Biology subjects

Thwaites, G.

Publications and source records attributed to Thwaites, G..

14 recordsLinked to original sources

bioRxiv2026

Whole blood transcriptional responses associated with bacterial burden in pulmonary tuberculosis

BackgroundPulmonary TB (PTB) patients present with a wide range of pre-treatment Mycobacterium tuberculosis (Mtb) burdens, which predict poor treatment outcomes. We sought to identify immune pathways and biomarkers associated with pre-treatment Mtb burden. MethodsWe conducted whole-blood RNA sequencing in 295 Vietnamese adults with PTB, quantifying bacterial load using GeneXpert Ct values. Weighted gene co-expression network analysis (WGCNA) identified gene modules, pathways, and hub genes associated with Mtb burden. Deconvolution analysis assessed contributions of immune cell types. Key findings were validated in independent PTB (n=171) and TB meningitis (TBM, n=281) cohorts, and publicly available animal datasets. We used non-linear regression for variable selection to identify gene predictors of Mtb burden and hurdle regression to model Mtb loads below the detection limit. FindingsHigher Mtb burden correlated with prolonged symptom duration, elevated neutrophil and monocyte counts, and severe lung pathology. WGCNA identified a 1,093-gene module associated with Mtb burden, characterized by coordinated innate-adaptive pathway interactions. Within this module, IFN-{gamma} signaling participates in modulating the increase of innate signaling (Toll-like, Nod-like receptors, TNF) and the decrease of adaptive signaling (T- and B-cell receptor) pathways in high-burden patients. These responses were primarily driven by neutrophils and classical monocytes. CNIH4 emerged as the strongest hub-gene and a top predictor of bacterial burden, with consistent validation across independent PTB and TBM cohorts. InterpretationOur study reveals systemic innate-adaptive immune dynamics underlying bacterial burden in PTB and identifies CNIH4 as a potential biomarker for treatment monitoring as well as a therapeutic target. FundingNational Institute of Health; Wellcome Trust, UK. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed from Jan 1, 2000, to Dec 10, 2025, without language restrictions, for human studies examining the relationship between Mycobacterium tuberculosis (Mtb) burden and host blood transcriptional responses in pulmonary tuberculosis. Search terms were used in combination as follows: ("Tuberculosis, Pulmonary" OR "pulmonary tuberculosis" OR PTB) AND ("Mycobacterium tuberculosis" OR mycobacter*) AND ("bacterial load" OR "bacterial burden" OR "sputum smear" OR "smear grade" OR xpert OR genexpert OR "cycle threshold" OR ct OR "time to positivity" OR TTP OR CFU OR "molecular bacterial load" OR MBLA)) AND (blood OR "whole blood" OR "peripheral blood") AND (RNA-seq OR "RNA sequencing" OR transcriptom* OR "gene expression" OR microarray). We included studies of active pulmonary tuberculosis that measured quantitative or semi-quantitative bacterial burden and profiled host blood transcriptome-wide responses at baseline, reporting either differential expression by burden strata or associations between bacterial burden and host gene expression. We excluded studies limited to latent tuberculosis, animal or in vitro models, diagnostic or prognostic signature studies without bacterial burden measurement, studies focused on treatment response, and studies using targeted assays without transcriptome-wide profiling. This search identified 12 articles describing blood transcriptional signatures for tuberculosis diagnosis, prognosis, and treatment response. However, only one study directly examined the relationship between pre-treatment bacterial burden and whole-blood transcriptome-wide profiles. That study demonstrated differences in systemic gene expression between patients with higher and lower sputum mycobacterial load and proposed a 20-gene blood signature associated with bacterial burden. However, the analysis was limited by small sample size, lack of pathway-level and cellular interpretation or assessment of correlation between signature with bacterial load. Added value of this studyOur study advances existing evidence by leveraging the wide spectrum of pre-treatment bacterial burden observed in routine clinical populations, quantified using GeneXpert Ct values, and integrating this with whole-blood RNA sequencing in large, well-characterized clinical cohorts. Through network-based transcriptomic analysis, immune cell deconvolution, and non-linear modelling, we identify a bacterial burden-associated gene network characterized by enhanced innate inflammatory signaling and relative suppression of adaptive immune pathways, predominantly driven by neutrophils and classical monocytes and modulated by IFN-{gamma} signaling. Within this network, CNIH4 emerges as a central hub gene and a robust predictor of bacterial burden, with consistent validation across independent pulmonary tuberculosis and tuberculous meningitis cohorts. Implications of all the available evidenceTaken together, the available evidence indicates that host blood transcriptional responses correlate with bacterial burden in pulmonary tuberculosis, but previous studies have provided limited insight into the underlying immune processes. Our findings strengthen the biological link between pre-treatment mycobacterial burden and systemic immune dysregulation, showing that higher bacterial burden is associated with transcriptional state marked by coordinated upregulation of innate immune responses and downregulation of adaptive immune pathways. These results support the use of host transcriptomic profiling as a biologically informative complement to sputum-based measures of bacterial burden and highlight burden-associated immune pathways, particularly CNIH4, as a potential target for treatment monitoring and host-directed therapeutic development.

immunology↗

bioRxiv2023

Multidrug resistance plasmids underlie clonal expansions and international spread of Salmonella enterica serotype 4,,12,i:- ST34 in Southeast Asia

Salmonella enterica serotype 4,[5],12,i:- (Typhimurium monophasic variant) of sequence type (ST) 34 has emerged as the predominant pandemic genotype in recent decades. Despite increasing reports of resistance to antimicrobials in Southeast Asia, Salmonella ST34 population structure and evolution remained understudied in the region. Here we performed detailed genomic investigations on 454 ST34 genomes collected from Vietnam and diverse geographical sources to elucidate the pathogens epidemiology, evolution and antimicrobial resistance. We showed that ST34 has been introduced into Vietnam in at least nine occasions since 2000, forming five co-circulating major clones responsible for paediatric diarrhoea and bloodstream infection. Most expansion events were associated with acquisitions of large multidrug resistance plasmids of IncHI2 or IncA/C2. Particularly, the self-conjugative IncA/C2 pST34VN2 (co-transferring blaCTX-M-55, mcr-3.1, and qnrS1) underlies local expansion and intercontinental spread in two separate ST34 clones. At the global scale, Southeast Asia was identified as a hotspot for the emergence and dissemination of multidrug resistant Salmonella ST34, and mutation analysis suggests of selection in antimicrobial responses and key virulence factors. Our work enriches the understanding on epidemiology and evolution of this variant in Southeast Asia, and determines that multidrug resistance plasmids have driven its local and potentially global success.

genomics↗

bioRxiv2022

Mucosal microbiomes and Fusobacterium genomics in Vietnamese colorectal cancer patients

Perturbations in the gut microbiome have been linked to the promotion and prognosis of colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite the increasing health burden inflicted by CRC in low- and middle-income countries like Vietnam, the CRC-specific microbiome in these populations remains underexplored. Here we conducted a study in Vietnam to enrol 43 CRC patients (cases) and 25 patients with non-cancerous colorectal polyps (controls) between December 2018 and January 2020. Our study investigated the mucosal microbiome signature and genomic diversity of Fusobacterium in Vietnamese CRC patients, using a combination of 16S rRNA gene profiling, anaerobic microbiology, and whole genome sequencing. We found that several oral bacteria, including F. nucleatum and Leptotrichia, were significantly more abundant in the tumour mucosa, and these two bacteria were also more enriched in tumours of advanced CRC stages (III-IV). We obtained 53 Fusobacterium genomes from the saliva, tumour and non-tumour mucosa of six CRC patients. Isolates from the gut mucosa belonged to diverse F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and a potential new subspecies of F. periodonticum. The Fusobacterium population within each individual was distinct and in many cases diverse, with minimal intra-clonal variation. Phylogenetic analyses showed that within each individual, tumour-associated Fusobacterium were clonal to those isolated from non-tumour mucosa, but distantly related to those isolated from saliva. Genes encoding major virulence factors (Fap2 and RadD) showed variability in length and evidence of horizontal gene transfer. Our work provides a framework to understand the genomic diversity of Fusobacterium within the CRC patients, which can be exploited for the development of CRC diagnostic and therapeutic options targeting this oncobacterium.

microbiology↗

bioRxiv2021

Exploring the genomic diversity and antimicrobial susceptibility of Bifidobacterium pseudocatenulatum in the Vietnamese population to aid probiotic design

Bifidobacterium pseudocatenulatum is a member of the human gut microbiota, and has previously been used as a probiotic to improve gut integrity and reduce inflammatory responses. We showed previously that B. pseudocatenulatum was significantly depleted during dysenteric diarrhea, suggesting the organism may aid in recovery from diarrhea. Here, in order to investigate its probiotic potential, we aimed to assess the genomic diversity and predicted metabolic profiles of B. pseudocatenulatum found colonizing the gut of healthy Vietnamese adults and children. We found that the population of B. pseudocatenulatum from each individual was distinct and highly diverse, with intra-clonal variation attributed to gain or loss of carbohydrate utilizing enzymes. The B. pseudocatenulatum genomes were enriched with glycosyl hydrolases that target plant-based non-digestible carbohydrates (GH13, GH43), but not host-derived glycans. Notably, the exopolysaccharide biosynthesis region from organisms isolated from healthy children showed greater genetic diversity, and was subject to a high degree of genetic modification. Antimicrobial susceptibility testing revealed that the Vietnamese B. pseudocatenulatum were uniformly susceptible to beta-lactams, but exhibited variable resistance to azithromycin, tetracycline, ciprofloxacin and metronidazole. The genomic presence of ermX and tet variants conferred resistance against azithromycin and tetracycline, respectively; ciprofloxacin resistance was associated with mutation(s) in the quinolone resistance determining region (GyrA, S115 and/or D119). Our work provides the first detailed genomic and antimicrobial resistance characterization of B. pseudocatenulatum found in the Vietnamese population, which could inform the next phase of rational probiotic design. ImportanceBifidobacterium pseudocatenulatum is a probiotic candidate with potential applications in several health conditions, but its efficacy is largely strain-dependent and associated with distinct genomic and biochemical features. However, most commercial probiotics have been developed by Western institutions, which may not have ideal efficacy when administered in developing countries. This study taps into the underexplored diversity of the organism in Vietnam, and provides more understanding to its lifestyles and antimicrobial susceptibility. These data are key for selecting an optimal probiotic candidate, from our established collection, for downstream investigations and validation. Thus, our work represents a model in identifying and characterizing bespoke probiotics from an indigenous population in a developing setting.

microbiology↗

bioRxiv2020

Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone

Adjunctive treatment with anti-inflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates with a C/T variant in Leukotriene A4 Hydrolase (LTA4H), which regulates expression of the pro-inflammatory mediator leukotriene B4 (LTB4). TT homozygotes, with increased LTB4, have the highest survival when treated with dexamethasone and the lowest survival without. While the T allele is present in only a minority of the worlds population, corticosteroids confer modest survival benefit worldwide. Using Bayesian methods, we examined how pre-treatment levels of cerebrospinal fluid (CSF) pro-inflammatory cytokines affect survival in dexamethasone-treated tuberculous meningitis. LTA4H TT homozygosity was associated with global cytokine increases, including TNF. Association between higher cytokine levels and survival extended to non-TT patients, suggesting that other genetic variants may also induce dexamethasone-responsive pathological inflammation. These findings warrant studies that tailor dexamethasone therapy to pre-treatment CSF cytokine concentrations, while searching for additional genetic loci shaping the inflammatory milieu.

immunology↗

bioRxiv2020

A novel method for measuring phenotypic colistin resistance in Escherichia coli populations from chicken flocks

Colistin is extensively used in animal production in many low- and middle-income countries. There is a need to develop methodologies to benchmark and monitor changes in resistance in commensal bacterial populations in farms. We aimed to evaluate the performance of a broth microdilution method based on culturing a pooled Escherichia coli suspension (30-50 organisms) from each sample. In order to confirm the biological basis and sensitivity of the method, we prepared 16 standard suspensions containing variable ratios of colistin-susceptible and mcr-1 encoded colistin-resistant E. coli which were grown in 2mg/L colistin. The optical density (OD600nm) readings over time were used to generate a growth curve, and were adjusted to the values obtained in the absence of colistin. The median limit of detection of the method was 1 colistin-resistant in 104 susceptible colonies [1st - 3rd quartile, 1:102 - 1:105]. We applied this method to 108 pooled faecal samples from 36 chicken flocks in the Mekong Delta (Vietnam) over the production cycle. The correlation between this method and the prevalence of colistin resistance in individual colonies harvested from field samples, determined by the Minimum Inhibitory Concentration (MIC), was established. The overall prevalence of colistin resistance at sample and isolate level was 38.9% and 19.4%, respectively. Increased colistin resistance was associated with recent (2 weeks) use of colistin and other, non-colistin antimicrobials (OR=3.67 and OR=1.84, respectively). Our method is a sensitive and affordable approach to monitor changes in colistin resistance in pooled E. coli populations from faecal samples over time. IMPORTANCEColistin (polymyxin E) is an antimicrobial with poor solubility properties, and therefore broth microdilution is the only appropriate method for testing colistin resistance. However, estimating colistin resistance in commensal mixed Escherichia coli populations is laborious since it requires individual colony isolation, identification and susceptibility testing. We developed a growth-based microdilution method suitable for pooled faecal samples. We validated the method by comparing it with results from individual MIC testing of 909 E. coli isolates. We used the method to investigate phenotypic colistin resistance in 108 pooled faecal samples from 36 healthy chicken flocks, each sampled three times over the production cycle. A higher level of resistance was seen in flocks recently supplemented with colistin in drinking water, although the observed generated resistance was short-lived. Our method is affordable, and may potentially be integrated into surveillance systems aiming at estimating the prevalence of resistance at colony level in flocks/herds. Furthermore, it may also be adapted to other complex biological systems, such as farms and abattoirs.

microbiology↗

bioRxiv2020

Reducing antimicrobial usage in small-scale chicken farms in Vietnam: A three-year intervention study

Indiscriminate antimicrobial use (AMU) in animal production is a driver of antimicrobial resistance globally, with a need to define sustainable AMU-reducing interventions in small-scale farms typical of low- and middle-income countries. We conducted a before-and-after intervention study on a random sample of small-scale chicken farms in the Vietnamese Mekong Delta from 2016 to 2019. A baseline was established before providing farms (n=102) with veterinary advice on chicken health and husbandry, and antimicrobial replacement products. Thirty-five (34.2%) farms entered the intervention phase; the remainder no longer continued raising chickens. The intervention reduced AMU (-66%) (hazard ratio [HR]=0.34; p=0.002) (baseline 343.4 Animal Daily Doses per 1,000 chicken-days) and mortality (-40%) (HR=0.60; p=0.005) (weekly baseline 1.60 per 100). Chicken bodyweight increased by 100g (p=0.002) in intervention flocks. Our findings demonstrate that in the Vietnamese context, AMU can be substantially reduced in small-scale chicken farms without compromising flock health by providing veterinary advice.

microbiology↗

bioRxiv2020

A Bayesian analysis of the association between Leukotriene A4 Hydrolase genotype and survival probability of tuberculous meningitis patients treated with adjunctive dexamethasone

Tuberculous meningitis (TBM) remains the most devastating form of tuberculosis (TB) with high mortality despite effective antimicrobial treatment. As mortality has been linked to excessive inflammation, anti-inflammatory glucocorticoids are now routinely used as adjunctive treatment with antimicrobial therapy. However, they reduce mortality by only ~ 30%, raising the possibility that only a subset of TBM deaths are caused by inflammatory pathophysiology. Studies in Vietnam found that the survival benefit of adjunctive glucocorticoids was limited to individuals with a common promoter variant in the leukotriene A4 hydrolase (LTA4H) gene encoding an enzyme that regulates inflammatory eicosanoid expression. The variant constitutes a C/T transition with TT homozygotes having increased expression over CT heterozygotes and CC homozygotes. In Vietnam, the LTA4H TT genotype predicted survival, consistent with dexamethasone benefiting only those individuals with a dysregulated hyper-inflammatory response. However, a study of TBM patients in Indonesia did not find the LTA4H TT genotype to confer a significant survival benefit. Given the potential of personalized life-saving anti-inflammatory therapies guided by LTA4H genotype, we have used Bayesian methods to analyze the data from both studies. Bayesian analysis reveals that the LTA4H TT genotype confers survival benefit in both the Vietnam and Indonesia cohorts that begins within days and continues long-term. However, its benefit is nullified in the most severe cases where other factors cause early mortality. LTA4H TT genotype is associated with increased survival in HIV-positive patients also. Thus, our analysis extends the association of LTA4H genotype with TBM survival to populations outside of Vietnam and to HIV-positive patients. Patient LTA4H genotyping used in conjunction with disease severity assessment may help to target glucocorticoids to patients most likely to benefit from this broadly-acting immunosuppressive regimen despite its significant adverse effects.

molecular biology↗

bioRxiv2020

Effects of prophylactic and therapeutic antimicrobial uses in small-scale chicken flocks

SynopsisO_ST_ABSBackgroundC_ST_ABSAntimicrobials are extensively used both prophylactically and therapeutically in poultry production. Despite this, there are little data on the effect of antimicrobial use (AMU) on disease incidence and mortality rate. ObjectiveWe investigated the relationships between AMU and disease and between AMU and mortality using data from a large (n=322 flocks) cohort of small-scale chicken flocks in the Mekong Delta, Vietnam, that were followed longitudinally from day-old to slaughter (5,566 observation weeks). MethodsWe developed a parameterized algorithm to categorize the observation weeks into non-AMU, prophylactic AMU and therapeutic AMU. To evaluate the prophylactic AMU effect, we compared the frequencies of clinical signs in non-AMU and prophylactic AMU periods. To analyse therapeutic AMU, we compared mortality rates between the weeks of disease episodes before and after AMU. Analyses were stratified by clinical signs (4) and antimicrobial classes (13). ResultsProphylactic AMU never reduced the probability of disease, some antimicrobial classes such as lincosamides, amphenicols and penicillins increased the risk. The risk of diarrhoea consistently increased with prophylactic AMU. Therapeutic AMU often had an effect on mortality but the pattern was inconsistent across the combinations of antimicrobial classes and clinical signs with 14/29 decreasing and 11/29 increasing the mortality rate. Lincosamides, methenamines and cephalosporins were the only three antimicrobial classes that always decreased the mortality rate when used therapeutically. Results were robust respective to the parameters values of the weeks categorization algorithm. ConclusionThis information should help support policy efforts and interventions aiming at reducing AMU in animal production.

pharmacology and toxicology↗

bioRxiv2020

Most-probable number based minimum duration of killing assay for determining the spectrum of rifampicin susceptibility in clinical M. tuberculosis isolates

Accurate antibiotic susceptibility testing is essential for successful tuberculosis treatment. Recent studies have highlighted the limitations of minimum inhibitory concentrations (MIC) based phenotypic susceptibility methods in detecting other aspects of antibiotic susceptibilities in bacteria. Duration and peak of antibiotic exposure, at or above the MIC required for killing the bacterial population, has emerged as another important factor for determining the antibiotic susceptibility. This is broadly defined as antibiotic tolerance. Antibiotic tolerance can further facilitate the emergence of antibiotic resistance. Currently there are limited methods to quantify antibiotic tolerance among clinical M. tuberculosis isolates. In this study, we develop a most-probable number (MPN) based minimum duration of killing (MDK) assay to quantify the spectrum of M. tuberculosis rifampicin susceptibility within subpopulations, based on time duration of rifampicin exposure required for killing the bacterial population. MDK90-99 and MDK99.99 defined as the minimum time duration of antibiotic exposure at or above MIC required for killing 90-99% and 99.99% of the initial (pre-treatment) bacterial population respectively. Results from the rifampicin MDK assay applied to 28 laboratory and clinical M. tuberculosis isolates showed that there is variation in rifampicin susceptibility among isolates. Rifampicin MDK99/99.99 time for isolates varied from less than 2 to 10 days. MDK duration was correlated with larger sub-populations of M. tuberculosis from clinical isolates that were rifampicin tolerant. Our study demonstrates the utility of MDK assays to measure the variation in antibiotic tolerance among clinical M. tuberculosis isolates and further expands clinically important aspects of antibiotic susceptibility testing.

microbiology↗

bioRxiv2020

Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections

BackgroundCentral nervous system (CNS) infections are common causes of morbidity and mortality worldwide. Rapid, accurate identification of the likely cause is essential for clinical management and the early initiation of antimicrobial therapy, which potentially improves clinical outcome. MethodsWe applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic protein biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in southern Vietnam. ResultsIn the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis. The analysis of the validation cohort showed that LCN2 could discriminate bacterial meningitis from other CNS infections, including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis (sensitivity: 0.88 (95% confident interval (CI): 0.77-0.94), specificity: 0.91 (95%CI: 0.88-0.94) and diagnostic odd ratio: 73.8 (95%CI: 31.8-171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2 and these four routine CSF markers resulted in the highest diagnostic performance for bacterial meningitis (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93-0.99). ConclusionsOur results suggest that LCN2 is a sensitive and specific biomarker for discriminating bacterial meningitis from a broad spectrum of CNS infections. A prospective study is needed to further assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.

microbiology↗

bioRxiv2019

Characterisation of gastrointestinal helminths and their impact in commercial small-scale chicken flocks in the Mekong Delta of Vietnam

Commercial small-scale chicken farms using all-in-all-out production but operating with low standards of hygiene/biosecurity are increasingly common in Vietnam. These conditions facilitate transmission of gastrointestinal helminths. However there are no published data on these parasites in these systems. The aims were: (1) to determine the prevalence/burden of gastrointestinal helminths in small-scale commercial flocks in commercial small-scale flocks in the Mekong Delta region; and (2) to investigate the association between worm burdens and birds weight and disease status. Randomly selected chickens (n=120) ( normal flocks) were investigated at the end of their production cycle ([~]18 weeks), as well as 90 chickens with signs of respiratory and/or severe disease. The gastrointestinal tract of chickens was dissected and all visible helminths were identified. 54.2% and 54.4% healthy and diseased chickens contained helminths. Diseased, colonized chickens harboured a higher mass of helminth worms (3.8 {+/-}SD 8.6g) than colonized, healthy chickens (1.9 {+/-}6.3g). Eight species were identified, three nematodes (Ascaridia galli, Cheilospirura hamulosa and Heterakis gallinarum), four cestodes (Hymenolepis, Raillietina cesticillus, Raillietina echinobothrida, Raillietina tetragona,) and one trematode (Echinostomatidae). Heterakis gallinarum was the most prevalent helminth (43.3% and 42.2% in healthy and sick chickens, respectively), followed by A. galli (26.7% and 41.1%). Colonized chickens weighed 101.5g less than non-colonized birds. Colonisation was significantly higher during the rainy months (May-November) for both H. gallinarum and A. galli. Anthelminthic usage was not associated with reduced helminth burdens. We recommend upgrading cleaning and disinfection and limiting access to ranging areas to control helminth infections in small-scale commercial chicken flocks.

systems biology↗

bioRxiv2017

Quantifying antimicrobial access and practices for paediatric diarrheal disease in an urban community setting in Southeast Asia

Antimicrobial-resistant infections are increasing across Asia. Aiming to evaluate antimicrobial access and practices in Ho Chi Minh City (HCMC) of Vietnam, we mapped pharmacy locations and used a simulated client method to calculate antimicrobial sales for paediatric diarrheal disease. We additionally evaluated healthcare choices for parents and caregivers when their children experienced diarrhoea. District 8 (population 396,175) of HCMC had 301 pharmacies (one for every 1,316 people), with a density of 15.8 pharmacies/km2. A wide range of different treatments (n=57) were sold for paediatric diarrheal disease, with 8% (3/37) and 22% (8/37) of the sampled pharmacies selling antimicrobials for watery and mucoid diarrhoea, respectively. Despite the apparent abundance of pharmacies, the majority of caregivers chose to take their child to a specialized hospital, with 81% (319/396) and 88% (347/396) of responders selecting this as their first, second, or third choice for watery and mucoid diarrhoea, respectively. Lastly, by combining denominators derived from caregiver interviews and diarrheal incidence figures, we calculated that 16% (2,359/14,427) of watery or mucoid diarrhoea episodes of the District 8 population aged 1 to <5 years would receive an antimicrobial for diarrhoea annually, but antimicrobial prescribing was almost ten times greater in hospitals than in the community. Our novel mixed-methods approach found that, whilst antimicrobials are commonly available for paediatric diarrhoea in the community of HCMC, usage is greater in hospitals. The observed non-standardized approach to diarrheal treatments is indicative of poor recommendations. We advocate better guidelines, training and dissemination of information regarding antimicrobials and their use in this location.

epidemiology↗

bioRxiv2016

Genomic analysis of Mycobacterium tuberculosis reveals complex etiology of tuberculosis in Vietnam including frequent introduction and transmission of Beijing lineage and positive selection for EsxW Beijing variant

Introduction Introduction Accession codes AUTHOR CONTRIBUTIONS COMPETING FINANCIAL INTERESTS Online Methods References Tuberculosis (TB) is a leading cause of death from infectious disease and the global burden is now higher than at any point in history 1,2 Despite coordinated efforts to control TB transmission, the factors contributing to its successful spread remain poorly understood. Vietnam is identified as one of 30 high burden countries for TB and MDR-TB with an incidence of 137 TB cases per 100,000 individuals in 2015 2 Recent phylogenomic analyses of the causative agent Mycobacterium tuberculosis (Mtb) in other high-prevalence regions have provided insights into the complex processes underlying TB transmission ...

genomics↗