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

FROM the WHO (https://www.who.int/news/item/06-03-2024-african-health-ministers-commit-to-end-malaria-deaths)

“Ministers of Health from African countries with the highest burden of malaria committed today to accelerated action to end deaths from the disease. They pledged to sustainably and equitably address the threat of malaria in the African region, which accounts for 95% of malaria deaths globally.

The Ministers, gathering in Yaoundé, Cameroon, signed a declaration committing to provide stronger leadership and increased domestic funding for malaria control programmes; to ensure further investment in data technology; to apply the latest technical guidance in malaria control and elimination; and to enhance malaria control efforts at the national and sub-national levels.

The Ministers further pledged to increase health sector investments to bolster infrastructure, personnel and programme implementation; to enhance multi-sectoral collaboration; and to build partnerships for funding, research and innovation. In signing the declaration, they expressed their “unwavering commitment to the accelerated reduction of malaria mortality” and “to hold each other and our countries accountable for the commitments outlined in this declaration.”

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

Prevention

 

Vaccines

Adamu AA & al. studied the success of the pilot implementation of the RS,S/AS01 vaccine in three countries.  Apparently of the many factors that were associated with the success of reaching the target population or lack thereof cluster somewhat. In Assessing the Implementation Determinants of Pilot Malaria Vaccination Programs in Ghana, Kenya, and Malawi through a Complexity Lens: A Rapid Review Using a Consolidated Framework for Implementation Research, Vaccines (Basel), 2024 Jan 23; 12(2):111, https://doi.org/10.3390/vaccines12020111 they state that a “causal loop diagram showed that these factors are interconnected and interrelated, identifying nine reinforcing loops and two balancing loops.” They recommend that “implementation studies that incorporate the causal loop diagram should be integrated into the malaria vaccine implementation program to enable immunization program managers and other key stakeholders to identify and respond to emerging … barriers.”

Hill, J & al. conducted a qualitative longitudinal study to investigate the contextual and dynamic factors shaping vaccine delivery and uptake during a pilot introduction in western Kenya. They report in Integration of the RTS,S/AS01 Malaria Vaccine into the Essential Programme on Immunisation in Western Kenya: A Qualitative Longitudinal Study from the Health System Perspective, Lancet Glob Health, 2024 Feb 28, https:doi.org/10.1016/s2214-109x(024)00013-5 that “[i]nitial challenges related to the complexity of the four-dose schedule (up to 24-months); however, self-efficacy increased over time as the health-care providers gained experience in vaccine delivery. Low uptake of the fourth dose remained a challenge. Health managers cited insufficient trained immunisation staff and inadequate funding for supervision. Confidence in the vaccine increased among all participant groups owing to reductions in malaria frequency and severity.”

Based on a review of 66 published papers on the subject, Chutiyami M & al., Malaria Vaccine Efficacy, Safety, and Community Perception in Africa: A Scoping Review of Recent Empirical Studies, Infection. 2024 Mar 5, https://doi.org/10.1007/s15010-024-02196-y reports that “[o]f the vaccines identified, overall efficacy at 12 months was highest for the R21 vaccine … at 77.0%, compared to the RTS,S vaccine … at 55%.” Other, as yet unapproved vaccines were also accounted for, with generally lower efficacies. “Mixed perceptions of malaria vaccines were found in African communities … awareness was generally low, ranging from 11% in Tanzania to 60% in Nigeria …, compared to willingness to accept the vaccines, which varied from 32.3% in Ethiopia to 96% in Sierra Leone…”

Amimo F, Malaria Vaccination: Hurdles to Reach High-Risk Children, BMC Med. 2024 Mar 13; 22(1):111, https://doi.org/10.1186/s12916-024-03321-2 appears to be and editorial without much in the way offering new information: e.g. “The analysis finds health system related risks with the potential to reduce the ability of malaria vaccines to provide equitable protection. Deployment of effective frameworks to tackle these risks so as to strengthen within-country equity and progress tracking should be entangled with the deployment of the vaccines.”

“Several studies suggest that higher levels of previous malaria exposure negatively impact RTS,S clinical efficacy.” In Previous Malaria Exposures and Immune Dysregulation: Developing Strategies to Improve Malaria Vaccine Efficacy in Young Children, Am J Trop Med Hyg. 2024 Mar 5: tpmd230696, https://doi.org/10.4269/ajtmh.23-0696, Dobbs KR & al. “summarize data suggesting that previous malaria exposures negatively impact the efficacy of RTS,S and other malaria vaccine candidates. [They] highlight recent evidence suggesting that increasing malaria exposure impairs the generation of functional antibody responses to RTS,S. Finally, [they] discuss how investigation of clinical and immune factors associated with suboptimal responses to RTS,S can be used to develop strategies to optimize RTS,S, which will remain relevant to R21 and next-generation vaccines.”

 

“Adjuvants are critical components for vaccines, which enhance the strength and longevity of the antibody response and influence the types of immune response. Limited research has been conducted on the immunogenicity and protective efficacy of various adjuvants in malaria transmission-blocking vaccines (TBVs).” Yu X & al. “formulated a promising TBV candidate antigen, the P. berghei ookinete surface antigen PSOP25,” with six different types of adjuvants. They discuss their results in Evaluation of Different Types of Adjuvants in a Malaria Transmission-Blocking Vaccine, Int Immunopharmacol. 2024 Mar 8; 131:111817, https://doi.org/10.1016/j.intimp.2024.111817.

Abebe A & al.’s report on Genetic Differentiation of Plasmodium vivax Binding Protein in Ethiopia and Comparison with Other Geographical Isolates, Malaria J, 2024 Feb 23, 23:55, https://doi.org/10.1186/s12936-024-04887-1 is essentially a basic science research paper; it is cited here because the genetic diversity in the protein that the authors describe has major implications for the development of a vaccine against P. vivax.

 

 

 

Vector control and protection from vectors

 

Even in the setting of appropriate use of insecticide treated nets (ITNs), Odero JI & al., Early Morning Anopheline Mosquito Biting, a Potential Driver of Malaria Transmission in Busia County, Western Kenya, Malaria J, 2024 Mar 4, 23:66, https://doi.org/10.1186/s12936-024-04893-3 documents significant exposure mosquito bites among early risers. “Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400–0700 h for An. gambiae and 0300–0700 h for An. funestus. … Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning.”

Durability and effectiveness of “long-lasting” insecticidal nets (LLINs) are the subjects of Djoufounna J & al., Physical Integrity and Bioefficacy of Used Long-Lasting Insecticidal Nets in Makenene, Centre Region of Cameroon, J Med Entomol. 2024 Mar 9: tjae035, https://doi.org/10.1093/jme/tjae035. Six years after distribution of nets, the authors found only 39.5% “fairly good” and 26.4% “acceptable” among 167 of them examined. More to the point, none (0%) of 30 nets tested were effective against locally caught An. gambiae s.s. or even the nuisance mosquito Culex pipiens. However, they were effective against “laboratory raised laboratory-reared pyrethroid-susceptible strain of An. coluzzii.” This latter finding seems to imply that the malaria vectors in the area studied have developed resistance to pyrethroid insecticides.

Ashu FA & al. found significant variation in tolerance to neonicotinoids between An. gambiae and An. coluzzii populations from Yaoundé. As they describe in Adult Mosquitoes of the Sibling Species Anopheles gambiae and Anopheles coluzzii Exhibit Contrasting Patterns of Susceptibility to Four Neonicotinoid Insecticides Along an Urban-to-Rural Gradient in Yaoundé, Cameroon, Malaria J, 2024 Mar 2, 23:65, https://doi.org/ 10.1186/s12936-024-04876-4, “this class of insecticides has low toxicity against Anopheles mosquitoes. Reduced susceptibility to the four neonicotinoids tested was detected in An. gambiae populations collected from rural and suburban areas. By contrast, adults of An. coluzzii that occurred in urbanized settings were susceptible to neonicotinoids except acetamiprid for which 80% mortality was obtained within 72 h of insecticide exposure. The cytochrome inhibitor, piperonyl butoxide (PBO), significantly enhanced the activity of clothianidin and acetamiprid against An. gambiae mosquitoes.”

 

Mosquitoes are increasingly resistant to a variety of insecticides.  Benin has chosen to use clothianidin, an insecticide that acts different from pyrethroids, for its indoor residual spraying (IRS) program.  Odjo EM & al. found that genetic markers of pyrethroid resistance were present in high frequency in treated and untreated areas and there were no differences in the rate of Plasmodium infection of mosquitoes with and without the markers. It is unclear what practical conclusions can be drawn from the results published in their paper, Malaria Transmission Potential of Anopheles gambiae s.l. in Indoor Residual Spraying Areas with Clothianidin 50 WG in Northern Benin, Trop Med Health. 2024 Feb 9; 52(1):18, https://doi.org/10.1186/s41182-024-00582-8.

Odufuwa OG & al. also addressed the phenomenon of insecticide resistance in Time of Exposure and Assessment Influence the Mortality Induced by Insecticides Against Metabolic Resistant Mosquitoes, Parasit Vectors. 2024 Mar 2; 17(1):103, https://doi.org/10.1186/s13071-024-06190-z. They exposed resistant mosquitoes to piperonyl butoxide (PBO) enhanced ITNs at various times of the day and found that those exposed at night had lower 24-hour mortality than those exposed during the day. Mortality after 72 hours was greater than that at 24 hours.

Joseph RJ & al. verified that in Namibia, Anopheles mosquitoes were developing resistance to deltamethrin, a pyrethroid insecticide. By pretreating resistant mosquitoes in the laboratory to “piperonyl butoxide (PBO) synergist,” the mosquitoes became susceptible to deltamethrin. In their paper, Insecticide Susceptibility Status of Anopheles gambiae Mosquitoes and the Effect of Pre-Exposure to a Piperonyl Butoxide (PBO) Synergist on Resistance to Deltamethrin in Northern Namibia, Malaria J, 2024 Mar 14, 23:77, https://doi.org/10.1186/s12936-024-04898-y they conclude that their data highlight “the promise of pyrethroid-PBO LLINs in addressing resistance issues in the region.”

 

Degefa T & al. explore the various methods of catching mosquito vectors and analyze the reliability of the sampling methods, as well as describing some new methods of sampling in Methods of Sampling Malaria Vectors and Their Reliability in Estimating Entomological Indices in Africa, J Med Entomol, q Feb 23: tjae015, https://doi.org/10.1093/jme/tjae015.

“Vector surveillance is among the World Health Organization global vector control response (2017–2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection.” Kosgei J & al., Comparison of Different Trapping Methods to Collect Malaria Vectors Indoors and Outdoors in Western Kenya, Malaria J, 2024 Mar 16, 23:81, https://doi.org/10.1186/s12936-024-04907-0 is a study of three other methods, UV light traps (UV-LT), CDC light traps (CD-LT) and Prokopack aspiration, as compared to human landing catches (HLC). After catching over 5300 mosquitoes, the authors conclude that “[m]ore mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs.”

Ebhodaghe FI & al. report in Sibling Species of the Major Malaria Vector Anopheles gambiae Display Divergent Preferences for Aquatic Breeding Sites in Southern Nigeria, Malaria J. 2024 Feb 27;23(1):60, https://doi.org/10.1186/s12936-024-04871-9 that the various species of An. gambiae s.l. appear to have different affinities for breeding sites, at least in the area they studied. “Anopheles arabiensis, An. coluzzii, and An. gambiae s.s. displayed preferences for turbid, lowland, and partially sunlit water bodies, respectively. Furthermore, An. arabiensis preferred breeding sites located outside 500 m of households, whereas An. gambiae s.s. and An. coluzzii had increased detection odds in sites within 500 m of households. Anopheles gambiae s.s. and An. coluzzii were also more likely to be present in natural water bodies; meanwhile, 96.77% of An. arabiensis were in man-made water bodies.” The authors found no specimens of An. stephensi in the course of their study.

 

HasapAla SM & al. studied the cost effectiveness of “Long-Lasting Insecticidal Nets (LLINs), Indoor Residual Spray (IRS) and Larval Source Management (LSM) in two areas of Sudan in 2017. As reported in Cost Effectiveness of Malaria Vector Control Activities in Sudan, Malaria J, 2024 Mar 15, 23:80, https://doi.org/ 10.1186/s12936-024-04900-7, “IRS and LLINs are cost effective control measures due to adequate inputs and organized process.”  LSM was the least costly per inhabitant, but also largely ineffective, probably because of the poor area coverage.

 

 

Smidler AL & al. “outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae.” As described in CRISPR-Mediated Germline Mutagenesis for Genetic Sterilization of Anopheles gambiae Males, Sci Rep. 2024 Feb 19;14(1):4057, https://doi.org/10.1038/s41598-024-54498-8, “[t]hese males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.” This is a gene drive process.

“Recently, bacterial endosymbionts, including Wolbachia and Microsporidia were found to limit the infection of Anopheles mosquitoes with Plasmodium falciparum.” Ahouandjinou MJ & al.aimed to investigate the natural presence of key transmission-blocking endosymbionts in Anopheles gambiae and Anopheles coluzzii in Southern Benin.” Their First Report of Natural Infection of Anopheles gambiae s.s. and Anopheles coluzzii by Wolbachia and Microsporidia in Benin: A Cross-Sectional Study, Malaria J, 2024 Mar 11, 23:72, https://doi.org/10.1186/s12936-024-04906-1 documents the presence of Wolbachia in about 5% of mosquitoes collected in three of the seven sites they studied, while Microsporidia was more prevalent (up to 57%) and more widespread (all seven sites). The authors aver that this is the first time these infections have been reported in Benin. None of the mosquitoes that harbored P. falciparum were infected by Wolbachia and only one colonized by Microsporidia.

Please see Msangi SJ & al., Challenges of Proper Disposal of Old Long-Lasting Insecticidal Nets and Its Alternative Uses in Rural South-Eastern Tanzania, PLoS One. 2024 Feb 15; 19(2):e0279143, https://doi.org/10.1371/journal.pone.0279143 under Epidemiology/environment

 

Chemoprophylaxis

None this month

 

Diagnosis

 

General diagnostics

None this month

 

Field diagnostics

 

In view of reports of unreliability of Rapid Diagnostic Tests (RDTs) in certain parts of Africa, Dembélé P & al. investigated its accuracy in Mali.  The authors report in Evaluation of the Performance of Rapid Diagnostic Tests for Malaria Diagnosis and Mapping of Different Plasmodium Species in Mali, Int J Environ Res Public Health, 2024 Feb 15; 21(2):228, https://doi.org/10.3390/ijerph21020228 that if the infective parasite was P. falciparum, the “RDT displayed acceptable diagnostic indices” and advocate developing similar tests for P. vivax, which seems to be somewhat prevalent in the North of Mali.

 

Whereas in Africa the reliability of RDTs is controversial, Çulha G & al., Investigation of Sensitivity of Rapid Diagnosis Tests in Patients with Suspected Malaria, Türkiye Parazitol Derg. 2024 Mar 5; 48(1):1-7, https://doi.org/10.4274/tpd.galenos.2024.38358 reports 100% sensitivity and 100% selectivity in RDT results in 30 cases of verified imported cases of P. falciparum or P. vivax. The conclusion is not inconsistent with other results if these infections were all with parasites that possessed the protein on whose presence the accuracy of RDT depends.

 

New diagnostic methods

None this month

 

Treatment

 

Treatment results

 

Focusing on the treatment of children with malaria, Dimbu PR & al. report in Therapeutic Response to Four Artemisinin-Based Combination Therapies in Angola, 2021, Antimicrob Agents Chemother. 2024 Feb 29: e0152523, https://doi.org/10.1128/aac.01525-23 that of the four artemisinin combinaton therapies utilized, artemether lumefantrine was efficacious less than 90% of the time in one of the three provinces studied. The other combinations were all reported to have efficacy over 95% in all locations.

Ramharter M & al. studied the result of administering granule administration of pyronaridine-artesunate (PA) to children over 5 kg in weight. They report in Safety and Efficacy of Pyronaridine–Artesunate Paediatric Granules in the Treatment of Uncomplicated Malaria in Children: Insights from Randomized Clinical Trials and a Real-World Study, Malaria J, 2024 Feb 28, 23:61, https://doi.org/10.1186/s12936-024-04885-3 that in comparison to artemether-lumefantrine (AL), which comes in tablet form and must be crushed.  They report on the basis of four studies published that effectiveness of PA was equal to that of AL with sight increase in vomiting, but reduction in changes in the ECG.

Adherence to guidelines

 

“Malaria in pregnancy (MiP) is associated with maternal anemia, spontaneous abortion, and infant and maternal death.” Tesha GE & al. “assessed coverage of key MiP care components, … to analyze uptake of the recommended three or more doses of intermittent preventive treatment in pregnancy (IPT3+), and assessed client satisfaction.  As they report in Understanding Antenatal Care Service Quality for Malaria in Pregnancy Through Supportive Supervision Data in Tanzania, Am J Trop Med Hyg. 2024 Feb 6: tpmd230399., https://doi.org/10.4269/ajtmh.23-0399, “[c]overage of most MiP care components exceeded 80%; however, only 38% of women received all components. Odds of receiving IPTp3+ were much lower among late ANC initiators than among those who initiated ANC during their first trimester… Just 54% of clients had anemia screening and only 46% received IPTp3+. Client satisfaction with services and provider communication was high…”

Side effects and complications

None this month

Drug resistance

 

van Loon W & al. describe one specimen out of 256 in which the gene that is a marker for artemisinin resistance in Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodium falciparum, South Kivu, Democratic Republic of the Congo, 2022, Am J Trop Med Hyg. 2024 Feb 20: tpmd230740, https://doi.org/10.4269/ajtmh.23-0740. The specimen also had characteristics of partial resistance to lumefantrine.  This is not surprising, since the province in which this was found is adjacent to Rwanda, where such resistance has been described before.

“Historically Plasmodium falciparum has followed a pattern of drug resistance first appearing in low-transmission settings before spreading to high-transmission settings.” Zupko RJ & al. tested “whether importation of drug-resistant parasites is more likely to lead to successful emergence and establishment in low-transmission or high-transmission periods of the same epidemiological setting, using a spatial, individual-based stochastic model of malaria and drug-resistance evolution calibrated for Burkina Faso.” They report in Role of Seasonal Importation and Genetic Drift on Selection for Drug-Resistant Genotypes of Plasmodium falciparum in High-Transmission Settings, J R Soc Interface. 2024 Mar; 21(212):20230619, https://doi.org/10.1098/rsif.2023.0619, that “drug-resistant genotypes imported during the low-transmission season were (i) more susceptible to stochastic extinction due to the action of genetic drift, and (ii) more likely to lead to establishment of drug resistance when parasites are able to survive early stochastic loss due to drift. This implies that rare importation events are more likely to lead to establishment if they occur during a high-transmission season, but that constant importation (e.g. neighbouring countries with high levels of resistance) may produce a greater risk during low-transmission periods.”

“The recent emergence of artemisinin partial resistance (ART-R) in Rwanda, Uganda and Eritrea is of great concern. In Tanzania, a nationwide molecular malaria surveillance in 2021 showed a high prevalence of the Kelch13 (K13) 561H mutation in Plasmodium falciparum from the north-western region, close to the border with Rwanda and Uganda.” Ishengoma DS & al. studied the effectiveness of artemisinin combination therapy (ACT) correlated with the presence of the above mutation in an area of Tanzania that borders on both Rwanda and Uganda. Their paper, Evidence of Artemisinin Partial Resistance in North-Western Tanzania: Clinical and Drug Resistance Markers Study, medRxiv. 2024 Feb 1: 2024.01.31.24301954, https://doi.org/10.1101/2024.01.31.24301954 contains data indicating that after treatment with ACT, children whose infective agents’ genome contained the mutation had parasitemia longer than other children, though the ACT regimens used were efficacious in 98+% of cases. The authors recommend continued vigilance for resistant mutations in Tanzania.  While this paper has significant implications, it was published in medRxiv, which does not subject papers to peer review prior to publication. Yet Bakari C & al., who published genetic studies of over 2000 specimens of P. falciparum obtained from patients with malaria from the same geographic area of Tanzania, found only a single instance of a genetic marker (different from above) associated with artemisinin resistance Their report is Trends of Plasmodium falciparum Molecular Markers Associated with Resistance to Artemisinins and Reduced Susceptibility to Lumefantrine in Mainland Tanzania from 2016 to 2021, Malaria J, 2024 Mar 9, 23:70, https://doi.org/10.1186/s12936-024-04896-0

 

Konaté-Touré A & al. found no evidence of the k13 mutations responsible for artemisinin resistance in SE Asia in P. falciparum collected from over 700 participants in Côte d’Ivoire; however other mutations of the same gene were present in up to 20% of specimens collected. However, “[c]omparing to previous studies in the country,” Their paper, Increase of Plasmodium falciparum Parasites Carrying Lumefantrine-Tolerance Molecular Markers and Lack of South East Asian Pfk13 Artemisinin-Resistance Mutations in Samples Collected from 2013 to 2016 in Cote D’Ivoire, J Parasit Dis. 2024 Mar; 48(1):59-66, https://doi.org/10.1007/s12639-023-01640-4 “showed an increase in lumefantrine tolerance of P. falciparum strains.”

“Increasing awareness of factors contributing to parasite resistance to antimalarials within communities is crucial.” Sofeu-Feugaing DD & al., Community Engagement and Antimalarial Drugs Medication as the First Line of Defense in the Fight Against Antimalarial Drug Resistance in Some Endemic Localities in Cameroon, IJID Reg. 2024 Feb 9; 10:207-213, https://doi.org/10.1016/j.ijregi.2024.02.001 “assessed how community knowledge, attitudes, and practices (KAPs) influence factors contributing to antimalarial resistance across four malaria ecological zones in Cameroon” by administering questionnaires to 980 volunteers from the communities studied. “Antimalarials commonly used were artemisinin-based combination therapies (37.96%), chloroquine (4.29%), quinine (22.24%), paracetamol (12.96%), and native drugs (19.80%). Up to 49.49% of the participants practiced self-medication, whereas 76.43% bought medications from licensed pharmacies, 10.61% bought from roadside vendors, and 23.57% relied on traditional/herbal medicines. [The suthors] observed significant and medium positive linear correlations at P <0.01 between knowledge-attitude (r = 0.528), knowledge-practice (r = 0.400), and attitude-practice (r = 0.496).” They conclude that despite “the general fair level of awareness of proper management and use of antimalarial drugs in the communities, the high level of self-medication and gross neglect of certain risk factors that may promote the emergence and spread of drug-resistant parasites is concerning.”

New drug research

“The synthesis and antiplasmodial evaluation of new hybrids combining the pharmacophore structures of artemisinin, ciprofloxacin or norfloxacin, and 7-chloroquinoline are reported” in Vamvoukaki G & al., Synthesis of Novel Artemisinin, Ciprofloxacin, and Norfloxacin Hybrids with Potent Antiplasmodial Activity, Antibiotics (Basel). 2024 Feb 1; 13(2):142, https://doi.org/10.3390/antibiotics13020142. Of 18 compounds synthesized, six had in vitro activity against chloroquine resistant P. falciparum; four in combination with ciprofloxacin, two with norfloxacin. “[T]he combination of artesunate with either ciprofloxacin or norfloxacin moieties in a single molecular entity proved to substantially enhance the activity and selectivity when compared to the administration of the unconjugated counterparts artesunate/ciprofloxacin and artesunate/norfloxacin.”

Quercetin is a flavonoid (antioxidant) present in fruits and vegetables, “particularly citrus fruits, apples, onions, parsley, sage, tea, and red wine. Olive oil, grapes, dark cherries, and dark berries such as blueberries, blackberries, and bilberries are also high in quercetin and other flavonoids.” {https://www.mountsinai.org/health-library/supplement/quercetin#}. Memariani H & al., Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues, Biomed Res Int. 2024 Feb 29; 2024:7632408, https://doi.org/10.1155/2024/7632408 states that “[r]ecently, there has been an explosion of research into the antiprotozoan properties of quercetin…,” including its effectiveness against Plasmodium parasites. “In vivo studies also show that quercetin is effective in reducing parasitic loads, histopathological damage, and mortality in animals. … clinical trials are needed to validate the efficacy of quercetin in treating various protozoan infections.”

Plant extracts and traditional treatments

Rotheca serrata (blue fountain bush or the beetle killer) is found and used in folk medicine in India and other parts of Asia, Chanu WK & al., Phytochemical Screening, Antioxidant Analyses, and in vitro and in vivo Antimalarial Activities of Herbal Medicinal Plant – Rotheca serrata (L.) Steane & Mabb, J Ethnopharmacol. 2024 Mar 1; 321:117466, https://doi.org/10.1016/j.jep.2023.117466 indicates that some of it leaves’ extracts are highly effective against the muse model of malaria in the laboratory. Very similar laboratory results are reported by Devi G & al. about two plants found in the Himalayans, Crambe kotschyana and Eremurus himalaicus in Exploring the Efficacy of Ethnomedicinal Plants of Himalayan Region Against the Malaria Parasite, J Ethnopharmacol. 2024 Mar 1; 321:117394, https://doi.org/10.1016/j.jep.2023.117394. If the results reported with regard to these plants fouind only in Asia lead to the development of effective antimalarial drugs, they should be useful wherever malaria is prevalent.

 

Campaigns and Policies

 

“Malaria elimination requires closely co-ordinated action between neighbouring countries. In Southern Africa several countries have reduced malaria to low levels, but the goal of elimination has eluded them thus far. The Southern Africa Development Community (SADC) Malaria Elimination Eight (E8) initiative was established in 2009 between Angola, Botswana, Eswatini, Mozambique, Namibia, South Africa, Zambia, and Zimbabwe to coordinate malaria interventions aiming to eliminate malaria by 2030.” Sikaala CH & al., Malaria Elimination and the Need for Intensive Inter-Country Cooperation. A Critical Evaluation of Regional Technical Co-Operation in Southern Africa, Malaria J, 2024 Feb 28, 23:62, https://doi.org/ 10.1186/s12936-024-04891-5 “describes how this collaboration is realized in practice, its achievements and challenges, and its significance for malaria elimination prospects.” Six accomplishments are enumerated. These are considered “groundwork for elimination …, but the challenge will be to maintain funding for collaboration at this level whilst reducing reliance on international donors and to build capacities necessary to prepare for malaria elimination.”

“As countries approach elimination of malaria, groups with increased exposure to malaria vectors or poor access to health services may serve as important human reservoirs of infection that help maintain transmission in the community. Parasitological testing and treatment targeted to these groups may reduce malaria transmission overall.” Bhamani B & al. “assessed the effectiveness of targeted testing and treatment (TTaT) to reduce malaria transmission, the contextual factors, and the results of modeling studies that estimated the intervention’s potential impact.” They report the analysis of three large studies in Targeted Testing and Treatment to Reduce Human Malaria Transmission in High-Risk Populations: A Systematic Review, Am J Trop Med Hyg. 2024 Mar 12: tpmd230097, https://doi.org/10.4269/ajtmh.23-0097, with their conclusion that these studies demonstrate the ineffectiveness to TTaT in reducing community-wide incidence of malaria and while “effects of TTaT on prevalence (malaria parasitemia) among those targeted by the intervention were found to include a short-term impact on reducing transmission. [it had] little to no impact on transmission for extended periods.”

In a companion article, Bhamani B & al., Mass Testing and Treatment to Accelerate Malaria Elimination: A Systematic Review and Meta-Analysis, Am J Trop Med Hyg. 2024 Mar 12: tpmd230127, https://doi.org/10.4269/ajtmh.23-0127 the same authors report on the analysis of seven articles about Mass Testing and Treatment.  Even though they report that “[t]hree studies [of the seven] contributing data on contextual factors concluded that MTaT is an acceptable, feasible, and cost-effective intervention,” their conclusion based on meta-analysis of all seven is as follows: “Mathematical modeling analyses … suggested that MTaT effectiveness depends on the baseline transmission level, diagnostic test performance, number of rounds, and other co-interventions. Based on the limited evidence available, MTaT has little to no impact on reducing malaria transmission.”

 

 

Onyinyechi OM & al., Prevention of Malaria in Pregnancy Through Health Education Intervention Programs on Insecticide-Treated Nets Use: A Systematic Review, BMC Public Health. 2024 Mar 11 ;24(1):755, https://doi.org/10.1186/s12889-024-17650-7 found 11 articles worthy of analysis from among over 2000 on the subject of malarias prevention in pregnancy.  The end points in these articles were enhanced knowledge of preventive measures and ITN use.  In this, they all reported improvement.  However, there was no mention of reduced incidence of malaria in pregnant women or newborns, or in the frequency of low-birthweight infants.

Epidemiology

 

Climate change, biodiversity and environment

 

“Deforestation has increased human exposure to mosquito vectors and malaria risk in Africa, but there is little understanding of how socioeconomic and ecological factors influence the relationship between deforestation and malaria risk.” Estifanos TK & al. “examined these interrelationships in six sub-Saharan African countries using demographic and health survey data linked to remotely sensed environmental variables for 11,746 children under 5 years old. [They] found that the relationship between deforestation and malaria prevalence varies by wealth levels. Deforestation is associated with increased malaria prevalence in the poorest households, but there was not significantly increased malaria prevalence in the richest households, suggesting that deforestation has disproportionate negative health impacts on the poor. In poorer households, malaria prevalence was 27%-33% larger for one standard deviation increase in deforestation across urban and rural populations. Deforestation is also associated with increased malaria prevalence in regions where Anopheles gambiae and Anopheles funestus are dominant vectors, but not in areas of Anopheles arabiensis.” The paper is Impacts of Deforestation on Childhood Malaria Depend on Wealth and Vector Biology, Geohealth. 2024 Feb 28; 8(3):e2022GH000764, https://doi.org/10.1029/2022gh000764.

What is being done with insecticide treated nets once they are no longer usable? Msangi SJ & al. addressed the question by conducting a survey in rural Tanzania. They report in Challenges of Proper Disposal of Old Long-Lasting Insecticidal Nets {LLINs} and Its Alternative Uses in Rural South-Eastern Tanzania, PLoS One. 2024 Feb 15; 19(2):e0279143, https://doi.org/10.1371/journal.pone.0279143 that “WHO has recommended proper ways of disposing or handling old LLINs, namely: 1) continuing to be used even if they have holes until they are replaced with new LLINs; 2) old LLINs should not be disposed of in water bodies; 3) collection of the old LLINs for disposal by NMCP {National Malaria Control program}; 4) incineration of old LLINs; and 5) formulating guidelines, policies, and regulations by the NMCP in collaboration with national environmental authorities.” Of “384 people surveyed, 97.0% were not aware of the WHO recommendations for the proper disposal of old LLINs” About 44% of individuals surveyed disposed of them by burning or burying them in garbage pits, which are at least not inconsistent with the recommendations, but alternate uses, such as using them for ropes or garden fencing have the potential of polluting the environment.

 

 

Risk factors

 

Zhou G & al. focus on risk stratification by diverse environments in Malaria Transmission Heterogeneity in Different Eco-Epidemiological Areas of Western Kenya: A Region-Wide Observational and Risk Classification Study for Adaptive Intervention Planning, Malaria J 2024 Mar 12, 23:74, https://doi.org/10.1186/s12936-024-04903-4. “The study area was classified into four zones based on clinical malaria incidence, parasite prevalence, vector density, and altitude. The two irrigated zones have either the highest malaria incidence, parasite prevalence, or the highest malaria vector density; the highlands have the lowest vector density and parasite prevalence; and the dryland and flooding area have the average clinical malaria incidence, parasite prevalence and vector density. Different zones have different vector species, species compositions and predominant species.”

General epidemiology

 

Balmith M & al., The Malaria Burden: A South African Perspective, J Trop Med. 2024 Feb 23; 2024:6619010, https://doi.org/10.1155/2024/6619010 is an article that reviews the epidemiology, treatment and pubic health implications of malaria in the Republic of South Africa.

Sampa M & al. report that there was “an increase in confirmed malaria cases {by a factor of 1.32} during the COVID-19 period compared to the non-COVID-19 period. The study also found Age, Province, and COVID-19 period to be significantly associated with malaria cases.” The paper is The Effect of COVID-19 on Malaria Cases in Zambia: A Mixed Effect Multilevel Analysis, Malaria J, 2024 Mar 22, 23:85, https://doi.org/10.1186/s12936-024-04882-6

 

The association of malaria with Epstein-Barr virus, which causes Burkitt’s Lymphoma is well described. Nalwoga A & al., Plasmodium falciparum Malaria Is Associated with Increased Kaposi Sarcoma-Associated Herpesvirus (KSHV) Seropositivity and Higher KSHV Antibody Breadth and Magnitude: Results of a Case-Control Study from Rural Uganda, J Infect Dis. 2024 Feb 14; 229(2):432-442, https://doi.org/10.1093/infdis/jiad308 review the evidence of association of asymptomatic P. falciparum infection with another virus, KSHV (which is also strongly associated with HIV). The evidence that they cite is specific antibody levels, which is the usual way of demonstrating exposure to viruses.

It has been a general impression that individuals negative for Duffy blood group are resistant to Plasmodium vivax infections. Bradley L & al. explore “the prevalence and rates of P. vivax malaria infection across Duffy phenotypes in clinical and community settings.” As they report in Epidemiology of Plasmodium vivax in Duffy Negatives and Duffy Positives from Community and Health Centre Collections in Ethiopia, Malaria J, 2024 Mar 14, 23:76, https://doi.org/10.1186/s12936-024-04895-1, while the infection rate with P. vivax “was 2–22 fold higher than Duffy negatives in asymptomatic volunteers from the community … Duffy negativity does not offer complete protection against infection by P. vivax, and cases of P. vivax in Duffy negatives are widespread in Ethiopia, being found in asymptomatic volunteers from communities and in febrile patients from health centres.”

 

Higgins M & al. note the recent rise in Africa of infections caused by Plasmodium ovale, which was recently reclassified as two distinct species. Their report, New Reference Genomes to Distinguish the Sympatric Malaria Parasites, Plasmodium ovale curtisi and Plasmodium ovale wallikeri, Sci Rep. 2024 Feb 15; 14(1):3843, https://doi.org/10.1038/s41598-024-54382-5 discloses the distinguishing features of the genomes of the two species.  This finding does not have clinical significance yet.

Low birthweight infants have been cited as frequent results of malaria in pregnancy. In startling contrast, Mukala J & al., Predictors of Birth Weight in Pregnant Women with Malaria: A Prospective Cohort Facility-Based Study in Webuye-Kenya, BMC Pregnancy Childbirth. 2024 Mar 8; 24(1):187, https://doi.org/10.1186/s12884-024-06355-9 reports that in a prospective study of 140 pregnant women in Western Kenya there was no difference in birthweight outcomes between the cohorts of 64 pregnant women with malaria (3 with low birthweight) and 67 pregnant women without malaria (3 with low birthweight). Whereas the article (not the abstract) note that the low birthweight rate in this population is much lower than that generally reported elsewhere in pregnant women in sub-Saharan Africa, neither the abstract nor the article make mention of if or how the women with malaria were treated for their infection.

Spatiotemporal studies

Tesfaye S & Yesuf A, Trend Analysis of Malaria Surveillance Data in West Wallaga, West Oromia, Ethiopia: A Framework for Planning and Elimination, Malaria J, 2024 Feb 21, 23:52, https://doi. 10.1186/s12936-024-04874-6.

Mougeni F & al., Bayesian Spatio-Temporal Analysis of Malaria Prevalence in Children Between 2 and 10 Years of Age in Gabon, Malaria J, 2024 Feb 23, 23:57, https://doi.org/10.1186/s12936-024-04880-8#Sec1

Mbama Ntabi JD & al., Contribution of Anopheles gambiae sensu lato Mosquitoes to Malaria Transmission During the Dry Season in Djoumouna and Ntoula Villages in the Republic of the Congo, Parasit Vectors. 2024 Mar 2; 17(1):104, https://doi.org/10.1186/s13071-023-06102-7

Kayiba NK & al., Malaria Infection Among Adults Residing in a Highly Endemic Region from the Democratic Republic of the Congo, Malaria J, 2024 Mar 18, 23:82, https://doi.org/10.1186/s12936-024-04881-7

 

 

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