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Risk of disease after isoniazid preventive therapy for mycobacterium tuberculosis exposure in young HIV uninfected children

Abstract:
Background: Childhood tuberculosis (TB) is usually Mycobacterium tuberculosis (MTB) culture negative. Furthermore, clinical presentation may be altered by active case finding, isoniazid prophylaxis and early treatment. We aimed to establish the value of presenting symptoms for intrathoracic TB case diagnosis among young children. Methods: Healthy, HIV-uninfected, South African infants in an efficacy trial of a novel TB vaccine (MVA85A) were followed for 2 years for suspected TB. When suspected, investigation followed a standardized algorithm comprising symptom history, QuantiFERON Gold-in-Tube, chest radiography (CXR), MTB culture and Xpert MTB/RIF from paired gastric lavage and induced sputa. Adjusted odds ratios and 95% confidence intervals describe the associations between symptoms and positive MTB culture or Xpert MTB/RIF, and CXR compatible with intrathoracic TB. Results: Persistent cough was present in 172/1017 (16.9%) of the children investigated for TB. MTB culture/Xpert MTB/RIF was positive in 38/1017 children (3.7%); and CXR was positive, that is, compatible with intrathoracic TB, in 131/1017 children (12.9%). Children with persistent cough had more than triple the odds of a positive MTB culture/Xpert MTB/RIF (adjusted odds ratios: 3.3, 95% confidence interval: 1.5–7.0) and positive CXR (adjusted odds ratios: 3.5, 95% confidence interval: 2.2–5.5). Persistent cough was the only symptom that differentiated children with severe (56.5%) from nonsevere intrathoracic TB disease (28.2%; P = 0.001). Conclusion: Persistent cough was the cardinal diagnostic symptom associated with microbiologic and radiologic evidence, and disease severity, of intrathoracic TB. Symptom-based definitions of TB disease for diagnostic, preventive and therapeutic studies should prioritize persistent cough above other symptoms compatible with childhood TB.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1097/INF.0000000000000874

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author


Publisher:
Wolters Kluwer Health, Inc.
Journal:
Pediatric Infectious Disease Journal More from this journal
Volume:
34
Issue:
11
Pages:
1218–1222
Publication date:
2015-11-01
Acceptance date:
2015-02-16
DOI:
EISSN:
1532-0987
ISSN:
0891-3668


Keywords:
Pubs id:
pubs:619178
UUID:
uuid:51cf2f98-0ec9-4ec5-b8d3-4d7a5afd55ed
Local pid:
pubs:619178
Source identifiers:
619178
Deposit date:
2016-05-03
ARK identifier:

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