Don Pascal Mathanga

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. We conducted causal mediation analyses to assess the proportion of SEP effect that is attributed to each mediator and combination of mediators. The mediation analysis shows that during the rainy season, improved housing and educational attainment explained 39.4% and 17.0% of the SEP effect on Pf infection, respectively, and collectively 66.4%. In the dry season, housing, educational attainment, and LLIN usage collectively mediated 33.4% of SEP’s effect with individual contributions of 15.6%, 11.2%, and 3.8%, respectively. Nutrition also played a role, particularly for children, mediating 9.2% of SEP’s effect in the rainy season and 3.7% in the dry season. The study concluded that multifaceted interventions targeting housing, education, LLIN usage, and nutrition are vital to reducing socioeconomic disparities in Pf infection risk in the Southern region of Malawi.

Background The RTS,S/AS01 malaria vaccine was introduced in Ghana, Kenya, and Malawi in 2019. Evaluation includes case-control studies designed to monitor individual-level safety and effectiveness to complement population-level estimates derived from the MVPE. Here, we discuss design and practical considerations for conducting case-control studies to measure vaccine effectiveness against severe malaria, the need for a 4th dose, and for assessment of safety outcomes. Methods For the severe malaria study we aimed to estimate the effectiveness of the primary 3 doses, and of the 4th dose. We also aimed to estimate rebound, if any, in children who received only the primary 3 doses. Cases were patients with severe malaria admitted to a study hospital, residing in an RTS,S/AS01 implementation area, and eligible to have received the 3rd or 4th dose of the vaccine. The case patient’s home is visited to collect data on vaccination status and other details. Four controls are then recruited from the same community, matched closely on date of birth. Vaccination status is determined from home-based records, and from clinic registers. Similar approaches were used for studies of safety outcomes. Results We share preliminary results and discuss the challenges encountered and lessons learned about implementing a multi-centre case control study for a malaria vaccine, and approaches to data collection which have proved effective, including establishing surveillance, the use of specific case definitions standardized across centres, recruiting closely age-matched community controls, and obtaining reliable information from both cases and controls on potential confounding factors which may be associated with both risk of the outcome and with access to vaccination. Conclusion Case control studies are an efficient means of monitoring vaccine effectiveness and safety, but require care in design and implementation. The lessons learned from the malaria vaccine pilots will be useful for countries planning introduction of a malaria vaccine.

Background: Control of malaria parasite transmission can be enhanced by understanding which human demographic groups serve as the infectious reservoirs. Because vector biting can be heterogeneous, some infected individuals may contribute more to human-to-mosquito transmission than others. Infection prevalence peaks in school-age children, but it is not known how often they are fed upon. Genotypic profiling of human blood permits identification of individual humans who were bitten. The present investigation used this method to estimate which human demographic groups were most responsible for transmitting malaria parasites to Anopheles mosquitoes. It was hypothesized that school-age children contribute more than other demographic groups to human-to-mosquito malaria transmission. Methods: In a region of moderate-to-high malaria incidence in southeastern Malawi, randomly selected households were surveyed to collect human demographic information and blood samples. Blood-fed, female Anopheles mosquitoes were sampled indoors from the same houses. Genomic DNA from human blood samples and mosquito blood meals of human origin was genotyped using 24 microsatellite loci. The resultant genotypes were matched to identify which individual humans were sources of blood meals. In addition, Plasmodium falciparum DNA in mosquito abdomens was detected with polymerase chain reaction. The combined results were used to identify which humans were most frequently bitten, and the P. falciparum infection prevalence in mosquitoes that resulted from these blood meals. Results: Anopheles females selected human hosts non-randomly and fed on more than one human in 9% of the blood meals. Few humans contributed most of the blood meals to the Anopheles vector population. Children ≤ 5 years old were under-represented in mosquito blood meals while older males (31–75 years old) were over-represented. However, the largest number of malaria-infected blood meals was from school age children (6–15 years old). Conclusions: The results support the hypothesis that humans aged 6–15 years are the most important demographic group contributing to the transmission of P. falciparum to the Anopheles mosquito vectors. This conclusion suggests that malaria control and prevention programmes should enhance efforts targeting school-age children and males.

: As countries of sub-Saharan Africa expand irrigation to improve food security and foster economic growth, it is important to quantify the malaria risk associated with this process. Irrigated ecosystems can be associated with increased malaria risk, but this relationship is not fully understood. We studied this relationship at the Bwanje Valley Irrigation Scheme (800 hectares) in Malawi. Household prevalence of malaria and indoor Anopheles density were quantified in two cross-sectional studies in 2016 and 2017 (5,829 residents of 1,091 households). Multilevel logistic regression was used to estimate the association between distance to the irrigation scheme and malaria infection and mosquito density. The prevalence of malaria infection was 50.2% (2,765/5,511) by histidine-rich protein 2–based malaria rapid diagnostic tests and 30.1% (1,626/5,403) by microscopy. Individuals residing in households within 3 km of the scheme had significantly higher prevalence of infection (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI] 1.18, 1.68); school-aged children had the highest prevalence among age groups (aOR = 1.34; 95% CI 1.11, 1.63). Individuals who reported bed net use, and households with higher socioeconomic status and higher level of education for household head or spouse, had lower odds of malaria infection. Female Anopheles mosquitoes (2,215 total; Anopheles arabiensis, 90.5%, Anopheles funestus, 9.5%) were significantly more abundant in houses located within 1.5 km of the scheme. Proximity of human dwellings to the irrigation scheme increased malaria risk, but higher household wealth index reduced risk. Therefore, multisectoral approaches that spur economic growth while mitigating increased malaria transmission are needed for people living close to irrigated sites.

: In endemic settings where asymptomatic malaria infections are common, malaria infection can complicate fever diagnosis. Factors influencing fever misdiagnosis, including accuracy of malaria rapid diagnostic tests (mRDTs) and the malaria-attributable fraction of fevers (MAF), require further investigation. We conducted facility-based surveillance in Malawi, from January 2012 through December 2013 in settings of high perennial (Chikhwawa), high seasonal (Thoylo), and moderate seasonal (Ndirande) malaria transmission. Consecutive patients presenting to outpatient departments were screened; those with suspected malaria illness were tested by mRDT or routine thick-smear microscopy. Test positivity rates (TPRs), positive predictive value (PPVs) of mRDTs, and MAFs were calculated by site, age, and season. Of 41,471 patients, 10,052 (24.2%) tested positive for malaria. The TPR was significantly greater in Chikhwawa (29.9%; 95% CI, 28.6–30.0) compared with Thyolo (13.2%; 95% CI, 12.5–13.7) and Ndirande (13.1%; 95% CI, 12.2–14.4). The overall PPV was 77.8% (95% CI, 76.8–78.7); it was lowest among infants (69.9%; 95% CI, 65.5–74.2) and highest among school-age children (81.9%; 95% CI, 80.3–83.4). Malaria infection accounted for about 50% of fevers in children younger than 5 years old with microscopy-confirmed Plasmodium falciparum infection, and less than 20% of such fevers in school-age children. Outpatient settings in Malawi had a high burden of malaria illness, but also possible overdiagnosis of malaria illness. Interventions to reduce malaria transmission and rapid testing for other common febrile illness may improve diagnostic clarity among outpatients in malaria endemic settings.

Anemia is a leading cause of morbidity in sub-Saharan Africa. The etiologies of anemia are multifactorial, and it is unclear what proportion of anemia is attributable to malaria in children of different ages in Malawi. We evaluated the population attributable fraction (PAF) of anemia due to malaria using multiple cross-sectional surveys in southern Malawi. We found a high prevalence of anemia, with the greatest proportion attributable to malaria among school-age children (5–15 years) in the rainy season (PAF = 18.8% [95% CI: 16.3, 21.0], compared with PAF = 5.2% [95% CI: 4.0, 6.2] among young children pooled across season [< 5 years] and PAF = 9.7% [95% CI: 6.5, 12.4] among school-age children in the dry season). Malaria control interventions will likely lead to decreases in anemia, especially among school-age children.

In areas where malaria remains entrenched, novel transmission-reducing interventions are essential for malaria elimination. We report the impact of screening-and-treatment of asymptomatic schoolchildren (N=705) on gametocyte - the parasite stage responsible for human-to-mosquito transmission - carriage and use concomitant household-based surveys to predict the potential reduction in transmission in the surrounding community. Among 179 students with gametocyte-containing infections, 84% had positive malaria rapid diagnostic tests. While gametocyte burden remained constant in untreated children, treatment with artemether-lumefantrine reduced the gametocyte prevalence (p<0.0001) from 51.8% to 9.7% and geometric mean gametocyte density (p=0.008) from 0.52 to 0.05 gametocytes/microliter. Based on these estimates, the gametocyte burden in the community could be reduced by 25-55% depending on the season and the measure used to characterize gametocyte carriage. Thus, school-based interventions to treat asymptomatic infections may be a high-yield approach to not only improve the health and education of schoolchildren, but also decrease malaria transmission.

Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. This 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 likely targets of naturally acquired immunity and that should be further characterized for their potential as vaccine candidates.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim–sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Background: Social innovation (SI) in health holds potential to contribute to health systems strengthening and universal health coverage (UHC). The role of universities in SI has been well described in the context of high-income countries. An evidence gap exits on SI in healthcare delivery in the context of low- and middle-income countries (LMICs) as well as on the engagement of universities from these contexts. There is thus a need to build capacity for research and engagement in SI in healthcare delivery within these universities. The aim of this study was to examine the adoption and implementation of network of university hubs focused on SI in healthcare delivery within five countries across Africa, Asia and Latin America. The objectives were to describe the model, components and implementation process of the hubs; identify the enablers and barriers experienced and draw implications that could be relevant to other LMIC universities interested in SI. Methods: A case study design was adopted to study the implementation process of a network of university hubs. Data from documentation, team discussions and post-implementation surveys were collected from 2013 to 2018 and analysed with aid of a modified policy analysis framework. Results/discussion: SI university-based hubs serve as cross-disciplinary and cross-sectoral platforms, established to catalyse SI within the local health system through four core activities: research, community-building, storytelling and institutional embedding, and adhering to values of inclusion, assets, co-creation and hope. Hubs were implemented as informal structures, managed by a small core team, in existing department. Enablers of hub implementation and functioning were the availability of strong in-country social networks, legitimacy attained from being part of a global network on SI in health and receiving a capacity building package in the initial stages. Barriers encountered were internal institutional resistance, administrative challenges associated with university bureaucracy and annual funding cycles. Conclusions: This case study shows the opportunity that reside within LMIC universities to act as eco-system enablers of SI in healthcare delivery in order to fill the evidence gap on SI and enhance cross-sectoral participation in support of achieving UHC.