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

This month’s collection is particularly rich in basic science articles, among which human physiology and pathophysiology are also included, in order to avoid opening another category.  If there is request for these articles to be separated, please let me know.  Of particular interest are several articles about vaccines, including a new approach, based on the success in developing vaccines against the novel coronavirus, SARS-CoV-19. Virtually all the articles reported today are available in their entirety.

Prevention:

Several articles deal with anti-malaria vaccine development: Lozano JM & al., The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes, Vaccines (Basel), 2021 Feb 2;9(2):115.  doi: 10.3390/vaccines9020115, Abuga KM & al., Immune Responses to Malaria Pre-Erythrocytic Stages: Implications for Vaccine Development, Parasite Immunol,  2021 Feb;43(2):e12795.  doi: 10.1111/pim.12795, Kanoi BN & al., Leveraging the Wheat Germ Cell-Free Protein Synthesis System to Accelerate Malaria Vaccine Development, Parasitol Int, 2021 Feb;80:102224. doi: 10.1016/j.parint.2020.102224.

The following online article describes the RNA-based approach to anti-malaria vaccine recently patented in the US: Ravisetti M, First Vaccine to Fully Immunize Against Malaria Builds on Pandemic-Driven RNA Tech, The Academic Times, https://academictimes.com/first-vaccine-to-fully-immunize-against-malaria-builds-on-pandemic-driven-rna-tech/ downloaded 1 March 2021.  The patent has been assigned to Yale University and Glaxo Smith Kline.  The vaccine is currently in Phase I research.

In addition, the following article in the February 13, 2021 US edition of The Economist is aimed to general audiences, rather than scientists: Broken arrow; Some people are unwilling to be vaccinated.  That will be a problem, (pp.20-22).  While it is published in light of the current  pandemic, it is relevant to our understanding of how vaccines are or are not accepted in certain communities. They also launched a podcast on the subject in February (economist.com/thejab).

Accrombessi M & al., Assessing the Efficacy of Two Dual-Active Ingredients Long-Lasting Insecticidal Nets for the Control of Malaria Transmitted by Pyrethroid-Resistant Vectors in Benin: Study Protocol for a Three-Arm, Single-Blinded, Parallel, Cluster-Randomized Controlled Trial,  BMC Infect Dis. 2021; 21: 194.  doi: 10.1186/s12879-021-05879-1 is said to be a “cluster randomised controlled trial to evaluate the efficacy of … next-generation LLINs to control malaria transmitted by insecticide-resistant mosquitoes. The results of this study will form part of the WHO evidence-based review to support potential public health recommendations of these nets and shape malaria control strategies of sub-Saharan Africa for the next decade.”

As reported by Chaccour C & al., Incremental Impact on Malaria Incidence Following Indoor Residual Spraying in a Highly Endemic Area with High Standard ITN Access in Mozambique: Results from a Cluster‐Randomized Study, Malar J. 2021; 20: 84. doi: 10.1186/s12936-021-03611-7, “in a highly endemic area with high [insecticide-treated net] access and emerging pyrethroid resistance, adding [indoor residual spraying] with pirimiphos-methyl resulted in significant additional protection for children under five years of age.”

Diagnosis:

“The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated.” The results are reported by Horning MP & al., Performance of a Fully‐Automated System on a WHO Malaria Microscopy Evaluation Slide Set, Malar J. 2021; 20: 110. doi: 10.1186/s12936-021-03631-3. The results showed that “The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to [the authors’} knowledge, the best performance of a fully-automated system on a WHO 55 set.”

Dorkenoo AM & al. report on The Use of Dried Tube Specimens of Plasmodium falciparum in an External Quality Assessment Programme to Evaluate Health Worker Performance for Malaria Rapid Diagnostic Testing in Healthcare Centres in Togo, Malar J. 2021; 20: 50. doi: 10.1186/s12936-020-03569-y.  Their results in 80 healthcare centers were highly variable.  The authors conclude that “[the] ease of use and stability of the DTS illustrates that this type of samples can be considered for the assessment of staff competency.”

Several press releases and an article on the web-based 360 Dx (by subscription only; Johnson, M, Hemex Health Brings Portable Malaria and Sickle Cell Disease Testing to India, Africa) report on a device called “Gazelle,” which is said to give rapid accurate diagnosis of malaria and of sickle cell disease.  Original work on the device was done at Case Western Reserve U. The device costs $ 800-1200 with cartridges $ 1-3.  It is unknown how many tests can be performed per cartridge. Hemex Health is based in Portland, OR; its press releases are available.

Treatment:

Miguel-Blanco C & al. report on a novel antimalarial chemical in The Antimalarial Efficacy And Mechanism of Resistance of the Novel Chemotype Ddd01034957, Sci Rep. 2021; 11: 1888. Doi: 10.1038/S41598-021-81343-Z.  They state that this is an “antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3.”

The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. Yang T & al., Malaria Accelerating Drug Consortium, MalDA, Accelerating Malaria Drug Discovery, Trends Parasitol, 2021 Feb 26;S1471-4922(21)00012-X.  doi: 10.1016/j.pt.2021.01.009 discuss the mission of the consortium and its scientific achievements, including the identification of new chemically and biologically validated targets, as well as future scientific directions.

Stokkermans TJ & al. review the hazards of some classical antimalarials still in use in Chloroquine and Hydroxychloroquine Toxicity, In: StatPearls [Internet] 2021 Jan. 13 Feb 2021. StatPearls Publishing, Treasure Island (FL).

Campaigns:

According to Nyarko PB and Claessens A, Understanding Host-Pathogen-Vector Interactions with Chronic Asymptomatic Malaria Infections, Trends Parasitol,  2021 Mar;37(3):195-204. doi: 10.1016/j.pt.2020.09.017, “The last malaria parasite standing will display effective adaptations to selective forces. While substantial progress has been made in reducing malaria mortality, eradication will require elimination of all Plasmodium parasites, including those in asymptomatic infections. These typically chronic, low-density infections are difficult to detect, yet can persist for months. [The authors] argue that asymptomatic infection is the parasite’s best asset for survival but it can be exploited if studied as a new model for host-pathogen-vector interactions. Regular sampling from cohorts of asymptomatic individuals can provide a means to investigate continuous parasite development within its natural host. State-of-the-art techniques can now be applied to such infections. This approach may reveal key molecular drivers of chronic infections – a critical step for malaria eradication.”  No article.

Epidemiology:

Land use and land cover changes, such as deforestation, agricultural expansion and urbanization, are one of the largest anthropogenic environmental changes globally. Recent initiatives to evaluate the feasibility of malaria eradication have highlighted impacts of landscape changes on malaria transmission and the potential of these changes to undermine malaria control and elimination efforts. Fornace KM & al. address these issues in Achieving Global Malaria Eradication in Changing Landscapes, Malar J. 2021; 20: 69. doi: 10.1186/s12936-021-03599-0.

Various epidemiological issues in three different countries are reviewed by Minwuyelet A & Aschale Y, Analysis of Five-Year Trend of Malaria at Bichena Primary Hospital, Amhara Region, Ethiopia, Parasitol Res. 2021; 2021: 6699373. doi: 10.1155/2021/6699373, Sayre D, & al., Combined Epidemiologic and Entomologic Survey to Detect Urban Malaria Transmission, Guinea, 2018, Emerg Infect Dis. 2021 Feb; 27(2): 599–602. doi: 10.3201/ eid2702.191701, and Sy, M & al., Genomic Investigation of Atypical Malaria Cases in Kanel, Northern Senegal, Malar J. 2021; 20: 103. doi: 10.1186/s12936-021-03637-x.

Basic Research:

Damelang T & al., Antibody Mediated Activation of Natural Killer Cells in Malaria Exposed Pregnant Women, Sci Rep. 2021; 11: 4130. doi: 10.1038/s41598-021-83093-4.

Feng Y & al., Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation, PLoS Pathogens 24 Feb 2021 https://doi.org/10.1371/journal.ppat.1009353

Natama HM & al., Genetic Variation in the Immune System and Malaria Susceptibility in Infants: a Nested Case–Control Study in Nanoro, Burkina Faso, Malar J. 2021; 20: 94.    doi: 10.1186/s12936-021-03628-y.

Pamplona A & Silva-Santos B, γδ T Cells in Malaria: a Double-Edged Sword, FEBS J, 2021 Feb;288(4):1118-1129.  doi: 10.1111/febs.15494. Epub 2020 Aug 14.

Possemiers H & al., Etiology of Lactic Acidosis in Malaria, PLoS Pathog. 2021 Jan; 17(1): e1009122. doi: 10.1371/journal.ppat.1009122.

Tonkin-Hill, G, Ruybal-Persántez S, Tiedie KE, & al., Evolutionary Analyses of the Major Variant Surface Antigen-Encoding Genes Reveal Population Structure of Plasmodium falciparum Within and Between Continents, PLoS Genetics, 2021, https://doi.org/10.1371/journal.pgen.1009269