The Topic of This Month Vol. 31, No. 5 (No. 363)

Scrub typhus and Japanese spotted fever in Japan 2006-2009
(IASR 31: 120-122, May 2010)

Scrub typhus (tsutsugamushi disease) and Japanese spotted fever are representative rickettsiosis in Japan.  They are category IV infectious diseases that require reporting of all the cases under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections.  The causative agent of scrub typhus is Orientia tsutsugamushi whose vector is larval trombiculid mite, and that of Japanese spotted fever is Rickettsia japonica whose vector is Ixodidae tick.  The infection is acquired through bites of the infected mite/tick during outdoor activities.  Fever, exanthema and eschar are the major clinical signs for the both infections.  Shorter incubation time and smaller eschar characterize Japanese spotted fever.  Exanthema of Japanese spotted fever tends to spread from the extremities to the trunk, while that of scrub typhus appears mainly in the trunk.  Despite of these different clinical pictures between both rickettsioses, laboratory differential diagnosis is indispensable.

Scrub typhus (tsutsugamushi disease): In 2006-2009, 417, 383, 447 and 458 cases were reported in the respective years (Fig. 1 and Table 1).  There were 895 male and 810 female cases.  The age peak was at 70-74 years.  Fukushima and Kagoshima Prefectures reported more than 50 cases every year, and Aomori, Akita, Chiba, Kanagawa, Niigata, Gifu and Miyazaki Prefectures around 20 cases/year (Fig. 2a and Table 1).  The incidents needing special attention in 2006-2009 could be (1) the first confirmation of infection that occurred in Okinawa Prefecture (IASR 30: 17-18, 2009), (2) one case that presumably acquired infection in the central area of Tokyo Metropolis, which is very rare (see p. 128 of this issue), and (3) report of a classical scrub typhus case due to bite by Leptotrombidium akamushi carrying Kato type O. tsutsugamushi after the lapse of 15 years (see p. 123 of this issue).

Two peaks of infection, one in May-June and the other in November-December, were observed as whole Japan in each year.  However, the pattern was variable among regions depending on the species of the carrier mites, their ecology, their geographical distribution and the climate (Fig. 3 and see also p. 124&125 of this issue and IASR 27: 27-29, 2006).  In Japan, L. akamushi , L. pallidum and L. scutellare are carriers of O. tsutsugamushi L. akamushi is localized in the northern part of Japan and carries Kato type O. tsutsugamushi L. pallidum is widely distributed in Japan and transmits Karp type and Gilliam type O. tsutsugamushi L. scutellare is distributed from Yamagata Prefecture (LAT. 38° N) to the southern part of Kyushu and transmits Kawasaki type and Kuroki type O. tsutsugamushi .

Japanese spotted fever: In 2006-2009, Japanese spotted fever was increasingly reported, i.e., 49, 98, 135 and 129 cases in the respective years (Fig. 1 and Table 1).  During these years, there were 199 male and 212 female cases.  The age peak was at 70-74 years.  Mie Prefecture reported the largest number of cases.  Prefectures, including Mie Prefecture, that report the infection are located in the western part of Japan of the Pacific side (Fig. 2b and Table 1).  New endemic areas where the patients are clustered have been confirmed in recent years (see p. 129, 132&134 of this issue).

As the whole Japan, the number of infection increased from May to October.  However, the pattern of monthly incidence was not the same among the regions as in the case of scrub typhus (Fig. 3 and see p. 129, 131&134 of this issue).  In 2009, an acute infectious fulminant purpura, a rare but extremely serious form of infection, was reported (see p. 135 of this issue).

Severe clinical consequences and therapy: While effective therapy is available, scrub typhus and Japanese spotted fever sometimes become fatal (Table 2) and some such cases fail to be reported (IASR 27: 37-38, 2006).  Tetracyclines are remarkably effective to scrub typhus; the fever subsides usually 24 hours after the administration.  Combination of a tetracycline and a fluoroquinolone prevents aggravation of Japanese spotted fever (IASR 27: 37-38, 2006).  Once rickettsiosis is suspected, immediate administration of appropriate antibiotics should be considered.  However, only minocycline is an anti-rickettsia therapeutics that is covered by the health insurance in Japan.

Other rickettsiosis: R. heilonjiangensis that had been reported from the Far East Eurasian Continent was detected from a patient in Miyagi Prefecture in 2008 by precise laboratory identification and epidemiological investigations.  The patient was originally reported as Japanese spotted fever (see p. 136 of this issue).  Similar cases may increase in the northern part of Japan in future.  Imported cases of rickettsiosis have been frequently reported (see p. 127 of this issue).  In 2008, three cases of murine typhus caused by R. typhi were confirmed; two of them came back from Bali Island in Indonesia and one from Hainan Island of China.  In 2009, it was found that two patients returning from Mozambique were infected with African tick bite fever caused by R. africae (see p. 137 of this issue).

Laboratory diagnosis: For scrub typhus, serodiagnosis, indirect immunofluorescence (IF) assay or indirect immunoperoxidase (IP) assay, is generally applied.  The IF assay using the standard three serotype antigens (Kato, Karp and Gilliam) is covered by the health insurance, and conducted in commercial laboratories.  However, O. tsutsugamushi infection with other serotypes may not be detected with these standard three antigens (IASR 22: 211-212, 2001).  To overcome this inconvenience, some prefectural and municipal public health institutes (PHIs) use antigens of locally circulating serotypes, such as Kawasaki, Kuroki, Shimokoshi, and other types (see p. 123, 124&127 of this issue).  The laboratory diagnosis of Japanese spotted fever can be conducted similarly, but only limited number of laboratories can afford the testing (see p. 139 of this issue).

For laboratory diagnosis of rickettsioses unknown in Japan or those imported from abroad, the standard set of the three serotype antigens is insufficient, and broad range of serological assay against rickettsiae including R. japonica are required.

For detection of rickettsia genome, acute phase of the patients' blood has routinely been used in Japan.  But in other countries, biopsy specimen derived from the site of mite/tick bite or exanthemas have also been used.  The usefulness of such samples for the genome detection has been confirmed in Japan.  Such practice may improve the detection rate and the accuracy of the diagnosis (see p. 125, 129, 136, 137&139 of this issue).

Conclusion: Scrub typhus and Japanese spotted fever are category IV infectious diseases whose report is constantly high in number.  Fatal cases are reported almost every year.  These and other rickettsial diseases may be now found in any part of Japan.  A physician should bear in mind that a rickettsiosis patient might consult him/her even outside of the endemic regions.  Warning should be made not only to the new type of scrub typhus but also to the re-emerging classical scrub typhus in summer and to newly appearing rickettsiosis.  Epidemiological analysis of rickettsiosis in each area and providing appropriate information to the local people and medical facilities are necessary for prevention of infection and timely and appropriate treatment of the patients.

The nationwide surveillance of rickettsial infections should be strengthened.  Importantly, the surveillance should be based on high quality laboratory diagnosis for case finding and epidemiological studies on wide range of rickettsiae and geographical distributions of their vectors.

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