Screening for an ivermectin slow-release formulation suitable for malaria vector control

Malaria Journal

Research

Felix Hammann¹  Hannah Slater²  Diego Martinez Urbistondo³  Carlos Chaccour⁴  Ana Gloria Gil Royo⁵  Ángel Irigoyen Barrio⁵  Jose Luis Del Pozo⁶ 

[1] Cantonal Hospital Baselland, Medical University Clinic, Liestal, Switzerland;Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, UK;Department of Internal Medicine, Clinica Universidad de Navarra, Pio XII 36, 31008, Pamplona, Spain;Department of Internal Medicine, Clinica Universidad de Navarra, Pio XII 36, 31008, Pamplona, Spain;Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain;Instituto de Salud Tropical, Universidad de Navarra, Pamplona, Spain;Faculty of Pharmacy, Universidad de Navarra, 31008, Pamplona, Spain;Drug Development Unit Universidad de Navarra (DDUNAV), Pamplona, Spain;Instituto de Salud Tropical, Universidad de Navarra, Pamplona, Spain;Infectious Disease Unit, Clinica Universidad de Navarra, Pamplona, Spain;Department of Microbiology, Clinica Universidad de Navarra, Pamplona, Spain;

关键词: Vector control;    Malaria;    Malaria elimination;    Ivermectin;    Slow release;    Anopheles gambiae;    Silicone;    Residual transmission;    Outdoor transmission;   

DOI  :  10.1186/s12936-015-0618-2

 received in 2014-12-04, accepted in 2015-02-20,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe prospect of eliminating malaria is challenged by emerging insecticide resistance and vectors with outdoor and/or crepuscular activity. Ivermectin can simultaneously tackle these issues by killing mosquitoes feeding on treated animals and humans. A single oral dose, however, confers only short-lived mosquitocidal plasma levels.MethodsThree different slow-release formulations of ivermectin were screened for their capacity to sustain mosquito-killing levels of ivermectin for months. Thirty rabbits received a dose of one, two or three silicone implants containing different proportions of ivermectin, deoxycholate and sucrose. Animals were checked for toxicity and ivermectin was quantified periodically in blood. Potential impact of corresponding long-lasting formulation was mathematically modelled.ResultsAll combinations of formulation and dose released ivermectin for more than 12 weeks; four combinations sustained plasma levels capable of killing 50% of Anopheles gambiae feeding on a treated subject for up to 24 weeks. No major adverse effects attributable to the drug were found. Modelling predicts a 98% reduction in infectious vector density by using an ivermectin formulation with a 12-week duration.ConclusionsThese results indicate that relatively stable mosquitocidal plasma levels of ivermectin can be safely sustained in rabbits for up to six months using a silicone-based subcutaneous formulation. Modifying the formulation of ivermectin promises to be a suitable strategy for malaria vector control.

【 授权许可】

CC BY   
© Chaccour et al.; licensee BioMed Central. 2015