Multilateral Initiative on Malaria (MIM) Pan-African Malaria Conference – 2024: Day 2

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

Plenary Session 4 – Vector Control Innovations for Malaria Elimination

Charles Wondji (Liverpool School of Tropical Medicine – LSTM, United Kingdom) emphasized the pivotal role of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in malaria vector control, stressing that they are fundamental for malaria prevention. He noted their effectiveness in reducing malaria cases by up to 60% across Africa since the 2000s. However, challenges such as insecticide resistance pose a significant threat to their efficacy. Wondji highlighted that over-reliance on pyrethroids, without new insecticides developed in the past three decades, has resulted in widespread resistance. To address this, he proposed developing new insecticides for IRS, like Sumisheild 50WG, and using combination insecticides such as Fludora Fusion-BAYER. Wondji suggested LLIN innovations like nets treated with pyrethroids and piperonyl butoxide (PBO) to combat metabolic resistance and dual AI pyrethroid nets to sterilize pyrethroid-resistant mosquitoes. Wondji however noted that these innovations face challenges like cross-resistance and require time to show impact. Wondji finally advocated for the consideration and promotion of alternative innovations like gene drive, spatial repellents, bait stations, lethal house lures, and endectocides.

Jessy Goupeyou-Youmsi (Pan-African Mosquito Control Association – PAMCA, Kenya) presented the importance of including women in vector control innovations. Goupeyou-Youmsi highlighted a study conducted in Malawi that showed that women were 80% more likely to be infectious to mosquitoes than men. Goupeyou-Youmsi mentioned biological differences between men and women such as pregnancy which makes women more susceptible to severe malaria, and also differences in gender roles related to malaria transmission. This pointed out the need for gender mainstreaming. She also mentioned other factors leading to unequal burden of malaria on women and girls including the gender gap in research and implementation, increased vulnerability of women and girls due to social factors, missed opportunities for empowerment, and the lack of collaborations and investments. Goupeyou-Youmsi emphasized the importance of having women and girls as agents of change. Goupeyou-Youmsi briefly described the role of the PAMCA Women in Vector Control Program, and lastly proposed a call to action in malaria eradication to improve, design, invest, empower and close the gender gap to end malaria for all.

Symposium 19 – Malaria in Children and Adolescents with Sickle Cell Anemia

Ruth Namazzi’s (Makerere University College of Health Sciences, Uganda) presentation underscored the need to prioritize sickle cell disease (SCD) as a public health concern in sub-Saharan Africa (SSA), where more than 300,000 babies are born with this condition annually. Namazzi highlighted that most of these cases occurred in the SSA region, with projections indicating a substantial increase by 2050. Notably, children with SCD face a shortened life expectancy, emphasizing the critical importance of addressing this issue. Moreover, Namazzi’s discussion highlights the variability in the prevalence and severity of malaria among children with sickle cell anemia across different regions of Uganda, depending on the level of malaria transmission. In conclusion, Namazzi emphasized that malaria and SCD pose significant public health challenges in SSA, underscoring the need for early detection and treatment of malaria in individuals with SCD. Namazzi advocated for tailored malaria prevention strategies for this vulnerable population, noting that these findings would contribute to a better understanding of the interaction between sickle cell anemia and malaria, and inform strategies to mitigate the impact of malaria on this vulnerable population. 

Carol Kamya (University of Bergen, Norway) explored insights into optimizing healthcare resources for children with sickle cell anemia (SCA) in malaria-endemic regions of Uganda and Malawi. By comparing the cost-effectiveness of weekly Dihydroartemisinin-Piperaquine (DP) with Sulphadoxine-Pyrimethamine (SP) for malaria chemoprevention in this vulnerable population, Kamya shed light on the economic implications of treatment choices. Kamya’s findings indicated that DP was a cost-effective alternative, offering higher quality-adjusted life years and reducing the incidence of clinical malaria and severe malaria hospitalizations compared to SP. This suggested that investing in DP for malaria chemoprevention in children with SCA could lead to better health outcomes while utilizing healthcare resources more efficiently. By posing the question “What does it cost to treat malaria in SCA?” and addressing it through comparative analysis, Kamya underscored the importance of considering both the clinical and economic aspects of treatment strategies. Kamya highlighted the potential benefits of prioritising cost-effective interventions like DP to improve the overall well-being of children with SCA in malaria-endemic areas.

Richard Idro (Makerere University College of Health Sciences, Uganda) presented on the CHEMCHA trial which investigated malaria chemoprevention in children with sickle cell anemia (SCA) in eastern (Uganda) and southern (Malawi) Africa. The study, involving 548 children studied over 18 months, compared dihydroartemisinin-piperaquine (DP) and sulfadoxine-pyrimethamine (SP) effectiveness. Weekly DP demonstrated superior efficacy in areas with high antifolate resistance, while monthly SP showed fewer non-malaria related illnesses, especially in older children lacking penicillin prophylaxis. These findings offer significant potential for improving malaria management in SCA-affected regions, where the disease poses a substantial health burden. By tailoring chemoprevention approaches to the specific needs and challenges of this vulnerable population, the CHEMCHA trial contributes valuable insights to global efforts in combating malaria, particularly in regions with high antimalarial drug resistance.  Idro suggests further trials combining DP, SP, and penicillin, aiming to optimize malaria prevention strategies. Pending analyses include assessing acceptability, cost-effectiveness, resistance risk, and uptake. Future research endeavours informed by these findings could lead to more targeted and effective interventions, ultimately reducing malaria-related morbidity and mortality among children with SCA. 

Symposium 22 – Malaria Elimination Efforts in the Horn of Africa: A Historical Perspective, Progress, Bottlenecks and Future Directions

Research by Gudisa Assefa (University of Gondar, Ethiopia), presented by Ashenafi Assefa, pointed out that progress has been made globally in fighting malaria, and Ethiopia has seen some of this progress. However, in recent years, we have seen a significant increase in malaria cases in the Horn of Africa. Assefa mentioned several reasons for this including; Anopheles stephensi invasion, climate change, and internal conflicts as major contributors to these negative changes. Assefa also noted pragmatic factors such as insufficient funds, the presence of refugees from neighbouring countries, insecticide resistance to commonly used tools, and the potential for antimalarial drug resistance as additional challenges. Assefa concluded by acknowledging the work that Ethiopia and collaborative partners were doing to combat malaria and called for more actions to eliminate the disease once and for all.

Abdoul Samatar (Global Fund, Djibouti) shared an update on efforts to control malaria in the country. From 2006 to 2012, the government worked on implementing measures to control malaria, leading to a significant reduction in malaria cases and entering a pre-elimination phase. However, the situation has changed, with malaria cases gradually increasing each year. This is mainly due to the presence of Anopheles stephensi, the main invasive mosquito species transmitting malaria in the area. This species is resistant to many insecticides and can efficiently transmit both Plasmodium falciparum and P. vivax. While there have not been reports of resistance to antimalarial drugs, there have been signs of resistance markers. Samatar emphasized the need for new approaches, such as gene drive mosquitoes, to regain previous progress and emphasized the importance of community involvement in ongoing malaria control efforts.

Bekuretsion Gidey (Ethiopian Public Health Institute – EPHI, Ethiopia) presented findings on diagnostic failure and partial ACT resistance in Ethiopia. Patient samples from 108 health facilities across 11 districts in the Tigray, Amhara, and Gambella regions were acquired from health center patients presenting with malaria between 2017 and 2018. RDTs were used to detect Pf positivity, and all discordant and 20% of concordant Pf tested by PCR. 64% of RDT discordant samples were PfHRP2-/3– by PCR, and 42% of HRP2-positive samples were negative for HRP3 by PCR. These findings prompted a nationwide PfHRP2/3 deletion survey in 2021, with sampling in 114 sites using both RDTs and microscopy, and further evaluation for drug resistance markers. Together, these data showed expansion of both HRP2/3 deletions and an 8% prevalence of K13 622I mutations in Ethiopia. From these data, the nationwide policy was revised in 2022 to change to non-HRP2/3 RDTs.

Abebe A. Fola (Brown University, United States) discussed the use of population genomic analyses to evaluate HRP2/3 deletion and ACT resistance markers in Ethiopia. MIP-based amplicon sequencing of 920 samples led to findings that partner drug mutations may augment antimalarial resistance. A higher prevalence of Pfcrt mutations were found in PfHRP2-/3– parasites compared to wild type, and 90% of PfK13 622I mutants also carried the PfMDR NFD mutation. Genomic analyses determined identity by descent (IBD), a measure of parasite relatedness. At a district level, K13 622I mutant parasites had higher IBD than wild type. HRP2/3 deleted parasites were shown to have a high IBD and low COI, suggesting that these mutants were able to outcompete other parasites. These data suggest that parasites clustered geographically based on gene deletions, and Fola emphasized the importance of supporting the simultaneous analysis of genomic and national malaria survey data.

Isabela Gerdes Gyuricza (UNC-Chapel Hill, United States) presented findings comparing genomics of PfHRP2/3 deleted Pf in Ethiopia and Peru. In Peru, RDTs have never been widely used for malaria detection, yet HRP2/3 deletions have been seen and have been expanding. Approximately 80% of the Pf population is HRP2-/3-, despite evidence of the negative effect of dual deletion on parasite fitness. Therefore, Guyricza is using genomic analyses to compare 2017-2018 samples from Iquitos, Peru (n=140) with those from Ethiopia (n=375), where similar mutants can be found and RDT use is high. Guyricza’s results from MIP-based amplicon sequencing suggest that chromosomal breakpoints may differ between Ethiopian and Peruvian parasites in both chromosomes 8 and 13, where HRP2 and 3 reside, respectively. Guyricza’s next steps are to use whole genome sequencing and additional sample sets to search for further evidence, including differences in genetic background.

Fitsum G. Tadesse (Armauer Hansen Research Institute – AHRI, Ethiopia and London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) highlighted the potential challenges posed by the spread of Anopheles stephensi in rapidly growing urban areas to malaria control efforts in Africa. He emphasized that stephensi  is particularly concerning due to its ability to breed in manmade containers commonly found in these settings. Additionally, it is resistant to several commonly used insecticides, displays flexible feeding behaviour on both animals and humans, and can effectively transmit both Plasmodium falciparum and P. vivax, further complicating malaria control efforts. These factors necessitate urgent attention and action to address the threat to malaria control programs.

Symposium 24 – Malaria in Pregnancy

Myriam El Gaaloul (Medicines for Malaria Venture – MMV, Switzerland) began the symposium by elucidating the meaning of MiMBa – ‘Malaria in Mothers and Babies’ Initiative, launched nearly five years ago by Medicines for Malaria Ventures (MMV). This initiative focuses on generating data on antimalarial use in pregnant and lactating women, who are often excluded from clinical trials due to concerns about potential harm. Gaaloul underscored that the symposium aimed to highlight and propose innovative approaches to shift the paradigm from shielding women from research and safeguarding women through research. Additionally, Gaaloul highlighted the gaps in the use of antimalarials in pregnant and lactating women, as well as some challenges faced by women living with HIV. Gaaloul emphasized that despite WHO guidelines in 2022 endorsing the use of Artemisinin Combination Therapy(ACTs) in the first trimester; there is a pressing need to expedite the generation of evidence for this use. Furthermore, she stressed the necessity to explore the use of other ACTs to gather safety and efficacy data for their utilization in pregnant and lactating women.

Brice Campo (Medicines for Malaria Venture – MMV, Switzerland) discussed their work on validating the routine use of innovative translational tools for antimalarials by collecting data, aiming to address the current gaps in the use of antimalarials in pregnant and breastfeeding women in malaria-endemic areas. Campo explored new approach methodologies such as Zebrafish and human induced pluripotent stem cells (hiPSCs) assays to test the potential teratogenicity of antimalarial compounds. Campo also mentioned the use of physiologically based pharmacokinetic (PBPK) modeling to generate high-quality data on the efficacy of antimalarials,  informing clinical trials and policy decisions. Campo outlined a work plan for evaluating additional models in antimalarial research and predicting the pharmacokinetics of compounds for use during pregnancy and lactation, as a means of generating evidence and optimizing clinical trials. He emphasized the importance of collaboration in terms of sharing ideas, datasets, or compounds.

Kassoum Kayentao (Malaria Research and Training Institute, Mali) discussed the PYRAPREG trial, which aims to evaluate the efficacy and safety of pyronaridine-artesunate(PA) for treating malaria in pregnant African women during the second and third trimesters. This study sought alternative therapeutic options due to the low post-therapeutic effect of other medications like dihydroartemisinin-piperaquine (DP). Kayentao explained that the study compared the safety and efficacy of PA to that of artemether-lumefantrine (AL) and DP, which are recommended and widely used. Kayentao briefly touched on the preliminary safety results of the PA study, noting that serious adverse events collected in women and newborns were not related to the study drug. Data cleaning is ongoing for the safety and efficacy of PA, with an expectation that the results will offer an alternative therapeutic option for treating uncomplicated malaria in the second and third trimesters of pregnancy, as well as in HIV-positive pregnant women.

Bernard Omondi (Center for Global Health Research – Kenya Medical Research Institute – KEMRI-CGHR, Kenya) discussed an antimalarial pregnancy exposure registry aimed at generating robust data on the safety of various antimalarials during pregnancy, particularly in the first trimester, to inform regulators and policymakers. He elaborated on the MiMBa study, a multicentre cohort study involving pregnant women aged 15-49 years who have been exposed to specific artemisinin combined therapies (ACTs) such as dihydroartemisinin-piperaquine (DP) and pyronaridine-artesunate (PA) in Kenya and Burkina Faso. This study compared the incidence of pregnancy outcomes (miscarriages or stillbirths) among pregnant women and major congenital anomalies in newborns to generate informative data for the safe use of the tested antimalarials in the first trimester. Omondi described that enrollment is still ongoing in Burkina Faso, while it has been completed in Kenya. More than half of the recruited participants have experienced pregnancy outcomes in the two sites.

Hellen Barsosio (Kenya Medical Research Institute – KEMRI, Kenya), presented the approach of the SAFIRE study, an adaptive trial assessing the safety and efficacy of non-artemisinin-based combination therapy (nACTs) for the treatment of malaria in the first trimester of pregnancy. The trial will be conducted in five countries – Burkina Faso, Mali, Kenya, Uganda, and the DRC. So far, data from the PYRAPREG and MiMBa trials have not shown developmental toxicity of antimalarials such as pyronaridine and piperaquine. Therefore, with the principle of justice in mind, there is an aim to generate more evidence for the use of these medicines in pregnancy during the first trimester, when they are more vulnerable. The composite primary endpoints for the trial are adverse birth outcomes, while key secondary outcomes include the efficacy of parasitological cure by day 42 as a long-term prophylaxis. Data from the trial will also inform the design of other trials conducted by the Liverpool School of Tropical Medicine and Medicines for Malaria Venture in the global south. The trial’s design will allow for adaptations to capture important components to generate data for the use of newer ACTs. 

Dorothy Fosah Achu (World Health Organization – WHO, Africa Regional Office, Republic of Congo) highlighted the burden of malaria in pregnancy and the current WHO guidelines on malaria case management during pregnancy. She pointed out research gaps in malaria treatment for pregnant women, such as the paucity and poor quality of data in the first trimester, which resulted in nearly  25 years between the registration of artemether-lumefantrine (AL) and its recommendation for use in the first trimester in past decades. She explained the process from evidence to the development of guidelines and policy, emphasizing the need for continued pharmacovigilance, clinical research, and monitoring of adverse events and pregnancy outcomes surveillance systems to reduce morbidity and mortality in women and children. Achu advocated for support and funding for prospective controlled trials on the efficacy and safety of antimalarial medicines in pregnancy, as well as for an enhanced role of the African Vaccine Regulatory Forum (AVAREF) on the continent to strengthen the capacity of National Regulatory Agencies (NRAs). She also highlighted the need to develop harmonized guidelines to facilitate the conduct of studies involving medicines in pregnant and lactating women in Africa.

Symposium 27 – Moving towards triple artemisinin combination therapies for multidrug resistant malaria in Africa and Asia

Mehul Dhorda (Mahidol Oxford Tropical Medicine Unit – MORU, Thailand) presented the preliminary findings on development of triple artemisinin combination therapies (TACT). A randomized partially blinded, placebo-collected, non-inferiority trial was carried out. The classes for the trials included ACT 1 (artemether-lumefantrine + placebo), TACT 1 (artemether-lumefantrine + placebo), TACT2* (artesunate-mefloquine + piperaquine and ACT2* (artesunate-mefloquine + placebo). The trial was done with TACT to ACT ratio of 2:1 in Africa and 1:1 in 8 countries in Asia. Preliminary data showed adverse effects such as vomiting among participants.

Chanaki Amaratunga (Mahidol Oxford Tropical Medicine Unit – MORU, Thailand) presented their work on the safety and efficacy of Artemether-lumefantrine plus amodiaquine treatment of multidrug-resistant malaria in Asia due to the establishment of artemisinin partial resistance followed by partnered drug resistance. One hundred and three participants were recruited in this study between July 2021-Nov 2022. A randomized, blinded placebo-controlled clinical trial with Artemether-lumefantrine plus amodiaquine (AL+AQ) or Artemether-lumefantrine plus placebo (AL+ placebo) was carried out for 63 days and patients were followed for recurrent infections, genotyping of recurrent infections and parasite clearance half-life calculation. Adverse effects (AE) for several parameters including hepatic,  renal, bone marrow and cardiotoxicity were monitored and physical examinations were conducted. Out of 103 patients, 9 recurrent infections were observed. More than 95% of the mutations observed after genotyping are PfK13 mutants. The results from this study showed that AL+AQ is safe, well tolerated and more efficient than AL against artemisinin-resistant Plasmodium falciparum malaria in Asia.

Zbynek Bozdech (Nanyang Technological University, China) evaluated artemisinin resistance as a complex genetic trait using a transcriptomic approach. Artemisinin-based combination therapies (ACTs) are the first-line malaria treatments. Associations of alternative splicing and antisense RNA transcripts with artemisinin resistance showed many genes both upregulated and downregulated. From a transcriptomic point of view, artemisinin resistance looks very complex. PfWD11, one of the genes obtained was a covariant with PfK13 and it occurred on the intron of the gene. The mutation occurred by alternative splicing which removed about 50 amino acids from the C-terminus within the WD40 domain. Another mutation in the promoter region of Pfcyp19B caused by upregulation of this gene was known to be driving artemisinin resistance. This study supports the fact that adding a dose of a third drug amodiaquine to artemether-lumefantrine can maintain the efficacy of drug therapy in the context of partial artemisinin resistance.

Scientific Session 8 – Vector Biology and Control 3

Doreen Siria (Ifakara Health Institute – IHI, Tanzania) highlighted the significance of mosquito age in malaria transmission and limitations of current methods like time consumption and human bias. A machine learning strategy utilizing mid-infrared spectroscopy (MIRS) was introduced to concurrently ascertain mosquito age and species. Approximately 40,000 mosquitoes; An. gambiae, Anopheles coluzzii, and Anopheles arabiensis, gathered under diverse conditions, underwent MIRS. Convolutional neural network (CNN) machine learning achieved over 80% accuracy in laboratory conditions and successfully identified all species in genetic variation. However, environmental variation resulted in poor accuracy. These results propose this method as a promising alternative for mosquito age determination, pending further accuracy improvements.

Pierre Marie Sovegnon (University of Abomey-Calavi, Benin) discussed the escalating threat to Africa’s primary vector control tool, treated bednets, due to increasing pyrethroid resistance in mosquitoes. Sovegnon stressed the necessity of novel insecticides with diverse modes of action to address this challenge. Experimental hut trials were conducted to assess the blood-feeding behaviour, and longevity of mosquitoes when exposed to three new nets: Interceptor G2 (IG2) (pyrethroid and chlorfenapyr), Royal Guard (RG) (pyrethroid and pyriproxyfen), and PermaNet 3.0 (pyrethroid and Piperonyl butoxide (PBO)). Results indicated a significant reduction in blood feeding rates with unwashed RG nets, while all three nets exhibited high 72-hour mortality rates, with IG2 nets recording the highest mortality.

Phocas Mazimpaka (Rwanda Biomedical Center – RBC, Rwanda) provided insights regarding community empowerment in integrated vector management (IVM), implemented in 2023, to boost local involvement in managing larval sources. Through a “learning by seeing and doing” strategy, local community leaders were trained to identify mosquitoes and breeding sites. By the program’s end, participants, including health workers, engineers, and agronomists, adeptly recognized Anopheles mosquitoes, with over 80% identifying breeding sites nearby. Conducted in the local language, this training extended across 300 sectors nationwide, with full compliance from the community. To further engage communities and expand the capacity building in IVM, increased national-level multisectoral collaboration, advocacy, and resource mobilization are necessary.

El Hadji Diouf (Cheikh Anta Diop University – UCAD, Senegal) contrasted resistant alleles identified in An. gambiae s.s, An. arabiensis, and An. coluzzii mosquitoes between districts receiving IRS (Indoor Residual Spraying) and the control districts. Vgsc- 1014F, Vgsc- 10145, and G1195 mutations were more common in An. arabiensis and An. gambiae s.s than in An. coluzzii, with G1195 being predominant in An. coluzzii. Kdr mutations were prevalent in IRS districts among An. gambiae s.s and An. coluzzii. Allele 1014F frequency was low in both districts, while Vgsc- 10145 frequencies were higher in control districts. These results suggest that implementing IRS with bendiocarb, followed by pirimiphos-methyl, might decrease the frequencies of alleles 1014F and 10145.

Scientific Session 10 – Phytomedicines and pharmacology

Toghueo Rufin (University of Yaounde, Cameroon) presented an exploration of the fungi microbiome from Cameroonian medicinal plants for antimalarial drug discovery. Highlighting the vast biodiversity in Sub-Saharan Africa, where indigenous populations utilize numerous medicinal plant species for malaria prevention and treatment, the study aimed to isolate and identify fungal endophytes producing compounds effective against Plasmodium falciparum. Four endophytes exhibited activity against P. falciparum strains, leading to the identification of one active compound (Auraperone A) and two potent fractions with multi-stage inhibition against the P. falciparum 3D7 strain. Dr. Rufin underscored the potential of advanced metabolomics and molecular networking in uncovering novel bioactive compounds against falciparum malaria.

Elliot Nyangumbo (Midlands State University, Zimbabwe) presented a systematic review of medicinal plants used for the treatment and management of malaria in Zimbabwe. The study underscored the significance of traditional medicines in combating malaria and addressing antimalarial drug resistance. Through a comprehensive review, 70 plant species were identified for their traditional use in malaria treatment in Zimbabwe and across Africa. Roots were predominantly cited compared to seasonal parts like flowers and fruits, raising conservation concerns. Toxicology and pharmacological tests were conducted, revealing that 53 out of 70 plants exhibited antiplasmodial activity, thus scientifically validating their efficacy in managing malaria symptoms.

Elliot Nyangumbo (Midlands State University, Zimbabwe) continued with a study on in-silico analysis of compounds from screened antimalarial medicinal plants against P. falciparum Hsp90_A, aiming for selective antimalarial drug design. Among the 53 plants exhibiting antiplasmodial activity, 22 were identified with high activity. Literature searches revealed that only four out of these 22 plants had information on isolated compounds, highlighting the necessity for further research on other plants. Ethno-directed and comprehensive literature searches played a pivotal role in narrowing down natural product compounds for targeted drug development. The findings advocate for additional research into anti-malarial compounds in African flora, potentially serving as direct medications or as lead compounds for the development of novel anti-malarial drugs.

Simon Nyarko (Kwame Nkrumah University of Science and Technology, Ghana) developed an RP-HPLC method for the simultaneous determination and quantification of artemether and lumefantrine in fixed-dose combination pharmaceutical forms. The objective was to establish and validate a rapid, precise, economical, and robust RP-HPLC technique and conduct drug assays on the sample medications. The solvent Azitronitra was utilized for the HPLC run, and the method’s specificity, linearity, accuracy, system suitability, and precision were validated using 8 tablets and 6 suspension brands. The method demonstrated high sensitivity, accuracy, and reliability, rendering it suitable for application in resource-constrained environments.

Adebanjo Adegbola (Obafemi Awolowo University, Nigeria) investigated how ciprofloxacin affects the pharmacokinetics of lumefantrine in both malaria patients and healthy volunteers. This inquiry stemmed from the common practice of combining antimalarials like artemether-lumefantrine (AL) with antibiotics due to malaria-bacteria co-infections. Ciprofloxacin has the potential to inhibit drug-metabolizing enzymes, thereby possibly increasing drug plasma levels and affecting the effectiveness of antimalarials. The study evaluated lumefantrine exposure with and without ciprofloxacin. Both healthy volunteers and malaria patients received AL alone or in combination with ciprofloxacin, and their blood samples were analyzed for pharmacokinetic parameters. The findings revealed higher lumefantrine levels when administered with ciprofloxacin, indicating prolonged drug activity. Further studies are necessary to ascertain the safety and efficacy of combining AL with ciprofloxacin.

Plenary Session 5 – Malaria Vaccines: The missing piece on the path to elimination?

Pedro Alonso (BioNTech, Germany) framed the plenary talk, laying out a comprehensive discussion framework for subsequent speakers who explored future scenarios of malaria elimination and eradication. While Alonso highlighted progress in malaria control efforts, and expressed doubt about achieving malaria eradication by 2050 with existing tools alone. Alonso stressed the pressing need for innovative solutions, particularly malaria vaccines, to complement existing interventions. The approval of RTS,S/AS01  and  R21/Matrix-M vaccines by the World Health Organization (WHO) represents significant progress in the fight against malaria – a milestone unimaginable  30 years ago when the MiM society was formed in Dakar, Senegal. Alonso’s message underscored the need to invest in research and development for new tools, including vaccines, crucial for advancing malaria control, elimination, and eradication efforts. Strong political commitment and international cooperation are essential to support these endeavours and drive progress toward eradicating malaria, leveraging innovative approaches and collaborative partnerships for a future where malaria poses no threat to public health.

Lindsey Wu (WHO Global Malaria Programme & Immunization, Vaccines and Biologicals, Switzerland) articulated the World Health Organization’s (WHO) strategic priorities for malaria vaccine development, emphasizing the importance of facilitating both global and country-specific research agendas. She outlined the preferred characteristics of an ideal malaria vaccine and provided insights into the current malaria vaccine pipeline, clinical pathways, and endpoints. Highlighting vaccines as integral to malaria elimination strategies, she underscored the significance of the RTS,S/AS01 vaccine as a major scientific breakthrough. However, she acknowledged challenges in improving vaccine access and efficacy. Wu stressed the necessity for additional tools to enhance vaccine effectiveness and the duration of protection, advocating for data-driven approaches to inform future vaccine development

Halidou Tinto (Institute of Research in Health Sciences (IRSS) – Clinical Research Unit of Nanoro (CRUN), Burkina Faso) discussed the integration of malaria vaccines, particularly RTS,S and R21, into existing prevention strategies in Africa to enhance malaria elimination efforts. While acknowledging the potential of these vaccines to reduce the malaria burden, Tinto highlighted the necessity of combining them with other preventive measures due to their inability to interrupt disease transmission alone. RTS,S, when combined with tools like seasonal malaria chemoprevention (SMC), showed promising results in trials in Burkina Faso and Mali, significantly reducing clinical malaria, severe cases, blood transfusions, and malaria-related deaths. The key takeaway emphasized the importance of political leadership and continued efforts in the face of ongoing developments in malaria vaccines and monoclonal antibodies.

Dorothy Fosah Achu’s (World Health Organization – WHO, Africa Regional Office, Republic of Congo) insights build on previous speakers’ discussions on malaria elimination strategies. She acknowledged that many countries have been progressing towards elimination through various methods, including insecticide vector control and integrated approaches to diagnosis and treatment. However, Achu raised the question of where vaccines fit into malaria control efforts, thus,  while vaccines play a crucial role, they alone cannot lead us to complete malaria eradication. Achu highlighted the need for vaccines targeting both children and adults, addressing a broader range of malaria parasites, including P. falciparum and P. vivax. Additionally, she stressed the importance of affordable vaccines to ensure equitable access, particularly in the WHO Africa region, and underscored the significance of initiatives like the Africa Malaria Vaccine Rollout Initiative in scaling up vaccine distribution for maximum impact. Ultimately, Achu’s key message emphasized the importance of continuing to utilize existing tools while exploring new interventions to combat malaria effectively.

Yvan Butera (Ministry of Health – MoH, Rwanda) highlighted the need for a comprehensive approach to public health in Africa and emphasized the importance of not only developing vaccines but also strengthening healthcare infrastructure for their effective deployment. Butera stressed the significance of combatting prevalent diseases like malaria while also building capacities for vaccine manufacturing within the continent, and the utilization of diverse expertise, particularly evident during the COVID-19 pandemic, to manage health crises effectively. Furthermore, Butera mentioned the necessity of sustainable financing mechanisms for vaccine procurement to ensure equitable access to healthcare resources. He emphasized the importance of data-driven strategies in strengthening health systems, enabling policymakers to allocate resources efficiently. Overall, Butera’s message aimed at fostering self-reliance, innovation, and resilience in Africa’s healthcare landscape.

Symposium 30 – Strategies to mitigate antimalarial drug resistance in Africa: grassroots engagement to next generation drugs

Charlotte Rasmussen (Global Malaria Programme, WHO, Switzerland) outlined the strategy to combat antimalarial drug resistance in Africa, focusing on artemisinin-based combination therapies (ACTs). ACTs rely on both artemisinin and a partner drug for efficacy, with artemisinin reducing parasite biomass rapidly and the partner drug eliminating remaining parasites. Partial artemisinin resistance is defined by delayed parasite clearance, associated with Pfkelch13 mutations. Confirmed resistance requires over 5% of the validated marker for Pk13 and evidence of delayed clearance, observed in Uganda, Rwanda, Eritrea, and Tanzania. High treatment failure is reported for amodiaquine, lumefantrine, and piperaquine, though partner drug resistance is unconfirmed. The response strategy, developed in November 2022, includes 20 interventions across four pillars namely: surveillance, regulation of diagnostics and therapeutics, limiting resistance spread, and fostering research and innovation. Rasmussen emphasized the need for continuous monitoring and updates to adapt to evolving evidence and challenges.

Maciej F. Boni (Temple University, United States) discussed modeling policy interventions to curb artemisinin resistance spread in Uganda and Tanzania,  outlining four strategies for success including preventing resistance, delaying spread, slowing resistance gene frequency increase, and controlling it. Boni focused on the average monthly treatment failures over five years, emphasizing diverse drug deployment for effective management. Uganda’s whole-country model and Tanzania’s whole-region model predicted a 75% Pfkelch13 mutation in Uganda and a 50% containment possibility in Tanzania over five years. Running the model to 2024, suggested interventions like switching to other ACTs, cycling through them, deploying multiple first-line ACTs (MFTs), or deploying triple ACTs by September. Running the model till 2029 showed that a near-term strategy of maximum ACT diversity (MFT or rapid cycling) is Uganda’s best strategy, while for Tanzania, a near-term switch to ASAQ is the optimal approach. 

Karen I. Barnes (University of Cape Town, South Africa) presented the potential role of single low-dose primaquine for tackling partial artemisinin resistance. She identified various factors contributing to this resistance, including mutations in the Plasmodium falciparum PKelch13 gene and the failure of artemisinin combination therapy (ACT). Barnes discussed the significance of gametocyte prevalence as a marker for infection, noting that while imperfect, it provides valuable baseline data and further highlights differences in gametocyte density between regions with varying transmission intensities. Moreover, Barnes emphasized the limitations of using gametocyte/membrane feeding experiments as markers of drug efficacy. In conclusion, she underscored the higher prevalence of gametocytes in artemisinin-resistant infections, particularly in areas with moderate to high transmission rates, and advocated for the use of single low-dose (SLD) primaquine in regions threatened by artemisinin resistance and stressed the importance of surveillance to assess the effectiveness of SLD Primaquine in combating resistant parasites.

Didier Leroy (Medicine for Malaria Venture – MMV, Switzerland), discussed strategies for addressing complicated malaria refractory to treatment. He emphasized the importance of adopting fast-acting, resistance-refractory approaches in the fight against drug resistance. Leroy advocated for simplifying therapy and overcoming resistance through vaccines and chemotherapy, including combinations like triple artemisinin combination therapy (TACT), non-artemisinin combinations like ganaplacid-lumefantrine, and novel drugs in clinical trials like ZY19489. Leroy categorised challenges into previous and new versions, citing factors such as screening and risk assessment for the former, and MIR determination and cross-resistance screening for the latter. He emphasized the urgency of prompt action against resistance, highlighting potential consequences of delays and the importance of proactive measures to combat drug resistance in malaria treatment.

Olugbenga A. Mokuolu (University of Ilorin, Nigeria) addressed the challenge of antimalarial drug resistance. He stressed the vital role of stakeholder engagement in combating this public health threat, emphasising the need for resource mobilisation, community empowerment, and fostering trust in malaria interventions. Mokuolu advocated for synergistic collaboration between evidence providers, policymakers, and regulators to tailor interventions to local contexts and ensure credibility. He highlighted the regulators’ responsibility in facilitating strategy implementation and maintaining marketing integrity. Drawing from numerous case studies in Nigeria, Mokuolu concluded that success in combating antimalarial drug resistance requires collective effort. Mokuolu reiterated the importance of unity, emphasising that victory over drug resistance cannot be achieved in isolation and requires concerted action from all stakeholders involved.

Symposium 32 – Anopheles stephensi in Africa: What has been done, what must be done, and how it could be done?

Roz Taylor (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom) delivered an analysis of Anopheles stephensi, a significant malaria vector, focusing on its distribution, behavior, and implications for malaria control in Africa. An. stephensi, native to South Asia and the Arabian Peninsula, has expanded its invasive range to urban areas across eight African countries. She conducted a narrative review, detailing the species’ bionomics, distribution, resting and feeding behaviors, insecticide resistance, and breeding sites. Notably, An. stephensi exhibits resistance to all four main classes of insecticides and breeds in diverse habitats, posing challenges for malaria control efforts. The presentation showed the urgency of addressing breeding sites amidst rapid urbanization in Africa to mitigate the spread of this vector. Further research is warranted to understand and combat the implications of An. stephensi‘s presence in urban environments.

Delenasaw Yewhalaw (Jimma University, Ethiopia) presented on adult An. stephensi feeding and resting behavior, and efficacy of candidate larvicides (SumiLarv 2MR and SumiLarv 0.5g) for control of An. stephensi larvae in Ethiopia. Yewhalaw pointed out the widespread presence of malaria-carrying mosquitoes in Ethiopia, with An. arabiensis being the most prevalent and An. stephensi increasingly spreading across the country since its first detection in 2016. An. funestus is also present but in limited areas. An. stephensi is emerging as an efficient malaria vector in the region capable of transmitting both Plasmodium falciparum and P. vivax. This mosquito species breeds in various aquatic environments, including urban, peri-urban, and rural settings, both natural and artificial. Results show that the species prefers animal to human blood and rests indoors and outdoors. Despite its resistance to many insecticides, SumiLarv shows promise as a larvicide for controlling An. stephensi larvae with over 80% adult emergence inhibition.

Yaw Afrane (University of Ghana, Ghana) presented on Anopheles stephensi in Ghana focusing on ecology and molecular surveillance. Potential breeding sites in Accra were sampled for malaria vector larvae which were grown to adults.  Results revealed a 0.341.4% unexpected discovery of An. stephensi, a species recently detected in East Africa, among the surveyed population of 1169 adult mosquitoes. This finding raised questions about the potential routes through which An. stephensi could have entered Ghana. Various possibilities were discussed, including long-range aerial migration, cargo transportation via airplanes or ships, and land travel such as bus journeys. However, conclusive evidence regarding the specific mode of transportation remains elusive, necessitating ongoing research efforts to assess all plausible scenarios. The integration of surveillance measures into routine entomological practices highlights the importance of proactive monitoring and response strategies to address emerging threats posed by malaria vectors. Surveillance efforts have been extended beyond Accra to assess An. stephensi in Ghana.

Louisa A. Messenger (London School of Hygiene and Tropical Medicine – LSHTM, United Kingdom, and University of Nevada, United States), emphasized the importance of molecular surveillance for Anopheles stephensi. This method informs targeted vector control and enhances our understanding of population dispersal dynamics. Direct molecular surveillance yields extensive genomic data, elucidating species dispersal and insecticide resistance mechanisms. As An. stephensi is not always captured by sampling traps, this technique offers viable alternatives, however, there are potential biases towards productive sites and limited genetic diversity due to sibling effects. Conversely, indirect molecular surveillance provides unbiased population sampling and detects An. stephensi’s presence in unknown areas. It requires minimal expertise and can involve community citizen scientists. However, reconstructing whole genome sequences from fragmented eDNA remains a challenge. While feasible in laboratory settings, field validation and operationalization are necessary. Messenger advocated for increased collaboration across surveillance of An. stephensi which has emerged as a threat for malaria control efforts in Africa.

Ayman Ahmed (University of Khartoum, Sudan) highlighted critical gaps and challenges in the surveillance and control of Anopheles stephensi in Africa. Key gaps include a lack of knowledge regarding its introduction and prevalence, technical limitations in combating An. stephensi, and resource constraints leading to delayed responses. An. stephensi poses a public health threat due to its presence in urban and rural areas, utilization of man-made breeding sites, and outdoor biting and resting habits. Policy challenges include determining its public health significance and developing effective strategies. Ahmed emphasizes the need for unified stakeholder positions, integrated vector management programs, regional coordination, and local capacity building. Recommendations focus on strengthening collaboration, community engagement, surveillance, and scaling up interventions for sustainable vector control. This comprehensive approach is crucial for addressing the emerging threat of An. stephensi in Africa. 

Scientific Session 11 – Malaria in Pregnancy 1

Tahina Razafiarijaona (Johns Hopkins Program for International Education in Gynecology and Obstetrics – Jhpiego, United States) presented data on at least 3 doses of intermittent preventive treatment of malaria for pregnant women (IPTp3) coverage and antenatal care (ANC) attendance in Madagascar, illustrating improvement over time attributed to the Transforming Intermittent preventive Treatment for Optimal Pregnancy (TIPTOP) project. The TIPTOP approach effectively enhanced IPTp3 coverage and ANC attendance, which were considered acceptable and feasible by healthcare providers and community health workers. Post-project follow-up in October 2023 further demonstrated the feasibility of interventions. The community IPTp (C-IPTp) strategy bolstered health systems at various levels, instilling increased confidence in the healthcare system. The Ministry of Health, supported by USAID/MOMENTUM and ACESS program, intends to expand the C-IPTp approach as part of the 2023-2027 National Strategic Plan. Implementation will continue in the three districts, with plans for scaling up to 41 additional districts in 2023 and beyond.

Tacilta Nhampossa (National Institute of Health – INS & Manhiça Health Research Centre – CISM, Mozambique) discussed the acceptability of dihydroartemisinin-piperaquine (DP) as intermittent preventive treatment of malaria for pregnant women living with HIV (PWLHIV) in Southern Mozambique. The quantitative study aimed to understand how clinical trials would impact HIV status confidentiality and acceptance of DP. The research spanned from 2019 to 2023, involving 44 PWLHIV, 35 HIV-negative pregnant women, and 8 health providers. Findings suggested that the acceptability of DP was influenced more by pregnant women’s trust in health providers than by the perceived benefits of DP in preventing malaria. To enhance acceptability, it is crucial to leverage this trust to provide clear information on DP administration.

Katherine Wolf (Johns Hopkins Program for International Education in Gynecology and Obstetrics – Jhpiego & President’s Malaria Initiative – PMI Impact Malaria, United States) presented findings from a cluster-randomised controlled trial in the Atlantique Department of Benin, evaluating the impact of Group Antenatal Care (G-ANC) on ANC retention and uptake of IPTp3+. The study aimed to determine if G-ANC improved IPTp uptake by comparing pregnant women in G-ANC facilities to those in control facilities and to assess its feasibility and acceptability. Approximately 40 health facilities were randomised, and household surveys conducted before and after implementation indicated higher ANC4 and IPTp3 rates among G-ANC participants. Despite challenges such as staffing shortages for enrolling women, G-ANC participants demonstrated higher ANC4 and IPTp3 uptake. However, overall enrolment remained low, with no significant community-level impact.