Efficacy and safety of different regimens in the treatment of patients with latent tuberculosis infection: a systematic review and network meta-analysis of randomized controlled trials

Abstract

Background Treatment of latent tuberculosis infection (LTBI) is effective in preventing progression to TB disease. This study aimed to synthesize available evidence on the efficacy, adherence, and safety of LTBI treatment in order to assist policymakers to design appropriate national treatment policies and treatment protocols. Method The PRISMA-NMA was used to review and report this research. Randomized controlled trials which compared the efficacy and safety of LTBI treatments were included. A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL). The network meta-analysis was done using R- studio Version 1.4.1103. Result In this review, 42 studies were included, which enrolled 46,022 people who had recent contact with patients with active tuberculosis, evidence radiological of previous tuberculosis, tuberculin test equal or greater than 5 mm, radiographs that indicated inactive fibrotic or calcified parenchymal and/or lymph node lesions, had conversion to positive results on a tuberculin skin test, participants living with HIV, chronic Silicosis, immigrants, prisoners, old people, and pregnant women who were at risk for latent TB were included. The incidence of TB among people living with HIV who have taken 3RH as TPT was lower, followed by 48%,followed by 6H (41%). However, 3HP has also the potential to reduce the incidence of TB by 36% among HIV negative patients who had TB contact history. Patients’ adherence to TPT was higher among patients who have taken 4R (RR 1.38 95% CI 1.0,1.89) followed by 3RH (34%). The proportion of subjects who permanently discontinued a study drug because of an adverse event were three times higher in the 3RH treatment group. Furthermore, the risk of grade 3 and 4 liver toxicity was significantly higher in 9H followed by 1HP, and 6H. Conclusion From this review, it can be concluded 3RH and 6H has a significant impact on the reduction of TB incidence among PLWH and 3HP among HIV negative people who had TB contact history. However, combinations of rifampicin either with isoniazid were significantly associated with adverse events which resulted in permanent discontinuation among adult patients. Furthermore, grade 3 and 4 liver toxicity was more common in patents who have taken 9H, 1HP, and 6H. This may support the current recommended TPT regimen of 3HP, 3RH, and 6H.

Tackling Drug-Resistant Tuberculosis: New Challenges from the Old Pathogen Mycobacterium tuberculosis

“…For people who cannot take a rifamycin-based regimen because of drug intolerance, the CDC recommended treatments include: (a) six months (for HIV-negative adults and children) or nine months of daily isoniazid; (b) three months of once-weekly isoniazid plus rifapentine [ 90 ]. Short-course regimens have both higher completion rates and a lower risk of hepatotoxicity than prolonged isoniazid monotherapy [ 91 ]. It is important to note that if treatment is not taken regularly or stopped too early, the bacteria can grow again and become resistant to the drugs.…”

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

“…In the US, most tuberculosis (TB) cases arise from the large group of approximately 13 million asymptomatic individuals with TB infection (TBI), also known as latent TBI, which can progress to active TB disease. 1 , 2 Although numerous studies have demonstrated the efficacy of TBI treatment to prevent progression to TB disease, 3 , 4 , 5 optimal TBI tests to identify individuals at risk of TB disease are needed. 6 The US Food and Drug Administration (FDA) has approved 2 test types: the tuberculin skin test (TST) and IFN-γ release assays (IGRAs), including QuantiFERON-TB Gold In-Tube (QFT-GIT; Qiagen) and T-SPOT.TB (TSPOT; Oxford Immunotec).…”

Mycobacterium tuberculosisFtsB and PerM interact via a C-terminal helix in FtsB to modulate cell division

“…Preventing establishment and reactivation of LTBI is a growing priority for TB elimination strategies, although uncertainties continue to limit measurements of the relative burdens of new TB infections and LTBI reactivation [3]. Protocols that reduce the duration and adverse effects of treatment can reduce LTBI burden by improving completion rates for preventative treatment [4]. Furthermore, imperfect treatment over long periods can contribute to acquisition of drug resistance [5].…”