As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9-12 months of age for measles vaccination.

Modelling risk of malaria in longitudinal studies is common, because individuals are at risk for repeated infections over time. Malaria infections result in acquired immunity to clinical malaria disease. Prospective cohorts are an ideal design to relate the historical exposure to infection and development of clinical malaria over time, and analysis methods should consider the longitudinal nature of the data. Models must take into account the acquisition of immunity to disease that increases with each infection and the heterogeneous exposure to bites from infected Anopheles mosquitoes. Methods that fail to capture these important factors in malaria risk will not accurately model risk of malaria infection or disease.

The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations.

Prevention of malaria infection during pregnancy in HIV-negative women currently relies on the use of long-lasting insecticidal nets together with intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). Increasing sulfadoxine-pyrimethamine resistance in Africa threatens current prevention of malaria during pregnancy. Thus, a replacement for IPTp-SP is urgently needed, especially for locations with high sulfadoxine-pyrimethamine resistance. Dihydroartemisinin-piperaquine is a promising candidate. We aimed to estimate the cost-effectiveness of intermittent preventive treatment in pregnancy with dihydroartemisinin-piperaquine (IPTp-DP) versus IPTp-SP to prevent clinical malaria infection (and its sequelae) during pregnancy.

Current World Health Organization guidelines for conducting anti-malarial drug efficacy clinical trials recommend genotyping Plasmodium falciparum genes msp1 and msp2 to distinguish recrudescence from reinfection. A more recently developed potential alternative to this method is a molecular genotyping assay based on a panel of 24 single nucleotide polymorphism (SNP) markers.

The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

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.

The effectiveness of sulphadoxine-pyrimethamine (SP) intermittent preventive treatment of malaria in pregnancy (IPTp) might be compromised by high prevalence of resistance-associated Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations. As a proxy for IPTp-SP effectiveness, the in vivo efficacy of SP to clear parasitaemia and prevent reinfection in asymptomatic parasitaemic pregnant women in an area with high SP resistance prevalence was assessed.

The World Health Organization recommends that persons of all ages suspected of malaria should receive a parasitological confirmation of malaria by use of malaria rapid diagnostic test (RDT) at community level, and that rectal artesunate should be used as a pre-referral treatment for severe malaria to rapidly reduce parasitaemia. This paper reports on findings from a pilot study that assessed the feasibility, acceptability and effects of integrating RDTs and pre-referral rectal artesunate into the integrated Community Case Management programme in Malawi.

Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. Immunity to disease is thought to reflect the acquisition of a repertoire of responses to multiple alleles in diverse parasite antigens. In previous studies, we identified polymorphic sites within individual antigens that are associated with parasite immune evasion by examining antigen allele dynamics in individuals followed longitudinally. Here we expand this approach by analyzing genome-wide polymorphisms using whole genome sequence data from 140 parasite isolates representing malaria cases from a longitudinal study in Malawi and identify 25 genes that encode possible targets of naturally acquired immunity that should be validated immunologically and further characterized for their potential as vaccine candidates.

Identifying design features and implementation strategies to optimise community health worker (CHW) programmes is important in the context of mixed results at scale. We systematically reviewed evidence of the effects of proactive case detection by CHWs in low-income and middle-income countries (LMICs) on mortality, morbidity and access to care for common childhood illnesses.

The urban-rural designation has been an important risk factor in infectious disease epidemiology. Many studies rely on a politically determined dichotomization of rural versus urban spaces, which fails to capture the complex mosaic of infrastructural, social and environmental factors driving risk. Such evaluation is especially important for Plasmodium transmission and malaria disease. To improve targeting of anti-malarial interventions, a continuous composite measure of urbanicity using spatially-referenced data was developed to evaluate household-level malaria risk from a house-to-house survey of children in Malawi.

Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy.

The World Health Organization recommends three or more doses of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to mitigate the negative effects of malaria in pregnancy (MIP). Many pregnant women in Malawi are not receiving the recommended number of doses. Community delivery of IPTp (cIPTp) is being piloted as a new approach to increase coverage. This survey assessed recently pregnant women's knowledge of MIP and their experiences with community health workers (CHWs) prior to implementing cIPTp.

Gaps remain in understanding how performance-based incentive (PBI) programs affect quality of care and service quantity, whether programs are cost effective and how programs could be tailored to meet client and provider needs while remaining operationally viable. In 2014, Malawi's Ministry of Health launched the Service Delivery Integration-PBI (SSDI-PBI) program. The program is unique in that no portion of performance bonuses are paid to individual health workers, and it shifts responsibility for infrastructure and equipment procurement from facility staff to implementing partners. This protocol outlines an approach that analyzes processes and outcomes, considers expected and unexpected consequences of the program and frames the program's outputs relative to its costs. Findings from this evaluation will inform the intended future scale-up of PBI in Malawi.

After increasing coverage of malaria interventions, malaria prevalence remains high in Malawi. Previous studies focus on the impact of malaria interventions among children under 5 years old. However, in Malawi, the prevalence of infection is highest in school-aged children (SAC), ages 5 to 15 years. This study examined the interaction between age group and insecticide-treated net (ITN) use for preventing individual and community-level infection in Malawi.

Substantial development assistance has been directed towards reducing the high malaria burden in Malawi over the past decade. We assessed changes in transmission over this period of malaria control scale-up by compiling community Plasmodium falciparum rate (PfPR) data during 2000-2011 and used model-based geostatistical methods to predict mean PfPR2-10 in 2000, 2005, and 2010. In addition, we calculated population-adjusted prevalences and populations at risk by district to inform malaria control program priority setting. The national population-adjusted PfPR2-10 was 37% in 2010, and we found no evidence of change over this period of scale-up. The entire population of Malawi is under meso-endemic transmission risk, with those in districts along the shore of Lake Malawi and Shire River Valley under highest risk. The lack of change in prevalence confirms modeling predictions that when compared with lower transmission, prevalence reductions in high transmission settings require greater investment and longer time scales.

Recent data from Malawi suggest that school-aged children (SAC), aged 5-15 years, have the highest prevalence of Plasmodium falciparum infection among all age groups. They are the least likely group to utilize insecticide-treated nets (ITNs), the most commonly available intervention to prevent malaria in Africa. This study examined the effects of a universal ITN distribution campaign, and their durability over time in SAC in Malawi. This study identified factors that influence net usage among SAC and how these factors changed over time.

In some areas of Africa, health facility data have indicated declines in malaria that might have resulted from increasingly effective control programs. Most such reports have been from countries where malaria transmission is highly seasonal or of modest intensity. In Malawi, perennial malaria transmission is intense, and malaria control measures have been scaled up during the past decade. We examined health facility data for children seen as outpatients and parasitemia-positive children hospitalized with cerebral malaria in a large national hospital. The proportion of Plasmodium falciparum-positive slides among febrile children at the hospital declined early in the decade, but no further reductions were observed after 2005. The number of admissions for cerebral malaria did not differ significantly by year. Continued surveillance for malaria is needed to evaluate the effects of the increased malaria control efforts.

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. We hypothesized that the beneficial effect of SP on birthweight is mediated by SP activity on maternal factors, including increased gestational weight gain and antibiotic activity on pathogens in the maternal gut.