December 2022 Science & Research Report

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

It may interest the readers that in late November, WHO issued its current Guidelines for the Treatment of Malaria 2022, which is a 400+ page document. In view of a recent implementation of seasonal preventive chemotherapy of children in Uganda, the sections dealing with chemoprevention are the following (51 pages):

4.2 Preventive chemotherapies
4.2.1 Intermittent preventive treatment of malaria in pregnancy (IPTp)
4.2.2 Perennial malaria chemoprevention (PMC) – formerly intermittent preventive treatment of malaria in infants (IPTi)
4.2.3 Seasonal malaria chemoprevention (SMC)
4.2.4 Intermittent preventive treatment of malaria in school-aged children (IPTsc)
4.2.5 Post-discharge malaria chemoprevention (PDMC)
4.2.6 Mass drug administration (MDA)

Other recent publications of interest are below:

Prevention:

Vaccines
Hayashi CTH & al. “evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP {Plasmodium falciparum circumsporozoite protein}, delivered as mRNA-LNP vaccines.” As they report in mRNA-LNP Expressing PfCSP and Pfs25 Vaccine Candidates Targeting Infection and Transmission of Plasmodium falciparum, NPJ Vaccines. 2022 Dec 1; 7(1):155, doi: 10.1038/s41541-022-00577-8, “[b]oth vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. Purified IgGs from Pfs25 mRNA-LNPs immunized mice were highly potent in reducing malaria transmission to mosquitoes.”
Another article emphasizing the importance of PfCSP in the development of immunity to the malaria parasite is Kucharska I & al., High-density Binding to Plasmodium falciparum Circumsporozoite Protein Repeats by Inhibitory Antibody Elicited in Mouse With Human Immunoglobulin Repertoire, PLoS Pathogens, 2022 Nov 28, doi: 10.1371/journal.ppat.1010999. The paper cites laboratory evidence.

Vaccines are useful only if the proposed recipient receives them. Sulaiman SK & al., A Systematic Review and Meta-Analysis of the Prevalence of Caregiver Acceptance of Malaria Vaccine for Under-Five Children in Low-Income and Middle-Income Countries (LMICs), PLoS One, 2022 Dec 1, 17(12):e0278224, doi: 10.1371/journal.pone.0278224 reports in a meta-analysis of 11 publications that in the three countries in which the RTS,S vaccine is being introduced, acceptance rates were 94.4% among others, with the lowest rate (in Tanzania) still above 92%.

Yeboah D & al., Predictors of Malaria Vaccine Uptake Among Children 6–24 Months in the Kassena Nankana Municipality in the Upper East Region of Ghana, Malaria J, 2022 Nov 16, vol 21 art 339, doi: 10.1186/s12936-022-04378-1 reports the following: “Malaria vaccine uptake was high among the study population in the municipality; however, dose four uptake coverage by age two was low. This indicates that mothers/caregivers did not understand the notion of immunization throughout the second year of life.” In fact, the first dose uptake was reported to be 94%; however, the dropoff seems to contradict the conclusion of the above paper.

Based on mathematical modeling, Thompson HA & al. found that “[s]easonally targeting RTS,S resulted in greater absolute reductions in malaria cases and deaths compared with an age-based strategy, averting an additional 14 000-47 000 cases per 100 000 children aged 5 years and younger over 15 years, dependent on seasonality and transmission intensity. [They] predicted that adding seasonally targeted RTS,S to SMC [seasonal malaria chemoprophylaxis] would reduce clinical incidence by up to an additional 42 000-67 000 cases per 100 000 children aged 5 years and younger over 15 years compared with SMC alone.” The article is Seasonal Use Case for the RTS,S/AS01 Malaria Vaccine: a Mathematical Modelling Study, Lancet Glob Health. 2022 Dec; 10(12):e1782-e1792. doi: 10.1016/s2214-109x(22)00416-8.

Beeson JG & al., The RTS,S Malaria Vaccine: Current Impact and Foundation for the Future, Sci. Transl. Med., 16 Nov 2022, Vol 14, Issue 671, doi: 10.1126/scitranslmed.abo6646 is an article with a very short and unrevealing abstract.

Kateta MW, Is the First Malaria Vaccine Worth the Cost?, Devex, 2022 Nov 17, https://www.devex.com/news/is-the-first-malaria-vaccine-worth-the-cost-104287 reports that there is no universal agreement that the RTS,S vaccine rollout currently in process, is worth the cost, given the imperfect protection it provides.

Not directly related to vaccines, but potentially so is the news that Plasmodium falciparum sporozoites can now be prepared in vitro. Eappen AG, Li T et al. report in In vitro Production of Infectious Plasmodium falciparum {PfSPZ} Sporozoites, Nature, 2022 Dec 7, doi: 10.1038/s41586-022-05466-7 that “[t]he ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research…” and claim that they have accomplished that, using mice with “humanized livers.”

Vector control and protection from vectors
Akello AR & al. studied the use of bed nets by families with small children and published the results in Factors Influencing Consistent Use of Bed Nets for the Control of Malaria Among Children Under 5 Years in Soroti District, North Eastern Uganda, Malaria J, 2022 Dec 2, vol 21, art 363, doi: 10.1186/s12936-022-04396-z. In the 400 households studied, only “56.8% of the 690 children under 5 years used bed nets consistently. The factors affecting consistent bed net use were age of the child, their use of bed nets the previous night, occupation of caretaker, respondents’ perceived susceptibility, perceived risk of getting malaria, size and shape of the bed nets. Rectangular nets were difficult to hang daily in huts according to most key informants.”

Van Bortel W & al. raise serious concerns about the true effective life span of bed nets, as reported in Long-Lasting Insecticidal Nets Provide Protection Against Malaria for Only a Single Year in Burundi, an African Highland Setting with Marked Malaria Seasonality, BMJ Glob Health. 2022 Dec; 7(12):e009674, doi: 10.1136/bmj-2022-009674.

Govoetchan R & al.’s article, VECTRON™ T500, a New Broflanilide Insecticide for Indoor Residual Spraying, Provides Prolonged Control of Pyrethroid-Resistant Malaria Vectors, Malar J. 2022 Nov 11; vol 21 art 324, doi: 10.1186/s12936-022-04336-x demonstrates the usefulness of a new compound that can be used for indoor residual spraying (IRS) in areas where mosquitoes are resistant to pyrethroids. The authors recommend rotating different compounds in sequential IRSs.

Another compound for IRS was investigated by Yewhalaw D & al. and reported in Residual Efficacy of Sumishield™ 50WG for Indoor Residual Spraying in Ethiopia, Malaria J, 2022 Dec 2, vol 21, art 364, doi: 10.1186/s12936-022-04395-0. They state that “Sumi Shield™ 50WG resulted in mortality rates of over 80% at 120 h post-exposure on all surface types for up to nine months post-spray, while Actellic 300CS yielded mortality rates of over 80% for eight months after spray.” They conclude that “[t]he results of this trial demonstrated that the residual efficacy of SumiShield™ 50WG extends up to nine months on all treated wall surface types. The long-lasting residual efficacy and unique mode of action of the SumiShield™ 50WG shows that it could be an ideal product to be considered as a potential candidate insecticide formulation for IRS in malaria endemic countries….”

Githu V & al., Comparative Evaluation of Different Versions of Exposure-Free Mosquito Electrocuting Traps and Barrier Screen Trap for Monitoring Outdoor Densities and Biting Time Phenotypes by Malaria and Filariasis Vectors in Tanzania, Parasit Vectors. 2022 Nov 11; 15(1):420, doi: 10.1186/s13071-022-05549-4 is a report on the comparison of a variety of traps that allow the estimation of vector densities and therefore the threat of malaria (and fliariasis).

“Anopheles gambiae, An. funestus and An. coustani are key malaria vectors in the Taveta region of Kenya, showing concurrent indoor and outdoor transmission. All of the vectors tested showed a higher propensity for bovine and goat blood than for human blood.” The article in question is Karisa J & al., Malaria Vector Bionomics in Taita-Taveta County, Coastal Kenya, Parasit Vectors. 2022 Nov 16; 15(1):430, doi: 10.1186/s13071-022-05527-w.

Modifying mosquito habitats is a long-accepted method of malaria control. Martello E & al., Mosquito Aquatic Habitat Modification and Manipulation Interventions to Control Malaria, Cochrane Database of Systematic Reviews 2022, issue 11 art CD008923, doi: 10.1002/14651858.CD008923.pub3 is a review of publications on the subject. The authors conclude that “[h]abitat modification and manipulation interventions for preventing malaria has some indication of benefit in both epidemiological and entomological outcomes.”

A study of insecticide resistance, Apetogbo Y & al., Insecticide Resistance Intensity and Efficacy of Synergists with Pyrethroids in Anopheles gambiae (Diptera: Culicidae) from Southern Togo, Malaria J, 2022 Nov 27, vol 21, art 353, doi: 10.1186/s12936-022-04377-2, verified resistance in some of the districts studied, but not in others. This story is obviously evolving.
Insecticide resistance is also the focus of Pinda PG & al., Relationships Between Biological Age, Distance from Aquatic Habitats and Pyrethroid Resistance Status of Anopheles funestus Mosquitoes in South-Eastern Tanzania, Malaria J, 2022 Dec 2, vol 21 art 365, doi: 10.1186/s12936-022-04389-y. INresetingly, they conclude that mosquities collected farthest from the aquatic habitats (near the centre of the village) were more susceptible to pyrethroids than the younger ones and those caught nearest to the habitats. These findings suggest that pyrethroid-based interventions may remain at least moderately effective despite widespread pyrethroid-resistance, by killing the older, less-resistant and potentially infective mosquitoes.

Mwema T & al. comment on the fact that in a country with low incidence of malaria, there are factors that influence infection rates. Their article, Human and Vector Behaviors Determine Exposure to Anopheles in Namibia, Parasit Vectors. 2022 Nov 17; 15(1):436, doi: 10.1186/s13071-022-05563-6, reports that several species of Anopheles are native and that human activities, including the use of preventive measures influence infection rates.

The recent spread of Anopheles stephensi in Africa is addressed by Ahmed A & al., Strategies for Conducting Anopheles stephensi Surveys in Non-Endemic Areas, Acta Trop. 2022 Dec; 236:106671, doi: 10.1016/j.actatropica.2022.106671. The article includes “suggestions on surveillance approaches for monitoring An. stephensi. The first step is to determine the aim of the study, as this will determine the specific activities conducted in each location. Challenges related to identification and detection of resistance and sporozoites are also discussed. Results should be communicated to relevant stakeholders in a timely manner, both in country and internationally, to help understand the introduction, distribution, and bionomics of An. stephensi in a given country and work towards cross-border and coordinated international response.”

Buehler J, Invasive Mosquito Spreads Malaria, Science News, 2022 Dec 3, pp. 10-11, www.sciencenews.org is a more detailed description of the discovery of An. stephensi in Ethiopia.

Chemoprophylaxis
Kalu S & al. “assessed knowledge, attitude, and practice regarding two malaria prevention measures (long-lasting impregnated mosquito nets, LLINs, and intermittent preventative therapy with sulphadoxine-pyrimethamine (IPTp-SP)) among pregnant women in Nigeria.” They report in Prevention of Malaria in Pregnancy: What Do the Pregnant Women of Nigeria Know and Do About It, Infect Dis Obstet Gynecol. 2022 Nov 18; 2022:7061548, doi: 10.1155/2022/7061548 that 384 women (88.0% third trimester, 90.0% literate, and 41.1% primigravidae) participated in their study. “About 80.0% suffered from malaria during their current pregnancy. The majority was aware of the cause of malaria, local name of malaria, mode of transmission, risk of malaria among pregnant women, etc. However, their knowledge and attitude were inadequate regarding the symptomatology and complications of malaria in pregnancy, benefits of sleeping under the net or taking chemoprophylactic doses, or the concurrent use of both. About 80.0% had LLINs, yet only 41.5% slept under it the previous night. Only 31.0% had IPTp-SP doses under direct observation. Only 35.9% had a good understanding of IPTp-SP during pregnancy.”

Lee EH & al., Quality and Integrated Service Delivery: A Cross-Sectional Study of the Effects of Malaria and Antenatal Service Quality on Malaria Intervention Use in Sub-Saharan Africa, Trop Med Infect Dis. 2022 Nov 9; 7(11):363, doi: 10.3390/tropicalmed7110363 also highlight insufficient adherence to guidelines in preventive treatment of pregnancy in all areas they studied, namely Kenya, Namibia, Senegal, and Tanzania.

Other prevention
The use of a specific monoclonal antibody against Plasmodium falciparum has been investigated in experimental infection settings. Kayentao K & al., Safety and Efficacy of a Monoclonal Antibody Against Malaria in Mali, New Eng J Med, 2022 Nov 17, 387:1833-42, doi: 10.1056/NEJMoa2206966 report on its use in “a phase 2 trial to assess the safety and efficacy of a single intravenous infusion” of the antibody. In a three-arm trial including 330 test subjects, two different concentrations of the monoclonal antibody were found to be safe and effective in preventing P. falciparum infection over a six-month period.

Jadir Fall AKD & al. found infants who possessed IgG antibodies to malaria and were resistant to symptomatic infections. The abstract of their paper, Naturally Acquired Antibodies from Beninese Infants Promote Plasmodium falciparum Merozoite-Phagocytosis by Human Blood Leukocytes: Implications for Control of Asymptomatic Malaria Infections, Malaria J, 2022 Nov 29, vol 21 art 356, doi: 10.1186/s12936-022-04361-w, does not disclose how these infants acquired these antibodies, leaving us to surmise that they may have been transferred through the placenta.

Diagnosis:

General diagnostics
Primarily of clinical relevance is the paper by Foko LPK & al., The Spectrum of Clinical Biomarkers in Severe Malaria and New Avenues for Exploration, Virulence, 2022 Dec; 13(1):634-653. doi: 10.1080/21505594.2022.2056966. Their conclusion is that general biomarkers of severe illness, such as C-reactive protein, etc., may be useful to detect severe illness in patients with malaria.

In another approach to gauge the severity of malaria, Srinamon K & al. report in The Prognostic and Diagnostic Value of Intraleukocytic Malaria Pigment in Patients with Severe Falciparum Malaria, Nat Commun. 2022 Nov 12; 13(1):6882, doi: 10.1038/s41467-022-34678-8 that “[i]n African children the proportion of pigment containing [white blood cells] helps distinguish severe malaria from other life-threatening febrile illnesses, and it adds to the prognostic assessment from simple bedside examination, and to the conventional malaria parasite count.”

Ramchandran A & Sharma A summarize “[i]nsights from humans, mice, and in vitro studies … to present a cohesive understanding of molecular mechanisms involved in CM pathology in Dissecting the Mechanisms of Pathogenesis in Cerebral Malaria, PLoS Pathogens, 2022 Nov 17, doi: 10.1371/journal.ppat.1010919.

Field diagnostics
Awosolu OB & al. compared diagnostic methods and reported in Performance Evaluation of Nested Polymerase Chain Reaction (Nested PCR), Light Microscopy, and Plasmodium falciparum Histidine-Rich Protein 2 Rapid Diagnostic Test (PfHRP2 RDT) in the Detection of Falciparum Malaria in a High-Transmission Setting in Southwestern Nigeria, Pathogens. 2022 Nov 9;11(11):1312, doi: 10.3390/pathogens11111312 that “[m]alaria RDT recorded higher false negativity, compared [with] microscopy (4.94% vs. 3.70%). A near perfect agreement was reported between microscopy and nested PCR, and between PfHRP2 RDT and nested PCR …” Nonetheless they claim that their “study revealed that PfHRP2 RDT and microscopy continues to remain sensitive and specific for falciparum malaria diagnosis in the study area.”

Rogier E & al. focused on RDT in Performance of Antigen Detection for HRP2-Based Malaria Rapid Diagnostic Tests in Community Surveys: Tanzania, July–November 2017, Malaria J, 2022 Dec 1, vol 21, art 361, doi: 10.1186/s12936-022-04383-4. “All participants had an RDT performed in the field and provided a blood sample for later laboratory multiplex antigen detection of HRP2. In assessing the continuous HRP2 levels in participant blood versus RDT result, dose–response logistic regression provided quantitative estimates for HRP2 limit of detection (LOD)… Both HRP2-only and pLDH/HRP2 combo RDTs utilized in a 2017 Tanzania cross-sectional survey of border regions generally performed well, and reliably detected HRP2 antigen in the low ng/mL range.”

The accuracy of HRP2-based RDTs depends on the genetics of the malaria parasite. Stabler TC & al., Gene Coverage Count and Classification (GC3): A Locus Sequence Coverage Assessment Tool Using Short-Read Whole Genome Sequencing Data, and Its Application to Identify and Classify Histidine-Rich Protein 2 And 3 Deletions in Plasmodium falciparum, Malaria J, 2022 Nov 29, vol 21 art 357, doi: 10.1186/s12936-022-04376-3 is description of a “computational approach …, termed Gene Coverage Count and Classification (GC3), to analyse genome-wide sequence coverage data and provide informative outputs to assess presence and coverage profile of a target locus in WGS data. GC3 was applied to detect deletions at hrp2 and hrp3 (hrp2/3) and flanking genes in different geographic regions and across time points.”

In a paper that could be cited under several headings, but is primarily diagnostic in focus, Maketa V & al. conclude that ultrasensitive RDT should be used for screening pregnant women for malaria, even if asymptomatic, and if positive, they should be treated with artemisinin-based combination therapy (ACT) rather than with the preventive regimen of sulfadoxine-pyrimethamine (SP). The article is Comparison of Intermittent Screening (Using Ultra-Sensitive Malaria Rapid Diagnostic Test) and Treatment (Using a Newly Registered Antimalarial Pyronaridine-Artesunate-PYRAMAX®) to Standard Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine, Trials. 2022 Nov 28; 23(1):963. doi: 10.1186/s13063-022-06884-8.

Just as in the article above for pregnant women, Turnbull LB & al. used usRDT among asymptomatic children. Their article, Evaluation of an Ultrasensitive HRP2–Based Rapid Diagnostic Test for Detection of Asymptomatic Plasmodium falciparum Parasitaemia Among Children in Western Kenya, Malaria J, 2022 Nov 16, vol 21 art 337, doi: 10.1186/s12936-022-04351-y claims that “[u]s-RDT is more sensitive than microscopy for detecting asymptomatic malaria parasitemia in children.”

New diagnostic methods
According to Ikerionwu C & al., “[h]uman error is identified to be a major cause of inaccurate diagnostics in the traditional microscopy malaria diagnosis method. Therefore, the method would be more reliable if human expert dependency is restricted or entirely removed…” Their paper, Application of Machine and Deep Learning Algorithms in Optical Microscopic Detection of Plasmodium Parasites: A Malaria Diagnostic Tool for the Future, Photodiagnosis Photodyn Ther. 2022 Nov; 12:103198, doi: 10.1016/j.pdpdt.2022.103198 is “a systematic review to understand the prevalent machine learning algorithms applied to a low-cost, portable optical microscope in the automation of blood film interpretation for malaria parasite detection” and concludes that early detection of the malaria parasite has improved through the application of [two identified] algorithms on microscopic malaria parasite detection.

Treatment:

Treatment results
Assefa A &al., Therapeutic Efficacies of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum and Chloroquine and Dihydro-artemisinin-Piperaquine for Uncomplicated Plasmodium vivax Infection in Ethiopia, Malaria J, 2022 Dec 1, vol 21 art 359, doi: 10.1186/s12936-022-04350-z is a four-arm study of the regimens described in the title and found all of them 100% effective within four days of treatment.

Just as the above article, Mohammed H & al., Therapeutic Efficacy of Dihydroartemisinin–Piperaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Seacha Area, Arbaminch Zuria District, South West Ethiopia, Malaria J, 2022 Nov 27, vol 21, art 351, doi: 10.1186/s12936-022-04380-7 reports that “treatment with DHA–PPQ demonstrated excellent efficacy for uncomplicated P. vivax, with no recurrences to day 42, and no safety concerns. This treatment, which is also effective against P. falciparum, appears to be an ideal alternative for P. vivax as part of the malaria elimination program.”

Rakotoarisoa MA & al. assigned 558 children with uncomplicated P. falciparum malaria, aged between 1 and 15 years to two different regimens and report the results in Comparative Effect of Artemether-Lumefantrine {AL} and Artesunate-Amodiaquine {ASAQ} on Gametocyte Clearance in Children with Uncomplicated Plasmodium falciparum Malaria in Madagascar, Malaria J, 2022 Nov 16, vol 21 art 331, doi: 10.1186/s12936-022-04369-2. They conclude that “AL has a more rapid effect on gametocyte clearance compared to ASAQ in children with uncomplicated Plasmodium falciparum malaria.”

With artemisinin-resistance becoming a problem, Moyeh MN & al. point out in Current Status of 4-Aminoquinoline Resistance Markers 18 Years After Cessation of Chloroquine Use for the Treatment of Uncomplicated Falciparum Malaria in the Littoral Coastline Region of Cameroon, Pathog Glob Health. 2022 Dec; 116(8):509-514, doi: 10.1080/20477724.2022.2056674 that it may be possible to return to chloroquine even for the treatment of falciparum malaria in some settings. They claim that that “there is a gradual erosion of the mutant Pfcrt and Pfmdr1 genotype and a gradual return to the sensitive P. falciparum genotype in Cameroon.”

Side effects and complications
Slutsker L & Leke RGF highlight a conundrum in First-Trimester Use of ACTs for Malaria Treatment in Pregnancy, Lancet, 2022 Nov 25: S0140-6736(22)02166-3, doi: 10.1016/s0140-6736(22)02166-3. “For first-trimester malaria, WHO recommends treatment with quinine alone or with clindamycin. However, compared with ACT, this treatment approach is less efficacious, poorly tolerated, requires a long and complex regimen that affects adherence, and is not regularly available. To date, ACTs in the first trimester have not been recommended due to safety concerns. Animal studies have shown that exposure to artemisinin in early pregnancy is associated with substantial embryolethal and teratogenic effects, including pregnancy loss, embryo resorption, and congenital anomalies of the skeleton and heart.”

Drug resistance
Cheng W & al. report a technique of detecting single nucleotide mutations in the malaria parasite in Detection of Antimalarial Resistance-Associated Mutations in Plasmodium falciparum via a Platform of Allele-Specific PCR Combined with a Gold Nanoparticle-Based Lateral Flow Assay, Microbiol Spectr. 2022 Nov 29: e0253522, doi: 10.1128/spectrum.02535-22. They claim that their method is readily applicable to point of care diagnostics.

Iwanaga S & al., Genome-Wide Functional Screening of Drug-Resistance Genes in Plasmodium falciparum, Nat Commun, 2022 Oct 18, 13(1):6163, doi:10.1038/s41467-022-33804-w is also focused in the genetics of drug resistance. They suggest that a process called “functional screening” without further elaboration in the abstract is a good process for identifying genetic causes of drug resistance.

Chaurasiya A & al. investigated an anti-hepatitis virus drug for use to treat patients infected with artemisinin-resistant malaria. In Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir, Antimicrob Agents Chemother. 2022 Nov 14:e0039222, doi: 10.1128/aac.00392-22 they report that “Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity…”

“Parasite isolates collected between 2008 and 2021 from individuals with naturally acquired P. falciparum infections presenting with uncomplicated malaria were tested for in vitro susceptibility to piperaquine {PPQ}, dihydroartemisinin, lumefantrine {LM}, artemether, {ART} and chloroquine” by Wakoli DM & al. They report in Impact of Parasite Genomic Dynamics on the Sensitivity of Plasmodium falciparum Isolates to Piperaquine and Other Antimalarial Drugs, BMC Med. 2022 Nov 18; 20(1):448, doi: 10.1186/s12916-022-02652-2. They report that “[c]irculating Kenyan parasites have remained sensitive to PPQ and other antimalarials, though the response to [ART and LM] is declining.”

Use of guidelines
Argaw MD & al. investigated Adherence of Healthcare Providers to Malaria Case Management Guidelines of the Formal Private Sector in North-Western Ethiopia: An Implication for Malaria Control and Elimination, Malaria J, 2022 Nov 21, vol 21 art 347, doi: 10.1186/s12936-022-04379-0. Their conclusion: “Private healthcare providers adhered to universal parasitological diagnosis, providing comprehensive counseling, and linking patients with community health workers. In addition, almost all laboratory negative patients were not treated with anti-malarial drugs. However, only one-fifth of confirmed patients were treated in line with national guideline recommendations.”

In a “study using key informant interviews amongst prescribers comprising medical doctors, physician assistants, nurses and a health extension worker from 16 health facilities in six districts in Ghana,” Kolekang AS & al., Challenges with Adherence to the ‘Test, Treat, and Track’ Malaria Case Management Guideline Among Prescribers in Ghana, Malaria J, 2022 Nov 16, vol 21 art 332, doi: 10.1186/s12936-022-04365-6 is the unhappy report of poor adherence to the guidelines, which they attribute to “irregular supply of malaria rapid diagnostic test kits (RDT), mistrust of laboratory tests, and the reluctance of prescribers to change from presumptive treatment.”

New drug research
Batra N & al. investigated the effect of so-called hybrid antimalarials and report in Synthesis and Antimalarial Activity of 7-Chloroquinoline-Tethered Sulfonamides and their [1,2,3]-Triazole Hybrids, Future Med Chem. 2022 Dec 1, doi: 10.4155/fmc-2022-0187 that all seven compounds tested had “significant antimalarial activity against Plasmodium falciparum.”

Another approach to new drug research is cited in de Lera Ruiz M & al., The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor Toward the Treatment of Malaria, ACS Med Chem Lett. 2022 Oct 12; 13(11):1745-1754, doi: 10.1021/acsmedchemlett.2c00355. They identify discovery of “WM382, a very potent dual PMIX/X inhibitor with robust in vivo efficacy at multiple stages of the malaria parasite life cycle and an excellent resistance profile.”

It is unclear whether Nguyen-Vo TH & al advocate for using traditional products in Predicting Antimalarial Activity in Natural Products Using Pretrained Bidirectional Encoder Representations from Transformers, J Chem Inf Model. 2022 Nov 14; 62(21):5050-5058, doi: 10.1021/acs.jcim.1c00584. More than likely, they promote “computational methods [to discover] prediction models to identify antimalarial natural products.”

Rathod GK & al., New Structural Classes of Antimalarials, Eur J Med Chem. 2022 Nov 15; 242:114653, doi: 10.1016/j.ejmech.2022.114653 may well be of interest, since it claims to be “a comprehensive review, addressed to the new structural classes of heterocyclic and natural compounds that have been identified during the last decade as antimalarial agents.” However, access to the article is restricted.

Traditional treatments
None this month

Campaigns and Policies:

The effectiveness of a campaign is investigated by Afakbedzi SK & al., Impact Evaluation of Long-Lasting Insecticidal Nets Distribution Campaign on Malaria Cases Reported at Outpatient Departments Across All the Regions in Ghana, Malaria J, 2022 Dec 4, vol 21 art 370, doi: 10.1186/s12936-022-04393-2. This was an “ecological study … to assess the change in proportion of uncomplicated confirmed malaria cases among OPDs in all types of health facilities in Ghana between 2015 and 2019 following the mass distribution campaign of LLINs in 2018. Malaria cases at the OPDs before and after the free LLIN mass distribution exercise were evaluated.” The authors conclude that the campaign was a success, because of the reduction of malaria cases, even though the reduction was in the general vicinity of 5%.

“Uganda conducted its third mass long-lasting insecticidal net (LLIN) distribution campaign in 2021. The target of the campaign was to ensure that 100% of households own at least one LLIN per two persons and to achieve 85% use of distributed LLINs. LLIN ownership, use and associated factors were assessed 3 months after the campaign.” Kwiringira A & al., Ownership and Use of Long-Lasting Insecticidal Nets Three Months After a Mass Distribution Campaign in Uganda, 2021, Malaria J, 2022 Dec 3, vol 21, art 367, doi: 10.1186/s12936-022-04401-5 reports that “5529 households with 27,585 residents and 15,426 LLINs were included in the analysis. Overall, 95% of households owned ≥ 1 LLIN, 92% of the households owned ≥ 1 LLIN < 3 months old, 64% of households owned ≥ 1 LLIN per two persons in the household. Eighty-seven per cent could sleep under an LLIN if every LLIN in the household were used by two people, but only 69% slept under an LLIN the night before the survey.”

Also in Uganda, Takada S V &al., Social Network Correlates of Free and Purchased Insecticide-Treated Bed Nets in Rural Uganda, Malaria J, 2022 Nov 24, vol 21 art 350, doi: 10.1186/s12936-022-04347-8 interviewed 1747 individuals, “accounting for 716 households. The median number of peer households to which a household was directly connected was seven. Eighty-six percent of households owned at least one bed net, and 41% of households met the WHO Universal Coverage Criterion.”

“Many national malaria programmes have set goals of eliminating malaria, but realistic timelines for achieving this goal remain unclear. In [their] investigation, [Cohen JM & al. collate] historical data …on countries that successfully eliminated malaria to assess how long elimination has taken in the past, and thus to inform feasible timelines for achieving it in the future. In their article, How Long is the Last Mile? Evaluating Successful Malaria Elimination Trajectories, Malaria J, 2022 Nov 15, vol 21 art 330, doi: 10.1186/s12936-022-04368-3, “[c]ase series declining to the first year with zero cases were compiled for 45/56 of the candidate elimination programmes, and statistically significant breakpoints were identified for 42. The median timeline from the breakpoint to the first year with zero local cases was 12 years, over which cases declined at a median rate of 54% per year.”

Epidemiology:

General epidemiology and surveillance
Mwai K & al., Malaria Attributable Fractions with Changing Transmission Intensity: Bayesian Latent Class vs Logistic Models, Malar J. 2022 Nov 11; vol 21 art 326, doi: 10.1186/s12936-022-04346-9 is a report on complicated mathematical analysis of the trends in children’s malaria in western Kenya over the years 2005-2017.

As indicated in the title of Amede PO & al.’s article, Evaluation of Malaria Surveillance System in Benue State, Nigeria, Malaria J, 2022 Nov 23, vol 21 art 348, doi: 10.1186/s12936-022-04367-4, the authors conducted inquiries to establish whether they system in question meets the criteria of US CDC for surveillance systems. As a result of interviewing 51 key individuals, they concluded that the system “is simple, useful, acceptable, and flexible, but it is not representative and timely. Public–private and public-public-partnerships should be strengthened to encourage reporting from both private and tertiary health facilities and improve representativeness, and frequent feedback to improve reporting timeliness.”
Thawer SG & al., The Use of Routine Health Facility Data for Micro-Stratification of Malaria Risk in Mainland Tanzania, Malaria J, 2022 Nov 18, vol 21 art 345, doi: 10.1186/s12936-022-04364-7 is a publication that emphasizes data collection from health-care facilities with regard to risk stratification, which is explained in some detail in the abstract.

Climate change, biodiversity, and environment
Seasonal patterns of malaria cases in many parts of Africa are generally associated with rainfall, yet in the dry seasons, malaria transmission declines but does not always cease. Duque C & al. investigated and modeled the Impact of Aerial Humidity on Seasonal Malaria: An Ecological Study in Zambia, Malar J. 2022 Nov 11; vol 21 art 325, doi: 10.1186/s12936-022-04345-w. They conclude that “throughout the dry season, periodic conditions of sustained humidity occur that may permit foraging by resting mosquitoes, and these periods are associated with increased incidence of malaria cases.”

Population dynamics
“Human mobility behaviour modelling plays an essential role in the understanding and control of the spread of contagious diseases by limiting the contact among individuals, predicting the spatio-temporal evolution of an epidemic and inferring migration patterns.” Haileselassie W & al. assessed “the human mobility pattern and analyse[d] its implication for malaria disease epidemiology. They report not only predictably high mobility in the morning and late afternoon periods, but also at night, which may predispose to more mosquito biting. The article is Mobile Phone Handover Data for Measuring and Analysing Human Population Mobility in Western Ethiopia: Implication for Malaria Disease Epidemiology and Elimination Efforts, Malar J. 2022 Nov 11; vol 21 art 323, doi: 10.1186/s12936-022-04337-w.

“While malaria morbidity has sharply declined in several areas in Senegal, it remains an important problem in the southern part of the country, particularly among adolescents.” Tairou F & al. “assessed malaria-related knowledge, attitudes, and practices (KAP) among adolescents living in a highly persistent transmission area in Senegal.” Not surprisingly, they report in Malaria Prevention Knowledge, Attitudes, and Practices (KAP) Among Adolescents Living in an Area of Persistent Transmission in Senegal: Results from a Cross-Sectional Study, PLoS One, 022 Dec 1; 17(12):e0274656, doi: 10.1371/journal.pone.0274656 that “adolescents, generally have poor levels of malaria knowledge and low uptake of malaria prevention and control interventions.”

“Malaria is the top public health problem in the Republic of Guinea, with more than 4 million cases and 10,000 deaths in 2021 among a population of approximately 13 million. It is also the second highest cause of death there.” Ravi N & al. conducted a “cross-sectional household survey in Timbi-Touni, Guinea using community workers. The survey included respondent demographic characteristics, malaria knowledge, child health, water and sanitation, and health services access.” Their report, A Malaria Knowledge, Attitudes and Practice Survey in a Rural Community in Guinea, Malar J. 2022 Nov 14; vol 21 art 329, doi: 10.1186/s12936-022-04357-6 disclosed that 86% of respondents “had received a free bed net during national campaigns and 61% slept under a bed net the night before the survey. Knowing mosquitoes to be the cause of malaria and receiving free bed net were significantly associated with sleeping under a bed net.”

Spatiotemporal studies
Biset G & al., Malaria Among Under-Five Children in Ethiopia: A Systematic Review and Meta-Analysis, Malaria J, 2022 Nov 16, vol 21 art 338, doi: 10.1186/s12936-022-04370-9.

Matambisso G & al., Gravidity and Malaria Trends Interact to Modify P. falciparum Densities and Detectability in Pregnancy: A 3-Year Prospective Multi-Site Observational Study, BMC Med. 2022 Nov 15; 20(1):396, doi: 10.1186/s12916-022-02597-6.

Orish VN & al., HIV and Malaria Prevalence Among Pregnant Women with and Without Pre-Eclampsia at the Atua Government Hospital in Ghana’s Eastern Region, Int J Gynaecol Obstet. 2022 Dec; 159(3):912-917, doi: 10.1002/ijgo.14255.

Other
Collins OC & Duffy KJ, A Mathematical Model for the Dynamics and Control of Malaria in Nigeria, Infect Dis Model. 2022 Nov 5; 7(4):728-741. doi: 10.1016/j.idm.2022.10.005 “incorporates drug resistance, treatment, and the use of mosquito nets as preventive strategies. …. Overall, the results indicate that the disease is likely to remain endemic in Nigeria unless better control measures are focused on the dominant resistant strain, treatment is improved and the use of mosquito nets become widespread.”