The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs.

The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realized.

Large-scale genomic analysis of antimicrobial resistance in the zoonotic pathogen Streptococcus suis.

BACKGROUND: Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. The use of antimicrobials in livestock production can lead to emergence of AMR, which can have direct effects on humans through spread of zoonotic disease. Pigs pose a particular risk as they are a source of zoonotic diseases and receive more antimicrobials than most other livestock. Here we use a large-scale genomic approach to characterise AMR in Streptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans. RESULTS: We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into 'resistant' and 'susceptible', highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treat S. suis, with many multidrug-resistant isolates. Similar levels of resistance were found in pigs and humans from regions associated with zoonotic transmission. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel in S. suis. The presence of these determinants explained most of the variation in MIC. But there were also interesting complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many core genome variants of small effect, appearing in a characteristic order. CONCLUSIONS: We present a large dataset allowing the analysis of the multiple contributing factors to AMR in S. suis. The high levels of AMR in S. suis that we observe are reflected by antibiotic usage patterns but our results confirm the potential for genomic data to aid in the fight against AMR.

Antibiotic prescribing and dispensing for acute respiratory infections in children: effectiveness of a multi-faceted intervention for health-care providers in Vietnam.

BACKGROUND: Appropriate antibiotic use is vital to effectively contain antibiotic resistance and improve global health. Acute respiratory infections (ARIs) remain the leading cause of disease and death in children under five in low-income countries. OBJECTIVE: To evaluate a multi-faceted intervention targeting health-care-providers' (HCPs) knowledge, practical competences and practices regarding antibiotic use for ARIs. METHODS: A multi-faceted educational intervention with a two-armed randomised controlled design targeting HCPs treating ARIs in children was conducted in Bavi district, a rural district in Northern Vietnam in 2010-2011. Thirty-two communes of the district were randomized into two arms, with 144 HCPs in the intervention arm and 160 in the control arm. The intervention, conducted over seven months, comprised: (i) education regarding appropriate-antibiotic use, (ii) case scenario discussion and (iii) poster distribution. Questionnaires to assess knowledge and dispensing/prescribing forms to assess practice were completed before-and after interventions. The main outcome measures were differences in improvement in knowledge and practice in the intervention and control group, respectively. RESULTS: Knowledge improved in the intervention group for ARI aetiology by 28% (ΔDecrement control arm 10%), antibiotic use for mild ARIs by 15% (ΔDecrement control arm 13%) and for severe ARIs by 14% (ΔImprovement control arm 29%). Practical competence for a mild ARI case scenario improved in the intervention and control groups by 20% and 11%, respectively. Total knowledge score increased statistically in the intervention group (Δmean improvement 1.17); less so in the control group (Δmean improvement 0.48). Practice regarding antibiotics for mild ARIs improved by 28% in the intervention group (ΔDecrement control arm 3%). CONCLUSIONS: The intervention significantly improved HCPs' knowledge of ARIs and practice of antibiotic use in treatment of ARIs. We suggest mixed method assessment and long-term follow-up of these interventions to enable better appreciation of the effects and effect sizes of our interventions.

High prevalence of antibiotic resistance in commensal Escherichia coli among children in rural Vietnam.

BACKGROUND: Commensal bacteria represent an important reservoir of antibiotic resistance genes. Few community-based studies of antibiotic resistance in commensal bacteria have been conducted in Southeast Asia. We investigated the prevalence of resistance in commensal Escherichia coli in preschool children in rural Vietnam, and factors associated with carriage of resistant bacteria. METHODS: We tested isolates of E. coli from faecal samples of 818 children aged 6-60 months living in FilaBavi, a demographic surveillance site near Hanoi. Daily antibiotic use data was collected for participating children for three weeks prior to sampling and analysed with socioeconomic and demographic characteristics extracted from FilaBavi's re-census survey 2007. Descriptive statistics were generated, and a logistic regression model was used to identify contributions of the examined factors. RESULTS: High prevalences of resistance were found to tetracycline (74%), co-trimoxazole (68%), ampicillin (65%), chloramphenicol (40%), and nalidixic acid (27%). Two isolates were resistant to ciprofloxacin. Sixty percent of isolates were resistant to three or more antibiotics. Recent sulphonamide use was associated with co-trimoxazole resistance [OR 3.2, 95% CI 1.8-5.7], and beta-lactam use with ampicillin resistance [OR 1.8, 95% CI 1.3-2.4]. Isolates from children aged 6-23 months were more likely to be resistant to ampicillin [OR 1.8, 95% CI 1.3-2.4] and co-trimoxazole [OR 1.5, 95% CI 1.1-2.0]. Associations were identified between geographical areas and tetracycline and ampicillin resistance. CONCLUSIONS: We present high prevalence of carriage of commensal E. coli resistant to commonly used antibiotics. The identified associations with recent antibiotic use, age, and geographical location might contribute to our understanding of carriage of antibiotic resistant commensal bacteria.

Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study.

BACKGROUND: Streptococcus pneumoniae is the most significant bacterial cause of community-acquired pneumonia among children under five years worldwide. Updated resistance information of S. pneumoniae among children is essential to adjust the recommendations for empirical treatment of community-acquired pneumonia, which will have immense implications for local and global health. This study investigated the prevalence of antibiotic resistance in isolated strains of S. pneumoniae and relationship with antibiotic use and demographic factors of children under five in rural Vietnam in 2007. METHODS: In Bavi district, 847 children 6 to 60 months were selected from 847 households. The main child-caregivers in the households were interviewed weekly using structured questionnaires to collect information of daily illness symptoms and drug use for the selected child over a four-week period (from March through June 2007). In the 3rd week, the children were invited for a clinical examination and to collect nasopharyngeal samples for S. pneumoniae identification. Etest and disk diffusion were used to test antibiotic susceptibility. RESULTS: Of 818 participating children, 258 (32%) had ongoing respiratory infections, 421 (52%) carried S. pneumoniae, and 477 (58%) had used antibiotics within the previous three weeks. Of the 421 isolates, 95% were resistant to at least one antibiotic (401/421). Resistance to co-trimoxazole, tetracycline, phenoxymethylpenicillin, erythromycin and ciprofloxacin was 78%, 75%, 75%, 70% and 28%, respectively. Low resistance was noted for amoxicillin (4%), benzylpenicillin (4%), and cefotaxime (2%). The intermediate resistance to amoxicillin was 32%. Multidrug-resistance was seen in 60%. The most common pattern was co-resistance to co-trimoxazole, tetracycline and erythromycin. The proportion of children carrying resistant bacteria was higher among the children who had used antibiotics in the previous three weeks. CONCLUSIONS: Resistance to commonly used antibiotics and multidrug-resistance of S. pneumoniae in the area is remarkably high. High-dose amoxicillin is the only investigated oral antibiotic that can possibly be used for treatment of community-acquired pneumococcal infections. Strategies to promote appropriate prescribing and dispensing of effective antibiotics should be immediately implemented for the benefit of local and global health.

Inequality in mortality in Vietnam during a period of rapid transition.

Vietnam has experienced rapid economic growth following the transition, which began in the mid 1980s, from a planned agriculture based economy to a more market orientated one. In this paper, the associations between socioeconomic variables and mortality for 41,000 adults in Northern Vietnam followed from January 1999 to March 2008 are estimated using Cox's proportionally hazard models. Also, we use decomposition techniques to investigate the relative importance of socioeconomic factors for explaining inequality in age-standardized mortality risk. The results confirm previously found negative associations between mortality and income and education, for both men and women. We also found that marital status, at least for men, explain a large and growing part of the inequality. Finally, estimation results for relative education variables suggest that there exist positive spillover effects of education, meaning that higher education of one's neighbors or spouse might reduce ones mortality risk.

Remaining life expectancy among older people in a rural area of Vietnam: trends and socioeconomic inequalities during a period of multiple transitions.

BACKGROUND: Better understanding of the trends and disparities in health at old age in terms of life expectancy will help to provide appropriate responses to the growing needs of health and social care for the older population in the context of limited resources. As a result of rapid economic, demographic and epidemiological changes, the number of people aged 60 and over in Vietnam is increasing rapidly, from 6.7% in 1979 to 9.2% in 2006. Life expectancy at birth has increased but not much are known about changes in old ages. This study assesses the trends and socioeconomic inequalities in RLE at age 60 in a rural area in an effort to highlight this vulnerable group and to anticipate their future health and social needs. METHODS: An abridged life table adjusted for small area data was used to estimate cohort life expectancies at old age and the corresponding 95% confidence intervals from longitudinal data collected by FilaBavi DSS during 1999-2006, which covered 7,668 people at age 60+ with 43,272 person-years, out of a total of 64,053 people with 388,278 person-years. Differences in life expectancy were examined according to socioeconomic factors, including socio-demographic characteristics, wealth, poverty and living arrangements. RESULTS: Life expectancies at age 60 have increased by approximately one year from the period 1999-2002 to 2003-2006. The increases are observed in both sexes, but are significant among females and relate to improvements among those who belong to the middle and upper household wealth quintiles. However, life expectancy tends to decrease in the most vulnerable groups. There is a wide gap in life expectancy according to poverty status and living arrangements, and the gap by poverty status has widened over the study period. The gender gap in life expectancy is consistent across all socioeconomic groups and tends to be wider amongst the more disadvantaged population. CONCLUSIONS: There is a trend of increasing life expectancy among older people in rural areas of Vietnam. Inequalities in life expectancy exist between socioeconomic groups, especially between different poverty levels and also patterns of living arrangements. These inequalities should be addressed by appropriate social and health policies with stronger targeting of the poorest and most disadvantaged groups.