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Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings

BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently...

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Autores principales: Bottomley, Christian, Isham, Valerie, Vivas-Martínez, Sarai, Kuesel, Annette C., Attah, Simon K., Opoku, Nicholas O., Lustigman, Sara, Walker, Martin, Basáñez, Maria-Gloria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908809/
https://www.ncbi.nlm.nih.gov/pubmed/27301567
http://dx.doi.org/10.1186/s13071-016-1605-3
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author Bottomley, Christian
Isham, Valerie
Vivas-Martínez, Sarai
Kuesel, Annette C.
Attah, Simon K.
Opoku, Nicholas O.
Lustigman, Sara
Walker, Martin
Basáñez, Maria-Gloria
author_facet Bottomley, Christian
Isham, Valerie
Vivas-Martínez, Sarai
Kuesel, Annette C.
Attah, Simon K.
Opoku, Nicholas O.
Lustigman, Sara
Walker, Martin
Basáñez, Maria-Gloria
author_sort Bottomley, Christian
collection PubMed
description BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. METHODS: We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. RESULTS: The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment. CONCLUSIONS: Our model supports the timelines proposed by APOC for post-MDA follow-up and surveillance surveys every 3–5 years. Two skin snips from the iliac region have reasonable sensitivity to detect residual infection, but the sensitivity can be significantly improved by taking 4 snips. The costs and benefits of using four versus two snips should be evaluated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1605-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-49088092016-06-16 Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings Bottomley, Christian Isham, Valerie Vivas-Martínez, Sarai Kuesel, Annette C. Attah, Simon K. Opoku, Nicholas O. Lustigman, Sara Walker, Martin Basáñez, Maria-Gloria Parasit Vectors Research BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. METHODS: We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. RESULTS: The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment. CONCLUSIONS: Our model supports the timelines proposed by APOC for post-MDA follow-up and surveillance surveys every 3–5 years. Two skin snips from the iliac region have reasonable sensitivity to detect residual infection, but the sensitivity can be significantly improved by taking 4 snips. The costs and benefits of using four versus two snips should be evaluated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1605-3) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-14 /pmc/articles/PMC4908809/ /pubmed/27301567 http://dx.doi.org/10.1186/s13071-016-1605-3 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bottomley, Christian
Isham, Valerie
Vivas-Martínez, Sarai
Kuesel, Annette C.
Attah, Simon K.
Opoku, Nicholas O.
Lustigman, Sara
Walker, Martin
Basáñez, Maria-Gloria
Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings
title Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings
title_full Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings
title_fullStr Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings
title_full_unstemmed Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings
title_short Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings
title_sort modelling neglected tropical diseases diagnostics: the sensitivity of skin snips for onchocerca volvulus in near elimination and surveillance settings
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908809/
https://www.ncbi.nlm.nih.gov/pubmed/27301567
http://dx.doi.org/10.1186/s13071-016-1605-3
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