Outcome of culture-confirmed isoniazid-resistant rifampicin-susceptible tuberculosis in children

Abstract

DECLARATIONBy submitting this thesis electronically, I declare that the entirety of the work contained therein is my own, original work, that I am the sole author thereof (save to the extent explicitly otherwise stated), that reproduction and publication thereof by Stellenbosch University will not infringe any third party rights and that I have not previously in its entirety or in part submitted it for obtaining any qualification. the most prevalent form of drug-resistant TB globally, and may be a risk factor for poor outcomes. HRRS-TB in children has been poorly described.Objective: To characterize the clinical presentation, treatment, and clinical and microbiological outcomes, and factors associated with poor outcomes among children with culture-confirmed HRRS-TB. Design:Retrospective hospital-based cohort study. Results:Of the 72 children included, median age 50.1 months (IQR 21.5-102.5), 42% were male. Forty-four (51%) had a potential source case; only 13 were confirmed HRRS-TB. Twelve of 66 tested (17%) were HIV-infected, and 36 of 60 (60%) with pulmonary TB had severe disease. Seventy had treatment data; median total duration was 11.3 months (IQR 9-12.3); 25 (36%) initiated treatment with a 3-drug intensive phase; 52 (74%) received a fluoroquinolone. Of 63 with known outcome, 55 (88%) had a favourable outcome; 1 died and 3 had treatment failure. Ten had positive follow-up cultures at ≥2 months after starting treatment (17% of all PTB and 27% of those with follow-up culture data); older age (p=0.008), previous TB treatment (p=0.023) and severe PTB (p=0.018) were associated with failure to cultureconvert at ≥2 months. Conclusions:Although overall outcomes were good, prolonged culture positivity and cases of treatment failure emphasize the need for additional attention to clinical management of children with HRRS-TB.Stellenbosch University https://scholar.sun.ac.za ACKNOWLEDGEMENTS

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis

“…6 Five of the contacted authors provided additional unpublished datasets; three have since been published. [13][14][15] Three regional or national surveillance datasets were provided by those responding to an invitation to all participants at a WHO European regional Resistant TB surveillance meeting. [16][17][18] Specific criteria for participation in this IPD were: the study authors agreed to share their data, regimens and outcomes were known for individual patients, and at least 20 subjects were treated for INH-R TB if a cohort study.…”

“…We received 33 datasets (27 from observational studies and 6 from RCT) with adequate treatment and outcome information for 5502 patients with pulmonary INH-R TB. In 10 datasets, with 762 patients, no patients received any of the regimens of interest; 13,[25][26][27][28][29][30][31][32][33] in the remaining 23 datasets, 3923 patients [14][15][16][17][18][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] received one of the regimens of the study questions, and 817 patients received other regimens. The characteristics of the patients from the 23 centers are summarized in table S1a.…”

3,6‐Dihydroxyflavone Has Antituberculosis Activity and Suppresses Lung Inflammation

“…It has been assumed that the main function of these fibroblasts is to isolate and repress the growth of Mtb. [8][9][10] These strains make TB difficult to cure due to limited treatment options even when expensive and toxic second-line drugs, requiring hospitalization, are used. 3 In human, fibroblast matrix metalloproteinase (MMP-1) upregulation occurs through p38 mitogen-activated protein kinase and NF-κB-dependent pathways.…”

“…To date, MDR is the most prevalent TB globally. XDR is resistant to either isoniazid or rifampicin, any fluoroquinolone, and at least one of the second‐line injectable drugs, amikacin, capreomycin, or kanamycin, used for the treatment of TB . These strains make TB difficult to cure due to limited treatment options even when expensive and toxic second‐line drugs, requiring hospitalization, are used.…”

Rapid detection of Mycobacterium tuberculosis DNA and genetic markers for Isoniazid resistance in Ziehl-Neelsen stained slides

“…There have been recurrent studies showing the agent Mycobacterium tuberculosis resistant to INH and sensitive to RIF; meaning a risk factor for unfavorable outcomes. (1) Globally, monoresistance to INH presented in 2014 an overall mean of 9.5% in new cases and 14% in previously treated TB. It is estimated that more than 1 million people develop INH resistant, each year.…”