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

From the WHO (2024 Apr 25, https://www.afro.who.int/countries/benin/news/major-step-malaria-prevention-three-west-african-countries-roll-out-vaccine):

“Cotonou/Freetown/Monrovia — In a significant step forward for malaria prevention in Africa, three countries—Benin, Liberia and Sierra Leone—today launched a large-scale rollout of the life-saving malaria vaccine targeting millions of children across the three West African nations. The vaccine rollout, announced on World Malaria Day, seeks to further scale up vaccine deployment in the African region.

Today’s launch brings to eight the number of countries on the continent to offer the malaria vaccine as part of the childhood immunization programmes, extending access to more comprehensive malaria prevention. Several of the more than 30 countries in the African region that have expressed interest in the vaccine are scheduled to roll it out in the next year through support from Gavi, the Vaccine Alliance, as efforts continue to widen its deployment in the region in coordination with other prevention measures such as long-lasting insecticidal nets and seasonal malaria chemoprevention.

Benin, which received 215 900 doses, has added the malaria vaccine to its Expanded Programme on Immunization. The malaria vaccine should be provided in a schedule of 4 doses in children from around 5 months of age. …

In Liberia, the vaccine was launched in the southern Rivercess County and will be rolled out afterwards in five other counties which have high malaria burden. At least 45 000 children are expected to benefit from the 112 000 doses of the available vaccine. …

In Sierra Leone, the first doses were administered to children at a health centre in Western Area Rural where the authorities kicked off the rollout of 550 000 vaccine doses. The vaccine will then be delivered in health facilities nationwide. …

Malaria remains a huge health challenge in the African region, which is home to 11 countries that carry approximately 70% of the global burden of malaria. The region accounted for 94% of global malaria cases and 95% of all malaria deaths in 2022, according to the World Malaria Report 2023.

“The African region is advancing in the rollout of the malaria vaccine – a game-changer in our fight against this deadly disease,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “Working with our member states and partners, we’re supporting the ongoing efforts to save the lives of young children and lower the malaria burden in the region.”

Aurelia Nguyen, Chief Programme Officer at Gavi, the Vaccine Alliance, noted: “Today we celebrate more children gaining access to a new lifesaving tool to fight one of Africa’s deadliest diseases. This introduction of malaria vaccines into routine programmes in Benin, Liberia, and Sierra Leone alongside other proven interventions will help save lives and offer relief to families, communities and hard-pressed health systems.”

“MalariaWorld has joined hands with the Free University of Amsterdam in the Netherlands to conduct a survey on malaria control interventions and what is needed to pave the path towards malaria elimination in Africa. So I am calling on you, with all your knowledge and experience. Please help us by taking the online survey below. Your feedback matters. Really, it does. We will share the results with you in due course. You may share the link to the survey with your malaria colleagues….” Survey: https://tinyurl.com/malariacontrolsurvey

In an opinion piece in Malaria World Journal (2024 Apr 23, 15:9), Uneasy Bedfellows: Public-Private Partnerships for Malaria Control, https://doi.org/10.5281/zenodo.11046816, Jacques D. Charlwood argues that “reducing poverty is likely to alleviate malaria transmission and that the way to do this is by reducing inequality. The present capitalist system (as opposed to a straightforward market) tends to erode equality and promote profit over product. This may extend to the manufacture of bednets, bought by agencies rather than individual consumers, whose products may suffer from built in obsolescence. It is argued that better quality nets that can be re-impregnated locally are both desired and required.”

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

Prevention

Vaccines

Juraska M & al., Genotypic Analysis of RTS,S/AS01(E) Malaria Vaccine Efficacy Against Parasite Infection as a Function of Dosage Regimen and Baseline Malaria Infection Status in Children Aged 5-17 Months In Ghana And Kenya: A Longitudinal Phase 2b Randomised Controlled Trial, Lancet Infect Dis. 2024 May 6: S1473-3099(24)00179-8, https://doi.org/10.1016/s1473-3099(24)00179-8 is a report on studies conducted in 2017-18 on the first vaccine endorsed by the WHO for use in children. Each of the four studied RTS,S/AS01E regimens “significantly reduced the mean number of new infections in the 20-month follow-up period …. Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria … than in those who were uninfected … at the first vaccination …”

During the Phase IV study of introduction of the RTS,S/AS01 vaccine in Malawi, it was noted that in at least one district the WHO goal of 80% of children receiving the full complement of vaccines was not met. Simbeye AJ & al., Factors Associated with Malaria Vaccine Uptake in Nsanje District, Malawi, Malaria J, 2024 Apr 17, 23:105, https://doi.org/10.1186/s12936-024-04938-7 is a report on the information gathered in pursuit of the reasons for that. “Uptake of malaria vaccine was 90.5% for dose 1, but reduced to 87.6%, 69.5% and 41.2% for dose 2, 3, and 4 respectively. Children of caregivers with secondary or upper education and those who attended antenatal clinic four times or more had increased odds of full uptake of malaria vaccine …. Children who ever suffered side-effects following immunization and those who travelled long distances to reach the vaccination centre had reduced odds of full uptake of malaria vaccine …. Only 17% (n = 65) of mothers/ caregivers knew the correct schedule for vaccination and 38.5% (n = 158) knew the correct number of doses a child was to receive.” Thus, the “primary modifiable factor influencing vaccine uptake was mother/caregiver knowledge about the vaccine.”

Osoro CB & al. “assessed the country status of implementation and delivery strategies for RTS,S/AS01 by searching websites for national malaria policies, guidelines and related documents. Direct contact with individuals working in malaria programmes was made to obtain documents not publicly available. 10 countries had documents with information relating to malaria vaccine implementation…” Their paper, Policy Uptake and Implementation of the RTS,S/AS01 Malaria Vaccine in Sub-Saharan African Countries: Status Two Years Following the WHO Recommendation, BMJ Glob Health. 2024 Apr 30; 9(4):e014719, https://doi.org/10.1136/bmjgh-2023-014719, lists the status of each country as of its publication.

Bongomin F & al., Malaria Vaccine Acceptance Among Next of Kin of Children Under 5 Years of Age in Gulu, Northern Uganda in 2023: A Community-Based Study, Ther Adv Infect Dis. 2024 Apr 18; 11:20499361241247467, https://doi.org/10.1177/20499361241247467 is a report of interviews of caregivers about perceived information about the vaccine and willingness of accepting it for their children under age five, when and if offered.  The authors report that among 432 caregivers queried “85.6% of respondents expressed willingness to accept a Ministry of Health-approved malaria vaccine” {this is a quote from the article – the abstract states 91%, which was apparently a generic “acceptance”}. The study evidently occurred before the vaccine was made available, so its results are not comparable to those reported from Malawi, above.

Chinawa AT & al. administered questionnaires to 491 mothers who presented with their children in nine hospitals in the area they studied. Just as in Uganda, above, Willingness to Accept Malaria Vaccines Amongst Women Presenting at Outpatient and Immunization Clinics in Enugu State, Southeast Nigeria, Malaria J, 2024 Apr 25, 23:117, https://doi.org/10.1186/s12936-024-04914-1 documents that a large majority of women (83.1%) stated readiness to accept the vaccine and an even larger majority (92.9%) “were willing to vaccinate baby with the malaria vaccine. The subjects who belong to the low socio-economic class were five times less likely to vaccinate self and baby with malaria vaccine when compared with those who were in the high socio-economic class (AOR = 0.2, 95% CI 0.1–0.5). Mothers who had good knowledge of malaria vaccination were 3.3 times more likely to vaccinate self and baby with malaria vaccine when compared with those who had poor knowledge of malaria vaccination.” {Again, it is uncertain whether these numbers will convert to full compliance with the recommended vaccine series.}

In contrast with the two articles above, Hussein MF & al. report significant vaccine hesitancy (VH) in Ghana in their article, Hesitancy Towards R21/Matrix-M Malaria Vaccine Among Ghanaian Parents and Attitudes Towards Immunizing Non-Eligible Children: A Cross-Sectional Survey, Malaria J, 2024 May 12, 23:142, https://doi.org/10.1186/s12936-024-04921-2. This particular WHO recommended vaccine was recently approved for use in Ghana in children aged 6 to 36 months. The subjects of the study were parents of children not currently eligible for the vaccine.  “About one-third (34.5%) of the parents were hesitant to give their children the R21/Matrix-M malaria vaccine. The following predictors were associated with VH: working in the healthcare sector …, having the other parent working in the healthcare sector …, and not taking scheduled routine vaccinations …” While the last of these factors seem logical, it is unclear why the other associated demographic factors were found.  The article (not the abstract) implies that fear of as yet unknown side effects may be driving VH among parents employed in the health care sector.

Cummings JF & al., A Phase IIa, Randomized, Double-Blind, Safety, Immunogenicity and Efficacy Trial of Plasmodium falciparum Vaccine Antigens Merozoite Surface Protein 1 and RTS,S Formulated with AS02 Adjuvant in Healthy, Malaria-Naive Adults, Vaccine. 2024 Apr 30; 42(12):3066-3074, https://doi.org/10.1016/j.vaccine.2024.03.072 is an article from the Walter Read Army Institute of Research that reports on a study conducted in 2001 (!) using a formulation of the RTS,S vaccine that is not is not the one recommended by WHO.  The conclusion of the article was that the combination of the two were less effective than the vaccine by itself in experimentally induced malaria. {Why this is published in 2024 is unclear from the abstract or the article.}

There has been considerable work in an attempt to create vaccines containing whole Plasmodium falciparum sporozoites that have been attenuated by radiation.  So far the WHO has declined to endorse the use of these vaccines. Senkpeil L & al., Innate Immune Activation Restricts Priming and Protective Efficacy of the Radiation-Attenuated PfSPZ Malaria Vaccine, JCI Insight. 2024 Apr 30: e167408, https://doi.org/10.1172/jci.insight.167408 contains immunologic data that indicate at least one reason why these vaccines are not efficacious.

Vectors

“Despite the efforts made by the National Malaria Elimination Programme (NMEP), including distribution of Long-Lasting Insecticide Nets (LLINs) to households through periodic … campaigns and continuous channels …, there is a gap between access and use of LLINs in Ghana.”  Glozah FN & al., Implementation and Effectiveness Outcomes of Community Health Advocacy Teams to Improve Long-Lasting Insecticide Net Distribution and Use in Six Districts In Ghana: A One-Group Pre-Post-Test Study, PLoS Glob Public Health. 2024 Apr 1; 4(4):e0002123, https://doi.org/10.1371/journal.pgph.0002123 “assesses the implementation outcomes and short-term effectiveness of the pilot implementation of co-created community health advocacy teams (CHAT) intervention in Ghanaian communities to plan and implement campaigns to increase LLIN use…Household members’ awareness of, access to, willingness to purchase, and use of LLINs increased significantly over the four-month period that the CHAT intervention was implemented. The study concludes that CHAT is an acceptable, appropriate, and feasible intervention…” (This paper could also be cited under Campaigns)

In a complicated four-year multi-country study of the use of insecticide-treated nets (ITNs), Shannon J & al. report that “[w]hile there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets.” The article is A Qualitative Look at Bed Net Access and Use in Burkina Faso, Mozambique, Nigeria, and Rwanda Following Piloted Distributions of Dual-Active Ingredient Insecticide-Treated Nets, Malaria J, 2024 May 7, 23:137, https://doi.org/10.1186/s12936-024-04868-4.

Ofili MI & Nwogueze BC administered questionnaires to Nigerian medical students regarding the awareness and use of ITNs.  However, it is difficult to tell from the abstract of their article, Level of Awareness and Utilization of Insecticide-Treated Bed Nets Among Medical Students as Measures for Reducing Malaria Episodes, Sci Rep, 2024 May 2; 14(1):10156, https://doi.org/10.1038/s41598-024-60523-7, how they concluded that “regular utilization of insecticide-treated bed nets due to adequate awareness eliminates contact with mosquitoes and prevents transmitting vectors of malaria from having contact with the users of insecticide-treated bed net,” given that they found that there was “significant difference between perception of medical students and the utilization of insecticide-treated bed nets on risk of malaria spread. In addition, there was significant difference between the benefits of using insecticide-treated bed nets and the prevention and control of malaria…”

Ipomoea staphylina is a type of morning glory Narayanan L & al. used its extract to construct silver and copper oxide nanoparticles, which they then tested as potential larvicides of Anopheles stephensi and Aedes aegypti. They report in An Investigation into the Larvicidal Activity of Biologically Synthesized Silver and Copper Oxide Nanoparticles Against Mosquito Larvae, Chem Biodivers. 2024 Apr; 21(4):e202301774, https://doi.org/10.1002/cbdv.202301774 that the ”nanoparticles exhibited robust larvicidal activity, with CuO nanoparticles surpassing silver nanoparticles in terms of LC50 and LC90 values. Moreover, the developmental toxicity of CuO and Ag NPs was evaluated in zebrafish embryos as part of non-target eco-toxicological studies conducted in a standard laboratory environment.” {The last sentence implies that no toxicity was detected, but the abstract does not explicitly state that.}

The development of pyrethroid resistance among malaria vectors has prompted the deployment of other agents to use in Indoor Residual Spraying (IRS). Often the two agents are used in combination, partly in order to delay the development of resistance to the new agent.  Syme T & al. hypothesized that pyrethroids being irritants as well as insecticides, they may cause the landed mosquito to take off quickly and not be exposed to the insecticides long enough. In their article,  Laboratory Evaluation of the Contact Irritancy of a Clothianidin Solo Formulation Vs. Clothianidin-Deltamethrin Mixture Formulations for Indoor Residual Spraying Against Pyrethroid-Resistant Anopheles gambiae sensu lato, Parasit Vectors. 2024 Apr 10; 17(1):183, https://doi.org/10.1186/s13071-024-06265-x, they report vector behavior on landing on walls treated with the combination versus the new insecticide alone, that is consistent with their hypothesis. However, they cite no data on the lethality of one preparation versus the other. Field tests, which may elucidate the latter are recommended by the authors.

“Vector control using insecticides is a key prevention strategy against malaria. Unfortunately, insecticide resistance in mosquitoes threatens all progress in malaria control. In the perspective of managing this resistance, new insecticide formulations are being tested to improve the effectiveness of vector control tools… [Using] a new micro-encapsulated formulation (CS) of Pirimiphos-methyl called Pirikool® 300,” Fodjo BK & al., report in Efficacy of Pirikool® 300 CS Used for Indoor Residual Spraying on Three Different Substrates in Semi-Field Experimental Conditions, Malaria J, 2024 May 15, 23:148, https://doi.org/10.1186/s12936-024-04912-3 that it outperformed the currently used formulations of the same chemical, especially on wood surfaces, on which it caused over 75% 24-hour mortality with the control was barely over 51% effective.

 

For the first time, a species of vector mosquito, Anopheles coluzii, is reported in Kenya by Kamau L & al. in The Anopheles coluzzii Range Extends into Kenya: Detection, Insecticide Resistance Profiles and Population Genetic Structure in Relation to Conspecific Populations in West and Central Africa, Malaria J, 2024 Apr 26, 23:122, https://doi.org/10.1186/s12936-024-04950-x. Genetically, the mosquito appears to be the same as those of the same species in Central Africa. They also share their propensity to be resistant to pyrethroid insecticides and DDT (“up to 64%” of those collected). “The profile and frequencies of the variants observed were similar to An. coluzzii from West and Central Africa but the … mutation linked to organophosphate and carbamate resistance present in An. coluzzii from coastal West Africa was absent in Kenya.”

“In Benin, clothianidin-based insecticides, have a long residual efficacy of 8 to 10 months in largescale in community trials on mud and cement walls, in contrast to pirimiphos-methyl 300 CS, which has a residual efficacy of 4 to 5 months.” Odjo EM & al. pose the question: Did the Prolonged Residual Efficacy of Clothianidin Products Lead to a Greater Reduction in Vector Populations and Subsequent Malaria Transmission Compared to the Shorter Residual Efficacy of Pirimiphos-Methyl? In Malaria J, 2024 Apr 25, 23:119, https://doi.org/10.1186/s12936-024-04949-4. After analyzing field test results comparing the two insecticides, and a third one, clothianidin-deltamethrin, the authors conclude that despite the shorted residual duration of pirimiphos-methyl, it is superior in suppressing mosquito bite rates and therefore presumably malaria infections.  {Of note: clothianidin is harmful to honeybees and is therefore banned by the EU, with an exception carved out for sugar beets.}

“Dichlorodiphenyltrichloroethane (DDT) usage has been prohibited in developed nations since 1972 but is exempted for use in indoor residual spraying (IRS) in developing countries, including African countries, for malaria control.” Based on 24 published articles, Makgoba L & al. reviewed “available research investigating the levels of DDT residues in water sources in Africa and [assessed] the consequent human health risks. They report in DDT Contamination in Water Resources of Some African Countries and Its Impact on Water Quality and Human Health, Heliyon. 2024 Mar 20; 10(7):e28054, https://doi.org/10.1016/j.heliyon.2024.e28054 that in “35% of the studies, DDT concentrations surpassed the World Health Organization (WHO) drinking water guideline of 1 μg/L in the sampled water sources. The highest DDT concentrations were found in South Africa (81.2 μg/L) and Egypt (5.62 μg/L). DDT residues were detected throughout the year in African water systems, but levels were found to be higher during the wet season. Moreover, water from taps, rivers, reservoirs, estuaries, wells, and boreholes containing DDT residues was used as drinking water.”

“Since insecticide resistance has been recorded for most of the existing insecticides used for indoor residual spraying, namely, DDT, pyrethroids, organophosphates and carbamates … new chemicals are necessary for the continued success of indoor residual spraying,” Maharaj R & al. studied three newly available substances for IRS for effectiveness, compared to DDT, which is still being used in South Africa (see article above). Field Evaluation of the Residual Efficacy of New Generation Insecticides for Potential Use in Indoor Residual Spray Programmes in South Africa, Malaria J, 2024 Apr 30, 23:127, https://doi.org/10.1186/s12936-024-04963-6 reports that depending on the wall surfaces studied, each of the tested substances offer some advantages.  Even though DDT was the most effective on cement walls, each of the three insecticides “usually resulted in 100% mortality for up to 12 months with a delayed mortality period of 96–144 h, depending on the insecticide evaluated and the surface type sprayed. [Thus, they] are suitable replacements for DDT. Each of these insecticides can be used for malaria vector control, requiring just one spray round. These insecticides can be used in rotation or as mosaic spraying.”

Chemoprophylaxis

“In Nigeria, seasonal malaria chemoprevention (SMC) is typically administered door-to-door to children under five by community medicine distributors during high transmission seasons. While door-to-door distribution (DDD) is exclusively employed in Nigeria as part of standard operating procedures of SMC programmes, some households access SMC through non-DDD channels, such as fixed-point distributions, health facilities, and private purchase.” Huang S & al. investigated why and how these sources of SMC are utilized.  They report in Predictors of Accessing Seasonal Malaria Chemoprevention Medicines Through Non-Door-To-Door Distribution in Nigeria, Malaria J, 2024 May 3, 23:131, https://doi.org/10.1186/s12936-024-04964-5 that fewer than 2% of the ~25,000 households surveyed used alternate sources. “Over 60% of non-DDD access was via health facility personnel and community medicine distributors from different locations.”

“Recently revised WHO guidelines on malaria chemoprevention have opened the door to more tailored implementation. Countries face choices on whether to replace old drugs, target additional age groups, and adapt delivery schedules according to local drug resistance levels and malaria transmission patterns.” As reported in 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, 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.” They conclude that  “[p]rotective efficacy was estimated with greater precision in high transmission settings, and power to detect differences by resistance genotype was lower in scenarios where the resistant genotype was either rare or too common.”

Ndayishimiye JC & Tabong PT-N conducted an analysis, “using the 2019 Ghana Malaria Indicator Survey dataset” in order to study the effectiveness of chemoprevention in pregnancy. “The data analysed were restricted to women aged 15-49 years who reported having a live birth within the two years preceding the survey…” Their paper, Spatial Distribution and Determinants of Intermittent Preventive Treatment for Malaria During Pregnancy: A Secondary Data Analysis of the 2019 Ghana Malaria Indicators Survey, BMC Pregnancy Childbirth, 2024 May 20; 24(1):379, https://doi.org/10.1186/s12884-024-06566-0, reports that “likelihood that pregnant women received optimal SP {sulfadoxine-pyrimethamine} correlated with early initiation of first antenatal care (ANC), number of ANC contacts, woman’s age, region of residence, and family size. Overall, the greater the number of ANC contacts, the more likely for pregnant women to receive optimal SP. Women with four or more ANC contacts were 2 times … more likely to receive optimal SP than pregnant women with fewer than four ANC contacts. In addition, early initiation and a high number of ANC contacts were associated with a high number of times a pregnant woman received SP.” Mass drug administration (MDA) has had its advocates and detractors; it is generally felt to be useful in the short run to prevent clinical and especially severe malaria, but has few sustainable effects. Robinsone E & al., Mixed-Method Evaluation Study of a Targeted Mass Drug Administration of Long-Acting Anti-Malarials Among Children Aged 3 Months to 15 Years in the Bossangoa Sub-Prefecture, Ouham, Central African Republic, During the COVID-19 Pandemic, Malaria J, 2024 May 15, 23:146, https://doi.org/10.1186/s12936-024-04968-1 seems to echo this conclusion, with the additional caveat of the cost of the program, especially in rural settings.  In two of three communities that this event took place, there was a significant (up to 73.7%) reduction of clinical malaria cases after the second of three administrations and a 25.2% reduction of hospital admissions for severe malaria across all three communities. Furthermore, “community members perceived less illness among children because of the MDA, as well as fewer hospitalizations. Other indirect benefits such as reduced household expenditure on healthcare were also described.” Yet the conclusion of the paper emphasized that it was “resource intensive” and emphasized the authors’ opinion that MDA may be an adjunct, but not a mainstay of malaria control.

Other

Following a successful Phase I trial of L9LS, a monoclonal antibody in adults, Kayentao K & al. now report on their Phase 2 trial in children ages 6 to 10, in Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria, New Eng J Med, 2024 Apr 26, 390(17):1549-49, https://doi.org/10.1056/NEJMoa2312775. Six months after subcutaneous administration of L9LS, the authors report no “safety concerns … identified in the dose-escalation part of the trial (part A)” nor in part B, in which they compared outcomes of two different dosages with placebo injection.  In this part, they report that “[e]fficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons).”

“The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials…” Arnzen A & al., Characteristics of the Western Province, Zambia, Trial Site for Evaluation of Attractive Targeted Sugar Baits for Malaria Vector Control, Malaria J, 2024 May 18, 23:153, https://doi.org/10.1186/s12936-024-04985-0 reports that Anopheles funestus is the predominant of 14 Anopheles mosquitoes in the area, “likely accounting for around 95% of all Plasmodium falciparum malaria infections.”

“Microsporidia MB, an endosymbiont naturally found in Anopheles mosquitoes inhibits transmission of Plasmodium and is a promising candidate for a transmission-blocking strategy that may involve mosquito release.” Bukhari T & al. carried out an assessment “to develop insight into sociodemographic factors, public health concerns, and malaria awareness, management, and prevention practices with the willingness to accept and participate in Microsporidia MB-based transmission-blocking strategy to develop an informed stakeholder engagement process.” They report in Willingness to Accept and Participate in a Microsporidia MB-Based Mosquito Release Strategy: A Community-Based Rapid Assessment in Western Kenya, Malaria J, 2024 Apr 20, 23:113, https://doi.org/10.1186/s12936-024-04941-y “a high level of willingness to accept and participate in a Microsporidia MB-based strategy in the community, which is influenced by several factors such as community, disease risk perception, gender, education level, knowledge, and experience of malaria. Further research will need to focus on understanding the concerns of women, educated, and employed community members…”

Another infectious agent in mosquitoes that appears to suppress the malaria parasite is Wolbachia. In Vandana V & al., Wolbachia Infection-Responsive Immune Genes Suppress Plasmodium falciparum Infection in Anopheles stephensi, PLoS Pathog. 2024 Apr 10; 20(4):e1012145, https://doi.org/10.1371/journal.ppat.1012145, the mechanism of this suppression is analyzed. Genetic testing of infected versus uninfected mosquitoes lead the authors to the conclusion that “Wolbachia infection modulates mosquito immunity and other processes that are likely to decrease Anopheles permissiveness to Plasmodium infection.”

Diagnosis

General diagnostics

“Accuracy of malaria rapid diagnostic tests is threatened by Plasmodium falciparum with pfhrp2/3 deletions.” Gatton ML & al., Comparison of Prevalence Estimates of Pfhrp2 and Pfhrp3 Deletions in Plasmodium falciparum Determined by Conventional PCR And Multiplex qPCR and Implications for Surveillance and Monitoring, Int J Infect Dis. 2024 Apr 15: 107061, https://doi.org/10.1016/j.ijid.2024.107061 “compares gene deletion prevalence determined by multiplex qPCR {quantitative polymerase chain reaction} and conventional PCR (cPCR) using existing samples with clonality previously determined by microsatellite genotyping… The authors conclude that “[m]ultiplex qPCR and cPCR produce comparable estimates of gene deletion prevalence when monoclonal infections dominate, but qPCR provides higher estimates where multiclonal infections are common,” such as in Eritrea.

Field diagnostics

“Histidine-rich protein-2 (HRP2) antigen detection RDTs {rapid diagnostic tests} are predominantly used to diagnose Plasmodium falciparum infection. However, the evolution and spread of P. falciparum parasite strains with deleted hrp2/3 genes, causing false-negative results, have been reported.”  Mekonen B & al. “assessed the diagnostic performance of HRP2-detecting RDTs for P. falciparum cases and the prevalence of pfhrp2/3 deletions among symptomatic patients seeking malaria diagnosis at selected health facilities in southern Ethiopia.”  They report in Wide-spread pfhrp2/3 Deletions and HRP2-Based False-Negative Results in Southern Ethiopia, Malaria J, 2024 Apr 17, 23:108, https://doi.org/10.1186/s12936-024-04904 that “using PCR as the gold standard test for P. falciparum infections, … the sensitivity of the SD Bioline PfHRP2-RDT test was 76.5% …” This finding largely corresponded to the findings of gene deletions and exceeded the WHO-recommended threshold of 5% or less for relying on RDTs in the field.

Kojom Foko LP & al., Protein 2/3 Genes in Natural Plasmodium falciparum Populations from Cameroon and India: Role of Asymptomatic and Submicroscopic Infections, Am J Trop Med Hyg. 2024 Apr 30: tpmd230896, https://doi.org/10.4269/ajtmh.23-0896 in yet another article devoted to publishing statistics on the frequency of pfhrp2/3 gene deletions and their effect on false negative RDTs.

Ngasala B & al. tested the accuracy of both HRP2-based and lactic dehydrogenase (LDH)-based RDTs in schoolchildren. Using PCR as control, they report in Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017, Am J Trop Med Hyg. 2024 Mar 19; 110(5):887-891, https://doi.org/10.4269/ajtmh.23-0771 that over eight districts, the two RDTs were 76.2% and 93.6% accurate, respectively.  Exception was a low transmission area, where positive RDTs were outnumbered by false negative ones, which the authors attributed to very low parasitemia.

Whyte M & al. “assessed the fidelity of implementation of the national guidelines on malaria diagnosis for children under-five years and examine its associated moderating factors in health care facilities in Rivers State, Nigeria. [Their findings included a] fidelity score for all participants [of] 65% … Informal private facilities (proprietary patent medicine vendors) had the lowest fidelity scores (47%) compared to formal private (69%) and public health facilities (79%) … [Thus,] testing all suspected cases with approved diagnostic methods before treatment are still not fully implemented [even] by health facilities.” The authors recommend addressing this issue for all sectors, but especially for private facilities. The article is Fidelity of Implementation of National Guidelines on Malaria Diagnosis for Children Under-Five Years in Rivers State, Nigeria, Malaria J, 2024 Apr 27, 23:123, https://doi.org/10.1186/s12936-024-04957-4.

Based on focus group discussions of 23 “primary health care (PHC) workers,” Omale UI’s article, 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 reports that “determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker’s knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients’ demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money.” This article may also be classified as belonging to Treatment/Guidelines.

New diagnostic methods

“Sensitive and accurate malaria diagnosis is required for case management to accelerate control efforts. Diagnosis is particularly challenging where multiple Plasmodium species are endemic, and where P. falciparum hrp2/3 deletions are frequent. 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.” Based on their data gathered in Ethiopia and Ghana, Ewnetu Y & al., 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 states that “the miLab was more sensitive than microscopy and thus is a valuable addition to the toolkit for malaria diagnosis, particularly for areas with high frequencies of hrp2/3 deletions.”

The reviewer hopes that the reader will understand the abstract of Zhang Z & al.’s article, DCDLN: A Densely Connected Convolutional Dynamic Learning Network for Malaria Disease Diagnosis, Neural Netw. 2024 Apr 29; 176:106339, https://doi.org/10.1016/j.neunet.2024.106339, because he does not.  It reads, in part: “…a densely connected convolutional dynamic learning network (DCDLN) is proposed for the diagnosis of malaria disease. Specifically, after data processing and partitioning of the dataset, the densely connected block is trained as a feature extractor. To classify the features extracted by the feature extractor, a classifier based on a dynamic learning network is proposed in this paper.” The abstract also claims that, “the proposed DCDLN method demonstrates a diagnostic accuracy rate of 97.23%, surpassing the diagnostic performance than existing advanced methods on an open malaria cell dataset…” without mentioning what the control was.

Treatment                                                                                           

Treatment results

Many articles published about malaria in the COVID era deal with difficulties that arose in preventive campaigns. In contrast, Mohamed AH & al. focus on outcomes of malaria treatment in this setting. Their paper, COVID-19 and Malaria Co-Infection: A Systematic Review of Clinical Outcomes in Endemic Areas, PeerJ, 2024 Apr 18; 12:e17160, https://doi.org/10.7717/peerj.17160 reflects 19 articles they found on the subject. Somewhat mysteriously, they state that “Plasmodium falciparum and vivax were identified as causative organisms in six studies” [,] which raises the question of whether in the other reports the infectious agents were other Plasmodium species, or if not, how the diagnosis of malaria was made. As to results, “[m]ost patients with COVID-19 and malaria co-infection experienced short-term hospitalization and mild to moderate disease severity. However, at presentation, co-morbidities and severe malaria were significantly associated with higher mortality or worse clinical outcomes.”

Thomford NE & al. studied 52 patients who received generic artemether-lumefantrine for the influence of pharmacogenetics on outcomes and metabolism of the drugs. They report in Therapeutic Efficacy of Generic Artemether–Lumefantrine in the Treatment of Uncomplicated Malaria in Ghana: Assessing Anti-Malarial Efficacy Amidst Pharmacogenetic Variations, Malaria J, 2024 Apr 29, 23:125, https://doi.org/10.1186/s12936-024-04930-1 that while all patients had excellent results (no parasites seen on microscopy on days 3 and 7), the metabolic residue of lumefantrine was higher in the system of patients with two genetic variations.  There is no mention in the abstract whether this finding is of clinical significance.

“The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether–lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites … in Niger.” Laminou IM & al., Therapeutic Efficacy and Tolerability of Artemether–Lumefantrine for Uncomplicated Plasmodium falciparum Malaria in Niger, 2020, Malaria J, 2024 May 13, 23:144, https://doi.org/10.1186/s12936-024-04945-8 reports that among 255 patients enrolled in the study, “parasitological response” was between 92.2% and 98.6% in the three sites. “No adverse events were observed.” Genetic testing disclosed some mutations of the parasites, but none associated with artemisinin resistance.

Guidelines

Please see 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 above, in Diagnosis/Field diagnostics.

The use of primaquine for radical cure of vivax malaria has two drawbacks: it must be used carefully in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and it must be taken daily up to two weeks, which reduces compliance. Sharma R & al. review the evidence of a related drug, tafenoquine, which can be administered as a single dose in Optimal Balance of Benefit Versus Risk for Tafenoquine in the Treatment of Plasmodium vivax Malaria, Malaria J, 2024 May 13, 23:145, https://doi.org/10.1186/s12936-024-04924-z. Tafenoquine is definitely contraindicated for people with G6PD, but the WHO has now recommended its use at a dose of 300mg for radical cure of vivax malaria, provided the patient in question is demonstrated not to be G6PD deficient. The paper reviews the evidence behind the recommendation but is silent on any cost implication that may exist.

Side effects and complications

None this month

Drug resistance

Schreidah C & al. report that in the Rwandaise district studied, the mutation that cuses ar2temisinin resistance has now become 32% prevalent. As detailed in Expansion of Artemisinin Partial Resistance Mutations and Lack of Histidine Rich Protein-2 And -3 Deletions in Plasmodium falciparum Infections from Rukara, Rwanda, Malaria J, 2024 May 16, 23:150, https://doi.org/10.1186/s12936-024-04981-4 the recent increase in prevalence in mutations seems to be a new mutation in the same k13 gene that is involved in most resistant mutations.  As a side issue, the authors found no instance of the phrp2/3 gene deletions, meaning that RDTs should continue to be reliable as field diagnostic methods.

New drug research

Rosado-Quiñones AM & al., Novel Hydrazone Compounds with Broad-Spectrum Antiplasmodial Activity and Synergistic Interactions with Antimalarial Drugs, Antimicrob Agents Chemother, 2024 Apr 19: e0164323, https://doi.org/10.1128/aac.01643-23 describes laboratory results of testing seven related compounds, five of which had variable inhibitory effects on different Plasmodium species. One of the compounds were also stated to have synergistic effects with “the FDA-approved antimalarial drugs, clindamycin and halofantrine.”

As Kimura SI & al. report in New Antimalarial Iromycin Analogs Produced by Streptomyces Sp. RBL-0292, J Antibiot (Tokyo). 2024 May; 77(5):272-277, https://doi.org/10.1038/s41429-024-00707-5, “[t]wo new antimalarial compounds, named prenylpyridones A (1) and B (2), were discovered from the actinomycete cultured material of Streptomyces sp. RBL-0292 isolated from the soil on Hamahiga Island in Okinawa prefecture. The structures of 1 and 2 were elucidated as new iromycin analogs having α-pyridone ring by MS and NMR analyses. Compounds 1 and 2 showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC50 values ranging from 80.7 to 106.7 µM.”

Adegunloye AP & Adebayo JO, Piperine Enhances Antimalarial Activity of Methyl Gallate and Palmatine Combination, Acta Parasitol, 2024 May 6, https://doi.org/10.1007/s11686-024-00850-x is a report of a laboratory evaluation of the ingredients mentioned in the title.  They conclude that the “3:2 combination of methyl gallate and palmatine in the presence of piperine exhibited antimalarial activity in vivo, possibly by synergistic inhibition of hemozoin formation which may cause accumulation of haem within the food vacuole of Plasmodium spp. and its death.”

In another report of the search for new antimalarials Borgohain P & al. conclude that one of the hybrid trimethoxy pyrazole 1,3,5-triazine derivatives they studied had activity against P. falciparum. However, the strain of parasite they used in the laboratory was chloroquine sensitive. Therefore, the relevance of the article, Design, in silico study, Synthesis and Evaluation of Hybrid Pyrazole Substituted 1,3,5-Triazine Derivatives for Antimalarial Activity, Exp Parasitol. 2024 Apr 26: 108767, https://doi.org/10.1016/j.exppara.2024.108767, to real life is uncertain.

Plant extracts and traditional treatments

Various parts of Strychnos lucida, a tree in SE Asia and Northern Australia have been used in folk medicine against numerous ailments. Khasanah U & al. studied a tablet for antiplasmodial action and toxicity. The tablet is apparently standardized by Indonesian Pharmacopoeia for concentration of brucine, a toxic substance. “Acute oral toxicity of S.lucida extract was determined using the Organization for Economic Co-operation and Development 420 procedure,” with the result claimed to show “low toxicity,” while the tablet was judged to have “inhibited Plasmodium growth and improved the hemoglobin, hematocrit, and red blood cell profiles.” Their research is published as  Oral Acute Toxicity Study and in vivo Antimalarial Activity of Strychnos lucida R. Br. Tablet, J Ethnopharmacol,  2024 Apr 13: 118200, https://doi.org/10.1016/j.jep.2024.118200, the final version of a draft that was posted with the same title in SSRN, 2024 Jan as https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4681364.

Buthelezi MN & al. studied extracts of two plants, colloquially known as buffalo thorn and milkwort, is use in Southern African folk medicine against malaria. They describe the chemical processes of extracts and the effectiveness of the extracts in vitro against a component of P. falciparum.  Finally, the identify two compounds that they consider the specific antimalarial components of the buffalo thorn. The article is Phytochemical Evaluation of Ziziphus mucronata and Xysmalobium undulutum Towards the Discovery and Development of Anti-Malarial Drugs, Malaria J, 2024 May 11, 23:141, https://doi.org/10.1186/s12936-024-04976-1.

 

Other

Ocan M & al., Access to Quality-Assured Artemisinin-Based Combination Therapy and Associated Factors Among Clients of Selected Private Drug Outlets in Uganda, Malaria J, 2024 Apr 30, 23:128, https://doi.org/10.1186/s12936-024-04956-5 is a companion article to one in last month’s report (on the price of Quality Assured ACT).  “A total of 1114 exit interviews were conducted among systematically sampled drug outlet clients. Over half, 54.9% (611/1114) of the participants were males. Majority, 97.2% (1083/1114) purchased an artemisinin-based combination anti-malarial. Most, 55.5% (618/1114) of the participants had a laboratory diagnosis of malaria. Majority, 77.9% (868/1114) of the participants obtained anti-malarial agents without a prescription. Less than a third, 27.7% (309/1114) of the participants obtained a QAACT.” {This article and its companion are perfect examples of a single research project generating multiple papers in different journals, submitted almost simultaneously, thereby increasing the authors’ academic ‘heft’ without adding much to our knowledge.}

“Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. [Mahamar A & al.] aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes.” They report in Artemether-Lumefantrine with or Without Single-Dose Primaquine and Sulfadoxine-Pyrimethamine Plus Amodiaquine with or Without Single-Dose Tafenoquine to Reduce Plasmodium falciparum Transmission: A Phase 2, Single-Blind, Randomised Clinical Trial in Ouele, Lancet Microbe. 2024 May 2: S2666-5247(24)00023-5, https://doi.org/10.1016/s2666-5247(24)00023-5 that the data of their study in 80 individuals “support the effectiveness of artemether-lumefantrine alone for preventing nearly all mosquito infections. By contrast, there was considerable post-treatment transmission after sulfadoxine-pyrimethamine plus amodiaquine; therefore, the addition of a transmission-blocking drug might be beneficial in maximising its community impact.”

Arntson L & al.’ study, Factors Influencing Fever Care-Seeking for Children Under Five Years of Age in The Gambia: A Secondary Analysis of 2019–20 DHS Data, Malaria J, 2024 Apr 27, 23:124, https://doi.org/10.1186/s12936-024-04951-w, reports that while urban and higher educated mothers are more likely to seek care for their febrile children under five, according to the data collected by the Department of Health  Services of The Gambia, they are more likely to access pharmacies rather than official public healthcare facilities.  As a result, they conclude the following: “Whether influenced by convenience, costs, perceived urgency, or other factors, given the likelihood of urban mothers and mothers in wealthier households to seek care from private pharmacies, it will be necessary to incorporate private pharmacies into malaria control strategies while building public sector capacity and workforce, and initiating more effective attitude and behavioural change among mothers and households.”

Mefloquine is not a new drug; and it has recently acquired a bad reputation with a “black box warning” by the FDA (notwithstanding which, this reviewer has used it for over 30 years without problems, whenever traveling in countries where malaria is endemic). Raza M & al. have developed a new formulation, which they demonstrated in the mouse model to be very effective for resolving cerebral malaria, one of the deadliest complications of infection by P. falciparum. They conclude in Enhanced Anti-Malarial Efficacy of Mefloquine Delivered Via Cationic Liposome in a Murine Model of Experimental Cerebral Malaria, Eur J Pharm Biopharm. 2024 Apr; 197:114210, https://doi.org/10.1016/j.ejpb.2024.114210 that “a cationic liposomal mefloquine formulation, administered at four successive doses of 3 mg/kg body weight, achieves complete resolution of cerebral malaria in the murine model while avoiding noticeable toxic repercussions. Altogether, our study furnishes pre-clinical validation for a therapeutic strategy that can remarkably a cationic liposomal mefloquine formulation, enhance the drug efficacy, offering a revitalizing solution for failing anti-malarials.”

Campaigns and Policies

Musoke D & al. explored “facilitators and barriers to using integrated malaria prevention in Wakiso district, Uganda.” As reported in Facilitators and Barriers to Integrated Malaria Prevention in Wakiso District, Uganda: A Photovoice Study, PLoS Glob Public Health. 2024 Apr 16; 4(4):e0002469, https://doi.org/10.1371/journal.pgph.0002469, they used photos and interviews in their study. “… various conventional and non-conventional measures were being used for preventing malaria such as: insecticide treated nets; clearing overgrown vegetation; draining stagnant water; mosquito coils; smouldering of cow dung; spraying insecticides; plant repellents near houses; eating of prophylactic herbs; as well as closing doors and windows on houses early in the evening. Facilitators … included: low cost and accessibility of some methods such as slashing overgrown vegetation; and support provided for certain methods such as receiving free mosquito nets from the government. Barriers … included: inadequate knowledge of some methods such as housing improvement; allergic reactions to … insecticide treated nets; unaffordability of … insecticide sprays; and inaccessibility of … body repellents.”

Katushabe J & al., Exploring the Role of Spending on Malaria Incidence in Uganda Using the Auto-Regressive Distributed Lag Approach, Malaria J, 2024 Apr 30, 23:129, https://doi.org/10.1186/s12936-024-04929-8 is a long and complicated statistical analysis of the factors that have raised or reduced the incidence of malaria in Uganda.  The increase of public spending by one percent apparently yielded a reduction of malaria by significantly less tan one percent, which is not comforting. A major weakness of the paper is that the analysis stops at the fourth quarter of 2019, which is when malaria cases stopped decreasing throughout Africa and started rising.  A benefit to the readers is a color map of Uganda (in the paper not the abstract) indicating where in the country malaria is most prevalent, district by district.

“Since 2018, there has been an ongoing conflict …, which has reduced access to healthcare for populations in affected regions, and little is known about the impact on access to malaria services. The objective of [Besem E.O. ME & al.] was to understand the current situation regarding access to malaria services in Cameroon.”  They conducted focus group interviews in various parts of the country and report in Exploring Existing Malaria Services and the Feasibility of Implementing Community Engagement Approaches Amongst Conflict-Affected Communities in Cameroon: A Qualitative Study, Malaria J, 2024 May 20, 23:155, https://doi.org/10.1186/s12936-024-04934-x. The results of this qualitative study hold no surprises: there are difficulties in recruiting community health workers, and “several barriers remain that limit uptake of these services including awareness, availability, cost, trust in competency, and supply of testing and treatment.”

In Uganda, village health workers (VHWs) manage childhood illness under the integrated community case management (iCCM) strategy. Care is provided for malaria, pneumonia, and diarrhoea in a community setting. Currently, there is limited evidence on the cost-effectiveness of iCCM in comparison to health facility-based management for childhood illnesses.” Mulogo E & al., Cost-Effectiveness of Village Health Worker-Led Integrated Community Case Management (iCCM) Versus Health Facility Based Management for Childhood Illnesses in Rural Southwestern Uganda, Malaria J, 2024 May 15, 23:147, https://doi.org/10.1186/s12936-024-04962-7 “examined the cost-effectiveness of the management of childhood illness using the VHW-led iCCM against health facility-based services in rural south-western Uganda.”  Even though the VHW-led iCCM proved to be more costly, the authors conclude that it is a cost-effective strategy.

Please see Glozah FN & al., Implementation and Effectiveness Outcomes of Community Health Advocacy Teams to Improve Long-Lasting Insecticide Net Distribution and Use in Six Districts in Ghana: A One-Group Pre-Post-Test Study, PLoS Glob Public Health. 2024 Apr 1; 4(4):e0002123 above, under Prevention/Vectors.

Epidemiology

Climate change, biodiversity and environment

Suh E & al. used “a mechanistic model fitted to experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae, is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, parasite development rate, and overall vector competence.” As a result, they have formed the opinion that “increases in malaria transmission due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted. The paper is Estimating the Effects of Temperature on Transmission of the Human Malaria Parasite, Plasmodium falciparum, Nat Commun. 2024 Apr 22; 15(1):3230, https://doi.org/10.1038/s41467-024-47265-w.

“The control of arthropod disease vectors using chemical insecticides is vital in combating malaria, however the increasing insecticide resistance (IR) poses a challenge. Furthermore, climate variability affects mosquito population dynamics and subsequently IR propagation.” In A Mathematical Model for Mapping the Insecticide Resistance Trend in the Anopheles gambiae Mosquito Population Under Climate Variability in Africa, Sci Rep. 2024 Apr 29; 14(1):9850, https://doi.org/10.1038/s41598-024-60555-z,  Agboka KM & al. “present a mathematical model to decipher the relationship between IR in Anopheles gambiae populations and climate variability. By adapting the susceptible-infected-resistant (SIR) framework and integrating temperature and rainfall data, our model examines the connection between mosquito dynamics, IR, and climate. Model validation using field data achieved 92% accuracy…”

In another modeling study Talib J & al. compare two specific methods of modeling, “the Liverpool Malaria Model (LMM) and Vector-Borne Disease Community Model of the International Centre for Theoretical Physics (VECTRI),”  to determine The Effect of Explicit Convection on Simulated Malaria Transmission Across Africa (PLoS One, 2024 Apr 16; 19(4):e0297744, https://doi.org/ 10.1371/journal.pone.0297744). The two models give widely divergent predictions, “[f]or instance, in the East African highlands, cooler temperatures when explicitly representing convection decreases LMM-predicted malaria transmission risk by approximately 55%, but has a negligible effect in VECTRI simulations.” The authors conclude that the “LMM is relatively insensitive to future changes in precipitation intensity, whilst VECTRI predicts increased risk across the Sahel due to enhanced rainfall. We postulate that VECTRI’s enhanced sensitivity to precipitation changes compared to the LMM is due to the inclusion of surface hydrology.”

Even though Abbas H & al., Exploring Mosquito Abundance and Plasmodium Infection Through Nested-PCR: Implications for Disease Surveillance and Control, Sci Rep. 2024 Apr 30; 14(1):9871, https://doi.org/10.1038/s41598-024-60662-x focuses on a small geographic area of Pakistan, the article is of interest, because it appears to correlate the abundance of Anopheles mosquitoes and their carrying rate of Plasmodium species with conditions such as temperature and humidity.

Risk factors

Isiko I & al., Factors Associated with the Risk of Malaria Among Children: Analysis of 2021 Nigeria Malaria Indicator Survey, Malaria J, 2024 Apr 17, 23:109, https://doi.org/10.1186/s12936-024-04939-6 reports several interesting results, some perhaps unexpected, of analyzing the survey data to which reference is made. “There was a positive association between the risk of malaria and heard/seen malaria messages in the last 6 months … houses with walls built using rudimentary materials …, at least 6 children living in the house …, children being 1 or 2 years old was associated with increased odds …, children from households with only treated nets … and those from the North West or South East regions …, respectively.” None of the other predictors were associated with the risk of malaria.

Schmidt N & al. found association of gut inflammation with clinical malaria in children in Mali. Their work included colonizing mice with fecal samples from “malaria-susceptible” and “malaria resistant” children, with the result of higher parasite burden in the mice of the former group. “Children were initially characterized as ‘susceptible’ if they experienced at least one febrile malaria episode during the study period and as ‘resistant’ if they had no febrile malaria episodes during the study period despite having at least one asymptomatic P. falciparum detected by PCR… analysis of the human fecal samples corroborated the existence of inflammatory and recovery-associated features within the gut microbiome of the susceptible children.” The article is Susceptibility to Febrile Malaria is Associated with an Inflammatory Gut Microbiome, Res Sq, 2024 Apr 4: rs.3.rs-3974068, https://doi.org/10.21203/rs.3.rs-3974068/v1. Research Square publishes papers without prior peer review.

Over four and a half years, Zeno EE & al. found that about 35% of over 1100 individuals suspected of malaria but with negative RDT, had detectable P. falciparum in their blood. {The abstract is silent on how this was diagnosed and the article is unavailable to this reviewer.} In the abstract of their paper, Risk of Malaria Following Untreated Subpatent Plasmodium falciparum Infections: Results Over 4 Years From a Cohort in a High-Transmission Area in Western Kenya, J Infect Dis. 2024 Apr 12; 229(4):969-978, https://doi.org/10.1093/infdis/jiad398, they assert that the “risk of developing clinical malaria among people with undetected subpatent infections is low. A slightly elevated risk in the low-transmission season may merit alternate management, but RDTs identify clinically relevant infections in the high-transmission season.” There is no mention of gene deletions that may contribute to the negative RDT results.

Pregnancy is a major risk factor for both parasitemia and clinical malaria. Melariri P & al., Plasmodium Parasitaemia and Urine Alterations among Pregnant Women Attending Antenatal Care in Aba Metropolis, Abia State, Nigeria, J Parasitol Res. 2024 Apr 4; 2024:6681943, https://doi.org/10.1155/2024/6681943 presents a study full of prevalence statistics, but some appear to have inconsistencies.  One finding that is consistent with other reports was that women who use LLINs at home were less likely to have parasitemia.

Gebreegziabher E & al. focused on occupation and other socioeconomic factors in identifying adult populations at higher-than-average risk of malaria. They report in Identifying and Characterizing High-Risk Populations in Pilot Malaria Elimination Districts in Madagascar: A Mixed-Methods Study, Malaria J, 2024 Apr 26, 23:121, https://doi.org/10.1186/s12936-024-04927-w that there were somewhat diverging results in the districts studied in this regard. In two districts, “rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In [a third one], respondents identified non-rice farmers, mobile vendors, and students” as high-risk populations (HRPs). “Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation.”

General epidemiology

According to Li J & al., Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges, J Epidemiol Glob Health. 2024 Apr 24, https://doi.org/10.1007/s44197-024-00228-2, “many challenges are emerging in the fight against malaria in Africa, such as climate change, poverty, substandard health services and coverage, increased outdoor transmission and the emergence of new vectors, and the growing threat of resistance to antimalarial drugs and insecticides. Joint prevention and treatment, identifying molecular determinants of resistance, new drug development, expanding seasonal malaria chemo-prevention intervention population, and promoting the vaccination of RTS, S/AS01 and R21/Matrix-M may help to solve the dilemma. China’s experience in eliminating malaria is conducive to Africa’s malaria prevention and control…”

Badiane AS & al. report on the recently appreciated presence of P. vivax in Senegal, though significantly less prevalent than P. falciparum and even P. malariae. Their article, Evidence of Plasmodium vivax Circulation in Western and Eastern Regions of Senegal: Implications for Malaria Control, Malaria J 2024 May 16, 23:149, https://doi.org/10.1186/s12936-024-04932-z reports that malaria prevalence was widely divergent in the provinces studied, from 12.3%to 37.6%. Of special importance may be that P. vivax monoinfections will mostly be negative on RDT.

 

Spatiotemporal studies

Yutura G & al., Prevalence of Malaria and Associated Risk Factors Among Household Members in South Ethiopia: A Multi-Site Cross-Sectional Study, Malaria J, 2023 May 12, 23:143, https://doi.org/10.1186/s12936-024-04965-4

Boresa K & al., Ten-year Trend Analysis of Malaria Prevalence in Gindabarat District, West Shawa Zone, Oromia Regional State, Western Ethiopia, Malaria J, 2024 May 16, 23:152, https://doi.org/10.1186/s12936-024-04975-2

 

 

 

 

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