The effects of placing an operational research fellow within the Viet Nam National Tuberculosis Programme.

In April 2009, an operational research fellow was placed within the Viet Nam National Tuberculosis Control Programme (NTP). Over the 6 years from 2010 to 2015, the OR fellow co-authored 21 tuberculosis research papers (as principal author in 15 [71%]). This constituted 23% of the 91 tuberculosis papers published in Viet Nam during this period. Of the 21 published papers, 16 (76%) contributed to changes in policy (n = 8) and practice (n = 8), and these in turn improved programme performance. Many papers also contributed important evidence for better programme planning. Highly motivated OR fellows embedded within NTPs can facilitate high-quality research and research uptake

Collaborative activities and treatment outcomes in patients with HIV-associated tuberculosis in Viet Nam.

SETTING: The National Tuberculosis (TB) Programme in Viet Nam and Ho Chi Minh City (HCMC). OBJECTIVES: To determine 1) at national level between 2011 and 2013, the relationship between human immunodeficiency virus (HIV) testing, uptake of TB-HIV interventions and adverse treatment outcomes among TB-HIV patients; and 2) in HCMC in 2013, patient characteristics associated with adverse outcomes. DESIGN: An ecological study reviewing aggregate nationwide data and a retrospective cohort review in HCMC. RESULTS: Nationwide, from 2011 to 2013, HIV testing increased in TB patients from 58% to 68% and antiretroviral therapy (ART) increased in TB-HIV patients from 54% to 63%. Adverse treatment outcomes in TB-HIV patients increased from 24% to 27%, largely due to transfer out (5-9% increase) and death. The Northern and Highland regions showed poor uptake of TB-HIV interventions. In HCMC, 303 (27%) of 1110 TB-HIV patients had adverse outcomes, with higher risks observed in those with previously treated TB, those diagnosed as HIV-positive before TB onset and those never placed on cotrimoxazole or ART. CONCLUSION: Despite improving HIV testing rates and TB-HIV interventions, adverse outcomes in TB-HIV patients remain at about 26%. Characteristics predicting higher risk of adverse outcomes must be addressed if Viet Nam wishes to end the TB epidemic by 2030

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam.

SETTING: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. OBJECTIVES: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010-2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010-2012. DESIGN: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. RESULTS: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. CONCLUSION: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection-currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation

Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese

Background: Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods: To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results: Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion: SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection. © 2014 Fox et al

Non-Medical Financial Burden in Tuberculosis Care: a Cross-Sectional Survey in Rural China

Background: Treatment of tuberculosis (TB) in China is partially covered by national programs and health insurance schemes, though TB patients often face considerable medical expenditures. For some, especially those from poorer households, non-medical costs, such as transport, accommodation, and nutritional supplementation may be a substantial additional burden. In this article we aim to evaluate these non-medical costs induced by seeking TB care using data from a large scale cross-sectional survey. Methods: A total of 797 TB cases from three cities were randomly selected using a stratified cluster sampling design. Inpatient medical costs, outpatient medical costs, and direct non-medical costs related to TB treatment were collected using in-person interviews by trained interviewers. Mean and median non-medical costs for different sub-groups were calculated and compared using Kruskal-Wallis and Mann–Whitney U tests. Regression analysis was conducted to assess the influence of different patient characteristics on total non-medical cost. Results: The median non-medical cost was RMB 1429, with interquartile range RMB 424–2793. The median non-medical costs relating to inpatient treatment, outpatient treatment, and additional nutrition supplementation were RMB 540, 91, and 900, respectively. Of the 797 cases, 20 % reported catastrophic expenditure on non-medical costs. Statistically significant differences were detected between different cities, age groups, geographical locations, inpatient/outpatient care, education levels and family income groups. Conclusions: Non-medical costs relating to TB treatment are a serious financial burden for many TB patients. Financial assistance that can limit this burden is urgently needed during the treatment period, especially for the poor

Antimicrobial usage and antimicrobial resistance in animal production in Southeast Asia: A review.

Southeast Asia is an area of great economic dynamism. In recent years, it has experienced a rapid rise in the levels of animal product production and consumption. The region is considered to be a hotspot for infectious diseases and antimicrobial resistance (AMR). We reviewed English-language peer-reviewed publications related to antimicrobial usage (AMU) and AMR in animal production, as well as antimicrobial residues in meat and fish from 2000 to 2016, in the region. There is a paucity of data from most countries and for most bacterial pathogens. Most of the published work relates to non-typhoidal Salmonella (NTS), Escherichia coli (E. coli), and Campylobacter spp. (mainly from Vietnam and Thailand), Enterococcus spp. (Malaysia), and methicillin-resistant Staphylococcus aureus (MRSA) (Thailand). However, most studies used the disk diffusion method for antimicrobial susceptibility testing; breakpoints were interpreted using Clinical Standard Laboratory Institute (CSLI) guidelines. Statistical models integrating data from publications on AMR in NTS and E. coli studies show a higher overall prevalence of AMR in pig isolates, and an increase in levels of AMR over the years. AMU studies (mostly from Vietnam) indicate very high usage levels of most types of antimicrobials, including beta-lactams, aminoglycosides, macrolides, and quinolones. This review summarizes information about genetic determinants of resistance, most of which are transferrable (mostly plasmids and integrons). The data in this review provide a benchmark to help focus research and policies on AMU and AMR in the region

Minimum inhibitory concentrations of commercial essential oils against common chicken pathogenic bacteria and their relationship with antibiotic resistance

Aims We investigated the antibacterial effect of seven essential oils (EOs) and one EO-containing liquid phytogenic solution marketed for poultry and pigs (&lsquo;Product A&rsquo;) on chicken pathogens, as well as the relationship between minimum inhibitory concentration (MIC) in EOs and antibiotics commonly administered to chicken flocks in the Mekong Delta (Vietnam). Methods and Results Micellar extracts from oregano (Origanum vulgare), cajeput (Melaleuca leucadendra), garlic (Allium sativum), black pepper (Piper nigrum), peppermint (Mentha&nbsp;&times;&nbsp;piperita&nbsp;L.), tea tree (Melaleuca alternifolia), cinnamon (Cinnamomum zeylanicum) EOs and Product A were investigated for their MIC against&nbsp;Avibacterium endocarditidis&nbsp;(N&nbsp;=&nbsp;10),&nbsp;Pasteurella multocida&nbsp;(N&nbsp;=&nbsp;7),&nbsp;Ornitobacterium rhinotracheale&nbsp;(ORT) (N&nbsp;=&nbsp;10),&nbsp;Escherichia coli&nbsp;(N&nbsp;=&nbsp;10) and&nbsp;Gallibacterium anatis&nbsp;(N&nbsp;=&nbsp;10). Cinnamon EO had the lowest median MIC across strains (median 0.5&nbsp;mg/ml [IQR, interquartile range 0.3&ndash;2.0&nbsp;mg/ml]), followed by Product A (3.8&nbsp;mg/ml [1.9&ndash;3.8&nbsp;mg/ml]), oregano EO (30.4&nbsp;mg/ml [7.6&ndash;60.8&nbsp;mg/ml]) and garlic 63.1&nbsp;mg/ml [3.9 to &gt;505.0&nbsp;mg/ml]. Peppermint, tea tree, cajeput and pepper EOs had all MIC &ge;219&nbsp;mg/ml. In addition, we determined the MIC of the 12&nbsp;most commonly used antibiotics in chicken flocks in the area. After accounting for pathogen species, we found an independent, statistically significant (p&nbsp;&lt;&nbsp;0.05) positive correlation between MIC of 10 of 28 (35.7%) pairs of EOs. For 67/96 (69.8%) combinations of EOs and antibiotics, the MICs were correlated. Of all antibiotics, doxycycline was positively associated with the highest number of EOs (peppermint, tea tree, black pepper and cajeput, all&nbsp;p&nbsp;&lt;&nbsp;0.05). For cinnamon, the MICs were negatively correlated with the MICs of 11/12 antimicrobial tested (all except colistin). Conclusions Increases in MIC of antibiotics generally correlates with increased tolerance to EOs. For cinnamon EO, however, the opposite was observed. Significance and Impact of the Study Our results suggest increased antibacterial effects of EOs on multi-drug resistant pathogens; cinnamon EO was particularly effective against bacterial poultry pathogens.</p

Effect of two alternative methods of pooling sputum prior to testing for tuberculosis with genexpert MTB/RIF

Background: Pooling sputum specimens is one potential strategy for reducing the cost of using Xpert MTB/RIF, a rapid polymerase chain reaction (PCR)-based test, for the diagnosis of pulmonary tuberculosis. We sought to compare the sensitivity of two alternative method of pooling. Methods: Patients referred for assessment for TB, whose initial sputum was Xpert MTB positive, were recruited and their sputum specimens were pooled for analysis with sputum specimens that were Xpert MTB negative. Two alternative pooling strategies were employed: one in which the concentration of sample reagent (buffer) was maintained at 2:1 (standard), in accordance with the manufacturer's instructions, and another in which the concentration of sample reagent was reduced to 1:1. Results: We tested 101 Xpert MTB positive sputum specimens. Among these, 96% of valid test results (95% confidence interval (CI) 89-99%) were positive using the "standard buffer method". Using the "reduced buffer pooling" method 94% of valid test results (95% CI 87-98%) were positive. McNemar's test for the difference in paired proportions did not reach statistical significance (P = 0.56). Conclusion: We have confirmed that pooling of two sputum specimens for testing in a single cartridge is a valid method of reducing the number of cartridges required when using Xpert MTB to detect pulmonary tuberculosis. Two alternative pooling strategies tested here yielded similar results. Trial registration: The present study was conducted within the Active Casefinding in Tuberculosis (ACT3) Trial. The ACT3 Trial had been registered with Australian and New Zealand Clinical Trials Register on 8th April, 2014

Antimicrobial consumption in medicated feeds in Vietnamese pig and poultry production

Antimicrobials are extensively used as growth promoters in animal feeds worldwide, but reliable estimates are lacking. We conducted an internet-based survey of commercial chicken and pig feed products officially approved for sale in Vietnam over the period March-June 2015. Information on the antimicrobial contents in feed products, alongside animal production data, was used to estimate in-feed antimicrobial consumption to produce one kilogram of live animal (chicken, pig), as well as to estimate country-wide antimicrobial consumption through animal feeds. A total of 1462 commercial feed formulations were examined. The survey-adjusted estimated antimicrobial contents were 25.7 and 62.3 mg/kg in chicken and pig feeds, respectively. Overall, it was estimated that 77.4 mg [95% CI 48.1-106.8] and 286.6 mg [95% CI 191.6-418.3] of in-feed antimicrobials were used to raise 1 kg of live chicken and pig, respectively. Bacitracin (15.5% feeds), chlortetracycline (11.4%), and enramycin (10.8%) were the most common antimicrobials present in chicken feed formulations, whereas bacitracin (24.8%), chlortetracycline (23.9%), and florfenicol (17.4%) were the most common in pig feed formulations. Overall, 57% of the total quantitative usage consisted of antimicrobials regarded by WHO of importance for human medicine, including amoxicillin, colistin, tetracyclines, neomycin, lincomycin, and bacitracin. These figures confirm a very high magnitude of in-feed consumption of antimicrobials, especially in pig production. Results from this study should encourage further monitoring of antimicrobials used in animal production, and foster discussion about existing policies on inclusion of antimicrobials in animal feed rations

Colonization of Enteroaggregative Escherichia coli and Shiga toxin-producing Escherichia coli in chickens and humans in southern Vietnam

Enteroaggregative (EAEC) and Shiga-toxin producing Escherichia coli (STEC) are a major cause of diarrhea worldwide. E. coli carrying both virulence factors characteristic for EAEC and STEC and producing extended-spectrum beta-lactamase caused severe and protracted disease during an outbreak of E. coli O104:H4 in Europe in 2011. We assessed the opportunities for E. coli carrying the aggR and stx genes to emerge in 'backyard' farms in south-east Asia.Faecal samples collected from 204 chicken farms; 204 farmers and 306 age- and gender-matched individuals not exposed to poultry farming were plated on MacConkey agar plates with and without antimicrobials being supplemented. Sweep samples obtained from MacConkey agar plates without supplemented antimicrobials were screened by multiplex PCR for the detection of the stx1, stx2 and aggR genes. One chicken farm sample each (0.5 %) contained the stx1 and the aggR gene. Eleven (2.4 %) human faecal samples contained the stx1 gene, 2 samples (0.4 %) contained stx2 gene, and 31 (6.8 %) contained the aggR gene. From 46 PCR-positive samples, 205 E. coli isolates were tested for the presence of stx1, stx2, aggR, wzx O104 and fliC H4 genes. None of the isolates simultaneously contained the four genetic markers associated with E. coli O104:H4 epidemic strain (aggR, stx2, wzx O104 and fliC H4 ). Of 34 EAEC, 64.7 % were resistant to 3(rd)-generation cephalosporins.These results indicate that in southern Vietnam, the human population is a more likely reservoir of aggR and stx gene carrying E. coli than the chicken population. However, conditions for transmission of isolates and/or genes between human and animal reservoirs resulting in the emergence of highly virulent E. coli strains are still favorable, given the nature of'backyard' farms in Vietnam