Enhanced effect of seasonal malaria chemoprevention when coupled with nutrients supplementation for preventing malaria in children under 5 years old in Burkina Faso: a randomized open label trial.

BACKGROUND: In rural African settings, most of the children under the coverage of Seasonal Malaria Chemoprevention (SMC) are also undernourished at the time of SMC delivery, justifying the need for packaging malarial and nutritional interventions. This study aimed at assessing the impact of SMC by coupling the intervention with nutrients supplementation for preventing malaria in children less than 5 years old in Burkina Faso. METHODS: A randomized trial was carried out between July 2020 and June 2021 in the health district of Nanoro, Burkina Faso. Children (n = 1059) under SMC coverage were randomly assigned to one of the three study arms SMC + Vitamin A (SMC-A, n = 353) or SMC + Vitamin A + Zinc (SMC-AZc, n = 353) or SMC + Vitamin A + PlumpyDoz(tm) (SMC-APd, n = 353)-a medium quantity-lipid-based nutrient supplement (MQ-LNS). Children were followed up for one year that included an active follow-up period of 6 months with scheduled monthly home visits followed by 6 months passive follow-up. At each visit, capillary blood sample was collected for malaria diagnosis by rapid diagnosis test (RDT). RESULTS: Adding nutritional supplements to SMC had an effect on the incidence of malaria. A reduction of 23% (adjusted IRR = 0.77 (95%CI 0.61-0.97) in the odds of having uncomplicated malaria in SMC-APd arm but not with SMC-AZc arm adjusted IRR = 0.82 (95%CI 0.65-1.04) compare to control arm was observed. A reduction of 52%, adjusted IRR = 0.48 (95%CI 0.23-0.98) in the odds of having severe malaria was observed in SMC-APd arm compared to control arm. Besides the effect on malaria, this combined strategy had an effect on all-cause morbidity. More specifically, a reduction of morbidity odds of 24%, adjusted IRR = 0.76 (95%CI 0.60-0.94) in SMC-APd arm compared to control arm was observed. Unlike clinical episodes, no effect of nutrient supplementation on cross sectional asymptomatic infections was observed. CONCLUSION: Adding nutritional supplements to SMC significantly increases the impact of this intervention for preventing children from malaria and other childhood infections. TRIAL REGISTRATION: NCT04238845.

Impact and operational feasibility of adding malaria infection screening using an ultrasensitive RDT for placental and fetal outcomes in an area of high IPTP-SP coverage in Burkina Faso: the ASSER MALARIA pilot study protocol.

BACKGROUND: Malaria infection during pregnancy (MIP) is not only deleterious to the woman, but it also puts her fetus at increased risk of adverse outcomes, such as preterm delivery, low birth weight, and intrauterine growth retardation. Additionally, all-cause mortality during the first year of life in babies born to women with malaria during pregnancy is also increased. Many interventions such as IPTp-SP and long-lasting insecticidal nets have proven to be efficient at reducing malaria in pregnancy burden but adherence to recommended policies remains poor. In sub-Saharan Africa, malaria in pregnancy is often asymptomatic and many malaria infections may be missed due to the inadequate performance of the current rapid diagnostic test to detect low-level parasitemias. Therefore, additional strategies such as intermittent screening with ultrasensitive rapid diagnostic tests and treatment with an effective artemisinin-based combination therapy in addition to IPTp-SP could reduce placental malaria, peripheral malaria infection at delivery, and low birth weight. METHODS: This pilot 2-group randomized open trial with a nested qualitative social behavioral will be carried out in Nanoro district in which 340 pregnant women will be recruited. Pregnant women will be randomized into two groups and followed on a monthly basis until delivery. In the intervention group, monthly screening using ultrasensitive rapid diagnostic tests and treatment of those found to be infected with dihydroartemisinin-piperaquine will be performed. In addition, a reminder will be sent to increase the uptake of IPTp-SP doses per woman. During scheduled and unscheduled visits, malaria infection, hemoglobin level, and other clinical outcomes will be assessed and compared by the group. The primary feasibility outcome will evaluate the study site's capacity to enroll participants and the women's perception and acceptability of the intervention. The primary clinical outcome will be the prevalence of placental malaria at delivery. DISCUSSION: The present protocol aims to evaluate the feasibility on a large-scale and also to demonstrate the impact and the operational feasibility of additional screening with ultrasensitive rapid diagnostic tests and treatment with DHA-PQ on placental malaria, low birth weight, and peripheral malaria infection at delivery in a high-burden setting in Burkina Faso. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04147546 (14 October 2019).

Development and evaluation of an electronic algorithm using a combination of a two-step malaria RDT and other rapid diagnostic tools for the management of febrile illness in children under 5 attending outpatient facilities in Burkina Faso.

BACKGROUND: In Sub-Saharan Africa (SSA), febrile illnesses remain a major public health problem in children. However, the persistence of hrp2 antigen and the low sensitivity of pLDH RDT negatively affect antimalarials and antibiotics prescription practices. These limitations lead to poor management of febrile diseases and antimicrobial resistance (AMR). To improve the diagnosis of these febrile diseases and subsequent prescription of antimicrobials, it is hypothesized that the implementation of an algorithm including a two-step malaria RDT PfHRP2/pLDH supported by point-of-care (PoC) tests for bacterial infections could significantly improve the management of febrile diseases and thereby tackling AMR. METHODS: To assess the value of the proposed algorithm, an open-label randomized controlled trial with three arms, enrolling febrile children from 6 to 59 months is proposed. In the control arm, febrile children will be managed according to the Integrated Management of Childhood Illnesses (IMCI), which is part of the standard of care in Burkina Faso. Treatment will be done according to national guidelines. In the RDT decisional algorithm (RDT-DA) arm (intervention), the clinical examination based on IMIC will be supported by a two-step malaria RDT and bacterial infections RDTs. Prescription will be left to the discretion of the healthcare workers based on clinical examination and PoC test results. In the e-algorithm arm (intervention), artificial intelligence integrating multiple layers of clinical information such as clinical examination, signs/symptoms and medical history, and biological information such as biomarkers (CRP and WBC) and pathogen-specific PoC tests, and oximetry will be developed. The e-algorithm will serve to guide the diagnostic and management of febrile infections in children. In the 3 arms, the case report forms will be digitalized. A final follow-up visit (day 7) will be scheduled for all participants. Patients will be asked to come back to the health facilities before the scheduled visit if the symptoms persist or in case of health condition worsening. DISCUSSION: If successful, this study could contribute to improve the management of febrile diseases and reduce inappropriate use of antimicrobials. TRIAL REGISTRATION: The trial is registered at ClinicalTrial.gov, NCT05285657. Enrolment started on 4 March 2022 with long-term outcome being assessed completely by 2023.

Assessment of a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy'Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT).

BACKGROUND: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage. METHODS: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. DISCUSSION: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845.