2015年にミャンマー国で発生したデング熱流行の臨床、ウイルス学、疫学解析

Hospital-based surveillance was conducted at two widely separated regions in Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected from 332 clinically diagnosed dengue patients during the peak season of dengue cases. Viremia levels were measured by quantitative real-time PCR and plaque assays using FcγRIIA-expressing and non-FcγRIIA-expressing BHK cells to specifically determine the infectious virus particles. By serology and molecular techniques, 280/332 (84・3%) were confirmed as dengue patients. All four serotypes of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients including two cases infected with two DENV serotypes. High percentage of primary infection was noted among the severe dengue patients. Patients with primary infection or DENV IgM negative demonstrated significantly higher viral loads but there was no significant difference among the severity groups. Viremia levels among dengue patients were notably high for a long period which was assumed to support the spread of the virus by the mosquito vector during epidemic. Phylogenetic analyses of the envelope gene of the epidemic strains revealed close similarity with the strains previously isolated in Myanmar and neighboring countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3) and genotype distributions were similar in both study sites.長崎大学学位論文 学位記番号:博(医歯薬)甲第984号 学位授与年月日:平成29年9月20日Author: A. K. KYAW, M. M. NGWE TUN, M. L. MOI, T. NABESHIMA, K. T. SOE, S. M. THWE, A. A. MYINT, K. T. T. MAUNG, W. AUNG, D. HAYASAKA, C. C. BUERANO, K. Z. THANT and K. MORITACitation: Epidemiology & Infection, 145(9), pp.1886-1897; 2017Nagasaki University (長崎大学)課程博

Identification of novel antiviral of fungus-derived brefeldin A against dengue viruses

Microbial natural products possess a wide range of biological and biochemical potential. Among them, fungal secondary metabolites are one of the most important sources for discovering new drugs or lead compounds. In the present study, we explored substances produced by the strain Penicillium sp. FKI-7127 for its antiviral activity. We identified brefeldin A as a novel antiviral agent against dengue viruses. The inhibitory effect of brefeldin A was confirmed by virus titer and immunofluorescence assay. Brefeldin A inhibited dengue viruses regardless of serotypes and other related viruses including Zika virus and Japanese encephalitis virus. Time-of-addition study showed that brefeldin A exerts its antiviral effect at an early stage of the dengue virus (DENV) life cycle. These studies demonstrate that (i) brefeldin A could be used as a lead compound for drug development of anti-DENV and other related viruses and (ii) fungal metabolites are a potential and valuable source for dengue virus drug discovery

Confirmation of Skywalker Hoolock Gibbon (Hoolock tianxing) in Myanmar extends known geographic range of an endangered primate

Characterizing genetically distinct populations of primates is important for protecting biodiversity and effectively allocating conservation resources. Skywalker gibbons (Hoolock tianxing) were first described in 2017, with the only confirmed population consisting of 150 individuals in Mt. Gaoligong, Yunnan Province, China. Based on river geography, the distribution of the skywalker gibbon has been hypothesized to extend into Myanmar between the N’Mai Kha and Ayeyarwaddy Rivers to the west, and the Salween River (named the Thanlwin River in Myanmar and Nujiang River in China) to the east. We conducted acoustic point-count sampling surveys, collected noninvasive samples for molecular mitochondrial cytochrome b gene identification, and took photographs for morphological identification at six sites in Kachin State and three sites in Shan State to determine the presence of skywalker gibbons in predicted suitable forest areas in Myanmar. We also conducted 50 semistructured interviews with members of communities surrounding gibbon range forests to understand potential threats. In Kachin State, we audio-recorded 23 gibbon groups with group densities ranging between 0.57 and 3.6 group/km2. In Shan State, we audio-recorded 21 gibbon groups with group densities ranging between 0.134 and 1.0 group/km2. Based on genetic data obtained from skin and saliva samples, the gibbons were identified as skywalker gibbons (99.54–100% identity). Although these findings increase the species’ known population size and confirmed distribution, skywalker gibbons in Myanmar are threatened by local habitat loss, degradation, and fragmentation. Most of the skywalker gibbon population in Myanmar exists outside protected areas. Therefore, the IUCN Red List status of the skywalker gibbon should remain as Endangered

Detection of genotype-1 of dengue virus serotype 3 for the first time and complete genome analysis of dengue viruses during the 2018 epidemic in Mandalay, Upper Myanmar

Background: Dengue (DEN) is a neglected tropical disease, and surveillance of dengue virus (DENV) serotypes and genotypes is critical for the early detection of outbreaks. Risk factors for outbreaks include the emergence of new genotypes and serotype shifting.Methodology and principal findings: To understand the genomic and viral characteristics of DENV-infected patients, we conducted a cross-sectional descriptive study among pediatric patients admitted at the 550-bedded Mandalay Children Hospital during the 2018 DEN endemic season. We conducted virus isolation, serological tests, viremia level measurement, and whole-genome sequencing. Among the 202 serum samples, we detected 85 samples with DENV (46 DENV-1, 10 DENV-3, 26 DENV-4 and three multiple serotype co-infections) via reverse transcription quantitative/real-time PCR (RT-qPCR), and we obtained 49 DENV isolates (31 DENV-1, 10 DENV-3 and 8 DEN-4). We did not detect DENV-2 in this study. The viral genome levels in serum did not differ significantly among virus serotypes, infection status (primary versus secondary) and disease severity. Based on the phylogenetic analysis, we identified DENV-1 genotype-1, DENV-4 genotype-1 and DENV-3 genotype-3 and genotype-1 which was detected for the first time. Next-generation sequencing analysis revealed greater frequencies of nonsynonymous and synonymous mutations per gene in the nonstructural genes. Moreover, mutation rates were also higher among DENV-1.Conclusion/Significance: In conclusion, there was an increasing trend of DENV-3 cases during DENV endemic season in 2018 with the first detection of the genotype 1. However, DENV-1 has remained the predominant serotype in this study area since 2013, and we identified stop codon mutations in the DENV-1 genome. This report is the first to feature a complete genome analysis of the strains of DENV-3 and DENV-4 circulating among pediatric patients in Myanmar. This study highlighted the importance of annual surveillance for a better understanding of the molecular epidemiology of DENVs

Prevalence of Zika virus neutralizing antibodies in healthy adults in Vietnam during and after the Zika virus epidemic season: a longitudinal population-based survey

Background: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant\u27s family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. Methods: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. Results: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer. Conclusions: ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures

ジカ熱流行期と流行後におけるベトナム健康人血清中のジカウイルスに対する中和抗体保有率の縦断的調査

Background: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant’s family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. Methods: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. Results: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5?years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer. Conclusions: ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.長崎大学学位論文 学位記番号:博(医歯薬)甲第1264号 学位授与年月日:令和2年9月18日Author: Co Thach Nguyen, Meng Ling Moi, Thi Quynh Mai Le, Thi Thu Thuy Nguyen, Thi Bich Hau Vu, Hai Tuan Nguyen, Thi Thu Hang Pham, Thi Hien Thu Le, Le Manh Hung Nguyen, Minh Huong Phu Ly, Chris Fook Sheng Ng, Taichiro Takemura, Kouichi Morita & Futoshi HasebeCitation: BMC Infectious Diseases, 20, 332; 2020Nagasaki University (長崎大学)課程博