The Topic of This Month Vol.27 No.2(No.312)

Scrub typhus and Japanese spotted fever in Japan, as of December 2005

(IASR 27: 27-29; Feb, 2006)

Scrub typhus (tsutsugamushi disease) is an infectious disease caused by Orientia tsutsugamushi possessed by a larval trombiculid mite, and Japanese spotted fever by Rickettsia japonica transmitted by Ixodidae tick, both being representative rickettsial disease endemic in Japan. They are grouped into the category IV notifiable infectious diseases in the National Epidemiological Surveillance of Infectious Diseases (NESID) in compliance with the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted in April 1999. Both diseases are often acquired during such outdoor work as farming, forestry, collecting edible wild plants, and recreation. Both are characterized by such three main signs as fever, rash, and eschar. Differential diagnosis is difficult only from clinical symptoms and laboratory diagnosis is indispensable.

Scrub typhus (tsutsugamushi disease): The classical type has been known as an endemic disease since the 17th century (Edo era). Although cases of the new type scrub typhus increased during 1980s, cases have been on the decreasing tendency since 1991 (see IASR 22:211-212, 2001). Yearly reported cases after enactment of the Infectious Diseases Control Law increased up to 794 in 2000, however cases were kept constant at about 400 during 2001-2005 (491, 339, 407, 314, and 334, figures reported as of January 26, 2006) (Fig. 1). During 2001-2005, cases were reported from the whole country except Hokkaido, Nara and Ehime Prefectures (Fig. 2a). However, a case in Okinawa Prefecture in 2001 was presumed to have acquired infection in other prefectures. As many as more than 100 cases were reported in certain prefectures, such as Kagoshima, Fukushima, Miyazaki, Akita, and Chiba, suggesting geographical accumulation. The cases cover all ages, with a peak at 70-74 years. There were slightly more male cases (968) than female cases (916).

Monthly cases exhibit a bimodal pattern; in the spring, one peak during March-May and another during the autumn toward early winter, November-December (Fig. 3). Occurrence of cases depends on the active season of larvae in the habitat of trombiculid mites. When larvae of mites hatched in the autumn pass the winter, a number of cases may occur in early spring. In Western Japan, such as Kagoshima and Miyazaki Prefecture, where snowfall is rare, cases occur in early autumn toward early winter. In Tohoku district such as Akita and Fukushima Prefectures where there is much snowfall, occurrence of cases is not constant. Many cases occur in autumn and the beginning of winter, and even more cases in spring. In Hokuriku district, most cases are reported to occur in November and December.

Laboratory diagnosis of scrub typhus is made at prefectural and municipal public health institutes (PHIs) by such serodiagnoses as either indirect immunofluorescence assay (IF) or indirect immunoperoxidase assay (IP) or by DNA detection by using PCR. For serodiagnosis, the antigens of three standard strains of O. tsutsugamushi (Karp, Kato, and Gilliam) are used mostly. In infection with other serotype strains (Kawasaki, Kuroki, etc.) than the three standard strains, significant elevation of antibody titer may not be detected clearly (see IASR 22:211-212, 2001), the use of antigen of O. tsutsugamushi serotype distributed in each district is important for accurate diagnosis of cases. In the survey in Kanagawa and Miyazaki Prefectures, infection with Kawasaki type accounted for about 2/3 and that with Kuroki type accounted for about 1/4 of all infections (see p. 29&30 of this issue). In Shimane Prefecture, a capture survey for trombiculid mites was carried out and it has been reported that most infection was with Karp or Gilliam type strain (see p. 33 of this issue). At some commercial laboratories, IF with three standard strains is being carried out.

For scrub typhus, tetracyclines are markedly effective. Regardless of the availability of reliable therapy, often seen are fatal cases. During 2001-2005, a total of 9 fatal cases (all aged over 60 years), one in each of Aomori, Iwate, Yamagata, Fukushima, Kyoto, and Shimane Prefectures and three in Niigata Prefecture were reported at the time of reporting.

Warning to residents for early consultation of a doctor and furnishing information necessary for demanding medical staffs for early diagnosis and treatment are important. For that it is necessary to collect data on the activity of trombiculid mites and the case incidence in each district and to make analysis after due consideration of the environment such as meteorological and geographical conditions. In the reports of 2001-2005, 9 cases of infection in foreign countries, including 2 cases in Korea and one case in Nepal, were estimated and we should never forget infection abroad.

Japanese spotted fever: This disease was first reported in Tokushima Prefecture in 1984. Although it is not so easy to differentiate it clinically from scrub typhus, the incubation period is 2-8 days, slightly shorter than that of scrub typhus, 10-14 days, rash appears more often on the limbs in typical cases (in scrub typhus, it is on the trunk) and the eschar is small in size. Before enactment of the Infectious Diseases Control Law, the nationwide surveillance had been conducted by the Working Group for Tsutsugamushi Disease Surveillance in Japan, the Association of Public Health Laboratories for Microbiological Technology (see IASR 20:211-212, 1999). During 1984-1998, 10-20 and several people yearly, or, a total of 213 cases, was confirmed in 10 prefectures west of the Kanto district. During 1999-2005, after enactment of the law, cases increased to 39 (from April through December 1999), 38, 40, 36, 53, 67, and 62 (reports as of January 26, 2006) (Fig. 1). After enactment, case reports came from additional 13 prefectures, and the endemic area of the disease has expanded (Fig. 2b). Although scrub typhus occurs widely from Kyushu through Honshu, while Japanese spotted fever only west of Kanto district. Similarly to scrub typhus, Japanese spotted fever affects all age groups, the peak being at 70-74 years of age. There were slightly more female cases (males 157: females 178).

Japanese spotted fever cases are reported from March through December. However, the peak of monthly reports differs from one district to another (Fig. 3). As is the case with scrub typhus, careful studies and analyses by each hot zone are important for preventive measures for the districts (see p. 31-35 of this issue).

Although for laboratory diagnosis of Japanese spotted fever, similar methods as those for scrub typhus are used, the supply systems for antigens for serum diagnosis and positive control sera have not sufficiently been established, therefore only limited laboratories undertake the work.

In July 2001 in Hyogo Prefecture, in August 2004 in Kochi Prefecture, and in September 2005 in Hyogo Prefecture, one fatal case each was reported at the time of reporting. Some of these cases were fulminant type, dying very rapidly from onset of the disease (see p. 36-38 of this issue). For therapy, tetracyclines are the drug of the first choice. In serious cases, combined therapy with fluoroquinolones, which are ineffective for scrub typhus, has been reported effective (see p. 37 of this issue).

Other rickettsial diseases: Cases suggestive of new spotted fever-group rickettsial infection not found in Japan have been reported (see p. 40 of this issue). Beside, cases of overseas infection with Mediterranean spotted fever or murine typhus (flea-borne typhus; R. typhi infection) have been reported (see p. 41&42 of this issue). Anaplasma phagocytophilum (formerly Rickettsiae family), the tick-borne pathological agent of human granulocytic anaplasmosis, was found in Japan and it is possible that new cases of anaplasmosis occur in future (see p. 44 of this issue).

Conclusion: For scrub typhus, it is necessary to cope with serotypes other than the three standard serotypes as diagnostic antigens, and for Japanese spotted fever, to spread techniques for antibody analysis and PCR diagnosis in districts where new cases have occurred. Under the present situation, laboratories preparing available resources for diagnosis of rickettsial diseases are few and restricted only to districts where there are many reports of occurrence. There are new issues of establishing laboratories capable of confirmatory diagnosis of new or imported rickettsial diseases and to strengthen a national laboratory examination system taking view of whole rickettsial infections. In order to save seriously ill cases, it is necessary to develop rapid diagnostic methods (see p. 38 of this issue).

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