The Global Fund to Fight AIDS, Tuberculosis and Malaria (the Global Fund) is launching a new Revolving Facility to negotiate improved supply terms for global health products for the countries it supports. This financial mechanism uses advanced market commitments, including volume guarantees, to drive more affordable access to quality-assured health products and accelerate health product introductions and innovations at greater scale.

“The Revolving Facility will help accelerate affordable access to more effective health products for people living in the poorest communities around the world,” said Peter Sands, Executive Director of the Global Fund. …

The first agreement to come through the Facility will be with Vestergaard, manufacturers of PermaNet® malaria mosquito nets, for its new dual active ingredient (Dual AI) insecticide-treated net. Dual AI nets are more effective against insecticide-resistant mosquitoes than conventional ones. By implementing an innovative operating model, the Global Fund aims to secure sustainable prices for a set of commonly used specifications for Dual AI nets that are comparable to existing nets. This makes it possible for countries to expand coverage with Dual AI nets despite constrained budgets.…

In March, WHO issued new recommendations for the use of Dual AI nets. This included a strong recommendation for the use of pyrethroid-chlorfenapyr nets to prevent malaria in adults and children in areas where mosquitoes have become resistant to pyrethroids.

The Global Fund’s Revolving Facility was established with an initial commitment of US$100 million from the Bill & Melinda Gates Foundation …

Source: https://reliefweb.int/report/world/global-fund-announces-new-mechanism-increase-access-more-effective-mosquito-nets-prevent-malaria via the MalariaWorld weekly newsletter




Dicko A & al. report in Seasonal Vaccination with RTS,S/AS01E Vaccine with or Without Seasonal Malaria Chemoprevention in Children Up to the Age of 5 Years in Burkina Faso and Mali: A Double-Blind, Randomised, Controlled, Phase 3 Trial, Lancet Infect Dis, 2023 Aug 22, https://doi.org/10.1016/ S1473-3099(23)00368-7 that vaccination with the named vaccine combined with yearly seasonal malaria chemoprevention (SMC) was superior to either intervention by itself in preventing malaria in children under age 5.  According to their data, the incidence of malaria in the group with vaccine and SMC was approximately 1/3 of that in the two groups with single intervention alone. “Hospital admissions for WHO-defined severe malaria were reduced by 66·8% …, for malarial anaemia by 65·9% …, for blood transfusion by …, for all-cause deaths by 44·5% …, and for deaths from malaria by 66·8% … in the combined group compared with the SMC alone group. No safety signals were detected.” Dutta S & Thera MA, Seasonal RTS,S/AS01E Vaccination with or Without Seasonal Malaria Chemoprevention, Lancet Infect Dis, 2023 Aug 22, https://doi.org/10.1016/ S1473-3099(23)00392-4 is a related editorial, confirming the benefit of using the vaccine with SMC but urging caution in that the R21 vaccine is also in Phase 3 trials and it is unclear which of the two vaccines will provide better protection in the long run.

Benefiting from the experience described the above paper, a workshop on implementing vaccination and SMC was held in Dakar, Senegal. “The objectives of this workshop were … to share experiences from countries that have introduced the RTS,S vaccine in routine child vaccination programmes, with SMC-implementing countries as they consider malaria vaccine introduction, and to explore implementation strategies in countries with seasonal transmission and where EPI coverage may be low especially in the second year of life. Practical implementation challenges, lessons learned for vaccine introduction, and research questions, towards facilitating the introduction of the RTS,S (and other malaria vaccines) in countries with seasonal malaria transmission were discussed.” The report is Merle CS & al., Implementation Strategies for the Introduction of the RTS,S/AS01 (RTS,S) Malaria Vaccine in Countries with Areas of Highly Seasonal Transmission: Workshop Meeting Report, Malaria J, 2023 Aug 23, 22:142, https://doi.org/10.1186/s12936-023-04657-5

“While Ghana has a good track record in the Expanded Programme on Immunization, there are substantial challenges with regard to subsequent vaccinations, particularly after the first year of life of the child. Given that the last dose of the RTS,S/AS01E vaccine against malaria is administered at 24 months, there is a high likelihood of default… [Okyere J & al.] explored why caregivers default on the RTS,S/AS01E vaccine …” RTS,S/AS01E Vaccine Defaults in Ghana: A Qualitative Exploration of the Perspectives of Defaulters and Frontline Health Service Providers, Malaria J, 2023 Sep 6, 22:260, https://doi.org/10.1186/s12936-023-04690-4 reports that reasons for defaulting included “the overlap of timing of the last dose and the child starting school, disrespectful attitudes of some health service providers, concerns about adverse side effects and discomforts, travel out of the implementing district, the perception that the vaccines are too many, and lack of support from partners.” The authors recommend that “stakeholders must reconsider the timing of the last dose of the vaccine. The schedule of the RTS, S/AS01E vaccine should be aligned with the established EPI schedule of Ghana.”


Watson FN & al., Ultra-Low Volume Intradermal Administration of Radiation-Attenuated Sporozoites with the Glycolipid Adjuvant 7DW8-5 Completely Protects Mice Against Malaria, Res Sq. 2023 Aug 11: rs.3.rs-3243319, https://doi.org/10.21203/rs.3.rs-3243319/v1 contrasts intradermal versus intravenous introduction of radiation-attenuated sporozoites in the mouse model and states that the experimental animals were fully protected from malaria through either route of administration.  How that ios relevant to vaccines currently administered intramuscularly is unclear. 

“Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector.” Salinas ND & al., A Potent and Durable Malaria Transmission-Blocking Vaccine Designed from a Single-Component 60-Copy Pfs230D1 Nanoparticle, NPJ Vaccines. 2023 Aug 18; 8(1):124, https://doi.org/10.1038/s41541-023-00709-8 describes the action of a small molecular moiety derived from a larger, effective transmission blocking vaccine that was effective in experimental rabbits, resulting in “potent and durable antibody response with high TRA [transmission reducing activity] when formulated in two distinct adjuvants suitable for translation to human use.”

Vector control and protection from vectors

In 2017-2019, Lynd A & al. “conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus the synergist piperonyl butoxide (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda.” In their article, LLIN Evaluation in Uganda Project (LLINEUP) – Plasmodium Infection Prevalence and Genotypic Markers of Insecticide resistance in Anopheles Vectors from 48 Districts of Uganda, medRxiv. 2023 Aug 5: 2023, 07.31.23293323, https://doi.org/10.1101/2023.07.31.23293323, the authors conclude that “[d]istribution of LLINs in Uganda was associated with reductions in parasite prevalence and vector density, but the proportion of infective mosquitoes remained stable, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors…”

Messenger LA & al. tested over 47,000 “wild Anopheles collected over 3 years to assess the longitudinal effects of dual-active-ingredient LLINs on insecticide resistance” and found that “chlorfenapyr PY-LLINs provided superior protection from malaria across multiple transmission seasons, with few effects on insecticide-resistance selection. Rapid pyrethroid-resistance intensification in the piperonyl butoxide PY-LLIN group and pre-existing tolerance of pyriproxyfen in vector populations might explain the poorer performance of these two interventions regarding malaria outcomes.” The paper is Effects of Next-Generation, Dual-Active-Ingredient, Long-Lasting Insecticidal Net Deployment on Insecticide Resistance in Malaria Vectors in Tanzania: An Analysis of a 3-Year, Cluster-Randomised Controlled Trial, Lancet Planet Health. 2023 Aug; 7(8):e673-e683, https://doi.org/10.1016/s2542-5196(23)00137-7.


Breeding a colony of Anopheles gambiae collected from the wild, Zoh MG & al. followed subsequent generations up to more than 30. During that time, resistance to two different pyrethroids made their appearance and these populations were segregated from each other, as well as from continuing susceptible generations. The conclusion of the report, Deltamethrin and Transfluthrin Select for Distinct Transcriptomic Responses in the Malaria Vector Anopheles gambiae, Malaria J, 2023 Sep 4, 22:256, https://doi.org/10.1186/s12936-023-04673-5, is that the mechanism for selection of the two differently resistant lines was unique to the specific drug.


Govella NJ & al. tested the changing behaviors of vectors as a result of implementation of insecticide treated bed nets (ITNs) and report in Heritability of Biting Time Behaviours in the Major African malaria vector Anopheles arabiensis, Malaria J, 2023 Aug 16, 22:238, https://doi.org/10.1186/s12936-023-04671-7 that in many cases feeding is now occurring earlier or later than before and that this behavior is persistent over generations even if the offspring are not exposed to ITNs. So they conclude that “some of the variation in biting time is attributable to additive genetic variation. Selection can, therefore, act efficiently on mosquito biting times…”


Barker TH & al. “investigated two forms of dual active-ingredient (DAI) insecticide-treated nets (ITNs) for malaria prevention. … The first DAI ITN investigated were those that combined a pyrethroid with a non-pyrethroid insecticides. The second DAI ITN investigated were those that combined a pyrethroid with an insect growth regulator.” According to Effectiveness of Dual Active Ingredient Insecticide-Treated Nets in Preventing Malaria: A Systematic Review and Meta-Analysis, PLoS One. 2023 Aug 16; 18(8):e0289469, https://doi.org/10.1371/journal.pone.0289469, 13 reports for three studies were included, [which] contained data from 186 clusters and all reported a low risk of bias… Compared to pyrethroid-only ITNs, clusters that received pyrethroid-non-pyrethroid DAI ITNs were associated with 305 fewer cases per 1000-person years …. However, this trend was not observed in clusters that received pyrethroid-insect growth regulator ITNs compared to pyrethroid-only ITNs.”

In four communities in Benin, Zoungbédji DM & al., Assessing the Susceptibility and Efficacy of Traditional Neurotoxic (Pyrethroid) and New-Generation Insecticides (Chlorfenapyr, Clothianidin, and Pyriproxyfen), on Wild Pyrethroid-Resistant Populations of Anopheles gambiae from Southern Benin, Malaria J, 2023 Aug 26, 22:245, https://doi.org/10.1186/s12936-023-04664-6 reports that “pyrethroid-resistant An. gambiae from the selected communes … are susceptible to chlorfenapyr, clothianidin, and pyriproxyfen. In addition, based on bioassay results, new and unused Interceptor® G2 and Royal Guard® nets were effective on … mosquito populations” of one of the communities.


Swai JK & al. investigated the Efficacy of the Spatial Repellent Product Mosquito Shield™ Against Wild Pyrethroid-Resistant Anopheles arabiensis in South-Eastern Tanzania, Malaria J, 2023 Aug 30, 22:249, https://doi.org/10.1186/s12936-023-04674-4 in experimental huts. The results indicated significant inhibition of mosquito landing and of blood-feeding, in treated as compared to untreated huts.  Although the study was said to have been over a month in duration, the abstract is unclear whether treatment with the spatial repellent was applied only at the beginning or during the duration of the study as well, calling into question the durability of the product.


Tchouakui M & al. “investigated the performance of piperonyl-butoxide (PBO)-pyrethroid [Permanet 3.0 (P3.0)] and dual active ingredients (AI) nets [Interceptor G2 (IG2): containing pyrethroids and chlorfenapyr and Royal Guard (RG): containing pyrethroids and pyriproxyfen] compared to pyrethroid-only net Royal Sentry (RS) against pyrethroid-resistant malaria vectors in Cameroon.” Their results in experimental hut trials showed that “Interceptor G2 was the most effective net against wild pyrethroid-resistant An. funestus followed by Permanet 3.0… Interceptor G2, Permanet 3.0, and Royal Guard provided better personal protection (blood-feeding inhibition 66.2%, 77.8%, and 92.8%, respectively) compared to pyrethroid-only net Royal Sentry… The article is High Efficacy of Chlorfenapyr-Based Net Interceptor® G2 Against Pyrethroid-Resistant Malaria Vectors from Cameroon, Infect Dis Poverty. 2023 Aug 29;12(1):81, https://doi.org/10.1186/s40249-023-01132-w.


“With growing resistance to existing malaria vector control insecticides and the introduction of new vector control products, national malaria control programs (NMCPs) increasingly need to make data-driven, subnational decisions to inform vector control deployment.” Burnett SM & al., Process and Methodological Considerations for Observational Analyses of Vector Control Interventions in Sub-Saharan Africa Using Routine Malaria Data, Am J Trop Med Hyg. 2023 Aug 21: tpmd220757, https://doi.org/10.4269/ajtmh.22-0757 claims to provide “practical guidance on the design of these evaluations, makes recommendations for key variables and data sources, and proposes methods to address challenges in data quality. Key recommendations include appropriate parameterization of impact and coverage indicators, incorporating explanatory covariates and contextual factors from multiple sources (including rapid diagnostic testing stockouts; insecticide susceptibility; vector density measures; vector control coverage, use, and durability; climate and other malaria and non-malaria health programs), and assessing data quality before the evaluation through either on-the-ground or remote data quality assessments.”

According to Onyinyechi OM & al., there is lack of evidence of the effectiveness of education in increasing use of proven methods of mitigating or preventing malaria. In Effectiveness of Health Education Interventions to Improve Malaria Knowledge and Insecticide-Treated Nets Usage Among Populations of Sub-Saharan Africa: Systematic Review and Meta-Analysis, Front Public Health. 2023 Aug 3; 11:1217052, https://doi.org/10.3389/fpubh.2023.1217052, they report on a meta-analysis of 11 papers on the subject and conclude that they show moderate effectiveness of health education “in improving malaria knowledge and ITN usage…”

“Evidence that house design can provide protection from malaria is growing. Housing modifications such as screening windows, doors, and ceilings, and attaching insecticide-impregnated materials to the eaves (the gap between the top of the wall and bottom of the roof), can protect against malaria.” Judged by direct observation and focus group discussions, Kayendeke M & al. report in House Modifications as a Malaria Control Tool: How Does Local Context Shape Participants’ Experience and Interpretation in Uganda? Malaria J, 2023 Aug 25, 22:244, https://doi.org/10.1186/s12936-023-04669-1 that “[m]ost residents supported the modifications.” However, they also state the following: “Experiences and interpretation of the housing modifications were shaped by the different types of housing in the area and the processes through which residents finished their houses, local forms of land and property ownership, and cultural and spiritual beliefs about houses.”


Odwe G & al. examined “the association between women’s empowerment indicators (decision-making power, control of assets, education, and employment status) and the uptake of three or more doses of IPTp-SP [intermittent preventive treatment in pregnancy with Sulfadoxine-Pyrimethamine] in the Lake endemic region of Kenya.” They report in Women’s Empowerment and Uptake of Sulfadoxine–Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy: Results from a Cross-Sectional Baseline Survey in the Lake Endemic Region, Kenya, Malaria J, 2023 Aug 23, 22:241, https://doi.org/10.1186/s12936-023-04679-z that among “the 3129 women surveyed, 1978 (65.7%) received 3+ doses of IPTp-SP during their most recent pregnancy. Controlling for individual characteristics and the number of ANC [antenatal control] visits, the odds of taking 3+ doses of IPTp-SP increased among women who had high decision-making …; and tertiary level of educational attainment …. However, the association between control of assets and uptake of IPTp-SP was positive but not statistically significant.

Scarsi KK & al. “sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation [by administering] questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia.” They report in Preferences of Patients and Providers in High-Burden Malaria Settings for Long-Acting Malaria Chemoprevention, Am J Trop Med Hyg. 2023 Aug 21: tpmd230245, https://doi.org/10.4269/ajtmh.23-0245 that among “202 patient respondents, 80% indicated that they ‘definitely would try’ malaria chemoprevention offered by injection instead of oral pills. Of parents or guardians, 84% of 113 responded that they ‘definitely would’ have their child age < 12 years and 90% of 88 ‘definitely would’ have their child ≥12 years receive an injection for malaria prevention.” The length of action of the long-acting formulation is not mentioned in the abstract.

Following a heavy flooding episode in their Western region, Uganda implemented special chemoprevention. Xu E & al., Evolution of Spatial Risk of Malaria Infection After a Pragmatic Chemoprevention Program in Response to Severe Flooding in Rural Western Uganda, J Infect Dis. 2023 Aug 16: jiad348, https://doi.org/10.1093/infdis/jiad348 reports on the analysis of malaria incidence after this episode.  The article concludes that there were “clusters of malaria risk emerging in areas that (i) showed the greatest changes in NDVI from pre- to post-flood and (ii) residents were displaced for longer periods of time and had lower access to long-lasting insecticidal nets, both of which were associated with a positive malaria rapid diagnostic test result. The disproportionate risk persisted despite a concurrent chemoprevention program that achieved high coverage.”


Rent S & al., Malaria in Pregnancy: Key Points for the Neonatologist, Neoreviews. 2023 Sep 1; 24(9):e539-e552, https://doi.org/10.1542/neo.24-9-e539 is focused both on prevention and treatment of malaria during pregnancy, with the obvious goal, given the readership of the journal, of preventing the consequences of malaria in newborns.

Despite good knowledge of 281 mothers of young children interviewed about malaria and its preventive measures, Adum P & al.  report in Knowledge, Attitude and Practices of Malaria Preventive Measures Among Mothers with Children Under Five Years in a Rural Setting of Ghana, Malaria J, 2023 Sep 12, 22:268, https://doi.org/10.1186/s12936-023-04702-3 that “35.5% of respondents were not actively engaged in malaria prevention practices in a day prior to the interview. Respondents’ occupation, level of education, and religion had a statistically significant association with mothers’ attitude towards prevention.”

Gabaldón Figueira JC & al., Topical Repellents for Malaria Prevention, Cochrane Database Syst Rev. 2023 Aug 21; 8:CD015422, https://doi.org/10.1002/14651858.CD015422.pub2 concludes after a systematic review and meta-analysis of the relevant literature that “[t]opical repellents may slightly reduce P falciparum infection and clinical incidence when both outcomes are considered together (incidence rate ratio (IRR) 0.74, … low-certainty evidence); but not when these two outcomes were considered independently.”

“The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. [Sady H & al.] tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6–18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them.” However, they report in Effect of Dietary Intervention on the Prevalence of Asymptomatic Malaria Among 6–18-Month-Old Children in Rural Malawi, Malaria J, 2023 Sep 11, 22:266, https://doi.org/10.1186/s12936-023-04701-4 that the “study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children.”

Similar to other studies, Lopez AR & Brown CA, Knowledge, Attitudes and Practices Regarding Malaria Prevention and Control in Communities in the Eastern Region, Ghana, 2020, PLoS One. 2023 Aug 30; 18(8):e0290822,  https://doi.org/10.1371/journal.pone.0290822 documents the disconnect between knowledge about malaria and behaviors that help prevent the infections. For example, while 85.4% of  respondents “had good knowledge score about malaria … [58.5%] of households …. had no bed nets and bed net usage was poor (10.1%).”


General diagnostics

None this month

Field diagnostics

Fola AA & al. noted that about 8% of patients with malaria may not be diagnosable by RDT because of genetic deletion of histidine rich protein. In Plasmodium falciparum Resistant to Artemisinin and Diagnostics Have Emerged in Ethiopia, Nat Microbiol. 2023 Aug 28, https://doi.org/10.1038/s41564-023-01461-4 they also state that this population of parasites also has a significant penetration of artemisinin resistance.  The abstract has no recommendations in it, but it is obviously questioning the efficacy of relying on RDT testing in the field and cautions against treatment resistance.

New diagnostic methods

“The most prevalent method now available for detecting malaria is the microscope. Under a microscope, blood smears are typically examined for malaria diagnosis. Despite its advantages, this method is time-consuming, subjective, and requires highly skilled personnel. Therefore, an automated malaria diagnosis system is imperative for ensuring accurate and efficient treatment,” according to Madhu G & al., Intelligent Diagnostic Model for Malaria Parasite Detection and Classification Using Imperative Inception-Based Capsule Neural Networks, Sci Rep. 2023 Aug 17; 13(1):13377, https://doi.org/10.1038/s41598-023-40317-z. They propose “an innovative approach utilizing an urgent, inception-based capsule network to distinguish parasitized and uninfected cells from microscopic images. This diagnostic model incorporates neural networks based on Inception and Imperative Capsule networks. … the dynamic imperative capsule neural network detects malaria parasites in microscopic images by classifying them into parasitized and healthy cells, enabling the detection of malaria parasites. … Compared to traditional manual microscopy, the proposed system is more accurate and faster.”


Treatment results

A study of artemisinin combination therapy and genetic analysis of the parasites, Issa MS & al., Therapeutic Efficacy of Artesunate–Amodiaquine and Artemether–Lumefantrine for the Treatment of Uncomplicated Falciparum Malaria in Chad: Clinical and Genetic Surveillance, Malaria J, 2023 Aug 23, 22:240, https://doi.org/10.1186/s12936-023-04644-w found that both treatments were highly effective and genetic analysis of the parasites involved in the confirmed cases of 215 children ages 6 to 59 months showed none of the mutations known to be associated with artemisinin resistance.

Anjani QK & al., Primaquine and Chloroquine Nano-Sized Solid Dispersion-Loaded Dissolving Microarray Patches for the Improved Treatment of Malaria Caused by Plasmodium vivax, J Control Release. 2023 Aug 8: S0168-3659(23)00505-9, https://doi.org/10.1016/j.jconrel.2023.08.009 describes the use of a novel delivery method for two standard medications against vivax malaria that have frequent GI side effects.  So far these patches have been studied in vitro, showing potential antimalarial effect. This study, conducted using two rodent species (rats and mice), demonstrated good absorption and persistence (up to 7 days) as well as excellent antiplasmodial effect.

Adherence to guidelines

Based on a “cross-sectional study … in 50 health facilities (HF) and 40 drug outlets (DO) using structured questionnaires to assess pregnancy detection, malaria diagnosis, and treatment choices by trimester, Osoro CB & al., Healthcare Provider and Drug Dispenser Knowledge and Adherence to Guidelines for the Case Management of Malaria in Pregnancy in the Context of Multiple First-Line Artemisinin-Based Combination Therapy in Western Kenya, Malaria J, 2023 Sep 8, 22:262, https://di.org/10.1186/s12936-023-04692-2 concludes that “[k]nowledge of national malaria in pregnancy treatment guidelines among providers in Western Kenya is suboptimal. Robust training on appropriate anti-malarial and dosage is needed, particularly given the recent change in recommendation for artemether-lumefantrine use in the first trimester. Supervision of … practices is essential for correct treatment of malaria in pregnancy…”

Bulafu D & al. “assessed the level of adherence to malaria treatment guidelines and associated factors among HCWs [healthcare workers] in private health facilities in Kampala’s informal settlements.” As reported in Adherence to Malaria Treatment Guidelines Among Health Care Workers in Private Health Facilities in Kampala’s Informal Settlements, Uganda, PLOS Glob Public Health. 2023 Sep 5; 3(9): e0002220, https://doi.org/10.1371/journal.pgph.0002220, a “cross-sectional study was conducted among 339 HCWs from private health facilities in slums of 4 selected divisions in Kampala, Uganda… Almost all of the respondents 98.8%(335/339) reported that they had malaria diagnostic equipment (microscopy or rapid diagnostic tests) at their facilities, 47.5% … had non-recommended anti-malarial drugs present in stock and 36.0% reported that they did not refer severely ill patients to higher health facilities in the previous 3 months. Although 92.6% … of the respondents had heard about the national malaria treatment guidelines, 63.1%…. of them adhered to these guidelines. Having a bachelor’s degree …, and having high levels of knowledge …. were positively associated with high adherence to malaria treatment guidelines…”

“Pyronaridine-artesunate was … recommended in the 2022 update of the WHO Guidelines for the Treatment of Malaria, becoming the newest artemisinin-based combination therapy (ACT) for both uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Pyronaridine-artesunate, …, is being adopted in regions where malaria treatment outcome is challenged by increasing chloroquine resistance.” Chu WY & Dorlo TPC, Pyronaridine: A Review of Its Clinical Pharmacology in the Treatment of Malaria, J Antimicrob Chemother. 2023 Aug 28: dkad260, https://doi.org/10.1093/jac/dkad260 reviews how the medication works and the history of its use.

Side effects and complications

None this month

Drug resistance

It has long been held that the way resistance to antibiotics spreads is by the existence of a small number of partially or fully resistant mutants that survive standard or especially inadequate antibiotic treatment.  If the Abstract of Stadler E & al., Propensity of Selecting Mutant Parasites for The Antimalarial Drug Cabamiquine, Nat Commun. 2023 Aug 25; 14(1):5205, https://doi.org/10.1038/s41467-023-40974-8 is a fully consistent reflection of the article, the report elegantly demonstrates this very effect occurring in the mouse model of Plasmodium falciparum infection.

Reacting to the spread of artemisinin resistance to Eastern Africa, Conrad MD & al. did genetic analysis of parasites from a variety of locations in Uganda.  They report in Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda, N Engl J Med. 2023 Aug 24; 389(8):722-732, https://doi.org/10.1056/nejmoa2211803 that “the prevalence of parasites with validated or candidate resistance markers reached more than 20% in 11 of the 16 districts where surveillance was conducted. The … mutations … seen in far northern Uganda in 2016-2017 … increased and spread thereafter, reaching a combined prevalence of 10 to 54% across much of northern Uganda, with spread to other regions. [Another] mutation reached a prevalence of 38 to 40% in one district in southwestern Uganda in 2021-2022. [A third] mutation, previously described in Rwanda, was first seen in southwestern Uganda in 2021, reaching a prevalence of 23% by 2022. [Yet another] mutation reached a prevalence of 12 to 23% in three districts in western Uganda in 2022.

In order to prevent or at least to delay the emergence of artemisinin resistance, Guissou RM & al. conducted a study including interviews and focus groups. They make the following recommendations in The Impact of Anti-Malarial Markets on Artemisinin Resistance: Perspectives from Burkina Faso, Malaria J, 2023 Sep 13, 22:269, https://doi.org/10.1186/s12936-023-04705-0: “(1) Address the suboptimal prescription of anti-malarial drugs, (2) Apply laws that prohibit the sale of anti-malarials without prescription, (3) Restrict the availability of street drugs, (4) Sensitize the population on the value of compliance regarding correct acquisition and intake of anti-malarials. Funding systems for anti-malarial drugs in terms of availability and accessibility must also be stabilized.”

Much of Shafi S & al., Tackling the Emerging Artemisinin-Resistant Malaria Parasite by Modulation of Defensive Oxido-Reductive Mechanism Via Nitrofurantoin Repurposing, Biochem Pharmacol. 2023 Aug 18: 115756, https://doi.org/10.1016/j.bcp.2023.115756 is taken up by reviewing the pharmacology of artemisinin resistance and how nitrofurantoin (NTF, an antibiotic used mostly for human urinary system infections) may specifically act against this resistance.  The addition of NTF to artemisinin in mice infected with resistant Plasmodium resulted in decreased parasite multiplication and increased survival of the experimental mice as compared to controls that didn’t receive NTF. 

While it is essentially a basic research article, Atul & al., Artemisinin Resistance in P. falciparum: Probing the Interacting Partners of Kelch13 Protein in Parasite, J Glob Antimicrob Resist. 2023 Aug 24: S2213-7165(23)00137-6, https://doi.org/10.1016/j.jgar.2023.08.012 elucidates a great deal of the intracellular mechanisms at play in expressing the Pf Kelch13 gene (i.e. the resistance gene) mechanisms in creating the drug resistance.


The drug resistance to which Wotodjo AN & al., Rebound of Multiple Infections and Prevalence of Anti-Malarial Resistance Associated Markers Following Malaria Upsurges in Dielmo Village, Senegal, West Africa, Malaria J, 2023 Sep 5, 22:257, https://doi.org/10.1186/s12936-023-04694-0 refers is resistance to chloroquine.  Apparently in the village studied, repeated malaria infections in the population was caused by increasing frequency of chloroquine resistant P. falciparum. Although the abstract does not explicitly states it, apparently the antimalarial(s) used in the area do(es) not include artemisinins.

New drug research

Aly NSM & al. “evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxa-spiro[7.11]-nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo.” As reported in Evaluating the Activity of N-89 as an Oral Antimalarial Drug, Parasites Hosts Dis. 2023 Aug; 61(3):282-291, https://doi.org/10.3347/phd.23044, the drug was effective. “In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days.” The authors state that “the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.”

The abstract of Nema S & Nitika N, Monoclonal Antibody: Future of Malaria Control and Prevention, Trans R Soc Trop Med Hyg. 2023 Sep 1; 117(9):673-674, https://doi.org/10.1093/trstmh/trad027 reads as follows: “Monoclonal antibodies (mAbs) are extremely specialized proteins that are cloned from B cells and bind to pathogen epitopes. There are currently no known prophylactic immune-based strategies or efficient, widespread treatments to stop the spread of malaria. In order to lower the prevalence of malaria and its associated mortality, we need mAbs that are capable of offering immediate passive protection against the disease. … Recently, mAb development for malaria prevention and control has greatly evolved and widespread use in public health settings is now a possibility.” Unfortunately, there is no access to the article itself to determine whether any concrete evidence is presented therein.

The claim made by Singh K & Tripathi RP is that “[w]ith the increased knowledge on protein-sugar interaction and glycomics of Plasmodium parasites, carbohydrate derivatives can surpass the existing biochemical pathways responsible for drug resistance. The new candidates with novel mode of action will prove to be a potent antimalarial drug candidate without any parasitic resistance.” Whether the article, Carbohydrate Derivatives Fight Against Malaria Parasite as Anti-Plasmodial Agents, Carbohydr Res. 2023 Sep; 531:108887, https://doi.org/10.1016/j.carres.2023.108887 sheds more light on the mechanisms involved than the abstract, is unclear.

Plant extracts and traditional treatments

Nortey NND & al. report the results of a survey of an unknown number of pharmacies in Herbs Used in Antimalarial Medicines: A Study in the Greater Accra Region of Ghana, Evid Based Complement Alternat Med. 2023 Aug 19; 2023:6697078, https://doi.org/10.1155/2023/6697078.  They found that 44 plant species were used, but that “Cryptolepis sanguinolenta (Ghanaian quinine or yellow dye root) and Azadirachta indica (neem tree) were the most cited plants. Cryptolepis and neem tree were used 17 and 15 times, respectively, in the finished herbal products for treating malaria.”

“Lophira lanceolata, commonly known as the dwarf red ironwood, is a species of tree in the family Ochnaceae which is native to tropical West and Central Africa. The timber is used for heavy construction, an edible oil can be extracted from the seeds and various parts of the plant are used in traditional medicine”(Wikipedia). Azizi MA & al., Antimalarial Efficacy and Antioxidant Activity of Lophira lanceolata Stem Bark Ethanol Extract Using Plasmodium berghei Induced-Malaria in Swiss Albino’s Mice, J Parasitol Res. 2023 Aug 18; 2023:9400650, https://doi.org/10.1155/2023/9400650 describes the studies the authors conducted with the result that the “ethanol extract of L. lanceolata showed a dose-dependent suppressive activity … … The ethanol extract of L. lanceolata caused a reduction of tissue markers, such as hepatic oxidative stress, as it increased the enzymatic activity of antioxidant enzymes…. However, further in vivo toxicity tests are required to guarantee their safety.”

Despite a name that calls up medicinal properties in humans, Senna occidentalis (coffee senna) is a potentially highly toxic plant. Mogaka S & al. used its root extracts and report in Antimalarial Efficacy and Safety of Senna occidentalis (L.) Link Root Extract in Plasmodium berghei-Infected BALB/c Mice, Biomed Res Int. 2023 Aug 7; 2023:8296195, https://doi.org/10.1155/2023/8296195 that they detected no toxicity in the mice they treated with the extract, while the substance showed strong antiplasmodial effect, as had been predicted by in vitro studies.


None this month

Campaigns and Policies

Dako-Gyeke P & al.’s study “aimed to explore the opportunities and barriers to the pilot implementation of co-created community health advocacy teams (CHATs) to improve the effectiveness of LLIN distribution through both campaigns and continuous channels in Ghana… The CHATs were pilot implemented in all study communities for 4 months after which … CHAT members participated in six focus group discussions.” They report in Pilot Implementation of Community Health Advocacy Teams to Improve the Effectiveness of Long-Lasting Insecticide Net Distribution Through Both Campaigns and Continuous Channels in Ghana: A Qualitative Study of Opportunities and Barriers to Implementation, Front Public Health. 2023 Jul 31; 11:1133151, https://doi.org/10.3389/fpubh.2023.1133151 that “CHATs were instrumental in sensitising community members through SBCC strategies. Moreover, there were changes in the behaviour of community members who were receptive towards and participated in CHAT activities. Community members were accurately informed about malaria … However, the CHAT[s] experienced barriers during implementation, including a lack of financial support to aid in transportation, organisation of meetings, and outreach activities.”

“Tanzania is undergoing an epidemiological transition for malaria transmission with some areas of the country having <10% (hypoendemic) and other areas 10% – 50% malaria prevalence (mesoendemic). It is not known whether there is a difference in the quality of malaria case management based on endemicity in Tanzania mainland.” Hussein AK & al. “examined the influence of endemicity on the quality of malaria case management at health facilities [and] conducted a cross-sectional analysis of 1713 health facilities in Tanzania mainland, using data collected by the National Malaria Control Program through an assessment tool to evaluate quality of malaria case management.” In The Quality of Malaria Case Management in Different Transmission Settings in Tanzania Mainland, 2017-2018, PLOS Glob Public Health. 2023 Aug 21; 3(8):e0002318, https://doi.org/10.1371/journal.pgph.0002318 they report that [f]acilities in mesoendemic regions scored higher than those in hypoendemic regions on the overall quality of services … site readiness …, availability of malaria reference materials …, availability of Health Management Information System tools … and patient satisfaction…”

“…Malawi [has] recently seen a reversal in malaria control progress with reported increases in confirmed malaria cases. This may be the result of inadequate access to effective malaria control interventions by key population groups that perpetuate transmission. [Mhango P & al.] aimed to assess the barriers to accessing malaria treatment among school-aged children (SAC) in Malawi.” They report in Barriers to Accessing Malaria Treatment Amongst School-Age Children in Rural Malawi, Malaria J, 2023 Sep 6, 22:258, https://doi.org/10.1186/s12936-023-04695-z that “[h]ealth system barriers to malaria treatment included long waiting hours and queues at clinics, frequent stock-outs of medical supplies, and travel time to the facility. Provider barriers included negative attitude and limited service hours. Individual and cultural barriers included fear of malaria tests and beliefs associating witchcraft as the best treatment for malaria. In addition, COVID-19-related barriers included the inability to follow preventive measures, a shift in focus from malaria to COVID-19, and fear of contracting COVID-19 and/or being tested for COVID-19 at the facility.”

Ozodiegwu ID & al., Description of the Design of a Mixed-Methods Study to Assess the Burden and Determinants of Malaria Transmission for Tailoring of Interventions (Microstratification) in Ibadan and Kano Metropolis, Malaria J, 2023 Sep 4, 22:255, https://doi.org/10.1186/s12936-023-04684-2 outlines “pioneering field study methods aimed at collecting data to inform the tailoring of malaria interventions in urban settings. The integration of multiple study types will provide valuable data for mapping malaria risk and comprehending the underlying determinants. Given the importance of location-specific data for microstratification, this study presents a systematic process and provides adaptable tools that can be employed in cities with limited data availability.”

Based on a meta-analysis of 96 papers published, Newby G & al. conclude that the proactive mass Test and Treat approach “is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD {reactive case detection} may indirectly reduce transmission by informing coordinated responses of intervention targeting.” The paper is Testing and Treatment for Malaria Elimination: A Systematic Review, Malaria J, 2023 Sep 3, 22:254, https://doi.org/10.1186/s12936-023-04670-8

Quaye IK & al., Malaria Elimination in Africa: Rethinking Strategies for Plasmodium vivax and Lessons from Botswana, Trop. Med. Infect. Dis. 2023, 8(8), 392, https://doi.org/10.3390/tropicalmed8080392 calls attention to the consequences of campaigns aimed at P. falciparum elimination in communities where coinfections with P. vivax or monoinfections by P. vivax may exist, such as in Botswana between 2008 and 2018.

Weston S & al. investigated whether the policy of informing research subjects of the results of research is useful and whether it is being invoked. Their paper, Sharing Results with Participants (and Community) in Malaria Related Research: Perspectives and Experience from Researchers, PLOS Glob Public Health. 2023 Sep 5; 3(9):e0002062, https://doi.org/10.1371/journal.pgph.0002062 appears to shed little light on the subject, because they used i) an initial qualitative phase to explore the topic and to inform the quantitative data collection, ii) a quantitative survey and somewhat fewer than 20% of invited survey subjects participated.  Still, the authors conclude that “[b]etter planning which includes adequate financial resourcing is required for meaningful dissemination of results to study participants. Improved institutional guidance and more stringent requirements by funders could support researchers who are generally interested and willing to complete the process.”


Climate change, biodiversity and environment

Filho WL & al. set about to describe “the association between average temperature and malaria incidence rates (IR) in nine sub-Saharan African countries” in Climate Change and Malaria: Some Recent Trends of Malaria Incidence Rates and Average Annual Temperature in Selected Sub-Saharan African Countries from 2000 to 2018, Malaria J, 2023 Aug 28, 22:248, https://doi.org/10.1186/s12936-023-04682-4. They state in the abstract that “[t]The incidence of malaria can vary both in areas where the disease is already present, and in regions where it is present in low numbers or absent. The increased vulnerability to the disease under increasing average temperatures and humidity is due to the new optimal level for vector breeding in areas where vector populations and transmission are low, and populations are sensitive due to low acquired immunity.” Yet, the data to which they refer show that “malaria IR [incidence rate] varies considerably, with high values in Uganda, Mozambique, Nigeria and Zambia, moderate values in Ghana, Zimbabwe, and Kenya, and low values in South Africa and Ethiopia in 2018. Evidence suggests varying IRs after average temperature fluctuations in several countries … Also, an inverse temperature-IR relationship occurs, the sharp decrease of IR during 2012–2014 and 2000–2003, respectively, occurred with increasing average temperatures in Ghana and Nigeria. The decreasing trends and fluctuations, partly accompanying the temperature, should result from the intervention programmes and rainfall variability. The vulnerability and changing climate could arrest the recent trends of falling IR.”  They are unable to reach any real conclusion relating to climate change.

General epidemiology

The transmission of malaria across land borders, especially from a country with endemic malaria to one that has been malaria free is the subject of Li X & al., Border Malaria: Defining the Problem to Address the Challenge of Malaria Elimination, Malaria J, 2023 Aug 21, 22:239, https://doi.org/10.1186/s12936-023-04675-3. The authors state that “[b]order malaria reflects the limitations of the current tools and interventions for malaria elimination and implies the need for social cohesion, basic health services, community economic conditions, and policy dialogue and coordination to achieve the expected impact of malaria interventions. Given the uniqueness of each border and the complex and multifaceted nature of border malaria, a situation analysis to define and characterize the determinants of transmission is essential to inform a problem-solving mindset and develop appropriate strategies to eliminate malaria in these areas.”

Agbemafle EE & al. evaluated the malaria surveillance system in Adaklu District of the Volta Region of Ghana to determine if the system was meeting its objectives and assessed its usefulness and attributes. In Evaluation of the Malaria Surveillance System – Adaklu District, Volta Region, Ghana, 2019, Public Health Pract (Oxf). 2023 Jul 29; 6:100414. https://doi.org/10.1016/j.puhip.2023.100414 they used “the Centers for Disease Control and Prevention updated guidelines for evaluating public health surveillance systems … Of the 80,441 suspected malaria cases recorded … from 2014 to 2018, 47,917 (59.6%) cases were confirmed. The system was meeting its objective of detecting malaria cases and monitoring trends in the population however, the system missed an epidemic in August 2016.”


 “As part of the large evaluation of the malaria vaccine implementation programme (MVIP),” Stanley CC & al. “analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics” As reported in Prompt Treatment-Seeking Behaviour Varies Within Communities Among Guardians of Children with Malaria-Related Fever in Malawi, Malaria J, 2023 Aug 26, 22:246, https://doi.org/10.1186/s12936-023-04680-6, “[f]ever prevalence was high in communities with low socio-economic status (SES) .. and low in areas with high SES … Among children with fever, 648 (39.5%) sought treatment … within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education … [and] in communities with high compared to low SES … Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km” of one.

“Zanzibar has made substantial progress in malaria control with vector control, improved diagnosis, and artemisinin-based combination therapy. Parasite prevalence in the population has remained around 1% but imported infections from mainland Tanzania contribute to sustained local transmission.” Fakih BS & al., Risk of Imported Malaria Infections in Zanzibar: A Cross-Sectional Study, Infect Dis Poverty. 2023 Aug 28; 12(1):80, https://doi.org/10.1186/s40249-023-01129-5 proposes “identifying population groups traveling to highly endemic areas in mainland Tanzania[,] based on data they cite that among “travellers to mainland Tanzania, those visiting highly endemic districts had higher odds of being qPCR-positive than those who travelled only to districts where malaria-endemicity was classified as low or very low.”

Neyer PJ & al. investigated genetic and other factors that may protect individuals from asymptomatic malaria and their paper, Exploring the Host Factors Affecting Asymptomatic Plasmodium falciparum Infection: Insights from a Rural Burkina Faso Study, Malaria J, 2023 Sep 1, 22:252, https://doi.org/10.1186/s12936-023-04686-0 cites Hemoglobin S as a protecting factor, but not other genetic variations.  Malnutrition is apparently a risk factor, although there is no comment on whether the association is actually causal.


While not strictly an epidemiologically focused article, Kirosingh AS & al., Malaria-Specific Type 1 Regulatory T Cells Are More Abundant in First Pregnancies and Associated with Placental Malaria, EBioMedicine. 2023 Aug 24; 95:104772, https://doi.org/10.1016/j.ebiom.2023.104772 is included here because it deal with the increased risk of malaria and placental malaria that women experiencing the first pregnancies face as compared to multigravidas. The article relates the increased risk to “[m]alaria-specific Tr1 cells [that] were highly prevalent in primigravid Ugandan women, and their presence correlated with a higher risk of malaria in pregnancy…”

Spatiotemporal studies

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

Debash H & al., Burden and Seasonal Distribution of Malaria in Ziquala District, Northeast Ethiopia: A 5-Year Multi-Centre Retrospective Study, BMJ Open. 2023 Aug 18; 13(8):e067103, https://doi.org/10.1136/bmjopen-2022-067103

Ujuju CN & al., Unravelling Factors Associated with Malaria Parasitaemia Among Children 6–24 Months to Inform Malaria Interventions in Nigeria: Evidence from 2021 Malaria Indicator Survey, Malaria J, 2023 Aug 28, 22:247, https://doi.org/10.1186/s12936-023-04683-3

Bittaye SO & al., Malaria in Adults After the Start of Covid-19 Pandemic: An Analysis of Admission Trends, Demographics, and Outcomes in a Tertiary Hospital in The Gambia, Malaria J, 2023 Sep 1, 22:253, https://doi.org/10.1186/s12936-023-04691-3

Lakew YY & al., Magnitude of Malaria and Associated Factors Among Febrile Adults in Siraro District Public Health Facilities, West Arsi Zone, Oromia, Ethiopia 2022: A Facility-Based Cross-Sectional Study, Malaria J, 2023 Sep 6, 22:259, https://doi.org/10.1186/s12936-023-04697-x






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