We examined factors associated with mixed-strain Mycobacterium tuberculosis infections among patients at high risk for drug-resistant tuberculosis in Botswana. Thirty-seven (10.0%) of 370 patients with tuberculosis had mixed M. tuberculosis infections, based on 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping. In log-binomial regression analysis, age <37 years (adjusted prevalence ratio [PR], 1.92; 95% confidence interval [CI], 1.01-3.57) and prior tuberculosis treatment (adjusted PR, 2.31; 95% CI, 1.09-4.89) were associated with mixed M. tuberculosis infections. Among human immunodeficiency virus-infected patients, prior tuberculosis treatment (adjusted PR, 2.11; 95% CI, 1.04-4.31) and CD4(+) T-cell count of <100 cells/μl (adjusted PR, 10.18; 95% CI, 2.48-41.71) were associated with mixed M. tuberculosis infections. Clinical suspicion of mixed M. tuberculosis infections should be high for patients with advanced immunosuppression and a prior history of tuberculosis treatment.

Comorbidity of tuberculosis (TB) and depression may lead to delayed TB treatment initiation. A cross-sectional study was conducted between January and December 2019 to examine the association between depression and delayed TB treatment initiation among newly diagnosed TB patients in Botswana. We used the Patient Health Questionnaire-9 and the ZUNG self-rating anxiety scale to assess depressive and anxiety symptoms, respectively. Delayed TB treatment was defined as experiencing common TB symptoms for more than 2 months before treatment initiation. We used Poisson regression models with robust variance to assess the association between covariates and delayed treatment initiation. Majority of the enrolled 180 study participants were males (n =116, 64.4%). Overall, 99 (55%) were co-infected with HIV; depression and anxiety symptoms were reported by 47.2% and 38.5% of the participants respectively. The prevalence of delayed TB treatment was 42.6% and 18.8% among participants who indicated symptoms of depression and among participants without depression respectively. After adjusting for age, HIV status, gender and anxiety symptoms, depression was still associated with delayed TB treatment (adjusted prevalence ratio [aPR] = 2.09; 95% CI = 1.23-3.57). Integrating management of depressive symptoms during TB treatment may help in improving overall TB treatment outcomes.

Background

Nosocomial transmission of pulmonary tuberculosis (PTB) is a problem in resource-limited settings. However, the degree of TB exposure and the intermediate- and long-term morbidity and mortality of hospital-associated TB is unclear. In this study we determined: 1) the nature, patterns and intensity of TB exposure occurring in the context of current TB cohorting practices in medical centre with a high prevalence of TB and HIV; 2) the one-year TB incidence after discharge; and 3) one-year TB-related mortality after hospital discharge.

Methods

Factors leading to nosocomial TB exposure were collected daily over a 3-month period. Patients were followed for 1-year after discharge. TB incidence and mortality were calculated and logistic regression was used to determine the factors associated with TB incidence and mortality during follow up.

Results

1,094 patients were admitted to the medical wards between May 01 and July 31, 2010. HIV was confirmed in 690/1,094 (63.1%) of them. A total of 215/1,094 (19.7%) patients were diagnosed with PTB and 178/1,094 (16.3%) patients died during the course of their hospitalization; 12/178 (6.7%) patients died from TB-related complications. Of the 896 (83.7%) discharged patients, 41 (4.6%) [corrected] were diagnosed with TB during the year of follow up. Overall, 123/896 (14%) patients died during the follow up period, of whom 26/123 (21%) died from TB. [corrected] One-year TB incidence rate and TB-associated mortality were associated with the number of days that the patient remained hospitalized, the number of days spent in the cohorting bay (regardless of whether the patient was eventually diagnosed with TB or not), and the number and proximity to TB index cases. There was no difference in the performance of each of these 3 measurements of nosocomial TB exposure for the prediction of one-year TB incidence.

Conclusion

Substantial TB exposure, particularly among HIV-infected patients, occurs in nosocomial settings despite implementation of cohorting measures. Nosocomial TB exposure is strongly associated with one-year TB incidence and TB-related mortality. Further studies are needed to identify strategies to reduce such exposure among susceptible patients.

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.

Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains (i.e., mixed infection) challenges clinical and epidemiologic paradigms. We explored possible transmission mechanisms of mixed infection in a population-based, molecular epidemiology study in Botswana during 2012-2016. We defined mixed infection as multiple repeats of alleles at >2 loci within a discrete mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) result. We compared mixed infection MIRU-VNTR results with all study MIRU-VNTR results by considering all permutations at each multiple allele locus; matched MIRU-VNTR results were considered evidence of recently acquired strains and nonmatched to any other results were considered evidence of remotely acquired strains. Among 2,051 patients, 34 (1.7%) had mixed infection, of which 23 (68%) had recently and remotely acquired strains. This finding might support the mixed infection mechanism of recent transmission and simultaneous remote reactivation. Further exploration is needed to determine proportions of transmission mechanisms in settings where mixed infections are prevalent.

Objective

To determine the association between food insecurity and HIV infection with depression and anxiety among new tuberculosis (TB) patients.

Design

Our cross-sectional study assessed depression, anxiety and food insecurity with Patient Health Questionnaire (PHQ-9), Zung Anxiety Self-Assessment Scale (ZUNG) and Household Food Insecurity Access Scale, respectively. Poisson regression models with robust variance were used to examine correlates of depression (PHQ-9 ≥ 10) and anxiety (ZUNG ≥ 36).

Setting

Gaborone, Botswana.

Participants

Patients who were newly diagnosed with TB.

Results

Between January and December 2019, we enrolled 180 TB patients from primary health clinics in Botswana. Overall, 99 (55·0 %) were HIV positive, 47 (26·1 %), 85 (47·2 %) and 69 (38·5 %) indicated depression, anxiety and moderate to severe food insecurity, respectively. After adjusting for potential confounders, food insecurity was associated with a higher prevalence of depression (adjusted prevalence ratio (aPR) = 2·30; 95 % CI 1·40, 3·78) and anxiety (aPR = 1·41; 95 % CI 1·05, 1·91). Prevalence of depression and anxiety was similar between HIV-infected and HIV-uninfected participants. Estimates remained comparable when restricted to HIV-infected participants.

Conclusions

Mental disorders may be affected by food insecurity among new TB patients, regardless of HIV status.

Cancer patients are at higher risk of tuberculosis (TB) infection, especially in hospital settings with high TB/HIV burden. The study was implemented among adult patients admitted to the largest tertiary-level referral hospital in Botswana. We estimated the TB prevalence at admission and the rate of newly diagnosed TB after hospitalization in the medical and oncology wards, separately. Presumptive TB cases were identified at admission through symptom screening and underwent the diagnostic evaluation through GeneXpert. Patients with no evidence of TB were followed-up until TB diagnosis or the end of the study. In the medical and oncology wards, four of 867 admitted patients and two of 240 had laboratory-confirmed TB at admission (prevalence = 461.4 and 833.3 per 100,000, respectively.) The post-admission TB rate from the medical wards was 28.3 cases per 1,000 person-year during 424.5 follow-up years (post-admission TB rate among HIV-positive versus. -negative = 54.1 and 9.8 per 1,000 person-year, respectively [Rate Ratio = 5.5]). No post-admission TB case was detected from the oncology ward. High rates of undetected TB at admission at both medical and oncology wards, and high rate of newly diagnosed TB after admission at medical wards suggest that TB screening and diagnostic evaluation should target all patients admitted to a hospital in high-burden settings.

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.

Multidrug-resistant tuberculosis (TB) is an alarming threat, and targeted deep sequencing (DS) may be an effective method for rapid identification of drug-resistant profiles, including detection of heteroresistance. We evaluated the sensitivity and specificity of targeted DS versus phenotypic drug susceptibility testing (pDST) among patients starting first-line anti-TB therapy in Botswana. Overall, we found high concordance between DS and pDST. Lower sensitivity of DS, which targets established high-confidence resistance variants, was observed for detecting isoniazid resistance among HIV-infected patients.