Partnerships to design novel regimens to treat childhood tuberculosis, Sui Generis: the road ahead
File(s)
Published version
Author(s)
Gumbo, T
Makhene, MK
Seddon, JA
Type
Journal Article
Abstract
There has been a recent expansion of preclinical models to predict the efficacy of regimens to treat adults with tuberculosis. Despite increasing global interest in childhood tuberculosis, these same tools have not been employed to develop pediatric regimens. Children differ from adults in bacillary burden, spectrum of disease, the metabolism and distribution of antituberculosis drugs, and the toxicity experienced. The studies documented in this series describe a proof-of-concept approach to pediatric regimen development. We propose a program of investigation that would take this forward into a systematic and comprehensive method to find optimal drug combinations to use in children, ideal exposures, and required dosing. Although the number of possible drug combinations is extensive, a series of principles could be employed to select likely effective regimens. Regimens should avoid drugs with overlapping toxicity or linked mechanisms of resistance and should aim to include drugs with different mechanisms of action and ones that are able to target different subpopulations of mycobacteria. Finally drugs should penetrate into body sites necessary for treating pediatric disease. At an early stage, this body of work would need to engage with regulatory agencies and bodies that formulate guidelines, so that once regimens and dosages are identified, translation into clinical studies and clinical practice can be rapid. The development of child-friendly drug formulations would need to be carried out in parallel so that pharmacokinetic studies can be undertaken as formulations are created. Significant research and development would be required and a wide range of stakeholders would need to be engaged. The time is right to consider a more thoughtful and systematic approach toward identifying, testing, and comparing combinations of drugs for children with tuberculosis.
Date Issued
2016-09-30
Date Acceptance
2016-09-01
Citation
Clinical Infectious Diseases, 2016, 63, pp.S110-S115
ISSN
1058-4838
Publisher
Oxford University Press (OUP)
Start Page
S110
End Page
S115
Journal / Book Title
Clinical Infectious Diseases
Volume
63
Copyright Statement
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/
4.0/), which permits non-commercial reproduction and distribution of the work, in any
medium, provided the original work is not altered or transformed in any way, and that the
work is properly cited. For commercial re-use, contact journals.permissions@oup.com.
America. This is an Open Access article distributed under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/
4.0/), which permits non-commercial reproduction and distribution of the work, in any
medium, provided the original work is not altered or transformed in any way, and that the
work is properly cited. For commercial re-use, contact journals.permissions@oup.com.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000387986500008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
tuberculosis
children
future
investment
PK
PD
hollow fiber
HOLLOW-FIBER MODEL
MYCOBACTERIUM-TUBERCULOSIS
RESISTANT TUBERCULOSIS
PHARMACOKINETICS-PHARMACODYNAMICS
ANTITUBERCULOSIS DRUGS
SYSTEM MODEL
EFFLUX-PUMP
CHILDREN
PYRAZINAMIDE
MICE
Publication Status
Published