Nitrite metabolism of several bacterial strains isolated from abattoir and swine wastewater after biogas treatment

In nitrogen treatment with biological methods, nitrite metabolism is an intermediate process that facilitates other processes involving different bacteria strains. In this study, we isolated two nitrite-oxidising bacteria strains from abattoir wastewater and wastewater from biogas tanks of an industrial pig farm in Ha Tinh province. The bacteria strains grow, develop, and metabolise nitrite at pH 6–8 and 30–37 °C. The samples with the nitrite concentration up to 750 mg·L–1 were oxidised within four days of incubation, and the nitrite metabolism rate was proportional to the concentration of nitrite tested. Under severe conditions (salinity up to 3% NaCl, a low dissolved oxygen level of 0.1 mg·L–1), the two isolated bacterial strains exhibited their effective growth and nitrite metabolism capacity. The results enrich the database of nitrite-oxidising bacteria and are prospective in wastewater treatment

Tuberculosis among economic migrants: a cross-sectional study of the risk of poor treatment outcomes and impact of a treatment adherence intervention among temporary residents in an urban district in Ho Chi Minh City, Viet Nam.

BACKGROUND Tuberculosis (TB) remains a major cause of avoidable deaths. Economic migrants represent a vulnerable population due to their exposure to medical and social risk factors. These factors expose them to higher risks for TB incidence and poor treatment outcomes. METHODS This cross-sectional study evaluated WHO-defined TB treatment outcomes among economic migrants in an urban district of Ho Chi Minh City, Viet Nam. We measured the association of a patient's government-defined residency status with treatment success and loss to follow-up categories at baseline and performed a comparative interrupted time series (ITS) analysis to assess the impact of community-based adherence support on treatment outcomes. Key measures of interest of the ITS were the differences in step change (β) and post-intervention trend (β). RESULTS Short-term, inter-province migrants experienced lower treatment success (aRR = 0.95 [95% CI: 0.92-0.99], p = 0.010) and higher loss to follow-up (aOR = 1.98 [95% CI: 1.44-2.72], p  55 years of age (aRR = 0.93 [95% CI: 0.89-0.96], p < 0.001), relapse patients (aRR = 0.89 [95% CI: 0.84-0.94], p < 0.001), and retreatment patients (aRR = 0.62 [95% CI: 0.52-0.75], p < 0.001) had lower treatment success rates. TB/HIV co-infection was also associated with lower treatment success (aRR = 0.77 [95% CI: 0.73-0.82], p < 0.001) and higher loss to follow-up (aOR = 2.18 [95% CI: 1.55-3.06], p < 0.001). The provision of treatment adherence support increased treatment success (IRR(β) = 1.07 [95% CI: 1.00, 1.15], p = 0.041) and reduced loss to follow-up (IRR(β) = 0.17 [95% CI: 0.04, 0.69], p = 0.013) in the intervention districts. Loss to follow-up continued to decline throughout the post-implementation period (IRR(β) = 0.90 [95% CI: 0.83, 0.98], p = 0.019). CONCLUSIONS Economic migrants, particularly those crossing provincial borders, have higher risk of poor treatment outcomes and should be prioritized for tailored adherence support. In light of accelerating urbanization in many regions of Asia, implementation trials are needed to inform evidence-based design of strategies for this vulnerable population

A comparative impact evaluation of two human resource models for community-based active tuberculosis case finding in Ho Chi Minh City, Viet Nam

Background: To achieve the WHO End TB Strategy targets, it is necessary to detect and treat more people with active TB early. Scale–up of active case finding (ACF) may be one strategy to achieve that goal. Given human resource constraints in the health systems of most high TB burden countries, volunteer community health workers (CHW) have been widely used to economically scale up TB ACF. However, more evidence is needed on the most cost-effective compensation models for these CHWs and their potential impact on case finding to inform optimal scale-up policies. Methods: We conducted a two-year, controlled intervention study in 12 districts of Ho Chi Minh City, Viet Nam. We engaged CHWs as salaried employees (3 districts) or incentivized volunteers (3 districts) to conduct ACF among contacts of people with TB and urban priority groups. Eligible persons were asked to attend health services for radiographic screening and rapid molecular diagnosis or smear microscopy. Individuals diagnosed with TB were linked to appropriate care. Six districts providing routine NTP care served as control area. We evaluated additional cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF by human resource model on TB case notifications. Results: We verbally screened 321,020 persons in the community, of whom 70,439 were eligible for testing and 1138 of them started TB treatment. ACF activities resulted in a + 15.9% [95% CI: + 15.0%, + 16.7%] rise in All Forms TB notifications in the intervention areas compared to control areas. The ITS analyses detected significant positive post-intervention trend differences in All Forms TB notification rates between the intervention and control areas (p = 0.001), as well as between the employee and volunteer human resource models (p = 0.021). Conclusions: Both salaried and volunteer CHW human resource models demonstrated additionality in case notifications compared to routine case finding by the government TB program. The salaried employee CHW model achieved a greater impact on notifications and should be prioritized for scale-up, given sufficient resources

Steroids from the blood cockle Anadara granosa

Using various chromatographic experiments, four sterols as 5α,8α-epidioxy-24(S)-ethylcholest-6-en-3β-ol (1), (22E,24S)-5α,8α-epidioxy-24-ethyl-cholesta-6,22-dien-3β-ol (2), 7-oxocholesterol (3), and (22E)-3β-hydroxycholesta-5,22-dien-7-one (4) were isolated from the methanol extract of the blood cockle Anadara granosa. The structures of isolated compounds were elucidated by 1D and 2D-NMR experiments in comparison with reported data. This is the first report of these compounds from A. granosa

Evaluation of Xpert MTB/RIF and MODS assay for the diagnosis of pediatric tuberculosis

BACKGROUND: Tuberculosis (TB) in children is rarely confirmed due to the lack of effective diagnostic tools; only 10 to 15% of pediatric TB is smear positive due to paucibacillary samples and the difficulty of obtaining high-quality specimens from children. We evaluate here the accuracy of Xpert MTB/RIF in comparison with the Micoroscopic observation drug susceptibility (MODS) assay for diagnosis of TB in children using samples stored during a previously reported evaluation of the MODS assay. METHODS: Ninety-six eligible children presenting with suspected TB were recruited consecutively at Pham Ngoc Thach Hospital in Ho Chi Minh City Viet Nam between May to December 2008 and tested by Ziehl-Neelsen smear, MODS and Mycobacterial growth Indicator (MGIT, Becton Dickinson) culture. All samples sent by the treating clinician for testing were included in the analysis. An aliquot of processed sample deposit was stored at −20°C and tested in the present study by Xpert MTB/RIF test. 183 samples from 73 children were available for analysis by Xpert. Accuracy measures of MODS and Xpert were summarized. RESULTS: The sensitivity (%) in detecting children with a clinical diagnosis of TB for smear, MODS and Xpert were 37.9 [95% CI 25.5; 51.6], 51.7 [38.2; 65.0] and 50.0 [36.6; 63.4], respectively (per patient analysis). Xpert was significantly more sensitive than smear (P=0.046). Testing of additional samples did not increase case detection for MODS while testing of a second sputum sample by Xpert detected only two additional cases. The positive and negative predictive values (%) of Xpert were 100.0 [88.0; 100.0] and 34.1 [20.5; 49.9], respectively, while those of MODS were 96.8 [83.3; 99.9] and 33.3 [19.6; 49.5]. CONCLUSION: MODS culture and Xpert MTB/RIF test have similar sensitivities for the detection of pediatric TB. Xpert MTB RIF is able to detect tuberculosis and rifampicin resistance within two hours. MODS allows isolation of cultures for further drug susceptibility testing but requires approximately one week to become positive. Testing of multiple samples by xpert detected only two additional cases and the benefits must be considered against costs in each setting. Further research is required to evaluate the optimal integration of Xpert into pediatric testing algorithms

Evaluating the yield of systematic screening for tuberculosis among three priority groups in Ho Chi Minh City, Viet Nam.

BACKGROUND In order to end tuberculosis (TB), it is necessary to expand coverage of TB care services, including systematic screening initiatives. However, more evidence is needed for groups among whom systematic screening is only conditionally recommended by the World Health Organization. This study evaluated concurrent screening in multiple target groups using community health workers (CHW). METHODS In our two-year intervention study lasting from October 2017 to September 2019, CHWs in six districts of Ho Chi Minh City, Viet Nam verbally screened three urban priority groups: (1) household TB contacts; (2) close TB contacts; and (3) residents of urban priority areas without clear documented exposure to TB including hotspots, boarding homes and urban slums. Eligible persons were referred for further screening with chest radiography and follow-on testing with the Xpert MTB/RIF assay. Symptomatic individuals with normal or without radiography results were tested on smear microscopy. We described the TB care cascade and characteristics for each priority group, and calculated yield and number needed to screen. Subsequently, we fitted a mixed-effect logistic regression to identify the association of these target groups and secondary patient covariates with TB treatment initiation. RESULTS We verbally screened 321 020 people including 24 232 household contacts, 3182 social and close contacts and 293 606 residents of urban priority areas. This resulted in 1138 persons treated for TB, of whom 85 were household contacts, 39 were close contacts and 1014 belonged to urban priority area residents. The yield of active TB in these groups was 351, 1226 and 345 per 100 000, respectively, corresponding to numbers needed to screen of 285, 82 and 290. The fitted model showed that close contacts [adjusted odds ratio (aOR) = 2.07; 95% CI: 1.38-3.11; P < 0.001] and urban priority area residents (aOR = 2.18; 95% CI: 1.69-2.79; P < 0.001) had a greater risk of active TB than household contacts. CONCLUSIONS The study detected a large number of unreached persons with TB, but most of them were not among persons in contact with an index patient. Therefore, while programs should continue to optimize screening in contacts, to close the detection gap in high TB burden settings such as Viet Nam, coverage must be expanded to persons without documented exposure such as residents in hotspots, boarding homes and urban slums

An Evaluation of Programmatic Community-Based Chest X-ray Screening for Tuberculosis in Ho Chi Minh City, Vietnam.

Across Asia, a large proportion of people with tuberculosis (TB) do not report symptoms, have mild symptoms or only experience symptoms for a short duration. These individuals may not seek care at health facilities or may be missed by symptom screening, resulting in sustained TB transmission in the community. We evaluated the yields of TB from 114 days of community-based, mobile chest X-ray (CXR) screening. The yields at each step of the TB screening cascade were tabulated and we compared cohorts of participants who reported having a prolonged cough and those reporting no cough or one of short duration. We estimated the marginal yields of TB using different diagnostic algorithms and calculated the relative diagnostic costs and cost per case for each algorithm. A total of 34,529 participants were screened by CXR, detecting 256 people with Xpert-positive TB. Only 50% of those diagnosed with TB were detected among participants reporting a prolonged cough. The study's screening algorithm detected almost 4 times as much TB as the National TB Program's standard diagnostic algorithm. Community-based, mobile chest X-ray screening can be a high yielding strategy which is able to identify people with TB who would likely otherwise have been missed by existing health services

Development of a Clinical Prediction Score Including Monocyte-to-Lymphocyte Ratio to Inform Tuberculosis Treatment Among Children With HIV: A Multicountry Study

BACKGROUND: Clinical pediatric tuberculosis (TB) diagnosis may lead to overdiagnosis particularly among children with human immunodeficiency virus (CHIV). We assessed the performance of monocyte-lymphocyte ratio (MLR) as a diagnostic biomarker and constructed a clinical prediction score to improve specificity of TB diagnosis in CHIV with limited access to microbiologic testing. METHODS: We pooled data from cohorts of children aged ≤13 years from Vietnam, Cameroon, and South Africa to validate the use of MLR ≥0.378, previously found as a TB diagnostic marker among CHIV. Using multivariable logistic regression, we created an internally validated prediction score for diagnosis of TB disease in CHIV. RESULTS: The combined cohort had 601 children (median age, 1.9 [interquartile range, 0.9-5.3] years); 300 (50%) children were male, and 283 (47%) had HIV. Elevated MLR ≥0.378 had sensitivity of 36% (95% confidence interval [CI], 23%-51%) and specificity of 79% (95% CI, 71%-86%) among CHIV in the validation cohort. A model using MLR ≥0.28, age ≥4 years, tuberculin skin testing ≥5 mm, TB contact history, fever >2 weeks, and chest radiograph suggestive of TB predicted active TB disease in CHIV with an area under the receiver operating characteristic curve of 0.85. A prediction score of ≥5 points had a sensitivity of 94% and specificity of 48% to identify confirmed TB, and a sensitivity of 82% and specificity of 48% to identify confirmed and unconfirmed TB groups combined. CONCLUSIONS: Our score has comparable sensitivity and specificity to algorithms including microbiological testing and should enable clinicians to rapidly initiate TB treatment among CHIV when microbiological testing is unavailable

Adjunctive dexamethasone for the treatment of HIV-uninfected adults with tuberculous meningitis stratified by Leukotriene A4 hydrolase genotype (LAST ACT): Study protocol for a randomised double blind placebo controlled non-inferiority trial [version 1; referees: 2 approved]

Background: Tuberculosis kills more people than any other bacterial infection worldwide. In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H), predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals. The primary aim of this study is to determine whether LTA4H genotype determines benefit or harm from adjunctive dexamethasone in HIV-uninfected Vietnamese adults with TBM. The secondary aim is to investigate alternative management strategies in individuals who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy.  Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled,  multi-centre Phase III non-inferiority trial, comparing dexamethasone versus placebo for 6-8 weeks in addition to standard anti-tuberculosis treatment in HIV-uninfected patients with TBM stratified by LTA4H genotype. The primary endpoint will be death or new neurological event. The trial will enrol approximately 720 HIV-uninfected adults with a clinical diagnosis of TBM, from two hospitals in Ho Chi Minh City, Vietnam. 640 participants with CC or CT- LTA4H genotype will be randomised to either dexamethasone or placebo, and the remaining TT- genotype participants will be treated with standard-of-care dexamethasone. We will also perform a randomised comparison of three management strategies for anti-tuberculosis DILI. An identical ancillary study will also be perfomed in the linked randomised controlled trial of dexamethasone in HIV-infected adults with TBM (ACT HIV).  Discussion: Previous data have shown that LTA4H genotype may be a critical determinant of inflammation and consequently of adjunctive anti-inflammatory treatment response in TBM. We will stratify dexamethasone therapy according to LTA4H genotype in HIV-uninfected adults, which may indicate a role for targeted anti-inflammatory therapy according to variation in LTA4H C/T transition. A comparison of DILI management strategies may allow the safe continuation of rifampicin and isoniazid

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke