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Norio Sugaya

Publications and source records attributed to Norio Sugaya.

At least 19 recordsLinked to original sources
PubMed2007

WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus.

Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

Animals↗
PubMed2006

Lower clinical effectiveness of oseltamivir against influenza B contrasted with influenza A infection in children.

BACKGROUND: Recently, many Japanese physicians have claimed that oseltamivir is less effective in children with influenza B virus infection. This study assesses the effectiveness of oseltamivir against influenza A (H3N2) and influenza B in children on the basis of the duration of febrile illness. METHODS: We used oseltamivir to treat 127 children with influenza A (H3N2; mean age, 6.97 years [range, 1-15 years]) and 362 children with influenza B (mean age, 5.16 years [range, 1-15 years]) in outpatient clinics. The duration of fever after the start of oseltamivir therapy was compared in the influenza A group and the influenza B group. RESULTS: The mean duration of fever after the start of oseltamivir therapy was significantly greater in the influenza B group than in the influenza A (H3N2) group (2.18 days vs. 1.31 days, respectively; P<.001). The difference was marked in young children (1-5 years old; 2.37 days for the influenza B group vs. 1.42 days for the influenza A group) but was not significant among older children (11-15 years old). The 50% inhibitory concentration of oseltamivir against influenza B virus was 75.4+/-41.7 nmol/L and was substantially higher than that for type A (H3N2) virus (0.3+/-0.1 nmol/L). Only 3 (1.6%) of 192 influenza B viruses were resistant to oseltamivir. CONCLUSIONS: Oseltamivir is much less effective against influenza B virus infection in young children, probably because of the low sensitivity of influenza B viruses to oseltamivir. The effectiveness of oseltamivir against influenza B is influenced by age and host immunity. A few oseltamivir-resistant influenza B strains were isolated before the start of oseltamivir therapy.

Adolescent↗
PubMed2006

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.

Adolescent↗
PubMed2006

[Diagnosis and Treatment of influenza--clinical investigation on viral shedding in children with influenza].

Children with influenza usually shed viruses from the several days before onset of clinical symptoms, and viruses are isolated for one or two weeks after onset. Point-of-care rapid diagnostic tests are useful to guide use of antiviral agents, appears over 90% sensitivity and specificity for influenza A with nasopharyngeal specimens compared with cell culture. The detection limits of these test kits are 103 pfu or over, so it is necessary to consider viral load in clinical specimens for diagnosis with these kits. Viral load are decreased after the start of antiviral agents, but influenza viruses are isolated in more than half of pediatric patients when fever get down, and resistant viruses are detected in some of these patients. It is very important for influenza control to investigate on viral shedding and resistant viruses.

Amantadine↗
PubMed2006

[Treatment of influenza virus infection with anti-virals].

Dramatic advances have been made in the diagnosis and treatment of influenza in Japan in recent years. Most patients with influenza-like illness are now tested with rapid diagnostic tests, and if the results are positive, they are treated with neuraminidase inhibitors, mostly oseltamivir. However, we experienced emergence of resistant strains to oseltamivir and variable side effects. Zanamivir will be used widely in Japan, because it is characterized of lower rate of resistance. Stockpiling of those antivirals is essential for pandemic preparedness plan.

Animals↗
PubMed2005

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.

Aged↗
PubMed2005

[Dosage of inactivated influenza vaccine for infants].

BACKGROUND: In Japan, the inoculation dosage of inactivated influenza vaccine for children under 1 year old is 0.1 mL per dose. The dosage is not half as much as that in Europe and the U.S.A. We considered that low efficacy fate of influenza vaccine in children under 1 year old results from its less dosage. So we designed this study to verify this hypothesis. MATERIALS AND METHODS: This study was prospective in design. Subjects were divided into two groups by age: 8 to 11 months old (n = 26) and 12 to 16 months old (n = 22). Infants received 0.1 mL of inactivated influenza vaccine and over 1 year, 0.2 mL. Forty-eight children were inoculated twice at intervals of over 4 weeks. Serum samples were drawn before the first inoculation and 1 month after the second vaccination. Pre- and post-immunization antibody titers were measured. The titers of hemaglutinatinin inhibiting antibodies to the 3 viral strains were assayed. Antibody titers were determined using HAI. RESULTS: The post-vaccination proportions of children with protective HAI antibody titers were significantly smaller in infants than those in children over 1 year old (A/H1N1; 23% vs. 77%, A/H3N2; 39% vs. 73%, B; 0% vs. 32%). The number of children with >four-fold increased antibodies were significantly smaller in infants than that in 1 year old (A/H1N1; 74% vs. 91%, B; 0% vs. 39%). In the mean antibody titer, there were signficant differences between infants and children over 1 year old (A/H1N1; 19 times vs. 56 times, B; 8 times vs. 14 times). CONCLUSION: We consider that significant differences in antibody titers between infants and children over 1 year old were caused by the difference of dosage in influenza vaccines. To obtain protective levels of antibodies by influenza vaccines in infants, they must be inoculated with enough dosage.

Antibodies, Viral↗
PubMed2005

Enhanced expression of an alpha2,6-linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor.

The extensive use of neuraminidase (NA) inhibitors to treat influenza virus infections mandates close monitoring for resistant variants. Cultured cells do not provide a reliable means of evaluating the susceptibility of human influenza virus isolates to NA inhibitors. That is, the growth of such viruses in cell lines (e.g., Madin-Darby canine kidney [MDCK] cells) is not inhibited by these drugs, even though their sialidase activity is drug-sensitive. Matrosovich et al. (J. Virol. 77:8418-8425, 2003) showed that an MDCK cell line overexpressing the human beta-galactoside alpha2,6-sialyltransferase I (ST6Gal I) gene has the potential to assess the sensitivity of human influenza virus isolates to NA inhibitors, based on studies with a limited number of viruses. Here, we asked whether clinical isolates of influenza virus are universally sensitive to an NA inhibitor (oseltamivir) in an MDCK cell line expressing the ST6Gal I gene. The sensitivity of viruses to oseltamivir correlated with the sensitivity of viral sialidase to the compound, demonstrating the potential utility of this modified cell line for detecting NA inhibitor-resistant viruses. Moreover, in ST6Gal I-overexpressing cells, the growth of human influenza viruses was up to 2 logs higher than in MDCK cells. We conclude that the human ST6Gal I-expressing MDCK cell line is useful not only for evaluating their sensitivity to NA inhibitors, but also for isolation of influenza viruses from clinical samples.

Acetamides↗
PubMed2005

[Anti-virals for influenza virus infection].

Dramatic advances in the diagnosis and treatment of influenza in Japan has been made in recent years. Rapid diagnosis tests for influenza are routinely performed in Japanese hospitals. Both zanamivir and oseltamivir have been approved for the treatment of influenza since 2001, in addition to amantadine. Japan has the highest figure of neuraminidase inhibitor-use in the world because the treatment of influenza with neuraminidase inhibitors is covered by Japan's National Health Insurance program. Therefore, we should carefully observe the appearance of resistance strains and side effects to neuraminidase inhibitors.

Acetamides↗
PubMed2004

Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus.

The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.

Adolescent↗
PubMed2004

[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.

Acetamides↗
PubMed2004

[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.

Adult↗
PubMed2003

High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza.

Clinical samples from 15 amantadine-treated children were collected serially-before, during, and/or after treatment-and were studied to determine the actual prevalence, timing, and clinical implications of M2 mutational events. After viral RNA extraction and reverse-transcriptase polymerase chain reaction amplification of the viral RNA encoding the M2 protein, the products were cloned into plasmids, and their sequences were determined. Five mutations known to confer amantadine resistance in clinical samples were identified in 12 (80%) of 15 evaluable patients, and 9 patients had >1 (2-4) mutant virus. The pattern of emergence of mutant strains was clarified from the study of 6 patients with at least 4 serial samples. Although viruses with M2 mutations tended to become the dominant populations, in 2 cases, wild-type viruses became dominant after decreasing to low levels. These results suggest that resistant viruses emerge in a much higher proportion of amantadine-treated patients than has been suggested by previous studies.

Adolescent↗
PubMed2003

[Influenza].

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Acetamides↗
PubMed2003

[Influenza virus infection in children].

Influenza virus infection is a leading cause of pediatric hospitalization in winter, as well as respiratory syncytial virus infection. Effective methods of prophylaxis not only for high-risk patients, but also for healthy young children is indispensable. In Japan, a mass immunization program for the prevention of influenza in schoolchildren was conducted between 1962 and 1993. Vaccinating schoolchildren against influenza reduces mortality from influenza among the elderly. Moreover, the programs probably protected young children from developing severe complications of influenza.

Acetamides↗
PubMed2002

Influenza encephalopathy associated with infection with human herpesvirus 6 and/or human herpesvirus 7.

Influenza-associated encephalopathy is often reported in young Japanese children, but its pathogenesis is unknown. Although influenza virus can be demonstrated by throat culture for patients with encephalopathy, cultures of samples of cerebrospinal fluids (CSF) do not yield the virus. Eight patients with encephalopathy or complicated febrile convulsions had influenza virus infection diagnosed by means of culture, polymerase chain reaction (PCR), or rapid diagnosis using throat swabs. In all 8 cases, the results of PCR testing of CSF specimens for influenza virus were negative. On the other hand, human herpesvirus 6 (HHV-6) DNA was demonstrated in CSF specimens obtained from 2 of 8 patients. In 3 of 8 patients, the presence of human herpesvirus 7 (HHV-7) DNA was demonstrated in CSF specimens. Some cases of influenza-associated encephalopathy reported in Japan may be attributable to a dual infection with influenza virus and HHV-6, -7, or both. Another possibility is that latent HHV-6 or HHV-7 in the brain is reactivated by influenza, causing encephalopathy or febrile convulsions.

Child, Preschool↗