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

Malaria continues to generate enormous professional interest.  The National Library of Medicine listed over 4700 publications on or related to the subject for 2020, which does not include those of WHO, and non-peer-reviewed publications.  Up to the 10th of this month, close to 300 are listed, which implies a rate increased beyond that of 2020.

In this setting, it is important to be selective as to what to report to MPI.  While these reports will continue to cover important articles that have general applicability, including basic research topics, otherwise only those that relate specifically to Sub-Saharan Africa (where MPI focuses its attention) will be covered, and only if the information contained therein is new and significant.

That said, this month’s report is one of the longest so far!

Prevention:

McCann RS, & al., Maximizing Impact: Can Interventions to Prevent Clinical Malaria Reduce Parasite Transmission? Trends Parasitol, 2020 Nov;36(11):906-913.  doi: 10.1016/j.pt.2020.07.013. Epub 2020 Sep 9. They “discuss the relationship between malaria parasite transmission and disease, including mechanisms by which disease-targeting interventions might also impact parasite transmission. [They] then focus on three malaria interventions with strong evidence for reducing the burden of clinical malaria disease and examine their potential for also reducing malaria parasite transmission.

As reported by Kwambai TK, & al., Malaria Chemoprevention in the Postdischarge Management of Severe Anemia, N Engl J Med, 2020 Dec 3;383(23):2242-2254. doi: 10.1056/NEJMoa2002820, “in areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo.“

Wotodjo AN, & al. investigated the impact of “repeated renewal of long-lasting insecticide-treated net (LLIN) universal coverage on malaria resurgence over a period of 10 years of net implementation in Dielmo (Senegal)” and found that “[t]he use of nets increased significantly after the third time the nets were renewed when compared with the year after the first and the second times the nets were renewed (P < 0.001).”  The article is The Impact of Renewing Long-Lasting Insecticide-Treated Nets in the Event of Malaria Resurgence: Lessons from 10 Years of Net Use in Dielmo, Senegal, Am J Trop Med Hyg, 2021 Jan;104(1):255-262.  doi: 10.4269/ajtmh.20-0127.

Nolan T, Control of Malaria-Transmitting Mosquitoes Using Gene Drives, Philos Trans R Soc Lond B Biol Sci, 2021 Feb 15;376(1818):20190803.  doi: 10.1098/rstb.2019.0803. Epub 2020 Dec 28 discusses the “relative merits of [CRISPR-based] gene drive, as well as barriers to its technical development and to its deployment in the field as malaria control. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.”  Article available.

On the other hand, Decreased Bioefficacy of Long-Lasting Insecticidal Nets and the Resurgence of Malaria in Papua New Guinea by Vinit R & al, points out the emerging adaptation of mosquitoes.  The article, which is available, is included here despite the region being outside of Africa, because of its relevance to the future of mosquito control.  It appeared in Nature Communications, doi: 10.1038/s41467-020-17456-2.

Orishaba P & al, Increased Malaria Parasitaemia Among Adults Living with HIV Who Have Discontinued Cotrimoxazole Prophylaxis in Kitgum District, Uganda, PLoS One, 2020 Nov 11;15(11): e0240838.  doi: 10.1371/journal.pone.0240838. eCollection 2020 points out a hazard in discontinuing prevention, even if recommended by competent professional authority. Article available.

Diagnosis:

Patel H & al. argue that there is a “need for better external validation in studies of outcome predictors and for the demonstration that predictors can be used to guide clinical management in a way that improves survival and long-term health” in Predictors of Outcome in Childhood Plasmodium falciparum Malaria, Virulence, 2020 Dec;11(1):199-221., doi: 10.1080/21505594.2020.1726570.  Article available.

Orieru EC & al., Seroprevalence and Parasite Rates of Plasmodium malariae in a High Malaria Transmission Setting of Southern Nigeria, Am J Trop Med Hyg, 2020 Dec;103(6):2208-2216. doi: 10.4269/ajtmh.20-0593. Epub 2020 Oct 22 is an article that highlights the existence of other Plasmodium infections in the geographic area studied, especially P. malariae. Article available.

Treatment:

Kishoyian G & al’s report, Efficacy of Artemisinin-lumefantrine for Treatment of Uncomplicated Malaria After More Than a Decade of Its Use in Kenya, Epidemiol Infect, 2021 Jan 5;1-24. doi: 10.1017/S0950268820003167 (Online ahead of print) focuses on successful treatment in children between the ages of 6 months and 5 years.  Article available.

Another article on children, Pessanha de Carvalho L & al., The Preclinical Discovery and Development of Rectal Artesunate for the Treatment of Malaria in Young Children: A Review of the Evidence, Expert Opin Drug Discov, 2021 Jan;16(1):13-22.  doi: 10.1080/17460441.2020.1804357. Epub 2020 Sep 14, recommends a course of action in the case of severely ill children by community first responders, before definitive treatment can be implemented.

Hanson J, & al. argue that a standard pragmatic treatment of severely ill children should also be implemented for adults, in Time for Pragmatic, Prospective Clinical Trials to Determine the Role of Empirical Antibacterial Therapy in Critically Ill Adults Hospitalized with Malaria, Int J Infect Dis, 2021 Jan;102:28-31.  doi: 10.1016/j.ijid.2020.09.1472. Epub 2020 Oct 2. Article available.

The danger of drug-resistant parasites in Rwanda is highlighted by Bergman c & al. in an article that explores the mechanism of resistance.  The article, Increase in Kelch13 Polymorphism in Plasmodium falciparum, Southern Rwanda, appeared in Emerging Inf Dis, 2021 Jan, 27(1):194-96. It is available.

Not in Africa, but relevant to the topic of resistance and how to overcome it is Van der Pluijm RW, & al., Triple Artemisinin-Based Combination Therapies for Malaria – A New Paradigm? Trends Parasitol,  2021 Jan;37(1):15-24.  doi: 10.1016/j.pt.2020.09.011. Epub 2020 Oct 12. Article available.

Campaigns:

Aborode AT & al., Fighting COVID-19 at the Expense of Malaria in Africa: The Consequences and Policy Options, Am J Trop Med Hyg, 2021 Jan;104(1):26-29. doi: 10.4269/ajtmh.20-1181 explores an important aspect of the current pandemic. As other articles on this topic, it argues: “Considering that the malaria burden is high in many low-income tropical countries with little capacity to fund malaria control and eradication programs, the fight against malaria in these regions is likely to be hindered by COVID-19.”

Likewise, an unsigned editorial, Tuberculosis and Malaria in the Age of COVID-19, Lancet Infect Dis 2021 Jan, 21:1 refers to the same phenomenon, citing several articles recently published.  In the same issue of Lancet Infect Dis (2021 Jan, 21:5) Tebow-Ewungkem MI and Ngwa GA published a Comment,  COVID-19 in Malaria-Endemic Regions: Potential Consequences for Malaria Intervention Coverage, Morbidity, and Mortality. They cite data from the paper by Weiss et al (see below) and others.

Blanco M and colleagues explore the topic of training of health workers in Knowledge and Practices Regarding Malaria and the National Treatment Guidelines Among Public Health Workers in Equatorial Guinea, Malar J, 2021 Jan 7;20(1):21. doi: 10.1186/s12936-020-03528-7.

In an Editorial, Lindblad KA & Kachur SP state the following: “…it is possible to interrupt malaria transmission in the Western highlands of Kenya, but sustaining this achievement will require a program that is fit-for-purpose for elimination. Such a well-documented setting, with decades of research collaboration can become a crucible for consolidating and testing malaria control capabilities that will eventually be used nationwide.”  The editorial,  Opportunities for Sub-National Malaria Elimination in High-Burden Countries, Am J Trop Med Hyg 2020, 103(6):2153-54 is available.

Epidemiology:

Hamre KES & al., Lack of Consistent Malaria Incidence Hotspots in a Highland Kenyan Area During a 10-Year Period of Very Low and Unstable Transmission, Am J Trop Med Hyg, 2020 Dec;103(6):2198-2207.  doi: 10.4269/ajtmh.19-0821. Epub 2020 Oct 27 is one of the articles that form the background of the editorial above, as are Hamre KES & al., Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission, Am J Trop Med Hyg 2020 Dec;103(6):2174-2182,  doi: 10.4269/ajtmh.18-0805. Epub 2020 Oct 27. and Ondigo BN & al., Antibody Profiles to P. falciparum Antigens Over Time Characterize Acute and Long-Term Malaria Exposure in an Area of Low and Unstable Transmission, Am J Trop Med Hyg, 2020 Dec;103(6):2189-2197.  doi: 10.4269/ajtmh.19-0480. Epub 2020 Oct 27.

Although not cited by the editorial above, Alegana VA, al., Malaria Micro-Stratification Using Routine Surveillance Data in Western Kenya, Malar J, 2021 Jan 7;20(1):22.  doi: 10.1186/s12936-020-03529-6, is also specifically relevant to the kind of sub-national efforts to which the editorial refers.

Returning to the issue of the influence of the pandemic on the burden of malaria, Weiss DJ & al. evaluated plausible effects on malaria incidence and mortality under different levels of disruption to malaria control.  They conclude that “[u]nder pessimistic scenarios, COVID-19-related disruption to malaria control in Africa could almost double malaria mortality in 2020, and potentially lead to even greater increases in subsequent years. [underlining mine] To avoid a reversal of two decades of progress against malaria, averting this public health disaster must remain an integrated priority alongside the response to COVID-19.” The reference is Indirect Effects of the COVID-19 Pandemic on Malaria Intervention Coverage, Morbidity, and Mortality in Africa: A Geospatial Modelling Analysis, Lancet Infect Dis, 2021 Jan;21(1):59-69.  doi: 10.1016/S1473-3099(20)30700-3. Epub 2020 Sep 21. Article available.

A different take on the epidemiology of malaria is evident in Zango SH & al., Malaria and Curable Sexually Transmitted Infections in Pregnant Women: A Two-Years Observational Study in Rural Burkina Faso, PLoS One, 2020 Nov 16; 15(11):e0242368.  doi: 0.1371/journal.pone.0242368.  eCollection 2020. Article available.

Basic Research:

Korbmacher F, Drepper B, Sanderson T & al., An Apicoplast-Resident Folate Transporter is Essential for Sporogony of Malaria Parasites, Cell Microbiol, 2021 Jan;23(1):e13266. doi: 10.1111/cmi.13266. Epub 2020 Oct 8.

Hollin T, & al., Dynamic Chromatin Structure and Epigenetics Control the Fate of Malaria Parasites, Trends Genet, 2021 Jan;37(1):73-85.  doi: 10.1016/j.tig.2020.09.003. Epub 2020 Sep 25. Article available.

The following articles relate to the pathophysiology of malaria:

Bucşan AN & Williamson KC, Setting the Stage: The Initial Immune Response to Blood-Stage Parasites, Virulence 2020 Dec;11(1):88-103. doi: 10.1080/21505594.2019.1708053.

Drewry LL & Harty JT, Balancing in a Black Box: Potential Immunomodulatory Roles for TGF-Β Signaling During Blood-Stage Malaria, Virulence, 2020 Dec;11(1):159-169. doi: 10.1080/21505594.2020.1726569.

Ndiabamoh CBC & al., The Immunoglobulin G Antibody Response to Malaria Merozoite Antigens in Asymptomatic Children Co-Infected with Malaria and Intestinal Parasites, PLoS One, 2020 Nov 10;15(11):e0242012. doi: 10.1371/journal.pone.0242012. eCollection 2020.

Possemiers H & al., Etiology of Lactic Acidosis in Malaria, PLoS Pathog, 2021 Jan 7;17(1):e1009122.  doi: 10.1371/journal.ppat.1009122. eCollection 2021 Jan.

Articles of all of the above pathophysiology articles are available; abstract only for the following:

Schureck MA & al., Malaria Parasites Use a Soluble RhopH Complex for Erythrocyte Invasion and an Integral Form for Nutrient Uptake, Elife, 2021 Jan 4;10:e65282.  doi: 10.7554/eLife.65282. Online ahead of print.