The safety of isoniazid tuberculosis preventive treatment in pregnant and postpartum women: systematic review and meta-analysis

BACKGROUND: The World Health Organization (WHO) recommends tuberculosis (TB) preventive treatment for high-risk groups. Isoniazid preventive therapy (IPT) has been used globally for this purpose for many years, including in pregnancy. This review assessed current knowledge about the safety of IPT in pregnancy. METHODS: We searched PubMed, Embase, CENTRAL, Global Health Library and HIV and TB-related conference abstracts, until May 15, 2019, for randomised controlled trials (RCTs) and non-randomised studies (NRS) where IPT was administered to pregnant women. Outcomes of interest were: 1) maternal outcomes, including permanent drug discontinuation due to adverse drug reactions, any grade 3 or 4 drug-related toxic effects, death from any cause and hepatotoxicity; and 2) pregnancy outcomes, including in utero fetal death, neonatal death or stillbirth, preterm delivery/prematurity, intrauterine growth restriction, low birth weight and congenital anomalies. Meta-analyses were conducted using a random-effects model. RESULTS: After screening 1342 citations, nine studies (of 34 to 51 942 participants) met inclusion criteria. We found an increased likelihood of hepatotoxicity among pregnant women given IPT (risk ratio 1.64, 95% CI 0.78-3.44) compared with no IPT exposure in one RCT. Four studies reported on pregnancy outcomes comparing IPT exposure to no exposure among pregnant women with HIV. In one RCT, adverse pregnancy outcomes were associated with IPT exposure during pregnancy (odds ratio (OR) 1.51, 95% CI 1.09-2.10), but three NRS showed a protective effect. CONCLUSIONS: We found inconsistent associations between IPT and adverse pregnancy outcomes. Considering the grave consequences of active TB in pregnancy, current evidence does not support systematic deferral of IPT until postpartum. Research on safety is needed

Framework for the evaluation of new tests for tuberculosis infection

The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. We also briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system patient, and operational characteristics

Global guidelines for treatment of tuberculosis among persons living with HIV: unresolved issues

The Revised National Tuberculosis Control Programme (RNTCP) in India uses a fully intermittent thrice-weekly rifampicin-containing regimen for all tuberculosis (TB) patients, including those who are human immunodeficiency virus (HIV) infected, whereas the World Health Organization (WHO) recommends daily anti-tuberculosis treatment at least during the intensive phase. The WHO recommendation was based on the results of a metaanalysis demonstrating increased risk of recurrence and failure among HIV-infected TB patients receiving intermittent TB treatment compared to a daily regimen. Review of the primary evidence indicates limited, lowquality information on intermittency, mostly from observational studies in the pre-antiretroviral treatment (ART) era. Molecular epidemiology in India indicates that most of the recurrences and many of the failures result from exogenous re-infection, suggesting poor infection control and high transmission rather than poor regimen e fficacy. Subsequently published studies have shown acceptable treatment outcomes among HIV-infected TB patients receiving intermittent anti-t uberculosis regimens with concomitant ART. Treatment outcomes among HIV-infected TB patients treated under programmatic conditions show low failure rates but high case fatality; death has been associated with lack of ART. The highest priority is therefore to reduce mortality by linking all HIV-infected TB patients to ART. While urgently seeking to reduce death rates among HIV-infected TB patients, given the poor evidence for change and operational advantages of an intermittent regimen, the RNTCP intends to collect the necessary evidence to inform national policy decisions through randomised clinical trials

TB preventive treatment among pregnant women with HIV

BACKGROUND: The WHO recommends TB preventive treatment (TPT) for people living with HIV, including pregnant women. Uptake of this policy recommendation in this subpopulation and country alignment with WHO guidance is unclear.METHODS: We conducted a policy review in 38 WHO high TB and TB-HIV burden countries to assess if the uptake of TPT policy among pregnant women living with HIV was in line with the WHO´s 2018 Updated and Consolidated Guidelines for Programmatic Management for LTBI. Data sources included TB national guidelines and HIV/AIDS/ART national guidelines, complemented by results from a previous survey on policy uptake held at the WHO.RESULTS: Uptake of WHO policy to provide TB preventive treatment among women with HIV accessing antenatal care was moderate: 64% (23 of 36 countries) explicitly recommended at least one clinical guideline or policy recommendation on screening, testing or treatment of LTBI among pregnant women living with HIV. There was considerable variation between countries on the stages in pregnancy that TPT should be provided. Two countries (5%) provided clinical monitoring recommendations for pregnant women.CONCLUSIONS: There is moderate uptake of TPT policy for pregnant women with HIV. Failure to provide TPT as part of antenatal or prevention of mother-to-child services is a missed opportunity for TB control