Contextual factors related to vector-control interventions for malaria: a scoping review and evidence and gap map protocol.

Objective: This scoping review will identify existing literature regarding contextual factors relevant to vector-control interventions to prevent malaria. We will use the findings of the scoping review to produce an interactive evidence and gap map. The map will assist in the priority setting, development, and conduct of targeted systematic reviews. These systematic reviews seek to assist the Vector Control and Insecticide Resistance Unit of the World Health Organization's Global Malaria Programme by informing recommendation development by their Guidelines Development Group. Introduction: Malaria contributes substantially to the global burden of disease, with an estimated 247 million cases and 619,000 deaths in 2021. Vector-control is key in reducing malaria transmission. Vector-control interventions directly target the mosquito, reducing the potential for parasite infections. These interventions commonly include insecticides used in indoor residual spraying or insecticide-treated nets and larval source management. Several new vector-control interventions are under evaluation to complement these. In addition to estimating the effects of interventions on health outcomes, it is critical to understand how populations at risk of malaria consider them in terms of their feasibility, acceptability, and values. Inclusion Criteria: Eligible studies will have assessed the contextual factors of feasibility or acceptability of the interventions of interest, or the valuation of the outcomes of interests. These assessments will be from the perspective of people who receive (residents) or deliver (workers or technicians) the vector-control intervention for the purpose of preventing malaria. Methods: We will conduct this scoping review in accordance with the JBI methodology for scoping reviews and report in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR). We will construct the evidence and gap map following guidance from the Campbell Collaboration.

[While the priest climbs a post, the devil climbs ten: major biological threats from parasite and vector to malaria control and elimination].

Malaria is one of the most serious mosquito-borne infectious diseases in the world. The global malaria control progress has stalled in recent years, which is largely due to the biological threats from the malaria pathogen Plasmodium and the vector Anopheles mosquitoes. This article provides an overview of biological threats to global malaria elimination, including antimalarial drug resistance, deletions in the malaria rapid diagnostic test target P. falciparum histidine-rich protein 2/3 (Pfhrp2/3) genes, vector insecticide resistance and emergence of invasive vector species, so as to provide insights into malaria and vector research and the formulation and adjustment of the malaria control and elimination strategy.

[Biological threats to global malaria elimination I Antimalarial drug resistance].

Malaria is an infectious disease that seriously threatens human health. Currently, malaria control mainly depends on antimalarial chemotherapy. However, antimalarial drug resistance is becoming increasingly severe, which poses a great challenge to malaria control, notably treatment of Plasmodium falciparum malaria. To address this challenge, there is a need to facilitate development of novel antimalarial drugs and innovation of treatment strategies, as well as reinforce surveillance and research on antimalarial drug resistance. This article reviews the main categories and use guidelines of current antimalarial agents, summarizes the current status and monitoring methods of antimalarial drug resistance, and proposes the response to antimalarial drug resistance, so as to provide insights into the use of antimalarial drugs and response to antimalarial drug resistance, and contribute to global malaria elimination.

[Biological threats to global malaria elimination â £ Emergence of invasive vector species].

Driven by international exchanges and climate changes, the invasion and spread of vector Anopheles mosquitoes posed a new challenge to achieving global malaria elimination. Taking the invasion of An. stephensi to exacerbate the malaria epidemic in Africa as an example, this article summarizes the current situation of global Anopheles invasion, and estimates the potential risk of vector Anopheles mosquitoes to unravel the difficulties and challenges in the global malaria elimination program, so as to provide insights into improved early earning and precision control of vector Anopheles mosquito invasion across the world.

[Biological threats to global malaria elimination â ¢ Vector insecticide resistance].

The insecticide resistance is becoming increasingly severe in malaria vectors and has become one of the most important threats to global malaria elimination. Currently, malaria vectors not only have developed high resistance to conventional insecticides, including organochlorine, organophosphates, carbamates, and pyrethroids, but also have been resistant to recently used neonicotinoids and pyrrole insecticides. This article describes the current status of global insecticide resistance in malaria vectors and global insecticide resistance management strategies, analyzes the possible major challenges in the insecticide resistance management, and proposes the response actions, so as to provide insights into global insecticide resistance management and contributions to global malaria elimination.

The effect on the equilibrium sickle cell allele frequency of the probable protection conferred by malaria and sickle cell gene against other infectious diseases.

If a mutated gene with heterozygous advantage against malaria, e.g., hemoglobin S (HbS) gene, is introduced in a small tribe, the gene (allele) frequency (fgene) increases until it reaches a steady state value (feq) where the total mortality from malaria and sickle cell disease is a minimum. This is a classic example of balanced-polymorphism named malaria hypothesis. In a previous in silico study, assuming realistic initial conditions, it has been shown that the feq is around 14%, far less than the fgene observed in certain parts of Africa, 24%. It seems that the malaria hypothesis, per se, could not explain such a high fgene, unless it is assumed that malaria and HbS gene can provide protection against other diseases. Using Monte-Carlo simulation, the current study was conducted to examine the effect on feq of five scenarios was examined. The studied scenarios consisted of different combinations of mortality of other diseases and the possible amounts of protections conferred by malaria and HbS gene against the diseases. Taking into account other diseases causing mortality in the population makes the fgene rate of change steeper over generations. feq is an increasing function of the amount of protection conferred by HbS gene against other diseases. The effect of protection provided by malaria against other diseases on feq, is however, variable-depending on the amount of protection conferred by HbS gene against other diseases, it may increase or decrease feq. If malaria and HbS gene provide protections of 1.5-fold and threefold against other diseases, respectively, the feq is around 24%, the amount reported in certain tribes of Africa. Under certain scenarios, the feq attained is even higher.

Malaria transmission blocking activity of Anopheles stephensi alanyl aminopeptidase N antigen formulated with MPL, CpG, and QS21 adjuvants.

BACKGROUNDS: Malaria, a preventive and treatable disease, is still responsible for annual deaths reported in most tropical regions, principally in sub-Saharan Africa. Subunit recombinant transmission-blocking vaccines (TBVs) have been proposed as promising vaccines to succeed in malaria elimination and eradication. Here, a provisional study was designed to assess the immunogenicity and functional activity of alanyl aminopeptidase N (APN1) of Anopheles stephensi, as a TBV candidate, administered with MPL, CpG, and QS21 adjuvants in the murine model. METHODOLOGY/PRINCIPAL FINDINGS: The mouse groups were immunized with recombinant APN1 (rAPN1) alone or formulated with CpG, MPL, QS-21, or a combination of adjuvants (CMQ), and the elicited immune responses were evaluated after the third immunization. The standard membrane feeding assay (SMFA) measured the functional activity of antibodies against bacterial-expressed APN1 protein in adjuvanted vaccine groups on transmission of P. falciparum (NF54) to An. stephensi mosquitoes. Evaluation of mice vaccinated with rAPN1 formulated with distinct adjuvants manifested a significant increase in the high-avidity level of anti-APN1 IgG and IgG subclasses; however, rAPN1 induced the highest level of high-avidity anti-APN1 IgG1, IgG2a, and IgG2b antibodies in the immunized vaccine group 5 (APN1/CMQ). In addition, vaccine group 5 (receiving APN1/CMQ), had still the highest level of anti-APN1 IgG antibodies relative to other immunized groups after six months, on day 180. The SMFA data indicates a trend towards higher transmission-reducing activity in groups 2 and 5, which received the antigen formulated with CpG or a combination of three adjuvants. CONCLUSIONS/SIGNIFICANCE: The results have shown the capability of admixture to stimulate high-affinity and long-lasting antibodies against the target antigen to hinder Plasmodium parasite development in the mid-gut of An. stephensi. The attained results authenticated APN1/CMQ and APN1/CpG as a potent APN1-based TBV formulation which will be helpful in designing a vaccine in the future.

Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control.

Increasing reports of insecticide resistance continue to hamper the gains of vector control strategies in curbing malaria transmission. This makes identifying new insecticide targets or alternative vector control strategies necessary. CLassifier of Essentiality AcRoss EukaRyote (CLEARER), a leave-one-organism-out cross-validation machine learning classifier for essential genes, was used to predict essential genes in Anopheles gambiae and selected predicted genes experimentally validated. The CLEARER algorithm was trained on six model organisms: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and employed to identify essential genes in An. gambiae. Of the 10,426 genes in An. gambiae, 1,946 genes (18.7%) were predicted to be Cellular Essential Genes (CEGs), 1716 (16.5%) to be Organism Essential Genes (OEGs), and 852 genes (8.2%) to be essential as both OEGs and CEGs. RNA interference (RNAi) was used to validate the top three highly expressed non-ribosomal predictions as probable vector control targets, by determining the effect of these genes on the survival of An. gambiae G3 mosquitoes. In addition, the effect of knockdown of arginase (AGAP008783) on Plasmodium berghei infection in mosquitoes was evaluated, an enzyme we computationally inferred earlier to be essential based on chokepoint analysis. Arginase and the top three genes, AGAP007406 (Elongation factor 1-alpha, Elf1), AGAP002076 (Heat shock 70kDa protein 1/8, HSP), AGAP009441 (Elongation factor 2, Elf2), had knockdown efficiencies of 91%, 75%, 63%, and 61%, respectively. While knockdown of HSP or Elf2 significantly reduced longevity of the mosquitoes (p<0.0001) compared to control groups, Elf1 or arginase knockdown had no effect on survival. However, arginase knockdown significantly reduced P. berghei oocytes counts in the midgut of mosquitoes when compared to LacZ-injected controls. The study reveals HSP and Elf2 as important contributors to mosquito survival and arginase as important for parasite development, hence placing them as possible targets for vector control.

Proactive home-based malaria management in rural communities of Bassar Health District in northern Togo from 2014 to 2017: PECADOM + , a pilot experiment.

BACKGROUND: Togo's National Malaria Control Programme has initiated an active home-based malaria management model for all age groups in rural areas of Bassar Health District. This report describes the model, reports its main results, and determines the factors associated with positive rapid diagnostic test results. METHODS: From 2014 to 2017, in three peripheral care units of Bassar Health District (Binaparba, Nangbani, and Baghan), community health workers visited residents' homes weekly to identify patients with malaria symptoms, perform rapid diagnostic tests in symptomatic patients, and give medication to positive cases. Univariate and multivariate logistic regression models were used to determine the factors associated with positive tests. RESULTS: The study covered 11,337 people (817 in 2014, 1804 in 2015, 2638 in 2016, and 6078 in 2017). The overall mean age was 18 years (95% CI 5-29; min-max: 0-112 years). The median age was 10 years (SD: 16.9). The proportions of people tested positive were 75.3% in Binaparba, 77.4% in Nangbani, and 56.6% in Baghan. The 5-10 age group was the most affected category (24.2% positive tests). Positive tests were more frequent during the rainy than during the dry season (62 vs. 38%) and the probability of positive test was 1.76 times higher during the rainy than during the dry season (adjusted OR = 1.74; 95% CI 1.60-1.90). A fever (37.5 °C or higher) increased significantly the probability of positive test (adjusted OR = 2.19; 95% CI 1.89-2.54). The risk of positive test was 1.89 times higher in passive than in active malaria detection (adjusted OR = 1.89; 95% CI 1.73-2.0). CONCLUSIONS: This novel experimental community and home-based malaria management in Togo suggested that active detection of malaria cases is feasible within 24 h, which allows rapid treatments before progression to often-fatal complications. This PECADOM + program will help Togo's National Malaria Control Programme reduce malaria morbidity and mortality in remote and hard-to-reach communities.

Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.

BACKGROUND: Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy. METHODS: Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively. RESULTS: The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004). CONCLUSION: Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP. TRIAL REGISTRATION: Registered 09/12/2016, PACTR201612001901313.

Efficacy of Interceptor G2, Royal Guard and PermaNet 3.0 against pyrethroid-resistant Anopheles gambiae s.l. from Za-Kpota, southern Benin: an experimental hut trial.

BACKGROUND: The widespread use of insecticide-treated nets (ITNs) has significantly contributed to the reduction in malaria cases and deaths observed across Africa. Unfortunately, this control strategy is threatened by the rapid spread of pyrethroid resistance in malaria vectors. Dual-active-ingredient insecticidal nets are now available to mitigate the impact of pyrethroid resistance. To facilitate evidence-based decisions regarding product selection in specific use settings, data are needed on the efficacy of these different nets against local mosquito populations. METHODS: Two experimental hut trials were performed in Za-Kpota, southern Benin in 2021 to evaluate the performance of Interceptor G2 (BASF), Royal Guard (Disease Control Technologies) and PermaNet 3.0 (Vestergaard Frandsen), all dual-active-ingredient bednets, in comparison to untreated or standard pyrethroid-treated bednets, against free-flying wild Anopheles gambiae mosquitoes. The performance of some of these next-generation nets was compared to the same type of nets that have been in use for up to 2 years. Mosquitoes collected in the huts were followed up after exposure to assess the sublethal effects of treatments on certain life-history traits. RESULTS: The predominant species in the study site was Anopheles gambiae sensu stricto (An. gambiae s.s.). Both Anopheles coluzzii and An. gambiae s.s. were resistant to pyrethroids (deltamethrin susceptibility was restored by piperonyl butoxide pre-exposure). In the experimental hut trials, the highest blood-feeding inhibition (5.56%) was recorded for the Royal Guard net, relative to the standard PermaNet 2.0 net (44.44% inhibition). The highest 72-h mortality rate (90.11%) was recorded for the Interceptor G2 net compared to the PermaNet 2.0 net (56.04%). After exposure, the risk of death of An. gambiae sensu lato (An. gambiae s.l.) was 6.5-fold higher with the Interceptor G2 net and 4.4-fold higher with the PermaNet 3.0 net compared to the respective untreated net. Lower mosquito mortality was recorded with an aged Interceptor G2 net compared to a new Interceptor G2 net. Oviposition rates were lower in mosquitoes collected from huts containing ITNs compared to those of untreated controls. None of the mosquitoes collected from huts equipped with Royal Guard nets laid any eggs. CONCLUSIONS: The Royal Guard and Interceptor G2 nets showed a potential to significantly improve the control of malaria-transmitting vectors. However, the PermaNet 3.0 net remains effective in pyrethroid-resistant areas.

Non-contact detection of pyrethroids widely used in vector control by Anopheles mosquitoes.

Pyrethroids are the most widely used insecticides to control vector borne diseases including malaria. Physiological resistance mechanisms to these insecticides have been well described, whereas those for behavioral resistance remain overlooked. Field data suggest the presence of spatial sensory detection by Anopheles mosquitoes of the pyrethroid molecules used in insecticide-based control tools, such as long-lasting insecticide nets or insecticide residual spraying. This opens the way to the emergence of a wide range of behavioral adaptations among malaria vectors. However, the spatial sensory detection of these molecules is controversial and needs to be demonstrated. The goal of this study was to behaviorally characterize the non-contact detection of three of the most common pyrethroids used for malaria vector control: permethrin, deltamethrin an ⍺-cypermethrin. To reach this goal, we recorded the behavior (takeoff response) of Anopheles gambiae pyrethroid-sensitive and resistant laboratory strains, as well as field collected mosquitoes from the Gambiae Complex, when exposed to the headspace of bottles containing different doses of the insecticides at 25 and 35°C, in order to represent a range of laboratory and field temperatures. We found the proportion of laboratory susceptible and resistant female mosquitoes that took off was, in all treatments, dose and the temperature dependent. Sensitive mosquitoes were significantly more prone to take off only in the presence of ⍺-cypermethrin, whereas sensitive and resistant mosquitoes showed similar responses to permethrin and deltamethrin. Field-collected mosquitoes of the Gambiae Complex were also responsive to permethrin, independently of the species identity (An. gambiae, An. coluzzii and An. arabiensis) or their genotypes for the kdr mutation, known to confer resistance to pyrethroids. The observed ability of Anopheles spp. mosquitoes to detect insecticides without contact could favor the evolution of behavioral modifications that may allow them to avoid or reduce the adverse effect of insecticides and thus, the development of behavioral resistance.

Livestock keeping, mosquitoes and community viewpoints: a mixed methods assessment of relationships between livestock management, malaria vector biting risk and community perspectives in rural Tanzania.

BACKGROUND: Livestock keeping is one of the potential factors related to malaria transmission. To date, the impact of livestock keeping on malaria transmission remains inconclusive, as some studies suggest a zooprophylactic effect while others indicate a zoopotentiation effect. This study assessed the impact of livestock management on malaria transmission risks in rural Tanzania. Additionally, the study explored the knowledge and perceptions of residents about the relationships between livestock keeping and malaria transmission risks in a selected village. METHODS: In a longitudinal entomological study in Minepa village, South Eastern Tanzania, 40 households were randomly selected (20 with livestock, 20 without). Weekly mosquito collection was performed from January to April 2023. Indoor and outdoor collections used CDC-Light traps, Prokopack aspirators, human-baited double-net traps, and resting buckets. A subsample of mosquitoes was analysed using PCR and ELISA for mosquito species identification and blood meal detection. Livestock's impact on mosquito density was assessed using negative binomial GLMMs. Additionally, in-depth interviews explored community knowledge and perceptions of the relationship between livestock keeping and malaria transmission risks. RESULTS: A total of 48,677 female Anopheles mosquitoes were collected. Out of these, 89% were Anopheles gambiae sensu lato (s.l.) while other species were Anopheles funestus s.l., Anopheles pharoensis, Anopheles coustani, and Anopheles squamosus. The findings revealed a statistically significant increase in the overall number of An. gambiae s.l. outdoors (RR = 1.181, 95%CI 1.050-1.862, p = 0.043). Also, there was an increase of the mean number of An. funestus s.l. mosquitoes collected in households with livestock indoors (RR = 2.866, 95%CI: 1.471-5.582, p = 0.002) and outdoors (RR = 1.579,95%CI 1.080-2.865, p = 0.023). The human blood index of Anopheles arabiensis mosquitoes from houses with livestock was less than those without livestock (OR = 0.149, 95%CI 0.110-0.178, p < 0.001). The majority of participants in the in-depth interviews reported a perceived high density of mosquitoes in houses with livestock compared to houses without livestock. CONCLUSION: Despite the potential for zooprophylaxis, this study indicates a higher malaria transmission risk in livestock-keeping communities. It is crucial to prioritize and implement targeted interventions to control vector populations within these communities. Furthermore, it is important to enhance community education and awareness regarding covariates such as livestock that influence malaria transmission.

WHO antenatal care policy and prevention of malaria in pregnancy in sub-Saharan Africa.

BACKGROUND: The WHO 2016 antenatal care (ANC) policy recommends at least eight antenatal contacts during pregnancy. This study assessed ANC8 uptake following policy implementation and explored the relationship between ANC attendance and intermittent preventive treatment in pregnancy (IPTp) coverage in sub-Saharan Africa following the rollout of the World Health Organization (WHO) 2016 ANC policy, specifically, to assess differences in IPTp uptake between women attending eight versus four ANC contacts. METHODS: A secondary analysis of data from 20 sub-Saharan African countries with available Demographic Health and Malaria Indicator surveys from 2018 to 2023 was performed. The key variables were the number of ANC contacts and IPTp doses received during a participant's last completed pregnancy in the past two years. Pooled crude and multivariable logistic regression models were used to explore factors associated with attendance of at least four or eight ANC contacts as well as receipt of at least three doses of IPTp during pregnancy. RESULTS: Overall, only a small proportion of women (median = 3.9%) completed eight or more ANC contacts (ANC8 +). Factors significantly associated with increased odds of ANC8 + included early ANC attendance (AOR: 4.61: 95% CI 4.30-4.95), literacy (AOR: 1.20; 95% CI 1.11-1.29), and higher wealth quintile (AOR: 3.03; 95% CI 2.67-3.44). The pooled estimate across all countries showed a very slight increase in the odds of IPTp3 + among women with eight (AOR: 1.06; 95% CI 1.00-1.12) compared to those with four contacts. In all but two countries, having eight instead of four ANC contacts did not confer significantly greater odds of receiving three or more doses of IPTp (IPTp3 +), except in Ghana (AOR: 1.67; 95% CI 1.38-2.04) and Liberia (AOR: 1.43; 95% CI 1.18-1.72). CONCLUSION: Eight years after the WHO ANC policy recommendation, all countries still had sub-optimal ANC8 + coverage rates. This paper is a call to action to actualize the vision of the WHO and the global malaria community of a malaria free world. Policies to improve ANC and IPTp coverage should be operationalized with clear actionable guidance and local ownership. Study findings can be used to inform multi-level policy, programmatic, and research recommendations to optimize ANC attendance and malaria in pregnancy prevention, thus improving maternal and child health outcomes, including the reduction of malaria in pregnancy.

Review on the impacts of indoor vector control on domiciliary pests: good intentions challenged by harsh realities.

Arthropod vectored diseases have been a major impediment to societal advancements globally. Strategies to mitigate transmission of these diseases include preventative care (e.g. vaccination), primary treatment and most notably, the suppression of vectors in both indoor and outdoor spaces. The outcomes of indoor vector control (IVC) strategies, such as long-lasting insecticide-treated nets (LLINs) and indoor residual sprays (IRSs), are heavily influenced by individual and community-level perceptions and acceptance. These perceptions, and therefore product acceptance, are largely influenced by the successful suppression of non-target nuisance pests such as bed bugs and cockroaches. Adoption and consistent use of LLINs and IRS is responsible for immense reductions in the prevalence and incidence of malaria. However, recent observations suggest that failed control of indoor pests, leading to product distrust and abandonment, may threaten vector control programme success and further derail already slowed progress towards malaria elimination. We review the evidence of the relationship between IVC and nuisance pests and discuss the dearth of research on this relationship. We make the case that the ancillary control of indoor nuisance and public health pests needs to be considered in the development and implementation of new technologies for malaria elimination.

Better methods, better data: landscaping the priorities for improving methodologies in vector control.

This article addresses the evolving challenges in evaluating insecticide-based tools for vector control. In response to the emergence of insecticide resistance in major malaria vectors, novel chemistries and products are coming to market, and there is a need to review the available testing methodologies. Commonly used methods for evaluating insecticides, such as the World Health Organization (WHO) cone bioassay, are inadequate for the diverse range of tools now available. Innovation to Impact (I2I) has studied the variability in laboratory methods, with the aim of identifying key factors that contribute to variation and providing recommendations to tighten up protocols. The I2I Methods Landscape is a living document which presents a review of existing methods for evaluating vector control tools, with the scope currently extending to insecticide-treated nets (ITNs) and indoor residual sprays (IRS). The review reveals a lack of validation for many commonly used vector control methods, highlighting the need for improved protocols to enhance reliability and robustness of the data that is generated to make decisions in product development, evaluation, and implementation. A critical aspect highlighted by this work is the need for tailored methods to measure endpoints relevant to the diverse modes of action of novel insecticides. I2I envisage that the Methods Landscape will serve as a decision-making tool for researchers and product manufacturers in selecting appropriate methods, and a means to prioritise research and development. We call for collective efforts in the pro-active development, validation, and consistent implementation of suitable methods in vector control to produce the data needed to make robust decisions.

Entomological effects of attractive targeted sugar bait station deployment in Western Zambia: vector surveillance findings from a two-arm cluster randomized phase III trial.

BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a novel tool with potential to complement current approaches to malaria vector control. To assess the public health value of ATSB station deployment in areas of high coverage with standard vector control, a two-arm cluster-randomized controlled trial (cRCT) of Sarabi ATSB® stations (Westham Ltd., Hod-Hasharon, Israel) was conducted in Western Province, Zambia, a high-burden location were Anopheles funestus is the dominant vector. The trial included 70 clusters and was designed to measure the effect of ATSBs on case incidence and infection prevalence over two 7-month deployments. Reported here are results of the vector surveillance component of the study, conducted in a subset of 20 clusters and designed to provide entomological context to guide overall interpretation of trial findings. METHODS: Each month, 200 paired indoor-outdoor human landing catch (HLC) and 200 paired light trap (LT) collections were conducted to monitor An. funestus parity, abundance, biting rates, sporozoite prevalence, and entomological inoculation rates (EIR). RESULTS: During the study 20,337 female An. funestus were collected, 11,229 from control and 9,108 from intervention clusters. A subset of 3,131 HLC specimens were assessed for parity: The mean non-parous proportion was 23.0% (95% CI 18.2-28.7%, total n = 1477) in the control and 21.2% (95% CI 18.8-23.9%, total n = 1654) in the intervention arm, an OR = 1.05 (95% CI 0.82-1.34; p = 0.688). A non-significant reduction in LT abundance (RR = 0.65 [95% CI 0.30-1.40, p = 0.267]) was associated with ATSB deployment. HLC rates were highly variable, but model results indicate a similar non-significant trend with a RR = 0.68 (95%CI 0.22-2.00; p = 0.479). There were no effects on sporozoite prevalence or EIR. CONCLUSIONS: Anopheles funestus parity did not differ across study arms, but ATSB deployment was associated with a non-significant 35% reduction in vector LT density, results that are consistent with the epidemiological impact reported elsewhere. Additional research is needed to better understand how to maximize the potential impact of ATSB approaches in Zambia and other contexts. TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov (NCT04800055, 16 March 2021).

Barriers to the quality delivery of seasonal malaria chemoprevention in Chad and Burkina Faso: a qualitative exploration of caregivers and community distributors' perspectives.

BACKGROUND: Recommended since 2012 by the World Health Organization (WHO), seasonal malaria chemoprevention (SMC) is a community-based intervention to prevent malaria in children in African regions where malaria transmission follows a seasonal pattern. Following the publication of consolidated WHO guidelines for malaria, SMC is expected to reach more children in new geographies in future years. Though SMC has been shown to reduce malaria-related morbidity and mortality, there is potential for quality improvement of the intervention implementation. Assisted by ten quality standards from a framework developed by Malaria Consortium, this paper aims to better understand the quality of SMC implementation and identify potential barriers to quality delivery of SMC. METHODS: A qualitative thematic analysis on data collected after the annual SMC rounds implemented in Burkina Faso and Chad in 2019 was conducted. Sixteen focus group discussions conducted with caregivers and community distributors were analysed. Three selected quality standards for SMC delivery; planning and enumeration; community engagement; and administration of SMC medicines provided overarching quality themes under which subthemes were identified. RESULTS: Eight subthemes relating to the three quality standards were identified. Although SMC was well accepted by communities in both settings, common barriers to the quality delivery of SMC were identified including difficulty ensuring adherence to the SMC administration protocol; difficulties reaching mobile populations; concerns around adverse drug reactions; rumours, and concerns about SMC safety; and community distributors' working conditions. Context-specific barriers included: the suboptimal timeliness of the SMC round in Burkina Faso, and the lack of involvement of female caregivers in mobilization activities in Chad. CONCLUSION: In the context of increased adoption of SMC, this paper provides relevant insights and recommendations for the improved implementation of SMC programmes. These include the integration of strategies addressing communities' concerns around adverse drug reactions, gender-specific mobilization strategies, and attention to community distributors' working conditions. It also highlights the importance and utility of further, robust research on the quality of SMC delivery.

RéSUMé EN FRANçAIS: BACKGROUND: Recommandée depuis 2012 par l'Organisation mondiale de la santé (OMS), la chimioprévention du paludisme saisonnier (CPS) est une intervention communautaire visant à prévenir le paludisme chez les enfants dans les régions d'Afrique où la transmission du paludisme suit un schéma saisonnier. Suite à la publication des lignes directrices consolidées de l'OMS sur le paludisme, la CPS devrait toucher davantage d'enfants dans de nouvelles zones géographiques dans les années à venir. Bien qu'il ait été démontré que la CPS réduisait la morbidité et la mortalité liées au paludisme, il y a du potentiel pour améliorer la qualité de l'implémentation l'intervention. En s'appuyant sur un cadre de normes de qualité de la CPS développé par le Malaria Consortium, cette publication vise à mieux comprendre la qualité de la mise en œuvre de la CPS et à identifier les obstacles potentiels à la qualité de la mise en œuvre de la CPS. METHODS: Une étude qualitative basée sur l'analyse secondaire des données collectées après les tournées annuelles du SMC mises en œuvre au Burkina Faso et au Tchad en 2019 a été menée. Une analyse thématique de 16 discussions de groupe menées avec des parents/tuteurs et des distributeurs communautaires a été faite. Trois des éléments clés du cadre des normes de qualité pour le déploiement de la CPS ont fourni les thèmes de qualité principaux sous lesquels les sous-thèmes identifiés ont été placés. RéSULTATS: Huit sous-thèmes relatifs aux normes de qualité ; la planification, la sensibilisation et l'engagement des communautés ainsi que l'administration des médicaments de la CPS ont été identifiés. Bien que la CPS ait été bien acceptée par les communautés dans les deux contextes, des obstacles communs à la qualité du déploiement de la CPS ont été identifiés, notamment : la difficulté d'assurer le respect du protocole d'administration de la CPS; atteindre les populations mobiles ; les préoccupations concernant les effets indésirables des médicaments ; les rumeurs et les préoccupations concernant le SMC; et les conditions de travail des distributeurs communautaires. D'autres barrières spécifiques au contexte de déploiement ont été identifiées, telles que le choix sous-optimal de la période de déploiement au Burkina Faso ou le manque d'implication des mères/tutrices dans les activités de mobilisation au Tchad. CONCLUSION: Dans le contexte de l'adoption croissante de la CPS, cette publication fournit des informations et des recommandations pertinentes pour l'amélioration de la mise en œuvre des programmes de CMS, telles que l'intégration de stratégies répondant aux préoccupations des communautés concernant les effets indésirables des médicaments, les stratégies de mobilisation spécifiques au genre, et/ou l'attention portée aux conditions de travail des distributeurs communautaires. Cette publication souligne également l'importance et l'utilité des recherches en cours sur la qualité du déploiement de la CPS.

RESUMO EM PORTUGUêS: INTRODUçãO: Recomendada desde 2012 pela Organização Mundial de Saúde (OMS), a quimioprevenção sazonal do paludismo (SMC) é uma intervenção de base comunitária para prevenir o paludismo em crianças em zonas da África onde a transmissão do paludismo segue um padrão sazonal. Após a publicação das diretrizes consolidadas da OMS sobre o paludismo, espera-se que a SMC chegue a mais crianças em novas zonas geográficas nos próximos anos. Embora se tenha demonstrado que a SMC reduz a morbilidade e a mortalidade causadas pelo paludismo, há potencial para melhorar a qualidade da implementação da intervenção. Com ajuda dum quadro de padrões de qualidade para a SMC desenvolvido pelo Malaria Consortium, a presente publicação visa compreender melhor a qualidade da implementação da SMC e identificar potenciais barreiras à qualidade da implementação da SMC. MéTODOS: Foi realizado um estudo qualitativo baseado na análise secundária dos dados recolhidos após as rondas anuais da SMC implementadas no Burkina Faso e no Chade em 2019. Foi efectuado uma análise temática de 16 discussões de grupos focais realizadas com cuidadores e distribuidores comunitários. Tres padrões do quadro de normas de qualidade para a implementação da SMC forneceu os principais temas de qualidade sob os quais os subtemas identificados foram colocados. RESULTADOS: Foram identificados oito sub-temas relacionados com padrões de qualidade; planeamento; sensibilização e envolvimento da comunidade; e administração de drogas da SMC. Embora a SMC tenha sido bem aceita pelas comunidades em ambos os contextos, foram identificadas barreiras comuns à implementação duma SMC de qualidade, incluindo: a dificuldade de assegurar o cumprimento do protocolo de administração da SMC; atingir populações móveis; preocupações com reacções adversas aos medicamentos; rumores e preocupações com a SMC; e as condições de trabalho dos distribuidores comunitários. Foram identificados outros obstáculos específicos ao contexto de implantação, tais como a escolha subaproveitada do período de implantação no Burkina Faso ou a falta de envolvimento das cuidadoras femininas nas actividades de mobilização no Chade. CONCLUSãO: No contexto do aumento da adopção da SMC, esta publicação fornece informações e recomendações relevantes para melhorar a implementação de programas de SMC, tais como estratégias integradoras que abordam as preocupações da comunidade sobre reacções adversas aos medicamentos, estratégias de mobilização específicas de género, e/ou atenção às condições de trabalho dos distribuidores comunitários. Salienta igualmente a importância e a utilidade das investigaçãos em curso sobre a qualidade da implementação da SMC.

Malaria prevalence and transmission in the Zakpota sub-district of central Benin: baseline characteristics for a community randomised trial of a new insecticide for indoor residual spraying.

BACKGROUND: Malaria transmission is known to be perennial and heterogeneous in Benin. Studies assessing local malaria prevalence, transmission levels and vector characteristics are critical for designing, monitoring and evaluating new vector control interventions in community trials. We conducted a study in the Zakpota sub-district of central Benin to collect baseline data on household characteristics, malaria prevalence, vector characteristics and transmission dynamics in preparation for a randomised controlled trial to evaluate the community impact of VECTRON™ T500, a new broflanilide indoor residual spraying (IRS) product. METHODS: A total of 480 children under 5 years of age from the 15 villages of the sub-district were tested for malaria by rapid diagnostic tests (RDTs). Mosquitoes were collected by human landing catches (HLCs), pyrethrum spray catches (PSCs) and Centers for Disease Control and Prevention miniature light traps (CDC-LTs) in selected houses in each village to assess vector density, composition, vector infectivity and prevalence of insecticide resistance markers. Bioassays were performed to detect vector susceptibility to pyrethroids, broflanilide (6 µg/bottle) and clothianidin (90 µg/bottle). RESULTS: A total of 9080 households were enumerated in the 15 study villages. Insecticide-treated net (ITN) usage was > 90%, with 1-2 ITNs owned per household. Houses were constructed mainly with cement (44%) and mud (38%) substrates or a mixture of cement and mud (18%), and 60% of them had open eaves. The overall prevalence of P. falciparum infection was 19% among surveyed children: 20% among females and 18% among males. The haemoglobin rate showed an anaemia (< 11 g/dl) prevalence of 66%. Anopheles coluzzii and An. gambiae sensu stricto (s.s.) were the two vector species present at an overall proportion of 46% versus 54%, respectively. The human biting rate was 2.3 bites per person per night (b/p/n) and biting occurred mostly indoors compared with outdoors (IRR = 0.776; P = 0.001). The overall proportion of outdoor biting was 44% and exceeded indoor biting in three villages. The sporozoite rate was 2% with a combined yearly entomological inoculation rate (EIR) of 16.1 infected bites per person per year (ib/p/y). There was great variability in malaria transmission risk across the villages, with EIR ranging from 0 to 29.3 ib/p/y. The vector population showed a high intensity of resistance to pyrethroids across the study villages but was largely susceptible to broflanilide and clothianidin. CONCLUSIONS: This study found high levels of malaria prevalence, vector density and transmission in the Zakpota sub-district despite the wide use of insecticide-treated nets. The vector population was mostly indoor resting and showed a high intensity of pyrethroid resistance but was generally fully susceptible to broflanilide. These findings demonstrated the suitability of the study area for the assessment of VECTRON™ T500 in a community randomised trial.

Assessing LLIN distribution implementation using evidence-informed intervention core elements: a qualitative study in a resource-constrained setting.

BACKGROUND: The National Malaria Elimination Programme implements the mass LLIN Distribution Campaigns in Ghana. Implementation science promotes the systematic study of social contexts, individual experiences, real-world environments, partnerships, and stakeholder consultations regarding the implementation of evidence-informed interventions. In this paper, we assess the core elements of the mass LLIN distribution campaign in a resource constrained setting to learn best implementation practices. Three core domains were assessed through the application of Galbraith's taxonomy (i.e., implementation, content, and pedagogy) for evidence-informed intervention implementation. METHODS: Six districts in two regions (Eastern and Volta) in Ghana participated in this study. Fourteen Focus Group Discussions (FGDs) were conducted across these communities. Eligible participants were purposively sampled considering age, occupation, gender, and care giving for children under 5 years and household head roles. All audio-recorded FGDs were transcribed verbatim, data was assessed and coded through deductive and inductive processes. NVivo software version 13 was used for the coding process. Themes were refined, legitimized, and the most compelling extracts selected to produce the results. RESULTS: Sixty-nine (69) caregivers of children under 5 years and sixty (60) household heads participated in the FGDs. All caregivers were females (69), whilst household heads included more males (41). Core elements identified under implementation domain of the LLIN distribution campaign in Ghana include the registration and distribution processes, preceded by engagement with traditional authorities and continuous involvement of community health volunteers during implementation. For pedagogy domain, core elements include delivery of intervention through outreaches, illustrations, demonstrations, and the use of multiple communication channels. Core elements realized within the content domain include information on effective malaria prevention, and provision of information to enhance their self-efficacy. Yet, participants noted gaps (e.g., misuse) in the desired behavioural outcome of LLIN use and a heavy campaign focus on women. CONCLUSION AND RECOMMENDATIONS: Although the implementation of the mass LLIN distribution campaigns exhibit components of core elements of evidence informed interventions (implementation, content and pedagogy), it has not achieved its desired behavioural change intentions (i.e. continuous LLIN use). Future campaigns may consider use of continuous innovative pedagogical approaches at the community level and lessons learnt from this study to strengthen the implementation process of evidence-based health interventions. There is also the need for standardization of core elements to identify the number of core elements required within each domain to achieve efficacy. ETHICAL APPROVAL: Ethical clearance was obtained from the Ghana Health Service Ethics Review Committee (GHS-ERC: 002/06/21) before the commencement of all data collection.