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.

Plasmodium gametocyte carriage in humans and sporozoite rate in anopheline mosquitoes in Gondar zuria district, Northwest Ethiopia.

Although the overall burden of malaria is decreasing in Ethiopia, a recent report of an unpredictable increased incidence may be related to the presence of community-wide gametocyte-carrier individuals and a high proportion of infected vectors. This study aimed to reveal the current prevalence of gametocyte-carriage and the sporozoite infectivity rate of Anopheles vectors for Plasmodium parasites. A community-based cross-sectional study was conducted from May 01 to June 30/2019. A total of 53 households were selected using systematic random sampling and a 242 study participants were recruited. Additionally,515 adult female Anopheles mosquitoes were collected using Center for Diseases Control and Prevention (CDC) light traps and mouth aspirators. Parasite gametocytemia was determined using giemsa stain microscopy, while sporozoite infection was determined by giemsa staining microscopy and enzyme linked immunosorbent assay (ELISA). Among the total 242 study participants, 5.4% (95%, CI = 2.9-8.3) of them were positive for any of the Plasmodium species gametocyte. Furthermore, being female [AOR = 15.5(95%, CI = 1.71-140.39)], age group between 15-29 years old [AOR = 16.914 (95%, CI = 1.781-160.63)], no ITNs utilization [AOR = 16.7(95%, CI = 1.902 -146.727)], and high asexual parasite density [(95%, CI = 0.057-0.176, P = 0.001, F = 18.402)] were identified as statistically significant factors for gametocyte carriage. Whereas sporozoite infection rate was 11.6% (95%, CI = 8.2-15.5) and 12.7% (95%, CI = 9.6-16.3) by microscopy and ELISA, respectively. Overall, this study indicated that malaria remains to be an important public health problem in Gondar Zuria district where high gametocyte carriage rate and sporozoite infection rate could sustain its transmission and burden. Therefore, in Ethiopia, where malaria elimination program is underway, frequent, and active community-based surveillance of gametocytemia and sporozoite infection rate is important.

[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.

Malaria Diagnosis at the Pediatric Emergency Unit of a Teaching Hospital in Makurdi, North Central Nigeria.

Background: Globally, there were 241 million cases of malaria in 2020, with an estimated 627,000 deaths with Nigeria accounting for 27% of the global malaria cases. In sub-Saharan Africa, testing is low with only 28% of children with a fever receiving medical advice or a rapid diagnostic test in 2021. In Nigeria, there are documented reports of over-diagnosis and over-treatment of malaria in children. Therefore, this study examined the diagnosis of malaria at the Benue State University Teaching Hospital, Makurdi. Methods: A 5-year (2018-2022) retrospective study was carried out at the Emergency Pediatric Unit (EPU). Records of all children presenting to the EPU with an assessment of malaria were retrieved and reviewed. Data was analyzed using SPSS 23. Results: Out of 206 children reviewed, 128 (62.1%) were tested using either malaria RDT or microscopy while 78(37.9%) were not tested. Out of the number tested, 59(46.1%) were negative while 69(53.9%) tested positive, of which 14(20.3%) had uncomplicated malaria while 55(79.7%) had severe malaria. However, while 97.1% (n=67) of the positive cases were treated with IV artesunate, 69.5% (n=41) of those who tested negative and 88.5% (69) of those who were not tested also received IV artesunate. Moreover, while 85.5% (n=59) of those who tested positive received oral artemisinin-based combination therapy (ACT), 72.9% (n=43) of those who tested negative and 67.9% (53) of those who were not tested also received oral ACT. Conclusion: There was over-diagnosis of malaria, and subsequently, over-treatment. Hence continued emphasis on parasitological confirmation of malaria before treatment is recommended.

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.

Identification of Southeast Asian Anopheles mosquito species using MALDI-TOF mass spectrometry.

Malaria elimination in Southeast Asia remains a challenge, underscoring the importance of accurately identifying malaria mosquitoes to understand transmission dynamics and improve vector control. Traditional methods such as morphological identification require extensive training and cannot distinguish between sibling species, while molecular approaches are costly for extensive screening. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as a rapid and cost-effective tool for Anopheles species identification, yet its current use is limited to few specialized laboratories. This study aimed to develop and validate an online reference database for MALDI-TOF MS identification of Southeast Asian Anopheles species. The database, constructed using the in-house data analysis pipeline MSI2 (Sorbonne University), comprised 2046 head mass spectra from 209 specimens collected at the Thailand-Myanmar border. Molecular identification via COI and ITS2 DNA barcodes enabled the identification of 20 sensu stricto species and 5 sibling species complexes. The high quality of the mass spectra was demonstrated by a MSI2 median score (min-max) of 61.62 (15.94-77.55) for correct answers, using the best result of four technical replicates of a test panel. Applying an identification threshold of 45, 93.9% (201/214) of the specimens were identified, with 98.5% (198/201) consistency with the molecular taxonomic assignment. In conclusion, MALDI-TOF MS holds promise for malaria mosquito identification and can be scaled up for entomological surveillance in Southeast Asia. The free online sharing of our database on the MSI2 platform (https://msi.happy-dev.fr/) represents an important step towards the broader use of MALDI-TOF MS in malaria vector surveillance.

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.

Prevalence of malaria in Arusha Region in the northern Tanzania.

BACKGROUND: The World Health Organization (WHO) reported an estimated 249 million malaria cases globally in 2023, of which 94% were reported from Africa. Tanzania, a Sub-Saharan African country, has an exceptionally high malaria prevalence (3.6 million in 2023). The aim of the present study was to assess malaria prevalence rates in the Arusha Region, northern Tanzania. This region is famous for its national parks and wildlife reserves, and it is visited by thousands of tourists from all over the world each year. The assessment of malaria prevalence in the region is important in the context of the necessity to administer antimalarial chemoprophylaxis to international travellers. MATERIAL AND METHODS: The study group consisted of 101 people, residents of the Karatu District in the Arusha Region, aged between 1 and 73 years, who volunteered to participate in the screening. Phase I of the study was conducted in July 2022 in the Karatu Lutheran Hospital in Karatu Town (located close to the Ngorongoro Conservation Area and the Serengeti National Park). During this phase a venous blood sample was collected from each patient. The samples were tested for malaria using a rapid diagnostic test (mRDT); the same samples were also used to measure haemoglobin concentration and next they were applied onto the Whatman FTA micro cards for further molecular diagnostics in Poland (phase II). RESULTS: mRDT detected two (2.0%) infections caused by Plasmodium (the etiological factor of malaria), the molecular tests (RT-PCR) confirmed the two positive results by mRDT but also detected infections in six other samples (7.9% in total). The study found that six patients were infected with the Plasmodium falciparum species, while two other subjects had co-infections (P. falciparum + P. ovale, P. falciparum + P. vivax + P. malariae). CONCLUSIONS: The study findings confirm the prevalence of malaria in areas located close to national parks in northern Tanzania and support the use of antimalarial chemoprophylaxis in international travellers visiting the area. The present study found co-infections caused by four different species of Plasmodium species which supports the prevalence of different parasitic species in Sub-Saharan Africa and is in line with CDC reports but contrary to WHO reports which estimate that 100% of malaria cases in Sub-Saharan Africa are caused by P. falciparum.

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.

GIS-based spatiotemporal mapping of malaria prevalence and exploration of environmental inequalities.

Malaria poses a significant threat to global health, with particular severity in Nigeria. Understanding key factors influencing health outcomes is crucial for addressing health disparities. Disease mapping plays a vital role in assessing the geographical distribution of diseases and has been instrumental in epidemiological research. By delving into the spatiotemporal dynamics of malaria trends, valuable insights can be gained into population dynamics, leading to more informed spatial management decisions. This study focused on examining the evolution of malaria in Nigeria over twenty years (2000-2020) and exploring the impact of environmental factors on this variation. A 5-year-period raster map was developed using malaria indicator survey data for Nigeria's six geopolitical zones. Various spatial analysis techniques, such as point density, spatial autocorrelation, and hotspot analysis, were employed to analyze spatial patterns. Additionally, statistical methods, including Principal Component Analysis, Spearman correlation, and Ordinary Least Squares (OLS) regression, were used to investigate relationships between indicators and develop a predictive model. The study revealed regional variations in malaria prevalence over time, with the highest number of cases concentrated in northern Nigeria. The raster map illustrated a shift in the distribution of malaria cases over the five years. Environmental factors such as the Enhanced Vegetation Index, annual land surface temperature, and precipitation exhibited a strong positive association with malaria cases in the OLS model. Conversely, insecticide-treated bed net coverage and mean temperature negatively correlated with malaria cases in the same model. The findings from this research provide valuable insights into the spatiotemporal patterns of malaria in Nigeria and highlight the significant role of environmental drivers in influencing disease transmission. This scientific knowledge can inform policymakers and aid in developing targeted interventions to combat malaria effectively.

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.

Antimalarial efficacy test of the aqueous crude leaf extract of Coriandrum sativum Linn.: an in vivo multiple model experimental study in mice infected with Plasmodium berghei.

BACKGROUND: Malaria continues to wreak havoc on the well-being of the community. Resistant parasites are jeopardizing the treatment. This is a wake-up call for better medications. Folk plants are the key starting point for antimalarial drug discovery. After crushing and mixing the leaves of Coriandrum sativum with water, one cup of tea is drunk daily for a duration of three to five days as a remedy for malaria by local folks in Ethiopia. Additionally, in vitro experiments conducted on the plant leaf extract elsewhere have also demonstrated the plant's malaria parasite inhibitory effect. There has been no pharmacologic research to assert this endowment in animals, though. This experiment was aimed at evaluating the antimalarial efficacy of C. sativum in Plasmodium berghei infected mice. METHODS: The plant's leaf was extracted using maceration with distilled water. The extract was examined for potential acute toxicity. An evaluation of secondary phytoconstituents was done. Standard antimalarial screening models (prophylactic, chemosuppressive, curative tests) were utilized to assess the antiplasmodial effect. In each test, thirty mice were organized into groups of five. To the three categories, the test substance was given at doses of 100, 200 and 400 mg/kg/day before or after the commencement of P. berghei infection. Positive and negative control mice were provided Chloroquine and distilled water, respectively. Rectal temperature, parasitemia, body weight, survival time and packed cell volume were ultimately assessed. Analysis of the data was performed using Statistical Package for Social Sciences. RESULTS: No toxicity was manifested in mice. The extract demonstrated a significant inhibition of parasitemia (p < 0.05) in all the models. The inhibition of parasite load was highest with the upper dose in the suppressive test (82.74%) followed by the curative procedure (78.49%). Likewise, inhibition of hypothermia, weight loss hampering, improved survival and protection against hemolysis were elicited by the extract. CONCLUSIONS: The results of our experimental study revealed that the aqueous crude leaf extract of C. sativum exhibits significant antimalarial efficacy in multiple in vivo models involving mice infected with P. berghei. Given this promising therapeutic attribute, in depth investigation on the plant is recommended.

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.