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 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 Community Acceptance of Reactive Focal Mass Drug Administration and Reactive Focal Vector Control Using Indoor Residual Spraying, a Mixed-Methods Study in Zambezi Region, Namibia

2020 ◽  
Author(s):  
Kathryn W. Roberts ◽  
Cara Smith Gueye ◽  
Kimberly Baltzell ◽  
Henry Ntuku ◽  
Patrick McCreesh ◽  
...  
Keyword(s):  
Mixed Methods ◽  
Vector Control ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Community Education ◽  
Indoor Residual Spraying ◽  
Mixed Methods Study ◽  
Community Based ◽  
Community Acceptance ◽  
Study Teams

Abstract BackgroundIn Namibia, as in many malaria elimination settings, reactive case detection (RACD), or malaria testing and treatment around index cases, is a standard intervention. Reactive focal mass drug administration (rfMDA), or treatment without testing, and reactive focal vector control (RAVC) in the form of indoor residual spraying, are alternative or adjunctive interventions, but there is limited data regarding their community acceptability.MethodsA parent trial aimed to compare the effectiveness of rfMDA versus RACD, RAVC versus RAVC, and rfMDA+RAVC versus RACD only. To assess acceptability of these interventions, we conducted a mixed-methods study that included key informant interviews (KIIs) and focus group discussions (FGDs) in three rounds (pre-trial and in years 1 and 2 of the trial), and an endline survey. ResultsIn total, 17 KIIs, 49 FGDs were conducted with 449 people over three annual rounds of qualitative data collection. Pre-trial, community members more accurately predicted the level of community acceptability than key stakeholders. Throughout the trial, key participant motivators included: malaria risk perception, access to free community-based healthcare and IRS, and community education by respectful study teams. RACD or rfMDA were offered to 1,372 and 8,948 individuals in Years 1 and 2, respectively and refusal rates were low (<2%). RAVC was offered to few households (n=72) in Year 1. In year 2, RAVC was offered to more households (n=944) and refusal were <1%. In the endline survey, 94.3% of 2,147 respondents said they would participate in the same intervention again.ConclusionsCommunities found both reactive focal interventions and their combination highly acceptable. Engaging communities and centering and incorporating their perspectives and experiences during design, implementation, and evaluation of this community-based intervention was critical for optimizing study engagement.

scholarly journals Mass Drug Administration With Dihydroartemisinin-piperaquine and Malaria Transmission Dynamics in The Gambia: A Prospective Cohort Study

2018 ◽  
Vol 69 (2) ◽  
pp. 278-286 ◽  
Author(s):  
Julia Mwesigwa ◽  
Jane Achan ◽  
Muna Affara ◽  
Miriam Wathuo ◽  
Archibald Worwui ◽  
...  
Keyword(s):  
Cohort Study ◽  
Malaria Transmission ◽  
Drug Administration ◽  
Prospective Cohort Study ◽  
Mass Drug Administration ◽  
Prospective Cohort ◽  
Dry Season ◽  
Clinical Disease ◽  
Infection Prevalence ◽  
Low Transmission

Abstract Background Mass drug administration (MDA) may further reduce malaria transmission in low-transmission areas. The impact of MDA on the dynamics of malaria transmission was determined in a prospective cohort study. Methods Annual rounds of MDA with dihydroartemisinin-piperaquine (DP) were implemented were implemented in 2014 and 2015 in six village pairs before the malaria transmission season. Blood samples were collected from residents between July and December for microscopy and nested PCR. Incidence and prevalence of infection, clinical disease, and risk of malaria reinfection post-MDA were determined. Results Coverage of three DP doses was 68.2% (2014) and 65.6% (2015), compliance was greater than 80%. Incidence of infection was significantly lower in 2014 (incidence rate [IR] = 0.2 per person year [PPY]) than in 2013 (IR = 1.1 PPY; P < .01); monthly infection prevalence declined in the first three months post-MDA. Clinical malaria incidence was lower in 2014 (IR = 0.1 PPY) and 2015 (IR = 0.2 PPY) than in 2013 (IR = 0.4 PPY; P < .01), but remained higher in eastern Gambia. Individuals infected before MDA had a 2-fold higher odds of reinfection post-MDA (adjusted odds ratio = 2.5, 95% confidence interval 1.5–4.3; P < .01). Conclusions MDA reduced malaria infection and clinical disease during the first months. The reduction was maintained in low-transmission areas, but not in eastern Gambia. Annual MDA could be followed by focal MDA targeting individuals infected during the dry season. Repeated MDA rounds, some during the dry season over larger geographical areas, may result in a more marked and sustained decrease of malaria transmission.

Sign in / Sign up

Export Citation Format

Share Document