GeneXpert or chest-X-ray or tuberculin skin testing for household contact assessment (GXT): protocol for a cluster-randomized trial.

BACKGROUND: The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5. METHODS: This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0-50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the "Comité Local d'Éthique Pour la Recherche Biomédicale (CLERB) de l'Université de Parakou," Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries. DISCUSSION: This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04528823.

Prevalence, acceptability, and cost of routine screening for pulmonary tuberculosis among pregnant women in Cotonou, Benin.

OBJECTIVES: We sought to evaluate the yield, cost, feasibility, and acceptability of routine tuberculosis (TB) screening of pregnant women in Cotonou, Benin. DESIGN: Mixed-methods, cross-sectional study with a cost assessment. SETTING: Eight participating health facilities in Cotonou, Benin. PARTICIPANTS: Consecutive pregnant women presenting for antenatal care at any participating site who were not in labor or currently being treated for TB from April 2017 to April 2018. INTERVENTIONS: Screening for the presence of TB symptoms by midwives and Xpert MTB/RIF for those with cough for at least two weeks. Semi-structured interviews with 14 midwives and 16 pregnant women about experiences with TB screening. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of pregnant women with cough of at least two weeks and/or microbiologically confirmed TB. The cost per pregnant woman screened and per TB case diagnosed in 2019 USD from the health system perspective. RESULTS: Out of 4,070 pregnant women enrolled in the study, 94 (2.3%) had a cough for at least two weeks at the time of screening. The average (standard deviation) age of symptomatic women was 26 ± 5 years and 5 (5.3%) had HIV. Among the 94 symptomatic women, 2 (2.3%) had microbiologically confirmed TB for a TB prevalence of 49 per 100,000 (95% CI: 6 to 177 per 100,000) among pregnant women enrolled in the study. The average cost to screen one pregnant woman for TB was $1.12 USD and the cost per TB case diagnosed was $2271 USD. Thematic analysis suggested knowledge of TB complications in pregnancy was low, but that routine TB screening was acceptable to both midwives and pregnant women. CONCLUSION: Enhanced screening for TB among pregnant women is feasible, acceptable, and inexpensive per woman screened, however in this setting has suboptimal yield even if it can contribute to enhance TB case finding.

Assessment of the Biosafety and Biosecurity in the Reference Veterinary Laboratory of Parakou in Benin.

Optimal biosafety and biosecurity are major requirements of global health security. This study assessed the biorisk management in the reference veterinary laboratory of Parakou (Benin). The study was cross-sectional, descriptive, and evaluative. The non-probability sampling method with the reasoned choice was used. The Food and Agriculture Organization laboratory mapping tool-safety was used to collect information from the laboratory team. Group discussion, working environment observation, and document exploitation were the data collection techniques. The biorisk management was rated good if the average indicator of the laboratory reached at least 80%. Otherwise, the biorisk management was rated insufficient. The overall laboratory biosafety and biosecurity score was insufficient (42.4%). Per area, the scores were 26.7% for engineering, 33.3% for administration, 53.8% for personal protective equipment, and 62.3% for the operational. There was no area or category score that reached 80%. Containment, waste disposal, and personal protective equipment disposal were the best performing categories with a score above 60%. The laboratory has no biosafety and accident prevention program. Its premises require renovation. The standard operating procedures for biosafety are not yet finalized, and the training mechanism is not optimal. Therefore, strong advocacy and implementation of a biorisk management improvement plan appear as urgent corrective actions which are required to help the reference veterinary laboratory of Parakou in its task to protect the livestock and, ultimately, the people of Benin from dangerous diseases and emerging pathogens.

Delayed versus standard assessment for excision surgery in patients with Buruli ulcer in Benin: a randomised controlled trial.

BACKGROUND: Surgical intervention was once the mainstay of treatment for Buruli ulcer disease, a neglected tropical disease caused by Mycobacterium ulcerans. Since the introduction of streptomycin and rifampicin for 8 weeks as standard care, surgery has persisted as an adjunct therapy, but its role is uncertain. We investigated the effect of delaying the decision to operate to 14 weeks on rates of healing without surgery. METHODS: In this randomised controlled trial, we enrolled patients aged 3 years or older with confirmed disease at one hospital in Lalo, Benin. Patients were randomly assigned (1:1) to groups assessing the need for excision surgery 8 weeks (standard care) or 14 weeks after initiation of antimicrobial treatment. The primary endpoint was the number of patients healed without the need for surgery (not including skin grafting), assessed in all patients in follow-up at 50 weeks (or last observation for those healed for >10 weeks). A doctor masked to treatment assignment checked the indications for surgery according to predefined criteria. This study is registered with ClinicalTrials.gov, number NCT01432925. FINDINGS: Between July 1, 2011, and Jan 15, 2015, 119 patients were enrolled, with two patients per group lost to follow-up. 55 (96%) of 57 participants in the delayed-decision group and 52 (90%) of 58 participants in the standard-care group had healed lesions 1 year after start of antimicrobial treatment (relative risk [RR] 1·08, 95% CI 0·97-1·19). 37 (67%) of 55 patients in the delayed-decision group had their lesions healed without surgical intervention, as did 25 (48%) of 52 in the standard-care group (RR 1·40, 95% CI 1·00-1·96). The time to heal and residual functional limitations did not differ between the two groups (median time to heal 21 weeks [IQR 10-27] in the delayed-decision group and 21 weeks [10-39] in the standard-care group; functional limitations in six [11%] of 57 and three [5%] of 58 patients; p=0·32). Postponing the decision to operate resulted in reduced median duration of hospitalisation (5 days [IQR 0-187] vs 131 days [0-224]; p=0·024) and wound care (153 days [IQR 56-224] vs 182 days [94-307]; p=0·036). INTERPRETATION: In our study, patients treated for Buruli ulcer benefited from delaying the decision to operate. Even large ulcers can heal with antibiotics alone, without delaying healing rate and without an increase in residual functional limitations. FUNDING: NWO-VENI grant 241500, BUG Foundation, and UBS OPTIMUS.

Rapid detection of extended-spectrum-ß-lactamase-producing Enterobacteriaceae in blood cultures using the ESBL NDP test in Cotonou, Benin.

PURPOSE: Rapid and inexpensive tests for detecting extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae are needed, particularly in low-resource countries where infections with these bacteria constitute a major public health issue. The recently described ESBL NDP test performed well in developed countries. This study was designed to assess performance, cost and feasibility of this test in positive blood cultures, in Cotonou, Benin (West Africa). METHODOLOGY: The test was performed on 175 positive Bactec broth blood cultures containing Enterobacteriaceae, and blindly compared with the double-disc synergy test (DDST) for the phenotypic detection of ESBL producers. RESULTS: There was a complete agreement between the ESBL NDP test and the DDST. On average, the time to give results was 37 min for a sample and the cost was US$ 7.3. CONCLUSION: The ESBL NDP test is rapid, relatively affordable and performed well in our setting.

National profile and treatment outcomes of adult smear-negative pulmonary TB patients in Benin.

BACKGROUND: In Benin, patients with smear-negative pulmonary TB (SNPTB) are of low priority in the National Tuberculosis Programme (NTP) and little is known about their profile or treatment outcomes. METHODS: A retrospective cohort study was carried out to determine characteristics and treatment outcomes in all adults registered with SNPTB in 2009. Findings were compared with patients with new smear-positive pulmonary tuberculosis (PTB) diagnosed in the same period. RESULTS: Of 3140 patients with PTB, 273 (8.7%) had SNPTB, with higher rates in northern and southwestern regions. SNPTB was associated with female gender, older age and HIV-positive status (p<0.01). Patients with SNPTB had a higher proportion of unsuccessful treatment outcomes compared with smear-positive PTB owing to death and loss to follow-up (LFU) (p<0.01). The region with the capital city had the highest rate of LFU. Differences in unsuccessful outcomes between SNPTB and smear-positive PTB were more apparent in persons who were HIV-negative, and among HIV-positives not on antiretroviral treatment. CONCLUSION: In Benin, treatment outcomes of SNPTB patients were inferior to those with smear-positive PTB, with LFU being a major problem. The Benin NTP needs to better address the problem of patients with SNPTB in terms of monitoring and reporting, treatment management including that associated with HIV care, and reducing LFU.

Assessment of organizational measures to prevent nosocomial tuberculosis in health facilities of 4 sub-Saharan countries in 2010.

BACKGROUND: The prevention of tuberculosis (TB) transmission in healthcare settings is a major issue, particularly because of the interaction between human immunodeficiency virus and TB and the emergence of multidrug-resistant TB. SETTING: Healthcare facilities involved in TB management in 4 African countries (Benin, Cameroon, Cote d'Ivoire, and Togo). METHODS: A questionnaire was developed by representatives of the 4 countries to evaluate the organizational measures implemented in facilities involved in TB management. On-site visits were performed between July 2010 and July 2011. RESULTS: A total of 115 facilities, including 10 university hospitals and 92 basic management units, were visited. None had a TB infection control plan, and only 5.2% provided education for staff about nosocomial TB. Overall, 48.3% of the facilities performed triage of suspected TB cases on hospital arrival or admission, 89.6% provided education for TB cases on cough etiquette, 20.0% segregated smear-positive TB cases, and 15.7% segregated previously treated cases. A total of 15.5% of the facilities registered TB among staff, for a global prevalence rate of 348 cases per 100,000 staff members. CONCLUSION: This survey identified simple and mostly costless administrative measures to be urgently implemented at the local level to prevent nosocomial TB, such as staff education, triage on admission, and segregation of previously treated patients.

Rapid detection of multidrug-resistant Mycobacterium tuberculosis in Cotonou (Benin) using two low-cost colorimetric methods: resazurin and nitrate reductase assays.

We have evaluated two simple, rapid and low-cost colorimetric methods for the detection of multidrug-resistant Mycobacterium tuberculosis. A total of 151 M. tuberculosis strains were tested for resistance to rifampicin (RMP) and isoniazid by resazurin microplate assay (REMA) and nitrate reductase assay (NRA) in comparison with the conventional proportion method (PM) on Löwenstein-Jensen medium. A complete agreement was found between NRA and PM, while one false RMP-susceptible result was found by REMA. REMA and NRA tests are rapid and inexpensive, and could be good alternatives to the conventional PM in low-resource countries.