The utility of a modified WHO TB screening tool among children at a Botswana child welfare clinic.

BACKGROUND: In high TB/HIV settings, the increased risk for TB amongst children exposed to HIV has been established through biomedical tests. Screening HIV exposed children for TB can improve early childhood TB detection and treatment. OBJECTIVE: This study assessed the utility of a modified World Health Organization (WHO) tool by including HIV variables, to determine TB exposure amongst HIV exposed children presenting to a "Well Child" Clinic (CWC). METHODS: Clinical data were obtained from medical records and/or from the caregivers of children presenting to CWC. Data was analyzed to explore factors associated with positive screening for TB, including being exposed to HIV and current HIV status. RESULTS: Five percent (55/1100) screened reported a close TB contact and 21% (n=231) had positive TB symptom screen. History of close TB contact was a risk factor for positive screening for TB symptoms (OR 1.89 CI 1.05-3.4) while being HIV negative was protective (OR 0.3, Cl 0.19-0.62). HIV exposure was associated with increased risk of TB exposure (OR 2.9 CI 1.61-5.19). CONCLUSION: Integrating HIV variables in the existing WHO screening tool for childhood TB can be useful in early detection and treatment of TB in HIV exposed children in resource limited settings.

The execution rate of procedures to diagnose extrapulmonary tuberculosis in Botswana.

BACKGROUND: Extra-pulmonary tuberculosis (EPTB) accounts for about 20% of TB cases worldwide. Its diagnosis is challenging. AIM: This study meant to assess the prevalence of EPTB types, procedures to diagnose EPTB and medical officers' (MOs) views on procedures performed in the diagnosis of EPTB over a 2-year period in Botswana. SETTING: The study was conducted in 13 urban and rural facilities of 29 health districts in Botswana. METHODS: This was a cross-sectional study that reviewed patients' TB data and administered a questionnaire to MOs. RESULTS: About 2 in 10 TB (n = 2996, 22.7%) cases were classified as EPTB. The most common site of EPTB was pleural (n = 1066, 36.7%) followed by lymph node (LN) (n = 546, 18.8%). A pleural tap was performed in 182 (17.0%) cases of pleural TB and a fine needle aspiration (FNA) in one-third (n = 160, 29.6%) of LN TB cases. There were statistical differences in work experience amongst MOs' responses regarding their self-reported confidence to undertake basic procedures to diagnose EPTB such as pleural tap (p = 0.032) or FNA (p 0.0001). CONCLUSION: This study reviewed and evaluated the proportion of EPTB and inquired about MO's experience in managing EPTB. Despite MOs' attendance at Botswana National Tuberculosis Programme (BNTP) TB case management (TBCM) training, the emphasis by the BNTP guidelines and availability of logistics, the execution rate of procedures to diagnose EPTB was still low in Botswana.

The execution rate of procedures to diagnose extrapulmonary tuberculosis in Botswana

Background: Extra-pulmonary tuberculosis (EPTB) accounts for about 20% of TB cases worldwide. Its diagnosis is challenging. Aim: This study meant to assess the prevalence of EPTB types, procedures to diagnose EPTB and medical officers' (MOs) views on procedures performed in the diagnosis of EPTB over a 2-year period in Botswana. Setting: The study was conducted in 13 urban and rural facilities of 29 health districts in Botswana. Methods: This was a cross-sectional study that reviewed patients' TB data and administered a questionnaire to MOs. Results: About 2 in 10 TB (n= 2996, 22.7%) cases were classified as EPTB. The most common site of EPTB was pleural (n= 1066, 36.7%) followed by lymph node (LN) (n= 546, 18.8%). A pleural tap was performed in 182 (17.0%) cases of pleural TB and a fine needle aspiration (FNA) in one-third (n= 160, 29.6%) of LN TB cases. There were statistical differences in work experience amongst MOs' responses regarding their self-reported confidence to undertake basic procedures to diagnose EPTB such as pleural tap (p= 0.032) or FNA (p< 0.0001). Conclusion: This study reviewed and evaluated the proportion of EPTB and inquired about MO's experience in managing EPTB. Despite MOs' attendance at Botswana National Tuberculosis Programme (BNTP) TB case management (TBCM) training, the emphasis by the BNTP guidelines and availability of logistics, the execution rate of procedures to diagnose EPTB was still low in Botswana

High incidence of tuberculosis in the first year of antiretroviral therapy in the Botswana National antiretroviral therapy programme between 2011 and 2015.

OBJECTIVE: Tuberculosis (TB) remains one of the leading causes of mortality and morbidity among people living with HIV. We sought to estimate the incidence of TB in a national database of HIV-infected patients receiving antiretroviral therapy (ART) in Botswana. DESIGN: A retrospective analysis of HIV-infected adult patients (≥18years) who initiated ART between 2011 and 2015 in the Botswana ART program. METHODS: Multivariable analysis using Cox regression included sex, age, viral load and CD4 T-cell counts. RESULTS: Of 45 729 patients, with a median follow-up of 1.7 years Q1 : Q3, 0.5, 3.1), 1791 patients developed TB over a median of 1.5 years (Q1 : Q3, 0.3, 3.1) of follow-up (incidence rate 1.9 per 100 person-years; 95% CI 1.8-2.0). At baseline, the median CD4 T-cell count was 272 cells/µl (Q1, Q3 146, 403). The risk of TB was greatest within the first year of ART (incidence rate 2.9 per 100 person-years; 95% CI 2.7-3.1) and in patients with CD4 T-cell counts below 50 cells/µl (incidence rate 8.3/100 person-years; 95% CI 7.1-9.7). Patients with viral loads above 10 000 copies/ml at 3 months post-ART initiation had two times higher risk of TB, hazard ratio 2.5 (95% CI 1.8-2.3). CONCLUSION: We report a high incidence of TB within the first year of ART and in patients with advanced immunodeficiency. Improved screening strategies and virologic monitoring during this early period on ART, coupled with TB preventive treatment, will reduce the burden of TB.

Detection of Second Line Drug Resistance among Drug Resistant Mycobacterium Tuberculosis Isolates in Botswana.

The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (M.tb) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates. A total of 66 M.tb isolates received at the National Tuberculosis Reference Laboratory between March 2012 and October 2013 with resistance to isoniazid, rifampicin or both were analyzed in this study. The genotypes of the M.tb isolates were determined by spoligotyping and second-line drug susceptibility testing was done using the Hain Genotype MTBDRsl line probe assay version 2.0. The treatment outcomes were defined according to the Botswana national and World Health Organization (WHO) guidelines. Of the 57 isolates analyzed, 33 (58%) were MDR-TB, 4 (7%) were additionally resistant to flouroquinolones and 3 (5%) were resistant to both fluoroquinolones and second-line injectable drugs. The most common fluoroquinolone resistance-conferring mutation detected was gyrA A90V. All XDR-TB cases remained smear or culture positive throughout the treatment. Our study findings indicate the importance of monitoring drug resistant TB cases to ensure rapid detection of second-line drug resistance.

Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana.

BACKGROUND: Dolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern. METHODS: We analyzed HIV and Tuberculosis (TB) treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest. RESULTS: A total of 1225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio = 1.56; 95% confidence interval = 1.06 to 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all antiretroviral therapy (ART) regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates. CONCLUSIONS: The use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.

Investigating Outcomes of Adolescents and Young Adults (10-24 Years of Age) Lost to Follow-up from Tuberculosis Treatment in Gaborone, Botswana.

This retrospective study investigated outcomes among lost to follow-up (LTFU) adolescents and young adults (AYAs: 10-24 years of age) with tuberculosis (TB) registered from 2008 to 2014 in Gaborone, using surveillance data. Of 68 LTFU AYAs, 16 repeated treatment; 8 completed and 6 were again LTFU. Of 4 confirmed deaths, 3 had TB/HIV coinfection. Approaches to improve AYA retention in TB care are needed.

Genetic diversity of Mycobacterium tuberculosis strains circulating in Botswana.

BACKGROUND: Molecular typing of Mycobacterium tuberculosis (M.tb) isolates can inform Tuberculosis (TB) control programs on the relative proportion of transmission driving the TB epidemic. There is limited data on the M. tb genotypes that are circulating in Botswana. The aim of this study was to generate baseline data on the genetic diversity of M.tb isolates circulating in the country. METHODS: A total of 461 M.tb isolates received at the Botswana National Tuberculosis Reference Laboratory between March 2012 and October 2013 were included in this study. Drug susceptibility testing was conducted using the BD BACTEC MGIT 960 System. M.tb strains were genotyped using spoligotyping and spoligotype patterns were compared with existing patterns in the SITVIT Web database. A subset of drug resistant isolates which formed spoligo clusters (n = 65) was additionally genotyped with 12-loci MIRU. Factors associated with drug resistance and clustering were evaluated using logistic regression. RESULTS: Of the 461 isolates genotyped, 458 showed 108 distinct spoligotype patterns. The predominant M.tb lineages were Lineage 4 (81.9%), Lineage 2 (9%) and Lineage 1 (7.2%). The predominant spoligotype families within Lineage 4 were LAM (33%), S (14%), T (16%), X (16%). Three hundred and ninety-two (86%) isolates could be grouped into 44 clusters (2-46 isolates per cluster); giving a clustering rate of 76%. We identified 173 (37.8%) drug resistant isolates, 48 (10.5%) of these were multi-drug resistant. MIRU typing of the drug resistant isolates allowed grouping of 46 isolates into 14 clusters, giving a clustering rate of 49.2%. There was no association between age, sex, treatment category, region and clustering. CONCLUSIONS: This study highlights the complexity of the TB epidemic in Botswana with multiple strains contributing to disease and provides baseline data on the population structure of M.tb strains in Botswana.

High Treatment Success Rates Among HIV-Infected Multidrug-Resistant Tuberculosis Patients After Expansion of Antiretroviral Therapy in Botswana, 2006-2013.

BACKGROUND: Few studies have examined multidrug-resistant (MDR) tuberculosis (TB) treatment outcomes among HIV-infected persons after widespread expansion of antiretroviral therapy (ART). We describe MDR-TB treatment outcomes among HIV-infected and HIV-uninfected patients in Botswana after ART expansion. METHODS: We retrospectively reviewed data from patients who started MDR-TB therapy in Botswana during 2006-2013. Multivariable regression models were used to compare treatment outcomes between HIV-infected and HIV-uninfected patients. RESULTS: We included 588 MDR-TB patients in the analysis, of whom, 47 (8.0%) and 9 (1.5%) were diagnosed with pre-extensively drug-resistant (XDR)-TB and XDR-TB, respectively. Of the 408 (69.4%) HIV-infected patients, 352 (86.0%) were on ART or started ART during treatment, and median baseline CD4 T-cell count was 234 cells/mm. Treatment success rates were 79.4% and 73.0% among HIV-uninfected and HIV-infected patients, respectively (P = 0.121). HIV-infected patients with CD4 T-cell count <100 cells/mm were more likely to die during treatment compared with HIV-uninfected patients (adjusted risk ratio = 1.890; 95% CI: 1.098 to 3.254). CONCLUSIONS: High rates of treatment success were achieved with programmatic management of MDR-TB and HIV in Botswana after widespread expansion of ART. However, a 2-fold increase in mortality was observed among HIV-infected persons with baseline CD4 <100 cells/mm compared with HIV-uninfected persons.