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

We continue to report monthly on publications that seem most relevant to MPI’s work.  However, if there is a desire on part of the readers of these reports for additional topics to be considered, please contact the compiler, of these reports at dppaster@gmail.com.

Prevention:

Continuing with last month’s most interesting news, we start with three articles relating to vaccines.  Pirahmadi S & al. highlight a critical element of vaccine development in A Review of Combination Adjuvants for Malaria Vaccines: A Promising Approach for Vaccine Development, Int J Parasitol, 2021 Aug; 51(9):699-717.  doi: 10.1016/j.ijpara.2021.01.006.  They state that “…it seems likely that no single adjuvant is capable of eliciting all the protective immune responses required in many malarial subunit vaccines and the use of combination adjuvants will be increasingly important as the science of malaria vaccines advances….[T]his review paper outlines some of the best known combination adjuvants used in malaria subunit vaccines, focusing on their proposed mechanisms of action, their immunological properties, and their notable results. The aim of the present review is to consolidate these findings to aid the application of these combination adjuvants in experimental malaria vaccines.”  The same authors also published How Can We Develop an Effective Subunit Vaccine to Achieve Successful Malaria Eradication?, Microb Pathog 2021 Nov; 160:105203.  doi: 10.1016/j.micpath.2021.105203, in which they argue that “[s]ubunit vaccines are the most promising malaria vaccines under development … [but] one of the major drawbacks of subunit vaccines is the lack of efficient and durable immune responses. . Consequently, subunit vaccines require several policies to overcome these challenges… In this review, [they] address common approaches that can improve the efficacy of subunit vaccines against malaria.”  Interestingly the first article above seems to be a logical afterthought of the second one, but the timing of publications is reversed.  The third article, Lyke KE & al., Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human Malaria Infection, Clin Infect Dis, 2021 Oct 5; 73(7):e2424-e2435.  doi: 10.1093/cid/ciaa1294 reports on their experience with whole organism vaccines.  These had to be administered for 4 times for optimal effectiveness.  The study groups were small and follow up was for up to 24 months.

In view of evidence that mosquitoes are developing resistance to the pyrethoids used in treating bed nets, Hien AS & al. studied two other compounds.  Their report, Evidence Supporting Deployment of Next Generation Insecticide Treated Nets in Burkina Faso: Bioassays with Either Chlorfenapyr or Piperonyl Butoxide Increase Mortality of Pyrethroid-Resistant Anopheles gambiae, Malaria J, 2021 Oct 18, vol 20, art 406.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03936-3, “provides evidence supporting the introduction of both Interceptor G2 nets and PBO nets, which were distributed in Burkina Faso in 2019 as part of a mass campaign.”

Eave ribbons “exploit the natural house-entry behaviours of major malaria vectors to deliver mosquito-cidal or repellent actives around eave spaces through which the Anopheles mosquitoes usually enter human dwellings” Kaindoa EW & al review the evidence of the technology in Insecticide-Treated Eave Ribbons for Malaria Vector Control in Low-Income Communities, Malaria J, 2021 Oct 23, vol 20, art 415.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03945-2, and report that they “confer protection by preventing biting indoors and in the peri-domestic outdoor spaces, and also killing a significant proportion of the mosquitoes. Current versions of eave ribbons are made of low-cost hessian fabric infused with candidate insecticides and can be easily fitted onto multiple house types without any additional modifications

“In rural sub-Saharan Africa, thatch roofs are being replaced by metal roofs. Metal roofing, however, increases indoor temperatures above human comfort levels, and thus makes it more likely that residents will not use an insecticide-treated bed net at night.” Carrasco-Tenezaca M & al., report in Effect of Roof Colour on Indoor Temperature and Human Comfort Levels, with Implications for Malaria Control: A Pilot Study Using Experimental Houses in Rural Gambia, Malaria J, 2021 Oct 29; vol 20 art 423. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03951-4 that houses “with a white roof were consistently cooler and more comfortable than those with a bare metal roof. Painting the roofs of houses white is a cheap way of making a dwelling more comfortable for the occupants and could potentially increase bed net use in hot humid countries.”

Utilizing an approach common to quality improvement in healthcare as well as in industry, the article by Doumbia I & al., The Provider’s Checklist to Improve Pregnant Women Coverage by Intermittent Preventive Malaria Treatment in Mali: A Pilot Implementation Study, Malaria J, 2021 Oct 16, vol 20, art 402. https://malariajournal.biomedcentral. com/articles/10.1186/s12936-021-03940-7 report that in tandem with cooperating gynecologists, checklists were used to enhance pregnant women’s adoption of information about [intermittent preventive treatment-sulfadoxine-pyrimethamine] uptake as immediate and sustained women practices. …. 83% of participants were not knowledgeable about malaria disease before checklist use versus 15% after. Similarly, coverage of women’s SP directly observed treatment rose from 0 to 59% after introducing the checklist.”

Sutcliffe JR, Yin S, Effects of Indoor Air Movement and Ambient Temperature on Mosquito (Anopheles gambiae) Behaviour Around Bed Nets: Implications for Malaria Prevention Initiatives, Malaria J 2021 Oct 30, vol 20 art 427. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03957-y concludes that house designs that promote indoor air movement make a difference in mosquito behavior around bed nets. “How mosquitoes approach a net is influenced both by indoor temperature and ventilation and their interaction. This system is in need of further study.”

“Mass drug administration … with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear.” Phiri MD & al., The Duration of Protection from Azithromycin Against Malaria, Acute Respiratory, Gastro-intestinal, and Skin Infections When Given Alongside Seasonal Malaria Chemoprevention [SMC]: Secondary Analyses of Data from a Clinical Trial in Houndé, Burkina Faso, and Bougouni, Mali, Clin Infect Dis, 2021 Oct 5; 73(7):e2379-e2386. doi: 10.1093/cid/ciaa1905 reports that “[r]elative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration.”

Diagnosis:

When access to fully trained health care professionals and other workers is lacking, families may turn to untrained drug sellers for advice when their children are ill.  Soniran OT & al. describe this situation in Factors Impacting Test-Based Management of Suspected Malaria Among Caregivers of Febrile Children and Private Medicine Retailers Within Rural Communities of Fanteakwa North District, Ghana, BMC Public Health, 2021 Oct 20; 21(1):1899. doi: 10.1186/s12889-021-11960-w.  They report that parasitological testing rate of febrile children was as low as 10.5% at over the counter medicine shops (OTCMS). They recommend “educating caregivers and community members on the need to test and confirm malaria in febrile children before treating them, and supply of subsidized RDT kits to OTCMS and re-training them to provide testing services to their clients.”

“Ultrasensitive molecular diagnostics are lowering the limit of detection for malaria parasites in the blood and providing insights not captured by conventional tools such as microscopy and rapid antigen tests. … While many ultrasensitive molecular methods require well-equipped laboratories, technologies such as loop-mediated isothermal amplification and recombinase polymerase amplification provide more portable and analytically sensitive solutions.” Kamaliddin C & al., The Role of Ultrasensitive Molecular Methods for Detecting Malaria-The Broader Perspective, Clin Infect Dis, 2021 Sep 15; 73(6):e1387-e1390. doi: 10.1093/cid/ciab221 asserts that these “tools may benefit asymptomatic patient screening, antenatal care, and elimination campaigns.”

Ayo D & al. report five cases of Plasmodium malariae infections from Eastern Uganda … that …were all initially mistaken for P. falciparum, but Plasmodium schizonts (up to 2080/µL) were identified by microscopy. Plasmodium malariae Infections as a Cause of Febrile Disease in an Area of High Plasmodium falciparum Transmission Intensity in Eastern Uganda,  Malaria J 2021 Oct 29,   vol 20, art 425. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03962-1. Their findings “highlight the importance of considering non-falciparum species as the cause of clinical malaria. In areas of intense P. falciparum transmission, where rapid diagnostic tests that detect only P.falciparum antigens are commonly used, non-falciparum malaria cases may be missed.”

It is not uncommon that malaria coexists with other infections. Kamau E & al., Epidemiological and Clinical Implications of Asymptomatic Malaria and Schistosomiasis Co-Infections in a Rural Community in Western Kenya, BMC Infect Dis, 2021 Sep 9; 21(1):937.  doi: 10.1186/s12879-021-06626-2 demonstrate the high burden of asymptomatic malaria parasitemia and schistosomiasis infection in … rural population in Western Kenya. Asymptomatic infection with malaria or schistosomiasis was associated with laboratory abnormalities including neutropenia, leukopenia and thrombocytopenia. … evaluating for co-infections is key when assessing individuals with laboratory abnormalities.”

“The spleen is a complex secondary lymphoid organ that plays a crucial role in controlling blood-stage infection with Plasmodium parasites. It is tasked with sensing and removing parasitized RBCs, erythropoiesis, the activation and differentiation of adaptive immune cells, and the development of protective immunity, all in the face of an intense inflammatory environment.” Ghosh D, Stumhofer JS, describe “how these processes are regulated following infection and recognizes the gaps in our current knowledge, highlighting recent insights from human infections and mouse models” in The Spleen: “Epicenter” in Malaria Infection and Immunity, J Leukoc Biol, 2021 Oct; 110(4):753-769.  doi: 10.1002/JLB.4RI1020-713R

Treatment:

Azizi H & al. share troublesome data in Health Workers Readiness and Practice in Malaria Case Detection and Appropriate Treatment: A Meta-Analysis and Meta-Regression, Malaria J, 2021 Oct 24, vol 20, art 420.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03954-1. This is a report of publications up to December 2020. “The inclusion criteria were any studies that assessed [health workers’] practice in early case detection by malaria testing and appropriate treatment… The study pooled data of 9245 HWs obtained from 15 included studies.” While pooled estimates for “appropriate malaria treatment and malaria testing were 60%; 95% CI: 53–67% and 57%; 95% CI: 49–65%, respectively, … [a]ppropriate malaria treatment based on test results was as low as 31% in a Worges study in Zambia to as high as 92% in Bonful in Ghana.”

Lubogo P & al., Cost-Effectiveness Analysis of Integrated Community Case Management Delivery Models [iCCM} Utilizing Drug Sellers and Community Health Workers [CHW] for Treatment of Under-Five Febrile Cases of Malaria, Pneumonia, Diarrhoea in Rural Uganda, Malaria J, 2021 Oct 18, vol 20, art 407.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03944-3 is relevant to the results above as well as to the issue of drug sellers mentioned in Soniran & al.’s article.  “This study was a cost-effectiveness analysis to compare the iCCM delivery model utilizing drug sellers against the model using CHWs… When the drug seller arm (intervention) was compared to the CHW arm (control), an incremental effect of 9 per 100 appropriately treated U5 children was observed.” The authors conclude that training drug sellers is cost-effective, compared to non-training.

Agamah FE & al., Network-Driven Analysis of Human–Plasmodium falciparum Interactome: Processes for Malaria Drug Discovery and Extracting in Silico Targets, Malaria J, 2021 Oct 26, vol 20, art 421. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03955-0 is a somewhat difficult article for this reviewer.  In this study, the authors state that “a network-based integrative computational framework was leveraged to predict protein targets that may be used to guide the rational design of pathogen- and host-directed therapies for malaria treatment.” They conclude that “[h]ost–pathogen network analysis reveals potential drug targets and biological processes and pathways subverted by P. falciparum to enhance its within malaria host survival. The results presented have implications for drug discovery and will inform experimental studies.”

McCarthy JS & al., Safety, Pharmacokinetics, and Anti-Malarial Activity of the Novel Plasmodium Eukaryotic Translation Elongation Factor 2 Inhibitor M5717: A First-in-Human, Randomised, Placebo-Controlled, Double-Blind, Single Ascending Dose Study and Volunteer Infection Study, Lancet Inf Dis, 2021 Oct 26, doi.org/10.1016/S1473-3099(21)000252-8 is a study of a drug identified only as M5717 and described as in the title. The ascending doses were administered to one person each with a matched placebo cohort each.  Larger doses were accompanied by some side effects, which led to the suspension of the highest dose volunteer infection study.  Parasites were apparently cleared at all doses administered, but there was a recrudescence of infection in three subjects who received lower doses.  The article contains some confusion about the demographics of the volunteers in the study; while “men and women” are listed as being eligible subjects, apparently only men were eventually included.

Möhrle JJ, Toward the Next Generation of Antimalaria Combination Therapies, Lancet Inf Dis 2021 Oct 26, doi.org/10.1016/S1473-3099(21)00270-X is an editorial tied to the above article.  It acknowledges the problem of resistance emerging from monotherapy and refers to ongoing studies that combine M5717 with one or more other drugs.

Dentinger CM & al. report on Efficacy of Artesunate-Amodiaquine and Artemether-Lumefantrine for Uncomplicated Plasmodium Falciparum Malaria in Madagascar, 2018, Malaria J 2021 Nov 3, vol 20 art 432.   https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03935-4.  These two combination therapies were judged to have “therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.”

“Since 2000, a good deal of progress has been made in malaria control. However, there is still an unacceptably high burden of the disease and numerous challenges limiting advancement towards its elimination and ultimate eradication. Among the challenges is the antimalarial drug resistance, which has been documented for almost all antimalarial drugs in current use. As a result, the malaria research community is working on the modification of existing treatments as well as the discovery and development of new drugs to counter the resistance challenges.”  Amelo W, Makonnen E, Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges, Biomed Res Int, 2021 Aug 30; 2021:5539544. doi: 10.1155/2021/5539544 discusses the challenges related to malaria elimination, ongoing approaches to tackle the impact of drug-resistant malaria, and upcoming antimalarial drugs.

According to Saidi AM & al., “[t]he recent emergence of a resistance-conferring genetic mutation in the P. falciparum parasite in Africa warrants continued monitoring throughout the continent.” They performed analysis “on data from a retrospective cohort study of Malawian children with cerebral malaria admitted between 2010 and 2019 to a public referral hospital, ascertaining parasite clearance times across years.” Their article, Plasmodium falciparum Clearance Time in Malawian Children with Cerebral Malaria: A Retrospective Cohort Study, Malaria J, 2021 Oct 18, vol 20, art 408. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03947-0 concludes that “[m]alaria parasite clearance times in Malawian children with cerebral malaria remained constant between 2014 and 2019, arguing against evolving artemisinin resistance in parasites in this region.”

Two articles refer to the use of molecular markers in Africa to assess the emergence of artemisinin resistant P. falciparum:  The implementation of molecular markers as a routine tool for anti-malarial drug resistance surveillance could greatly improve surveillance of anti-malarial drug efficacy, making it possible to detect resistance before it translates to treatment failures. When possible, ex vivo assays should be included as their data could be useful complementary, especially when no molecular markers are validated. This is the opinion expressed by Nsanzabana C in Time to Scale up Molecular Surveillance for Anti-Malarial Drug Resistance in Sub-Saharan Africa, Malaria J, 2021 Oct 13, vol 20, art 401. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03942-5. Also, “[d]ue to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and the prevalence of polymorphisms in the pfk13, pfcrt, and pfmdr1 genes associated with drug resistance was investigated by Chidimatembue A & al., Their report, Molecular Surveillance for Polymorphisms Associated with Artemisinin-Based Combination Therapy Resistance in Plasmodium falciparum Isolates Collected in Mozambique, 2018,  Malaria J, 2021 Oct 12, vol 20, art 398. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03930-9 concludes that in 2018, “no markers of artemisinin resistance were documented.” Nonetheless, “[m]olecular surveillance should continue to monitor the prevalence of these markers to inform decisions on malaria treatment in Mozambique.”

 

 

Campaigns:

“In public health epidemiology, quasi-experimental methods are widely used to estimate the causal impacts of interventions. Thomas R & al. demonstrate the contribution the synthetic control method (SCM) can make in evaluating public health interventions, when routine surveillance data are available and the validity of other quasi-experimental approaches may be in question. As reported in The Short-Term Impact of a Malaria Elimination Initiative in Southern Mozambique: Application of the Synthetic Control Method to Routine Surveillance Data, Health Econ, 2021 Sep; 30(9):2168-2184.  doi: 10.1002/hec.4367, they evaluate “the short-term effects of a large-scale Mass Drug Administration based malaria elimination initiative in Southern Mozambique. [They applied] the SCM to district level weekly malaria incidence data and compared the observed reduction in age group specific malaria incidence.”

Abamecha F & al., Acceptability and Feasibility of The School-Engaged Social and Behavior Change Communication [SBCC] Approach on Malaria Prevention In Ethiopia: Implications for Engagement, Empowerment, and Retention (EER) of Education Sectors in Malaria Elimination Efforts, BMC Public Health, 2021 Oct 21; 21(1):1909.  doi: 10.1186/s12889-021-11995-z.  “A school-engaged SBCC strategy involving various communication and capacity-building interventions aimed to advance malaria preventive practices in primary schools in Jimma were implemented from 2017 to 2019. A cross-sectional study was conducted with 205 key stakeholders at the end of the intervention. Both acceptability and feasibility were measured using standardized tools.” The authors conclude that “the school-engaged SBCC strategy to enhance malaria preventive practices seems feasible. … The result implicates the benefit of intensifying such a strategy to engage, empower, and retain the education sectors in malaria elimination efforts and beyond.”

In an article that appears more philosophical than data driven, Monroe A & al., Unlocking the Human Factor to Increase Effectiveness and Sustainability of Malaria Vector Control, Malaria J, 2021 Oct 16, vol 20, art 404.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03943-4 argue that “factors such as acceptance of insecticide-treated nets (ITNs) and indoor residual spraying (IRS), ability and willingness to consistently use and appropriately care for ITNs and refraining from post-spray wall modifications can all impact the success of core vector control interventions. Understanding factors that can drive or inhibit these behaviours can contribute to improved social and behaviour change

Epidemiology:

Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high. Coldiron MF & al. performed “[f]our cross-sectional, household-based malaria prevalence surveys [in this District] between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3–59 months, 5–9 years, and 10 years and above) were sampled in randomly-selected households.” They report the results in Prevalence of Malaria in an Area Receiving Seasonal Malaria Chemoprevention in Niger, Malaria J, 2021 Oct 24, vol 20 art 419. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03953-2, and conclude that “[a]symptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5–9 years warrants considering their inclusion in SMC programmes…”

Laron PS & al. refer to the concept of “urbanicity” in An Urban-to-Rural Continuum of Malaria Risk: New Analytic Approaches Characterize Patterns in Malawi, Malaria J, 2021 Oct 24, vol 20, art 418.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03950-5.  They state that “[u]sing [a] composite urbanicity measure, the manner in which rural-like environments exist within, and proximate to, urban areas was analysed, as well as how urban-like contexts have emerged within otherwise rural settings. Malaria, a disease known to vary between urban and rural contexts, was evaluated for whether there are consistent and predictable patterns of risk along an urbanicity gradient.” The study included children from over 7500 households and found that “[i]nfection probability declined with increasing urbanicity.”

Roberts SA & al., Seasonal Patterns of Malaria, Genital Infection, Nutritional and Iron Status in Non-Pregnant and Pregnant Adolescents in Burkina Faso: A Secondary Analysis of Trial Data, BMC Public Health, 2021 Sep 27; 21(1):1764.  doi: 10.1186/s12889-021-11819-0.  “Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation.”  They consider the finding that about 75% of all those followed “were parasitaemic at the peak of the wet season is a clear indicator of the need to lower wet season malaria transmission in this older age group. … In this study, 96% of malaria infections in non-pregnant and pregnant women were asymptomatic.  Asymptomatic P. falciparum parasitaemias in young pregnant women are also described in Mali, Ghana and Gambia, but pregnant women are easier to reach for treatment than non-pregnant adolescents.”

Sayre D & al. studied Baseline Malaria Prevalence and Care-Seeking Behaviours in Rural Madagascar Prior to a Trial to Expand Malaria Community Case Management to All Ages, Malaria J, 2021 Oct 26, vol 20, art 422. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03956-z. “There is growing interest in expanding malaria community case management (mCCM) to older individuals, but limited empirical evidence exists to guide this expansion. As part of a two-year cluster-randomized trial of mCCM expansion to all ages in southeastern Madagascar, a cross-sectional survey was conducted to assess baseline malaria prevalence and healthcare-seeking behaviours.” They found that among those children seeking care for febrile illness, the age group 5–14 had higher positivity on Rapid diagnostic tests than younger children and suggest expanding mCCM to this age group.

Given that “[a]symptomatic malaria infections largely remain undetected and act as a reservoir for continuous transmission. [Hayuma PM & al.] assessed the prevalence of submicroscopic asymptomatic malaria infections and anaemia in two rural low (300 m above sea level) and highland (700 m asl) settings of Korogwe District NE Tanzania. They report in Prevalence of Asymptomatic Malaria, Submicroscopic Parasitaemia and Anaemia in Korogwe District, North-Eastern Tanzania, Malaria J, 2021 Oct 29, vol 20, art 424. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03952-3 that “of 565 individuals tested, 211 (37.3%) were malaria positive based on RDT, whereas only 81 (14.3%) were positive by microscopy. There was no significant difference in the prevalence between the highland and the lowland village…”

Likewise, in Ethiopia, Zerdo Z & al studied Prevalence and Associated Risk Factors of Asymptomatic Malaria and Anaemia Among School-Aged Children in Dara Mallo and Uba Debretsehay Districts: Results from Baseline Cluster Randomized Trial, Malaria J, 2021 Oct 13, vol 20, art 400. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03937-2.  They collected data from 2167 school age children.  In this cohort, the prevalence of malaria on RDT was low (1.62%).  Ab out a third of these had P. vivax infections along with or without P. falciparum. Further, malaria was significantly lower among children from literate household head and residence house located at an altitude range above 1100 meters above sea level.

As already cited in Kamau & al above, Watts C & al., Rethinking the Economic Costs of Hospitalization for Malaria: Accounting for the Comorbidities of Malaria Patients in Western Kenya, Malaria J 2021 Oct 30, vol 20 art 429 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03958-x focus on patients who have not only malaria, but other infections.  They analyze the economic implication of co-infections with malaria and report the expected conclusion that the “economic burden of malaria is increased by comorbidities which are associated with longer hospital stays and higher medical costs to patients and the health system.”   

“Anopheles stephensi mosquitoes are urban malaria vectors in Asia that have recently invaded the Horn of Africa.” Ahmed A & al detected “emergence of An. stephensi mosquitoes in 2 noncontiguous states of eastern Sudan.” Their report is Invasive Malaria Vector Anopheles stephensi Mosquitoes in Sudan, 2016-2018, Emerg Infect Dis, 2021 Nov; 27(11):2952-2954.  doi: 10.3201/eid2711.210040. “Results of mitochondrial DNA sequencing suggest the possibility of distinct invasions, potentially from a neighboring country.”

Yokoly FN & al., Assessing Anopheles Vector Species Diversity and Transmission of Malaria in Four Health Districts Along the Borders of Côte d’Ivoire, Malaria J, 2021 Oct 18, vol 20 art 409.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03938-1 is a report on the density and diversity of malaria vectors. “Anopheles gambiae s.l. and An. funestus s.l. were found to be highly infected with Plasmodium in the health districts of Bloléquin and Odienné where higher malaria incidence was observed than the other districts.”

Looking to the future Antinori S & al. are concerned that non-human malaria infectious agents may expand their reach.  In Non-Human Primate and Human Malaria: Past, Present and Future, J Travel Med, 2021 Jul 7;28(5):taab036, doi: 10.1093/jtm/taab036, they state that “[a]dvances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites …in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria.

Basic Research:

Beyer K & al., Limited Plasmodium Sporozoite Gliding Motility in the Absence of TRAP Family Adhesins, Malaria J 2021 Oct 30, vol 20 art 430 https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-03960-3.

Cassiano GC & al., Targeting Malaria Protein Kinases, Adv Protein Chem Struct Biol, 2021, 124:225-274.  doi: 10.1016/bs.apcsb.2020.10.004.

Singh B & al., Purification of Native Histidine-Rich Protein 2 (nHRP2) from Plasmodium falciparum Culture Supernatant, Infected RBCs, and Parasite Lysate, Malaria J, 2021 Oct 18, vol 20, art 405. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03946-1