Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial (Preprint)

BACKGROUND With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. OBJECTIVE The study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. METHODS The study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. RESULTS The MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. CONCLUSIONS This is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. CLINICALTRIAL ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/20904

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Mass Drug Administration With High-Dose Ivermectin and Dihydroartemisinin-Piperaquine for Malaria Elimination in an Area of Low Transmission With High Coverage of Malaria Control Interventions: Protocol for the MASSIV Cluster Randomized Clinical Trial

JMIR Research Protocols ◽

10.2196/20904 ◽

2020 ◽

Vol 9 (11) ◽

pp. e20904

Author(s):

Edgard Diniba Dabira ◽

Harouna M Soumare ◽

Steven W Lindsay ◽

Bakary Conteh ◽

Fatima Ceesay ◽

...

Keyword(s):

Clinical Trial ◽

Malaria Transmission ◽

Randomized Clinical Trial ◽

Drug Administration ◽

Malaria Control ◽

Mass Drug Administration ◽

High Coverage ◽

River Region ◽

Cluster Randomized ◽

The Impact

Background With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. Objective The study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. Methods The study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. Results The MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. Conclusions This is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. Trial Registration ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 International Registered Report Identifier (IRRID) DERR1-10.2196/20904

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Optimising systemic insecticide use to improve malaria control

BMJ Global Health ◽

10.1136/bmjgh-2019-001776 ◽

2019 ◽

Vol 4 (6) ◽

pp. e001776 ◽

Cited By ~ 1

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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Does Medication Sampling Improve Compliance with Brief Advice? Results from a Pragmatic Randomized Clinical Trial

The Journal of Smoking Cessation ◽

10.1155/2021/6638872 ◽

2021 ◽

Vol 2021 ◽

pp. 1-4

Author(s):

Nathaniel J. Silvestri ◽

Jennifer Dahne ◽

Amy E. Wahlquist ◽

Benjamin Toll ◽

Matthew J. Carpenter

Keyword(s):

Primary Care ◽

Clinical Trial ◽

Randomized Clinical Trial ◽

Standard Care ◽

Secondary Data ◽

Tobacco Treatment ◽

Improve Compliance ◽

Cluster Randomized ◽

Brief Advice ◽

The Impact

Introduction. The 5As model is a standard component of most guidelines for tobacco treatment. Unfortunately, provider adherence to this model is modest. Aims. Providing physicians with adjunctive tools to adhere to 5As guidelines may serve as a catalyst for brief advice delivery. Methods. This was a secondary data analysis of a cluster randomized clinical trial assessing the uptake and impact of free nicotine replacement therapy (NRT) sampling versus standard care in primary care. Patients reported receipt of separate elements of the 5As model, assessed one month following a baseline visit. Analyses compared patients who recalled receipt of brief advice among those who received NRT vs. standard care. Additional analyses examined demographic predictors of receiving brief advice. Results/Findings. Medication sampling did not improve compliance with ask, advise, or assess. Receipt of “assistance” was significantly higher among NRT recipients (70%) ( p ≤ 0.0001 ). The NRT sampling group was more likely to have received all components ( p = 0.004 ). As age increased, being asked ( p = 0.006 ), advised ( p = 0.05 ), and assessed ( p = 0.003 ) decreased. Non-Whites reported higher rates of assessment ( p = 0.02 ). Conclusions. Provision of NRT sampling increased provider compliance with some elements of the brief advice model, thus enhancing the impact of cessation advice within primary care. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02096029.

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Malaria Elimination in Costa Rica: Changes in Treatment and Mass Drug Administration

Microorganisms ◽

10.3390/microorganisms8070984 ◽

2020 ◽

Vol 8 (7) ◽

pp. 984 ◽

Cited By ~ 2

Author(s):

Luis F. Chaves ◽

John H. Huber ◽

Obdulio Rojas Salas ◽

Melissa Ramírez Rojas ◽

Luis M. Romero ◽

...

Keyword(s):

Costa Rica ◽

Malaria Transmission ◽

Drug Administration ◽

Mass Drug Administration ◽

Day Treatment ◽

Treatment Protocol ◽

Treatment Delivery ◽

Appropriate Treatment ◽

Imported Cases ◽

The Impact

Costa Rica is a candidate to eliminate malaria by 2020. The remaining malaria transmission hotspots are located within the Huétar Norte Region (HNR), where 90% of the country’s 147 malaria cases have occurred since 2016, following a 33-month period without transmission. Here, we examine changes in transmission with the implementation of a supervised seven-day chloroquine and primaquine treatment (7DCPT). We also evaluate the impact of a focal mass drug administration (MDA) in January 2019 at Boca Arenal, the town in HNR reporting the greatest local transmission. We found that the change to a seven-day treatment protocol, from the prior five-day program, was associated with a 98% reduction in malaria transmission. The MDA helped to reduce transmission, keeping the basic reproduction number, RT, significantly below 1, for at least four months. However, following new imported cases from Nicaragua, autochthonous transmission resumed. Our results highlight the importance of appropriate treatment delivery to reduce malaria transmission, and the challenge that highly mobile populations, if their malaria is not treated, pose to regional elimination efforts in Mesoamerica and México.

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