Multilateral Initiative on Malaria (MIM) Pan-African Malaria Conference – 2024: Day 3

MESA Correspondents bring you cutting-edge coverage from the MIM 2024 Conference “Grassroots Mobilization to End Malaria: Invest, Innovate & Integrate”.

Plenary Session 6 – Malaria Drug Development and Innovations for Malaria Elimination

Okwu Daerie Glory (Lambaréné Medical Research Center – CERMEL, Gabon) gave an insightful talk focused on next generation antimalarial drugs currently under clinical development. Following the current challenges the world is facing with resistance to artemisinin, chloroquine, and sulfadoxine-pyrimethamine in Plasmodium falciparum, there is an urgent need to develop better medicines for children and pregnant women. Daerie pointed out the progress made by companies in the development of sophisticated phenotypic screens that have led to the identification of new drug candidates and antimalarial targets which are now under clinical development. She pursued by recognizing and commending the endeavors of various entities and initiatives working on the discovery, development and delivery of new, effective, and affordable antimalarial drugs to reduce malaria burden in endemic countries.  Highlighted examples included the Medicines for Malaria Ventures (MMV), the ASSAP project, the West African Network for Clinical Trials of Antimalarial drugs (WANECAM), the PAMAfrica consortium, the SINDOFO consortium and the clinical trial ‘PLATINUM’.

Cristina Donini (Medicines for Malaria Venture – MMV, Switzerland) presented on malaria drug development and innovations for malaria elimination. She started by giving an overview of malaria statistics from the World malaria report 2022. She highlighted the challenges posed by artemisinin drug resistance and the need for innovative approaches in malaria case management. She urged the need to address antimicrobial resistance, optimize vaccine strategies, and introduce innovative tools in the final stages of malaria eradication efforts. She emphasized the significance of tackling drug resistance by exploring single-dose solutions and advancing vector control measures. Additionally, Donini highlighted the importance of integrating malaria interventions within the broader health system in countries. She discussed the role of partnerships, particularly the MMV, in driving research and development of new treatments. By leveraging the African experience in drug discovery and embracing innovative approaches, the session aimed to advance the malaria drug development agenda.

Symposium 39 – African solutions to an African problem: practical approaches to antimalarial resistance mitigation

Aimable Mbituyumuremyi (Rwanda Biomedical Centre, Rwanda) outlined the practical strategies employed to combat antimalarial resistance in Rwanda. He highlighted the objectives of the Malaria National Strategic Plan (NSP 2020 – 2027), aimed at reducing malaria morbidity and mortality by at least 90% of 2019 levels. Malaria incidence showed a significant reduction from around five million cases to 600,000 cases between 2008 and 2013, indicating the effectiveness of implemented strategies. However, there is a concerning trend of increasing malaria resistance. In his presentation, Mbituyumuremyi discussed new treatment guidelines (2024) focusing on vector control, high-burden areas, surveillance of antimalarial resistance, and community-based management. In Rwanda, dihydroartemisinin (DHAP) and artesunate pyronaridine (ASPY) have been introduced for first-line malaria treatment, but they are also used for second-line due to limited options. Hence, to close his talk, Mbituyumuremyi emphasized the need for additional antimalarials to be made available in the country to ensure appropriate management of cases with recommended medication options.

Gilbert Kokwaro (Strathmore University, Kenya) presented on the multiple first-line treatment (MFT) approach for uncomplicated malaria. He addressed the challenge of partial resistance to artemisinin combination therapies (ACTs) in some sub-Saharan countries, emphasizing the importance of mitigating resistance spread and safeguarding partner drugs. Kokwaro outlined the study objectives, which focused on health system challenges associated with MFTs, patient and healthcare worker experiences with MFT implementation, and the cost implications of MFT implementation in Sub-Saharan Africa. He summarized the findings, noting that rotational MFT is operationally feasible, with both healthcare providers and patients favoring simplified dosing regimens over alternative options. To overcome health system challenges of MFTs, Kokwaro emphasized the importance of i) accurate estimation of drug requirements; ii) timely procurement and distribution; iii) training for healthcare providers on new medications; iv) involvement of the private sector; and v) community sensitization activities to support MFT implementation.

Issiaka Soulama (Health Sciences Research Institute – IRSS, Burkina Faso) presented a study assessing the feasibility, acceptability, and cost of deploying multiple first-line treatment (MFT) in Kaya, Burkina Faso. The pilot study aimed to provide evidence for the effective deployment of MFT not only in Burkina Faso but also potentially in other Sub-Saharan African countries. Soulama examined various aspects, including administrative and regulatory considerations, logistical and financial aspects, and operational implementation. The findings indicated that implementing MFT is operationally feasible and well-received, underlining its potential for broader integration within the health system infrastructure, particularly in areas with diverse malaria transmission patterns. Given the impact of MFT strategies on routine prescription and administration of antimalarials, Soulama emphasized the importance of healthcare worker involvement and training, as well as monitoring antimalarial use to ensure successful implementation. Finally, he recommended monitoring molecular resistance markers as a crucial component of MFT strategies.

Maciej Boni (Temple University, United States) presented a modeling approach aimed at slowing down artemisinin resistance evolution in Rwanda through therapy strategies and geographic drug distribution models. Boni emphasized the ‘district ranking’ approach and outlined the first phase of model development. The approach compared multiple first-line treatment (MFT) strategies to extended artemisinin combined therapies (ACTs), drug switches, and triple ACTs. This initial phase is completed, and the focus has shifted to comparing geographic MFT strategies in districts using artemether-lumefantrine (AL) as first-line therapy with those using dihydroartemisinin–piperaquine (DHA–PPQ). Analysis in Rwanda indicates that geographic MFT effectively delays resistance only when deployed with rotations. Boni recommended further steps to deploy the model using drugs such as pyronaridine–artesunate (ASPYr) or artesunate-amodiaquine (ASAQ).

Andrew Omandi Cole (Strathmore University, Kenya) presented a modeling study focusing on near real-time monitoring of resistance development during the development of multiple first-line treatment (MFT) for malaria. He described a mathematical modeling approach aimed at mitigating resistance to antimalarials. The proposed methodology involves infecting red blood cells (RBCs) with merozoites and subsequently assessing them for susceptibility, resistance, infection, and recovery. The modeling study aims to examine the dynamics between Plasmodium falciparum merozoites and human erythrocytes within human hosts. The collected data will be visualized through an interactive web-based dashboard, providing insights into malaria parasite distribution across different regions of the country. Cole emphasized that this research will contribute evidence supporting the effectiveness of artemisinin combination therapy (ACTs) while also identifying potential avenues for drug and vaccine development.

Symposium 42 – Fighting malaria with genomics in Africa: Current status, achievements and prospects

Nana Aba Williams (MESA at Barcelona Institute of Global Health – ISGlobal, Spain) gave insight into mapping the landscape of ongoing research and investments in fighting malaria with genomics. Integrated Malaria Molecular Surveillance (IMMS) offers the potential for a holistic understanding of how the human genomes, parasites, and vectors respond to malaria control interventions which in turn informs programmatic decisions on the optimal mix of interventions. This study implied the systematic data collection from multiple sources, screening, and selection of projects, extracting and verifying project details with project leads, classifying projects based on common objectives to create a community of researchers and stakeholders to discuss protocols and finally build a living group of useful information. The landscaping review captured a total of 118 projects with funds of over $187.9M with 35 projects being active and representing $69.3M distributed all over the world. Williams also emphasized the importance of organizing symposiums to encourage sharing active projects and investments.

Osoti Victor (KEMRI-Wellcome Trust Research Program, Kenya) presented his study on integrating malaria molecular epidemiology into routine surveillance in Kenya. Artemisinin resistance has been reported in several countries in East Africa. One hundred blood spots were collected from 8 counties and 81 schools in western Kenya in 2019. A rapid diagnostic test (RDT) was used to screen for malaria and 28% positive samples were obtained. DNA was further extracted from these samples and the pfkelch13 gene was validated in this population. A high frequency of other genes involved in resistance was also observed in 2019 and several others in 2022 including A469 and A625. A database and a strategy document were developed for reporting, and guiding data from the malaria molecular surveillance (MMS) platform which was set up at the end of this study.

Deus Ishengoma (National Institute for Medical Research – NIMR, Tanzania) presented the progress, challenges, and opportunities made in building the capacity of malaria molecular surveillance in Tanzania. The aim of this study was to establish local molecular, genetic, and genomic laboratories, and analytical capacity to support MMS in the country. A whole team of students, postdocs, and other stakeholders was set up in collaboration with personnel from the National Malaria Control Program (NMCP). Thirty thousand blood samples out of the 600,000 collected from all the regions in the country were resistant to artemisinin and were sequenced. The results from this study showed the status of hrp2/3 gene deletions, artemisinin partial resistance, sulfadoxine-pyrimethamine (SP) resistance, and the mapping of Plasmodium falciparum (Pf) and non-falciparum species. A genomic laboratory, established field sites, and platforms for malaria molecular surveillance (MMS) were set up and effective capacity building of postdocs, staff, interns, and students was done.

Mulenga Mwenda (PATH, Zambia) explored in-country nanopore sequencing using the NOMADS assay to identify drug resistance markers in Zambia. This study was done to integrate surveillance of Plasmodium falciparum (Pf) via nanopore sequencing into routine surveillance, empower others to use the assay, optimize existing and develop novel sequencing assays in the country in collaboration with the National Malaria Elimination Centre (NMEC). Five hundred samples were collected and sequenced to assess the treatment efficacy of frontline ACTs and provide genetic evidence from Solwezi and Kasama which are two high-transmission sites. Three hundred samples were analyzed with a high number of Pfdhfr mutations recorded. Other mutations including the P667S, P675V, P667A, P441L, and R622T were also found to exist in some samples. The pfkelch13 mutation was only found in Solwezi.

Jonathan Juliano (University of North Carolina, United States) presented on strengthening malaria molecular surveillance capacity in the Democratic Republic of the Congo (DRC) through the PaluSeq (séquençage du paludisme) project. The objective of the project was to strengthen malaria molecular surveillance capacity in the country. The goals are to identify emerging antimalarial drug-resistance mutations in the DRC in near real-time and to train and equip new generations of Congolese malaria molecular epidemiologists. They started with updating national maps of Plasmodium falciparum and drug resistance mutations. They are actively enrolling people with malaria symptoms, with a staged roll-out by province, where 9 provinces will be considered. Sequencing of malaria drug-resistance markers will be done on about 14,000 samples collected for the study. The project is also currently training and building capacity in bioinformatics by recruiting Congolese students.

Christian Nsanzabana (Swiss Tropical and Public Health Institute – SwissTPH, Switzerland) discussed the potential and hurdles of expanding malaria molecular surveillance (MMS) in Africa. Use cases encompass monitoring drug resistance markers, hrp2/3 deletions, insecticide resistance, and therapeutic efficacy studies (TES). Future applications of MMS include detecting asymptomatic reservoirs, using genomics for transmission tracking, and understanding transmission chains. Molecular markers serve as early warning signs for resistance emergence. Presently, countries like Uganda, Kenya, and South Africa utilize these methods, albeit with limited insecticide resistance markers. Reports of vaccine resistance highlight the need for surveillance to gauge efficacy. Effective sampling strategies are crucial, despite genotyping challenges such as daily parasite density fluctuations and infection complexity. Nsanzabana stressed the importance of integrating molecular surveillance into routine antimicrobial resistance and diagnostic monitoring and advocated for the adoption of Next-Generation Sequencing due to its sensitivity to minor variants. He closed his presentation by pointing out the need for further research to develop predictive models based on molecular markers for efficacy dynamics.

Simone Boene (National Malaria Control Program – NMCP, Mozambique) discussed the utilization of malaria molecular surveillance for programmatic decisions in Mozambique, the fourth-highest malaria burden country. With heterogeneous malaria distribution, key questions revolved around diagnostics efficacy, ACT resistance, transmission sources, and intervention impact. Funded by the Bill & Melinda Gates Foundation (BMGF), the GenMoz project aimed to enhance Next-Generation Sequencing (NGS) capabilities at the Manhiça Health Research Center (CISM), generate local molecular data, and support the National Malaria Control Program (NMCP) in utilizing it effectively. The project addressed five areas: i) antimalarial resistance, ii) diagnostic resistance, iii) transmission stratification, iv) pregnant women’s role in assessing community transmission, and v) intervention impact. Findings revealed low hrp2/3 deletion rates, absence of pfkelch13 mutations, and high quintuple mutant prevalence with low dhps-581 mutations. Three doses of sulfadoxine-pyrimethamine (SP) showed sustained IPTp-SP benefits despite quintuple mutants. Importantly, pregnant women reflected community trends, revealing high genetic complexity in the north. The results informed NMCP protocols, with the use of a dedicated dashboard for antimalarial resistance markers, demonstrating the integration of molecular diagnostics into national protocols.

Scientific Session 14 – Drug Resistance 1

Alassane Mbengue (Institut Pasteur Dakar, Senegal) presented on the first appearance of partial artemisinin resistance (pArt-R) in Senegal, tracking pArt-R with translational research in the African context. Plasmodium falciparum has complex antimalarial resistance mechanisms leading to a long-lasting antimalarial drug resistance problem. This study used a model that combined clinical investigations and fundamental science to determine the genetic diversity of pfkelch13 and the functional relevance of its single nucleotide polymorphisms (SNPs), where 15 SNPs were detected. The presenter also elaborated on other ongoing projects to strengthen antimalarial resistance surveillance including genome editing and the development of a protocol to generate and screen select transgenic lines.

Emma Filtenborg Hocke (University of Copenhagen, Denmark) presented research linking a novel intron variant (431V) to dihydropteroate synthase (dhps) resistance haplotypes in P. falciparum from West Africa. The study aimed to i) investigate the geographical distribution of the novel dhps intron mutation across five African countries, ii) assess the association between the novel mutation and haplotypes lacking the 431V mutation, and iii) examine whether the length of microsatellites is correlated with specific haplotypes. Analysis included 964 samples, with 701 representing full haplotypes and 114 samples containing 431V, including 94 full 431V haplotypes. Her findings indicated that the 431V mutation emerged independently multiple times, without a common ancestor, and recent selection pressures have led to a loss of diversity. The novel mutation was associated with a fitness advantage, likely due to its role in transcription regulation. Moreover, the study demonstrated that the expansion of microsatellites can lead to intron retention.

Balla Gibba (Ministry of Health, The Gambia) presented findings from a therapeutic efficacy study on antimalarial resistance markers in The Gambia. Despite low malaria transmission, the country faces challenges like residual and imported malaria, hrp2/3 deletions, and resistance. Seasonal malaria chemoprevention (SMC) was adopted in the country in 2012 with sulphadoxine-pyrimethamine plus amodiaquine (SPAQ). The study aimed to assess mutations in malaria preventive drugs. Clinical cases underwent diagnostic PCR and sequencing, revealing widespread chloroquine resistance. Fixed dhfr mutants and the emergence of K540E were notable, especially in the eastern region of The Gambia. He highlighted that molecular surveillance is crucial for monitoring local and regional malaria interventions to aid control and elimination efforts. 

Nkemngo Francis Nongley (Centre for Research in Infectious Diseases – CRID, Cameroon) presented research on the geographical emergence of sulfadoxine-pyrimethamine (SP) drug resistance associated with P. falciparum alleles in co-existing Anopheles mosquitoes and asymptomatic human populations across Cameroon. He highlighted the threat posed by mutations to the effectiveness of SP as a chemoprevention tool. In his study, Nongley observed a high infection rate of both P. falciparum and P. malariae in natural Anopheles vectors. Additionally, he noted an increasing frequency of SP mutant alleles in both mosquito and human systems, including the emergence of 1431V alleles and a low frequency of the K540E allele. Nongley emphasized the evolution of mutant Pmdhfr and Pmdhps haplotype populations within the population. He concluded that the hidden circulation of P. malariae significantly contributes to malaria in Cameroon, often in mixed infections with P. falciparum. Nongley called for enhanced molecular surveillance for drug resistance and emphasized the importance of validating the role of novel and emerging mutations in SP drug resistance.

Ntui Vincent Ntui-Njock (University of Buea, Cameroon), assessed the molecular markers dhfr and dhps of P. falciparum resistance to sulfadoxine-pyrimethamine (SP) among pregnant women across various zones. With one in four pregnant women at risk of malaria, intermittent treatment and long-lasting insecticide-treated treated nets (LLINs) are recommended. Despite these interventions, resistance to SP persists. This was a cross-sectional study done between 2019-2022 and it analyzed 3313 clinical samples, revealing P. falciparum as the most frequent, followed by P. malariae and P. ovale, and the highest malaria infection in the coastal equatorial forest zone. A high prevalence of Pfdhfr was observed, while Pfdhps prevalence was low and no K540E mutation was detected.

Sara Cantoreggi (Swiss Tropical and Public Health Institute – SwissTPH, Switzerland) presented a study on antifolate drug resistance in Rwanda. In total, 256 samples were collected from three sites: Bugarama, Nasaka, and Rukara, and then sequenced for k13 and mdr–1 mutations. She stated that despite stopping the use of sulfadoxine-pyrimethamine (SP) in 2008, the prevalence of dhps and dhfr mutations is very high and rising, possibly due to a spill-over from neighboring countries or high cotrimoxazole use in Rwanda. Cantoreggi noted variations in resistance in the three sites. For the crt mutation, there was a high prevalence in the sites sampled (highest in Bugarama) and a slow and partial recovery of chloroquine susceptibility. All k13 mutants were found to be wild types. She further discussed the ubp1 mutant, stating a low prevalence in Rwanda, highest in Bugarama, where no delayed parasite clearance was reported. There was no selection of ubp1 mutants in Rwanda. Additional studies are planned to explore the differences in mutations in the three sites and to further investigate the mutations and their implication on antifolate drug resistance.

Jacques Mari Ndong Ngoma (University of Health Sciences – USS, Gabon) discussed the rise of dhfr and dhps quintuple mutation in P. falciparum samples from sentinel sites in Gabon. The study aimed to compare molecular resistance markers to sulfadoxine-pyrimethamine (SP) in rural and urban areas. From 2014 to 2018, this prospective study gathered samples from febrile children, with more from rural settings. Dhfr frequency was higher in rural than urban areas, with unique dhps mutations in rural locales. Absent in urban settings, quintuple mutations may stem from rural self-medication and parasite recombination. Continued molecular surveillance and genetic analysis are crucial for understanding parasite dynamics in both urban and rural regions.

Moussa Diallo (Cheikh Anta Diop University – UCAD, Senegal) presented research on the evolution of Vgsc-1014, Acel, and Gste2 mutations and their potential implications for the use of insecticides in Indoor Residual Spraying (IRS) to control Anopheles gambiae s.l. in Senegal. Diallo’s study traced the presence and evolution of these resistance genes in wild populations of Anopheles gambiae s.l. collected at various time points corresponding to shifts from pyrethroids to carbamates and then organophosphates, which are used for IRS in selected health districts of Senegal. Spatial and temporal analyses revealed the evolution of Vgsc-1014, Acel, and Gste2 mutations in certain hotspots across Senegal since 2013. While Acel and Gste2 mutations were detected at a low frequency, their spread poses a concern that could negatively impact vector control efforts in the country. Towards the end of his talk, Diallo recommended further studies to monitor the distribution and evolution of these mutations and their association with phenotypic resistance to safeguard the effectiveness of limited insecticide-based vector control tools.

Scientific Session 16 – Treatment and case management 1

Margaret Ebob Besem (Reach Out NGO, Cameroon) explored the challenges of accessing community health services for malaria in conflict-affected areas in Cameroon. Several factors such as limited healthcare infrastructure, displacement, and insecurity hinder access. Besem presented innovative approaches such as community dialogue to enhance knowledge and practices. Community health workers face limitations due to conflict, necessitating improved training and supply systems. While cash assistance helps, it is most effective alongside functional health facilities. Besem concluded her presentation by highlighting the importance of coordinated implementation of these strategies to alleviate malaria burden and improve health outcomes in vulnerable populations.

Rowartz Kevin (Kisii County Government, Kenya) presented a promising healthcare approach that utilizes community health volunteers (CHVs) to manage malaria cases at the grassroots level which showed a significant improvement in primary healthcare delivery. By involving CHVs in case management, the time taken to administer treatment decreased, resulting in better patient outcomes. Additionally, this approach alleviated the burden on higher-level healthcare facilities. Continuous support and capacity building for CHVs were key factors contributing to lower morbidity and mortality rates. Kevin recommended integrating CHVs into the formal health system to ensure the sustainability of these benefits and further enhance health outcomes in malaria-endemic regions. This approach not only improves access to healthcare but also empowers communities to take charge of their health.

Paul Boateng (National Malaria Elimination Program – NMEP, Ghana) highlighted an important aspect of malaria management, emphasizing that not all malaria admissions necessarily indicate a severe case. In Ghana where malaria is endemic, individuals may be admitted to healthcare facilities for malaria treatment even if their condition is not severe due to patient concern, healthcare provider caution, or local healthcare protocols. The study aimed at understanding the relationship between admission rates and the severity of malaria cases. The key finding suggests that while many people are admitted for malaria treatment, not all of them have severe forms of the disease. This finding could have implications for healthcare resource allocation, treatment protocols, and public health strategies aimed at malaria elimination.

Tonny Wambua (Population Services, Kenya) provided valuable insights into the impact on facility workload in his presentation on implementing community case management of malaria in Busia County, Kenya. The increase in the number of Community Health Units (CHUs) practicing Community Case Management of malaria (CCMm) from 24% to 84% resulted in a significant rise in patients receiving interventions at the community level. Key findings included a notable increase in the number of malaria patients tested at the community level, rising from 14% to 54%, and patients treated increased from 9% to 58%. Conversely, there was a drastic decrease in testing and treatment numbers at the facility level, dropping from 91% to 42% and 86% to 46%, respectively. These figures highlight the impact of CCMm in reducing the workload at health facilities. Erratic commodity supplies, however, have the potential to undermine the gains made in implementing CCMm. To address these challenges, Wambua recommended continuous capacity building and supportive supervision of Community Health Practitioners (CHPs). Additionally, he emphasized the need for further analysis and study on severe malaria incidences at health facilities to inform future interventions effectively.

Elizabeth Ayuk Ndip (Reach Out NGO, Cameroon) discussed malaria case management by Community Health Workers (CHW) in conflict-affected areas of the Southwest Region of Cameroon. She gave an overview of epidemiological data on the malaria burden in Cameroon and further emphasized that CHWs are instrumental in getting malaria interventions to the communities even though they are not trained to manage severe malaria cases. The study was targeted at scaling up diagnosis, treatment, creating awareness, distribution of malaria interventions such as insecticide-treated nets (ITNSs), referrals, and review of report and matrix. Results showed a steady reduction in malaria between January and December 2023 particularly between July and September. More men tested positive than women and children. The study was significant in the availability of CHW through which malaria intervention gets to communities as well as building the trust of residents in them. Finally, she emphasized the need for the recruitment of CHWs due to their closeness and intimacy with the residents and being the first-line health respondents.   

Muhammed Afolabi (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) addressed the development of a simple pragmatic tool to improve the documentation of severe malaria in a post-Ebola community in northern Sierra Leone. It was a pilot study for the Ebola vaccine trial. He reiterated the importance of data in providing valuable insights into disease burden in a population in the health care system. Tools developed included staff training, chief complaints, draft tool, feedback incorporated, emergency trial assessment and treatment (ETAT) and training, etc which were tested between August 2019 and July 2021 in Kambia. Results showed that severe malaria occurred more in children between ages 1-14 months. He explained that some of the factors affecting clinical outcomes included neonatal age (0-27 months), underage, poverty, distance to the hospital, non-operation of the hospitals after staff closing hours of 4 pm, etc. The study showed that malaria and severe malaria are the major causes of admission and death respectively, limitation of rapid diagnostic test (RDT), overdiagnosis, and standardizing documentation of admissions and outcomes. 

Scientific Session 17 – Pathogenesis and co-morbidities 1

Andrea L. Conroy (Indiana University, United States) talked about ferritin’s role in severe malaria and its correlation with mortality. Conroy and colleagues conducted a cohort study in Uganda with 1300 children (community children without malaria and children with severe malaria symptoms). Ferritin levels were measured at enrollment, and children were followed for a year. The study found higher ferritin levels in children with severe malaria, remaining high in survivors up to a month after the onset of symptoms. Study findings also revealed a correlation between severe malaria complications and ferritin levels. Moreover, an elevated level of ferritin was linked to higher all-cause mortality risk and predicted recurrent hemolytic events in children post-discharge. Based on these findings, Conroy suggests the use of   ferritin as a biomarker for identifying children at risk of hemolytic complications and increased long-term mortality.

Katja Wyss (Karolinska Institute, Sweden) conducted a prospective cross-sectional study in two hospital settings in Cameroon to explore the association between diabetes, obesity, metabolic syndrome, and severe malaria in adults. The research revealed that type 2 diabetes and metabolic syndrome are associated with severe malaria in both patients diagnosed outside malaria-prone areas and adults diagnosed in high-endemic regions. Obesity was also associated with malaria severity in endemic settings, and Wyss suggested considering comorbidities in managing malaria patients, regardless of endemicity. Moreover, in regions with high incidences of both diseases, screening for diabetes alongside malaria treatment could be beneficial.

Samuel C. Wassmer (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom)  presented the effects of P. falciparum infection on the brain, focusing on cerebral malaria (CM). Wassmer assessed brain swelling in 176 CM patients in India. In the study, fatal CM in children was linked to severe brain swelling, while in adults, it was associated with hypoxic injury and high plasma levels of S100B. The study also showed brain involvement in severe non-cerebral malaria (SNCM), suggesting a broader impact of the disease. Additionally, higher kidney impairment was linked to more severe hypoxia, leading to the hypothesis of a kidney-brain pathogenic axis. Wassmer highlighted the need for further research to better understand the long-term effects of P. falciparum malaria on the adult brain.

Rosauro Varo (Barcelona Institute for Global Health – ISGlobal, Spain) presented findings from a matched case-control study in Mozambique that explored the association between host and parasite biomarkers and malaria severity. The study focused on identifying biomarkers in plasma that differ between children with uncomplicated malaria and severe malaria. The goal was to understand how these biomarkers relate to clinical symptoms in severe malaria patients and to assess their connection in uncomplicated and severe malaria. Varo found that HRP-2 reliably predicts SM, independently from parasitemia, and correlates with other biomarkers elevated in SM, such as Angpt-2, Tie-2, sFIt1, and sTREM-1. The study suggested that these biomarkers could enhance the management of malaria with future use in cost-effective point-of-care diagnostics.

Scientific Session 20 – Capacity Building 1

Graziella Scudu (Clinton Health Access Initiative – CHAI, United States) presented an analysis of the anticipated malaria commodities landscape in Sub-Saharan Africa, highlighting potential market disruptions. Collaborating with partners, CHAI developed short- and long-term forecasts to project current and future demand and to identify gaps in supply that can pinpoint where additional resources will be needed. The demand forecast covered rapid diagnostic tests (RDTs), treatments, insecticide-treated nets (ITNs), indoor residual spraying (IRS), and seasonal malaria chemoprevention (SMC). The analysis involved integrating historical data, statistical analysis, transmission modeling, and partner input for additional context-specific information. Projections suggest increased demand for all commodities except IRS,  attributed to population growth. SMC is anticipated to expand to more regions and age groups. Global funding constraints will affect vector control volumes, intervention choices, and product selection.

Hulda Shaidi Swai (Nelson Mandela African Institution of Science and Technology – NM-AIST, Tanzania) emphasized the potential of nanotechnology in combating malaria by manipulating matter at the atomic level. Nanocarriers can traverse biological barriers, aiding in drug delivery. Nanomedicine offers promise in reformulating existing drugs to enhance bioavailability and prolong drug efficacy in the bloodstream. Swai aims to utilize nanotechnology to develop nano-encapsulated malaria drugs targeting parasites in the liver stage. She envisions establishing a regional nanotechnology hub to drive research, innovation, and commercialization in health solutions. However, challenges such as lack of infrastructure, expensive equipment, and funding hinder progress. Creating regional hubs could mitigate these obstacles and facilitate the advancement of nanotechnology applications.

Taneshka Kruger (University of Pretoria, South Africa) presented training aimed at enhancing leadership and management capacities among senior leaders, managers, and specialists within the National Malaria Control Program (NMCP) involved in the Southern Africa Development Community (SADC) malaria elimination initiative across eight countries (SADC E8). The training focused on equipping participants with vital leadership skills, effective management techniques, and decision-making tools to navigate dynamic situations while also providing networking opportunities. Strengthening leadership and management capabilities is crucial for advancing the malaria elimination agenda and ensuring the establishment of resilient public health systems in the region. Plans include expanding training to other SADC NMCPs beyond E8 and involving additional consortia in training delivery.

Amu Mudenda (Faith Leader Advocacy for Malaria Elimination – FLAME, Zambia) presented on Southern African leaders’ efforts to garner broad-based and high-level national support for malaria through FLAME, stressing the importance of local country ownership and multisectoral commitment. He highlighted the significance of faith leaders as influential figures deeply embedded within communities, testifying to their ability to bridge gaps between government and citizens. Examples from Namibia and Zambia demonstrated how faith leaders contribute to policy adoption, strategy implementation, and securing necessary funding for malaria eradication. Notably, Mudenda emphasizes FLAME’s decentralized approach tailored to local contexts, with partnerships with various stakeholders and sustained advocacy efforts. In his presentation, Mudenda underscored faith leaders’ autonomy and commitment to community welfare, positioning FLAME as a transformative movement driving malaria elimination efforts in the region.

Rosalia Joseph (Pan-African Mosquito Control Association – PAMCA, Kenya) presented on leadership capacity building of African women in malaria and other vector-borne diseases through training in effective communication and professional development. Joseph showcased a workshop designed to enhance women’s leadership and communication skills, involving 25 participants from 17 African countries. Conducted in collaboration with expert consultants, the workshop focused on effective communication and leadership, and participants’ reports indicate a positive impact on career advancement and confidence. However, limited knowledge transfer and funding constraints were highlighted as key challenges. Towards the end of her presentation, Joseph advocated for sustained investment in women to strengthen disease control efforts, emphasizing the importance of holistic approaches and partnerships.

Welmoed Van Loon (Charité – University Medicine Berlin, Germany) presented on the emergence of partial artemisinin resistance in Africa, posing one of the most significant threats to malaria control. Van Loon highlighted the threat of partial artemisinin resistance, characterized by delayed parasite clearance and in vitro resistance, particularly in East Africa. Urgent priorities include understanding the spread and significance of K13 variants, strengthening the molecular surveillance capacity, and identifying risk factors. Their objectives include building capacities, characterizing mutations, and extending in vitro confirmation. The next steps involve data dissemination, risk factor analysis, and preparation for treatment trials. Finally, his next efforts will focus on fostering on-site research, developing improved surveillance methods, and enhancing polymerase chain reaction (PCR) tests to address this critical challenge in malaria control.

Plenary Session 7 – Climate changes and its impact on malaria elimination

Peter Gething (Curtin University and Telethon Kids Institute, Australia) gave a talk on the intersection of climate change and malaria, emphasizing the health risks associated with climate change and its impact on malaria outcomes. He introduced the climate vulnerability index, attributing 67% of the carbon footprint implicated in climate change to ten countries. Gething highlighted that the fifty countries most vulnerable to climate change are predominantly low-income or lower-middle-income countries, most of them located in the African continent. He discussed historical climate-malaria relationships and showcased how mechanistic models have been utilized to visualize the anticipated changes in climate and their potential impact on malaria transmission. Gething pointed out the worsening state of climate change in Africa and the need for tailored strategies for both mitigation and adaptation. He referenced projections by the Intergovernmental Panel on climate change (IPCC) through five ‘Socioeconomic Pathway’ scenarios to address the effects of malaria. Gething pointed out fluctuations in health expenditure, particularly a significant decrease in 2020 likely due to the pandemic. He concluded his talk by stressing the need for increased funding to address the effects of climate change on malaria outcomes in the most vulnerable countries in Africa.

Abdisalan Noor (Harvard University, United States) focused his presentation on the estimated direct effects of climate change on malaria. Noor described climate change as a ‘Great Displacer’, stressing its role in disrupting malaria prevention efforts, limiting access to healthcare services, and contributing to disease outbreaks such as malaria. He underscored that climate change poses a serious threat to development trajectories and health systems. He further emphasized the programmatic implications of the relationship between climate change and malaria, emphasizing the need for a strategic, technical, global, and operational approach to the global response. He advocated for investments in research and development and insisted on the necessity of securing funding to effectively address the intersection of climate change and malaria.

Scientific Session 23 – Malaria in Pregnancy 3

Claudia Demarta Gatsi (Merck KGaA, Germany)  presented findings from non-clinical studies supporting accelerated inclusion of pregnant women in clinical trials with cabamiquine. Specifically, findings from the Developmental and Reproductive Toxicity (DART) studies on embryo-fetal development (EFD) and pre-and postnatal development (PPND) toxicology in rats using cabamiquine during pregnancy were presented. Gatsi reported a promising non-clinical safety and efficacy profile of cabamiquine for malaria prevention or treatment during the first trimester. She asserted that the data package from the studies supports the inclusion of pregnant women and/or women of childbearing potential in earlier stages of clinical developmental studies evidence. With this talk, Gatsi emphasizsed the critical need to address the medical needs of pregnant women and children in malaria prevention. 

Oscar Okoth (Kisumu Medical and Education Trust, Kenya) presented research data on the revitalization of intermittent preventive treatment of malaria in pregnancy (Revive IPTp-SP) project, which piloted a self-care intervention to promote the uptake of sulfadoxine-pyrimethamine (SP) for IPTp in Suna West-Migori and Kisumu counties, Kenya since 2021. The study aimed to empower and sensitize pregnant women on the importance of the use of SP and improved access to the drug at the community level. Results showed a noticeable increase in  SP usage in both sub-counties and a rise in the number of pregnant women who received the recommended 3+ doses. Hence, Okoth concluded that self-care interventions to promote the uptake of SP be a promising approach to improving health outcomes of malaria in pregnancy in communities.

Yvonne Dube (University of Melbourne, Australia) presented the Malawi IMPROVE cohort study, a study on placental malaria involving pregnant women at mid-pregnancy. The study was conducted to address the lack of a specific VAR2CSA vaccine, despite progress with vaccines based on other parasite antigens.  In the study, Dube utilized a systems serology approach to investigate whether antibodies to antigens other than VAR2CSA contribute to protecting against malaria in pregnancy. From her preliminary results, Yvonne concluded that antibodies to non-VAR2CSA proteins may serve as markers of exposure to malaria in pregnancy rather than markers of protection, as they showed no association with protection against malaria in pregnancy.

Scientific Session 24 – Control and Elimination 2

Esdras Mahoutin Odjo (National Malaria Control Program, Benin) evaluated whether the prolonged residual efficacy of clothianidin resulted in a greater reduction in vector populations and subsequent malaria transmission compared to the shorter residual efficacy of pirimiphos-methyl (PM 300 CS). Mosquitoes were sampled using human landing catches (HLC) and pyrethrum spray catches (PSC) from six communities selected and monitored for indoor residual spray (IRS) between 2019 and 2021. A total of 50,645 mosquitoes were collected with Culex quinquefasciatus (58.5%) being the most predominant, followed by An. gambiae (38.8%). The human biting rate, entomological inoculation rate, and sporozoite rate were assessed and showed no overall impact between clothianidin + deltamethrin and clothianidin alone due to its slow activity. The biting rate was found to be greater with PM 300 CS.

Nancy S. Matowo (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) assessed the effectiveness of dual-active ingredient long-lasting insecticidal nets (LLINs) on major malaria vectors through a secondary analysis of a three-year cluster randomized controlled trial in rural Tanzania. In 2019, over 140 thousand nets including Olyset Plus, Interceptor G2, and Royal Guard all dual active-ingredient (AI) long-lasting insecticidal nets) and Interceptor was distributed in Misungwi to evaluate the entomological inoculation rate (EIR) as an indicator for malaria transmission in both An. gambiae and An. funestus. Mosquitoes were collected using CDC light traps. Interceptor G2 showed the best activity reducing the EIR from 92% in year 1 to 64% in year 3. All three dual AI LLINs had a strong effect on An. funestus which is the main malaria vector in the study area.

Bless Hayford (7th Day Adventist Hospital, Ghana) presented the demographic and socio-economic factors influencing bed net ownership, usage, and malaria transmission among adult patients seeking healthcare in two urban cities in Ghana. Bed net usage was more prevalent among vulnerable groups in rural communities compared to urban areas with low bed net coverage. Venous and capillary blood samples were collected from 550 participants for malaria microscopy, parasite detection, density calculation, and species identification in two hospitals: the 7th Day Adventist hospital and the Sunyani Municipal Hospital, spanning from January to September 2021. The malaria prevalence was 7.8%, with only 21.5% of participants reporting sleeping under bed nets, and 83 % of the malaria-positive patients earning less than $150 per month. The majority of participants were female between 18 and 30 years old, indicating that malaria is endemic among adult populations in Ghana overall.

Mavuto Mukaka (University of Oxford, United Kingdom) conducted a study on the safety of age-based regimens of primaquine for uncomplicated Plasmodium falciparum infection in G6PD African children through a randomized control trial. The objective was to gather pharmacokinetic data on single low-dose primaquine (SLDPQ) for transmission-blocking in African children. Children aged 6 months to 11 years with acute uncomplicated P. falciparum infection were included. The study utilized a novel age-based regimen with five age bands, while controls received ACTs. Results indicated variable primaquine exposure depending on body weight-adjusted dose, age, baseline hemoglobin, and CYP2DC metaboliser status, not on G6PD status. The data supports age-dosed SLDPQ for transmission-blocking in Sub-Saharan Africa, aligning weight-based regimens with ACTs.

Blessings Msango Kapumba (Liverpool School of Tropical Medicine – LSTM, United Kingdom) presented an ethnographic study on the Shire Valley Transformation Programme (SVTP) in southern Malawi, a large-scale irrigation plan implemented in an area with high malaria and schistosomiasis risk. SVTP involves a shareholder-owned commercial farming enterprise (SOCFE), where landowners lease land for shared farming from SOCFE, which also controls water distribution. The ShireVec vector control program conducted the study to comprehend participants’ experiences and perspectives. Participants noted that improved water access could enhance socio-economic status but might also lead to increased migration and risks of vector-borne diseases. Lack of trust in government and authorities raised concerns about over-promises, under-delivery, and reduced land access.

Orezi Adhekoyibo (Catholic Relief Fund, Nigeria) presented a study on integrating seasonal malaria chemoprevention (SMC) and insecticide-treated nets (ITNs) in Kwara State, Nigeria. The study objective was to assess the effectiveness, efficiency, and cost-benefits of these two interventions. Methods involved door-to-door household mobilization and SMC administration followed by ITN distribution at designated points. Both interventions saw significant improvements in coverage and acceptance. Cost-efficiency analysis revealed savings of over $200,000, representing 20% of the original budget. Additionally, the project enhanced campaign personnel’s capacity by providing training in the administration of both interventions and in optimizing the utilization of resources. Adhekoyibo concluded that integrating ITN and SMC campaigns was efficient, effective, and scalable, especially in settings like Kwara State with limited resources and large populations.

Ruth Boniface Mbwambo (University of Nairobi, Kenya) presented a cross-sectional study conducted in five regions of Tanzania to enhance understanding of bed net use, misuse, and misconceptions. The study collected data on demographics, socio-economic status, land use, and malaria control practices, followed by statistical analysis. Female participation and acceptance exceeded that of males in all regions. In Kagera, the region with the highest malaria prevalence, low bed net ownership and use were noted. However, overall, the study found high ownership and proper use of bed nets. Misuse and misconceptions were minimal, with the most common misconception being that bed nets reduce sexual pleasure, and the most common misuse being repurposing nets for the fences to contain poultry.

Scientific Session 26 – Insecticide resistance 2

Fleuriane Metissa Djondji Kamga (Centre for Research in Infectious Diseases – CRID, Cameroon) presented the contrasting roles of Asaia spp bacteria in mediating pyrethroid resistance escalation in Anopheles funestus and Anopheles gambiae thereby addressing the gap in knowledge regarding the influence of Asaia spp. in the context of insecticide resistance within Cameroon. The bacterium works by detoxifying insecticides, thereby affecting the susceptibility of mosquitoes to insecticide treatments. She found that Asaia was associated with resistance phenotype and genotype in An. funestus hybrids mosquitoes. A negative correlation between the abundance of the symbiont and permethrin resistance phenotype and genotype was observed with An. gambiae hybrid mosquitoes. This result laid the groundwork for understanding bacterial mechanisms in the exacerbation of pyrethroid resistance in malaria vectors. Kamga closed his talk by highlighting the need for additional studies to better understand how Asaia bacteria could contribute to this process and how this varies between different vector species.

Carlos Simeon Djoko Tagme (Centre for Research in Infectious Diseases – CRID, Cameroon) found that a single mutation (G454A) in the P450 CYP9K1 enzyme causes pyrethroid resistance in Anopheles funestus mosquitoes in East and Central Africa. Ugandan samples from 2014 showed reduced diversity, with the G454A mutation fixed. Over six years, this mutation became prevalent in Cameroon but remains absent in Ghana and Malawi. The mutated allele metabolizes pyrethroids better, increasing resistance in transgenic Drosophila melanogaster. DNA-based diagnostics using the G454A marker accurately detect pyrethroid resistance, suggesting its inclusion in monitoring tools for An. funestus populations in Eastern and Central Africa.

Cynthia Awuor Odhiambo (Jomo Kenyatta University of Agriculture and Technology, Kenya) used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via the average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Four specific genes stood out: serine protease, E3 ubiquitin-protein ligase, cuticular protein RR2, and leucine-rich immune protein, which were top hub genes in both species and could serve as potential markers and targets for monitoring insecticide resistance in these malaria vectors.

Isaiah Debrah (West Africa Centre for Cell Biology of Infectious Pathogens – WACCBIP, Ghana) presented his research on the mechanisms of pyrethroid resistance in Anopheles funestus populations in Western Kenya. He identified several non-coding RNAs (ncRNAs) as potential players in this phenomenon. Non-coding RNA refers to RNA molecules that do not encode proteins but play various regulatory roles in the cell. These were found to influence the expression of genes involved in detoxification pathways and target site insensitivity resulting in mosquito insecticide resistance. His study observed pyrethroid resistance in all the sites with an average mortality rate of 57.6%. Identifying specific ncRNAs involved in pyrethroid resistance in Anopheles funestus populations is crucial for understanding the underlying mechanisms and developing strategies to combat resistance. Debrah underlined the need for further research on the functional roles of these ncRNAs and their interactions with target genes to gain more in-depth insights into the biology of resistance and potential avenues for intervention.