Effectiveness and safety of available preventive tuberculosis treatment regimens for children and adolescents: protocol for a systematic review and network meta-analysis

Abstract

IntroductionApproximately 5%–10% of individuals with untreated latent tuberculosis infection (LTBI) will progress to active tuberculosis (TB). Children are at a higher risk for progression to TB disease than adults. Isoniazid prophylaxis treatment period is long and can cause liver damage. Alternatives to isoniazid, such as rifamycin containing regimens, should be considered for prophylaxis. Previous systematic reviews, with different study designs and data combining results on children and adults, have evaluated the comparative efficacy and harms of LTBI treatment regimens. We aim to determine the effectiveness and safety of all the different regimens available for the treatment of LTBI for children and adolescents less than 18 years of age, contacts of drug-susceptible TB, without HIV infection.Methods and analysisMEDLINE, Embase and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials without any language or publication date restriction. Screening and extraction will be performed in duplicate. Risk of bias will be performed in duplicate with Cochrane Risk of Bias tool V.2. Pairwise meta-analysis of direct comparisons and network meta-analyses (NMAs) will be performed. Heterogeneity will be assessed using I2 and Cochrane thresholds. Direct and indirect estimates in an NMA will be combined if justifiable. Subgroups analyses will be performed in different mean age and study year groups. Sensitivity analysis based on the risk of bias will be conducted. Publication bias will be investigated using funnel plots and Egger’s regression test. Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria will assess certainty of the evidence for the direct comparisons. GRADE approach for NMA will assess the quality of the evidence from the indirect and NMA.Ethics and disseminationEthical approval is not required as no primary data are collected. This systematic review will be disseminated in a peer-reviewed journal.PROSPERO registration numberCRD42021271512.

Screening, prophylaxis, and challenges: Tumor necrosis factor inhibitors and latent tuberculosis infection nexus in rheumatology

“…After excluding active TB, both the WHO and the CDC of USA recommend starting the application of TNFi after 3–4 weeks of preventive treatment for TB in advance if the clinical condition allows 19,20 . Some scholars have also proposed that if the condition is urgent, TNFi and preventive treatment can be initiated simultaneously after thorough evaluation 21 . There is currently no consensus on the span and plan of preventive treatment for TB.…”

“…In principle, isoniazid and rifampicin monotherapy or combination therapy can be used, the combination of isoniazid and rifampicin for 3–4 months could be more recommended, especially in patients with exposure to infectious TB patients, or in patients who seroconvert (conversion of TST/IGRA from negative to positive). Compared to isoniazid/rifampicin monotherapy, combination therapy can shorten the treatment time and achieve higher treatment completion rates 21 . Although expert comments proposed that after proper LTBI screening, proactive TB therapy has been demonstrated to be effective and well‐tolerated to reduce the risk of TB reactivation in RD patients requiring TNFi, 22 there are still case reports of TB reactivation and subsequent poor prognosis in patients with preventive treatment 23 .…”