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

Prevention:

Arora N, & al., Towards Eradication of Malaria: Is the WHO’s RTS,S/AS01 Vaccination Effective Enough? Risk Manag Healthc Policy, . 2021 Mar 12;14:1033-1039 state that “[a]mong many potential candidates, the RTS,S/AS01 vaccine (MosquirixTM) remains the leading candidate.” It is “a recombinant pre-erythrocytic vaccine containing Plasmodium falciparum surface-protein (circumsporozoite) antigen, is safe, well-tolerated, and immunogenic in children. Three doses, along with a booster, have a modest efficacy of about 36% in children (age 5-17 months) and about 26% in infants (age 6-12 weeks) against clinical malaria during a 48-month follow-up… [I]t should be considered another addition to the malaria-control program and not as an eradication tool because of its relatively low to modest efficacy.” Article available.

From Brazil, de Almeida MEM& al., Circumsporozoite Surface Protein-Based Malaria Vaccines: a Review, Rev Inst Med Trop S o Paulo, 2021 Jan 29;63:e11. doi: 10.1590/S1678-9946202163011 also deals with the same vaccine. “The purpose of this review was to provide a bibliographic survey of historical researches that led to the development of RTS’S and its performance analysis over the decade. The search for new adjuvants to be associated with this antigen seems to be a way to obtain higher percentages of protection for a future malaria vaccine.” Article available.

Adjuvants are the subject of Pirahmadi S & al., A Review of Combination Adjuvants for Malaria Vaccines: a Promising Approach for Vaccine Development, Int J Parasitol, 2021 Mar 30;S0020-7519(21)00117-X.  doi: 10.1016/j.ijpara.2021.01.006. Online ahead of print. “Owing to the importance of a multi-adjuvanted approach in subunit malaria vaccine development, this review paper outlines some of the best known combination adjuvants used in malaria subunit vaccines, focusing on their proposed mechanisms of action, their immunological properties, and their notable results. The aim of the present review is to consolidate these findings to aid the application of these combination adjuvants in experimental malaria vaccines.”

Focusing on maternal and child health, Gamain B & al., Progress and Insights Toward an Effective Placental Malaria Vaccine, Front Immunol, 2021 Feb 25;12:634508.  doi: 10.3389/fimmu.2021.634508.  They state that “[p]lacental malaria is characterized by the massive accumulation of P. falciparum infected erythrocytes and monocytes in the placental intervillous spaces leading to maternal anaemia, hypertension, stillbirth and low birth weight due to premature delivery, and foetal growth retardation. Remarkably, the prevalence of placental malaria sharply decreases with successive pregnancies. This protection is associated with the development of antibodies directed towards the surface of P. falciparum-infected erythrocytes from placental origin… This review discusses recent advances in placental malaria vaccine development, with a focus on the recent clinical data, and discusses the next clinical steps to undertake in order to better comprehend vaccine-induced immunity and accelerate vaccine development.

Still on the subject of newborns, Callaway PC & al., Malaria and Early Life Immunity: Competence in Context, Front Immunol, 2021 Feb 19;12:634749. doi: 10.3389/fimmu.2021.634749 is optimistic. “While much of the literature on fetal and neonatal immunity has focused on the early life propensity toward immune tolerance, recent studies indicate that the fetus is more immunologically capable than previously thought, and can, in some circumstances, mount adaptive B and T cell responses to perinatal pathogens in utero. Although significant hurdles remain before these findings can be translated into vaccines and other protective strategies, they should lend optimism to the prospect that neonatal and even fetal vaccination is achievable.” Article available.

Nkoka O & al. reviewed the effect of communication to mothers of young children in Influence of Maternal Exposure to Malaria Social and Behavioral Change Messages and Effectiveness of Communication Media on Bed Net Use and Malaria Infection in Malawi, Health Educ Behav, 2021 Apr;48(2):179-189. doi: 10.1177/1090198120964201.  “Children whose mothers had reported hearing any malaria-related message in the past 6 months were more likely to sleep under an ITN and less likely to have malaria infection compared with those whose mothers had not heard any malaria-related message. Region and sex of the child were effect modifiers on the relationship between exposure to any malaria-related message and malaria infection. Knowledge regarding cause or protection methods partially mediated the relationship between exposure to any malaria message and malaria infection.”

Diagnosis:

Morris U and Aydin-Schmidt B analyzed the Performance and Application of Commercially Available Loop-Mediated Isothermal Amplification (LAMP) Kits in Malaria Endemic and Non-Endemic Settings, Diagnostics (Basel), 2021 Feb 18;11(2):336. doi: 10.3390/diagnostics11020336. Their conclusion is that “[d]espite LAMP being a promising near point-of-care tool for use in low resource settings, it is unlikely that commercially available LAMP will replace conventional diagnostic tools in the diagnosis of clinical malaria in endemic areas.  They may, however, provide a sensitive molecular alternative for use in malaria elimination programs, as well ass in malaria screening in pregnancy in low transmission settings, and in returning travelers in non-endemic settings.  Nevertheless, further improvements of the already available commercial kits and detailed assessments of cos-effectiveness cold improve their uptake on a larger scale.” Article available.

Rahman A & al.  focus on computer-aided diagnostics in A Comparative Analysis of Deep Learning Architectures on High Variation Malaria Parasite Classification Dataset, Tissue Cell,  2021 Apr;69:101473. doi: 10.1016/j.tice.2020.101473. “Computer-aided diagnosis of malaria is a challenging task owing to the fine-grained variability in the appearance of some uninfected and infected class. In this paper, [they] transform a malaria parasite object detection dataset into a classification dataset, making it the largest malaria classification dataset (63,645 cells), and evaluate the performance of several state-of-the-art deep neural network architectures pretrained on both natural and medical images on this new dataset. [They] provide detailed insights into the variation of the dataset and qualitative analysis of the results produced by the best models. [They] also evaluate the models using an independent test set to demonstrate the model’s ability to generalize in different domains. Finally, [they] demonstrate the effect of conditional image synthesis on malaria parasite detection…”

Malaria and the Heart: JACC State-of-the-Art Review, J Am Coll Cardiol . 2021 Mar 2;77(8):1110-1121.  doi: 10.1016/j.jacc.2020.12.042 by Gupta S & al. is sharply focused on one complication of malaria and its treatment, stating that “[a]lthough there is a paucity of data regarding cardiac manifestations of malaria, an algorithm for appropriate use of diagnostic tools to assess cardiac involvement has been developed in this paper. Furthermore, it is important to note that typical antimalarial treatment regimens can have fatal cardiac side-effects.

Treatment:

Pregnant women in malaria-endemic regions are susceptible to malaria in pregnancy, which has adverse consequences on birth outcomes, including having small for gestational age and preterm babies. These babies are likely to have low birthweights, which predisposes to infant mortality and lifelong morbidities. During malaria in pregnancy, Plasmodium falciparum-infected erythrocytes express a unique variant surface antigen, VAR2CSA, that mediates sequestration in the placenta. This process may initiate a range of host responses that contribute to placental inflammation and dysregulated placental development, which affects placental vasculogenesis, angiogenesis and nutrient transport. Chua CLL & al., Poor Birth Outcomes in Malaria in Pregnancy: Recent Insights Into Mechanisms and Prevention Approaches, Front Immunol, 2021 Mar 15;12:621382. doi: 10.3389/fimmu.2021.621382 provide an overview of malaria in pregnancy and the different pathological pathways leading to malaria in pregnancy-associated low birthweight. [They] also discuss current prevention and management strategies for malaria in pregnancy, and some potential therapeutic interventions that may improve birth outcomes. Article available.

Iribhogbe OI, Odoya EM, investigate the effects of Self-Medication Practice with Antimalarials & the Determinants of Malaria Treatment-Seeking Behavior Among Postpartum Mothers in a Rural Community in Nigeria, published in Pharmacoepidemiol Drug Saf, 2021 Apr;30(4):435-444. doi: 10.1002/pds.5178. It “is a cross-sectional study that was conducted using a purposive sampling technique. In the study, 150 respondents were administered questionnaires by one-on-one interviews, and results were presented as frequencies and proportions. A chi-square test was done to determine the association between independent categorical variables and the dependent variable.”  The results show “that the practice of self-medication and inappropriate malaria treatment behavior is common in postpartum women in rural settings hence public health intervention that will develop standardized self-treatment guidelines for uncomplicated malaria will be useful in promoting appropriate self-treatment practice in this population… Of the 60.7% of women who claimed they did malaria screening test, only half of them sought professional care after the test.”

In Zhou M & al., Multi-omics Approaches to Improve Malaria Therapy, Pharmacol Res, 2021 Mar 22;105570. doi: 10.1016/j.phrs.2021.105570, the authors state that [i]n recent years, multi-omics technologies have been extensively applied to provide a more holistic view of functional principles and dynamics of biological mechanisms. [They] briefly review multi-omics technologies and focus on recent malaria progress conducted with the help of various omics methods. Then, [they] present up-to-date advances for multi-omics approaches in malaria. Next, [they] describe resistance phenomena to established antimalarial drugs and underlying mechanisms.” They conclude that “[m]ulti-omics approaches will foster a better understanding of the molecular mechanisms of Plasmodium that are essential for the development of novel drugs and vaccines to fight this disastrous disease.  Unfortunately, the abstract does not define what is meant by “multi-omics” and the article is available only upon payment of a fee.

Two articles assess the use and benefits of herbal products:

Dkhil MA & al., Medicinal Plants as a Fight Against Murine Blood-Stage Malaria, Saudi J Biol Sci, 2021 Mar;28(3):1723-1738. doi: 10.1016/j.sjbs.2020.12.014. Epub 2020 Dec 19. “Medicinal plants of families Asteraceae, Meliaceae Fabaceae and Lamiaceae are the most abundant for use in laboratory animal antimalarial studies. According to region, published articles from 33 different countries were reviewed. Most of malaria published articles are from Africa especially Nigeria and Ethiopia. Leaves were the most common plant part used for the experimental malaria research. In many regions, research using medicinal plants to eliminate parasites and as a defensive tool is popular.”

Kumatia EK & al. aim standardizing “the ethanol leaf extract of Annickia polycarpa (APLE) and investigate its anti-malaria properties and the effect of its treatment on hematological indices in Plasmodium berghei infected mice in the Rane’s test”. According to their report, Intervention of Standardized Ethanol Leaf Extract of Annickia polycarpa, (DC.) Setten and Maas ex I.M. Turner. (Annonaceae), in Plasmodium berghei Infested Mice Produced Anti-Malaria Action and Normalized Gross Hematological Indices, J Ethnopharmacol, 2021 Mar 1;267:113449.  doi: 10.1016/j.jep.2020.113449. “…APLE possessed significant anti-malaria, immunomodulatory, erythropoietic and hematinic actions against malaria infection. APLE also has the ability to revoke deleterious physiological alteration produced by malaria and hence, promote clinical cure. These properties of APLE are due to its constituents especially, aporphine and oxoaporphine alkaloids.”

Campaigns:

Nkya TE & al., Malaria in Eswatini, 2012-2019: a Case Study of the Elimination Effort, Malar J, 2021 Mar 20;20(1):159.  doi: 10.1186/s12936-021-03699-x.  The campaign that started in 2012 envisaged the elimination of malaria in this small country (formerly Swaziland) by 2020.  The reported incidence of malaria, which was low to begin with, actually increased, with a peak in 2017, though whether that is an artifact of better reporting is unknown.  Indoor residual spraying was not carried out consistently. Article available.

Ngatu NR, Muzembo BA, Choomplang N & al., Malaria Rapid Diagnostic Test (HRP2/pLDH) Positivity, Incidence, Care Accessibility and Impact of Community WASH Action Programme in DR Congo: Mixed Method Study Involving 625 Households, Malar J, 2021 Feb 27;20(1):117. doi: 10.1186/s12936-021-03647-9 aimed “to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory Water, Sanitation and Hygiene (WASH) Action programme.”  In this area of extremely high prevalence of malaria, “mean incident household malaria cases decreased significantly at WASH action site, … whereas it remained unchanged at the Control site.”

Samuels AM & al., Mass Testing and Treatment on Malaria in an Area of Western Kenya, Clin Infect Dis, 2021 Mar 15;72(6):1103-1104. doi: 10.1093/cid/ciaa813 is a letter, referencing an article from before the start of this literature search (Samuels AM & al., Clin Infect Dis 2020, doi: 10/1093/cid/ciaa471) and a response to it (Hamer & al., Clin Infect Dis 2020, doi: 10/1093/cid/ciaa477).  Both the original article and the letter reflect the finding that a mass testing campaign in Western Kenya resulted in no significant decrease in the prevalence of malaria and possible causes for this lack of beneficial effect.

Wimberly MC & al., Satellite Observations and Malaria: New Opportunities for Research and Applications, Trends Parasitol, 2021 Mar 25;S1471-4922(21)00055-6. doi: 10.1016/j.pt.2021.03.003.  The authors state that “[s]atellite remote sensing provides a wealth of information about environmental factors that influence malaria transmission cycles and human populations at risk.” The purpose of this review is to present an up-to-date assessment of satellite missions relevant to malaria and identify opportunities where new sources of remote sensing data can be leveraged to support novel applications.  They present the capabilities of satellite imaging and analysis and state that data derived from same should be helpful to future malaria control projects. Article available.

Epidemiology:

Kendie FA & al., Prevalence of Malaria among Adults in Ethiopia: A Systematic Review and Meta-Analysis, Trop Med, 2021 Mar 4;2021:8863002. “The pooled prevalence of malaria among adults in Ethiopia was 13.61%. Subgroup analysis based on types of malaria cases showed that the prevalence of malaria among symptomatic and asymptomatic adults was 15.34% and 11.99%, respectively. Similarly, regional subgroup analysis showed that the highest malaria prevalence was recorded in Southern Nations, Nationalities, and Peoples’ Region (SNNPR) (16.17%) followed by Oromia Regional State (13.11%) and Amhara Regional State (12.41%).” Article available.

Awosolu OB & al., Epidemiology of Falciparum Malaria Among Residents of Some Rural and Periurban Communities in Ekiti State, Southwestern Nigeria, Trop Biomed, 2021 Mar 1;38(1):14-21. doi: 10.47665/tb.38.1.003.  The authors found prevalence of malaria is present in over 90% of the adult  population, male and female, and conclude “that falciparum malaria is heavily prevalent in this study area and as such urgent management control measures and interventions should be made available and fully utilized.”

Geographically more widely-based, but otherwise restricted to children is Obasohan PE l., A Scoping Review of Selected Studies on Predictor Variables Associated with the Malaria Status among Children under Five Years in Sub-Saharan Africa, Int J Environ Res Public Health, 2021 Feb 22;18(4):2119. doi: 10.3390/ijerph18042119. The review “is aimed at identifying studies that have used multivariate classical regression analysis to determine the pre Factors ranging from child-related (age, birth order and use of a bed net), parental/household-related (maternal age and education status, household wealth index) and community-related variables (community wealth status, free bed net distribution) were some of the identified significant predictors.” Article available.

“A non-piped source of domestic water was independently associated with positive testing for malaria. Moreover, regions with a high percentage of non-piped domestic water had a correspondingly high prevalence of malaria,” according to Shayo FK & al., Is the Source of Domestic Water Associated with the Risk of Malaria Infection? Spatial Variability and a Mixed-Effects Multilevel Analysis, Int J Infect Dis,  2021 Mar;104:224-231. doi: 10.1016/j.ijid.2020.12.062. Epub 2020 Dec 24.

Basic Research:

Broichhagen J & Kilian N, Chemical Biology Tools to Investigate Malaria Parasites, Chembiochem, 2021 Feb 11. doi: 10.1002/cbic.202000882. Online ahead of print.

Lu XM &, Le Roch K, Strand-Specific RNA-Seq Applied to Malaria Samples, Methods Mol Biol, 2021;2170:19-33. doi: 10.1007/978-1-0716-0743-5_2.

Sardar R & al., In-silico Profiling and Structural Insights into the Impact of nSNPs in the P. falciparum acetyl-CoA transporter Gene to Understand the Mechanism of Drug Resistance in Malaria, J Biomol Struct Dyn, 2021 Feb;39(2):558-569.  doi: 10.1080/07391102.2020.1711807.

Sena-Dos-Santos C & al., Unraveling Cell Death Pathways during Malaria Infection: What Do We Know So Far? Cells, 2021 Feb 23;10(2):479.  doi: 10.3390/cells10020479.

Tan MSY & Blackman MJ, Malaria Parasite Egress at a Glance, J Cell Sci, 2021 Mar 8;134(5):jcs257345. doi: 10.1242/jcs.257345.