Dynamics of malaria vector composition and Plasmodium falciparum infection in mainland Tanzania: 2017-2021 data from the national malaria vector entomological surveillance.

BACKGROUND: In 2015, Tanzania National Malaria Control Programme (NMCP) established a longitudinal malaria vector entomological surveillance (MVES). The MVES is aimed at a periodical assessment of malaria vector composition and abundance, feeding and resting behaviours, and Plasmodium falciparum infection in different malaria epidemiological strata to guide the NMCP on the deployment of appropriate malaria vector interventions. This work details the dynamics of malaria vector composition and transmission in different malaria epidemiological strata. METHODS: The MVES was conducted from 32 sentinel district councils across the country. Mosquitoes were collected by the trained community members and supervised by the NMCP and research institutions. Three consecutive night catches (indoor collection with CDC light trap and indoor/outdoor collection using bucket traps) were conducted monthly in three different households selected randomly from two to three wards within each district council. Collected mosquitoes were sorted and morphologically identified in the field. Thereafter, the samples were sent to the laboratory for molecular characterization using qPCR for species identification and detection of P. falciparum infections (sporozoites). ELISA technique was deployed for blood meal analysis from samples of blood-fed mosquitoes to determine the blood meal indices (BMI). RESULTS: A total of 63,226 mosquitoes were collected in 32 district councils from January 2017 to December 2021. Out of which, 39,279 (62%), 20,983 (33%) and 2964 (5%) were morphologically identified as Anopheles gambiae sensu lato (s.l.), Anopheles funestus s.l., and as other Anopheles species, respectively. Out of 28,795 laboratory amplified mosquitoes, 13,645 (47%) were confirmed to be Anopheles arabiensis, 9904 (34%) as An. funestus sensu stricto (s.s.), and 5193 (19%) as An. gambiae s.s. The combined average entomological inoculation rates (EIR) were 0.46 (95% CI 0.028-0.928) for An. gambiae s.s., 0.836 (95% CI 0.138-1.559) for An. arabiensis, and 0.58 (95% CI 0.165-0.971) for An. funestus s.s. with variations across different malaria transmission strata. Anopheles funestus s.s. and An. arabiensis were predominant in the Lake and South-Eastern zones, respectively, mostly in high malaria transmission areas. Monthly mosquito densities displayed seasonal patterns, with two peaks following the rainy seasons, varying slightly across species and district councils. CONCLUSION: Anopheles arabiensis remains the predominant vector species followed by An. funestus s.s. in the country. Therefore, strengthening integrated vector management including larval source management is recommended to address outdoor transmission by An. arabiensis to interrupt transmission particularly where EIR is greater than the required elimination threshold of less than one (< 1) to substantially reduce the prevalence of malaria infection.

Relative importance of VECTRI model parameters in the malaria disease transmission and prevalence.

In this study, a sensitivity analysis on a VECTRI dynamical model of malaria transmission is investigated to determine the relative importance of model parameters to disease transmission and prevalence. Apart from being most climatic prone, Odisha is a highly endemic state for malaria in India. The lack in sufficient modeling studies severely impacts the malarial process studies which further hinder the possibility of malaria early warning systems and preventive measures to be undertaken beforehand. Therefore, modeling studies and investigating the relationship between malaria transmission process studies and associated climatic factors are the need of the hour. Environmental conditions have pronounced effects on the malaria transmission dynamics and abundance of the poikilothermic vectors, but the exact relationship of sensitivity for these parameters is not well established. Sensitivity analysis is a useful tool for ascertaining model responses to different input variables. Therefore, in order to perform the requisite study, a dynamical model, VECTRI, is utilized. The study period ranges from 2000 to 2013, where several sensitivity tests are performed using different model parameters such as infiltration and evaporation rate loss of ponds, degree-days for parasite development, threshold temperature for parasite development, threshold temperature for egg development in the vector, and maximum and minimum temperature for larvae survival. The experiments suggest that the lower value of minimum temperature for larvae survival (rlarv_tmin), i.e., 16 °C, provides higher vector density and entomological inoculation rate (EIR) values. EIR reaches its maximum, when the threshold temperature for parasite development (rtsporo) is 22 °C and degree-days for parasite development (dsporo) is 8 degree-days. No change is observed in the vector density; even when rtsporo is 30 °C, values of EIR are close to 0. A successive increment of infiltration and evaporation rate loss of ponds (rwaterfrac evap126) values from 130 to 200 mm/day result in approximately 5% consistent decline in vector density and EIR. The study concludes that the most sensitive parameters are dsporo, rlarv_tmin, and rwaterfrac evap126. The VECTRI model is rather insensitive to maximum temperature for larvae survival (rlarv_tmin) for vector density and EIR variables. Further certain modifications and improvements are required in VECTRI to predict out variables like vector density and EIR more accurately in highly endemic region.

Spatial-temporal vector abundance and malaria transmission dynamics in Nchelenge and Lake Mweru islands, a region with a high burden of malaria in northern Zambia.

BACKGROUND: Over a decade of vector control by indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) distribution on the mainland, and only LLINs on islands had a minimal impact on disease burden in Nchelenge district, northern Zambia. Anopheles funestus and Anopheles gambiae are vectors known only from the mainland. Understanding vector bionomics in the district is necessary for planning and targeting effective vector control. This study aimed to provide information on abundance, seasonality, and Plasmodium falciparum sporozoite infectivity of malaria vectors in Nchelenge, including islands. METHODS: Mosquitoes were collected in 192 CDC indoor light traps set in 56 households between January 2015 and January 2016. Morphological and molecular species identifications and P. falciparum circumsporoites by ELISA were performed. Mosquito counts and relative abundances from the islands and mainland were compared, and household factors associated with vector counts were determined. RESULTS: A total of 5888 anophelines were collected during the study. Of these, 5,704 were female Anopheles funestus sensu lato (s.l.) and 248 female An. gambiae s.l. The highest proportion of An. funestus (n = 4090) was from Chisenga Island and An. gambiae (n = 174) was from Kilwa Island. The highest estimated counts per trap for An. funestus s.l. were from Chisenga island, (89.9, p < 0.001) and from the dry season (78.6, p < 001). For An. gambiae the highest counts per trap were from Kilwa island (3.1, p < 0.001) and the rainy season (2.5, p = 0.007). The highest estimated annual entomological inoculation rate was from Chisenga Island with 91.62 ib/p/y followed by Kilwa Island with 29.77 ib/p/yr, and then Mainland with 19.97 ib/p/yr. CONCLUSIONS: There was varied species abundance and malaria transmission risk across sites and seasons. The risk of malaria transmission was perennial and higher on the islands. The minimal impact of vector control efforts on the mainland was evident, but limited overall. Vector control intervention coverage with effective tools needs to be extended to the islands to effectively control malaria transmission in Nchelenge district.

Anopheles rufipes implicated in malaria transmission both indoors and outdoors alongside Anopheles funestus and Anopheles arabiensis in rural south-east Zambia.

BACKGROUND: The primary malaria vector-control interventions, indoor residual spraying and long-lasting insecticidal nets, are effective against indoor biting and resting mosquito species. Consequently, outdoor biting and resting malaria vectors might elude the primary interventions and sustain malaria transmission. Varied vector biting and resting behaviour calls for robust entomological surveillance. This study investigated the bionomics of malaria vectors in rural south-east Zambia, focusing on species composition, their resting and host-seeking behaviour and sporozoite infection rates. METHODS: The study was conducted in Nyimba District, Zambia. Randomly selected households served as sentinel houses for monthly collection of mosquitoes indoors using CDC-light traps (CDC-LTs) and pyrethrum spray catches (PSC), and outdoors using only CDC-LTs for 12 months. Mosquitoes were identified using morphological taxonomic keys. Specimens belonging to the Anopheles gambiae complex and Anopheles funestus group were further identified using molecular techniques. Plasmodium falciparum sporozoite infection was determined using sandwich enzyme-linked immunosorbent assays. RESULTS: From 304 indoor and 257 outdoor light trap-nights and 420 resting collection, 1409 female Anopheles species mosquitoes were collected and identified morphologically; An. funestus (n = 613; 43.5%), An. gambiae sensu lato (s.l.)(n = 293; 20.8%), Anopheles pretoriensis (n = 282; 20.0%), Anopheles maculipalpis (n = 130; 9.2%), Anopheles rufipes (n = 55; 3.9%), Anopheles coustani s.l. (n = 33; 2.3%), and Anopheles squamosus (n = 3, 0.2%). Anopheles funestus sensu stricto (s.s.) (n = 144; 91.1%) and Anopheles arabiensis (n = 77; 77.0%) were the dominant species within the An. funestus group and An. gambiae complex, respectively. Overall, outdoor CDC-LTs captured more Anopheles mosquitoes (mean = 2.25, 95% CI 1.22-3,28) than indoor CDC-LTs (mean = 2.13, 95% CI 1.54-2.73). Fewer resting mosquitoes were collected with PSC (mean = 0.44, 95% CI 0.24-0.63). Sporozoite infectivity rates for An. funestus, An. arabiensis and An. rufipes were 2.5%, 0.57% and 9.1%, respectively. Indoor entomological inoculation rates (EIRs) for An. funestus s.s, An. arabiensis and An. rufipes were estimated at 4.44, 1.15 and 1.20 infectious bites/person/year respectively. Outdoor EIRs for An. funestus s.s. and An. rufipes at 7.19 and 4.31 infectious bites/person/year, respectively. CONCLUSION: The findings of this study suggest that An. rufipes may play an important role in malaria transmission alongside An. funestus s.s. and An. arabiensis in the study location.

Entomological longitudinal surveys in two contrasted eco-climatic settings in Cameroon reveal a high malaria transmission from Anopheles funestus associated with GSTe2 metabolic resistance.

BACKGROUND: The impact of metabolic resistance to insecticides on malaria transmission remains poorly characterised notably through application of entomological parameters. The lack of resistance markers has been one of the limiting factors preventing a robust assessment of such impact. To this end, the present study sought to investigate how the L119F-Gste2 metabolic gene influences entomological parameters underpinning mosquitos' propensity to transmit Plasmodium spp. METHODS: Longitudinal studies were carried out in Mibellon and Elende, two different eco-climatic settings in Cameroon and mosquitoes were collected using Human Landing Catch (HLC), Centre for Disease Control Light Trap (CDC-LT) and Pyrethrum Spray Catch (PSC) technics. Plasmodium sporozoite parasites were detected by TaqMan and Nested PCR, and blood meal origin by ELISA. The allele-specific PCR (AS-PCR) method was used to genotype the L119F-GSTe2 marker and association with malaria transmission was established by comparing key transmission parameters such as the Entomological Inoculation Rate (EIR) between individuals with different L119F-GSTe2 genotypes. RESULTS: An. funestus s.l was the predominant malaria vector collected during the entomological survey in both sites (86.6% and 96.4% in Elende and Mibellon, respectively) followed by An. gambiae s.l (7.5% and 2.4%, respectively). Sporozoite infection rates were very high in both collection sites (8.7% and 11% in Elende and Mibellon, respectively). An. funestus s.s exhibited a very high entomological inoculation rate (EIR) (66 ib/h/month and 792 ib/h/year) and was responsible for 98.6% of all malaria transmission events occurring in both sites. The Human Blood Index was also high in both locations (HBI = 94%). An. funestus s.s. mosquitoes with both 119 F/F (RR) and L119F (RS) genotypes had a significantly higher transmission intensity than their susceptible L/L119 (SS) counterparts (IRR = 2.2, 95%CI (1.1-5.2), p = 0.03; IRR = 2.5, 95% CI (1.2-5.8), p = 0.01 respectively). CONCLUSION: This study highlights the major role that An. funestus s.s plays in malaria transmission in Cameroon with an aggravation from GSTe2-based metabolic resistance.

Large-scale (Phase III) evaluation of broflanilide 50WP (VECTRON™ T500) for indoor residual spraying for malaria vector control in Northeast Tanzania: study protocol for a two-arm, non-inferiority, cluster-randomised community trial.

BACKGROUND: Indoor residual spraying (IRS) is a major method of malaria vector control across sub-Saharan Africa. Effective control is being undermined by the rapid spread of insecticide resistance. There is major investment in development of new insecticides for IRS that possess novel modes of action, long residual activity, low mammalian toxicity and minimal cross-resistance. VECTRON™ T500, a new IRS product containing the active ingredient broflanilide as a 50% wettable powder (WP), has been shown to be efficacious against pyrethroid susceptible and resistant vector species on mud and concrete substrates in experimental hut (Phase II) trials. METHODS: A two-arm non-inferiority cluster randomized controlled trial (Phase III) will be undertaken in Muheza District, Tanga Region, Tanzania. VECTRON™ T500 will be compared to the IRS product Fludora® Fusion (clothianidin 50% WP + deltamethrin 6.25% WP). The predominant malaria vectors in the study area are pyrethroid-resistant Anopheles gambiae s.s., An. arabiensis and An. funestus s.s. Sixteen village clusters will be pair-matched on baseline vector densities and allocated to reference and intervention arms. Consenting households in the intervention arm will be sprayed with VECTRON™ T500 and those in the reference arm will be sprayed with Fludora® Fusion. Each month, CDC light traps will collect mosquitoes to estimate changes in vector density, indoor biting, sporozoite and entomological inoculation rates (EIR). Susceptibility to IRS active ingredients will be assessed using World Health Organisation (WHO) bottle bioassays. Target site and metabolic resistance mechanisms will be characterised among Anopheles field populations from both trial arms. Residual efficacy of both IRS products will be monitored for 12 months post intervention. Questionnaire and focus group discussions will explore factors that influence adherence, adverse effects and benefits of IRS. DISCUSSION: This protocol describes a large-scale non-inferiority evaluation of a novel IRS product to reduce the density and EIR of pyrethroid-resistant Anopheles vectors. If VECTRON™ T500 proves non-inferior to Fludora® Fusion, it will be considered as an additional vector control product for malaria prevention and insecticide resistance management. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05150808, registered on 26 November 2021. Retrospectively registered.

Integrating Parasitological and Entomological Observations to Understand Malaria Transmission in Riverine Villages in the Peruvian Amazon.

BACKGROUND: Remote rural riverine villages account for most of the reported malaria cases in the Peruvian Amazon. As transmission decreases due to intensive standard control efforts, malaria strategies in these villages will need to be more focused and adapted to local epidemiology. METHODS: By integrating parasitological, entomological, and environmental observations between January 2016 and June 2017, we provided an in-depth characterization of malaria transmission dynamics in 4 riverine villages of the Mazan district, Loreto department. RESULTS: Despite variation across villages, malaria prevalence by polymerase chain reaction in March 2016 was high (>25% in 3 villages), caused by Plasmodium vivax mainly and composed of mostly submicroscopic infections. Housing without complete walls was the main malaria risk factor, while households close to forest edges were more commonly identified as spatial clusters of malaria prevalence. Villages in the basin of the Mazan River had a higher density of adult Anopheles darlingi mosquitoes, and retained higher prevalence and incidence rates compared to villages in the basin of the Napo River despite test-and-treat interventions. CONCLUSIONS: High heterogeneity in malaria transmission was found across and within riverine villages, resulting from interactions between the microgeographic landscape driving diverse conditions for vector development, housing structure, and human behavior.

Urban malaria in sub-Saharan Africa: dynamic of the vectorial system and the entomological inoculation rate.

Sub-Saharan Africa is registering one of the highest urban population growth across the world. It is estimated that over 75% of the population in this region will be living in urban settings by 2050. However, it is not known how this rapid urbanization will affect vector populations and disease transmission. The present study summarizes findings from studies conducted in urban settings between the 1970s and 2020 to assess the effects of urbanization on the entomological inoculation rate pattern and anopheline species distribution. Different online databases such as PubMed, ResearchGate, Google Scholar, Google were screened. A total of 90 publications were selected out of 1527. Besides, over 200 additional publications were consulted to collate information on anopheline breeding habitats and species distribution in urban settings. The study confirms high malaria transmission in rural compared to urban settings. The study also suggests that there had been an increase in malaria transmission in most cities after 2003, which could also be associated with an increase in sampling, resources and reporting. Species of the Anopheles gambiae complex were the predominant vectors in most urban settings. Anopheline larvae were reported to have adapted to different aquatic habitats. The study provides updated information on the distribution of the vector population and the dynamic of malaria transmission in urban settings. The study also highlights the need for implementing integrated control strategies in urban settings.

Indoor and outdoor malaria transmission in two ecological settings in rural Mali: implications for vector control.

BACKGROUND: Implementation and upscale of effective malaria vector control strategies necessitates understanding the multi-factorial aspects of transmission patterns. The primary aims of this study are to determine the vector composition, biting rates, trophic preference, and the overall importance of distinguishing outdoor versus indoor malaria transmission through a study at two communities in rural Mali. METHODS: Mosquito collection was carried out between July 2012 and June 2016 at two rural Mali communities (Dangassa and Koïla Bamanan) using pyrethrum spray-catch and human landing catch approaches at both indoor and outdoor locations. Species of Anopheles gambiae complex were identified by polymerase chain reaction (PCR). Enzyme-Linked -Immuno-Sorbent Assay (ELISA) were used to determine the origin of mosquito blood meals and presence of Plasmodium falciparum sporozoite infections. RESULTS: A total of 11,237 An. gambiae sensu lato (s.l.) were collected during the study period (5239 and 5998 from the Dangassa and Koïla Bamanan sites, respectively). Of the 679 identified by PCR in Dangassa, Anopheles coluzzii was the predominant species with 91.4% of the catch followed by An. gambiae (8.0%) and Anopheles arabiensis (0.6%). At the same time in Koïla Bamanan, of the 623 An. gambiae s.l., An. coluzzii accounted for 99% of the catch, An. arabiensis 0.8% and An. gambiae 0.2%. Human Blood Index (HBI) measures were significantly higher in Dangassa (79.4%; 95% Bayesian credible interval (BCI) [77.4, 81.4]) than in Koïla Bamanan (15.9%; 95% BCI [14.7, 17.1]). The human biting rates were higher during the second half of the night at both sites. In Dangassa, the sporozoite rate was comparable between outdoor and indoor mosquito collections. For outdoor collections, the sporozoite positive rate was 3.6% (95% BCI [2.1-4.3]) and indoor collections were 3.1% (95% BCI [2.4-5.0]). In Koïla Bamanan, the sporozoite rate was higher indoors at 4.3% (95% BCI [2.7-6.3]) compared with outdoors at 2.4% (95% BCI [1.1-4.2]). In Dangassa, corrected entomological inoculation rates (cEIRs) using HBI were 13.74 [95% BCI 9.21-19.14] infective bites/person/month (ib/p/m) at indoor, and 18.66 [95% BCI 12.55-25.81] ib/p/m at outdoor. For Koïla Bamanan, cEIRs were 1.57 [95% BCI 2.34-2.72] ib/p/m and 0.94 [95% BCI 0.43-1.64] ib/p/m for indoor and outdoor, respectively. EIRs were significantly higher at the Dangassa site than the Koïla Bamanan site. CONCLUSION: The findings in this work may indicate the occurrence of active, outdoor residual malaria transmission is comparable to indoor transmission in some geographic settings. The high outdoor transmission patterns observed here highlight the need for additional strategies to combat outdoor malaria transmission to complement traditional indoor preventive approaches such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) which typically focus on resting mosquitoes.

Assessing the efficacy of two dual-active ingredients long-lasting insecticidal nets for the control of malaria transmitted by pyrethroid-resistant vectors in Benin: study protocol for a three-arm, single-blinded, parallel, cluster-randomized controlled trial.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are currently the primary method of malaria control in sub-Saharan Africa and have contributed to a significant reduction in malaria burden over the past 15 years. However, this progress is threatened by the wide-scale selection of insecticide-resistant malaria vectors. It is, therefore, important to accelerate the generation of evidence for new classes of LLINs. METHODS: This protocol presents a three-arm superiority, single-blinded, cluster randomized controlled trial to evaluate the impact of 2 novel dual-active ingredient LLINs on epidemiological and entomological outcomes in Benin, a malaria-endemic area with highly pyrethroid-resistant vector populations. The study arms consist of (i) Royal Guard® LLIN, a net combining a pyrethroid (alpha-cypermethrin) plus an insect growth regulator (pyriproxyfen), which in the adult female is known to disrupt reproduction and egg fertility; (ii) Interceptor G2® LLIN, a net incorporating two adulticides (alpha-cypermethrin and chlorfenapyr) with different modes of action; and (iii) the control arm, Interceptor® LLIN, a pyrethroid (alpha-cypermethrin) only LLIN. In all arms, one net for every 2 people will be distributed to each household. Sixty clusters were identified and randomised 1:1:1 to each study arm. The primary outcome is malaria case incidence measured over 24 months through active case detection in a cohort of 25 children aged 6 months to 10 years, randomly selected from each cluster. Secondary outcomes include 1) malaria infection prevalence (all ages) and prevalence of moderate to severe anaemia in children under 5 years old, measured at 6 and 18 months post-intervention; 2) entomological indices measured every 3 months using human landing catches over 24 months. Insecticide resistance intensity will also be monitored over the study period. DISCUSSION: This study is the second cluster randomised controlled trial to evaluate the efficacy of these next-generation LLINs to control malaria transmitted by insecticide-resistant mosquitoes. The results of this study will form part of the WHO evidence-based review to support potential public health recommendations of these nets and shape malaria control strategies of sub-Saharan Africa for the next decade. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03931473 , registered on 30 April 2019.

Understanding the effect of climate change in the distribution and intensity of malaria transmission over India using a dynamical malaria model.

Efforts have been made to quantify the spatio-temporal malaria transmission intensity over India using the dynamical malaria model, namely, Vector-borne Disease Community Model of International Centre for Theoretical Physics Trieste (VECTRI). The likely effect of climate change in the variability of malaria transmission intensity over different parts of India is also investigated. The Historical data and future projection scenarios of the rainfall and temperature derived from the Coupled Model Intercomparison Project Phase 5 (CMIP5) model output are used for this purpose. The Entomological Inoculation Rate (EIR) and Vector are taken as quantifiers of malaria transmission intensity. It is shown that the maximum number of malaria cases over India occur during the Sept-Oct months, whereas the minimum during the Feb-Apr months. The malaria transmission intensity as well as length of transmission season over India is likely to increase in the future climate as a result of global warming.

Contribution of Asymptomatic Plasmodium Infections to the Transmission of Malaria in Kayin State, Myanmar.

BACKGROUND: The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously. METHODS: MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression. RESULTS: Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6-100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8-6.0-fold) increase in the vector infection rate. CONCLUSION: Asymptomatic infections are a major source of malaria transmission in Southeast Asia.

Modelled and observed mean and seasonal relationships between climate, population density and malaria indicators in Cameroon.

BACKGROUND: A major health burden in Cameroon is malaria, a disease that is sensitive to climate, environment and socio-economic conditions, but whose precise relationship with these drivers is still uncertain. An improved understanding of the relationship between the disease and its drivers, and the ability to represent these relationships in dynamic disease models, would allow such models to contribute to health mitigation and adaptation planning. This work collects surveys of malaria parasite ratio and entomological inoculation rate and examines their relationship with temperature, rainfall, population density in Cameroon and uses this analysis to evaluate a climate sensitive mathematical model of malaria transmission. METHODS: Co-located, climate and population data is compared to the results of 103 surveys of parasite ratio (PR) covering 18,011 people in Cameroon. A limited set of campaigns which collected year-long field-surveys of the entomological inoculation rate (EIR) are examined to determine the seasonality of disease transmission, three of the study locations are close to the Sanaga and Mefou rivers while others are not close to any permanent water feature. Climate-driven simulations of the VECTRI malaria model are evaluated with this analysis. RESULTS: The analysis of the model results shows the PR peaking at temperatures of approximately 22 °C to 26 °C, in line with recent work that has suggested a cooler peak temperature relative to the established literature, and at precipitation rates at 7 mm day-1, somewhat higher than earlier estimates. The malaria model is able to reproduce this broad behaviour, although the peak occurs at slightly higher temperatures than observed, while the PR peaks at a much lower rainfall rate of 2 mm day-1. Transmission tends to be high in rural and peri-urban relative to urban centres in both model and observations, although the model is oversensitive to population which could be due to the neglect of population movements, and differences in hydrological conditions, housing quality and access to healthcare. The EIR follows the seasonal rainfall with a lag of 1 to 2 months, and is well reproduced by the model, while in three locations near permanent rivers the annual cycle of malaria transmission is out of phase with rainfall and the model fails. CONCLUSION: Malaria prevalence is maximum at temperatures of 24 to 26 °C in Cameroon and rainfall rates of approximately 4 to 6 mm day-1. The broad relationships are reproduced in a malaria model although prevalence is highest at a lower rainfall maximum of 2 mm day-1. In locations far from water bodies malaria transmission seasonality closely follows that of rainfall with a lag of 1 to 2 months, also reproduced by the model, but in locations close to a seasonal river the seasonality of malaria transmission is reversed due to pooling in the transmission to the dry season, which the model fails to capture.

Seasonal malaria vector and transmission dynamics in western Burkina Faso.

BACKGROUND: In the context of widespread mosquito resistance to currently available pesticides, novel, precise genetic vector control methods aimed at population suppression or trait replacement are a potentially powerful approach that could complement existing malaria elimination interventions. Such methods require knowledge of vector population composition, dynamics, behaviour and role in transmission. Here were characterized these parameters in three representative villages, Bana, Pala and Souroukoudingan, of the Sudano-Sahelian belt of Burkina Faso, a region where bed net campaigns have recently intensified. METHODS: From July 2012 to November 2015, adult mosquitoes were collected monthly using pyrethroid spray catches (PSC) and human landing catches (HLC) in each village. Larval habitat prospections assessed breeding sites abundance at each site. Mosquitoes collected by PSC were identified morphologically, and then by molecular technique to species where required, to reveal the seasonal dynamics of local vectors. Monthly entomological inoculation rates (EIR) that reflect malaria transmission dynamics were estimated by combining the HLC data with mosquito sporozoite infection rates (SIR) identified through ELISA-CSP. Finally, population and EIR fluctuations were fit to locally-collected rainfall data to highlight the strong seasonal determinants of mosquito abundance and malaria transmission in this region. RESULTS: The principal malaria vectors found were in the Anopheles gambiae complex. Mosquito abundance peaked during the rainy season, but there was variation in vector species composition between villages. Mean survey HLC and SIR were similar across villages and ranged from 18 to 48 mosquitoes/person/night and from 3.1 to 6.6% prevalence. The resulting monthly EIRs were extremely high during the rainy season (0.91-2.35 infectious bites/person/day) but decreased substantially in the dry season (0.03-0.22). Vector and malaria transmission dynamics generally tracked seasonal rainfall variations, and the highest mosquito abundances and EIRs occurred in the rainy season. However, despite low residual mosquito populations, mosquitoes infected with malaria parasites remained present in the dry season. CONCLUSION: These results highlight the important vector control challenge facing countries with high EIR despite the recent campaigns of bed net distribution. As demonstrated in these villages, malaria transmission is sustained for large parts of the year by a very high vector abundance and high sporozoite prevalence, resulting in seasonal patterns of hyper and hypo-endemicity. There is, therefore, an urgent need for additional vector control tools that can target endo and exophillic mosquito populations.

Blood feeding behaviour comparison and contribution of Anopheles coluzzii and Anopheles gambiae, two sibling species living in sympatry, to malaria transmission in Alibori and Donga region, northern Benin, West Africa.

BACKGROUND: The main goal of this study was to assess the blood feeding behaviour and the contribution Anopheles coluzzii and Anopheles gambiae, 2 sibling species of An. gambiae sensu stricto. present and living in sympatry in 2 regions of northern Benin targeted for indoor residual spraying (IRS). METHODS: The study was carried out in 6 districts of 2 regions of Benin (Alibori and Donga). Human landing catches (HLC) performed inside and outside of the households and pyrethrum spray captures (PSC) carried out in bedrooms were used to sample vector populations (An. gambiae and An. coluzzii). Collected mosquitoes were analysed to estimate the human biting rate indoors and outdoors, the circumsporozoite antigen positivity, and the anthropophagic index using ELISA methodology. Polymerase chain reaction was used to estimate the frequency of the knockdown resistance (kdr) L1014F and the ace-1 mutations, 2 markers associated respectively with pyrethroids and carbamate/organophosphate insecticide resistance. RESULTS: A higher blood feeding rate was observed in An. gambiae compared to An. coluzzii as well as, a non-pronounced outdoor biting behavior in both species. The latter showed similar anthropophagic and sporozoite rates. However the analysis indicates a seasonal difference in the contribution of each species to malaria transmission associated with shifts in resting behaviour. Anopheles coluzzii females accounted for most of the detected infections: 86% in Alibori and 79% in Donga, during the dry season versus 14.4% and 21.2%, respectively for An. gambiae during the same period. This relationship was reversed in Donga during the rainy season (66% for An. gambiae against 34% for An. coluzzii). Results also indicated lower frequencies of kdr L1014F and ace-1 in An. coluzzii versus An. gambiae. CONCLUSION: Despite similarity in some parameters related to malaria transmission in both surveyed species, An. coluzzii is potentially a more important malaria vector because of high density in the region. It is also characterized by lower frequencies of the ace-1 mutation than is An. gambiae. The ongoing use of pirimiphos methyl (organophosphate) for IRS should continue to show a good impact in Alibori and Donga because of the very low level of the ace-1 mutation in both species.

A reduction in malaria transmission intensity in Northern Ghana after 7 years of indoor residual spraying.

BACKGROUND: Indoor residual spraying (IRS) is being implemented as one of the malaria prevention methods in the Northern Region of Ghana. Changes in longevity, sporozoite and entomological inoculation rates (EIRs) of major malaria vectors were monitored to assess the impact of IRS in selected districts. METHODS: Monthly human landing catches (HLCs) were used to collect mosquitoes from sentinel sites in three adjacent districts between July 2009 and December 2014: Savelugu Nanton (SND) where IRS had been implemented from 2008 to 2014; Tolon Kumbungu (TKD) where IRS had been implemented between 2008 and 2012 and Tamale Metropolis (TML) with no history of IRS. Mosquitoes were morphologically identified to species level and into sibling species, using PCR. Samples of Anopheles gambiae sensu lato (s.l.) were examined for parity and infectivity. EIR was calculated from biting and infectivity rates of malaria vectors. RESULTS: Parity rates of An. gambiae s.l. decreased significantly (p < 0.0001) in SND from 44.8% in 2011 to 28.1% by 2014, and in TKD from 53.3% in 2011 to 46.6% in 2012 (p = 0.001). However 2 years after IRS was discontinued in TKD, the proportion of parous An. gambiae s.l. increased significantly to 68.5% in 2014 (p < 0.0001). Parity rates in the unsprayed district remained high throughout the study period, ranging between 68.6% in 2011 and 72.3% in 2014. The sum of monthly EIRs post-IRS season (July-December) in SND ranged between 2.1 and 6.3 infective bites/person/season (ib/p/s) during the 3 years that the district was sprayed with alphacypermethrin. EIR in SND was reduced to undetectable levels when the insecticide was switched to pirimiphos methyl CS in 2013 and 2014. Two years after IRS was withdrawn from TKD the sum of monthly EIRs (July-December) increased by about fourfold from 41.8 ib/p/s in 2012 to 154.4 ib/p/s in 2014. The EIR in the control area, TML, ranged between 35 ib/p/s in 2009 to 104.71 ib/p/s by 2014. CONCLUSIONS: This study demonstrates that IRS application did have a significant impact on entomological indicators of malaria transmission in the IRS project districts of Northern Ghana. Transmission indicators increased following the withdrawal of IRS from Tolon Kumbungu District.

The effectiveness of non-pyrethroid insecticide-treated durable wall lining to control malaria in rural Tanzania: study protocol for a two-armed cluster randomized trial.

BACKGROUND: Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management. METHODS/DESIGN: A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted. DISCUSSION: This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts. TRIAL REGISTRATION: NCT02533336 registered on 13 July 2014.

House Screening Reduces Exposure to Indoor Host-Seeking and Biting Malaria Vectors: Evidence from Rural South-East Zambia.

This study evaluated the impact of combining house screens with long-lasting insecticidal nets (LLINs) on mosquito host-seeking, resting, and biting behavior. Intervention houses received house screens and LLINs, while control houses received only LLINs. Centre for Disease Control light traps, pyrethrum spray collections and human landing catches were used to assess the densities of indoor and outdoor host-seeking, indoor resting, and biting behavior of malaria vectors in 15 sentinel houses per study arm per sampling method. The protective efficacy of screens and LLINs was estimated through entomological inoculation rates (EIRs). There were 68% fewer indoor host-seeking Anopheles funestus (RR = 0.32, 95% CI 0.20-0.51, p < 0.05) and 63% fewer An. arabiensis (RR = 0.37, 95% CI 0.22-0.61, p < 0.05) in screened houses than unscreened houses. There was a significantly higher indoor biting rate for unscreened houses (6.75 bites/person/h [b/p/h]) than for screened houses (0 b/p/h) (χ2 = 6.67, df = 1, p < 0.05). The estimated indoor EIR in unscreened houses was 2.91 infectious bites/person/six months, higher than that in screened houses (1.88 infectious bites/person/six months). Closing eaves and screening doors and windows has the potential to reduce indoor densities of malaria vectors and malaria transmission.

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.

Efficacy of chlorfenapyr-pyrethroid and piperonyl butoxide-pyrethroid long-lasting insecticidal nets (LLINs) compared to pyrethroid-only LLINs for malaria control in Côte d'Ivoire: a three group, cluster randomised trial.

BACKGROUND: The massive scale-up of long-lasting insecticidal nets (LLIN) has led to a major reduction in malaria burden in many sub-Saharan African (SSA) countries. The World Health Organization (WHO) has recently issued a strong recommendation for the use of chlorfenapyr-pyrethroid LLINs compared to standard pyrethroid-only LLINs in areas of high insecticide resistance intensity. However, there is still a lack of conclusive evidence on the efficacy of piperonyl butoxide-pyrethroid (PBO-py) LLINs, especially in West Africa, where vector composition and resistance mechanisms may be different from vectors in East Africa. METHODS: This is a three-arm, superiority, triple-blinded, cluster randomised trial, with village as the unit of randomisation. This study conducted in Côte d'Ivoire will evaluate the efficacy on epidemiological and entomological outcomes of (1) the control arm: MAGNet® LN, which contains the pyrethroid, alpha-cypermethrin, (2) VEERALIN® LN, a net combining the synergist PBO and alpha-cypermethrin, and (3) Interceptor® G2 LN, which incorporates chlorfenapyr and alpha-cypermethrin, two adulticides with different mechanisms of action. A total of 33 villages with an average of 200 households per village will be identified, mapped, and randomised in a ratio of 1:1:1. Nets will be distributed at a central point following national guidelines with 1 net for every 2 people. The primary outcome of the trial will be incidence of malaria cases (confirmed by rapid diagnostic test (RDT)) in a cohort of 50 children aged 6 months to 10 years in each cluster, followed for 12 months (active case detection). Secondary outcomes are cross-sectional community prevalence of malaria infection (confirmed by RDT) in the study population at 6 and 12 months post-intervention (50 randomly selected persons per cluster), vector density, entomological inoculation rate (EIR), and phenotypic and genotypic insecticide resistance at baseline and 12 months post-intervention in 3 sentinel villages in each treatment arm. DISCUSSION: In addition to generating further evidence for next-generation LLINs, this study will also provide the first evidence for pyrethroid-PBO nets in a West African setting. This could further inform WHO recommendations on the pragmatic use of pyrethroid-PBO nets. TRIAL REGISTRATION: ClinicalTrials.gov NCT05796193. Registered on April 3, 2023.