Background: Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP.
Methods: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed.
Findings: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline.
Interpretation: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission.
Funding: European and Developing Countries Clinical Trials Partnership.
Translation: For the French translation of the abstract see Supplementary Materials section.
Background: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.
Methods: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria.
Findings: The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001).
Interpretation: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings.
Funding: National Institute of Health Fogarty International Center.
Background: With numerous trials investigating novel drug combinations to treat tuberculosis, we aimed to evaluate the extent to which future improvements in tuberculosis treatment regimens could offset potential increases in drug costs.
Methods: In this modelling analysis, we used an ingredients-based approach to estimate prices at which novel regimens for rifampin-susceptible and rifampin-resistant tuberculosis treatment would be cost-neutral or cost-effective compared with standards of care in India, the Philippines, and South Africa. We modelled regimens meeting targets set in the WHO's 2023 Target Regimen Profiles (TRPs). Our decision-analytical model tracked cohorts of adults initiating rifampin-susceptible or rifampin-resistant tuberculosis treatment, simulating their health outcomes and costs accumulated during and following treatment under standard-of-care and novel regimen scenarios. Price thresholds included short-term cost-neutrality (considering only savings accrued during treatment), medium-term cost-neutrality (additionally considering savings from averted retreatments and secondary cases), and cost-effectiveness (incorporating willingness-to-pay for improved health outcomes).
Findings: Total medium-term costs per person treated using standard-of-care regimens were estimated at US$450 (95% uncertainty interval 310-630) in India, $560 (350-860) in the Philippines, and $730 (530-1090) in South Africa for rifampin-susceptible tuberculosis (current drug costs $46) and $2100 (1590-2810) in India, $2610 (2090-3280) in the Philippines, and $3790 (3090-4630) in South Africa for rifampin-resistant tuberculosis (current drug costs $432). A rifampin-susceptible tuberculosis regimen meeting the optimal targets defined in the TRPs could be cost-neutral in the short term at drug costs of $140 (90-210) per full course in India, $230 (130-380) in the Philippines, and $280 (180-460) in South Africa. For rifampin-resistant tuberculosis, short-term cost-neutral thresholds were higher with $930 (720-1230) in India, $1180 (980-1430) in the Philippines, and $1480 (1230-1780) in South Africa. Medium-term cost-neutral prices were approximately $50-100 higher than short-term cost-neutral prices for rifampin-susceptible tuberculosis and $250-550 higher for rifampin-resistant tuberculosis. Health system cost-neutral prices that excluded patient-borne costs were 45-70% lower (rifampin-susceptible regimens) and 15-50% lower (rifampin-resistant regimens) than the cost-neutral prices that included patient costs. Cost-effective prices were substantially higher. Shorter duration was the most important driver of medium-term savings with novel regimens, followed by ease of adherence.
Interpretation: Improved tuberculosis regimens, particularly shorter regimens or those that facilitate better adherence, could reduce overall costs, potentially offsetting higher prices.
Background: The Cancer Survival in Africa, Asia, and South America project (SURVCAN-3) of the International Agency for Research on Cancer aims to fill gaps in the availability of population-level cancer survival estimates from countries in these regions. Here, we analysed survival for 18 cancers using data from member registries of the African Cancer Registry Network across 11 countries in sub-Saharan Africa.
Methods: We included data on patients diagnosed with 18 cancer types between Jan 1, 2005, and Dec 31, 2014, from 13 population-based cancer registries in Cotonou (Benin), Abidjan (CÔte d'Ivoire), Addis Ababa (Ethiopia), Eldoret and Nairobi (Kenya), Bamako (Mali), Mauritius, Namibia, Seychelles, Eastern Cape (South Africa), Kampala (Uganda), and Bulawayo and Harare (Zimbabwe). Patients were followed up until Dec 31, 2018. Patient-level data including cancer topography and morphology, age and date at diagnosis, vital status, and date of death (if applicable) were collected. The follow-up (survival) time was measured from the date of incidence until the date of last contact, the date of death, or until the end of the study, whichever occurred first. We estimated the 1-year, 3-year, and 5-year survival (observed, net, and age-standardised net survival) by sex, cancer type, registry, country, and human development index (HDI). 1-year and 3-year survival data were available for all registries and all cancer sites, whereas availability of 5-year survival data was slightly more variable; thus to provide medium-term survival prospects, we have focused on 3-year survival in the Results section.
Findings: 10 500 individuals from 13 population-based cancer registries in 11 countries were included in the survival analyses. 9177 (87·4%) of 10 500 cases were morphologically verified. Survival from cancers with a high burden and amenable to prevention was poor: the 3-year age-standardised net survival was 52·3% (95% CI 49·4-55·0) for cervical cancer, 18·1% (11·5-25·9) for liver cancer, and 32·4% (27·5-37·3) for lung cancer. Less than half of the included patients were alive 3 years after a cancer diagnosis for eight cancer types (oral cavity, oesophagus, stomach, larynx, lung, liver, non-Hodgkin lymphoma, and leukaemia). There were differences in survival for some cancers by sex: survival was longer for females with stomach or lung cancer than males with stomach or lung cancer, and longer for males with non-Hodgkin lymphomas than females with non-Hodgkin lymphomas. Survival did not differ by country-level HDI for cancers of the oral cavity, oesophagus, liver, thyroid, and for Hodgkin lymphoma.
Interpretation: For cancers for which population-level prevention strategies exist, and with relatively poor prognosis, these estimates highlight the urgent need to upscale population-level prevention activities in sub-Saharan Africa. These data are vital for providing the knowled
Background: There are 1·3 billion people with disabilities globally. On average, they have poorer health than their non-disabled peers, but the extent of increased risk of premature mortality is unknown. We aimed to systematically review the association between disability and mortality in low-income and middle-income countries (LMICs).
Methods: We searched MEDLINE, Global Health, PsycINFO, and EMBASE from Jan 1, 1990 to Nov 14, 2022. Longitudinal epidemiological studies in any language with a comparator group that measured the association between disability and all-cause mortality in people of any age were eligible for inclusion. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to calculate the pooled hazard ratio (HR) for all-cause mortality by disability status. We then conducted meta-analyses separately for different impairment and age groups.
Findings: We identified 6146 unique articles, of which 70 studies (81 cohorts) were included in the systematic review, from 22 countries. There was variability in the methods used to assess and report disability and mortality. The meta-analysis included 54 studies, representing 62 cohorts (comprising 270 571 people with disabilities). Pooled HRs for all-cause mortality were 2·02 (95% CI 1·77-2·30) for people with disabilities versus those without disabilities, with high heterogeneity between studies (τ2=0·23, I2=98%). This association varied by impairment type: from 1·36 (1·17-1·57) for visual impairment to 3·95 (1·60-9·74) for multiple impairments. The association was highest for children younger than 18 years (4·46, [3·01-6·59]) and lower in people aged 15-49 years (2·45 [1·21-4·97]) and people older than 60 years (1·97 [1·65-2·36]).
Interpretation: People with disabilities had a two-fold higher mortality rate than people without disabilities in LMICs. Interventions are needed to improve the health of people with disabilities and reduce their higher mortality rate.
Funding: UK National Institute for Health and Care Research; and UK Foreign, Commonwealth and Development Office.
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