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In late July, a news release informed the world that the R21/Matrix-MTM vaccine has now been authorized for use in Burkina Faso, in addition to Ghana and Nigeria, where the authorities have also endorsed the use of this vaccine.  There has been no official word from the World Health Organization (WHO) about this development so far.

“A novel testing platform under development by researchers at the Yale School of Public Health and CytoAstra, LLC could provide a new noninvasive test for malaria that doesn’t require a blood sample. The platform technology, known as cytophone, detects malaria infection in blood cells using lasers and ultrasound. Researchers … believe it could provide more sensitive and reliable testing results compared to the more traditional blood tests for malaria, which require a blood sample and tend to detect malaria only at higher parasite burdens, hindering effective detection and treatment” reads a press release on July 28 from https://www.news-medical.net/news/20230728/Novel-noninvasive-test-for-malaria-does-not-require-a-blood-sample.aspx.  Although this technology has been reported in medical diagnostics, there has been no peer reviewed mention of its use in malaria diagnostics as of August 15.

On August 1, WHO published a report of the proceedings of the 18th meeting of the world-wide Vector Control Advisory Group, which took place in April.  On August 15, the pamphlet “The WHO Initiative to Stop the Spread of Anopheles stephensi” was published. These documents are available for downloading from the who.int website. 

PEER REVIEWED ARTICLES

Prevention

Vaccines

Genito CJ & al., Protective Antibody Threshold of RTS,S/AS01 Malaria Vaccine Correlates Antigen and Adjuvant Dose in Mouse Model, NPJ Vaccines, 2023 Aug 10; 8(1):114. https://doi.org/10.1038/s41541-023-00714-x reports on mouse studies of the vaccine that is already in use in humans under the aegis of WHO approval.  This type of study will be of value in the future if and when reports purporting to the lack of effectiveness and/or of harm to recipients of the vaccine come to be published.

Despite the title of Björkman A & al., RTS,S/AS01 Malaria Vaccine-Proven Safe and Effective, Lancet Infect Dis. 2023 Aug; 23(8):e318-e322, https://doi.org/10.1016/s1473-3099(23)00126-3, the article, as judged by its abstract, is actually critical of reports that claim safety and effectiveness of the vaccine, raising several objections to the methodology of the investigations. They “conclude that the claimed impact of the MVIP [Malaria Vaccine Implementation Programme] on mortality is not based on enough scientific evidence and that the MVIP findings do not rule out the possibility of increased mortality among vaccinated girls compared with vaccinated boys, as observed in the phase 3 studies.”

One of several “perception and acceptance” articles this month is Bam V & al., Caregivers’ Perception and Acceptance of Malaria Vaccine for Children, PLoS One. 2023 Jul 26; 18(7):e0288686, https://doi.org/10.1371/journal.pone.0288686. This one reports on ten (!) mothers in Ghana, who underwent structured interviews. They conclude that “[t]he caregivers had positive perceptions about the malaria vaccine for children, with fewer hospital admissions and saving money as some benefits. Health workers played a significant role in influencing the acceptance of the vaccine. However, the fear of the unknown concerning the side effects of the vaccine serve as a possible barrier to recommending the vaccine to other caregivers.”

Mak J & al. performed a return on investment (ROI) study on the use of the RTS,S/AS01 vaccine, projected out several years. Their paper, An Estimate of the Return on Investment of a Malaria Vaccine in 20 Sub-Saharan African Countries, 2021-30, Health Aff (Millwood). 2023 Aug; 42(8):1091-1099, https://doi.org/10.1377/hlthaff.2022.01328 reports on computations using two different models.  Both of them yield the conclusion that the ROI is insufficient and therefore “decision makers should continue to improve delivery platforms, decrease vaccine delivery costs, deliver the malaria vaccine in fewer doses, and provide access to vaccine resources.’

Inactivated sporozoite-based vaccines have been the subject of many articles. Richie TL, & al. add to these with Sporozoite Immunization: Innovative Translational Science to Support the Fight Against Malaria, Expert Rev Vaccines, 2023 Aug 11, https://doi.org/10.1080/14760584.2023.2245890. They claim that “[s]porozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection.” Based on the authors’ literature review “PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years.”

According to Silk SE & al., “RH5 is a leading blood-stage candidate antigen for a Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown.” They conducted huma subjects research and report in Superior Antibody Immunogenicity of a Viral-Vectored RH5 Blood-Stage Malaria Vaccine in Tanzanian Infants as Compared to Adults, Med, 2023 Aug 7; S2666-6340(23)00226-X, https://doi.org/10.1016/j.medj.2023.07.003 that “[v]accinations were well tolerated, with profiles comparable across groups.” No serious adverse events were reported.

Yet another approach to vaccine development is the subject of Rosenkranz M & al., Multifunctional IGg/IGm Antibodies and Cellular Cytotoxicity are Elicited by The Full-Length Msp1 Sumayavac-1 Malaria Vaccine, NPJ Vaccines, 2023 Aug 9; 8(1):112, https://doi.org/10.1038/S41541-023-00701-2. They report on what they describe as the first experiments administering the vaccine to humans. Apparently, the vaccine elicits significant immunologic response.  Efficacy studies have not been reported yet.

Ganley M & al. report on the development of an mRNA Vaccine Against Malaria Tailored for Liver-Resident Memory T Cells in Nat Immunol. 2023 Jul 20, https://doi.org/10.1038/s41590-023-01562-6. The studies are in animal models only at this time and the reported increase in liver-resident T memory calls was dependent on the introduction of “an agonist that recruits T cell help from type I natural killer T cells.” The development of this type of vaccine awaits proof of effectiveness in humans.

A very different approach to vaccination is reported in Sagara I & al., Malaria Transmission-Blocking Vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in Healthy Malian Adults; A Phase 1, Randomised, Controlled Trial, Lancet Infect Dis, 2023 Jul 24, https://doi.org/10.1016/S1473-3099(23)00276-1. These vaccines target mosquito-stage parasites.  The authors compared two such preparations, identified in the title of the article. Transmission blockage was measured by “18–50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents” allowing controlled mosquito feeding and then having the mosquitoes assayed for parasites.  The results confirmed previous experience, namely that the former preparation was superior to the latter.  The authors also report that the vaccines were “well tolerated.” Beeson JG & Chan J-A, A Step Forward for Plasmodium falciparum Malaria Transmission Blocking Vaccines, Lancet Infect Dis, 2023 Jul 24, https://doi.org/10.1016/S1473-3099(23)00288-8 is an editorial in support of the above article.

Another Plasmodium species is the target of vaccine research as well. Hou MM & al. “conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivax Duffy-binding protein region II (PvDBPII).” They report in Vaccination with Plasmodium vivax Duffy-Binding Protein {DBP} Inhibits Parasite Growth During Controlled Human Malaria Infection, Sci Transl Med. 2023 Jul 12; 15(704):eadf1782, https://doi.org/10.1126/scitranslmed.adf1782 that the vaccine preparation “elicited … antibody responses and reduced the mean parasite multiplication rate after [controlled human malaria infection] by 51% (n = 6) compared with unvaccinated controls (n = 13)…” Meanwhile, Dickey TH & Tolia NH, “discuss the reasons for targeting DBP, the challenges associated with developing a vaccine, and modern structural vaccinology methods that could be used to create an effective DBP vaccine” in Designing an Effective Malaria Vaccine Targeting Plasmodium vivax Duffy-Binding Protein, Trends Parasitol. 2023 Jul 21: S1471-4922(23)00147-2, https://doi.org/10.1016/j.pt.2023.06.011.   

Vector control and protection from vectors

Nuñez L & al. published two articles relating to Insecticide Treated Bed Net (ITN) distribution program in Ghana. One, Successful Implementation of ITN Distribution Through Health Facilities in Ghana, Malaria J, 2023 Aug 2, 22:224, https://doi.org/10.1186/s12936-023-04592-5 concludes after reviewing “[m]onthly data on routine ITN distribution was provided from Ghana’s national health information management system for the years 2016–2021” that “[b]y 2021, Ghana had improved its ITN issuing rates since the initial year of analysis, surpassing the 80% target by issuing nets to over 90% of pregnant women and young children” attending antenatal clinics and/or child welfare clinics. The other article, Measuring Quality of Facility-Based ITN Distribution in Ghana, Malaria J, 2023 Aug 2, 22:222, https://doi.org/10.1186/s12936-023-04626-y “looks at ITN distributions at health facilities in Ghana, with the aim of providing insights on how quality can be measured and monitored.” The quality measures implemented are not specifically mentioned in the abstract, but it asserts that “the approaches assessed (1) service data management, (2) logistics data management, and (3) observation of service provision (ITN issuance, malaria education, ITN use and care education).” The article concludes that “data reported to the national [health management information system are] accurate” but “there [was] no clear guidance on how to measure quality of facility-based ITN distribution, so there is also need for the global community to agree on standardized indicators and approaches to measuring quality of facility-based ITN distribution.”

“Pyrethroid-chlorfenapyr (CFP) and pyrethroid-piperonyl butoxide (PBO) nets are being scaled across endemic countries to improve control of malaria transmitted by pyrethroid-resistant mosquitoes.” Syme T & al. address the possibility of combining the two types of nets in a double net configuration. Can the Performance of Pyrethroid-Chlorfenapyr Nets Be Reduced When Combined with Pyrethroid-Piperonyl Butoxide (PBO) Nets? Malaria J, 2023 Jul 21, 22:214, https://doi.org/10.1186/s12936-023-04648-6 reports that adding the PBO nets actually reduces the killing power of pyrethroid-CFP nets. They suggest that “this effect may be partly attributable to antagonism between CFP and PBO.”

Syme T & al. also authored PermaNet Dual, a New Deltamethrin-Chlorfenapyr Mixture Net, Shows Improved Efficacy Against Pyrethroid-Resistant Anopheles gambiae sensu lato in Southern Benin, Sci Rep. 2023 Jul 28; 13(1):12232, https://doi.org/10.1038/s41598-023-39140-3. “PermaNet Dual is a new deltamethrin-chlorfenapyr net developed … to provide more options to malaria control programmes.” In experimental hut settings, Permanent Dual outperformed nets impregnated with pyrethroid only and with pyrethroid-PBO. It was “non-inferior” to pyrethroid-CFP nets, using “a provisional non-inferiority margin defined” by WHO.

Teshome A & al. collected An. stephensi from the field and tested them against several insecticides in use in ITNs and Indoor Residual Spraying (IRS). They report in Resistance of Anopheles stephensi to Selected Insecticides Used for Indoor Residual Spraying and Long-Lasting Insecticidal Nets in Ethiopia, Malaria J, 2023 Jul 27, 22:218, https://doi.org/10.1186/s12936-023-04649-5 that these vectors were resistant to all insecticides currently in use in IRS and all but one of the ITNs in use.

Kassie GA & al., Insecticide-Treated Bed Net Utilization and Associated Factors Among Pregnant Women in Ethiopia: A Systematic Review and Meta-Analysis, Malaria J, 2023 Aug 2, 22:223, https://doi.org/10.1186/s12936-023-04655-7 is yet again a demonstration of the public not using insecticide treated bed nets (ITNs) even when they have access to them.  This time they did a meta-analysis of several articles, covering “7,161 participants …The pooled prevalence of ITN utilization among all pregnant women who had access to ITN in Ethiopia was 59.42%…” The conclusion does not seem to point to imaginative solutions to the problem.

Related to the above issue, Zerdo Z & al., Effect of Malaria Prevention Education on Bed Net Utilization, Incidence of Malaria and Treatment Seeking Among School-Aged Children in Southern Ethiopia; Cluster Randomized Controlled Trial, BMC Infect Dis. 2023 Jul 20; 23(1):486, https://doi.org/10.1186/s12879-023-08464-w found that malaria prevention education “had no significant effect on the use of malaria prevention measures considered, treatment seeking from a health facility and reported cumulative incidence of malaria, though bed net use was associated with [lower] malaria incidence.”

“From 2008 to 2016, an IRS program was implemented in the district of Koulikoro [Mali]. After a significant reduction in malaria indicators, IRS was stopped in 2016.” Keïta M & al., Resurgence of Malaria Transmission and Incidence After Withdrawal of Indoor Residual Spraying in the District of Koulikoro, Mali, Am J Trop Med Hyg. 2023 Aug 7: tpmd220808, https://doi.org/10.4269/ajtmh.22-0808 “evaluated the effect of IRS withdrawal on entomological parameters of malaria transmission and incidence in children aged 6 months to 10 years … [P]arameters of malaria transmission during the last year of IRS implementation in 2016 were compared with those … 2 years after IRS withdrawal in 2018… The average entomological inoculation rate, which was undetectable before, was 1.22 infected bites per person per month 2 years after IRS was withdrawn, and the cumulative malaria incidence rate … after IRS was 4.12 times (15.2% versus 3.7%) higher than that … in 2016 in the villages before IRS withdrawal.” 

Kouadio F-PA & al. used multiple different insecticides to test against An. gambiae obtained from a variety of different agricultural sites.  They report in Relationship Between Insecticide Resistance Profiles in Anopheles gambiae sensu lato and Agricultural Practices in Côte d’Ivoire, Parasit Vectors, 2023 Aug 9; 16(1):270, https://doi.org/10.1186/s13071-023-05876-0 that the patterns of insecticide resistance appear to vary according to the crops being reared.

Iga J & al. collected mosquito larvae from multiple breeding sites from a limited geographic area and found that most of them were Anopheles arabiensis.  Subjecting them to the substances used for indoor residual spraying (IRS) there was susceptibility of these populations to the usual components was high (24-hour mortality in excess of 98%).  The paper is Sibling Species Composition and Susceptibility Status of Anopheles gambiae s.l. to Insecticides Used for Indoor Residual Spraying in Eastern Uganda, J Parasitol Res. 2023 Jul 10; 2023:2225233, https://doi.org/10.1155/2023/222523.

“With escalating insecticide resistance against almost all conventional insecticides, identification of agents that simultaneously act at multiple stages of Anopheles life cycle presents a cost-effective opportunity.” Rants’o TA & al. address this issue in Bioactivity of Select Essential Oil Constituents Against Life Stages of Anopheles arabiensis (Diptera: Culicidae), Exp Parasitol. 2023 Aug; 251:108569, https://doi.org/10.1016/j.exppara.2023.108569. “This study aimed to identify essential oil constituents (EOCs) with potential toxic effects against multiple stages of An. arabiensis life cycle. Five EOCs were assessed for inhibition of Anopheles egg hatching and ability to kill larvae, pupae and adult mosquitoes of An. arabiensis species… [A]ll five EOCs exhibited potent larvicidal activity …, with four of them….also possessing potent pupicidal effects …. Finally, all EOCs showed only moderate lethality against adult mosquitoes.”  Although the abstract mentions the name of the oils, it is silent on their sources.

“Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as ‘attract-and-kill’ or ‘push-and-pull’, have been suggested as complementary tools to [IRS and LLINs]. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions,” according to Fillinger U & al., A Randomized, Double-Blind Placebo-Control Study Assessing the Protective Efficacy of an Odour-Based ‘Push-Pull’ Malaria Vector Control Strategy in Reducing Human-Vector Contact, Sci Rep. 2023 Jul 11;13(1):11197, https://doi.org/10.1038/s41598-023-38463-5. “A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a ‘push’ intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a ‘pull’ intervention placing an odour-baited mosquito trap at a 5 m distance from a house… None of the interventions provided any protection from outdoor biting malaria vectors. The ‘push’ reduced indoor vector densities dominated by Anopheles funestus by around two thirds. The ‘pull’ device did not add any benefit.”

The gene drive approach to vector control is covered by several papers this month. Carballar-Lejarazú R,  & al., Dual Effector Population Modification Gene-Drive Strains of the African Malaria Mosquitoes, Anopheles gambiae and Anopheles coluzzii, Proc Natl Acad Sci USA, 2023 Jul 18; 120(29):e2221118120, https://doi.org/10.1073/pnas.2221118120 claims to “demonstrate the potential of Cas9/guide RNA (gRNA)-based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations.” This seems to be more favorable in the case of An. coluzii, since the authors report that the An. gambiae strain of males “were less competitive than wild types.”   Quresi A & Connolly JB, Bioinformatic and Literature Assessment of Toxicity and Allergenicity of a CRISPR-Cas9 Engineered Gene Drive to Control Anopheles gambiae the Mosquito Vector of Human Malaria, Malaria J, 2023 Aug 14, 22:234, https://doi.org/10.1186/s12936-023-04665-5 focus on potential human, animal and environmental toxicity through literature search and finds no evidence for it. Smidler AL & al., Eliminating Malaria Vectors with Precision Guided Sterile Males, bioRxiv. 2023 Jul 21: 2023.07.20.549947, https://doi.org/10.1101/2023.07.20.549947, focuses on sterile insect technique (SIT), which “is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass-releases of non-biting, non-driving, sterile males which seek out and mate with monandrous wild females… Using a binary CRISPR strategy, [the authors crossed] separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male-sterility and >99.9% female-lethality in hybrid progeny. [They] demonstrate that these genetically sterilized males have good longevity, are able to induce population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models…”  In early July these same authors published A Confinable Female-Lethal Population Suppression System in the Malaria Vector, Anopheles gambiae, Sci Adv. 2023 Jul 7; 9(27):eade8903, https://doi.org/10.1126/sciadv.ade8903. It is unclear whether articles published in Science Advances are peer reviewed.

Chemoprophylaxis

“The efficacy and effectiveness of antimalarial drugs are threatened by increasing levels of resistance and therefore require continuous monitoring. Chemoprevention is increasingly deployed as a malaria control measure, but there are no generally accepted methods of assessment.” In A Proposed Method of Grading Malaria Chemoprevention Efficacy, Trans R Soc Trop Med Hyg. 2023 Jul 10: trad042, https://doi.org/10.1093/trstmh/trad042, WhiteNJ & al. “propose a simple method of grading the parasitological response to chemoprevention (focusing on seasonal malaria chemoprevention) that is based on pharmacometric assessment.”

Although Mtove G & al., Fetal Growth and Birth Weight Are Independently Reduced by Malaria Infection and Curable Sexually Transmitted and Reproductive Tract Infections in Kenya, Tanzania, and Malawi: A Pregnancy Cohort Study, Int J Infect Dis. 2023 Jul 27:S1201-9712(23)00662-8, https://doi.org/10.1016/j.ijid.2023.07.012 is not a chemoprophylaxis article as such, it is reported here because the data quoted in the paper were obtained in the course of a study of chemoprevention during pregnancy. The article’s conclusion as to malaria in pregnant women is that it is associated with poor fetal growth, especially among women who have had few pregnancies and those with additional, sexually transmitted infections.

Other

Mizushima D & al. point to an intriguing possible approach to parasite control in their paper, A Rare Sugar, Allose, Inhibits the Development of Plasmodium Parasites in the Anopheles Mosquito Independently of Midgut Microbiota, Front Cell Infect Microbiol. 2023 Jul 20; 13:1162918, https://doi.org/10.3389/fcimb.2023.1162918. “Antibiotic-treated and antibiotic-untreated Anopheles stephensi were fed fructose with or without allose. The mosquitoes were infected with … Plasmodium berghei, and parasite development was evaluated …. Bacterial composition analysis in gut of their mosquitoes was performed … [A]llose inhibited the development of oocysts in mosquitoes regardless of prior antibiotic treatment. Microbiome analysis showed that the midgut bacterial composition in mosquitoes before and after blood feeding was not affected by allose. … Additional 15 sugars … were tested, however, no inhibitory effect against Plasmodium development in mosquitoes was observed. These results indicated that allose inhibits parasite development in midgut stage of the mosquito independently of midgut microbiota.”

“The massive and inappropriate use of synthetic insecticides is causing significant and increasing environmental disruption. Therefore, developing effective natural mosquitocidal compounds could be an alternative tool for malarial vector control” according to Wangrawa DW & al., Methanol and Acetone Extracts from The Leaves of Selected Aromatic Plants Affect Survival of Field Collected Anopheles arabiensis (Diptera: Culicidae) from Kisumu, Kenya, J Med Entomol. 2023 Jul 21: tjad066. https://doi.org/10.1093/jme/tjad066. The authors investigated “the larvicidal and adulticidal effect of methanol and acetone extracts of leaves from” four different plants found in Western Kenya. All four substances tested demonstrated killing effect using one or another of the extracting methods.  The authors state that “the plant extracts tested may represent effective means to control An. arabiensis when used to treat the surface of the marshes.”

The beneficial effect of fungal products on human health may gain another example if Kianifard L & al., A Recombinant Aspergillus oryzae Fungus Transmitted from Larvae to Adults of Anopheles stephensi Mosquitoes Inhibits Malaria Parasite Oocyst Development, Sci Rep. 2023 Jul 27;13(1):12177, https://doi.org/10.1038/s41598-023-38654-0 results in successful large-scale efforts to apply the findings of this paper. “The … fungus strain was genetically modified to secrete two anti-plasmodial effector peptides, … transmission of the fungus from larvae to adult mosquitoes was confirmed following inoculation of A. oryzae-R in the water trays used for larval rearing. Secretion of the anti-plasmodial effector peptides inside the mosquito midguts inhibited oocyst formation of P. berghei parasites. These results indicate that A. oryzae can be used … to inhibit malaria parasite development in An. stephensi. Further studies are needed to determine if this recombinant fungus can be adapted under natural conditions, with a minimal or no impact on the environment, to target mosquito-borne infectious disease agents inside their vectors.”

Vaccines and ivermectin are not the only ways of blocking transmission. Challenger JD & al. report the results of Modeling the Impact of a Highly Potent Plasmodium falciparum Transmission-Blocking Monoclonal Antibody in Areas of Seasonal Malaria Transmission in J Infect Dis. 2023 Jul 14; 228(2):212-223, https://doi.org/10.1093/infdis/jiad101. According to their report, “[c]ommunity-wide annual administration (at 80% coverage) of TB31F {the antibody studied} over a 3-year period was predicted to reduce clinical incidence by 54% (381 cases averted per 1000 people per year) in a high-transmission seasonal setting, and 74% (157 cases averted per 1000 people per year) in a low-transmission seasonal setting. Targeting school-aged children gave the largest reduction in terms of cases averted per dose.”

Diagnosis

General diagnostics

Lazrek Y & al. used “a multiplex real-time PCR assay to detect and identify the five human malaria parasites.” As reported in Molecular Detection of Human Plasmodium Species Using a Multiplex Real Time PCR {polymerase chain reaction}, Sci Rep. 2023 Jul 14; 13:11388, https://doi.org/10.1038/s41598-023-38621-9, DNA samples were extracted from whole blood or dried blood spots drawn from patients. Based on the External Quality Assessment (whole blood), this method shows 100% sensitivity and specificity” for each of the five species of Plasmodium known to infect humans.

“C reactive protein (CRP), a marker for the presence of inflammation, has been extensively studied for distinguishing bacterial from non-bacterial infection in febrile patients, but its role in excluding malaria in the febrile child has not been thoroughly evaluated.” Ngwengi Y & al., Evaluation of CRP as a Marker for Bacterial Infection and Malaria in Febrile Children at the Douala Gyneco-Obstetric and Pediatric Hospital, PLoS One. 2023 Jul 21; 18(7):e0289012, https://doi.org/10.1371/journal.pone.0289012 reports that CRP levels of children with malaria were indistinguishable from levels in the presence of bacterial infection.  Therefore “negative CRP” may be used to exclude malaria in the diagnosis of a febrile child.

Field diagnostics

“Accurate malaria diagnosis and timely treatment are requirements for effective management of the disease. However, treatment efficacy may be significantly reduced in resource-constrained healthcare facilities with poorly equipped laboratories and frequent drug and rapid diagnostic test kit (RDT) stock-outs.” Omondi CJ & al. recount in Malaria Diagnosis in Rural Healthcare Facilities and Treatment-Seeking Behavior in Malaria Endemic Settings in Western Kenya, PLoS Glob Public Health. 2023 Jul 20; 3(7):e0001532, https://doi.org/10.1371/journal.pgph.0001532 that individuals with fever or their families seldom access healthcare facilities for diagnosis, because they know of the shortcomings, and often self-treat or skip treatment altogether.

“Histidine-rich protein 2- (HRP2-) based rapid diagnostic tests (RDTs) are widely used to detect Plasmodium falciparum in sub-Saharan Africa. Reports of parasites with pfhrp2 and/or pfhrp3 (pfhrp2/3) gene deletions in Africa raise concerns about the long-term viability of HRP2-based RDTs.” François R, & al. “evaluated changes in pfhrp2/3 deletion prevalence over time using a 2018-2021 longitudinal study of 1,635 enrolled individuals in Kinshasa Province, Democratic Republic of the Congo (DRC)” and found no evidence of either of these deletions in over 1,500 samples genotyped. The article is Plasmodium falciparum with Pfhrp2/3 Deletion Not Detected in a 2018-2021 Malaria Longitudinal Cohort Study in Kinshasa Province, Democratic Republic of the Congo, Am J Trop Med Hyg. 2023 Jun 20; 109(2):273-276, https://doi.org/10.4269/ajtmh.22-0715.

At significant variance with the above results, Diallo AO & al. report in Impact of Malaria Diagnostic Choice on Monitoring of Plasmodium falciparum Prevalence Estimates in the Democratic Republic of the Congo and Relevance to Control Programs in High-Burden Countries, PLoS Glob Public Health. 2023 Jul 26; 3(7):e0001375, https://doi.org/10.1371/journal.pgph.0001375 that “[a]mong 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA {bead-based immunoassays} were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection.”

According to Wei H & al., “a rapid and ultrasensitive point-of-care testing (POCT) platform for malaria detection is urgently needed and necessary.”  They describe a “platform based on recombinase polymerase amplification (RPA) followed by CRISPR/Cas12a (referred to as RPA-CRISPR/Cas12a) … optimized for the determination of Plasmodium spp. parasites, particularly Plasmodium falciparum, using a fluorescence-based assay (FBDA), lateral flow test strips (LFTS), or naked eye observation (NEO).” As expressed in Rapid and Ultrasensitive Detection of Plasmodium spp. Parasites Via the RPA-CRISPR/Cas12a Platform, ACS Infect Dis. 2023 Jul 26, https://doi.org/10.1021/acsinfecdis.3c00087, the authors claim that this method is suitable for POCT.

New diagnostic methods

“Early and accurate detection of infection by pathogenic microorganisms, such as Plasmodium, the causative agent of malaria, is critical for clinical diagnosis and ultimately determines the patient’s outcome.”  Oliveira MJ & al.’s article, A Simple Polystyrene Microfluidic Device for Sensitive and Accurate SERS-Based Detection of Infection by Malaria Parasites, Analyst. 2023 Aug 2,  https://doi.org/10.1039/d3an00971h claims that this diagnostic method has an approximately “7-fold higher sensitivity than that attained by most rapid diagnostic tests…” 

Treatment

Treatment results

Hutchins H & al., Protocol for a Cluster Randomised Placebo-Controlled Trial of Adjunctive Ivermectin Mass Drug Administration for Malaria Control on the Bijagós Archipelago of Guinea-Bissau: The MATAMAL Trial, BMJ Open. 2023 Jul 7; 13(7):e072347, https://doi.org/10.1136/bmjopen-2023-072347 is at this time simply the research protocol involving the addition of ivermectin to mass administration of artemisinin combination therapy.

In an analysis of the contribution of ivermectin to the antimalarial action of ACT in situations of combining the two therapies, Yipsirimetee A & al., Activity of Ivermectin and Its Metabolites Against Asexual Blood Stage Plasmodium falciparum and Its Interactions with Antimalarial Drugs, Antimicrob Agents Chemother. 2023 Jul 18; 67(7):e0173022, https://doi.org/10.1128/aac.01730-22 concludes that “ivermectin does not have clinically relevant activity against the asexual blood stages of P. falciparum. It also does not affect the in vitro antimalarial activity of artemisinins or ACT-partner drugs against asexual blood stages of P. falciparum.”

“The artemisinins are potent and widely used antimalarial drugs that are eliminated rapidly. A simple concentration-effect pharmacometric model does not explain why dosing more frequently than once daily fails to augment parasite clearance and improve therapeutic responses in vivo.” Saralamba S & al. propose a “within-host pharmacometric model … in which it is hypothesized that some malaria parasites enter a temporary drug refractory state after exposure to artemisinin antimalarials, which is followed by delayed parasite death or reactivation” in An Artesunate Pharmacometric Model to Explain Therapeutic Responses in Falciparum Malaria, J Antimicrob Chemother. 2023 Jul 20: dkad219, https://doi.org/10.1093/jac/dkad219. “The model fitted the observed sequential parasite density data from patients with acute P. falciparum malaria, and it supported reduced ring stage activity in artemisinin-resistant infection.”

Adherence to guidelines

Baraka V & al., Prescription Patterns and Compliance with World Health Organization Recommendations for the Management of Uncomplicated and Severe Malaria: A Prospective, Real-World Study in Sub-Saharan Africa, Malaria J, 2023 Jul 25, 22:215, https://doi.org/10.1186/s12936-023-04650-y is “a multicentre, observational study conducted between October 2020 and March 2021 in which patients of all ages with symptoms suggestive of malaria and who visited a healthcare facility were prospectively enrolled in six countries in sub-Saharan Africa… Of 1001 enrolled patients, 735 (73.4%) patients had confirmed malaria … at baseline (uncomplicated malaria: 598 [81.4%] and severe malaria: 137 [18.6%]). Of the confirmed malaria patients, 533 (72.5%) were administered a malaria rapid diagnostic test… In patients with uncomplicated malaria, the most prescribed treatments were artemisinin-based combination therapy (ACT; n = 564 [94.3],… in line with the World Health Organization (WHO) treatment guidelines. … However, in those with severe malaria, only 66 (48.2%) patients received parenteral treatment followed by oral ACT as per WHO guidelines, whereas 62 (45.3%) received parenteral treatment only.”

Side effects and complications

None this month

Drug resistance

“Artemisinin-based combinations therapy (ACT) is the current frontline curative therapy for uncomplicated malaria in Burkina Faso. Sulfadoxine-pyrimethamine (SP) is used for the preventive treatment of pregnant women (IPTp), while SP plus amodiaquine (SP-AQ) is recommended for children under five in seasonal malaria chemoprevention (SMC).” Tarama CW & al., Plasmodium falciparum Drug Resistance-Associated Mutations in Isolates from Children Living in Endemic Areas of Burkina Faso, Malaria J, 2023 Jul 20, 22:213, https://doi.org/ 10.1186/s12936-023-04645-9 aimed to assess the proportions of [various drug resistant] mutations in genes [from isolates of P. falciparum] collected during household surveys in Burkina Faso.” The authors conclude that “[t]he efficacy of ACT partner drugs and drugs used in IPTp and SMC does not appear to be affected by the low proportion of highly resistant mutants observed in this study.”

“The emergence of parasites resistant to artemisinin… has led to ACT treatment failure.” Azmi WA & al., Molecular Insights into Artemisinin Resistance in Plasmodium falciparum: An Updated Review, Infect Genet Evol. 2023 Aug; 112:105460, https://doi.org/10.1016/j.meegid.2023.105460 discusses the genetic and molecular details that have led to resistance, with the assertion that “[b]etter understanding of the molecular mechanisms underlying artemisinin resistance will accelerate implementation of scientific findings to solve problems with malarial infection.”

Sanmoung W & al. advocate the Application of Loop-Mediated Isothermal Amplification Combined with Lateral Flow Assay Visualization of Plasmodium falciparum Kelch 13 C580Y Mutation for Artemisinin Resistance Detection in Clinical Samples in Acta Trop. 2023 Aug 4: 106998, https://doi.org/10.1016/j.actatropica.2023.106998.  They state that this method is “faster and simpler than conventional polymerase chain reaction/DNA sequencing and has the potential to support antimalarial management policies, malaria control, and global elimination efforts.”

Ehrlich HY & al., Tracking Antimalarial Drug Resistance Using Mosquito Blood Meals: A Cross-Sectional Study, Lancet Microbe, 2023 Jun; 4(6):e461-e469, https://doi.org/10.1016/S2666-5247(23)00063-0 “aimed to assess the utility and feasibility of using blood-fed mosquitos (xenomonitoring) to conduct rapid surveillance of molecular markers associated with [antimalarial drug] resistance in human populations.”  Based on data provided in the abstract, the results failed to point to specific trends despite the authors’ assertion in the conclusion that temporal trends were established.

Osborne A & al. generated “resistance profiles on seventy asymptomatic and low-density P. falciparum infections from [an MDA] program implemented on Ngodhe island between 2015 and 2016. [The] assay encompasses established molecular markers” on genes associated with drug resistance. In Drug Resistance Profiling of Asymptomatic and Low-Density Plasmodium falciparum Malaria Infections on Ngodhe Island, Kenya, Using Custom Dual-Indexing Next-Generation Sequencing, Sci Rep. 2023 Jul 14; 13(1):11416, https://doi.org/10.1038/s41598-023-38481-3, the authors claim to have “presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.”

“Mass drug administration … with antimalarials has been shown to reduce prevalence and interrupt transmission in small populations … with reliable access to antimalarial drugs,” as stated in Nguyen TD & al., Antimalarial Mass Drug Administration in Large Populations and the Evolution of Drug Resistance, PLoS Glob Public Health. 2023 Jul 26; 3(7):e0002200. https://doi.org/10.1371/journal.pgph.0002200.  However, they also mention “that artemisinin-resistance evolution at the kelch13 locus can be accelerated by MDA when all three of the following conditions are met: (1) strong genetic bottlenecking that falls short of elimination, (2) re-importation of artemisinin-resistant genotypes, and (3) continued selection pressure during routine case management post-MDA. Accelerated resistance levels are not immediate but follow the rebound of malaria cases post-MDA, if this is allowed to occur.”

“Despite numerous efforts to control malaria, it persists, and the emergence and spread of resistance to ACTs {artemisinin combination therapy} make the development of new drugs or the possible reintroduction of discontinued drugs increasingly urgent. Sofeu-Feigeang DD & al., Status of the Multidrug Resistance-1 Gene of Plasmodium falciparum in Four Malaria Epidemiological Strata, Two Decades After the Abolition of Chloroquine as First-Line Treatment for Uncomplicated Malaria in Cameroon, J Trop Med, 2023 Jul 1; 2023:6688380, https://doi.org/10.1155/2023/6688380 reports that among 400 P. falciparum monoinfected samples… [t]he results suggest that P. falciparum … species with the susceptible genotype are gradually recapturing the parasite population” at least in the study areas of Cameroon.

New drug research

According to Mandal A & al., Transition Metal Complexes as Antimalarial Agents: A Review, ChemMedChem. 2023 Jul 12: e202300326, https://doi.org/10.1002/cmdc.202300326, “[s]everal recent reports have successfully demonstrated that the metal complexation of known organic antimalarial drugs can overcome drug resistance by showing enhanced activities than the parent drugs. This review [covers] research … done in the past few years [on the subject]. Based on transition metal series (3d, 4d, or 5d), the antimalarial metal complexes have been … compared with the similar control complexes as well as the parent drugs.” The authors also comment “on the potential issues and their possible solution for translating these metal-based antimalarial complexes into the clinic.”

Ravindar L, & al. published two articles about new approaches to antimalarial treatment. According to Triazole Hybrid Compounds: A New Frontier in Malaria Treatment, Eur J Med Chem, 2023 Jul 29; 259:115694, https://doi.org/10.1016/j.ejmech.2023.115694, “the emergence of triazole hybrid compounds stands out as a groundbreaking development…[The authors focus] on their broad spectrum of antimalarial activity of diverse hybridized 1,2,3-triazoles and 1,2,4-triazoles, structure-activity relationship (SAR), drug-likeness, bioavailability and pharmacokinetic properties reported since 2018 targeting multiple stages of the Plasmodium life cycle.” The other article, Recent Developments in Antimalarial Activities of 4-Aminoquinoline Derivatives, Eur J Med Chem. 2023 Aug 5; 256:115458, https://doi.org/10.1016/j.ejmech.2023.115458 states that [s]ince the 1960s, 4-aminoquinoline[s] {such as chloroquine, amodiaquine, and piperaquine} [have been] important antimalarial drug[s] due to [their] low toxicity, high tolerability, and rapid absorption after administration. This review focused on the antimalarial efficacy of the 4-aminoquinoline moiety hybridised with various heterocyclic scaffolds developed by scientists since 2018 against diverse Plasmodium clones.

“… urgent attention is needed for addressing the issues of drug resistance in falciparum malaria. High throughput screening methods have paved the way for rapid identification of anti-malarials … [D]rug repurposing helps in shortening the time required for drug safety approvals.”  Rai S & al., summarize “the recent computational approaches used for identifying novel antimalarials” in Drug Repurposing Against Novel Therapeutic Targets in Plasmodium falciparum for Malaria: The Computational Perspective, Curr Med Chem. 2023 Aug 7, https://doi.org/10.2174/0929867331666230807151708

According to Viswanathan NK & al, Synthesis and Activity of β-Carboline Antimalarials Targeting the Plasmodium falciparum Heat Shock 90 Protein, Bioorg Med Chem Lett. 2023 Jul 19: 129410, https://doi.org/10.1016/j.bmcl.2023.129410, a “collection of β-carbolines based on the natural product harmine, a compound known to target the heat shock 90 protein of Plasmodium falciparum, was synthesized and tested for antimalarial activity and potential toxicity. Several of these novel compounds display promising bioactivity, providing a new potential therapeutic with a mode of action that differs versus any currently available clinical treatment.”

Not a new drug, but a new delivery system is the subject of Li Y & al., Glutaraldehyde Modified Red Blood Cells Delivering Artesunate to the Liver as a Dual Therapeutic and Prophylactic Antimalaria Strategy, J Mater Chem B. 2023 Jul 17, https://doi.org/10.1039/d3tb00315a.  The authors state that “short half-life [of artesunate] in the blood makes it difficult to control the malaria infection completely.”  They devised a system of packaging the drug in red blood cells that have been treated with glutaraldehyde. In the mouse model, they demonstrated persistence of the drug in the liver up to nine days and propose that this points to improved efficacy of the drug.  The abstract is silent on the fact that this requires IV therapy and also on any potential red blood cell compatibility problems. 

Plant extracts and traditional treatments

“Malaria is the most widespread endemic disease in Cameroon, and asymptomatic Plasmodium (gametocyte) carriers … constitute more than 95% of infectious human reservoirs in malaria endemic settings.” Suh Nchang A & al., Knowledge About Asymptomatic Malaria and Acceptability of Using Artemisia afra Tea Among Health Care Workers (HCWs) in Yaoundé, Cameroon: A Cross-Sectional Survey, Int J Environ Res Public Health. 2023 Jul 6; 20(13):6309, https://doi.org/10.3390/ijerph20136309 “assesses the knowledge of asymptomatic malaria (ASM) among health care workers (HCWs) in health facilities … in the Centre Region of Cameroon and the acceptability of using Artemisia afra tea to treat” asymptomatic carriers.  Results of the survey used indicate that “[t]wo-thirds (67%) of respondents knew about Artemisia afra tea, …, and 79% were willing to prescribe it if authorized [for ASM]. There was a fair level of knowledge of ASM among HCWs in the study settings.”

Jeje TO & al., Antiplasmodial and Interferon-Gamma-Modulating Activities of the Aqueous Extract of Stone Breaker (Phyllanthus niruri Linn.) in Malaria Infection, Parasitol Int. 2023 Jul 18: 102789, https://doi.org/10.1016/j.parint.2023.102789 asserts that this plant that has been used in folk medicine to prevent kidney stones yields an aqueous extract that had in vitro antiplasmodial effect, as well as being effective in the mouse model of malaria. 

Caesalpina decapetala or Mysore thorn is an invasive plant introduced in a number of African countries as well as elsewhere in the world. Ochora DO & al., Ex Vivo and In Vitro Antiplasmodial Activity and Toxicity of Caesalpinia decapetala (Roth) Alston (Fabaceae), J Ethnopharmacol. 2023 Aug 5: 117007, https://doi.org/10.1016/j.jep.2023.117007 state that unspecified parts of it have been used in traditional medicine against malaria.  In their own study, they tested extracts of leaves, stem and roots and found that extracts of all three had beneficial effects in the mouse malaria model, roots being the strongest in this regard. They conclude that the plant “has the potential to suppress the growth of P. falciparum thereby contributing to combating the recurrent emergence of antimalarial drug resistance.”

Terminalia macroptera is a species of flowering plant known by the Hausa common name kwandari; it is native to Africa, where it is used in folk medicine, though not necessarily against malaria.  Sidiki NNA & al. nonetheless tested some of its extracts in the mouse model of malaria and found the ethanolic extract of stem bark to be suppressive in a dose-dependent way, though not equaling the suppression caused by chloroquine. The article is Antimalarial and Antioxidant Activities of Ethanolic Stem Bark Extract of Terminalia macroptera in Swiss Albino Mice Infected with Plasmodium berghei, J Parasitol Res. 2023 Jul 3; 2023:3350293, https://doi.org/10.1155/2023/3350293.

Two of the three plants combined in Abdulai SI & al.’s article about plant-based antimalarials, Antimalarial Activities of a Therapeutic Combination of Azadirachta indica, Mangifera indica and Morinda lucida Leaves: A Molecular View of its Activity on Plasmodium falciparum Proteins, Acta Parasitol. 2023 Jul 21, https://doi.org/10.1007/s11686-023-00698-7, are natives of India and one of West Africa.  Thus, it is somewhat puzzling that these combinations are recommended for further evaluation as folk-based remedies.

Although Maenpuen S & al., Mangiferin Is a New Potential Antimalarial and Anticancer Drug for Targeting Serine Hydroxymethyltransferase, Arch Biochem Biophys. 2023 Aug 3; 745:109712, https://doi.org/10.1016/j.abb.2023.109712 is an article primarily with Southeast Asia relevance, it is included in this report because of the almost universal availability of mangoes, the primary source of substance discussed.  Its antiplasmodial effect is said to be driven by its inhibition of serine hydroxy-methyltransferase. The primary thrust of the article, however, is the substance’s anti-cancer potential.

Other

“Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines and [Armstrong JF & al.] link pharmacological data clearly to the parasite stages to which it [sic] applies.” Their article, Advances in Malaria Pharmacology and the Online Guide to MALARIA PHARMACOLOGY: IUPHAR Review 38, Br J Pharmacol. 2023 Aug; 180(15):1899-1929, https://doi.org/10.1111/bph.16144 also highlights “the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology.”

“Zinc supplementation has been explored as a potential intervention to reduce the risk of malaria parasitaemia in randomised controlled trials (RCTs).” Based on extensive literature search, Kotepui M & al., Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials, Nutrients. 2023 Jun 23; 15(13):2855, https://doi.org/10.3390/nu15132855 reveals that there is no convincing evidence that zinc alone or in combination reduces the risk of Plasmodium parasitemia.

Successful treatment of malaria depends on access to it in space and time. Brunner NC & al., Starting at the Community: Treatment-Seeking Pathways of Children with Suspected Severe Malaria in Uganda, PLoS Glob Public Health. 2023 Jul 5; 3(7):e0001949, https://doi.org/10.1371/journal.pgph.0001949 is “an observational study in Uganda enrolled children below five years presenting to CHWs with signs of severe malaria. Children were followed up 28 days after enrolment to assess their condition and treatment-seeking history, including referral advice and provision of antimalarial treatment from visited providers.” The article concludes that children with severe malaria who were referred to a public referral facility and followed that advice (only 56%) were most likely to receive artemisinin combination therapy.  However, the abstract is silent on clinical outcomes.

Campaigns and Policies

Tine R & al. “conducted a broad stakeholder consultation process to identify pressing evidence gaps in malaria control and elimination across sub-Saharan Africa (SSA), and developed a priority list of country-driven malaria operational research (OR) and programme evaluation (PE) topics to address these gaps.” Their paper, Defining Operational Research Priorities to Improve Malaria Control and Elimination in Sub-Saharan Africa: Results from a Country-Driven Research Prioritization Setting Process, Malaria J, 2023 Jul 31, 22:219, https://doi.org/10.1186/s12936-023-04654-8 identified “33 emergent OR and PE topics … through the consultation process [that] were subsequently evaluated and prioritized by an external evaluation committee of experts from [National Malaria Programs], research institutions, and the WHO. The resulting prioritized OR and PE topics predominantly focused on generating evidence needed to close gaps in intervention coverage, address persistent challenges faced by NMPs in the implementation of core strategic interventions, and inform the effective deployment of new tools.”

Balikuddembe JK & al. “explored the trends in floods, as well as the association of their occurrence and duration with the malaria incidence in children < 5 years in five [East African] partner countries of Forum for China-Africa Cooperation (FOCAC), including Ethiopia, Kenya, Somalia, Sudan, and Tanzania between 1990 and 2019.” They report in Public Health Priorities for Sino-Africa Cooperation in Eastern Africa in Context of Flooding and Malaria Burden in Children: A Tridecadal Retrospective Analysis, BMC Public Health. 2023 Jul 11; 23(1):1331, https://doi.org/10.1186/s12889-023-16220-7 that “[b]etween 1990 and 2019, the occurrence and duration of floods among the five … partner countries of FOCAC increased and showed an upward trend. On the contrary, however, this had an inverse and negative weak correlation on the malaria incidence in children under five years.” In Kenya the negative correlation was very strong.  The authors acknowledge that many other factors may have influenced the changes.

“Large-scale irrigation schemes have the potential to permanently transform the landscape with health, nutritional and socio-economic benefits; yet this also leads to a shift in land-use patterns that can promote endemic and invasive insect vectors and pathogens. The balance between ensuring food security and preventing emerging infectious disease is a necessity; yet the impact of irrigation on vector-borne diseases at the epidemiological, entomological and economic level is uncertain and depends on the geographical and climatological context.” Jones CM & al. “highlight the risk factors and challenges facing vector-borne disease surveillance and control in an emerging agricultural ecosystem in the lower Shire Valley region of southern Malawi” in Integrating Vector Control Within an Emerging Agricultural System in a Region of Climate Vulnerability in Southern Malawi: A Focus on Malaria, Schistosomiasis, and Arboviral Diseases, Curr Res Parasitol Vector Borne Dis, 2023 Jul 13; 4:100133, https://doi.org/10.1016/j.crpvbd.2023.100133. 

Over the last two decades, global stakeholders and the Nigerian government have invested approximately $2 billion in malaria control, reducing parasite prevalence to 23% from 42% to 2010. However, there is a risk that the modest gains will be reversed due to unmet resource gaps. Backward integration is presented by Mokuolu OA & al. in A Conceptual Framework on the Role of Backward Integration in Sustainable Access to Malaria Intervention Commodities in Nigeria, Malaria J, 2023 Jul 26, 22:216, https://doi.org/10.1186/s12936-023-04641-z “as a viable option for sustainable funding of malaria intervention commodities in Nigeria… The funding shortfall was … 52.7% of the needs. Various funding scenarios were evaluated for their relative merits and limitations, including advocacy for more external funding, bank borrowing, increased domestic resources, and backward integration… The study concluded that backward integration should be used, based on a government-led public-private partnership that will increase local production of malaria intervention commodities that are accessible and affordable through market-based demand and supply arrangements.”

Opigo J & Guyer AL “searched two databases of peer-reviewed literature and one malaria-focused journal for examinations of strategic communications for malaria governance and found no publications that deal directly with the topic.” Rethinking Communications for Governance of Malaria Programs, PLoS Glob Public Health. 2023 Jul 31; 3(7):e0001132, https://doi.org/10.1371/journal.pgph.0001132 “proposes a framework for strategic communications for malaria governance that involves five key elements: knowing the audience, defining the message, designing a medium, identifying a messenger, and selecting the timing. … [The authors] draw on experiences from Uganda, where one of [them] leads the country’s National Malaria Control Division. Strategic communications can trigger improvements in malaria control by driving and supporting decision-making by individuals and leaders.

“Behaviour change communication (BCC) remains a central component of the interventions used in the fight against malaria in Ghana. However, there is limited evidence of its effectiveness. [Orkoh E & Efobi U] evaluated the effects of BCC strategies on knowledge (symptoms, causes and prevention) and overall knowledge of malaria among Ghanaian women aged 15-49 years.” As reported in Effects of Behaviour Change Communication on Knowledge and Prevention of Malaria Among Women in Ghana, Eval Rev, 2023 Aug 11; 193841X231194565, https://doi.org/10.1177/0193841X231194565, “[w]omen who participated in community-level education or heard/saw media messages on malaria, or both, had significantly more knowledge of the disease than women who lacked access to any of these mediums of communication. … Further analysis showed that improved knowledge of the disease is associated with higher preventive measures taken by women for themselves and for their children. The results are more significant in rural and poor households than in urban and non-poor households.”

Epidemiology

Climate change, biodiversity and environment

None this month

General epidemiology

“The objective to reduce global health inequalities and inequities is integral to the global development agenda, from the Universal Declaration of Human Rights to the Sustainable Development Goals and the ongoing response to COVID-19. Yet summary measures of global health gains or of the cost-effectiveness of global health programs barely capture how well they improve the lives of the most disadvantaged populations.” Haacker M, Contributions of Declining Mortality, Overall and from HIV, TB, and Malaria, to Reduced Health Inequality and Inequity Across Countries, Health Policy Plan. 2023 Jul 6: czad046, https://doi.org/10.1093/heapol/czad046 “instead explores the distribution of global health gains across countries, and the implications for health inequality and inequity … across countries. Specifically, it studies the distribution of gains in life expectancy across countries (overall and owing to reduced mortality from HIV, TB, and malaria), using the Gini index and a concentration index ranking countries by GDP per capita as indicators of health inequality and inequity. By these counts, global inequality in life expectancy across countries declined by one-third between 2002 and 2019. Reduced mortality from HIV, TB, and malaria accounted for one-half of this decline. 15 countries in sub-Saharan Africa, containing 5 percent of the global population, accounted for 40 percent of the global decline in inequality, with nearly six-tenth[s] of this contribution coming from HIV, TB, and malaria.

Munsey A & al. compared “[m]alaria test positivity rates and questionnaire data from ANC attendees at 39 health facilities … to questionnaire data and positivity rates among children from two cross-sectional surveys in the facilities’ corresponding catchment areas [and] investigated whether data collected during antenatal care (ANC) can provide relevant information for decision-makers.” Assessing the Utility of Pregnant Women as a Sentinel Surveillance Population for Malaria in Geita, Tanzania, 2019 – 2021, Int J Infect Dis, 2023 Aug 9; S1201-9712(23)00691-4, https://doi.org//10.1016/j.ijid.2023.08.007 reports that “[t]rends in parasitemia among ANC attendees were predictive of trends in parasitemia among children at the council level … Primigravid ANC attendees had the lowest rates of net ownership … and use … ANC attendees reported higher levels of care seeking, … malaria testing, … and treatment for children with fever … compared to women surveyed in households, raising concerns about social desirability bias disproportionately impacting ANC surveys.”

In Mozambique, Pujol A & al., Detecting Temporal and Spatial Malaria Patterns from First Antenatal Care Visits, Nat Commun, 2023 Jul 6; 14(1):4004, https://doi.org/10.1038/S41467-023-39662-4 also reports that “ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status…”

“…children with asymptomatic Plasmodium falciparum (Pf) malaria infection had higher Kaposi sarcoma-associated herpesvirus (KSHV) viral load, increased risk of KSHV seropositivity and higher KSHV antibody levels.” In Plasmodium falciparum Malaria Is Associated with Increased KSHV Seropositivity and Higher KSHV Antibody Breadth and Magnitude: Results of a Case-Control Study from Rural Uganda, J Infect Dis. 2023 Aug 4: jiad308, https://doi.org/10.1093/infdis/jiad308, Nalwoga A& al. report on their investigation of “the association between clinical malaria and KSHV seropositivity and antibody levels.” Over 15 months, 308 children aged 5 to 10 years were tested for malaria and KSVH.  Among Pf uninfected children, 60% were seropositive for KSHV, whereas among children with clinical malaria, 95% were seropositive for KSHV.  “Furthermore, … children [with clinical malaria] had higher KSHV IgG and IgM antibody levels and reacted to more KSHV antigens compared to uninfected children.” The authors suggest that “Pf is affecting KSHV immunity.”

“The control of asymptomatic malaria is considered a key aspect of malaria control. Orish VN & al., aimed to assess the knowledge and perception of asymptomatic malaria among people in Ho municipality of the Volta region [of Ghana]. In their article, Knowledge and Perception of Asymptomatic Malaria in the Volta Region of Ghana, Trans R Soc Trop Med Hyg. 2023 Aug 3: trad049, https://doi.org/10.1093/trstmh/trad049, they describe generalized awareness of the population of asymptomatic malaria, but not of the fact that it is transmissible.

“Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown.” Andronescu LR & al. monitored “[i]nfants from two birth cohorts in Malawi … at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria.” Plasmodium falciparum Infection and Disease in Infancy Associated with Increased Risk of Malaria and Anaemia in Childhood, Malaria J, 2023 Jul 26, 22:217, https://doi.org/10.1186/s12936-023-04646-8 reports that “[i]nfants with at least one P. falciparum infection during their first 6 months had increased incidence ratio … of P. falciparum infection … and clinical malaria … compared to infants without infection. … Exposure to malaria was associated with lower … haemoglobin levels than unexposed infants at every time interval…”

Biswas S & al., Role of Human Twin Studies to Identify Genetic Linkage of Malaria Pathogenesis and Outcomes, Am J Trop Med Hyg. 2023 Jun 5; 109(2):241-247, https://doi.org/10.4269/ajtmh.23-0028 analyzes “the available literature on malaria and human twins and discuss the significance and benefits of twin studies to help in better understanding malaria.”

“Antibody responses to Plasmodium falciparum parasites persist after infection and therefore measuring antibodies has the potential to overcome several of the current obstacles to accurate malaria surveillance.” Bérubé S & al., Novel Bioinformatic Methods and Machine Learning Approaches Reveal Candidate Biomarkers of the Intensity and Timing of Past Exposure to Plasmodium falciparum, PLoS Glob Public Health. 2023 Aug 2; 3(8):e0001840, https://doi.org/10.1371/journal.pgph.0001840 notes that “analysis of 479 serum samples from individuals in three regions in southern Africa with different historical levels of P. falciparum malaria transmission … revealed regional differences in antibody responses to P. falciparum antigens among children under 5 years of age … [The authors] used antibody responses to Plasmodium antigens as predictors … [to] classify samples from adults into… three regions of differing historical malaria transmission with high accuracy… Measuring antibody responses to these antigens could lead to improved malaria surveillance.”

Gómez-Pérez GP & al., Reduced Incidence of Respiratory, Gastrointestinal and Malaria Infections Among Children During the COVID-19 Pandemic in Western Kenya: An Analysis of Facility-Based and Weekly Diaries Data, J Glob Health. 2023 Jul 14; 13:06024, https://doi.org/10.7189/jogh.13.06024 asserts that “COVID-19-related containment measures in Western Kenya were accompanied by a decline in respiratory infections, enteric illnesses, and malaria / fever mainly in children. Data from a population-based survey and facility-based records aligned regarding this finding despite the temporary shift to non-facility-based consultations and confirmed that the drop in utilization of health care services was not due to decreased accessibility, but rather to a lower incidence of these infections.”

Hassou-Djossou D & al., Attitudes and Prevention Towards Malaria in the Context of COVID-19 Pandemic in Urban Community in Benin, West Africa, Malaria J, 2023 Aug 4, 22:228, https://doi.org/10.1186/s12936-023-04663-7 “was conducted to describe the potential effects of the pandemic on urban dwellers attitudes, prevention and treatment against malaria in four major cities of Benin… More than 90% of the participants interviewed had a good level of knowledge about the transmission and prevention of malaria in the cities surveyed. In contrast, low proportions of participants reported visiting health-care facilities when they suspected malaria…. Among the reasons for not seeking care, [those] related to COVID-19 were the most mentioned. … which might have increased the fear to go to the health facilities. Finally, high proportions of self-medication practice were mentioned with high use of malaria drugs to treat both malaria and to protect against COVID-19.”

Tiedje KE & al. “introduce a new endpoint ‘census population size’ to evaluate the epidemiology and control of Plasmodium falciparum infections, where the parasite, rather than the infected human host, is the unit of measurement. To calculate census population size, [the authors] rely on a definition of parasite variation known as multiplicity of infection (MOI var), based on the hyper-diversity of the var multigene family… [They] track changes in this parasite population size and structure through sequential malaria interventions by indoor residual spraying (IRS) and seasonal malaria chemoprevention (SMC) from 2012 to 2017 in an area of high-seasonal malaria transmission in northern Ghana. Following IRS, which reduced transmission intensity by > 90% and decreased parasite prevalence by ∼40-50%, significant reductions in var diversity, MOI var, and population size were observed in ∼2,000 humans across all ages. These changes… were short lived and 32-months after IRS was discontinued and SMC was introduced, var diversity and population size rebounded in all age groups except for the younger children (1-5 years) targeted by SMC. The article is Measuring Changes in Plasmodium falciparum Census Population Size in Response to Sequential Malaria Control Interventions, medRxiv. 2023 Aug 2: 2023.05.18.23290210, https://doi.org/10.1101/2023.05.18.23290210.

The objective of Miezan AJS & al.’s study, Molecular Epidemiology of Non-Falciparum Plasmodium Infections in Three Different Areas of the Ivory Coast, Malaria J. 2023 Jul 19; 22(1):211, https://doi.org/10.1186/s12936-023-04639-7 “was to determine the molecular epidemiology of plasmodial infection due to P. malariae and P. ovale in Côte d’Ivoire.”  Among 360 patients recruited (approximately 50% each men and women), “[t]he overall Plasmodium positive rate was 72.5% … The specific index was 77.4% and 1.5% for P. falciparum and P. malariae in mono-infection, respectively. There was also 15% P. falciparum and P. malariae co-infection, 3.4% P. falciparum and P. ovale co-infection and 2.3% P. falciparum, P. malariae and P. ovale triple-infection.”

Plasmodium vivax is the second-most common malaria pathogen globally but is considered very rare in the predominantly Duffy-negative sub-Saharan African population,” state van Loon W & al. in Plasmodium vivax Malaria in Duffy-Positive Patients in Rwanda, Am J Trop Med Hyg. 2023 Aug 7: tpmd230143, https://doi.org/10.4269/ajtmh.23-0143. “In 259 malaria patients from highland southern Rwanda, [the authors] assessed Plasmodium species and Duffy blood group status by polymerase chain reaction (PCR). … P. vivax, [was] seen in … 8.1%, …. Plasmodium vivax occurred more frequently as a monoinfection than in combination with P. falciparum. All P. vivax-infected individuals showed heterozygous Duffy positivity, whereas this was the case for only 3.1% of patients with P. falciparum monoinfection and malaria-negative control subjects (P < 0.01).”

“WHO now only recognises malaria elimination in countries with negligible risks of zoonotic malaria, making zoonotic simian malaria a critical barrier to malaria elimination globally.” Fornace KM & al., Simian Malaria: A Narrative Review on Emergence, Epidemiology and Threat to Global Malaria Elimination, Lancet Infect Dis, 2023 Jul 13, https://doi.org/10.1016/S1473-3099(23)00298-0 reviews “the global distribution and drivers of simian malaria and identif[ies] priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and [vice versa]. …. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally.”

“In parts of the east and southern Africa region, … Anopheles funestus, has established itself as an exceptionally dominant vector in some areas, it is responsible for more than 90% of all malaria transmission events.” Odero JO & al., Advances in the Genetic Characterization of the Malaria Vector, Anopheles funestus, and Implications for Improved Surveillance and Control, Malaria J, 2023 Aug 8, 22:230, https://doi.org/10.1186/s12936-023-04662-8. The article concentrates on “four research themes relevant to the biology and control of An. funestus in Africa, namely: (i) the taxonomic characterization of different vector species within the Funestus group and their role in malaria transmission; (ii) insecticide resistance profile; (iii) population genetic diversity and gene flow, and (iv) applications of genetic technologies for surveillance and control.”

“Characterizing the entomological profile of malaria transmission at fine spatiotemporal scales is essential for developing and implementing effective vector control strategies.” Taconet P & al., Anopheles Sampling Collections in the Health Districts of Korhogo (Côte D’Ivoire) and Diébougou (Burkina Faso) Between 2016 and 2018, GigaByte. 2023 Jun 30; 2023:gigabyte83 https://doi.org/10.46471/gigabyte.83 presents a “fine-grained dataset of Anopheles mosquitoes” collected in two adjacent health districts in West Africa. “Over 60,000 Anopheles were collected (mainly A. gambiae s.s., A. coluzzii, and A. funestus). The dataset is published as a Darwin Core archive in the Global Biodiversity Information Facility, comprising four files: events, occurrences, mosquito characterizations, and environmental data.”

“The widespread emergence of insecticide resistance in the population of adult female malaria mosquitoes is considered to pose a potential challenge” to the eradication of malaria. Mohammed-Awel J & Gumel AB, Can Insecticide Resistance Increase Malaria Transmission? A Genetics-Epidemiology Mathematical Modeling Approach, J Math Biol. 2023 Jul 12; 87(2):28, https://doi.org/10.1007/s00285-023-01949-x describes “a genetics-epidemiology modeling framework that incorporates a detailed genotype structure of the gene that confers insecticide resistance in mosquitoes, malaria epidemiology in mosquitoes and humans (stratified based on whether or not they are protected by Long-lasting insecticide-treated nets (LLINs) indoors), genotype-specific mosquito repellance property of LLINs and mosquito biting behavior (indoor and outdoor bites).”

Spatiotemporal studies

Ibrahim AO & al., Malaria Infection and Its Association with Socio-Demographics, Long Lasting Insecticide Nets Usage and Hematological Parameters Among Adolescent Patients in Rural Southwestern Nigeria, PLoS One. 2023 Jul 14; 18(7):e0287723, https://doi.org/10.1371/journal.pone.0287723

Seidu Z & al., Plasmodium falciparum Infection and Naturally Acquired Immunity to Malaria Antigens Among Ghanaian Children in Northern Ghana, Parasite Epidemiol Control. 2023 Jul 20; 22:e00317, https://doi.org/10.1016/j.parepi.2023.e00317

Lelisa K & al., Malaria Positivity Rate Trend Analysis at Water Resources Development Project of Wonji Sugar Estate Oromia, Ethiopia, Parasitol Res. 2023 Jul 29, https://doi.org/10.1007/s00436-023-07923-2

Olani Z & al., A Five-Year (2016-2020) Trend Analysis of Malaria Surveillance Data in Oromia Regional State, Ethiopia, Biomed Res Int, 2023 Aug 5; 2023:5278839, https://doi.org/10.1155/2023/5278839. 

Teka H & al., Trend Analysis of Malaria in Urban Settings in Ethiopia from 2014 to 2019, Malaria J, 2023 Aug 14, 22:235, https://doi.org/10.1186/s12936-023-04656-6

 

 

 

 

Reflections on our Malaria Work in Zambia – How we got here, where we go next

Reflections on our Malaria Work in Zambia – How we got here, where we go next

On September 8th, 2023, the Rotary International President Gordon McInally announced that Rotary and its partners World Vision and the Bill and Melinda Gates Foundation will be implementing the Rotary Healthy Communities Challenge which will build on the successes of the Partners for a Malaria-Free Zambia project and scale that work to 3 other countries.

Malaria Ends With Me

Malaria Ends With Me

By Peter Mubanga Ng’andu – Rotaract Club of Lusaka
As a Project Management & M&E professional, I believe in data driven interventions and that’s why when an opportunity to volunteer in Data Quality Audits (DQA) emerged, I gladly took it in the spirit of service above self.

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