Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study.

BACKGROUND: Treatment for post-kala-azar dermal leishmaniasis (PKDL) in Sudan is currently recommended only for patients with persistent or severe disease, mainly because of the limitations of current therapies, namely toxicity and long hospitalization. We assessed the safety and efficacy of miltefosine combined with paromomycin and liposomal amphotericin B (LAmB) for the treatment of PKDL in Sudan. METHODOLOGY/PRINCIPAL FINDINGS: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with persistent (stable or progressive disease for ≥ 6 months) or grade 3 PKDL, aged 6 to ≤ 60 years in Sudan. The median age was 9.0 years (IQR 7.0-10.0y) and 87% of patients were ≤12 years old. Patients were randomly assigned to either daily intra-muscular paromomycin (20mg/kg, 14 days) plus oral miltefosine (allometric dose, 42 days)-PM/MF-or LAmB (total dose of 20mg/kg, administered in four injections in week one) and oral miltefosine (allometric dose, 28 days)-LAmB/MF. The primary endpoint was a definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesion resolution) and no additional PKDL treatment between end of therapy and 12-month follow-up assessment. 104/110 patients completed the trial. Definitive cure at 12 months was achieved in 54/55 (98.2%, 95% CI 90.3-100) and 44/55 (80.0%, 95% CI 70.2-91.9) of patients in the PM/MF and AmB/MF arms, respectively, in the mITT set (all randomized patients receiving at least one dose of treatment; in case of error of treatment allocation, the actual treatment received was used in the analysis). No SAEs or deaths were reported, and most AEs were mild or moderate. At least one adverse drug reaction (ADR) was reported in 13/55 (23.6%) patients in PM/MF arm and 28/55 (50.9%) in LAmB/MF arm, the most frequent being miltefosine-related vomiting and nausea, and LAmB-related hypokalaemia; no ocular or auditory ADRs were reported. CONCLUSIONS/SIGNIFICANCE: The PM/MF regimen requires shorter hospitalization than the currently recommended 60-90-day treatment, and is safe and highly efficacious, even for patients with moderate and severe PKDL. It can be administered at primary health care facilities, with LAmB/MF as a good alternative. For future VL elimination, we need new, safe oral therapies for all patients with PKDL. TRIAL REGISTRATION: ClinicalTrials.gov NCT03399955, https://clinicaltrials.gov/study/NCT03399955 ClinicalTrials.gov ClinicalTrials.gov.

Effect of a lay counselor delivered integrated maternal mental health and early childhood development group-based intervention in Siaya County, Kenya: A quasi-experimental longitudinal study.

BACKGROUND: Maternal mental health is linked to early childhood development; yet there is a gap in evidence-based interventions for low-resource settings. This study estimates the impact of 'Integrated Mothers and Babies Course and Early Childhood Development' (iMBC/ECD), a cognitive-behavioral, group-based intervention, on maternal depression and early childhood social-emotional development in Siaya County, Kenya. METHODS: This quasi-experimental study enrolled 417 pregnant women and mothers of children under age 2 across two sub-counties in Siaya County. The intervention area had 193 women in 23 groups implementing iMBC/ECD and the control area had 224 women in 30 groups exposed to ECD only content. Mother/index child dyads were followed for two years. To estimate the causal treatment effect from the non-randomized design, we implemented the propensity score weighting method with inverse probability weights. RESULTS: At baseline, 10.2% of participants endorsed moderate/severe depressive symptoms. At 14-months post-intervention, 7.4% endorsed moderate/severe depression. Overall, iMBC/ECD intervention did not have a significant impact on reducing maternal depression or improving children's social and emotional development. However, sub-group analyses revealed that iMBC/ECD was associated with lowered depressive symptoms among women with no/low education, four or more children and/or no experience of intimate partner violence in the past year. Women with high program attendance (more than half of 14 sessions) also experienced consistently fewer depressive symptoms compared to those with lower attendance. LIMITATIONS: Non-randomized study, sub-group analyses are exploratory. CONCLUSIONS: The iMBC/ECD program may have the potential to improve maternal mental health and early child development for more targeted vulnerable populations.

The right to health, health systems development and public health policy challenges in Chad.

BACKGROUND: There is increasing consensus that the right to health can provide ethical, policy and practical groundings for health systems development. The goals of the right to health are congruent with those of health systems development, which are about strengthening health promotion organizations and actions so as to improve public health. The poor shape and performance of health systems in Chad question the extent of realization of the right to health. Due to its comprehensiveness and inclusiveness, the right to health has the potential of being an organizational and a normative backbone for public health policy and practice. It can then be understood and studied as an integral component of health systems development. METHOD: This paper uses a secondary data analysis of existing documents by the Ministry of Public Health, Institut National de la Statistique, des Etudes Economiques et Démographiques (INSEED), the Ministry of Economy and Agence Française de Cooperation to analyze critically the shape and performance of health systems in Chad based on key concepts and components of the right to health contained in article 12 of the International Covenant on Economic, Social and Cultural Rights, and on General Comment 14. RESULTS: The non-realization of the right to health, even in a consistently progressive manner, raises concerns about the political commitment of state officials to public health, about the justice of social institutions in ensuring social well-being and about individual and public values that shape decision-making processes. Social justice, democratic rule, transparency, accountability and subsidiarity are important groundings for ensuring community participation in public affairs and for monitoring the performance of public institutions. CONCLUSION: The normative ideals of health systems development are essentially democratic in nature and are rooted in human rights and in ethical principles of human dignity, equality, non-discrimination and social justice. These ideals are grounded in an integrated vision of society as a place for multi-level interactions, where government plays its role by equitably providing institutions and services that ensure people's welfare. Inter-sectoral collaboration, which calls for a conceptual shift in health and public policy, can be instrumental in improving health systems through concerted efforts of various governmental institutions and civil society.