2nd Women in Malaria (WiM) Virtual Conference – 2025: Day 1
Wednesday, 19th March 2025
Published: 22/03/2025
This report is brought to you by the MESA Correspondents Kevin Rowartz Ogola, Flavia Kaduni Bawa, Geoffrey Githinji, Rebecca Pwalia, and Akua Obenewaa Danquah Yirenkyi. Senior editorial support has been facilitated by Divya Beri and Joanne Power
THEMES: THEMES: Drug Resistance | Epidemiology | Immunology | Surveillance | Vector Control
MESA Correspondents bring you cutting-edge coverage from the 2nd Women in Malaria (WiM) Conference.
Welcome and Introduction
Elena Gómez-Díaz (Institute of Parasitology and Biomedicine Lopez-Neyra – IPBLN, CSIC, Spain) welcomed everyone to the 2nd online Women in Malaria (WiM) Conference. This conference aims to support, empower, and connect women and non-binary scientists in malaria research, both in the fight against malaria and the fight for equity in science. The WiM Initiative was created in 2018 with a very specific vision of building a diverse and inclusive community of women and non-binary scientists in the field of malaria research, because gender-based bias and violence is still very present in today’s world. WiM exists to be a safe space for all these women to communicate and to lift each other up. The WiM community came together for its first virtual conference in 2021 (link) and we are now celebrating the second edition. Then Silvie Huijben (Arizona State University, USA) chair of the second WiM conference organizing committee dedicated a few words to all the attendees and encouraged everyone to enjoy, learn, engage with the speakers, and create meaningful connections to support and empower one another.
Plenary Talk 1 – The state of malaria in Africa – where do we go from here?”
Dorothy Achu (World Health Organization, Africa Region) presented the current state of malaria in Africa. She began by briefly discussing the epidemiology of malaria globally and then gave a detailed overview of malaria in Africa.She highlighted transmission drivers including socioeconomic factors, Plasmodium falciparum prevalence, climate change impacts, and insufficient funding—creating what she refers to as “the perfect storm.” She outlined initiatives since 1998 that revitalized malaria control, from the Roll Back Malaria Partnership to the 2024 Yaoundé Declaration and Big Push Initiative. Progress since 2000 includes 3 billion long-lasting insecticidal nets (LLINs) distributed, widespread implementation of indoor residual spraying (IRS), seasonal chemoprevention for 53 million children, and vaccines benefiting 5 million children, resulting in a 35% case reduction and 13 million deaths averted. Despite this, Africa faces challenges: weak health infrastructure, climate change, insecticide resistance, and intervention gaps—over 50% of women and children don’t use ITNs, and many lack prompt diagnosis and treatment. Achu proposed integrating vertical programs into broader health systems, sub-national tailored interventions, country-led approaches, community mobilization and strengthened surveillance for emerging resistance. She briefly discussed guidelines to address biological threats that include insecticide resistance, ACT resistance, spread of Anopheles stephensi and pfhrp2/3 deletions. She concluded by highlighting the case study of Rwanda which substantially reduced malaria cases through political commitment, data-driven interventions, community engagement, adequate response to insecticide resistance and the lessons that can be learned from Rwanda’s success.
Session 1 – Immunology and vaccines
Christine Hopp‘s (Bernhard Nocht Institute for Tropical Medicine, Germany) presentation sought to challenge the notion that infection is a trigger for autoimmune diseases. Her team conducted a 10-year longitudinal cohort study among children and adults in the malaria-endemic region of Mali to show how repeated malaria episodes impactselective pressure for autoimmune disorders. In this study, plasma, peripheral blood mononuclear cells (PBMCs), and clinical data were collected at baseline and at different time points to assess the role of autoantibodies in malaria infection. Participants were screened for autoantibodies using the antinuclear antibody test. They found that 50% of children between the ages of 6 and 12 had autoantibodies which correlated with a 40% lower risk of febrile malaria. To decipher the mechanism, the researchers purified autoantibodies to test for inhibition of P. falciparum 3D7 in vitro and observed a significant growth inhibition compared to IgG, translating to growth inhibition in vivo. Hopp linked these findings to prior genetic studies showing that certain autoimmune-related genes are associated with malaria protection. She deduced from the evidence generated that chronic exposure to malaria prevents autoimmune disease by inducing immunoregulation which prevents autoimmune pathology.
Jenna Dick (University of Minnesota Medical School, United States) presented her research on the phenotypes of natural killer (NK) cells in malaria immunity. Her research examined transcription factors of adaptive NKs, and the different phenotypes that enhance cytokine production and antibody-dependent cellular cytotoxicity (ADCC) function in the context of malaria. After her initial screen of FcRɣ negative NK cells yielded negative results, an unbiased approach using flow cytometry was used to look at cell surface receptors. Malaria-exposed samples from Mali had a high number of SIGLEC-7 negative NK cells. This was explored further using CRISPR to determine its actual function. Using infected RBCs and antibodies, it was confirmed that SIGLEC-7 knockout led to degranulation and production of CD107A whereas the malaria naïve plasma showed no difference. Overall, her study showed that NK cells with reduced SIGLEC 7 correlate with FcRɣ negative NK cells which enhance the killing of iRBCs, thereby reducing parasite loads.
Maya Aleshnick (Vaccine and Gene Therapy Institute, Oregon Health and Science University, United States) presented the use of non-human models to study Plasmodium infections and response to vaccination. Previous studies in her lab involved Rhesus macaques challenged with P. knowlesi which is comparable to P. falciparum infection in humans. Her current study uses weanlings to investigate the immunological features of vaccine-reduced response in young infants with underdeveloped immune systems. In acute infection models of infant Rhesus macaques, the parasite increased rapidly requiring early treatment to prevent severe disease and mortality. Pig-tailed macaques on the other hand showed extended asymptomatic infection, characteristic of chronic human infection. For studies involving P. vivax which cannot be cultured in vitro for extended periods, a transgenic P. cynomolgi parasite expressing the P. vivax circumsporozoite protein was produced using CRISPR/Cas editing. Further experiments demonstrated the use of transgenic P. cynomolgi in place of P. vivax for vaccine challenge experiments.
Kristina Burrack’s (Hennepin Healthcare Research Institute, University of Minnesota, United States) research investigates the use of IL-15 to enhance whole sporozoite malaria vaccines. Her lab studies a genetically attenuated parasite (GAP) vaccine that induces strong immune responses, for which improvements are needed for durability. Burrack’s team tested whether the IL-15 complex could boost vaccine effectiveness. In mice, IL-15 treatment significantly increased TRM-like CD8 and CD4 T cells in the liver. When combined with the GAP vaccine, the IL-15 complex enhanced the number of antigen-specific T cells and improved their function, increasing interferon-gamma production—a key factor in killing infected hepatocytes. Additionally, IL-15 complex boosted CSP-specific IgG antibody levels, which are important for malaria protection. A pilot study showed that IL-15-treated mice had significantly reduced liver parasite burden after being challenged with wild-type sporozoites, suggesting improved vaccine efficacy. These findings highlight the IL-15 complex as a promising tool for enhancing malaria vaccine durability by strengthening both cellular and antibody-mediated immunity.
Angela Minassian (University of Oxford, United Kingdom) presented about advancements in malaria vaccine development. Her team initially focused on blood-stage malaria vaccines but is now advancing toward multi-stage vaccines. Her team identified RH5, a conserved parasite protein essential for red blood cell invasion, as a promising target. Preclinical studies in non-human primates demonstrated that RH5 vaccination led to parasite clearance or sterile protection, correlating with growth inhibition activity (GIA) levels above 60% in vitro. Clinical trials demonstrated its efficacy and strong immunogenicity in vaccinated adults and children in the UK and Africa. Over a decade, iterative vaccine improvements have increased GIA, exceeding protective thresholds in African children. A phase 2B trial is underway in Burkina Faso to assess its effectiveness in preventing clinical malaria in real-world settings. In this study, about 360 children in malaria-endemic settings were vaccinated with RH5 vaccine formulated with the Matrix-M adjuvant or a Rabivax-S and M-Matrix adjuvant. Significantly high levels of anti-RH5 antibodies were recorded in the RH5 vaccinated group compared to the Rabies vaccinated group and levels at baseline. Overall, this vaccine recorded an efficacy of 55% for participants who took a delayed third dose. Trials are currently underway for multistage vaccines and sequential administrations of different vaccine combinations.
Session 2 – Vector biology and ecology
Rosine Danale Metisti Tesongang (University of Yaoundé I – UY1, Cameroon) presented a study investigating housing improvements as a malaria control strategy in Cameroon’s forest zones, where plank houses exhibit higher malaria prevalence compared to brick or cement structures. The study assessed Anopheles species diversity, biting behavior, and the impact of house improvements on mosquito abundance. Mosquitoes were collected via human landing catches (HLC) in Nyabessan before and after interventions, with morphological and molecular identification. Ten houses were selected; five improved with netted windows and doors, and five left as unimproved controls. Seven Anopheles species were identified, with An. paludis being the most abundant. Biting behavior analysis revealed peak activity between 10 pm and midnight, and 5-6 am for some species. Post-improvement, indoor Anopheles density decreased significantly, with improved houses showing a 2.52-fold reduction in mosquito numbers. The study also observed a decline in entomological inoculation rates (EIR), highlighting the effectiveness of housing improvements in reducing malaria transmission. Tesongang’s findings demonstrate that improved housing, particularly with netted windows and doors, significantly reduced indoor Anopheles density. This approach serves as a valuable supplementary malaria control measure, especially in high-transmission areas. The research underscores the potential of integrating housing improvements with existing strategies to enhance malaria control efforts in endemic regions.
Emma Camacho (Johns Hopkins University – JHU, United States) discussed mosquito melanization, crucial for survival through cuticle hardening, wound healing, and immune defence, that is often inhibited by environmental factors like glyphosate. The research explored enhancing this defence mechanism using L-DOPA, a melanin precursor found in plants. Feeding Anopheles gambiae mosquitoes L-DOPA in sugar meals significantly reduced Plasmodium parasite numbers in vivo and killed 70% in vitro. L-DOPA also darkened mosquito cuticles, thickened them, and increased resistance to insecticides by reducing penetration. While mosquitoes showed increased cuticular melanization, they remained susceptible to deltamethrin in WHO tube assays. The study concluded that L-DOPA promotes cuticular melanization, impairs P. falciparum development, and offers a potential environmentally friendly malaria control strategy.
Chia Yu Chen (Center for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases – NICD, South Africa) explored the link between histone modifications, immunity, and longevity on Anopheles arabiensis mosquitoes. Their studies showed that larvae exposed to either Gram-negative or Gram-positive bacteria after being reared in the presence of histone modulators (one that increased histone acetylation or one that decreased histone acetylation), both groups showed significant reduction in lifespan. Histone H4 underwent fewer modifications compared to H3, with H4 playing a structural role and H3 serving as the primary target for gene regulation. Immune stimulation led to decreased H3 acetylation and increased repressive marker H3K27me3, both contributing to gene silencing. Gram-positive bacteria had a stronger impact than Gram-negative, indicating that more foreign pathogens trigger greater epigenetic changes. These modifications, particularly on H3, likely affect longevity by altering gene expression. Chen’s finding further highlights the critical role of histone modifications in regulating immune responses and lifespan in An. arabiensis. She further emphasized that future steps include identifying silenced genes, especially those in immune pathways, and repeating experiments with Plasmodium infection to better understand malaria transmission.
Nicole Vargas Garcia (Entomological Research Group, Universidad del Valle, Colombia) presented her work on integrating vector control into malaria elimination strategies on Colombia’s Pacific coast. In her presentation, she emphasized the effectiveness of combining diagnosis, treatment, investigation, and response (DTI-R) with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) to significantly reduce malaria transmission. Garcia highlighted the challenges posed by the region’s diverse geography, high mosquito diversity, ethnic and cultural complexities, internal armed conflicts, and human migration. She concluded that entomological data played a crucial role in mapping the spatial distribution of malaria transmission risk at a local scale, enabling precise stratification for targeted vector control planning. At the end of her presentation, Garcia noted that her findings underscore the importance of multi-sector collaboration and innovation in malaria elimination efforts.
Carolina Barillas-Mury (National Institute of Allergy and Infectious Diseases – NIAID, National Institutes of Health – NIH, United States) shared her pioneering research on mosquito immunity and malaria transmission. She investigated the critical role of Pfs47, a Plasmodium falciparum surface protein that enables the parasite to evade the mosquito’s immune system and facilitate malaria transmission. Her work revealed that the Pfs47 surface protein acts as a molecular “key” that must match the mosquito’s immune “lock” (a Pfs47 receptor (P47Rec)) to ensure parasite survival. Specifically, Pfs47 haplotypes (genetic variants) show remarkable geographic adaptation, interacting with sympatric mosquito species’ P47 receptors to suppress complement-mediated immunity in the mosquito. Barillas-Mury’s studies demonstrate that the compatibility between Pfs47 haplotypes and the mosquito’s immune genotype varies across different Anopheles species and populations, influencing geographic patterns of malaria transmission. This co-evolutionary adaptation highlights the intricate arms race between Plasmodium and its mosquito vector. Her findings have significant implications for malaria control, suggesting that disrupting the Pfs47-mediated immune evasion could block transmission. Potential strategies include genetically modifying mosquitoes to recognize and eliminate Plasmodium regardless of Pfs47 haplotypes or developing transmission-blocking interventions targeting Pfs47. Barillas-Mury’s presentation provided a deeper understanding of host-parasite interactions and opened new avenues for innovative malaria control strategies by targeting the molecular mechanisms that enable parasite survival in mosquitoes.
Round Table Discussion – What if women were leading the fight against malaria?
Rinki Deb (Principal Investigator, Vestergaard) led an insightful roundtable discussion titled “What if women were leading the fight against malaria?” The session brought together expert panelists to explore the challenges and opportunities for women in malaria research and leadership. The panel featured leading female scientists and professionals, including Jackline Martin (i2i Vector Control Product Associate, Vestergaard), Anita Ghansah (Senior Research Fellow and Head of the Department of Parasitology, Noguchi Memorial Institute of Medical Research, University of Ghana), Elena Marbán Castro (Operational & Implementation Research Scientist, FIND and Women in Global Health Spain), Ingrid Etoke (Senior Program Officer, Gates Foundation) and Corine Ngufor (Associate Professor, CREC/LSHTM Collaborative Research Programme).
The discussion opened with a series of thought-provoking questions, prompting panelists to reflect on the hurdles women face in the field. Topics included work-life balance challenges, limited leadership opportunities, and gender discrimination.
Corine Ngufor emphasized discrimination as a major obstacle, with Anita Ghansah noting that societal norms often silence women in decision-making spaces. She stressed the importance of challenging these biases by increasing awareness and fostering recognition of women’s leadership contributions. She also encouraged women to assert their voices when given a platform.
Panelists highlighted the unique strengths women bring to malaria research and healthcare. Ingrid Etoke and Elena Marbán Castro noted that women often build trust within communities through empathetic engagement, strong multitasking, and organizational skills abilities that remain undervalued, particularly among community health workers in informal healthcare systems. She underscored the role of gender-intentional grants, like those provided by her institution, in addressing inequities and supporting women in these roles. Corine Ngufor acknowledged the value of existing mentorship programs but called for a more sustained effort to guide young female researchers beyond short-term training. She cited successful initiatives, such as Women in Global Health and the MIM Mentorship Program, as models for long-term career support.
The conversation also explored practical ways to foster female empowerment in the field. Anita Ghansah proposed creating more sponsorship opportunities to enhance networking and career advancement for early-career researchers. Jackline Martin championed the importance of knowledge-sharing, emphasizing that entrusting young researchers with meaningful responsibilities builds their confidence and helps address gender imbalances in the long run. Corine Ngufor shared examples from her own institution, illustrating how concrete measures can break down barriers. One initiative provided on-field accommodation for mothers and their children, ensuring that early-career female researchers could participate in fieldwork while feeling supported in their roles as both professionals and mothers.
The discussion underscored the need for systemic change to foster gender equity in malaria research and leadership. Through mentorship, funding, and institutional support, women can not only overcome barriers but also drive progress in the fight against malaria.
Malaria in Mothers and Babies Initiative: Accelerating appropriate treatments for pregnant and lactating women
Maud Majeres Lugand (Medicines for Malaria Venture – MMV, Switzerland) highlighted key advancements in the Malaria in Mothers and Babies (MiMBA) initiative. Led by Medicines for Malaria Venture (MMV), this program seeks to accelerate research and improve access to antimalarial treatments for pregnant and lactating mothers. Majeres highlights that in 2023, 36% of pregnant women in Sub-Saharan Africa were infected with malaria, a major problem as pregnant and lactating mothers are more susceptible to severe illness due to compromised immunity. She outlined several challenges faced by these women with malaria, including the limited availability of treatments, exclusion from clinical trials, and physiological differences that complicate treatment approaches. To address these gaps, she explained MMV’s strategy, which focuses on expanding clinical trial inclusion, developing new technologies, increasing access to medicines, and advocating for policy change. Current projects are generating crucial evidence on the safety and efficacy of antimalarials, while a newly established pregnancy registry is helping to track outcomes and inform future interventions. MMV is also actively engaging with communities to ensure recruitment strategies are culturally appropriate and capable of detecting pregnancies at an early stage, improving overall care and treatment opportunities. In the future, MMV aims to provide new treatment options for pregnant women, conduct studies to increase safe treatment for pregnant women, and secure resources to maintain progress in malaria treatment for maternal healthcare. She underscored the importance of collaboration, innovation, policy advocacy, and increased funding to improve antimalarial treatment for pregnant women.
Session 3 – Host-parasite-vector interactions
Lisa H. Verzier (Harvard T.H. Chan School of Public Health, United States) presented her groundbreaking research on mapping Plasmodium falciparum transitions and interactions within the female Anopheles mosquito at single-cell resolution. In her presentation, she detailed how her study employs single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to unravel the parasite’s developmental journey from gametocytes to ookinetes and oocysts while navigating the mosquito’s immune defenses and microenvironment. She highlighted key molecular pathways and cellular interactions that enable P. falciparum survival, emphasizing specific mosquito cell types and immune responses that either facilitate or impede the parasite’s progression. Verzier concluded by noting the intricate co-evolutionary dynamics between the parasite and its vector, underscoring how these insights reveal mechanisms of immune evasion and nutrient acquisition. Her findings have profound implications for malaria control, offering potential targets for disrupting the parasite’s life cycle, such as genetically enhancing mosquito immunity or developing transmission-blocking interventions. At the end of her presentation, she emphasized that these high-resolution insights into host-parasite interactions could drive transformative advances in global disease prevention strategies.
Eliana Real (Institut Pasteur, France) presented how the host protein CD36 primes Plasmodium falciparum sporozoites for liver infection, considered a crucial step in malaria transmission. CD36, a receptor involved in immune responses and lipid metabolism, interacts with the sporozoite Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) during their transit from the mosquito bite site to the liver. This interaction enhances the sporozoites’ ability to invade hepatocytes by triggering molecular changes that upregulate key proteins essential for hepatocyte recognition and entry. Results revealed CD36’s dual role of facilitating sporozoite infection while modulating host immune responses. This highlights its complex involvement in malaria pathogenesis. Real finished the presentation by suggesting that targeting the CD36-sporozoite interaction could block liver-stage infection, thus, opening avenues for innovative interventions to disrupt the parasite’s life cycle and reduce malaria transmission.
Patience Chipiliro Simbi (Malaria Alert Centre, Kamuzu University of Health Sciences, Malawi) presented a study conducted in southern Malawi. The study aimed to identify demographic factors linked to Plasmodium falciparum infectiousness in southern Malawi’s high-transmission Mashinga district. This longitudinal study, conducted during peak malaria season (Nov 2022-July 2023), used membrane-feeding assays to measure transmission to Anopheles mosquitoes. Participants from four household clusters were screened fortnightly through 18S qPCR. Those with low parasitemia underwent membrane feeding assays, with eight feeds carried out weekly. After ten days, mosquito midguts were examined. Infectiousness was rare (7.9%), concentrated in a few individuals, primarily school children aged 5 – 15 years old. Higher gametocyte density correlated with increased infectiousness, with 60.8% of infectious feeds from male participants and 91% of oocysts derived from males in the 5 – 15 year old category. Future regression analysis will be used to explore the impact of gametocyte density. Chipiliro ended the talk stating the importance of this study which marks the first population-level membrane-feeding assay results from Malawi.
Petra Schneider (University of Edinburgh, United Kingdom) examined the question “Are regular mealtimes more important for Artemisinin-resistant malaria parasites?”. She discussed environmental impacts on mosquito-borne disease transmission, focusing on how parasite rhythms align with host feeding. Using the Plasmodium chabaudi rodent malaria model, misalignment of the parasite life cycle rhythm was achieved by the passage of blood-stage parasites from one mouse to another, with one mouse kept on a regular light-dark cycle and the second mouse housed in reversed light-dark conditions. Transferring parasites from an active period of the host circadian rhythm to a non-active period incurred a fitness cost and reduced gametocyte production. With rising artemisinin resistance, they investigated if resistant parasites face higher costs when misaligned. Using Plasmodium chabaudi in mice, both drug-sensitive and resistant genotypes were tested. Schneider presented results showing that misalignment caused a greater fitness cost in resistant asexual stages. However, gametocyte production, the sexual transmission stage, showed minimal cost from misalignment. This suggests artemisinin-resistant parasites may rely more on rhythmic mealtimes. Future research will be carried out to confirm these findings, with the results having the potential to inform if the precise timing of drug regimens could potentially have clinical benefits in malaria treatment strategies.
Courtney Murdock (Cornell University, United States) presented the effects of variations in temperature and relative humidity on mosquito-borne pathogen transmission. She explored ecological factors influencing mosquito-borne disease transmission, emphasizing environmental and human impacts. Environmental changes like land alteration and climate change facilitate urban vector invasions, exemplified by Anopheles stephensi. While temperature effects on mosquito life cycles and parasite development are well-studied, the role of relative humidity is often overlooked. This research aimed to determine if variations in relative humidity in an urban environment affected malaria transmission. Experiments examined larval, adult, and parasite traits across eight temperatures and five humidity levels. Anopheles stephensi larvae were subjected to varying evaporation conditions, with pupae collected to assess development rates. Adult mosquitoes were monitored for lifespan and egg production. Results showed that decreased relative humidity shifted larval thermal performance, development, and survival, with increased body size at warmer temperatures. In adult mosquitoes, though there is a negative correlation between temperature and wingspan, greater relative humidity mitigated this effect, with greater humidity resulting in increased wingspan, even at higher temperature. These findings suggest temperature-only models may overpredict Anopheles stephensi environmental suitability. Murdock ended the talk by remarking on the aim of the study to improve predictive models by incorporating humidity data for better malaria outbreak forecasting.
Session 4 – Therapeutics and drug resistance
Rebecca Edgar (University of Dundee, United Kingdom) presented her study investigating resistance mechanisms in Plasmodium parasites by screening six compounds. Two of these compounds were deprioritized after sequencing due to PI4K mutations. The remaining four compounds underwent resistance selection, where parasites were cultured and monitored for genetic changes indicating potential targets. From the initial whole genome screening, one of the selected compounds displayed the most stable resistance shift, with whole-genome sequencing identifying eight consistent single nucleotide polymorphisms (SNPs) across resistant clones. One key gene of interest was KRAS2, a lysyl-tRNA synthetase localized in the parasite’s apicoplast, an essential organelle involved in isoprenoid synthesis. Resistance tests using KRAS1 mutant parasites showed no cross-reactivity, suggesting that this compound selectively targets KRAS2. To validate KRAS2 as the target, they plan to use CRISPR-based mutagenesis to insert a resistance-associated SNP and assess parasite survival. Also, the selected compound showed resistance in ZIP1-knockout parasites similar to a previous study that identified ZIP1 as a potential novel resistance mechanism, reinforcing its potential to target the apicoplast. She added that further investigations are ongoing to confirm KRAS2 as a drug target and to understand ZIP1’s role in apicoplast resistance. These findings could contribute to novel antimalarial strategies, particularly in targeting essential apicoplast functions.
Eline Kattenberg (Institute of Tropical Medicine Antwerp – ITM, Belgium) presented her research on genetic surveillance of malaria in Vietnam. In 2019, first-line treatment shifted from dihydroartemisinin-piperaquine to Pyramax (pyronaridine-artesunate), initially in two provinces which was later on expanded to five. Sentinel site surveillance was conducted in high-burden provinces, where dried blood swabs were collected and analyzed for P. falciparum and P. vivax using qPCR. A subset of P. falciparum-positive samples underwent AmpliSeq analysis, targeting 14 resistance-related genes. The results confirmed that there were persistent high levels of C580Y mutations, especially in previously affected regions and, for the first time, in one province. Around 80% of the samples analyzed carried this mutation, indicating widespread artemisinin resistance and chloroquine resistance. They observed high clonality in parasites and low genetic diversity among parasites in the region. Similarly, plasmepsin amplifications linked to piperaquine resistance remained stable, while chloroquine resistance markers increased. Her study underscores the need for ongoing resistance monitoring, particularly as Vietnam transitions to treatment with Pyramax. She stressed the need for continuous genetic surveillance in achieving malaria elimination.
Ijeoma Okoye (Drexel University College of Medicine, United States) presented findings on a mitochondrial and evolutionarily conserved protein, PfATAD3.The lab identified 123 putative mitochondrial proteins through proximity labelling, and characterized PfATAD3. Using a CRISPR-Cas9-based system, Okoye’s team conditionally regulated PfATAD3 expression to study its function. Knockdown experiments showed that parasites lacking PfATAD3 could complete one asexual replication cycle but die before the second, indicating its essentiality. Further investigations revealed that mitochondrial RNA transcripts declined upon PfATAD3 depletion, suggesting a role in transcription or RNA stability. Loss of PfATAD3 also led to mitochondrial membrane potential collapse. The team tested whether supplementing ubiquinone could rescue parasites. Despite the partial restoration of electron transport chain function, PfATAD3-deficient parasites still died, implying additional critical roles. These findings suggest that PfATAD3 is vital for Plasmodium survival, making it a potential drug target. Their research is now directed to understand the protein’s role in sexual stages of the parasite.
Iyanuoluwa Adufe (Osun State University, Nigeria) presented her research on the emergence of artemisinin-based combination therapies (ACTs)-resistant malaria in Nigeria using mathematical modeling. The study focused on understanding the complex interactions driving the spread of resistance and informing control measures. Time series analysis was performed on district-level data which revealed seasonal fluctuations in malaria cases, with peaks during the rainy season. Forecasting models indicated a consistent trend in malaria cases. Geospatial risk mapping identified 12 high-risk local government areas (LGAs), with six considered very high-risk, emphasizing the need for targeted interventions. Simulation models demonstrated that in low ACT resistance scenarios, effective treatment leads to higher recovery rates. However, in high-resistance scenarios, infections persist as treatments become ineffective. Sensitivity and scenario analyses highlighted that increased ACT sensitivity reduces transmission, while decreased sensitivity leads to higher infection rates. She concluded, by underscoring the need for proactive measures to monitor and control ACT resistance, ensuring effective malaria management in Nigeria.
Elizabeth Winzeler (University of California San Diego – UCSD, United States) presented the challenges in antimalarial drug development and potential avenues towards its solution To overcome the limitations of existing malaria drugs, Winzeler was invited in 2005 to join a Wellcome Trust-funded project aimed at identifying new antimalarials. At the time, the Plasmodium genome had been sequenced, but essential targets were unknown. Traditional target-based drug discovery proved challenging due to emerging resistance, leading researchers to adopt empirical approaches. Her team developed an ultra-high throughput screening method using a modified SYBR Green assay to test millions of compounds for activity against malaria parasites. This led to the discovery of novel antimalarial candidates, including Ganaplacide, which have progressed to phase III trials in combination with lumefantrine. This drug combination targets multiple parasite stages, including the liver, blood, and gametocytes, though resistance remains a concern. Winzeler also discussed their research on genetic resistance mechanisms in Plasmodium. Her team analyzed mutations in the PfCARL gene, showing that only mutations in conserved regions conferred resistance. Similar patterns were observed in PfATP4 and MDR1. A PhD student in her lab is currently using machine learning to predict resistance-associated alleles by comparing known resistance genes with neutral variants.
Published: 22/03/2025
This report is brought to you by the MESA Correspondents Kevin Rowartz Ogola, Flavia Kaduni Bawa, Geoffrey Githinji, Rebecca Pwalia, and Akua Obenewaa Danquah Yirenkyi. Senior editorial support has been facilitated by Divya Beri and Joanne Power
THEMES: Drug Resistance | Epidemiology | Immunology | Surveillance | Vector Control



