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

The WHO World Malaria Report 2022, a 300+ page document appeared in December.  Its 18-page summary, the World Malaria Report at a Glance is included as an Appendix to this report, because it will be of great value to all who have not already read it by now.  Otherwise, publications took a very slight downturn in numbers over the holidays but have already rebounded in the new year.  Prevention was overwhelmingly the most studied aspect of malaria control this month.

Prevention

Vaccines

Silal SP, Seasonal Targeting of the RTS,S/AS01 Vaccine: A Complementary Tool But Sustained Funding Is Required, Lancet Global Health, 2022 Dec, 10:e1693-94, refers to an article reported last month (Thompson HA & al.) and states that “[p]hase 3b clinical trials in Mali and Burkina Faso showed that seasonally targeted vaccination was noninferior to seasonal malaria chemoprevention (SMC) at reducing clinical disease in children aged 5–17 months for 3 years following vaccination…” The author also states that it is “more important than ever that funding for vaccination, vaccine development, and supporting malaria interventions be sustained to realise the full value of vaccination.”

Parums DV, Editorial: Current Status of Two Adjuvanted Malaria Vaccines and the World Health Organization (WHO) Strategy to Eradicate Malaria by 2030, Med Sci Monit. 2023 Jan 1; 29:e939357. https://tinyurl.com/ms66kk4u  “aims to give an update on recent findings from key clinical trials on the safety and efficacy of RTS,S/ASO1 and R21/MM malaria vaccines and to provide an insight into the importance of key ongoing clinical trials that will report in early 2023.”

Another avenue of malaria vaccine development is highlighted in Sirima SB & al., A Randomized Controlled Trial Showing Safety and Efficacy of a Whole Sporozoite Vaccine Against Endemic Malaria, Sci Transl Med. 2022 Dec 7; 14(674):eabj3776, doi: 10.1126/scitranslmed.abj3776. Apparently, this method of immunization consists of a controlled infection, treated with artesunate monotherapy.  The authors state that after a trial in Mali, their trial in Burkina Faso also “demonstrated safety and efficacy against malaria infection in malaria-experienced adults.”

Vector control and protection from vectors

Babalola S & al. describe “sociodemographic, psychosocial, and household factors associated with consistent” insecticide treated net (ITN) use in Cameroon, Côte d’Ivoire and Sierra Leone in Ideational Factors Associated with Consistent Use of Insecticide-Treated Nets: A Multi-Country, Multilevel Analysis, Malaria J, 2022 Dec 6, vol 21 art 374, doi: 10.1186/s12936-022-04384-3.  Consistency of use in the three countries varied between 65% and 77%.  “Household net sufficiency was strongly and positively associated with consistent use in all three countries.” Less consistent factors included the perception of ITN use as a community norm and perceived vulnerability to malaria.

“Since 2013, the National Malaria Control Programme in mainland Tanzania and the Zanzibar Malaria Elimination Programme have implemented mass insecticide-treated net (ITN) distribution campaigns, routine ITN distribution to pregnant women and infants, and continuous distribution through primary schools (mainland) and community leaders (Zanzibar) to further malaria control efforts. Mass campaigns are triggered when ITN access falls below 40%.” Koenker H & al., Estimating Population ITN Access at Council Level in Tanzania, Malaria J, 2023 Jan 5, 22:4, doi: 10.1186/s12936-022-04432-y found that in “regions with the same ITN strategy for all councils, predicted council-level ITN access was consistent with regional-level survey data for 79% of councils. Regions where ITN strategy varied by council had regional estimates of ITN access that diverged from the council-specific estimates. Predicted ITN access reached 60% only when “nets issued as a percentage of the council population” (NPP) exceeded 15% and approached 80% ITN access when NPP was at or above 20%.”

Worges M & al., Estimation of Bed Net Coverage Indicators in Tanzania Using Mobile Phone Surveys: A Comparison of Sampling Approaches, Malaria J, 2022 Dec 10, vol 21 art 379, doi: 10.1186/s12936-022-04408-y is focused on sampling approaches, but found consistently that the availability of bed nets varied greatly among regions in the country, with Dodoma, the administrative capital, showing the highest utilization.

Yukich JO & al. conducted a household survey “as part of a planned randomized controlled trial in Magoe District, Mozambique… 1667 mother–child dyads were interviewed” and the results reported in Ideational Factors and Their Association with Insecticide Treated Net Use in Magoe District, Mozambique, Malaria J, 2022 Dec 17, vol 21 art 387, doi: 10.1186/s12936-022-04405-1. Based on the abstract, the results seemed to indicate the unexpected result that mothers’ perceived belief in the efficacy of bed nets was negatively associated with bed net use by their children.

Budu E & al. assessed “the inequalities in insecticide-treated nets use by pregnant women in Ghana… The analyses indicated a rise in pregnant women’s insecticide-treated nets use from 32.6% in 2011 to 49.7% in 2017. Except sub-national region, all the [predetermined] factors showed mild inequality in insecticide-treated nets use.”  However, there was marked inequality in regional terms.  The article is , Inequalities in the Use of Insecticide-Treated Nets By Pregnant Women in Ghana, 2011 and 2017, Malaria J, 2022 Dec 9, vol 21 art 376, doi: 10.1186/s12936-022-04388-z.

The effectiveness of bed nets is the subject of Koinari M & al., WHO Cone Bioassay Boards with or Without Holes: Relevance for Bioassay Outcomes in Long-Lasting Insecticidal Net Studies, Malaria J, 2022 Dec 19, vol 21 art 389, doi: 10.1186/s12936-022-04412-2. Tha authors report that “[a]necdotal evidence suggests that bioassay boards with holes behind the LLIN samples lead to greater exposure to insecticide, as the mosquitoes are ‘forced to stand on the net material’. This may increase the key assay outcomes of 60 min knockdown (KD60) and 24h mortality (M24).” They conclude this is a valid concern.

Insecticides play a key role in rural farming; however, their over- or misuse has been linked with a negative impact on malaria vector control policies. Kouamé RMA & al.’s study, Education and Socio-Economic Status Are Key Factors Influencing Use of Insecticides and Malaria Knowledge in Rural Farmers in Southern Côte d’Ivoire, BMC Public Health. 2022 Dec 28;22(1):2443, doi: 10.1186/s12889-022-14446-5, was “conducted amongst agricultural communities in Southern Côte d’Ivoire to identify which insecticides are used by local farmers and how it relates to the perception of farmers on malaria… A questionnaire was administered to 1399 farming households across ten villages” with results that indicated that educational level of farmers was significantly associated with their socioeconomic status and “[i]ndoor application of pyrethroid insecticides was … widespread among farmers as well as the use of such insecticide for crops protection.”

The provision of aid, monetary or other, to a population is always subject to possible diversion or misuse. That is the subject of Gutiérrez-Jara JP & al., Collateral Effects of Insecticide-Treated Nets on Human and Environmental Safety in an Epidemiological Model for Malaria with Human Risk Perception, Int J Environ Res Public Health. 2022 Dec 6; 19(23):16327, doi: 10.3390/ijerph192316327. The authors relay “concerns about improper handling and misuse of nets, producing possible health effects from intoxication and collateral environmental damage. The latter is caused, for instance, from artisanal fishing. [They] formulate a model … to describe the interplay between malaria dynamics, human intoxication, and ecosystem damage; affected by human awareness to these risks and levels of net usage. Our results show that an increase in mosquito net coverage reduces malaria prevalence and increases human intoxications.” The abstract is silent on the benefits versus potential harm.

“Despite the scale-up of insecticide-treated nets and indoor residual spraying, the bulk of malaria transmission in western Kenya still occurs indoors, late at night. House improvement is a potential long-term solution to further reduce malaria transmission in the region.” Abong’o B & al. evaluated the “impact of eave screening on mosquito densities” in two rural villages in western Kenya and conclude in Screening Eaves of Houses Reduces Indoor Mosquito Density in Rural, Western Kenya, Malaria J, 2022 Dec 9, vol 21 art 377, doi: 10.1186/s12936-022-04397-y that “ [s]imple house modification by eave screening has the potential to reduce the indoor occurrence of both Anopheles and Culex mosquito species. Community acceptance was very high…”

Seyoum TF & al. “aimed to assess ITN use and associated factors among households having under-five children in East Africa.” They report in Insecticide-Treated Bed Net Use and Associated Factors Among Households Having Under-Five Children in East Africa: A Multilevel Binary Logistic Regression Analysis, Malaria J, 2023 Jan 7, 22:10, doi: 10.1186/s12936-022-04416-y that “the proportion of ITN use among households having under-five children in East Africa was 46.32% …, ranging from 11.8% in Zimbabwe to 70.03% in Rwanda. In the … analysis, being in the age group 25–34 years, married, widowed, and divorced, primary and post-primary education, wealthy households, having a lower household size, many under-five children, having media exposure, and male-headed households were associated with higher odds of ITN use. Moreover, respondents from a rural place of residence, communities with a higher level of media exposure, communities with lower poverty levels, and communities with higher education levels had higher odds of ITN use.” Some of these findings seem internally contradictory.

Perhaps it is well known to everyone but this reporter, but collecting mosquitoes by using human volunteers to be bitten is the subject Eckert J & al., Which Trap Is Best? Alternatives to Outdoor Human Landing Catches for Malaria Vector Surveillance: A Meta-Analysis, Malaria J, 2022 Dec 9, vol 21 art 379, doi: 10.1186/s12936-022-04332-1.  The article is not encouraging in finding reliable alternatives to this practice.

“Human landing catches (HLCs) are considered the gold standard for collecting malaria vectors. However, HLCs are labour intensive, can expose collectors to transmission risk, and are difficult to implement at scale.” Mawejje HD & al. “compared alternative methods to HLCs for collecting Anopheles mosquitoes in eastern Uganda.” They report in Impact of Different Mosquito Collection Methods on Indicators of Anopheles Malaria Vectors in Uganda, Malaria J, 2022 Dec 19, vol 21 art 388, doi: 10.1186/s12936-022-04413-1 that collecting mosquitoes “indoors with prokopack aspirators, and outdoors with pit traps” gave variable results and were probably not to be relied upon.

Mawejje HD is also the first author (among many) of Characterizing Pyrethroid Resistance and Mechanisms in Anopheles gambiae (s.s.) and Anopheles arabiensis from 11 Districts in Uganda, Curr Res Parasitol Vector Borne Dis, 2022 Dec 10; 3:100106, doi: 10.1016/j.crpvbd.2022.100106. They report that “[r]esistance to pyrethroids was widespread and higher in An. gambiae (s.s.) [than in An. arabiensis.] … Addition of [piperonyl butoxide] to pyrethroids increased mortality [of the vectors]…”

Soumalia H & al. tested the susceptibility of Anopheles gambiae mosquitoes raised from collected larvae to chlorfenapyr and pyrethroid insecticides used in ITNs and IRS and report in Countrywide Insecticide Resistance Monitoring and First Report of the Presence of the L1014S Knock Down Resistance in Niger, West Africa, Malaria J, 2022 Dec 16, vol 21 art 385, doi: 10.1186/s12936-022-04410-4 that there was virtually consistent resistance to pyrethroids, but not to chlorfenapyr.  The addition of piperonyl butoxide enhanced susceptibility to all insecticides tested.

“Tororo District, in Eastern Uganda, experienced a dramatic decline in malaria burden starting in 2014 following the implementation of indoor residual spraying of insecticide (IRS) in the setting of repeated long-lasting insecticide treated nets (LLINs) distribution campaigns. However, in 2020 malaria began to resurge in Tororo following a change in the active ingredient used for IRS.” Nankabirwa JI & al.’s paper, Measures of Malaria Transmission, Infection, and Disease in an Area Bordering Two Districts with and Without Sustained Indoor Residual Spraying of Insecticide in Uganda, PLoS One. 2022 Dec 30; 17(12):e0279464, doi: 10.1371/journal.pone.0279464 reports that while mosquito biting was most prevalent in the sub-region where IRS had never been implemented, the ratio of infected mosquitoes was the same in all regions studied and the incidence of malaria was highest in a region that had IRS implemented regularly.  According to the authors, this reflects a “complex relationships between measures of malaria transmission, infection, and disease…”

One of many articles reporting on the use of ivermectin for vector control is Eba K & al., Effect of Ivermectin^® on Survivorship and Fertility of Anopheles arabiensis in Ethiopia: an in vitro Study, Malaria J, 2023 Jan 9; 22:12, doi: 10.1186/s12936-023-04440-6.  On the basis of a study of feeding moquitoes on cattle blood plus invermectin, they conclude that “ivermectin application in cattle could be used as a supplementary vector control method to tackle residual malaria transmission and ultimately achieve malaria elimination in Ethiopia.”

“Anopheles stephensi sets itself apart from other malaria vectors due to its ability to efficiently transmit malaria in urban areas. Thus, the invasion and establishment of An. stephensi poses a substantial threat to malaria control efforts, particularly in the rapidly urbanising Sub-Saharan African region.”  The Anopheles stephensi Deep Dive Synthesis Report from MESA (mesa@isglobal.org), no author identified, “is a description of the status quo vis-a-vis funding, research goals and participating institutions. It concludes with an expert opinion which ties everything together.” https://media.malariaworld.org/Anopheles_stephensi_Deep_Dive_synthesis_report_56a1aa75b3.pdf

Singh OP & al., Molecular Tools for Early Detection of Invasive Malaria Vector Anopheles stephensi Mosquitoes, Emerg Infect Dis. 2023 Jan; 29(1):36-44. https://tinyurl.com/ycychm6e comments on the difficulty of distinguishing among species of Anopheles and proposes a molecular tool specific to An. stephensi.

A study of vector epidemiology, Bedasso AH &al., Malaria Vector Feeding, Peak Biting Time and Resting Place Preference Behaviors in Line with Indoor Based Intervention Tools and Its Implication: Scenario from Selected Sentinel Sites of Ethiopia, Heliyon. 2022 Dec 8; 8(12):e12178, doi: 10.1016/j.heliyon.2022.e12178. reports that “[e]ntomological investigations were conducted in three sentinel sites for five consecutive months during the major malaria transmission season. The species composition, population dynamics, biting and resting behaviours of malaria vectors were determined … 43.3% of An. gambiae s.l. (primary vector) were collected between 18:00 and 22:00 h. Biting activity declined between 00:00 and 02:00 h.”

Agyemang-Badu & al. conducted an “exploratory qualitative study aimed to assess the prospects of environmental management and sanitation (EMS) as a malaria vector control strategy.”  This was supplemented by focus group meetings structured around specific research questions.  They report in Environmental Management and Sanitation as a Malaria Vector Control Strategy: A Qualitative Cross-Sectional Study Among Stakeholders, Sunyani Municipality, Ghana, Environ Health Insights, 2023 Jan 3; 17:11786302221146890, doi: 10.1177/11786302221146890 that the “prospects of environmental management and sanitation (EMS) as a vector control strategy, look promisingly very high, pertinent, and workable and a likelihood game changer of winning the fight against malaria due to the residual transmission that is happening outdoors.” However, they also identify multiple real and potential barriers to implementation.

Chemoprophylaxis

“To fight against malaria infection in pregnancy, Kenya integrated the issuance of an insecticide-treated net (ITN) and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) with antenatal care (ANC) for pregnant women.” Mkubwa B & al., Determinants of Utilization of Malaria Preventive Measures During Pregnancy Among Women Aged 15 To 49 Years in Kenya: An Analysis of the Malaria Indicator Survey 2020, Malaria J, 2022 Dec 29, vol 21 art 398, doi: 10.1186/s12936-022-04425-x reports that “uptake of malaria preventive measures is still below 80% for both ITN and IPTp-SP during pregnancy in Kenya” and suggest ways to improve on this situation.

A study by Peters GO & Naidoo M, Factors Influencing Intermittent Preventive Treatment for Malaria Prevention Among Pregnant Women Accessing Antenatal Care in Selected Primary Health Care Facilities of Bwari Area Council, Abuja, Nigeria, PLoS One. 2022 Dec 15;17(12):e0277877, doi: 10.1371/journal.pone.0277877 found that among 422 pregnant women interviewed, [m]ost respondents (68.5%) did not know who could take IPTp-SP and 58.5% of respondents did not know when and how many times IPTp-SP should be taken during pregnancy. Nearly all participants (99.5%) did not take SP at the facility under direct observation of the health worker. … The knowledge of the use of SP was significantly influenced by respondents’ parity, ward of residence, antenatal clinic (ANC) attendance history and education…”

Chemoprophylaxis in pregnancy is an effective way of reducing malaria burden on a population.  Therefore, it is of concern that Cohen O & al., Effect of Sulfadoxine-Pyrimethamine Chemoprophylaxis in Pregnant Women on Selection of the New P. falciparum dhps Quintuple Mutant Carrying the I431V Mutation, J Antimicrob Chemother, 2023 Jan 6; dkac432, doi: 10.1093/jac/dkac432 reports the occurrence of resistance to the IPTp-SP regimen.  This article could be cited under drug resistance.

Bakai TA & al., Effectiveness of Seasonal Malaria Chemoprevention {SMC} in Three Regions of Togo: A Population-Based Longitudinal Study from 2013 to 2020, Malaria J, 2022 Dec 31, vol 21 art 400, doi: 10.1186/s12936-022-04434-w describes the results of using four rounds over four months of SMC with one dose of sulfadoxine-pyrimethamine (SP) and three daily doses of amodiaquine (AQ).  “The overall coverage was 98% (7,971,877 doses for 8,129,668 children). Contraindication was the main reason for non-administration. Over the study period, confirmed malaria cases decreased from 11,269 (1st round of 2016) to 1395 (4th round of 2020).” The prevalence of adverse reactions was 3/10,000.

“Seasonal malaria chemoprevention (SMC) consists of the intermittent administration of a 3-day course of anti-malarial medications during the months of highest malaria risk in the Sahel region, where malaria transmission is highly seasonal.” Koko DC & al., Analysis of Attitudes and Practices Influencing Adherence to Seasonal Malaria Chemoprevention in Children Under 5 Years of Age in the Dosso Region of Niger, Malaria J, 2022 Dec 6, vol 21 art 375, doi: 0.1186/s12936-022-04407-z concludes that “coverage of SMC and adherence by caregivers to completing the full 3 day medication course was high. The survey also showed that knowledge, attitudes, and practices of some caregivers regarding adherence to medications during the SMC campaign could be improved. Expanding distributors’ training, developing and providing them with tools for interpersonal communication, and strengthening supervision could lead to even higher adherence.”

Intermittent chemoprevention is practiced in regions other than the Sahel as well. However, as described by Makenga G & al. in Implementation Research of a Cluster Randomized Trial Evaluating the Implementation and Effectiveness of Intermittent Preventive Treatment for Malaria Using Dihydroartemisinin-Piperaquine [DP]on Reducing Malaria Burden in School-Aged Children in Tanzania: Methodology, Challenges, and Mitigation, Malaria J, 2023 Jan 6, 22:7, doi: 10.1186/s12936-022-04428-8, the timing is different in that “DP was given to schoolchildren three times a year in four-month intervals.” The abstract is focused on feasibility of implementation, rather than results of this practice.

Other

An interesting potential method of reducing the prevalence of malaria is the topic of Hamelman NM & al., Single-Chain Polymer Nanoparticles Targeting the Ookinete Stage of Malaria Parasites, ACS Infect Dis, 2022 Dec; doi: 10.1021/acsinfecdis.2c00336.   The authors describe the use of “single-chain polymer nanoparticles (SCNPs) to target the parasite at the ookinete stage, which is one of the stages in the mosquito. This nanocarrier system provides uniquely sized and monodispersed particles of 5–20 nm, via thiol-Michael addition. … The biodistribution of SCNPs in mosquitos was studied, showing the presence of SCNPs in mosquito midguts. The presented results demonstrate the potential of anionic SCNPs for the targeting of malaria parasites in mosquitos and may lead to progress in the fight against malaria.”

Diagnosis

General diagnostics

Aqeel S & al., Towards Digital Diagnosis of Malaria: How Far Have We Reached [sic], J Microbiol Methods. 2022 Nov 28; 204:106630, doi: 10.1016/j.mimet.2022.106630 “highlights the progression, strengths, and limitations of various computing techniques so far employed to diagnose malaria” in a hospital setting.

Dong L, Li W, Xu Q & al. “aimed to establish a new multiplex dPCR detection system for four main Plasmodium species: P. vivax, P. falciparum, P. ovale and P. malariae, which can distinguish exact species of malaria by one PCR reaction” and report success in A Rapid Multiplex Assay of Human Malaria Parasites by Digital PCR, Clin Chim Acta. 2022 Dec 7: S0009-8981(22)01403-6, doi: 10.1016/j.cca.2022.12.001, claiming sensitivity of 98.0% and a specificity of 100% in clinical samples…” They also conclude that the method described “is suitable for mixed-infection diagnosis and multi-sample continuous monitoring and presents a promising candidate as an absolute quantitative tool in clinical practice.”

Yon JLT & al. searched “[r]elevant studies that assessed the diagnostic performance of LAMP for the detection of malaria in pregnancy … in health-related electronic databases.” The article, Loop-Mediated Isothermal Amplification (LAMP) Test in The Detection of Uncomplicated Malaria in Pregnancy: A Meta-Analysis of Diagnostic Accuracy, Malaria J, 2022 Dec 22, vol 21 art 391, doi: 10.1186/s12936-022-04419-9 states that “the findings suggest that LAMP is more sensitive than traditional tests used at facilities, … Due to the limited number of studies with bias in their methodological quality, variation in the study design, and different types of reference tests further research is likely to change the estimate.”  In other words, the authors were not impressed by the quality of some of articles reviewed.

Field diagnostics

Aghaba BB & al. tested 288 children aged 2–15 years “for the presence of malaria parasites using rapid diagnostic tests (RDTs) and blood smear microscopy between January to May 2022.”  They report in Asymptomatic Malaria Infection, Associated Factors and Accuracy of Diagnostic Tests in a Historically High Transmission Setting in Northern Uganda, Malaria J, 2022 Dec 26, vol 21 art 392, doi: 10.1186/s12936-022-04421-1 that “the prevalence of asymptomatic infection was 34.7% … with the highest observed in children 5–10 years 45.9% … Plasmodium falciparum was the dominant parasite species however the presence of P. malariae and Plasmodium ovale was observed, which may have implication for the choice and deployment of diagnostic tools. Individuals who slept under mosquito net or had presence of functional [village health teams] were less likely to have asymptomatic malaria…”

New diagnostic methods

None this month

Treatment

Treatment results

In a hospital setting, Gubae K & al. studied 88 patients, of whom 69 completed the course of treatment with arthemeter-lumefantrine.  They report 98% success rate by “outcome classification … in accordance with the 2009 WHO methods for surveillance of anti-malarial drug efficacy guidelines.” No serious adverse events were reported.  The article is Safety and Therapeutic Efficacy of Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium falciparum Malaria at Shecha Health Centre, Arba Minch, Ethiopia, Malaria J, 2023 Jan 7, 22:9, doi: 10.1186/s12936-022-04436-8.

Fukuda N & al. argue in The Impact of Sequestration on Artemisinin-Induced Parasite Clearance in Plasmodium falciparum Malaria in Africa, Clin Infect Dis. 2022 Dec 15:ciac944, doi: 10.1093/cid/ciac944 that measures of effectiveness of artemisinin treatment may be hampered by the propensity of parasites to be “sequestered to the endothelium {lining of blood vessels} and undetectable in the peripheral blood” under some conditions.  Their method of estimating sequestration was dependent on histidine-rich protein concentrations.  If the conclusions are correct, “intensive sequestration delays parasite clearance after treatment, which may contribute to reduced artemisinin efficacy.”

Funwei RI & al. analyzed 120 dried blood spots from days 3 and 14 after initiation of animalarial therapy and report in High Prevalence of Persistent Residual Parasitemia on Days 3 and 14 After Artemether-Lumefantrine or Pyronaridine-Artesunate Treatment of Uncomplicated Plasmodium falciparum Malaria in Nigeria, Parasitol Res. 2022 Dec 13, doi: 10.1007/s00436-022-07753-8 that even after 14 days, residual parasitemia was evident in a large percentage of cases, especially after the former drug combination.  Their explanation differs from that of Fukuda & al.

Mohammed H & al. treated 51 adult patients with Plasmodium vivax infection and report in Efficacy and Safety of Pyronaridine-Artesunate (Pyramax^®) for the Treatment of Uncomplicated Plasmodium vivax Malaria in Northwest Ethiopia, Malaria J, 2022 Dec 31, vol 21 art 401, doi: 10.1186/s12936-022-04422-0 that after three days of treatment, 95% of patients had “adequate clinical and parasitological response. … There were no serious adverse events.”

Tafenoquine has been shown to be effective in eliminating the P. vivax entity that is sequestered in the liver, thereby eliminating recurrent symptoms. Watson JA & al., The Clinical Pharmacology of Tafenoquine in the Radical Cure of Plasmodium vivax Malaria: An Individual Patient Data Meta-Analysis, Elife. 2022 Dec 6; 11:e83433. doi: 10.7554/elife.83433 concludes that “tafenoquine dose is the primary determinant of efficacy. [The authors] estimate the currently recommended 300 mg dose in a 60 kg adult (5mg/kg) results in 70% of the maximal obtainable … effect. Increasing the dose to 7.5 mg/kg (i.e. 450 mg) would result in 90% reduction in the risk of P. vivax recurrence. … Clinical trials of higher tafenoquine doses are needed to characterise their efficacy, safety and tolerability.”

Side effects and complications

The well-known vulnerability of patients with G6PDdeficiency to primaquine is the subject of Taylor WR & al., Safety of Age-Dosed, Single Low-Dose Primaquine in Children with Glucose-6-Phosphate Dehydrogenase Deficiency who are Infected with Plasmodium falciparum in Uganda and the Democratic Republic of the Congo: A Randomised, Double-Blind, Placebo-Controlled, Non-Inferiority Trial, Lancet Infect Dis. 2022 Nov 30: S1473-3099(22)00658-2, doi: 10.1016/s1473-3099(22)00658-2.  This was a very complex study of 1137 children with median age of 5, who had malaria.  About 25% of children were G6PD deficient.  Severe anemia occurred with equal, very low, frequency in both G6PD deficient and non-deficient children after a single dose of primaquine.  Based on these results, the authors conclude that this is a safe practice.

Drug resistance

None other than Cohen O & al. cited above

New drug research

Another artesunate, artefenomel, is the subject of Gansane A & al., Randomized, Open-Label, Phase 2a Study to Evaluate the Contribution of Artefenomel to the Clinical and Parasiticidal Activity of Artefenomel Plus Ferroquine in African Patients with Uncomlicated Plasmodium falciparum Malaria, Malaria J, 2023 Jan 3, 22:2, doi: 10.1186/s12936-022-04420-2.  Apparently, the addition of artefenomel to the compound ferroquine did not influence the effectiveness of the latter drug to significant extent.

Aly NSM & al., Formulation and Evaluation of the Antimalarial N-89 as a Transdermal Drug Candidate, Parasitol Int. 2022 Dec 11:102720, doi: 10.1016/j.parint.2022.102720 is a report on animal work with a new drug, as of yet unnamed.  The authors clam good results in mice and suggest that this drug in transdermal formulation is an “effective and safe alternative route for the treatment of malaria, especially in children.”

Plant extracts and traditional treatments

Tadege G & al., Antimalarial Activity of the Hydroalcoholic Crude Extract and Solvent Fractions of Commelina latifolia Hochst. ex C.B.Clarke (Commelinaceae) Leaves Against Plasmodium berghei in Mice, Heliyon. 2022 Dec 10; 8(12):e12045, doi: 10.1016/j.heliyon.2022.e12045 is a mouse-model study of the extract of a plant used in traditional medicine against malaria.  The plant is one of over 150 species of a genus prevalent throughout the world.  The authors conclude that the “oral dose of Commelina latifolia is safe, and reveals promising antimalarial activity. The findings backed up the utilization of the plant in traditional medicine to treat malaria” [at least in mice].

“Flavanones are a group of compounds that belong to the flavonoid family and are chemically obtained…[They are] isolated and characterized from diverse plant parts” according to Boniface PK & al., The Role of Flavanones as Scaffolds for the Development of New Treatments against Malaria and African and American Trypanosomiases, Mini Rev Med Chem. 2022 Dec 29, doi: 10.2174/1389557523666221229122543.  This article reflects the result of literature search of in vitro studies of these compounds’ effectiveness against multiple parasites.  The authors cite positive results and urge further research into flavanones.

Similar to the above in a way, Diao HM & al., Flavonoids from Scutellaria likiangensis Diels and their Antimalarial Activities, Fitoterapia. 2022 Nov 29:105357, doi: 10.1016/j.fitote.2022.105357 found one of 23 compounds extracted from the plant’s roots to have effectiveness in mice “close to artemisinin” as well as several other compounds exhibiting “moderate antimalarial activities.”  The plant is one of many varieties of flower commonly known as “skullcaps.”

Yet another plant-based extract is the subject of Obegi Matundura J & al., Antiplasmodial and Antimicrobial Activities of Ent-Abietane Diterpenoids from the Roots of Suregada zanzibariensis, Nat Prod Res. 2022 Dec 28:1-5, doi: 10.1080/14786419.2022.2158463.  One of the six compounds extracted (“mangiolide”) “showed strong in vitro antiplasmodial activity against chloroquine sensitive (D6) and resistant (W2) strains of Plasmodium falciparum.” The plant is an evergreen bush found in East Africa and Madagascar.  It has been the subject of previous reports in a similar vein.

Other

Rajwar TK & al., Opportunity in Nanomedicine to Counter the Challenges of Current Drug Delivery Approaches Used for the Treatment of Malaria; A Review, J Drug Target, 2023 Jan 5; 1-23, doi: 10.1080/1061186X.2022.2164290 is a review that “focuses on the numerous nanotherapeutic strategies utilized to treat malaria as well as the benefits of nanotechnology as a potentially effective therapeutic.”

Campaigns and Policies

Elmardi KA & al., Impact of Malaria Control Interventions on Malaria Infection and Anaemia in Low Malaria Transmission Settings: A Cross-Sectional Population-Based Study in Sudan, BMC Infect Dis. 2022 Dec 10; 22(1):927, doi: 10.1186/s12879-022-07926-x. “The study analysis involved 26,469 individuals over 242 clusters. Malaria infection rate was 7.6%, overall anaemia prevalence was 47.5% and moderate-to-severe anaemia prevalence was 4.5%. … There was strong evidence that utilization of malaria diagnosis at the community level was highly protective against malaria infection. No protective effect was seen for community utilization of ACTs or LLINs. …. This lack of effectiveness could be due to the low utilization of interventions or the low level of malaria transmission in the study area.”

WHO “recommended the Test, Treat and Track (T3) strategy for malaria control, that every suspected malaria case should be tested prior to treatment with Artemisinin-based combination therapy (ACT) and tracked.” Kweku M & al. “assessed the performance and challenges in the implementation of T3 strategy among children under-five years in Volta and Oti Regions of Ghana.” Assessment of the Performance and Challenges in the Implementation of the Test, Treat and Track (T3) Strategy for Malaria Control Among Children Under-Five Years in Ghana, PLoS One. 2022 Dec 7; 17(12):e0278602, doi:10.1371/journal.pone.0278602 is a report of a cross-sectional study in 69 health facilities. “Exit interviews were conducted for caregivers of children with fever…  Clinicians were interviewed at the out-patient department in each facility… Testing fever cases for malaria before treatment and treating positive cases with ACTs was high. Treating negative cases and those not tested with ACTs was also high. … Clinician’s [sic] not trusting RDT results can affect the T3 strategy in malaria control.”

Over the past two decades, a considerable expansion of malaria interventions has occurred at the national level in Angola, together with cross-border initiatives and regional efforts in southern Africa. Currently, Angola aims to consolidate malaria control and to accelerate the transition from control to pre-elimination, … However, the tremendous heterogeneity in malaria prevalence among Angolan provinces, as well as internal population movements and migration across borders, represent major challenges ….” Tavares M & al., Malaria in Angola: Recent Progress, Challenges and Future Opportunities Using Parasite Demography Studies, Malaria J, 2022 Dec 28, vol 21 art 396, doi: 10.1186/s12936-022-04424-y “aims to contribute to the understanding of factors underlying the complex malaria situation in Angola and to encourage future research studies on transmission dynamics and population structure of Plasmodium falciparum, important areas to complement host epidemiological information and to help reenergize the goal of malaria elimination in the country.”

Epidemiology

Climate change, biodiversity and environment

Liu Q & al. assert that Millions of Excess Cases and Thousands of Excess Deaths of Malaria Occurred Globally in 2020 During the COVID-19 Pandemic, J Glob Health. 2022 Dec 17; 12:05045, doi: 10.7189/jogh.12.05045.  Based on data from the World Health Organization Global Observatory, [the authors] used estimated annual percentage changes (EAPCs) from 2000 to 2019 (model A) and from 2015 to 2019 (model B) to predict the malaria burden in 2020… In 2020, African countries suffered the most from malaria, with the largest number of malaria cases (64.7 million) and deaths (151 thousand) observed in Nigeria… During the COVID-19 pandemic in 2020, there was a total of 18 million excess malaria cases and 83 291 excess deaths per model A, and 7.4 million excess cases and 33 528 excess deaths per model B globally.”

Aheto JMK utilized data from the 2019 Malaria Indicators Survey (MIS) of the Demographic and Health Survey Program of Ghana. His article, Mapping Under-Five Child Malaria Risk That Accounts for Environmental and Climatic Factors to Aid Malaria Preventive and Control Efforts in Ghana: Bayesian Geospatial and Interactive Web-Based Mapping Methods, Malaria J, 2022 Dec 15, vol 21 art 384, doi: 10.1186/s12936-022-04409-x reflects the very large variations depending on geography.

In Optimal Control of a Two-Group Malaria Transmission Model with Vaccination, Netw Model Anal Health Inform Bioinform. 2023;12(1):7, doi: 10.1007/s13721-022-00403-0, Tchoumi SY & al. assert that “[s]imulations results show that concurrently applying the three intervention measures, namely: personal protection, treatment, and vaccination of children under-five is the best strategy for fighting against malaria epidemic in a community, relative to using either single or any dual combination of intervention(s) at a time.”  However, the body of the abstract is beyond the understanding of this reviewer.

Gebreegziabher E & al. cite statistics in, The Association Between Malnutrition and Malaria Infection in Children Under 5 Years in Burkina Faso: A Longitudinal Study, Am J Trop Med Hyg, 2023 Jan 9; tpmd220573, doi: 10.4269/ajtmh.22-0573 that shed little, if any light on any purported association inherent in the title of the paper. 

Population dynamics

Difficulties in population surveys for malaria inherent in highly mobile societies is the topic covered in Das AM & al., The Impact of Reactive Case Detection on Malaria Transmission in Zanzibar in the Presence of Human Mobility, Epidemics. 2022 Dec; 41:100639, doi: 10.1016/j.epidem.2022.100639.  The authors assert that “in the absence of imported cases from mainland Tanzania, malaria would likely cease to persist on Zanzibar.”

In an article that was primarily obstetrical in focus, Abuku VG & al., Clinical and Laboratory Presentation of First-Time Antenatal Care Visits of Pregnant Women in Ghana, a Hospital-Based Study, PLoS One, 2023 Jan 4; 18(1):e0280031, doi: 10.1371/journal.pone.0280031 report an incidence of malaria at 2.4%.  This seems low in comparison to general population-based studies, but they may have studied a unique population. As an example, the article by Aheto cited above states that the overall predicted malaria prevalence in Ghana was 16.3% with an extremely wide spatial distribution of 0.7% to 51.4%.

Reddy V & al. “used estimates from the Malaria Atlas Project on the total population living in areas of P falciparum and P vivax transmission, combined with country-specific demographic data on women of reproductive age, fertility rates, induced abortions, and stillbirths, to derive the annual number of pregnancies overall, by parasite species.” Their paper, Global Estimates of the Number of Pregnancies at Risk of Malaria from 2007 to 2020: A Demographic Study, Lancet Glob Health. 2023 Jan; 11(1):e40-e47, doi: 10.1016/s2214-109x(22)00431-4, concludes that “[b]etween 2007 and 2020, substantial declines in the number of pregnancies at risk of malaria were seen globally. However, in AFRO {The African Region of WHO}, 25.4% more pregnancies were at risk of P falciparum or P vivax malaria than in 2007. This increase in the number at risk in AFRO comes despite the decline in malaria rates due to the rapidly rising population and the corresponding number of pregnancies in endemic areas.

Over the years there has been some controversy as to whether malaria predisposes children to endemic Burkitt’s lymphoma (eBL) {a tumor linked to and possibly caused by the Epstein Barr virus}. Broen K & al., Burkitt Lymphoma Risk Shows Geographic and Temporal Associations with Plasmodium falciparum Infections in Uganda, Tanzania, and Kenya, Proc Natl Acad Sci. 2023 Jan 10; 120(2):e2211055120, doi: 10.1073/pnas.2211055120 is a review of some of the “data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship.”  The authors conclude that there is “population-level evidence that eBL is a phenotype related to heavy lifetime exposure to P. falciparum malaria and support emphasizing the link between malaria and eBL.”  Apparently, the risk peaks among children aged 5 to 11 and declines thereafter.

Spatiotemporal studies

Kojom Foko LP & al. report extremely high prevalence (82.4%) of malaria parasitemia in the areas they studied in a small sample (119 patients), as reported in Non-Falciparum Species and Submicroscopic Infections in Three Epidemiological Malaria Facets in Cameroon, BMC Infect Dis. 2022 Dec 2; 22(1):900, doi: 10.1186/s12879-022-07901-6.  Of the number above, 12% were asymptomatic. Although most infections, including all asymptomatic ones, were caused by P. falciparum, P. ovale curtisi, and P. vivax were also found, but the latter only in co-infection with P. falciparum.

Other spatiotemporal studies this month were:

Azongnibo KRM & al., Spatiotemporal Analysis of Malaria Incidence in Côte d’Ivoire from 2015 to 2019, Trans R Soc Trop Med Hyg. 2022 Dec 6:trac112, doi: 10.1093/trstmh/trac112.

Djoufounna J & al., High Prevalence of Asymptomatic Plasmodium falciparum Malaria in Makenene, a Locality in the Forest-Savannah Transition Zone, Centre Region of Cameroon, Curr Res Parasitol Vector Borne Dis. 2022 Nov 28; 2:100104, doi: 10.1016/j.crpvbd.2022.100104.

Ilombe G & al., Malaria Among Children Under 10 Years in 4 Endemic Health Areas in Kisantu Health Zone: Epidemiology and Transmission, Malaria J, 2023 Jan 5, 22:3, doi: 10.1186/s12936-022-04415-z.

Tavares W & al., Malaria in Angola: Recent Progress, Challenges and Future Opportunities Using Parasite Demography Studies, Malaria J, 2022 Dec 28, vol 21 art 396, doi: 10.1186/s12936-022-04424-y.

Tiono AB & al., Hospital-Based Surveillance of Paediatric Malaria in Two Malaria Transmission Ecological Zones of Burkina Faso, Malaria J, 2023 Jan 6, 22:6, doi: 10.1186/s12936-022-04433-x.

Other

“Plasmodium malariae is a ‘neglected malaria parasite’ in as much as the amount of research conducted on it pales into insignificance when compared to that pertaining to Plasmodium falciparum and Plasmodium vivax, …. There has, however, been an increase in interest in this parasite over the past decade. Principally, this is because of the increasing use of … techniques that have revealed a wider than previously recorded prevalence in some regions (particularly in Africa), and high numbers of chronic, asymptomatic infections.” The article is Culleton R & al., Plasmodium malariae: The Persisting Mysteries of a Persistent Parasite, Trends Parasitol. 2022 Dec 12: S1471-4922(22)00281-1, doi: 10.1016/j.pt.2022.11.008.

The abstract of Davis L & al., The Value Added of Incorporating Qualitative Approaches into Malaria Surveillance, Monitoring, and Evaluation, Am J Trop Med Hyg. 2022 Dec 12:tpmd220191, doi: 10.4269/ajtmh.22-0191 does not reveal much about the article other than its title, but Table 2 of the article itself, “Summary of qualitative elements in SME-related tools” may be of interest.