We have experienced an outbreak of dysentery in Nagasaki. Shigella sonnei were positively cultured from 467 patients out of suspected 821 cases, and 346 patients were admitted. 121 patients were treated with oral antimicrobials in the outpatient clinic. Five patients were diagnosed as secondary infection. We treated a total of 96 patients in Nagasaki Municipal Medical Center, and studied the clinical and bacterial features in these 96 patients. Chief complaints included fever, abdominal pain and diarrhea. Most diarrheal patients showed waterly diarrhea and only a few were bloody (3 of 47). Treatment of levofloxacine 300mg a day for 5 days successfully eliminated S. sonnei from all culture positive patients. An environmental surveillance revealed that water in a well at the university to which many patients were using was the origin of the infection with positive cultures of S. sonnei. No difference between the clinical and environmental isolates was observed in results on biochemical, serological and enzymatic tests. All isolates were susceptible to levofloxacin and to ofloxacin, but three isolates showed resistance to fosfomycin with MIC above 64μg/ml. In analysis of pulsed-field gel electrophoresis, both clinical and environmental isolates were considered to be closely related.
MMR (measles-mumps-rubella) immunization in Japan was suspended in 1993 due to the high incidence of mumps meningitis as a complication. As a result, immunization coverage for rubella still remains at the 50-60% level in Japan. One way to increase the coverage rate is to increase the frequency of immunization. We calculated the predicted positivity rate of the antibody and cost and the benefits is three models of double vaccination, i. e., vaccination twice. The first model consists of simply two identical vaccinations. The second model consists of two vaccinations with mass vaccination at school for the second immunization. The third model consists of two vaccinations with screening of the urinary antibody for rubella in the second immunization. To calculate the predicted values we used coefficients from Ibara City. The predicted positivity rates and cost increases ranged from 60% to 90% and from 7.3 billion to 12.8 billion yen from the first to third models, respectively. Screening for the urinary antibody should be much cheaper than the presumed price because more than a million subjects will be screened. Since it would cost less than half the price, the third model should be best for the positivity rate of the antibydy and cost and benefits. Therefore, we think that third model is the best correction until MMR immunization can be reintroduced.
To compare the morphology among Chlamydia pneumoniae (C. pneumoniae), strain TW183 and strains which were isolated in the area of Kasumigaura, Ibaraki from 1992 to 1995. C. pneumoniae were infected on HL cell monolayers and cultured in 5% CO2 at 35.5°C for about 60 hrs. The cells were harvested and fixed with 2.5% glutaraldehyde, and then the regular procedure for observation of Chlamydia in inclusion by transmission electron microscope was performed. Immunoblot assay was carried out by using highly and partially purified C. pneumoniae TW183 and 4 isolates with partial purification as antigens. The results were as follows: the shape of TW 183 and the isolates included pear and round shapes, respectively. Immunoblotting profiles were the same in terms of bandformation patterns with the serum from a patient infected with C. pneumoniae. These results may indicate that the round shape of C. pneumoniae elementary body (EB) is predominantly pandemic in Japan, although pear-shaped EBs of C. pneumoniae were found in the neighboring prefecture of Chiba.
First, four disinfectants were tested for virucidal activity on viruses coated upon materials. Disinfectants of the aldehyde and halogen groups had a destructive effect on both enveloped and nonenveloped DNA and RNA viruses coated on a cotton guaze, stainless chips, wood shavings, polyplopylene resin chips and latex resin chips, respectively. Disinfectant of the biguanide group had a virucidal activity on both enveloped DNA and RNA viruses. Secondaly, five disinfectants were tested for the durability of their virucidal activity on two DNA and RNA viruses after preparing working solutions. The disinfectants of the aldehyde group maintained their virucidal efficiency for 2 to 3 days. Disinfectants of the invert and amphoteric soap groups, the biguanide group and the halogen group maintained their virucidal efficiency for 1 to 2 days. In the presence of bovine serum, the virucidal activity of the aldehyde group and the halogen group were not influenced but that of the invert and amphoteric soap groups were strongly influenced and lost their effect.
The DirectigenTM Flu A+B kit, a rapid diagnostic device for influenza virus A and B was evaluated. The nasopharyngeal aspirates were obtained from 239 patients who visited our hospital, between January and March, 2000, presenting flu-like symptoms. Influenza virus AH1: 77 and AH3: 51 were isolated from 128 specimens and none from 111 specimens. DirectigenTM Flu A+B showed 115 specimens positive and 106 specimens negative. The sensitivity and specificity of this kit were 89.8% (115/128) and 95.5% (106/111) compared with viral isolation. Agreement on positive and negative interpretations between DirectigenTM Flu A and this kit was 97.9% (234/239). In the evaluation of this kit for influenza B virus, 60 frozen nasopharyngeal aspirates collected from February to April, 1999 were used. The sensitivity and specificity of this kit were 88.9% (16/18) and 88.1% (37/42) compared with viral isolation. Agreement on positive and negative interpretations between FLU OIA® and this kit was 91.7% (55/60). The DirectigenTM A+B demonstrated sensitivity and specificity equivalent to the conventional kits in nasopharingeal aspirates. This kit can also differentiate influenza A and B viruses, a feature which is useful for treatment using anti-viral agents such as amantadine and neuraminidase inhibitor. To date, the kit is the most effective tool for the rapid diagnosis of influenza.
Sensitivity and specificity of the DirectigenTM Flu A+B kit, a rapid test for influenza virus A and B, were evaluated. This test detects influenza A and B viruses separately by EIA. Reactivity of the kit was tested using a total of 23 isolates: 13 isolates of human influenza virus A (H1N1, H3N2) and 10 isolates of human influenza virus B. All of the isolates were tested positive and no difference in reactivity was found in antigenic variables and subtypes. The kit was only reactive to influenza virus A and B, not reactive to other viruses. Typical influenza A and B strains were tested for detection limit. 7.8×103pfu/ml was a detection limit for influenza virus A (H1N1: Beijing/262/95), 4.7×104pfu/ml for influenza virus A (H3N2: Kitakyusyu/159/93), and 3.1×104pfu/ml for influenza virus B (Guangdong/05/94). The DirectigenTM Flu A+B kit was a easy-to-use, rapid detection device and the kit has sensitivity and specificity equivalent to other diagnostic devices, suggesting the kit are useful in medical institutions.
We conducted the placebo-controlled double-blind multicenter Phase III trial of newly developped selective oral neuraminidase inhibitor, oseltamivir phosphate (Ro 64-0796), in order to evaluate the efficacy and safety, when Ro64-0796 was administered orally to both type A and type B influenzavirus infected patients. Patients were randomly assigned to either Ro64-0796 75mg twice daily group or matching placebo group for five days. A total of 316 patients (Ro64-0796 group; 154 and placebo group; 162) were recruited, and intent-to-treat infected population, which was defined as the patients that study drug was administered one or more and laboratory-confirmed influenzavirus infection was demonstrated, were 122 and 130, respectively. Ro64-0796 decreased significantly median viral titers after 72 hours (p=0.0009, Analysis of covariance), indicating the rapid inhibition of virus replication, and duration of illness which was primary variable of efficacy, was reduced statistically significant by one day (23.3hours) (p=0.0216, generalized Wilcoxon test). Ro64-0796 treatment also resulted in the reduction of the fever duration and severity of clinical symptoms. Concerning the safety evaluation, the main accompanied symptoms with Ro64-0796 application were gastrointestinal disorders such as bellyache, nausea and vomiting. Most of these events were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our data suggests that Ro64-0796 is useful in treating the acute influenzavirus infection.
We have investigated the long-term prophylactic efficacy and safety of oseltamivir phosphate (Ro64-0796), an orally bioavailable prodrug of novel, potent and selective type A and type B influenzavirus neuraminidase inhibitor, when Ro64-0796 was administered orally to the healthy volunteers. Partcipants older than 16 year-old were randomly assigned to either Ro64-0796 75mg once daily group or matching placebo group for six weeks. A total of 308 participants (Placebo group; 153 and Ro64-0796 group; 155) were enrolled in this trial. The primary variable of efficacy, incidence of laboratory-confirmed influenzavirus infected subjects accompanied by both fever of 37.5°C or higher and at least two influenza symptoms (group 1) were 1.3% in Ro64-0796 group in contrast with 8.5% in placebo group, inducing 85% inhibition of infection (p=0.00323, Fisher's exact test). As secondary variable, incidence of laboratory-confirmed influenzavirus infected subjects who lack either fever (37.5°C or higher) or at least two influenza symptoms (group 2) and incidence of asymptomatic infected subjects (group 3) were tend to decrease in Ro64-0796 group, and finally cumulative inhibition rate was 76% in group 1+2 combined (p=0.000891, Fisher's exact test), and 63% in group 1+2+3 combined (p=0.002150, Fisher's exact test). As for the safety evaluations, Ro64-0796 was well tolerated but was associated with gastrointestinal disorders such as nausea and vomiting which were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our results demonstrate that oseltamivir is safe and effective for the prevention of influenza.
We report here two cases of HIV infection with a borderline personality disorder. Case 1 was a 25-year-old male patient who was diagnosed with HIV infection 4 years ago. Borderline personality disorder was also diagnosed at that time. Although he was referred to our hospital in 1999, we had to refer him to another hospital for his regular outpatient hemodialysis. Case 2 was a 24-year-old male patient who had borderline personality disorder since 1996. He was diagnosed with HIV infection in 1999 and referred to our hospital. Be ignored rules in visiting clinics such as prior reservations and frequently called doctors, case-workers and nurses. After several visit he intentionally took excessive sedative medicines and called a case-worker at our hospital. Be was admitted to our hospital for three days. After he was discharged, we set limitations for his behavior not to harm himself and to obey the rules in visiting clinics. In other countries investigators report that borderline personality disorder is more common in HIV-infected persons. It may be because persons with borderline personality disorder are more likely to engage in high-risk sexual behavior, which is also applicable to these two cases. As HIV infection is rapidly prevailing in Japan, it is possible that the chance are that this disoder will be seen more frequently in HIV infected cases.
On Aug. 3, 1999, a 73-year-old male was admitted to our hospital with the chief complaint of pain in the neck, high fever, and numbness in the arm. MRI of the cervix showed high intensity at the C3/C4 disc space. Laboratory data showed several signs of inflammation. Haemophilus aphrophilus was detected from the specimen of the disc space, and the diagnosis of pyogenic vertebral osteomyelitis caused by H. aphrophilus was made. After the identification of H. aphrophilus, antibiotic therapy with Cefotiam (2g/day) was given but his vertebral collapsed. Surgical treatment consisted of curettage and anterior spinal body fusion using the iliac bone, was performed on his 23rd hospital day, successfully. The antibiotic therapy of Cefazolin (2g/day) was continued for the first 3 days, followed by Cefotiam (2g/day) and later Levofloxacin (300mg/day). The patient was discharged on the 88th hospital day. The origin of infecting H. aphrophilus in this patient was not clear, but oral source was suspected. We reported the first case of pyogenic vertebral osteomyelitis caused by H. aphrophilus in Japan.