By Dr. Derick Pasternak, Ambassador, Malaria Science & Research Coordinator, MPI
Plasmodium vivax is a significant cause of malaria in Ethiopia and to some extent the surrounding countries. During the 9th International Conference on P. vivax research in Puducherry, India, between 11 and 14 February, the following topics were discussed:
- Unveiling vivaxDynamics: Transmission, Genomics & Surveillance
- Rethinking Relapse: In vivo Studies & Human Challenge Models
- Curing Malaria: Clinical Trials, Therapeutics, & Vaccines
- Targeting vivax: Decoding Host-Parasite Interactions
- Immunology Unmasked: Natural Infections, Cryptic Reservoirs
- Diagnostics Unlocked: Omics, Single-Cell & Serological Advancements
- Duffy Enigma: Epidemiology & Invasion Mechanisms
- Bridging the Gap: Advanced Model Systems for Plasmodium vivax
- Climate Change & Malaria: An Emerging Threat
Among other presentations, a poster presentation reviewed the current status of the search for a vaccine against P. vivax, which cannot be reproduced here because of copyright considerations, but can be accessed at https://mesamalaria.org/resource-hub/towards-a-vaccine-for-plasmodium-vivax-landscaping-review-updated-poster/
According to a press release by Pilgrim Africa in early March, “Uganda has taken a bold step in the fight against malaria by dispatching 2.7 million doses of the R21 malaria vaccine to 105 districts, prioritizing areas with high and moderate transmission. … The vaccine will be integrated into routine immunization, given in four doses at 6, 7, 8, and 18 months. … With support from partners like Gavi and UNICEF, the malaria vaccine is expected to save thousands of lives, reduce hospital admissions, and boost economic productivity by keeping children and parents healthier. The main rollout is set for April 2 in Apac District, a high-burden area.”
On 4 March the Reuters News agency reported that the U.S. Food and Drug Administration has placed a clinical hold on BioNTech’s early-to-mid stage trial of an experimental malaria vaccine.
The trial was to evaluate the safety and efficacy of the RNA-based vaccine called BNT165e for prevention of malaria caused by P. falciparum in healthy adults who have never had malaria before. The reason for the hold was not revealed.
PEER REVIEWED ARTICLES (see notes after citations from non-peer-reviewed publications)
Prevention
Vaccines
Yanik S & al., iDC-Targeting PfCSP mRNA Vaccine Confers Superior Protection Against Plasmodium Compared to Conventional mRNA, NPJ Vaccines. 2025 Feb 19;10:34, https://doi.org/10.1038/s41541-025-01089-x reports on modifying the currently experimental mRNA antimalarial vaccine to target different cels in the host in order to improve the immune response. The authors state that their preparation “provided significantly greater protection from liver infection” in mouse model malaria.
Schmid M & al., Generation of a Genetically Double-Attenuated Plasmodium berghei Parasite that Fully Arrests Growth During Late Liver Stage Development, PLoS One, 2024 Dec 31, https://doi.org/10.1371/journal.pone.0316164 was published at about the same time as on Roozen GVT & al., Single Immunization with Genetically Attenuated PfΔmei2 (GA2) Parasites by Mosquito Bite in Controlled Human Malaria Infection: A Placebo-Controlled Randomized Trial, Nature Med. 2025 Jan 3, https://doi.org/10.1038/s41591-024-03347-2, reported in January and reports on the same idea, namely developing a strain of parasite with double gene deletion, which renders it incapable of maturing in the liver. The attenuated parasite then may be used as the immunizing agent in the development of a vaccine.
Another vaccine under investigation uses radiation-attenuated whole malaria sporozoites. Berry AA & al., Safety, Tolerability and Immunogenicity of a Condensed, Multi-Dose Prime Regimen of PfSPZ Vaccine for the Prevention of Plasmodium falciparum Malaria Infection, Malaria J, 2025 Mar 17, 24:88, https://doi.org/10.1186/s12936-025-05299-5 refer to previous work with this vaccine, which has been found to be 100% effective against inoculated P. falciparum infections after a four-dose regime. In addition, in 14 previous trials the vaccine had caused no serious adverse events. This trial was intended to use an accelerated schedule of injections but had to be stopped early due to poor quality of the preparation supplied to the researchers. Nonetheless, avfter only two doses of the vaccine, the “regimen was safe, well tolerated and highly immunogenic. Larger studies may better define the adverse event profile of condensed regimens of PfSPZ Vaccine in malaria-naive adults.”
In yet another vaccine acceptance study, Ntihebuwayo E & al. asked caregivers of 447 sick children under age five, selected at random within five districts whether they would accept a malaria vaccine. Sample size was derived from the total number who visited a health facility within a given time, using statistical calculation. As reported in Acceptance of a Malaria Vaccine Among Caregivers of Sick Children Under 5 Years of Age in Burundi, Malaria J, 2025 Mar 20, 24:90, https://doi.org/10.1186/s12936-025-05327-4, 405 (90.6%) of the caregivers responded in the affirmative. Although there was extensive analysis of the population queried, there is no indication either in the abstract or the paper whether the caregivers were fully informed of the recommended vaccination schedule.
It is unclear why Venkatraman N & al., Evaluation of a Novel Malaria Anti-Sporozoite Vaccine Candidate, R21 in Matrix-M Adjuvant, in the UK and Burkina Faso: Two Phase 1, First-In-Human Trials, Lancet Microbe. 2025 Mar; 6(3):100868, https://doi.org/10.1016/s2666-5247(24)00084-3, a report of a Phase One study of a vaccine approved by WHO two years ago is published now.
Adeleke MA studied various aspects of two potential transmission blocking vaccines and reports in Computational Development of Transmission-Blocking Vaccine Candidates Based on Fused Antigens of Pre- and Post-fertilization Gametocytes Against Plasmodium falciparum, Bioinform Biol Insights. 2025 Mar 3; 19:11779322241306215, https://doi.org/10.1177/11779322241306215 that one of them (FAVC-FSE) is the more promising candidate.
Vectors
Hamwata W & al. studied vector species in various settings in a total of 166 housing units and 90 larval breeding sites. They conclude that the “emergence of An. funestus s.s in an area previously dominated by An. gambiae s.s and its coexistence with An. gambiae s.s in the dry season pose a risk of sustaining malaria transmission all year round. Agricultural practices in urban areas resulted in highly productive mosquito breeding sites; thus, there is a need for targeted vector control.” The article is Implications for Malaria Transmission: A Cross-Sectional Study on the Bionomics and Susceptibility of Local Malaria Vectors in Urban and Periurban Settings of Ndola District, BMJ Open. 2025 Mar 5; 15(3):e091319, https://doi.org/10.1136/bmjopen-2024-091319.
Zanzibar “relies on insecticide-treated nets as the principal vector control method, supplemented by reactive focal indoor residual spraying, [yet] local malaria transmission persists, and the underlying reasons for sustained transmission remain unclear,” state Khatib B & al. in Early Evening Outdoor Biting by Malaria-Infected Anopheles arabiensis Vectors Threatens Malaria Elimination Efforts in Zanzibar, Malaria J, 2025 Mar 20, 24:92, https://doi.org/10.1186/s12936-025-05333-6. Using human volunteers who allowed themselves to be bitten by mosquitoes, they determined that An. arabiensis, the chief vector for malaria on the islands, was significantly more likely to bit outdoors than inside dwellings, and often during hours when people are still outside. They state that their findings “highlight the potential risk of human exposure to outdoor transmission.”
“Monitoring insecticide-treated net (ITN) coverage and use generally relies on household surveys.” Worges M & al. studied the reliability of performing such surveys via mobile phones and report in Assessing Trends in Non-Coverage Bias in Mobile Phone Surveys for Estimating Insecticide-Treated Net Coverage: A Cross-Sectional Analysis in Tanzania, 2007-2017, BMJ Public Health. 2025 Mar 4; 3(1):e001379, https://doi.org/10.1136/bmjph-2024-001379 that while mobile phone surveys “can reliably estimate ITN coverage at the population level when both ITN coverage and mobile phone ownership are high. However, as ITN coverage declines, the gap between phone-owning and non-phone-owning households widens…”
The emergence of resistance to insecticides has caused a search for solutions. Gonahasa S & al., LLIN Evaluation in Uganda Project (LLINEUP2) – Effect of Long-Lasting Insecticidal Nets (LLINs) Treated with Pyrethroid Plus Pyriproxyfen vs LLINs Treated with Pyrethroid Plus Piperonyl Butoxide in Uganda: A Cluster-Randomised Trial, PLOS Glob Public Health. 2025 Feb 26; 5(2):e0003558, https://doi.org/10.1371/journal.pgph.0003558 is a report of a study of two additional compounds to the nets distributed. “Two years post-distribution, ownership of at least one [net] for every two household residents was low in both arms (41.1% pyrethroid-PBO vs 38.6% pyrethroid-pyriproxyfen). … The effectiveness of pyrethroid-PBO [nets] and pyrethroid-pyriproxyfen [nets] was no different in Uganda, but two years after mass distribution, [net] coverage was inadequate. {Reviewer’s note: Given these and other similar results, one has to doubt the validity of calling ITNs “long-lasting.”}
Yovogan B & al. performed genetic studies on mosquitoes collected from Southern Benin, where insecticide resistance is known to be high among the Anopheles population. After analysis of over 4000 insects tested, the authors conclude in Impact of Dual Active Ingredients Long-Lasting Insecticidal Nets on the Genetic Structure of Insecticide Resistant Populations of Anopheles gambiae in Southern Benin, Malaria J, 2025 Mar 4, 24:72, https://doi.org/10.1186/s12936-025-05308-7 that “[c]onsistent changes in allele frequencies were not observed in any of the treatment arms suggesting that the pyrethroid component of dual AI (active ingredients) nets continues to select for the resistant allele and there is little if any evidence that the non-pyrethroid insecticide selects for the wild-type kdr allele.”
Ogidan OC & al. analyzed data from questionnaires completed by 14,476 women of reproductive age (15–49 years) in the course of the 2021 Nigeria Malaria Indicator Survey (NMIS). They searched for evidence of insecticide treated net (ITN) ownership. As they report in Prevalence and Determinants of Insecticide-Treated Net Ownership Among Women of Reproductive Age in Nigeria: A Mixed-Effect Insight from the 2021 Malaria Indicator Survey, Malaria J, 2025 Mar 5, 25:75, https://doi.org/10.1186/s12936-025-05314-9, the “prevalence of ITN ownership was 62.6% … Women aged 25–34 and 35–49 had 12% … reduction in ITN ownership, when compared with women aged 15–24 years. Women who had … living children … had higher odds of ITN ownership when compared with those with no living child … Women from non-poor households had higher odds of ITN ownership, when compared with their poor counterparts…” There is no mention of how or whether the ITNs were used.
Investigating the emergence of mosquitoes resistant to insecticides Hougbe SZ & al. collected larval specimens from a variety of sites in Benin and tested their survival after metamorphosis when exposed to clothianidin. They report in Susceptibility of Anopheles gambiae s.l. to the Neonicotinoid Insecticide Clothianidin in Eighteen Sites Located Along the South-North Transect of Benin, Trop Med Health. 2025 Feb 12; 53:21, https://doi.org/10.1186/s41182-025-00694-9 that four different subspecies demonstrated very high susceptibility to the insecticide.
Opondo KO & al. also found most anopheles species collected in Sierra Leone to be sensitive to clothianidine as well as chlorphenyrapir and primiphos-methyl, while they were unifromly resistant to “pyrethroids: deltamethrin, permethrin and alpha-cypermethrin.” Their paper is Characterization of Insecticide Resistance Mechanisms in the Anopheles gambiae Population of Sierra Leone, Malaria J, 2025 Mar 13, 24:80, https://doi.org/10.1186/s12936-025-05267-z.
One the other coast of Africa, Kiuru C & al. studied “the insecticide resistance profiles of the main malaria vector, Anopheles funestus sensu lato in Mopeia district, a malaria holoendemic area of the Zambezia province of Mozambique” and conclude in Multiple Insecticide Resistance in Anopheles funestus from Mopeia, Central Mozambique, Malaria J, 2025 Mar 14, 234:81, https://doi.org/10.1186/s12936-025-05321-w that “[m]alaria vectors in Mopeia exhibit resistance to all four major public health insecticide classes: pyrethroids, organophosphates, organochlorides and carbamates. This highlights the urgent need to adopt new insecticide classes for vector control interventions.”
Machani MG & al. assessed “Anopheles diversity, abundance, behaviour, … in Kisumu city, Kenya” and conclude in their article, Bionomics and Distribution of Malaria Vectors in Kisumu City, Western Kenya: Implications for Urban Malaria Transmission, Malaria J, Mar 15, 24:85, https://doi.org/10.1186/s12936-025-05332-7 that there is “a shift in Anopheles diversity towards urban areas with increased outdoor activity and outdoor malaria transmission in rural and peri-urban areas, underscoring the need for tools targeting outdoor-biting mosquitoes. The presence of An. funestus in urban settings emphasizes the need for sustained entomological surveillance to inform integrated vector control.”
“Attractive targeted sugar baits (ATSBs) are a potential addition to an integrated vector management strategy against malaria. ATSB stations, which include a sugar bait and an ingestion toxicant, could potentially be deployed to attract-and-kill mosquitoes and thereby prevent malaria transmission. The physical durability of these stations is likely to be an important factor in decisions around future use strategies. [Karabo RY & al.] measured the duration of physical integrity of the ATSB Sarabi v1.2 stations used in Western Zambia…” 1107 ATSBs were installed and Time to Loss of Physical Integrity of Attractive Targeted Sugar Bait (ATSB) Stations in Western Province, Zambia: A Survival Analysis, Malaria J, 2025 Mar 15, 24:84, https://doi.org/10.1186/s12936-025-05316-7 concludes “that the majority of ATSB stations deployed in this setting will remain intact for a 7-month seasonal deployment period if stations are installed in locations protected from weather elements, such as underneath the overhang of thatched roof.”
Larviciding by means of introduction of bacteria has been shown to be successful. Munyakanage D & al., Factors Affecting Community Participation in Drone-Based Larviciding Using Bacillus thuringiensis var. israelensis (Bti) for Bio-Control of Malaria Vectors in Rwanda, Malaria J, 2025 Mar 01, 24:67, https://doi.org/10.1186/s12936-025-05310-z reports on “community knowledge, perception, acceptance, and willingness to participate in drone-based larviciding for malaria control in Kigali City” and concludes that there is “strong community awareness and acceptance of drone-based larviciding, with its effectiveness in reducing mosquito abundance and malaria risks, along with the safety of Bti and drones.” The authors advocate expanding the reach of this method of vector control.
Chemoprophylaxis
According to a survey of 7000+ women, Nicolas P & al., Access and Usage of Malaria Control Measures by Women of Reproductive Age in Mopeia Mozambique, Malaria J, 2025 Mar 1, 24:66, https://doi.org/10.1186/s12936-025-05306-9#Sec7 reports that “[a]ccess to malaria vector control tools was high, with 89.9% of women self-referred as pregnant, 87.9% of women self-referred as not- pregnant living in a household with at least one long-lasting insecticidal net and 69.6% of women self-referred as pregnant and 73.4% of women self-referred as not-pregnant living in household that received indoor residual spraying in the past 12 months. Intermittent preventive treatment coverage was moderate-low, with 53.1% of women self-reported as pregnant having taken at least one dose.” The authors voice their concern over the low percentage of women who participate in intermittent preventive treatment of pregnancy (IPTp) as recommended by WHO.
In a study of pregnant women attending antenatal care, Ansong D & al. report in Knowledge, Uptake and Therapeutic Effectiveness of Sulfadoxine-Pyrimethamine (IPTp-SP) Among Pregnant Women Attending the Antenatal Clinic at Ayeduase Health Centre in Oforikrom Municipality in the Ashanti Region, Ghana, BMC Pregnancy Childbirth. 2025 Mar 8; 25(1):265, https://doi.org/10.1186/s12884-024-07089-4 the following: “All pregnant women … heard of IPTp-SP, and 94.7% knew of its benefits in pregnancy. Notably, health providers were the major source of information for approximately 94% of pregnant women, and a higher level of knowledge on IPTp-SP was found among 92.0% of pregnant women. … Optimal uptake (≥ 3 doses) of IPTp-SP was … 61.3% … Late antenatal clinic initiation … period of IPTp-SP intake … good knowledge … were significantly associated with ≥ 3 doses of IPTp-SP.”
Diagnosis
General diagnostics
Cherkos T & al. investigated the power of microscopy against loop mediated isothermal amplifaction (LAMP) among 150 asymptomatic individuals in an Ethiopian community. Their article, Unveiling the Silent Threat: Investigating Asymptomatic Plasmodium Infections in Gorgora, Ethiopia Through Microscopy and Loop-Mediated Isothermal Amplification, PLoS One. 2025 Mar 6;20(3):e0313746, https://doi.org/10.1371/journal.pone.0313746 reports that while microscopy identified seven parasitemic individuals, LAMP uncovered an additional six, highlighting the importance of more accurate diagnostic methods.
The microscopists participating in Muyidi AA & al.’s study, Evaluation of Two Multiplexed qPCR Assays for Malaria Detection and Speciation: A Comparative Study with Nested PCR and Microscopy, J Parasitol Res. 2025 Feb 25; 2025:4950793, https://doi.org/10.1155/japr/4950793 did a bgreat deal better than those reportedin the study above: Light microscopy detected 92.4% of cases, NM-PCR [nested multiplex PCR] detected 73.9%, and RealStar and Viasure [two brands of qPCR kits] detected 92.4% and 95.7%, respectively. Viasure showed the highest sensitivity (97.6%) and NPV (50%), while NM-PCR had superior specificity (71.4%). For species identification, Plasmodium falciparum detection was highest with RealStar (85%). Mixed infections were better identified by Viasure (34.6%). RealStar excelled in Plasmodium vivax detection (area under the curve [AUC] = 90%). qPCR detected low parasitemia levels missed by microscopy.”
Field diagnostics
None this month
New diagnostic methods
Studying biomarkers that may aid in reliable malaria diagnosis, Harmonis JA & al., Exploring Biomarkers for Malaria: Advances in Early Detection and Asymptomatic Diagnosis, Biosensors (Basel). 2025 Feb 12; 15(2):106, https://doi.org/10.3390/bios15020106 states that in addition to the two biomarkers currently used in Rapid Diagnostic Tests (RDTs), Histidine-Rich Protein, and Lactic Dehydrogenase, there are at least three others that may be ideal. “These biomarkers distinguished themselves markedly from the others in terms of specificity in Plasmodium detection, sensitivity in analysis, and the use of non-invasive samples. Several other biomarkers, such as CRP, Ang-1, Ang-2, and PCT, show potential for malaria detection in terms of their ability to differentiate disease severity, and the levels of these biomarkers can be determined in the body for comparison with malaria parasitemia.”
Alam MS & al., Aptamer-Based Diagnosis for Plasmodium vivax Specific Malaria, ACS Infect Dis. 2025 Mar 5, https://doi.org/10.1021/acsinfecdis.4c01047 is a description of a diagnostic method that distinguishes P. vivax from P. falciparum. The authors propose its development for use in the field.
Treatment
Treatment results
Despite the title of Abate B & al.’s article, Increasing Day Three Parasitaemia is Observed After Treatment of Patients with Artemether-Lumefantrine and Single Dose of Primaquine for Uncomplicated Plasmodium falciparum Malaria in Arbaminch Zuria District, Southwest Ethiopia, Malaria J, 2025 Mar 18, 24:89, https://doi.org/10.1186/s12936-025-05337-2, the results of treating 88 patients with the regimen described above indicated over 96% eventual cure rate. However, 17% of patients exhibited parasitemia on the third day after treatment was started.
“Artemisinin-based combination therapy (ACT) effectively clears Plasmodium falciparum asexual parasites and immature gametocytes but has a limited impact on mature gametocytes, which mosquitoes ingest during a blood meal. To address this gap, the World Health Organization recommends adding a single low dose of primaquine (PQ) to ACT regimens.” Habtamu K & al., Post-Treatment Transmissibility of Plasmodium falciparum Infections: An Observational Cohort Study, Malaria J, 2025 Mar 17, 24:87, https://doi.org/10.1186/s12936-025-05279-9 reports that among 192 patients studied, “11 human-to-mosquito transmission cases were identified on day 7. Participants receiving ACT + SLD-PQ were significantly less likely to be infectious on day 7 … and had a significantly reduced prevalence of gametocytes … compared to those receiving ACT alone.”
Side effects and complications
In the medical literature, readmission of a patient to a hospital within a certain period for the same diagnosis as before is considered a complication. Some of the cases, which made up 26.8% of 759 discharges, cited in Nambozo B & al.’s article, Severe Malaria Readmissions in Northern Uganda: A Cross-Sectional Study, Malaria J, 2024 Feb 27, 24:64, https://doi.org/10.1186/s12936-025-05307-8 may not qualify for this category because the period in the authors worked with was six months, however we don’t know how many of these children were readmitted within one month, the usual criterion for calling a complication. In any event, the authors cite “[f]actors significantly associated with readmission” as “having sickle cell anaemia …, living in houses constructed with straw and thatch walls …, and seeking care after 12 h when the child has a fever…” The extensive data cited in the article do not include information as to how soon within the 6 months after discharge were these children readmitted.
Guidelines
Even though the title of Sao Babawo L & al.’s article, Assessment of Malaria Treatment Interventions: A Critical Analysis of Government Initiatives and Causes of Treatment Failure at Port Loko Government Hospital, Sierra Leone, Malaria J, 2025, Mar 14, 24:83, https://doi.org/10.1186/s12936-025-05330-9 implies hospital treatment results, the article seems to focus on community workers’ and patients’ adherence to treatment guidelines and best practices. The most relevant data show that only 68% of 150 health workers interviewed adhered to guidelines, even though 90% expressed familiarity with them. Among 150 “women of childbearing age, 40% sought malaria treatment at drug stores or pharmacies due to financial constraints…”
Drug resistance
Dakorah MP & al. “aimed to evaluate the prevalence of known mutations in [four] drug resistance genes … in the Central Region of Ghana.” Utilizing dried blood spots from 522 patients diagnosed with falciparum malaria, As theyr report in Profiling Antimalarial Drug-Resistant Haplotypes in Pfcrt, Pfmdr1, Pfdhps and Pfdhfr Genes in Plasmodium falciparum Causing Malaria in the Central Region of Ghana: a Multicentre Cross-Sectional Study, Ther Adv Infect Dis. 2025 Feb 17; 12:20499361251319665, https://doi.org/10.1177/20499361251319665, the large majority of samples yielded mutations that are associated with partial or full resistance to sulfadoxine-pyrimethamine prophylactic regimens.
Plasmodium malariae infests the population of West African countries is significant numbers, if not as frequently as P. falciparum. Soulama A & al. focus on the susceptibility of P. malariae specimens obtained from infected patients to various drugs in comparison to the susceptibility of P. falciparum from the same geographic regions. Their paper, Differential ex vivo Susceptibility of Plasmodium malariae and Plasmodium falciparum Clinical Isolates from Ghana and Mali to Current and Lead Discovery Candidate Antimalarial Drugs, Microbiol Spectr. 2025 Mar 10: e0217624, https://doi.org/10.1128/spectrum.02176-24 highlights not only species differences in drug resistance, but geographic ones as well, noting different results in Ghana from those in Mali.
“In September 2024, the US President’s Malaria Initiative; the Global Fund for AIDS, Tuberculosis, and Malaria; the Gates Foundation; and Unitaid called for malaria partners to increase the availability and lower the cost of alternative artemisinin-based combination therapies (ACTs) for countries with growing evidence of resistance to artemisinin and current ACT partner drugs, particularly in sub-Saharan Africa.” Barat LM, Mitigating Resistance to Malaria Treatments in Sub-Saharan Africa Requires More than New Drugs, Am J Trop Med Hyg. 2025 Feb 25: tpmd240781, https://doi.org/10.4269/ajtmh.24-0781 is a “Perspective” {i.e. opinion piece} that also states: “Although these global leaders should be applauded for raising this challenge to the highest levels, they missed the opportunity to highlight a major driver of resistance to malaria treatments: the limited access to high-quality health services for malaria. Progress has been made in scaling up integrated community case management and clinical and laboratory quality improvement programs, but few malaria-affected countries have achieved national scale. If affected countries and their partners do not want to confront resistance to these newer alternative ACTs in the near future, they must take more decisive action now to expand access and improve the quality of malaria services.”
New drug research
Kuemmerle A & al., First-in-Human Safety, Tolerability, Pharmacokinetics and Pilot Food-Effect Study of the Candidate Antimalarial Compound MMV367, Br J Clin Pharmacol. 2025 Feb 16, https://doi.org/10.1002/bcp.70000 is a report on the safety of a potential antimalarial drug that has been under laboratory investigation for some time. The study in 38 human volunteers disclosed two drug-related adverse events, but no serious or severe events “or clinically relevant changes in electrocardiograms, vital signs or laboratory tests.” The authors conclude that “MMV367 demonstrated acceptable safety, tolerability and pharmacokinetic profiles supporting further development as an antimalarial drug.”
Gefitinib is a drug used in lung cancer treatment that inhibits an enzyme that is critical in the development t of Plasmodium parasites. Gorki V & al., Gefitinib as an Antimalarial: Unveiling Its Therapeutic Potential, Inflammopharmacology. 2025 Feb 28, https://doi.org/10.1007/s10787-025-01682-5 investigated its effect on P. falciparum in the laboratory as well as ir=ts clinical effect in combination with an artesunate against mouse malaria. In both instances the authors reports effectiveness and recommend further research to evaluate its potential as an antimalarial.
Cethromycin is a new antibiotic under research and is said to have “broad spectrum antibacterial and antiprotozoan activity.” Kennedy GJ & al. studied the drug’s effect on the liver stages of mouse malaria. They report in Cethromycin Pharmacokinetics and Pharmacodynamics for Single Dose Cure of Plasmodium berghei Liver Stages, bioRxiv [Preprint]. 2025 Feb 15: 2025.02.10.637401, https://doi.org/10.1101/2025.02.10.637401 that they “observed complete cure of P. berghei liver stage infection by single oral dose of 60 mg/kg in mice which is equivalent to the 5 mg/kg human dose of 300 mg a day used in bacterial pneumonia studies. Cethromycin at 60 mg/kg daily for 7 days was curative in the high parasitemic P. berghei mouse model…” Note: bioRxiv publishes articles that have not undergone peer review.
Plant extracts and traditional treatments
Enantia chlorantha, also known as African yellow wood, is the source of folk medicine in Nigeria against many symptoms such a fevers. Evbuomwan IO & al. investigated the potential of an extract of its stem bark against experimental malaria in mice. Their article, Aqueous Extract of Enantia chlorantha Oliv. Demonstrates Antimalarial Activity and Improves Redox Imbalance and Biochemical Alterations in Mice, BMC Complement Med Ther, 2025 Feb 24; 25:73, https://doi.org/10.1186/s12906-025-04745-w reports that the extract “inhibited parasitaemia dose-dependently…” In addition, the article describes anti-oxidant and anti-inflammatory effects as well.
Chike-Ekwughe A & al. studied another plant in Nigeria, Irvingia wombolu, which has edible seeds but whose bark is also used in folk medicine against malaria. The paper, Molecular Modeling of the Interactions of Compounds of Irvingia wombolu Against Dihydrofolate Reductase-Thymidylate Synthase in Plasmodium falciparum Towards Development of Anti-Malarial Drug, In Silico Pharmacol. 2025 Feb 19; 13:31, https://doi.org/10.1007/s40203-025-00317-5, describes the results in the laboratory of extract of this plant against a P. falciparum enzyme that is a target of antimalarial drugs. The authors consider their results to be promising toward development of drug(s) based on the extract of Ir. wombolu.
Other
Sundamaran SA & al., Prodrug Activation in Malaria Parasites Mediated by an Imported Erythrocyte Esterase, Acylpeptide Hydrolase (APEH), Proc Nat Acad Sci, 2025 Mar 4, 122 (10) e2417682122, https://doi.org/10.1073/pnas.2417682122 is a basic science paper that may have profound implications in overcoming drug resistance by the malaria parasite. “Rising antimalarial drug resistance threatens current gains in malaria control. New antimalarial drugs are urgently needed. Unfortunately, many drug candidates have undesirable drug-like properties, such as poor absorbability in the gastrointestinal tract or poor accumulation at the site of action. This can be overcome using a prodrug approach, the addition of promoieties which mask undesirable drug features until they are removed by an activating enzyme. Here, [the authors] show that a red blood cell enzyme, acylpeptide hydrolase (APEH), is taken up by malaria parasites and serves as the activating enzyme for multiple lipophilic ester prodrugs. [Their] findings highlight a mechanism for prodrug activation, which could be leveraged to design future prodrugs with high barriers to drug resistance.
Campaigns and Policies
Smith JL & al. carried out a “controlled intervention study … in farming and cattle herding populations in northern Namibia to evaluate the impact of a targeted malaria intervention package.” The reasons for the campaign in a low endemic area were “workers’ high mobility, low intervention coverage and occupational exposures … eligible individuals within worksites in intervention areas received targeted drug administration with artemether-lumefantrine, mop-up indoor residual spraying and long-lasting insecticidal nets, combined with distribution of topical repellent.” The authors report in Targeting Malaria in High-Risk Populations in Low Endemic Regions in Northern Namibia: A Quasi-Experimental Controlled Trial to Reduce Malaria in Seasonal Agricultural Workers and Cattle Herders, BMJ Glob Health. 2025 Feb 17; 10(2):e015565, https://doi.org/10.1136/bmjgh-2024-015565 that “[d]elivery of a single intervention round was associated with a reduction in the prevalence of malaria … Coverage of at least one intervention increased … among the target population in intervention compared with control areas.”
According to Diallo OO & al., “Guinea’s national malaria programme adopted an innovative subnational tailoring (SNT) approach, including engagement of stakeholders, data review, and data analytics, to update their malaria operational plan for 2024–2026 and identify the most appropriate interventions for each district considering the resources available.” As described in Subnational Tailoring of Malaria Interventions to Prioritize the Malaria Response in Guinea, Malaria J, 2025 Feb 25, 24:62, https://doi.org/10.1186/s12936-025-05302-z, “[m]alaria incidence, malaria prevalence, and all-cause under-5 mortality were used for … epidemiological stratification…. Additional indicators relevant for decision-making include[ed] seasonality patterns, insecticide resistance, historical malaria interventions and vaccine coverage were also stratified. Stratified layers were used to inform the targeting criteria for each intervention to identify districts to prioritize for indoor residual spray, dual-action insecticide-treated nets, seasonal malaria chemoprevention (SMC), including number of cycles for each eligible district, malaria vaccine, and perennial malaria chemoprevention.” The data were used to secure funding from The Global Fund.
Epidemiology
Climate change, biodiversity and environment
Githinji E & al. investigated “the impact of water harvesting, sugarcane farming, and mining activities on Plasmodium falciparum positivity rates and parasitemia densities in five selected sites” in Kenya. “The study had five different arms of investigation; the first arm was the control (C), second dam (D) site, third sugarcane (S) site, fourth mining (M) site, and fifth dam-sugarcane-mining (DMS) site.” Each site had 1025 consenting participants. The authors report in Impact of Titanium Mining and Other Anthropogenic Activities on Malaria Positivity Rates and Parasitemia in Five Selected Study Sites in Msambweni Subcounty, Kwale County, Kenya, J Parasitol Res. 2025 Feb 5; 2025:6967797, https://doi.org/10.1155/japr/6967797 that working in DMS site was most conducive to becoming infected by P. falciparum, followed by the S site. The authors conclude that “[m]alaria vector and human host interactions are often enhanced by suitable environmental conditions especially ambient temperature which accelerate parasite growth in the mosquito and humidity. Anthropogenic activities may open up new breeding sites for the vector or increase human-Anopheles infective contact hours, hence the different positivity rates and intensities in P. falciparum transmission.”
Lyimo E & al., Changing Plasmodium falciparum Malaria Prevalence in Two Villages of Northeastern Tanzania Between 2003 and 2021 in Relation to Vectors, Interventions and Climatic Factors, Malaria J, 2025 Mar 3, 24:68, https://doi.org/10.1186/s12936-025-05311-y is a longitudinal study of malaria prevalence in the two villages. Malaria prevalence in [the two villages] dropped from ~ 25% and ~ 80% to 0% and 1%, respectively, between 2003 and 2011, reaching 0% in both villages by 2014. This decline was associated with increased bed net use and reduced exposure to Anopheles bites. However, between 2018 and 2021, prevalence resurged, with [one of the villages] reaching 2003–2004 levels despite high bed net use. Between 2003 and 2021 there was an increasing trend in average monthly maximum temperatures …, and precipitation … as well as minimum relative humidity …, while maximum relative humidity slightly decreased. Furthermore, during 2003–2011, malaria prevalence was positively associated with temperature, maximum temperature, and relative humidity, while precipitation showed a negative association …. Between 2012–2021, all climatic factors, including temperature …, maximum temperature …, relative humidity …, and precipitation …, showed positive associations.”
Risk factors
Migrant workers in Africa have been found to be at increased risk of malaria in the past. Su Q & al. studied a special population, expatriates from China who work on economic and infrastructure projects in South Sudan. In a questionnaire-based study of 402 expats, who had never had malaria before their journey to Africa, 166 (41%) were found to have suffered malaria in country. In answering questions that sought evidence of knowledge about malaria, how it is transmitted and recognized, there was great variability among the respondents, ranging from 19% correct responses to close to 100%. Statistically, the authors detected a correlation between “Knowledge Scores” and “Practice Scores.” The paper is Survey on Knowledge, Attitudes and Practices (KAP) of Malaria Prevention and Control Among Chinese Expatriates in South Sudan, J Health Popul Nutr. 2025 Feb 28; 44(1):52, https://doi.org/10.1186/s41043-025-00737-1
Although not focused on malaria exclusively, Aremu DO & al., The Interplay of Socio-Demographic Factors and Disease Prevalence: Insights into Malaria, Hepatitis B, and Hepatitis C in Lafia, Nasarawa State, Nigeria, J Health Popul Nutr. 2025 Mar 6; 44:67, https://doi.org/10.1186/s41043-025-00779-5 reports the following correlations: A “negative correlation between male sex and malaria infection … a negative correlation between the use of mosquito nets and malaria infection … [and] higher income levels correlated with reduced mosquito net usage.”
General epidemiology
In a computer-based modeling study of a society like Zambia, Chiziba C & al., Advancing Malaria Reactive Case Detection in a Zambia-Like Setting: A Modeling Study, PLOS Glob Public Health. 2025 Feb 20; 5(2):e0004288, https://doi.org/10.1371/journal.pgph.0004288 “assessed the impact of potential improvement measures designed to address the identified operational challenges affecting RCD [Reactive Case Detection]. Improvement measures included increasing CHWs [Community Heath OWrkers], adjusting response times, improving RDT sensitivity, and incorporating focal mass drug administration (fMDA). A shortage of CHWs and limited availability of RDTs have the most negative impact on RCD’s ability to reduce cases. In scenarios where CHWs or RDT availability for RCD were reduced by 50%, annual cases increased by approximately 22%. Only the incorporation of fMDA as an improvement measure succeeded countering the situation, resulting in a 43% reduction. Increasing CHWs to offset RCD inefficiencies caused by limited RDT sensitivity and difficulties finding individuals reduced cases by approximately 13 and 14%, respectively…”
Weiss DJ & al., Mapping the Global Prevalence, Incidence, and Mortality of Plasmodium falciparum and Plasmodium vivax Malaria, 2000-22: A Spatial and Temporal Modelling Study, Lancet. 2025 Mar 5: S0140-6736(25)00038-8, https://doi.org/10.1016/s0140-6736(25)00038-8 illustrates on a global scale what has already been reported. After great improvement in malaria morbidity and mortality world-wide, the years 2020 to 2022 witness retrogression, at least in part related to the COVID pandemic.
Using genetic analysis of a particular parasite enzyme, Ashagre A & al. demonstrate in their paprr, Plasmodium falciparum Merozoite Surface Protein 2 Genetic Polymorphism and Multiplicity of Infection in Selected Malarious Areas of Northwest Ethiopia, BMC Infect Dis. 2025 Feb 26;25(1):282 https://doi.org/10.1186/s12879-025-10676-1 that many patents’ malaria are in fact the result of being infected multiple times. The authors conclude that “[m]ost patients contained multiple infections, and the mean multiplicity of infection was 3.46. There was no statistically significant difference in the multiplicity of infection in relation to the age of patients …) However, a statistically significant correlation was found between parasite density and the multiplicity of infection…” and surmise that this “genetic variability could complicate malaria treatment and control efforts, as it can facilitate the emergence and spread of drug-resistant strains.”
Akowe E & al. call attention to the fact that there are several ways of acquiring malaria other than through mosquito bite. As a result of their study, A Novel Malaria Mathematical Model: Integrating Vector and Non-Vector Transmission Pathways, BMC Infect Dis. 2025 Mar 6; 25(1):322, https://doi.org/10.1186/s12879-025-10653-8 the potentially significant risk of transmission through blood transfusion is highlighted, especially in an environment where malaria testing of donors is not universal and/or the skills of microscopists are variable.
Spatiotemporal studies
Animut Y & al., Spatial Distribution of Malaria Among Under-Five Children and Associated Factors in Tanzania: A Spatial and Multilevel Analysis, Malaria J, 2025 Mar 15, 24:86, https://doi.org/10.1186/s12936-025-05313-w