Multilateral Initiative on Malaria (MIM) Pan-African Malaria Conference – 2024: Day 1

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

Plenary Session 2 – Vector Control Innovations For Malaria Elimination

Dyann Wirth (Harvard T. H. Chan, United States) highlighted the trajectory of malaria control efforts, noting progress from 2000 to 2015 followed by a resurgence in cases and deaths in 2022. She emphasized the need for a reevaluation of the global malaria program to rethink several aspects including its governance at all levels, from community to the nation and to the world taking into consideration interruptions and lessons learned from COVID-19. Wirth underlined two biological challenges one being the highly efficient transmission of parasites and the second the continuous evolution of mosquitoes. She then referred to the Malaria Threats Map and several other threats that are depicted there as well as current responses such as new nets, increased surveillance, and new drugs. She concluded her talk by highlighting the importance of leadership, innovation, real-time data usage, and healthcare support.

Charles Adekunle (RBM Partnership to End Malaria) started his talk by reminding the audience of the intolerable human toll the disease is causing by sharing a personal story from his time in a clinic two decades ago when he lost four children to malaria in just 30 minutes. Despite tremendous improvement since the year 2000, malaria still claims up to 600,000 children today.  He went on to describe the current challenges posed by biological threats, insecticide and drug resistance, RDT efficacy loss, and climate change which urge an accelerated action plan.  Adekunle introduced the action plan RBM is developing and defined action as A – accelerate, C – coordination, T – transformation, I – innovation or integration, O – opportunities, and N – networking, based on key actions to fight malaria. He finished the talk with an appeal to the audience “It is possible, let’s not pass the battle to our children”.

Joy Phumaphi (African Leaders Malaria Alliance – ALMA, Botswana) presented the government’s involvement in the fight against malaria and underlined the crucial role that grassroots mobilization should have in politics. She then elaborated on different tools developed to monitor malaria cases at community and country levels, advocating for collaborative efforts between countries and communities to eliminate malaria based on the accountability of cases and the creation of opportunities. She further emphasized the need to integrate gender considerations into the efforts to eliminate malaria. She closed her talk by highlighting the need for joint action, the combination of government and public sector innovations, and endorsement of the Yaounde declaration by heads of state.

Symposium 1 – Modeling for malaria decision making in Africa: Enhanced Technical Support and Capacity Strengthening

Susan Rumisha (Malaria Atlas Project – MAP, Australia) introduced the new decentralised MAP, now with two nodes one in Perth, Australia and one in Dar es Salaam, Tanzania. The talk commenced by providing some background to MAPs core science in risk mapping and burden estimation. She introduced MAP’s purpose as utilizing innovative data analytics to support national and international partners in more impactful malaria control efforts, with an increased focus on decentralization and African leadership. Rumisha outlined the mission, vision and key milestones, highlighting the recent establishment of the 2023 East Africa Node at the Ifakara Health Institute. The East Africa Node envisions becoming a Centre of Excellence for Innovation and Application of Geospatial Analysis for Malaria in Sub-Saharan Africa. After the establishment of the required infrastructure, the objectives include fostering innovation, nurturing African leadership, and providing technical support to National Malaria Control Programs and partners across Sub-Saharan Africa.

Samuel Oppong (Malaria Atlas Project – MAP  and Curtin University, Australia) shared his experience as a MAP PhD student to showcase a career path in geospatial analytics after previously working in the National Malaria Control Program (NMCP) in Ghana. In his talk, he focused on utilizing geospatial mapping to support malaria control decisions in Ghana. He discussed key spatial mapping initiatives in Ghana, including the development of a stratified risk map for malaria incidence, prevalence, and mortality. Oppong gave an overview of his PhD research, which aims to understand the variations in malaria burden at subnational levels to aid decision-making. His research objectives include describing the spatial distribution of malaria in Ghana at lower administrative levels, assessing challenges in malaria prevalence, evaluating the impact of interventions such as ITNs, and understanding climatic factors influencing malaria risk. He underscored the importance of contextual interpretation of models and effective communication of models to NMCPs for integration into routine systems. Oppong concluded by emphasizing the significance of geospatial mapping in addressing data gaps and guiding decision-making in malaria control.

In his talk, Samson Kiware (Ifakara Health Institute – IHI, Tanzania) shared his approach to successfully cultivating a critical mass of skilled African modellers to support NMCPs. He described the established program and skill sets students acquire, through the wide variety of training offered, including data analytics, mathematical modeling, software development, machine learning and artificial intelligence. He further emphasized the importance of involving a diverse team that mentors early-career researchers, ranging from interns to master’s and PhD students, but also including to staff at NMCPs and staff at IHI. Importantly, the team maintains gender balance in their endeavors. Additionally, Kiware also presented its innovative tools, including the MosquitoDB application for mobile mosquito database management and the Vector Control Optimisation Model (VCOM) for enhancing the impact of vector control interventions. He showcased various vector control modeling methods applied by the trainees and highlighted collaboration with the Zanzibar Malaria Elimination team.

Damaris Matoke (Pan-African Mosquito Control Association – PAMCA, Kenya) emphasized the importance of prioritizing women in malaria control efforts and modeling to ensure that diverse perspectives and experiences are incorporated into malaria modeling efforts. She outlined initiatives undertaken by PAMCA to address a significant gender gap in the field and to achieve more equitable and effective outcomes in the fight against malaria. Through the PAMCA Women in Vector Control initiative, efforts include capacity building for country chapters and NMCP, mentorship programs such as “LiftHer2” aimed at enhancing the technical expertise of female modelers, networking opportunities like webinars and female modeler networks, and provision of travel awards and recognition. These efforts promote inclusion and equity for female modelers. Matoke also mentioned plans to develop a website to further support these initiatives and address challenges faced by women in fully participating in these initiatives. She closed her talk by highlighting the need to ensure that women’s voices and contributions are fully integrated into malaria control and modeling efforts, which is crucial for enhancing the effectiveness of strategies in combating malaria.

Sheetal Silal (University of Cape Town, South Africa) presented the Malaria Modelling and Analytics (MMALA) program at the University of Cape Town. The program aims to bolster analytics and modeling capabilities in Sub-Saharan Africa and currently includes 13 PhD candidates from 12 different countries. The training includes innovations such as a comprehensive curriculum covering malaria systems, mathematical modeling, and soft skills like leadership, short-term consulting, and scientific communication. Each student works as closely as possible with their country’s NMCP to gain practical experience in how modeling can inform policy decisions. Hence, the students apply their mathematical modeling skills to address malaria challenges specific to their country. Projects undertaken by students include targeted drug administration in Botswana, sustainability of malaria elimination in South Africa, and investment cases for cross-border initiatives in the Zambezi region. Two of the projects were described directly via video recording by two of the PhD students (Thabo Bogopa and Hijila Eelu), who also shared their insights into the MMALA program. To close,  Silal highlighted the program’s purposeful and adaptive nature, aiming to cultivate a cohort of 12 PhD students who will contribute to malaria elimination efforts.

Symposium 5 – Methods validation: improving the generation of high-quality data to make strong evidence-based decisions in vector control

Rosemary Lees (Liverpool School of Tropical Medicine, United Kingdom) presented an overview of the Innovation to Impact (I2I) work packages, with a focus on the importance of identifying and addressing methodological weaknesses in the development and evaluation of vector control tools. She emphasized the validation work package and the importance of a multi-phase, multi-site approach to assess methods and understand the performance of vector control tools by defining and measuring their analytical error to show quality, reliability and consistency. Lees mentioned the benefits of validating methods for the tools which included ensuring appropriateness for its intended use, allowing comparison between different methods designed to measure the same endpoint, and identifying sources of variability which will aid in data interpretation across studies and time, and be used to power experiments. Lastly, she highlighted the importance of consensus SOPs which can be easily adopted by everyone to generate more standardized data to facilitate comparison between studies.

Katherine Gleave (Liverpool School of Tropical Medicine – LSTM, United Kingdom) presented the Methods Landscaping project by LSTM, and the development of novel methods to assess new vector control products. She introduced the motivation for the project by outlining the different ways in which insecticide resistance in major malaria vectors has prompted development of new chemistries and products.  As previously robust methods for evaluation and monitoring are increasingly considered inadequate for the diverse range of tools available to date, new products would be needed. Initiatives are underway to validate methods and ensure their reliability, reproducibility, and comparability across various labs, locations, and testing conditions. Gleave described the testing process and a framework which has been devised to optimize and characterize methods, offering a robust approach for evaluating novel evaluation techniques. The process includes impact assessment of altering testing parameters and ensures high-level sensitivity of methods to capture different modes of action adequately. Furthermore, the presented framework would also allow to determine the impact on various vector populations and comparability of results within and between testing sites.   

Graham Small (Innovative Vector Control Consortium – IVCC, United Kingdom) highlighted the importance of facilities conducting vector control research to have reliable and reproducible data in the development and evaluation of malaria vector control products. He then discussed the types of entomological data required which could be divided into three phases; product development, product registration and product rollout. Small explained that IVCC has been supporting a network of seven African trial facilities towards Good Laboratory Practices (GLP) certification in Côte d’Ivoire, Ghana, Benin, Tanzania, and Kenya which are now generating reliable, repeatable, and auditable data. Each facility has developed a GLP-compliant quality management system (QMS), received funds for infrastructure improvement, received support for extensive internal and external training, and developed a GLP compliance management system including SOPs covering standard test methods like insecticide susceptibility testing, equipment use and maintenance. He also noted that there is a formal process for documenting protocol amendments and deviations, to ensure adherence to best practices in laboratory and semi-field testing of vector control products.

Duncan Kobia Athinya (Vestergaard), discussed the guidelines for evaluating and testing LLINs from the perspective of a manufacturer. He explained the evaluation process which is done through net survivorship, fabric integrity, and insecticidal activity. He also highlighted the methodological gap in the WHO 2013 guidelines such as lack of mechanism for monitoring the quality of nets, and the resultant threat of insecticide resistance. Athinya highlighted the need for testing nets to ensure effectiveness, mentioning specific criteria and percentages for acceptable performance. He described his commitment to characterize the performance of their LLINs through long term studies of net performance. He also mentioned the need for continual improvement and adaptation based on field trials done across different settings. Overall, Athinya underscored the importance of learning from set guidelines, identifying gaps and the opportunity to understand product performance and make informed decisions in programmatic fields.

Kyeba Swai (Ifakara Health Institute, Tanzania), presented methods for evaluating spatial repellents. He explained that repellency can be through deterrence where there is reduced entry of mosquitoes into areas occupied by humans, or through excito-repellency/ non-contact irritancy where there is non-directional movement away from a host due to excitement or through feeding inhibition. Swai mentioned a few studies that have been conducted to show the efficacy of spatial repellents as a useful public health intervention. He suggested that revision of the guidelines for efficacy testing of spatial repellents is required so that manufacturers or testing labs can generate data required for WHO PQ dossier, and national regulatory authorities for registering the product. Lastly, to generate robust local efficacy data, Swai suggested measuring the spatial repellents through four mechanisms: i) Laboratory tests (measure product emanation rate and bioefficacy), ii) Semi-field systems (to understand other modes of action and inform models), iii) Experimental Huts (to generate consistent data on local wide mosquito populations), and iv) In-Home tests.

Symposium 10 – Evaluation of the BOHEMIA Cluster Randomized Trials of Mass Drug Administration of Ivermectin in Mopeia District in Rural Mozambique and Kwale District in rural Kenya: Results on Safety, Efficacy, Entomology, Social Science, and Economic Assessment

Regina  Rabinovich (Barcelona Institute for Global Health – ISGlobal, Spain) introduced the BOHEMIA Randomized Controlled Trial, addressing the inadequacy of current vector control tools in areas where mosquitoes feed outdoors during the day. She highlighted ivermectin as a complementary strategy capable of killing mosquitoes that feed on treated blood hosts with minimal safety concerns. The project focused on two sites: Mopeia in Mozambique with high transmission and Kwale in Kenya with moderate to high transmission, aiming to establish ivermectin as a new-class vector control strategy for malaria. She briefly mentioned other ivermectin clinical trials in African countries, for example, ivermectin-artemisinin combination therapy in Uganda. Carlos Chaccour (Barcelona Institute for Global Health – ISGlobal, Spain) highlighted differences between sites, including varied trial arms, dosing timings, and durations, impacting study outcomes. These included delayed and prolonged dosing in Mozambique compared to Kenya’s shorter dosing period before the onset of rains, influencing the effectiveness of the intervention.

Francisco Saute (Manhiça Health Research Centre – CISM, Mozambique) presented findings from the BOHEMIA study indicating persistently high malaria rates among children under five years of age despite the use of long-lasting insecticidal nets (LLINs). Challenges like dosing delays after flooding caused a loss of study clusters, though dosing targets were achieved. Bio-efficacy in wild Anophelines mosquitoes was confirmed, yet entomological data revealed vector resistance across all insecticide classes. Mozambique’s ivermectin mass drug administration (MDA) found a high prevalence of malaria by RDT.  There was no measurable effect on malaria prevalence, age structure, or entomological inoculation rate (EIR). Joseph Mwangangi (Kenya Medical Research Institute – KEMRI, Kenya) highlighted successful ivermectin dosing coverage, split into separate visits over ten days. Marta Maia (KEMRI-Wellcome Trust Programme – KWTRP, Kenya) reported pyrethroid resistance in Kenyan vectors, with an unexpected 30% RDT prevalence. However, the ivermectin MDA showed no vector density reduction and it potentially influenced age structure. In Kenya, ivermectin’s bio-efficacy was confirmed, showing a 20-28% measurable effect in reduction of malaria prevalence.

Carlos Chaccour (Barcelona Institute for Global Health – ISGlobal, Spain) discussed the challenge of developing new malaria medicines due to the safety and rarity of adverse events with current treatments (1:10,000). He emphasized that any new medicine must meet this safety standard, aiming for serious adverse events (SAEs) < 1:20,000. SAEs occurred in both study sites but were unrelated to the drugs used. For example, in Mozambique, most of the SAEs observed were stemming from a cholera outbreak. Systemic adverse events were the most common for all the study participants, while others were transient. Pregnant participants were monitored until delivery, with ongoing follow-up in Kenya. Both sites met WHO’s safety criteria, pending data analysis in Kenya, demonstrating alignment with Medicines for Malaria Venture’s safety standards.

Cassidy Rist (Center for Public and Corporate Veterinary Medicine, United States) presented the cost-effectiveness analysis (CEA) of ivermectin MDA for malaria control in Mozambique, as data analysis is still ongoing in Kenya. She highlighted the objectives of the study as i) To determine the incremental cost per case averted (ivermectin MDA vs control) and ii) To determine the incremental cost per disability adjusted life years (DALY) averted (ivermectin MDA vs control). The CEA included measurement of health effects, intervention costs, and economic burden with and without ivermectin MDA, for children under five years of age and children above the age of five. The cost of the intervention was found highest in the amount spent on ivermectin, and the salaries for personnel administering ivermectin, hence both factors provide an opportunity for cost reduction. In conclusion, ivermectin appears to be cost-effective, and the ivermectin MDA programmatic costs appear to be within the same range as those for SMC programs that use similar door-to-door methods for drug distribution over multiple months.

Caroline Jones (KEMRI-Wellcome Trust Programme, Kenya) presented on community perceptions and experiences of ivermectin MDA for malaria control. This study was a 3-phase longitudinal qualitative study based on an ethnographic approach through in-depth interviews, participant observations, and photovoice sessions. Using a participant-focused approach enhanced a sense of involvement for the participants. The participants also reported having trust in implementing institutions, and the rigorous trial processes, which facilitated uptake of ivermectin. There was a perception of a reduction of mosquitoes and malaria during the ivermectin MDA. Additional positive effects included clearing of bed bugs and scabies. Gender norms were found to have affected the participation and experiences of some participants. Positive and negative bodily effects were reported by the participants; with the positive effects of the ivermectin MDA outweighing any minor side effects. Overall, participants of the BOHEMIA trial in Mopeia and Kwale perceived the study to be making a positive contribution to malaria control in the study sites.

Symposium 11 – R21/Matrix-M: A high impact malaria vaccine

Mehreen Datoo (University of Oxford, United Kingdom) introduced the R21/Matrix-M vaccine candidate for malaria during his presentation which WHO recommended as the second malaria vaccine, and is set for rollout next year. It employs Matrix-M, an adjuvant, to enhance the immune response against pathogens. Phase III trials rigorously assessed safety, efficacy, and immunogenicity through a randomized, placebo-controlled design involving a large participant pool. Safety data, monitored for adverse events, showed no significant concerns after over 15,000 doses administered to African children aged 5-36 months. Efficacy (reduction in clinical malaria episodes) data revealed high rates 67-75% over 12 months for standard and seasonal sites, with similar efficacy (66-76%) up to 18 months post 4 doses and maintained efficacy of 71-73% at seasonal sites over 24 months. The vaccine’s data underscore its potential to combat malaria globally. These findings pave the way for regulatory approval and widespread deployment, showcasing the vaccine’s safety, effectiveness, and longevity in protecting against malaria.

Emma Beaumont (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) presented vaccine efficacy (reduction in clinical malaria episodes) of the R21 Matrix-M over 18 months examining various demographic characteristics such as age, gender, nutritional status, seasonal malaria chemoprevention (SMC), and peak anti-NANP IgG antibody titre. The results revealed several key points: i) Age: vaccine efficacy over 18 months was higher among children vaccinated between 7 and 17 months of age compared to those aged 18 to 36 months at vaccination. ii) Gender and nutritional status: there was no difference in vaccine efficacy between males and females or between underweight children and those of normal weight at the time of vaccination. iii) Seasonal malaria chemoprevention (SMC): vaccine efficacy differed based on the number of SMC rounds received, particularly among those who received no SMC. However, the sample size for this group was very small. iv) Peak anti-NANP IgG antibody titre: vaccine efficacy increased with increasing peak anti-NANP IgG antibody titre. These findings shed light on the effectiveness of the R21 Matrix-M vaccine over an extended period and highlighted the importance of considering various demographic factors in assessing vaccine efficacy.

Hamtandi M. Natama (Research Institute of Health Sciences – IRSS, Burkina Faso) presented findings regarding the efficacy and safety of the R21/Matrix-M malaria vaccine. The study, conducted over 2 years with 450 participants aged 5 to 17 months, demonstrated high efficacy in preventing clinical malaria. Participants who received R21 with a higher dose of Matrix-M adjuvant showed an efficacy of 80% at 12 months following the booster vaccination. Notably, the vaccine’s efficacy was sustained over multiple episodes of malaria. The study also identified a correlation between vaccine efficacy and anti-NANP antibody concentrations, with a potential threshold of 6500 ELISA units associated with a 77% reduction in malaria risk. These promising results support the advancement of R21/Matrix-M to phase 3 licensure trials, indicating its potential to significantly impact the malaria burden in highly endemic areas. With this evidence WHO also stated its policy recommendations in October 2023.

Peter Winskill (Imperial College London, United Kingdom) presented a mathematical transmission model of malaria to estimate malaria cases, deaths and disability-adjusted life years (DALY) averted, and cost-effectiveness of R21/Matrix-M over 15 years across different transmission settings. He highlighted the role of modeling in bridging trial data and implementation strategies. Using data from phase 2 and phase 3 trials, the model predicted significant vaccine efficacy against clinical malaria, with age-based introduction estimated to avert a substantial number of cases and deaths across different transmission settings. The model demonstrated robustness in predicting vaccine delivery cost effectiveness depending on the implementation. Cost-effectiveness estimates indicated favorable outcomes compared to existing malaria interventions and childhood vaccines. Winskill emphasized on refinement of the ongoing model as more trial data becomes available. 

Jane Grant (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) presented the results of a qualitative study on the acceptability of the R21 vaccine alongside existing malaria prevention interventions in the R21 phase III trial site in Mali. Caregivers and community members had confidence in the vaccine’s effectiveness, resulting in high demand for the R21 vaccine alluding to the significant malaria burden. Trust in the trial team and positive experiences with childhood vaccinations also contributed to the vaccine’s acceptability. While some caregivers still considered seasonal malaria chemoprevention (SMC) important after R21 vaccination, others believed the vaccine, combined with bed nets, provided sufficient protection. Grant emphasized the importance of assessing acceptability to inform vaccine implementation’s strategies and highlighted the need for further research to ensure comprehensive coverage of complementary interventions during vaccine scale-up.

Sandesh Bharati (Serum Institute of India Private Limited, India) presented on R21/Matrix-M: manufacturing capacity, vaccine implementation plans and phase 4 study design. He described GSK’s plan to produce 18 million doses of RTS´S between 2023 and 2025, with a commitment to supply with a cost of  €9.30 per dose. Serum Institute will supply the R21 vaccine through UNICEF and Gavi, with a capacity to produce 100 million doses annually, expandable to meet demand. The initial price for R21 is set at USD 3.90 per dose. Implementation will begin in selected countries, including South Sudan, Central African Republic, Nigeria, and Uganda. Post-licensure studies will assess vaccine effectiveness against clinical malaria and all-cause mortality. Bharati expressed gratitude to collaborators and highlighted Serum Institute’s commitment to meeting vaccine demand and conducting rigorous post-licensure research.

Adrian V. S. Hill (University of Oxford, United Kingdom) provided an overview of the future prospects for the R21/Matrix-M malaria vaccine. He highlighted the remarkable efficacy (reduction in clinical malaria episodes) of the vaccine (78%) over one year in the primary endpoint of the phase three trial, particularly in children aged 5 to 17 months. Hill underlined the ongoing evolution in vaccine design, transitioning from RTS´S to R21 with significantly higher  impact in malaria case reduction. He discussed the potential for better durability and functionality due to the increased density of antigens on the nanoparticle surface. Hill also outlined future trials, including combination vaccine studies with other malaria antigens and transmission-blocking vaccines. He expressed gratitude to collaborators and emphasized the importance of continued research efforts to combat malaria effectively.

Lister Stockton and Fernando Ramos Lopez (University of Oxford, United Kingdom) presented the safety and immunogenicity data from ongoing trials assessing the co-administration of EPI vaccines with R21/ Matrix-M in African children and the use of this vaccine in HIV positive children. Stockton presented findings on the co-administration of the R21/Matrix-M vaccine with EPI scheduled vaccines in different groups. The arm, which received only EPI vaccines showed no increase in anti-NAMP IgG levels. However, another arm receiving R21 with EPI vaccines demonstrated a significant increase in IgG levels. Local and systemic reactions were mostly mild and resolved within a few days. Tetanus and diphtheria levels were consistent across groups. Co-administration of R21 with EPI vaccines showed no significant impact on antibody levels compared to EPI vaccines alone. These results showed  the compatibility of R21 with existing vaccination schedules and the importance of ongoing research to optimize vaccine administration. Most participants experienced mild to moderate adverse events and serious adverse events were rare. On the other hand, He also pondered if they will be successful in delivering vaccines to millions of children who will need them.

Scientific Session 1 – Immunology and Vaccines 1

Soulama Ben Idriss  (Action Health Research Group – GRAS, Burkina Faso) presented his study on the safety, immunogenicity and transmission-blocking activity of R0.6C and ProC6C: a phase 1b clinical trial in adults living in a high burden malaria transmission setting in Burkina Faso. This study explored the efficacy of two promising vaccines R0.6C and ProC6C over the currently approved vaccines (RTS,S/AS01E, and R21 vaccines) for malaria elimination. R0.6C and ProC6C reduce the anti-sporogonic activities. Two doses of the vaccines with different formulations were tested against populations between ages 20 – 45 years. Two cohorts were selected and a total of above two hundred were screened. The groups generated higher levels of antibodies specific to Pfs48/45. The standard membrane feeding assay (SMFA) was used to assess the functionality of antibodies elicited after vaccination. He concluded that both vaccines are promising in their transmission and anti-sporogonic abilities and safety.

Michael Emch (University of North Carolina, United States) presented his study assessing the effect of malaria transmission intensity on the modification of RTS,S efficacy due to a rebound effect in Ghana, Malawi, and Gabon. He stressed the effect of parasite ecology and host on vaccine efficacy, as efficacy decreases with an increase in background malaria incidence. Malaria transmission intensity was estimated in 16 sites using geospatial data. In the analysis, 2009-2014 Phase III vaccine trial data in Malawi, Gabon, and Ghana were used (n=2427). Results showed that rebound malaria occurred in the highest transmission sites after the third dose. The study highlighted that the lower reported efficacies of RTS,S in higher transmission areas were due to rebound malaria.

Jordan Plieskatt (Statens Serum Institut, Denmark) elaborated on a novel multi-stage vaccine, ProC6C which elicits functional antibodies against two P. falciparum life cycle stages in adults. The ProC6C vaccine is in its Phase I stage in Burkina Faso and Phase II stage in Mali. He stated that its efficacy lies in its immunogenicity with or without a matrix regime. The vaccine has 36 amino acids, 6 copies of NAnP, and 3 copies of NVDP along with a high transmission reduction potential in eliciting antibodies reactive to full-length CSP. The peak antibody response is 14 days post-third vaccination compared to RTS,S/AS01E. Similarly, it improves the longevity of antibodies by delaying the third booster doses of 0, 1, and 6. This study supports the selection and further development of ProC6C as a promising transmission-blocking vaccine candidate.

Katie Patterson (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) evaluated the effect of RTS,S/AS01E, and seasonal malaria chemoprevention (SMC) alone or combined on antimalarial antibody responses. The synergistic effect of RTS,S/AS01E, and SMC is promising in destroying the malaria parasite due to their different modes of action. It requires a single dose to be administered for five years. A multiplex assay was used to detect multiple antibodies to measure protective immunity. Two cohorts were used: cohort 1 (1 – 5 yrs) and cohort 2 (5 – 12 months). Blood samples were collected and immunoglobulin was detected. Results showed a lower response in cohort 2 and the combined group and a higher response in Mali.  

Maria Del Pilar Quintana (University of Copenhagen, Denmark) evaluated the high-throughput isolation of cross-reactive and adhesion-inhibitory VAR2CSA-specific monoclonal antibodies from Plasmodium falciparum-exposed pregnant women using LIBRAseq. Samples were collected from pregnant women with isolated medium as a source of cells merging the binding antigen to the antibodies. This technique permitted the identification of hundreds of VAR2CSA-specific monoclonals with naturally acquired VAR2CSA-specific mABs, most cross-reactive and targeting complex epitopes. Very few mAbs were targeting minimal binding regions.

Thiery Masserey (Swiss Tropical and Public Health Institute – Swiss TPH, Switzerland) presented results from a mathematical modeling study that assessed the selective pressure induced by malaria vaccines on Plasmodium parasites. Findings from the study indicate that more of the genotype was resistant to RTS,S/AS01E than to other vaccine types. Results further showed a rapid spread of the vaccine-resistant genotype depending on the degree of resistance and vaccine type. Masserey pointed out the necessity to better assess the existence of genotypes with reduced efficacy to vaccines, prioritizing the development of vaccines with lower risk and finally combining vaccines that target different antigens.

Isobel Walker (University of Melbourne, Australia) presented her work on identifying new target antibody responses to the PfEMP1 gene that protects children from severe malaria. This study was carried out in Papua New Guinea in an area with high transmission of malaria on 142 children who had severe malaria. About six features added to the regression model were needed to differentiate between severe and uncomplicated malaria giving an accuracy of 75%. Walker’s study pointed out the fact that a vaccine with monoclonal antibody therapy which promotes neutrophil phagocytosis of ICAM-1 binding IE may provide protection from severe malaria.

Scientific Session 2 – Vector biology and control 1

Denis Richard Kailembo (Swiss Tropical and Public Health Institute – Swiss TPH, Switzerland) monitored the effect of community-based larviciding in Tanga region, Tanzania with the aim of eliminating immature mosquito larvae using existing larviciding protocols. Three rounds of 2 locally produced biolarvicides, BTi and BS, were administered during periods of low rainfall. Weekly data collection and monitoring included the number of habitats, larval abundance, the number and proportion of habitats sprayed, and the amount of biolarvicide used. The results revealed a drop in larval occupancy over time, with over 1.6 million dollars spent on implementation. Kailembo emphasized that Incorporating health systems and working with smaller habitats will be critical in future tests.

Nehemie Nzoyikorera (National Public Health Institute, Burundi) evaluated the distribution of Anopheles mosquitoes in nine representative provinces of Burundi using both morphological and molecular identification tools. Molecular identification for each complex was done using standard PCR techniques with specific primers. Out of the 493 samples identified, 82,6% were from the An. gambiae complex with An. arabiensis being the most predominant species and 17.6% were from the An. funestus complex based on the phenotypic characteristic. Some samples were unidentified using the protocol. This study establishes a framework for better understanding malaria transmission patterns and defining effective vector control tools in Burundi.

Helen Nwanosike (MESA at Barcelona Institute of Global Health – ISGlobal, Spain) provided an overview of the MESA platform, which is used to collect and disseminate knowledge, as well as to inform decisions in malaria-endemic countries. She began the landscaping review with a recap of Anopheles stephensi’s detection as an invasive species in ten countries, eight of these in Africa. It is resistant to the major insecticide classes and transmits Plasmodium vivax and falciparum, posing a serious threat to vector control. A comprehensive data search identified 68 relevant projects by 39 lead institutions and four National Malaria Control Programs (NMCPs). The total amount of funding reached $89 million from 25 different funding sources. Apart from these statistics, the analysis of these projects also identified potential knowledge gaps in An. stephensi research. 

Javan Chanda (PATH, Zambia) presented a project focused on scaling up Malaria Case Detection (MCI) tools using community health workers (CHWs). The 1-3-7 approach was implemented for rapid case response. The approach involves reporting a malaria case on day one, investigating the case within three days, and responding with foci entomological investigation and treatment within seven days. The study, in Mazabuka and Chikankata, monitored entomological and vector control from January 2021 to December 2022. Foci investigation was triggered by an index case and involved identifying, mapping and treating vector breeding sites within two kilometres of the house within seven days. Results showed a decrease in Anopheles breeding site positivity and increased larvicide coverage. Operational successes include high training rates and MCI DHIS2 implementation. Challenges include transport, finances, mobile network, and insecticide supply. Opportunities lie in resource mobilization, stakeholder engagement, coordination, and potential drone use for larviciding.

Adeogun O. Adedapo (Nigerian Institute of Medical Research, Nigeria) presented a research project using geospatial mapping to understand the distribution of secondary malaria vectors in Nigeria. Entomological data were aggregated from 172 sites across Nigeria. Geospatial modeling was performed using a Random Forest algorithm to predict the distribution of mosquito species using remote-sensing data on 19 climatic and four topographic variables. Results showed a wide distribution of non-gambiae Anopheles species, with temperature influencing major species more than precipitation. Predictive maps were generated, and model accuracy was high. The study findings highlight the importance of including secondary vector species in operational strategies and call for increased surveillance and attention to their expanding ranges.

Plenary Session 3 – Malaria Drug Resistance: Key Perspectives  

Arjen Dondorp (Mahidol Oxford Tropical Medicine Research Unit, Thailand) provided insights into the impact of malaria drug resistance in Africa, with a focus on artemisinin resistance and its implications for treatment effectiveness. This resistance can lead to partner drug resistance and reduce the efficacy of artemisinin-based combination therapies (ACTs). Validated pfk13 mutations and delayed parasite clearance serve as key indicators of this resistance, as confirmed in Eritrea, Rwanda, Tanzania, and Uganda. The spread of artemisinin partial resistance across Africa necessitates the implementation of transmission-blocking drugs like primaquine, along with enhancing surveillance and monitoring drug efficacy. Strategies include optimizing diagnostics and therapeutics, fostering collaboration for new tools such as non-artemisinin-based drugs or monoclonal antibodies, and ensuring access to malaria vaccines such as RTS,S/AS01E and R21. Effective implementation of multiple first-line therapies is crucial in combating resistance and improving malaria control efforts.

Abdoulaye Djimde (University of Bamako, Mali) began his talk by underlining the persistent threat of malaria, particularly in Africa, where over 95% of cases and deaths occur. Antimalarial drug resistance is emerging as a critical obstacle to controlling and eradicating malaria globally. The resistance to artemisinin, observed in Plasmodium falciparum, has been detected in East Africa, specifically in Rwanda, Uganda, and Tanzania. These findings suggest a potential decrease in the effectiveness of artemisinin-based combination therapies across the African continent. Djimde urges swift, unified action from stakeholders and funders to prevent a surge in malaria cases that may arise due to the rapid spread of resistance against antimalarial drugs. This includes regional coordination for data sharing, empowering local communities to tackle operational challenges, and strengthening surveillance using genomic and phenotypic analyses. Additionally, basic research is crucial to address key questions for malaria control and elimination efforts.

Symposium 14 – Malaria Vector Genomics Surveillance in Africa: a Pan-African-led initiative to deliver an accessible data platform for research and public health

Luna Kamau (Kenya Medical Research Institute – KEMRI, Kenya) Highlighted the importance of integrating genomic surveillance with vector surveillance to understand malaria transmission dynamics and enhance control measures. In 2013, Anopheles coluzzii, previously unseen in Kenya, was discovered and linked genetically to West African strains. Mosquito populations exhibited genetic diversity, resembling those from arid regions. Sequencing 564 mosquitoes from five locations revealed the V4022L +l1527T mutation, potentially compromising the efficacy of PBO nets. Ongoing surveillance is crucial to monitor the presence of newly identified Anopheles stephensi species and track the spread and evolution of Anopheles coluzzii, essential for effective malaria control in Kenya.

Joel Odero (Ifakara Health Institute – IHI, Tanzania) investigated knock-down resistance (kdr) in Anopheles funestus in Tanzania. The spread of kdr across Africa in major malaria vectors has been well described, however, it has never been reported in East and Southern Africa where An. funestus is the principal vector. Whole-genome-sequencing (WGS) on population-samples of An. funestus across Tanzania. Eight novel amino acid substitutions in the Vgsc gene were found, including the kdr variant L976F and P18425, especially in the Morogo region. These mutations decreased between 2017 and 2023. Haplotype clustering analysis was performed on the Vgsc gene and revealed a selective sweep in the Morogo region. A strong association between survivorship to DDT insecticide and L976F was found, however no association with a pyrethroid insecticide was found. The authors hypothesize that DDT contamination from stockpiles in regions where kdr alleles were discovered may have been responsible for this evolution.

Rosine Wolie (Institute Pierre Richet and Nangui Abrogoua University, Côte d’Ivoire) researched utilizing genomic surveillance to investigate population structures and resistance mechanisms in Anopheles (An.) gambiae species against pyrethroids and organophosphates. Employing genomic wide selection scans (WGSS), she identified genes associated with resistance. Mosquito samples were collected from six locations across the country, revealing reproductive isolation between An. gambiae and An. coluzzii. Double target site mutations, which could cause pyrethroid and DDT resistance were observed. Various metabolic resistance mechanisms, particularly in An. coluzzii from the central region were evident against pyrethroids. Additionally, multiple mechanisms of metabolic resistance to organophosphates, including recently discovered carboxylesterase genes, were detected in An. gambiae.

Cynthia Awuor (Kenya Medical Research Institute – KEMRI, Kenya) presented her research using a systems biology approach to answer three questions i) how insecticide resistance is developed, ii) what methods can be used to detect mosquitoes that are resistant, and iii) what strategies can be used to enhance effectiveness of insecticides. Mosquitoes were experimentally exposed to insecticides, and bioassays and sequencing were performed before bioinformatics analysis. The phenotypic effects were measured using Weighted-Gene Coexpression Network Analysis (WGCNA). Highly connected (hub) genes were identified for An. arabiensis and An. gambiae. Notably, four hub genes were shared between these two species. These findings were validated by differential gene expression and by qPCR. The molecular mechanisms of insecticide intake were investigated, revealing immune modulation may be implicated in resistance development. Recommendations were made for functional validation of the four hub genes and for all insecticide resistance mechanisms to be considered during insecticide development.

Scientific Session 4 – Control and Elimination 1

Chi Tchampo Fru (University of Bamenda & Coordination Organization for the Fight against Endemics in Central Africa – OCEAC, Cameroon) explored natural methods for controlling Anopheles mosquito populations, investigating plant extracts from Momordica foetida, Gnidia glauca, and Vepris soyauxii. These extracts effectively killed mosquito larvae, disrupting their life cycle to prevent disease transmission. Acute oral toxicity tests demonstrated the extracts for humans and non-target organisms. Both aqueous and methanolic extracts exhibited larvicidal activity suitable for use as biological larvicides. Animals displayed no adverse effects during oral toxicity testing, indicating the safety of the extracts. The presenter recommends the commercial development of these environmentally friendly methods to control mosquito populations and reduce disease spread, such as malaria. For further information, Fru pointed towards an article on the larvicidal activity of Momordica foetida published in Fortune journal.

Uchechukwu Chukwuocha (Federal University of Technology, Nigeria) presented a study on a school-based intervention called the “Malaria Classroom Corner”, aimed at educating school children about malaria awareness and control practices. The intervention involved creating a designated corner in one school with materials such as pictures, drawings, and write-ups related to malaria, encouraging interaction during free time. Another school served as the control group, receiving only standard health education. Results showed better outcomes related to malaria awareness and preventive practices in school children from the intervention school compared to children from the control school. The interactive and participatory nature of the intervention enhanced students’ understanding, attitudes, and behaviors regarding malaria. Additionally, the intervention was found to be cost-effective. The findings emphasize the importance of investing in similar interventions for school children to improve both health outcomes and academic performance. The recommendation is to scale up the intervention to other schools to contribute to malaria elimination efforts. By implementing the Malaria Classroom Corner, communities can cultivate a culture of malaria awareness and empower school children to advocate for change.

Muhammed Afolabi (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) described in his presentation the potential benefits of integrating MDA for helminth control with seasonal malaria chemoprevention (SMC) to address multiple health challenges simultaneously in resource-limited settings. He conducted a study in Senegal with a focus on assessing the feasibility, safety, and effectiveness of the combined approach. In the study, the intervention arm received both Praziquantel (PZQ) for helminth control and SMC drugs, while the control arm only received SMC drugs. Afolabi highlighted three main results: First, integrating MDA with SMC drugs was safe, well-tolerated, and feasible among Senegalese children. Second, malaria parasitaemia was significantly higher in the control group compared to the intervention group. Third, the children who received both PZQ and SMC drugs had a lower risk of developing severe anemia than those who received SMC drugs alone. These findings support further evaluation of integrating MDA with SMC in settings with high prevalence of malaria, schistosomiasis, and Soil-transmitted helminths. Further information on this study is available from the publication. 

Lamin Jadama (Liverpool School of Tropical Medicine – LSTM, United Kingdom), presented findings on the entomological impact of mass drug administration (MDA) of ivermectin and dihydroartemisinin-piperaquine (DHA–PPQ) over two malaria seasons in the Gambia. Specifically, the study assessed the effect of the intervention on mosquito life span as well as other entomological outcomes such as mosquito density, sporozoite rate, biting rate and entomological inoculation rate. Previous studies in this area have found varying impacts, with effects on mosquito survival only, to effects on mosquito survival, sporozoite rate, EIR and parity, or effects on mosquito survival, density and EIR. In the presented study a significant effect of ivermectin MDA on vector density was found, with a notable reduction in mosquito survival up to 21 days post intervention when coverage was high. The study demonstrated the potential of MDA of ivermectin and DHS-PPQ as an effective strategy for reducing malaria transmission by targeting both the human host and the mosquito vector populations. Results from this study have been published in Parasites and Vectors (link).

Yacouba Poumachu (Medical Entomology at the Malaria Research Unit at OCEAC in Yaounde, Cameroon) discussed the necessity of mass rearing, sterilization and release of male Anopheles arabiensis mosquitoes to mate with wild females, resulting in non-viable offspring and reducing the overall population size amidst vector and parasite diversity and resistance. The presenter emphasized that this requirement is in line with the WHO 2008 recommendation to develop complementary tools against malaria. The process involves constructing an Anopheles arabiensis Y-autosome translocation line, which entails manipulating the mosquito’s genetic material to induce a translocation of genetic material between the Y chromosome and one of the autosomes (non-sex chromosomes). The potential benefits of utilizing a Y-autosome translocation line for SIT-based applications include increased sterilization efficiency and reduced impact on mating competitiveness compared to other sterilization techniques. However, the presenter cautioned the importance of conducting thorough risk assessments and engaging with local communities to ensure the safety and effectiveness of such interventions.

Manfred Accrombessi (Population Services International – PSI, Benin) presented findings from a study that compared two long-lasting insecticidal nets (LLINs) with dual-active ingredients, Interceptor®  G2 (IG2) and Royal Guard®  (RG), to standard LLINs in a 3-arm randomized controlled trial. The study, conducted in areas with prevalent vector resistance to pyrethroids like southern Benin, aimed to assess the impact on pregnancy outcomes and community protection against malaria. Results showed that IG2 and RG LLINs provided similar community protection as standard LLINs against poor birth outcomes over three years. Moreover, among women using their allocated study nets, IG2 and RG LLINs offered greater protection compared to standard LLINs. Limitations of the study included its quasi-experimental design and reliance on self-declaration of net use. Accrombess suggested further investigation to confirm the findings and recommended that the national malaria control program consider integrating these new generation LLINs for malaria control during pregnancy.

Scientific Session 5 – Social and Health Economics 1

Sikai Huang (Vante School of Public Health, China) presented a study that employed a repeated wave survey to determine the household wealth index and the effect of seasonal malaria chemoprevention (SMC) in South Sudan conducted during the wet season (September-December). Results showed that SMC had a high protection effectiveness during high transmission areas and that household wealth was not associated with SMC outcomes but there was a significant association between wealth and malaria prevention. 

Ladisla Nshimiyimana (Rwanda Biomedical Centre – RBC, Rwanda). The research identified three funding sources for malaria control and elimination in Rwanda: governmental funds, accounting for 42% of the total funds, and major funders,  the Global Fund (GF), and the President’s Malaria Initiative (PMI) accounting for 33% and 25% respectively. Malaria intervention in the country includes the acquisition of indoor residual spray (IRS), insecticide-treated nets (ITNs), medicines, surveillance, employee compensation and others. The results indicate that government prioritization of health funding consistently results in a significant reduction in malaria incidence by 85.3%, deaths by 81.2%, severe cases by 81.3%, and slide positivity by 68.9%. Even though government funds have slightly declined, interventions have been maintained due to collaboration with external funders. Thus, maintaining domestic funds is key in the fight against malaria. The Rwandan model could serve as a model for other African countries.

Hamidou Niangaly (National Institute of Public Health, Mali) presented a study that assessed the potential impact of decreased malaria incidence on child education, as well as how increased household income could result in investments in education. The study was done in remote villages in the center of Mali and it enrolled children under the age of five years between June and December 2015. The study had two groups, the control group with SMC only, and the intervention group with SMC in combination with other strategies.  The results reveal that the reduction in malaria has a significant positive impact on children’s education as it allows households to save and invest in their wards. These results could inform policy decisions on the deployment of interventions to improve socio-economic performance. 

Katherine Snyman (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) shared a study that employed the collection demographic data to evaluate the economic impact of malaria treatment using correlation and regression statistics for data analysis for economic evaluation. The result shows that investment in malaria prevention helps to avoid some treatment costs. The outpatient treatment costs (with uncomplicated malaria) are much lower than inpatient costs (with complicated malaria). Furthermore, affluent households spend only slightly more than those with lower income levels. Additionally, households with members aged 16 and above incur  $5 more than those with members aged 15 and below.

Valerie Makoge (Institute of Medical Research and Medical Plants Studies, Cameroon) talked about malaria prevalence and malaria-related health-seeking behavior among street children in Yaoundé, Cameroon using mixed methods. Almost 150 male street children were included in the study. Results showed the prevalence of malaria parasites among asymptomatic street children was 34.3%, and that they perceived malaria to be the most common disease. Health-related actions concerning malaria were dynamic and depended on financial considerations, perceived severity of the disease, and healthcare accessibility. Makoge suggested establishing special units tailored for these vulnerable children and directly engaging them in health campaigns to improve their access to healthcare. 

Carol Kamya (University of Bergen, Norway) discussed the cost-effectiveness of weekly dihydroartemisinin piperaquine (DP) versus sulfadoxine-pyrimethamine (SP) for malaria chemoprevention in children with sickle cell anemia (SSA) in Eastern and Southern Africa. The study design was a two-arm, multicenter, randomized parallel group. Kamya found that the new drug DP had a high probability of being a cost-effective alternative for malaria chemoprevention among children living with SSA compared to the standard of care SP even though DP has a higher cost. This was observed in both Uganda and Malawi. The new drug was associated with higher quality-adjusted life years (QALYS), reduced incidence of clinical malaria and less number of severe malaria hospitalizations. 

Scientific Session 6 – Chemoprevention 1

Alassane Haro (Institute of Research and Health Science – IRSS, Burkina Faso) presented on the association between CYP2C8 variant and the occurrence of clinical adverse events among children 3-59 months of age receiving Seasonal Malaria Chemoprevention (SMC) in 2023 in the village of Samandeni, Burkina Faso. A prospective cohort study was conducted during 4 SMC cycles, screening 1,002 children out of which 408 samples were randomly genotyped for CYP2C8*2 (mutant) and CYP2C8*1 (wild type). Common adverse events were identified with vomiting being the most frequent. Haro’s preliminary results suggest little evidence of minor adverse events related to CYP2C8*2 variants after SMC drug administration.

Steve M. Taylor (Duke University, United States) presented results from an open-label, randomized clinical trial in children with sickle cell anemia who were given daily proguanil, monthly sulfadoxine-pyrimethamine-amodiaquine (SP-AQ), or monthly dihydroartemisinin piperaquine (DP) for malaria prevention and followed up for a period of twelve months in Homa Bay, Kenya. Serious adverse events were common with no overall significant difference but more deaths were recorded in the SP-AQ group. However, DP was associated with a lower rate of dactylitis and asymptomatic P. falciparum infection. The study’s limitations included low malaria transmission in the study area and enhanced care for participants. 

Sol Richardson (Vanke School of Public Health Tsinghua University, China) presented the complex association between caregiver satisfaction with door-to-door distribution and channels of information received on seasonal malaria chemoprevention (SMC) and malaria-related outcomes in Nigeria and Mozambique. The study targeted children aged 3 – 59 months and their caregivers for four cycles per annual round in the high transmission season (each circle included one dose of SP+AQ and two doses of AQ). His key findings showed a strongly unmediated association between caregiver satisfaction and a range of SMC outcomes. Information received through all channels was associated with caregiver adherence to AQ administration and these associations were fully mediated through knowledge, attitudes, and level of education.

Hamma Maiga (National Institute of Public Health – INSP, Mali) Presented on the impact of Seasonal Malaria Chemoprevention (SMC) implementation with sulphadoxine – pyrimethamine (SP) + amodiaquine (AQ) on P. falciparum resistance in Koutiala, Mali. This included two cross-sectional surveys before and after ten years of SMC implementation and analysis of genetic markers of resistance (Pfdhfr-dhps quadruple mutant genotype) in children receiving SMC and those who did not. Results showed an increased prevalence of quadruple mutation in the Pfdhfr gene owing to SPAQ resistance in SMC treated children and a significantly low prevalence of Pfdhps540E. However, there was no significant increase in these molecular markers in the general parasite population. 

Vito Baraka (National Institutes of Medical Research – NIMR Tanzania) presented a study that investigated if Intermittent Preventive Treatment-seasonal chemoprevention (IPTsc) with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) may impair IgG reactivity to six Plasmodium falciparum antigens. Samples were collected from school children in a clinical trial in Muheza District, Tanzania. The results showed that the number of malaria antigens recognised significantly increased, IgG reactivity to GLURP was significantly lower at all follow-ups and lower against MSP3 at visit 6. Baraka concluded that IPTsc has a limited impact on the acquisition of natural acquired immunity to malaria and further study is required to explore a wider range of antibodies using a longer IPTsc program.

Myness Kasanda Ndambo (Malawi Epidemiology and Intervention Research Unit, Malawi) presented touch points and strategies for implementing Post-discharge Malaria Chemoprevention (PDMC) in Malawi. The study addressed delivery mechanisms and evaluated the barriers and facilitators to implementing PDMC in the healthcare system. Results showed that co-designing the implementation enhanced the acceptance of PDMC and feasibility by stakeholders. Stakeholders suggested renaming PDMC to Post-discharge malaria continuum of care (PDMCC) denoting a continuation of the management of the initial severe anemia events that brought the child to the hospital. Stakeholders also recommended using DP, increasing the number of village clinics, expanding the availability of drugs, training and developing monitoring, recording, and tracking tools before scaling up PDMCC in Malawi.