Quantitative bacterial counts in the bone marrow of Vietnamese patients with typhoid fever

Background Bone marrow culture (BMC) is the reference standard for typhoid fever diagnosis. We studied the additional yield of BMC over blood culture (BC) and the relationship between quantitative BMC counts and severe disease. Methods Hospitalised Vietnamese patients with suspected typhoid fever were prospectively investigated with a BC, BMC, faecal culture and quantitative BMC counts. Results Salmonella typhi was isolated in 195 of 231 patients: from BC and BMC in 144 (73.8%), from BMC alone in 33 (16.9%), from BC alone in 12 (6.2%) and from faeces alone in 6 (3.1%). In 167 patients the median extracellular count of S. typhi was 2.5 cfu/mL (interquartile range [IQR] 0–10) and the intracellular count was 10.5 cfu/mL (IQR 2–42) with a ratio of 1.3 bacteria/cell (IQR 0.6–2.5). The median count of intracellular bacteria in 24 patients with severe disease was 46 bacteria/cell (IQR 9–105) compared with 6.5 bacteria/cell (IQR 2–34) in 143 with non-severe disease (p=0.005). The intracellular BMC count was negatively correlated with the peripheral white cell count and positively correlated with hepatomegaly, splenomegaly, aspartate transaminase, a positive BC and the fever clearance time following treatment with azithromycin, ofloxacin or a combination of the two. Conclusions BMC gave a moderate additional yield over BC. Intracellular BMC counts may reflect the bacterial load in typhoid fever

Prevalence of carbapenem resistance and its potential association with antimicrobial use in humans and animals in rural communities in Vietnam

Background Vietnam and Southeast Asia are hotspots for antimicrobial resistance; however, little is known on the prevalence of carriage of carbapenem resistance in non-hospitalized humans and in animals. Carbapenem-resistant Enterobacteriaceae (CRE), particularly Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) and also Acinetobacter baumannii (CRAB) are emerging threats worldwide. Methods We investigated healthy humans (n = 652), chickens (n = 237), ducks (n = 150) and pigs (n = 143) in 400 small-scale farms in the Mekong Delta of Vietnam. Samples (rectal swabs, faecal swabs) were investigated for carriage of CRE/CRAB and were further characterized phenotypically and genotypically. Results In the Mekong Delta of Vietnam, the prevalence of CRE isolates in human rectal swabs was 0.6%, including 4 CREC and 1 CRKP. One pig was infected with CREC (prevalence 0.7%). CRAB was isolated from chickens (n = 4) (prevalence 2.1%) and one duck (prevalence 0.7%). CRKP was isolated from a human who was also colonized with CREC. The CRKP strain (ST16), from an 80 year-old person with pneumonia under antimicrobial treatment, genetically clustered with clinical strains isolated in a hospital outbreak in southern Vietnam. The prevalence of CRE was higher among humans that had used antimicrobials within 90 days of the sampling date than those had not (4.2% versus 0.2%) (P = 0.005). All CRE/CRAB strains were MDR, although they were susceptible to colistin and neomycin. The carbapenemase genes identified in study strains were blaNDM and blaOXA. Conclusions The finding of a CRKP strain clustering with previous hospital outbreak raises concerns about potential transmission of carbapenem-resistant organisms from hospital to community settings or vice-versa

Rodents and risk in the Mekong delta of Vietnam: seroprevalence of selected zoonotic viruses in rodents and humans

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Reducing Antimicrobial Usage in Small-Scale Chicken Farms in Vietnam: A 3-Year Intervention Study

Indiscriminate antimicrobial use (AMU) in animal production is a driver of antimicrobial resistance globally. There is a need to define sustainable interventions to reduce AMU in small-scale production systems, which currently represent the most widespread farming systems in South East Asia and many low- and middle-income countries. We conducted a before-and-after intervention study on a random sample of small-scale chicken farms in the Mekong Delta of Vietnam from 2016 to 2019. The study included a baseline followed by an intervention phase where farmers were provided with regular veterinary advice on flock health and husbandry, as well as antimicrobial replacement products. Of 102 recruited farms (raising &amp;gt;100 chickens per flock cycle), thirty-five (34.2%) entered the intervention phase, whilst the rest stopped raising chickens, mainly due to suboptimal flock performance. Through the implementation of our intervention, chicken flocks reduced levels of AMU by 66% [adjusted hazard ratio (HR) = 0.34; p = 0.002) from a baseline of 343.4 Animal Daily Doses per 1,000 chicken-days and decreased weekly mortality by 40% (adjusted HR = 0.60; p = 0.005) from a baseline mortality of 1.60 per 100 birds. Chicken bodyweight increased by 100 g (p = 0.002) in intervention flocks. Our findings demonstrate that the provision of veterinary advice can achieve substantial reductions in AMU in small-scale production systems without compromising flock health and productivity.</jats:p

A Multi-Center Randomised Controlled Trial of Gatifloxacin versus Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adults in Vietnam

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944

Large-scale screening and characterization of enteroviruses and kobuviruses infecting pigs in Vietnam

A recent survey of pigs in Dong Thap province, Vietnam identified a high frequency of enterovirus species G (EV-G) infection (144/198; 72.7%). Amongst these was a plethora of EV-G types (EV-G1, EV-G6 and four new types EV-G8-EV-G11). To better characterize the genetic diversity of EV-G and investigate the possible existence of further circulating types, we performed a larger-scale study on 484 pig and 45 farm-bred boar faecal samples collected in 2012 and 2014, respectively. All samples from the previous and current studies were also screened for kobuviruses. The overall EV infection frequency remained extremely high (395/484; 81.6%), but with comparable detection rates and viral loads between healthy and diarrhoeic pigs; this contrasted with less frequent detection of EV-G in boars (4/45; 8.9%). EV was most frequently detected in pigs ≤ 14 weeks old (∼ 95%) and declined in older pigs. Infections with EV-G1 and EV-G6 were most frequent, whilst less commonly detected types included EV-G3, EV-G4 and EV-G8-EV-G11, and five new types (EV-G12-EV-G16). In contrast, kobuvirus infection frequency was significantly higher in diarrhoeic pigs (40.9 versus 27.6%; P = 0.01). Kobuviruses also showed contrasting epizootiologies and age associations; a higher prevalence was found in boars (42%) compared with domestic pigs (29%), with the highest infection frequency amongst pigs >52 weeks old. Although genetically diverse, all kobuviruses identified belonged to the species Aichivirus C. In summary, this study confirms infection with EV-G was endemic in Vietnamese domestic pigs and exhibits high genetic diversity and extensive inter-type recombination

Modelling the impact of antimicrobial use and external introductions on commensal E. coli colistin resistance in small‐scale chicken farms of the Mekong delta of Vietnam

International audienceColistin is a critically important antimicrobial for human medicine, and colistin-resistant Escherichia coli are commonly found in poultry and poultry products in Southeast Asia. Here, we aim at disentangling the within-farm and outside-farm drivers of colistin resistance in small-scale chicken farms of the Mekong delta of Vietnam. Nineteen Vietnamese chicken farms were followed up along a whole production cycle, during which weekly antimicrobial use data were recorded. At the beginning, middle and end of each production cycle, commensal E. coli samples from birds were collected, pooled and tested for colistin resistance. Twelve models were fitted to the data using an expectation-maximization algorithm and compared. We further tested the spatial clustering of the occurrence of resistance importations from external sources using the local Moran's I statistic. In the best model, colistin resistance in E. coli from chickens was found to be mostly affected by importations of resistance, and, to a lesser extent, by the use of antimicrobials in the last 1.73 weeks [0.00; 2.90], but not by the use of antimicrobials in day-olds, nor their colistin resistance carriage from hatchery. The occurrence of external source importations proved to be sometimes spatially clustered, suggesting a role of local environmental sources of colistin resistance

Veterinary Drug Shops as Main Sources of Supply and Advice on Antimicrobials for Animal Use in the Mekong Delta of Vietnam

In the Mekong Delta of Vietnam, small-scale poultry farmers use large amounts of antimicrobials to raise their flocks, and veterinary drug shops owners and their staff are a key source of advice to farmers on antimicrobial use (AMU). We described the network of veterinary drug shops (n = 93) in two districts within Dong Thap province (Mekong Delta). We also interviewed a randomly selected sample of chicken farmers (n = 96) and described their linkages with veterinary drug shops. Antimicrobials represented 15.0% [inter quartile range (IQR) 6.0–25.0] of the shops’ income. Fifty-seven percent shop owners had been/were affiliated to the veterinary authority, 57% provided diagnostic services. The median number of drug shops supplying antimicrobials to each farm during one production cycle was 2 [IQR 1–2]. Visited shops were located within a median distance of 3.96 km [IQR 1.98–5.85] to farms. Drug shops owned by persons affiliated to the veterinary authority that did not provide diagnostic services had a higher fraction of their income consisting of antimicrobial sales (β = 1.913; p &lt; 0.001). These results suggest that interventions targeting veterinary drug shop owners and their staff aiming at improving their knowledge base on livestock/poultry diseases and their diagnosis may contribute to reducing overall levels of AMU in the area.</jats:p

Labelling and quality of antimicrobial products used in chicken flocks in the Mekong Delta of Vietnam

Background: The Mekong Delta of Vietnam is a hotspot of antimicrobial use (AMU), but there is no information on the quality of the labelling and strength of antimicrobial products used in poultry production. Methods: Based on a large random sample of farms, we identified the 20 most used antimicrobial products in the area, and investigated their antimicrobial active ingredient (AAI) content by UPLC‐MS/MS (91 analytical tests). Results: Only 17/59 (28.8%) batches contained all AAIs within 10% of the declared strength. Worryingly, 65.0% products provided in their label preparation guidelines for both therapeutic and prophylactic use. Withdrawal times for both meat and eggs were stated in 8/20 (40%) products. Conclusion: Results highlight deficiencies in quality and labelling contents that undermine authorities’ efforts to discourage inappropriate use of antimicrobials

Randomized Controlled Comparison of Ofloxacin, Azithromycin, and an Ofloxacin-Azithromycin Combination for Treatment of Multidrug-Resistant and Nalidixic Acid-Resistant Typhoid Fever

Isolates of Salmonella enterica serovar Typhi that are multidrug resistant (MDR, resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and have reduced susceptibility to fluoroquinolones (nalidixic acid resistant, Nar) are common in Asia. The optimum treatment for infections caused by such isolates is not established. This study compared different antimicrobial regimens for the treatment of MDR/Nar typhoid fever. Vietnamese children and adults with uncomplicated typhoid fever were entered into an open randomized controlled trial. Ofloxacin (20 mg/kg of body weight/day for 7 days), azithromycin (10 mg/kg/day for 7 days), and ofloxacin (15 mg/kg/day for 7 days) combined with azithromycin (10 mg/kg/day for the first 3 days) were compared. Of the 241 enrolled patients, 187 were eligible for analysis (186 S. enterica serovar Typhi, 1 Salmonella enterica serovar Paratyphi A). Eighty-seven percent (163/187) of the patients were children; of the S. enterica serovar Typhi isolates, 88% (165/187) were MDR and 93% (173/187) were Nar. The clinical cure rate was 64% (40/63) with ofloxacin, 76% (47/62) with ofloxacin-azithromycin, and 82% (51/62) with azithromycin (P = 0.053). The mean (95% confidence interval [CI]) fever clearance time for patients treated with azithromycin (5.8 days [5.1 to 6.5 days]) was shorter than that for patients treated with ofloxacin-azithromycin (7.1 days [6.2 to 8.1 days]) and ofloxacin (8.2 days [7.2 to 9.2 days]) (P < 0.001). Positive fecal carriage immediately posttreatment was detected in 19.4% (12/62) of patients treated with ofloxacin, 6.5% (4/62) of those treated with the combination, and 1.6% (1/62) of those treated with azithromycin (P = 0.006). Both antibiotics were well tolerated. Uncomplicated typhoid fever due to isolates of MDR S. enterica serovar Typhi with reduced susceptibility to fluoroquinolones (Nar) can be successfully treated with a 7-day course of azithromycin