Monthly Science & Research Report for July 2021

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

Many of the articles on malaria contain information from other published studies, this report highlights the most relevant articles in recent months. 

Prevention:

Science News quoted Nature magazine on 30 June (A Malaria Vaccine with Live Parasites Shows Promise in a Small Trial, by E. Garcia de Jesús), referring to a study during which volunteers were inoculated with live sporozoites and then received wither chloroquine or pyrimethamine.  Seven of eight people who received 200,000 sporozoites and the pyrimethamine were resistant to the same parasite strain three months later.  The number of study subjects was very small so caution is advised until studies with larger numbers of study subjects are reported.

One month earlier, Murphy SC & al., reported in PfSPZ-CVac Efficacy Against Malaria Increases from 0% to 75% when Administered in the Absence of Erythrocyte Stage Parasitemia: A Randomized, Placebo-Controlled Trial with Controlled Human Malaria Infection, PLoS Pathogens, 2021 May 28, doi.org/10.1371/journal.ppat.1009594 that they administered the live sporozoites several times and if they avoided the times the subjects’ parasites were in their erythrocytic phase.  Vaccine efficacy was said to be 75% with a larger inoculation.  It is of note that “[p]arasitemia was associated with systemic symptoms which were severe in 25% of subjects.”  This was also a study with very few subjects (8).

Ndegwa DN & al., Using Plasmodium knowlesi as a Model for Screening Plasmodium Vivax Blood-Stage Malaria Vaccine Targets Reveals New Candidates, PLoS Pathogens, 2021 Jul 1, doi.org/10.1371/ journal.ppat.1008864 focus on vaccine against P. vivax, which is less well studied than the vaccine against falciparum malaria.  They state that “the lack of a continuous in vitro culture system for P. vivax limits systematic screening of new [vaccine] candidates.”  Therefore they turned to “P. knowlesi, for which an in vitro culture system in human erythrocytes exists, to test the scalability of systematic reverse vaccinology to identify and prioritise P. vivax blood-stage targets.”

While the focus of Wragge S-E, & al., New Distribution Record of Anopheles rivulorum-like from Sadiola, Mali, with Notes on Malaria Vector Insecticide Resistance, Trans R Soc Trop Med Hyg, 2021 May 8;115(5):495-499. doi: 10.1093/trstmh/traa113 is on a newly found species of mosquito in a certain area in Mali (the country where we recently provided a limited grant), the article also reports that resistance to the chemicals used in spraying “appeared to decrease after pyrethroids were discontinued for house spraying.”

Diagnosis:

Plucinski M & al advocate the use recently developed methods for the detection of malaria antigens in  Laboratory Detection of Malaria Antigens: A Strong Tool for Malaria Research, Diagnosis, and Epidemiology, Clin Microbiol Rev, 2021 Jun 16;34(3):e0025020. doi: 10.1128/CMR.00250-20.  Their “focus is primarily on antigens that are currently known to be detectable in human specimens and on their impact on the understanding of malaria in human populations. [They] highlight historical and contemporary laboratory assays for malaria antigen detection, the concept of an antigen profile for a biospecimen, and ways in which binary results for a panel of antigens could be interpreted and utilized for different analyses. Particular emphasis is given to the direct comparison of field-level malaria diagnostics and laboratory antigen detection…”

Rakislova N, & al., reviewed post-mortem diagnoses of malaria 264 deaths, occurring at a tertiary level hospital in Mozambique, using three techniques, as reported in Accuracy of Verbal Autopsy, Clinical Data and Minimally Invasive Autopsy in the Evaluation of Malaria-Specific Mortality: An Observational Study, BMJ Glob Health, 2021 Jun;6(6):e005218. doi: 10.1136/bmjgh-2021-005218. Their conclusion was that only minimally invasive autopsy gave accurate results.

The development of hematologic abnormalities in patients suffering from malaria is well known.  Elkhalifa AME & al., Hematological Indices and Abnormalities Among Patients With Uncomplicated Falciparum Malaria in Kosti City of The White Nile State, Sudan: A Comparative Study, BMC Infect Dis, 2021 May 31;21(1):507. doi: 10.1186/s12879-021-06228-y concludes the following: “Falciparum malaria among patients in Kosti city of the White Nile State, Sudan is predominantly of low-level parasitemia. It is significantly associated with anemia, low MCV, low MCH, low MCHC, high RDW, thrombocytopenia and neutropenia. However, parasitemia level is not a significant predictor of anemia severity. On the other hand, leucopenia is not useful to predict falciparum malaria.”

Treatment:

The following two articles each focus on treatment of malaria in children: Shibeshi W & al., Efficacy and Safety of Artemisinin-Based Combination Therapies for the Treatment of Uncomplicated Malaria in Pediatrics: A Systematic Review and Meta-Analysis, BMC Infect Dis, 2021 Apr 7;21(1):326.  doi: 10.1186/s12879-021-06018-6 conclude that these regimens are effective and safe. Based on Nineteen reports, they state: Artemisinin-Based Combination Therapies (ACTs) “demonstrated a high crude efficacy and tolerability against P. falciparum. The high treatment success and tolerability with low heterogeneity conferred by DP has implication for policy makers who plan the use of ACTs for uncomplicated falciparum malaria treatment in pediatrics.” The second article, Sondo P & al., Assessment of a Combined Strategy of Seasonal Malaria Chemoprevention and Supplementation with Vitamin A, Zinc and Plumpy’Doz™ to Prevent Malaria and Malnutrition in Children Under 5 Years Old in Burkina Faso: A Randomized Open-Label Trial (SMC-NUT), Trials, 2021 May 24;22(1):360. doi: 10.1186/s13063-021-05320-7 is a description of a study that was about to begin at the time the article was submitted.

Likewise, two articles highlight intermittent treatment of pregnant women.  Muhammad FM  & al., Malaria Intermittent Preventive Treatment in Nigeria: A Qualitative Study to Explore Barriers, BMC Infect Dis, 2021 May 13;21(1):438. doi: 10.1186/s12879-021-06135-2. “While the use of sulphadoxine pyrimethamine (SP) is effective in preventing malaria infection during pregnancy, there are challenges limiting its uptake…” This study found that “[p]oor policy implementation, poor antenatal care attendance, inadequate access to intermittent preventive treatment at the community levels, lack of sustainable funding, and poor community engagement emerged as major barriers to IPTp use in Nigeria.”  More broadly based is Pons-Duran C & al., Coverage of Intermittent Preventive Treatment of Malaria in Pregnancy in Four Sub-Saharan Countries: Findings from Household Surveys, Int J Epidemiol, 2021 May 17;50(2):550-559. doi: 10.1093/ije/dyaa233.  They collected information about IPTp coverage in eight districts from four sub-Saharan countries: Democratic Republic of Congo (DRC), Madagascar, Mozambique and Nigeria “as part of the TIPTOP (Transforming IPT for Optimal Pregnancy) project.” A total of 3911 women were interviewed from March to October 2018. Coverage of at least three doses of IPTp was variable, but low (11-23%), with the exception of Mozambique, where one district had 34% and another 63%.  Interestingly, in view of the previous article, Nigeria had the lowest rates.

Campaigns:

Evidence on what makes … school-engaged social and behavior change communication (SBCC) interventions on malaria prevention more sustainable are limited in literature partly due to its recent emergence. Enrolling the key stakeholders, Abamecha F & al. explored the perceived sustainability of the SBCC interventions on malaria prevention through primary school communities in rural Ethiopia. Their results, reported in Perceived Sustainability of the School-Based Social and Behavior Change Communication (SBCC) Approach on Malaria Prevention in Rural Ethiopia: Stakeholders’ Perspectives, BMC Public Health, 2021 Jun 18;21(1):1171. doi: 10.1186/s12889-021-11216-7 are difficult to interpret from the abstract.  They conclude that their “study identified key predictive variables such as stakeholders’ perceived risk to malaria, self-efficacy, perceived fidelity of implementation and degree of adoption that could help to improve the sustainment of the school-based SBCC approach on malaria prevention and control.” 

Epidemiology:

Yamim Y & al., A Systematic Review and Meta-Analysis of Asymptomatic Malaria Infection in Pregnant Women in Sub-Saharan Africa: A Challenge for Malaria Elimination Efforts, PLoS One, 2021 Apr 1;16(4):e0248245. doi: 10.1371/journal.pone.0248245 is an example of recycled information to which this month’s introduction refers.  The conclusion of the article is that in Sub-Saharan Africa “asymptomatic malaria infection in pregnant women is prevalent, and it is associated with an increased likelihood of anemia compared to non-infected pregnant women. Thus, screening of asymptomatic pregnant women for malaria and anemia should be included as part of antenatal care.”

The country of Namibia experiences relatively low rates of malaria. “In support of the Namibian National Vector Borne Disease Program’s drive to better target interventions based upon risk,” Smith JL & al.,  “implemented a health facility-based case control study aimed to identify risk factors for symptomatic The Importance of Occupation, Age and Mobility in Characterizing High-Risk Populations,  PLoS One, 2021, 16(6):e0252690 doi: 10.1371/journal.pone.0252690 identifies certain professions (e.g. cattle herders, police), ages (e.g. children), environmental factors (e.g. higher rainfall, lower temperatures), and other factors (e.g. traditional housing) that increased the risk of disease.  The preventive activities of ITN and IRS coverage was apparently even across the risk groups.

To investigate spatial variation in malaria prevalence at the sub-regional scale in Madagascar, Rice BL & al. “sampled 1476 households (7117 total individuals, all ages) from 31 rural communities divided among five ecologically distinct regions. The sampled regions range from tropical rainforest to semi-arid, spiny forest and include communities near protected areas. Malaria prevalence was estimated by rapid diagnostic test (RDT) cross-sectional surveys performed during malaria transmission seasons over 2013-2017.” The results, reported in Fine-Scale Variation in Malaria Prevalence Across Ecological Regions in Madagascar: A Cross-Sectional Study, BMC Public Health, 2021 May 29;21(1):1018. doi: 10.1186/s12889-021-11090-3 indicate that “malaria prevalence varied more than 10-fold between nearby (< 50 km) communities in some cases.” They recommend that “the southeast and west coast ecological regions warrant further attention from disease control efforts. Conservation and development efforts in these regions may benefit from consideration of the high, and variable, malaria prevalences among communities in these areas.”

Similarly, McMahon A & al.,  Remote Sensing of Environmental Risk Factors for Malaria in Different Geographic Contexts, Int J. Health Geogr, 2021, 20:28 . doi: 10.1186/s12942-021-00282-0 reports great variation from Ethiopia.  They used “[g]eospatial datasets [that] were derived from multiple sources and characterized climate, vegetation, land use, topography, and surface water … [and] analyzed the associations between environmental data and malaria cases. … [I]ndices related to land cover greenness (NDVI) and moisture (NDWI) showed negative associations with malaria, as the highest malaria rates were found in landscapes with low vegetation cover and moisture during the months that follow the rainy season. Climatic factors, including precipitation and land surface temperature, had positive associations with malaria. Settlement structure also played an important role, with different effects in the two study areas. Variables related to surface water, such as irrigated agriculture, wetlands, seasonally flooded waterbodies, and height above nearest drainage did not have strong influences on malaria.”

The focus is different in Raham TF,  Influence of Malaria Endemicity and Tuberculosis Prevalence on Covid-19 Mortality, Public Health, 2021 May;194:33-35.  doi: 10.1016/j.puhe.2021.02.018. “Eighty malaria-endemic countries were enrolled in this cross-sectional study. Data subjected to testing included TB prevalence, Bacillus Calmette-Guérin (BCG) vaccine coverage, malaria incidence, and COVID-19 mortality. … The results showed with robust statistical support that standardized TB prevalence was significantly associated with reduced COVID-19 mortality. Malaria had an additional effect in reducing COVID-19 mortality, with a highly significant association.”

Basic Research:

Chhibber-Goel J & al., Structural Analyses of the Malaria Parasite Aminoacyl-tRNA Synthetases Provide New Avenues for Antimalarial Drug Discovery, Protein Sci, 2021 Jun 28. doi: 10.1002/pro.4148.

Fraser M & al., Of Membranes and Malaria: Phospholipid Asymmetry in Plasmodium Falciparum-Infected Red Blood Cells, Cell Mol Life Sci, 2021 May;78(10):4545-4561. doi: 10.1007/s00018-021-03799-6.

Grau GER & al., Extracellular Vesicles and Cerebral Malaria, Subcell Biochem, 2021;97:501-508. doi: 10.1007/978-3-030-67171-6_20.

Sumam de Olivera D & al., Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy, Front Cell Infect Microbiol, 2021 Jun 10;11:685866. doi: 10.3389/fcimb.2021.685866.