scholarly journals Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial

The Lancet ◽  
2020 ◽  
Vol 395 (10233) ◽  
pp. 1361-1373 ◽  
Author(s):  
Michelle S Hsiang ◽  
Henry Ntuku ◽  
Kathryn W Roberts ◽  
Mi-Suk Kang Dufour ◽  
Brooke Whittemore ◽  
...  
Keyword(s):  
Vector Control ◽  
Factorial Design ◽  
Malaria Transmission ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Open Label ◽  
Endemic Setting ◽  
Cluster Randomised ◽  
Randomised Controlled

scholarly journals Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia

BMJ Open ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. e019294 ◽  
Author(s):  
Oliver F Medzihradsky ◽  
Immo Kleinschmidt ◽  
Davis Mumbengegwi ◽  
Kathryn W Roberts ◽  
Patrick McCreesh ◽  
...  
Keyword(s):  
Vector Control ◽  
Factorial Design ◽  
Malaria Transmission ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Indoor Residual Spraying ◽  
Health Facilities ◽  
Infection Prevalence ◽  
Cluster Randomised ◽  
Randomised Controlled

IntroductionTo interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia.Methods and analysisThis is an open-label cluster randomised controlled trial with 2×2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness.Ethics and disseminationFindings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia.Trial registration numberNCT02610400; Pre-results.

scholarly journals Serological evaluation of a cluster randomised trial on the use of reactive focal mass drug administration and reactive vector control to reduce malaria transmission in Zambezi Region, Namibia

2021 ◽  
Author(s):  
Lindsey Wu ◽  
Michelle Hsiang ◽  
Lisa M. Prach ◽  
Leah Schrubbe ◽  
Henry Ntuku ◽  
...  
Keyword(s):  
Vector Control ◽  
Malaria Transmission ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Quantitative Polymerase Chain Reaction ◽  
Randomised Trial ◽  
Antibody Responses ◽  
Cluster Randomised Trial ◽  
Serological Markers ◽  
Cluster Randomised

Due to challenges in measuring changes in malaria in low transmission settings, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal cohort studies have shown serological markers, such as Etramp5.Ag1, to be particularly discriminatory of spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials. This study is an extended analysis of a 2017 cluster randomised trial conducted in Zambezi Region, Namibia, evaluating the effectiveness of reactive focal mass drug administration (rfMDA) and reactive vector control (RAVC). A panel of eight serological markers of Plasmodium falciparum infection - Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175, PfMSP119, PfAMA1, and PfGLURP.R2 - was used on a multiplex immunoassay to measure population antibody responses as trial endpoints. Reductions in sero-prevalence to antigens Etramp.Ag1, PfMSP119, Rh2.2030, and PfAMA1 were observed in study arms combining rfMDA and RAVC, but only effects for Etramp5.Ag1 were statistically significant. Etramp5.Ag1 sero-prevalence was significantly lower in all intervention arms. Compared to the reference arms, adjusted Etramp5.Ag1 prevalence ratio (aPR) was 0.77 (95%CI 0.65 - 0.90, p<0.001) for rfMDA and 0.79 (95%CI 0.67 - 0.92, p=0.001) for RACD. For combined rfMDA plus RAVC, aPR was 0.58 (95%CI 0.45 - 0.75, p<0.001). Significant reductions were also observed based on continuous antibody responses. Sero-prevalence as an endpoint was found to achieve higher study power (99.9% power to detect a 50% reduction in prevalence) compared to quantitative polymerase chain reaction (qPCR) prevalence (72.9% power to detect a 50% reduction in prevalence). The use of serological endpoints to evaluate trial outcomes was comparable to qPCR and measured effect size with improved precision. Serology has clear application in cluster randomised trials, particularly in settings where measuring clinical incidence or infection is less reliable due to seasonal fluctuations, limitations in health care seeking, or incomplete testing and reporting.

scholarly journals Effectiveness and safety of reactive focal mass drug administration (rfMDA) using dihydroartemisinin–piperaquine to reduce malaria transmission in the very low-endemic setting of Eswatini: a pragmatic cluster randomised controlled trial

2021 ◽  
Vol 6 (6) ◽  
pp. e005021
Author(s):  
Sibonakaliso Vilakati ◽  
Nontokozo Mngadi ◽  
Jade Benjamin-Chung ◽  
Nomcebo Dlamini ◽  
Mi-Suk Kang Dufour ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Malaria Transmission ◽  
Mass Drug Administration ◽  
Index Case ◽  
Controlled Trial ◽  
Cluster Randomised Controlled Trial ◽  
Endemic Setting ◽  
Cluster Randomised ◽  
Randomised Controlled ◽  
Index Cases

IntroductionTo reduce malaria transmission in very low-endemic settings, screening and treatment near index cases (reactive case detection (RACD)), is widely practised, but the rapid diagnostic tests (RDTs) used miss low-density infections. Reactive focal mass drug administration (rfMDA) may be safe and more effective.MethodsWe conducted a pragmatic cluster randomised controlled trial in Eswatini, a very low-endemic setting. 77 clusters were randomised to rfMDA using dihydroartemisin–piperaquine (DP) or RACD involving RDTs and artemether–lumefantrine. Interventions were delivered by the local programme. An intention-to-treat analysis was used to compare cluster-level cumulative confirmed malaria incidence among clusters with cases. Secondary outcomes included safety and adherence.ResultsFrom September 2015 to August 2017, 222 index cases from 47 clusters triggered 46 RACD events and 64 rfMDA events. RACD and rfMDA were delivered to 1455 and 1776 individuals, respectively. Index case coverage was 69.5% and 62.4% for RACD and rfMDA, respectively. Adherence to DP was 98.7%. No serious adverse events occurred. For rfMDA versus RACD, cumulative incidences (per 1000 person-years) of all malaria were 2.11 (95% CI 1.73 to 2.59) and 1.97 (95% CI 1.57 to 2.47), respectively; and of locally acquired malaria, they were 1.29 (95% CI 1.00 to 1.67) and 0.97 (95% CI 0.71 to 1.34), respectively. Adjusting for imbalance in baseline incidence, incidence rate ratio for rfMDA versus RACD was 0.95 (95% CI 0.55 to 1.65) for all malaria and 0.82 (95% CI 0.40 to 1.71) for locally acquired malaria. Similar results were obtained in a per-protocol analysis that excluded clusters with <80% index case coverage.ConclusionIn a very low-endemic, real-world setting, rfMDA using DP was safe, but did not lower incidence compared with RACD, potentially due to insufficient coverage and/or power. To assess impact of interventions in very low-endemic settings, improved coverage, complementary interventions and adaptive ring trial designs may be needed.Trial registration numberNCT02315690.

scholarly journals Optimising systemic insecticide use to improve malaria control

2019 ◽  
Vol 4 (6) ◽  
pp. e001776 ◽  
Author(s):  
Hannah R Meredith ◽  
Luis Furuya-Kanamori ◽  
Laith Yakob
Keyword(s):  
Vector Control ◽  
Malaria Transmission ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Companion Animals ◽  
Malaria Vectors ◽  
Systemic Insecticide ◽  
Blood Concentrations ◽  
Systemic Insecticides ◽  
The Impact

BackgroundLong-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability.MethodsHere, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation.ResultsThe review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations.ConclusionsThese findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission.

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