RESUMO
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.
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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: 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.
Assuntos
Controle de Mosquitos , Zâmbia , Controle de Mosquitos/métodos , Humanos , Animais , Feminino , Malária/prevenção & controle , Açúcares , Estudos Transversais , Mosquitos Vetores/fisiologia , Anopheles/fisiologia , MasculinoRESUMO
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: 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: In 2020, the Zambia National Malaria Elimination Centre targeted the distribution of long-lasting insecticidal nets (LLINs) and indoor-residual spraying (IRS) campaigns based on sub-district micro-planning, where specified geographical areas at the health facility catchment level were assigned to receive either LLINs or IRS. Using data from the 2021 Malaria Indicator Survey (MIS), the objectives of this analysis were to (1) assess how well the micro-planning was followed in distributing LLINs and IRS, (2) investigate factors that contributed to whether households received what was planned, and (3) investigate how overall coverage observed in the 2021 MIS compared to the 2018 MIS conducted prior to micro-planning. METHODS: Households' receipt of ≥ 1 LLIN, and/or IRS within the past 12 months in the 2021 MIS, was compared against the micro-planning area under which the households fell. GPS points for 3,550 households were overlayed onto digitized micro-planning maps in order to determine what micro-plan the households fell under, and thus whether they received their planned intervention. Mixed-effects regression models were conducted to investigate what factors affected whether these households: (1) received their planned intervention, and (2) received any intervention. Finally, coverage indicators between the 2021 and 2018 MIS were compared. RESULTS: Overall, 60.0% (95%CI 55.4, 64.4) of households under a micro-plan received their assigned intervention, with significantly higher coverage of the planned intervention in LLIN-assigned areas (75.7% [95%CI 69.5, 80.9]) compared to IRS-assigned areas (49.4% [95%CI: 44.4, 54.4]). Regression analysis indicated that households falling under the IRS micro-plan had significantly reduced odds of receiving their planned intervention (OR: 0.34 [95%CI 0.24, 0.48]), and significantly reduced odds of receiving any intervention (OR: 0.51 [95%CI 0.37, 0.72] ), compared to households under the LLIN micro-plan. Comparison between the 2021 and 2018 MIS indicated a 27% reduction in LLIN coverage nationally in 2021, while IRS coverage was similar. Additionally, between 2018 and 2021, there was a 13% increase in households that received neither intervention. CONCLUSIONS: This analysis shows that although the micro-planning strategy adopted in 2020 worked much better for LLIN-assigned areas compared to IRS-assigned areas, there was reduced overall vector control coverage in 2021 compared to 2018 before micro-planning.
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Mosquiteiros Tratados com Inseticida , Inseticidas , Malária , Humanos , Controle de Mosquitos , Zâmbia/epidemiologia , Malária/prevenção & controleRESUMO
BACKGROUND: Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria. METHODS: This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose-response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia's interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding. RESULTS: The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75-0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66-0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population. CONCLUSIONS: CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.
Assuntos
Antimaláricos , Sistemas de Informação em Saúde , Malária , Criança , Humanos , Antimaláricos/uso terapêutico , Zâmbia/epidemiologia , Administração de Caso , Estudos Retrospectivos , Pacientes Internados , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária/tratamento farmacológico , Malária/prevenção & controle , Malária/epidemiologia , Agentes Comunitários de SaúdeRESUMO
Efforts to eliminate malaria transmission need evidence-based strategies. However, accurately assessing end-game malaria elimination strategies is challenging due to the low level of transmission and the rarity of infections. We hypothesised that presumptively treating individuals during reactive case detection (RCD) would reduce transmission and that serology would more sensitively detect this change over standard approaches. We conducted a cluster randomised control trial (NCT02654912) of presumptive reactive focal drug administration (RFDA-intervention) compared to the standard of care, reactive focal test and treat (RFTAT-control) in Southern Province, Zambia-an area of low seasonal transmission (overall incidence of ~3 per 1,000). We measured routine malaria incidence from health facilities as well as PCR parasite prevalence / antimalarial seroprevalence in an endline cross-sectional population survey. No significant difference was identified from routine incidence data and endline prevalence by polymerase chain reaction (PCR) had insufficient numbers of malaria infections (i.e., 16 infections among 6,276 children) to assess the intervention. Comparing long-term serological markers, we found a 19% (95% CI = 4-32%) reduction in seropositivity for the RFDA intervention using a difference in differences approach incorporating serological positivity and age. We also found a 37% (95% CI = 2-59%) reduction in seropositivity to short-term serological markers in a post-only comparison. These serological analyses provide compelling evidence that RFDA both has an impact on malaria transmission and is an appropriate end-game malaria elimination strategy. Furthermore, serology provides a more sensitive approach to measure changes in transmission that other approaches miss, particularly in very low transmission settings. Trial Registration: Registered at www.clinicaltrials.gov (NCT02654912, 13/1/2016).
RESUMO
BACKGROUND: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, 2 months apart (coverage 70% and 57%, respectively). We evaluated the impact of 1 year of pMDA on malaria incidence using routine data. METHODS: We conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. Programmatic mass drug administration was conducted in HFCAs with greater than 50 cases/1000 people per year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared with 20 HFCAs marginally below (comparison group). RESULTS: The pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio = 0.536; confidence interval = 0.337-0.852); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption. CONCLUSIONS: Programmatic mass drug administration, implemented during 1 year with imperfect coverage in low transmission areas with suboptimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses.
Assuntos
Antimaláricos , Malária , Antimaláricos/uso terapêutico , Humanos , Incidência , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/prevenção & controle , Administração Massiva de Medicamentos , Zâmbia/epidemiologiaRESUMO
BACKGROUND: Malaria programmes in countries with low transmission levels require evidence to optimize deployment of current and new tools to reach elimination with limited resources. Recent pilots of elimination strategies in Ethiopia, Senegal, and Zambia produced evidence of their epidemiological impacts and costs. There is a need to generalize these findings to different epidemiological and health systems contexts. METHODS: Drawing on experience of implementing partners, operational documents and costing studies from these pilots, reference scenarios were defined for rapid reporting (RR), reactive case detection (RACD), mass drug administration (MDA), and in-door residual spraying (IRS). These generalized interventions from their trial implementation to one typical of programmatic delivery. In doing so, resource use due to interventions was isolated from research activities and was related to the pilot setting. Costing models developed around this reference implementation, standardized the scope of resources costed, the valuation of resource use, and the setting in which interventions were evaluated. Sensitivity analyses were used to inform generalizability of the estimates and model assumptions. RESULTS: Populated with local prices and resource use from the pilots, the models yielded an average annual economic cost per capita of $0.18 for RR, $0.75 for RACD, $4.28 for MDA (two rounds), and $1.79 for IRS (one round, 50% households). Intervention design and resource use at service delivery were key drivers of variation in costs of RR, MDA, and RACD. Scale was the most important parameter for IRS. Overall price level was a minor contributor, except for MDA where drugs accounted for 70% of the cost. The analyses showed that at implementation scales comparable to health facility catchment area, systematic correlations between model inputs characterizing implementation and setting produce large gradients in costs. CONCLUSIONS: Prospective costing models are powerful tools to explore resource and cost implications of policy alternatives. By formalizing translation of operational data into an estimate of intervention cost, these models provide the methodological infrastructure to strengthen capacity gap for economic evaluation in endemic countries. The value of this approach for decision-making is enhanced when primary cost data collection is designed to enable analysis of the efficiency of operational inputs in relation to features of the trial or the setting, thus facilitating transferability.
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Erradicação de Doenças/economia , Malária/prevenção & controle , Projetos Piloto , Etiópia , Humanos , Senegal , ZâmbiaRESUMO
From 2014 to 2016, a community-randomized controlled trial in Southern Province, Zambia, compared mass drug administration (MDA) and focal MDA (fMDA) with the standard of care. Acceptability of the intervention was assessed quantitatively using closed-ended and Likert scale-based questions posed during three household surveys conducted from April to May in 2014, 2015, and 2016 in 40 health catchments that implemented MDA and fMDA and 20 catchments that served as trial controls. In 2014 and 2015, 47 households per catchment were selected, targeting 1,880 households in MDA and fMDA trial arms; in 2016, 55 households per catchment were selected for a target of 2,200 households in MDA and fMDA trial arms. Concurrently, 27 focus group discussions and 23 in-depth interviews with 248 participants were conducted on reasons for testing and treatment refusal, reasons for nonadherence, and community perception of the MDA campaign. Results demonstrated that the MDA campaign was highly accepted with more than 99% of respondents stating that they would take treatment if positive for malaria. High acceptability at baseline could be associated with test-and-treat campaigns recently conducted in the study area. There was a large increase in the acceptability of prophylactic treatment if negative for malaria from the baseline to follow-up survey for adults and children, from 62% to 96% for each. This likely resulted from an intensive community-wide sensitization program that occurred before the first treatment round at each household during community health worker visits.
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Artemisininas/administração & dosagem , Atitude Frente a Saúde , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Aceitação pelo Paciente de Cuidados de Saúde , Quinolinas/administração & dosagem , Adulto , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Feminino , Grupos Focais , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Quinolinas/uso terapêutico , Zâmbia/epidemiologiaRESUMO
Rigorous evidence of effectiveness is needed to determine where and when to apply mass drug administration (MDA) or focal MDA (fMDA) as part of a malaria elimination strategy. The Zambia National Malaria Elimination Centre recently completed a community-randomized controlled trial in Southern Province to evaluate MDA and fMDA for transmission reduction. To assess the role of MDA and fMDA on infection incidence, we enrolled a longitudinal cohort for an 18-month period of data collection including monthly malaria parasite infection detection based on polymerase chain reaction and compared time to first infection and cumulative infection incidence outcomes across study arms using Cox proportional hazards and negative binomial models. A total of 2,026 individuals from 733 households were enrolled and completed sufficient follow-up for inclusion in analysis. Infection incidence declined dramatically across all study arms during the period of study, and MDA was associated with reduced risk of first infection (hazards ratio: 0.36; 95% CI: 0.16-0.80) and cumulative infection incidence during the first rainy season (first 5 months of follow-up) (incidence rate ratio: 0.34; 95% CI: 0.12-0.95). No significant effect was found for fMDA or for either arm over the full study period. Polymerase chain reaction infection status at baseline was strongly associated with follow-up infection. The short-term effects of MDA suggest it may be an impactful accelerator of transmission reduction in areas with high coverage of case management and vector control and should be considered as part of a malaria elimination strategy.
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Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos , Adolescente , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Incidência , Estudos Longitudinais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Adulto Jovem , Zâmbia/epidemiologiaRESUMO
Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.
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Antimaláricos/economia , Artemisininas/economia , Erradicação de Doenças/economia , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/economia , Quinolinas/economia , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Análise Custo-Benefício , Erradicação de Doenças/métodos , Custos de Medicamentos , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Custos de Cuidados de Saúde , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/economia , Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos/métodos , Plasmodium falciparum/efeitos dos fármacos , Anos de Vida Ajustados por Qualidade de Vida , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Zâmbia/epidemiologiaRESUMO
Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.
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Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/métodos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Humanos , Incidência , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologiaRESUMO
As Zambia continues to reduce its malaria incidence and target elimination in Southern Province, there is a need to identify factors that can reintroduce parasites and sustain malaria transmission. To examine the relative contributions of types of human mobility on malaria prevalence, this analysis quantifies the proportion of the population having recently traveled during both peak and nonpeak transmission seasons over the course of 2 years and assesses the relationship between short-term travel and malaria infection status. Among all residents targeted by mass drug administration in the Lake Kariba region of Southern Province, 602,620 rapid diagnostic tests and recent travel histories were collected during four campaign rounds occurring between December 2014 and February 2016. Rates of short-term travel in the previous 2 weeks fluctuated seasonally from 0.3% to 1.2%. Travel was significantly associated with prevalent malaria infection both seasonally and overall (adjusted odds ratio [AOR]: 2.55; 95% CI: 2.28-2.85). The strength of association between travel and malaria infection varied by travelers' origin and destination, with those recently traveling to high-prevalence areas from low-prevalence areas experiencing the highest odds of malaria infection (AOR: 7.38). Long-lasting insecticidal net usage while traveling was associated with a relative reduction in infections (AOR: 0.74) compared with travelers not using a net. Although travel was directly associated with only a small fraction of infections, importation of malaria via human movement may play an increasingly important role in this elimination setting as transmission rates continue to decline.
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Malária Falciparum/transmissão , Plasmodium falciparum , Viagem , Adolescente , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Masculino , Administração Massiva de Medicamentos/métodos , Prevalência , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco , Zâmbia/epidemiologiaRESUMO
Mass drug administration (MDA) is currently being considered as an intervention in low-transmission areas to complement existing malaria control and elimination efforts. The effectiveness of any MDA strategy is dependent on achieving high epidemiologic coverage and participant adherence rates. A community-randomized controlled trial was conducted from November 2014 to March 2016 to evaluate the impact of four rounds of MDA or focal MDA (fMDA)-where treatment was given to all eligible household members if anyone in the household had a positive malaria rapid diagnostic test-on malaria outcomes in Southern Province, Zambia (population approximately 300,000). This study examined epidemiologic coverage and program reach using capture-recapture and satellite enumeration methods to estimate the degree to which the trial reached targeted individuals. Overall, it was found that the percentage of households visited by campaign teams ranged from 62.9% (95% CI: 60.0-65.8) to a high of 77.4% (95% CI: 73.8-81.0) across four rounds of treatment. When the maximum number of visited households across all campaign rounds was used as the numerator, program reach for at least one visit would have been 86.4% (95% CI: 80.8-92.0) in MDA and 83.5% (95% CI: 78.0-89.1) in fMDA trial arms. As per the protocol, the trial provided dihydroartemisinin-piperaquine treatment to an average of 58.8% and 13.3% of the estimated population based on capture-recapture in MDA and fMDA, respectively, across the four rounds.
Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Quimioterapia Combinada , Características da Família , Humanos , Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologiaRESUMO
Malaria burden in Zambia has significantly declined over the last decade because of improved coverage of several key malaria interventions (e.g., vector control, case management, bed net distributions, and enhanced surveillance/responses). Campaign-based mass drug administration (MDA) and focal MDA (fMDA) were assessed in a trial in Southern Province, Zambia, to identify its utility in elimination efforts. As part of the study, a longitudinal cohort was visited and tested (by PCR targeting the 18s rRNA and a Plasmodium falciparum-specific rapid diagnostic test [RDT] from SD Bioline) every month for the trial duration (18 months). Overall, there was high concordance (> 97%) between the PCR and RDT results, using the PCR as the gold standard. The RDTs had high specificity and negative predictive values (98.5% and 98.6%, respectively) but low sensitivity (53.0%) and a low positive predictive value (53.8%). There was evidence for persistent antigenemia affecting the low specificity of the RDT, while false-negative RDTs were associated with a lower parasite density than true positive RDTs. Plasmodium falciparum was the dominant species identified, with 98.3% of all positive samples containing P. falciparum. Of these, 97.5% were mono-infections and 0.8% coinfections with one other species. Plasmodium malariae was found in 1.4% of all positive samples (50% mono-infections and 50% coinfections with P. falciparum), whereas Plasmodium ovale was found in 1.1% of all positive samples (90% mono-infections and 10% coinfections with P. falciparum). Although MDA/fMDA appeared to reduce P. malariae prevalence, P. ovale prevalence appeared unchanged.
Assuntos
Antimaláricos/administração & dosagem , Malária Falciparum/epidemiologia , Malária/epidemiologia , Administração Massiva de Medicamentos/métodos , Plasmodium falciparum , Reação em Cadeia da Polimerase em Tempo Real/métodos , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Quimioterapia Combinada/métodos , Humanos , Estudos Longitudinais , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/prevenção & controle , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/genética , Prevalência , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Zâmbia/epidemiologiaRESUMO
Mass drug administration (MDA) with artemisinin combination therapy is a potentially useful tool for malaria elimination programs, but its success depends partly on drug effectiveness and treatment coverage in the targeted population. As part of a cluster-randomized controlled trial in Southern Province, Zambia evaluating the impact of MDA and household focal MDA (fMDA) with dihydroartemisinin-piperaquine (DHAp), sub-studies were conducted investigating population drug adherence rates and effectiveness of DHAp as administered in clearing Plasmodium falciparum infections following household mass administration. Adherence information was reported for 181,534 of 336,821 DHAp (53.9%) treatments administered during four rounds of MDA/fMDA, of which 153,197 (84.4%) reported completing the full course of DHAp. The proportion of participants fully adhering to the treatment regimen differed by MDA modality (MDA versus fMDA), RDT status, and whether the first dose was observed by those administering treatments. Among a subset of participants receiving DHAp and selected for longitudinal follow-up, 58 were positive for asexual-stage P. falciparum infection by microscopy at baseline. None of the 45 participants followed up at days 3 and/or 7 were slide positive for asexual-stage parasitemia. For those with longer term follow-up, one participant was positive 47 days after treatment, and two additional participants were positive after 69 days, although these two were determined to be new infections by genotyping. High completion of a 3-day course of DHAp and parasite clearance in the context of household MDA are promising as Zambia's National Malaria Programme continues to weigh appropriate interventions for malaria elimination.
Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Adesão à Medicação , Aceitação pelo Paciente de Cuidados de Saúde , Plasmodium falciparum , Quinolinas/administração & dosagem , Adolescente , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Entrevistas como Assunto , Malária Falciparum/epidemiologia , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/psicologia , Administração Massiva de Medicamentos/estatística & dados numéricos , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/uso terapêutico , Zâmbia/epidemiologiaRESUMO
BACKGROUND: Zambia is pushing for, and has made great strides towards, the elimination of malaria transmission in Southern Province. Reactive focal test and treat (RFTAT) using rapid diagnostic tests and artemether-lumefantrine (AL) has been key in making this progress. Reactive focal drug administration (RFDA) using dihydroartemisinin-piperaquine (DHAP), may be superior in accelerating clearance of the parasite reservoir in humans due to the provision of enhanced chemoprophylactic protection of at-risk populations against new infections. The primary aim of this study is to quantify the relative effectiveness of RFDA with DHAP against RFTAT with AL (standard of care) for reducing Plasmodium falciparum prevalence and incidence. METHODS/DESIGN: The study will be conducted in four districts in Southern Province, Zambia; an area of low malaria transmission and high coverage of vector control. A community randomized controlled trial of 16 health facility catchment areas will be used to evaluate the impact of sustained year-round routine RFDA for 2 years, relative to a control of year-round routine RFTAT. Reactive case detection will be triggered by a confirmed malaria case, e.g., by microscopy or rapid diagnostic test at any government health facility. Reactive responses will be performed by community health workers (CHW) within 7 days of the index case confirmation date. Responses will be performed out to a radius of 140 m from the index case household. A subset of responses will be followed longitudinally for 90 days to examine reinfection rates. Primary outcomes include a post-intervention survey of malaria seropositivity (n = 4800 children aged 1 month to under 5 years old) and a difference-in-differences analysis of malaria parasite incidence, as measured through routine passive case detection at health facilities enrolled in the study. The study is powered to detect approximately a 65% relative reduction in these outcomes between the intervention versus the control. DISCUSSION: Strengths of this trial include a robust study design and an endline cross-sectional parasite survey as well as a longitudinal sample. Primary limitations include statistical power to detect only a 65% reduction in primary outcomes, and the potential for contamination to dilute the effects of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02654912 . Registered on 12 November 2015.
Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Etanolaminas/administração & dosagem , Fluorenos/administração & dosagem , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/administração & dosagem , Adolescente , Adulto , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina , Artemisininas/efeitos adversos , Criança , Pré-Escolar , Protocolos Clínicos , Serviços de Saúde Comunitária , Esquema de Medicação , Combinação de Medicamentos , Etanolaminas/efeitos adversos , Feminino , Fluorenos/efeitos adversos , Humanos , Incidência , Lactente , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/patogenicidade , Prevalência , Quinolinas/efeitos adversos , Projetos de Pesquisa , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , Zâmbia/epidemiologiaRESUMO
BACKGROUND AND METHODS: In areas where malaria transmission has been suppressed by vector control interventions many malaria control and elimination programmes are actively seeking new interventions to further reduce malaria prevalence, incidence and transmission. Malaria infection prevalence and incidence has been shown to cluster geographically, especially at lower transmission levels, and as such a reactive strategy is frequently used, by which index cases presenting to a passive surveillance system are used to target small areas for testing and treatment, reactive case detection (RCD), or focal drug administration (fDA). This study utilizes geo-located data from a census with parasitological testing with rapid diagnostic tests (RDTs) and treatment-seeking data collection conducted in southern Zambia to estimate the coverage of RCD or fDA in terms of the population and parasite reservoir as well as the operational requirements of such strategies, using a re-sampling algorithm developed exclusively for this purpose. This re-sampling algorithm allows for the specification of several parameters, such that different operational variants of these reactive strategies can be examined, including varying the search radius, screening for fever, or presumptive treatment (fDA). RESULTS: Results indicate that RCD, fDA and active fever screening followed by RCD, even with search radii over several hundered meters will only yield limited coverage of the RDT positive parasite reservoir during a short period. Long-term use of these strategies may increase this proportion. Reactive strategies detect a higher proportion of the reservoir of infections than random searches, but this effect appears to be greater in areas of low, but not moderate malaria prevalence in southern Zambia. DISCUSSION: Increases in the sensitivity of RDTs could also affect these results. The number of individuals and households that need to be searched increase rapidly, but approximately linearly with search radius. CONCLUSIONS: Reactive strategies in southern Zambia yield improved identification of the parasite reservoir when targeted to areas with prevalence less than 10%. The operational requirements of delivering reactive strategies routinely are likely to prevent their uptake until prevalence falls far below this level.
Assuntos
Antimaláricos/uso terapêutico , Testes Diagnósticos de Rotina/estatística & dados numéricos , Reservatórios de Doenças , Malária/parasitologia , Programas de Rastreamento/organização & administração , Febre/patologia , Prevalência , ZâmbiaRESUMO
BACKGROUND: Reactive case detection could be a powerful tool in malaria elimination, as it selectively targets transmission pockets. However, field operations have yet to demonstrate under which conditions, if any, reactive case detection is best poised to push a region to elimination. This study uses mathematical modelling to assess how baseline transmission intensity and local interconnectedness affect the impact of reactive activities in the context of other possible intervention packages. METHODS: Communities in Southern Province, Zambia, where elimination operations are currently underway, were used as representatives of three archetypes of malaria transmission: low-transmission, high household density; high-transmission, low household density; and high-transmission, high household density. Transmission at the spatially-connected household level was simulated with a dynamical model of malaria transmission, and local variation in vectorial capacity and intervention coverage were parameterized according to data collected from the area. Various potential intervention packages were imposed on each of the archetypical settings and the resulting likelihoods of elimination by the end of 2020 were compared. RESULTS: Simulations predict that success of elimination campaigns in both low- and high-transmission areas is strongly dependent on stemming the flow of imported infections, underscoring the need for regional-scale strategies capable of reducing transmission concurrently across many connected areas. In historically low-transmission areas, treatment of clinical malaria should form the cornerstone of elimination operations, as most malaria infections in these areas are symptomatic and onward transmission would be mitigated through health system strengthening; reactive case detection has minimal impact in these settings. In historically high-transmission areas, vector control and case management are crucial for limiting outbreak size, and the asymptomatic reservoir must be addressed through reactive case detection or mass drug campaigns. CONCLUSIONS: Reactive case detection is recommended only for settings where transmission has recently been reduced rather than all low-transmission settings. This is demonstrated in a modelling framework with strong out-of-sample accuracy across a range of transmission settings while including methodologies for understanding the most resource-effective allocations of health workers. This approach generalizes to providing a platform for planning rational scale-up of health systems based on locally-optimized impact according to simplified stratification.