Hideki Yanai

Association between nasopharyngeal load of Streptococcus pneumoniae, viral coinfection, and radiologically confirmed pneumonia in Vietnamese children.

Background: The interplay between nasopharyngeal bacterial carriage, viral coinfection, and lower respiratory tract infections (LRTIs) is poorly understood. We explored this association in Vietnamese children aged less than 5 years. Methods: A hospital-based case-control study of pediatric LRTIs was conducted in Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy controls were randomly selected from the community. Polymerase chain reaction-based methods were used to measure bacterial loads of Streptococcus pneumoniae (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13 respiratory viruses and bacterial serotypes in nasopharyngeal samples of study participants. Results: The median nasopharyngeal bacterial load of SP was substantially higher in children with RCP compared with healthy controls or children with other LRTIs (P < 0.001). SP load was 15-fold higher in pneumonia children with viral coinfection compared with those children without viral coinfection (1.4 × 107/mL vs. 9.1 × 105/mL; P = 0.0001). SP load was over 200-fold higher in serotypeable SP compared with nontypeable SP (2.5 × 106/mL vs. 1 × 104/mL; P < 0.0001). These associations were independent of potential confounders in multiple regression models. No clear association was found between nasopharyngeal load of Haemophilus influenzae or Moraxella catarrhalis and viral coinfection in either RCP or other LRTIs groups. Conclusions: An increased load of SP in the nasopharynx was associated with RCP, viral coinfection, and presence of pneumococcal capsule.

Population density, water supply, and the risk of dengue fever in Vietnam: cohort study and spatial analysis.

Results from 75,000 geo-referenced households in Vietnam during two dengue epidemics reveal that human population densities typical of villages are most prone to dengue outbreaks; rural areas may contribute as much to dissemination of dengue fever as do cities.

Maternal body mass index and gestational weight gain and their association with perinatal outcomes in Viet Nam

OBJECTIVE To examine the association between gestational weight gain and maternal body mass index (BMI) among Vietnamese women and the risk of delivering an infant too small or too large for gestational age. METHODS A prospective health-facility-based study of 2989 pregnant Vietnamese women was conducted in the city of Nha Trang in 2007-2008. Cubic logistic regression was used to investigate the association of interest. Infants were classified into weight-for-gestational-age categories according to weight centiles for the Asian population. Gestational age was based on the date of last menstrual period and adjusted by the results of first-trimester ultrasound. FINDINGS BMI was low (< 18.5), normal (18.5-22.9) and high (≥ 23.0) in 26.1%, 65.4% and 8.5% of the women, respectively. In each of these BMI categories, the percentage of women who delivered infants too small for gestational age was 18.1, 10.0 and 9.4, respectively, and the mean gestational weight gain was 12.5 kg (standard deviation, SD: ± 3.6), 12.2 kg (SD: ± 3.8) and 11.5 kg (SD: ± 4.7), respectively. Among women with low BMI, the risk of delivering an infant too small for gestational age ranged from approximately 40% if the gestational weight gain was < 5 kg to 20% if it was 5-10 kg. CONCLUSION Having a low BMI, commonly found in Viet Nam, puts women at risk of delivering an infant too small for gestational age, especially when total maternal gestational weight gain is < 10 kg.

Genome-wide association studies of tuberculosis in Asians identify distinct at-risk locus for young tuberculosis

Tuberculosis (TB) is one of the most devastating chronic infectious diseases, but the role of host genetics in disease development after infection in this disease remains unidentified. Genome-wide association studies (GWASs) in Thais and Japanese were carried out and separately analyzed, attempted replication, then, combined by meta-analysis were not yielding any convincing association evidences; these results suggested that moderate to high effect-size genetic risks are not existed for TB per se. Because of failure in replication attempt of the top 50 single-nucleotide polymorphisms (SNPs) identified form meta-analysis data, we empirically split TB cases into young TB case/control data sets (GWAS-Tyoung=137/295 and GWAS-Jyoung=60/249) and old TB case/control data sets (GWAS-Told=300/295 and GWAS-Jold=123/685), re-analyzed GWAS based on age-stratified data and replicated the significant findings in two independent replication samples (young TB; Rep-Tyoung=155/249, Rep-Jyoung=41/462 and old TB; Rep-Told=212/187, Rep-Jold=71/619). GWAS and replication studies conducted in young TB identified at-risk locus in 20q12. Although the locus is located in inter-genic region, the nearest genes (HSPEP1-MAFB) from this locus are promising candidates for TB susceptibility. This locus was also associated with anti-TNF responsiveness, drug with increased susceptibility for TB. Moreover, eight SNPs in an old TB meta-analysis and six SNPs in young TB meta-analysis provided replication evidences but did not survive genome-wide significance.These findings suggest that host genetic risks for TB are affected by age at onset of TB, and this approach may accelerate the identification of the major host factors that affect TB in human populations.

Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population

Abstract We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2′,5′-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p =0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position −88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p =0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.

Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam

Background: The association between environmental tobacco smoking (ETS) and childhood pneumonia has not been established in developed or developing countries. A study was conducted to assess the effect and impact of ETS exposure on pneumonia among children in central Vietnam. Methods: A population-based large-scale cross-sectional survey was conducted covering all residents of 33 communes in Khanh Hoa Province, the central part of Vietnam. Information on demographics, socioeconomic status and house environment, including smoking status of each household member, was collected from householders. Hospital admissions for pneumonia among children aged <5 years in each household in the previous 12 months were recorded based on caregiver’s report. Results: A total of 353 525 individuals living in 75 828 households were identified in the study areas. Of these, 24 781 (7.0%) were aged <5 years. The prevalence of ETS was 70.5% and the period prevalence of hospital admissions for pneumonia was 2.6%. Multiple logistic regression analysis showed that exposure to ETS was independently associated with hospital admissions for pneumonia (adjusted odds ratio 1.55, 95% CI 1.25 to 1.92). The prevalence of tobacco smoking was higher among men than women (51.5% vs 1.5%). It is estimated that 28.7% of childhood pneumonia in this community is attributable to ETS. Conclusions: Children in Vietnam are exposed to substantial levels of ETS which results in 44 000 excess hospital admissions due to pneumonia each year among children aged <5 years.

Viral pathogens associated with acute respiratory infections in central Vietnamese children.

Hospitalized Vietnamese children with acute respiratory infection were investigated for 13 viral pathogens using multiplex-polymerase chain reaction. We enrolled 958 children of whom 659 (69%) had documented viral infection: rhinovirus (28%), respiratory syncytial virus (23%), influenza virus (15%), adenovirus (5%), human metapneumo virus (4.5%), parainfluenza virus (5%), and bocavirus (2%). These Vietnamese children had a range of respiratory viruses which underscores the need for enhanced acute respiratory infection surveillance in tropical developing countries.

Adherence to tuberculosis preventive therapy among HIV-infected persons in Chiang Rai Thailand.

Objective:To determine the level of and reasons associated with adherence to tuberculosis preventive therapy among asymptomatic HIV-infected individuals in northern Thailand. Design:A prospective cohort study with a 9-month follow-up. Methods:A total of 412 HIV-infected persons were enrolled in a tuberculosis preventive therapy programme in a hospital. A 9-month isoniazid regimen was prescribed. Adherence was determined by pill count. Participants who missed a scheduled appointment for more than a month were interviewed. Five focus group discussion sessions were held among those who successfully completed the therapy. Results:Of the 412 participants, 69.4% (286) completed the 9-month regimen. The adherence rate, defined as the proportion of those who took more than 80% of pills, was 67.5% (n = 278). Sex, source of participants and history of physical symptoms were associated with adherence. A significant portion of defaults took place at the beginning of the therapy. Out-migration, denial of HIV status, and perceived side effects of isoniazid were frequently cited as reasons for non-adherence. For those adhering participants, the acceptance of personal HIV status, concern about children and family, and a good health provider relationship were important reasons motivating adherence. Several reminder systems were developed by the participants. Conclusions:Although an isoniazid preventive therapy programme was shown to be feasible, further adjustments on the selection of participants, enrolment process, and follow-up system based on these findings are necessary to increase the adherence.

Genome-wide SNP-based linkage analysis of tuberculosis in Thais.

Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics=3.01, logarithm of odds (LOD) score=2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score=2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.

Rapid increase in HIV-related tuberculosis, Chiang Rai, Thailand, 1990-1994.

Objective:Chiang Rai, the northernmost province of Thailand, has experienced an explosive HIV epidemic since 1989. This study assessed the impact of HIV infection on tuberculosis (TB) in the area. Methods:We analyzed the incidence of reported TB in the province from 1982 through 1993 and TB registry data at Chiang Rai Hospital from 1985 through 1994. Results:Following a steady decline in reported TB from 1982 through 1991, the incidence of TB increased sharply after 1991. TB registry data from Chiang Rai Hospital, which began confidential HIV testing in October 1989, indicated a steady and rapid increase in the number and proportion of HIV-seropositive TB patients from four (1.5% of all TB patients) in 1990 to 207 (45.5%) in 1994 (P < 0.001). Compared with HIV-negative TB patients, HIV-positive TB patients were more likely to be men, aged 20–39 years and have extrapulmonary TB (P < 0.001). Treatment completion rates were similar. Twelve months after beginning TB treatment, HIV-positive TB patients had a mortality rate of 68.6% [95% confidence interval (CI), 62.7–74.3] compared with 10.0% (95% CI, 8.3–12.1%) in HIV-negative patients (P < 0.001). Conclusion:Thailand and other Asian countries where HIV is spreading rapidly must promptly address the dual epidemic of TB and HIV in order to reduce preventable morbidity and mortality.