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

For those interested in diminishing the world’s burden of malaria, it was telling that 29 of the close to 50 sub-Saharan African countries were represented at the annual meeting of the American Society for Tropical Medicine (ASTMH) and Hygiene recently.  Aside from the extensive coverage of all aspects of the fight against malaria at the ASTMH meeting, the published literature was also rich in important information.  Particularly noteworthy were a series of articles that originated from the various country and regional branches of the International Center of Excellence for Malaria Research, which were published in the periodical of the ASTMH.  The section on Campaigns, which is hereby renamed Campaigns and Policies includes these articles.     

As a reminder, abstracts of all publications mentioned in this and every monthly report are available from the compiler at dppaster@gmail.com. 

Prevention: 

Vaccines  

In contrast to the ASTMH meeting at which work on malaria vaccines were prominently discussed, there were few articles on the subject in the literature this month.  However, an important document was published by WHO, Learning Lessons from the Pilots: Overcoming Knowledge Gaps Around the Malaria Vaccine Schedule in Support of Vaccine Uptake, 2022 Oct 5, available on www.who.int.  

Negative results in vaccine research are also important. “Plasmodium falciparum (Pf) Sporozoite (SPZ) Chemoprophylaxis Vaccine (PfSPZ-CVac) involves concurrently administering infectious PfSPZ and malaria drug, often chloroquine (CQ), to kill liver-emerging parasites.”  Coulibaly D & al. “investigated the hypothesis that PfSPZ-CVac (CQ) is safe and efficacious against seasonal, endemic Pf in malaria-exposed adults.”  They report in PfSPZ-Cvac Malaria Vaccine Demonstrates Safety Among Malaria-Experienced Adults: A Randomized, Controlled Phase 1 Trial, EClinicalMedicine. 2022 Jul 30; 52:101579, doi: h10.1016/j.eclinm.2022.101579 that “PfSPZ-CVac (CQ) was well-tolerated [but the] tested dosing regimen failed to significantly protect against Pf infection.”  

Vaccine research also extends to P. vivax malaria, as reported by Pasini EM & al., Sterile Protection Against Relapsing Malaria with a Single-Shot Vaccine, NPJ Vaccines. 2022 Oct 27; 7(1):126, doi: 10.1038/s41541-022-00555-0, a very preliminary “proof-of-concept” study, and by White M & Chitnis CE, Potential Role of Vaccines in Elimination of Plasmodium vivax, Parasitol Int. 2022 Oct; 90:102592, doi: 10.1016/j.parint.2022.102592.   

Duffy PE, Current Approaches to Malaria Vaccines, Curr Opin Microbiol, 2022 Nov 4; 70:102227, doi: 10.1016/j.mib.2022.102227 purports to be a review of the field, but the abstract is not enlightening.  

Vector control and protection from vectors 

UNICEF Report – Long-Lasting Insecticidal Nets Market and Supply Update, October 2022. This update reports on UNICEF’s historical and projected long-lasting insecticidal nets supply, demand, and market developments. In 2021, UNICEF reviewed and extended its long-term arrangements for prequalified products with ten suppliers until December 2023.  Both a summary and the 11-page report are available. 

“In 2020–2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted [by Okiring J & al.] to evaluate the impact of the campaign 1–5 months after LLIN distribution.” They conclude in LLIN Evaluation in Uganda Project (LLINEUP2)—Factors Associated with Coverage and Use of Long Lasting Insecticidal Nets Following the 2020–21 National Mass Distribution Campaign: A Cross-Sectional Survey of 12 Districts, Malaria J, 2022 Oct 19, vol 21 art 293, doi: 10.1186/s12936-022-04302-7 that “Uganda’s 2020–21 campaign was successful, despite the COVID-19 pandemic.” Nonetheless the utilization of the LLINs remained suboptimal.  

Adageba SK & al., report in Bio-Efficacy, Physical Integrity, Use and Attrition of Long-Lasting Insecticidal Nets Under Operational Conditions for Malaria Prevention in Ghana, PLoS One. 2022 Oct 14; 17(10):e0275825, doi: 10.1371/journal.pone.0275825, that the nets distributed in a particular district in Ghana remained effective after one year of use, although their utilization was less than desirable.  Interestingly, homes with electricity were less likely to report continuing usage. 

Roh ME,  & al. studied the effect of indoor residual spraying (IRS) on pregnancy outcomes. Their paper, Association Between Indoor Residual Spraying and Pregnancy Outcomes: A Quasi-Experimental Study from Uganda, PLOS Glob Public Health 2(9): e0000676, doi: 10.1371/journal.pgph.0000676 concludes that IRS has beneficial effects on birthweight of infants, but only in the case of women who were not infected by HIV.  Miscarriage rates were not affected, however. 

Resistance to insecticides that are used in vector control programs is the subject of a number of articles this month.  Mugenzi LMJ & al., Escalating Pyrethroid Resistance in Two Major Malaria Vectors Anopheles funestus and Anopheles gambiae (s.l.) in Atatam, Southern Ghana, BMC Infect Dis. 2022 Oct 25; 22(1):799, doi: 10.1186/s12879-022-07795-4. “High intensity of resistance to 5 × and 10 × the discriminating concentration (DC) of pyrethroids was observed in [two Anopheles] species inducing a considerable loss of efficacy of long-lasting insecticidal nets (LLINs).” 

“[V]ectors are evolving in response to the deployment of vector control tools (VCTs), state Oke CE & al. in Vector Control: Agents of Selection on Malaria Parasites, Trends Parasitol. 2022 Oct; 38(10):890-903, doi: 10.1016/j.pt.2022.07.006. “By examining how mosquito responses to VCTs impact upon malaria parasite ecology, [the authors] derive a framework for predicting parasite responses.” 

Gene drives are generally aimed at skewing the mosquito population toward males, which do not transmit malaria to humans.  Champer SE al. found that the particular gene drive they studied was less than optimally effective.  Their report is Anopheles Homing Suppression Drive Candidates Exhibit Unexpected Performance Differences in Simulations with Spatial Structure, Elife. 2022 Oct 14; 11:e79121, doi: 10.7554/elife.79121. 

The recent experience of the MPI-sponsored project in which malaria incidence rebounded after conclusion of a very effective campaign in Uganda are echoed in more than one publication, for example, Nabatanzi M & al., Malaria Outbreak Facilitated by Increased Mosquito Breeding Sites Near Houses and Cessation of Indoor Residual Spraying, Kole District, Uganda, January-June 2019, BMC Public Health. 2022 Oct 12; 22(1):1898, doi: 10.1186/s12889-022-14245-y. “Longitudinal analysis of surveillance data showed decline in cases after an IRS campaign in 2017 but an increase after IRS cessation in 2018-2019. Overlay of rainfall and case data showed two malaria upsurges during 2019, occurring 35-42 days after rainfall increases.”  Meanwhile, Epstein A & al., Resurgence of Malaria in Uganda Despite Sustained Indoor Residual Spraying and Repeated Long Lasting Insecticidal Net Distributions, PLoS Glob Public Health 2(9): e0000676, doi: 10.1371/journal.pgph.0000676 reports that the IRS campaign continued but the agent used was changed. 

As recently discussed with some MPI Board members by the Chief Entomologist in The Gambia, home design is an important element in reducing the transmission of malaria to people. Jones C & al., House Screening for Malaria Control: Views and Experiences of Participants in the RooPfs Trial, Malaria J, 2022 Oct 21, vol 21 art 294, doi: 10.1186/s12936-022-04321-4 describes the influence of a design trial on the participating population.  Msoffe R & al., Participatory Development of Practical, Affordable, Insecticide-Treated Mosquito Proofing for a Range of Housing Designs in Rural Southern Tanzania, Malaria J, 2022 Nov 5, vol 21 art 318, doi: 10.1186/s12936-022-04333-0 also examines the population’s reaction to optimal screening of homes. They also suggest that “installed screens may be suitable targets for residual insecticide treatments.” 

According to Makhanthisa TI & al., Social Acceptance of Livestock-Administered Endectocides for Malaria Control in Vhembe District, Limpopo Province, South Africa, Malaria J, 2022 Oct 28, vol 21 art 307, doi: 10.1186/s12936-022-04334-z#Sec8, “[t]he use of livestock-administered endectocides appears to be a feasible and acceptable approach for control of animal-feeding malaria vector species in the malaria endemic villages …. This is based on a high percentage of rural residents keeping suitable livestock close to their homes and expressing willingness to use endectocides for mosquito control.” 

A rarely reported vector control strategy is trapping of swarming male Anopheles mosquitoes, which is expected to reduce the opportunity of females to be fertilized.  As reported in Assogba BS & al., Anopheles gambiae s.l. Swarms Trapping as a Complementary Tool Against Residual Malaria Transmission in Eastern Gambia, Sci Rep. 2022 Oct 12; 12(1):17057, doi: 10.1038/s41598-022-21577-7, “[f]ollowing the intervention, Anopheles gambiae s.l. indoor resting density was 44% lower in intervention than in control villages …; the odds of malaria infections were 68% lower in intervention than in control villages.” 

Faiman R & al. emphasize in Isotopic Evidence that Aestivation Allows Malaria Mosquitoes to Persist Through the Dry Season in the Sahel, Nat Ecol Evol. 2022 Oct 10, doi: 10.1038/s41559-022-01886-w that vector control will have to account for the persistent contribution of mosquito survival during the dry season, which lasts 7 months in the Sahel.   

Tsegaye A & al. measured the propensity of mosquitoes to be infected by malaria parasites and report their results in Susceptibility of Primary, Secondary and Suspected Vectors to Plasmodium vivax and Plasmodium falciparum Infection in Ethiopia, Parasit Vectors. 2022 Oct 21; 15(1):384, doi: 10.1186/s13071-022-05467-5.  

Plant based extracts have been repeatedly reported to be effective to a degree against malaria. Muhammed M & al. look at anti-mosquito effects of three species of plants Calpurnia aurea, Momordica foetida, and Zehneria scabra and report in Insecticidal Effects of Some Selected Plant Extracts Against Anopheles Stephensi (Culicidae: Diptera), Malaria J, 2022 Oct 21, vol 21, art 295, doi: 10.1186/s12936-022-04320-5, that their “results suggest that the leaf extracts of the three test plants have the potential of being used for the control of vector An. stephensi larvae and adult[s]”… 

Pundir H & al., Identification of Essential Oil Phytocompounds as Natural Inhibitors of Odorant-Binding Protein to Prevent Malaria Through in silico approach, J Biomol Struct Dyn. 2022 Oct, 10:1-11, doi: 10.1080/07391102.2022.2132419 is also a paper devoted to the study of plant-derived compounds that inhibit mosquito biting habits. 

Chemoprophylaxis 

A number of articles from various countries report that despite the known benefit of Intermittent Prophylactic Therapy during pregnancy (IPTp) with three doses of sulfamethoxide-pyrimethamine (SP), its use in accordance with the recommendation is spotty, sometimes as low as 35%.  These include Barry I & al., Variations in the Use of Malaria Preventive Measures Among Pregnant Women in Guinea: A Secondary Analysis of the 2012 and 2018 Demographic and Health Surveys, Malaria J, 2022 Nov 1, vol 21 art 309, doi: 10.1186/s12936-022-04322-3, Biteghe-Bi-Essone JC & al., Intermittent Preventive Treatment and Malaria Amongst Pregnant Women Who Give Birth at the Centre Hospitalier Régional Paul Moukambi de Koula-Moutou in Southeastern Gabon, Malaria J, 2022 Nov 4, vol 21 art 315, doi: 10.1186/s12936-022-04305-4, Nana RRD & al., Intermittent Preventive Treatment with Sulfadoxine Pyrimethamine for Malaria: A Global Overview and Challenges Affecting Optimal Drug Uptake in Pregnant Women, Pathog Glob Health, 2022 Sep 30: 1-14, doi: 10.1080/20477724.2022.2128563. 

Ouédraogo S & al. Impact of Mobile Phone Intervention on Intermittent Preventive Treatment of Malaria During Pregnancy in Burkina Faso : A Pragmatic Randomized Trial, Rev Epidemiol Sante Publique. 2022 Oct;70(5):209-214, doi: 10.1016/j.respe.2022.07.002 reaches similar conclusion, including the fact that reminders by mobile calls did not improve compliance with the regimen. 

“To determine if more effective malaria chemoprevention in mothers and their children results in better neurodevelopment,” Bangirana P &al. randomly assigned 305 pregnant women to three different chemopreventive regimens during pregnancy.”  Somewhat in contrast to other reports, Effect of Malaria and Malaria Chemoprevention Regimens in Pregnancy and Childhood on Neuro-developmental and Behavioral Outcomes in Children At 12, 24 and 36 Months: A Randomized Clinical Trial, Clin Infect Dis. 2022 Oct 11:ciac815, doi: 10.1093/cid/ciac815 concludes that “[m]alaria in pregnancy was associated with worse cognitive, behavioral and executive function scores in affected children, but more effective malaria chemoprevention measures did not result in better outcomes.” 

In Botswana, the chemoprophylactic agents used for pregnant women are chloroquine and proguanil. “Antimalarial prophylaxis was associated with improved birth outcomes in the most malaria-endemic region of Botswana, but not elsewhere,” according to Olaleye OA & al., Impact of Prophylactic Antimalarials in Pregnant Women Living with HIV on Birth Outcomes in Botswana, Trop Med Int Health. 2022 Oct 2, doi: 10.1111/tmi.13823. Further, the benefit was confined to women who were not infected by HIV (similar to Roh & al. above).  

Diagnosis: 

General diagnostics 

WHO, Quality and Safety Practices for Malaria Rapid Testing Services, https://media.malariaworld.org/ 9789240058972_eng_5daf97b707.pdf “is a guide defining requirements for quality and safety for malaria rapid diagnostic testing services to safeguard the quality of the results, the safety of the operators and patients and that of the environment for use by national malaria control programmes, regulators, implementers and rapid diagnostic providers.” 

Although it is primarily a study of nutrition in children, Traoré SG & al., Dietary Diversity in Primary Schoolchildren of South-Central Côte d’Ivoire and Risk Factors for Non-Communicable Diseases, BMC Pediatr, 2022 Nov 9; 22(1):651. doi: 10.1186/s12887-022-03684-6 reports that among the 620 children studied, “significant association was found between prediabetes and malaria infection, … Overweight was associated with malaria infection and moderate anaemia.” 

Field diagnostics 

Avanceña ALV & al., Achieving Malaria Testing and Treatment Targets for Children Under Five in Mozambique: A Cost-Effectiveness Analysis, Malaria J, 2022 Nov 7, vol 21 art 320, doi: 10.1186/s12936-022-04354-9. “This study aimed to estimate the costs and health benefits of six variations of the World Health Organization’s “test-and-treat” strategy among children under five.” They conclude that improving testing alone without improving compliance with optimal treatment may be beneficial, but not optimally so from a cost effectiveness analysis point of view.  

New diagnostic methods 

Lee S & al. “developed a paper-based microfluidic device capable of remote biofluid collection followed by an analysis of the dried clinical samples using a miniature mass spectrometer. [They] evaluated a portable mass spectrometer as a possible surveillance platform by analyzing the clinical malaria samples (whole blood) collected from Ghana.” They claim in Malaria Diagnosis Using Paper-Based Immunoassay for Clinical Blood Sampling and Analysis by a Miniature Mass Spectrometer, Anal Chem. 2022 Oct 4, doi: 10.1021/acs.analchem.2c03105 that “[t]he stability and sensitivity of the developed paper-based immunoassay platform will allow miniature mass spectrometers to be used for point-of-care malaria detection as well as in large-scale surveillance screening to aid eradication programs.” 

The application of convolutional neural networks (CNN) to microscopy of thin smears is the subject of  Khan SH & al., Malaria Parasite Classification Framework Using a Novel Channel Squeezed and Boosted CNN, Microscopy (Oxf). 2022 Oct 6; 71(5):271-282, doi: 10.1093/jmicro/dfac027. 

Treatment: 

reatment results 

“ A cross-sectional study was conducted amongst 857 children under 5 years of age who presented with fever at [two] general hospitals” by Zalwango JF & al., Malaria Diagnostic and Treatment Practices for Febrile Children Under 5 Years at Two General Hospitals in Karamoja, A High Transmission Setting in Uganda, Malaria J, 2022 Nov 3, vol 21 art 312, doi: 10.1186/s12936-022-04329-w. Their report concludes that between 35 and 40 percent of children had inadequate treatment, either not using the guideline recommended drugs or using them in the wrong dose. 

“Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment” is the conclusion of Kouakou YI & al., Pre-Referral Intranasal Artesunate Powder for Cerebral Malaria: A Proof-of-Concept Study, Malaria J, 2022 Oct 11, vol 21 art 291, doi: 10.1186/s12936-022-04309-0.  

Kavuma M and Mars M investigated The Effect of an Integrated Electronic Medical Record System [EMR] on Malaria Out-Patient Case Management in a Ugandan Health Facility, Health Informatics J, 2022 Oct-Dec; 28(4):14604582221137446, doi: 10.1177/14604582221137446.  While their conclusions cite positive changes in information recording, there is no mention of changes in clinical outcomes.  

Ampofo GD & al., Malaria in Pregnancy Control and Pregnancy Outcomes: A Decade’s Overview Using Ghana’s DHIMS II Data, Malaria J, 2022 Oct 27, vol 21 art 303, doi: 10.1186/s12936-022-04331-2 concludes: “Maternal anaemia and low birth weight prevalence showed marginal upward trends over the last decade despite reduced malaria infection rate and improved uptake of malaria in pregnancy control interventions.” 

Likewise, Mtove G & al., The Choice of Reference Chart Affects the Strength of the Association Between Malaria in Pregnancy and Small for Gestational Age: An Individual Participant Data Meta-Analysis Comparing the Intergrowth-21 with a Tanzanian Birthweight Chart, Malaria J, 2022 Oct 12, vol 21 art 292, doi: 10.1186/s12936-022-04307-2 is a birth outcome study without reference to chemo-prophylaxis.  It is reported here, because of its conclusion, which calls into question the common conclusion that malaria during pregnancy results in small birthweight children, arguing that the wrong reference data may have been used in arriving that conclusion.   

Side effects and complications 

Hernandez Maldonado J & Grundmann O claim in Drug-Drug Interactions of Artemisinin-Based Combination Therapies in Malaria Treatment: A Narrative Review of the Literature, J Clin Pharmacol. 2022 Oct;62(10):1197-1205., doi: 10.1002/jcph.2073 that certain genotypes of cytochrome P450 (CYP) enzymes are primarily involved in the metabolism of artemisinin and its derivatives. Reduced functions in the enzymes “can lead to subtherapeutic concentrations of the active metabolite, dihydroartemisinin, that may cause treatment failure, which has been shown in some studies with cardiovascular, antibiotic, and antiparasitic drugs. Although the clinical importance remains unclear to date, clinicians should be aware of potential drug-drug interactions and monitor patients on ACT closely.”  

Drug resistance 

Kay K & al. state that their article, Impact of Drug Exposure on Resistance Selection Following Artemether-Lumefantrine Treatment for Malaria in Children with and Without HIV in Uganda, Clin Pharmacol Ther. 2022 Oct 19, doi: 10.1002/cpt.2768 “demonstrates selection for reduced lumefantrine susceptibility” among children under treatment for HIV, “a concern as we confront the threat to ACTs posed by emerging artemisinin resistance in Africa.” 

According to Mbye H & al., Plasmodium falciparum Merozoite Invasion Ligands, Linked Antimalarial Resistance Loci and ex vivo Responses to Antimalarials in The Gambia, J Antimicrob Chemother. 2022 Oct 28; 77(11):2946-2955, doi: 10.1093/jac/dkac244, “[m]ultiple linked genic loci correlating with drug response phenotypes suggest a genomic backbone may be under selection by antimalarials. This calls for further analysis of molecular pathways to drug resistance in African P. falciparum.” 

Resistance may develop to antimalarials other than artesunates. Okombo J & al., Piperaquine-resistant PfCRT Mutations Differentially Impact Drug Transport, Hemoglobin Catabolism and Parasite Physiology in Plasmodium falciparum Asexual Blood Stages, PLoS Pathogens, 2022 Oct 28, doi: doi.org/10.1371/journal.ppat.1010926 explores the mechanism so far seen only in Southeast Asia.  

Tumwebaze PK & al. “evaluated 99 P. falciparum isolates collected in 2021 from northern Uganda, where resistance-associated … mutations have emerged, and eastern Uganda, where these mutations are uncommon.” As reported in Decreased Susceptibility of Plasmodium falciparum to Both Dihydroartemisinin and Lumefantrine in Northern Uganda, Nat Commun. 2022 Oct 26; 13(1):6353 doi: 10.1038/s41467-022-33873-x, they “identified multiple polymorphisms associated with altered drug susceptibility, notably … with decreased susceptibility to lumefantrine … and … mutations with chloroquine resistance… [They] raise concern regarding activity of artemether-lumefantrine, the first-line antimalarial in Uganda.” 

New drug research 

Johnson TO & al. tested five compounds for anti-plasmodial efficacy in Plasmodium berghei-infected mice, Elucidation of the Anti-Plasmodial Activity of Novel Imidazole and Oxazole Compounds Through Computational and in vivo Experimental Approaches, J Biomol Struct Dyn. 2022 Oct 30:1-9, doi: 10.1080/07391102.2022.2139761. Three of the five compounds tested “significantly reduced parasitemia over a four-day treatment period when compared to the infected untreated animal.” 

Lowe MA & al., Discovery and Characterization of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors and Preclinical Safety Assessment of UCB7362, J Med Chem. 2022 Oct 27; 65(20):14121-14143, doi: 10.1021/acs.jmedchem.2c01336 reports the discovery of potent, orally active [compounds] with in vivo antimalarial efficacy. … UCB7362 …had an improved in vitro and in vivo safety profile [and] is estimated to achieve 9 log 10 unit reduction in asexual blood-stage parasites with once-daily dosing of 50 mg for 7 days.” 

“L9LS, a potent and safe antimalarial monoclonal antibody, demonstrated 88% protective efficacy against infection in a phase 1 trial in healthy adults. These promising results are the first of many to usher in a potential new era of malaria prevention.”  This is the statement of Nekkab N & Penny MA, Accelerated Development of Malaria Monoclonal Antibodies, Cell Rep Med. 2022 Oct 18; 3(10):100786, doi: 10.1016/j.xcrm.2022.100786. 

Traditional treatments 

Djikam Sime G & al. report on a plant somewhat related to Cinchona, the source of quinine, in Secondary Metabolites of the Leaves of Tricalysia atherura N. Hallé (Rubiaceae) and Their Potential Antiplasmodial Activity, Nat Prod Res. 2022 Oct 25: 1-11, doi: 1080/14786419.2022.2137796. “Four of the metabolites were screened in vitro against both chloroquine (CQ)-sensitive (3D7) and -resistant (Dd2) strains of Plasmodium falciparum; they were found to exhibit moderate activity against chloroquine-resistant (Dd2) … Meanwhile, crude extract possesses high antiplasmodial activity against both 3D7 and Dd2 strains of P. falciparum.” 

“Sarcocephalus latifolius [African peach] is one of the most used plants in West African traditional medicine to treat malaria.” Tittikpina NK & al., Strategy for the Quality Control of Herbal Preparations Made of Sarcocephalus latifolius: Development and Validation of a UHPLC-PDA Method for Quantification of Angustoline and Strictosamide and Chemical Profiling Using LC-QToF, Phytochem Anal. 2022 Oct 25, doi: 10.1002/pca.3183 proposes “a strategy to control the quality of herbal preparations made from S. latifolius.” 

Other 

“Proof-of-concept studies demonstrate that antimalarial drugs designed for human treatment can also be applied to mosquitoes to interrupt malaria transmission,” state Kamiya T & al. in Targeting Malaria Parasites Inside Mosquitoes: Ecoevolutionary Consequences, Trends Parasitol. 2022 Oct 5: S1471-4922(22)00208-2, doi: 10.1016/j.pt.2022.09.004.  They argue “that targeting parasites inside mosquitoes (i) can be modelled by readily expanding existing epidemiological frameworks; (ii) provides a functionally novel control method that has potential to be more robust to resistance evolution than targeting parasites in humans; and (iii) could extend the lifespan and clinical benefit of antimalarials used exclusively to treat humans.” 

Campaigns and Policies: 

This is a new title to this section, since national or international policies are sometimes intertwined with campaigns, but some publications deal uniquely with principles or policies.  Opening a new category for these latter seems excessive, so they will be reported here. 

An example of a document not strictly related to campaigns, but to strategies and policies is the WHO Report, Global Framework for the Response to Malaria in Urban Areas, 2022 Nov 1, which was developed as part of a Memorandum of Understanding between WHO and UN-Habitat signed in 2021, aimed at improving urban health. The 92 page report is available on demand from the compiler or WHO. 

Also on policies, Omo-Imafidon ES & al. conducted interviews with Nigerian malaria researchers, policy advisors, and program managers. In Towards Improvement in Malaria Policy Implementation in Nigeria: A Qualitative Study on Factors Influencing the Translation of Malaria Policies to Practice, Trans R Soc Trop Med Hyg. 2022 Oct 2; 116(10):910-916, doi: 10.1093/trstmh/trac005, they report that “[i]nsufficient planning, lack of commitment, poor finance, manpower shortages, and a lack of synergy between academics and policymakers, … were recognized as important barriers to the malaria policy implementation process by respondents.” 

“In answer to the continuous challenge of malaria, the African Union has started a ‘zero malaria starts with me’ campaign that seeks to personalize malaria prevention and bring it down to the grass-root level.” Sarpong E & al., Zero Malaria: A Mirage or Reality for Populations of Sub-Saharan Africa in Health Transition, Malaria J, 2022 Nov 4, vol 21 art 314, doi: 10.1186/s12936-022-04340-1 “discusses the contribution of sub-Saharan Africa, whose population is in a health transition, to malaria elimination. In addition, the review explores the challenges that health systems in these countries face, that may hinder the attainment of a zero-malaria goal.” 

Sokunbi TO & al., Nigeria End Malaria Council: What to Expect, Ann Med Surg (Lond). 2022 Sep 15; 82:104690, doi: 10.1016/j.amsu.2022.104690 states the following: “The President of Nigeria, on August 16, 2022, inaugurated the Nigeria End Malaria Council” and claims this is “an intervention that has been tested with proven track records of progressive success in malaria control and reduction in the countries where it has been established. With the establishment of the Nigeria End Malaria Council, we can be expectant of a malaria-free country in no time if the aims and objectives of the council are sustained and effectively carried out.” 

Bagenda F& al., Contribution of Community Health Workers [CHWs] to the Treatment of Common Illnesses Among Under 5-Year-Olds in Rural Uganda, Malaria J, 2022 Oct 21, vol 21 art 296, doi: 10.1186/s12936-022-04316-1. “A retrospective review of monthly morbidity data for children less than 5 years of age for the period April 2014–December 2018 for CHWs in rural … Uganda was done. The total number reviewed was 18,430 records. … pneumonia was the highest cause of illness among the infants (< 1 year), while malaria was the highest among the children 1 year–59 months… Community Health Workers in rural Uganda are contributing significantly to the management of all the three commonest illnesses among under-5 years-old children. The trend of the commonest illness is changing from malaria to pneumonia.” 

In many countries in Africa, professional healthcare providers and community health workers are also supplemented by so-called “over the counter medicine sellers,” who may be the only ones consulted by parents of a child with fever, because of access and cost considerations.  Soniran OT & al., Improved Adherence To Test, Treat, And Track (T3) Malaria Strategy Among Over-The-Counter Medicine Sellers (OTCMS) Through Interventions Implemented in Selected Rural Communities of Fanteakwa North District, Ghana, Malaria J, 2022 Nov 5. Vol 21 art 317, doi: 10.1186/s12936-022-04338-9 reports the result of training given to these individuals.  They conclude that the training was effective in having them better adhere to “malaria protocols.”  Training also included households, which increasingly turned to trained individuals for assistance for their febrile children.  

Recognizing the reality of inadequate compliance with WHO’s recommendations for IPTp, demonstrated above in the Prevention section, Busari SS & al. approasch the problem using quality management techniques. Their paper, Strengthening the Capacity of Healthcare Providers to Administer Intermittent Preventive Therapy for Malaria in Pregnancy in Nigeria Using a Quality Improvement Strategy, Int J Health Plann Manage. 2022 Oct 30, doi: 10.1002/hpm.3588 states that “[t]he total duration of the intervention was for a period of 4 weeks which comprises of four training sessions conducted over a period of 2 weeks and four coaching sessions conducted for a period of another 2 weeks.”  They conclude that the process brought positive results, but the Abstract does not provide enough data to reach any conclusion. 

Another report on staff training is Okyere Boadu R & al., Assessment of Health Staff’s Proficiency and Quality of Key Malaria Indicators in Rural District of Ghana, PLoS One. 2022 Oct 27; 17(10):e0274700, doi: 10.1371/journal.pone.0274700. They focused on whether staffs received training in malaria-related information management  In their assessment they found generally disappointing results in that staff members were unable to use to system at all or could not properly enter or interpret data.  

Cheng NI & al. reviewed the results of mass administration in Ghana through focus group interviews. In The Impact of COVID-19 on Implementation of Mass Testing, Treatment and Tracking [MTTT] of Malaria in Rural Communities in Ghana: A Qualitative Study, PLoS One. 2022 Oct 13;17(10):e0275976, doi: 10.1371/journal.pone.0275976 they cite “an increase in the number of people reporting with complications of malaria in health facilities in the study communities during the COVID-19 period. Some participants were of the view that COVID-19 rumours and misinformation could largely be responsible for the low coverage and uptake of the MTTT of malaria intervention…” 

Also on the topic of malaria control in the era of COVID, Patrick SM & al., COVID-19 and the Malaria Elimination Agenda in Africa: Re-Shifting the Focus, Glob Public Health. 2022 Oct 4: 1-12, doi: 10.1080/17441692.2022.2129729 “explores the impact of COVID-19 on progress made with malaria control and prevention strategies in Africa; and discusses possible mitigation steps to aid community resilience building, through proactive planning and implementation of integrated, inclusive and sustainable strategies to re-shift the focus to attain the malaria elimination goals. [The authors] propose strengthening community partnerships, where academia and communities should collaborate and these knowledge-sharing strategies be implemented in order for awareness and interventions to become more networked, inclusive, resilient and effective.” 

The cost of malaria control programs exceed the monetary outlays necessary to conduct them. Chinkhumba J & al., Impact of School-Based Malaria Intervention on Primary School Teachers’ Time in Malawi: Evidence from a Time and Motion Study, Malaria J, 2022 Oct 27, vol 21 art 301, doi: 10.1186/s12936-022-04324-1 assesses “the impact of school-based malaria diagnosis and treatment using the Learner Treatment Kit (LTK) on teachers’ time.” The teachers increased their time in the classroom as a result of this additional task, and the authors conclude that “[s]chool-based health (SBH) programmes are not detrimental to teaching activities. Teachers manage their time to ensure additional time required for SBH services is not at the expense of teaching duties.” 

Andrade MV & al. look at costs more broadly in The Economic Burden of Malaria: A Systematic Review, Malar J. 2022 Oct 5;21(1):283, doi: 10.1186/s12936-022-04303-6, since, as they state, “the availability of comprehensive and comparable estimates of malaria costs across endemic countries is scarce.”  Having reviewed 45 publications on the subject, they conclude that “[c]ost estimates currently available are not comparable, hindering broad statements on the costs of malaria, and constraining advocacy efforts towards investment in malaria control and elimination, particularly with the finance and development sectors of the government.” 

As already mentioned, a recent supplement to the American Journal of Tropical Medicine and Hygiene carried several articles that originated in various branches of the International Center of Excellence for Malaria Research (ICEMR).  These generally recited the accomplishments of these Centers over their tenure. Rao MR & Hall BF, International Centers of Excellence for Malaria Research: Achievements of the Collaborative Network during the Past Decade, Am J Trop Med Hyg, 2022 Oct 11; 107(4_Suppl):1-4. doi: 10.4269/ajtmh.22-0209 is the introduction to these papers (no abstract).  The following are those articles in this supplement with relevance to Africa: 

Yan, G & al., Impact of Environmental Modifications on the Ecology, Epidemiology, and Pathogenesis of Plasmodium falciparum and Plasmodium vivax Malaria in East Africa, Am J Trop Med Hyg, 2022 Oct 11;107(4_Suppl):5-13, doi: 10.4269/ajtmh.21-1254.   

Githure JI & al., Enhancing Malaria Research, Surveillance, and Control in Endemic Areas of Kenya and Ethiopia, Am J Trop Med Hyg. 2022 Oct 11; 107(4_Suppl):14-20, doi: 10.4269/ajtmh.21-1303. 

Nankabirwa JI & al., East Africa International Center of Excellence for Malaria Research: Summary of Key Research Findings, Am J Trop Med Hyg, 2022 Oct 11; 107(4_Suppl):21-32.  doi: 10.4269/ajtmh.21-1285.  

Cohee LM & al., Understanding the Intransigence of Malaria in Malawi, Am J Trop Med Hyg. 2022 Oct 11; 107(4_Suppl):40-48, doi: 10.4269/ajtmh.21-1263. 

Mangani C & al., Malawi ICEMR Malaria Research: Interactions and Results Influencing Health Policies and Practices, Am J Trop Med Hyg. 2022 Oct 11; 107(4_Suppl):49-54, doi: 10.4269/ajtmh.21-1265. 

Ippolito MM et al., Scientific Findings of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe, Am J Trop Med Hyg. 2022 Oct 11; 107(4_Suppl):55-67, doi: 10.4269/ajtmh.21-1287. 

Wesolowski A & al., Policy Implications of the Southern and Central Africa International Center of Excellence for Malaria Research: Ten Years of Malaria Control Impact Assessments in Hypo-, Meso-, and Holoendemic Transmission Zones in Zambia and Zimbabwe, Am J Trop Med Hyg. 2022 Oct 11 ;107(4_Suppl):68-74, doi:  10.4269/ajtmh.21-1288. 

Doumbia S et al., A Decade of Progress Accelerating Malaria Control in Mali: Evidence from the West Africa International Center of Excellence for Malaria Research, Am J Trop Med Hyg. 2022 Oct 11; 107(4_Suppl):75-83, doi: 10.4269/ajtmh.21-1309. 

Doumbia S & al., The West Africa ICEMR Partnerships for Guiding Policy to Improve the Malaria Prevention and Control, Trop Med Hyg. 2022 Oct 11; 107(4_Suppl):84-89, doi: 10.4269/ajtmh.21-1330. 

Epidemiology: 

Climate change, biodiversity, and environment 

Atuh NI & al., High Genetic Complexity but Low Relatedness in Plasmodium falciparum Infections from Western Savannah Highlands and Coastal Equatorial Lowlands of Cameroon, Pathog Glob Health. 2022 Oct; 116(7):428-437, doi: 10.1080/20477724.2021.1953686 takes cognizance of the differences in parasite population between two diverse areas within the country and notes that the differences tend to remain over time.  

Graboyes M & al. explore awareness of the relationship between the environment and malaria in, Mazingira and the Malady of Malaria: Perceptions of Malaria as an Environmental Disease in Contemporary Zanzibar, Stud Hist Philos Sci. 2022 Oct; 95:134-144, doi: 10.1016/j.shpsa.2022.07.005. Mazingira is a local term referring to the environment, one that apparently allows for human intervention.  Fifty local interviewees indicated their understanding that changing mazingira may mitigate the incidence of malaria.  

“Irrigation not only helps to improve food security but also creates numerous water bodies for mosquito production.” Ondeto BM & al., Malaria Vector Bionomics and Transmission in Irrigated and Non-Irrigated Sites in Western Kenya, Parasitol Res. 2022 Oct 7, doi: 10.1007/s00436-022-07678-2 assessed “the effect of irrigation on malaria vector bionomics and transmission in a semi-arid site with ongoing malaria vector control program… The mosquito samples were identified to species and assayed for host blood meal source and Plasmodium spp. sporozoite infection…” As was probably expected, irrigated agriculture apparently increased “the risk of malaria transmission in irrigated areas compared to the non-irrigated areas..” They recommend complementing “the existing malaria vector interventions with novel tools targeting the larvae and both indoor and outdoor biting vector populations.” 

Population dynamics 

Hodson DZ & al. studied how malaria strikes urban populations and report in Clinical Characteristics of Plasmodium falciparum Infection Among Symptomatic Patients Presenting to a Major Urban Military Hospital in Cameroon, Malaria J, 2022 Oct 22, vol 21, art 298, doi:10.1186/s12936-022-04315-2 that about 37% of patients presenting with fever had falciparum malaria and peak malaria infection rates were in children aged 10 to 14. 

“Malaria persists at low levels on Zanzibar despite the use of vector control and case management.” Das AM & al., The impact of Reactive Case Detection on Malaria Transmission in Zanzibar in The Presence of Human Mobility, Epidemics, 2022 Oct 20; 41:100639, doi: 10.1016/j.epidem.2022.100639 find that “in the absence of imported cases from mainland Tanzania, malaria would likely cease to persist on Zanzibar.” Furthermore, while “some additional cases are removed by reactive case detection, a large proportion of cases are missed due to many infections having a low parasite density that go undetected by rapid diagnostic tests, a low rate of those infected with malaria seeking treatment, and a low rate of follow up at the household level of malaria cases detected at health facilities.” 

Mbah CE & al. used rapid diagnostic testing on randomly enrolled asymptomatic people in rural and urban settings. Among the rural population, prevalence of asymptomatic malaria was as high as 41.5%, while in the urban environment it was low at 5.1%. The paper is A Comparative Study of Asymptomatic Malaria in a Forest Rural and Depleted Forest Urban Setting During a Low Malaria Transmission and COVID-19 Pandemic Period, Biomed Res Int. 2022 Oct 15; 2022:2545830, doi: 10.1155/2022/2545830.  

 

Ehiem RC & al. administered questionnaires to 849 participants in their study, Malaria Knowledge-Base and Prevalence of Parasitaemia in Asymptomatic Adults in the Forest Zone of Ghana, Acta Parasitol. 2022 Oct 19, doi: 10.1007/s11686-022-00629-y. Of the participants, 111 were proven to have asymptomatic malaria.  Analysis of the answers disclosed that “[a]wareness and knowledge of malaria was satisfactory but this did not translate into mosquito avoidance behaviour due to deep-seated perceptions and myths.” 

In a paper that could also have been cited under Diagnosis, Kayange M & al. used a specific hematology analyzer to screen potential blood donors for asymptomatic malaria. In their paper, Automated Measurement of Malaria Parasitaemia Among Asymptomatic Blood Donors in Malawi Using the Sysmex XN-31 Analyser: Could Such Data be Used to Complement National Malaria Surveillance in Real Time?, Malaria J, 2022 Oct 26, vol 21 Art 299, doi: 10.1186/s12936-022-04314-3, they also suggest using this type of data in national surveillance. 

Spatiotemporal studies 

Duguma T & al., Trends of Malaria Prevalence in Selected Districts of Kaffa Zone, Southwest Ethiopia, J Trop Med. 2022 Oct 14; 2022:3556140, doi: 10.1155/2022/3556140.  

Debash H & al., Prevalence and Associated Risk Factors of Malaria Among Febrile Under-Five Children Visiting Health Facilities in Ziquala District, Northeast Ethiopia: A Multicenter Cross-Sectional Study, PLoS One. 2022 Oct 27; 17(10):e0276899, doi: 10.1371/journal.pone.0276899.  

Earland DE & al., Plasmodium falciparum Community Prevalence and Health-Seeking Behaviours in Rural Sussundenga District, Mozambique, Malaria J, 2022 Oct 28, vol 21 art 305, doi: 10.1186/s12936-022-04326-z.  

Ibeji JU & al., Bayesian Spatio-Temporal Modelling and Mapping of Malaria and Anaemia Among Children Between 0 and 59 Months in Nigeria, Malaria J, 2022 Nov 1, vol 21 art 311, doi: 10.1186/s12936-022-04319-y.  

Adugna F & al., Prevalence of Malaria and Its Risk Factors in Lake Tana and Surrounding Areas, Northwest Ethiopia, Malaria J, 2022 Nov 4, vol 21, art 314, doi: 10.1186/s12936-022-04310-7. 

Other 

Shah MP & al. selected a “random sample of 4670 malaria RDT negative dried blood spot samples were selected from a mass testing and treatment trial in … Western Kenya” in order to estimate RDT negative positivity in populations.  They contend in Novel Application of One-Step Pooled Molecular Testing and Maximum Likelihood Approaches to Estimate the Prevalence of Malaria Parasitaemia Among Rapid Diagnostic Test Negative Samples in Western Kenya, Malaria J, 2022 Nov 6, vol 21 art 319, doi: 10.1186/s12936-022-04323-2 that the way they analyzed subsets of dried blood spots and the resultant data provide a cost-effective “one-step” estimate of the prevalence of RDT-negative malaria. 

The aim of Zewude BT & al., Multilevel Logistic Regression Modelling to Quantify Variation in Malaria Prevalence in Ethiopia, PLoS One. 2022 Sep 29; 17(9):e0273147, doi: 10.1371/journal.pone.0273147 “was to quantify the variation in the prevalence of malaria between sample enumeration areas (SEAs) or clusters, the effects of cluster characteristics on the prevalence of malaria using the intra-class correlation coefficient as well as to identify significant factors that affect the prevalence of malaria… The multilevel logistic regression with random effects model used in this paper identified five individual household and two SEA-level risk factors of malaria infection. Therefore, the public health policy makers should pay attentions to those significant factors, such as improving the availability of pure drinking water. Further, the findings of spatial clustering provide information to health policymakers to plan geographically targeted interventions to control malaria transmission.”