Prospective surveillance for atypical pathogens in children with community-acquired pneumonia in Japan.

A total of 141 children with community-acquired pneumonia (CAP) were studied prospectively to determine the causative microorganisms. Microbial investigations included examination of postnasal swabs, cultures, polymerase chain reaction (PCR), and serology. The atypical pathogens occurring most frequently were Mycoplasma pneumoniae (58 patients [41.1%]), Chlamydia pneumoniae (4 patients [2.8%]), and concurrent occurrence of both pathogens (1 patient [0.7%]). Patients aged under 4 years showed a relatively lower rate of atypical bacterial etiology compared with those aged 4 years or older. Major bacterial pathogens were detected in 89 patients (atypical pathogens were detected in 28 patients simultaneously), including Streptococcus pneumoniae in 34 patients, Haemophilus influenzae in 60, Moraxella catarrhalis in 48, and multiple pathogens in 42. In patients suspected of having atypical pneumonia, macrolides are recommended.

Mass vaccination of schoolchildren against influenza and its impact on the influenza-associated mortality rate among children in Japan.

BACKGROUND: Influenza control based on mass vaccination of schoolchildren was implemented in Japan in the 1960s and was associated with a decrease in the overall mortality rate. The program was discontinued in 1994. The discontinuation was followed by a seasonal increase in the mortality rate. Lately, young children and elderly persons have been receiving influenza vaccines. The purpose of this study was to investigate changes in influenza-related mortality among young children before and after discontinuation of mass vaccination of schoolchildren. METHODS: We calculated the monthly all-cause mortality rates during 1972-2003 and the pneumonia and influenza (P&I) mortality rates during 1972-1999 for young children (age, 1-4 years). We estimated the excess mortality rates attributable to influenza by computing the baseline annual mortality rate as a centered, 3-year moving average of the number of deaths reported during the 2 preceding and the following Decembers. RESULTS: Prominent winter peaks in monthly all-cause mortality rates among young children occurred in the 1990s. They coincided with the winter peaks in monthly P&I mortality rates among young children and were very similar to the winter peaks observed among elderly persons. The number of excess deaths of young children was estimated to be 783 in the 11 winter seasons from 1990 to 2000, whereas no winter peaks in the number of deaths were seen after 2000. CONCLUSIONS: It is likely that discontinuation of mass vaccination of schoolchildren was responsible for the increase in influenza-associated deaths among young children in the 1990s. The recent increase in influenza vaccinations among young children, together with the routine therapeutic use of neuraminidase inhibitors, has led to a decrease in the influenza-associated mortality rate.

[Evaluation of flow-through immunoassay for rapid detection of influenza A and B viruses].

We evaluated a flow-through immunoassay for rapid detection of influenza A and B viral antigens, RapidTesta FLU AB (Daiichi Pure Chemicals Co., Ltd., Tokyo, Japan), by using 507 specimens collected from patients with influenza-like symptoms during the 2002/2003 influenza season in Japan. The specimens consisted of 239 nasal swabs and 268 nasal aspirates; 374 specimens were collected from pediatric patients (under 16 years of age) and 133 from adult patients. RapidTesta FLU AB was compared with cell culture and nested reverse transcription-polymerase chain reaction (RT-PCR). Cell culture detected influenza virus from 66.7% of the 507 specimens (influenza AH3: 44.0%, B: 22.7%). For nasal swabs, it had a sensitivity of 81.9% (77/94), a specificity of 97.9% (142/145) and an efficiency of 91.6% (219/239) for influenza A virus as well as a sensitivity of 80.0% (52/65), a specificity of 98.3% (171/174) and an efficiency of 93.3% (223/239) for influenza B. For nasal aspirates, RapidTesta FLU AB had a sensitivity of 83.2% (109/131), a specificity of 98.5% (135/137) and an efficiency of 91.0% (244/268) for influenza A as well as a sensitivity of 82.7% (43/52), a specificity of 97.7% (211/216) and an efficiency of 94.8% (254/268) for influenza B. RapidTesta FLU AB is characterized by high specificity, low false positive rate, and 10-minute detection of influenza virus. These advantages suggest that RapidTesta FLU AB is a useful kit to assist physicians in making a diagnosis of influenza on candidates for antiviral therapy.

[Evaluation of an immunochromatography test using enzyme immunoassay for rapid detection of influenza A and B viruses].

We evaluated the performance of an improved version of Espline Influenza A & B-N (Fujirebio Inc., Japan), an immunochromatography test using enzyme immunoassay for rapid diagnosis of influenza A and B. The test produced positive results for four strains of influenza viruses and thirty-one influenza viral antigens and negative results for all of thirty strains of other respiratory viruses that were tested. The detection limit of this test was 5.8 x 10(2) to 5.8 x 10(3) pfu/assay, which is more sensitive than the old version of Espline. Furthermore, 715 respiratory specimens collected from the patients (children, 79.4%; adults, 18.5%; unknown, 2.1%) with influenza-like illnesses during the 2002/2003 influenza season in Japan were tested as part of a clinical evaluation of this test. The relative performance of this test compared to cell culture and nested RT-PCR results were examined. In the cell cultures, influenza viruses were detected in 488 of the 715 specimens (overall, 68.3%; AH3, 41.7%; B, 26.4%; AH3 and B, 0.1%). For influenza A, the sensitivity of this test was 95.4% (125/131) for nasal aspirates, 96.8% (92/95) for nasal swabs, and 85.1% (63/74) for throat swabs. For influenza B, the sensitivity of this test was 91.2% (52/57) for nasal aspirates, 88.1% (59/67) for nasal swabs, and 71.6% (48/67) for throat swabs. The new test exhibited a remarkably higher sensitivity to influenza A in throat swabs than the old version of Espline. Only two false positive results were obtained out of a total of 223 virus negative specimens; the specificity of the test was 100% (88/88) for nasal aspirates, 97.6% (81/83) for nasal swabs, and 100% (52/52) for throat swabs. We conclude that the new Espline Influenza A&B-N rapid diagnostic test is easy to use and has a high sensitivity and specificity, especially for influenza A.

[Effect of post-exposure prophylaxis with oseltamivir for those in contacts with influenza patients in pediatric wards].

During the influenza season, outbreaks of influenza may occur in the pediatric wards due to spread from the patients hospitalized with influenza, or from those hospitalized during the latency period and develop influenza afterwards. Post-exposure prophylaxis with neuraminidase inhibitors has been reported to be effective in preventing outbreaks among household members and nursing home residents. However, for nosocomial spread, its effectiveness and possible adverse effects are to be determined. During the 2002/2003 influenza season, we experienced a total of 3 nosocomial outbreaks of influenza in the pediatric wards in two hospitals in the Kanto district, Japan. Since the number of contacts who developed influenza had been increasing despite the isolation precaution implemented, post-exposure prophylaxis with oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, once a day for 7-10 days) was implemented with a permission from the parents to terminate the outbreaks. In the outbreaks (one with influenza A, two with influenza B), a total of 29 inpatients had contact with influenza patients: among those 29, 13 were given post-exposure prophylaxis, 16 were not. Out of 16 patients who did not receive post-exposure prophylaxis, 11 (69%) developed influenza: out of 13 with post-exposure prophylaxis, none developed influenza. Those patients who developed influenza were given oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, twice a day for 5 days) and accommodated in a private room or a room with other patients with influenza of the same type. No significant adverse effects due to oseltamivir were observed among those who were enrolled in this study.

[Amantadine].

Amantadine is the first antiviral drug for human which was developed by duPont chemical company in 1964. Amantadine causes a selective, dose-related effectiveness of type A influenza virus and cost performance is very high. Amantadine should be given within 48 hours from onset of influenza. Daily doses should not exceed 150 mg in children, 200 mg in adults and less than 100 mg for renal insufficiency. The faulty point of amantadine is that influenza virus becomes easily resistant to the drug through aminoacids change of ionchannel of M2 protein. Fortunately resistant virus is less virulent and has short life in practical meaning. As rapid diagnostic kits are conveniently available for influenza, you should choice amantadine when the patient was positive for type A influenza by kit, especially neuraminidase inhibitor drugs became shortage.

[Study of a respiratory syncytial virus diagnostic test kit based on immunochromatography].

We carried out clinical and basic studies of the Directigen Lateral Flow RSV (Becton, Dickinson and Company, USA), a rapid test kit that detects respiratory syncytial virus (hereinafter referred to as "RSV") antigens based on immunochromatography. For the clinical study, 103 nasopharyngeal aspirates from patients with acute respiratory infections were used to evaluate the kit. Compared to the cell culture method, the Directigen Lateral Flow RSV showed a sensitivity of 100% (16/16) and a specificity of 94.3% (82/87), and an agreement rate of 95.1% (98/103). When compared to conventional testing kits, we found that the total agreement rate with the Directigen RS (Nippon Becton Dickinson and Company) was 88.3% (91/103) and with RSV TestPack (Dainabot Co., Ltd.) was 91.3% (94/103). The detection limit of the Directigen Lateral Flow RSV was 2 x 10(3) PFU/ml for both RSV subgroups A and B. In the crossreactivity test, only RSV was found positive. No other microorganisms were crossreactive. We also studied storage stability of nasopharyngeal aspirates and found that stability was not affected by storage at room and refrigerator temperatures for 14 days. Taken all together, the Directigen Lateral Flow RSV is useful for the diagnosis of RSV infection in a clinical setting because its performance is equivalent to conventional testing kits and is easy to use.

[Field trial of combined measles and rubella live attenuated vaccine].

We investigated the antibody responses and clinical adverse reactions after immunization with live combined measles and rubella vaccine (HF vaccine) in 442 healthy children, aged 12-90 months of age. We obtained 368 paired sera. Among them, 363 were initially sero-negative against measles virus and 343 (94.5%) became sero-positive after immunization. Sero-conversion against rubella virus was demonstrated in 349 (96.7%) of 361 initially sero-negatives against rubella virus. We investigated the clinical adverse reactions in 406 recipients. In 102 (25.1%) recipients, febrile reaction (> 37.5 C) developed on the day 6.7 of vaccination on average, with a mean duration of 2.2 days. Only two (0.5%) developed high body temperature over 39.5 C. Skin rash was noted in 87 (21.4%) on day 7.1 of vaccination on average, with a mean duration of 4.8 days. Lymphoadenopathy was demonstrated in 12 (3.0%). Thus, measles and rubella combined vaccine was safe and sufficiently immunogenic as well as each monovalent one, having clinical advantage in immunization practice.

[Effectiveness of oseltamivir treatment against influenza type A and type B infection in children].

We investigated the effectiveness of oseltamivir treatment against influenza virus infection in children. We treated 131 patients (mean age, 5.8 +/- 3.6 years) with oseltamivir (4 mg/kg/day for 5 days) during the 2001-2002 epidemic. All of the patients had been diagnosed with influenza using a rapid diagnosis kit. When treatment was initiated within 48 hours of the onset of fever, 44% of the patients became afebrile (< 37.5 degrees C) within one day, and 86% of them recovered within two days. The average duration of fever after the initiation of oseltamivir treatment was 1.7 days. Oseltamivir was equally effective against both influenza type A and type B. No differences in the effectiveness of oseltamivir treatment were observed between young children (< 4 years of age) and school-aged children (> 6 years of age). No obvious side effects were observed.