Dihydroartemisinin-piperaquine versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a systematic review and individual participant data meta-analysis.

Background: High-grade resistance to sulfadoxine-pyrimethamine in East and Southern Africa has prompted numerous trials evaluating intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine.

Methods: We conducted individual participant data meta-analyses of randomised trials comparing IPTp with dihydroartemisinin-piperaquine to sulfadoxine-pyrimethamine on maternal, birth, and infant outcomes. We searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.

Socioeconomic disparities in Plasmodium falciparum infection risk in Southern Malawi: mediation analyses.

This study investigated the mediators of the association between socioeconomic position (SEP) and Plasmodium falciparum (Pf) infection in Southern region of Malawi. We utilized data from the 2014 International Center of Excellence for Malaria Research (ICEMR) surveys from Malawi in which blood samples of all individuals from selected households in Blantyre, Thyolo and Chikhwawa were tested for Pf parasitemia. We assessed household SEP and potential mediators - housing quality, food security, education status of household heads, and use of long-lasting Insecticide-treated nets (LLINs) and nutritional status.

Comparing approaches for chemoprevention for school-based malaria control in Malawi: an open label, randomized, controlled clinical trial.

Background: School-age children in sub-Saharan Africa suffer an underappreciated burden of malaria which threatens their health and education. To address this problem, we compared the efficacy of two school-based chemoprevention approaches: giving all students intermittent preventive treatment (IPT) or screening and treating only students with detected infections (IST).

Methods: In a three-arm, open-label, randomized, controlled trial (NCT05244954) in Malawi, 746 primary school students, aged 5-19 years, were individually randomized within each grade-level to IPT (n = 249), IST with a high-sensitivity rapid diagnostic test (hs-RDT, n = 248), or control (n = 249).

Impact of Sulfadoxine-Pyrimethamine and Dihydroartemisinin-Piperaquine as Intermittent Preventive Treatment in Pregnancy on Stool Antimicrobial Resistance Gene Abundance.

Increasing antimicrobial resistance (AMR) is a global public health emergency. Although chemoprevention has improved malaria-related pregnancy outcomes, the downstream effects on AMR have not been characterized. We compared the abundance of 10 AMR genes in stool samples from pregnant women receiving sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment against malaria in pregnancy (IPTp) to that in samples from women receiving dihydroartemisinin-piperaquine (DP) for IPTp.

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022.

Background: Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda.

Competing risks modeling of length of hospital stay enhances risk-stratification of patient care: application to under-five children hospitalized in Malawi.

Introduction: Length of hospital stay (LOS), defined as the time from inpatient admission to discharge, death, referral, or abscondment, is one of the key indicators of quality in patient care. Reduced LOS lowers health care expenditure and minimizes the chance of in-hospital acquired infections. Conventional methods for estimating LOS such as the Kaplan-Meier survival curve and the Cox proportional hazards regression for time to discharge cannot account for competing risks such as death, referral, and abscondment.

Prompt treatment-seeking behaviour varies within communities among guardians of children with malaria-related fever in Malawi.

Background: In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission.

Methods: As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics.

Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood.

Background: Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown.

Methods: Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria.

The RTS,S malaria vaccine: Current impact and foundation for the future.

The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of vaccine protection and longevity, implementation considerations, and future research needed to increase the vaccine's health impact, including vaccine modifications for higher efficacy and longevity of protection.

Impact of school-based malaria intervention on primary school teachers' time in Malawi: evidence from a time and motion study.

Background: School-based health (SBH) programmes that are contingent on primary school teachers are options to increase access to malaria treatment among learners. However, perceptions that provision of healthcare by teachers may be detrimental to teaching activities can undermine efforts to scale up school-based malaria control. The objective of this study was to assess the impact of school-based malaria diagnosis and treatment using the Learner Treatment Kit (LTK) on teachers' time.

Understanding the Intransigence of Malaria in Malawi.

Despite the scale-up of interventions against malaria over the past decade, this disease remains a leading threat to health in Malawi. To evaluate the epidemiology of both Plasmodium falciparum infection and malaria disease, the Malawi International Center of Excellence for Malaria Research (ICEMR) has developed and implemented diverse and robust surveillance and research projects. Descriptive studies in ICEMR Phase 1 increased our understanding of the declining effectiveness of long-lasting insecticidal nets (LLINs), the role of school-age children in malaria parasite transmission, and the complexity of host-parasite interactions leading to disease.

Malawi ICEMR Malaria Research: Interactions and Results Influencing Health Policies and Practices.

Malaria remains a threat to public health in Malawi. It is well acknowledged that malaria research and robust evidence can have an impact on malaria policy and practice, resulting in positive population health gains. We report policy-relevant research contributions that the Malawi International Center of Excellence for Malaria Research (ICEMR) in partnership with local and international collaborators has made.

The choice of reference chart affects the strength of the association between malaria in pregnancy and small for gestational age: an individual participant data meta-analysis comparing the Intergrowth-21 with a Tanzanian birthweight chart.

Background: The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA.

Methods: Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003-2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age.

Analysis of Recurrent Times-to-Clinical Malaria Episodes and Parasitemia: A Joint Modeling Approach Applied to a Cohort Data.

Background: Recurrent clinical malaria episodes due to parasite infection are common in endemic regions. With each infection, acquired immunity develops, making subsequent disease episodes less likely. To capture the effect of acquired immunity to malaria, it may be necessary to model recurrent clinical disease episodes jointly with parasitemia data.

A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Malawi.

Background: Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women.

Description of global innovative methods in developing the WHO Community Engagement Package.

Objectives: Development of a Community Engagement Package composed of (1) database of community engagement (CE) experiences from different contexts, (2) CE learning package of lessons and tools presented as online modules, and (3) CE workshop package for identifying CE experiences to enrich the CE database and ensure regular update of learning resources. The package aims to guide practitioners to promote local action and enhance skills for CE.

Setting And Participants: The packages were co-created with diverse teams from WHO, Social Innovation in Health Initiative, UNICEF, community practitioners, and other partners providing synergistic contributions and bridging existing silos.

School-Based Malaria Screening and Treatment Reduces Plasmodium falciparum Infection and Anemia Prevalence in Two Transmission Settings in Malawi.

Background: In areas highly endemic for malaria, Plasmodium falciparum infection prevalence peaks in school-age children, adversely affecting health and education. School-based intermittent preventive treatment reduces this burden but concerns about cost and widespread use of antimalarial drugs limit enthusiasm for this approach. School-based screening and treatment is an attractive alternative.

Blood-feeding patterns of Anopheles vectors of human malaria in Malawi: implications for malaria transmission and effectiveness of LLIN interventions.

Background: Access to human hosts by Anopheles mosquitoes is a key determinant of vectorial capacity for malaria, but it can be limited by use of long-lasting insecticidal nets (LLINs). In Malawi, pyrethroid-treated LLINs with and without the synergist piperonyl butoxide (PBO) were distributed to control malaria. This study investigated the blood-feeding patterns of malaria vectors and whether LLINs containing pyrethroid and PBO led to a reduction of human blood feeding than those containing only pyrethroids.

The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogens.

Background: Poor pregnancy and birth outcomes are common in sub-Saharan Africa and have complex aetiologies. Sulfadoxine-pyrimethamine (SP), given for intermittent preventive therapy of malaria in pregnancy (IPTp), is one of few existing interventions that improves outcomes of both mother and baby despite widespread SP-resistant malaria. Compelling evidence exists that malaria-independent pathways contribute to this protective effect, but the exact sources of non anti-malarial protection remained unknown.

Comparison of statistical methods for the analysis of recurrent adverse events in the presence of non-proportional hazards and unobserved heterogeneity: a simulation study.

Background: In preventive drug trials such as intermittent preventive treatment for malaria prevention during pregnancy (IPTp), where there is repeated treatment administration, recurrence of adverse events (AEs) is expected. Challenges in modelling the risk of the AEs include accounting for time-to-AE and within-patient-correlation, beyond the conventional methods. The correlation comes from two sources; (a) individual patient unobserved heterogeneity (i.

Effect of adverse events on non-adherence and study non-completion in malaria chemoprevention during pregnancy trial: A nested case control study.

Background: In drug trials, adverse events (AEs) burden can induce treatment non-adherence or discontinuation. The non-adherence and discontinuation induce selection bias, affecting drug safety interpretation. Nested case-control (NCC) study can efficiently quantify the impact of the AEs, although choice of sampling approach is challenging.