Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

Wiseman, C. A.; Mandalakas, Anna M.; Kirchner, H. Lester; Gie, Robert P.; Schaaf, H. Simon; Walters, Elisabetta; Hesseling, Anneke C.

doi:10.5588/ijtld.14.0585

Cited by 11 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although an inverse relationship between MDSC accumulation and IP‐10 production was reported previously and others demonstrated that thrombospondin‐2 is differentially expressed in a mouse model of transplant activated MDSCs, this is the first report linking plasma levels of these analytes, to peripheral MDSC frequencies in HIV and TB infections. M‐CSF is a tumour‐derived growth factor involved in monocytic differentiation, promoting in vitro expansion of MDSCs through stimulation of myelopoiesis . Counterintuitively, our results show a reduction in plasma M‐CSF in children with higher peripheral MDSC frequencies.…”

Section: Discussionsupporting

confidence: 58%

“…High levels of IDO and arginase activity has been described previously during human M.tb infection. Reports of robust IDO expression in pulmonary TB patients and lung lesions of BCG vaccinated non‐human primates , have resulted in its classification as promising prognostic marker of pulmonary TB . Similarly, increased arginase expression in TB granulomas , signify a central role for this molecule during TB disease.…”

Section: Discussionmentioning

confidence: 99%

“…Children were diagnosed with TB within the last three months of study enrolment through standardized symptom screening at baseline, including chest radiography (anteroposterior and lateral), mycobacterial culture (MGIT; Becton‐Dickinson, Franklin Lakes, NJ) of gastric aspirates or sputum as well as positive immunological tests including Quantiferon‐TB Gold assays (Cellestis, Ltd., Carnegie, Australia). Two independent experts read chest radiographs, using a standardized pediatric tool .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

et al. 2016

View full text Add to dashboard Cite

Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T-cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV-infected and -uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV-exposed, -infected and -uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric- and fluorescence arrays. Peripheral frequencies of cells phenotypically resembling MDSCs were significantly increased in HIV-exposed uninfected (HEU) and M.tb-infected children, but peaked in children with TB disease and remained high following treatment. MDSC in HIV-infected (HI) children were similar to unexposed uninfected controls; however, HAART-mediated MDSC restoration to control levels could not be disregarded. Increased MDSC frequencies in HHC coincided with enhanced indoleamine-pyrrole-2,3-dioxygenase (IDO), whereas increased MDSC in TB cases were linked to heightened IDO and arginase-1. Increased MDSC were paralleled by reduced plasma IP-10 and thrombospondin-2 levels in HEU and significantly increased plasma IL-6 in HI HHC. Current investigations into MDSC-targeted treatment strategies, together with functional analyses of MDSCs, could endorse these cells as novel innate immune regulatory mechanism of infant HIV/TB susceptibility.

show abstract

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…9 A recent publication by Wiseman et al in which the NIH case definitions were applied to a contact investigation study, indicated that asymptomatic patients with bacterial confirmation of TB represent a continuum of disease that do warrant further evaluation. 10 CXR while useful for diagnosing intrathoracic TB, is limited by poor inter-rater agreement. 11,12 Refinement of NIH definitions to be sensitive to early disease might warrant consideration.…”

Section: Discussionmentioning

confidence: 99%

Understanding NIH clinical case definitions for pediatric intrathoracic TB by applying them to a clinical trial

Beneri

Aaron

Kim

et al. 2016

int j tuberc lung dis

View full text Add to dashboard Cite

Setting and Objective Currently, standardized clinical case definitions represent the best option for pediatric tuberculosis (TB) disease diagnosis and classification. We applied clinical case definitions for intrathoracic TB classification, developed by an expert panel for use in reporting diagnostic studies with passive case finding, to TB suspects from IMPAACT P1041, a trial of INH prophylaxis in healthy HIV-exposed, BCG vaccinated infants which employed active surveillance, to assess novel application of these guidelines in this setting. Methods P1041 TB suspects were retrospectively cross-classified by protocol-defined and NIH classifications and agreement assessed. Results Of 219 TB suspects, 166 had signs/symptoms (S/S), with 158 considered TB (21 confirmed, 92 probable, 45 possible) and 8 not TB (6 TB unlikely, 2 alternative diagnoses). Weight loss and failure to thrive represented the majority of observed S/S. Among those with S/S, agreement between definitions was poor. Additionally, 53 TB suspects were without S/S, including 33 classified by the P1041 protocol as TB. Conclusion The poor agreement between P1041 and NIH classifications reflects cases that are identified through active versus passive surveillance, the latter reflecting the intended use of NIH definitions. Given the interest in having standardized definitions for broader application, future efforts could focus on expanding TB disease classification for detection and classification of suspects identified through active surveillance.

show abstract

“…A useful classification system has been proposed by Wiseman et al which provides guidance on how to classify children as having severe vs. non-severe disease. 28 It may be appropriate to include only children with a confirmed diagnosis (i.e. microbiologic confirmation of the presence of Mycobacterium tuberculosis shown to be resistant by genotypic or phenotypic testing) as this gives an unambiguous entry point and allows changes in microbiological status to provide microbiological endpoints.…”

Section: Selection Of Study Population Design and Treatment Arms Fomentioning

confidence: 99%

Pediatric multidrug-resistant tuberculosis clinical trials: challenges and opportunities

McAnaw¹,

Hesseling²,

Seddon³

et al. 2017

International Journal of Infectious Diseases

View full text Add to dashboard Cite

Objectives On June 17, 2016, RESIST-TB, IMPAACT, Vital Strategies, and New Ventures jointly hosted the Pediatric Multidrug Resistant Tuberculosis Clinical Trials Landscape Meeting in Arlington, VA. The meeting provided updates on current multidrug-resistant tuberculosis (MDR-TB) trials targeting pediatric populations and adult trials that included pediatric patients. Methods A series of presentations were given that discussed site capacity needs, community engagement, and additional interventions necessary for clinical trials to improve the treatment of pediatric MDR-TB. This article presents a summary of topics discussed, including: current trials ongoing and planned; the global burden of MDR-TB in children; current regimens for MDR-TB treatment in children; pharmacokinetics of second-line anti-tuberculosis medications in children; design, sample size, and statistical considerations for MDR-TB trials in children; selection of study population, design, and treatment arms for a trial of novel pediatric MDR-TB regimens; practical aspects of pediatric MDR-TB treatment trials; and strategies for integrating children into adult tuberculosis trials. Results These discussions elucidated barriers to pediatric MDR-TB clinical trials and provided insight into necessary next steps for progress in this field. Conclusions Investigators and funding agencies need to respond to these recommendations so that important studies can be implemented, leading to improved treatment for children with MDR-TB.

show abstract

Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study

Cited by 11 publications

References 29 publications

Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

Phenotypically resembling myeloid derived suppressor cells are increased in children with HIV and exposed/infected with Mycobacterium tuberculosis

Understanding NIH clinical case definitions for pediatric intrathoracic TB by applying them to a clinical trial

Pediatric multidrug-resistant tuberculosis clinical trials: challenges and opportunities

Contact Info

Product

Resources

About