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By Dr. Derick Pasternak, Ambassador, Malaria Science & Research Coordinator, MPI

On 10 May, the WHO Weekly Epidemiological Record (99:225-48, www.who.int/wer) published its bilingual updated Malaria Vaccines: Position Paper, which supersedes a similarly titled document published in 2022. “It includes the updated WHO recommendations on the use of the RTS,S/AS01 and R21/Matrix-M vaccines for the reduction of malaria morbidity and mortality in children living in endemic areas, prioritizing areas of moderate and high malaria transmission. It also incorporates findings from the evaluation of the WHO-coordinated Malaria Vaccine Implementation Programme (MVIP), through which the RTS,S/AS01 vaccine was introduced in routine immunization programmes through large pilot programmes from 2019 through to 2023 in Ghana, Kenya and Malawi”

The position paper then discusses various preventive strategies utililized as well as WHO’s recommendations for use of the two endorsed vaccines, RTS,S/AS01 and R21/Matirx-M.
The full text is available from the reviewer.

News release from the Harvard T.H. Chan School of Public Health, 14 May: https://www.hsph.harvard.edu/news/hsph-in-the-news
Dyann Wirth of Harvard T.H. Chan School of Public Health has received a top award from the Multilateral Initiative on Malaria (MIM) Society for playing a pivotal role in the global fight against malaria.
Wirth, Richard Pearson Strong Professor of Infectious Diseases, received an Ogobara Doumbo MIM Award for Lifetime Achievements in Malaria Research and Capacity Building. The award was presented at the 8th Pan-African Malaria Conference, held in Kigali, Rwanda in late April.

Press release by WHO on 24 May on its website:

“UNICEF delivered over 43 000 doses of the R21/Matrix-M malaria vaccine by air to Bangui, Central African Republic, today, with more than 120 000 doses to follow in the next days. It is the first country to receive the R21 malaria vaccine for use in routine childhood immunization, marking another step forward in preventing the disease and saving children’s lives.

R21 is the second malaria vaccine to be recommended by WHO for children living in endemic areas. Along with the earlier WHO recommendation of the RTS,S vaccine, there is now sufficient vaccine supply to scale up malaria vaccination in Africa. The rollout of both vaccines is funded by Gavi, the Vaccine Alliance…

The R21 and RTS,S vaccines are proven safe and effective in preventing malaria in children. The RTS,S vaccine was delivered to more than 2 million children in Ghana, Kenya, and Malawi in a four-year pilot programme that demonstrated a 13% reduction in all-cause mortality…

The Central African Republic has one of the highest rates of malaria incidence globally. In 2022, an estimated 1 733 000 malaria cases were reported in the country, averaging about 4747 cases a day. The disease also claimed around 5180 lives over the year, or 14 deaths each day…

Central African Republic, along with Chad, Cote d’Ivoire, Democratic Republic of Congo, Mozambique, Nigeria, South Sudan, and Uganda, are preparing to receive R21 shipments.

Around 4.33 million doses of RTS,S have been delivered to 8 countries so far – Benin, Burkina Faso, Cameroon, Ghana, Kenya, Liberia, Malawi, and Sierra Leone – that are offering the vaccine in their routine child immunization programmes as part of national malaria control plans. Burundi and Niger are next on the list for RTS,S shipments.

UNICEF reported on its website on 31 May that “[i]n a historic step towards safeguarding children’s lives and alleviating the high incidence of malaria in the country, the first consignment of the R21 malaria vaccine arrived in Juba {South Sudan} today. The Ministry of Health received over 645,000 doses, which will be distributed to 28 counties with the highest malaria burden as plans continue to scale up nationwide…”

PEER REVIEWED ARTICLES (see notes after citations from non-peer-reviewed publications)

Prevention

Vaccines

“The World Health Organization novel malaria vaccine for at-risk children has the potential to greatly reduce the current malaria burden in sub-Saharan Africa. However, most studies have reported contradictory findings regarding community willingness for the vaccine, which could easily undermine the expected benefits of the vaccine.” Kigongo E & al. announce a study to be performed, Community Readiness and Acceptance for the Implementation of a Novel Malaria Vaccine Among At-Risk Children in Sub-Saharan Africa: A Systematic Review Protocol, Malaria J, 2024 Jun10, 23:182, https://doi.org/10.1186/s12936-024-04995-y, “to ascertain the current state of community readiness and acceptance for the implementation of a novel malaria vaccine (RTS,S/ASO1) among at-risk children in sub-Saharan Africa,” and describe the method to be used.

“In the last 2 years, the first and second malaria vaccines, both targeting Plasmodium falciparum circumsporozoite proteins (PfCSP), have been recommended by the World Health Organization to prevent P. falciparum malaria in children living in moderate to high transmission areas.” Miura K & al., Vaccines and Monoclonal Antibodies: New Tools for Malaria Control, Clin Microbiol Rev. 2024 Jun 13; 37(2):e0007123, https://doi.org/10.1128/cmr.00071-23 “summarizes the development of the anti-PfCSP vaccines and mAbs {monoclonal antibodies}, and recent topics in the blood- and transmission-blocking-stage vaccine candidates and mAbs. [The authors] further discuss issues of the current vaccines and the directions for the development of next-generation vaccines.”

In yet another review of anti-malaria vaccination programs, Olawade DB & al., Malaria Vaccination in Africa: A Mini-Review of Challenges and Opportunities, Medicine (Baltimore). 2024 Jun 14; 103(24):e38565, https://doi.org/10.1097/md.0000000000038565 recounts successes and travails in a journal aimed at practicing physicians in the United States.

Abuelazm MT & al., Protective Efficacy and Safety of Radiation-Attenuated and Chemo-Attenuated Plasmodium falciparum Sporozoite Vaccines Against Controlled and Natural Malaria Infection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, Infection. 2024 Jun; 52(3):707-722, https://doi.org/10.1007/s15010-024-02174-4 is an article that reviews 19 case controlled studies of two types of attenuated whole sporozoite vaccines administered to human volunteers, who were then infected with chloroquine sensitive laboratory-reared Plasmodium falciparum. The 19 studies were culled from 90 articles that received full text review.  The Abstract concludes that both types of vaccines were reported to be equally efficacious. {The review of the article itself, however, yields the following information that may limit the validity of its sources’ conclusions: 1) The article, but not the abstract, calls the results with the chemically attenuated vaccine relying on “poor quality evidence.” 2) The authors “observed that all the studies had authors from Sanaria (a company in Rockville, MD, that manufactures both types of vaccines); hence, they all considered high risk in the ‘other bias domain’”.}

“Immunization through repeated direct venous inoculation of Plasmodium falciparum (Pf) sporozoites (PfSPZ) under chloroquine chemoprophylaxis, using the PfSPZ Chemoprophylaxis Vaccine (PfSPZ-CVac), induces high-level protection against controlled human malaria infection (CHMI). Humoral and cellular immunity contribute to vaccine efficacy but only limited information about the implicated Pf-specific antigens is available.” Wistuba-Hamprecht J & al., Machine Learning Prediction of Malaria Vaccine Efficacy Based on Antibody Profiles, PLoS Comput Biol. 2024 Jun 7; 20(6):e1012131, https://doi.org/10.1371/journal.pcbi.1012131 is a report of studies of individual antibody profiles in experimental subjects.  These profiles are said to allow predictions on the efficacy of malaria vaccines.

Not all vaccine preparations are successful in preventing malaria. The preparation used by Friedman-Klabanoff DJ & al. and reported in Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted with Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing with Malaria Challenge, J Infect Dis. 2024 Jun 14; 229(6):1883-1893, https://doi.org/10.1093/infdis/jiae062 was shown to be safe in a Phase 1 study, but “[a]ll 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks.”

“A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant…” Silk AE & al., Blood-Stage Malaria Vaccine Candidate RH5.1/Matrix-M in Healthy Tanzanian Adults and Children; an Open-Label, Non-Randomised, First-in-Human, Single-Centre, Phase 1b Trial, Lancet Infect Dis, 2024 Jun 13, https://doi.org/10.1016/S1473-3099(24)00312-8 reports that in “a non-randomised, phase 1b, single-centre” study of 12 adults and 48 children aged 5 to 17 months, they gave three inoculations of the vaccine at various time intervals and doses.  They then studied antibodies and cellular immunity that developed in the test subjects.  In this aspect, each group studied demonstrated “reactogenicity.”  Whereas there were “five serious adverse events involving four child participants during the trial, none … were deemed related to vaccination.”

Although the primary thrust of Zhang B & al., Evaluation of Transmission-Blocking Potential of PvPSOP25 Using Transgenic Murine Malaria Parasite and Clinical Isolates, PLoS Negl Trop Dis. 2024 Jun 12; 18(6):e0012231, https://doi.org/10.1371/journal.pntd.0012231 is toward validation of a laboratory method to evaluate the effectiveness of a P. vivax transmission blocking vaccine, it is included here to call attention to parallel efforts to develop vaccine(s) against P. vivax, which is of great importance in the Horn of Africa and Ethiopia.

Vectors

Takken W & al., The Behaviour of Adult Anopheles gambiae, Sub-Saharan Africa’s Principal Malaria Vector, and Its Relevance to Malaria Control: A Review, Malaria J, 2024 May 23, 23:161, https://doi.org/10.1186/s12936-024-04982-3 reviews the life cycle and habits of the most prevalent spreader of Plasmodium falciparum in Africa and concludes that while “traditional interventions, using insecticides, target mosquitoes indoors, additional protection can be achieved using spatial repellents outdoors, attractant traps or house modifications [may] prevent mosquito entry. Future research on the variability of species-specific behaviour, movement of mosquitoes across the landscape, the importance of light and vision, reproductive barriers to gene flow, male mosquito behaviour and evolutionary changes in mosquito behaviour could lead to an improvement in malaria surveillance and better methods of control reducing the current over-reliance on the indoor application of insecticides.”

Mapua SA & al. investigated the various species that are vectors of malaria in Tanzania. In a study of mosquitoes “collected inside homes in 12 regions across Tanzania between 2018 and 2022, they report in Entomological Survey of Sibling Species in the Anopheles funestus Group in Tanzania Confirms the Role of Anopheles parensis as a Secondary Malaria Vector, Parasit Vectors. 2024 Jun 17; 17(1):261, https://doi.org/10.1186/s13071-024-06348-9 that whereas “An. funestus s.s. is the dominant malaria vector in the Funestus group in Tanzania, this survey confirms the occurrence of Plasmodium-infected An. parensis, an observation previously made in at least two other occasions in the country.”

The abstract of Waymire E & al., A Decade of Invasive Anopheles stephensi Sequence-Based Identification: Toward A Global Standard, Trends Parasitol,  2024 May 15: S1471-4922(24)00094-1, https://doi.org/10.1016/j.pt.2024.04.012 reads in its entirety as follows: “Anopheles stephensi is an invasive malaria vector in Africa that has been implicated in malaria outbreaks in the Horn of Africa. In 10 years, it has been detected as far east as Djibouti and as far west as Ghana. Early detections were mostly incidental, but now active surveillance in Africa has been updated to include An. stephensi. Morphological identification of An. stephensi from native vectors can be challenging, thus, sequence-based assays have been used to confirm identification during initial detections. Methods of sequence-based identification of An. stephensi have varied across initial detections to date. Here, we summarize initial detections, make suggestions that could provide a standardized approach, and discuss how sequences can inform additional genomic studies beyond species identification.”

Osborne A & Bangura C studied the prevalence of insecticide-treated net (ITN) use among 900 pregnant women in Sierra Leone. Their paper, Predictors of Insecticide-Treated Bed Nets Use Among Pregnant Women in Sierra Leone: Evidence from the 2019 Sierra Leone Demographic Health Survey, Malaria J, 2024 Jun 19, 23:193, https://doi.org/10.1186/s12936-024-05018-6, reports that educated women, those living in the East of the country, Christians, women with five or more children, and those married and living in male head of household families were more likely to use ITNs than their counterparts.  The very last statistic seems inconsistent with some other published reports.

“Mosquito nets, particularly insecticide-treated nets {ITNs}, are the most recommended method of malaria control in endemic countries. However, individuals do not always have access to insecticide-treated nets or use them as recommended.” Ladu HI & al., Reasons for Mosquito Net Non-Use in Malaria-Endemic Countries: A Review of Qualitative Research Published Between 2011 and 2021, Trop Med Int Health. 2024 May 25, https://doi.org/10.1111/tmi.14006 is a review of papers published on the subject over ten years.  The article mostly concerns itself with the quality of the articles and concludes that reasons for non-use have not changed over ten years. The article (not the abstract) lists these: Human factors (response efficacy, discomfort, mosquito density, prioritizing nets, net repurpose, socio-cultural beliefs and practices), net factors (net materials, net setup), house structure, and net access (distribution practices, net cost).

Building on previously reported studies, (e.g. Accrombessi M & al., BMC Infect Dis. 2021; 21: 194.  doi: 10.1186/s12879-021-05879-1), Accrombessi M & al., Effectiveness of Pyriproxyfen-Pyrethroid and Chlorfenapyr-Pyrethroid Long-Lasting Insecticidal Nets (LLINs) Compared with Pyrethroid-Only LLINs for Malaria Control in the Third Year Post-Distribution: A Secondary Analysis of a Cluster-Randomised Controlled Trial in Benin, Lancet Infect Dis. 2024 Jun; 24(6):619-628, https://doi.org/10.1016/s1473-3099(24)00002-1 reports greatly diminished utilization of all LLINs in their third year after distribution and also that the two two-insecticide impregnated nets were no more effective in preventing malaria than nets that were impregnated by pyrethroid only.

Okiring J & al., LLIN Evaluation in Uganda Project (LLINEUP): Modelling the Impact of COVID-19-Related Disruptions on Delivery of Long-Lasting Insecticidal Nets on Malaria Indicators in Uganda, Malaria J, 2024 Jun 6, 23:180, https://doi.org/10.1186/s12936-024-05008-8 “suggests” that “the disruptions in the 2020–2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.” They come to this conclusion by using a model that used data “on the planned LLIN distribution schedule for 2020–2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017–2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN dstributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned… After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected.”

Durability and efficacy of ITNs is the subject of Raharintjatovo J & al., Physical and Insecticidal Durability of Interceptor®, Interceptor® G2, and Permanet® 3.0 Insecticide-Treated Nets in Burkina Faso: Results of Durability Monitoring in Three Sites from 2019 to 2022, Malaria J, 2024 Jun 4, 23:173, https://doi.org/10.1186/s12936-024-04989-w. Whereas the Permanet brand lasted longer than the other two, its residual efficacy at the end of its useful life was inferior to that of the other two nets studied, though they also had lost significant potency. The authors conclude that “[s]ignificant decreases in chemical content and resulting impact on bioefficacy warrant more research in other countries to better understand dual AI {active ingredient} ITN insecticidal performance.”

Progress in malaria control in Côte d’Ivoire “is threatened by insecticide resistance and behavioral changes in Anopheles gambiae sensu lato (s.l.) populations and residual malaria transmission, and complementary tools are required.” Tia J-PB & al., Combined Use of Long-Lasting Insecticidal Nets and Bacillus thuringiensis israelensis Larviciding, A Promising Integrated Approach Against Malaria Transmission in Northern Côte d’Ivoire, Malaria J, 2024 May 29, 23:168, https://doi.org/10.1186/s12936-024-04953-8 is a report on the efficacy of the combined use of long-lasting insecticidal nets (LLINs) and Bacillus thuringiensis israelensis (Bti), in comparison with LLINs alone. End points included larval densities, mosquito biting rates, and the incidence of malaria. In all instances the combination resulted in increasing suppression than by LLINs alone.

“Ivermectin (IVM) … is toxic on vectors feeding on treated humans or cattle.” That led Hamid-Adiamoh M & al. to speculate “whether IVM may have a direct mosquitocidal effect when applied on bed nets or sprayed walls.” As they report in Mosquitocidal Effect of Ivermectin-Treated Nettings and Sprayed Walls on Anopheles gambiae s.s. Sci Rep. 2024 Jun 1; 14(1):12620, https://doi.org/10.1038/s41598-024-63389-x, they performed experiments, exploring the effects of ivermectin impregnated nets and walls sprayed with ivermectin on laboratory-reared mosquitoes known to be vectors of malaria.  Their “results showed a direct mosquitocidal effect of IVM on this mosquito strain as all mosquitoes died by 24 h after exposure to IVM. The effect was slower on the IVM-sprayed walls compared to the treated nettings.” They conclude that “[f]Further work to evaluate possibility of IVM as a new insecticide formulation in LLINs and IRS will be required.”

The effect of improved housing on malaria rates is studied by Gonahasa S & al. They define improved as having “synthetic walls and roofs, eaves closed or absent.” Analyzing data of close to 4893 children from 3518 houses of which 1389 were “improved,” their paper, LLIN Evaluation in Uganda Project (LLINEUP2): Association Between Housing Construction and Malaria Burden in 32 Districts, Malaria J, 2024 Jun 17, 23:190, https://doi.org/10.1186/s12936-024-05012-y reports that “[c]hildren living in improved houses had 58% lower odds … of parasitaemia than children living in less-improved houses. Communities with > 67% of houses improved had a 63% lower parasite prevalence … and 60% lower malaria incidence … compared to communities with < 39% of houses improved.” They conclude that “[i]mproved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control.”

Chen CY & Oliver SV, The Effect of Larval Exposure to Acids and Detergents on the Life History of the Major Malaria Vector Anopheles arabiensis Patton (Diptera: Culicidae), Pest Manag Sci. 2024 May 27, https://doi.org/10.1002/ps.8189 demonstrates that the various polluting acids and bases that find their way into urban standing water have significant effect on the larval development of An. arabiensis, which is a malaria vector that bites outdoors and is therefore not much affected by indoor preventive methods such as LLINs and IRS.

“Anopheles mosquito resistance to insecticide remains a serious threat to malaria vector control affecting several sub-Sahara African countries, including Côte d’Ivoire, where high pyrethroid, carbamate and organophosphate resistance have been reported.” Ekra AK & al. tested clothianidin (a neonicotinoid) and chlorfenapyr (a pyrrole) “against the field-collected Anopheles gambiae populations from [three provinces] using the WHO standard insecticide susceptibility biossays.” They conclude in Can Neonicotinoid and Pyrrole Insecticides Manage Malaria Vector Resistance in High Pyrethroid Resistance Areas in Côte d’Ivoire? Malaria J, 2024 May 23, 23:160, https://doi.org/10.1186/s12936-024-04917-y that “clothianidin and chlorfenapyr insecticides induce high mortality in the natural and pyrethroid-resistant An. gambiae populations in Côte d’Ivoire. These results could support a resistance management plan by proposing an insecticide rotation strategy for vector control interventions.”

To judge by the frequency of articles published on the subject, there appears to be increasing recognition of the genetic background of insecticide resistance. Odero JO & al. report in Genetic Markers Associated with the Widespread Insecticide Resistance in Malaria Vector Anopheles funestus Populations Across Tanzania, Parasit Vectors. 2024 May 17; 17(1):230, https://doi.org/10.1186/s13071-024-06315-4 that “[p]yrethroid resistance was universal but reversible by piperonyl-butoxide (PBO). However, carbamate resistance was observed in only five of the nine districts, and dichloro-diphenyl-trichloroethane (DDT) resistance was found only in [one]. Conversely, there was universal susceptibility to the organophosphate pirimiphos-methyl in all sites. Genetic markers of resistance had distinct geographical patterns… Since this was the first large-scale survey of resistance in Tanzania’s An. funestus, [the authors] recommend regular updates with greater geographical and temporal coverage.”

In a review of 174 relevant artiocles in the literature, Wangrawa DW & al. found “that An. funestus was increasingly resistant to the four classes of insecticides recommended by the World Health Organisation for malaria vector control; however, this varied by country. Insecticide resistance appears to reduce the effectiveness of vector control methods, particularly IRS and ITN.” Their article, Distribution and Insecticide Resistance Profile of the Major Malaria Vector Anopheles funestus Group Across the African Continent, Med Vet Entomol. 2024 Jun; 38(2):119-137, https://doi.org/10.1111/mve.12706, also states that while “An. funestus has shown resistance to the recommended insecticide classes, notably pyrethroids and, in some cases, organochlorides and carbamates, it remains susceptible to other classes of insecticides such as organophosphates and neonicotinoids, providing potential alternative options for vector control strategies.”

There is a definite increase in articles that report on the application of artificial intelligence to the science of parasitology.  In the sphere of vector control, Ibrahim EA & al., Spatio-Temporal Characterization of Phenotypic Resistance in Malaria Vector Species, BMC Biol. 2024 May 20; 22(1):117, https://doi.org/10.1186/s12915-024-01915-z reports on the use of the “cellular automata (CA)” model, which, according to the authors, “introduces a dynamic spatio-temporal approach to characterize phenotypic resistance in Anopheles gambiae complex and Anopheles arabiensis.” They applied the model to data from five sub-Saharan African countries and conclude that the “CA model demonstrated robustness in capturing the spatio-temporal dynamics of confirmed IR {insecticide resistance} states in the vector populations. In [their] model, the key driving factors included insecticide usage, agricultural activities, human population density, Land Use and Land Cover (LULC) characteristics, and environmental variables.”

“The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role.” Mwaanga G & al., Residual Bioefficacy of Attractive Targeted Sugar Bait Stations Targeting Malaria Vectors During Seasonal Deployment in Western Province of Zambia, Malaria J, 2024 May 29, 23:269, https://doi.org/10.1186/s12936-024-04990-3 reports the examination of efficacy of deployed sugar bait stations for lethality.  The testing was done under laboratory conditions.  It resulted in overall mortality of over 80% of all mosquitoes, males more than females.

Controlling mosquito larvae by promoting the population of insects that prey on them is the subject of Onen H & al., A Review of Applications and Limitations of Using Aquatic Macroinvertebrate Predators for Biocontrol of the African Malaria Mosquito, Anopheles gambiae sensu lato, Parasit Vectors. 2024 Jun 12; 17(1):257, https://doi.org/10.1186/s13071-024-06332-3. The authors “reviewed the literature on the use of aquatic macroinvertebrate predators for biocontrol of malaria vectors from the An. gambiae s.l. complex. The available information from laboratory and semi-field studies has shown that aquatic macroinvertebrates have the potential to consume large numbers of mosquito larvae and could thus offer an additional approaches in integrated malaria vector management strategies. The growing number of semi-field structures available in East and West Africa provides an opportunity to conduct ecological experimental studies to reconsider the potential of using aquatic macroinvertebrate predators as a biocontrol tool.”

While there remain ethical controversies about the implementation of gene drive to alter a whole species, the technique seems to be favored when applied to mosquitoes that are vectors of infectious diseases. Connolly JB & al. discuss the “use of low-threshold gene drive in Anopheles vector species, where a ‘causal pathway’ would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence.” They state in Considerations for First Field Trials of Low-Threshold Gene Drive for Malaria Vector Control, Malaria J, 2024 May 22, 23:156, https://doi.org/10.1186/s12936-024-04952-9 that “the considerations here advance the realization of developer ambitions for the first field trials of low-threshold gene drive for malaria vector control within the next 5 years.”

Although the primary thrust of Myers A & al., Identifying Suitable Methods for Evaluating the Sterilizing Effects of Pyriproxyfen on Adult Malaria Vectors: A Comparison of the Oviposition and Ovary Dissection Methods, Malaria J, 2024 May 24, 23:164, https://doi.org/10.1186/s12936-024-04983-2 has to do with methods of testing mosquitoes for sterility, the article is included here, because the substance used to impregnate treated nets is not an insecticide, but one that interrupts insect growth from sterility to maturation. Thus, if pyriproxyfen is added to insecticides, the net will have long range effects on those mosquitoes that survive.

Chemoprophylaxis

Huang S & al. assert that “[w]hile the overall population-level impact of seasonal malaria chemoprevention [SMC] on malaria control has been documented in various countries and time periods, there is no clear evidence regarding [SMC] impact based on the number of medicine doses children receive in one cycle in routine programmatic conditions. They report the results of data analysis “from Nigeria’s routinely collected seasonal malaria chemoprevention end-of-round coverage surveys (2021, 2022)” in Impact of Seasonal Malaria Chemoprevention Based on the Number of Medicines Doses Received on Malaria Burden Among Children Aged 3-59 Months in Nigeria: A Propensity Score-Matched Analysis, Trop Med Int Health. 2024 Jun 6, https://doi.org/10.1111/tmi.14019 and conclude that “[a]dherence to at least one daily dose of amodiaquine administration following receipt of Day 1 sulfadoxine-pyrimethamine plus amodiaquine by eligible children is crucial to ensure the effectiveness” of SMC.

Mousa A & al. “apply a novel modelling approach to aid the design and analysis of chemoprevention trials and generate measures of protection that can be applied across a range of transmission settings” Using their analysis, they found that a “single-arm trial with an extended follow-up (>42 days), which allows measurement of the underlying infection risk after drug   currently recommended 28-day follow-up in a single-arm trial results in low precision of estimated 30-day chemoprevention efficacy and low power in determining genotype differences of 12 days in the duration of protection (power = 1.4%). Extending follow-up to 42 days increased precision and power (71.5%) in settings with constant transmission over this time period.” The article is  Measuring Protective Efficacy and Quantifying the Impact of Drug Resistance: A Novel Malaria Chemoprevention Trial Design and Methodology, PLoS Med. 2024 May 9; 21(5):e1004376, https://doi.org/10.1371/journal.pmed.1004376.

Replacing seasonal malaria chemoprevention (SMC) with perennial chemoprevention (PMC) for children is the topic of Birane Faye SL & al., Field Testing of User-Friendly Perennial Malaria Chemoprevention Packaging in Benin, Côte d’Ivoire and Mozambique, Malaria J, 2024 May 21, 23:157, https://doi.org/10.1186/s12936-024-04977-0. Their study involved focus group discussions and interviews. They noted that caregivers appreciated the trusted status of community health workers (CHWs) in the community, “whereas health authorities preferred clinic-based deployment of PMC by health professionals. Empirical testing of the prototype blister packs, dispensing boxes and job aids highlighted the context-specific expectations of respondents, such as familiar situations and equipment, and identified areas of confusion or low acceptance. A key finding was the need for a clear product identity reflecting malaria.”

“In 2022 the WHO recommended the discretionary expansion of the eligible age range for seasonal malaria chemoprevention (SMC) to children older than 4 years. Older children are at lower risk of clinical disease and severe malaria so there has been uncertainty about the cost-benefit for national control programmes. However, emerging evidence from laboratory studies suggests protecting school-age children reduces the infectious reservoir for malaria and may significantly impact on transmission. [Soremekun S & al.] aimed to assess whether these effects were detectable in the context of a routinely delivered SMC programme.” In 2021, The Gambia extended the maximum eligible age for SMC from 4 to 9 years.  Using “a household-level mixed modelling approach to quantify impacts of SMC on malaria transmission… [the authors] demonstrate that the hazard of clinical malaria in older participants aged 10+ years ineligible for SMC decreases by 20% for each additional SMC round per child 0-9 years in the same household.” The article is Household-Level Effects of Seasonal Malaria Chemoprevention in The Gambia, Commun Med (Lond). 2024 May 22; 4(1):97, https://doi.org/10.1038/s43856-024-00503-0.

“Women in malaria-endemic areas receive sulfadoxine-pyrimethamine (SP) as Intermittent Preventive Treatment in Pregnancy (IPTp) to reduce malaria. While dihydroartemisinin-piperaquine (DP) has superior antimalarial properties as IPTp, SP is associated with superior fetal growth. As maternal inflammation influences fetal growth, [Cheng K & al.] investigated whether SP alters the relationship between inflammation and birth outcomes. Whereas the authors claim that they have uncovered “modulation” of relationship between immunologic markers in the mother and adqverse birth outcomes, Intermittent Preventive Treatment with Sulphadoxine-Pyrimethamine but not Dihydroartemisinin- Modulates the Relationship Between Inflammatory Markers and Adverse Pregnancy Outcomes in Malawi, PLOS Glob Public Health. 2024 May 16; 4(5):e0003198, https://doi.org/10.1371/journal.pgph.0003198 does not provide evidence on how this modulation affects the birth outcome.

“Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria.” VonWowern F & al. explored “whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in P. falciparum genes associated with resistance in children in seven schools in [Northeast] Tanzania.” Lack of Selection of Antimalarial Drug Resistance Markers After Intermittent Preventive Treatment of Schoolchildren (IPTsc) Against Malaria in Northeastern Tanzania, Int J Infect Dis. 2024 Jun 12: 107102, https://doi.org/10.1016/j.ijid.2024.107102. When they tested the children’s blood for residual P. falciparum, they found that virtually all of the ones that had been positive before IPTsc were also positive afterwards.  However, this was not a study of the effectiveness of ITPsc, but of whether there was any shift toward genetic markers of resistance; there was none.

Other

In their paper, Genetic Surveillance of Insecticide Resistance in African Anopheles Populations to Inform Malaria Vector Control, Trends Parasitol. 2024 May 16: S1471-4922(24)00115-6, https://doi.org/10.1016/j.pt.2024.04.016, Hancock PA & al. state that they “developed a catalogue of genetic-resistance mechanisms in African malaria vectors that could guide molecular surveillance. [They] highlight situations where intervention deployment has led to resistance evolution and spread, and identify challenges in understanding and mitigating the epidemiological impacts of resistance.”

Diagnosis

General diagnostics

Ibekpobaoku AN & al. tested 121 pregnant women for malaria with rapid diagnostic tests (RDTs), among whom eight tested positive for malaria, of which only four were positive by microscopy. As reported in Sub-Microscopic Plasmodium falciparum Infections and Multiple Drug Resistant Single Nucleotide Polymorphic Alleles in Pregnant Women from Southwestern Nigeria, BMC Res Notes. 2024 May 9; 17(1):129, https://doi.org/10.1186/s13104-024-06763-2, the percentages documented int abstract are significantly incorrect.

“The Noul miLab is a fully automated portable digital microscope that prepares a blood film from a droplet of blood, followed by staining and detection of parasites by an algorithm. Infected red blood cells are displayed on the screen of the instrument”. Ewnetu Y & al. describe its use in Ethiopia and Ghana for malaria diagnosis in A Digital Microscope for the Diagnosis of Plasmodium falciparum and Plasmodium vivax, Including P. falciparum with hrp2/hrp3 Deletion, PLOS Glob Public Health. 2024 May 20; 4(5):e0003091, https://doi.org/10.1371/journal.pgph.0003091. “Across both countries combined, the sensitivity of the miLab for P. falciparum was 94.3% at densities >200 parasites/μL by qPCR, and 83% at densities >20 parasites/μL. The miLab was more sensitive than local microscopy, and comparable to RDT. In Ethiopia, the miLab diagnosed 51/52 (98.1%) of P. falciparum infections with hrp2 deletion at densities >20 parasites/μL. Specificity of the miLab was 94.0%. For P. vivax diagnosis in Ethiopia, the sensitivity of the miLab was 97.0% at densities >200 parasites/μL (RDT: 76.8%, microscopy: 67.0%), 93.9% at densities >20 parasites/μL, and specificity was 97.6%.”

Mujahid M & al. state that the “conventional methods for identifying malaria are not efficient. Machine learning approaches are effective for simple classification challenges but not for complex tasks.” In Efficient Deep Learning-Based Approach for Malaria Detection Using Red Blood Cell Smears, Sci Rep. 2024 Jun 10; 14(1):13249, https://doi.org/10.1038/s41598-024-63831-0, they  propose “a deep learning-based approach for detecting [m]alaria …that uses red blood cell images.” The authors claim that “the proposed approach is 97.57% accurate in detecting Malaria from red blood cell images and can be beneficial practically for medical healthcare staff.”

Likewise, Tilahun A & al., Comparison of Malaria Diagnostic Methods for Detection of Asymptomatic Plasmodium Infections Among Pregnant Women in Northwest Ethiopia, BMC Infect Dis. 2024 May 14; 24(1):492, https://doi.org/10.1186/s12879-024-09369-y reports that among 166 pregnant women, asymptomatic P. falciparum was diagnosed “9.6%, 11.4% and 18.7% using RDT, microscopy and RT-PCR {real-time polymerase chain reaction}, respectively.” In their conclusion, the authors consider the asymptomatic infection rate high and without mentioning specifics, argue in favor of “better sensitive and specific laboratory diagnostic tools.”

Field diagnostics

In a companion piece to an article reported in May (Omale UI, A Qualitative Study on Determinants of the Use of Malaria Rapid Diagnostic Test and Anti-Malarial Drug Prescription Practices by Primary Healthcare Workers in Ebonyi State, Nigeria, Malaria J, 2024 Apr 25, 23:120, https://doi.org/10.1186/s12936-024-04958-3), Omale UI & al., Use of Malaria Rapid Diagnostic Test and Anti-Malarial Drug Prescription Practices Among Primary Healthcare Workers in Ebonyi State, Nigeria: An Analytical Cross-Sectional Study, PLoS One. 2024 Jun 4; 19(6):e0304600, https://doi.org/10.1371/journal.pone.0304600 reports on the results of questionnaires, as opposed to focus group discussions, but with essentially the same conclusions, namely that there is a need for “policy actions and interventions for optimal use of MRDT {malaria RDT} and anti-malarial drug prescription practices among the PHC workers in Ebonyi state, Nigeria, and similar settings.”

New diagnostic methods

Dong L & al. promote the use of a laboratory-based diagnostic method of identifying Plasmodium species in the blood, called EasyNAT. In their paper, EasyNAT Malaria: A Simple, Rapid Method to Detect Plasmodium Species Using Cross-Priming Amplification Technology, Microbiol Spectr. 2024 Jun 13: e0058324, https://doi.org/10.1128/spectrum.00583-24, they describe the processes performed through this method, which they demonstrate to compare favorably with microscopy and essentially match the accuracy of RDT.  The test takes 50 minutes.

Other

According to Holla P & al., “[d]espite having the highest risk of progressing to severe disease due to lack of acquired immunity, the youngest children living in areas of highly intense malaria transmission have long been observed to be infected at lower rates than older children. Whether this observation is due to reduced exposure to infectious mosquito bites from behavioral and biological factors, maternally transferred immunity, genetic factors, or enhanced innate immunity in the young child has intrigued malaria researchers for over half a century. Recent evidence suggests that maternally transferred immunity may be limited to early infancy and that the young child’s own immune system may contribute to control of malarial symptoms early in life ….” In their article, Mature Beyond Their Years: Young Children Who Escape Detection of Parasitemia Despite Living in Settings of Intense Malaria Transmission, Biochem Soc Trans. 2024 May 16: BST20230401, https://doi.org/10.1042/bst20230401, they “summarize the observational evidence for this phenotype in field studies and examine potential reasons why these children escape detection of parasitemia, covering factors that are either extrinsic or intrinsic to their developing immune system. .. [They] also identify gaps in our knowledge regarding cellular immunity in the youngest age group and propose directions that researchers may take to address these gaps.”

Rotimi K & al. studied the availability of diagnostic and treatment supplies for suspected and/or diagnosed malaria in children in 1858 facilities in seven Northern Nigerian states.  They report in Examining Public Sector Availability and Supply Chain Management Practices for Malaria Commodities: Findings from Northern Nigeria, Glob Health Sci Pract. 2024 Jun 13, https://doi.org/10.9745/ghsp-d-22-00547 that “[m]ore than 50% of health facilities in 5 states were stocked out of malaria rapid diagnostic tests (mRDTs), and stock-out rates for artemisinin-based combination therapies (ACTs) were over 50% for almost all assessed ACTs across all states… The top 2 logistics challenges were insecurity and inadequate funding.

Treatment                                                                                           

Treatment results

“Malaria drug resistance, along with several other factors, presents a significant challenge to malaria control and elimination efforts. Numerous countries in sub-Saharan Africa have documented the presence of confirmed or potential markers of partial resistance against artemisinin,” which led Tesfaye M & al. to study the effectiveness of artemisinin combination therapy, using Artemether-Lumefantrine (AL) for patients with uncomplicated falciparum malaria. They report in Therapeutic Efficacy and Safety of Artemether-Lumefantrine for Uncomplicated Plasmodium falciparum Malaria Treatment in Metehara, Central-East Ethiopia, Malaria J, 2024 Jun 13, 23:184, https://doi.org/10.1186/s12936-024-04991-2 that among 80 patients enrolled in their study (using WHO-endorsed criteria for selection), the “cure rate for AL treatment was 100%, demonstrating its high efficacy in effectively eliminating malaria parasites in patients. No serious adverse events related to AL treatment were reported during the study.”

Goodwin J & al. state in Persistent and Multiclonal Malaria Parasite Dynamics Despite Extended Artemether-Lumefantrine Treatment in Children, Nat Commun. 2024 May 7; 15(1):3817, https://doi.org/10.1038/s41467-024-48210-7 that according to their study results, prevalence of parasite-derived 18S rRNA is >70% in children throughout follow-up, and the ring-stage marker SBP1 is detectable in over 15% of children on day 14 despite effective treatment. [The authors conclude] that the extended regimen significantly lowers the risk of recurrent ring-stage parasitemia compared to the standard 3 day regimen.”

Mare AK & al. focus on P. vivax, because of its high prevalence in Ethiopia.  They report in in Chloroquine Has Shown High Therapeutic Efficacy Against Uncomplicated Plasmodium Vivax Malaria in Southern Ethiopia: Seven Decades After Its Introduction, Malaria J, 2024 Jun 10, 23:183, https://doi.org/10.1186/s12936-024-05009-7 that among 88 patients studied, 97% had adequate clinical and parasitological responses. They conclude that “[d]espite previous reports of declining chloroquine efficacy against P. vivax, [chloroquine] retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines.”

“Pyronaridine [has] potent antimalarial and potential antiviral activities. It has been used as an antimalarial agent for over 50 years against Plasmodium falciparum and Plasmodium vivax. In the 1970s, pyronaridine was first synthesized and used in China as a monotherapy regimen, under the trade name Malaridine… In 1996, a landmark clinical trial concluded that pyronaridine demonstrated outstanding efficacy and good tolerability in adults and children with acute uncomplicated P. falciparum malaria… Currently, pyronaridine is formulated in a 3:1 ratio with artesunate (pyronaridine-artesunate) as a fixed-dose ACT under the brand name Pyramax®, [which] is prescribed as a once-daily, 3 day therapy for the treatment of uncomplicated P. falciparum and P. vivax malaria in adults and children.” (Chu W-Y & Dorlo TPC, Pyronaridine: A Review of Its Clinical Pharmacology in the Treatment of Malaria, J Antimicrob Chemother. 2023 Oct; 78(10): 2406–2418, reported in Sep 2023). Barber BE & al. report a small (10 subject) experiment with pyronaridine monotherapy.  6 of 9 subjects given medium or low doses experienced “parasite regrowth” after apparent clearance from the bloodstream and were treated with standard AL therapy.  The authors nonetheless consider the drug as a suitable candidate for combination therapy with artesunate. The paper is Characterizing the Blood Stage Antimalarial Activity of Pyronaridine in Healthy Volunteers Experimentally Infected with Plasmodium falciparum, Int J Antimicrob Agents,  2024 May 9: 107196, https://doi.org/10.1016/j.ijantimicag.2024.107196.

Guidelines

Eboumbou Moukoko CE & al. analyzed “practices toward ACTs [artemisinin combination therapy] use for treating the treatment of uncomplicated malaria (UM) in an urban community.” They report that artemether+lumefantrine/AL (81%) and dihydroartemisinin+piperaquine (63.5%) were the most commonly used first- and second-line drugs respectively. Biological tests were requested in 99.2% (128/129) of patients in health facilities, 60.0% (74) were performed and 6.2% were rationally managed. Overall 266 (35%) of 760 customers purchased antimalarial drugs, of these, 261 (98.1%) agreed to participate and of these, 69.4% purchased antimalarial drugs without a prescription. ACTs accounted for 90.0% of antimalarials purchased from pharmacies, of which AL was the most commonly prescribed antimalarial drug (67.1%), [but] only 19.5% of patients were appropriately dispensed.” As they conclude in their article, Rationalizing Artemisinin-Based Combination Therapies Use for Treatment of Uncomplicated Malaria: A Situation Analysis in Health Facilities and Private Pharmacies of Douala 5e-Cameroon, PLoS One. 2024 May 7; 19(5):e0299517, https://doi.org/10.1371/journal.pone.0299517, there is a “gap between the knowledge and practices of prescribers as well as patients’ and customers’ misconceptions regarding the use of ACTs …. Despite government efforts to increase public awareness regarding the use of ACTs as first-line treatment for UM, [there is] a critical need for the development, implementation and scaling-up of control strategies and continuing health education for better use of ACTs (prescription and dispensing) in Cameroon.”

“Nonadherence to national standards for malaria diagnosis and treatment has been reported in Sudan.” In Mohamed SK & al., Health Workers’ Adherence to Malaria Case Management Protocols in Northern Sudan: A Qualitative Study, Malaria J, 2024 May 30, 23:170, https://doi.org/10.1186/s12936-024-04998-9, “qualitative research examined the clinical domains of nonadherence, factors influencing nonadherent practices and health workers’ views on how to improve adherence… Nonadherent practices included disregarding parasitological test results, suboptimal paediatric artemether–lumefantrine (AL) dosing, lack of counselling, use of prohibited artemether injections for uncomplicated and severe malaria, artesunate dose approximations and suboptimal preparations, lack of AL follow on treatment for severe malaria; and rare use of primaquine for radical Plasmodium vivax treatment and dihydroartemisinin-piperaquine as the second-line treatment for uncomplicated malaria. Factors influencing nonadherence included stock-outs of anti-malarials and RDTs; staff shortages; lack of training, job aids and supervision; malpractice by specialists; distrust of malaria microscopy and RDTs; and patient pressure for diagnosis and treatment.”

Side effects and complications

None this month

Drug resistance

According to Brown N & al., “Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets.” In Antimalarial Resistance Risk in Mozambique Detected by a Novel Quadruplex Droplet Digital PCR Assay, Antimicrob Agents Chemother. 2024 May 21: e0034624, https://doi.org/10.1128/aac.00346-24 they identify CNVs that are associated with resistance to several drugs that are not artemisinins but part of ACT.  They then show, using the assay mentioned in the title of the article, that among 229 parasite DNAs tested, 13 showed evidence of the CNVs specifically looked for. While this is a low percentage (5.7%), the authors emphasize “the need for continued molecular surveillance across the region.”

Angwe MK & al. found that 18.8 % DNA samples collected from 80 patients with uncomplicated malaria showed evidence of mutation in the pfkelch13 region of the parasite. The presence of these mutations was highly associated with persistent parasitemia on day 3 after treatment with artemether-lumefantrine. The authors conclude that “the presence of the K13 mutation associated with artemisinin resistance by P. falciparum in Adjumani district, Uganda, necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.” The paper is Day 3 Parasitemia and Plasmodium falciparum Kelch 13 Mutations Among Uncomplicated Malaria Patients Treated with Artemether-Lumefantrine in Adjumani District, Uganda, PLoS One. 2024 Jun 5; 19(6):e0305064, https://doi.org/10.1371/journal.pone.0305064.

Mukhongo HN & al., Screening for Antifolate and Artemisinin Resistance in Plasmodium falciparum Dried-Blood Spots from Three Hospitals of Eritrea, F1000Res. 2024 Jun 12; 10:628, https://doi.org/10.12688/f1000research.54195.3 is a report on genetic findings that are consistent with sulfadoxine-pyrimethamine and with artemisinin resistance in dried blood spots collected from patierntd treated for malaria.  However, the abstract is silent on how many patients’ blood spots were examined. Further, the blood spots were collected in 2014; it is unknown when the genetic analysis was carried out. F1000Research publishes articles without first subjecting them to peer review.

New drug research

Strasseriolides belong to a group of antibiotics called “macrolides,” that include Erythromycin. These compounds have been shown to have antiplasmoidial effects. Isak D & al., Collective and Diverted Total Synthesis of the Strasseriolides: A Family of Macrolides Endowed with Potent Antiplasmodial and Antitrypanosomal Activity, Angew Chem Int Ed Engl. 2024 Jun 12: e202408725, https://doi.org/10.1002/anie.202408725 reports confirmation of “the potency of the compounds and … lack of noticeable cytotoxicity” after conducting bioassays of derivative compounds against P. falciparum and Trypanosoma cruzi, the infectious agent of Chagas Disease.

Askarani HK & al. noted “the highly synergistic effect of the physical hybrid of dihydroartemisinin (DHA) with eosin B (EB). Therefore, a chemical hybrid of the two compounds (DHA-EB) was synthesized, and its antimalarial activity was investigated in vitro and in vivo.” The authors state in the body of the paper that EB is “a highly selective, potent inhibitor of varied drug-sensitive and drug-resistant malarial strains.” Using P. falciparum blood stage and P. berghei infected mice, they demonstrated significant antiparasite activity of the hybrid, without evidence of toxicity in the mice. The paper is In vitro and in vivo Antiplasmodial Activity of a Synthetic Dihydroartemisinin-Eosin B Hybrid, Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun; 397(6):4013-4024, https://doi.org/10.1007/s00210-023-02815-9.

Achan J & al. state that in view of the spreading of artemisinin resistance, “new treatments for severe malaria are needed, and it is prudent to define their characteristics now.” Their paper, Defining the Next Generation of Severe Malaria Treatment: A Target Product Profile, Malaria J, 2024 Jun 5, 23:174, https://doi.org/10.1186/s12936-024-04986-z, “focuses on the target product profile (TPP) for new treatments for severe malaria … Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. …. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed.”

Plant extracts and traditional treatments

Croton dichogamus and Ehretia cymosa are two tropical plants that are widely used in folk medicine in Eastern and Central Africa against a variety of illnesses, including malaria. Hashim D & al. report a study of leaf extracts of both in In-vivo Anti-Malarial Activity of 80% Methanol Leaf Extract of Croton dichogamus Pax and Ehretia cymosa Thonn in Plasmodium berghei Infected Mice, J Exp Pharmacol, 2024 May 29, 6:221-229, https://doi/org/10.2147/JEP.S457659. E. cymosa exhibited a more pronounced anti-plasmodial effect than C. dichogamus. Neither extract caused toxic effects in laboratory animals. “The activities of both plants observed in this study support their traditional use as antimalarial drugs. Further studies on these plants using solvent fractions are required to identify their active ingredients.”

Tadege G & al. studied various extracts of the leaf of a tree used in Ethiopian folk medicine against malaria and found that the “crude extract” of the leaf worked best on suppressing experimental malaria in mice, but that more purified extracts were effective as well. As they recommend in Efficacy of Albizia malacophylla (A.Rich.) Walp. (Leguminosae) Methanol (80%) Leaf Extract and Solvent Fractions Against Plasmodium berghei-Induced Malaria in Mice Model, J Ethnopharmacol. 2024 May 31: 118413, https://doi.org/10.1016/j.jep.2024.118413, further work on this plant’s potential as a source of antimalarials is required.

Other

Please see the description of Rotimi K & al., Examining Public Sector Availability and Supply Chain Management Practices for Malaria Commodities: Findings from Northern Nigeria, Glob Health Sci Pract. 2024 Jun 13, https://doi.org/10.9745/ghsp-d-22-00547 in Diagnosis/Other, above.

Campaigns and Policies

“The Walter Reed Project is a collaboration between the Walter Reed Army Institute of Research of the United States Department of Defense and the Kenya Medical Research Institute. The Kisumu field station, comprising four campuses, has until recently been devoted primarily to research on malaria countermeasures.” Sifuna PM & al., The Walter Reed Project, Kisumu Field Station: Impact of Research on Malaria Policy, Management, and Prevention, Am J Trop Med Hyg. 2024 Apr 23; 110(6):1069-1079, https://doi.org/10.4269/ajtmh.23-0115 describes the four components of this effort, concentrated in a high malaria area in Northwest Kenya.

Shomuyiwa DO & al. contend that the experience of Cabo Verde, which became certified by the WHO as malaria free in January of this year, can potentially be followed by other countries in Africa. Their Letter to the Editor, Cabo Verde’s Malaria-Free Certification: A Blueprint for Eradicating Malaria in Africa, J Taibah Univ Med Sci. 2024 Apr 9; 19(3):534-536 (a Saudi Arabian publication), https://doi.org/10.1016/j.jtumed.2024.04.001 reports with pride that the “country prioritized vector control, diagnostic quality, and surveillance, highlighting multisectoral collaboration.” {However, the letter fails to mention that the country, while not unique, is highly atypical in Africa, in that it consists of ten volcanic islands in the Atlantic Ocean.}

According to Garchitorena A & al., “[c]ommunity health workers (CHWs) can play a key role in improving access to malaria care for children under 5 years (CU5), but national policies rarely permit them to treat older individuals.” The authors “conducted a two-arm cluster randomized trial in rural Madagascar to assess the impact of expanding malaria community case management (mCCM) to all ages on health care access and use.” One arm included the CHW’s concentrating on children under age 5, whereas the other included children up to 13 years of age. The results showed that “care-seeking for fever and malaria diagnosis nearly tripled in both arms (from less than 25% to over 60%), driven mostly by increases in CHW care. Age-expanded mCCM yielded additional improvements for individuals over 5 years in the intervention arm (6-13-year-olds).”

Expanding Community Case Management of Malaria to All Ages Can Improve Universal Access to Malaria Diagnosis and Treatment: Results from a Cluster Randomized Trial in Madagascar, BMC Med. 2024 Jun 10; 22(1):231, https://doi.org/10.1186/s12916-024-03441-9 is their paper.

Bilgo E, The Unseen Battle: Interpreting The 2023 World Malaria Report from Burkina Faso’s Frontlines, Malaria J, 2024 Jun 17, 23:191, https://doi.org/ 10.1186/S12936-024-05016-8 is an opinion piece arguing that the Report “suggests significant underreporting, especially in remote areas with limited healthcare access. In addition, the confusion arising from similar diseases, such as dengue, further complicates the situation.” The author urges “tailored strategies in high-burden areas by emphasizing community involvement in data collection awareness campaigns for effective disease management to combat the invisible crisis lurking within communities.”

Epidemiology

Climate change, biodiversity and environment

“Changes in climate shift the geographic locations that are suitable for malaria transmission because of the thermal constraints on vector Anopheles mosquitos and Plasmodium spp. malaria parasites and the lack of availability of surface water for vector breeding… [Smith MW & al.] applied a validated and weighted ensemble of global hydrological and climate models to estimate present and future areas of hydroclimatic suitability for malaria transmission” and state in Future Malaria Environmental Suitability in Africa is Sensitive to Hydrology, Science. 2024 May 10; 384(6696):697-703, https://doi.org/10.1126/science.adk8755 that “[w]ith explicit surface water representation, we predict a net decrease in areas suitable for malaria transmission from 2025 onward, greater sensitivity to future greenhouse gas emissions, and different, more complex, malaria transmission patterns. Areas of malaria transmission that are projected to change are smaller than those estimated by precipitation-based estimates but are associated with greater changes in transmission season lengths.”

Savi MK & al. state that “[e]xisting studies indicate that as urbanization increases, there is corresponding decrease in malaria prevalence. However, in malaria-endemic areas, the prevalence in some rural areas is sometimes lower than in some peri-urban and urban areas. Therefore, the relationship between the degree of urbanization, the impact of living in urban areas, and the prevalence of malaria remains unclear.”  Their paper, Urbanization and Malaria Have a Contextual Relationship in Endemic Areas: A Temporal and Spatial Study in Ghana, PLOS Glob Public Health. 2024 May 30; 4(5):e0002871, https://doi.org/10.1371/journal.pgph.0002871 used “epidemiological data at the district level (2015-2018) and data on health, hygiene, and education” in order to explore the relationships. They found “that prevalence is impacted by seasonality, but the trend of the seasonal signature is not noticeable in urban and peri-urban areas. While urban districts have a slightly lower prevalence, there are still pockets with higher rates within these regions. These areas of high prevalence are linked to proximity to water bodies and waterways, but the rise in these same variables is not associated with the increase of prevalence in peri-urban areas. … [Eventually the authors] conclude that urbanization is not the main factor driving the decline in malaria.” {Note that the data collected by the authors are from a period before the appearance of Anopheles stephensi in West Africa.}

Huijser L & al. state that “[h]ydrogeomorphic changes, encompassing erosion, waterlogging, and siltation, disproportionately threaten impoverished rural communities. Yet, they are often marginalized in discussions of disasters. This oversight is especially concerning as vulnerable households with limited healthcare access are most susceptible to related diseases and displacement. However, our current understanding of how these risks intersect remains limited. In From Erosion to Epidemics: Understanding the Overlapping Vulnerability of Hydrogeomorphic Hotspots, Malaria Affliction, and Poverty in Nigeria, Sci Total Environ. 2024 Jun 1; 927:172245, https://doi.org/10.1016/j.scitotenv.2024.172245, the authors “explore the complex relationships between hydrogeomorphic hazards, malaria incidence, and poverty in Nigeria.”

Risk factors

Mbishi JV & al. studied risk factors for 35,624 children in seven high-risk sub-Saharan countries, analyzing data from “Malaria Indicator Surveys (MIS) spanning from 2010 to 2023.” They report in  Malaria in Under-Five Children: Prevalence and Multi-Factor Analysis of High-Risk African Countries, BMC Public Health,  2024 Jun 24; 24(1):1687, https://doi.org/10.1186/s12889-024-19206-1 that “[t]he overall pooled prevalence of malaria among the studied population was 26.2%, with substantial country-specific variations observed. …, a child’s age was significantly associated with malaria prevalence … Children of mothers with higher education levels … and Fansidar uptake during pregnancy … were associated with lower malaria risk. Children from middle-wealth … and rich … households had considerably lower malaria prevalence compared to those from poor households. …, rural residency was associated with a higher risk of malaria compared to urban residency.

Khan O & al. use “a predictive model for malaria outbreaks in each district of The Gambia, leveraging historical meteorological data. To achieve this objective, [they] employ and compare the performance of eight machine learning algorithms… {The] findings reveal that extreme gradient boosting and decision trees exhibit the highest prediction accuracy on the testing set, achieving 93.3% accuracy, followed closely by random forests with 91.5% accuracy…” The paper is Predicting Malaria Outbreak in The Gambia Using Machine Learning Techniques, PLoS One. 2024 May 16; 19(5):e0299386, https://doi.org/10.1371/journal.pone.0299386

Xing S-Y & al. consider it a paradox that children under the age of 5 who live in female-headed households in Nigeria have higher risk of malaria than those in male-headed ones. They point out that the data they studied (the 2021 National Malaria Indicator Survey) showed education levels and wealth index was higher in female headed households, yet they had a smaller proportion of children sleeping under bednets and the rate of testing for malaria of children with fever were higher in male headed households. The paper is Examining the Paradox: Increased Malaria Risk in Children Under 5 in Female-Headed Households in Nigeria, Malaria J, 2024 May 31, 23:171, https://doi.org/10.1186/s12936-024-04997-w. {Reviewer comment: there are two items in this abstract that seem to belie the validity of the survey: 1. Only 7.8% of the 10,988 households surveyed were headed by females, whereas the Nigerian National Bureau of statistics reports that 18.8% is the correct country-wide figure, higher in urban areas, see https://nigerianstat.gov.ng/ elibrary/read/1123#; 2. It is contrary to consistent world-wide statistics that female headed households have higher income levels than male headed households; even the authors claim “entrenched gender inequality and the challenges women face in accessing critical assets.”}

Amesa EG & al. report on the risk factors behind a particular outbreak of malaria in a community in Investigating the Determinants of Malaria Outbreak in Nono Benja Woreda, Jimma Zone, Ethiopia: A Case-Control Study, Risk Manag Healthc Policy, 2024 May 28, 17:1395-1405, https://doi.org/10.2147/RMHP.S456958. They conclude that a “number of factors, including lack of ITNs, lack of malaria health education, stagnant water, and IRS [sic], were significantly linked with the occurrence of malaria outbreaks.”

According to Keita S & al., Prognostics of Multiple Malaria Episodes and Nutritional Status in Children Aged 6 to 59 Months from 2013 to 2017 in Dangassa, Koulikoro Region, Mali, Malaria J, 2024 Jun 13, 23:186, https://doi.org/10.1186/s12936-024-04999-8, the occurrence of multiple malaria episodes is much more likely in children who are undernourished and are anemic than in normal weight and non-anemic children in the area of Mali that the authors studied ove the period indicated. This was especially true during periods of low transmission.

General epidemiology

According to Markwalter CF & al., “[t]he human infectious reservoir of Plasmodium falciparum is governed by transmission efficiency during vector-human contact and mosquito biting preferences.” The authors tested this over 15 months in a community in Kenya. As they report in their paper, Plasmodium falciparum Infection in Humans and Mosquitoes Influence Natural Anopheline Biting Behavior and Transmission, Nat Commun. 2024 May 30; 15(1):4626, https://doi.org/10.1038/s41467-024-49080-9, “[b]iting was highly unequal; 20% of people received 86% of bites. Biting rates were higher on males …, children 5-15 years …, and P. falciparum-infected individuals …. In aggregate, P. falciparum-infected school-age (5-15 years) boys accounted for 50% of bites potentially leading to onward transmission…” In addition, they noted a “preference of infected mosquitoes to feed upon infected people.”

Belay AK & al., Vectorial Drivers of Malaria Transmission in Jabi Tehnan District, Amhara Regional State, Ethiopia, Sci Reps, 2024 Jun; 14:13669, https://doi.org/10.1038/s41598-024-64436-3 is a compilation of the various vectors found in traps and found to be infected with P. falciparum (89%) and P. vivax (11%) over 12 months in 2020-2021.

Spatiotemporal studies

Adugna T & al., Blood Smears Examination and Prevalence of Malaria in Addis Zemen Town, Northwest Ethiopia (2013-2021): A Retrospective Study, Trop Dis Travel Med Vaccines. 2024 May 15; 10(1):12, https://doi.org/10.1186/s40794-024-00219-y

Tairou F & al., Malaria Prevalence and Use of Control Measures in an Area with Persistent Transmission in Senegal, PLoS One. 2024 May 16; 19(5):e0303794, https://doi.org/10.1371/journal.pone.0303794

Ferriss E & al., Malaria Transmission at The Zimbabwe-Mozambique Border: An Observational Study of Parasitemia by Travel History and Household Location, Am J Trop Med Hyg. 2024 May 21: tpmd230466, https://doi.org/10.4269/ajtmh.23-0466

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