Susumu Ukae

Members of the Family Caliciviridae (Norwalk Virus and Sapporo Virus) Are the Most Prevalent Cause of Gastroenteritis Outbreaks among Infants in Japan

Norwalk virus (NV) and Sapporo virus (SV) were approved as type species of the genus Norwalk-like viruses and the genus Sapporo-like viruses, respectively, within the family Caliciviridae. To clarify the importance of NV and SV as causes of gastroenteritis outbreaks in infants, stool samples obtained from 36 outbreaks of nonbacterial gastroenteritis that occurred during 1976-1995 in an infant home in Sapporo, Japan, were examined for diarrhea viruses using electron microscopy, enzyme immunoassays, reverse transcriptase-polymerase chain reaction (PCR), and sequencing of the PCR products. NV and SV were associated with 15 (42%) of the 36 outbreaks and were more prevalent than rotavirus (RV) A, which was associated with 10 (28%) of the 36 outbreaks. Our data indicate that NV and SV were the most common cause of outbreaks of viral gastroenteritis in infants and were indeed more prevalent than RV-A in Sapporo, Japan, during 1976-1995.

Epidemiological study of the G serotype distribution of group A rotaviruses in Kenya from 1991 to 1994.

An epidemiological study on the G serotype distribution of group A rotaviruses (GARV) isolated in Kenya was carried out in one urban hospital in Nairobi and in two rural hospitals in Nanyuki and Kitui to clarify the prevalent G serotypes before future introduction of the ready licensed rotavirus vaccine in Kenya. A total of 1,431 stool specimens were collected from children, who were mainly outpatients, aged from 0 to 6 years old with acute gastroenteritis from August 1991 to July 1994. Samples positive for GARV by conventional ELISA were then analyzed by subgrouping and serotyping ELISA and by PAGE. To ascertain the G serotypes of viruses in samples that were unable to be typed by serotyping ELISA, polymerase chain reaction was also attempted. The prevalence of GARV was 28.4% in the urban hospital, 22.5% in Nanyuki, and 13.7% in Kitui. Among rotavirus‐positive samples, subgroup II rotaviruses were detected in 63.1%, and subgroup I rotaviruses were 25.9%. Serotype G4 was most prevalent, accounting for 41.6% followed by 23.3% of serotype G1, 17.0% of serotype G2, and serotype G3 was rarely isolated. Seven strains of serotype G8/P1B rotavirus was detected for the first time in Kenya by RT‐PCR. Eleven specimens with an unusual composition of subgroup, serotype, and electropherotype were atypical GARV in which the P‐serotype was P1A, P1B, or P2. Although uncommon GARV serotype G8/P1B and atypical GARV were detected, the four major GARV serotypes, G1 through G4, should be targeted at this moment for vaccination to control this diarrheal disease in Kenya. Continuous monitoring of the G‐ and P‐serotype distribution of GARV should provide important information about the impact of rotavirus vaccination in Kenya. J. Med. Virol. 58:296–303, 1999.

Comparison of an Immunochromatography Test with Multiplex Reverse Transcription-PCR for Rapid Diagnosis of Respiratory Syncytial Virus Infections

ABSTRACT A new commercial rapid 10-min one-step immunochromatography (IC) test, SAS RSV test, was compared to another IC test, Directigen EZ RSV, employing RT-PCR as the “gold standard” for detecting respiratory syncytial virus. Of 102 clinical samples, 79 were positive by RT-PCR, 66 (82.5%) were positive with the SAS RSV test, and 55 (69.6%) were positive with Directigen EZ RSV. The specificity of the new test was 91.3% (21 of 23), similar to that of Directigen EZ RSV (100% [23 of 23]). This test performs well enough to be used for patient care.

Efficacy and safety of pentavalent rotavirus vaccine in Japan: A randomized, double-blind, placebo-controlled, multicenter trial

Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; p < 0.001)], moderate-to-severe [80.2% (95% CI: 47.4%, 94.1%)], and severe [100% (95% CI: 55.4%, 100%)] RVGE caused by viruses with serotypes contained in the vaccine. The observed cases of RVGE included rotavirus types G1 (n = 19), G3 (n = 9), G9 (n = 5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

Efficacy of rhesus rotavirus vaccine MMU-18006 against gastroenteritis due to serotype 1 rotavirus.

We conducted a clinical trial of rhesus rotavirus vaccine MMU-18006 (RRV, serotype 3) to assess the immunogenicity, transmissibility and booster effect of this vaccine in a welfare nursery in Sapporo, from September 1986 to October 1988. After the trial, in March 1989, an outbreak of gastroenteritis due to a wild strain of serotype 1 rotavirus (RV-1) occurred in the study population. Infants were divided into three groups based on vaccination history: five booster vaccinees, 18 one-dose vaccinees and 18 control infants who did not receive vaccine. There was a significant relationship between asymptomatic infection and higher levels of preoutbreak antibody titres against KU (serotype 1) but not RRV. Significant protection from rotavirus illness was observed both in the booster vaccine group and in the one-dose vaccine group but not in the control group. Rotavirus-specific serum IgA immune response was considered to be one of the indicators of recent rotavirus infection, and did not correlate with resistance to rotavirus illness. Our results revealed that protection from rotavirus illness was serotype-specific and that previous rotavirus infection, including vaccination, was important to induce the heterotypic immune response, and that ageing or booster inoculation of RRV might play a role in the protection against serotype 1 rotavirus infection. From our findings, a booster administration was thought to be important to induce effective heterotypic immunity and should be included in a future rotavirus vaccine trial to obtain sufficient protection against four major serotypes of rotavirus.

Preschool sarcoidosis manifesting as juvenile rheumatoid arthritis: A case report and a review of the literature of Japanese cases

Nine Japanese cases of sarcoidosis in children of 4 years of age or younger have been reported in the literature, including the case presented here. Clinically, preschool sarcoidosis is distinctly different from that of older children; it is characterized by a triad of skin, joint and eye lesions without pulmonary involvement. It is easily confused with juvenile rheumatoid arthritis which also presents the symptoms of arthritis and uveitis. We report on a patient with preschool sarcoidosis who was initially diagnosed as having juvenile rheumatoid arthritis. We recommend prompt skin biopsy to differentiate between these conditions.

Outbreaks of nosocomial rotavirus gastro-enteritis in a paediatric ward.

Faecal samples were collected from patients with gastro-enteritis during two winter seasons on a paediatric ward. Three outbreaks of nosocomial rotavirus gastro-enteritis were identified by latex agglutination and the virus strains were characterized by polyacrylamide gel electrophoresis of the genome nucleic acid and by subgrouping and serotyping enzyme-linked immunosorbent assays (ELISA). One outbreak was caused by serotype 1 rotavirus, one by serotype 2 and the remaining outbreak was caused by a mixture of serotypes 1 and 4. Identical electrophoretic patterns of the rotavirus genome in each outbreak combined with the ELISA results indicate that these three outbreaks were hospital-acquired cases. The index cases in the three outbreaks were community-acquired and one of two index cases in the second outbreak was hospital-acquired. On each occasion, susceptible roommates were easily infected from the index cases and then cross-infection occurred in the paediatric ward. Possible vehicles were the medical staff, especially doctors, parents of infected patients and infected patients who were moved to other rooms. One patient who had been treated with a series of antitumour therapies excreted rotaviruses in faeces for a long time period and probably played a role as a source.of the outbreak. Moreover, some patients still excreted rotaviruses in their normal stool 1 week after recovery from gastro-enteritis. These findings indicate that continual examination of stool samples for rotaviruses until they are negative may be important to prevent the spread of rotavirus infection.

Therapeutic effect of clarithromycin for respiratory-tract infections in children caused by Chlamydia pneumoniae

Children infected with Chlamydia pneumoniae sometimes experience lower respiratory tract infections such as pneumonia and bronchitis. Although numerous anti-microbial compounds have been reported to be active against the organism, most of them have not been in a clinical trial in infants and children with C. pneumoniae infection. Clarithromycin has been shown to express anti-chlamydial effects in vitro. In this study, we evaluated the clinical anti-C. pneumoniae properties of clarithromycin in children with mainly lower respiratory tract infection. We administered clarithromycin orally to 21 infants and children at a dose of 10-15 mg/kg/day divided into two or three doses for 4-21 days. Clinical symptoms, roentgenographic and laboratory abnormal findings improved. The overall clinical efficacy rate was 85.7% (18 of 21 cases). Administration of clarithromycin was considered to be a suitable treatment for improving lower respiratory infections in infants and children caused by C. pneumoniae.