Science & Research Report for September 2021

By Dr. Derick Pasternak, Malaria Science & Research Coordinator, Malaria Partners International 

This month, Malaria Journal’s publicly available website was particularly rich in sources of relevant articles. We also added Google Scholar to our search sources, but found little there that was not otherwise available. We have only two articles on the subject of malaria diagnosis; one of them (actually a letter to the editor) cited in the section reports on finding a number of interesting cases that did not fit anywhere else. 

Prevention: 

Several articles deal with insecticide treated bednets. 

Perhaps the most substantial of these is Skovmand O & al.,  From the Factory to the Field: Considerations of Product Characteristics for Insecticide-Treated Net (ITN) Bioefficacy Testing, Malaria J, 2021 Sep 6, vol. 20, art. 363, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03897-7.  Their somewhat long results and recommendations are worth quoting: “ITNs are not homogenous products. They vary within panels and between the sides and the roof. Running tests of wash resistance using a before/after tests on the same sample or band within a net reduces test variability. As mosquitoes frequently interact with ITN roofs, additional sampling of the roof when evaluating ITNs is advisable because in nets where roof and sides are of the same material, the contribution of roof sample (20–25%) to the average is less than the tolerance for the specification (25%). Mosquito mortality data cannot be reliably used to evaluate net surface concentration to determine regeneration time (RT) and resistance to washing as nets may regenerate beyond the insecticide concentrations needed to kill 100% of susceptible mosquitoes. Chemical assays to quantify surface concentration are needed. The Wash Resistance Index (WRI) averaged over the first four washes is only informative if the product has a log linear loss rate of insecticide. Using a WRI that excludes the first wash off gives more reliable results. Storage conditions used for product specifications are lower than those encountered under product shipping and storage that may exceed 50 °C, and should be reconsidered. Operational monitoring of new ITNs and linking observed product performance, such as bioefficacy after 2 or 3 years of use, with product characteristics, such as WRI, will aid the development of more robust test methods and product specifications for new products coming to market.” 

Considerably less broadly focused is Tungu PK & al., Effectiveness of a Long-Lasting Insecticide Treatment Kit (ICON® Maxx) For Polyester Nets Over Three Years Of Household Use: a WHO Phase III Trial in Tanzania, Malaria J, 2021 Aug 16, vol. 20 art 345. https://malariajournal.biomedcentral.com/ articles/10.1186/s12936-021-03871-3.  They assessed the durability of ICON Maxx-treated nets over 3 years in north-eastern Tanzania. Conventional treated nets (with lambda-cyhalothrin, but without binder) served as a positive control. They used “cone and tunnel tests” to assess insecticidal efficacy, while also monitoring net use and integrity and inhibitory chemical content of the nets.  Although the nets contained significant number of holes after 36 months, over 90% of nets treated with ICON met  the criteria of “combined cone and tunnel tests.”  These nets are now recommended by WHO.  The authors also conclude that “[u]ntreated polyester nets may be made long-lastingly insecticidal in Africa through simple household treatment using ICON Maxx pyrethroid-binder kits.” 

Lindsay SW & al. argue in Threats to the Effectiveness of Insecticide-Treated Bednets for Malaria Control: Thinking Beyond Insecticide Resistance, Lancet Glob Health, 2021 Sep;9(9):e1325-e1331. doi: 10.1016/S2214-109X(21)00216-3 that the recent stall in decline of malaria morbidity and mortality in Sub-Saharan Africa is not due to increasing resistance in malaria vectors to the pyrethroid insecticides used for treating insecticide treated bednets (ITNs), because “there is presently little evidence to reach this conclusion…” They recommend that in order “[t]o improve the effects of ITNs, net coverage should increase by increasing funding for programmes, adopting improved strategies for increasing ITN uptake, and enhancing the longevity of the active ingredients and the physical integrity of nets, while simultaneously accelerating the development and evaluation of novel vector control tools.” 

Tambwe MM & al. address the resistance issue in Transfluthrin Eave-Positioned Targeted Insecticide (EPTI) Reduces Human Landing Rate (HLR) Of Pyrethroid Resistant and Susceptible Malaria Vectors in a Semi-Field Simulated Peridomestic Space, Malaria J, 2021 Aug 30, vol 20 art 357. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03880-2 by studying a volatile pyrethroid, transfluthrin, which has been “proven to reduce human–vector contact for mosquito vectors.” They exposed several different strains of two Anopheles species, known to carry the malaria parasite.  Their ultimate conclusion was that the studies did not conclusively demonstrate the efficacy of transfluthrin. 

Another preventive measure, indoor residual spraying (IRS) is the subject of Ngwey LM & al.,  Variable Residual Activity of K-Othrine® PolyZone and Actellic® 300 CS in Semi-Field and Natural Conditions in the Democratic Republic of the Congo, Malaria J, 2021 Aug 30, vol 30 art 358, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03892-y. “With mortality as the primary endpoint, the persistence of residual efficacy of a polymer-enhanced pyrethroid suspension concentrate containing deltamethrin (K-Othrine® PolyZone—KOPZ) … was compared with a microencapsulated organophosphate suspension formulation of pirimiphos-methyl (Actellic® 300CS—ACS) … in simulated semi-field conditions. Similarly, two types of existing walls in occupied houses (painted cement and baked clay) were sprayed and examined.” They conclude that “KOPZ provided longer residual activity on all surfaces compared to ACS. Painted cement walls provided better residual longevity for both insecticides compared to other surfaces. Insecticides also performed better in an occupied house environment compared to semi-field constructed walls. This study illustrates the importance of collecting field-based observations to determine appropriate product active ingredient formulations and timing for recurring IRS cycles.” 

Gaudinski MR et al. conducted a Phase I clinical study of the preventive pharmacokinetics, efficacy, and safety, of “CIS43LS, an antimalarial monoclonal antibody with an extended half-life.”  Their report, A Monoclonal Antibody for Malaria Prevention, New Eng J Med 2021, 385:803-14, DOI: 10.1056/ NEJMoa2034031, states that “[n]o safety concerns were identified” and concludes that “[a]mong adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection.”  The question as to whether the economics of this approach is justified in parts of the world where malaria is rampant is not addressed in the abstract.  

One article deals with vaccination: Greenwood R and Tanyslaw N, Combining Malaria Vaccination With Chemoprevention: A Promising New Approach to Malaria Control, Malaria J, 2021 Aug 26, vol. 30, art 361, alariajournal.biomedcentral.com/articles/10.1186/s12936-021-03888-8.  They refer to “…a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone…” Based on that report, they consider several courses of action, which “…include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia.” They advocate exploring a variety of combinations “of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen.” 

Two articles focus on travelers.  Islam, N  & al., Efficacy of a 3-day Pretravel Schedule of Tafenoquine for Malaria Chemoprophylaxis: A Network Meta-Analysis, J Travel Med, 2021 Jul 7;28(5):taab057.  doi: 10.1093/jtm/taab057 and Baird JK, Single Loading-Dose Tafenoquine for Malaria Chemoprophylaxis During Brief Travel?, J Travel Med 2021 Jul 7;28(5):taab081. doi: 10.1093/jtm/taab081.  The former compared various regimens of tafenoquine as prophylaxis, compared to mefloquine. Based on analysis of nine randomized controlled trials, it concludes that for short-term travelers, defined as 28 days or less, a “loading dose of tafenoquine alone was equally effective, had possibly lower rate of [adverse effects], and likely better compliance than standard tafenoquine or mefloquine chemoprophylaxis schedules with maintenance doses.” For long-term travelers (longer than 28 days), this regimen was less effective than loading dose followed by maintenance with either drug. They also assert that “[s]tudies are needed to confirm if short-term travelers remain free of infection after long-term follow-up.”  The other citation is an editorial in the same journal, which speculates on whether a smaller dose than those used in the studies may be effective as well. 

Finally, interesting in view of the current attention on ivermectin, we have de Souza DK & al., Ivermectin Treatment in Humans for Reducing Malaria Transmission, Cochrane Database Syst Rev, 2021 Jun 29 6(6):CD013117.  doi: 10.1002/14651858.CD013117.pub2.  After extensive literature search, they included one published randomized study and identified six ongoing trials. There were no conclusions. They are “uncertain whether community administration of ivermectin has an effect on malaria transmission, based on [the] one trial published to date.’ 

Diagnosis:  

Moodley B & al., Improving the Quality of Malaria Diagnosis in Southern Africa Through the Development of a Regional Malaria Slide Bank, Malaria J, 2021 Sep 8, vol 20 art 365 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03899-5 describes the benefits of the use of standard malaria slides for diagnosis.  Eight countries benefited from the preparation of a regional malaria slide bank by South African professionals.   

As mentioned in the preamble, Kho S & al. (Letter to the ed.), Hidden Biomass of Intact Malaria Parasites in the Human Spleen, New Eng J Med 2021, 384:2067-69. DOI: 10.1056/NEJMc2023884, reports on several patients who underwent splenectomy and were found to have unsuspected clusters of Plasmodium parasites within their resected organs.  The report originated from Southeast Asia. 

Treatment: 

Shrivastava N & al., Recent Advances in the Development of Chemotherapeutic Agents for Malaria, Mini Rev Med Chem, 2021;21(12):1487-1508.  doi: 10.2174/ 1389557521666201221161750 is stated to be “aimed to provide the reader with the recent advances and progress made in the development of chemotherapeutic agents for malaria.”  Unfortunately the abstract is vague as to the sources reviewed and concludes with the imprecise opinion that “the multi-target conjugated hybrid approach is the best strategy to discover and develop effective antimalarial agents.” 

Another article that reviews multiple sources is Assefa DG & al. Efficacy of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria Among Children in Africa: A Systematic Review and Meta-Analysis Of Randomized Control Trials, Malaria J, 2021 Aug 12, vol.20, art 340. https://malariajournal.biomedcentral.com/ articles/10.1186/s12936-021-03873-1. “The aim of this review was to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHA-PQ) compared to artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria among children in Africa…25 studies which involved a total of 13,198 participants were included.” The results showed that “PCR {polymerase-chain-reaction} unadjusted treatment failure in children aged between 6 months and 15 years was significantly lower in the DHA-PQ treatment arm on day 28 than that of AL and the PCR-adjusted treatment failure was significantly lower with DHA-PQ treatment group on day 28 … and on day 42.” However, both regimens were effective in over 95% of cases. 

Focusing on a West African country, Maiga FO & al., Artemisinin-Based Combination Therapy for Uncomplicated Plasmodium falciparum Malaria in Mali: A Systematic Review and Meta-Analysis, Malaria J, 2021 Aug 30, vol 20 art 356, https://malariajournal.biomedcentral.com/articles/10.1186/ s12936-021-03890-0 analyzes results from eleven published studies.  The combination therapy studied was artemether-lumefantrine (AL, the combination found less efficacious is the citation above) versus apparently inconsistent “non-AL” regimens.  The rationale for the study was stated to be reported artemisinin resistance in Africa (Rwanda). The authors report high effectiveness of AL in Mali for uncomplicated falciparum malaria, but recommends continuing monitoring of the effectiveness of the regimen. 

Focusing on the reported resistance to artemisinin, L’Episcopia M  & al., Artemisinin Resistance Surveillance in African Plasmodium falciparum Isolates from Imported Malaria Cases to Italy, J Travel Med 2021 Jul 7;28(5):taaa231. doi: 10.1093/jtm/taaa231 cited genetic information of the parasite that is said to be linked to reduced susceptibility to the regimen.  Of the infective agents obtained from 54 patients in 2014-15 in a single institution, none were noted to have the genetic makeup said to associated with reduced sensitivity to artemisinin.  Other genetic variability was found in a small number of cases, however.    

Wanzira H & al. consider different aspects of malaria treatment, as reported in An Assessment of the Knowledge, Practices and Resources During the Delivery of Malaria Health Care Services Among Private Health Care Practitioners: A Cross Section Study in the Mid-Western Region of Uganda, BMC Health Serv Res, 2021 Aug 10;21(1):788.  doi: 10.1186/s12913-021-06849-8.  In this region, they selected fifteen private-for-profit facilities from each district and administered verbal questionnaires on malaria treatment to 135 “health facilities staff.” They concluded that “[t]his study revealed sub-optimal malaria case management knowledge and practices at private health facilities with approximately 14 % of health care workers demonstrating correct malaria case management cascade practices.”  While detailed results are given on  a variety of aspects of the case management, it is unclear how the professional background of respondents (said to be 72% “clinical,” but only 12 of the 135 were “medical officers” and 45 “clinical officers,” the rest nurses, midwives, and nursing assistants) influenced the adequacy of responses.  

Coulibaly B & al., Effect of a Single Dose of Oral Azithromycin on Malaria Parasitaemia in Children: A Randomized Controlled Trial, Malaria J, 2021 Aug 31, vol. 20 art.360,  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03895-9 start from the reported reduction of all-cause mortality of children in Sub-Saharan Africa that is the result of administering a single dose of azithromycin.  They studied 450 children in a randomized, controlled study, and were unable to detect any significant difference between treated and placebo groups in the development of malaria parasitemia after 14 days and 6 months.  

Finally, Taibakhsh E & al. reported on the status of knowledge of medicinal plants in Antiplasmodial, Antimalarial Activities and Toxicity of African Medicinal Plants: A Systematic Review of Literature, Malaria J, 2021 Aug 26, vol 20 art 349, https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03866-0.   Two hundred research articles were identified, a majority of which were studies conducted in Nigeria. The plants belonged to seven different families.  Several individual plants were said to have good or very good antiplasmodial activity. Over 80% of studies reported in vitro testing; however, only 4.3% of studies used pure compounds; these latter had higher antiplasmodial activity relative to crude extracts.  The authors conclude that “[a]lthough there are many indigenous plants with considerable antiplasmodial and anti-malarial activity, the progress in the development of new anti-malarial drugs from African medicinal plants is still slothful, with only one clinical trial with Cochlospermum planchonii (Bixaceae) conducted to date. There is, therefore, the need to scale up anti-malarial drug discovery in the African region.” 

 PS: It may of interest of the readers that Khaya senegalensis is listed among the plants studied and its  extract (without specification of how it was obtained) is reported in a single study published in 2008 to have “moderate” antiplasmodial activity in vitro.  So, if there are clinical trials of this plant ongoing in Australia, there have been apparently no reports of results published. 

 Campaigns: 

“The COVID-19 pandemic has resulted in unprecedented challenges to health systems worldwide, including the control of non-COVID-19 diseases. Malaria cases and deaths may increase due to the direct and indirect effects of the pandemic in malaria-endemic countries, particularly in Sub-Saharan Africa (SSA).” Heuschen A & al. reviewed “publications and manuscripts on preprint servers, in peer-reviewed journals and in grey literature documents from 1 December, 2019 to 9 June, 2021.”  Their article, Public Health-Relevant Consequences of the COVID-19 Pandemic on Malaria in Sub-Saharan Africa: A Scoping Review, Malar J, 2021 Aug 11;20(1):339. doi: 10.1186/s12936-021-03872-2 reports that modeling papers “have predicted a significant increase in malaria cases and malaria deaths in SSA due to the effects of the COVID-19 pandemic.” In actuality, while “highly endemic countries reported evidence of decreased malaria cases in health facilities, low endemic countries reported overall higher numbers of malaria cases and deaths in 2020.”  Causes for the discrepancy require further investigation. 

Kebede Y & al., Comparing Insecticide-Treated Nets Access-Use Based on Universal Household and Population Indicators Vis-A-Vis Measures Adapted to Sleeping Spaces in Ethiopia, Malaria J, 2021 Aug 28, vol 20 art 355,  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03887-9 reports that conventional studies of insecticide treated bednets (ITN) may be overestimating their use, because of incorrect assumptions about ITN distribution and sleeping spaces within households. 

Niang A & al. state that in view of the relatively high resistance to pyrethoids by mosquitoes in the geographic area studied, elimination may be facilitated by predicting when and where mosquito swarms occur and focusing efforts accordingly.  The article is  Entomological Baseline Data Collection and Power Analyses in Preparation of a Mosquito Swarm-Killing Intervention in South-Western Burkina Faso, Malaria J, 2021 Aug 23, vol 20 art 346, https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03877-x 

Njau J & al., Investment Case for Malaria Elimination in South Africa: A Financing Model for Resource Mobilization to Accelerate Regional Malaria Elimination, Malaria J, 2021 Aug 16, vol. 20 art. 344, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03875-z is a discussion of business financing principles applied to malaria eradication in Southern Africa. A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of P. falciparum malaria between 2018 and 2030 in [three endemic provinces]. Local financial, economic, and epidemiological data were used to calibrate the transmission model. Three primary simulated scenarios were developed: Business as Usual, Accelerate and Source Reduction. The authors conclude that “[m]alaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period.” 

Epidemiology: 

Using data from the Global Burden of Disease Study 2019, Liu Q & al., Trends of the Global, Regional and National Incidence of Malaria in 204 Countries from 1990 to 2019 and Implications for Malaria Prevention, J Travel Med 2021 Jul 7;28(5):taab046. doi: 10.1093/jtm/taab046 report that “[g]lobally, the malaria [age-standardized incidence rate] ASR decreased by an average 0.80% (95% confidence interval 0.58-1.02%) per year from 1990 to 2019; however, it slightly increased from 3195.32 per 100 000 in 2015 to 3247.02 per 100 000 in 2019. The incidence rate of children under 5 was higher than other age groups. A total of 40 countries had higher ASRs in 2019 than in 2015, with the largest expansion in Cabo Verde…” 

Doumbe-Belisse & al. studied the spread of malaria in urban environments, where the population of Sub-Saharan Africa is beginning to gravitate.  Their article, Malaria in Sub-Saharan Africa: Dynamic of the Vectorial System and the Entomological Inoculation Rate, Malaria J, 2021 Sep 8. Vol 20 art 364, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03891-z “summarizes findings from studies conducted in urban settings between the 1970s and 2020 to assess the effects of urbanization on the entomological inoculation rate pattern and anopheline species distribution… Species of the Anopheles gambiae complex were the predominant vectors in most urban settings. Anopheline larvae were reported to have adapted to different aquatic habitats. The study provides updated information on the distribution of the vector population and the dynamic of malaria transmission in urban settings. The study also highlights the need for implementing integrated control strategies in urban settings.” 

Paton RS & al., Malaria Infection and Severe Disease Risks in Africa, Science, 2021 Aug 20; 373(6557):926-931. doi: 10.1126/science.abj0089. and accompanying editorial Taylor T & Slutsker L, Tracking Severe Malaria Disease, Science, 2021 Aug 20, 353 (6557):855056. “The relationship between community prevalence of Plasmodium falciparum and the burden of severe, life-threatening disease remains poorly defined. To examine the three most common severe malaria phenotypes from catchment populations across East Africa, [the authors] assembled a dataset of 6506 hospital admissions for malaria in children aged 3 months to 9 years from 2006 to 2020. Admissions were paired with data from community parasite infection surveys. A Bayesian procedure was used to calibrate uncertainties in exposure (parasite prevalence) and outcomes (severe malaria phenotypes). Each 25% increase in prevalence conferred a doubling of severe malaria admission rates. Severe malaria remains a burden predominantly among young children (3 to 59 months) across a wide range of community prevalence typical of East Africa.” Thus, the authors find that the higher the prevalence of malaria infection in a given community, the higher the incidence of severe malaria disease. These findings may be useful in tracking the impact of various malaria control measures over time. 

Lubinda J & al., Climate Change and the Dynamics of Age-Related Malaria Incidence in Southern Africa, Environ Res, 2021 Jun;197:111017.  doi: 10.1016/j.envres.2021.111017 revisits a topic increasingly in the crosshairs of epidemiologists. They focus on Zambia, where rates of malaria in children under 5 years of age have been declining, but increasing in other age groups. They assert that “[i]n parts of Zambia, changing climatic and environmental factors are among those suspectedly behind high malaria incidence.” Using “parametric and non-parametric statistics to model the effects of climatic and socio-demographic variables on age-specific malaria incidence vis-à-vis control interventions,” they claim that “climate parameters negatively impact malaria control efforts by exacerbating the transmission conditions via more conducive temperature and rainfall environments, which are augmented by cultural and socioeconomic exposure mechanisms.”     

Further to the East, the population of Mozambique has the fifth highest malaria prevalence in the world.  Ferrão JL & al., Malaria Temporal Variation and Modelling Using Time-Series in Sussundenga District, Mozambique, Int J Environ Res Public Health, 2021 May 26;18(11):5692. doi: 10.3390/ijerph18115692 review weekly and yearly variations in incidence overall, in one District in the West Central portion of the country.  Nor surprisingly, malaria infections peak during the wet season, but there are weekly variations.  The authors recommend studying the variations in incidence and fashioning control strategies accordingly. 

A recurrent theme in malaria research is the occurrence of the infection during pregnancy. Yaro JB & al., Risk Factors for Plasmodium falciparum Infection in Pregnant Women in Burkina Faso: a Community-Based Cross-Sectional Survey, Malaria J, vol. 20 art 363. https://malariajournal.biomedcentral.com/ articles/10.1186/s12936-021-03896-8 addresses this issue. A total of 356 pregnant women were enrolled in their surveys, 174 during the dry season and 182 during the wet season. “The mean number of doses of sulfadoxine–pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night.” They conclude that “compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy.” 

An interesting association between the distribution of cattle and the incidence of malaria is the subject of Mburu MM & al., Impact of Cattle on the Abundance of Indoor and Outdoor Resting Malaria Vectors in Southern Malawi, Malaria J, 2021 Aug 26 vol 20 art 353, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03885-x  They conclude that “differences between malaria vector species and their interactions with potential blood meal hosts … may have implications for malaria risk. Whereas An. arabiensis remained unaffected, the reduction of An. funestus s.s. in houses near cattle suggests a potential protective effect of cattle. However, the low abundance of mosquitoes reduced the power of some analyses and limited the generalizability of the results to other settings. Therefore, further studies incorporating the vectors’ host-seeking behaviour/ human biting rates are recommended to fully support the primary finding.” 

Basic Research: 

Ofir-Birin Y & al.,  Malaria Parasites Both Repress Host CXCL10 and Use It as a Cue for Growth Acceleration, Nature Comm 2021 Aug 11, vol. 12 art. 4851. https://www.nature.com/articles/s41467-021-24997-7. 

Miao J & al., A Unique GCN5 Histone Acetyltransferase Complex Controls Erythrocyte Invasion and Virulence in The Malaria Parasite Plasmodium falciparum, PLoS Pathogens August 17, 2021, https://doi.org/10.1371/journal.ppat.100935. 

Neafsey DE, & al., Advances and Opportunities In Malaria Population Genomics, Nature Reviews Genetics, 2021, 22:502-17, https://www.nature.com/articles/s41576-021-00349-5