (Table 1). The patients of the year 2000 were reported from 37 prefectures nationwide (Fig. 2). According to the Vital Statistics of Japan, the deaths reported during the 5 years from the year 1996 to 2000 counted at 10.
According to NESID, during the period from the 14th week of 1999 after enactment of the Infectious Diseases Control Law through the 30th week of 2001, the peak incidence is seen during the 21st-23rd weeks (May-June) and during the 45th-50th weeks (November-December) consecutively (Fig. 3). In Tohoku and Hokuriku Districts, where it is relatively cold and snowy in winter, incidents occur both in autumn-winter and spring, while in the area including from Kyushu to Kanto Districts, where it is warm, incidence is high in autumn-winter. The high incidence is related to the active season of infected larval mites (see p. 213-215 of this issue). The patients reported during April 1999 through December 2000 included more males than females, counting at 722 and 628, respectively, and peaked at the ages of 65-74 years, accounting for 31% (Fig. 4).
The working group for tsutsugamushi disease, the Association of Public Health Laboratories for Microbiological Technology organized by the National Institute of Infectious Diseases and local public health institutes has been making detailed questionnaire surveys for the patients since 1989. The following is a summary of such questionnaires collected as of 1998 (see Kansenshogaku Zasshi, 75: 353-364, 2001). Of 583 cases suspected of tsutsugamushi disease, 416 were confirmed. The estimated places of acquiring infection were mostly mountains and mountainous areas, accounting for 50%, and acquiring infection on riversides, where the classical type of tsutsugamushi disease used to be frequently acquired, decreased markedly to 3.3%. The types of work at the time of infection were farming in 32%, forestry in 14%, collecting edible wild plants in 11%, recreation in 6.5%, and construction in 3.5%.
The prevailing types were estimated from the serum antibody titration of 212 patients in Kyushu Districts. Most of them were infected with either Kawasaki type or Kuroki type (Fig. 5). Some serum samples reacted to Kawasaki or Kuroki strain but not to Kato, Karp, or Gilliam strains, that used to serve as standard strain. In the areas where mites are infected with Kawasaki type or Kuroki type of O. tsutsugamushi , it became clear that these strains should be used as the antigen. If no serum antibody is detected in acute phase blood, it will often be possible to detect O. tsutsugamushi DNA at a high rate by PCR in the blood clot. Therefore, combined use of both serum diagnosis and PCR is recommended (see IASR, Vol. 18, No. 1 and p. 213 of this issue).
The three main signs of tsutsugamushi disease, eschar (the punched-out ulcer covered with a blackened scab that indicates the location of the mite bite), fever, and exanthema were observed at high rates, 87, 98, and 92%, respectively. Disseminated intravascular coagulation (DIC) was recognized in 21 patients. Eschar was located on such trunks as chest, abdomen, back, buttocks, and genitals in 35% and on lower limbs in 23%. The form of eschars at the first medical examination was scab in 60%. Lymphadenopathy, particularly swellings near eschars, was observed in about half of the patients. In blood chemical examinations, increased CRP, GOT, GPT, and LDH were found in 96, 85, 78, and 91% of the patients, respectively.
Penicillins or β-lactam antibiotics, usually used to treat febrile bacterial infections are not effective on tsutsugamushi disease. Early treatment with tetracyclines as soon as tsutsugamushi disease is suspected is important to prevent the worsening of the disease since it is effective on O. tsutsugamushi and no resistant strain has been found. Information on an incident of tsutsugamushi disease in a district is of a great help for suspected patients to visit physicians and for physicians in making clinical diagnosis. It will also be possible to give warnings to inhabitants and tourists without any protection to keep out from suspicious infection spots. For these reasons, it is a prerequisite for physicians to notify cases promptly after the etiological diagnosis to nearby health centers and for local and national infectious disease surveillance centers to disseminate the information to health providers and the public as a fundamental control measure against tsutsugamushi disease.
Tsutsugamushi larvae (0.2 mm) attach to mammals (including man) and birds once before developing to adults. The larvae attach firmly to the surface of the host's body with the mouth parts (chelicera) and suck up liquefied tissue for a few days. Because the chelicera is too short to reach venous capillaries, blood is not ingested.