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ObjectiveTo test the effect of proactive home visits by trained community health workers (CHWs) on child survival.MethodsWe conducted a two arm, parallel, unmasked cluster-randomized trial in 137 village-clusters in rural Mali. From February 2017 to January 2020, 31 761 children enrolled at the trial start or at birth. Village-clusters received either primary care services by CHWs providing regular home visits (intervention) or by CHWs providing care at a fixed site (control). In both arms, user fees were removed and primary health centres received staffing and infrastructure improvements before trial start. Using lifetime birth histories from women aged 15-49 years surveyed annually, we estimated incidence rate ratios (IRR) for intention-to-treat and per-protocol effects on under-five mortality using Poisson regression models.FindingsOver three years, we observed 52 970 person-years (27 332 in intervention arm; 25 638 in control arm). During the trial, 909 children in the intervention arm and 827 children in the control arm died. The under-five mortality rate declined from 142.8 (95% CI: 133.3-152.9) to 56.7 (95% CI: 48.5-66.4) deaths per 1000 live births in the intervention arm; and from 154.3 (95% CI: 144.3-164.9) to 54.9 (95% CI: 45.2-64.5) deaths per 1000 live births in the control arm. Intention-to-treat (IRR: 1.02; 95% CI: 0.88-1.19) and per-protocol estimates (IRR: 1.01; 95% CI: 0.87-1.18) showed no difference between study arms.ConclusionThough proactive home visits did not reduce under-five mortality, system-strengthening measures may have contributed to the decline in under-five mortality in both arms.

The Proactive Community Case Management (ProCCM) trial in Mali reinforced the health system across both arms with user fee removal, professional Community Health Workers (CHWs), and upgraded primary health centres (PHCs)-and randomized village-clusters to receive proactive home visits by CHWs (intervention) or fixed site-based services by passive CHWs (control). Across both arms, sick children's 24-hour treatment and pregnant women's four or more antenatal visits doubled, and under-five mortality halved, over three years compared to baseline. In the intervention arm, proactive CHW home visits had modest effects on children's curative and women's antenatal care utilization, but no effect on under-five mortality, compared to the control arm. We aimed to explain these results by examining implementation, mechanisms, and context in both arms. We conducted a process evaluation with a mixed method convergent design that included 79 in-depth interviews with providers and participants over two time-points, surveys with 195 providers, and secondary analyses of clinical data. We embedded realist approaches in novel ways to test, refine, and consolidate theories about how ProCCM worked, generating three context-intervention-actor-mechanism-outcome nodes that unfolded in a cascade. First, removing user fees and deploying professional CHWs in every cluster enabled participants to seek health sector care promptly and created a context of facilitated access. Second, health systems support to all CHWs and PHCs enabled equitable, respectful, quality healthcare, which motivated increased, rapid utilization. Third, proactive CHW home visits facilitated CHWs and participants to deliver and seek care, and build relationships, trust, and expectations, but these mechanisms were also activated in both arms. Addressing multiple structural barriers to care, user fee removal, professional CHWs, and upgraded clinics interacted with providers' and patients' agency to achieve rapid care and child survival in both arms. Proactive home visits expedited or compounded mechanisms that were activated and changed the context across arms.

The effects of persistent Plasmodium falciparum (Pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. A longitudinal cohort study was conducted in a seasonal and high-transmission area of Mali, in which 500 subjects aged 1–65 years were followed for 1 year. Blood samples were collected every 2 weeks, and incident malaria cases were diagnosed and treated. Pf infection in each individual at each time point was assessed by species-specific nested-PCR, and Pf longitudinal prevalence per person (PfLP, proportion of Pf-positive samples over 1 year) was calculated. Multiclonality of Pf infection was measured using a 24-SNP DNA barcoding assay at 4 time-points (two in wet season, and two in dry season) over one year. PfLP was positively correlated with multiclonality at each time point (all r≥0.36; all P≤0.011). When host factors (e.g., age, gender), PfLP, and multiclonality (at the beginning of the transmission season) were analyzed together, only increasing age and high PfLP were associated with reduced clinical malaria occurrence or reduced number of malaria episodes (for both outcomes, P<0.001 for age, and P = 0.005 for PfLP). When age, PfLP and baseline Pf positivity were analyzed together, the effect of high PfLP remained significant even after adjusting for the other two factors (P = 0.001 for malaria occurrence and P<0.001 for number of episodes). In addition to host age and baseline Pf positivity, both of which have been reported as important modifiers of clinical malaria risk, our results demonstrate that persistent parasite carriage, but not baseline multiclonality, is associated with reduced risk of clinical disease in this population. Our study emphasizes the importance of considering repeated parasite exposure in future studies that evaluate clinical malaria risk.

Heterozygous hemoglobin (Hb) AS (sickle-cell trait) and HbAC are hypothesized to protect against Plasmodium falciparum malaria in part by enhancing naturally-acquired immunity to this disease. To investigate this hypothesis, we compared antibody levels to four merozoite antigens from the P. falciparum 3D7 clone (apical membrane antigen 1, AMA1-3D7; merozoite surface protein 1, MSP1-3D7; 175 kDa erythrocyte-binding antigen, EBA175-3D7; and merozoite surface protein 2, MSP2-3D7) in a cohort of 103 HbAA, 73 HbAS and 30 HbAC children aged 3 to 11 years in a malaria-endemic area of Mali. In the 2009 transmission season we found that HbAS, but not HbAC, significantly reduced the risk of malaria compared to HbAA. IgG levels to MSP1 and MSP2 at the start of this transmission season inversely correlated with malaria incidence after adjusting for age and Hb type. However, HbAS children had significantly lower IgG levels to EBA175 and MSP2 compared to HbAA children. On the other hand, HbAC children had similar IgG levels to all four antigens. The parasite growth-inhibitory activity of purified IgG samples did not differ significantly by Hb type. Changes in antigen-specific IgG levels during the 2009 transmission and 2010 dry seasons also did not differ by Hb type, and none of these IgG levels dropped significantly during the dry season. These data suggest that sickle-cell trait does not reduce the risk of malaria by enhancing the acquisition of IgG responses to merozoite antigens. [ABSTRACT FROM AUTHOR]

Background:Naturally-acquired antibody responses to antigens on the surface of Plasmodium falciparum-infected red blood cells (iRBCs) have been implicated in antimalarial immunity. To profile the development of this immunity, we have been studying a cohort of Malian children living in an area with intense seasonal malaria transmission. Methodology/Principal Findings:We collected plasma from a sub-cohort of 176 Malian children aged 3-11 years, before (May) and after (December) the 2009 transmission season. To measure the effect of hemoglobin (Hb) type on antibody responses, we enrolled age-matched HbAA, HbAS and HbAC children. To quantify antibody recognition of iRBCs, we designed a high-throughput flow cytometry assay to rapidly test numerous plasma samples against multiple parasite strains. We evaluated antibody reactivity of each plasma sample to 3 laboratory-adapted parasite lines (FCR3, D10, PC26) and 4 short-term-cultured parasite isolates (2 Malian and 2 Cambodian). 97% of children recognized ≥1 parasite strain and the proportion of IgG responders increased significantly during the transmission season for most parasite strains. Both strain-specific and strain-transcending IgG responses were detected, and varied by age, Hb type and parasite strain. In addition, the breadth of IgG responses to parasite strains increased with age in HbAA, but not in HbAS or HbAC, children. Conclusions/Significance:Our assay detects both strain-specific and strain-transcending IgG responses to iRBCs. The magnitude and breadth of these responses varied not only by age, but also by Hb type and parasite strain used. These findings indicate that studies of acquired humoral immunity should account for Hb type and test large numbers of diverse parasite strains. [ABSTRACT FROM AUTHOR]

Introduction: Despite recommendations from the WHO, antenatal care (ANC) coverage remains low in many low-income and middle-income countries (LMICs). Community health workers (CHWs) can play an important role in expanding ANC coverage through pregnancy identification, provision of health education, screening for complications, delivery of therapeutic care and referral to higher levels of care. However, despite the success of CHW programmes in various countries, WHO has called for additional research to develop evidence-based models that optimise CHW service delivery and that can be replicated across geographies., Methods: The ProCCM Trial was a cluster-randomised controlled trial to compare proactive home visits by CHWs (intervention, 69 village clusters) to the provision of CHW care at community fixed sites only (control, 68 village clusters) in the Bankass health district in Central Mali. In this study, we conducted a cost-effectiveness analysis of proactive CHW home visits in improving ANC utilisation, a secondary outcome of the ProCCM trial. We analysed five ANC outcomes: (1) number of ANC contacts, (2) at least one ANC contact, (3) at least four ANC contacts, (4) at least eight ANC contacts and (5) ANC initiated in the first trimester. We assumed two perspectives, a CHW programme's and the Full ANC programme's perspective, which included facility-based as well as community-based ANC. We estimated programme costs, incremental cost-effectiveness ratios (ICERs) and probabilities of the intervention being more cost-effective than the control at different willingness-to-pay (WTP) thresholds., Results: Proactive home visits were cost-saving from the CHW programme's perspective (ICERs: -$21.39 to -$79.20 per ANC utilisation outcome) and from the Full ANC programme perspective (ICERs: -$1.70 to -$6.30 per ANC utilisation outcome) compared with the fixed-site CHW care. The likelihood of the intervention being more cost-effective than the control was 100% at WTP thresholds $0 per ANC utilisation outcome and between $12.5 and $50.00 per ANC utilisation outcome in the CHW- and Full ANC programme perspectives, respectively., Conclusion: Our results provide evidence that proactive home visits produce more value per dollar spent as a means of improving the uptake of ANC services compared with fixed-site CHW services., Trial Registration Number: NCT02694055., Competing Interests: Competing interests: OO, MS and AZ report other grants from the Bill and Melinda Gates Foundation. OO also reports grants and consulting fees from the Partnership for Maternal Newborn and Child Health. OO is a board member of the Health Economics and Financing Programme at the Africa Centers for Disease Control. CW was employed by Muso at the time of the trial. AJ is the CEO of Muso Health and also serves as a voluntary member of the WHO’s external review group for the development of a curriculum guide for community health workers and as advisory board chair of the community health impact coalition., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Proactive Community Case Management (ProCCM) trial in Mali reinforced the health system across both arms with user fee removal, professional community health workers (CHWs) and upgraded primary health centres (PHCs)-and randomized village-clusters to receive proactive home visits by CHWs (intervention) or fixed site-based services by passive CHWs (control). Across both arms, sick children's 24-hour treatment and pregnant women's four or more antenatal visits doubled, and under-5 mortality halved, over 3 years compared with baseline. In the intervention arm, proactive CHW home visits had modest effects on children's curative and women's antenatal care utilization, but no effect on under-5 mortality, compared with the control arm. We aimed to explain these results by examining implementation, mechanisms and context in both arms We conducted a process evaluation with a mixed method convergent design that included 79 in-depth interviews with providers and participants over two time-points, surveys with 195 providers and secondary analyses of clinical data. We embedded realist approaches in novel ways to test, refine and consolidate theories about how ProCCM worked, generating three context-intervention-actor-mechanism-outcome nodes that unfolded in a cascade. First, removing user fees and deploying professional CHWs in every cluster enabled participants to seek health sector care promptly and created a context of facilitated access. Second, health systems support to all CHWs and PHCs enabled equitable, respectful, quality healthcare, which motivated increased, rapid utilization. Third, proactive CHW home visits facilitated CHWs and participants to deliver and seek care, and build relationships, trust and expectations, but these mechanisms were also activated in both arms. Addressing multiple structural barriers to care, user fee removal, professional CHWs and upgraded clinics interacted with providers' and patients' agency to achieve rapid care and child survival in both arms. Proactive home visits expedited or compounded mechanisms that were activated and changed the context across arms., (© The Author(s) 2024. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

In 2006, the Malian government established a program for free insecticide-treated net (ITNs) distribution during antenatal care visit (ANC) and intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) for pregnant women. In March to November of 2009, we conducted a cross-sectional study in peri-urban areas of Bamako, Mali to determine the malaria prevalence among pregnant women and their newborn children in the context of this policy. We included 379 pregnant women aged 15 to 45 years. At delivery, malaria was diagnosed using peripheral thick smears in mothers and newborns, as well as umbilical cord blood and placental blood. The prevalence of Plasmodium falciparum malaria was 2.4, 1.6 and 0.5% respectively in mother, placenta and cord samples; we observed a low birth weight rate of 12.1%. Approximately 77% of our parturient were housewives. The illiteracy rate among this group was 72.3%. Of the 379 women, 73% had at least three prenatal visits, 83% had received at least one free ITNs and 72% had received IPTp-SP during antenatal visit. Among them, 81% claimed to have complied with IPTp-SP. No congenital malaria was found. The prevalence of malaria in both mother and newborn has show a significant decrease in Bamako, compared with previous studies before the implementation of IPTp-SP policy in Mali. A high rate of coverage and use of IPTp-SP and ITNs correlate with lower malaria prevalence in pregnant women.