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).

Therapeutic efficacy and safety of artesunate + amodiaquine and artemether + lumefantrine in treating uncomplicated Plasmodium falciparum malaria in children on the rainy south-east coast of Madagascar.

Malaria is a major public health problem in Madagascar, particularly in coastal areas. We conducted a randomized, controlled, parallel-group study of artemisinin-based combination therapy (ACT) in Mananjary and Farafangana, two localities on the rainy south-east coast of Madagascar, from March to September 2018. The efficacy and safety of artesunate + amodiaquine (ASAQ) and artemether + lumefantrine (AL) were assessed according to the WHO protocol with a 28-day follow-up. Children aged 6 months to 14 years with uncomplicated Plasmodium falciparum malaria were randomized to receive ASAQ or AL for three days (1:1). 347/352 (98.5%) randomized patients reached the study endpoint on day 28. Crude adequate clinical and parasitological response (ACPR) rates were 100% (95% CI: 98.8-100%) in the ASAQ group and 96% (95% CI: 93.1-98.9%) in the AL group (per protocol population). However, the PCR-corrected ACPR rate was 97.7% (95% CI: 95.4-100%) in the AL group. Two cases of recrudescence and three of re-infection were observed. Mild and moderate adverse events, including gastrointestinal and/or nervous disorders, were reported in 11.9% (42/352) of patients. We found that ASAQ and AL were safe and efficacious for treating uncomplicated P. falciparum malaria. They may be used for treatment at health facilities and at the community level, and for mass drug administration campaigns.

Title: Efficacité thérapeutique et sécurité de l'artésunate + amodiaquine et de l'artéméther + luméfantrine pour le traitement du paludisme simple à Plasmodium falciparum chez les enfants sur la côte sud-est pluvieuse de Madagascar. Abstract: Le paludisme demeure un problème majeur de santé publique à Madagascar notamment dans les régions côtières. Nous avons réalisé une étude multisite, randomisée, contrôlée, en groupes parallèles sur la combinaison thérapeutique à base des dérivés d'artémisinine (CTA) à Mananjary et Farafangana, deux localités sur la côte sud-est pluvieuse de Madagascar, de mars au septembre 2018. L'efficacité et la sécurité de l'artésunate + amodiaquine (ASAQ) et de l'artéméther + luméfantrine (AL) ont été évaluées selon le protocole de l'OMS avec un suivi de 28 jours. Des enfants âgés de 6 mois à 14 ans souffrant de paludisme non compliqué à Plasmodium falciparum ont été randomisés (1:1) pour recevoir ASAQ ou AL pendant trois jours. 347/352 (98,5 %) des patients randomisés ont pu être suivis jusqu'au jour 28. Le taux de réponse clinique et parasitologique adéquate (RCPA) était de 100 % (95 % CI : 98,8 ­ 100 %) dans le bras thérapeutique ASAQ et de 96 % (95 % CI : 93,1 ­ 98,9 %) dans le bras thérapeutique AL (population per protocole). Cependant, après correction par PCR, le taux de RCPA était de 97,7 % (95 % CI : 95,4 ­ 100 %) dans le bras thérapeutique AL. Deux cas de recrudescence et trois cas de réinfections ont été observées. Des effets indésirables légers et modérés, notamment des troubles gastro-intestinaux et/ou nerveux, ont été rapportés chez 11,9 % (42/352) des patients. Nos résultats démontrent que l'ASAQ et l'AL sont sûrs et efficaces pour le traitement du paludisme non compliqué à P. falciparum. Ces deux CTA peuvent par conséquent être utilisés pour traiter le paludisme dans les centres de santé et au niveau communautaire, et aussi pendant les campagnes de traitement de masse.

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.