Dataset Information

Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.

ABSTRACT: Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed Anopheles, Aedes, and Culex mosquitoes and Phlebotomus sand flies after feeding on a drug-supplemented blood meal, with IC₅₀ values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance to common insecticides. Based on allometric scaling of preclinical pharmacokinetics data, we predict that a single human median dose of 260 mg (IQR, 177-407 mg) for afoxolaner, or 410 mg (IQR, 278-648 mg) for fluralaner, could provide an insecticidal effect lasting 50-90 days against mosquitoes and Phlebotomus sand flies. Computational modeling showed that seasonal mass drug administration of such a single dose to a fraction of a regional population would dramatically reduce clinical cases of Zika and malaria in endemic settings. Isoxazolines therefore represent a promising new component of drug-based vector control.

SUBMITTER: Miglianico M

PROVIDER: S-EPMC6055183 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.

Miglianico Marie M Eldering Maarten M Slater Hannah H Ferguson Neil N Ambrose Pauline P Lees Rosemary S RS Koolen Karin M J KMJ Pruzinova Katerina K Jancarova Magdalena M Volf Petr P Koenraadt Constantianus J M CJM Duerr Hans-Peter HP Trevitt Graham G Yang Baiyuan B Chatterjee Arnab K AK Wisler John J Sturm Angelika A Bousema Teun T Sauerwein Robert W RW Schultz Peter G PG Tremblay Matthew S MS Dechering Koen J KJ

Proceedings of the National Academy of Sciences of the United States of America 20180702 29

Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed Anopheles, Aedes, and Culex mosquitoes and Phlebotomus sand flies after feeding on a drug-supplemented blood meal, with IC50 values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance ...[more]

PMID: 29967151

Similar Datasets

Project description:After a request from the European Commission, EFSA's Panel on Animal Health and Welfare summarised the main characteristics of 36 vector-borne diseases (VBDs) in https://efsa.maps.arcgis.com/apps/PublicGallery/index.html?appid=dfbeac92aea944599ed1eb754aa5e6d1. The risk of introduction in the EU through movement of livestock or pets was assessed for each of the 36 VBDs individually, using a semiquantitative Method to INTegrate all relevant RISK aspects (MINTRISK model), which was further modified to a European scale into the http://www3.lei.wur.nl/mintrisk/ModelMgt.aspx. Only eight of the 36 VBD-agents had an overall rate of introduction in the EU (being the combination of the rate of entry, vector transmission and establishment) which was estimated to be above 0.001 introductions per year. These were Crimean-Congo haemorrhagic fever virus, bluetongue virus, West Nile virus, Schmallenberg virus, Hepatozoon canis, Leishmania infantum, Bunyamwera virus and Highlands J. virus. For these eight diseases, the annual extent of spread was assessed, assuming the implementation of available, authorised prevention and control measures in the EU. Further, the probability of overwintering was assessed, as well as the possible impact of the VBDs on public health, animal health and farm production. For the other 28 VBD-agents for which the rate of introduction was estimated to be very low, no further assessments were made. Due to the uncertainty related to some parameters used for the risk assessment or the instable or unpredictability disease situation in some of the source regions, it is recommended to update the assessment when new information becomes available. Since this risk assessment was carried out for large regions in the EU for many VBD-agents, it should be considered as a first screening. If a more detailed risk assessment for a specific VBD is wished for on a national or subnational level, the EFSA-VBD-RISK-model is freely available for this purpose.

Project description:BackgroundClimate-based disease forecasting has been proposed as a potential tool in climate change adaptation for the health sector. Here we explore the relevance of climate data, drivers and predictions for vector-borne disease control efforts in Africa.MethodsUsing data from a number of sources we explore rainfall and temperature across the African continent, from seasonality to variability at annual, multi-decadal and timescales consistent with climate change. We give particular attention to three regions defined as WHO-TDR study zones in Western, Eastern and Southern Africa. Our analyses include 1) time scale decomposition to establish the relative importance of year-to-year, decadal and long term trends in rainfall and temperature; 2) the impact of the El Niño Southern Oscillation (ENSO) on rainfall and temperature at the Pan African scale; 3) the impact of ENSO on the climate of Tanzania using high resolution climate products and 4) the potential predictability of the climate in different regions and seasons using Generalized Relative Operating Characteristics. We use these analyses to review the relevance of climate forecasts for applications in vector borne disease control across the continent.ResultsTimescale decomposition revealed long term warming in all three regions of Africa - at the level of 0.1-0.3 °C per decade. Decadal variations in rainfall were apparent in all regions and particularly pronounced in the Sahel and during the East African long rains (March-May). Year-to-year variability in both rainfall and temperature, in part associated with ENSO, were the dominant signal for climate variations on any timescale. Observed climate data and seasonal climate forecasts were identified as the most relevant sources of climate information for use in early warning systems for vector-borne diseases but the latter varied in skill by region and season.ConclusionsAdaptation to the vector-borne disease risks of climate variability and change is a priority for government and civil society in African countries. Understanding rainfall and temperature variations and trends at multiple timescales and their potential predictability is a necessary first step in the incorporation of relevant climate information into vector-borne disease control decision-making.

Dataset Information

Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.

Publications

Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets