Botswana tuberculosis (TB) stakeholders broadly support scaling up next-generation whole genome sequencing: Ethical and practical considerations for Botswana and global health.

Global health agencies are increasingly promoting the scale-up of next-generation whole genome sequencing (NG-WGS) of pathogens into infectious disease control programs, including for tuberculosis (TB). However, little is known about how stakeholders in low-to-middle income countries (LMICs) understand the ethics, benefits, and risks of these proposals. We conducted a qualitative study in Greater Gaborone, Botswana to learn how TB stakeholders there viewed a potential scale-up of NG-WGS into Botswana's TB program. We conducted 30 interviews and four deliberative dialogues with TB stakeholders based in Greater Gaborone, the country's largest city and capital. We created and showed participants an animated video series about a fictional family that experienced TB diagnosis, treatment, contact tracing, and data uses that were informed by NG-WGS. We analyzed transcripts using reflexive thematic analysis. We found broad support for the scale-up of TB NG-WGS in Botswana, owing to perceived benefits. Support was qualified with statements about ensuring adequate planning, resource-allocation, community and stakeholder engagement, capacity-building, and assessing ethical norms around publishing data. Our results suggest that scaling up NG-WGS for TB in Botswana would be supported by stakeholders there, contingent upon the government and other entities adequately investing in the initiative. These findings are relevant to other LMICs considering scale-ups of NG-WGS and related technologies for infectious diseases and suggest the need for sustained research into the acceptability of pathogen sequencing in other contexts.

Undetected tuberculosis at enrollment and after hospitalization in medical and oncology wards in Botswana.

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.

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.

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.