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Background: Shigella sonnei is a pathogen of growing global importance as a cause of diarrhoeal illness in childhood, particularly in transitional low-middle income countries (LMICs). Here, we sought to determine the incidence of childhood exposure to S. sonnei infection in a contemporary transitional LMIC population, where it represents the dominant Shigella species. Methods: Participants were enrolled between the age of 12–36 months between June and December 2014. Baseline characteristics were obtained through standardized electronic questionnaires, and serum samples were collected at 6-month intervals over two years of follow-up. IgG antibody against S. sonnei O-antigen (anti-O) was measured using an enzyme-linked immunosorbent assay (ELISA). A four-fold increase in ELISA units (EU) with convalescent IgG titre >10.3 EU was taken as evidence of seroconversion between timepoints. Results: A total of 3,498 serum samples were collected from 748 participants; 3,170 from the 634 participants that completed follow-up. Measures of anti-O IgG varied significantly by calendar month (p = 0.03). Estimated S. sonnei seroincidence was 21,451 infections per 100,000 population per year (95% CI 19,307–23,834), with peak incidence occurring at 12–18 months of age. Three baseline factors were independently associated with the likelihood of seroconversion; ever having breastfed (aOR 2.54, CI 1.22–5.26), history of prior hospital admission (aOR 0.57, CI 0.34–0.95), and use of a toilet spray-wash in the household (aOR 0.42, CI 0.20–0.89). Conclusions: Incidence of S. sonnei exposure in Ho Chi Minh City is substantial, with significant reduction in the likelihood of exposure as age increases beyond 2 years. Author summary: Bacteria belonging to the genus Shigella are a leading cause of childhood diarrhea globally. In Vietnam and other transitional low-middle income countries (LMIC), S. sonnei has recently emerged as the dominant Shigella species, displacing S. flexneri, which usually predominates in industrializing regions. Little is known about the epidemiology of S. sonnei and how common infection is amongst children in such settings. In this study, we used regular blood sampling from a large cohort of children in Ho Chi Minh City over a two year period to examine changes in antibody concentrations against S. sonnei, using this to detect evidence of exposure to the bacteria. Importantly, this approach allowed us to identify exposures irrespective of whether the children had experienced symptoms or not. Our findings showed that exposure to S. sonnei was common in this cohort, with the highest incidence of exposure occurring in children observed between the ages of 12 months and 18 months. This is the first study of its kind to describe the epidemiology of S. sonnei infection in a LMIC setting and will be useful in informing future vaccine development and deployment strategies against this important pathogen. [ABSTRACT FROM AUTHOR]

Salmonella enterica serotype 1,4,[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 pathogen's 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 potential hub for the emergence and dissemination of multidrug resistant Salmonella ST34, and mutation analysis suggests of selection in antimicrobial responses and key virulence factors. A genomic epidemiology approach describes the population structure of Salmonella monophasic Typhimurium ST34 from Vietnam, and identifies Southeast Asia as a potential hub for the emergence and international spread of multidrug resistant Salm. ST34. [ABSTRACT FROM AUTHOR]

Antimicrobials are a key group of therapeutic agents. Given the animal/human population density and high antimicrobial consumption rate in Southeast Asia, the region is a focal area for monitoring antimicrobial resistance (AMR). Hypothesizing that the gastrointestinal tract of healthy individuals in Vietnam is a major source of AMR genes that may be transferred to pathogens, we performed shotgun metagenomic sequencing on fecal samples from 42 healthy Vietnamese people (21 children and 21 adults). We compared their microbiome profiles by age group and determined the composition of AMR genes. An analysis of the taxonomic profiles in the gut microbiome showed a clear differentiation by age, with young children (age <2 years) exhibiting a unique structure in comparison to adults and older children. We identified a total of 132 unique AMR genes, with macrolide, lincosamide, and streptogramin class resistance genes (ermB and lnuC) and tetracycline resistance genes being almost ubiquitous across the study population. Notably, samples from younger children were significantly associated with a greater number of AMR genes than other age groups, including key signature genes associated with AMR pathogens (eg, blaCTX-M, mphA). Our data suggest that the gut microbiome of those living in Vietnam, particularly young children, is a substantial reservoir of AMR genes, which can be transferred to circulating enteric pathogens. Our data support the generation of longitudinal cohort studies of those living in urban and rural areas of developing countries to understand the behavior of these AMR reservoirs and their role in generating multidrug-resistant and extensively drug-resistant pathogens. [ABSTRACT FROM AUTHOR]

Streptococcus suis infections are an emerging zoonotic agent causing severe disease in humans and a major pig pathogen worldwide. We investigated the colonization of S. suis in healthy chickens in different flocks (n = 59) as well as in‐contact pigs in farms with S. suis‐positive chickens (n = 44) in the Mekong Delta of Vietnam. Streptococcus suis was isolated from 20 (33.9%) chicken flocks and from all pigs investigated. Chicken isolates formed a distinct genotypic cluster compared with pig and human strains, although two chicken isolates (10%) clustered with pig isolates. Chicken isolates had unusually high levels of resistance against tetracycline (100%), clindamycin (100%) and erythromycin (95%); and intermediate resistance against penicillin (35%) and ceftriaxone (15%). Our findings suggest that chickens may potentially represent a source of S. suis infection to in‐contact humans and pigs. [ABSTRACT FROM AUTHOR]

The accurate assessment of antimicrobial use (AMU) requires relating quantities of active ingredients (AAIs) with population denominators. These data can be used to prioritize potential sources of selective pressure for antimicrobial resistance and to establish reduction targets. Here, we estimated AMU in Vietnam (human population 93.4 M in 2015), and compared it with European Union (EU) data (population 511.5 M in 2014). We extrapolated AMU data on each key animal species and humans from different published sources to calculate overall AMU (in tonnes) in Vietnam. We then compared these data with published statistics on AMU in the European Union (EU). A total of 3838 t of antimicrobials were used in Vietnam, of which 2751 (71.7%) corresponded to animal use, and the remainder (1086 t; 28.3%) to human AMU. This equates to 261.7 mg and 247.3 mg per kg of human and animal biomass, compared with 122.0 mg and 151.5 mg in the EU. The greatest quantities of antimicrobials (in decreasing order) were used in pigs (41.7% of total use), humans (28.3%), aquaculture (21.9%) and chickens (4.8%). Combined AMU in other species accounted for < 1.5%. These results are approximate and highlight the need to conduct targeted surveys to improve country-level estimates of AMU. [ABSTRACT FROM AUTHOR]

This paper investigates the contamination of floodwaters in the urban center of Can Tho city, Vietnam. We sampled water from sewers, surface water bodies, and flood, before, during, and after specific flooding events. Total nucleic acid was extracted from the samples and subjected to a quantitative polymerase chain reaction (qPCR) to detect specific enteric pathogens. The difference between pathogen concentrations in floodwater and sewer water was compared by using the Mann Whitney U test. Correlations between the different pathogens were determined using the non-parametric Spearman test. E. coli and Rotavirus-A were the most prevalent pathogens in floodwater. We observed a weak association between E. coli and Rotavirus in flood-related waters (r < 0.5). Floodwater quality showed no difference to sewer water quality in terms of the E. coli and Rotavirus A concentrations (p > 0.05). Our results indicate that floodwater poses a significant urban public health risk due to the presence of enteric pathogens. [ABSTRACT FROM AUTHOR]

Background The highest burden of disease from hepatitis C virus (HCV) is found in Southeast Asia, but our understanding of the epidemiology of infection in many heavily burdened countries is still limited. In particular, there is relatively little data on acute HCV infection, the outcome of which can be influenced by both viral and host genetics which differ within the region. We studied HCV genotype and IL28B gene polymorphism in a cohort of acute HCV-infected patients in Southern Vietnam alongside two other cohorts of chronic HCV-infected patients to better understand the epidemiology of HCV infection locally and inform the development of programs for therapy with the increasing availability of directly acting antiviral therapy (DAAs). Methods We analysed plasma samples from patients with acute and chronic HCV infection, including chronic HCV mono-infection and chronic Human Immunodeficiency Virus (HIV)-HCV coinfection, who enrolled in four epidemiological or clinical research studies. HCV infection was confirmed with RNA testing. The 5’ UTR, core and NSB5 regions of HCV RNA positive samples were sequenced, and the genotype and subtype of the viral strains were determined. Host DNA from all HCV positive patients and age- and sex-matched non-HCV-infected control individuals were analysed for IL28B single nucleotide polymorphism (SNP) (rs12979860 and rs8099917). Geolocation of the patients were mapped using QGIS. Results 355 HCV antibody positive patients were analysed; 54.6% (194/355) and 46.4% (161/355) were acute and chronic infections, respectively. 50.4% (81/161) and 49.6.4% (80/161) of chronic infections had HCV mono-infection and HIV-HCV coinfection, respectively. 88.7% (315/355) and 10.1% (36/355) of the patients were from southern and central regions of Vietnam, respectively. 92.4% (328/355) of patients were HCV RNA positive, including 86.1% (167/194) acute and 100% (161/161) chronic infections. Genotype could be determined in 98.4% (322/328) patients. Genotypes 1 (56.5%; 182/322) and 6 (33.9%; 109/322) predominated. Genotype 1 including genotype 1a was significantly higher in HIV-HCV coinfected patients compared to acute HCV patients [43.8% (35/80) versus 20.5% (33/167)], (p = <0.001), while genotype 6 was significantly higher in chronic HCV mono-infected patients [(44.4% (36/81) versus 20.0% (16/80)] (p = < 0.004) compared to HIV-HCV coinfected patients. The prevalence of IL28B SNP (rs12979860) homozygous CC was 86.46% (83/96) in control individuals and was significantly higher in acutely-infected compared to chronically-infected patients [93.2 (82/88) versus 76.1% (35/46)] (p = < 0.005). Conclusion HCV genotype 6 is highly prevalent in Vietnam and the high prevalence in treatment naïve chronic HCV patients may results from poor spontaneous clearance of acute HCV infection with genotype 6. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C infection is a major public health concern in low- and middle-income countries where an estimated 71.1 million individuals are living with chronic infection. The World Health Organization (WHO) has recently released new guidance for hepatitis C virus (HCV) treatment programs, which include improving the access to new direct-acting antiviral agents. In Vietnam, a highly populated middle-income country, the seroprevalence of HCV infection is approximately 4% and multiple genotypes co-circulate in the general population. Here we review what is currently known regarding the epidemiology of HCV in Vietnam and outline options for reducing the significant burden of morbidity and mortality in our setting.Methods: We performed a systematic review of the currently available literature to evaluate what has been achieved to date with efforts to control HCV infection in Vietnam.Results: This search retrieved few publications specific to Vietnam indicating a significant gap in baseline epidemiological and public health data. Key knowledge gaps identified included an understanding of the prevalence in specific high-risk groups, characterization of circulating HCV genotypes in the population and likely response to treatment, and the extent to which HCV treatment is available, accessed and utilized.Conclusions: We conclude that there is an urgent need to perform up to date assessments of HCV disease burden in Vietnam, especially in high-risk groups, in whom incidence is high and cross infection with multiple genotypes is likely to be frequent. Coordinating renewed surveillance measures with forthcoming HCV treatment studies should initiate the traction required to achieve the WHO goal of eliminating HCV as a public health threat by 2030, at least in this region. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to assess the presence of mcr-1 in Shigella sonnei isolated in Vietnam.Methods: WGS data were analysed for the presence of the mcr-1 gene sequence. The association of mcr-1 with a plasmid was assessed by PCR and by conjugation.Results: Through genome sequencing we identified a plasmid-associated inactive form of mcr-1 in a 2008 Vietnamese isolate of Shigella sonnei. The plasmid was conjugated into Escherichia coli and mcr-1 was activated upon exposure to colistin, resulting in highly colistin-resistant transconjugants.Conclusions: This is the first description of the mcr-1 gene in Shigella, which is atypical given that colistin is not ordinarily used to treat diarrhoea. Our data suggest the mcr-1 gene has been circulating in human-restricted pathogens for some time but likely carries a selective fitness cost. [ABSTRACT FROM AUTHOR]

Background: Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. Methods/design: This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events. Discussion: In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens. Trial registration: ClinicalTrials.gov: NCT02597556. Registered on 3 November 2015. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally.Methods: Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time-kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species.Results: Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin.Conclusions: We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission. [ABSTRACT FROM AUTHOR]

It is predicted that the integration of climate-based early warning systems into existing action plans will facilitate the timely provision of interventions to diarrheal disease epidemics in resource-poor settings. Diarrhea remains a considerable public health problem in Ho Chi Minh City (HCMC), Vietnam and we aimed to quantify variation in the impact of environmental conditions on diarrheal disease risk across the city. Using all inpatient diarrheal admissions data from three large hospitals within HCMC, we developed a mixed effects regression model to differentiate district-level variation in risk due to environmental conditions from the overarching seasonality of diarrheal disease hospitalization in HCMC. We identified considerable spatial heterogeneity in the risk of all-cause diarrhea across districts of HCMC with low elevation and differential responses to flooding, air temperature, and humidity driving further spatial heterogeneity in diarrheal disease risk. The incorporation of these results into predictive forecasting algorithms will provide a powerful resource to aid diarrheal disease prevention and control practices in HCMC and other similar settings. [ABSTRACT FROM AUTHOR]

Novel multiplex real-time PCR assays reveal a high prevalence of diarrhoeagenic Escherichia coli pathotypes in healthy and diarrhoeal children in the south of Vietnam. B Correction: BMC Microbiol 20, 192 (2020) b https://doi.org/10.1186/s12866-020-01878-5 Following publication of the original article [[1]], the authors subsequently identified an error in one of the probe sequences. [Extracted from the article]

Abstract: Group A rotaviruses (ARoVs) are a common cause of severe diarrhea among children worldwide and the cause of approximately 45% of pediatric hospitalizations for acute diarrhea in Vietnam. ARoVs are known to cause significant economic losses to livestock producers by reducing growth performance and production efficiencies, however little is known about the implications of asymptomatic endemic circulation of ARoV. We aimed to determine the prevalence and predominant circulating genotypes of ARoVs on pig farms in a southern province of Vietnam. We found overall animal-level and farm-level prevalence of 32.7% (239/730) and 74% (77/104), respectively, and identified six different G types and 4 P types in various combinations (G2, G3, G4, G5, G9, G11 and P[6], P[13], P[23], and P[34]). There was no significant association between ARoV infection and clinical disease in pigs, suggesting that endemic asymptomatic circulation of ARoV may complicate rotavirus disease attribution during outbreaks of diarrhea in swine. Sequence analysis of the detected ARoVs suggested homology to recent human clinical cases and extensive genetic diversity. The epidemiological relevance of these findings for veterinary practitioners and to ongoing pediatric ARoV vaccine initiatives in Vietnam merits further study. [Copyright &y& Elsevier]

Background Typhoid fever is a systemic infection caused by the bacterium Salmonella enterica serovar Typhi. Age, sex, prolonged duration of illness, and infection with an antimicrobial resistant organism have been proposed risk factors for the development of severe disease or fatality in typhoid fever. Methods We analysed clinical data from 581 patients consecutively admitted with culture confirmed typhoid fever to two hospitals in Vietnam during two periods in 1993-1995 and 1997-1999. These periods spanned a change in the antimicrobial resistance phenotypes of the infecting organisms i.e. fully susceptible to standard antimicrobials, resistance to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole (multidrug resistant, MDR), and intermediate susceptibility to ciprofloxacin (nalidixic acid resistant). Age, sex, duration of illness prior to admission, hospital location and the presence of MDR or intermediate ciprofloxacin susceptibility in the infecting organism were examined by logistic regression analysis to identify factors independently associated with severe typhoid at the time of hospital admission. Results The prevalence of severe typhoid was 15.5% (90/581) and included: gastrointestinal bleeding (43; 7.4%); hepatitis (29; 5.0%); encephalopathy (16; 2.8%); myocarditis (12; 2.1%); intestinal perforation (6; 1.0%); haemodynamic shock (5; 0.9%), and death (3; 0.5%). Severe disease was more common with increasing age, in those with a longer duration of illness and in patients infected with an organism exhibiting intermediate susceptibility to ciprofloxacin. Notably an MDR phenotype was not associated with severe disease. Severe disease was independently associated with infection with an organism with an intermediate susceptibility to ciprofloxacin (AOR 1.90; 95% CI 1.18-3.07; p = 0.009) and male sex (AOR 1.61 (1.00- 2.57; p = 0.035). Conclusions In this group of patients hospitalised with typhoid fever infection with an organism with intermediate susceptibility to ciprofloxacin was independently associated with disease severity. During this period many patients were being treated with fluoroquinolones prior to hospital admission. Ciprofloxacin and ofloxacin should be used with caution in patients infected with S. Typhi that have intermediate susceptibility to ciprofloxacin. [ABSTRACT FROM AUTHOR]

Objective To assess the proportion of, and reasons for, households not utilising the policy of free healthcare for children under 6 years of age ( FCCU6) for hospitalisation with diarrhoea, and assess the risk of catastrophic expenditure for households that forgo FCCU6 and pay out of pocket. Methods Invoices detailing insurance information and charges incurred from 472 hospitalised diarrhoeal cases in one paediatric hospital in Ho Chi Minh City were retrieved. Hospital charges and the utilisation of elective services were analysed for patients utilising and not utilising FCCU6. Associations between socio-economic factors with non-utilisation of FCCU6 were evaluated. Results Overall, 29% of patients were FCCU6 non-users. The FCCU6 non-users paid a median hospital charge of $29.13 (interquartile range, IQR: $18.57-46.24), consuming no more than 1.4% of a medium-income household's annual income. Seventy per cent of low-income FCCU6 non-users utilised less-expensive elective services, whereas only 43% of medium income patients and 21% of high-income patients did ( P = 0.036). Patients from larger households and those with a parent working in government were more likely to use FCCU6. Conclusions The rate of FCCU6 non-usage in this study population was 29%. A significant proportion of those that did not use FCCU6 was from lower income households and may perceive a justifiable cost-benefit ratio when forgoing FCCU6. Although a single diarrhoeal hospitalisation is unlikely to induce a catastrophic expenditure, FCCU6 non-usage may disproportionately increase the risk of catastrophic expenditure for lower income households over multiple illnesses. [ABSTRACT FROM AUTHOR]

We performed a case-controlled investigation to identify risk factors for norovirus infections among children in Vietnam. Of samples from 1,419 children who had diarrhea and 609 who were asymptomatic, 20.6% and 2.8%, respectively, were norovirus positive. Risk factors included residential crowding and symptomatic contacts, indicating person-to-person transmission of norovirus. [ABSTRACT FROM AUTHOR]

Background: Diarrhoeal disease is a major global health problem, particularly affecting children under the age of 5 years. Besides oral rehydration solution, probiotics are also commonly prescribed to children with acute watery diarrhoea in some settings. Results from randomised clinical trials (RCTs) in which investigators studied the effect of probiotics on diarrhoeal symptoms have largely shown a positive effect; yet, the overall quality of the data is limited. In Vietnam, probiotics are the most frequently prescribed treatment for children hospitalised with acute watery diarrhoea, but there is little justification for this treatment in this location. We have designed a RCT to test the hypothesis that an oral preparation of Lactobacillus acidophilus is superior to placebo in the treatment of acute watery diarrhoea in Vietnamese children. Methods: This RCT was designed to study the effect of treatment with L. acidophilus (4 × 109 colony-forming units/ day) for 5 days for acute watery diarrhoea against a placebo in 300 children ages 9 to 60 months admitted to hospitals in Vietnam. Clinical and laboratory data plus samples will be collected on admission, daily during hospitalisation, at discharge, and at follow-up visits for a subset of participants. The primary end point will be defined as the time from the first dose of study medication to the start of the first 24-hour period without diarrhoea as assessed by the on-duty nurse. Secondary endpoints include the time to cessation of diarrhoea as recorded by parents or guardians in an hourly checklist, stool frequency over the first 3 days, treatment failure, rotavirus and norovirus viral loads, and adverse events. Discussion: The existing evidence for the use of probiotics in treating acute watery diarrhoea seems to favour their use. However, the size of the effect varies across publications. An array of different probiotic organisms, doses, treatment durations, study populations, designs, settings, and aetiologies have been described. In this trial, we will investigate whether probiotics are beneficial as an adjuvant treatment for children with acute watery diarrhoea in Vietnam, with the aim of guiding clinical practice through improved regional evidence. [ABSTRACT FROM AUTHOR]

Background: Infection with Salmonella enterica serovar Typhi (S. Typhi) with reduced susceptibility to fluoroquinolones has been associated with fluoroquinolone treatment failure. We studied the relationship between ofloxacin treatment response and the ofloxacin minimum inhibitory concentration (MIC) of the infecting isolate. Individual patient data from seven randomised controlled trials of antimicrobial treatment in enteric fever conducted in Vietnam in which ofloxacin was used in at least one of the treatment arms was studied. Data from 540 patients randomised to ofloxacin treatment was analysed to identify an MIC of the infecting organism associated with treatment failure. Principal Findings: The proportion of patients failing ofloxacin treatment was significantly higher in patients infected with S. Typhi isolates with an MIC≥0.25 µg/mL compared with those infections with an MIC of ≤0.125 µg/mL (p<0.001). Treatment success was 96% when the ofloxacin MIC was ≤0.125 µg/mL, 73% when the MIC was between 0.25 and 0.50 µg/mL and 53% when the MIC was 1.00 µg/mL. This was despite a longer duration of treatment at a higher dosage in patients infected with isolates with an MIC≥0.25 µg/mL compared with those infections with an MIC of ≤0.125 µg/mL. Significance: There is a clear relationship between ofloxacin susceptibility and clinical outcome in ofloxacin treated patients with enteric fever. An ofloxacin MIC of ≥0.25 µg/mL, or the presence of nalidixic acid resistance, can be used to define S. Typhi infections in which the response to ofloxacin may be impaired. Author Summary: Typhoid fever is an infection of the bloodstream caused by the organism Salmonella Typhi (S. Typhi). Treatment with antimicrobials is critical for preventing severe infection and even death, yet antimicrobial resistant organisms have become a problem in many places where typhoid is common. Fluoroquinolones are a group of antimicrobials that are commonly used to treat typhoid, we analysed data from 540 enteric fever patients treated with ofloxacin (a fluoroquinolone) to identify a level of resistance (minimum inhibitory concentration (MIC)) from the infecting organism which is associated with treatment failure. The proportion of patients failing treatment was higher in those infected with a bacterium with an MIC≥0.25 µg/mL, compared with those infections with an MIC of ≤0.125 µg/mL. Treatment success was 96% when the ofloxacin MIC was ≤0.125 µg/mL, yet only 53% when the MIC was 1.00 µg/mL. Our data demonstrates that an S. Typhi bacterium with an ofloxacin MIC of ≥0.25 µg/mL correlates with a poor outcome when treated with this antimicrobial. Therefore, we propose an amendment in the current MIC guidelines for microbiology laboratories to aid clinicians treating typhoid and suggest the use of alternative therapy in these patients. [ABSTRACT FROM AUTHOR]

Background: Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. Principal Findings: The population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. Significance: The H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam. Author Summary: Typhoid fever remains a serious public health issue in some parts of Vietnam, including the Mekong delta region. Typhoid is caused by the bacterium Salmonella Typhi, which is frequently multidrug resistant and shows reduced susceptibility to fluoroquinolone-based drugs. We assayed single nucleotide variation in the genomes of S. Typhi organisms isolated from 267 patients with typhoid fever in the Mekong delta between 2004 and 2005, and identified genetically distinct S. Typhi strains. We also detected the presence of genes or mutations that confer drug resistance in those strains. We found that the vast majority of typhoid cases were caused by one of two subgroups of H58 S. Typhi, referred to as H58-C and H58-E2. The H58-E2 group appeared to cause an outbreak in 2004, affecting patients living in a small zone near the Mekong River. The other group, H58-C, was present throughout the study period and affected patients living in a broader area of the Mekong River delta. Most of the H58-C strains were resistant to multiple drugs and carried a plasmid encoding multiple resistance genes. However very few H58-E2 strains were multidrug resistant, which may explain why the strain did not persist after the initial outbreak. [ABSTRACT FROM AUTHOR]

Background: Typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. Principal Findings: The population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông Hâu branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. Significance: The H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam. [ABSTRACT FROM AUTHOR]

The article discusses the listeria monocytogenes meningitis cases in Ho Chi Minh City (HCMC), Vietnam. It says that the patients had fever and headaches and were subjected to lumbar puncture (LP). It tells that diagnosis of bacterial meningitis was made to the two patients while a tuberculous meningitis was made to the other since findings showed that the two patients had red cell contamination. It adds that the treatment for listeria monocytogenes meningitis is high dose intravenous ampicillin.

Background: Plasmid mediated antimicrobial resistance in the Enterobacteriaceae is a global problem. The rise of CTX-M class extended spectrum beta lactamases (ESBLs) has been well documented in industrialized countries. Vietnam is representative of a typical transitional middle income country where the spectrum of infectious diseases combined with the spread of drug resistance is shifting and bringing new healthcare challenges. Methodology: We collected hospital admission data from the pediatric population attending the hospital for tropical diseases in Ho Chi Minh City with Shigella infections. Organisms were cultured from all enrolled patients and subjected to antimicrobial susceptibility testing. Those that were ESBL positive were subjected to further investigation. These investigations included PCR amplification for common ESBL genes, plasmid investigation, conjugation, microarray hybridization and DNA sequencing of a blaCTX–M encoding plasmid. Principal Findings: We show that two different blaCTX-M genes are circulating in this bacterial population in this location. Sequence of one of the ESBL plasmids shows that rather than the gene being integrated into a preexisting MDR plasmid, the blaCTX-M gene is located on relatively simple conjugative plasmid. The sequenced plasmid (pEG356) carried the blaCTX-M-24 gene on an ISEcp1 element and demonstrated considerable sequence homology with other IncFI plasmids. Significance: The rapid dissemination, spread of antimicrobial resistance and changing population of Shigella spp. concurrent with economic growth are pertinent to many other countries undergoing similar development. Third generation cephalosporins are commonly used empiric antibiotics in Ho Chi Minh City. We recommend that these agents should not be considered for therapy of dysentery in this setting. Author Summary: Shigellosis is a disease caused by bacteria belonging to Shigella spp. and is a leading cause of bacterial gastrointestinal infections in infants in unindustrialized countries. The Shigellae are dynamic and capable of rapid change when placed under selective pressure in a human population. Extended spectrum beta lactamases (ESBLs) are enzymes capable of degrading cephalosporins (a group of antimicrobial agents) and the genes that encode them are common in pathogenic E. coli and other related organisms in industrialized countries. In southern Vietnam, we have isolated multiple cephalosporin-resistant Shigella that express ESBLs. Furthermore, over two years these strains have replaced strains isolated from patients with shigellosis that cannot express ESBLs. Our work describes the genes responsible for this characteristic and we investigate one of the elements carrying one of these genes. These finding have implications for treatment of shigellosis and support the growing necessity for vaccine development. Our findings also may be pertinent for other countries undergoing a similar economic transition to Vietnam's and the corresponding effect on bacterial populations. [ABSTRACT FROM AUTHOR]

Background: Plasmid mediated antimicrobial resistance in the Enterobacteriaceae is a global problem. The rise of CTX-M class extended spectrum beta lactamases (ESBLs) has been well documented in industrialized countries. Vietnam is representative of a typical transitional middle income country where the spectrum of infectious diseases combined with the spread of drug resistance is shifting and bringing new healthcare challenges. Methodology: We collected hospital admission data from the pediatric population attending the hospital for tropical diseases in Ho Chi Minh City with Shigella infections. Organisms were cultured from all enrolled patients and subjected to antimicrobial susceptibility testing. Those that were ESBL positive were subjected to further investigation. These investigations included PCR amplification for common ESBL genes, plasmid investigation, conjugation, microarray hybridization and DNA sequencing of a blaCTX-M encoding plasmid. Principal Findings: We show that two different blaCTX-M genes are circulating in this bacterial population in this location. Sequence of one of the ESBL plasmids shows that rather than the gene being integrated into a preexisting MDR plasmid, the blaCTX-M gene is located on relatively simple conjugative plasmid. The sequenced plasmid (pEG356) carried the blaCTX-M-24 gene on an ISEcp1 element and demonstrated considerable sequence homology with other IncFI plasmids. Significance: The rapid dissemination, spread of antimicrobial resistance and changing population of Shigella spp. concurrent with economic growth are pertinent to many other countries undergoing similar development. Third generation cephalosporins are commonly used empiric antibiotics in Ho Chi Minh City. We recommend that these agents should not be considered for therapy of dysentery in this setting. [ABSTRACT FROM AUTHOR]

Background: Most cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome. Methods: A prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome. Results: 57 patients were studied. Cryptococcus neoformans var grubii molecular type VN1 caused 70% of infections; C. gattii accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age ≥ 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for C. neoformans var grubii compared with C. gattii (p < 0.001 and p = 0.01 respectively). Conclusion: In HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to C. neoformans var grubii. The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear. [ABSTRACT FROM AUTHOR]

Redondoviridae is a recently discovered DNA virus family consisting of two species, vientovirus and brisavirus. Here we used PCR amplification and sequencing to characterize redondoviruses in nasal/throat swabs collected longitudinally from a cohort of 58 individuals working with animals in Vietnam. We additionally analyzed samples from animals to which redondovirus DNA-positive participants were exposed. Redondoviruses were detected in approximately 60% of study participants, including 33% (30/91) of samples collected during episodes of acute respiratory disease and in 50% (29/58) of baseline samples (with no respiratory symptoms). Vientovirus (73%; 24/33) was detected more frequently in samples than brisaviruses (27%; 9/33). In the 23 participants with at least 2 redondovirus-positive samples among their longitudinal samples, 10 (43.5%) had identical redondovirus replication-gene sequences detected (sampling duration: 35–132 days). We found no identical redondovirus replication genes in samples from different participants, and no redondoviruses were detected in 53 pooled nasal/throat swabs collected from domestic animals. Phylogenetic analysis described no large-scale geographical clustering between viruses from Vietnam, the US, Spain, and China, indicating that redondoviruses are highly genetically diverse and have a wide geographical distribution. Collectively, our study provides novel insights into the Redondoviridae family in humans, describing a high prevalence, potentially associated with chronic shedding in the respiratory tract with lack of evidence of zoonotic transmission from close animal contacts. The tropism and potential pathogenicity of this viral family remain to be determined. [ABSTRACT FROM AUTHOR]

Nontyphoidal Salmonella (NTS) are associated with both diarrhea and bacteremia. Antimicrobial resistance (AMR) is common in NTS in low-middle income countries, but the major source(s) of AMR NTS in humans are not known. Here, we aimed to assess the role of animals as a source of AMR in human NTS infections in Vietnam. We retrospectively combined and analyzed 672 NTS human and animal isolates from four studies in southern Vietnam and compared serovars, sequence types (ST), and AMR profiles. We generated a population structure of circulating organisms and aimed to attribute sources of AMR in NTS causing invasive and noninvasive disease in humans using Bayesian multinomial mixture models. Among 672 NTS isolates, 148 (22%) originated from human blood, 211 (31%) from human stool, and 313 (47%) from animal stool. The distribution of serovars, STs, and AMR profiles differed among sources; serovars Enteritidis, Typhimurium, and Weltevreden were the most common in human blood, human stool, and animals, respectively. We identified an association between the source of NTS and AMR profile; the majority of AMR isolates were isolated from human blood (p < 0.001). Modelling by ST-AMR profile found chickens and pigs were likely the major sources of AMR NTS in human blood and stool, respectively; but unsampled sources were found to be a major contributor. Antimicrobial use in food animals is hypothesized to play role in the emergence of AMR in human pathogens. Our cross-sectional population-based approach suggests a significant overlap between AMR in NTS in animals and humans, but animal NTS does explain the full extent of AMR in human NTS infections in Vietnam. • The major source(s) of antimicrobial resistance (AMR) in nontyphoidal Salmonella (NTS) are unknown. • We analyzed 672 NTS isolates, 148 (41%) from human blood, 211 (59%) from human stool, and 136 (43%) from animal stool. • Enteritidis, Typhimurium, and Weltevreden were the common serovars in human blood, human stool, and animals, respectively. • The majority of AMR isolates were associated with human blood. • NTS from animals does explain the full extent of AMR in human NTS infections. [ABSTRACT FROM AUTHOR]

Background: Chromobacterium violaceum is a proteobacterium found in soil and water in tropical regions. The organism rarely causes infection in humans, yet can cause a severe systemic infection by entering the bloodstream via an open wound. Case presentation: We recently identified a case of severe bacteremia caused by Chromobacterium violaceum at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Here, we describe how rapid microbiological identification and a combination of antimicrobials was used to successfully treat this life threatening infection in a four-year-old child. Conclusions: This case shows the need for rapid diagnosis when there is the suspicion of a puncture wound contaminated with water and soil in tropical regions. We suggest that the aggressive antimicrobial combination used here is considered when this infection is suspected. [ABSTRACT FROM AUTHOR]

We investigated antimicrobial residues, non-typhoidal Salmonella (NTS), Vibrio spp. and their associated antimicrobial resistance (AMR), in shrimps locally purchased in Ho Chi Minh City (Vietnam). In addition, we investigated the relationship between AMR in NTS, Vibrio spp. and antimicrobial residue in the same sample. A total of 40 samples of shrimp heads/shells from different retail sources was cultured using ISO 6579–1:2017 (NTS) and ISO/TS 21872–1:2007 (Vibrio spp.). Phenotypic antimicrobial susceptibility was investigated using Vitek (NTS, 34 antimicrobials) and disk diffusion (Vibrio spp., 12 antimicrobials). A total of 9 (22.5%) samples contained antimicrobial residue, including tetracyclines, fluoroquinolones, sulfonamides and macrolides (in 7.5%, 7.5%, 2.5% and 2.5% of samples, respectively). Shrimp samples from supermarkets had a higher prevalence of antimicrobial residue than those purchased in street markets (50% vs. 13.3%) (p = 0.049). A total of 30 (75%) samples were contaminated with NTS. All samples contained Vibrio spp., with V. parahaemolyticus being most common (87.5% samples). A total of 58.9% NTS isolates were multidrug resistant. With regards to the highest priority, critically important antimicrobials, the highest resistance corresponded to quinolones (14.4–47.8%), followed by 3rd and 4th generation cephalosporins (3.3–7.8%). Vibrio spp. isolates were characterised by their high resistance against ampicillin (82.7%) and 3rd generation cephalosporins (8.3–16.5%). Extended Spectrum Beta-Lactamase (ESBL) activity was detected in 28.1% V. parahaemolyticus isolates. Half of ESBL-positive V. parahaemolyticus strains harboured bla CTX-M1. We found an association between the presence of residues and the number of resistances for NTS (p = 0.075) and Vibrio spp. isolates (p = 0.093) from the same sample. These findings suggest that the presence of residues may contribute to the selection of AMR in foodborne pathogens in shrimps. Authorities should strengthen policies aiming at restricting inappropriate antimicrobial usage in shrimp farming, and step up monitoring of antimicrobial residues and food-borne pathogens at retail in Vietnam. • Highest prevalence of antimicrobial residues found in shrimps from supermarkets. • 75% samples were contaminated with non-typhoidal Salmonella (NTS). • Isolates from samples with antimicrobial residues had highest prevalence of phenotypic resistance. • Extended Spectrum Beta-Lactamase activity detected in 28.1% V. parahaemolyticus isolates. [ABSTRACT FROM AUTHOR]

Background: Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam.Methods/design: This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events.Discussion: In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens.Trial Registration: ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015. [ABSTRACT FROM AUTHOR]