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

The World Health Organization has just released its 299 page World Malaria Report 2020: 20 Years of Global Progress & Challenges.  It is accessible at who.int/publications/i/item/9789240015791.

Also, we introduce a new category this month:  Epidemiology; up to now these articles were categorized as Campaigns, but they don’t really belong there.

Prevention:

The Rts S Epidemiology Epi-Mal-Study Group, based in London, published  Estimating Annual Fluctuations in Malaria Transmission Intensity and in the Use of Malaria Control Interventions in Five Sub-Saharan African Countries, Am J Trop Med Hyg, 2020 Nov;103(5):1883-1892.   doi: 10.4269/ajtmh.19-0795.  The article addressed malaria vaccine safety, effectiveness, and impact in pre- and post-vaccine introduction studies, comparing the occurrence of malaria cases and adverse events in vaccinated versus unvaccinated children. Article available.

As reported by Kalinjuma & al. in Factors Associated with Sub-Microscopic Placental Malaria and Its Association with Adverse Pregnancy Outcomes Among HIV-Negative Women in Dar Es Salaam, Tanzania: a Cohort Study, BMC Infect Dis, 2020 Oct 27;20(1):796.  doi: 10.1186/s12879-020-05521-6:

“Malaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and [small for gestational age outcome}.” Article available.

Diagnosis:

Molina A, Alférez S, Boldú L & al., Sequential Classification System for Recognition of Malaria Infection Using Peripheral Blood Cell Images, J Clin Pathol, 2020 Oct;73(10):665-670.  doi: 10.1136/jclinpath-2019-206419. Epub 2020 Mar 16. describes one of several automated diagnostic approaches for the evaluation of red blood cell inclusions, specifically to distinguish between malaria inclusions, Howell-Jolly bodies, and others.

Dumas & al., Flagging Performance of Sysmex XN-10 Haematology Analyser for Malaria Detection, J Clin Pathol, 2020 Oct;73(10):676-677. doi: 10.1136/jclinpath-2019-206382. Epub 2020 Feb 7. reports on another automated diagnostic approach to patients suspected of having malaria, a method using a “Sysmex XN-10 haematology analyser for malaria detection through the parasitic red blood cell (‘pRBC’) alarm,” followed by “rapid review of the blood smear looking for Plasmodium, mostly if the patient had fever and had not been tested for malaria.”

Yu & al., Malaria Screener: a Smartphone Application for Automated Malaria Screening, BMC Infect Dis, 2020 Nov 11;20(1):825. doi: 10.1186/s12879-020-05453-1. introduces “an Android mobile application called Malaria Screener, which makes smartphones an affordable yet effective solution to light microscopy.”  The screener is attached to a microscope with a thin or thick smear on the table, and reports the result through a built-in algorithm.  The article (available in its entirety) claims accuracy, sensitivity and specificity at levels comparable to other methods and facilitates database record keeping.

 Treatment:

The Lancet 2020 (Apr 25) 395:1316-17 (doi.org/10.1016/50140-6736(20)30560-2) is a brief opinion piece by P.J. Rosenthal, entitled Are Three Drugs for Malaria Better Than Two?  He is in favor of the three drug combination given the emerging resistance of the parasite, but contends that this may be a temporary solution, awaiting more potent initial drugs.  Article available.

Rwandan Researchers Discover New Malaria Strain, is a brief reference to the paper Emergence and Clonal Expansion of in vitro Artemisinin-resistant Plasmodium falciparum kelch13/R561H Mutant Parasites in Rwanda, published in Nature www.nature.com/articles/s41591-020-1005-2.

Adebayo & al., Enhancing the Antimalarial Activity of Artesunate, Parasitol Res, 2020 Sep;119(9):2749-2764.  doi: 10.1007/s00436-020-06786-1. Epub 2020 Jul 7 is a review of the various techniques employed to make artesunate more effective against l=malaria, including molecular modification, addition of second drugs, etc.

Cohen & al., Quality of Clinical Management of Children Diagnosed with Malaria: A Cross-Sectional Assessment in 9 Sub-Saharan African Countries Between 2007-2018, PLoS Med, 2020 Sep 14;17(9):e1003254. doi: 10.1371/journal.pmed.1003254. eCollection 2020 Sep is an article from England, studying various treatment regimens employed for children with malaria and concluding that “a majority of children diagnosed with malaria across the 9 surveyed sub-Saharan African countries did not receive recommended care. Clinical management is positively correlated with the stocking of essential commodities and is somewhat improved in more recent years, but important quality gaps remain in the countries studied.” Article available.

Ackerman H & al. studied the use of transfusion in six tertiary care hospitals in The Gambia, Malawi, Gabon, Kenya, and Ghana that participated in the Severe Malaria in African Children network and reported in The Effect of Blood Transfusion on Outcomes Among African Children Admitted to Hospital With Plasmodium falciparum Malaria: a Prospective, Multicentre Observational Study, Lancet Haematol, 2020 Nov;7(11):e789-e797.  doi: 10.1016/S2352-3026(20)30288-X.  They state that their “findings suggest that whole blood transfusion was associated with improved survival among children hospitalised with P falciparum malaria. Among those with impaired consciousness or hyperlactataemia, transfusion was associated with improved survival at haemoglobin concentrations above the currently recommended transfusion threshold. These findings highlight the need to do randomised controlled trials to test higher transfusion thresholds among African children with severe malaria complicated by these factors.”

Campaigns:

Nankabirwa JI, Arinaitwe E, Rek J, & al., Malaria Transmission, Infection, and Disease following Sustained Indoor Residual Spraying of Insecticide in Tororo, Uganda,  Am J Trop Med Hyg, 2020 Oct;103(4):1525-1533.  doi: 10.4269/ajtmh.20-0250. “Tororo, a district in Uganda with historically high malaria transmission intensity, has recently scaled up control interventions, including universal long-lasting insecticidal net distribution in 2013 and 2017, and sustained indoor residual spraying (IRS) of insecticide since December 2014.” They conclude that “[a]fter 5 years of intensive vector control measures in Tororo, the burden of malaria was reduced to very low transmission levels. However, a significant proportion of the population remained parasitemic, primarily school-aged children with submicroscopic parasitemia, providing a potential reservoir for malaria transmission.”

A major malaria control campaign is Mozambique is described by Galatas & al., A Multiphase Program for Malaria Elimination in Southern Mozambique (the Magude Poject): A Before-After Study, PLoS Med 2020 Aug 14;17(8):e1003227. doi: 10.1371/journal.pmed.1003227. eCollection 2020 Aug. Their impressive results included the following:  “Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction).”  Nonetheless they concluded “that the interventions deployed during the Magude project fell short of interrupting P. falciparum transmission with the coverages achieved. While new tools and strategies may be required to eventually achieve malaria elimination in stable transmission areas of sub-Saharan Africa, this project showed that innovative mixes of interventions can achieve large reductions in disease burden, a necessary step in the pathway towards elimination.” Article available.

Allafrica.com quotes the Malaria Consortium (www.malariaconsortium.org/news-centre/covid-19-and-malaria-how-surveillance-can-adapt-to-fight-both.htm) describing guidance by the Monitoring and evaluation Research Group.

Epidemiology:

The allafrica.com website also quotes  New Malaria Mosquito Threatens Mass Outbreaks in Africa, and Invasive Mosquito Species Could Bring More Malaria to Africa’s Urban Areas, reporting on the spread of Anopheles stephensi, which has been found on the continent since 2016 and is seen to be spreading through transportation routes.  What is worrisome about this species is that it is more at home in urban areas than other Anopheles species that can host the malaria parasite.

Malaria Parasites in Nigeria are Genetically Diverse – a Danger, but Also a Useful Tool, also from allafrica.com, republished from https://theconversation.com/africa, is by S. Oyedeji, who concludes that “P. falciparum parasites exhibit high genetic diversity in natural population, including the micro environment, in areas where malaria transmission is high.” Further, it is “a way to keep a watch for mutants that may be resistant to drugs.”

A team led by researchers at Heidelberg University Hospital in Germany compared P. falciparum in blood samples of asymptomatic individuals from Mali collected during the dry season and during the wet season. As they reported in Nature Medicine in November, the researchers found that parasites isolated during the dry season had a different gene expression profile than those isolated during the wet season. Samples further differed in how long infected red blood cells circulated and how they adhered to the vascular endothelium. The summary by Genome News, A Malaria-Causing Parasite Shifts Its Gene Expression During the Dry Season, When Mosquitoes That Typically Spread It Are Scarce, a New Study Has Found, is available.

According to a research paper presented  by lead author C. Andolina at the Annual meeting of the American Society of Tropical Medicine and Hygiene, even a small number of infected children can transmit malaria parasites to many mosquitoes, which can then go on to infect more humans.  Reference to the paper is summarized in Live Science as Children Can Be Superspreaders of Malaria to Mosquitoes, a copy of which is available.

Other articles focused on epidemiology include:

Zerdo & al., Parents’ Perception on Cause of Malaria and Their Malaria Prevention Experience Among School-Aged Children in Kutcha District, Southern Ethiopia; Qualitative Study, PLoS One 2020 Oct 13;15(10):e0239728. doi: 10.1371/journal.pone.0239728. eCollection 2020.  Article available.

Kamau A, Mtanje G, Mataza C & al., The Relationship Between Facility-Based Malaria Test Positivity Rate and Community-Based Parasite Prevalence, PLoS One, 2020 Oct 7;15(10):e0240058. doi: 10.1371/journal.pone.0240058. eCollection 2020. Article available.

Björkman & al., Why Asymptomatic Plasmodium falciparum Infections Are Common in Low-Transmission Settings, Trends Parasitol, 2020 Nov;36(11):898-905. doi: 10.1016/j.pt.2020.07.008. Epub 2020 Aug 25.

Smith & al., Will More of the Same Achieve Malaria Elimination? Results from an Integrated Macroeconomic Epidemiological Demographic Model, Am J Trop Med Hyg 2020 Nov;103(5):1871-1882. doi: 10.4269/ajtmh.19-0472. Article available

Basic Research:

Dobbs KR, Crabtree JN, Dent AE, Innate Immunity to Malaria-The Role of Monocytes, Immunol Rev, 2020 Jan;293(1):8-24.  doi: 10.1111/imr.12830. Epub 2019 Dec 16.

Rivera-Correa & al. Autoimmune Anemia in Malaria, Trends Parasitol, 2020 Feb;36(2):91-97. doi: 10.1016/j.pt.2019.12.002. Epub 2019 Dec 18.

Jensen &al., Cerebral Plasmodium falciparum Malaria: The Role of PfEMP1 in Its Pathogenesis and Immunity, and PfEMP1-based Vaccines to Prevent It, Immunol Rev,  2020 Jan;293(1):230-252.  doi: 10.1111/imr.12807. Epub 2019 Sep 27.

Colvin & al., Insights into Malaria Pathogenesis Gained from Host Metabolomics, PLoS Pathogens 2020 Nov 12, 16(11): e1008930 https://doi.org/10.1371/journal.ppat.1008930.