By Dr. Derick Pasternak, Malaria Science & Research Coordinator, Malaria Partners International 

Readers of these reports will have noticed that the Epidemiology section and to a lesser extent the Prevention section contain numerous articles that essentially repeat themselves, only cover different, usually small, geographic areas.  This is particularly true about articles coming out of Ethiopia, Nigeria, Burkina Faso, and to a lesser extent, Kenya.  

Prevention: 

Vaccines   

The WHO-endorsed vaccine is the subject of Samuels AM & al., Efficacy of RTS.S/AS01E Malaria Vaccine Administered According to Different Full, Fractional, and Delayed Third or Early Fourth Dose Regimens in Children Aged 5-17 Months in Ghana and Kenya: An Open Label Phase 2b, Randomised Controlled Trial, Lancet Infect Dis, 2022 Jun 22, doi: 10.1016/S1473-3099(22)00273-0.  This study compared the efficacy of reduced doses (20% of full dose) of the vaccine for injections at each of four dates, compared with full doses and also with only three injection dates of the fractional doses.  The authors conclude that all three “regimens provided substantial, similar protection against clinical malaria, suggesting potential flexibility in the recommended dosing regimen and schedule. This, and the effect of annual boosters, will be further evaluated through 50 months of follow-up.”  Also of interest is their conclusion of “no safety signals [were] observed.” The article was accompanied by an editorial, Ntoumi F & Kremsner PG, Vaccination with Fractional Doses: Promise or Illusion? Lancet Infect Dis, 2022 Jun 23, doi: 10.1016/S1473-3099(22)00310-3. Unfortunately, without a subscription to the journal, the conclusions of this editorial remain elusive. 

Nouatin O, & al. studied a different vaccine, GMZ2, which is a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of Plasmodium falciparum. Their report, Cellular and Antibody Response in GMZ2-Vaccinated Gabonese Volunteers in a Controlled Human Malaria Infection Trial, Malaria J, 2022 Jun 17, vol 21 art 191, doi: 10.1186/s12936-022-04169-8 focused on the immune response in 50 volunteers, as well as on protection from controlled infection.  They conclude a lack of efficacy of this vaccine in both spheres.  

Addressing immune response to yet another vaccine, Molta D & al. review in A Guide to Investigating Immune Responses Elicited by Whole-Sporozoite Pre-Erythrocytic Vaccines Against Malaria, Fed Eur Biochem Soc J, 2022 Jun; 289(12):3335-3359, doi: 10.1111/febs.16016 the main methodologies employed to dissect the humoral and cellular immune responses observed in the context of whole sporozoite against pre-erythrocytic forms of Plasmodium vaccine clinical trials and discuss future strategies to further deepen the knowledge generated by these studies, providing a toolbox for the in-depth analysis of vaccine-induced immunogenicity. 

Emameh RZ & al., A Reverse Vaccinology Approach on Transmembrane Carbonic Anhydrases from Plasmodium Species as Vaccine Candidates for Malaria Prevention, Malaria J, 2022 Jun 15 vol 21 art 189, doi: 10.1186/s12936-022-04186-7 is an assertion that transmembrane carbonic anhydrases from Plasmodium spp. can be potential targets for vaccination against malaria. 

In animal studies, Visweswaran GRR & al. report the results of administering circumsporozoite protein vaccine to mice in Germinal Center Activity and B Cell Maturation Are Associated with Protective Antibody Responses Against Plasmodium Pre-Erythrocytic Infection, PLoS Pathogens, 2022 Jul 6, doi: 10.1371/journal.ppat.1010671. 

Sulemane & al. address a letter to the Editor of J Prev Med Hyg (2022; 63:E1-E1) entitled Vaccine Hesitancy in Africa: How COVID-19 Pandemic May Affect Malaria Vaccination Campaigns. They advise that “[v]accination against malaria should be introduced effectively, and trust toward regular immunization programmes would be regained only through transparent information on vaccines’ risks and benefits at all levels, and according to age groups and health conditions.  History shows that once people’s confidence in vaccines is compromised, it is difficult to gain it back…[The authors] urge reinforcing the importance of public policies and health interventions, and to address societal health determinants. Within this framework, commitments to health equity and social justice, and whole of society inter-sectoral policy action are required, targeting structural determinants of health and the social mechanisms at the roots of inequity and distrust.”  

Vector control and protection from vectors 

Four articles address long lasting impregnated bednets (LLINs). Diouf EH & al., Evaluation of the Residual Efficacy and Physical Durability of Five Long-Lasting Insecticidal Nets (LLINs) in Senegal, Malaria J, 2022 Jul 2, vol 21 art 210, doi: 10.1186/s12936-022-04230-6 reports that in a rural community “[f]ive brands of LLIN were distributed, and every six months, retention rates, net use, maintenance, physical integrity, insecticide chemical content, and biological efficacy were examined for each type of LLIN.” The authors’ conclusion states “Although some net types retained sufficient insecticidal activity, based on all durability parameters measured, none of the net types survived longer than 2 years.”   

Glozah F & al.  Creating Interventions to Transition Long-Lasting Insecticide Net Distribution in Ghana, BMJ Open, 2022 Jun 1; 12(6):e063121, doi: 10.1136/bmjopen-2022-063121 “presents the process and outcome of creating an innovative social intervention, which focuses on community mobilisation and capacity building of community health officers” and concludes that the “establishment of a Community Health Advocacy Team” would facilitate acceptability and proper use of LLINs.  

“The WHO cone test is one of three tests currently used to evaluate the efficacy of insecticide-treated bed nets (ITNs). It generates two test outputs, knockdown and 24-h mortality, both indicative of immediate toxicity” Hughes A & al. added a human arm within 5 cm of the net being tested and noted increased landing of mosquitoes on the nets.  Their report is A Closer Look at the WHO Cone Bioassay: Video Analysis of the Hidden Effects of a Human Host on Mosquito Behaviour and Insecticide Contact, Malaria J, 2022 Jul 1, vol 21 art 208, doi: 10.1186/s12936-022-04232-4. 

Monitoring the use of bednets is the subject of Alexander SM & al., A Qualitative Study of the Acceptability of Remote Electronic Bednet Use Monitoring in Uganda, BMC Public Health, 2022 May 19; 22(1):1010, doi: 10.1186/s12889-022-13393-5.  “SmartNet is a remote electronic monitor that provides objective measurements of bednet use over weeks at a time.”  The authors installed these nets in a small number of homes that already had experience with standard LLINs. Based on intrerviews of heads of households, they conclude that “[o]bjective monitoring of bednet use with SmartNet appears acceptable to these households in Uganda. Use of SmartNet seems to be similar to … use of standard LLINs. Viewpoints on many aspects of SmartNet were generally favorable. Concerns around ethicality of bednet monitoring are present and indicate the need for continuing community education.”     

Sherrard-Smith E & al. refer to both bednet use and indoor residual spraying in their paper, Inferring the Epidemiological Benefit of Indoor Vector Control Interventions Against Malaria from Mosquito Data, Nat Commun, 2022 Jul 5; 13(1):3862, doi: 10.1038/s41467-022-30700-1.  They point to the paucity of reliable “endpoint” data on the use of these methodologies and suggest that modeling has a role in predicting when and how to use them. 

Boussougou-Sambe ST, Assessment of Malaria Transmission Intensity and Insecticide Resistance Mechanisms in Three Rural Areas of the Moyen Ogooué Province of Gabon, Parasit Vectors, 2022 Jun 20; 15(1):217, doi: 10.1186/s13071-022-05320-9 is an epidemiological investigation of vector populations, which were found to be heterogenous with respect to species, and malaria parasites carried, though Anopheles gambiae and Plasmodium falciparum were predominant.  Over 95% of mosquitoes studied were found to have two of the three insecticide resistance genes studied. 

The results of Wolie RZ & al. in Côte d’Ivoire were very similar, as reported in Entomological Indicators of Malaria Transmission Prior to a Cluster-Randomized Controlled Trial of a ‘Lethal House Lure’ Intervention in Central Côte d’Ivoire, Malaria J, 2022 Jun 15, vol 21 art 188, doi: 10.1186/s12936-022-04196-5.  Anopheles coluzii, An. funestus and An. gambiae s.s. were the predominant species and they all possessed significant resistance to insecticides. 

Gebhardt ME & al. describe a species of Anopheles mosquitoes in Northern Zambia that had been found to be a vector for malaria in Kenya. Their paper is Expanded Geographic Distribution and Host Preference of Anopheles gibbinsi (Anopheles Species 6) in Northern Zambia, Malaria J, 2022 Jul 3, vol 21 art 211, doi: 10.1186/s12936-022-04231-5. 

Wang G-H & al. describe Symbionts and Gene Drive: Two Strategies to Combat Vector-Borne Disease, Trends Genet, 2022 Jul; 38(7):708-723, doi: 10.1016/j.tig.2022.02.013. They state: “Symbiotic bacteria like Wolbachia are maternally inherited and manipulate mosquito host reproduction to enhance their vertical transmission. Genome engineering-based gene drive methods, in which mosquitoes are genetically altered to spread drive alleles throughout wild populations, are also proving to be a potentially powerful approach in the laboratory.” This paper is not specific to Anopheles species. 

Paton DG & al. assert that Using an Antimalarial in Mosquitoes Overcomes Anopheles and Plasmodium Resistance to Malaria Control Strategies, PLoS Pathogens, 2022 Jun 10, doi: 10.1371/journal.ppat.1010609. They claim to “show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum… proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions…” 

Chemoprophylaxis 

Doe MTT & al. Antenatal Care Positive Responses to Pregnant Women in Preventing and Controlling Malaria in Pregnancy: The Sub-Saharan African Perspective, World J Pediatr, 2022 Jul; 18(7):453-462, doi: 10.1007/S12519-022-00549-x identifies antenatal care of pregnant women as being critical in getting the latter to accept intermittent preventive treatment with sufadoxine-pyrimethamine (IPTp-SP).  Current participation in antenatal pregnancy care in SubSaharan Africa is low.  

According to Kumah E & al., Intermittent Preventive Treatment of Malaria in Pregnancy With Sulphadoxine-Pyrimethamine and Its Associated Factors in the Atwima Kwanwoma District, Ghana, Ann Glob Health, 2022 Apr 27; 88(1):27, doi: 10.5334/aogh.3560, 98% of women in their study had received chemoprophylaxis during pregnancy.  Yet the authors call for increased awareness of the benefit of chemoprophylaxis among pregnant women.  Perhaps the issue is timing of the drug administration. 

Ogba P & al found significantly less use of IPTp-SP in Nigeria during a meta-analysis of 31 papers on the subject as they reported in the article, Barriers and Facilitators to Access and Uptake of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine Among Pregnant Women in Nigeria: A Scoping Review, Malaria World J, 2022 Jun 21; 13(4), media.malariaworld.org/mwj_2022_13_4_0c9bf0d226.pdf. According to them, “[p]oor provider knowledge of the IPTp-SP protocol and lack of essential [supplies] for sulphadoxine-pyrimethamine administration in clinics are significant barriers to IPTp-SP use. Staff shortages and poor remuneration of health care professionals are obstacles to IPTp-SP utilisation.” 

Similarly, In Malawi, Rubenstein BL  & al., A Cluster Randomized Trial of Delivery of Intermittent Preventive Treatment of Malaria in Pregnancy at the Community Level in Malawi, Malaria J, 2022 Jun 21, vol 21 art 195, doi: 10.1186/s12936-022-04216-4 found the utilization of IPTp-SP to be less than desirable.  The utilization of community health workers to administer the drugs did not improve the situation. 

Diagnosis: 

“Rapid diagnostic tests (RDTs) detecting Plasmodium falciparum histidine-rich protein 2 (HRP2) have been an important tool for malaria diagnosis, especially in resource-limited settings lacking quality microscopy. Plasmodium falciparum parasites with deletion of the pfhrp2 gene encoding this antigen have now been identified in dozens of countries across Asia, Africa, and South America, with new reports revealing a high prevalence of deletions in some selected regions.” Beshir KB & al., Screening Strategies and Laboratory Assays to Support Plasmodium falciparum Histidine-Rich Protein Deletion Surveillance: Where We Are and What is Needed, Malaria J, 2022 Jun 27, vol 21 art 201, 10.1186/s12936-022-04226-2 discusses contemporary assays for the evaluation of P. falciparum HRP2 status, consider their strengths and weaknesses, and highlight key concepts relevant to timely and resource-conscious workflows required for efficient diagnostic policy decision making. 

Bouzayene A  & al., Evaluation of Two Commercial Kits and Two Laboratory-Developed qPCR Assays Compared to LAMP for Molecular Diagnosis of Malaria, Malaria J, 2022 Jun 27, vol 21 art 204, doi: 10.1186/s12936-022-04219-1 is an article that focuses on molecular diagnosis of malaria that appears more sensitive than microscopy.  Well equipped laboratories are required for the methods described. 

Badiane A, & al., Sensitivity and Specificity for Malaria Classification of Febrile Persons by Rapid Diagnostic Test, Microscopy, Parasite DNA, Histidine-Rich Protein 2, and IgG: Dakar, Senegal 2015, Int J Infect Dis, 2022 Aug; 121:92-97, doi: 10.1016/j.ijid.2022.04.060 is also a description of multiple laboratory methods, all with very high sensitivity.  The authors suggest that these methods are most useful for research purposes. 

A  third article on diagnostic methods this month is Oyegoke OO & al., Malaria Diagnostic Methods with the Elimination Goal in View, Parasitol Res, 2022 Jul; 121(7):1867-1885.  doi: 10.1007/s00436-022-07512-9. “In this review, [the authors] looked at the various approaches used in malaria diagnostics with a focus on methods favorably used during pre-elimination and elimination phases as well as in endemic regions. Microscopy, rapid diagnostic testing (RDT), loop-mediated isothermal amplification (LAMP), and polymerase chain reaction (PCR) are common methods applied depending on prevailing factors, each with its strengths and limitations. …, the search for ideal, simple, fast, and reliable point-of-care diagnostic tools is needed more than ever before to be used in conjunction with a functional surveillance system supported by the ideal vaccine.” 

Edwards HM & al. conducted a market survey consisting of a “survey targeting private pharmacies and Proprietary and Patent Medicine Vendors (PPMVs) across different regions of Nigeria… and a household survey to determine demand-side factors.” They conclude in The Private Sector Market for Malaria Rapid Diagnostic Tests in Nigeria: Results of the 2018 Market Survey, Malaria J, 2022 Jun 16, vol 21 art 190, doi: 10.1186/s12936-022-04209-3 that “[l]ow availability of RDTs among PPMVs and pharmacies may be attributed to lack of demand, supply-side issues and cost. Increasing household knowledge of RDTs may aid increasing demand, while subsidized RDTs may address supply and price issues.” 

Rapid identification of severe malaria in children is critical if they are to be treated effectively. Stefanova V & al., suPAR to Risk-Stratify Patients with Malaria, Front Immunol, 2022 Jun 10; 13:931321. doi: 10.3389/fimmu.2022.931321 describes “soluble urokinase-type plasminogen activator receptor (suPAR) as a novel and early predictor of severe and fatal malaria and discuss its potential utility for malaria triage and management.” 

Sánchez KE & Spencer LM, Pregnancy-Associated Malaria: Effects of Cytokine and Chemokine Expression, Travel Med Infect Dis, May-Jun 2022; 47:102282 doi: 10.1016/j.tmaid.2022.102282 is a  review of relevant literature that “aims to provide an update on the immune response in pregnant women and the role of cytokines and chemokines in modulating immunity after infection by the Plasmodium parasite.” 

Treatment: 

“Controlled human infection studies have contributed significantly to the understanding of pathogeneses and treatment of infectious diseases. In malaria, deliberately infecting humans with malaria parasites was used as a treatment for neurosyphilis in the early 1920s. More recently, controlled human malaria infection (CHMI) has become a valuable, cost-effective tool to fast-track the development and evaluation of new anti-malarial drugs and/or vaccines.” Kibwana E & al.,, Controlled Human Malaria Infection Studies in Africa-Past, Present, and Future,  Curr Top Microbiol Immunol, 2022 Jun 16, doi: 10.1007/82_2022_256 endorses this approach; however the abstract fails to reflect the ethical considerations inherent in this approach.  

Hien D & al., Stakeholder Perceptions on the Deployment of Multiple First-Line Therapies for Uncomplicated Malaria: A Qualitative Study in the Health District of Kaya, Burkina Faso, Malaria J, 2022 Jun 27, vol 21 art 202, 10.1186/s12936-022-04225-3. “Semi-structured interviews … were conducted with key stakeholders including malaria control policymakers and implementers, health system managers, health workers and community members … The interviews revealed a positive perception of stakeholders on the implementation of the planned MFT programme. They saw the strategy as an opportunity to strengthen the supply of anti-malarial drugs and improve the management of fever and malaria. However, due to lack of experience with the products, health workers and care givers expressed some reservations about the effectiveness and side-effect profiles of the two anti-malarial drugs included as first-line therapy in the MFT programme (pyronaridine–artesunate, dihydroartemisinin–piperaquine). Questions were raised about the appropriateness of segmenting the population into three groups and assigning a specific drug to each group. 

“[I]n Madagascar, care-seeking for febrile illness is often delayed. To describe factors influencing decisions for prompt care-seeking among caregivers of children aged < 15 years and pregnant women, a mixed-methods assessment was conducted with providers (HP), community health volunteers (CHV) and community members” by Favero R & al. Their report, Experiences and Perceptions of Care-Seeking for Febrile Illness Among Caregivers, Pregnant Women, and Health Providers in Eight Districts of Madagascar, Malaria J, 2022 Jul 7, vol 21 art 212, doi: 10.1186/s12936-022-04190-x indicated the following: “Key care-seeking determinants for caregivers and pregnant women included cost, travel time and distance, and perception that the quality of care in [private healthcare facilities] (HFs) was poor. HPs felt that lack of commodities and heavy workloads hindered their ability to provide quality malaria care services. Malaria commodities were generally more available in public versus private HFs. CHVs were generally not consulted for malaria care…” 

The safety of artemisinin in pregnancy is the topic dealt with in Clerk RL, Safety of Treating Malaria with Artemisinin-Based Combination Therapy in the First Trimester of Pregnancy, Reproductive Toxicology, Aug 2022, 111:204-10, doi: 10.1016/j.reprotox.2022.05.016, in view of the recent WHO’s guidance that there is not enough data to assure the clinical safety of this use. The article goes into detail, supporting the WHO guidance for a readership that may not be familiar with malaria literature. 

Kobia FM &al., Potential Pharmacologic Interventions Targeting TLR Signaling in Placental Malaria, Trends Parasitol, 2022 Jul; 38(7):513-524, doi: 10.1016/J.Pt.2022.04.002 describes the means by which placental malaria impairs the health of the fetus and leads to poor pregnancy outcomes. “Many of these complications are driven by maternal innate proinflammatory responses to the sequestration of Plasmodium falciparum in the placenta. However, recent studies show that, in reaction to maternal innate immune responses that are detrimental to the fetus, the fetus mounts innate immune counter-responses that ameliorate pregnancy outcomes. Such fetal-maternal conflict in placental malaria has potential for pharmacologic modulation for better pregnancy outcomes.”  

The management of the potentially lethal complication of cerebral malaria is reviewed by Das N & Prabhu P in Emerging Avenues for the Management of Cerebral Malaria, J Pharm Pharmacol, 2022 Jun 9; 74(6):800-811, doi: 10.1093/jpp/rgac003. While the article does not endorse any specific therapeutic breakthrough, it lists a series of approaches that has promise in being able to deliver effective antimalarials to the brain without unacceptable toxicity. 

In an editorial, Plucinski MM & al., STARTER Checklist for Antimalarial Therapeutic Efficacy Reporting, Malaria J, 2022 Jun 13, vol 21 art 187, doi: 10.1186/s12936-022-04182-x, report the development of a “Standardized Antimalarial Therapeutic Efficacy Reporting (STARTER) Checklist, which lays out best practices for reporting results of antimalarial efficacy studies … [They also] emphasize that checklists are not replacements for peer-review but rather tools to promote uniformity in reporting. Filling out the checklist does not substitute for careful adherence to the global WHO standards for efficacy trials. Efficacy trial investigators and sponsors that follow WHO’s guidance and verify their adherence at the protocol development, implementation, analysis, and reporting stages will likely find the STARTER checklist facilitates their manuscript development.” 

Interruption of malaria transmission is another strategy in reducing the community’s burden of malaria. van der Watt ME & al., Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination, Front Cell Infect Microbiol, 2022 Jun 9; 12:901971, doi: 10.3389/fcimb.2022.901971 “presents an update of our molecular understanding of gametocyte and gamete biology as well as the status of transmission-blocking activities of current antimalarials and lead development compounds. By defining the biological components associated with transmission, considerations for the development of new transmission-blocking drugs to target such untapped but unique biology is suggested as an important, main driver for transmission-blocking drug discovery.” There is a related editorial in the same publication by Chan J-A & al., Advances on the Gametocyte Biology, Host Immunity and Vector Stages to Interrupt the Transmission of Malaria, Front Cell Infect Microbiol, 2022 May 20; 12:918489, doi: 10.3389/fcimb.2022.918489.   

Resistance to antimalarials is no longer a problem only in SE Asia. Kagoro FM & al., Making Data Map-Worthy—Enhancing Routine Malaria Data to Support Surveillance and Mapping of Plasmodium falciparum Anti-Malarial Resistance in a Pre-Elimination Sub-Saharan African Setting: A Molecular and Spatiotemporal Epidemiology Study, Malaria J, 2022 Jun 29, vol 21 art 207, doi: 10.1186/s12936-022-04224-4 is a report on seeking detailed information about resistance in a specific area in South Africa.  While no evidence of artemisinin resistant mutations were found, many samples studied showed genetic profiles “potentially associated with decreased lumefantrine susceptibility.” 

One potential strategy to deal with drug resistance is to reintroduce chloroquine after many years of not using the drug, in the hope that the parasite will have reverted to sensitivity to the drug. Njiro BJ & al., Molecular Surveillance of Chloroquine-Resistant Plasmodium falciparum in Sub-Saharan African Countries After Withdrawal of Chloroquine for Treatment of Uncomplicated Malaria: A Systematic Review, J Infect Public Health, 2022 May; 15(5):550-557, doi: 10.1016/j.jiph.2022.03.015 addresses this strategy. In this systematic review of relevant literature from 2000 to 2020, the following is reported: “Low prevalence of resistant genotypes … was reported in Zambia (0%) in 2013, Malawi (0.1%) in 2009, Tanzania (0.2%) in 2018 and Madagascar (0.3%) in 2007 with significant variations in the included studies … [Thus the article concludes that] Chloroquine-resistant P. falciparum continues to disappear in countries with withdrawal of chloroquine. Areas with significant susceptible parasites, reintroduction of chloroquine can be considered, preferably in combination with other safe and affordable antimalarials.” 

In view of the emergence of artemisinin resistance, new drugs are being sought to control malaria. Tamaki F & al. report on an assay “platform” that targets the ability of Plasmodium falciparum to synthetize protein.  High-Throughput Screening Platform to Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria, Antimicrob Agents Chemother, 2022 Jun 21; 66(6):e0023722, doi: 10.1128/aac.00237-22 is their article describing the process. 

Although it reports very preliminary laboratory experiments, Asih PBS & al., Treatment with Specific and Pan-Plasma Membrane Calcium ATPase (PMCA) Inhibitors Reduces Malaria Parasite Growth in vitro and in vivo, Malaria J, 2022 Jun 29, vol 21 art 207, doi: 10.1186/s12936-022-04228-0 is included in this report, because it concerns another potential avenue of new anti-plasmodial drug development. 

Campaigns: 

Cohen JM & al. are concerned that the gains in reducing malaria world-wide over the first 20 years of the century may be slowing owing to a multiplicity of factors, which they elaborate in, The Fight Against Malaria: Diminishing Gains and Growing Challenges, Sci Transl Med, 2022 Jun 29; 14(651):eabn3256, doi: 10.1126/scitranslmed.abn3256.  

Mumba N & al., Undertaking Community Engagement for a Controlled Human Malaria Infection Study in Kenya: Approaches and Lessons Learnt, Front Public Health, 2022 Apr 29; 10:793913, doi: 10.3389/fpubh.2022.793913 addresses the elements of controlled infection studies that may be lacking in the article by Kibwana & al. cited above. “This article outlines the community engagement approaches that were used to engage stakeholders and communities for malaria HIS-controlled human malaria infection (CHMI), undertaken in Kilifi, Kenya. It outlines the engagement activities across the research cycle, from activities conducted during protocol development, to planning, and implementation of the study. We discuss the challenges experienced, lessons learnt, and provide some recommendations for engagement around HIS.” 

Epidemiology: 

Oyegoke OO & al.,   A Systematic Review and Meta-Analysis of Malaria Test Positivity Outcomes and Programme Interventions in Low Transmission Settings in Southern Africa, 2000-2021, Int J Environ Res Public Health, 2022 Jun 1;19(11):6776, doi: 10.3390/Ijerph19116776. “[T]he objective of this systematic review and meta-analysis is to pool estimates of the incidence of the malaria positivity rate, which is the first of its kind in South African countries. A literature search [was] performed to identify all published articles reporting the incidence of malaria positivity in Southern Africa…… the overall random pooled incidence [was] 10% (95%CI: 8-13%, I2 = 99.91%) in the malaria positivity rate” with a great deal of heterogeneity in the various geographic areas from which reports were published. 

Ikegbunam MN & al., Malaria Surveillance Amongst Pregnant Women Attending Antenatal Care in Private Hospitals in Onitsha Metropolis, South Eastern Nigeria, Malaria World J, 2022 Jun 21, 13(2)  media.malariaworld.org/MWJ_2022_13_2_d45134361a. : “Venous blood samples were collected from 270 pregnant women during [antenatal care] visits between October 2016 and December 2017. A questionnaire was used to collect demographic data, gestational age, knowledge of malaria and preventive measures while clinical presentations and symptoms were extracted from the physician’s [notes].” In contrast with the reports from general populations, in this selected population and geographic area, “P. falciparum prevalence was 42.6%. Prevalence varied with the maternal age, gestational age, preventive measures adopted by the pregnant women and clinical presentations.” The high prevalence was found “despite strong adherence to use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy (IPTp) and other malaria preventive measures.” 

Debash H & al. report troubling trends in Malaria Threatens to Bounce Back in Abergele District, Northeast Ethiopia: Five-Year Retrospective Trend Analysis From 2016-2020 in Nirak Health Center, Biomed Res  Int, 2022 Jun 7; 2022:6388979, doi: 10.1155/2022/6388979. Over the years 2016 to 2020, the highest rate of malaria prevalence was in 2020.  Despite the usual peak incidence of malaria in the rainy season, this study found the highest number of cases during the dry season. The authors conclude that “the malaria control and elimination strategy in the area were not properly implemented or failed to achieve its designed goal.” 

“High levels of genetic diversity are common characteristics of Plasmodium falciparum parasite populations in high malaria transmission regions. There has been a decline in malaria transmission intensity over 12 years of surveillance in the community in Kilifi, Kenya. Kimanyi KM & al. sought to investigate whether there was a corresponding reduction in P. falciparum genetic diversity…” They report in Maintenance of High Temporal Plasmodium falciparum Genetic Diversity and Complexity of Infection in Asymptomatic and Symptomatic Infections in Kilifi, Kenya From 2007 To 2018, Malaria J, 2022 Jun 20, vol 21 art 192, doi: 10.1186/s12936-022-04213-7 that the parasites in the area are “still highly diverse and polyclonal, despite the reduction in malaria transmission in the community.” 

Another country where the incidence of malaria has decreased significantly is Senegal. Tairou F & al.’s paper, Malaria-Associated Risk Factors Among Adolescents Living in Areas with Persistent Transmission in Senegal: A Case–Control Study, Malaria J, 2022 Jun 20, vol 21 art 193, doi: 10.1186/s12936-022-04212-8, reports results from studying a population of 246 adolescents [aged 10 to 19] with uncomplicated malaria, compared with matched healthy controls. “[F]actors associated with clinical malaria included non-use of long-lasting insecticidal net …, non-use of other preventive measures …, and indoor sleeping … Protective factors included 15–19 years of age …, absence of stagnant water around the house … having a female as head of household …, [and gainful employment in an] occupation such as apprentice…” 

Golubeanu M & al. use a “mathematical model of malaria transmission dynamics … to simulate deployment and predict potential impact of new malaria interventions by considering operational, health-system, population, and disease characteristics., Their article, Leveraging Mathematical Models of Disease Dynamics and Machine Learning to Improve Development of Novel Malaria Interventions, Infect Dis Poverty, 2022 Jun 4; 11(1):61, doi: 10.1186/S40249-022-00981-1 mentions five interventions included in the modeling; however, the abstract does not specify what these interventions are. The authors claim that “by evaluating the intervention capabilities in relation to the targeted health goal, [their] analysis allows prioritization of interventions…” 

Ukawuba I & Shaman J, Inference and Dynamic Simulation of Malaria Using a Simple Climate-Driven Entomological Model of Malaria Transmission, PLoS Comput Biol, 2022 Jun 9; 18(6):e1010161. 

 doi: 10.1371/journal.pcbi.1010161 is a report on mathematical modeling of mosquito bite rates based on vector dynamics and climate variables.  The authors report that “the model unsurprisingly failed to reproduce large declines in malaria transmission during 2018 and 2019 due to elevated anti-malaria measures, which were not accounted for in the model structure.” 

“Maps of disease burden are a core tool needed for the control and elimination of malaria,” according to Lucas TCD & al., Improving Disaggregation Models of Malaria Incidence by Ensembling Non-Linear Models of Prevalence, Spat Spatiotemporal Epidemiol, 2022 Jun; 41:100357.  doi: 10.1016/ j.sste.2020.100357. The authors “find that using a disaggregation regression model to combine predictions from machine learning models improves model accuracy relative to a baseline model.”