Expanding community case management of malaria to all ages can improve universal access to malaria diagnosis and treatment: results from a cluster randomized trial in Madagascar.

BACKGROUND: Global progress on malaria control has stalled recently, partly due to challenges in universal access to malaria diagnosis and treatment. Community health workers (CHWs) can play a key role in improving access to malaria care for children under 5 years (CU5), but national policies rarely permit them to treat older individuals. We conducted a two-arm cluster randomized trial in rural Madagascar to assess the impact of expanding malaria community case management (mCCM) to all ages on health care access and use. METHODS: Thirty health centers and their associated CHWs in Farafangana District were randomized 1:1 to mCCM for all ages (intervention) or mCCM for CU5 only (control). Both arms were supported with CHW trainings on malaria case management, community sensitization on free malaria care, monthly supervision of CHWs, and reinforcement of the malaria supply chain. Cross-sectional household surveys in approximately 1600 households were conducted at baseline (Nov-Dec 2019) and endline (Nov-Dec 2021). Monthly data were collected from health center and CHW registers for 36 months (2019-2021). Intervention impact was assessed via difference-in-differences analyses for survey data and interrupted time-series analyses for health system data. RESULTS: Rates of care-seeking for fever and malaria diagnosis nearly tripled in both arms (from less than 25% to over 60%), driven mostly by increases in CHW care. Age-expanded mCCM yielded additional improvements for individuals over 5 years in the intervention arm (rate ratio for RDTs done in 6-13-year-olds, RRRDT6-13 years = 1.65; 95% CIs 1.45-1.87), but increases were significant only in health system data analyses. Age-expanded mCCM was associated with larger increases for populations living further from health centers (RRRDT6-13 years = 1.21 per km; 95% CIs 1.19-1.23). CONCLUSIONS: Expanding mCCM to all ages can improve universal access to malaria diagnosis and treatment. In addition, strengthening supply chain systems can achieve significant improvements even in the absence of age-expanded mCCM. TRIAL REGISTRATION: The trial was registered at the Pan-African Clinical Trials Registry (#PACTR202001907367187).

Proactive community case management decreased malaria prevalence in rural Madagascar: results from a cluster randomized trial.

BACKGROUND: Malaria remains a leading cause of morbidity and mortality worldwide, with progress in malaria control stalling in recent years. Proactive community case management (pro-CCM) has been shown to increase access to diagnosis and treatment and reduce malaria burden. However, lack of experimental evidence may hinder the wider adoption of this intervention. We conducted a cluster randomized community intervention trial to assess the efficacy of pro-CCM at decreasing malaria prevalence in rural endemic areas of Madagascar. METHODS: Twenty-two fokontany (smallest administrative unit) of the Mananjary district in southeast Madagascar were selected and randomized 1:1 to pro-CCM (intervention) or conventional integrated community case management (iCCM). Residents of all ages in the intervention arm were visited by a community health worker every 2 weeks from March to October 2017 and screened for fever; those with fever were tested by a rapid diagnostic test (RDT) and treated if positive. Malaria prevalence was assessed using RDTs on all consenting study area residents prior to and following the intervention. Hemoglobin was measured among women of reproductive age. Intervention impact was assessed via difference-in-differences analyses using logistic regressions in generalized estimating equations. RESULTS: A total of 27,087 and 20,475 individuals participated at baseline and endline, respectively. Malaria prevalence decreased from 8.0 to 5.4% in the intervention arm for individuals of all ages and from 6.8 to 5.7% in the control arm. Pro-CCM was associated with a significant reduction in the odds of malaria positivity in children less than 15 years (OR = 0.59; 95% CI [0.38-0.91]), but not in older age groups. There was no impact on anemia among women of reproductive age. CONCLUSION: This trial suggests that pro-CCM approaches could help reduce malaria burden in rural endemic areas of low- and middle-income countries, but their impact may be limited to younger age groups with the highest malaria burden. TRIAL REGISTRATION: NCT05223933. Registered on February 4, 2022.

Experiences and perceptions of care-seeking for febrile illness among caregivers, pregnant women, and health providers in eight districts of Madagascar.

BACKGROUND: Prompt diagnosis and treatment of malaria contributes to reduced morbidity, particularly among children and pregnant women; however, in Madagascar, care-seeking for febrile illness is often delayed. To describe factors influencing decisions for prompt care-seeking among caregivers of children aged < 15 years and pregnant women, a mixed-methods assessment was conducted with providers (HP), community health volunteers (CHV) and community members. METHODS: One health district from each of eight malaria-endemic zones of Madagascar were purposefully selected based on reported higher malaria transmission. Within districts, one urban and one rural community were randomly selected for participation. In-depth interviews (IDI) and focus group discussions (FGD) were conducted with caregivers, pregnant women, CHVs and HPs in these 16 communities to describe practices and, for HPs, system characteristics that support or inhibit care-seeking. Knowledge tests on malaria case management guidelines were administered to HPs, and logistics management systems were reviewed. RESULTS: Participants from eight rural and eight urban communities included 31 HPs from 10 public and 8 private Health Facilities (HF), five CHVs, 102 caregivers and 90 pregnant women. All participants in FGDs and IDIs reported that care-seeking for fever is frequently delayed until the ill person does not respond to home treatment or symptoms become more severe. Key care-seeking determinants for caregivers and pregnant women included cost, travel time and distance, and perception that the quality of care in HFs was poor. HPs felt that lack of commodities and heavy workloads hindered their ability to provide quality malaria care services. Malaria commodities were generally more available in public versus private HFs. CHVs were generally not consulted for malaria care and had limited commodities. CONCLUSIONS: Reducing cost and travel time to care and improving the quality of care may increase prompt care-seeking among vulnerable populations experiencing febrile illness. For patients, perceptions and quality of care could be improved with more reliable supplies, extended HF operating hours and staffing, supportive demeanors of HPs and seeking care with CHVs. For providers, malaria services could be improved by increasing the reliability of supply chains and providing additional staffing. CHVs may be an under-utilized resource for sick children.

Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018.

BACKGROUND: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. METHODS: Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. RESULTS: Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76. CONCLUSION: PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

Baseline malaria prevalence and care-seeking behaviours in rural Madagascar prior to a trial to expand malaria community case management to all ages.

BACKGROUND: Integrated community case management of malaria, pneumonia, and diarrhoea can reduce mortality in children under five years (CU5) in resource-poor countries. There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours. METHODS: Two enumeration areas (EAs) were randomly chosen from each catchment area of the 30 health facilities (HFs) in Farafangana district designated for the mCCM age expansion trial; 28 households were randomly selected from each EA for the survey. All household members were asked about recent illness and care-seeking, and malaria prevalence was assessed by rapid diagnostic test (RDT) among children < 15 years of age. Weighted population estimates and Rao-Scott chi-squared tests were used to examine illness, care-seeking, malaria case management, and malaria prevalence patterns. RESULTS: Illness in the two weeks prior to the survey was reported by 459 (6.7%) of 8050 respondents in 334 of 1458 households surveyed. Most individuals noting illness (375/459; 82.3%) reported fever. Of those reporting fever, 28.7% (112/375) sought care; this did not vary by participant age (p = 0.66). Most participants seeking care for fever visited public HFs (48/112, 46.8%), or community healthcare volunteers (CHVs) (40/112, 31.0%). Of those presenting with fever at HFs or to CHVs, 87.0% and 71.0%, respectively, reported being tested for malaria. RDT positivity among 3,316 tested children < 15 years was 25.4% (CI: 21.5-29.4%) and increased with age: 16.9% in CU5 versus 31.8% in 5-14-year-olds (p < 0.0001). Among RDT-positive individuals, 28.4% of CU5 and 18.5% of 5-14-year-olds reported fever in the two weeks prior to survey (p = 0.044). CONCLUSIONS: The higher prevalence of malaria among older individuals coupled with high rates of malaria testing for those who sought care at CHVs suggest that expanding mCCM to older individuals may substantially increase the number of infected individuals with improved access to care, which could have additional favorable effects on malaria transmission.

Prevalence and factors associated to disclosure of same-sex practices to family members and health care workers among men who have sex with men in Togo.

Disclosure of same-sex practices is associated with improved access to health services and better health outcomes. Our aim was to estimate the prevalence of same-sex practice disclosure to family members and health care workers (HCW) in two cities in Togo. 683 MSM ≥18 years of age were surveyed using respondent driven sampling (RDS) for a cross-sectional survey using a structured questionnaire in Lomé (354 (51.8%)) and Kara (n = 329 (48.2%)). Median age was lower in Lomé than in Kara. A significantly higher proportion of MSM in Lomé (RDSa: 37.0%; 95% CI: 29.7, 44.3) than in Kara (RDSa: 8.0%; 95% CI: 4.7, 11.3) told a HCW that they have sex with men. Disclosure to a family member was associated with female gender, living with HIV, difficulties accessing health services, and blackmail. Disclosure to a HCW was associated with living with HIV, and physical abuse. MSM had decreased odds of disclosure to a HCW if they were living in Kara, reported female gender or intersex, or if had difficulties accessing health services. These data highlight the positive health outcomes associated with disclosure contextualized by the complex environments in which disclosure of same-sex practices takes place.

Using a social ecological framework to characterize the correlates of HIV among men who have sex with men in Lomé, Togo.

In the mixed and concentrated HIV epidemics of West Africa, the relative disproportionate burden of HIV among men who have sex with men (MSM) compared to other reproductive-age men is higher than that observed in Southern and Eastern Africa. Our aim is to describe the correlates of HIV infection among MSM living in Lomé, Togo, using the Modified Social Ecological Model (MSEM). A total of 354 MSM ≥18 years of age were recruited using respondent driven sampling (RDS) for a cross-sectional survey in Lomé, Togo. Participants completed a structured questionnaire and were tested for HIV and syphilis. Statistical analyses included RDS-weighted proportions, bootstrapped confidence intervals (CI), and logistic regression models. Mean age of participants was 22 years; 71.5% were between 18 and 24 years. RDS-weighted HIV prevalence was 9.2% (95% CI=5.4-13.2). In RDS-adjusted (RDSa) bivariate analysis, HIV infection was associated with disclosure of sexual orientation to a family member, discriminatory remarks made by family members, forced sex, ever being blackmailed because of being MSM, community and social stigma and discrimination, and health service stigma and discrimination. In the multivariable model, HIV infection was associated with being 25 years or older (RDSa adjusted OR (aOR)=4.3, 95% CI=1.5-12.2), and having sex with a man before age 18 (RDSa aOR=0.3, 95% CI=0.1-0.9). HIV prevalence was more than seven times higher than that estimated among adults aged 15-49 living in Togo. Using the MSEM, network, community, and policy-level factors were associated with HIV infection among MSM in Lomé, Togo. Through the use of this flexible risk framework, a structured assessment of the multiple levels of HIV risk was characterized, highlighting the need for evidence-based and human-rights affirming combination HIV prevention and treatment programs that address these various risk levels for MSM in Lomé.

Identifying Strengths and Gaps in Data Management and Reporting through Malaria Routine Data Quality Assessment: Results from Two Health Regions in Madagascar.

In 2021, the U.S. President's Malaria Initiative Measure Malaria project provided support to the National Malaria Program to conduct a data quality assessment. The main goal was to help health centers enhance the quality of their malaria data. The assessment involved reviewing data from outpatient registers, monthly reports, and DHIS2 data. Reporting timeliness, completeness, data element completeness, and availability of source documents were assessed. For timeliness, the assessment measured the proportion of reports that were submitted on time out of the expected total. The results showed that the reporting timeliness was inadequate in Atsinanana (85%) and adequate for Atsimo-Andrefana (95%). Data elements completeness, which refers to reports without missing data, was inadequate in Atsinanana (43%) and Atsimo-Andrefana (68%). The availability of source documents, such as records forms, was assessed and found to be 59% in Atsimo-Andrefana and 48% in Atsinanana. The use of standard reporting forms, which ensures consistency and accuracy in reporting, was reported to be 44% in Atsinanana and 54% in Atsimo-Andrefana. Data discrepancies were identified between outpatient registers, monthly reports, and DHIS2 data. A verification factor (VF) was used to compare the figures in these different sources. The VF was 1.2 in Atsinanana and 1.1 in Atsimo-Andrefana for both monthly reports and DHIS2 data, indicating an overreporting of fever cases tested in 6- to 13-year-olds. Overall, the assessment revealed gaps in data elements completeness, reporting accuracy, and availability of data recording guidelines. The findings suggest that regular data quality assessments should be implemented to guide decision making in Madagascar.

A qualitative analysis of obstetric violence in rural Madagascar.

In Madagascar, a country where maternal mortality remains high, the quality of obstetric care as perceived by users has been little explored. In this paper, we examine the perception of the quality of care in rural areas, by identifying women's experiences and expectations for basic and emergency obstetric care and how providers are meeting them. Data were collected in 2020, in three rural regions (Fenerive-Est, Manakara and Miandrivazo). 58 semi-structured interviews were conducted with women who had given birth in basic health centers or at home, and with other key informants including caregivers, birth attendants (known as matrones), grandmothers and community agents. 6 focus groups took place with mothers who had given birth at home and at a basic health centers and 6 observations took place during prenatal consultations. This article highlights the major dysfunctions perceived in the services offered and their influence on healthcare use. The women highlighted a lack of consideration of their expectations in obstetric care, with a defective caregiver/patient relationship, unforeseen costs and inadequate infrastructures incapable of guaranteeing intimacy. The women also complained of a lack of consideration of their fady (cultural prohibitions that can lead to misfortune) that surround pregnancy. These local practices conflict with the medical requirements of priority interventions in maternal care, and the respect of these practices by the women leads to reprimands and humiliation from caregivers. This obstetric violence, which emanates from the structure of society, gender relations and the biomedical practices governing pregnancy and childbirth in health facilities in Madagascar, constitutes an obstacle to the use of obstetric services. We hope that this description of the various dimensions of obstetric violence in Madagascar will make it possible to identify the structural obstacles limiting the capacity to provide quality care and to engender positive improvements in obstetric care in Madagascar.

Using routine health data to evaluate the impact of indoor residual spraying on malaria transmission in Madagascar.

INTRODUCTION: Indoor residual spraying (IRS) and insecticide-treated bed nets (ITNs) are cornerstone malaria prevention methods in Madagascar. This retrospective observational study uses routine data to evaluate the impacts of IRS overall, sustained IRS exposure over multiple years and level of spray coverage (structures sprayed/found) in nine districts where non-pyrethroid IRS was deployed to complement standard pyrethroid ITNs from 2017 to 2020. METHODS: Multilevel negative-binomial generalised linear models were fit to estimate the effects of IRS exposure overall, consecutive years of IRS exposure and spray coverage level on monthly all-ages population-adjusted malaria cases confirmed by rapid diagnostic test at the health facility level. The study period extended from July 2016 to June 2021. Facilities with missing data and non-geolocated communes were excluded. Facilities in IRS districts were matched with control facilities by propensity score analysis. Models were controlled for ITN survivorship, mass drug administration coverage, precipitation, enhanced vegetation index, seasonal effects and district. Predicted cases under a counterfactual no IRS scenario and number of cases averted by IRS were estimated using the fitted models. RESULTS: Exposure to IRS overall reduced case incidence by an estimated 30.3% from 165.8 cases per 1000 population (95% CI=139.7 to 196.7) under a counterfactual no IRS scenario, to 114.3 (95% CI=96.5 to 135.3) over 12 months post-IRS campaign in nine districts. A third year of IRS reduced malaria cases 30.9% more than a first year (incidence rate ratio (IRR)=0.578, 95% CI=0.578 to 0.825, p<0.001) and 26.7% more than a second year (IRR=0.733, 95% CI=0.611 to 0.878, p=0.001). There was no significant difference between the first and second year (p>0.05). Coverage of 86%-90% was associated with a 19.7% reduction in incidence (IRR=0.803, 95% CI=0.690 to 0.934, p=0.005) compared with coverage ≤85%, although these results were not robust to sensitivity analysis. CONCLUSION: This study demonstrates that non-pyrethroid IRS appears to substantially reduce malaria incidence in Madagascar and that sustained implementation of IRS over three years confers additional benefits.

Using Population-Size Estimation and Cross-sectional Survey Methods to Evaluate HIV Service Coverage Among Key Populations in Burkina Faso and Togo.

OBJECTIVES: The objective of our study was to measure progress toward the UNAIDS 90-90-90 HIV care targets among key populations in urban areas of 2 countries in West Africa: Burkina Faso and Togo. METHODS: We recruited female sex workers (FSWs) and men who have sex with men (MSM) through respondent-driven sampling. From January to July 2013, 2738 participants were enrolled, tested for HIV, and completed interviewer-administered surveys. We used population-size estimation methods to calculate the number of people who were engaged in the HIV continuum of care. RESULTS: HIV prevalence ranged from 0.6% (2 of 329) of MSM in Kara, Togo, to 32.9% (115 of 350) of FSWs in Bobo Dioulasso, Burkina Faso. Of those confirmed to be HIV infected, a range of 0.0% (0 of 2) of MSM in Kara to 55.7% (64 of 115) of FSWs in Bobo Dioulasso were using ART. Based on population estimates, the percentage gap between HIV-infected people who should be using ART (per the 90-90-90 targets) and those who reported using ART ranged from 31.5% among FSWs in Bobo Dioulasso to 100.0% among MSM in Kara. CONCLUSIONS: HIV service coverage among MSM and FSWs in Burkina Faso and Togo was low in 2013. Interventions for improving engagement of these at-risk populations in the HIV continuum of care should include frequent, routine HIV testing and linkage to evidence-based HIV treatment services. Population-size estimates can be used to inform governments, policy makers, and funding agencies about where elements of HIV service coverage are most needed.

Scaling-up HIV responses with key populations in West Africa.

BACKGROUND: Despite decades of HIV responses in pockets of West and Central Africa (WCA), the HIV response with key populations remains an understudied area. Recently, there has been a proliferation of studies highlighting epidemiologic and behavioral data that challenge attitudes of complacency among donors and country governments uncomfortable in addressing key populations. METHODS: The articles in this series highlight new studies that provide a better understanding of the epidemiologic and structural burden facing key populations in the WCA region and how to improve responses through more effective targeting. RESULTS: Key populations face pervasive structural barriers including institutional and sexual violence and an intersection of stigma, criminalization, and marginalization as sexual minorities. Despite decades of smaller interventions that have shown the importance of integrated services for key populations, there remains incongruent provision of outreach or testing or family planning pointing to sustained risk. There remains an incongruent resource provision for key populations where they shoulder the burden of HIV and their access to services alone could turn around HIV epidemics within the region. CONCLUSIONS: These proximal and distal determinants must be addressed in regional efforts, led by the community, and resourced for scale, targeting those most at risk for the acquisition and transmission of HIV. This special issue builds the knowledge base for the region focusing on interventions that remove barriers to service access including treatment uptake for those living with HIV. Better analysis and use of data for strategic planning are shown to lead to more effective targeting of prevention, care, and HIV treatment programs with key populations. These articles further demonstrate the immediate need for comprehensive action to address HIV among key populations throughout the WCA region.

Building the evidence base for urgent action: HIV epidemiology and innovative programming for men who have sex with men in sub-Saharan Africa.

While still an understudied area, there is a growing body of studies highlighting epidemiologic data on men who have sex with men (MSM) in sub-Saharan Africa (SSA) which challenge the attitudes of complacency and irrelevancy among donors and country governments that are uncomfortable in addressing key populations (KPs). While some of the past inaction may be explained by ignorance, new data document highly elevated and sustained HIV prevalence that is seemingly isolated from recent overall declines in prevalence. The articles in this series highlight new studies which focus on the stark epidemiologic burden in countries from concentrated, mixed and generalized epidemic settings. The issue includes research from West, Central, East and Southern Africa and explores the pervasive impact of stigma and discrimination as critical barriers to confronting the HIV epidemic among MSM and the intersecting stigma and marginalization found between living with HIV and sexual minority status. Interventions to remove barriers to service access, including those aimed at training providers and mobilizing communities even within stigmatized peri-urban settings, are featured in this issue, which further demonstrates the immediate need for comprehensive action to address HIV among MSM in all countries in the region, regardless of epidemic classification.