Risk of obstructive sleep apnea among taxi-motorbike drivers in Parakou city in West Africa and associated factors with road traffic accidents.

OBJECTIVES: Obstructive sleep apnea (OSA) is an underdiagnosed chronic respiratory disease, causing excessive daytime sleepiness (EDS) and road traffic accidents (RTA). This study aimed to determine the risk of OSA among taxi-motorbike drivers (TMD) and factors associated with RTA in Parakou, Benin. METHODS: A cross-sectional comparative study was carried out between July and September 2020, including 225 TMD and 450 motorbike drivers other than TMD (non-TMD). A multiple logistic regression was then performed to determine factors associated with RTA. RESULTS: The mean age of participants was 38.2 ± 10.2 and 36.6 ±10.9 years, respectively, for TMD and non-TMD (p = .048). The average daily working time was 10.7 ± 2.3H and 9.1±3.5H, respectively, for TMD and non-TMD (p < .001). Average sleeping time was comparable in both groups (7.5±1.4H vs 7.4±1.4H; p = .415). TMD significantly more complained of non-restorative sleep (38.7% vs 18.4%; p < .001) but less of EDS (20.0% vs 28.7%; p = .015). Abdominal obesity predominated in TMD (13.8% vs 4.4%; p < .001). An increased risk of OSA (NoSAS score ≥8) was diagnosed in 25.8% TMD and 26.7% non-TMD (p = .805). Overall, 25.8% of TMD and 18.4% of non-TMD (p = .027) reported at least one RTA in the last 12 months. After adjusted analysis, the unique factor associated with RTA was a daily sleeping pills consumption (aOR=2.2; 95%CI = 1.2-3.8; p = .006). CONCLUSION: There is need to improve systematic screening and diagnosis of OSA in both TMD and non-TMD and reinforce the regulation and consumption of sleeping pills.

Safety and Side Effects of Rifampin versus Isoniazid in Children.

BACKGROUND: The treatment of latent infection with Mycobacterium tuberculosis is important in children because of their vulnerability to life-threatening forms of tuberculosis disease. The current standard treatment - 9 months of isoniazid - has been associated with poor adherence and toxic effects, which have hampered the effectiveness of the drug. In adults, treatment with 4 months of rifampin has been shown to be safer and to have higher completion rates than 9 months of isoniazid. METHODS: In this multicenter, open-label trial, we randomly assigned 844 children (<18 years of age) with latent M. tuberculosis infection to receive either 4 months of rifampin or 9 months of isoniazid. The primary outcome was adverse events of grade 1 to 5 that resulted in the permanent discontinuation of a trial drug. Secondary outcomes were treatment adherence, side-effect profile, and efficacy. Independent review panels whose members were unaware of trial-group assignments adjudicated all adverse events and progression to active tuberculosis. RESULTS: Of the children who underwent randomization, 829 were eligible for inclusion in the modified intention-to-treat analysis. A total of 360 of 422 children (85.3%) in the rifampin group completed per-protocol therapy, as compared with 311 of 407 (76.4%) in the isoniazid group (adjusted difference in the rates of treatment completion, 13.4 percentage points; 95% confidence interval [CI], 7.5 to 19.3). There were no significant between-group differences in the rates of adverse events, with fewer than 5% of the children in the combined groups with grade 1 or 2 adverse events that were deemed to be possibly related to a trial drug. Active tuberculosis, including 1 case with resistance to isoniazid, was diagnosed in 2 children in the isoniazid group during 542 person-years of follow-up, as compared with no cases in the rifampin group during 562 person-years (rate difference, -0.37 cases per 100 person-years; 95% CI, -0.88 to 0.14). CONCLUSIONS: Among children under the age of 18 years, treatment with 4 months of rifampin had similar rates of safety and efficacy but a better rate of adherence than 9 months of treatment with isoniazid. (Funded by the Canadian Institutes of Health Research and Conselho Nacional de Pesquisa; ClinicalTrials.gov number, NCT00170209 .).

Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults.

BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels. RESULTS: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events. CONCLUSIONS: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings.

BACKGROUND: Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen. OBJECTIVE: To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid. DESIGN: Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209). SETTING: High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). PARTICIPANTS: Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection. MEASUREMENTS: Health system costs per participant. RESULTS: A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population. LIMITATION: Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines. CONCLUSION: A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Work environment and hypertension in industrial settings in Benin in 2019: a cross-sectional study.

OBJECTIVE: To determine the association between occupational factors, particularly psychosocial factors, and hypertension. DESIGN: Descriptive and analytical cross-sectional study using logistic multivariate regression. SETTING: Fifteen cotton ginning plants in Benin. PARTICIPANTS: Permanent and occasional workers in the cotton ginning industry. DATA COLLECTION: Data on sociodemographic, occupational, behavioural and clinical history characteristics were collected using a number of standardised, interviewer-administered questionnaires. These questionnaires were based on the WHO's non-communicable disease questionnaire, Karasek questionnaire and Siegrist questionnaire. Weight, height and blood pressure were measured. Any worker with systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg according to the WHO criteria was considered hypertensive, as was any subject on antihypertensive treatment even if blood pressure was normal. RESULTS: A total of 1883 workers were included, with a male to female ratio of 9.08. Of these, 510 suffered from hypertension (27.1%, 95% CI 25.1 to 29.2). In the multivariate analysis, the risk factors identified were occupational stress (adjusted OR (aOR)=3.96, 95% CI 1.28 to 12.2), age ≥25 years (aOR=2.77, 95% CI 1.55 to 4.96), body mass index of 25-30 kg/m2 (aOR=1.71, 95% CI 1.32 to 2.2), body mass index >30 kg/m2 (aOR=2.74, 95% CI 1.84 to 4.09), permanent worker status (aOR=1.66, 95% CI 1.44 to 2.41) and seniority in the textile sector >5 years (aOR=2.18, 95% CI 1.7 to 2.8). Recognition at work emerged as an effect-modifying factor subject to stratification. CONCLUSIONS: Occupational factors, particularly job strain and recognition at work, are modifiable factors associated with hypertension in the ginning plants sector and deserve to be corrected through occupational health promotion and prevention.

Sustainability and impact of an intervention to improve initiation of tuberculosis preventive treatment: results from a follow-up study of the ACT4 randomized trial.

Background: In a cluster randomized trial (clinicaltrials.gov: NCT02810678) a flexible but comprehensive health system intervention significantly increased the number of household contacts (HHC) identified and started on tuberculosis preventive treatment (TPT). A follow-up study was conducted one year later to test the hypotheses that these effects were sustained, and were reproducible with a simplified intervention. Methods: We conducted a follow-up study from May 1, 2018 until April 30, 2019, as part of a multinational cluster randomized trial. Eight sites in 4 countries that had received the intervention in the original trial received no further intervention; eight other sites in the same countries that had not received the intervention (control sites in the original trial) now received a simplified version of the intervention. This consisted of repeated local evaluation of the Cascade of care for TB infection, and stakeholder decision making. The number of HHC identified and starting TPT were repeatedly measured at all 16 sites and expressed as rates per 100 newly diagnosed index TB patients. The sustained effect of the original intervention was estimated by comparing these rates after the intervention in the original trial with the last 6 months of the follow-up study. The reproducibility was estimated by comparing the pre-post intervention changes in rates at sites receiving the original intervention with the pre-post changes in rates at sites receiving the later, simplified intervention. Findings: With regard to the sustained impact of the original intervention, compared to the original post-intervention period, the number of HHC identified and treated per 100 newly diagnosed TB patients was 10 more (95% confidence interval: 84 fewer to 105 more), and 1 fewer (95% CI: 22 fewer to 20 more) respectively up to 14 months after the end of the original intervention. With regard to the reproducibility of the simplified intervention, at sites that had initially served as control sites, the number of HHC identified and treated per 100 TB patients increased by 33 (95% CI: -32, 97), and 16 (-69, 100) from 3 months before, to up to 6 months after receiving a streamlined intervention, although differences were larger, and significant if the post-intervention results were compared to all pre-intervention periods. Interpretation: Up to one year after it ended, a health system intervention resulted in sustained increases in the number of HHC identified and starting TPT. A simplified version of the intervention was associated with non-significant increases in the identification and treatment of HHC. Inferences are limited by potential bias due to other temporal effects, and the small number of study sites. Funding: Funded by the Canadian Institutes of Health Research (Grant number 143350).

Human resource implications of expanding latent tuberculosis patient care activities.

Introduction: The World Health Organization (WHO) declared increasing services for latent tuberculosis infection (LTBI) a priority to eliminate tuberculosis (TB) by 2035. Yet, there is little information about thehuman resource needs required to implement LTBI treatment scale-up. Our study aimed to estimate the change in healthcare workers (HCW) time spent on different patient care activities, following an intervention to strengthen LTBI services. Methods: We conducted a time and motion (TAM) study, observing HCW throughout a typical workday before and after the intervention (Evaluation and Strengthening phases, respectively) at 24 health facilities in five countries. The precise time spent on pre-specified categories of work activities was recorded. Time spent on direct patient care was subcategorized as relating to one of three conditions: LTBI, active or suspected TB, and non-TB (i.e., patients with any other medical condition). A linear mixed model (LMM) was fit to estimate the change in HCW time following the intervention. Results: A total of 140 and 143 HCW participated in the TAMs during the Evaluation and Strengthening phases, respectively. Results from intervention facilities showed an increase of 9% (95% CI: 3%, 15%) in the proportion of HCW time spent on LTBI-related services, but with a corresponding change of -11% (95% CI: -21%, -1%) on active TB services. There was no change in the proportion of time spent on LTBI care in control facilities; this remained low in both phases of the study. Discussion: Our findings suggest that additional HCW personnel will be required for expansion of LTBI services to ensure that this expansion does not reduce the time available for care of active TB patients.

Occupational stress in industry setting in Benin 2019: A cross-sectional study.

BACKGROUND: Occupational stress is a psychosocial risk in the workplace. Working conditions in industrial settings may lead to occupational stress. In Benin, however, there is little epidemiological data on occupational stress in industrial settings. We aimed to determine the prevalence and factors associated with occupational stress in industrial settings in Benin in 2019. METHODS: This was a prospective, cross-sectional study conducted from January 31 to April 11, 2019, among 15 cotton ginning plants. Sampling was exhaustive for permanent workers and stratified in clusters by shift for occasional cotton gin workers. Data were collected through Karasek and Siegrist questionnaires. Data analysis was performed using R software. Binary multivariable logistic regression was performed. The significance level was p < 0.05. RESULTS: Of 1883 workers included, 90.8% were male. The median age was 38 years (IQR: 28 years to 49 years). The prevalence of occupational stress was 77.7% (95% CI: 75.8-79.6). Psychological demand was high in 93.0% of workers and 83.9% had low decision latitude. Among the workers, 16.3% had low social support and 89.9% had a low recognition score at work. Factors associated with occupational stress were: being an occasional vs. permanent worker (aOR 6.43, 95% CI 4.18 to 9.88); age less than 38 years (aOR 0.55, 95% CI 0.41 to 0.76); high intensity physical activity at work (aOR 1.33, 95% CI 1.03 to 1.73); working in production vs. administration (aOR 1.59, 95% CI 1.03 to 2.45); spending fewer than 4 years at the current work location (aOR 1.60, 95% CI 1.05 to 2.44); and scoring low for recognition at work (aOR 1.53, 95% CI 1.04 to 2.23). Noise exposure and being a shift worker were significant in univariable analysis, but not multivariable analysis. CONCLUSION: Occupational stress is very common among workers in industrial settings. The implementation and evaluation of preventive measures against these risk factors is necessary.

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.

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.

Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial.

BACKGROUND: Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases. METHODS: ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either a three-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care). Tuberculin and isoniazid were provided to control and intervention sites if not routinely available. Randomisation was stratified by country and restricted to ensure balance of index patients with tuberculosis by arm and country. The primary outcome was the number of household contacts who initiated tuberculosis preventive treatment at each health facility within 4 months of the diagnosis of the index case, recorded in the first or last 6 months of our 20-month study. To ease interpretation, this number was standardised per 100 newly diagnosed index patients with tuberculosis. Analysis was by intention to treat. Masking of staff at the coordinating centre and sites was not possible; however, those analysing data were masked to assignment of intervention or control. An economic analysis of the intervention was done in parallel with the trial. ACT4 is registered at ClinicalTrials.gov, NCT02810678. FINDINGS: The study was done between Aug 1, 2016, and March 31, 2019. During the first 6 months of the study the crude overall proportion of household contacts initiating tuberculosis preventive treatment out of those eligible at intervention sites was 0·21. After the implementation of programme strengthening activities, the proportion initiating tuberculosis preventive treatment increased to 0·35. Overall, the number of household contacts initiating tuberculosis preventive treatment per 100 index patients with tuberculosis increased between study phases in intervention sites (adjusted rate difference 60, 95% CI 4 to 116), while control sites showed no statistically significant change (-12, -33 to 10). There was a difference in rate differences of 72 (95% CI 10 to 134) contacts per 100 index patients with tuberculosis initiating preventive treatment associated with the intervention. The total cost for the intervention, plus LTBI clinical care per additional contact initiating treatment was estimated to be CA$1348 (range 724 to 9708). INTERPRETATION: A strategy of standardised evaluation, local decision making, and implementation of health systems strengthening activities can provide a mechanism for scale-up of tuberculosis prevention, particularly in low-income and middle-income countries. FUNDING: Canadian Institutes of Health Research.

Asthma Symptoms in Bakeries at Parakou, Benin.

Background and Objectives. There is a dearth of information on asthma among bakers in low-income settings. The objectives of this study were to determine (i) the prevalence of asthma symptoms, (ii) factors associated with probable occupational asthma (OA), and (iii) work habits that might lead to a dusty workplace environment, Parakou, Benin. Materials and Methods. This was a mixed methods (cross-sectional quantitative and qualitative) study carried out between March and September 2018. RESULTS: Of 210 employees/apprentices in 26 bakeries, 190 (91.48%) were included in the study: median age was 25.50 (IQR = 22 - 32) years, 157 (82.63%) were aged <40 years, and the male-to-female ratio was 26.14. Of these, 111 (58.42%) worked in a salted bread and 79 (41.58%) in a sweet bread bakery. An asthma history was reported by 3.68%. Symptoms consistent with asthma, work-related asthma, OA, and work-aggravated asthma were found in 13.68%, 12.63%, 10%, and 2.63%, respectively. Asthma confirmation was obtained in 15.79% of bakers with probable OA and in 23.08% of all bakers with suspected asthma. A history of allergic rhinoconjunctivitis was associated with probable OA (aOR = 106; 95%CI = 17.79 - 2093; p < 0.001). Of the 24 bakers with probable work-related asthma, 3 (12.50%) were prescribed a short-acting beta2-agonist and 2 (8.33%) an inhaled corticosteroid. No worker had had a systematically planned annual medical visit; some habits at work were identified as leading to flour and dust suspension at the workplace. CONCLUSION: Clinical manifestations of OA were common among bakers in Parakou and were associated with allergic rhinoconjunctivitis. There is a need to improve technical preventive measures and treatment, as well as to institute systematic medical visits for these workers.

Adverse events in adults with latent tuberculosis infection receiving daily rifampicin or isoniazid: post-hoc safety analysis of two randomised controlled trials.

BACKGROUND: An important problem limiting treatment of latent tuberculosis infection is the occurrence of adverse events with isoniazid. We combined populations from phase 2 and phase 3 open-label, randomised controlled trials, to establish risk factors for adverse events during latent tuberculosis infection treatment. METHODS: We did a post-hoc safety analysis based on data from two open-label, randomised controlled trials done in health-care facilities in Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, and South Korea. Participants were consenting adults (aged ≥18 years) with a positive latent tuberculosis infection diagnostic test, indication for treatment, and without contraindications to rifampicin or isoniazid. Patients were centrally randomly assigned 1:1 to 4 months of daily 10 mg/kg rifampicin or 9 months of daily 5 mg/kg isoniazid. The primary outcome evaluated was adverse events (including grade 1-2 rash and all events of grade 3-5) resulting in permanent discontinuation of study medication and judged possibly or probably related to study drug by a masked, independent, three-member adjudication panel (trial registration: NCT00170209; NCT00931736). FINDINGS: Participants were recruited from April 27, 2004, up until Jan 31, 2007 (phase 2), and Oct 1, 2009, up until Dec 31, 2014 (phase 3). The safety populations for each group comprised 3205 individuals receiving isoniazid and 3280 receiving rifampicin. Among those receiving isoniazid, 86 (2·7%) of 3205 had grade 1-2 rash or any grade 3-5 adverse events, more than the 50 (1·5%) of 3280 who had these events with rifampicin (risk difference -1·2%, 95% CI -1·9 to -0·5). Age was associated with adverse events in adults receiving isoniazid. Compared with individuals aged 18-34 years, the adjusted odds ratio (OR) for adverse events was 1·8 (95% CI 1·1-3·0) for individuals aged 35-64 years and 3·0 (1·2-6·8) for individuals aged 65-90 years. With rifampicin, adverse events were associated with inconsistent medication adherence (adjusted OR 2·0, 1·1-3·6) and concomitant medication use (2·8, 1·5-5·2), but not age, with an adjusted OR of 1·1 (0·6-2·1) for individuals aged 35-64 years and 1·7 (0·5-4·7) for individuals aged 65-90 years. One treatment-related death occurred in the isoniazid group. INTERPRETATION: In patients without a contraindication, rifampicin is likely to be the safest latent tuberculosis infection treatment option. With more widespread use of rifampicin, rare, but serious adverse events might be seen. However, within these randomised trials, rifampicin was safer than isoniazid and adverse events were not associated with older age. Therefore, rifampicin should become a primary treatment option for latent tuberculosis infection based on its safety. FUNDING: Canadian Institutes of Health Research.

Enhancing the public health impact of latent tuberculosis infection diagnosis and treatment (ACT4): protocol for a cluster randomised trial.

INTRODUCTION: Treatment of latent tuberculosis (TB) infection (LTBI) is an important component of the End-TB strategy. However, the number of individuals who successfully complete LTBI treatment remains low as there are losses at all steps in the LTBI 'cascade-of-care'. The reasons for these losses are variable and highly dependent on the setting. We have planned a trial of a standardised public health approach to strengthen the management of household contacts (HHCs) of newly diagnosed patients with pulmonary TB. Assessing costs related to approach is a secondary objective of the study. METHODS AND ANALYSIS: A cluster randomised trial will be conducted in 24 randomisation units (health facilities or groups of health facilities) in five countries. In Phase 1, at intervention sites, we will conduct a standardised assessment of the current LTBI programme, with a focus on cascade-of-care endpoints. Standardised open-ended questionnaires on practices, knowledge, attitudes and beliefs regarding TB prevention are then administered to key patient groups and healthcare workers. At each site, local stake-holders will review study findings and select solutions based on their acceptability, cost and effectiveness. In Phase 2, intervention clinics will implement the selected solutions, along with contact measurement registries and regular in-service LTBI management training. Control sites will continue their usual LTBI care with no explicit evaluation, strengthening or training activities. The primary study outcome is the number of HHC initiating LTBI treatment per newly diagnosed active TB patient, within 3 months of diagnosis of the index patient. An intention-to-treat analysis will be performed, using a Poisson regression approach. ETHICS AND DISSEMINATION: Ethics approval from the MUHC ethical review board (ERB) was obtained in November 2015. During the study standardised tools will be developed and made publicly available. Key study findings and novel methodologic contributions will be detailed in publications and other dissemination activities. TRIAL REGISTRATION NUMBER: NCT02810678; Pre-Results.

Operational research within the national tuberculosis control programme in Benin.

OBJECTIVE: To document whether the placement of operational research (OR) fellows within disease control programmes in low and middle income countries leads to the implementation of operational research and improvements in policy and practice. RESULT: In 2012, an OR fellow was placed within the National TB Programme, Benin, to strengthen the implementation of operational research. From 2012 to 2015, eight OR projects were implemented, of which three contributed to changes in programme practice and five provided information which was not previously available from quarterly/annual reports. Two of these projects-one on the burden and treatment outcomes of childhood TB and one on tracing patients who had discontinued treatment-are discussed in more detail. OR should be strongly encouraged within national TB programme settings and an OR fellow facilitates this process.

Tuberculosis Case Finding in Benin, 2000-2014 and Beyond: A Retrospective Cohort and Time Series Study.

Objective. To determine any changes in tuberculosis epidemiology in the last 15 years in Benin, seasonal variations, and forecasted numbers of tuberculosis cases in the next five years. Materials and Methods. Retrospective cohort and time series study of all tuberculosis cases notified between 2000 and 2014. The "R" software version 3.2.1 (Institute for Statistics and Mathematics Vienna Austria) and the Box-Jenkins 1976 modeling approach were used for time series analysis. Results. Of 246943 presumptive cases, 54303 (22%) were diagnosed with tuberculosis. Annual notified case numbers increased, with the highest reported in 2011. New pulmonary bacteriologically confirmed tuberculosis (NPBCT) represented 78% ± SD 2%. Retreatment cases decreased from 10% to 6% and new pulmonary clinically diagnosed cases increased from 2% to 8%. NPBCT notification rates decreased in males from 2012, in young people aged 15-34 years and in Borgou-Alibori region. There was a seasonal pattern in tuberculosis cases. Over 90% of NPBCT were HIV-tested with a stable HIV prevalence of 13%. The ARIMA best fit model predicted a decrease in tuberculosis cases finding in the next five years. Conclusion. Tuberculosis case notifications are predicted to decrease in the next five years if current passive case finding is used. Additional strategies are needed in the country.