Science & Research Report for January 2021

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

The plethora of articles relevant to malaria did not abate during the holiday season.  PubMed lists over 5,000 articles on the subject of malaria for the year of 2021. That averages to 400+ articles per month.  Even with our geographic selectivity, it is impossible to report on every publication relevant to the subjects of Prevention, Diagnosis, Treatment, Campaigns, and Epidemiology.  As of this month, articles relating to Basic Science will no longer be reported, since there has never been a reaction or question raised relating to this subject.  This decision is subject to reversal, if there is a demand for reintroducing the subject. 

Prevention: 

Within the subject of prevention, it is becoming clear that there are clusters of subtopics.   

Starting with vaccines, Wang LT & al., Protective Effects of Combining Monoclonal Antibodies and Vaccines Against the Plasmodium falciparum Circumsporozoite Protein, PLOS Pathogens, 2021 Dec 6, doi.org/10.1371/journal.ppat.1010133 state that “[c]ombinations of monoclonal antibodies (mAbs) against different epitopes on the same antigen synergistically neutralize many viruses. However, there are limited studies assessing whether combining human mAbs against distinct regions of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) enhances in vivo protection against malaria compared to each mAb alone or whether passive transfer of PfCSP mAbs would improve protection following vaccination against PfCSP.”  Their conclusion is that “while combining mAbs against the repeat and C-terminal regions of PfCSP provide no additional protection in vivo, repeat mAbs do provide increased protection when combined with vaccine-induced polyclonal antibodies.” 

Takashima E & al. assert that the efficacy of RTS,S/AS01 (the only vaccine so far endorsed by the WHO) “is modest, and therefore the development of more efficacious vaccines is still needed.” Their article,   Identification of Novel Malaria Transmission-Blocking Vaccine Candidates, Front Cell Infect Microbiol, 2021 Nov 30; 11:805482. doi: 10.3389/fcimb.2021.805482.  They conclude that vaccines that block the transmission from humans to mosquitoes are needed, but while the abstract mentions barriers to this approach, it does not shed further light on how these vaccines may be developed. 

The effect of one alternate experimental vaccine was studied in Brazil by Baptista BO & al.  As reported in Naturally Acquired Antibody Response to a Plasmodium falciparum Chimeric Vaccine Candidate GMZ2.6c and Its Components (MSP-3, GLURP, and Pfs48/45) in Individuals Living in Brazilian Malaria-Endemic Areas, Malaria J, 2022 Jan 4, vol 21 art 6. https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-04020-6, this vaccine is being studied in Africa, where there have been some promising results in preventing disease. This article focuses on the immunogenicity of the vaccine in a different geographic area.  The results showed significant immune responses to the vaccine. 

“Plasmodium vivax Reticulocyte Binding Protein 1a (PvRBP1a) is a blood-stage parasite antigen which is associated with invasion of red blood cells and induces antibody responses. Thus, PvRBP1a is considered as a target for design of a blood-stage vaccine against vivax malaria.  Kochayoo P & al. document the “ability of PvRBP1a protein to induce the generation and maintenance of antibody and memory B cell responses” in The Presence of Circulating Antibody Secreting Cells and Long-Lived Memory B Cell Responses to Reticulocyte Binding Protein 1a in Plasmodium vivax Patients, Malaria J, 2021 Dec 20, vol 20 art 474. malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04015-3.  The authors recommend that “PvRBP1a … be considered as a vaccine candidate against the blood-stage of P. vivax.” 

The second sub-area of Prevention may be described as the protection of humans from exposure to malaria-carrying mosquitoes.  Many recent articles address this topic, several of them deal with the emergence of resistance of mosquitoes to the insecticide in treated nets. 

One such article is In Mwagira-Maina & al., Genetic Markers Associated with Insecticide Resistance and Resting Behaviour In Anopheles gambiae Mosquitoes in Selected Sites in Kenya, Malaria J, 2021 Dec 13, vol 20 art 461. malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03997-4, which reports on well-known genetic markers of resistant mosquitoes.  In Central Africa, Bandibabone J & al., Investigating Molecular Mechanisms of Insecticide Resistance in The Eastern Democratic Republic of the Congo, Malaria J 2021 Dec 14 vol 20 art 464. malariajournal.biomedcentral.com/articles/10.1186/ s12936-021-04002-8, identifies several previously unknown mutations in the DNA of mosquitoes. Using a different approach, Medjigbodo AA & al., Putative Pleiotropic Effects of the Knockdown Resistance (L1014F) Allele on the Life-History Traits of Anopheles gambiae, Malaria J, 2021 Dec 20, vol 20 art 480. malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04005-5 reviews the life history and behavior of resistant mosquitoes collected in “West Africa” (country not identified). 

“Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying,” state Gansané A & al. in Design and Methods for a Quasi-Experimental Pilot Study to Evaluate the Impact of Dual Active Ingredient Insecticide-Treated Nets on Malaria Burden in Five Regions in Sub-Saharan Africa, Malaria J 2022 Jan 10, vol 21, art 19. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04026-0. In view of the increased presence of insecticide resistant Anopheles mosquitoes, the authors report on an ongoing study of dual active ingredient insecticide treated nets in five countries.  These devices are costly and their introduction has been slow, so it is important to obtain reliable data on their effectiveness. 

Even in areas where insect resistance is not high, the nets are effective only if they are intact and people use them correctly.  Bawuah A and Ampaw S studied factors that influence correct usage.  Their article, Ownership and Use of Insecticide-Treated Nets Under Ghana’s National Malaria Control Program: What Are the Correlates? Trop Med Int Health, 2021 Dec; 26(12):1593-1608. doi: 10.1111/Tmi.13689 reports that “[r]Residence (rural-urban), wealth, and administrative region emerged as the most important predictors of ITN ownership and usage in Ghana. The results favoured rural and non-Greater Accra residents. However, wealth had a contrasting association with ITN ownership and use. Whereas affluent households owned more ITNs than the extremely poor, the latter used them more. Also, age and household size were significant for ITN ownership. … In contrast, the proportion of household members under 5 and the bed net-to-household size ratio were positive and statistically significant determinants of ITN use.” 

With regard to damaged nets, use, physical integrity, and survival were assessed by Smith T & al. in a cohort of 4514 LLINs followed for up to 4 years in Kenya. They report in Incidence and Consequences of Damage to Insecticide-Treated Mosquito Nets in Kenya, Malaria J, 2021 Dec 20, vol 20, art 476  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03978-7 that “18% of the impact on vectorial capacity was estimated to be lost because of damage. The estimated median lifetime of the LLINs was 2.9 years, but this was extended to 5.7 years … without physical damage.”   

Another study, “aimed to assess the association between the physical integrity of LLINs and their use” in Ethiopia and found after 5000+ observations that Long Lasting Insecticide Treated Nets, (LLINs) “that were in torn physical condition had higher odds (AOR [95% CI] = 1.76 [1.41, 2.19]) of not being used compared to LLINs with no holes. Other factors that showed significant association included the age of the LLIN, sleeping place type, washing status of LLINs, perceptions towards net care and repair, LLIN to people ratio, economic status, and study site. The results were published by Hiruy HN & al. in The Effect of Long-Lasting Insecticidal Nets (LLINs) Physical Integrity on Utilization, Malaria J, 2021 Dec 18, vol 20 art 468. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03976-9.  

Finally with regard to nets, Roh ME & al., A Quasi-Experimental Study Estimating the Impact of Long-Lasting Insecticidal Nets with And without Piperonyl Butoxide on Pregnancy Outcomes,  

Malaria J, 2022 Jan 4 vol 21 art 5 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04034-0 looks at the outcome of pregnancies, based on net use in a region of Uganda, where pyrethoid resistant mosquitoes are prevalent. A “mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, … Results from the exploratory analyses comparing PBO {piperonyl butoxide, a chemical synergist known to partially restore pyrethroid sensitivity} and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals …” 

Another aspect of prevention is the administration of chemoprophylaxis, which is practiced during pregnancy.  Aberese-Ako M & al., An Ethnographic Study of How Health System, Socio-Cultural and Individual Factors Influence Uptake of Intermittent Preventive Treatment of Malaria in Pregnancy with Sulfadoxine-Pyrimethamine in a Ghanaian Context, PLoS One, 2021 Oct 7; 16(10):e0257666.  doi: 10.1371/journal.pone.0257666 explores why the WHO recommended practice is not universally followed.  The results reported are somewhat non-specific: “Health system, socio-cultural and individual factors influence uptake of optimum doses of IPTp-SP.” The authors recommend focusing on “regular and sufficient supply of SP to health facilities, effective implementation of free {antenatal care}, provision of appropriate and adequate information to women and community outreach programmes to encourage early and regular … visits.” 

Ejeta D & al. studied the effect of extracts of five of fifteen plants used by the population in NE Ethiopia to kill mosquito larvae.  They report in Insecticidal Effect of Ethnobotanical Plant Extracts Against Anopheles arabiensis Under Laboratory Conditions, Malaria J 2021 Dec 14 vol 20 art 466. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04004-6 that ethanol extract of one of them, Azadirachta indica, {also known as neem tree or Indian lilac} “exerted a remarkable larvicidal effect against An. arabiensis and thus it can be used for botanical mosquito insecticide development…” 

Diagnosis:  

The diagnosis of fever is the focus of Ehounoud BCH & al., Assessment of the Burden of Malaria and Bacteraemia by Retrospective Molecular Diagnosis in Febrile Illnesses and First-Line Anti-Infectives in Côte d’Ivoire, Travel Med Infect Dis, Sep-Oct 2021; 43:102105. doi: 10.1016/j.tmaid.2021.102105.  “Blood samples from 438 febrile and 346 afebrile people were screened using molecular tools. Plasmodium falciparum was the most common microorganism associated with fever (46.8%)” Of interest is that in this population, 23.4% of blood samples from afebrile individuals also contained P. falciparum. Over 10% of all samples indicated simultaneous infections by more than one agent; P. falciparum was involved in 82% of these samples. 

Several papers deal with diagnostic methods that are deemed to be more sensitive than microscopy. 

Baptista V & al., The Future in Sensing Technologies for Malaria Surveillance: A Review of Hemozoin-Based Diagnosis, ACS Sens, 2021 Nov 26; 6(11):3898-3911. doi: 10.1021/acssensors.1c01750 concentrates on the crystalline byproduct hemozoin as an “attractive biomarker for malaria detection.” This paper reviews “the hemozoin-based malaria detection methods and critically discuss their challenges and potential for the development of an ideal diagnostic device.” 

“Real-time polymerase chain reaction (RT-PCR) targeting P. falciparum 18S rRNA gene” is the topic reported by Ochwedo KO & al. in Hyper-Prevalence of Submicroscopic Plasmodium falciparum Infections in a Rural Area of Western Kenya with Declining Malaria Cases, Malaria J, 2021 Dec 20 vol 20 art 472. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04012-6. “Microscopic inspection of blood smears was positive for asexual P. falciparum parasites in 14.7% (54/367) of cases. All of these samples were confirmed by RT-PCR. 35.8% (112/313) of blood smear negative cases were positive by RT-PCR, i.e., submicroscopic infection, resulting in an overall prevalence by RT-PCR alone of 45.2% compared to 14.7% for blood smear alone..”  Likewise, in Ethiopia, Belachew M & al., Evaluating Performance of Multiplex Real Time PCR for the Diagnosis of Malaria at Elimination Targeted Low Transmission Settings of Ethiopia, Malaria J, 2022 Jan 6, vol 21, art 9. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04029-x found that “real-time PCR had an advanced performance in parasite detection and species identification on febrile patients’ samples than did microscopy and RDT in low malaria transmission settings.” 

Yet another diagnostic method is the subject of Ashraf S & al. OPD (Online Plasmodium Diagnosis): An ALA-PpIX Based Functional Assay to Predict Active Malaria, Photodiagnosis Photodyn Ther, 2021 Dec; 36:102510.  doi: 10.1016/j.pdpdt.2021.102510. They state that in view of the poor sensitivity of current diagnostic method, they sought “an in-vitro functional assay to predict active malarial infections…  Plasmodium falciparum (3D7) parasites were incubated with delta-aminolevulinic acid (ALA) for 7 h and imaged using a confocal microscope for protoporphyrin IX (PpIX) fluorescence… ALA was only taken up by infected RBCs. When the parasites were loaded with ALA, they fluoresced.”  The abstract does not address the practicality of this method in areas where malaria is prevalent. 

Schubert L & al report a case of Pandemic-Related Delay of Falciparum Malaria Diagnosis in a Traveller Leading to Cerebral Malaria, J Travel Med, 2021 Dec 29; 18(8):Taab159.  Doi: 10.1093/Jtm/Taab159. 

Treatment: 

Many articles reported the results of treatment this past month. Dalaba MA & al., Health-Seeking Behaviour and Cost of Fever Treatment to Households in a Malaria-Endemic Setting of Northern Ghana: A Cross-Sectional Study, BMJ Open, 2021 Sep 13;11(9):E052224.  Doi: 10.1136/Bmjopen-2021-052224. “Out of 1845 households visited, 21% (393 of 1845) reported an episode of fever. About 50% (195 of 393) of the fever cases had blood sample taken for testing by microscopy or Rapid Diagnostic Test, and 73.3% (143 of 195) were confirmed to have malaria. Of the 393 people with fever, 70% (271 of 393) reported taking an antimalarial and 24.0% (65 of 271) took antimalarial within 24 hours of the onset of illness. About 54% (145 of 271) of the antimalarials were obtained from health facilities.”  The abstract does not specify the antimalarial regimens used. 

Ebong C & al., Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria and Prevalence of Molecular Markers Associated with Artemisinin and Partner Drug Resistance in Uganda, Malaria J, 2021 Dec 24, vol 20, art 484 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04021-5 evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria.  There were no early treatment failures with either combination.  However, “[r]ecurrent infections with AL were common, {while} DP remains highly effective and safe for the treatment of uncomplicated malaria in Uganda.” 

Also in Uganda, Humphries D & al. explored “the influence of two key equity factors, socioeconomic position and rurality, on whether children with fever in eastern Uganda receive timely access to appropriate treatment for suspected malaria.”  They report in The Impact of Equity Factors on Receipt of Timely Appropriate Care for Children with Suspected Malaria In Eastern Uganda, BMC Public Health, 2021 Oct 16; (1):1870.  doi: 10.1186/s12889-021-11908-0 that “[c]hildren from rural households were statistically more likely to receive prompt and appropriate treatment with artemisinin-combination therapy than their semi-urban counterparts,” which may be a surprise to the reader, as was another conclusion, namely that “[w]ealth index in its own right did not exert a significant effect for children with reported fever.” 

Koehne E & al., Pharmacotherapy for Artemisinin-Resistant Malaria, Expert Opin Pharmacother, 2021 Dec; 22(18):2483-2493. doi: 10.1080/14656566.2021.1959913 acknowledge that the problem at this time is primarily in Southeast Asia, but may soon have relevance in Africa as well.  They conclude that artemisinin-based combination therapies (ACT) remain the most effective, but cite “Artesunate-pyronaridine, the ‘newest’ recommended ACT, and atovaquone-proguanil .. {as} effective, and safe treatments for uncomplicated falciparum malaria. 

The safety of treatment of uncomplicated Plasmodium falciparum malaria among children is the subject of Assefa DG & al., Safety of Dihydroartemisinin-Piperaquine Versus Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria Among Children in Africa: A Systematic Review and Meta-Analysis of Randomized Control Trials, Malaria J, 2022 Jan 4, vol 21, art 4. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04032-2. In this meta-analysis, 18 studies, involving 10,498 participants were included.  “[E]arly vomiting, diarrhoea, and cough were common were significantly more frequent in patients who were treated with the DHA-PQ than that of AL, {but} both drugs are well tolerated. 

Atroosh WM & al., Plasmodium falciparum Histidine Rich Protein 2 (Pfhrp2): An Additional Genetic Marker Suitable for Anti-Malarial Drug Efficacy Trials, Malaria J, 2022 Jan 4, vol 21 art 2. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04014-4. “The suitability of the polymorphic P. falciparum histidine-rich protein 2 (pfhrp2) gene was assessed to serve as an alternative marker using a PCR-sequencing or a PCR–RFLP protocol for genotyping of samples in drug efficacy clinical trials… The findings suggest that … pfhrp2 can serve as an additional molecular marker for monitoring anti-malarials efficacy. However, its use is restricted to endemic areas where only a minority of P. falciparum parasites lack the pfhrp2 gene. 

Three articles focus on treatment of Plasmodium vivax.  Although this cause of malaria does not cause illness as serious as that by P. falciparum, it has the disadvantage that treatment usually does not reach the parasite when it is hiding in the infected person’s liver (the hypnozoite stage).  So P. vivax can be, for many persons a life- long recurrent disease, despite seemingly adequate treatment of the acute phase. Also, P. vivax infection is prevalent in some African countries, such as Ethiopia where it accounts for up to 40% of cases (see the Ketema article below).  “Radical cure,” which eliminates the hypnozoite stage as well as the blood stage is desirable, but not always achieved. 

Attempts to achieve radical cure of P. vivax infections by adding primaquine to the primary treatment has been shown to be effective to a variable extent (65 to 94%) in a number of studies, according to Huber JH & al., How Radical Is Radical Cure? Site-Specific Biases in Clinical Trials Underestimate the Effect of Radical Cure on Plasmodium vivax Hypnozoites, Malaria J, 2021 Dec 20,  vol 20, art 479. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04017-1. However, the authors’ analysis leads them to the conclusion that the above figures are overly optimistic. 

The meta-analysis by Ketema T & al., In Vivo Efficacy of Anti-Malarial Drugs Against Clinical Plasmodium vivax Malaria in Ethiopia: A Systematic Review and Meta-Analysis, Malaria J, 2021 Dec 24, vol 20, art 483. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04016-2, encompassed 14 articles that presented data on 29 treatment options. These studies enrolled 2144 clinical vivax malaria patients. “Regardless of evidence of sporadic efficacy reduction reported in the country, chloroquine (CQ), the first-line regimen in Ethiopia, remained highly efficacious, supporting its continuous utilization for confirmed P. vivax mono-infections. The addition of primaquine (PQ) to CQ is recommended for radical cure.” 

Penna-Coutinho J & al., MEFAS, a Hybrid of Artesunate-Mefloquine Active Against Asexual Stages of Plasmodium vivax in Field Isolates, Inhibits Malaria Transmission, Int J Parasitol Drugs Drug Resist, 2021 Dec; 17:150-155.  Doi: 10.1016/J.Ijpddr.2021.09.003 approaches the treatment from a public health prospective, using a novel combination of two drugs to inhibit the transmission of P. vivax from infected persons to mosquitoes that bite them. 

The search for new drugs against artesunate resistant malaria is addressed by Ndayisaba G & al., Hepatic Safety and Tolerability of Cipargamin (KAE609), in Adult Patients with Plasmodium falciparum Malaria: A Randomized, Phase II, Controlled, Dose-Escalation Trial in sub-Saharan Africa, Malaria J, 2021 Dec 20, vol 20 art 479 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04009-1.  This drug is currently in Phase II trials.  While it is stated that it has “potent, rapid activity against Plasmodium falciparum,” some reports have indicated impaired liver function as a result of administration of the drug.  In this study, “[h]epatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether–lumefantrine. Cipargamin was well tolerated with no safety concerns.”  The authors are uncertain what caused the liver problems reported elsewhere. 

Campaigns: 

Lindblade KA & al.analyzed the outcome of WHO’s E-2020 campaign goals, which identified 21 countries which could potentially eliminate malaria by 2020. According to their report, Supporting Countries to Achieve Their Malaria Elimination Goals: The WHO E-2020 Initiative, Malaria J, 2021 Dec 20, vol 20 art 481, https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03998-3, while the majority of these countries experienced a reduction of indigenous cases, only seven (33%) had no cases reported in 2020, and of them, four (19%) were certified by WHO to be malaria free. “Two countries experienced outbreaks … attributed, in part, to the COVID-19 pandemic.”    

Zanzibar is not a country, but sufficiently separated from the rest of Tanzania to be evaluated for success in reducing or eliminating malaria. Mkali HR & al., Risk Factors Associated with Malaria Infection Identified Through Reactive Case Detection in Zanzibar, 2012–2019, Malaria J, 2021 Dec 24, vol 20, art 485. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04025-1 makes a statement that the burden of disease in Zanzibar is being reduced, but focuses more on the factors that mitigate for continuing occurrence of malaria on the island.  Travel to the mainland, “younger age” (without defining the term), and living in one particular community were associated with higher incidence of malaria, whereas male gender, insecticide impregnated net use and having had indoor residual spraying were associated with d\reduced odds of positive diagnosis. 

In a somewhat similar type of analysis, Elmardi KA & al., Impact of Malaria Control Interventions on Malaria Infection and Anaemia in Areas with Irrigated Schemes: A Cross-Sectional Population-Based Study in Sudan, BMC Infect Dis, 2021 Dec 14; 21(1):1248. doi: 10.1186/s12879-021-06929-4 reports that only indoor residual spraying was associated with reduced malaria diagnosis; however, net use was very low (18.6% in the population). 

In Ethiopia, Asale A & al. report in Community Knowledge, Perceptions, and Practices Regarding Malaria and its Control in Jabi Tehnan District, Amhara Region, Northwest Ethiopia, Malaria J, 2021 Dec 9, vol 20 art 459. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-03996-5 that despite reasonably good general knowledge availability of insecticide treated net, their utilization in the population under study was low and reporting of illness often delayed.  The burden of malaria was highest in individuals 15 years of age or older (50%), and lowest in children under 5 (14%).  It is unclear how these figures relate to the frequency of these ages within the population. 

Several articles report on experience with mass drug administration in The Gambia.  Fehr A & al. “assessed how social cohesion, as expressed by the trial population, affects trial coverage through an in-depth ethnographic analysis of two trial villages.” Their report, The Role of Social Cohesion in the Implementation and Coverage of a Mass Drug Administration Trial for Malaria Control in The Gambia: An In-Depth Comparison of Two Intervention Villages, Soc Sci Med, 2021 Dec; 291:114487, doi: 10.1016/J.Socscimed.2021.14487 states that “[t]he village with low coverage expressed a form of social cohesion where members followed advice to participate through a hierarchal system but did not actively participate in the MDA or its implementation. The village with high coverage expressed social cohesion as more participatory: individuals took the directive to participate but contextualized the trial implementation to their needs and wants.” 

Dabira ED & al., Mass Drug Administration of Ivermectin and Dihydroartemisinin-Piperaquine Against Malaria is Settings with High Coverage of Standard Control Interventions: A Cluster-Randomised Controlled Trial in Gambia, Lancet Inf Dis, 2021 Dec 14, doi.org/10.1016/S1473-3099(21)00557-0 is a report on adding ivermectin, a mosquitocidal drug to standard DP regime conferred additional benefit when communities were treated in two sequential high transmission seasons.  In this “area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin–piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed.” Byakika-Kibwika P & al., Ivermectin for Mass Drug Administration Against Malaria, Lancet Inf Dis, 2021 Dec 14, doi.org/10.1016/S1473-3099(21)00647-2 is an editorial related to the above study that does not add significant additional knowledge. 

Ivermectin is also mentioned in Jackson CL & al., Design and Analysis of a 2-Year Parallel Follow-Up of Repeated Ivermectin Mass Drug Administrations for Control of Malaria: Small Sample Considerations for Cluster-Randomized Trials with Count Data, Clin Trials, 2021 Oct; 18(5):582-593. doi: 10.1177/ 17407745211028581, but this paper focuses on the design and methodology of trials, rather than on any specific study.  No clinical or population based results are quoted. 

Young AJ & al. address the issue of limited resources in A Practical Approach for Geographic Prioritization and Targeting of Insecticide-Treated Net Distribution Campaigns During Public Health Emergencies and in Resource-Limited Settings, Malaria J, 2022 Jan 4 vol 21 art 10.  https://malariajournal.biomedcentral.com/articles/10.1186/ s12936-021-04028-y. They assert that their paper “provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources… {and that they} provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted.” 

Epidemiology: 

Kyomuhangi I & Giorgi E, A Threshold-Free Approach with Age-Dependency for Estimating Malaria Seroprevalence, Malaria J, 2022 Jan 3, vol 21 art 1.  https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-04022-4 argues that in analyzing seropositivity for malaria, age deoendency must be taken into account. 

Giorgi E & al., Maplaria: A User Friendly Web-Application for Spatio-Temporal Malaria Prevalence Mapping, Malaria J, 2021 Dec 20, vol 20 art 471, https://malariajournal.biomedcentral.com/articles/ 10.1186/s12936-021-04011-7 asserts that “[t]he application is a useful tool that can be used to foster ownership, among policy makers, of disease risk maps and promote better use of data for decision-making in low resource settings.” 

“Peaceful coexistence with the infected host, commonly not causing clinical symptoms, is a frequent but poorly understood effect for many human pathogens, including Plasmodium falciparum. The continuous production of gametocytes (the transmissible parasite stage) by persisting P falciparum in individuals with asymptomatic infections possibly constitutes a primordial source for transmission. As the drive towards elimination intensifies, the following question arises: is there added benefit to identifying and treating asymptomatic infections to interrupt transmission?” This is what Mayor A & Bassat Q, Sizing the Reservoirs of Malaria Transmission: The Contribution of School-Aged Children, Lancet Infect Dis, 2021 Nov; 21(11):1478-1480.  Doi: 10.1016/S1473-3099(21)00130-4 seeks to answer. 

Tizifa TA & al. also focus on children. Their paper, Incidence of Clinical Malaria, Acute Respiratory Illness, and Diarrhoea in Children in Southern Malawi: A Prospective Cohort Study, Malaria J, 2021 Dec 20, vol 20 art 473.  https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04013-5, encompasses more than just malaria.  The children in the community were followed for one year.  Malaria incidence was low. 

Mwaiswelo RO, Mmbando BP, Chacky F & al., Malaria Infection and Anemia Status in Under-Five Children From Southern Tanzania Where Seasonal Malaria Chemoprevention is Being Implemented, PLoS One, 2021 Dec 2; 16(12):e0260785. doi: 10.1371/journal.pone.0260785. “A community-based cross-sectional survey was conducted between August and September 2020. Finger-prick blood samples collected from children aged 3-59 months were used to test for malaria infection using malaria rapid diagnostic test (mRDT), thick smears for determination of asexual and sexual parasitemia, and thin smear for parasite speciation.” Malaria prevalence was high in both communities tested, but much higher in one than the other. “… no formal education, household number of people, household number of under-fives, not having a bed net, thatched roof, open/partially open eave, sand/soil floor, and low socioeconomic status were major risks for malaria infection.”   

Another focus of much attention is malaria during pregnancy Thirty-six (36) studies, conducted over 1994–2019, were included in the review conducted by Osarfo J & al., Trends of Malaria Infection in Pregnancy in Ghana Over the Past Two Decades: A Review, Malaria J, 2022 Jan 4, vol 21 art 3. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04031-3.  While they conclude that “[t]here appears to be a decline in asymptomatic parasite prevalence in pregnancy in Ghana though this has not been uniform across the different transmission zones,” some of the data they cite seem to indicate real significant declines. “The greatest declines were noticeably in urban settings. Submicroscopic parasitaemia remains a challenge for control efforts.”   

Nega D & al., Baseline Malaria Prevalence at the Targeted Pre-Elimination Districts in Ethiopia, BMC Public Health, 2021 Nov 3; 21(1):1996.  doi: 10.1186/s12889-021-12036-5 is a statistical survey of a limited number of low-prevalence areas (overall prevalence 1.17%), which are designated for elimination drive.  “The study shows a decrease in malaria prevalence compared to the reports of previous malaria indicator surveys in the country. The finding can be used as a baseline for measuring the achievement of ongoing malaria elimination efforts. Particularly, the high prevalence of asymptomatic individuals (0.88%) in these transmission settings indicates there may be sustaining hidden transmission. Therefore, active case detection with more sensitive diagnostic techniques is suggested to know more real magnitude of residual malaria in the elimination-targeted areas.” 

Two reports dealt with the genetic makeup of the parasite. 

A total of 1223 biological samples obtained in the period 1999 to 2019 were studied by Berzosa P & al. in Equatorial Guinea, as well as “[s]creening for mutations in the pfdhfr, pfdhps, pfmdr1, and pfcrt genes..” The report, Temporal Evolution of the Resistance Genotypes of Plasmodium falciparum in Isolates from Equatorial Guinea During 20 Years (1999 To 2019), Malaria J, 2021 Dec 14 vol 20 art 463. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04000-w  “The partially and fully resistant haplotypes (pfdhfr + pfdhps) were found to increase over time… A continued decline in pfmdr1 and pfcrt gene mutations over time was also found. The number of mutations detected in pfk13 has increased since 2008, when artemisinin-based combination therapy (ACT) were first introduced, with more mutations being observed in 2019, with two synonymous and five non-synonymous mutations being detected, although these are not related to resistance to ACT.” 

Chen Y-A & al. reported a somewhat similar study project in Dynamic Changes in Genetic Diversity, Drug Resistance Mutations, and Treatment Outcomes of Falciparum Malaria from the Low-Transmission to the Pre-Elimination Phase on the Islands of São Tomé and Príncipe, Malaria J 2021 Dec 14, vol 20 art 467 https://malariajournal.biomedcentral.com/articles/10.1186/s12936-021-04007-3. In a study of 118 dried blood spots collected 2010-2016, “[m]utations in the multi-drug resistance I (pfmdr1), chloroquine resistance transporter (pfcrt), and kelch 13 (pfk13) genes were analysed…” Clinically “total of 7482 cases that completed a 28-day follow-up were evaluated for treatment outcomes based on the microscopic results…” They conclude that “Plasmodium falciparum in STP had experienced changes in prevalent strains, and increased mutation frequencies in drug-resistance genes from the low-transmission to the pre-elimination settings. ..[P]atients with younger age and receiving quinine treatment were more likely to show parasitological treatment failure during follow-up.” 

There is also a report on the genetics of Anopheles mosquitoes, reported by  Mustafa MSEK & al., Population Genetics of Anopheles arabiensis, the Primary Malaria Vector in The Republic of Sudan, Malaria J, 2021 Dec 19, vol 20 art 469. https://malariajournal.biomedcentral.com/articles/10.1186/ s12936-021-03994-7. “Bayesian clustering analysis revealed two gene pools, grouping samples into two population clusters; one includes four and the other includes two populations.” “This study revealed low levels of population differentiation with high gene flow among the An. arabiensis populations investigated in Sudan.”