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PubMed1995

[Epidemiological study of tsutsugamushi disease in Gunma prefecture. A special field study and serotype].

An epidemiologically investigated of invasion of Rickettsia tsutsugamushi, inhabitant of mites and serum sample from patients with Tsutsugamushi disease in Gunma prefecture from 1984 to 1994 was made. Our data clearly indicated that Rickettsia tsutsugamushi was not located but widely spreaded throughout the Prefecture. Mites on rodents, were classified into 4 genus and 12 species and about 15% of them were Leptotrombidium pallidum and Leptotrombidium scuttellare, well known virulent vectors. The highest incidence rate of this disease was observed in the northwest area of the Prefecture from October to December, while a smaller number of patients occurred in other areas and in other months. About fifty percent of the serum samples from the patients were positive to the Karp strain. These results suggest that the major cause of this disease is the Karp strain and the disease could occur potentially in various areas of the Prefecture.

Animals↗
PubMed1995

[A case of tsutsugamushi disease which occurred in south western Shikoku].

We report a case of tsutsugamushi disease found in south western Shikoku. A 64-year-old male who lived in Towa Village in Kochi, developed a fever and headache on April 6, 1994, and was admitted to Uwajima City Hospital on April 15, with a ten-day history of illness. He had an eschar on the right anterior side of the breast and an enlargement of the right axillary lymph node, without a rash. Laboratory data showed mild liver injury and atypical lymphocytes with 6% in peripheral blood. After his blood was drawn for rickettsial isolation, the minocycline was administered. His symptoms improved rapidly and was discharged in good condition. We successfully isolated the causative agent, Rickettsia tsutugamushi, and designated it as the Shiba strain. High antibody titer against the Kato, Karp and Gilliam strains was detected in serum on admission and increased during the course of the disease. In Shikoku, tsutsugamushi disease is rare and only 13 cases were reported during last ten years. Especially in south western district of Shikoku, there have been no case reported since 1960. This case is important epidemiologically and suggests that we should pay attention to this disease.

Anti-Bacterial Agents↗
PubMed1996

[A case of Tsutsugamushi disease infected by mountain climbing in the Republic of Korea].

A 47-year-old male was infected with Tsutsugamushi disease showing typical findings after mountain climbing in the Republic of Korea (ROK). Immunoserological examinations suggested that he had been infected in ROK. In this case, detection of the characteristic sting was useful for early diagnosis and treatment. Until now, Tsusugamushi disease has not been reported in Hokkaido. It is the first case registered in Hokkaido. With extensive international intercourse these days, this case suggests that Tsutsugamushi disease can occur potentially all over Japan.

Humans↗
PubMed1997

[Clinical and serological study of tsutsugamushi disease in northern Osumi, Kagoshima Prefecture].

We report 34 cases of tsutsugamushi disease seen from 1989 to 1993 at Yagi Clinic, northern Osumi, Kagoshima Prefecture. Nineteen patients (55.9%) showed the highest antibody titers against the Kawasaki strain Orientia tsutsugamushi (Ot) and 13 (38.2%) against the Kuroki strain Ot. It is suggested that two antigenic types (Kawasaki and Kuroki) of Ot were distributed in Kagoshima Prefecture, and the Kawasaki type Ot more or less dominates Kuroki type Ot. There was no difference in clinical features between the two groups of patients.

Adolescent↗
PubMed1997

[Analysis of clinical severity of tsutsugamushi disease according to the serotype of pathogenic rickettsia].

We compared the severity of clinical symptoms and laboratory test results of tsutsugamushi disease patients in Oita Prefecture according to the serotype of infected R. tsutsugamushi. Of the 45 patients, except one with the Karp-type, who were suffering in Oita Prefecture between 1992 and 1994, 20 were the Irie-type and 24 were the Hirano-type. There was no apparent difference with regard to clinical symptoms between the two groups of patients. Laboratory tests showed that CRP increased almost equally in the two groups. The ESR level was slightly higher in the Irie-type patients than in the Hirano-type, but did not differ significantly between the two groups. Both leukocyte count in the acute stage and platelet count decreased in the Hirano-type, as compared with those of normal ranges in the Irie-type. GPT values elevated in proportion to the day of illness in the acute stage. This trend continued after the initiation of specific chemotherapy in the Hirano-type. The median GOT, GPT and LDH values were 71, 65 and 709 IU/l for the patients in the Hirano-type, as compared with 37, 36.5 and 546.5 for the patients in the Irie-type, respectively. Above results show that the Hirano-type rickettsiae produces a more severe illness than the Irie-type ricketsia. Platelet count had a significant correlation with ESR, suggesting the pathophysiologic changes leading to disseminated intravascular coagulation, a symptom of severe tsutsugamushi disease. There may be common causes in leukopenia and thrombopenia, as being suggested by the significant correlation between leukocyte count and platelet count.

Aged↗
PubMed1997

[A case of Tsutsugamushi disease as an imported infection].

Tsutsugamushi disease is widely spread throughout Japan. A case of tsutsugamushi disease was seen in October, 1996. A 64-year-old male developed typical symptoms of tsutsugamushi disease with Rickettsia tsutsugamushi, after he returned to Japan from Cheju Island, Korea. Not only in Japan but also in other Asian countries including Korea, China, Taiwan, and Thailand, tsutsugamushi disease is one of the most important rickettsial diseases carried by ticks or mites. If a traveller returning from an Asian country has symptoms such as high fever, skin eruption, and lymphadenitis, we should suspect that he is suffering from tsutsugamushi disease and should search if he has an eschar on any area of his body. We should not forget that tsutsugamushi disease is an imported disease. Patients of tsutsugamushi disease often have hematological disorders. They are sometimes referred to the hematological section of the hospital. Hematologists should be familiar with this disease.

Anti-Bacterial Agents↗
PubMed1999

[Analysis of prevalent Orientia tsutsugamushi in Aichi Prefecture].

Orientia tsutsugamushi was isolated from one of 8 patients' sera in Aichi Prefecture, and was identified to have the same antigenicity with the KN-2 strain (KN-2 like) based on the reactivity with 13 types of strain-specific or cross-reactive monoclonal antibodies to Karp, Gilliam, and Kato strains. Four isolates from 4 unfed larvae and adult of Leptotrombidium pallidum were also classified as the KN-3 like strains. Using indirect immunofluorescence, sera from 20 patients with tsutsugamushi disease were tested for reactivity with KN-1, KN-2, KN-3, and GJ-1 strains, isolated from patients in Gifu Prefecture. Fifteen sera showed the highest titer against KN-2 strain in Immunogloburin M (IgM). Of the other 5, three were higher for KN-3 strain in IgM, and two were KN-1 or GJ-1, respectively. These results suggested that KN-2 like strains were prevalent in the region where the number of patients has been ranked the highest in Aichi Prefecture. KN-1, KN-3, and GJ-1 like strains were also existed in this area. KN-3 like strain was likely to be distributed in another area. Aichi Prefecture.

Animals↗
PubMed2001

[Epidemiological analysis on many cases of tsutsugamushi disease found in Hiroshima Prefecture, Japan].

The clinical findings of tsutsugamushi disease and the fauna of trombiculid mites in Hiroshima Prefecture were studied in this report. We reviewed 63 cases of tsutsugamushi disease occurring between 1990 and 1999, and most of cases were contracted in the area around the midportion of the Oota River (55 cases; 87.3%). Of these, 30 cases (47.1%) lived in Asakita-ku in Hiroshima City. Eschar was detected in 33/19 (84.6%) cases, and 97.6% (40/41), 88.9% (16/18) patients showed eruption and lymphadenopathy respectively. Biochemical examination revealed liver dysfunction in 38.1% (8/21) patients. Of the 11 cases examined on peripheral blood smear, atypical lymphocytes were detected in 10 cases (90.9%). Fifty-five cases (90.2%) occurred during the restricted season between September and December each year. The predominance of Leptotrombidium scutellare was verified by collection of trombiculid mites along the basin of the Oota River. Serum antibody titration on a patient in Asakita-ku showed reaction to Kawasaki type antigen definitive to L. scutellare. Therefore, we speculate that L. scutellare is a candidate for the vector of Orientia tsutsugamushi in Hiroshima Prefecture.

Adult↗
PubMed2003

[Tsutsugamushi disease found in the northern districts of Awaji Island--epidemiological study of the outbreak season temperature].

Ten cases of tsutsugamushi disease which were diagnosed and treated among the outpatients from 1987 through 1999 in a clinic of internal medicine locating at the northern districts of Awaji Island were investigated. The patients were consisted of 8 males and 2 females and their ages ranged from 6 to 69 years old. The infected areas were distributed in hilly districts extending over three towns. The outbreak season was from November through December. The following two facts seemed to be worthy of notice. 1) There was a time lag on the patient's onset among the different years. 2) When the incidences were more than two cases a year, the time difference of onset was within a few days each other. Then the relationship between atmospheric temperature and the date of onset was studied. Meterological observing records at Gunge Ichinomia Town near the northern districts of Awaji Island were investigated into the temperature every 10 days from 1987 to 1999. Average temperature every 10 days including the presumable day when each patient was infected with Orientia tsutsugamushi (O.T) ranged between 9.1 degrees C and 13.3 degrees C and in 7 of 10 cases ranged between 11.6 degrees C and 13.3 degrees C. The maximum temperature ranged between 11.3 degrees C and 17.5 degrees C, the minimum one between 6.6 degrees C and 9.1 degrees C. It is likely that the seasonal occurrence of tsutsugamushi disease greatly depends upon the optimum temperature for the activity of tsutsugamushi mites in these areas. The high titer of serum IgM and IgG antibody to Karp, Gilliam Kato type O. tsutsugamushi was detected by an immunofluorescense assay (IF) in all cases. IgG antibody, titers fell drastically to 20 or 10 times within a few years but 10 times titer was still detected in three cases in more than ten years. It is suggested that IgG antibody titer more than 10 times in healthy people indicates the infection in the past and titer more than 20 times implies the infection during the past few years.

Adolescent↗
PubMed2004

[Present status of Tsutsugamushi disease detection at regional public health laboratories--a comparison between the results from a questionnaire survey and the National Notifiable Diseases Surveillance System].

Tsutsugamushi disease has been a notifiable disease in Japan since the implementation of the Infectious Diseases Control Law in April 1999. In order to assess the role of public health laboratories in detecting Tsutsugamushi disease, a questionnaire regarding routine testing of suspected cases of Tsutsugamushi disease was sent to 73 regional public health laboratories (47 prefectural laboratories and 26 municipal laboratories) in July 2001. The response rate was 92% (67/73 laboratories). It was found that most prefectural laboratories are well prepared to routinely receive and test specimens of suspected Tsutsugamushi disease cases. Additionally, we found that some regional public health laboratories are using two or more detection methods to improve the accuracy of their routine tests. In southern Japan. Kawasaki and Kuroki strains, strains endemic to the region, are widely used in addition to Kato, Karp, and Gilliam strains, the standard strains used for serum antibody tests in Japan. For the years 2000 and 2001, we found that for some prefectures, the annual number of cases confirmed by regional public health laboratories was nearly equal to the annual number of cases the prefecture reported to the National Notifiable Diseases Surveillance System. In these prefectures, it appears that an effective communication network has been established between physicians, public health laboratories, and local health centers, ensuring laboratory confirmation and proper notification.

Cities↗
PubMed2003

Development of a recombinant protein-based enzyme-linked immunosorbent assay and its applications in field surveillance of rodent mice for presence of immunoglobulin G against Orientia tsutsugamushi.

A recombinant protein containing the immunodominant conserved epitope region of the 56-kDa outer membrane protein of the Karp strain of Orientia tsutsugamushi was purified to near homogeneity using recombinant DNA techniques. The purified protein was used to immunize rabbits and produced an antibody that could recognize different strains of O. tsutsugamushi, as demonstrated both by Western blotting and immunofluorescence assay. An enzyme-linked immunosorbent assay (ELISA) based on this recombinant protein was developed to detect antibody (immunoglobulin G [IgG]) against O. tsutsugamushi in mice captured in different districts of Taiwan during 2000 to 2001. A significant difference was found in the antibody seroprevalence rates of Suncus murinus mice captured in different districts of Taiwan (chi(2)(4, 0.95) = 26.64; P < 0.05). Furthermore, a significant difference of IgG seropositivity rates was observed among different kinds of mice (chi(2)(5, 0.95) = 93.85; P < 0.05). Antibody seropositivity rates were higher in Bandicota indica (100%), Rattus flavipectus (96.17%), and Rattus losea (95.83%) than in Rattus norvegicus (86.05%) and Rattus mindanensis (83.67%) (chi(2)(diff, 5, 0.95) = 12.59, P < 0.05). The lowest antibody seropositivity rate (54.4%) was observed in Suncus murinus. Antibody seropositivity rates of mice from different districts differed significantly because of the significant difference in antibody seroprevalence rates for S. murinus. The results of this study indicated that the recombinant protein ELISA developed in this study could be used to conduct large-scale surveillance of rodent mice for the presence of antibody against O. tsutsugamushi. The high seroprevalence rates in rodent mice (except S. murinus) suggest that people residing in these districts are at increased risk of developing O. tsutsugamushi infection.

Amino Acid Sequence↗
PubMed1978

Vole agent identified as a strain of the trench fever rickettsia, Rochalimaea quintana.

The vole agent described by Baker in 1946 was studied as an example of a bacterium that has been mistakenly regarded a rickettsia. Unlike rickettsiae, the vole agent killed chicken embryos with great irregularity, multipled primarily at the surface of avian or mammalian cells and not intracellularly, produced colonies rather than plaques on chicken embryo monolayers under agar, and developed small colonies after 4 to 7 days of cultivation on blood plates. It was most conveniently cultivated on monolayers of irradiated L cells and was purified by minor modifications of the Renografin gradient procedure used for rickettsiae. It actively catabolized glutamate, glutamine, succinate, and pyruvate, but not glucose or glucose-6-phosphate. Enzymatic activities of cell extracts were consistent with above findings. The base ratio (molar percent guanine plus cytosine) of its deoxyribonucleic acid was shown to be 39, which was identical to the base ratio of the deoxyribonucleic acid of Rochalimaea quintana tested simultaneously. Serological studies indicated no cross-reactivity with Rickettsia tsutsugamushi, but strong cross-reaction with R. quintana was observed when a hyperimmune rabbit serum and a convalescent human serum were tested. We conclude that the vole agent is a strain of the trench fever rickettsia, R. quintana.

Animals↗
PubMed1983

Development of specific and cross-reactive lymphocyte proliferative responses during chronic immunizing infections with Rickettsia tsutsugamushi.

The development of antigen-responsive lymphocytes was followed in mice immunized with the Gilliam, Karp, or Kato strains of Rickettsia tsutsugamushi by utilizing an in vitro lymphocyte proliferation assay. Subcutaneous immunization with viable rickettsiae of all three strains resulted in the appearance of lymphocytes in the spleen responding to irradiated tissue culture-grown rickettsiae used as stimulating antigens. Although all animals demonstrated antigen-induced proliferation elicited by homologous antigen by 14 days after immunization, the time of peak responsiveness varied, depending on the strain of rickettsiae used for immunization. In all cases, peak proliferative responses occurred at a time after immunization that was after the previously reported time after immunization at which resistance to rechallenge was observed. Reactivity to heterologous strains of R tsutsugamushi developed roughly in parallel with homologous reactivity in Karp- and Gilliam-immunized mice, with a marked degree of heterologous reactivity evident. Kato-immunized mice demonstrated greater reactivity to heterologous antigens early in the development of antigen reactivity and demonstrated a somewhat greater degree of cross-reactivity, relative to homologous responses, than the other groups. It was found that nylon wool-nonadherent immune cells, if cultured with antigen and adherent cells obtained from normal spleens or peritoneal exudates, responded in culture. The thymus-derived lymphocyte nature of the responding cell was further suggested when treatment of immune spleen cells with anti-Thy 1.2 serum and complement eliminated antigen response.

Animals↗
PubMed1983

Role of T-lymphocytes in production of antibody to antigens of Rickettsia tsutsugamushi and other Rickettsia species.

The requirement of thymus-dependent lymphocytes for antibody production to Rickettsia tsutsugamushi, Rickettsia akari, Rickettsia conorii, and Rickettsia typhi was investigated by comparing antibody production in athymic (nu/nu) or thymus-bearing BALB/c mice. Athymic BALB/c mice produced antibody after infection with R. akari, R. conorii, and R. typhi as measured by indirect fluorescent antibody titration or radioimmunoassay. Antibody production in these mice was a great or greater than in the thymus-bearing mice and demonstrated similar kinetics. In contrast, athymic BALB/c mice infected either intraperitoneally or subcutaneously with the Gilliam strain of R. tsutsugamushi failed to produce demonstrable antibody. The requirement of thymus-dependent lymphocytes for antibody production to R. tsutsugamushi was further suggested by the demonstration of antibody production after transfer of immune thymus-dependent lymphocytes to athymic mice and the demonstration of R. tsutsugamushi-specific T helper cells in immune thymus-bearing mice. The antibody produced in athymic mice after infection with R. akari, R. conorii, and R. typhi was predominantly immunoglobulin M, based on isotype-specific radioimmunoassays and sucrose gradient fractionation. Furthermore, the antibody produced by athymic mice in response to R. akari infection reacted with a carbohydrate-containing outer membrane component.

Animals↗
PubMed1983

Association of an inflammatory I region-associated antigen-positive macrophage influx and genetic resistance of inbred mice to Rickettsia tsutsugamushi.

Strains of C3H mice differing in susceptibility to intraperitoneal infection with the Gilliam strain of Rickettsia tsutsugamushi were used to investigate the role of the I region-associated (Ia) antigen-bearing macrophage in the genetic resistance of mice to this organism. Resistant mice (C3H/RV) were found to produce a quantitatively greater Ia antigen-positive macrophage response after infection compared to mice (C3H/HeDub) which underwent a lethal infection. The macrophage influx produced in response to infection of the C3H/HeDub mice was deficient in Ia antigen-bearing cells, as evaluated by antigen presentation function and by the use of macrophages as stimulator cells in a mixed lymphocyte response. The resistance to infection, as well as the Ia-positive macrophage response in C3H/RV mice, was sensitive to 450 to 600 rads of irradiation. C3H/HeDub mice produced exudates rich in Ia-positive macrophages if stimulated with concanavalin A or after challenge with R. tsutsugamushi (if previously immunized), ruling out an innate inability of this strain of mice to produce Ia-positive macrophages exudates. Challenge of either strain of mice immunized by a prior subcutaneous infection resulted in a rapid (3 to 5 days) peak of Ia-positive macrophages responding to the peritoneal cavity. It also was noted that subcutaneous infection alone resulted in an increase in the proportion and number of "resident" macrophages which were Ia positive. These data suggest that the macrophage influx in terms of Ia-bearing cells is at least associated with the genetic resistance of C3H/RV mice to infection with this rickettsiae and may play a role in resistance. Furthermore, it would appear that the Ia-positive macrophage is a factor in acquired immunological resistance to reinfection.

Animals↗
PubMed1984

Gamma interferon production in response to homologous and heterologous strain antigens in mice chronically infected with Rickettsia tsutsugamushi.

The ability of antigen-responsive, thymus-derived lymphocytes to produce immune (gamma) interferon was investigated during the development and expression of cellular immunity to Rickettsia tsutsugamushi. C3H/HeDub mice infected subcutaneously with the Gilliam strain developed the ability to produce serum interferon in response to intravenously inoculated antigen which correlated with the development of resistance to intraperitoneal rechallenge. Antigen-responsive lymphocytes, measured by interferon production and proliferation, were first apparent in draining lymph node cells, but spleen cell responses were detectable relatively soon after the appearance of reactive lymph node cells. The peak spleen cell response was of a greater magnitude and was found to be relatively long-lived. Reactivity to heterologous strains of R. tsutsugamushi also developed after immunization and paralleled the homologous responses, although reactivity was greatest to homologous antigens. Responses to heterologous strains differed in magnitude and time of appearances; however, immune mice resisted challenge with all strains of R. tsutsugamushi tested.

Animals↗