Scaling up target regimens for tuberculosis preventive treatment in Brazil and South Africa: An analysis of costs and cost-effectiveness.

BACKGROUND: Shorter, safer, and cheaper tuberculosis (TB) preventive treatment (TPT) regimens will enhance uptake and effectiveness. WHO developed target product profiles describing minimum requirements and optimal targets for key attributes of novel TPT regimens. We performed a cost-effectiveness analysis addressing the scale-up of regimens meeting these criteria in Brazil, a setting with relatively low transmission and low HIV and rifampicin-resistant TB (RR-TB) prevalence, and South Africa, a setting with higher transmission and higher HIV and RR-TB prevalence. METHODS AND FINDINGS: We used outputs from a model simulating scale-up of TPT regimens meeting minimal and optimal criteria. We assumed that drug costs for minimal and optimal regimens were identical to 6 months of daily isoniazid (6H). The minimal regimen lasted 3 months, with 70% completion and 80% efficacy; the optimal regimen lasted 1 month, with 90% completion and 100% efficacy. Target groups were people living with HIV (PLHIV) on antiretroviral treatment and household contacts (HHCs) of identified TB patients. The status quo was 6H at 2019 coverage levels for PLHIV and HHCs. We projected TB cases and deaths, TB-associated disability-adjusted life years (DALYs), and costs (in 2020 US dollars) associated with TB from a TB services perspective from 2020 to 2035, with 3% annual discounting. We estimated the expected costs and outcomes of scaling up 6H, the minimal TPT regimen, or the optimal TPT regimen to reach all eligible PLHIV and HHCs by 2023, compared to the status quo. Maintaining current 6H coverage in Brazil (0% of HHCs and 30% of PLHIV treated) would be associated with 1.1 (95% uncertainty range [UR] 1.1-1.2) million TB cases, 123,000 (115,000-132,000) deaths, and 2.5 (2.1-3.1) million DALYs and would cost $1.1 ($1.0-$1.3) billion during 2020-2035. Expanding the 6H, minimal, or optimal regimen to 100% coverage among eligible groups would reduce DALYs by 0.5% (95% UR 1.2% reduction, 0.4% increase), 2.5% (1.8%-3.0%), and 9.0% (6.5%-11.0%), respectively, with additional costs of $107 ($95-$117) million and $51 ($41-$60) million and savings of $36 ($14-$58) million, respectively. Compared to the status quo, costs per DALY averted were $7,608 and $808 for scaling up the 6H and minimal regimens, respectively, while the optimal regimen was dominant (cost savings, reduced DALYs). In South Africa, maintaining current 6H coverage (0% of HHCs and 69% of PLHIV treated) would be associated with 3.6 (95% UR 3.0-4.3) million TB cases, 843,000 (598,000-1,201,000) deaths, and 36.7 (19.5-58.0) million DALYs and would cost $2.5 ($1.8-$3.6) billion. Expanding coverage with the 6H, minimal, or optimal regimen would reduce DALYs by 6.9% (95% UR 4.3%-95%), 15.5% (11.8%-18.9%), and 38.0% (32.7%-43.0%), respectively, with additional costs of $79 (-$7, $151) million and $40 (-$52, $140) million and savings of $608 ($443-$832) million, respectively. Compared to the status quo, estimated costs per DALY averted were $31 and $7 for scaling up the 6H and minimal regimens, while the optimal regimen was dominant. Study limitations included the focus on 2 countries, and no explicit consideration of costs incurred before the decision to prescribe TPT. CONCLUSIONS: Our findings suggest that scale-up of TPT regimens meeting minimum or optimal requirements would likely have important impacts on TB-associated outcomes and would likely be cost-effective or cost saving.

Estimating HIV incidence from surveillance data indicates a second wave of infections in Brazil.

Emerging evidence suggests that HIV incidence rates in Brazil, particularly among men, may be rising. Here we use Brazil's integrated health systems data to develop a mathematical model, reproducing the complex surveillance systems and providing estimates of HIV incidence, number of people living with HIV (PLHIV), reporting rates and ART initiation rates. An age-structured deterministic model with a flexible spline was used to describe the natural history of HIV along with reporting and treatment rates. Individual-level surveillance data for 1,077,295 cases (HIV/AIDS diagnoses, ART dispensations, CD4 counts and HIV/AIDS-related deaths) were used to calibrate the model using Bayesian inference. The results showed a second wave of infections occurring after 2001 and 56,000 (95% Credible Interval 43,000-71,000) new infections in 2015, 37,000 (95% CrI 28,000-54,000) infections in men and 16,000 (95% CrI 10,000-23,000) in women. The estimated number of PLHIV by end-2015 was 838,000 (95% CrI 675,000-1,083,000), with 80% (95% CrI 62-98%) of those individuals reported to the Ministry of Health. Women were more likely to be diagnosed and reported than men; 86.8% of infected women had been reported compared with 75.7% of men. Likewise, ART initiation rates for women were higher than those for men. The second wave contradicts previous estimates of HIV incidence trends in Brazil and there were persistent differences in the rates of accessing care between men and women. Nevertheless, the Brazilian HIV program has achieved high rates of detection and treatment, making considerable progress over the past ten years.

Murine typhus in Caldas, Colombia.

In the north of Caldas, Colombia, febrile syndromes with positive Weil-Felix reactions have been reported as Murine typhus to the national health authorities. We used indirect immunofluorescence assay (IFA) of serial paired samples to confirm the diagnosis of murine typhus in 14 of 120 patients with a compatible febrile syndrome.