Factors associated with never treatment and acceptability of mass drug administration for the elimination of lymphatic filariasis in Guyana, 2021.

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those with scores above the acceptability threshold (score ≥22.5) reported participating in MDA two or more times. Factors strongly and positively associated with scoring above the acceptability threshold include beliefs in importance of participation in MDA for their community (aOR = 2.8, 95%CI (1.1-7.2)), perception of importance of LF treatment (6.9 (3.2-14.7)), receiving treatment in 2021 (2.9 (1.5-5.4)), and the number of self-reported times taking treatment for LF (2.2 (1.1-4.4)). Ten percent of respondents participated in the MDA for the first time in 2021, while 15% reported never treatment during any round of LF MDA. Three factors were statistically associated with participation in MDA across the two levels of the models (level 1: took LF treatment once versus never, and level 2: took LF treatment twice versus never) included: 1) scoring above the acceptability threshold (aOR = 6.2, 95%CI(3.8-10.0)), 2) self-reported importance of participation in MDA for their community (7.1 (2.9-17.8)), and 3) personal beliefs that they should take LF treatment even if they are not sick (2.6 (1.7-3.9)). As Guyana moves closer to LF elimination, these results provide further insight and understanding into programmatic results and could inform further action following MDA activities-particularly if an approach is needed to address never treatment during MDA.

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.

Malaria Burden and Associated Risk Factors in an Area of Pyrethroid-Resistant Vectors in Southern Benin.

Malaria remains the main cause of morbidity and mortality in Benin despite the scale-up of long-lasting insecticidal nets (LLINs), indoor residual spraying, and malaria case management. This study aimed to determine the malaria burden and its associated risk factors in a rural area of Benin characterized by high net coverage and pyrethroid-resistant mosquito vectors. A community-based cross-sectional survey was conducted in three districts in southern Benin. Approximately 4,320 randomly selected participants of all ages were tested for malaria using rapid diagnostic tests within 60 clusters. Risk factors for malaria infection were evaluated using mixed-effect logistic regression models. Despite high population net use (96%), malaria infection prevalence was 43.5% (cluster range: 15.1-72.7%). Children (58.7%) were more likely to be infected than adults (31.2%), with a higher malaria prevalence among older children (5-10 years: 69.1%; 10-15 years: 67.9%) compared with young children (< 5 years: 42.1%); however, young children were more likely to be symptomatic. High household density, low socioeconomic status, young age (< 15 years), poor net conditions, and low net usage during the previous week were significantly associated with malaria infection. Malaria prevalence remains high in this area of intense pyrethroid resistance despite high net use. New classes of LLINs effective against resistant vectors are therefore crucial to further reduce malaria in this area.

Effectiveness and cost-effectiveness against malaria of three types of dual-active-ingredient long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs in Tanzania: a four-arm, cluster-randomised trial.

BACKGROUND: Long-lasting insecticidal nets (LLINs) have successfully reduced malaria in sub-Saharan Africa, but their effectiveness is now partly compromised by widespread resistance to insecticides among vectors. We evaluated new classes of LLINs with two active ingredients with differing modes of action against resistant malaria vectors. METHODS: We did a four-arm, cluster-randomised trial in Misungwi, Tanzania. Clusters were villages, or groups of hamlets, with at least 119 households containing children aged 6 months to 14 years living in the cluster's core area. Constrained randomisation was used to allocate clusters (1:1:1:1) to receive one of four types of LLIN treated with the following: α-cypermethrin only (pyrethroid-only [reference] group); pyriproxyfen and α-cypermethrin (pyriproxyfen group); chlorfenapyr and α-cypermethrin (chlorfenapyr group); or the synergist piperonyl butoxide and permethrin (piperonyl butoxide group). At least one LLIN was distributed for every two people. Community members and the field team were masked to group allocation. Malaria prevalence data were collected through cross-sectional surveys of randomly selected households from each cluster, in which children aged 6 months to 14 years were assessed for Plasmodium falciparum malaria infection by rapid diagnostic tests. The primary outcome was malaria infection prevalence at 24 months after LLIN distribution, comparing each of the dual-active-ingredient LLINs to the standard pyrethroid-only LLINs in the intention-to-treat population. The primary economic outcome was cost-effectiveness of dual-active-ingredient LLINs, based on incremental cost per disability-adjusted life-year (DALY) averted compared with pyrethroid-only LLINs, modelled over a 2-year period; we included costs of net procurement and malaria diagnosis and treatment, and estimated DALYs in all age groups. This study is registered with ClinicalTrials.gov (NCT03554616), and is ongoing but no longer recruiting. FINDINGS: 84 clusters comprising 39 307 households were included in the study between May 11 and July 2, 2018. 147 230 LLINs were distributed among households between Jan 26 and Jan 28, 2019. Use of study LLINs was reported in 3155 (72·1%) of 4378 participants surveyed at 3 months post-distribution and decreased to 8694 (40·9%) of 21 246 at 24 months, with varying rates of decline between groups. Malaria infection prevalence at 24 months was 549 (45·8%) of 1199 children in the pyrethroid-only reference group, 472 (37·5%) of 1258 in the pyriproxyfen group (adjusted odds ratio 0·79 [95% CI 0·54-1·17], p=0·2354), 512 (40·7%) of 1259 in the piperonyl butoxide group (0·99 [0·67-1·45], p=0·9607), and 326 [25·6%] of 1272 in the chlorfenapyr group (0·45 [0·30-0·67], p=0·0001). Skin irritation or paraesthesia was the most commonly reported side-effect in all groups. Chlorfenapyr LLINs were the most cost-effective LLINs, costing only US$19 (95% uncertainty interval 1-105) more to public providers or $28 (11-120) more to donors per DALY averted over a 2-year period compared with pyrethroid-only LLINs, and saving costs from societal and household perspectives. INTERPRETATION: After 2 years, chlorfenapyr LLINs provided significantly better protection than pyrethroid-only LLINs against malaria in an area with pyrethroid-resistant mosquitoes, and the additional cost of these nets would be considerably below plausible cost-effectiveness thresholds ($292-393 per DALY averted). Before scale-up of chlorfenapyr LLINs, resistance management strategies are needed to preserve their effectiveness. Poor textile and active ingredient durability in the piperonyl butoxide and pyriproxyfen LLINs might have contributed to their relative lack of effectiveness compared with standard LLINs. FUNDING: Joint Global Health Trials scheme (UK Foreign, Commonwealth and Development Office; UK Medical Research Council; Wellcome; UK Department of Health and Social Care), US Agency for International Development, President's Malaria Initiative.

A mixed-methods exploration into the resilience of community drug distributors conducting mass drug administration for preventive chemotherapy of lymphatic filariasis and onchocerciasis in Côte d'Ivoire and Uganda.

Volunteer community drug distributors (CDDs) have been vital to progress made in the elimination of onchocerciasis and lymphatic filariasis; two neglected tropical diseases amenable to preventive chemotherapy (PC-NTDs). However, formative work in Côte d'Ivoire and Uganda revealed that CDDs can encounter considerable challenges during mass drug administration (MDA). CDDs must be resilient to overcome these challenges, yet little is known about their resilience. This mixed-methods study explored the resilience of CDDs in Côte d'Ivoire and Uganda. The characteristics and experiences of 248 CDDs involved in the 2018 MDAs in Côte d'Ivoire (N = 132) and Uganda (N = 116) were assessed using a micronarrative survey. Thematic analysis of CDDs' micronarratives was used to identify challenges they encountered during MDA. Resilience was assessed using the Connor-Davidson Resilience Scale 25 (CD-RISC-25). Variables from the micronarrative survey found to be individually associated with mean CD-RISC-25 score (P<0.05) through bivariate analyses were included in a multiple linear regression model. Post-hoc, country-specific analyses were then conducted. Thematic analysis showed that CDDs encountered a wide range of challenges during MDA. The aggregate model revealed that CDDs who had positive relationships or received support from their communities scored higher on the CD-RISC-25 on average (P<0.001 for both), indicating higher resilience. These trends were also observed in the country-specific analyses. Mean CD-RISC-25 scores were unaffected by variations in district, age, gender, and length of involvement with the NTD program. Community support during MDA and positive community-CDD relationships appear to be associated with CDDs' personal capacity to overcome adversity. Involving communities and community leadership in the selection and support of CDDs has the potential to benefit their well-being. This study establishes the CD-RISC-25 as a useful tool for assessing the resilience of CDDs. Further research is needed to understand, promote, and support the resilience of this valuable health workforce, upon which NTD programs depend.

Assessing factors influencing communities' acceptability of mass drug administration for the elimination of lymphatic filariasis in Guyana.

BACKGROUND: Guyana is one of four countries in the Latin American Region where lymphatic filariasis (LF) remains endemic. In preparation for the introduction of a new triple drug therapy regimen (ivermectin, diethylcarbamazine, and albendazole (IDA)) in 2019, an acceptability study was embedded within sentinel site mapping in four regions to assess mass drug administration (MDA) coverage and compliance, acceptability, and perceptions about treatment and disease. The results from this survey would inform the rollout of IDA in Guyana in 2019. METHODS: Data collection for the study occurred in August 2019, using a validated questionnaire administered by trained enumerators. Across all regions, a total of 1,248 participants were sampled by the Filarial Mapping team. Four-hundred and fifty-one participants aged over 18 years were randomly selected for participation in an expanded acceptability questionnaire. All data were captured in Secure Data Kit (SDK). RESULTS: Acceptability was measured using a mean acceptability score. Unadjusted mean scores ranged from 24.6 to 29.3, with 22.5 as the threshold of acceptability. Regional variation occurred across many indicators of interest: self-rated understanding about LF, mechanisms of LF transmission, LF drug safety and history of treatment during MDA. Region IV (Georgetown) recorded higher knowledge about LF, but lower compliance and acceptability. Number of pills was not perceived as a concern. CONCLUSION: Acceptability of MDA was good across all four regions under study. Results from this study set a baseline level for key indicators and acceptability, from which the acceptability of IDA can be measured. Regional variations across indicators suggest that localized approaches should be considered for social mobilization and MDA delivery to capture these contextual differences.

Spatial variability in factors influencing maternal health service use in Jimma Zone, Ethiopia: a geographically-weighted regression analysis.

BACKGROUND: Persisting within-country disparities in maternal health service access are significant barriers to attaining the Sustainable Development Goals aimed at reducing inequalities and ensuring good health for all. Sub-national decision-makers mandated to deliver health services play a central role in advancing equity but require appropriate evidence to craft effective responses. We use spatial analyses to identify locally-relevant barriers to access using sub-national data from rural areas in Jimma Zone, Ethiopia. METHODS: Cross-sectional data from 3727 households, in three districts, collected at baseline in a cluster randomized controlled trial were analysed using geographically-weighted regressions. These models help to quantify associations within women's proximal contexts by generating local parameter estimates. Data subsets, representing an empirically-identified scale for neighbourhood, were used. Local associations between outcomes (antenatal, delivery, and postnatal care use) and potential explanatory factors at individual-level (ex: health information source), interpersonal-level (ex: companion support availability) and health service-levels (ex: nearby health facility type) were modelled. Statistically significant local odds ratios were mapped to demonstrate how relevance and magnitude of associations between various explanatory factors and service outcomes change depending on locality. RESULTS: Significant spatial variability in relationships between all services and their explanatory factors (p < 0.001) was detected, apart from the association between delivery care and women's decision-making involvement (p = 0.124). Local models helped to pinpoint factors, such as danger sign awareness, that were relevant for some localities but not others. Among factors with more widespread influence, such as that of prior service use, variation in estimate magnitudes between localities was uncovered. Prominence of factors also differed between services; companion support, for example, had wider influence for delivery than postnatal care. No significant local associations with postnatal care use were detected for some factors, including wealth and decision involvement, at the selected neighbourhood scale. CONCLUSIONS: Spatial variability in service use associations means that the relative importance of explanatory factors changes with locality. These differences have important implications for the design of equity-oriented and responsive health systems. Reductions in within-country disparities are also unlikely if uniform solutions are applied to heterogeneous contexts. Multi-scale models, accommodating factor-specific neighbourhood scaling, may help to improve estimated local associations.

Protocol for a four parallel-arm, single-blind, cluster-randomised trial to assess the effectiveness of three types of dual active ingredient treated nets compared to pyrethroid-only long-lasting insecticidal nets to prevent malaria transmitted by pyrethroid insecticide-resistant vector mosquitoes in Tanzania.

INTRODUCTION: The massive scale-up of long-lasting insecticidal nets (LLINs) has led to major reductions in malaria burden in many sub-Saharan African countries. This progress is threatened by widespread insecticide resistance among malaria vectors. This cluster-randomised controlled trial (c-RCT) compares three of the most promising dual active ingredients LLINs (dual-AI LLINs), which incorporate mixtures of insecticides or insecticide synergists to standard LLINs in an area of pyrethroid insecticide resistance. METHODS: A four-arm, single-blinded, c-RCT will evaluate the effectiveness of three types of dual-AI LLINs (1) Royal Guard, combining two insecticides, pyriproxyfen and the pyrethroid alpha-cypermethrin; (2) Interceptor G2, combining chlorfenapyr and alpha-cypermethrin; (3) Olyset Plus, an LLIN combining a synergist, piperonyl butoxide and the pyrethroid permethrin, compared with; (4) Interceptor LN, a standard LLIN containing the pyrethroid alpha-cypermethrin as the sole AI. The primary outcomes are malaria infection prevalence in children aged 6 months-14 years and entomological inoculation rate (EIR), as a standard measure of malaria transmission at 24 months postintervention and cost-effectiveness. ETHICS AND DISSEMINATION: Ethical approval was received from the institutional review boards of the Tanzanian National Institute for Medical Research, Kilimanjaro Christian Medical University College, London School of Hygiene and Tropical Medicine, and University of Ottawa. Study findings will be actively disseminated via reports and presentations to stakeholders, local community leaders, and relevant national and international policy makers as well as through conferences, and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03554616.

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.

A multi-year assessment of blacklegged tick (Ixodes scapularis) population establishment and Lyme disease risk areas in Ottawa, Canada, 2017-2019.

Canadians face an emerging threat of Lyme disease due to the northward expansion of the tick vector, Ixodes scapularis. We evaluated the degree of I. scapularis population establishment and Borrelia burgdorferi occurrence in the city of Ottawa, Ontario, Canada from 2017-2019 using active surveillance at 28 sites. We used a field indicator tool developed by Clow et al. to determine the risk of I. scapularis establishment for each tick cohort at each site using the results of drag sampling. Based on results obtained with the field indicator tool, we assigned each site an ecological classification describing the pattern of tick colonization over two successive cohorts (cohort 1 was comprised of ticks collected in fall 2017 and spring 2018, and cohort 2 was collected in fall 2018 and spring 2019). Total annual site-specific I. scapularis density ranged from 0 to 16.3 ticks per person-hour. Sites with the highest density were located within the Greenbelt zone, in the suburban/rural areas in the western portion of the city of Ottawa, and along the Ottawa River; the lowest densities occurred at sites in the suburban/urban core. B. burgdorferi infection rates exhibited a similar spatial distribution pattern. Of the 23 sites for which data for two tick cohorts were available, 11 sites were classified as "high-stable", 4 were classified as "emerging", 2 were classified as "low-stable", and 6 were classified as "non-zero". B. burgdorferi-infected ticks were found at all high-stable sites, and at one emerging site. These findings suggest that high-stable sites pose a risk of Lyme disease exposure to the community as they have reproducing tick populations with consistent levels of B. burgdorferi infection. Continued surveillance for I. scapularis, B. burgdorferi, and range expansion of other tick species and emerging tick-borne pathogens is important to identify areas posing a high risk for human exposure to tick-borne pathogens in the face of ongoing climate change and urban expansion.

Species distribution models for the eastern blacklegged tick, Ixodes scapularis, and the Lyme disease pathogen, Borrelia burgdorferi, in Ontario, Canada.

The blacklegged tick, Ixodes scapularis, is established in several regions of Ontario, Canada, and continues to spread into new geographic areas across the province at a rapid rate. This poses a significant public health risk since I. scapularis transmits the Lyme disease-causing bacterium, Borrelia burgdorferi, and other pathogens of potential public health concern. The objective of this study was to develop species distribution models for I. scapularis and B. burgdorferi to predict and compare the potential distributions of the tick vector and the Lyme disease pathogen as well as the ecological factors most important for species establishment. Ticks were collected via tick dragging at 120 sites across southern, central, and eastern Ontario between 2015 and 2018 and tested for tick-borne pathogens. A maximum entropy (Maxent) approach was used to model the potential distributions of I. scapularis and B. burgdorferi. Two independent datasets derived from tick dragging at 25 new sites in 2019 and ticks submitted by the public to local health units between 2015 and 2017 were used to validate the predictive accuracy of the models. The model for I. scapularis showed high suitability for blacklegged ticks in eastern Ontario and some regions along the shorelines of the Great Lakes, and moderate suitability near Algonquin Provincial Park and the Georgian Bay with good predictive accuracy (tick dragging 2019: AUC = 0.898; ticks from public: AUC = 0.727). The model for B. burgdorferi showed a similar predicted distribution but was more constrained to eastern Ontario, particularly between Ottawa and Kingston, and along Lake Ontario, with similarly good predictive accuracy (tick dragging 2019: AUC = 0.958; ticks from public: AUC = 0.863. The ecological variables most important for predicting the distributions of I. scapularis and B. burgdorferi included elevation, distance to deciduous and coniferous forest, proportions of agricultural land, water, and infrastructure, mean summer/spring temperature, and cumulative annual degree days above 0°C. Our study presents a novel application of species distribution modelling for I. scapularis and B. burgdorferi in Ontario, Canada, and provides an up to date projection of their potential distributions for public health knowledge users.

Landscape determinants of density of blacklegged ticks, vectors of Lyme disease, at the northern edge of their distribution in Canada.

In eastern North America, including Canada, Lyme disease is caused by Borrelia burgdorferi sensu stricto and transmitted to humans by the blacklegged tick, Ixodes scapularis. The last decade has seen a growing incidence of Lyme disease in Canada, following the northward range expansion of I. scapularis tick populations from endemic areas in eastern United States. This may be attributable to movement of the many hosts that they parasitize, including songbirds, deer and small mammals. In this study, we wanted to test the effect of spatial, temporal and ecological variables, on blacklegged tick density and infection rates, near the northern limit of their distribution in Ontario and Quebec, Canada. We found an effect of both proportion of forested areas and distance to roads, on density of I. scapularis ticks and prevalence of infection by B. burgdorferi. We also found an effect of both sampling year and ordinal sampling data on prevalence of infection by B. burgdorferi. In six adjacent sites showing evidence of reproducing I. scapularis populations, we found that forest composition and structure influenced density of I. scapularis ticks. Our results suggest that blacklegged tick density and infection rate in Canada may be influenced by a variety of factors.