Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone.

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There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy (ART) in sub-Saharan Africa. Patients typically attend clinics every 1–3 months for clinical assessment, with clinic costs being comparable with costs of drugs themselves, CD4 counts are measured every 6 months, yet patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes a transition to more cost-effective ART deliver is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (“viral load”) provides a direct measure of current treatment effect. Viral load informed differentiated care is a means of tailoring care whereby those with suppressed viral load have less frequent clinical visits and attention is paid to those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach in many countries to measure viral load is by collecting dried blood spot (DBS) samples for testing in regional laboratories, although there have been concerns over the sensitivity/specificity of DBS to define treatment failure and the delay in receiving results. We use modelling to synthesize available evidence and evaluate the cost-effectiveness of viral load-informed differentiated care, account for limitations of DBS. We find that viral load-informed differentiated care using DBS is expected to be cost-effective and is recommended as the strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of future availability of point-of-care (POC) viral load tests.

BackgroundIn Mozambique during 2004–2007 numbers of adult patients (≥15 years old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from <5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART program outcomes, and determinants of outcomes, have not yet been reported.Methodology/Principal FindingsIn a retrospective cohort study, we investigated rates of mortality, attrition (death, loss to follow-up, or treatment cessation), immunologic treatment failure, and regimen-switch, as well as determinants of selected outcomes, among a nationally representative sample of 2,596 adults initiating ART during 2004–2007. At ART initiation, median age of patients was 34 and 62% were female. Malnutrition and advanced disease were common; 18% of patients weighed <45 kilograms, and 15% were WHO stage IV. Median baseline CD4+ T-cell count was 153/µL and was lower for males than females (139/µL vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or efavirenz were prescribed to 88% of patients; only 31% were prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and 19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2 attritions per 100 patient-years in the first 90 days. Predictors of attrition included male sex [adjusted hazard ratio (AHR) 1.5; 95% confidence interval (CI), 1.3–1.8], weight <45 kg (AHR 2.1; 95% CI, 1.6–2.9, reference group >60 kg), WHO stage IV (AHR 1.7; 95% CI, 1.3–2.4, reference group WHO stage I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI, 1.0–1.8), and later calendar year of ART initiation (AHR 1.5; 95% CI, 1.2–1.8). Rates of immunologic treatment failure and regimen-switch were 14.0 and 0.6 events per 100-patient years, respectively.ConclusionsART initiation at earlier disease stages and scale-up of co-trimoxazole among ART patients could improve outcomes. Research to determine reasons for low regimen-switch rates and increasing rates of attrition during program expansion is needed.

Although the overall TB case number among children is declining in the United States, certain groups of children (eg, younger children, racial and ethnic minorities, foreign-born) are at higher risk for TB. As the United States moves toward the elimination of TB, future efforts should endeavor to prevent all cases of childhood TB.

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Through district system strengthening, integrated services, and community engagement interventions, the Saving Mothers, Giving Life initiative increased emergency obstetric care coverage and access to, and demand for, improved quality of care that led to rapid declines in district maternal and perinatal mortality. Significant reductions in intrapartum stillbirth rate and maternal mortality ratios around the time of birth attest to the success of the initiative.