Lay Myint Yoshida

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.

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.

Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred

Several mutations in the surfactant protein C (SP-C) gene (SFTPC) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood. We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced their SFTPC and ABCA3 genes. We also established a cell line stably expressing the mutant gene. All the patients had similar radiological and histopathological characteristics. Their histopathological pattern was that of usual interstitial pneumonia, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest high-resolution computed tomography. No child had respiratory symptoms in the kindred. Sequencing of SFTPC showed a novel heterozygous mutation, c.298G>A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. However, in the ABCA3 gene, no mutation was found. In vitro expression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed. The mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.

Molecular Epidemiology and Disease Severity of Human Respiratory Syncytial Virus in Vietnam

Respiratory syncytial virus (RSV) is a major cause of acute respiratory infections (ARIs) in children worldwide and can cause high mortality, especially in developing countries. However, information on the clinical and molecular characteristics of RSV infection in developing countries is limited. From April 2010 to May 2011, 1,082 nasopharyngeal swabs were collected from children with ARI admitted to the Childrens Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for RSV and genotyped by reverse transcription-PCR and sequencing. Demographic and clinical data was also recorded. RSV was found in 23.8% (257/1,082) of samples. RSV A was the dominant subgroup, accounting for 91.4% (235/257), followed by RSV B, 5.1% (13/257), and 9 cases (3.5%) were mixed infection of these subgroups. The phylogenetic analysis revealed that all group A strains belonged to the GA2 genotype. All group B strains belonged to the recently identified BA genotype, and further clustered into 2 recently described subgenotypes BA9 and BA10. One GA2 genotype strain had a premature stop codon which shortened the G protein length. RSV infection was significantly associated with younger age and higher severity score than those without. Co-infection with other viruses did not affect disease severity. RSV A caused more severe disease than RSV B. The results from this study will not only contribute to the growing database on the molecular diversity of RSV circulating worldwide but may be also useful in clinical management and vaccine development.

Molecular evolution of human respiratory syncytial virus attachment glycoprotein (G) gene of new genotype ON1 and ancestor NA1

We conducted a comprehensive genetic analysis of the C-terminal 3rd hypervariable region of the attachment glycoprotein (G) gene in human respiratory syncytial virus subgroup A (HRSV-A) genotype ON1 (93 strains) and ancestor NA1 (125 strains). Genotype ON1 contains a unique mutation of a 72 nucleotide tandem repeat insertion (corresponding to 24 amino acids) in the hypervariable region. The Bayesian Markov chain Monte Carlo (MCMC) method was used to conduct phylogenetic analysis and a time scale for evolution. We also calculated pairwise distances (p-distances) and estimated the selective pressure. Phylogenetic analysis showed that the analyzed ON1 and NA1 strains formed 4 lineages. A strain belonging to lineage 4 of ON1 showed wide genetic divergence (p-distance, 0.072), which suggests that it might be a candidate new genotype, namely ON2. The emergence of genotype NA1 was estimated to have occurred in 2000 (95% of highest probability density, HPD; 1997-2002) and that of genotype ON1 in 2005 (95% HPD; 2000-2010) based on the time-scaled phylogenetic tree. The evolutionary rate of genotype ON1 was higher than that of ancestral genotype NA1 (6.03×10(-3) vs. 4.61×10(-3) substitutions/site/year, p<0.05). Some positive and many negative selection sites were found in both ON1 and NA1 strains. The results suggested that the new genotype ON1 is rapidly evolving with antigenic changes, leading to epidemics of HRSV infection in various countries.

Surveillance of Pneumococcal-Associated Disease among Hospitalized Children in Khanh Hoa Province, Vietnam

BACKGROUND To understand the epidemiology of childhood bacterial diseases, including invasive pneumococcal disease, prospective surveillance was conducted among hospitalized children in Nha Trang, Vietnam. METHODS From April 2005 through August 2006, pediatricians at the Khanh Hoa General Hospital used standardized screening criteria to identify children aged <5 years who had signs and symptoms of invasive bacterial disease. All cerebrospinal fluid (CSF) and blood specimens collected were tested by bacterial culture. Selected culture-negative specimens were tested for Streptococcus pneumoniae by antigen detection or for Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, and S. pneumoniae by polymerase chain reaction (PCR). RESULTS A total of 987 children were enrolled (794 with pneumonia, 76 with meningitis, and 117 with other syndromes consistent with invasive bacterial disease); 84% of children were aged 0-23 months, and 57% were male. Seven (0.71%) of 987 blood cultures and 4 (15%) of 26 CSF cultures were positive for any bacterial pathogen (including 6 for H. influenzae type b and 1 for S. pneumoniae). Pneumococcal antigen testing and PCR identified an additional 16 children with invasive pneumococcal disease (12 by antigen testing and 4 by PCR). Among children aged <5 years who lived in Nha Trang, the incidence rate of invasive pneumococcal disease was at least 48.7 cases per 100,000 children (95% confidence interval, 27.9-85.1 cases per 100,000 children). CONCLUSIONS S. pneumoniae and H. influenzae type b were the most common causes of laboratory-confirmed invasive bacterial disease in children. PCR and antigen testing increased the sensitivity of detection and provided a more accurate estimate of the burden of invasive bacterial disease in Vietnam.

Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review.

Background The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries. Methods We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000–2010 for each country, region and globally. Results The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4–61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46–195) in the Western Pacific, excluding China, to 116 (95% CI: 56–235) and 121 (95% CI: 31–238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000–80,000) and SE Asia (49,000, 95% CI: 11,000–97,000). In 2010, 105,000 (95% CI: 54,000–158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000–169,000) in 1996. Conclusions Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.

Does respiratory virus coinfection increases the clinical severity of acute respiratory infection among children infected with respiratory syncytial virus

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection in children less than 5 years of age. The impact of non-RSV respiratory virus coinfection on the severity of RSV disease is unknown. Methods: This hospital-based prospective study was conducted in Nagasaki, Japan, on all children less than 5 years of age with acute respiratory infection (ARI) who had undergone a rapid RSV diagnostic test between April 2009 and March 2010. Thirteen respiratory viruses were identified from nasopharyngeal swab samples using a multiplex polymerase chain reaction; polymerase chain reaction–positive samples were considered as confirmed respiratory virus infections. The cases were classified into 3 categories (pneumonia, moderate-to-severe nonpneumonic ARI and mild ARI) according to the findings of the chest radiograph and the hospitalization records. Results: Among 384 cases enrolled, 371 were eligible for analysis, of whom 85 (23%) were classified as pneumonia cases; 137 (37%) as moderate-to-severe nonpneumonic ARI cases and 162 (40%) as mild ARI cases. RSV was detected in 172 cases (61.6%), and 31 cases (18.0%) had double or triple infections with other respiratory viruses. RSV infection was more frequently observed in pneumonia cases (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.31–3.9) and moderate-to-severe nonpneumonic ARI cases (OR: 2.95; 95% CI: 1.82–4.78) than in mild ARI cases. The association with moderate-to-severe nonpneumonic ARI cases was stronger with RSV/non-RSV respiratory virus coinfection (adjusted OR: 4.91; 95% CI: 1.9–12.7) than with RSV single infection (adjusted OR: 2.77; 95% CI: 1.64–4.7). Conclusions: Non-RSV respiratory virus coinfection is not uncommon in RSV-infected children and may increase the severity of RSV disease.