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

The attention of readers of these summaries is directed to a CAVEAT at the conclusion of this report, which applies to all of these monthly reports as well to the biomedical literature in general.







Dieng CC & al. were concerned that the target peptide of the current malaria vaccine in use may be subject to genetic variation, adversely influencing the effectiveness of the RTS,S vaccine. In their paper, Genetic Variations of Plasmodium falciparum Circumsporozoite Protein and the Impact on Interactions with Human Immunoproteins and Malaria Vaccine Efficacy, Infect Genet Evol. 2023 Feb 23: 105418, https://doi.org/10.1016/j.meegid.2023.105418, they found significant variability in the protein, though apparently none of the 27 haplotypes they observed had reduced affinity to the experimental substance they used.  Still, they suggest use of a “longer” peptide in future vaccine design.

As the result of the recently successful use of RNA vaccines against COVID-19, Hayashi CTH & al. studied how the technology might be used in designing an effective malaria vaccine. They “evaluated the immunogenicity of two leading P. falciparum vaccine candidates, Pfs25 and PfCSP, delivered as mRNA-LNP vaccines. Both vaccines induced extremely potent immune responses when administered alone or in combination, which were superior to Pfs25 and PfCSP DNA vaccine formulations. They also report in   , mRNA-LNP Expressing PfCSP and Pfs25 Vaccine Candidates Targeting Infection and Transmission of Plasmodium falciparum, npj Vaccines, 2022 Dec 1, 7:155, https://www.nature.com/articles/s41541-022-00577-8#Abs1 that in mice, there was evidence for varying degrees of protection against sporozoite challenge, when mRNA-based vaccine was used.

da Silveira Mariano RM & al., A Review of Major Patents on Potential Malaria Vaccine Targets, Pathogens, 2023 Feb 3; 12(2):247, https://doi.org/10.3390/pathogens12020247discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite’s replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures.”

In view of the recognized incomplete coverage by the current RTS,S vaccine, Vigdorovich V & al. advocate accompanying the vaccine with another preventive injection. Their paper, Coimmunization with Preerythrocytic Antigens Alongside Circumsporozoite Protein Can Enhance Sterile Protection Against PlasmodiumSporozoite Infection, Microbiol Spectr. 2023 Feb 27: e0379122, https://doi.org/10.1128/spectrum.03791-22 reports on targeting multiple proteins or peptides in an in vitro model that resulted in what they call “compelling evidence that a multiantigen preerythrocytic vaccine approach may enhance protection compared to CSP-only vaccines.”

Vector control and protection from vectors

Two articles reflect on the need to optimize housing to the extent possible from the point of view of vector control. Chisanga B & al., The Economic Impacts of House Screening Against Malaria Transmission: Experimental Evidence from Eastern Zambia, Soc Sci Med. 2023 Feb 19; 321:115778. https://doi.org/10.1016/j.socscimed.2023.115778 concludes from survey data, including condition of housing, and economic indicators that improving “screening is a promising and cost-effective approach to reduce malaria infections.” 

“Despite evidence that well-constructed and mosquito-proofed houses can reduce malaria risk, housing improvement is rarely included in malaria control toolboxes,” according to Bofu RM & al., The Needs and Opportunities for Housing Improvement for Malaria Control in Southern Tanzania, Malar J. 2023 Feb 27; 22:69, https://doi.org/10.1186/s12936-023-04499-1. They studied “19 villages … in southern Tanzania. A structured survey was [used] to assess need, perceptions, and opportunities for housing improvement for malaria control. …[H]ousing improvement was among the best understood and most preferred by community members. Of the 735 survey respondents who needed housing improvements, a majority needed window screening (91.1%), repairs of holes in walls (79.4%), door covers (41.6%), closing of eave spaces (31.2%) and better roofs (19.0%)”

“Nigeria accounts for a quarter of malaria cases worldwide, which can be prevented with the use of insecticide treated nets (ITN)” state Adejoh SO & al. in Regional Variations in Child and Mother’s Characteristics Influencing the Use of Insecticide Treated Net in Nigeria, J Biosoc Sci. 2023 Mar; 55(2):326-343. https://doi.org/10.1017/s0021932022000050. They posit that maternal and childhood data can best reflect the use of these nets. The “2015 Nigeria Malaria Indicator Survey … comprised 6524 mothers … aged 15-49.” The authors found that “less than half (47.9%) of the respondents reported no access to a mosquito net in the north compared to 70.8% in the south. More than half (51.4%) of the northern respondents used ITN for the child compared to 27.1% of southern mothers. … [P]lace of residence, mother’s age, mother’s education, wealth, religion, number of children in the household and previous … child mortality were associated with the use of ITN.”

Just as the above paper, multiple authors have reported that the use of ITNs, even when available, is far short of the desired 100%.  Koenker H & al. attempts to find the reasons for non-use. Reported Reasons for Non-Use of Insecticide-Treated Nets in Large National Household Surveys, 2009–2021, Malar J, 2023 Feb 21, 23:61, https://doi.org/10.1186/s12936-023-04490-w reports on a variety of surveys conducted between 2003 and 2021.  “Reported reasons for why a net goes unused fell largely into three categories—nets that are extra/being saved for future use; the perception that there is little risk of malaria (particularly in dry season); and “other” responses. Net attributes such as colour, size, shape, and texture, and concerns related to chemicals were the least frequent reasons given.”

Challenger JD & al. “utilised disaggregated data from 15 previous EHTs {experimental hut trials} to gain insight into the behaviour typically observed. Using simulations from generalised linear mixed models to obtain power estimates for EHTs, [they] show how factors such as the number of mosquitoes entering the huts each night and the magnitude of included random effects can influence study power. A wide variation in behaviour is observed in both the mean number of mosquitoes collected per hut per night (ranging from 1.6 to 32.5) and overdispersion in mosquito mortality. This variability in mortality is substantially greater than would be expected by chance.” The paper is Assessing the Variability in Experimental Hut Trials Evaluating Insecticide-Treated Nets Against Malaria Vectors, Curr Res Parasitol Vector Borne Dis, 2023 Feb 9; 3:100115. https://doi.org/10.1016/j.crpvbd.2023.100115.

Gene drive technologies to eliminate certain mosquito populations have sometimes been controversial. de Graeff N & al., Alleviating the Burden of Malaria with Gene Drive Technologies? A Biocentric Analysis of the Moral Permissibility of Modifying Malaria Mosquitoes, J Med Ethics. 2023 Feb 28: medethics-2022-108359, https://doi.org/10.1136/jme-2022-108359 look at the issue from an ethical perspective and conclude that their “ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met.”

Eshetu T & al. caught mosquitoes in a malarious area and analyzed the content of their gut. As reported in Cattle Feeding Tendency of Anopheles Mosquitoes and Their Infection Rates in Aradum Village, North Wollo, Ethiopia: An Implication for Animal-Based Malaria Control Strategies, Malar J. 2023 Mar 7;22(1):81, https://doi.org/10.1186/s12936-023-04516-3, that much of blood found in the mosquitoes’ digestive system was of bovine origin.  They conclude that “[s]ince the Anopheles mosquitoes in the area prefer to bite cattle, it may be best to target them with an animal-based intervention.” Please see CAVEAT below, since the authors use the word “majority” even though the word does not completely agree with the data they cite.

A JOHNS HOPKINS PODCAST, Anopheles stephensi Found in Marsabit, Kenya states:The migration of Anopheles stephensi, an invasive mosquito species, threatens to redefine malaria in Africa. We ask what makes the mosquito so dangerous for malaria on the continent.”  I have not heard this podcast.

At least four other papers also concern themselves with the expansion of An. stephensi habitat in Africa.

Whittaker C & al., Seasonal Dynamics of Anopheles stephensi and its Implications for Mosquito Detection and Emergent Malaria Control in the Horn of Africa, Proc Natl Acad Sci U S A. 2023 Feb 21; 120(8):e2216142120, https://doi.org/10.1073/pnas.2216142120 addresses the seasonal variation or lack thereof of malaria transmitted by the species in the area where it originally invaded the continent. The authors’ “analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi.” The accompanying editorial by Tian H will be briefly mentioned under Epidemiology.

Kristan M & al., Towards Environmental Detection, Quantification, and Molecular Characterization of Anopheles stephensi and Aedes aegypti from Experimental Larval Breeding Sites, Sci Rep. 2023 Feb 15; 13(1):2729, https://doi.org/10.1038/s41598-023-29657-y reports on detection of the two species. “Using new multiplex TaqMan assays, specifically targeting An. stephensi and Ae. aegypti, [the authors] validated the use of environmental DNA (eDNA) for simultaneous vector detection in shared artificial breeding sites. Study findings demonstrated that An. stephensi and Ae. aegypti eDNA deposited by as few as one second instar larva in 1L of water was detectable… Attractive toxic sugar bait (ATSB) is a promising “attract and kill”-based approach for mosquito control. It is a combination of flower nectar/ fruit juice to attract the mosquitoes, sugar solution to stimulate feeding, and a toxin to kill them.”

Kumar S, & al. focus on this way to eliminate the newly resident vector in Laboratory Evaluation of the Efficacy of Deltamethrin-Laced Attractive Toxic Sugar Bait Formulation on Anopheles stephensi, Malar J, 2023 Mar 11, 23:92, https://doi.org/10.1186/s12936-023-04524-3. I laboratory-based studies, “ATSB formulated with guava juice-ASB and deltamethrin (0.0015625–0.8%) in 9:1 ratio showed promising results against two laboratory strains of An. stephensi. Field assessment of these formulations is being conducted to estimate their feasibility for use in mosquito control.” 

Chanda J & al. also studied the feasibility of ATSB. In Feeding Rates of Malaria Vectors from a Prototype Attractive Sugar Bait Station in Western Province, Zambia: Results of an Entomological Validation Study,Malar J. 2023 Mar 1; 22:70, https://doi.org/10.1186/s12936-023-04491-9 they found all malaria vectors among the insects trapped. While the calculated “daily feeding rate” was 8.9% for An. funestus and 3.9% for An. gambiae, they conclude that using these traps laced with insecticide achieve material “reductions in malaria transmission when used in combination with conventional control methods.”.

Lees RS, & al., Insecticides for Mosquito Control: Improving and Validating Methods to Strengthen the Evidence Base, Insects, 2023 Jan 23; 14(2):116. https://doi.org/10.3390/insects14020116 is a thorough discussion of insecticide resistance. There is no abstract available, but the article is accessible either through the doi site or through PubMed.

Das S & al. look at the genetic structure of two mosquito species, one uniformly resistant, the other uniformly sensitive to a specific insecticide and assert in Fine-Scale Spatial Distribution of Deltamethrin Resistance and Population Structure of Anopheles funestus and Anopheles arabiensis Populations in Southern Mozambique, Malar J,2023 Mar 14, 23:94, https://doi.org/10.1186/s12936-023-04522-5 that in view of this homogeneity, “strategies, such as transgenic mosquito release” programs should be   promising.

In Côte d’Ivoire, N’Dri BP & al. found the vector An. gambiae uniformly resistant to all insecticides except malathion. In Species Composition and Insecticide Resistance in Malaria Vectors in Ellibou, Southern Côte d’Ivoire and First Finding of Anopheles arabiensis in Côte d’Ivoire, Malar J, 2023 Mar 13, 23:93, https://doi.org/10.1186/s12936-023-04456-y they note that An. arabiensis demonstrates different behaviors than others of the An gambiae family, thus requiring new control measures.

To deal with pyrethroid resistance, another substance, chlorphenapyr has been used in some ITNs.  Tchouakui M & al. tested this substance against two species of Anopheles in a variety of Sub-Saharan countries.  As mentioned in the title of their article, Detection of a Reduced Susceptibility to Chlorfenapyr in the Malaria Vector Anopheles gambiae Contrasts with Full Susceptibility In Anopheles funestus Across Africa, Sci Rep. 2023 Feb 9; 13(1):2363, https://tinyurl.com/4efw36fu, a significant percentage of An. gambiae tested were resistant to this substance in every country tested, while An. funestus was invariably sensitive to it.

Another way of dealing with insecticide resistant mosquitoes is addressed in Rants’o TA & al., The Insecticidal Activity of Essential Oil Constituents Against Pyrethroid-Resistant Anopheles funestus (Diptera: Culicidae),Parasitol Int, 2023 Mar 8; 102749. https://doi.org/10.1016/j.parint.2023.102749, which describes the effects of six substances in the category of essential oils, of which three were found to be “potential agents for further investigation as novel bioinsecticides against pyrethroid-resistant An. funestus strain.”

A highly unusual, but potentially effective way of dealing with vectors is using parasitic fungi.  Renuka S & al., Entomopathogenic Fungi as a Potential Management Tool for the Control of Urban Malaria Vector, Anopheles stephensi (Diptera: Culicidae), J Fungi (Basel). 2023 Feb 8; 9(2):223. https://doi.org/10.3390/jof9020223 address the vector that is currently raising the alarm in urban environments in Africa.  They prepared “isolates” of two species of entomopathogenic fungi and applied them to adult and larval A. stephensi. All the adult mosquitoes were killed by the fungi with carrying survival times.  The larvae survived the treatments, but experienced delayed maturation.

Forson AO & al. studied the prevalence of mosquito larvae in certain locations and report in Larval Habitat Stability and Productivity in Two Sites in Southern Ghana, Malar J. 2023 Mar 2; 22:74, https://doi.org/10.1186/s12936-023-04498-2 that in these two sites 22.6% of larvae were from Anopheles, species, chiefly Anopheles gambiae, s.l. Their location was most frequent in wells, lowest in furrows and man-made ponds.  They conclude that to “optimize the vector control measures of malaria interventions in southern Ghana, larval control should be focused on larval habitats that are fed by underground water, as these are more productive habitats.”

Adelaja OJ & al. studied multiple plant and fruit extracts as potential mosquito larvicides in the laboratory.  In Toxicity of Insecticidal Plant Oils on the Larval and Adult Stages of a Major Malaria Vector (Anopheles gambiae Giles 1920), Parasitol Res. 2023 Mar 9, https://doi.org/10.1007/s00436-023-07806-6, they report that two of the oils they studied (Hyptis suevolens or “pignut” and Citrus sinensis or “sweet orange”) were remarkably effective in killing Anopheles gambiae larvae, while Nicotiana tabacum (tobacco) were best (100%!) against the adults of the same species. 

In view of recent articles in the press about the proliferation of seaweeds, it is interesting to see Mathivanan D & al.,Seaweed Sargassum wightii Mediated Preparation of TiO2 Nanoparticles, Larvicidal Activity Against Malaria and Filariasis Vectors, and Its Effect on Non-Target Organisms, Environ Res. 2023 Feb 25:115569, https://doi.org/10.1016/j.envres.2023.115569. This is essentially a basic research article, apparently using the seaweed as a catalyst in the development of larvicides.

A novel way of vector control is reported in Mang’are PA & al., Optimal Efficacy in Mosquito-Host Interaction Inhibition by 35-60 KHz Animal Sounds for Malaria Control, Biophys J. 2023 Feb 10; 122(3S1):553a, https://doi.org/10.1016/j.bpj.2022.11.2927.  While it is understandable that a frog sound (Odorrana tormota) would deter mosquitoes, it is unclear how the authors came to use the sound of beluga whales (Delphinapterus leucas).  Nonetheless, sounds of both, as well as the sound of male mosquito swarms apparently repelled mated female Anopheles, with the frog being the most potent.





WHO strongly recommends the use of intermittent preventive treatment of pregnancy (IPTp). Agyeman YN & al.assessed the predictors of three or more doses of sulfadoxine-pyrimethamine (SP) for this purpose in Northern Ghana and report in Predictors of Optimal Uptake of Intermittent Preventive Treatment of Malaria in Pregnancy Using Sulfadoxine-Pyrimethamine and Outcome of Pregnancy in Selected Health Facilities: A Cross-Sectional Study in Northern Ghana, Malar J, 2023 Mar 9, 23:80, https://doi.org/10.1186/s12936-023-04501-w that of “1146 women, 42.4% received 3 or more doses of IPTp-SP as recommended by the national malaria control strategy. SP uptake was significantly associated with antenatal care (ANC) attendance … primary education … four or more antenatal care visits … ANC care visit in second trimester … and third trimester … and malaria infection during late gestation.” Overall, the “percentage of pregnant women who received three or more doses is below the target of the National Malaria Control Programme…”

Lingani M & al. hypothesized that adding azithromycin to the standard IPTp regimen may prevent other infections during pregnancy and thereby improve the outcome of pregnancy in terms of low birthweight babies.  They report in Effects of Maternal Antenatal Treatment with Two Doses of Azithromycin Added to Monthly Sulfadoxine-Pyrimethamine for the Prevention of Low Birth Weight in Burkina Faso: An Open-Label Randomized Controlled Trial, Malar J, 2023 Mar 17, 23:101, https://doi.org/ 10.1186/s12936-023-04530-5 that such was not the case; “[a]dding azithromycin to the regimen does not offer further benefits.”

Henderson E, New Antimalarial Prevents Malaria More Effectively than Current Treatments but Does Not Improve Birth Outcomes, (downloaded 10 March from https://www.news-medical.net/news/ 20230310/New-antimalarial-prevents-malaria-more-effectively-than-current-treatments-but-does-not-improve-birth-outcomes.aspx) refers to a recently published Lancet article that reports on a large trial of using dihydroartemisinin-piperaquine instead of SP for IPTp.  The outcome on maternal malaria was improved over SP, but there were “no differences in the number of babies born too early, pregnancy loss or early infant deaths. The study also revealed that mothers in the SP arm had better weight gain during pregnancy and better nutritional status at delivery. The results were seen in all three countries, including northern Tanzania, which had the highest rates of SP resistance in sub-Saharan Africa.” 

In an apparent contradiction the WHO’s finding moderate strong evidence that IPTp, administered at least three times to all pregnant women improves birth outcomes to both mother and infant, Uwimana A & al., Effectiveness of Intermittent Screening and Treatment of Malaria in Pregnancy on Maternal and Birth Outcomes in Selected Districts in Rwanda: A Cluster Randomized Controlled Trial, Clin Infect Dis, 2023 Mar 10; ciad128, http://doi.org/10.1093/cid/ciad128 claims that in their study population, mothers diagnosed with malaria during pregnancy and treated with SP, that is the IPTp protocol, had more low birth weight babies than mothers not treated.  However, careful reading of the abstract discloses that only mothers who tested positive for malaria received the protocol, not all mothers in prenatal care.  The control group may also have consisted only of mothers with positive PRC.  This paper is an example of those requiring close scrutiny, as described in the paragraph on CAVEAT below.


Nuwa A & al. “assessed the protective effectiveness of monthly administration of SP + [Amodiaquine] (SPAQ) to children aged 3–59 months in [a region of] Uganda, where parasite resistance is assumed to be high and malaria transmission is seasonal.”  A Non-Randomized Controlled Trial to Assess the Protective Effect of SMC in the Context of High Parasite Resistance in Uganda, Malar J, 2023 Feb 22, 23:63, https://doi.org/10.1186/s12936-023-04488-4 reports that “malaria incidence rate was 3.0 and 38.8 per 100 person-months in the intervention and control groups, respectively. In the intervention areas 90.0% (361/400) of children did not experience any malaria episodes during the study period, compared to 15% (29/200) in the control area.” They state that SMC is highly efficacious in this setting.


Transmission blocking from cattle to humans is the aim of the project described in Pooda SH & al., Proof-of-Concept Study for a Long-Acting Formulation of Ivermectin Injected in Cattle as a Complementary Malaria Vector Control Tool, Parasit Vectors. 2023 Feb 14; 16(1):66, https://doi.org/10.1186/s13071-022-05621-z. The authors “assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure.” The used two different formulations of long acting ivermectin and found that both “treatments significantly reduced mosquito survival, with average median survival time of 4-5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations.”

Baden L & al., Malaria – Epidemiology, Treatment, and Prevention, N Engl J Med. 2023 Feb 2; 388:e9, https://doi.org/10.1056/nejmp2216703. In this documentary video (which I have not seen), “physicians and scientists from across the world discuss the epidemiology of malaria and outline key strategies for prevention and treatment of the disease. The narrative takes a deep dive into prevention of the disease, including strategies to control mosquito vectors, new vaccines, and monoclonal antibodies. The video anticipates the challenges of eliminating malaria, given the emergence of drug-resistant strains, and looks to promising new therapies on the horizon.”

It is difficult to classify Balta VA & al., Transmissibility of Clinically Relevant Atovaquone-Resistant Plasmodium falciparum by Anopheline Mosquitoes, bioRxiv. 2023 Feb 9: 2023.02.07.527535, https://doi.org/10.1101/2023.02.07.527535.  They state as the conclusion of their study of the survival of atovaquone-resistant P. falciparum in the vector host, that this laboratory-bred parasite did not thrive in the vector and was not transmitted to “humanized mice.”  Therefore, they state that atovaquone may be a good preventive drug, since the parasite that survives it will not survive in the vector.



General diagnostics

Ding XC & al. focus on the diagnosis of malaria during pregnancy, but their paper, Malaria in Pregnancy (MiP) Studies Assessing the Clinical Performance of Highly Sensitive Rapid Diagnostic Tests (HS-RDT) for Plasmodium falciparum Detection, Malar J, 2023 Feb 20, 23:60, https://doi.org/10.1086/s12936-023-04445-1 is likely to be applicable to all situations in which accurate diagnosis of malaria is required. In various geographic areas the sensitivities of both tests were highly variable.  Still HS-RDT consistently outperformed conventional RDT in situations where parasite densities were low or very low.  The economic implications of using one test versus the other is not addressed.

van Dijk NJ & al., Laboratory Evaluation of the Miniature Direct-On-Blood PCR Nucleic Acid Lateral Flow Immunoassay (mini-dbPCR-NALFIA), a Simplified Molecular Diagnostic Test for Plasmodium, Malar J, 2023 Mar 17, 23:98, https://doi.org/ 10.1186/s12936-023-04496-4 describes another RDT that they state can easily performed in the field and has excellent sensitivity and specificity for Plasmodium and can distinguish between falciparum and non-falciparum malaria. 

Field diagnostics

While the WHO recommends microscopy as a definitive test, using it versus RDTs in the diagnosis has been studied repeatedly.  Opoku Afriyie S & al. embarked on this comparison in Ghana.  They report in Accuracy of Diagnosis Among Clinical Malaria Patients: Comparing Microscopy, RDT and a Highly Sensitive Quantitative PCR Looking at the Implications for Submicroscopic Infections, Malar J. 2023 Mar 4; 22:76, https://doi.org/10.1186/s12936-023-04506-5 that while RDT outperformed microscopy especially in low parasite density situations, both methods missed over 40% of infections diagnosed by highly sensitive PCR.

New diagnostic methods

Three papers deal with machine learning/artificial intelligence:

Hemachandran K & al., Performance Analysis of Deep Learning Algorithms in Diagnosis of Malaria Disease, Diagnostics (Basel). 2023 Feb 1;13(3):534, https://doi.org/10.3390/diagnostics13030534,

Li JX & al., Identifying Effective Diagnostic Biomarkers for Childhood Cerebral Malaria in Africa Integrating Coexpression Analysis with Machine Learning Algorithm, Eur J Med Res. 2023 Feb 13; 28(1):76m, https://doi.org/10.1186/s40001-022-00980-w, and

Siłka W & al., Malaria Detection Using Advanced Deep Learning Architecture, Sensors (Basel). 2023 Jan 29;23(3):1501, https://doi.org/10.3390/s23031501.

Regrettably, your reviewer’s inability to fathom this subject renders him unable to summarize even the conclusions of the abstracts.



Treatment results

WHO strongly recommends intramuscular artesunate as immediate treatment for severe malaria, but “[w]here intramuscular injection of artesunate is not available, treat children < 6 years with a single rectal dose (10mg/kg bw) of artesunate” with immediate referral for further treatment. Signorelli A & al. tested compliance with this guideline and report in Health Worker Compliance with Severe Malaria Treatment Guidelines in the Context of Implementing Pre-Referral Rectal Artesunate in the Democratic Republic Of The Congo, Nigeria, And Uganda: An Operational Study, PLoS Med. 2023 Feb 21; 20(2):e1004189, https://doi.org/10.1371/journal.pmed.1004189 that proper follow up was incomplete in all three countries studied.  They are concerned that the lack of follow up treatment is likely to lead to higher incidence of artemisinin resistance.

Agbemafle EE & al. refer to a guideline for treatment of febrile patients in two hospital outpatient departments in Adherence to the Test, Treat and Track Strategy for Malaria Control Among Prescribers, Mfantseman Municipality, Central Region, Ghana, PLoS One. 2023 Feb 21; 18(2):e0279712, https://doi.org/10.1371/journal.pone.0279712.  While adherence to the guidelines was better among physicians than other healthcare providers, overall statistics showed poor compliance.  This paper did not extend its discussion to results of the treatment.

In a human volunteer study Barber BE & al. investigated whether tafenoquine in a single low dose may be administered to glucose-6-dehydrogenase (G6PD) deficient individuals, and therefore be a good candidate for MDA campaigns. They report in Characterizing the Blood Stage Antimalarial Activity of Tafenoquine in Healthy Volunteers Experimentally Infected with Plasmodium falciparum, Clin Infect Dis. 2023 Feb 16: ciad075, https://doi.org/10.1093/cid/ciad075 that the single dose of tafenoquine required to clear P. falciparum was too large to administer safely to those deficient in G6PD.

Side effects and complications

Primaquine, the drug most effective against recurrent P. vivax and other non-falciparum malaria, is considered dangerous for individuals deficient in G6PD and is therefore recommended only those who test positive for that enzyme. Basen on review of 16 publications, Nelwan EJ & al. claim in Association of G6PD Status and Haemolytic Anaemia in Patients Receiving Anti-Malarial Agents: A Systematic Review and Meta-Analysis, Malar J. 2023 Mar 5; 22:77, https://doi.org/10.1186/s12936-023-04493-7 that when specific low doses of primaquine are given to children, “[t]he risk ratio of developing anaemia in G6PDd patients was 1.02… Single or daily standard doses of PQ (0.25 mg/kg/day) and weekly PQ (0.75 mg/kg/week) did not increase the risk of anaemia in G6PDd patients.”

Drug resistance

In a small study of 115 children in Accra, Ghana, less than 3% of children under age 5 who were treated with artemisinin combination therapy (ART) had residual disease after three days. Yet, Ahorhorlu SY & al., Assessment of Artemisinin Tolerance in Plasmodium falciparum Clinical Isolates in Children with Uncomplicated Malaria in Ghana, Malar J, 2023 Feb 19, 23:58, https://doi.org/10.1086/s12936-023-04482-w reports that about 8% of parasites obtained from 90 patients pre-treatment showed “tolerance” to dihydroartemisinin under laboratory conditions. The authors refer to the implications of development of tolerance.

Mbacham HF & al. found a large proportion of isolates from pregnant women to carry mutations associated with resistance to SP, which is used in IPTp. Their paper, Sub-Microscopic Plasmodium falciparum Parasitaemia, Dihydropteroate Synthase (Dhps) Resistance Mutations to Sulfadoxine-Pyrimethamine, Transmission Intensity and Risk of Malaria Infection in Pregnancy in Mount Cameroon Region, Malar J. 2023 Mar 2; 22:73, https://doi.org/10.1186/s12936-023-04485-7 actually contains  statistics relating to risks of infection, seasonality, and other factors.

New drug research

“Due to Plasmodium‘s resistance to available treatments, there is a need to search for new low-cost drugs that act through different mechanisms of action to contain this disease.” Dantas LC & al., A Short Review of Antimalarial Compounds with Sulfonamide Moiety, Mini Rev Med Chem. 2023 Feb 27, https://doi.org/10.2174/1389557523666230227113231 shows that compounds with sulfonamide moiety, possibly, act as inhibitors of P. falciparum carbonic anhydrases, moreover, when linked to a variety of heterocycles potentiate the activities of these compounds and may be used in the design of new antimalarial drugs.


Another approach to new drug development is what Tremblay T & al. call hybridization, specifically creating “molecular hybrids incorporating the hydroxychloroquine scaffold.” Squaramide Tethered Clindamycin, Chloroquine, and Mortiamide Hybrids: Design, Synthesis, and Antimalarial Activity, ACS Med Chem Lett. 2023 Jan 25; 14(2):217-222, https://doi.org/10.1021/acsmedchemlett.2c00531 states that some of the hybrids described in the title of the article showed excellent in vitro activity against the parasite strain tested.

Gao X & al. identified several extracts of artemisinin that were effective against P. falciparum. Whether these truly add to the armamentarium of antimalarials is questionable in view of emerging resistance, especially in Asia. The paper is Combined Chemical Transformation and Biological Transformation of Artemisinin: A Facile Approach to Diverse Artemisinin Derivatives, Front Chem. 2023 Jan 24; 10:1089290, https://doi.org/10.3389/fchem.2022.1089290.


Plant extracts and traditional treatments

“Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities,” as reported after a thorough literature search by Angupale JR & al. in A Review of Efficacy and Safety of Ugandan Anti-Malarial Plants with Application of RITAM Score, Malar J, 2023 Mar 17, 23:97, https://doi.org/10.1186/s12936-023-04486-6. They focus on three of these, Artemisia annua, known as the source of artemisinins, Vernonia amygdalina, also known as bitter leaf and apparently possessing antimalarial properties, and Microglossa pyrifolia, which they propose to combine with the other two herbals in uncertain proportions to treat malaria.  

The root of a poisonous plant known throughout Sub-Saharan Africa is used in folk medicine to treat malaria. Bizuneh GK & al., Antimalarial Activity of the 80% Methanol Extract and Solvent Fractions of Cucumis ficifolius A. Rich Roots Against Plasmodium berghei in Mice, Heliyon. 2023 Feb 11;9(2): e13690, https://doi.org/10.1016/j.heliyon.2023.e13690 studied extracts of the root against a different Plasmodium species in mice and found that some extracts increased survival time in the infected mice.  Whether that represented an actual cure is unknown, though the authors consider the substance promising enough to investigate further.

Trichilia monadelpha is an evergreen tree whose bark is used extensively in West Africa in folk medicine, primarily as an analgesic, but also for other conditions. Djoumessi AK & al. explored components of the bark as possible antimalarials.  Their report, Constituents of the Stem Bark of Trichilia monadelpha (Thonn.) J. J. De Wilde (Meliaceae) and Their Antibacterial and Antiplasmodial Activities, Metabolites. 2023 Feb 17; 13(2):298, https://doi.org/10.3390/metabo13020298, showed than in addition to anti-bacterial action, two of the extracts had suppressive effects on partially resistant P. falciparum strain.

Campaigns and Policies


Authored by individuals well known to MPI, Ashton RA & al., Effectiveness of Community Case Management of Malaria on Severe Malaria and Inpatient Malaria Deaths in Zambia: A Dose–Response Study Using Routine Health Information System Data, Malar J, 2023 Mar 17, 23:96, https://doi.org/ 10.1186/s12936-023-04525-2 reports on the 64 month ramp-up to community health workers (CHW) in Zambia to the point of one “service point (health facility of CHW) per 1000 population.”  The authors state that after accounting for covariates, this increase in service points “was associated with a 19% reduction in severe malaria admissions among children under … and 23% reduction in malaria deaths among under-fives…” They anticipate further gains as Zambia is moving toward one service point per 750 population.

Musoke D, & al., Integrated Malaria Prevention in Low- and Middle-Income Countries: A Systematic Review,Malar J. 2023 Mar 6; 22:79, https://doi.org/10.1186/s12936-023-04500-x has an intriguing title. “Literature on integrated malaria prevention, defined as the use of two or more malaria prevention methods holistically, was searched [by the authors] from 1st January 2001 to 31st July 2021.” Eventually they settled on 57 articles out of over 10,000 initially identified (much work for some Ph.D. students?). The only conclusive comment was the following: “There was reduced incidence and prevalence of malaria when multiple malaria prevention methods were used compared to single methods.”

The Malaria Frontline Project (MFP) of Nigeria “supported the National Malaria Elimination Program for effective program implementation in … high malaria-burden states … adapting the National Stop Transmission of Polio (NSTOP) program elimination strategies… The MFP developed training materials and job aids tailored to expected service delivery for primary and district health facilities and strengthened supportive supervision.” Adewole A & al., Malaria Frontline Project: Strategic Approaches to Improve Malaria Control Program Leveraging Experiences from Kano and Zamfara States, Nigeria, 2016-2019, BMC Health Serv Res. 2023 Feb 11; 23(1):147, https://doi.org/10.1186/s12913-023-09143-x reports on the outcome, which included significant improvement in both health care worker knowledge of proper diagnosis and practice in following treatment guidelines, though the latter remained short of 75% compliance in the areas studies.

Using direct observation and extensive interviews Otambo WO & al. explored the [performance of Community Health Volunteers (CHVs) in dealing with patients with fever.  They report in Community Case Management of Malaria in Western Kenya: Performance of Community Health Volunteers in Active Malaria Case Surveillance, Malar J.2023 Mar 8; 22:83, https://doi.org/10.1186/s12936-023-04523-4#citeas that the “qualification of the CHV had a significant influence on the quality of their service. The number of health trainings received by the CHVs was significantly related to the correctness of using job aid … and safety procedures during [active case detection]. Male CHVs were more likely than female CHVs to correctly refer RDT-negative febrile residents to a health facility for further treatment … Febrile residents in clusters managed by CHVs with more than 10 years of experience … and were over the age of 50 … were more likely to seek malaria treatment in public hospitals. All RDT positive febrile residents were given anti-malarial by the CHVs, and RDT negatives were referred to the nearest health facility for further treatment.”

Malpass A & al. report on a review of 23 published articles relating to the Status of Malaria in Pregnancy Services in Madagascar 2010–2021: A Scoping Review, Malar J, 2023 Feb 20, 23:59, https://doi.org/10.1086/s12936-023-04497-3. “Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women’s KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers.”



Climate change, biodiversity and environment

Carlson CJ & al. used “one of the most comprehensive datasets ever compiled by medical entomologists to track the observed range limits of African malaria mosquito vectors … from 1898 to 2016.” They estimate in Rapid Range Shifts in African Anopheles Mosquitoes over the Last Century, Biol Lett. 2023 Feb; 19(2):20220365, https://doi.org/10.1098/rsbl.2022.0365 “that these species’ ranges gained an average of 6.5 m of elevation per year, and the Southern limits of their ranges moved polewards 4.7 km per year. These shifts would be consistent with the local velocity of recent climate change and might help explain the incursion of malaria transmission into new areas over the past few decades.”

While Tian H, Modeling Malaria Elimination with Changing Landscapes, Climate, and Potentially Invasive Vectors, Proc Natl Acad Sci U S A. 2023 Mar 14; 120(11): e2301653120. https://doi.org/10.1073/pnas.2301653120 is an editorial specifically related to the Whittaker & al. paper cited above under vector control, the author emphasizes the possible role to climate change in the changing range of An. stephensi.

General epidemiology

“In Eastern Gambia, an all-age cohort from four villages was followed up from 2012 to 2016” by Ahmad A & al.  “Each year, cross-sectional surveys were conducted at the end of the malaria transmission season (January) and just before the start of the next one (June) to determine asymptomatic P. falciparum carriage. Passive case detection was conducted during each transmission season (August to January) to determine incidence of clinical malaria. Association between carriage at the end of the season and at start of the next one and the risk factors for this were assessed.” The report, Asymptomatic Plasmodium falciparum Carriage and Clinical Disease: A 5-Year Community-Based Longitudinal Study in The Gambia, Malar J. 2023 Mar 7; 22:82. https:/doi.org/10.1186/s12936-023-04519-0 concludes the “[a]symptomatic P. falciparum carriage at the end of a transmission season strongly predicted carriage just before start of the next one. Interventions that clear persistent asymptomatic infections when targeted at the subpopulation with high risk of carriage may reduce the infectious reservoir responsible for launching seasonal transmission.”

“The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania, and continued local transmission.” Connelly SV & al. claim in Strong Isolation by Distance and Evidence of Population Microstructure Reflect Ongoing Plasmodium falciparum Transmission in Zanzibar, medRxiv. 2023 Feb 23: 2023.02.15.23285960, https://doi.org/10.1101/2023.02.15.23285960 that their data “support that importation remains a main source of genetic diversity and contribution to the parasite population on Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission.”

A rare paper from Equatorial Guinea, García GA & al., Identifying Individual, Household and Environmental Risk Factors for Malaria Infection on Bioko Island to Inform Interventions, Malar J. 2023 Mar 1; 22:72, https://doi.org/10.1186/s12936-023-04504-7 reports on a situation very similar to the one identified in Zanzibar in the article above.  The island had greatly reduced its malaria prevalence, only to have it be reintroduced time and again by travelers from the mainland, since the vectors persist.

Choutos D & al., Malaria in Children: Updates on Management and Prevention, Pediatr Infect Dis J. 2023 Feb 8, https://doi.org/10.1097/inf.0000000000003746 is a comprehensive world-wide overview of the topics mentioned in the title. Approximately half the global population resides in malaria-endemic regions. “An estimated 241 million cases of malaria and 627,000 deaths occurred globally in 2020. More than half of the malaria deaths annually are in children younger than 5 years, their vast majority caused by P. falciparum in sub-Saharan Africa. P. falciparum is the most prevalent malaria parasite in all areas except the Americas; P. vivax is now recognized as the predominant cause of malaria in children and infants in the Asia-Pacific region and the Americas, with significant morbidity and mortality. In non-endemic areas, malaria occurs mainly in returning travelers, an increasing proportion of immigrants and refugees, and people visiting friends and relatives in endemic regions. Children constitute 15%–20% of imported malaria cases worldwide.” There is much in the article about prevention, including prevention for travelers, as well. 

Hollowell TY & al. state in their introduction that “[m]alaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality.” However, their article, Public Health Determinants of Child Malaria Mortality: A Surveillance Study Within Siaya County, Western Kenya, Malar J, 2023 Feb 23, 22:65, https://doi.org/10.1186/s12936-023-04502-9 concludes that there was “a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death … Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age.”  

Population dynamics

Hauser M & al. conducted a study in Northern Zambia among Congolese refugee children. Malaria in Refugee Children Resettled to a Holoendemic Area of Sub-Saharan Africa, Clin Infect Dis. 2023 Feb 8; 76(3):e1104-e1113, https://doi.org/10.1093/cid/ciac417 reports that while the overall incidence of malaria among these children reflects the incidence of the general population, “outcomes were more favorable in refugee children referred from a highly outfitted refugee transit center than those referred later from a permanent refugee settlement. Refugee children experienced higher in-hospital malaria mortality due in part to delayed presentation and higher rates of malnutrition.”


Emerson C & al. state that “malaria parasitaemia prevalence among women attending antenatal care (ANC) correlates with prevalence among children under 5 years old and that pregnant women could be a sentinel population for tracking malaria prevalence.” Women Attending Antenatal Care as a Sentinel Surveillance Population for Malaria in Geita Region, Tanzania: Feasibility and Acceptability to Women and Providers, Malar J, 2023 Feb 24, 22:66, https://doi.org/10.1186/s12936-023-04480-y reports on the results of questionnaires administered to pregnant women and their health care providers in the region identified in the title. “All pregnant women reported that introduction of ANC surveillance and spending 10 more minutes with providers answering questions about their health would be neutral or beneficial. They perceived being asked about their health as standard of care. Providers and in-charges reported that introduction of ANC surveillance was within their scope of practice.”

Similar to the above article, Pujol A &al., Detecting Temporal and Spatial Malaria Patterns from First Antenatal Care Visits, Res Sq. 2023 Feb 20: rs.3.rs-2592126, https://doi.org/10.21203/rs.3.rs-2592126/v1 uses maternity care as the anchor of malaria prevalence studies, this time in Mozambique. “ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status … with a 2-3 months’ lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, multigravidae showed lower rates than children.”

Gutman JR & al. announce a muti-country study to determine whether the method covered in the two papers above should be more broadly practiced.  The article is entitled Using Antenatal Care as a Platform for Malaria Surveillance Data Collection: Study Protocol, Malar J, 2023 Mar 17, 23:99, https://doi.org/10.1186/s12936-023-04521-6.

Pourtois D & al.’s study, Climatic, Land-Use and Socio-Economic Factors Can Predict Malaria Dynamics at Fine Spatial Scales Relevant to Local Health Actors: Evidence from Rural Madagascar, PLoS Glob Pub Health, 2023 Feb 23, https://doi.org/10.1371/journal.pgph.0001607 “integrates climate, land-use, and representative household survey data to explain and predict malaria dynamics at a high spatial resolution (i.e., by Fokontany, a cluster of villages) relevant to health care practitioners.” They state the following: “…predictions from our model were able to identify 58% of the Fokontany in the top quintile for malaria incidence and account for 77% of the variation in the Fokontany incidence rank. These results suggest that it is possible to build a predictive framework using environmental and social predictors that can be complementary to standard surveillance systems and help inform control strategies by field actors at local scales.”

Anjorin S & al., Malaria Profile and Socioeconomic Predictors Among Under-Five Children: An Analysis of 11 Sub-Saharan African Countries, Malar J, 2023 Feb 14, 23:55, https://doi.org/10.1086/s12936-023-04484-8 is another intriguing study of 11 sub-Saharan countries.  The following variables are stated in the paper “to be statistically associated with the prevalence of malaria infection among under-five children: under-five child’s age, maternal education, sex of household head, household wealth index, place of residence, and African region where mother–child pair lives. Children whose mothers have secondary education have about 56% lower risk … of malaria infection and 73% lower … among children living in the richest households, compared to children living in the poorest households.” {While these conclusions appear reasonable and consistent with other studies, questions must be raised about the sampling method; for example, Rwanda, with its population about 6% that of Nigeria, contributed 1.13 times as many children to the sample as the latter.  Also, Uganda, one of the most malarious countries but one where data collection is relatively easy, was not part of the sampling. See CAVEAT below.}

Along the same lines as above, Sarfo JO & al., Malaria Amongst Children Under Five in Sub-Saharan Africa {SSA}: A Scoping Review of Prevalence, Risk Factors and Preventive Interventions, Eur J Med Res. 2023 Feb 17; 28(1):80, https://doi.org/10.1186/s40001-023-01046-1 claims similar conclusions in a generally uninformative abstract.  The article itself states that the “research questions for this scoping review included: (1) what is the prevalence of malaria amongst children UN5 [under the age of 5] in SSA? (2) What are the risk factors associated with malaria infection amongst children UN5 in SSA? and (3) What are the health education and promotion interventions reported by studies to prevent malaria amongst UN5 in SSA?” Most of the studies were dated between 2013 and 2021.  After reviewing 100 out of over 22,000 articles initially identified, the authors identify poor housing, general poverty and pre-existing health conditions as increasing risk, while the availability of education programs, parental education and prosperity, and preventive interventions in the community reduce risk.  Climate change is mentioned as a factor of uncertain influence in this paper.


Spatiotemporal studies

Another instance of potential influence of geography on the spread of malaria is described in Haieselassie W & al., International Border Malaria Transmission in The Ethiopian District of Lare, Gambella Region: Implications for Malaria Spread into South Sudan, Malar J, 2023 Feb 22, 23:64, hgttps://doi.org/10.1186/s12936-023-04479-5. However, despite the title, the paper is simply a description of what is happening in the Ethiopian District, without any information about the implication for South Sudan, immediately to the West.

Semakula M & al., Spatio-Temporal Bayesian Models for Malaria Risk Using Survey and Health Facility Routine Data in Rwanda, Int J Environ Res Public Health, 2023 Feb 28; 20(5):4283, https://doi.org/10.3390/ijerph20054283.

Daba C & al., A Retrospective Study on the Burden of Malaria in Northeastern Ethiopia from 2015 to 2020: Implications for Pandemic Preparedness, Infect Drug Resist. 2023 Feb 11; 16:821-828,   https://doi.org/10.2147/idr.s399834


Ibrahim AO & al., Prevalence of Asymptomatic Malaria Infection by Microscopy and its Determinants Among Residents of Ido-Ekiti, Southwestern Nigeria, PLoS One. 2023 Feb 14; 18(2): e0280981, https://doi.org/10.1371/journal.pone.0280981


Imboumy-Limoukou RK & al., Severe Malaria in Gabon: Epidemiological, Clinical and Laboratory Features in Amissa Bongo Hospital of Franceville, Malar J, 2023 Mar 9, 23:88, https://doi.org/10.1186/s12936-023-04512-7

Oviedo A & al., Plasmodium falciparum Infection Prevalence Among Children Aged 6-59 Months from Independent DHS and HIV Surveys: Nigeria, 2018, Sci Rep 2023 Feb 3; 13(1):1998, https://doi.org/10.1038/s41598-023-28257-0



The British-American political/economic weekly, The Economist, included an article entitled “Doctored data” in its February 25th edition.  The lengthy article explored the history of dealing with scientific fraud and came to the doleful conclusion that it is becoming more rampant.  Based on work done by scientific sleuths, they conclude that world-wide, the incidence of published articles with unreliable data (on a spectrum of erroneous, plagiarized and manipulated to simply invented) is as high as 2%.  They state that “…fakes had authors from more than 70 countries,” though China, Russia, Iran, Malaysia, and Egypt led as the sources of papers that had to be retracted after publication because their data were found unreliable.  This caveat is included in this report, because of the 400+ papers that have to be sorted or even the 40 or so reported every month are too overwhelming for me to analyze as to data integrity and frankly even if I had the time to do so, I do not possess the expertise.  While we have not reported on many papers that originated from the above countries, no other country, including the US and UK, is immune to this phenomenon. Therefore, it is highly likely that over the two years that these reports have been published, a few with unreliable data have been included.  This will probably continue to occur; so papers with conclusions that materially differ from previous known findings should be treated with caution until their conclusions are supported from elsewhere.  In fact, there is one such paper in this report, which is highlighted above, as well as others that deserved a reference to this paragraph in the course of their descriptions. 

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