By Dr. Derick Pasternak, Ambassador, Malaria Science & Research Coordinator, MPI
“In a historic step toward combating malaria in Nigeria, the first-ever malaria vaccines have been delivered to the Government of Nigeria, thanks to efforts by Gavi, the Vaccine Alliance, UNICEF and WHO” according to a press release on 17 October by GAVI… “The malaria vaccine, which requires four doses, will be administered to children under one year of age as part of Nigeria’s Routine Immunization schedule.” The press release is silent on which WHO approved vaccine was delivered.
On 20 October, the WHO certified Egypt as malaria-free. “Egypt is the third country to be awarded a malaria-free certification in the WHO Eastern Mediterranean Region following the United Arab Emirates and Morocco, and the first since 2010. Globally, a total of 44 countries and 1 territory have reached this milestone.”
Medicines for Malaria Venture (MMV) and Quotient Sciences have dosed the first participants in a trial of MMV371, a long-acting injectable (LAI) for the prevention of malaria. Taking place at Quotient Science’s clinic in Nottingham, UK, healthy participants are being administered with MMV371, a derivative of atovaquone that is already approved as Malarone (atovaquone-proguanil), as a LAI the companies state may provide up to three months of protection from malaria with a single intramuscular dose. The Phase I, randomised, dose-escalation trial (NCT06558643) will evaluate the drug’s safety, tolerability, and pharmacokinetics… https://www.clinicaltrialsarena.com/news/first-participants-dosed-in-trial-of-long-acting-malaria-preventative/
“Chad has launched three vital new vaccines in its Expanded Programme on Immunization. These are vaccines against malaria (unspecified as to which one), pneumococcal infections and rotavirus diarrhea, making Chad one of the first countries to introduce three vaccines at the same time. The introductions are being implemented by the Ministry of Health with support from Gavi, the Vaccine Alliance, UNICEF and WHO. … The deployment of these vaccines will be … in several phases for the malaria vaccine, with an initial launch in 28 health districts.” https://www.gavi.org/news/media-room/chad-launches-vaccination-against-malaria-pneumococcal-disease-and-rotavirus
The Democratic Republic of Congo also received malaria vaccines on 31 October, this time specified as the R21-Matrix M. https://www.afro.who.int/countries/democratic-republic-of-congo/news/democratic-republic-congo-introduces-r21-malaria-vaccine
On the same day, the WHO reported a significant increase in malaria in Ethiopia, where between 1 January and 20 October this year, there were “over 7.3 million malaria cases and 1157 deaths… [In Ethiopia] approximately 75% of the land mass is considered to be endemic to malaria. Around 69% of the population residing in these areas face the risk of infection where periodic outbreaks contribute to up to 20% of deaths among children under the age of five.” https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON542
As of 4 November, Sudan also received its first batch of malaria vaccines (again, not specified in the press release). https://www.unicef.org/sudan/press-releases/sudan-rolls-out-first-malaria-vaccines-0
Knols, BGJ, A Shot in the Foot: Could Chemical Control of Malaria Vectors Threaten Food Security? Malaria World J, 2024 Oct 22, 15:13 https://www.malariaworld.org/malariaworld-journal/a-shot-in-the-foot-could-chemical-control-of-malaria-vectors-threaten-food-security is an opinion piece (subtitled MWJ Hardtalk), elaborating the notion that the increasing amount of insecticidal chemicals used in malaria prevention may eventually harm the environment, especially when considering the likely disposal practices of insecticide treated nets. The author points out other promising approaches to vector control, such as symbiont bacteria and fungi and gene drive practices and expresses regret that that they received less attention by researchers than the chemicals. The issue of threatening the food supply appears to be speculative.
PEER REVIEWED ARTICLES (see notes after citations from non-peer-reviewed publications)
Prevention
Vaccines
“The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6–12 weeks compared with children aged 5–17 months (for whom this vaccine is recommended). [Macià D & al.] aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies.” In their paper, The Effect of Plasmodium falciparum Exposure and Maternal Anti-Circum-sporozoite Protein Antibodies on Responses to RTS,S/AS01E Vaccination in Infants and Children: An Ancillary Observational Immunological Study to a Phase 3, Randomised Clinical Trial, Lancet Infect Dis, 2024 Oct 23, https://doi.org/10.1016/S1473-3099(24)00527-9 , they disclose their findings, which relate to the interference of passive immunity obtained from maternal antibodies that are present in very young infants. There is also a related commentary, Palacpac NMQ & Horii T, Understanding the Immunogenicity of RTS,S in Infants, Lancet Infect Dis, 2024 Oct 23, https://doi.org/10.1016/S1473-3099(24)00590-5.
Mitchell RA & al. (the same research group as above) also published a paper on the specific effect of the booster (fifth) dose of the vaccine, Effect of RTS,S/AS01E Vaccine Booster Dose on Cellular Immune Responses in African Infants and Children, NPJ Vaccines. 2024 Oct 25; 9:200, https://doi.org/10.1038/s41541-024-00977-y. The authors conclude that there is “moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.”
“Despite existing interventions, such as long-lasting insecticidal nets, indoor residual spraying, and intermittent preventive treatment, the re-emergence of malaria underscores the need for innovative preventive strategies.” Eneh S & al. “explore the potential of utilizing mobile phone caller tunes to raise awareness and promote the uptake [i.e. acceptance] of the RTS,S malaria vaccine” in their article, Designing and Deploying Caller Tunes on Mobile Phones to Promote Malaria Vaccine Uptake in Africa: Can the Technology Acceptance Model (TAM) Help? Malaria J, 2024 Nov 2, 23:325, https://doi.org/10.1186/s12936-024-05134-3. The article appears to be speculative, weighing the extensive collaborative efforts required to produce the messages to be included in caller tunes and the likelihood of the population reacting favorably to them.
Ghazy RM & al. report on a survey among 818 parents in Examining Vaccine Hesitancy Among Ghanaian Parents for the R21/Matrix-M Malaria Vaccine, J Pediatr Health Care. 2024 Oct 3: S0891-5245(24)00141-X, https://doi.org/10.1016/j.pedhc.2024.05.010. Close to 30% of those interviewed were hesitant to vaccinate their children. People living in forests, with younger children, having the youngest child aged 1-3 years, [and] skipping antenatal care or scheduled vaccinations … were vaccine-hesitant. However, healthcare workers, those having a relative who died from malaria, and those who vaccinated their child against malaria were less hesitant.”
Vaccines developed from attenuated whole P. falciparum sporozoites are investigated in many locations. Tumbo A & al., PfSPZ Vaccine Induces Focused Humoral Immune Response in HIV Positive and Negative Tanzanian Adults, EBioMedicine. 2024 Sep 30; 108:105364, https://doi.org/10.1016/j.ebiom.2024.105364 focuses on the development of humoral [i.e. circulating] antibody formation in volunteer subjects and report that there is no difference in response between HIV positive and HIV negative individuals.
Yet another vaccine under development (PfRH5) is to a specific binding protein on the surface of P. falciparum. Thiam LG & et al., Vaccine-Induced Human Monoclonal Antibodies to PfRH5 Show Broadly Neutralizing Activity Against P. falciparum Clinical Isolates, NPJ Vaccines. 2024 Oct 24; 9:198, https://doi.org/10.1038/s41541-024-00986-x is a report on exposing laboratory-grown P. falciparum to antibodies developed by volunteer vaccinees in the UK. The authors claim their article to be “the first report on the susceptibility of P. falciparum clinical isolates from natural infections to vaccine-induced human [monoclonal antibodies] to PfRH5.”
Vectors
Oberlin A & al., Effect of Indoor Residual Spraying [IRS] on Malaria in Pregnancy and Pregnancy Outcomes: A Systematic Review, Am J Trop Med Hyg. 2024 Oct 29: tpmd240435, https://doi.org/10.4269/ajtmh.24-0435 is a review of 17 studies meeting the criteria of the subject. “Thirteen studies reported on the effect of IRS on malaria endpoints during pregnancy, five on birth outcomes, and one on a fetal anomaly. Twelve of the 13 studies exploring maternal malaria and 3 of 3 studies reporting on placental malaria demonstrated a reduction among those exposed to IRS during pregnancy. Results were more mixed for obstetric outcomes. Two of the best-quality studies showed reductions in preterm birth, low birthweight, and fetal/neonatal mortality; a third high-quality study did not demonstrate a reduction in perinatal mortality but did not evaluate preterm birth.” In view of the “MW Hardtalk” article above, it is interesting that one study concluded that IRS was associated with increased frequency of preterm brtih, though the authors considered it a “study of lower quality.”
“Intense pyrethroid resistance threatens the effectiveness of the primary vector control intervention, insecticide-treated nets (ITNs), in Nigeria, the country with the largest malaria burden globally.” Davis KM & al., An Observational Analysis of the Impact of Deltamethrin + Piperonyl Butoxide Insecticide-Treated Nets on Malaria Case Incidence and Entomological Indicators in Ebonyi State, Nigeria, 2017–2021, Malaria J, 2024 Oct 19, 23:317, https://doi.org/10.1186/s12936-024-05137-0 compared the incidence of malaria in a state where piperonyl butoxide (PBO) was also used to impregnate ITNs with as state where PBO was not added and also with modeled data. In both instances, the addition of PBO gave favorable results in terms of reduction of incidence of malaria.
Ogutu N & al. compared the effectiveness of three net products impregnated with two active insecticides in experimental hut trials with volunteer sleepers. They report in Efficacy of PermaNet® Dual Compared to Interceptor® G2 and Permanet 3.0 in Experimental Huts in Siaya County, Western Kenya, Malaria J, 2024 Nov 2, 23:326, https://doi.org/10.1186/s12936-024-05157-w that the newer preparation of PermaNet® Dual matches the efficacy of the Interceptor® G2 brand already in widespread use. The results, which confirm other publications on the same subject, indicate that “PermaNet® Dual met the WHO criteria for non-inferiority to Interceptor® G2” and was superior to Permanent 3.0.
Like many other authors all over sub-Saharan Africa, Oroge O & al. found on interviewing 1642 households in Nigeria that ITN ownership does not necessarily lead to appropriate use, nor are the nets as durable as they might be. They report in Preserving Nets, Protecting Children: An Evaluation of Factors Influencing the Utilization and Physical Integrity of Long-Lasting Insecticidal Nets Among Under-Five Children in Osun State, Nigeria, Malaria J, 2024 Nov 5, 23:329, https://doi.org/10.1186/s12936-024-05149-w that 10.4% of those interviewed never “hang their net. Holes were present in [ITNs] in 360 (22.7%) households and 196 (12.4%) had dusty or stained nets. … survey participants reported that 1331 (83.9%) under-fives slept under an [ITN] the night before the survey. Factors associated with reported [ITN] use were; older parents/guardians aged 50–59 years …, having a post-secondary education …, having [ITN] obtained < 12 months …, households with one [ITN] for every 2 members … and households with clean nets …”
Although Hien AS & al., What Happens to Old Insecticide-Treated Nets After Households Use in Burkina Faso? Malaria J, 2024 No 20, 23:350, https://doi.org/10.1186/s12936-024-05181-w was published after the cautionary opinion of Knols (see above, MW Hardtalk), it echoes some of the themes in the latter. Use of old nets included among others fencing and bed covers, which may expose humans and animals to direct contact with pyrethroids, which, while not as toxic as organophosphates, are still harmful to mammals as well as to insects. The authors recommend the following: “Addressing gaps in disposal guidelines, promoting safe and beneficial reuse practices, and actively involving communities in the decision-making process can help mitigate health risks associated with the improper disposal and repurposing of old insecticide-treated nets and improve the overall effectiveness of malaria control programmes.”
The so-called “knock-down resistance” in Anopheles has never been observed in An. funestus, the major malaria vector in Tanzania, according to Odero JO & al., Discovery of Knock-Down Resistance in the Major African Malaria Vector Anopheles funestus, Mol Ecol. 2024 Oct 7: e17542, https://doi.org/10.1111/mec.17542. This article reports on a study that identifies the gene responsible for the resistance in Tanzania. This resistance is primarily against DDT, which has been banned in Tanzania for many years, so the authors consider this finding as evidence that the banned substance persists in the environment or is being illegally used.
Gueye A & al. report on genetic studies on insecticide resistance in Senegal in Insecticide Resistance and Target-Site Mutations kdr, N1575Y, and Ace-1 in Anopheles gambiae s.l. Populations in a Low-Malaria-Transmission Zone in the Sudanian Region of Senegal, Genes (Basel). 2024 Oct 16; 15(10):1331, https://doi.org/10.3390/genes15101331
Insecticide resistance is not the only reason for persistence of malaria even in communities that utilize ITNs and other preventive measures indoors. Mukisa MC& al., Analysis of the 24-h Biting Patterns and Human Exposures to Malaria Vectors in South-Eastern Tanzania, Parasit Vectors. 2024 Oct 30; 17:445, https://doi.org/10.1186/s13071-024-06521-0 reports that the three species of Anopheles that thrive in SE Tanzania all have feeding patters that include daytime hours when adults and children are active outdoors.
Liang Y & al. state that they were able to create a stable, genetically transmissible symbiont mosquito line in their article, Stable Introduction of Wolbachia wPip into Invasive Anopheles stephensi for Potential Malaria Control, PLoS Negl Trop Dis. 2024 Sep 26; 18(9):e0012523, https://doi.org/10.1371/journal.pntd.0012523. The authors’ rationale is that “successful use of the maternally inherited endosymbiotic bacterium Wolbachia for arbovirus control has inspired the exploration of similar strategies for managing malaria vectors, necessitating the establishment of a stable Wolbachia-Anopheles symbiosis.”
Another microorganism that becomes a symbiont of Anopheles and blocks transmission of Plasmodium is the fungus Microsporidia MB. Onchuru TO & al. review the mechanism of this organism’s vertical transmission in The Plasmodium Transmission-Blocking Symbiont, Microsporidia MB, is Vertically Transmitted Through Anopheles arabiensis Germline Stem Cells, PLOS Pathogens, 2024 Nov 14, https://doi.org/10.1371/journal.ppat.1012340.
Mwema T & al. reviewed the literature on control of An. stephensi. While most of these articles come from Asia, where the vector as long been known to transit the parasite, the findings are just as relevant to the various African countries where this species has now been discovered to exist. The authors seem to take issue with some of the control measures advocated in some of the literature, advocating biologic control and larviciding in their article, A Quantitative and Systematic Analysis of Anopheles stephensi Bionomics and Control Approaches, Acta Trop. 2024 Oct 18: 107431, https://doi.org/10.1016/j.actatropica.2024.107431.
Ogoyi DO & al. conducted published data on gene drive projects in Africa. “Review of genetic biocontrol technologies showed only limited lessons from post-release monitoring regimes with a focus largely limited to efficacy. For genetically modified organisms general surveillance and case-specific monitoring is expected in some of the regions. A number of post-release monitoring concerns in relation to the protection goals of human and animal health, biodiversity, and water quality were identified. Their paper is Post-Release Monitoring Pathway for the Deployment of Gene Drive-Modified Mosquitoes for Malaria Control in Africa, Malaria J, 2024 Nov 20, 23:351, https://doi.org/10.1186/s12936-024-05179-4.
Muhoro AM & al. report on their laboratory study of an alternative toxin as part of attractive toxic sugar bait (ATSB) for Anopheles mosquitoes, They report in A Study on the Effectiveness of (+)-Usnic Acid as Oral Toxic Sugar Bait Against Adult Male and Female Anopheles gambiae, Malaria J, 2024 Oct 17, 23:311, https://doi.org/10.1186/s12936-024-05141-4 that there was “high mortality of both male and female An. gambiae after ingestion of the toxic sugar bait. 15 mg/ml usnic acid [UA] caused the highest mortality (50%) within the first 4 h compared to 5 and 10 mg/ml (+)-UA… High mortality was observed among females over the first 4 h (60%) compared to males (40%) due to higher feeding rate of the toxic agent…(+)-UA may be an alternative active ingredient as toxic bait in the effort to reduce and eliminate the transmission of Plasmodium falciparum …”
“Malaria is epidemic … due to the limited viability of Anopheles species in the desert climate” such as Northern Mali. Traore MM & al. demonstrate in The Efficacy of Attractive Targeted Sugar Baits in Reducing Malaria Vector Abundance in Low-Endemicity Settings of Northwest Mali, Malaria J, 2024 Oct 23, 23:319, https://doi.org/10.1186/s12936-024-05098-4 that the use of attractive targeted sugar baits (ATSBs) in the area they studied resulted in a lower proportion of older female Anopheles gambiae mosquitoes and lower proportion of mosquitoes that were infected by malaria sporozoites. Why this shift in population mix is the result of deploying ATSBs is unexplained.
Kahamba NF & al. “examined how communities use aquatic habitats and how these practices may impact LSM [larval source management] strategies, with a focus on habitats used by An. funestus.” They report that 90% of the habitats studied “were used by communities, including 95% of those with An. funestus larvae, for activities such as domestic chores, agriculture, livestock rearing, brickmaking, and fishing. Focus group discussions revealed a willingness to adopt LSM, with a preference for larviciding and habitat modification over habitat removal, as the water sources were vital for daily use.” The article is Societal Uses of the Main Water Bodies Inhabited by Malaria Vectors and Implications for Larval Source Management, Malaria J, 2024 Nov 9, 23:336, https://doi.org/10.1186/s12936-024-05154-z,
According to Nyasvisvo DS & al., Characterization of Anopheles Mosquito Breeding Habitats for Malaria Vector Control in Mazowe and Shamva Districts, Zimbabwe, J Vector Borne Dis. 2024 Oct 5, https://doi.org/10.4103/jvbd.jvbd_85_24, four different Anopheles species prefer different portions of the wetland environment for oviposition. The authors conclude that “[s]ize, origin, and type of breeding habitat were positive indicators for different Anopheles species in the study area. Potential malaria vector breeding habitats should be targeted for larval control under the current malaria control and elimination phases in the two districts.’
Belay AK & al., Feeding Habits and Malaria Parasite Infection of Anopheles Mosquitoes in Selected Agroecological Areas of Northwestern Ethiopia, Parasit Vectors. 2024 Oct 3; 17(1):412, https://doi.org/10.1186/s13071-024-06496-y is an enumeration of a number of different malaria vector mosquitoes found in field sampling and their feeding habits based on gut content analysis. Three of five Anopheles species found were infected with Plasmodium parasites.
Similar to the above paper, Tarekegn M & al. “investigated the feeding preference, biting behaviours and resting behaviours of Anopheles mosquitoes in selected localities…” Thgey conclude in A Survey of Malaria Vectors Feeding Preference, Biting Site and Resting Behaviour in the Malaria Elimination Settings of Dembiya District, North-Western Ethiopia, Malaria J, 2024 Nov 20, 23:352, https://doi.org/10.1186/s12936-024-05148-x that “Anopheles mosquitoes in Dembiya district were more likely to seek a host and rest outdoors than indoors. A reevaluation of vector control strategies is needed to ensure Ethiopia remains on the path to malaria elimination.”
See Adeniyi L & al., Delivering Insecticide-Treated Nets (ITNs) Through a Digitized Single-Phase Door-to-Door Strategy: Lessons from Ondo state, Nigeria, Malaria J, 2024 Oct 28, 23:322, https://doi.org/10.1186/s12936-024-05145-0 and Garcia GA, & al. The Challenge of Improving Long-Lasting Insecticidal Nets Coverage on Bioko Island: Using Data to Adapt Distribution Strategies, Malaria J, 2024 Oct 29, 23:324, https://doi.org/10.1186/s12936-024-05139-y under Campaigns and Policies.
Chemoprophylaxis
Echoing the findings of other reports on intermittent treatment of pregnancy (IPTp-SP), Iddrisu H, & al. report in their paper, Adherence to Sulfadoxine-Pyrimethamine Five-Dose Policy Among Pregnant Women in an Urban Slum in Ghana: A Mixed-Methods Study, Malaria J, 2024 Oct 17, 23:310, https://doi.org/10.1186/s12936-024-05127-2 that only 20 of 232 nursing mothers reported adhering to the Ghana authorities’ recommendation of five doses (IPT5, as opposed to WHO’s three doses) of sulfadoxine-pyrimethamine during their pregnancies. “Respondents who began [antenatal care] in the second trimester were 81% less likely to adhere to IPT5 than those who began in the first trimester …. Healthcare provider and health system factors that influence IPT5 uptake include healthcare providers’ knowledge of IPTp-SP guidelines, the practice of Directly Observed Therapy, education of pregnant women, training of healthcare providers, and availability of water.”
Adegbola AJ & al., Assessment of Uptake of Sulphadoxine-Pyrimethamine for Intermittent Preventive Treatment Among Pregnant Women in Osun State, Nigeria, Trans R Soc Trop Med Hyg. 2024 Oct 14: trae076, https://doi.org/10.1093/trstmh/trae076 largely reflects the same results as above from one particular State in Nigeria. Here even the three-dose regimen had as low an adherence rate as 12.58%, though the total number of patients studied is not available from the abstract. The authors’ recommendations are “advocacy” and “direct observation.”
In an article intended for audiences not routinely dealing with malaria, Gill J & Anvikar AR, New Strides in Prevention of Malaria During Pregnancy Present Multitudinous Opportunities, ACS Infect Dis, 2024 Oct 15, https://doi.org/10.1021/acsinfecdis.4c00566 covers the subjects of IPTp and other strategies used to reduce the burden of malaria in pregnant women {ACS is the American Chemical Society}.
Namusoke F & al.’ s paper, Perspectives of Postpartum Women on Intermittent Presumptive Treatment in Uganda: Implications for Malaria Prevention: A Qualitative Study, Malaria J, 2024 Nov 7, 23:331, https://doi.org/10.1186/s12936-024-05135-2 reiterates what has been published elsewhere, including evidence of patient resistance to intermittent preventive treatment during pregnancy, due to a number of factors beyond ignorance of the benefits. These include what the authors call “socioeconomic and cultural constraints, fear of side effects, a high pill burden, and experience of health system challenges.”
Chloroquine and artemisinins are not the only drugs that are potentially targets of parasite resistance. Two papers deal with this subject: (1) Bohissou FET & al., Evolution of Pfdhps and Pfdhfr Mutations Before and After Adopting Seasonal Malaria Chemoprevention in Nanoro, Burkina Faso, Sci Rep. 2024 Oct 16; 14:24224, https://doi.org/10.1038/s41598-024-75369-2 is a review of genetic changes in parasites collected before and after the introduction of Seasonal Malaria Chemoprevention (SMC) in children. The genes studies were the ones known to result in resistance to pyrimethamine, one of the two drugs used in SMC. In fact, the prevalence of these mutations increased significantly after the SMC campaigns. (2) Zhou R & al., Prevalence of Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from West Africa During 2012-2022, Sci Rep. 2024 Nov 4; 14:26567, https://doi.org/10.1038/s41598-024-75828-w is covered below, under Treatment/Drug resistance.
El Gaaloul M & al., Chemoprevention of Malaria with Long-Acting Oral and Injectable Drugs: An Updated Target Product Profile, Malaria J, 2024 Oct 18, 23:315, https://doi.org/10.1186/s12936-024-05128-1 is an article that reviews the various modes of chemoprevention and the principles that should guide the development of chemoprevention medications.
Other
Bannor R & Asare AK use the implementation of ITNs in Ghana to study application of protection motivation theory (PMT), which considers the following elements: “perceived severity, perceived vulnerability, perceived response efficacy, and perceived self-efficacy.” They report on a small sample of subjects (10) in Healthcare Innovation Adoption in Africa: The Case of Long-Lasting Insecticide Nets in Ghana Using Protection Motivation Theory, Psychol Health. 2024 Oct 11: 1-18, https://doi.org/10.1080/08870446.2024.2413361. They assert that the “constructs of PMT are important in the decision to use [ITNs]. Misconceptions about malaria infection and prevention could undermine the decision to use” ITNs.
Diagnosis
General diagnostics
Obeagu EI & al. present several possible biomarkers in people, including chemical included in the breath of those infected by malaria in Revolution in Malaria Detection: Unveiling Current Breakthroughs and Tomorrow’s Possibilities in Biomarker Innovation, Ann Med Surg (Lond). 2024 Jul 17; 86(10):5859-5876, https://doi.org/10.1097/ms9.0000000000002383. The authors claim benefits such as more accurate diagnosis and non-invasive technique resulting from the use of biomarkers.
Karemere J & al. explore “both the benefits and challenges of implementing … digital health technologies[for the diagnosis of malaria] in primary health facilities in” Evaluating the Implementation of Automated Malaria Rapid Diagnostic Test Readers in Health Facilities in the Democratic Republic of Congo: Process, Challenges, and Lessons Learned, Am J Trop Med Hyg. 2024 Oct 22: tpmd230670, https://tinyurl.com/2s49thvx. “Key considerations for successful deployment include careful planning, adequate training and supervision, and taking into account local infrastructure, especially internet connectivity.”
Field diagnostics
Yadav A & al. present a review of alternative means of developing Rapid Diagnostic Tests (RDTs) for malaria, in view of the apparently increasing frequency of genetic changes that undermine the accuracy of RDTs that depend on the presence of histidine rich protein. The article is Analysis of Diagnostic Biomarkers for Malaria: Prospects on Rapid Diagnostic Test Development, Microb Pathog. 2024 Sep 23: 106978, https://doi.org/10.1016/j.micpath.2024.106978.
Using nested PCR assays on 601 dried blood spots from a past malaria survey, Silva R & al. “detected submicroscopic P. falciparum infections in 20.3% … of individuals microscopically negative for Plasmodium species in the general population and in 21.4% … of microscopically negative pregnant women. Submicroscopic Plasmodium malariae infections were also detected as co-infections in 3.0% individuals who were microscopically positive only for P. falciparum.” The authors of Assessing the Burden of Submicroscopic Plasmodium Infections in a Pre-Elimination Malaria Setting in Sub-Saharan Africa, Guinea-Bissau, Malaria J. 2024 Oct 19; 23:316, https://doi.org/10.1186/s12936-024-05138-z conclude that the results obtained “highlight the contribution of asymptomatic and submicroscopic P. falciparum infections to malaria transmission in high malaria-transmission areas and the need for molecular-based tools to detect submicroscopic Plasmodium species.”
New diagnostic methods
None this month
Treatment
Treatment results
Chloroquine remains an effective part of the fight against malaria. “Plasmodium vivax is the second most common malaria parasite in Ethiopia.” In view of the development of chloroquine resistance in other Plasmodium parasites, Asfaw & al. evaluated the efficacy of chloroquine and primaquine “combination therapy against clinical P. vivax mono-infection in one of the malaria-endemic areas of Ethiopia.” They report in In vivo Efficacy of Chloroquine Plus Primaquine Combination Therapy Against Uncomplicated Plasmodium vivax Malaria in Limu Kossa District, Jimma Zone, Southwest Ethiopia, Malaria J. 2024 Oct 8; 23:300, https://doi.org/10.1186/s12936-024-05124-5 that among 108 patients with proven P. vivax infection studied over six months, 100 completed the treatment and all of those were disease-free after a six-week follow-up period.
Guidelines
Ezenyi IC & al., Factors Influencing Health Workers’ Adherence to Malaria Treatment Guidelines in Under-Five Children in Nigeria: A Scoping Review, Malaria World J, 2024 Oct 17, 15:11, https://doi.org/10.5281/zenodo.13934643 is a review of 19 published studies on the subject expressed in the title. “Training and supervision, RDT and antimalarial availability, good knowledge of, and positive perception of RDTs promoted adherence to mRDT use. A lack of confidence in RDTs and age (≥ 40 years) fuelled presumptive treatment, especially among clinicians. mRDT and artemisinin-based combination therapy (ACT) stockouts dissuaded HWs from adhering to case management guidelines. Caregiver pressure for treatment was identified as a barrier to compliance with test results.”
Side effects and complications
None this month
Drug resistance
Zheng D & al. “discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs” in Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives, Trop Med Infect Dis. 2024 Sep 20; 9(9):223, https://doi.org/10.3390/tropicalmed9090223
Wernsman Young N & al., High Frequency of Artemisinin Partial Resistance Mutations in the Great Lakes Region Revealed Through Rapid Pooled Deep Sequencing, J Infect Dis. 2024 Oct 5: jiae475, https://doi.org/10.1093/infdis/jiae475 is a report on expanding genetic variations of artemisinin drug resistance in Rwanda and surrounding countries.
Sadler JM & al. advocate the use of a polymerase chain reaction (PCR) based tool to evaluate parasite resistance to sulfadoxine-pyrimethamine in Application of a New Highly Multiplexed Amplicon Sequencing Tool to Evaluate Plasmodium Falciparum Antimalarial Resistance and Relatedness in Individual and Pooled Samples from Dschang, Cameroon, medRxiv [Preprint]. 2024 Oct 10: 2024.10.03.24314715, https://doi.org/10.1101/2024.10.03.24314715. Although on applying the tool to 100 samples detected no artemisinin resistance, the authors imply that the technique should be effective in that sphere also. {This publication presents articles that have not been peer-reviewed.}
White NJ & Chotivanich K, Artemisinin-Resistant Malaria, Clin Microbiol Rev. 2024 Oct 15: e0010924, https://doi.org/10.1128/cmr.00109-24 is a general review of the phenomenon that is now spreading in Eastern and Central Africa. The authors counsel that “[t]riple artemisinin combination therapies should be deployed as soon as possible to protect the ACT partner drugs and thereby delay the emergence of higher levels of resistance. As new affordable antimalarial drugs are still several years away, the control of artemisinin resistance must depend on the better use of available tools.”
Makau M & al. review the K13 mutations found in Africa, including a graphic representation of the 13 mutations validated as inducing artemisinin resistance (and an additional nine possible ones). In a county with high malaria endemicity, the authors sampled 226 patients, among whom 63 had slow response to artemisinin therapy. Three of these patients harbored parasites with one of the validated mutations. According to the authors these are the first validated instances of resistance in Kenya and they consider it likely that the strains originated in neighboring Uganda, where they had been described before. The article is Presence of Plasmodium falciparum Strains with Artemisinin-Resistant K13 Mutation C469Y in Busia County, Western Kenya, Trop Med Health. 2024 Oct 18; 52(1):72, https://doi.org/10.1186/s41182-024-00640-1 (the graphic is in the article, not the abstract).
In order to predict the prevalence of artemisisin resistance in a high transmission area, Agaba BB & al. conducted genomic surveillance at 50 surveillance sites across four regions of Uganda. As they report in Emerging Threat of Artemisinin Partial Resistance Markers (pfk13 Mutations) in Plasmodium falciparum Parasite Populations in Multiple Geographical Locations in High Transmission Regions of Uganda, Malaria J, 2024 Nov 4, 23:330, https://doi.org/10.1186/s12936-024-05158-9, among 238 samples analyzed, close to 20% demonstrated one or another of three variations of the pfkelch gene. In view of these findings, “periodic genomic surveillance is recommended to detect and monitor levels of pfk13 mutations in other regions,” by the authors.
Zhou R & al. analyzed “508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012-2022.” They report in Prevalence of Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from West Africa During 2012-2022, Sci Rep. 2024 Nov 4; 14:26567, https://doi.org/10.1038/s41598-024-75828-w that “[h]igh mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed.” These were the mutations also observed by Bohissou & al. above, in Burkina Faso. The authors comment on the implication of their findings on the future use of SP in chemoprevention. {All of these patients, who returned from 11 different countries, were adults and the vast majority of them males; the likelihood is that none had been exposed to SP chemoprevention.}
Resistance to chloroquine is now also found in P. vivax. Although Kaur D & al., Optimization of Loop Mediated Isothermal Amplification Assay (LAMP) for Detection of Chloroquine Resistance in P. vivax malaria, Sci Rep. 2024 Oct 27; 14:25608, https://doi.org/10.1038/s41598-024-76479-7 reports on experience in India, the fact P. vivax is relatively common in Ethiopia and a few other African countries leads to the need to remain alert to the possibility of this resistance arising there as well.
New drug research
According to Cox A & al., Repositioning Brusatol as a Transmission Blocker of Malaria Parasites, ACS Infect Dis. 2024 Oct 1, https://doi.org/10.1021/acsinfecdis.4c00434, “primaquine is the only malaria transmission-blocking drug recommended by the WHO.” The authors claim to have “identified potent transmission blockers, as illustrated by the discovery of the transmission-blocking efficacy of brusatol. As a member of a large family of biologically active natural products, this discovery provides a critical next step…” The abstract is silent on the many articles citing the effectiveness of ivermectin as a transmission blocking agent.
In what appear to be very preliminary results, Lopez-Mercado S & al.’s paper, Exploring the Antibacterial and Antiparasitic Activity of Phenylaminonaphthoquinones-Green Synthesis, Biological Evaluation and Computational Study, Int J Mol Sci. 2024 Oct 3; 25(19):10670, https://doi.org/10.3390/ijms251910670 identifies compounds synthesized 12 compounds, six of which were effective against bacteria and two of them against chloroquine-sensitive P. falciparum.
Plant extracts and traditional treatments
Ngouana V & al. report on laboratory testing of leaf extracts of two West African trees used in folk medicine. They found that they both inhibited two laboratory strains of P. falciparum. However, their paper, Exploring the Antimalarial Potential of Entandrophragma utile and Melochia umbellata Extracts, Chem Biodivers. 2024 Oct 14: e202401314, https://doi.org/10.1002/cbdv.202401314 cover very preliminary work, wich the authors acknowledge.
Ziziphus mucronata, known as buffalo thorn, is a tree whose roots, bark and leaves are extensively in use in folk medicine in Southern Africa. Masia KJ & al. report in Antiplasmodial Potential of Compounds Isolated from Ziziphus mucronata and Their Binding to Plasmodium falciparum HGXPRT Using Biophysical and Molecular Docking Studies, Naunyn Schmiedebergs Arch Pharmacol, 2024 Nov 19, https://doi.org/10.1007/s00210-024-03611-9 that several extracts of the bark of this plant exhibited significant anitplasmoidial activity in the laboratory. The authors conclude that that “Z. mucronata could serve as a reservoir of effective agents for treating malaria, while also scientifically validating its use in traditional medicine. However, further experimental studies are required to substantiate its relevant therapeutic effects.”
Other
None this month
Campaigns and Policies
Adeniyi L & al. used computerized support in delivering close to 3 million bed nets to over 1 million households and report in Delivering Insecticide-Treated Nets (ITNs) Through a Digitized Single-Phase Door-to-Door Strategy: Lessons from Ondo State, Nigeria, Malaria J, 2024 Oct 28, 23:322, https://doi.org/10.1186/s12936-024-05145-0 that “[s]ingle phase door-to-door strategy using digital tools was an effective method to increase coverage of ITNs while closely tracking the progress of distribution campaigns.”
The use of long-lasting insecticidal nets (LLINs) by the population of Bioko Island, Equatorial Ginea, remains below expectations. In contrast to the above report, Garcia GA, & al. conclude in The Challenge of Improving Long-Lasting Insecticidal Nets Coverage on Bioko Island: Using Data to Adapt Distribution Strategies, Malaria J, 2024 Oct 29, 23:324, https://doi.org/10.1186/s12936-024-05139-y that distribution strategies may affect the usage rate, the results favoring fixed distribution points and constant availability as opposed to mass distribution campaigns.
The above two articles may also be cited under Prevention/Vectors
Khan J & al. also report on the Usability of a Digital Tool to Support Long-Lasting Insecticide Net Distribution in Northern Bahr el Ghazal State, South Sudan, in Malaria J, 2024 Oct 21, 23:318, https://doi.org/10.1186/s12936-024-05092-w. However, the focus of this paper is the impression of health care workers on how the digitization of information improves their working efficacy and satisfaction. The reports from the use of 93 completed questionnaires collected were as follows: “The majority of users agreed the tool was useful for managing the LLIN distribution workflow, was easy to use, reduced workload, and supported stock management and real-time campaign monitoring. There was no significant difference in the usability scores across genders, roles, and counties. Respondents with experience of both paper-based and the digital tool tended to express a preference for the digital tool over paper-based systems. The majority of respondents also reported they would recommend the digital tool to colleagues.”
Mthembu Z & Chimbari MJ investigated “the collaborative phase of community engagement, specifically within a co-developed framework implemented in uMkhanyakude District, South Africa. A qualitative case study approach was employed to explore the experiences of key community stakeholders during the collaborative phase of project implementation. … The findings demonstrate the potential for effective collaboration among village headmen, community advisory board members, and community research assistants to address local health challenges. Community research assistants played a particularly valuable role in facilitating participatory research and hands-on engagement with researchers. However, several barriers hindered the collaborative process, including demanding work conditions, communication issues regarding compensation, inappropriate behavior from the research team, and culturally insensitive interactions. While community-based participatory research offers a promising collaborative approach for addressing health issues, a careful consideration of local socio-cultural dynamics is essential to avoid misunderstandings and overcome potential barriers. The paper is Community Engagement and Collaboration between Researchers and Community Stakeholders for Schistosomiasis and Malaria Projects in Ingwavuma, uMkhanyakude District, KwaZulu-Natal, Trop Med Infect Dis. 2024 Oct 11; 9(10):236, https://doi.org/10.3390/tropicalmed9100236.
In a very large study (over 25,000 participants) Hutchins H & al. studied the anticipated benefit from adding ivermectin to a mass drug administration (MDA) campaign. They report in Adjunctive Ivermectin Mass Drug Administration for Malaria Control on the Bijagos Archipelago of Guinea-Bissau (MATAMAL): a Quadruple-Blinded, Cluster-Randomised, Placebo-Controlled Trial, Lancet Infect Dis, 2024 Nov 14, https://doi.org/10.1016/S1473-3099(24)00580-2 that [a]dding ivermectin to dihydroartemisinin–piperaquine MDA had no additional effect on reducing malaria prevalence or vector parity in this setting. In an accompanying editorial, Mouline K & Costantini C, Is Ivermectin Surviving Expectations in Residual Malaria Control? Lance Infect Dis, 2024 Nov 14, https://doi.org/1016/S1473-3099(24)00652-2 the authors urge caution in extending the conclusions to populations on the African mainland.
Epidemiology
Climate change, biodiversity and environment
Nimlang NH & al. “utilized environmental risk factors and spatial multi-criteria decision analysis techniques to analyze and map the spatial variations in malaria-endemic prone areas…” and report in Spatial Analysis and Mapping of Malaria Endemic-Prone Areas Using Environmental Risk Factors and Spatial Multi Criteria Decision Analysis in the Northern Zone of Plateau State, Nigeria, J Vector Borne Dis. 2024 Oct 5, https://doi.org/10.4103/jvbd.jvbd_63_24 that “60% of the study areas were characterized by high risk of malaria transmission…” The authors conclude that “malaria risk analysis and mapping … offers a deeper comprehension of the appropriate intervention measures to be implemented.”
In Kenya, Nyawanda BO & al. found “causal links between climatic drivers, bed net use, and malaria incidence.” As reported in Forecasting Malaria Dynamics Based on Causal Relations Between Control Interventions, Climatic Factors, and Disease Incidence in Western Kenya, J Glob Health. 2024 Oct 11; 14:04208, https://doi.org/10.7189/jogh.14.04208, daytime land surface temperature (LTSD) “lagged over the previous month; rainfall and [relative humidity] lagged over the previous two months; and wind speed in the current month had the highest predictive skills. Increases in LSTD, wind speed, and bed net use negatively affected incidence, while increases in rainfall and humidity had positive effects.”
Focusing on various elements of climate’s effect on P. falciparum, Brown O & al., A Global Mathematical Model of Climatic Suitability for Plasmodium falciparum Malaria, Malaria J. 2024 Oct 10; 23:306, https://doi.org/10.1186/s12936-024-05122-7 report “weak agreement between the Malaria Atlas Project estimates of P. falciparum prevalence in Africa and the estimates of suitability solely based on temperature …. The addition of humidity and then rainfall improves the comparison …. By incorporating the impacts of humidity and rainfall, this model identifies arid regions that are not climatically suitable for transmission of P. falciparum malaria.”
The impact of agricultural irrigation on the prevalence of malaria was studied by Getachew T & al., who report in Impact of a Large-Scale Fruit and Vegetable Irrigation Scheme on the Micro-Epidemiology of Malaria in Southwest Ethiopia, BMC Public Health. 2024 Oct 18; 24(1):2878, https://doi.org/10.1186/s12889-024-20405-z that “[i]ndividuals living in the irrigated villages were 2.53 … times at higher risk of Plasmodium infection as compared to those living in the non-irrigated village.” Thae authors advocate “tailored interventions that are both targeted and customized.”
Taconet P & al. compared the abundance and variability of vectors in an agricultural area in Côte d’Ivoire and compared it to a similar study conducted earlier in Burkina Faso. They conclude in Landscape and Meteorological Determinants of Malaria Vectors’ Presence and Abundance in the Rural Health District of Korhogo, Cote d’Ivoire, 2016-2018, and Comparison with the Less Anthropized Area of Diebougou, Burkina Faso, PLoS One. 2024 Oct 21; 19(10):e0312132, https://doi.org/10.1371/journal.pone.0312132 that the more “anthropized” (i.e. more subject to human activity) area now studied influences toward less diversity of vectors but increased biting activity.
Mariën J & al., A Century of Medical Records Reveal Earlier Onset of the Malaria Season in Haut-Katanga Induced by Climate Change, BMJ Glob Health. 2024 Oct 22; 9(10):e015375, https://doi.org/10.1136/bmjgh-2024-015375 documents that the rate of infection in the region studied has essentially reverted to that about a hundred years ago. During the years that DDT was in use, the incidence of malaria dropped, but it has now climbed again. The authors refer to climate change as a major reason for the recent rise in cases.
Risk factors
The influence of patients’ blood groups on whether they suffer severe malaria has been controversial. Abebe W & al., Prevalence and Association of Malaria with the Blood Group on Febrile Patients at Woldia Comprehensive Specialized Hospital, Northeast Ethiopia, J Parasitol Res. 2024 Sep 28; 2024:9942758, https://doi.org/10.1155/2024/9942758 cite several papers with conflicting conclusions in their article, especially with regard to the apparent protective influence of Blood Group O. In this instance, their conclusion is that “[i]ndividuals with the A blood type had a 2.35-fold higher risk of malaria infection … than those with the O blood type. However, in the other blood types, the relationships were not statistically significant.” {Reviewer’s comment: The abstract of this paper is unhelpful in determining the validity of the study. Also, the total number of infected patients cited is very small (16).}
It is generally observed that individuals who carry the sickle cell gene (HbAS) tend to be resistant to malaria. Dicko I & al., Relationship Between Red Blood Cell Polymorphisms and Effectiveness of Seasonal Malaria Chemoprevention in 2020 in Dangassa, Mali, Parasitol Res. 2024 Oct 14; 123(10):350, https://doi.org/10.1007/s00436-024-08372-1 explores how this dynamic may affect response to seasonal chemoprevention in the location of their study. Unfortunately, while the authors report no infection in children with HbAS blood during the period of study, the abstract then becomes difficult to interpret.
War and displacement are severe risk factors for the development of disease Debash H & al. studied 422 temporarily displaced febrile children in a war zone of Ethiopia and found that close to 2/3 of them were suffering from malaria. While more than half of the children were also mildly to severely undernourished, it is unclear whether that was a factor in the development of malaria. The paper is Prevalence and Correlates of Malaria and Undernutrition Among Acutely Febrile Children Visiting Temporary Malaria Screening Sites in War-Torn Areas of Northeast Ethiopia, PLoS One. 2024 Oct 17; 19(10):e0311931, https://doi.org/10.1371/journal.pone.0311931.
Nyawanda BO & al. studied data obtained from over 10,000 children over six years in order to ascertain the dual effects of climate change and malaria intervention. Their report, The Influence of Malaria Control Interventions and Climate Variability on Changes in the Geographical Distribution of Parasite Prevalence in Kenya Between 2015 and 2020, Int J Health Geogr. 2024 Oct 27; 23:22, https://doi.org/10.1186/s12942-024-00381-8#citeas is difficult to interpret because the authors cannot plausibly attribute the divergent changes in age-related malaria prevalence in children to either major factor.
General epidemiology
“Some settings continue to experience a high malaria burden despite scale-up of malaria vector control to high levels of coverage.” In their study of 1237 children, Ashton RA & al report in Why Does Malaria Transmission Continue at High Levels Despite Universal Vector Control? Quantifying Persistent Malaria Transmission by Anopheles funestus in Western Province, Zambia, Parasit Vectors, 2024 Oct 14; 17(1):429, https://doi.org/10.1186/s13071-024-06457-5 that “[c]hildren not sleeping under insecticide-treated nets (ITNs) experienced 13.6 infectious bites per person per 6 month season, 8% of which occurred outdoors, while ITN users received 1.3 infectious bites per person per 6 month season, 86% of which were received outdoors. Sleeping under an ITN can prevent approximately 90% of potential An. funestus bites among children.” Still, “despite high household possession of ITNs (>90%) and high individual use (>70%), children in this setting experience more than one infectious bite per person per 6 month transmission season, sufficient to maintain high malaria transmission and burden.”
Silva R & al., Assessing the Burden of Submicroscopic Plasmodium Infections in a Pre-Elimination Malaria Setting in Sub-Saharan Africa, Guinea-Bissau, Malaria J, 2024 Oct 19, 23:316, https://doi.org/10.1186/s12936-024-05138-z is a report on finding up to 20% of a population to be positive for P falciparum even when negative on microscopy. Submicroscopic P malariae was also found. The implication of these findings extend to unexpected transmission of malaria from these individuals, who may not be treated if microscopy is the predominant mode of diagnosis.
Spatiotemporal studies
Bardoe D & al., Assessing the Prevalence, Risk Factors, and Socio-Demographic Predictors of Malaria Among Pregnant Women in The Bono East Region of Ghana: A Multicentre Hospital-Based Mixed-Method Cross-Sectional Study, Malaria J. 2024 Oct 9; 23:302, https://doi.org/10.1186/s12936-024-05120-9
Merga H & al., Urban Malaria and Its Determinants in Eastern Ethiopia: The Role of Anopheles stephensi and Urbanization, Malaria J. 2024 Oct 9; 23:303, https://doi.org/10.1186/s12936-024-05126-3
Isiko I & al., Determinants of Malaria Spread Among Under-Five Children in Nigeria: Results from a 2021 Nigerian Malaria Indicator Cross-Sectional Survey, BMC Pediatr. 2024 Oct 10; 24(1):646, https://doi.org/10.1186/s12887-024-05135-w
Badoum ES & al., Force of Infection (FOI) and Multiplicity of Infection (MOI) in Plasmodium falciparum Infected Children Aged 1.5-12 Years Living in the Malaria Endemic Area of Banfora, Burkina Faso, Pathogens. 2024 Oct 10; 13(10):883, https://doi.org/10.3390/pathogens13100883
Kayange NM & al., Malaria and Dengue Fever in Febrile Children Entering Healthcare Facilities in Mwanza, Tanzania, PLoS One. 2024 Oct 11; 19(10):e0309613, https://doi.org/10.1371/journal.pone.0309613