We experienced 5 cases of tsutusgamushi disease from October to November 1993 at Hokusyo Central Hospital.
All patients showed high fever, skin rash and eschar and four patients showed lymphnode swelling. All cases were diagnosed serologically by indirect-immunofluorescense technique and treated with minocycline.
In a survey of and-Karp, Kato, Gilliam, Kawasaki, Kuroki antibodies, all patients showed the highest antibody titers against the Kawasaki strain and they were considered Kawasaki type.
In Nagasaki Prefecture, the number of patients with tsutsugamushi disease has been increasing since 1982. We carried out immunologic and epidemiologic studies about this disease in Nagasaki Prefecture.

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From January to December in 1992, an epidemic of aseptic meningitis occurred in Gifu Prefecture in children. Epidemiological, virological and serological investigations were performed. The results are as follows:
1) Cases involved ranged from 0 to 15 years of age, and 75.9% of them were in the 3 to 7 year of age group.
2) Six types of viruses were isolated from 73 of 108 cases (67.6%), and the Echovirus 6 was recovered from 68 cases (93.2%).
3) In 1992 by the cross neutralizing test between the prototype and isolated strains of Echovirus 6, a remarkable antigenic variation was not found.
4) In serological studies, the positive rates of neutralizing antibodies to Echovirus 6 in infant sera aged 0-9 years in 1992-1993, was 41.1%. The highest positive rates of antibodies was in the 5 year age group.

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We analysed 467 isolates of Vibrio parahaemolyticus for possession of tdh/trh gene in comparison with urease production and serotypes. Strains possessing tdh⁺/trh^-, tdh⁺/trh⁺, tdh^-/trh^-, and tdh^-/trh^- show positive urease production 2.1, 100, 65.7, 100%, respectively. Serotypes of O1: K69, O3: K6, O3: K72, 06: K18, O6: K46 and O1: KUT were frequently positive (100% except 91.7% of the latest one) in urease production. All isolates of O3: K6 prossessed trh, whereas all isolates of certain serotypes including O1: K69 and O3: K72 possessed both trh and trh and tdh genes. Among these, most of O1: K69 and 03: K72 were urease producer. From these results, we speculate that urease prodution is closely related to the presence of the trh gene or/and lesser production of TDH. We also found the new combination of serovar, O3: K25, O4: K37 and O13: K72 in Kanagawa phenomenon-positive strains.

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An ascending urinary tract infection was induced by transurethral instillation of Escherichia coli mice which had an impaired T cell function from the administration of cyclosporine (impaired T cell function group). We investigated the time course fluctuation of local immune response at the infected sites in terms of immune response cells as compared with that in normal mice (control group). 100 mg/kg of Cyclosporine was administered a total of 4 times at 7, 5, 3 days and 1 day before the day of infection. Using this method of administration, the T cell function, for which we used delayed type hypersensitivity as an indicator, significantly suppressed the impaired T cell function group.
When the ascending urinary tract infection was induced by Escherichia coli, the occurrence of pyelonephritis increased and the survival rate significantly decreased in the impaired T cell function group compared to the control group, indicating a high incidence of infection.
By the time course observation of the immune response cells at the infected sites, marked infiltration of neutrophils was recognized in the impaired T cell function group as compared withthat in the control group and such infiltration remained on the same higher level thereafter. On the other hand, T, B cell infiltration was weaker in the impaired T cell function group compared to the control group.
It was therefore suggested that other immune response cells compensated for the infiltration of T cells when their function was suppressed, and that these cells on the whole possibly responded toward the preservation of their protective mechanisim against infection.

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We described three septicemia cases in which blood cultures yielded gram-positive cocci identified as Leuconostoc spp. and Pediococcus spp. Patients were three male adults aged 63 to 71 years with severe underlying diseases, pancreatic cancer, esophageal cancer and diabetes mellitus with chronic renal failure. They had fever and chills at the onsets of septicemia with acute obstructive suppurative cholangitis, acute pneumonia, and infection complicated with invasion sites of esophageal cancer contagious to bronchus and subcutaneous tissue. Blood cultures yielded catalase and oxidase negative highly vancomycin-resistant (MIC: 1024 μg/ml<) grampositive cocci showing α or γ hemolysis on blood agar plates. Two cases were polymicrobial infections. In one case with esophageal cancer, clinical symptons persisted after the start of antimicrobial chemotherapy and the patient died 10 days later associated with complications of esophageal cancer. Leuconostoc lactis, Leuconostoc mesenteroides subsp. dextranicum, and Pediococcus acidilactici wee identified by physiological reactions. These strains were also highly resistant to teicoplanin and fosfomycin, and tolerant to all rested β-lactams such as benzylpenicillin. This is the first report in Japan to our knowledge on the identification of Leuconostoc spp. and Pediococcus spp. isolated from human infectious diseases.

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The efficacy of KRN8601 for neutropenia associated with HIV infection was evaluated in 24 patients.
KRN8601 was infused intravenously at a dosage of 200μg/m² for 14 consecutive days. Neutrophil counts recovered in 19 (90.5%) out of 21 evaluable patients by KRN8601 treatment. The concomitant myelosuppressive agents for the treatment of HIV infection and complications could be continued without dose reduction in 15 (88.2%) out of 17 patients.The clinical improvement was observed in 66.7%(12/18) of patients who were treated with anti-mycrobial agents for opportunistic infections which indicates that KRN8601 shows an additive effect on infections when it was given with anti-mycrobial agents.Adverse events and abnormal laboratory findings were observed in 3 and 7 patients, respectively, and they were reversible and tolerable.This study demonstrated that KRN8601 improved neutropenia with HIV infection, made possible to continue the full dose of myelosuppressive treatments and have additive effect on the treatment of secondary infections.

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Ten to forty percent of the patients with acquired immunodeficiency syndrome (AIDS) develop sight-or life-threatening cytomegalovirus (CMV) infections. In some patients with AIDS, CMV is detected in the bronchoalveolar lavage fluid (BALF), urine, and other specimens, even when there are no symptoms of CMV disease. An indicator of active CMV infection is needed to facilitate the diagnosis of CMV disease in patients with AIDS or HIV infection and the evaluation of the efficacy of subsequent treatment.
The present study was conducted during the period from 1993 to 1994. The subjects consisted of three patients with AIDS and a confirmed diagnosis of CMV disease (one case of retinitis, one case of gastrointestinal disease and one case of pneumonia), and five HIV-positive patients in whom CMV associated disease was ruled out. Those patients were monitored occasionally for the following parameters of active CMV infection and disease: expression of CMV antigen in the nucleus of polymorphonuclear leukocyte (CMV antigenemia), as it was determined with a monoclonal antibody against a lower matrix protein (p65); infectious CMV detected by shell vial method; CMV DNA detected by PCR; anti-CMV antibody titer; and histological findings.
CMV p65 antigen was detected in the leukocytes of both the peripheral blood and BALF during the early phase of CMV disease in three out of three cases of the CMV disease group, and this antigen became negative in two out of two cases who responded to the therapy. All the five patients in the CMV-related-disese-negative group were negative for CMV antigenemia. By shell vial test, the urine or ascites was positive for CMV in two patients in the acute phase. PCR applied to the BALF and pulmonary tissue of the patient with pneumonia revealed the presence of CMV DNA both before and after the combined therapy of ganciclovir and foscarnet. These results did not correlate with the histological findings.
CMV antigen detection is useful for rapid diagnosis and monitoring of CMV diseases in AIDS.

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A case of streptococcal toxic shock-like syndrome in a previously healthy, 57 year old Japanese female has been reported. Initially, she had a sore thoat and low grade fever for 5 days. Because of sudden severe pain on the extremites and erythema on bilateral forearms, she was hospitalized. On admission, her conciousness was clear. Although profound hypotension, anuria and prolonged blood coagulation were observed. Antibiotics, fluid therapy and dopamine were given. Four hours after admission, she died in spite of resuscitation efforts, by sudden cardiac arrest. Streptococcus pyogenes was isolated in her blood. At the same time as when she died, three of the five people of the patient's family living with her, had pharingitis or pneumonia. From the pharynxs of the three people with pharingitis, Streptococcus pyogenes was also isolated. The serotype of all organisms was Til, and they produced exotoxintype B in vitro. This case suggests that infection of Streptococcus pyogenes is not essential for the development of toxic shock-like syndrome.

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An unusual case of a 67-year-old man is reported with fulminant pneumococcal sepsis. Hehad been healthy before, and the identified predisposing factors were only that he was a chronic alcohol drinker and was a HCV carrier. He presented signs of acute renal failure, liver dysfunction, adult respiratory distress syndrome and disseminated intravascular coagulation. Subsequently purpura fulminans (symmetrical peripheral gangrene) with major extremity involvement developed. He finally survived with amputation of both legs, right forearm and two fingers of left hand.
Purpura fulminans is a rare catastophic disease, with initial hemorrhagic skin lesions that progress to gangrene. It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults with predisposing factors such as alcoholic, asplenia, AIDS and so on. In adults, pneumococcus and meningococcus are microorganisms that have been reported most frequently as caused agents in Europe and America. But in Japan the previously reported adult case was the only one complicating Xanthomonas maltophilia sepsis, and none accompanying pneumococcal sepsis.
Congenital protein C deficiency is recognized to be able to cause purpura fulminans especially in patients with risk factors. In our case, protein C antigen was decreased in the acute stage but gradually increased later toward normal, so this decrease was thought to be concomitant with the initial disseminated intravascular coagulation rather than compatible with protein C deficiency.

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[in Japanese]

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