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.

scholarly journals 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

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

scholarly journals 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)

2020 ◽  
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. CLINICALTRIAL ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/20904

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 Optimizing systemic insecticide use to improve malaria control

2019 ◽  
Author(s):  
Hannah R. Meredith ◽  
Luis Furuya-Kanamori ◽  
Laith Yakob
Keyword(s):  
Mathematical Model ◽  
Malaria Transmission ◽  
Malaria Control ◽  
Mass Drug Administration ◽  
Mosquito Control ◽  
Pyrethroid Resistance ◽  
Control Strategies ◽  
Systemic Insecticide ◽  
Systemic Insecticides ◽  
Long Lasting Insecticidal Nets

AbstractLong 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 over-dependence 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. Here, 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 a mathematical model simulation. The review identified drugs from four classes commonly used in livestock and companion animals: avermectics, milbemycins, isoxazolines, and spinosyns. Simulations predicted that isoxazoline and spinosyn drugs were promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations. These findings will provide a guide for investigating and applying different systemic insecticides to achieve better mosquito control strategies.SignificanceThe widespread use of long lasting insecticidal nets (LLINs) and indoor residual spray has selected for mosquitoes that are resistant to pyrethroids or avoid exposure by feeding outdoors or on livestock. Systemic insecticides, drugs that render a host’s blood toxic to feeding mosquitoes, could be an effective control strategy for mosquitoes with pyrethroid resistance and/or outdoor feeding tendencies. Here, a number of existing systemic insecticide candidates are identified and their pharmacokinetic properties in different drug-host-route scenarios consolidated. These data were used to parameterise a mathematical model that illustrated the projected gains achievable in malaria control programmes already employing LLINs. The findings provide a guide for investigating and applying different systemic insecticides to improve mosquito control strategies and reduce malaria transmission.

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

2020 ◽  
Vol 8 (7) ◽  
pp. 984 ◽  
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.

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 Feasibility of onchocerciasis elimination using a “test-and-not-treat” strategy in Loa loa co-endemic areas

2020 ◽  
Author(s):  
David J Blok ◽  
Joseph Kamgno ◽  
Sebastien D Pion ◽  
Hugues C Nana-Djeunga ◽  
Yannick Niamsi-Emalio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Treatment Duration ◽  
Loa Loa ◽  
Serious Adverse Events ◽  
Endemic Areas ◽  
The Individual ◽  
The Impact ◽  
Main Strategy

Abstract Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

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