Will a lack of fabric durability be their downfall? Impact of textile durability on the efficacy of three types of dual-active-ingredient long-lasting insecticidal nets: a secondary analysis on malaria prevalence and incidence from a cluster-randomized trial in north-west Tanzania.

BACKGROUND: The Dual-Active Ingredient long-lasting insecticidal nets (Dual-AI LLIN) have been developed to counteract the reduced efficacy of pyrethroid (PY)-only nets due to widespread pyrethroid insecticide resistance in malaria vector mosquitoes. They constitute half of the nets distributed in sub-Saharan Africa between 2022 and 2024. However, their effectiveness once they develop holes is unclear, particularly in pyrethroid-resistant settings. This study evaluates the textile integrity of three dual- AI LLINs compared to standard PY LLN, over 3 years of use in a community in Tanzania and the associated impact on malaria prevalence and incidence. METHODS: A secondary analysis of data from a randomized controlled trial (RCT) in North-western Tanzania was conducted to evaluate the effectiveness of α-cypermethrin only; pyriproxyfen and α-cypermethrin (PPF-PY); chlorfenapyr and α-cypermethrin (chlorfenapyr-PY); and the synergist piperonyl butoxide and permethrin (PBO-PY) LLINs on malaria infection prevalence and case incidence. The association between the net textile condition and 1/malaria prevalence over 3 years of use between 2019 and 2022, and 2/malaria case incidence in a cohort of children over 2 years of follow-up was assessed between 2019 and 2021. RESULTS: There was no significant association between damaged (OR 0.98, 95% CI 0.71-1.37, p-value = 0.655) and too-torn (OR 1.07, 95% CI 0.77-1.47, p-value = 0.694) compared to intact nets on malaria prevalence for all net types. However, there were reduced rates of malaria case incidence in children sleeping under a net in good condition compared to too-torn nets (incidence rate ratio (IRR) 0.76 [95% CI 0.63-0.92], p = 0.005). Malaria incidence was also consistently lower in too-torn PBO-PY LLIN (IRR = 0.37 [95% CI 0.19-0.72], p = 0.003) and chlorfenapyr-PY LLIN (IRR = 0.45 [95% CI 0.33-0.97], p = 0.053) compared to an intact PY-only LLIN during the first year of follow up. In year 2, the incidence was only significantly lower in intact chlorfenapyr-PY LLIN (IRR = 0.49 [95% CI 0.29-0.81], p = 0.006) compared to intact PY LLIN. CONCLUSION: The study confirmed that sleeping under a chlorfenapyr-PY LLIN or PBO-PY LLIN offered superior protection to pyrethroid-only nets even when torn. Preventing the development of holes is essential as they impact the level of protection offered against malaria infection. TRIAL REGISTRATION: ClinicalTrials.gov, number (NCT03554616).

Ixodes scapularis density and Borrelia burgdorferi prevalence along a residential-woodland gradient in a region of emerging Lyme disease risk.

The environmental risk of Lyme disease, defined by the density of Ixodes scapularis ticks and their prevalence of Borrelia burgdorferi infection, is increasing across the Ottawa, Ontario region, making this a unique location to explore the factors associated with environmental risk along a residential-woodland gradient. In this study, we collected I. scapularis ticks and trapped Peromyscus spp. mice, tested both for tick-borne pathogens, and monitored the intensity of foraging activity by deer in residential, woodland, and residential-woodland interface zones of four neighbourhoods. We constructed mixed-effect models to test for site-specific characteristics associated with densities of questing nymphal and adult ticks and the infection prevalence of nymphal and adult ticks. Compared to residential zones, we found a strong increasing gradient in tick density from interface to woodland zones, with 4 and 15 times as many nymphal ticks, respectively. Infection prevalence of nymphs and adults together was 15 to 24 times greater in non-residential zone habitats. Ecological site characteristics, including soil moisture, leaf litter depth, and understory density, were associated with variations in nymphal density and their infection prevalence. Our results suggest that high environmental risk bordering residential areas poses a concern for human-tick encounters, highlighting the need for targeted disease prevention.

Study protocol for a scoping review of Lyme disease prediction methodologies.

INTRODUCTION: In the temperate world, Lyme disease (LD) is the most common vector-borne disease affecting humans. In North America, LD surveillance and research have revealed an increasing territorial expansion of hosts, bacteria and vectors that has accompanied an increasing incidence of the disease in humans. To better understand the factors driving disease spread, predictive models can use current and historical data to predict disease occurrence in populations across time and space. Various prediction methods have been used, including approaches to evaluate prediction accuracy and/or performance and a range of predictors in LD risk prediction research. With this scoping review, we aim to document the different modelling approaches including types of forecasting and/or prediction methods, predictors and approaches to evaluating model performance (eg, accuracy). METHODS AND ANALYSIS: This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines. Electronic databases will be searched via keywords and subject headings (eg, Medical Subject Heading terms). The search will be performed in the following databases: PubMed/MEDLINE, EMBASE, CAB Abstracts, Global Health and SCOPUS. Studies reported in English or French investigating the risk of LD in humans through spatial prediction and temporal forecasting methodologies will be identified and screened. Eligibility criteria will be applied to the list of articles to identify which to retain. Two reviewers will screen titles and abstracts, followed by a full-text screening of the articles' content. Data will be extracted and charted into a standard form, synthesised and interpreted. ETHICS AND DISSEMINATION: This scoping review is based on published literature and does not require ethics approval. Findings will be published in peer-reviewed journals and presented at scientific conferences.

Knowledge, protective behaviours, and perception of Lyme disease in an area of emerging risk: results from a cross-sectional survey of adults in Ottawa, Ontario.

BACKGROUND: The number of Lyme disease risk areas in Canada is growing. In regions with emerging tick populations, it is important to emphasize peridomestic risk and the importance of protective behaviours in local public health communication. This study aims to identify characteristics associated with high levels of Lyme disease knowledge and adoption of protective behaviours among residents in the Ottawa, Ontario region. METHODS: A geographically stratified web survey was conducted in November 2020 (n = 2018) to determine knowledge, attitudes, and practices regarding Lyme disease among adult residents. Responses were used to calculate: (i) composite scores for knowledge and adoption of protective practices; and (ii) an exposure risk index based on reported activity in woodlands during the spring-to-fall tick exposure risk period. RESULTS: 60% of respondents had a high knowledge of Lyme disease, yet only 14% indicated they often use five or more measures to protect themselves. Factors strongly associated with a high level of Lyme disease knowledge included being 55 or older (Odds Ratio (OR) = 2.04), living on a property with a yard (OR = 3.22), having a high exposure index (OR = 1.59), and knowing someone previously infected with Lyme disease (OR = 2.05). Strong associations with the adoption of a high number of protective behaviours were observed with membership in a non-Indigenous racialized group (OR = 1.70), living on a property with a yard (OR = 2.37), previous infection with Lyme disease (OR = 2.13), prior tick bite exposure (OR = 1.62), and primarily occupational activity in wooded areas (OR = 2.31). CONCLUSIONS: This study highlights the dynamics between Lyme disease knowledge, patterns of exposure risk awareness, and vigilance of personal protection in a Canadian region with emerging Lyme disease risk. Notably, this study identified gaps between perceived local risk and protective behaviours, presenting opportunities for targeted enhanced communication efforts in areas of Lyme disease emergence.

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.

Health systems impacts of the COVID-19 pandemic on malaria control program implementation and malaria burden in Benin: A mixed-method qualitative and mathematical modelling and study.

The COVID-19 pandemic has sent ripple effects across health systems and impacted the burden of many other diseases, such as malaria in sub-Saharan Africa. This study takes a mixed method approach to assess the impact of COVID-19 on malaria control programs in three rural communes in Benin. We conducted individual semi-structured interviews with key informants who play important roles in malaria control in Benin at three levels of the health system-national, health zone, and commune. Using a purposive sampling technique, informants were interviewed regarding their roles in malaria control, the impact of the pandemic on their activities, and the mitigation strategies adopted. Relevant themes were identified by content analysis. We then formulated an agent-based model of malaria epidemiology to assess the impacts of treatment disruption on malaria burden. The key informant interviews revealed that essential aspects of malaria control were upheld in Benin due to the close collaboration of public health practitioners and health care providers at all levels of the health system. There were some disruptions to case management services for malaria at the start of the pandemic due to the public avoiding health centers and a brief shortage of malaria treatment that may not be entirely attributable to the pandemic. Results from the agent-based model suggest that duration, severity, and timing of treatment disruption can impact malaria burden in a synergistic manner, though the effects are small given the relatively mild disruptions observed. This study highlights the importance of top-down leadership in health emergencies, as well as the critical role of community health workers in preventing negative health outcomes for their communities. We also showcased the integration of qualitative research and mathematical models-an underappreciated form of mixed methods research that offer immense value in the continued evaluation of rapidly evolving health emergencies.

Have there been efforts to integrate malaria and schistosomiasis prevention and control programs? A scoping review of the literature.

Malaria and schistosomiasis are two important parasitic diseases that are a particular threat to young children and pregnant women in sub-Saharan Africa. Malaria and schistosomiasis prevention and control strategies primarily focus on the distribution of long-lasting insecticidal nets and the delivery of praziquantel tablets to at-risk populations in high burden settings through mass drug administration, respectively. The objective of this scoping review was to identify previous efforts to integrate malaria and schistosomiasis prevention and control programs in the literature and to summarize the strategies and approaches used in these programs following the PRISMA-ScR guidelines. We reviewed published and grey literature using a combination of keywords and search terms following themes surrounding "malaria", "Plasmodium falciparum", "Anopheles", "schistosomiasis", "Schistosoma haematobium", "Schistosoma mansoni", and "snails". Neither a date limit nor relevant terms for prevention and control were used. Out of 6374, eight articles were included in the scoping review-three articles investigated the integration of mass drug administration for schistosomiasis with the administration of antimalarials, four articles investigated the effect of administering antimalarials on malaria, schistosomiasis, and their co-infection, and one article assessed the impact of an educational intervention on malaria and schistosomiasis knowledge and preventative behaviors. Our findings suggest that there is an opportunity to link disease control programs to increase access and coverage of interventions to improve outcomes for malaria, schistosomiasis, and their co-infection. Further research is needed on the potential benefits, feasibility, and cost-effectiveness of integrating malaria and schistosomiasis prevention and control programs.

Effectiveness of long-lasting insecticidal nets with pyriproxyfen-pyrethroid, chlorfenapyr-pyrethroid, or piperonyl butoxide-pyrethroid versus pyrethroid only against malaria in Tanzania: final-year results of a four-arm, single-blind, cluster-randomised trial.

BACKGROUND: New classes of long-lasting insecticidal nets (LLINs) containing two active ingredients have been recently recommended by WHO in areas where malaria vectors are resistant to pyrethroids. This policy was based on evidence generated by the first 2 years of our recently published trial in Tanzania. In this Article, we report the final third-year trial findings, which are necessary for assessing the long-term effectiveness of new classes of LLIN in the community and the replacement intervals required. METHODS: A third year of follow-up of a four-arm, single-blind, cluster-randomised controlled trial of dual active ingredient LLINs was conducted between July 14, 2021, and Feb 10, 2022, in Misungwi, Tanzania. Restricted randomisation was used to assign 84 clusters to the four LLIN groups (1:1:1:1) to receive either standard pyrethroid (PY) LLINs (reference), chlorfenapyr-PY LLINs, pyriproxyfen-PY LLINs, or piperonyl butoxide (PBO)-PY LLINs. All households received one LLIN for every two people. Data collection was done in consenting households in the cluster core area with at least one child between 6 months and 15 years of age who permanently resided in the selected household. Exclusion criteria were householders absent during the visit, living in the cluster buffer area, no adult caregiver capable of giving informed consent, or eligible children who were severely ill. Field staff and study participants were masked to allocation, and those analysing data were not. The primary 24-month endpoint was reported previously; here, we present the secondary outcome, malaria infection prevalence in children at 36 months post LLIN distribution, reported in the intention-to-treat analysis. The trial was registered with ClinicalTrials.gov (NCT03554616) and is now complete. FINDINGS: Overall usage of study nets was 1023 (22·3%) of 4587 people at 36 months post distribution. In the standard PY LLIN group, malaria infection was prevalent in 407 (37·4%) of 1088 participants, compared with 261 (22·8%) of 1145 in the chlorfenapyr-PY LLIN group (odds ratio 0·57, 95% CI 0·38-0·86; p=0·0069), 338 (32·2%) of 1048 in the PBO-PY LLIN group (0·95, 0·64-1·42; p=0·80), and 302 (28·8%) of 1050 in the pyriproxyfen-PY LLIN group (0·82, 0·55-1·23; p=0·34). None of the participants or caregivers reported side-effects. INTERPRETATION: Despite low coverage, the protective efficacy against malaria offered by chlorfenapyr-PY LLINs was superior to that provided by standard PY LLINs over a 3-year LLIN lifespan. Appropriate LLIN replacement strategies to maintain adequate usage of nets will be necessary to maximise the full potential of these nets. FUNDING: Department for International Development, UK Medical Research Council, Wellcome Trust, Department of Health and Social Care, and Bill & Melinda Gates Foundation via the Innovative Vector Control Consortium.

Assessing risk factors for malaria and schistosomiasis among children in Misungwi, Tanzania, an area of co-endemicity: A mixed methods study.

Malaria and schistosomiasis are two major parasitic vector-borne diseases that are a particular threat to young children in Sub-Saharan Africa. In the present study, we investigated factors that are associated with malaria, schistosomiasis, and co-infection among school-aged children, using an explanatory sequential mixed-methods approach. A cross-sectional study was conducted in January 2022 in Misungwi, Tanzania, that sampled 1,122 children aged 5 to 14 years old for malaria and schistosomiasis infection. Mixed-effect logistic regression models were used to assess the association between infection prevalence or seroprevalence, and environmental determinants that create favorable conditions for vectors and parasites and social determinants that relate to disease exposure. Community mapping combined with direct field observations were conducted in August 2022 in three selected villages from the cross-sectional study to understand specific water use behaviors and to identify potential malaria mosquito larval breeding sites and freshwater snail habitat. The prevalence of malaria, seroprevalence of schistosomiasis, and co-infection in this study were 40.4%, 94.3%, and 38.1%, respectively. Individual-level factors emerged as the primary determinants driving the association with infection, with age (every one-year increase in age) and sex (boys vs girls) being statistically and positively associated with malaria, schistosomiasis, and co-infection (P<0.05 for all). Community maps identified many unimproved water sources in all three villages that were used by humans, cattle, or both. We found that children primarily fetched water, and that unprotected wells were dedicated for drinking water whereas ponds were dedicated for other domestic uses and cattle. Although not identified in the community maps, we found hand pumps in all three villages were not in use because of unpleasant taste and high cost. This study improves our understanding of individual, social and environmental factors that are associated with malaria, schistosomiasis, and co-infection, which can inform potential entry points for integrated disease prevention and control.

Ecological Niche and Positive Clusters of Two West Nile Virus Vectors in Ontario, Canada.

West Nile virus (WNV) is a mosquito-borne pathogen associated with uncommon but severe neurological complications in humans, especially among the elderly and immune-compromised. In Northeastern North America, the Culex pipiens/restuans complex and Aedes vexans are the two principal vector mosquito species/species groups of WNV. Using a 10-year surveillance dataset of WNV vector captures at 118 sites across an area of 40,000 km2 in Eastern Ontario, Canada, the ecological niches of Cx. pipiens/restuans and Aedes vexans were modeled by random forest analysis. Spatiotemporal clusters of WNV-positive mosquito pools were identified using Kulldorf's spatial scan statistic. The study region encompasses land cover types and climate representative of highly populated Southeastern Canada. We found highest vector habitat suitability in the eastern half of the study area, where temperatures are generally warmer (variable importance > 0.40) and residential and agricultural cropland cover is more prominent (variable importance > 0.25). We found spatiotemporal clusters of high WNV infection rates around the city of Ottawa in both mosquito vector species. These results support the previous literature in the same region and elsewhere suggesting areas surrounding highly populated areas are also high-risk areas for vector-borne zoonoses such as the WNV.

Assessment of Odontometric and Osteologic Traits for Gender Determination in South Indians: An Original Research.

In forensic, odontologic, genetic, and anthropological aspects, odontometric and osteologic features have long been a valuable source. The goal of this research was to correlate both the osteologic and odontometric characteristics to determine the most accurate approach for determining gender. A retrospective study involving 1000 adults, with equal gender distribution, was carried out utilizing digital panoramic radiography. The archives were searched for radiographic images of the subjects that were procured for the various procedures that ranged from implantations to rehabilitations. The measurement process was carried out with Image-Pro. There was a noticeable gender difference in the mesodistal breadth, which ranged from 17 to 47. Asymmetry of the lower jaw was considerable in both genders, as was gender variance in osseologic characteristics including ramus diameter and gonial angle. The two groups of attributes exhibited a substantial positive predictive value and thus can be used indetermining gender.

Comparison of Different Reconstruction Flap for Maxillofacial Region: An Original Research.

Introduction: Large chunks of the tissue are sacrificed during the surgical procedures for the treatment if oral cancers. Our goal was to assess the viability of "Buccal reconstruction using the anterolateral thigh (ALT) flaps, platysma myocutaneous (PM), and radial forearm free (RFF)". Material and Methods: Sixty subjects were included in this investigation, and they were divided into 3 groups. The follow-up as accompanied for six months. Comparisons were made for the time for the operations, reduction in the width of the mouth opening and the survival rates of the flaps. The data that was collected for the above two parameters and compared for the significance using the ANOVA, keeping P < 0.05 as significant. Results: In the subjects with the PM, the width of the mouth opening reduced comparatively greater than that of the subjects who received other two flaps. The reduction in the mouth opening in the PM was significantly greater compared to that of the ALT and RFF. Survival was greater for the groups ALT and RFF compared to PM. Time of the surgery was the greatest for the ALT and least for the PF. Conclusion: The observations point to the fact that the PF requires more time than that of the other two flaps. The survival was however better for the ALT and RFF. Further research is suggested for suggesting an appropriative flap design.

Fracture Resistance of Different Post-Core Systems: An In vitro Study.

Reasons for the failed endodontic teeth which had an extensive restoration can be attributed to the multiple materials that were used in it. Various post-core materials that are commonly used are compared for fracture resistance in the current study. Fourty maxillary incisors that needed root canal therapy were allocated into four groups of 10 each. Using adhesive resin cement, teeth were repaired in three experimental groups with ceramic fiber post, glass post, and stainless steel post. All these posts with composite post and core. Samples that still had their coronal structure were considered as controls that were without any post-cores. Every sample was ready for the best abutment preparation. Using the universal testing machine, all the specimens were examined for the compressive strength at 130° until fracture was experienced. The data for the force levels at which the fracture occurred were noted and compared for significance using analysis of variance (ANOVA), keeping P < 0.05 as significant. The fracture resistance values were significantly variable among all the groups, with P < 0.05. The stainless steel post exhibited the highest strength before it succumbed to the fracture. The glass posts showed better restorability and were esthetically acceptable. The least fracture resistance was demonstrated by teeth that had no post-core, highlighting the necessity of strengthening the tooth. Among all the experimental groups, the one that demonstrated the highest fracture resistance was composite core and steel posts.

Risk factors for Lyme disease resulting from residential exposure amidst emerging Ixodes scapularis populations: A neighbourhood-level analysis of Ottawa, Ontario.

Lyme disease is an emerging health threat in Canada due to the continued northward expansion of the main tick vector, Ixodes scapularis. It is of particular concern to populations living in expanding peri-urban areas where residential development and municipal climate change response impact neighbourhood structure and composition. The objective of this study was to estimate associations of socio-ecological characteristics with residential Lyme disease risk at the neighbourhood scale. We used Lyme disease case data for 2017-2020 reported for Ottawa, Ontario to determine where patients' residential property, or elsewhere within their neighbourhood, was the suspected site of tick exposure. Cases meeting this exposure definition (n = 118) were aggregated and linked to neighbourhood boundaries. We calculated landscape characteristics from composited and classified August 2018 PlanetScope satellite imagery. Negative binomial generalized linear models guided by a priori hypothesized relationships explored the association between hypothesized interactions of landscape structure and the outcome. Increases in median household income, the number of forest patches, the proportion of forested area, forest edge density, and mean forest patch size were associated with higher residential Lyme disease incidence at the neighbourhood scale, while increases in forest shape complexity and average distance to forest edge were associated with reduced incidence (P<0.001). Among Ottawa neighbourhoods, the combined effect of forest shape complexity and average forest patch size was associated with higher residential Lyme disease incidence (P<0.001). These findings suggest that Lyme disease risk in residential settings is associated with urban design elements. This is particularly relevant in urban centres where local ecological changes may impact the presence of emerging tick populations and how residents interact with tick habitat. Further research into the mechanistic underpinnings of these associations would be an asset to both urban development planning and public health management.

Effects of next-generation, dual-active-ingredient, long-lasting insecticidal net deployment on insecticide resistance in malaria vectors in Tanzania: an analysis of a 3-year, cluster-randomised controlled trial.

BACKGROUND: Insecticide resistance among malaria-vector species is a pervasive problem that might jeopardise global disease-control efforts. Novel vector-control tools with different modes of action, including long-lasting insecticidal nets (LLINs) incorporating new active ingredients, are urgently needed to delay the evolution and spread of insecticide resistance. We aimed to measure phenotypic and genotypic insecticide-resistance profiles among wild Anopheles collected over 3 years to assess the longitudinal effects of dual-active-ingredient LLINs on insecticide resistance. METHODS: For this analysis, data nested in a 3-year, four parallel-arm, superiority cluster-randomised controlled trial (cRCT) in Tanzania, collected from 84 clusters (39 307 households) formed of 72 villages in the Misungwi district, were used to measure insecticide-resistance profiles among female Anopheles mosquitoes via insecticide-resistance bioassays and quantitative RT-PCR of metabolic-resistance genes. Wild, blood-fed, indoor-resting mosquitoes were collected annually during the rainy seasons from house walls in clusters from all four trial groups. Mosquitoes were morphologically identified as An gambiae sensu lato (SL) or An funestus SL before separate bioassay testing. The primary outcomes were lethal-dose values for α-cypermethrin, permethrin, and piperonyl butoxide pre-exposure plus permethrin-resistance intensity bioassays, mortality 72 h after insecticidal exposure for chlorfenapyr bioassays, fertility reduction 72 h after insecticidal exposure for pyriproxyfen bioassays, and fold change in metabolic-enzyme expression relative to an insecticide-susceptible laboratory strain. All primary outcomes were measured in An funestus SL 1 year, 2 years, and 3 years after LLIN distribution. Primary outcomes were also assessed in An gambiae SL if enough mosquitoes were collected. The cRCT is registered with ClinicalTrials.gov (NCT03554616). FINDINGS: Between May 24, 2019, and Oct 25, 2021, 47 224 female Anopheles were collected for resistance monitoring. In the pyrethroid (PY)-LLIN group, there were significant increases in α-cypermethrin-resistance intensity (year 1 LD50=9·52 vs year 2 76·20, p<0·0001) and permethrin-resistance intensity (year 1 13·27 vs year 2 35·83, p=0·0019) in An funestus SL. In the pyriproxyfen PY-LLIN group, there was similar increase in α-cypermethrin-resistance intensity (year 1 0·71 vs year 2 81·56, p<0·0001) and permethrin-resistance intensity (year 1 5·68 vs year 2 50·14, p<0·0001). In the piperonyl butoxide PY-LLIN group, α-cypermethrin-resistance intensity (year 1 33·26 vs year 3 70·22, p=0·0071) and permethrin-resistance intensity (year 1 47·09 vs year 3 2635·29, p<0·0001) also increased over time. In the chlorfenapyr PY-LLIN group, there were no effects on α-cypermethrin-resistance intensity (year 1 0·42 vs year 3 0·99, p=0·54) or permethrin-resistance intensity (data were not estimable due to nearly 100% mortality). There were also minimal reductions in chlorfenapyr susceptibility. However, in the chlorfenapyr PY-LLIN group, a significant decline in piperonyl-butoxide synergy was seen by year 3 (year 1 0·02 vs year 3 0·26, p=0·020). Highly over-expressed detoxification enzymes showed dynamic patterns of selection throughout the trial. INTERPRETATION: Our phenotypic data supports trial epidemiological findings; chlorfenapyr PY-LLINs provided superior protection from malaria across multiple transmission seasons, with few effects on insecticide-resistance selection. Rapid pyrethroid-resistance intensification in the piperonyl butoxide PY-LLIN group and pre-existing tolerance of pyriproxyfen in vector populations might explain the poorer performance of these two interventions regarding malaria outcomes. Further work is required to elucidate the potential mechanisms driving cross-resistance between pyrethroids and novel active ingredients to better inform the design of pre-emptive resistance-management strategies. FUNDING: UK Department for International Development; UK Medical Research Council; Wellcome Trust; UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; and The Bill and Melinda Gates Foundation via the Innovative Vector Control Consortium.

Pyrethroid genetic resistance in the dengue vector (Aedes aegypti) in Posadas, Argentina.

Pyrethroids are extensively used to control adult populations of the arboviral vector Aedes aegypti, raising concerns regarding the increasing frequency and distribution of insecticide resistance mutations (kdr: knock-down resistance) in the voltage-gated sodium channel gene (Nav). The widespread use of pyrethroids imposes a threat to the success of mosquito control and the environment. In this study, we investigated the presence of two kdr mutations (V1016I and F1534C) in the Nav gene and their distribution across four neighborhoods in Posadas, Argentina, with different Ae. aegypti abundance and contrasting socioeconomic status (SES). Alleles at each locus were interrogated using TaqMan SNP genotyping assays in DNA extracted from adult females collected in a longitudinal study. We report the presence of both pyrethroid resistance alleles (kdr 1016I = 29.08%; kdr 1534C = 70.70%) among adult females. The frequency of combined kdr genotypes reveals that approximately 70% of local adult females have enhanced resistance to pyrethroids. Both, the proportion of resistant adult females (with at least one kdr allele in each locus) and Ae. aegypti abundance showed an uneven distribution between neighborhoods with different SES (p < 0.001). In high-SES neighborhoods, we found more mosquitoes and a higher frequency of pyrethroid resistance, possibly as a consequence of different public health interventions, social habits, and insecticide use. This is the first report of kdr mutations in Ae. Aegypti in the northeast region of Argentina. Our results focus on the need for within-population (city) distribution analyses of kdr mutations and highlight the relevance of incorporating insecticide resistance monitoring within the Integrated Vector Management initiative.

Differential impact of dual-active ingredient long-lasting insecticidal nets on primary malaria vectors: a secondary analysis of a 3-year, single-blind, cluster-randomised controlled trial in rural Tanzania.

BACKGROUND: Gains in malaria control are threatened by widespread pyrethroid resistance in malaria vectors across sub-Saharan Africa. New long-lasting insecticidal nets (LLINs) containing two active ingredients (dual active-ingredient LLINs) have been developed to interrupt transmission in areas of pyrethroid resistance. We aimed to evaluate the effectiveness of three dual active-ingredient LLINs compared with standard pyrethroid LLINs against pyrethroid-resistant malaria vectors in rural Tanzania. METHODS: In this study, we did a secondary analysis of entomological data from a four-group, 3 year, single-blind, cluster-randomised controlled trial carried out between Feb 18, 2019, and Dec 6, 2021. We conducted quarterly indoor mosquito collections using the Centers for Disease Control and Prevention light trap, in eight houses in each of the 84 study clusters in the Misungwi district, northwestern Tanzania. Anopheles vectors were then tested for malaria parasites and identified at species level, to distinguish between sibling species of the Anopheles gambiae and Anopheles funestus groups, using molecular laboratory techniques. The primary outcomes were density of different malaria vector species measured as the number of female Anopheles collected per household per night, the entomological inoculation rate (EIR), an indicator of malaria transmission, and sporozoite rate. Entomological outcomes were assessed on the basis of intention to treat, and the effect of the three dual active-ingredient LLINs was compared with the standard pyrethroid LLINs at household level. FINDINGS: Dual active-ingredient LLINs had the greatest effect on Anopheles funestus sl, the most efficient vector in the study area, with comparatively weak effect on An arabiensis. An funestus density was 3∙1 per house per night in the pyrethroid LLIN group, 1∙2 in the chlorfenapyr pyrethroid LLIN group (adjusted density ratio [aDR]=0∙26, 95% CI 0∙17-0∙14, p<0∙0001), 1∙4 in the piperonyl-butoxide pyrethroid LLIN group (aDR=0∙49, 0∙32-0∙76, p=0∙0012), and 3∙0 in the pyriproxyfen pyrethroid LLIN group (aDR=0∙72, 0∙47-1∙11, p=0∙15). Malaria transmission intensity was also significantly lower in the chlorfenapyr pyrethroid group, with 0∙01 versus 0∙06 infective bites per household per night in the pyrethroid LLIN group (aDR=0∙21, 0∙14-0∙33, p<0∙0001). Ecological niche models indicated that vector-species distribution was stable following LLIN intervention despite the reductions observed in An funestus sl density. INTERPRETATION: Chlorfenapyr pyrethroid LLINs were the most effective intervention against the main malaria vector An funestus sl over 3 years of community use, whereas the effect of piperonyl-butoxide pyrethroid LLIN was sustained for 2 years. The other vector, An arabiensis, was not controlled by any of the dual active-ingredient LLINs. Additional vector control tools and strategies targeted to locally prevalent vector species evading dual active-ingredient LLINs should be deployed to further reduce malaria transmission and achieve elimination. FUNDING: The Department for International Development, UK Medical Research Council, Wellcome Trust, the Department of Health and Social Care, and The Bill & Melinda Gates Foundation via the Innovative Vector Control Consortium.

Community-level impacts of the coronavirus pandemic on malaria prevention and health-seeking behaviours in rural Benin: A mixed methods study.

Globally, negative impacts of the COVID-19 pandemic on malaria prevention and control efforts have been caused by delayed distributions of long-lasting insecticidal nets (LLIN), decreased outpatient attendance, and disruptions to malaria testing and treatment. Using a mixed methods approach, we aimed to evaluate the impact of COVID-19 on community-level malaria prevention and health-seeking practices in Benin more than one year after the start of the COVID-19 pandemic. We collected data through community-based cross-sectional surveys with 4200 households and ten focus group discussions (FGDs). Mixed effect logistic regression models accounting for a clustered sampling design were used to identify variables associated with main outcomes (good COVID-19 knowledge, LLIN usage and access, and avoidance of health centres). Consistent with the experiences of FGD participants, receiving information from radios or televisions was significantly associated with good COVID-19 knowledge and avoiding health centres because of the pandemic (p<0.001 for both). Qualitative findings also revealed varying and polarizing changes in health-seeking behaviours with participants noting that they either did not change their health-seeking behaviours or went to health centres less or more often because of the pandemic. LLIN usage and access did not decrease in the study area because of the pandemic (LLIN usage: 88% in 2019 to 99.9% in 2021; LLIN access: 62% in 2019 to 73% in 2021). An unexpected change and unintended challenge for sustained malaria prevention included families socially distancing in their homes, resulting in a shortage of LLINs. Our findings showed that there were minimal community-level impacts of the coronavirus pandemic on malaria prevention and health seeking behaviours in rural Benin, which highlights the importance of efforts to sustain malaria prevention and control interventions in the context of the COVID-19 pandemic.

Accounting for complex intracluster correlations in longitudinal cluster randomized trials: a case study in malaria vector control.

BACKGROUND: The effectiveness of malaria vector control interventions is often evaluated using cluster randomized trials (CRT) with outcomes assessed using repeated cross-sectional surveys. A key requirement for appropriate design and analysis of longitudinal CRTs is accounting for the intra-cluster correlation coefficient (ICC). In addition to exchangeable correlation (constant ICC over time), correlation structures proposed for longitudinal CRT are block exchangeable (allows a different within- and between-period ICC) and exponential decay (allows between-period ICC to decay exponentially). More flexible correlation structures are available in statistical software packages and, although not formally proposed for longitudinal CRTs, may offer some advantages. Our objectives were to empirically explore the impact of these correlation structures on treatment effect inferences, identify gaps in the methodological literature, and make practical recommendations. METHODS: We obtained data from a parallel-arm CRT conducted in Tanzania to compare four different types of insecticide-treated bed-nets. Malaria prevalence was assessed in cross-sectional surveys of 45 households in each of 84 villages at baseline, 12-, 18- and 24-months post-randomization. We re-analyzed the data using mixed-effects logistic regression according to a prespecified analysis plan but under five different correlation structures as well as a robust variance estimator under exchangeable correlation and compared the estimated correlations and treatment effects. A proof-of-concept simulation was conducted to explore general conclusions. RESULTS: The estimated correlation structures varied substantially across different models. The unstructured model was the best-fitting model based on information criteria. Although point estimates and confidence intervals for the treatment effect were similar, allowing for more flexible correlation structures led to different conclusions based on statistical significance. Use of robust variance estimators generally led to wider confidence intervals. Simulation results showed that under-specification can lead to coverage probabilities much lower than nominal levels, but over-specification is more likely to maintain nominal coverage. CONCLUSION: More flexible correlation structures should not be ruled out in longitudinal CRTs. This may be particularly important in malaria trials where outcomes may fluctuate over time. In the absence of robust methods for selecting the best-fitting correlation structure, researchers should examine sensitivity of results to different assumptions about the ICC and consider robust variance estimators.

Rurality, Socioeconomic Status, and Residence in Environmental Risk Areas Associated with Increased Lyme Disease Incidence in Ontario, Canada: A Case-Control Study.

Background: Lyme disease (LD) is the most common tick-borne illness in North America. LD is acquired through exposure to the tick vector, Ixodes scapularis, known as the blacklegged tick. In Canada, LD is rapidly emerging, with the establishment of I. scapularis in many newly endemic regions posing a growing risk to local communities. In the Canadian context, many environmental and socioeconomic risk factors for human LD infection are yet to be ascertained and the degree of risk associated with residential and community exposure to ticks is not well known. Methods: We conducted a matched case-control study in southeastern Ontario, using LD patient data from provincial laboratory databases and uninfected population controls from 2014 to 2018. We aimed to identify area-level risk factors for LD and associations with residence in environmental risk areas, defined as areas with high model-predicted probability of I. scapularis occurrence, using the neighborhood dissemination area as the unit of analysis. Results: Using multivariable conditional logistic regression analysis, we identified that patients with LD had higher odds (odds ratio, OR; 95% confidence interval, CI) of living in neighborhoods with high probability of tick occurrence in the environment (OR = 2.2; 95% CI: 2.0-2.5), low walkability (OR = 1.6; 95% CI: 1.2-2.1), low material deprivation (OR = 1.4; 95% CI: 1.2-1.7), and low ethnic concentration (OR = 8.1; 95% CI: 6.7-9.9). We also found that the odds of LD infection for individuals residing in environmental risk areas was highest for those living in public health units (PHUs) with <250,000 population (OR = 3.0; 95% CI: 2.4-3.9) compared to those living in PHUs with >1,000,000 population (OR = 1.5; 95% CI: 1.1-2.1). Conclusion: This study shows that odds of human LD infection in Ontario, Canada is higher in less urbanized areas with higher socioeconomic status and indicates that exposure to ticks around the home residence or neighborhood is linked to increased odds of LD.