The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by n...

Full description

Bibliographic Details
Published in:PLoS Neglected Tropical Diseases
Main Authors: Becky L Rivoire, Stephen TerLouw, Nathan A Groathouse, Patrick J Brennan
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2014
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0002791
https://doaj.org/article/40e3bb9e66dd4794a3789d0f034eb511
id ftdoajarticles:oai:doaj.org/article:40e3bb9e66dd4794a3789d0f034eb511
record_format openpolar
spelling ftdoajarticles:oai:doaj.org/article:40e3bb9e66dd4794a3789d0f034eb511 2023-05-15T15:12:38+02:00 The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy. Becky L Rivoire Stephen TerLouw Nathan A Groathouse Patrick J Brennan 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002791 https://doaj.org/article/40e3bb9e66dd4794a3789d0f034eb511 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4038479?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002791 https://doaj.org/article/40e3bb9e66dd4794a3789d0f034eb511 PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2791 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002791 2022-12-31T09:49:45Z True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 5 e2791
institution Open Polar
collection Directory of Open Access Journals: DOAJ Articles
op_collection_id ftdoajarticles
language English
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Becky L Rivoire
Stephen TerLouw
Nathan A Groathouse
Patrick J Brennan
The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
topic_facet Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
description True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.
format Article in Journal/Newspaper
author Becky L Rivoire
Stephen TerLouw
Nathan A Groathouse
Patrick J Brennan
author_facet Becky L Rivoire
Stephen TerLouw
Nathan A Groathouse
Patrick J Brennan
author_sort Becky L Rivoire
title The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
title_short The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
title_full The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
title_fullStr The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
title_full_unstemmed The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
title_sort challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doi.org/10.1371/journal.pntd.0002791
https://doaj.org/article/40e3bb9e66dd4794a3789d0f034eb511
geographic Arctic
geographic_facet Arctic
genre Arctic
genre_facet Arctic
op_source PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2791 (2014)
op_relation http://europepmc.org/articles/PMC4038479?pdf=render
https://doaj.org/toc/1935-2727
https://doaj.org/toc/1935-2735
1935-2727
1935-2735
doi:10.1371/journal.pntd.0002791
https://doaj.org/article/40e3bb9e66dd4794a3789d0f034eb511
op_doi https://doi.org/10.1371/journal.pntd.0002791
container_title PLoS Neglected Tropical Diseases
container_volume 8
container_issue 5
container_start_page e2791
_version_ 1766343294551326720