RESUMO
BACKGROUND: The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055). METHODS: This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony. RESULTS: A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field. CONCLUSION: While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.
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Anopheles , Controle de Mosquitos , Mosquitos Vetores , Zâmbia , Animais , Controle de Mosquitos/métodos , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/fisiologia , Feminino , Masculino , Estudos Transversais , Malária/prevenção & controle , Malária/transmissão , Estações do Ano , Inseticidas/farmacologia , Açúcares , Humanos , Comportamento AlimentarRESUMO
BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement. METHODS: ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission. RESULTS: A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition. DISCUSSION: ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy. CONCLUSIONS: Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.
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Controle de Mosquitos , Zâmbia , Controle de Mosquitos/métodos , Humanos , Animais , Feminino , Malária/prevenção & controle , Açúcares , Estudos Transversais , Mosquitos Vetores/fisiologia , Anopheles/fisiologia , MasculinoRESUMO
BACKGROUND: Community acceptance is an important criterion to assess in community trials, particularly for new tools that require high coverage and use by a target population. Installed on exterior walls of household structures, the attractive targeted sugar bait (ATSB) is a new vector control tool designed to attract and kill mosquitoes. ATSBs were evaluated in Western Zambia during a two-year cluster randomized controlled trial to assess the efficacy of ATSBs in reducing malaria transmission. Community acceptance of ATSBs was critical for successful trial implementation. METHODS: A community engagement strategy outlined activities and key messages to promote acceptance. Annual cross-sectional surveys, conducted during the peak transmission period, assessed households for presence of ATSBs as well as perceived benefits, concerns, and willingness to use ATSBs. Sixteen focus group discussions and 16 in-depth interviews, conducted at the end of each ATSB station deployment period, obtained a range of perceptions and household experiences with ATSB stations, as well as ITN use in the context of ATSB deployment. RESULTS: Methods used during the study to promote acceptance and continued use of ATSBs were effective in achieving greater than 90% coverage, a high (greater than 70%) level of perceived benefits, and fewer than 10% of households reporting safety concerns. Common facilitators of acceptance included the desire for protection against malaria and reduction of mosquitoes, trust in health initiatives, and understanding of the product. Common barriers to acceptance included misconceptions of product impact on mosquitoes, continued cases of malaria, association with satanism, and damage to household structures. DISCUSSION: Future use of the ATSB intervention will likely require activities that foster community acceptance before, during, and after the intervention is introduced. Additional research may be needed to understand the impact of different levels of community engagement on ATSB station coverage, ATSB station perception, and ITN use. CONCLUSION: There was high acceptance of ATSB stations during the trial in Western Zambia. Continuous and intense community engagement efforts contributed to sustained ATSB coverage and trust in the product. Acceptance of ATSBs during programmatic delivery requires further research.
Assuntos
Malária , Controle de Mosquitos , Zâmbia , Controle de Mosquitos/métodos , Humanos , Malária/prevenção & controle , Estudos Transversais , Feminino , Masculino , Adulto , Animais , Pessoa de Meia-Idade , Açúcares/administração & dosagem , Adulto Jovem , Inseticidas , AdolescenteRESUMO
BACKGROUND: The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials of the Westham ATSB Sarabi version 1.2. The trial sites in Kenya, Mali, and Zambia were selected to represent a range of different ecologies and malaria transmission settings across sub-Saharan Africa. This case study describes the key characteristics of the ATSB Zambia trial site to allow for interpretation of the results relative to the Kenya and Mali sites. METHODS: This study site characterization incorporates data from the trial baseline epidemiological and mosquito sugar feeding surveys conducted in 2021, as well as relevant literature on the study area. RESULTS: CHARACTERIZATION OF THE TRIAL SITE: The trial site in Zambia was comprised of 70 trial-designed clusters in Kaoma, Nkeyema, and Luampa districts. Population settlements in the trial site were dispersed across a large geographic area with sparsely populated villages. The overall population density in the 70 study clusters was 65.7 people per square kilometre with a total site population of 122,023 people living in a geographic area that covered 1858 square kilometres. However, the study clusters were distributed over a total area of approximately 11,728 square kilometres. The region was tropical with intense and seasonal malaria transmission. An abundance of trees and other plants in the trial site were potential sources of sugar meals for malaria vectors. Fourteen Anopheles species were endemic in the site and Anopheles funestus was the dominant vector, likely accounting for around 95% of all Plasmodium falciparum malaria infections. Despite high coverage of indoor residual spraying and insecticide-treated nets, the baseline malaria prevalence during the peak malaria transmission season was 50% among people ages six months and older. CONCLUSION: Malaria transmission remains high in Western Province, Zambia, despite coverage with vector control tools. New strategies are needed to address the drivers of malaria transmission in this region and other malaria-endemic areas in sub-Saharan Africa.
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Anopheles , Malária , Controle de Mosquitos , Mosquitos Vetores , Açúcares , Zâmbia , Controle de Mosquitos/métodos , Controle de Mosquitos/estatística & dados numéricos , Mosquitos Vetores/efeitos dos fármacos , Animais , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Humanos , Malária/prevenção & controle , Malária/transmissão , Feminino , Inseticidas/farmacologiaRESUMO
BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a novel tool with potential to complement current approaches to malaria vector control. To assess the public health value of ATSB station deployment in areas of high coverage with standard vector control, a two-arm cluster-randomized controlled trial (cRCT) of Sarabi ATSB® stations (Westham Ltd., Hod-Hasharon, Israel) was conducted in Western Province, Zambia, a high-burden location were Anopheles funestus is the dominant vector. The trial included 70 clusters and was designed to measure the effect of ATSBs on case incidence and infection prevalence over two 7-month deployments. Reported here are results of the vector surveillance component of the study, conducted in a subset of 20 clusters and designed to provide entomological context to guide overall interpretation of trial findings. METHODS: Each month, 200 paired indoor-outdoor human landing catch (HLC) and 200 paired light trap (LT) collections were conducted to monitor An. funestus parity, abundance, biting rates, sporozoite prevalence, and entomological inoculation rates (EIR). RESULTS: During the study 20,337 female An. funestus were collected, 11,229 from control and 9,108 from intervention clusters. A subset of 3,131 HLC specimens were assessed for parity: The mean non-parous proportion was 23.0% (95% CI 18.2-28.7%, total n = 1477) in the control and 21.2% (95% CI 18.8-23.9%, total n = 1654) in the intervention arm, an OR = 1.05 (95% CI 0.82-1.34; p = 0.688). A non-significant reduction in LT abundance (RR = 0.65 [95% CI 0.30-1.40, p = 0.267]) was associated with ATSB deployment. HLC rates were highly variable, but model results indicate a similar non-significant trend with a RR = 0.68 (95%CI 0.22-2.00; p = 0.479). There were no effects on sporozoite prevalence or EIR. CONCLUSIONS: Anopheles funestus parity did not differ across study arms, but ATSB deployment was associated with a non-significant 35% reduction in vector LT density, results that are consistent with the epidemiological impact reported elsewhere. Additional research is needed to better understand how to maximize the potential impact of ATSB approaches in Zambia and other contexts. TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov (NCT04800055, 16 March 2021).
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Anopheles , Controle de Mosquitos , Mosquitos Vetores , Zâmbia , Anopheles/fisiologia , Animais , Mosquitos Vetores/fisiologia , Controle de Mosquitos/métodos , Feminino , Humanos , Açúcares , Malária/prevenção & controleRESUMO
BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a promising new approach to malaria vector control that could compliment current tools by exploiting the natural sugar feeding behaviors of mosquitoes. Recent proof of concept work with a prototype ATSB® Sarabi Bait Station (Westham Co., Hod-Hasharon, Israel) has demonstrated high feeding rates and significant reductions in vector density, human biting rate, and overall entomological inoculation rate for Anopheles gambiae sensu lato (s.l.) in the tropical savannah of western Mali. The study reported here was conducted in the more temperate, rainier region of Western Province, Zambia and was designed to confirm the primary vector species in region and to estimate corresponding rates of feeding from prototype attractive sugar bait (ASB) Sarabi Bait Stations. METHODS: The product evaluated was the Sarabi v1.1.1 ASB station, which did not include insecticide but did include 0.8% uranine as a dye allowing for the detection, using UV fluorescence light microscopy, of mosquitoes that have acquired a sugar meal from the ASB. A two-phase, crossover study design was conducted in 10 village-based clusters in Western Province, Zambia. One study arm initially received 2 ASB stations per eligible structure while the other initially received 3. Primary mosquito sampling occurred via indoor and outdoor CDC Miniature UV Light Trap collection from March 01 through April 09, 2021 (Phase 1) and from April 19 to May 28, 2021 (Phase 2). RESULTS: The dominant vector in the study area is Anopheles funestus s.l., which was the most abundant species group collected (31% of all Anophelines; 45,038/144,5550), had the highest sporozoite rate (3.16%; 66 positives out of 2,090 tested), and accounted for 94.3% (66/70) of all sporozoite positive specimens. Of those An. funestus specimens further identified to species, 97.2% (2,090/2,150) were An. funestus sensu stricto (s.s.). Anopheles gambiae s.l. (96.8% of which were Anopheles arabiensis) is a likely secondary vector and Anopheles squamosus may play a minor role in transmission. Overall, 21.6% (9,218/42,587) of An. funestus specimens and 10.4% (201/1,940) of An. gambiae specimens collected were positive for uranine, translating into an estimated daily feeding rate of 8.9% [7.7-9.9%] for An. funestus (inter-cluster range of 5.5% to 12.7%) and 3.9% [3.3-4.7%] for An. gambiae (inter-cluster range of 1.0-5.2%). Feeding rates were no different among mosquitoes collected indoors or outdoors, or among mosquitoes from clusters with 2 or 3 ASBs per eligible structure. Similarly, there were no correlations observed between feeding rates and the average number of ASB stations per hectare or with weekly rainfall amounts. CONCLUSIONS: Anopheles funestus and An. gambiae vector populations in Western Province, Zambia readily fed from the prototype Sarabi v1.1.1 ASB sugar bait station. Observed feeding rates are in line with those thought to be required for ATSB stations to achieve reductions in malaria transmission when used in combination with conventional control methods (IRS or LLIN). These results supported the decision to implement a large-scale, epidemiological cluster randomized controlled trial of ATSB in Zambia, deploying 2 ATSB stations per eligible structure.
Assuntos
Anopheles , Malária , Humanos , Animais , Açúcares , Zâmbia , Estudos Cross-Over , Fluoresceína , Malária/prevenção & controle , Mosquitos VetoresRESUMO
BACKGROUND: While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. METHODS: This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. RESULTS: This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey-derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. CONCLUSION: ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.
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Malária , Cuidado Pré-Natal , Gravidez , Feminino , Humanos , Estudos Transversais , Malária/diagnóstico , Malária/epidemiologia , Malária/prevenção & controle , Número de Gestações , Tanzânia/epidemiologia , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Malaria is a major cause of morbidity and mortality globally, especially in sub-Saharan Africa. Widespread resistance to pyrethroids threatens the gains achieved by vector control. To counter resistance to pyrethroids, third-generation indoor residual spraying (3GIRS) products have been developed. This study details the results of a multi-country cost and cost-effectiveness analysis of indoor residual spraying (IRS) programmes using Actellic®300CS, a 3GIRS product with pirimiphos-methyl, in sub-Saharan Africa in 2017 added to standard malaria control interventions including insecticide-treated bed nets versus standard malaria control interventions alone. METHODS: An economic evaluation of 3GIRS using Actellic®300CS in a broad range of sub-Saharan African settings was conducted using a variety of primary data collection and evidence synthesis methods. Four IRS programmes in Ghana, Mali, Uganda, and Zambia were included in the effectiveness analysis. Cost data come from six IRS programmes: one in each of the four countries where effect was measured plus Mozambique and a separate programme conducted by AngloGold Ashanti Malaria Control in Ghana. Financial and economic costs were quantified and valued. The main indicator for the cost was cost per person targeted. Country-specific case incidence rate ratios (IRRs), estimated by comparing IRS study districts to adjacent non-IRS study districts or facilities, were used to calculate cases averted in each study area. A deterministic analysis and sensitivity analysis were conducted in each of the four countries for which effectiveness evaluations were available. Probabilistic sensitivity analysis was used to generate plausibility bounds around the incremental cost-effectiveness ratio estimates for adding IRS to other standard interventions in each study setting as well as jointly utilizing data on effect and cost across all settings. RESULTS: Overall, IRRs from each country indicated that adding IRS with Actellic®300CS to the local standard intervention package was protective compared to the standard intervention package alone (IRR 0.67, [95% CI 0.50-0.91]). Results indicate that Actellic®300CS is expected to be a cost-effective (> 60% probability of being cost-effective in all settings) or highly cost-effective intervention across a range of transmission settings in sub-Saharan Africa. DISCUSSION: Variations in the incremental costs and cost-effectiveness likely result from several sources including: variation in the sprayed wall surfaces and house size relative to household population, the underlying malaria burden in the communities sprayed, the effectiveness of 3GIRS in different settings, and insecticide price. Programmes should be aware that current recommendations to rotate can mean variation and uncertainty in budgets; programmes should consider this in their insecticide-resistance management strategies. CONCLUSIONS: The optimal combination of 3GIRS delivery with other malaria control interventions will be highly context specific. 3GIRS using Actellic®300CS is expected to deliver acceptable value for money in a broad range of sub-Saharan African malaria transmission settings.
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Inseticidas , Malária , Compostos Organotiofosforados , Piretrinas , Análise Custo-Benefício , Coleta de Dados , Humanos , Malária/epidemiologia , Mali , Controle de Mosquitos/métodosRESUMO
BACKGROUND: Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings. METHODS: Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data. CONCLUSIONS: Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact.
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Efeitos Psicossociais da Doença , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/prevenção & controle , Controle de Mosquitos/estatística & dados numéricos , África Subsaariana/epidemiologia , Humanos , Incidência , Mosquiteiros Tratados com Inseticida/classificação , Malária/epidemiologia , Projetos Piloto , PrevalênciaRESUMO
Spatial repellents (SRs) reduce human-mosquito contact by preventing mosquito entrance into human-occupied spaces and interfering with host-seeking and blood-feeding. A new model to synthesize experimental data on the effects of transfluthrin on Aedes aegypti explores how SR effects interact to impact the epidemiology of diseases vectored by these mosquitoes. Our results indicate that the greatest impact on force of infection is expected to derive from the chemical's lethal effect but delayed biting and the negative effect this may have on the mosquito population could elicit substantial impact in the absence of lethality. The relative contributions of these effects depend on coverage, chemical dose, and housing density. We also demonstrate that, through an increase in the number of potentially infectious mosquito bites, increased partial blood-feeding and reduced exiting may elicit adverse impacts, which could offset gains achieved by other effects. Our analysis demonstrates how small-scale experimental data can be leveraged to derive expectations of epidemiological impact of SRs deployed at larger scales.
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Aedes/microbiologia , Repelentes de Insetos , Controle de Mosquitos/métodos , Mosquitos Vetores , Aedes/virologia , Animais , Ciclopropanos/farmacologia , Fluorbenzenos/farmacologiaRESUMO
BACKGROUND: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. METHODS: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. RESULTS: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. CONCLUSION: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1.
Assuntos
Anopheles , Análise Custo-Benefício , Inseticidas , Controle de Mosquitos/economia , Mosquitos Vetores , Compostos Organotiofosforados , Animais , Incidência , Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Malária/epidemiologia , Malária/transmissão , Moçambique/epidemiologia , PrevalênciaRESUMO
BACKGROUND: The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. METHODS: The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. RESULTS: The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI95 33-59%; p < 0.001) in indoor light traps and by 74% (CI95 38-90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI95 1.00-1.21) in no-IRS villages and 0.88 (CI95 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI95 47-88%; p = 0. < 0.001) and outdoors (68% reduction: CI95 22-87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI95 7-53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. CONCLUSION: IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.
Assuntos
Inseticidas/farmacologia , Malária/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores/efeitos dos fármacos , Compostos Organotiofosforados/farmacologia , Animais , Anopheles/efeitos dos fármacos , Entomologia/métodos , Monitoramento Ambiental/estatística & dados numéricos , Feminino , Humanos , Mosquiteiros Tratados com Inseticida , Moçambique , Propriedade/estatística & dados numéricos , Piretrinas/farmacologiaRESUMO
BACKGROUND: Ghana has been implementing the indoor residual spraying (IRS) of insecticides since 2006, focusing operations in the north. Insecticide resistance concerns prompted a switch from pyrethroids to organophosphates, beginning gradually in 2011 and switching fully to the micro-encapsulated formulation of pirimiphosmethyl (PM CS), Actellic® 300CS, a third-generation indoor residual spraying (3GIRS) product, by 2014. Entomological surveillance studies have shown IRS to be a highly effective malaria control tool, but epidemiological evidence is needed as well. Countrywide prevalence surveys have shown that malaria parasite prevalence in children under 5 years of age in Northern, Upper East, and Upper West Regions had declined to less than 40% in each region by 2016. Similarly, malaria deaths in children under 5 years of age have also been declining nationally since 2009. Although IRS is suspected to have contributed to this decline, stronger evidence is needed to link the IRS interventions to the epidemiological impact. METHODS: To assess the epidemiological impact of Ghana's IRS programmatic activities, a retrospective, observational analysis using routine epidemiological data was conducted to compare malaria incidence rates from IRS and non-IRS districts in Northern, Upper East, and Upper West Regions. Routine epidemiological data consisted of passive malaria case surveillance data reported in the District Health Information System 2 (DHIS2); with cases representing patients with suspected malaria who had sought care in the public health system and had received a confirmatory diagnosis with a positive malaria RDT result. Final routine data were extracted in September 2018. All districts that had received IRS were included in the analysis and compared to all non-IRS districts within the same region. In the Northern Region, only PMI districts were included in the analysis, as they had similar historical data. RESULTS: District-level analysis from Northern Region from 2015 to 2017 of the aggregate malaria incidence reported from IRS districts relative to non-IRS comparator districts showed 39%, 26%, and 58% fewer confirmed malaria cases reported from IRS districts in 2015, 2016, and 2017, respectively. This translates to approximately 257,000 fewer cases than expected over the three years. In Upper East Region, the effect on reported malaria cases of withdrawing IRS from the region was striking; after spray operations were suspended in 2015, incidence increased an average of 485% per district (95% confidence interval: 330% to 640%) compared to 2014. CONCLUSIONS: The current observational analysis results are in line with the entomological studies in demonstrating the positive contribution of IRS with a 3GIRS product to malaria control programmes in northern Ghana and the value of using routine surveillance and implementation data to rapidly assess the impact of vector control interventions in operational settings, even in complex implementation environments.
Assuntos
Inseticidas/administração & dosagem , Malária/epidemiologia , Controle de Mosquitos/estatística & dados numéricos , Gana/epidemiologia , Humanos , Incidência , Malária/prevenção & controle , Controle de Mosquitos/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: The National Malaria Control Programme (NMCP) of Mali has had recent success decreasing malaria transmission using 3rd generation indoor residual spraying (IRS) products in areas with pyrethroid resistance, primarily in Ségou and Koulikoro Regions. In 2015, national survey data showed that Mopti Region had the highest under 5-year-old (u5) malaria prevalence at 54%-nearly twice the national average-despite having high access to long-lasting insecticidal nets (LLINs) and seasonal malaria chemoprevention (SMC). Accordingly, in 2016 the NMCP and other stakeholders shifted IRS activities from Ségou to Mopti. Here, the results of a series of observational analyses utilizing routine malaria indicators to evaluate the impact of this switch are presented. METHODS: A set of retrospective, eco-observational time-series analyses were performed using monthly incidence rates of rapid diagnostic test (RDT)-confirmed malaria cases reported in the District Health Information System 2 (DHIS2) from January 2016 until February 2018. Comparisons of case incidence rates were made between health facility catchments from the same region that differed in IRS status (IRS vs. no-IRS) to describe the general impact of the 2016 and 2017 IRS campaigns, and a difference-in-differences approach comparing changes in incidence from year-to-year was used to describe the effect of suspending IRS operations in Ségou and introducing IRS operations in Mopti in 2017. RESULTS: Compared to communities with no IRS, cumulative case incidence rates in IRS communities were reduced 16% in Ségou Region during the 6 months following the 2016 campaign and 31% in Mopti Region during the 6 months following the 2017 campaign, likely averting a total of more than 22,000 cases of malaria that otherwise would have been expected during peak transmission months. Across all comparator health facilities (HFs) where there was no IRS in either year, peak malaria case incidence rates fell by an average of 22% (CI95 18-30%) from 2016 to 2017. At HFs in communities of Mopti where IRS was introduced in 2017, peak incidence fell by an average of 42% (CI95 31-63%) between these years, a significantly greater decrease (p = 0.040) almost double what was seen in the comparator HFCAs. The opposite effect was observed in Ségou Region, where peak incidence at those HFs where IRS was withdrawn after the 2016 campaign increased by an average of 106% (CI95 63-150%) from year to year, also a significant difference-in-differences compared to the comparator no-IRS HFs (p < 0.0001). CONCLUSION: Annual IRS campaigns continue to make dramatic contributions to the seasonal reduction of malaria transmission in communities across central Mali, where IRS campaigns were timed in advance of peak seasonal transmission and utilized a micro-encapsulated product with an active ingredient that was of a different class than the one found on the LLINs used throughout the region and to which local malaria vectors were shown to be susceptible. Strategies to help mitigate the resurgence of malaria cases that can be expected should be prioritized whenever the suspension of IRS activities in a particular region is considered.
Assuntos
Controle de Doenças Transmissíveis/estatística & dados numéricos , Erradicação de Doenças/estatística & dados numéricos , Malária Falciparum/prevenção & controle , Resíduos de Praguicidas , Humanos , Incidência , Malária Falciparum/epidemiologia , Mali/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Ségou Region in central Mali is an area of high malaria burden with seasonal transmission. The region reports high access to and use of long-lasting insecticidal nets (LLINs), though the principal vector, Anopheles gambiae, is resistant to pyrethroids. From 2011 until 2016, several high-burden districts of Ségou also received indoor residual spraying (IRS), though in 2014 concerns about pyrethroid resistance prompted a shift in IRS products to a micro-encapsulated formulation of the organophosphate insecticide pirimiphos-methyl. Also in 2014, the region expanded a pilot programme to provide seasonal malaria chemoprevention (SMC) to children aged 3-59 months in two districts. The timing of these decisions presented an opportunity to estimate the impact of both interventions, deployed individually and in combination, using quality-assured passive surveillance data. METHODS: A non-randomized, quasi-experimental time series approach was used to analyse monthly trends in malaria case incidence at the district level. Districts were stratified by intervention status: an SMC district, an IRS district, an IRS + SMC district, and control districts that received neither IRS nor SMC in 2014. The numbers of positive rapid diagnostic test (RDT +) results reported at community health facilities were aggregated and epidemiological curves showing the incidence of RDT-confirmed malaria cases per 10,000 person-months were plotted for the total all-ages and for the under 5 year old (u5) population. The cumulative incidence of RDT + malaria cases observed from September 2014 to February 2015 was calculated in each intervention district and compared to the cumulative incidence reported from the same period in the control districts. RESULTS: Cumulative peak-transmission all-ages incidence was lower in each of the intervention districts compared to the control districts: 16% lower in the SMC district; 28% lower in the IRS district; and 39% lower in the IRS + SMC district. The same trends were observed in the u5 population: incidence was 15% lower with SMC, 48% lower with IRS, and 53% lower with IRS + SMC. The SMC-only intervention had a more moderate effect on incidence reduction initially, which increased over time. The IRS-only intervention had a rapid, comparatively large impact initially that waned over time. The impact of the combined interventions was both rapid and longer lasting. CONCLUSION: Evaluating the impact of IRS with an organophosphate and SMC on reducing incidence rates of passive RDT-confirmed malaria cases in Ségou Region in 2014 suggests that combining the interventions had a greater effect than either intervention used individually in this high-burden region of central Mali with pyrethroid-resistant vectors and high rates of household access to LLINs.
Assuntos
Anopheles , Antimaláricos/uso terapêutico , Controle de Doenças Transmissíveis/métodos , Inseticidas , Malária Falciparum/prevenção & controle , Controle de Mosquitos/métodos , Mosquitos Vetores , Compostos Organotiofosforados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Mali/epidemiologia , Pessoa de Meia-Idade , Resíduos de Praguicidas , Adulto JovemRESUMO
BACKGROUND: Ségou Region in Central Mali is an area of high malaria burden with seasonal transmission, high access to and use of long-lasting insecticidal nets (LLINs), and resistance to pyrethroids and DDT well documented in Anopheles gambiae s.l. (the principal vector of malaria in Mali). Ségou has recently received indoor residual spraying (IRS) supported by Mali's collaboration with the US President's Malaria Initiative/Africa Indoor Residual Spraying programme. From 2012 to 2015, two different non-pyrethroid insecticides: bendiocarb in 2012 and 2013 and pirimiphos-methyl in 2014 and 2015, were used for IRS in two districts. This report summarizes the results of observational analyses carried out to assess the impact of these IRS campaigns on malaria incidence rates reported through local and district health systems before and after spraying. METHODS: A series of retrospective time series analyses were performed on 1,382,202 rapid diagnostic test-confirmed cases of malaria reported by district routine health systems in Ségou Region from January 2012 to January 2016. Malaria testing, treatment, surveillance and reporting activities remained consistent across districts and years during the study period, as did LLIN access and use estimates as well as An. gambiae s.l. insecticide resistance patterns. Districts were stratified by IRS implementation status and all-age monthly incidence rates were calculated and compared across strata from 2012 to 2014. In 2015 a regional but variable scale-up of seasonal malaria chemoprevention complicated the region-wide analysis; however IRS operations were suspended in Bla District that year so a difference in differences approach was used to compare 2014 to 2015 changes in malaria incidence at the health facility level in children under 5-years-old from Bla relative to changes observed in Barouéli, where IRS operations were consistent. RESULTS: During 2012-2014, rapid reductions in malaria incidence were observed during the 6 months following each IRS campaign, though most of the reduction in cases (70% of the total) was concentrated in the first 2 months after each campaign was completed. Compared to non-IRS districts, in which normal seasonal patterns of malaria incidence were observed, an estimated 286,745 total fewer cases of all-age malaria were observed in IRS districts. The total cost of IRS in Ségou was around 9.68 million USD, or roughly 33.75 USD per case averted. Further analysis suggests that the timing of the 2012-2014 IRS campaigns (spraying in July and August) was well positioned to maximize public health impact. Suspension of IRS in Bla District after the 2014 campaign resulted in a 70% increase in under-5-years-old malaria incidence rates from 2014 to 2015, significantly greater (p = 0.0003) than the change reported from Barouéli District, where incidence rates remained the same. CONCLUSIONS: From 2012 to 2015, the annual IRS campaigns in Ségou are associated with several hundred thousand fewer cases of malaria. This work supports the growing evidence that shows that IRS with non-pyrethroid insecticides is a wise public health investment in areas with documented pyrethroid resistance, high rates of LLIN coverage, and where house structures and population densities are appropriate. Additionally, this work highlights the utility of quality-assured and validated routine surveillance and well defined observational analyses to rapidly assess the impact of malaria control interventions in operational settings, helping to empower evidence-based decision making and to further grow the evidence base needed to better understand when and where to utilize new vector control tools as they become available.
Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Inseticidas/administração & dosagem , Malária/epidemiologia , Malária/prevenção & controle , Controle de Mosquitos/métodos , Compostos Organotiofosforados/administração & dosagem , Fenilcarbamatos/administração & dosagem , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Mali/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Campaigns for the continued reduction and eventual elimination of malaria may benefit from new and innovative vector control tools. One novel approach being considered uses a push-pull strategy, whereby spatial repellents are used in combination with outdoor baited traps. The desired effect is the behavioural manipulation of mosquito populations to elicit movement of vectors away from people and into traps. METHODS: Here, a prototype push-pull intervention was evaluated using an experimental hut methodology to test proof-of-principle for the strategy against two natural vector populations, Anopheles albimanus and Anopheles vestitipennis, in Belize, Central America. A Latin square study design was used to compare mosquito entry into experimental huts and outdoor traps across four different experimental conditions: 1) control, with no interventions; 2) pull, utilizing only outdoor traps; 3) push, utilizing only an indoor spatial repellent; and 4) push-pull, utilizing both interventions simultaneously. RESULTS: For An. vestitipennis, the combined use of an indoor repellent and outdoor baited traps reduced average nightly mosquito hut entry by 39% (95% CI: [0.37-0.41]) as compared to control and simultaneously increased the nightly average densities of An. vestitipennis captured in outdoor baited traps by 48% (95% CI: [0.22-0.74]), compared to when no repellent was used. Against An. albimanus, the combined push-pull treatment similarly reduced hut entry, by 54% (95% CI: [0.40-0.68]) as compared to control; however, the presence of a repellent indoors did not affect overall outdoor trap catch densities for this species. Against both anopheline species, the combined intervention did not further reduce mosquito hut entry compared to the use of repellent alone. CONCLUSIONS: The prototype intervention evaluated here clearly demonstrated that push-pull strategies have potential to reduce human-vector interactions inside homes by reducing mosquito entry, and highlighted the possibility for the strategy to simultaneously decrease human-vector interactions outside of homes by increasing baited trap collections. However, the variation in effect on different vectors demonstrates the need to characterize the underlying behavioral ecology of target mosquitoes in order to drive local optimization of the intervention.
Assuntos
Anopheles , Repelentes de Insetos , Insetos Vetores , Malária/prevenção & controle , Controle de Mosquitos/métodos , Animais , Belize , Feminino , Humanos , Malária/transmissãoRESUMO
To achieve maximum success from any vector control intervention, it is critical to identify the most efficacious tools available. The principal aim of this study was to evaluate the efficacy of 2 commercially available adult mosquito traps for capturing Anopheles albimanus and An. vestitipennis, 2 important malaria vectors in northern Belize, Central America. Additionally, the impact of outdoor baited traps on mosquito entry into experimental huts was assessed. When operated outside of human-occupied experimental huts, the Centers for Disease Control and Prevention (CDC) miniature light trap, baited with human foot odors, captured significantly greater numbers of female An. albimanus per night (5.1 ± 1.9) than the Biogents Sentinel™ trap baited with BG-Lure™ (1.0 ± 0.2). The 2 trap types captured equivalent numbers of female An. vestitipennis per night, 134.3 ± 45.6 in the CDC trap and 129.6 ± 25.4 in the Sentinel trap. When compared to a matched control hut using no intervention, the use of baited CDC light traps outside an experimental hut did not impact the entry of An. vestitipennis into window interception traps, 17.1 ± 1.3 females per hour in experimental huts vs. 17.2 ± 1.4 females per hour in control huts. However, the use of outdoor baited CDC traps did significantly decrease the entry of An. albimanus into window interception traps from 3.5 ± 0.5 females per hour to 1.9 ± 0.2 females per hour. These results support existing knowledge that the underlying ecological and behavioral tendencies of different Anopheles species can influence trap efficacy. Furthermore, these findings will be used to guide trap selection for future push-pull experiments to be conducted at the study site.
Assuntos
Anopheles , Controle de Mosquitos/métodos , Mosquitos Vetores , Animais , Belize , Feminino , Malária/transmissão , Odorantes/análise , Especificidade da EspécieRESUMO
The first record of Aedes albopictus in northern Belize was made in Orange Walk Town, Orange Walk District, on November 3, 2011. Aedes spp. larvae were collected during a routine Ministry of Health mosquito survey and reared to adults. Upon emergence, a mixed population of Aedes aegypti (35) and Ae. albopictus (11) was observed (aegypti:albopictus = 3:1). Subsequent larval and adult surveys in Orange Walk and Corozal District, also in northern Belize, have confirmed the presence of Ae. albopictus, thereby indicating the range expansion and establishment of this nuisance biter and potential disease vector in Belize.