Science & Research Report For April 2022

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

On March 31, 2022, the World Health Organization published its new Guidelines for malaria.  As stated in its overview, “[t]he WHO Guidelines for malaria bring together the Organization’s most up-to-date recommendations for malaria in one user-friendly and easy-to-navigate online platform.

The WHO Guidelines for malaria  supersedes 2 previous WHO publications: the Guidelines for the treatment of malaria, third edition and the Guidelines for malaria vector control. Recommendations on malaria will continue to be reviewed and, where appropriate, updated based on the latest available evidence. Any updated recommendations will always display the date of the most recent revision in the MAGICapp platform. With each update, a new PDF version of the consolidated guidelines will also be available for download on the WHO website.

This version of the Guidelines includes updates to the vector control section and replaces the versions published on 16 February 2021, 13 July 2021 and 18 February 2022.” The Guidelines may be downloaded from https://www.who.int/publications/i/item/WHO-UCN-GMP-2022.01-Rev.1.

In this issue of the Newsletter, there is also an article that refers to an important mass media publication, The Economist, which published a graph and short article extolling development of a useful malaria vaccine.  The projection of greatly diminished burden of malaria over the next few decades is dramatic.

Prevention:

Vaccines 

A few weeks before the publication of the above mentioned Guideline, WHO issued the bilingual Malaria Vaccine: WHO Position Paper – March 2022, WHO Weekly Epidemiological Record, 2022 Mar 4; 97(9):61-80 https://www.who.int/wer. On the same day, WHO published a related news release.

Moncunill G & al., Transcriptional Correlates of Malaria in RTS,S/AS01-Vaccinated African Children: a Catched Case-Control Study, Elife, 2022 Jan 21; 11:e70393. doi: 10.7554/eLife.70393 is a mostly pathophysiologic study of immune system alterations as a result of administration of the vaccine.

Similarly, Ragotte RJ & al. analyze antibody responses to the use of a not yet approved malaria vaccine candidate in Heterotypic Interactions Drive Antibody Synergy Against a Malaria Vaccine Candidate, Nat Commun, 2022 Feb 17; 13(1):933. doi: 10.1038/S41467-022-28601-4.

Vector control and protection from vectors

“ Progress achieved by long-lasting insecticidal nets … against malaria is threatened by widespread selection of pyrethroid resistance among vector populations.” Martin JL & al. report on an ongoing study, of which results are not available yet: Durability of Three Types of Dual Active Ingredient Long-Lasting Insecticidal Net Compared to a Pyrethroid-Only LLIN in Tanzania: Methodology for a Prospective Cohort Study Nested in a Cluster Randomized Controlled Trial, Malaria J, 2022 Mar 19, vol 21 art 96. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04119-4.

“Between 2000 and 2019, more than 1.8 billion long-lasting insecticidal nets (LLINs) were distributed in Africa. While the insecticidal durability of LLINs is around 3 years, nets are commonly discarded 2 years post distribution.” Madoumia EP & al., “investigated the factors associated with the decision of users to discard LLINs” in “In Starvation, a Bone Can Also Be Meat”: A Mixed Methods Evaluation of Factors Associated with Discarding of Long-Lasting Insecticidal Nets in Bagamoyo, Tanzania, Malaria J, 2022 Mar 24, vol 21 art 101, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04126-5 and reported that integrity of LLIN played a role in discarding a net. “Those of older age, women, and householders with lower income were more likely to classify a WHO ‘too-torn’ net as ‘good’.”

Madgwick PG & Kanitz R report on a theoretical level in Modelling New Insecticide-Treated Bed Nets for Malaria-Vector Control: How to Strategically Manage Resistance?  Malaria J, 2022 Mar 24, vol 21 art 102, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04083-z

Koudou GB & al. published a method to assess the use of bed nets in households.  The method was tested in England and reported as Evaluation of an Accelerometer-Based Monitor for Detecting Bed Net Use and Human Entry/Exit Using a Machine Learning Algorithm, Malaria J, 2022 Mar 12, vol 21 art 85, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04102-z.

One method of vector control is releasing sterile male mosquitoes in malaria-endemic areas. Yao FA & al. report in Mark-Release-Recapture Experiment in Burkina Faso Demonstrates Reduced Fitness and Dispersal of Genetically-Modified Sterile Malaria Mosquitoes, Nat Commun, 2022 Feb 10; 13(1):796. doi: 10.1038/S41467-022-28419-0.  The abstract of the article does not allow us to draw conclusions about any effect on malaria prevalence in the area studied.

Vectors are also the target of another potential approach in which microorganisms interact with Plasmodium parasites in the mosquito gut and prevent the transmission of the parasite, even if the mosquito bites a susceptible person. Yu S & al. describe this approach in Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages, Front Cell Infect Microbiol, 2022 Feb 16; 12:820650.  doi: 10.3389/fcimb.2022.820650.

Consalvi S & al. also describe potential approaches to prevent the transmission of parasites in Malaria Transmission Blocking Compounds: A Patent Review, Expert Opin Ther Pat, 2022 Mar 11;1-18. doi: 10.1080/13543776.2022.2049239.

Chemoprophylaxis

The use of chemoprophylaxis during pregnancy is the subject of Mama A & al., Intermittent Preventive Treatment in Pregnancy With Sulfadoxine–Pyrimethamine and Parasite Resistance: Cross-Sectional Surveys from Antenatal Care Visit and Delivery in Rural Ghana, Malaria J, 2022 Mar 26, vol 21 art 107, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04124-7. The use of three doses of the prophylactic agent reduced parasite prevalence in the treated women and their babies weighed more at birth than those who did not have prophylaxis.  The study also found a worrying trend in parasites still prevalent in treated women, in that the incidence of a genetic marker in the surviving parasites raises a question of future emergence of resistance to this mode of prevention.

Vincenz C & al studied Risk Factors for Placental Malaria, Sulfadoxine-Pyrimethamine Doses, and Birth Outcomes in a Rural to Urban Prospective Cohort Study on the Bandiagara Escarpment and Bamako, Mali, Malaria J, 2022 Mar 31, vol 21 art 110. https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-022-04125-6 and had the unsurprising findings that ‘[b]irth outcomes improved … for women who had ≥ 3 doses of SP compared to no doses… at 2 instead of ≥ 3 doses placentas were 36 g lighter and the odds of low birth weight (< 2500 g) were 14% higher. Severe parasite densities … significantly associated with decreases in birth weight, birth length, and placental weight, as were chronic PM infections. The women who received no SP during pregnancy (7% of the study total) were younger and lacked primary school education. The women who received ≥ 3 doses of SP came from more affluent families.”

Another prophylactic approach is the administration of medications to uninfected individuals during the high-incidence season.  Moukénet A & al., Extending Delivery of Seasonal Malaria Chemoprevention to Children Aged 5-10 Years in Chad: A Mixed-Methods Study, Glob Health Sci Pract, 2022 Mar 1; 10(1):e2100161. doi: 10.9745/GHSP-D-21-00161 describes the pros and cons of extending this approach to children older than 5 years and concludes that given funding constraints, extension is problematic.

As recommended by WHO, a full seasonal malaria chemoprevention (SMC) course in Burkina Faso “is administered over four monthly cycles from July to October, coinciding with the rainy season. However, an analysis of rainfall patterns suggests that the malaria transmission season is longer and starts as early as June in the south of Burkina Faso, leading to a rise in cases prior to the first cycle.” Traore A & al., Extending Seasonal Malaria Chemoprevention to Five Cycles: A Pilot Study of Feasibility and Acceptability in Mangodara District, Burkina Faso, BMC Public Health, 2022 Mar 5; 22(1):442.  doi: 10.1186/S12889-022-12741-9 examined the outcome of a fifth cycle in early June and found that while it reduced the cases of malaria, access issues prevented full implementation.

Other and mixed preventive approaches

Fatunia OA & al. studied “the various methods employed to prevent malaria and their effects on malaria parasite prevalence among children living in a rural community in Nigeria.” In their report, Malaria Prevention Practices and Malaria Prevalence Among Children Living in a Rural Community in Southwest Nigeria, J Infect Dev Ctries, 2022 Feb 28; 16(2):352-361. doi: 10.3855/jidc.14894, they found that “[m]alaria prevention methods were mostly practiced by participants of the high social class while children under-five considerably used mosquito nets.” However, their statistical analysis also revealed, perhaps surprisingly, that “[n]one of the methods employed to prevent malaria had a statistically significant effect on malaria parasite prevalence among participants (p > 0.050).” Perhaps this latter finding is related to the relatively small sample of children studied (357).

Iddrisu D & Moyer CA, report the following in Using the Ghana Malaria Indicator Survey to Understand the Difference Between Female and Male-Headed Households and Their Prevention and Testing for Malaria Among Children Under 5, Malaria J, 2022 Apr 2; vol 21 art 112. doi: 10.1186/S12936-022-04135-4: Male heads of households “were significantly more likely to own an [impregnated bednet] than [female heads of households] …, whereas [the latter] were more likely to report taking malaria prevention steps such as spraying the house with insecticide, filling in stagnant puddles, and keeping surroundings clear (all significant at P < 0.001). Nonetheless, there was “no difference in febrile episodes, malaria testing, and rates of positivity” in children growing up in the two different environments.

Diagnosis:

Wambani J & Okoth P, Impact of Malaria Diagnostic Technologies on the Disease Burden in the Sub-Saharan Africa, J Trop Med, 2022 Mar 22; 2022:7324281. doi: 10.1155/2022/7324281 is a review that “summarizes the principle, performance, gaps, accomplishments, and applicability of numerous malaria diagnostic techniques and their potential role in reducing the malaria disease burden ….”

Mpina M & al. state that “infections persisting at low parasite densities comprise a large reservoir contributing to ongoing malaria transmission and are difficult to detect. Therefore they compared several diagnostic methods and reported their results in, Diagnostic Performance and Comparison of Ultrasensitive and Conventional Rapid Diagnostic Test, Thick Blood Smear and Quantitative PCR for Detection of Low-Density Plasmodium falciparum Infections During a Controlled Human Malaria Infection Study in Equatorial Guinea, Malaria J, 2022 Mar 24, vol 21 art 99. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04103-y.  “Thick blood smears and uRDTs [ultrasensitive Rapid Diagnostic Tests] had similar sensitivities, both were more sensitive than cRDTs [conventional Rapid Diagnostic Tests] and neither matched qPCR [quantitative polymerase chain reaction] for detecting low-density parasitaemia.”

In Northern Côte d’Ivoire, Benié & al. found 20% of asymptomatic participants in a study to be infected with the malaria parasite.  They were reporting the results of their study in Accuracy of a Rapid Diagnosis Test, Microscopy and Loop-Mediated Isothermal Amplification in the Detection of Asymptomatic Plasmodium Infections in Korhogo, Northern Côte d’Ivoire, Malaria J, 2022 Apr 2, vol 21 art 111. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04133-6.  The sensitivity of histidine-rich protein-based RDT was 17%. Loop mediated isothermal amplification test (LAMP) was close to 100% sensitive, as compared to PCR.

Ebong CE & al. Diagnosis of Malaria in Pregnancy: Accuracy of CareStart™ Malaria Pf/PAN Against Light Microscopy Among Symptomatic Pregnant Women at The Central Hospital in Yaoundé, Cameroon, Malaria J, 2022 Mar 9, vol 21 art 78, https://malariajournal.biomedcentral.com/ articles/10.1186/s12936-022-04109-6 appears to have results (based on the Abstract) that strike this reviewer as problematic.  First, it uses light microscopy results as a reference, without specifying whether thin or thick smears were used.  Second, the results seem to indicate that the RDT had more sensitivity than specificity, which is in contrast with many other reports of RDTs.

Most RDTs are dependent on the presence of histidine-rich protein 2.  However, some gene deletions in the parasite threaten the reliability of the test Rogier E & al. studied the prevalence of these deletions in four African countries over 2016-2018.  Their report, Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions from Persons with Symptomatic Malaria Infection in Ethiopia, Kenya, Madagascar, and Rwanda, Emerg Infect Dis, 2022 Mar; 28(3):608-616. doi: 10.3201/Eid2803.211499 concludes that these deletions were rare during the period studied.

“Ill infants aged one to six months in out-patient and in-patient care were recruited over an 11-month period” by Follarin OF & al. “Clinical examinations and blood film for malaria parasite were done for all the study participants. Heavy parasitaemia was defined as > 5000 parasites/µl. Clinical predictors of heavy parasitaemia were determined.” As reported in Heavy Malaria Parasitaemia in Young Nigerian Infants: Prevalence, Determinants and Implication for the Health System, West Afr J Med, 2022 Feb 28; 39(2):154-161, “[p]resence of fever at presentation …, excessive crying … and pallor … were associated with heavy malaria parasitaemia. However, pallor … was the only independent predictor of heavy parasitaemia among the young infants.”

McLaughlin M & al., Development and Validation of Manually Modified and Supervised Machine Learning Clinical Assessment Algorithms for Malaria in Nigerian Children, Front Artif Intell, 2022 Feb 3; 4:554017. doi: 10.3389/frai.2021.554017 is a complicated review of combining RDT with other clinical observations and using artificial intelligence in enhancing diagnostic accuracy.

Not strictly covering a diagnostic subject, but an important paper is Achan J & al., Current Malaria Infection, Previous Malaria Exposure, and Clinical Profiles and Outcomes of COVID-19 in a Setting of High Malaria Transmission: An Exploratory Cohort Study in Uganda, Lancet Microbe, 2022 Jan; 3(1):e62-e71. doi: 10.1016/S2666-5247(21)00240-8.  The paper describes clinical features of the co-infection, which must be common in our times.

Similarly not strictly diagnostic is the focus of Sánchez K & Spencer LM, Pregnancy-Associated Malaria: Effects of Cytokine and Chemokine Expression, Travel Med Infect Dis, 2022 Mar 18; 47:102282. Doi: 10.1016/J.Tmaid.2022.102282.  This paper describes the unique features of malaria in pregnancy and its effects on the immune system, specifically on cytokines.

Treatment:

Care seeking

Treatment of children with malaria has to start with a parent or other caregiver recognizing that care is needed. Cassy A & al., Factors Associated with Malaria Care Seeking Among Children Under 5 Years of Age in Mozambique: A Secondary Analysis of the 2018 Malaria Indicator Survey, Malaria J, 2022 Mar 24, vol 21 art 100. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04128-3 is a “weighted analysis … based on data reported by surveyed mothers or caregivers of children aged 0–59 months who had fever in the two weeks prior to the [2018 Malaria Indicator] Survey… Care was …sought for 69.1% of children aged 0–59 months old with fever. Care-seeking was significantly higher among younger children… as compared with older children (48–59 months old). …mothers from the middle … and richest … wealth quintiles were more likely to report having sought care for their febrile children than mothers from the poorest wealth quintile. … mothers with secondary or higher education level were more likely to seek care … than mothers with no education. … The main reasons reported for not seeking care included distance to health facility …, the perception that the fever was not severe … and the perception that treatment was not available at the health facility …”

“Fever and malaria are highly prevalent among children under five across sub-Saharan Africa, but utilization and quality of care for febrile illness remain insufficient.” Lewis TP & al. examine associations of women’s empowerment with: a) care utilization for children with fever and malaria and b) the quality of that care in 16 sub-Saharan African countries. Their report, Associations Between Women’s Empowerment, Care Seeking, and Quality of Malaria Care for Children: A Cross-Sectional Analysis of Demographic and Health Surveys in 16 Sub-Saharan African Countries, J Glob Health, 2022 Mar 19;12:04025. doi: 10.7189/Jogh.12.04025, demonstrates “substantial gaps in women’s empowerment and poor utilization and quality of care for fever and malaria among children. Increased women’s empowerment is associated with seeking care and, separately, obtaining high-quality care.”

Drugs to prevent transmission

The title of Mwaiswelo RO & al.’s article, A Single Low Dose of Primaquine Is Safe and Sufficient to Reduce Transmission of Plasmodium falciparum Gametocytes Regardless of Cytochrome P450 2D6 Enzyme Activity in Bagamoyo District, Tanzania, Malaria J, 2022 Mar 12, vol 21 art 84, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04100-1 is sufficient summary of the authors’ conclusion. They found this administration safe even in children who were known to have glucose-6-dehydrogenase (G6PD) deficiency.

Drug resistance

Although Peto TJ & al.’s report, Triple Therapy with Artemether-Lumefantrine Plus Amodiaquine Versus Artemether-Lumefantrine Alone for Artemisinin-Resistant, Uncomplicated falciparum Malaria: An Open-Label, Randomized, Multicenter Trial, Lancet Infect Dis, 2022 Mar 8, doi.org/10.1016/S1473-23099(21)00692-7 originates in Southeast Asia, the topic of resistance is of importance for treatment of malaria in Africa as well. In this two-branch open-label study, the vast majority of patients with incomplete clearance of infection were in the group that did not receive amodiaquine. Triple therapy did cause more gastrointestinal (GI) side effects than double therapy. Chen I & Hsiang MS, Triple Artemisinin-Based Combination-Based Therapies for Malaria: A Timely Solution to Counter Anti-malarial Drug Resistance, Lancet Infect Dis, 2022 Mar 8, doi.org/10.1016/S1473-3099(21)00748-9 is an editorial that accompanies the above article.

Another article from Asia, Nima MK & al., Assessment of Plasmodium falciparum Artemisinin Resistance Independent of kelch13 Polymorphisms and with Escalating Malaria in Bangladesh, mBio, 2022 Jan 25, 13(1):e03444-21, doi: 10.1128/mbio.03444-21 appears to describe a resistant mutant with a mechanism of resistance that may be a hitherto undescribed new one.

Das S & al. found no artemisinin resistance-related mutations, but some mutations that drive resistance to other drugs in parasites studied. The paper is Molecular Surveillance for Operationally Relevant Genetic Polymorphisms in Plasmodium falciparum in Southern Chad, 2016–2017, Malaria J, 2022 Mar 12, vol 21, art 83, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04095-9.

Nkemngo FN & al. studied parasites obtained from Anopheles mosquitoes and reported in Xeno-Monitoring of Molecular Drivers of Artemisinin and Partner Drug Resistance in P. falciparum Populations in Malaria Vectors Across Cameroon, Gene, 2022 May 5; 821:146339. doi: 10.1016/ J.Gene.2022.146339 firstly the parasite infestations of these mosquitoes was very high and that a significant number of them carried parasites with gene mutations that have been associated with artemisinin resistance elsewhere.

Ataba E & al. develop a theory that popular use of herbal derivatives of Artemisia annua may result in the eventual loss of artemisisin-based drugs’ efficacy in Potential Emergence of Plasmodium Resistance to Artemisinin Induced by the Use of Artemisia annua for Malaria and COVID-19 Prevention in Sub-African Region, Acta Parasitol,  2022 Mar; 67(1):55-60.  doi: 10.1007/s11686-021-00489-y.  PubMed reports that a correction to this article was issued later in March by the same publication, but the nature of the Erratum is unclear.

New drug development

Mukherjee A & al.,  A Phosphoinositide-Binding Protein Acts in the Trafficking Pathway of Hemoglobin in the Malaria Parasite Plasmodium falciparum, mBio, 2022 Feb 15, 13(1):03239-21, doi: 10.1128/mbio03239-21 is a basic science paper, but it points in the direction of an approach that may lead to the development of a new category of antimalarials.  This is emphasized by the press release by Laval University (Montreal) , Discovery of Key Protein in Malaria Parasite Opens Door to Novel Treatment, 2022 Feb 18, https://medicalxpress.com/news/2022-02-discovery-key-protein-malaria-parasite.html, which quotes the senior author of the above paper, Professor Dave Richard: “The protein we discovered, PfPX1, is involved in transporting hemoglobin to … digestive vacuoles…. When we deactivate PfPX1, we deprive the parasite of its main source of amino acids. … We could block the parasite’s PfPX1 protein from performing its functions. Since the protein isn’t present in humans, there would be a decreased risk of disrupting any important functions in the human body.”

Gujjari L & al., Current Challenges and Nanotechnology-Based Pharmaceutical Strategies for the Treatment and Control of Malaria, Parasite Epidemiol Control, 2022 Feb 16; 17:E00244. doi: 10.1016/ J.Parepi.2022.E00244 appears to be a somewhat speculative exposition of possible applications of nanotechnology to the development of new antimalarials, based on the abstract.

Natural and herbal medicinal products

Kingston DGI & Cassera MB, Antimalarial Natural Products, Prog Chem Org Nat Prod, 2022; 117:1-106. doi: 10.1007/978-3-030-89873-1_1 is a 100+ page historical review of the use of quinine and its derivatives, followed by “a discussion of synthetic antimalarial agents based on quinine’s structure. The volume then covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of other natural products with significant antiplasmodial activity, classified by compound type.”

Campaigns:

Cogswell I & al., Examining the Relationship Between Malaria Burden and Domestic Spending on Malaria in 106 Countries, 2000-2019, Lancet Glob Health, 2022 Mar; 10 Suppl 1:S28. doi: 10.1016/ S2214-109x(22)00157-7 is a financial analysis of various types of spending and malaria rates across the globe, using “panel regression methods to explore the relationship between malaria burden and domestic spending on malaria.” They conclude that as “countries succeed in reducing the malaria burden, prioritizing investments in malaria surveillance and prevention is paramount to strengthen health systems, prevent resurgence, and provide financial protection to people affected by malaria.”

“Under-five malaria in Nigeria is a leading cause of global child mortality, accounting for 95,000 annual child deaths. High out-of-pocket medical expenditure contributes to under-five malaria mortality by discouraging care-seeking and use of effective anti-malarials in the poorest households.” Dasgupta RR & al. examine how this situation may be improved in Addressing Child Health Inequity Through Case Management of Under-Five Malaria in Nigeria: An Extended Cost-Effectiveness Analysis, Malaria J, 2022 Mar 9, vol 21 art 81, malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04113-w. They recommend subsidies for access to healthcare and care itself, focused on those in the poorest segments of the population.

Runge M & al. describe “how mathematical modeling was used in mainland Tanzania to support the strategic revision that followed the mid-term review of the 2015–2020 national malaria strategic plan… intervention mixes included combinations of insecticide-treated bed nets (ITN), indoor residual spraying, larval source management, and intermittent preventive therapies for school children (IPTsc).” As described in Sub-National Tailoring of Malaria Interventions in Mainland Tanzania: Simulation of the Impact of Strata-Specific Intervention Combinations Using Modelling, Malaria J, 2022 Mar 17, vol 21 art 92, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04099-5, modeling “supported the choice of intervention per malaria risk strata by providing impact comparisons of various alternative intervention mixes to address specific questions relevant to the country.”

Ewnetu Y & Lemma W noted a drastic increase in cases of malaria in a previously moderate-risk area over 2019 to 2021.  As reported in Highland Malaria Transmission Dynamics in Space and Time Before Pre-elimination Era, Northwest Ethiopia, J Epidemiol Glob Health, 2022 Mar 27. doi: 10.1007/s44197-022-00034-8, they attribute the increase in “the interruption of residual insecticide application in Gondar Zuria district during the transition period …. Study on climate variability also indicated that the rainfall variability in different months might have also favored high malaria transmission in 2020 and 2021 compared to 2019.”  However, the abstract does not refer to the impact, if any, of the civil disturbance in Northern Ethiopia, even if that may be further to the East and North.

Fitchett JM & Swatton D-A, Exploring Public Awareness of the Current and Future Malaria Risk Zones in South Africa Under Climate Change: A Pilot Study, Int J Biometeorol, 2022 Feb; 66(2):301-311.  doi: 10.1007/S00484-020-02042-4 reports on the lack of public awareness of malaria risk and highlights the need for an educational campaign on the subject.

Epidemiology:

Chan K & al. conclude that “[i]rrigated rice-growing communities in sub-Saharan Africa are exposed to greater malaria risk, as well as more mosquitoes. As increasing rice production and eliminating malaria are two major development goals in Africa, there is an urgent need to improve methods for growing rice without producing mosquitoes.”  Their report is Malaria Transmission and Prevalence in Rice-Growing Versus Non-Rice-Growing Villages in Africa: A Systematic Review and Meta-Analysis, Lancet Planet Health, 2022 Mar; 6(3):E257-E269. doi: 10.1016/S2542-5196(21)00349-1.

“Certain host genetic factors are known to influence symptomatic malaria; however, not much is known about how host genetics influences the acquisition of asymptomatic malaria, state Fugtagbi G & al. in Association of TNF-Alpha, MBL2, NOS2, and G6PD with Malaria Outcomes in People in Southern Ghana, Genet Res (Camb), 2022 Feb 28; 2022:6686406. doi: 10.1155/2022/6686406.  They found that “[i]ndividuals in Southern Ghana carrying the TNF-α 308 GA genotype are more likely to exhibit symptoms of malaria when infected with the malaria parasite as opposed to harboring an asymptomatic infection. Also, the B allele of the G6PD gene is likely to prevent a P. falciparum-infected person from exhibiting symptoms and thereby promote asymptomatic parasite carriage.”

A study was conducted from February to March 2020 among 210 febrile patients by Negatu GA & al. As reported in Prevalence of Malaria and Associated Factors Among Malaria-Suspected Patients Attending Hamusit Health Center, Northwest Ethiopia: A Cross-Sectional Study, J Parasitol Res, 2022 Mar 22; 2022:1306049. doi: 10.1155/2022/1306049, they found that “Plasmodium falciparum and P. vivax monoinfections were detected in 41 (19.5%) and 10 (4.8%) participants, respectively. Mixed infection was detected in 10 (4.8%) participants. Female participants … and those having family members with history of malaria … had higher odds of acquiring Plasmodium infection … Using insecticide-treated bed net and draining stagnant water were the most commonly mentioned malaria prevention measures reported by 71.9% and 8.1% of the respondents, respectively.”

Hassen J & Dinka H, Magnitude of Urban Malaria and Its Associated Risk Factors: the Case of Batu Town, Oromia Regional State, Ethiopia, J Int Med Res, 2022 Mar; 50(3):3000605221080686. doi: 10.1177/03000605221080686: “This health-facility based prospective cross-sectional study enrolled 356 febrile malaria patients to assess risk factors associated with malaria infection. An overall positivity rate of 17.13% (61/356) for malaria infection was observed. Among the malaria-positive patients, 50.8% (31/61) of them were positive for Plasmodium vivax, 45.90% (28/61) were positive for Plasmodium falciparum, and 3.3% (2/61) had mixed infections of P. falciparum and P. vivax.” As expected, those “who possessed insecticide-treated net … and whose houses were sprayed with insecticides … were significantly less likely to have a malaria infection. Individuals living closer to stagnant water had a significantly greater chance of malaria infection than those who lived a distance from stagnant water.”

Another non-falciparum cause of malaria is Plasmodium ovale. Tarimo BB & al. conclude in Seasonality and Transmissibility of Plasmodium ovale in Bagamoyo District, Tanzania, Parasit Vectors, 2022 Feb 14; 15(1):56. doi: 10.1186/S13071-022-05181-2 , that “Plasmodium ovale is circulating at 4-15% prevalence among asymptomatic individuals in coastal Tanzania, largely invisible to field diagnostics.” Specifically, “surveillance of asymptomatic individuals revealed a P. ovale prevalence of 11% …, compared to 29% … for P. falciparum. Prevalence for P. ovale was highest at the beginning of the long rainy season (15.5%, …) in contrast to P. falciparum, which peaked later in both the long and short rainy seasons. Considering that these early-season P. ovale infections were low-density mono-infections …, [the authors] speculate [that] many were due to hypnozoite-induced relapse.”

Holzschuh A & Koepfli C investigated the accuracy of malaria surveillance data, depending on the methods used.  As reported in Tenfold Difference in DNA Recovery Rate: Systematic Comparison of Whole Blood vs. Dried Blood Spot Sample Collection for Malaria Molecular Surveillance, Malaria J, 2022 Mar 15, vol 21 art 88, malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04122-9, they found that whole blood as a source was significantly more effective in yielding parasite DNA, but even using whole blood, the method of extracting DNA made a significant difference.  These results may call into question many published population-based surveillance data.

Ibadin MO & Eghafona N report that malaria parasites were found more frequently in children treated for HIV than in non-HIV apparently healthy children, They report thiir findings in Evaluation of Asymptomatic Malaria Antigenaemia and Parasitaemia in Human Immunodeficiency Virus-Infected Children in Benin City, Nigeria, West Afr J Med, 2022 Jan 31;39(1):45-51.

Mitchell CL  al. studied the extent to which environmental and land cover risk factors for malaria may influence malaria transmission intensity and concluded in Evaluating Malaria Prevalence and Land Cover Across Varying Transmission Intensity in Tanzania Using a Cross-Sectional Survey of School-Aged Children, Malaria J, 2022 Mar 9, vol 21 art 80, https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-022-04107-8, that “greater cropland cover was positively associated with increased malaria prevalence in areas with low transmission intensity and presents an actionable target for environmental vector control interventions to complement current malaria control activities.”

Shah HA & al. also report in Exploring Agricultural Land-Use and Childhood Malaria Associations in Sub-Saharan Africa, Sci Rep, 2022 Mar 8; 12(1):4124. doi: 10.1038/s41598-022-07837-6 that “rainfed cropland was associated with increased malaria in rural … but not urban areas, while irrigated or post-flooding cropland was associated with malaria in urban … but not rural areas.”

Another potential risk factor for malaria is ethnicity. In the article Do Socio-Demographic Factors Modify the Effect of Weather on Malaria in Kanungu District, Uganda?, Malaria J, vol 21 art 98. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04118-5 Ort K & al. explore this factor in a geographic area of ethnic diversity.  They found that Batwa (pygmy) children had twice the hospital admission rate for malaria as compared to similarly situated Bakiga children.

Takarinda KP & al. investigated the risk factors behind an outbreak of malaria in a refugee camp and reported results in Factors Associated with a Malaria Outbreak at Tongogara Refugee Camp in Chipinge District, Zimbabwe, 2021: A Case–Control Study, Malaria J, 2022 Mar 19, vol 21 art 94, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-022-04106-9. “Malaria cases were distributed throughout the 10 residential sections … Despite constituting 11% of the total population, Mozambican nationals accounted for 45% cases. Males constituted 59% among cases which was comparable to controls …(54%) … Several natural and man-made potential vector breeding sites were observed around the camp. Risk factors associated with contracting malaria were engaging in outdoor activities at night …, wearing clothes that do not cover the whole body during outdoor activities …, while residing in a refugee housing unit reduced the risk of contracting malaria …”

Roe MS & al., look at populations in which spontaneous falciparum malaria clearance in the absence of treatment is reported and state that “understanding of the phenomenon of spontaneous clearance will advance our knowledge of malaria epidemiology, transmission potential of malaria parasites, as well as inform interventions for malaria control and elimination” in Can Malaria Parasites Be Spontaneously Cleared? Trends Parasitol, 2022 Mar 4; S1471-4922(22)00035-6.  Doi: 10.1016/J.Pt.2022.02.005.

Although not strictly related to the epidemiology of malaria as such, Garrison A & al.’s article, The Effects of Malaria in Pregnancy on Neurocognitive Development in Children at 1 and 6 Years of Age in Benin: A Prospective Mother-Child Cohort, Clin Infect Dis, 2022 Mar 9; 74(5):766-775.  doi: 10.1093/ cid/ciab569 contributes significantly to the epidemiology of impaired childhood development as a result of maternal malaria during pregnancy.