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

 

Although it does not come from the scientific literature, the most important malaria-related information this month came on 6 October when the WHO announced its recommendation that GSK’s RTS,S antimalaria vaccine be administered to children in Sub-Saharan Africa and in other regions with moderate or high Plasmodium falciparum transmission.  Multiple news outlets, paper, electronic, and over the air, have carried this information along variable content about the vaccine, its administration regimen and malaria in general. NOTE: As per news sources, “the next step is for Gavi, the global vaccine alliance, to determine that the vaccine is a worthwhile investment.  If the organization’s board approves the vaccine – not guaranteed, given the vaccine’s moderate efficacy and the many competing priorities – Gavi will purchase the vaccine for countries that request it, a process expected to take at least a year.” (Source: NY Times, via the Seattle Times)

The surfeit of articles relevant to malaria continues.  PubMed now has over 3000 publications listed this year alone.  While it is very difficult to choose among them, we continue to place emphasis on those that are most relevant to the disease in Africa. Nonetheless, there are quite a few items in the “basic research” category this month, because of the potential that some of the reported findings will be relevant to practice in the field in the not too distant future 

Prevention:

Please see the information about the WHO’s action above. WHO’s news release may be accessed at https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk.  The text is also available from the author of these monthly reports.

Chandramohan D & al., Seasonal Vaccination with or without Seasonal Chemoprevention, New Eng J Med 2021 Sep 9, 385:1005-17, doi:a056/NEJMoa2026330 may well have been the final piece of information that led the WHO to issue its recommendation. In a study conducted by scientists from London School of Hygiene and Tropical Medicine, 6861 children in Mali and Burkina Faso were treated either by seasonal chemoprevention, or three doses of the RTS/SA01E vaccine plus boosters, as well a combination of both to a third group.  The results showed that while chemoprevention and vaccine alone were of equivalent efficacy, combination of the two reduced infection by 62.8% as compared to chemoprevention alone, reduced severe malaria by 70.6% and death by 72.9%.

Oneko M & al., Safety, Immunogenicity and Efficacy of PfSPZ Vaccine Against Malaria in Infants in Western Kenya: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Trial, Nature Medicine, 2021 Sep 13  27:1636–1645. https://www.nature.com/articles/s41591-021-01470-y. “Preclinical studies show that T cell-mediated immunity is required for protection and is readily induced in humans after vaccination. However, previous malaria exposure can limit immune responses and vaccine efficacy (VE) in adults. [The authors] hypothesized that infants with less previous exposure to malaria would have improved immunity and protection. [They] conducted a multi-arm, randomized, double-blind, placebo-controlled trial in 336 infants aged 5–12 months to determine the safety, tolerability, immunogenicity and efficacy of the PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya.” After analyzing the results, they found that “[t]here was no significant protection against P. falciparum infection in any dose group at 6 months… Since there was no significant VE at 6 months in these infants, these vaccine regimens will likely not be pursued further in this age group.”

A short review about various PfSPZ vaccines is Venkatesan P, Malaria Vaccine Development-Where Are We? Lancet Infect Dis, 2021 Sep;21(9):1218. doi: 10.1016/S1473-3099(21)00489-8.  These vaccines use various attenuated infectious P. falciparum sporozoites with simultaneous administration of antimalarial drugs. An unsigned editorial a month later in the same journal, A Brighter Future in Malaria Prevention? Lancet Infect Dis, 2021 Oct;21(10)1333. doi.org/10.1016/S1473-3099(21)00569-7 concerns all recent vaccine trials, including the circumsporozoite protein-based vaccine R21. The use of a monoclonal antibody to prevent malaria infection is also covered.

“Gene drive mosquitoes are one potential new technology in the control of malaria vectors. Target Malaria is one of the research projects developing this technology, and in July 2019, the project proceeded to an important step for this evaluation pathway: the small-scale release of non-gene drive sterile male mosquitoes in a village in Burkina Faso.” Toe LP & al.,  Small-Scale Release of Non-Gene Drive Mosquitoes in Burkina Faso: From Engagement Implementation to Assessment, a Learning Journey, Malaria J 2021 Oct 9, vol 20 art 395. https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03929-2 “provides a review of engagement activities relevant to field trials on non-gene drive genetically-modified mosquitoes as well as an assessment framework—using both qualitative and quantitative studies as well as an audit procedure. The latter was implemented to evaluate whether the release activities could proceed with the appropriate level of agreement from the community… The assessments demonstrated ways to increase understanding and ensure effective progress with field studies and, therefore, the pathway for responsible research.”

“ICON® Maxx is a twin-sachet ‘home-treatment kit’ of pyrethroid plus binding agent, recommended by the World Health Organization (WHO) for long-lasting, wash-fast treatment of polyester nets.”  Tungu PK & al., Bio-Efficacy and Wash-Fastness of a Lambda-Cyhalothrin Long-Lasting Insecticide Treatment Kit (ICON® Maxx) Against Mosquitoes on Various Polymer Materials, Malaria J 2021 Sep 28, vol 20 art: 387. https://malariajournal.biomedcentral.com/ articles/10.1186/s12936-021-03909-6 pursued this investigation and concluded that “[t]he bio-efficacy of ICON Maxx against mosquitoes on netting washed up to 20 times demonstrated wash durability on a range of synthetic polymer and natural fibres: polyester, polyethylene, nylon and cotton. This raises the prospect of making insecticide-binder kits into an effective approach for turning untreated nets, [and other materials] into effective malaria prevention products. It may provide a solution to the problem of reduced LLIN coverage … by converting commercially sourced untreated nets into LLINs…”

In an ideal world, once malaria prevention campaigns begin, all of its components, including indoor residual spraying (IRS) will continue indefinitely until the disease is eradicated in a wide geographic area. Namuganga JF & al., The Impact of Stopping and Starting Indoor Residual Spraying on Malaria Burden in Uganda, Nature Comm, 2021 May 11;12(1):2635.  doi: 10.1038/s41467-021-22896-5 deal with the real life situation in which IRS is not sustained, such as during the current COVID-19 pandemic. The authors state that “in areas where IRS was initiated and sustained, malaria incidence dropped by 85% after year 4.”  However, “stopping IRS was associated with a 5-fold increase in malaria incidence within 10 months…”  The good news in their report is that “reinstating IRS was associated with an over 5-fold decrease within 8 months … [thus] IRS could play a critical role in achieving global malaria targets, particularly in areas where progress has stalled.”

In addition to indoor residual spraying, Anaele BI & al., The Efficacy of Insecticide-Treated Window Screens and Eaves Against Anopheles Mosquitoes: A Scoping Review, Malaria J 2021 Sep 29, vol 20 art 388.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03920-x reports the results of several studies in which eaves and window screens were treated with good results in ter3ms of mosquito death.  Results were persistent after washing the surfaces.

Diagnosis:

One of the key tools “to integrated community case management in malaria-endemic areas is the application of the most suitable rapid diagnostic test (RDT) to inform the decision to treat, or to refute the diagnosis of malaria in a febrile individual…” This introduces an editorial in Clinical Infectious Diseases, Petersen E & Grobusch MP, Accurate Malaria Diagnosis: Not Only Essential for Malaria Case Management, but Prerequisite for Managing Febrile Disease in the Tropics, Clin Infect Dis, 2021 Sep 7; 73(5):e1168-e1169. doi: 10.1093/cid/ciaa1945.  It refers to the problematic results of the study by Mischlinger J & al., Predictive Performance of Rapid Diagnostic Tests for Falciparum Malaria and Its Modeled Impact on Integrated Community Case Management [iCCM]of Malaria in Sub-Saharan African Febrile Children, Clin Infect Dis, 2021 Sep 1; 73(5) e1158-e1167 e1167. https://doi.org/10.1093/cid/ciaa1942. These authors “modeled diagnostic predictive values for all malaria-endemic African regions as an indicator of the programmatic usefulness of RDTs in iCCM campaigns on malaria.”  They did this because of their expectation that “due to a changing epidemiology of fever causes in Africa, positive RDT results might not correctly reflect malaria.”  In fact they encountered wide variability in the positive predictive value (PPV) of RDTs between less than 40% (Ethiopia) and more than 95 % (Guinea).  In contrast, negative predictive value was 90% or more in each area studied. These results “suggest that the administration of antimalarials alone may not constitute causal treatment in the presence of a positive RDT result for a substantial proportion of patients, particularly in low-PPV settings.”  Thus, other severe infectious diseases may be missed in the care of these patients.

Similarly, Oboh MA & al., Comparative Analysis of Four Malaria Diagnostic Tools and Implications for Malaria Treatment in Southwestern Nigeria, Int J Infect Dis, 2021 Jul;108:377-381. doi: 10.1016/j.ijid.2021.05.049 found false positivity rate of mRDT over 40%, as well as false negativity over 12% (i.e. sensitivity of about 87.5%, coupled with low specificity). Microscopy, on the other hand, had high specificity, but compared to other, laboratory-based, testing (such as nested polymerase chain reaction), it missed well over half of the patients who were proven to have malaria.  

In Zambia, Mwenda MC & al. also found that “RDT diagnostic accuracy was predominantly affected by a high rate of false positives. Nonetheless their report, Performance Evaluation of RDT, Light Microscopy (LM), and PET-PCR for Detecting Plasmodium falciparum Malaria Infections in the 2018 Zambia National Malaria Indicator Survey, Malaria J,  2021 Sep 28, vol 20 art: 386. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03917-6 concludes that “RDTs and LM both perform well across a range of transmission intensities within their respective target applications, i.e., in the community, for the former, where ease of use and speed of result is critical, and at the health facility, for the latter, where accuracy is prioritized. However, the performance of both diagnostic methods is adversely affected by low parasitaemia infections. As Zambia moves towards elimination more sensitive tools may be required to identify the last cases.”

Perhaps in contrast to all the above, Omale UI & al., Demand for Malaria Rapid Diagnostic Test, Health Care-Seeking Behaviour, and Drug Use Among Rural Community Members with Fever or Malaria-Like Illness in Ebonyi State, Nigeria: A Cross-Sectional Household Survey, BMC Health Serv Res, 2021 Aug 21; 21(1):857. doi: 10.1186/s12913-021-06865-8 appears to champion the value of “Malaria Rapid Diagnostic Testing” (MRDT), without specifying which type of test they refer to.  The thrust of the article is that many parents or carers of febrile children assume that the child has malaria and seek treatment from various sources, not necessarily from those who will ensure correct diagnosis and treatment tailored to the diagnosis.

Likewise, Feleke DG et al. state that they reviewed 29 publications between 2001 and 2020 and concluded that “RDT had an excellent diagnostic accuracy … when compared with microscopy. Its specificity was quite good (93%–100%) except for one outlier (28%). … This indicates RDT had a good diagnostic accuracy (AUC = 0.83).” Based on the title of their article, Performance of Rapid Diagnostic Tests, Microscopy, Loop-Mediated Isothermal Amplification (LAMP) and PCR for Malaria Diagnosis in Ethiopia: A Systematic Review and Meta-Analysis, Malaria J 2021 Sep 27, vol 20, art: 384. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03923-8, these studies all must have been confined to Ethiopia.  Their statement provides a stark contrast to the conclusion of Mischlinger & al (above), which while quoting a different measure (positive predictive value), presents RDT in a much less favorable light in that country.

Perhaps some light is shed at the discrepancies in reliability of RDTs by Alamayehu GS & al., Genetic Variation of Plasmodium Falciparum Histidine-Rich Protein 2 and 3 in Assosa Zone, Ethiopia: Its Impact on the Performance of Malaria Rapid Diagnostic Tests, Malaria J 2021 Oct 9 vol 20 art:394  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03928-3. Their study highlighted this genetic variability that may affect the predictive value of RDTs. 

In countries or areas of relatively low prevalence of malaria, the identification of low density infections and asymptomatic carriers is very important in moving toward elimination of the disease.  Colbert AJ & al., Towards The Use of a Smartphone Imaging-Based Tool for Point-Of-Care Detection of Asymptomatic Low-Density Malaria Parasitaemia, Malaria J 2021 Sep 25, vol 20 art: 380. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03894-w present data on the use of two imaging-based sensing techniques. “[P]article diffusometry (PD), is combined with loop mediated isothermal amplification (LAMP) on a smartphone-enabled device to detect low levels of parasitaemia…”  They state that “Plasmodium falciparum parasites were detected from asymptomatic individuals’ whole blood samples with 89% sensitivity and 100% specificity when compared to quantitative polymerase chain reaction (qPCR).”

Ampadu Owusu ED & al., Acceptance and Perceived Value of Non-Invasive Malaria Diagnostic Tests in Malaria-Endemic Countries, Malaria J 2021 Sep 24, vol 20, art: 379. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03911-y explored the premise that malaria testing may be acceptable to a larger segment of the population if it were non-invasive, that is not require obtaining a blood sample. The study utilized questionnaires to a limited number of National Malaria Control Program (NMCP) “stakeholders.” A slight majority of the 70 responders felt that blood-based testing we acceptable, except perhaps in the case of children, who would prefer saliva-based or urine-based tests.  Many stakeholders also added the cost of the test as a possible factor in determining acceptability.  Based on the abstract, the predictive value of saliva and urine-based tests was not an aspect of these tests covered in the article.

“Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission.” Salgado C & al. conclude in their report, The Prevalence and Density of Asymptomatic Plasmodium falciparum Infections Among Children and Adults in Three Communities of Western Kenya, Malaria J 2021 Sep 17, vol 20 art 371. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03905-w that there is a “substantial …infectious reservoir among asymptomatic carriers of P. falciparum.” Specifically, “[a]cross all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults … had sub-microscopic parasitaemia.”

An unusual way of detecting malaria is the subject of Shuai Y & al., Oral Manifestations Related to Malaria: A Systematic Review, Oral Dis, 2021 Oct;27(7):1616-1620. doi: 10.1111/odi.13549. Their article, aimed at dentists, draw attention to the “oral manifestations of malaria …, including gingival bleeding, glossitis, oral ulcer, abnormal oral pigmentation, pericoronitis, herpes labialis, herpes gingivostomatitis, bitter taste, sore throat, Burkitt lymphoma of the jaw, alveolar bone resorption, and enamel hypoplasia.”

Ateba FF & al., The Effect of Malaria on Stunting: An Instrumental Variables Approach, Trans R Soc Trop Med Hyg, 2021 Sep 3;115(9):1094-1098. doi: 10.1093/trstmh/traa183 does not exactly fit into the category of malaria diagnosis, but calls attention to their estimate “that one additional clinical malaria episode per year increases the odds of a child being stunted by 6%…”

Treatment:

Balikagala B et al. studied the effect of artesunate treatment for malaria in Northern Uganda.  They report in Evidence of Artemisinin-Resistant Malaria in Africa, New Eng J Med, 2021 Sep 23, 385(13): 1163-71 doi:10.1056/NEJMoa2101746 that 14 of 240 patients studied had evidence of in vivo artemisinin resistance.  Of these 14 patients, 13 had parasites with mutations in the kelch13 gene.  Apparently these mutations were different from those evident in artemisinin-resistant parasites in Southeast Asia, leading to the conclusion that these modes of resistance arose independently in Africa.

Nhama A & al found that the WHO-recommended first line therapy for malaria is effective and safe in Mozambique, at least it was so up to the time of their study. They reported In Vivo Efficacy and Safety of Artemether–Lumefantrine And Amodiaquine–Artesunate for Uncomplicated Plasmodium Falciparum Malaria in Mozambique, 2018, Malaria J 2021 Oct 3 vol 20 art 390. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03922-9

“Primaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention of Plasmodium falciparum malaria transmission.” Mosha D & al.,  Safety Monitoring Experience of Single-Low Dose Primaquine Co-Administered with Artemether–Lumefantrine Among Providers and Patients in Routine Healthcare Practice: A Qualitative Study in Eastern Tanzania, Malaria J 2021 Oct 9, vol 20 art: 392.  https://malariajournal.biomedcentral.com/articles/10.1186/ s12936-021-03921-w explored “the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT)… Single-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers.”

Mullard A, Monoclonal Antibodies Show Promise in Phase I Malaria Trial, Nature, 2021 Sep 6 https://www.nature.com/articles/d41573-021-00157-w and O’Leary K, An Antibody for Malaria Prevention, Nature Medicine, 2021 Sep 6, https://www.nature.com/articles/d41591-021-00055-z both refer to a phase 1 trial involving controlled infection that “showed that CIS43LS was safe to use and effectively prevented infection with the malaria parasite.”

A different approach to future therapy for malaria may involve the interference with hemozoin synthesis in the parasite.  de Villiers KA and Egan TJ report on their experimental work in this regard in Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development, Acc Chem Res, 2021 Jun 1;54(11):2649-2659.  doi: 10.1021/acs.accounts.1c00154.  Their studies “have shown that hemozoin inhibitors cause a dose-dependent increase in exchangeable heme, correlated with decreased parasite survival.” At this point it is not yet clear how this may be utilized in the treatment of malaria.

Another article referring to asymptomatic children with parasitemia concludes that there is evidence that these children have more than average susceptibility to other infections, including those by Salmonella species. Post A & al., Altered Ex-Vivo Cytokine Responses in Children With Asymptomatic Plasmodium falciparum Infection in Burkina Faso: An Additional Argument to Treat Asymptomatic Malaria? Front Immunol, 2021 Jun 9;12:614817.  doi: 10.3389/fimmu.2021.614817 report their conclusions from measurement of these children’s cytokine responses when also bacteremic.  They state that “[i]n children with asymptomatic malaria, cytokine responses upon ex-vivo bacterial stimulation are downregulated.”  

No month goes by without reference to traditional therapies in communities affected by malaria.  Baldé AM & al., Malaria in Guinean Rural Areas: Prevalence, Management, and Ethnotherapeutic Investigations in Dionfo, Sub-Prefecture of Labe, Planta Med, 2021 Aug;87(10-11):850-859. doi: 10.1055/a-1519-5847 report from Guinea that of 63 various plants used for treatment by the public, Terminalia albida (Combretaceae) was the most commonly cited. According to the authors, “[e]thnotherapeutic evaluation of a remedy based on T. albida was applied to 9 voluntary patients suffering from uncomplicated malaria. Treatment of 7 to 14 days led to an improvement of clinical symptoms and a complete parasite clearance achievement of 8/9 patients without side effects.” {JSTOR Global Plants, https://plants.jstor.org/stable/10.5555/al.ap.upwta.1_799 does not cite a common name for this plant, frequently found in West Africa} 

Campaigns:

Schapira A and Kondrashin A, Prevention of Re-Establishment of Malaria, Malar J, 2021 May 31; 20(1):243.  doi: 10.1186/s12936-021-03781-4 argue that “prevention of re-establishment of malaria transmission should be integrated with prevention of malaria mortality in cases of imported malaria, and that this requires collaboration with entities dealing with travellers’ health and the availability of chemoprophylaxis and other measures for travellers to malaria endemic countries.”

It appears that fears about the COVID pandemic adversely affecting malaria campaigns are justified. Gavi S & al. report in Malaria Incidence and Mortality in Zimbabwe During the COVID-19 Pandemic: Analysis of Routine Surveillance Data, Malar J, 2021 May 24;20(1):233.  doi: 10.1186/s12936-021-03770-7 that “[c]ompared to the same period in 2017, 2018 and 2019, there was an excess of over 30,000 malaria cases from January to June 2020. The number of malaria deaths recorded in January to June 2020 exceeded the annual totals for 2018 and 2019. District level maps indicated that areas outside high malaria burden provinces experienced higher than expected malaria incidence and mortality, suggesting potential outbreaks.”

While China is outside of our area of main interest, it is worth reporting that on June 30 of this year, China was certified malaria-free after 4 consecutive years of no indigenous cases and 70 years of tremendous control efforts.  This is reported in Burki T, Triumph in China as it is Certified Malaria-Free by WHO, Lancet Infect Dis, 2021 Sep; 21(9):1220-1221. doi: 10.1016/S1473-3099(21)00491-6.

Epidemiology:

Looking at the influence of the pandemic coexisting with malaria in another direction Anyanwu MU, The Association Between Malaria Prevalence and COVID-19 Mortality, BMC Infect Dis, 2021 Sep 19; 21(1):975.  doi: 10.1186/s12879-021-06701-8 claims that that “there are reduced COVID-19 deaths in malaria endemic countries, although the results need to be proved further by clinical trials.”

 

Ngole Sumbele IU & al. report on another aspect of asymptomatic parasitemia in Asymptomatic and Sub-Microscopic Plasmodium falciparum Infection in Children in the Mount Cameroon Area: A Cross-Sectional Study on Altitudinal Influence, Haematological Parameters and Risk Factors, Malaria J 2021 Sep 26, vol 20 art 382 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03916-7. “Malaria parasite, asymptomatic malaria parasitaemia and sub-microscopic Plasmodium infection and anaemia were prevalent in 36.4%, 34.0%, 43.8% and 62.3% of the children, respectively.”  Children with sub-microscopic infection had lower hematologic indices than their negative counterparts. The authors noted variability in infection rates to be influenced by the altitude at which the children lived.

Takeregn M  & al., Malaria Prevalence and Associated Risk Factors in Dembiya District, North-Western Ethiopia, Malaria J  2021 Sep 17, vol 20 art:372. https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03906-9. This was a study based on examining thick smear slides, correlated with medical records and questionnaires.  “The 6-year retrospective malaria prevalence trend indicates an overall malaria prevalence of 22.4%, out of which Plasmodium falciparum was the dominant species. [P. vivax and mixed infections were also found]… Males were 2.6 times more likely to be infected with malaria than females … and individuals with frequent outdoor activity were 16.4 times more vulnerable than individuals with limited outdoor activities …”  

Studying dried blood spots (DBS), Markwalter CF & al., Antibody Signatures of Asymptomatic Plasmodium falciparum Malaria Infections Measured from Dried Blood Spots, Malaria J 2021 Sep 23, vol 20, art: 37. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03915-8 conclude that “[m]alaria-specific antibody responses can be reliably detected, quantified, and analysed from DBS, opening the door to serological studies in populations where serum collection, transport, and storage would otherwise be impossible. While test characteristics of antibody signatures were insufficient for individual diagnosis, serological testing may be useful for identifying exposure to asymptomatic, low-density malaria infections…”

In the Kinshasa area, Nundu SS & al. found that schoolchildren infected by malaria parasites had multiple species of Plasmodium detected.  Although the majority of cases were caused by P. falciparum singly or mixed with other species, P. malariae and P. ovale were also found in significant numbers. The article is Malaria Parasite Species Composition of Plasmodium Infections Among Asymptomatic and Symptomatic School-Age Children in Rural and Urban Areas of Kinshasa, Democratic Republic of Congo, Malaria J 2021 Oct 2, vol 20 art: 389.  https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03919-4

 The association between malaria and endemic Burkitt’s Lymphoma (eBL) has been described in a number of publications. Now come Kotepui KU and Kutepui M, who report the following in Malaria Infection and Risk for Endemic Burkitt Lymphoma: A Systematic Review and Meta-Analysis, Int J Environ Res Public Health, 2021 May 30;18(11):5886. doi: 10.3390/ijerph18115886: “We searched PubMed, Web of Science, Scopus, and reference lists of publications for potentially relevant studies on malaria infection and eBL. …. Random-effects meta-analysis was used to summarize whether the odds of eBL can be increased by (1) malaria infection or (2) elevated titer of IgGs to malaria antigen.” Based on ten studies reviewed (five studied malaria infection and the odds of eBL; five studied the burden of IgGs to malarial antigens and the odds of eBL), they conclude that “the odds of eBL was not increased by malaria infection…” They acknowledge that the number of studies cited is small, and individual studies come to widely divergent conclusions, therefore they urge that longitudinal studies be organized.

Chang M & al., Application of Dried Blood Spot Sample Pooling Strategies for Plasmodium 18S rRNA Biomarker Testing to Facilitate Identification of Infected Persons in Large-Scale Epidemiological Studies, Malaria J 2021 Oct 7, vol 20 art 391. https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03907-8 describes a method “to provide efficient means to test large quantities of DBS samples.”

Some economic aspects of malaria are explored by Broekhuizen H & al. in Costs and Barriers Faced by Households Seeking Malaria Treatment in the Upper River Region, The Gambia, Malaria J  2021 Sep 16, vol20 art: 368. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03898-6. “A household survey was carried out through in-person interviews. Respondents were asked about malaria prevention methods, their treatment-seeking behaviour, and any costs incurred for transport, services, food, and/or overnight stays. The survey included 864 respondents, mainly subsistence farmers. Most respondents (87%) considered malaria to be a problem affecting their ability to perform their regular duties. Respondents preferred going to a health facility for treatment. The primary reason for not going was related to costs… 66% reported productivity loss of 5 working days on average during a malaria episode of them or their child.”

Wimberly MC & al., Satellite Observations and Malaria: New Opportunities for Research and Applications, Trends Parasitol, 2021 Jun;37(6):525-537. doi: 10.1016/j.pt.2021.03.003. “Satellite remote sensing provides a wealth of information about environmental factors that influence malaria transmission cycles and human populations at risk. Long-term observations facilitate analysis of climate-malaria relationships, and high-resolution data can be used to assess the effects of agriculture, urbanization, deforestation, and water management on malaria. New sources of very-high-resolution satellite imagery … will increase the precision and frequency of observations. … Further collaboration between the malaria and remote sensing communities … will support global efforts toward malaria control, elimination, and eradication.”

Basic Research:

Beck JR and Ho C-M, Transport Mechanisms at the Malaria Parasite-Host Cell Interface, PLoS Pathog, 2021 Apr 1;17(4):e1009394.  doi: 10.1371/journal.ppat.1009394.

Dessens JT & al., Crystalloids: Fascinating Parasite Organelles Essential for Malaria Transmission, Trends Parasitol, 2021 Jul;37(7):581-584. doi: 10.1016/j.pt.2021.04.002. 

File T & al., Detection of High Frequency of MAD20 Allelic Variants of Plasmodium falciparum Merozoite Surface Protein 1 Gene from Adama and its Surroundings, Oromia, Ethiopia, Malaria J 2021 Sep 27 vol 20 art: 385 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03914-9#Abs1

Neveu G, Lavazec C, Erythroid Cells and Malaria Parasites: It’s a Match! Curr Opin Hematol, 2021 May 1; 28(3):158-163. doi: 10.1097/MOH.0000000000000641.

Ofori EA & al., Comparison of the Impact of Allelic Polymorphisms in PfAMA1 on the Induction of T Cell Responses in High and Low Malaria Endemic Communities in Ghana, Malaria J vol 20 art 367. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03900-1

Shahinas D & Pillai DR, Role of Hsp90 in Plasmodium falciparum Malaria, Adv Exp Med Biol, 2021; 1340:125-139. doi: 10.1007/978-3-030-78397-6_5.

Sutcliffe AC & al., Adaptation of ELISA Detection of Plasmodium falciparum and Plasmodium vivax Circumsporozoite Proteins in Mosquitoes to a Multiplex Bead-Based Immunoassay, Malaria J 2021 Sep 23, vol 20, art: 377. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03910-z

Van de Vegte-Bolmer M & al., A Portfolio of Geographically Distinct Laboratory-Adapted Plasmodium Falciparum Clones with Consistent Infection Rates in Anopheles Mosquitoes, Malaria J 2021 Sep 26, vol 20 art: 381 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03912-x