Treating BCG-induced disease in children

Centre for Evidence Based Practice Tecnológico de Monterrey, Escuela de Medicina-ITESM, Monterrey NL, .
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 01/2013; 1(1):CD008300. DOI: 10.1002/14651858.CD008300.pub2
Source: PubMed


Bacillus Calmette-Guerín (BCG) is a live attenuated vaccine to prevent tuberculosis, routinely administered at birth as part of the World Health Organization global expanded immunisation programme. Given intradermally, it can cause adverse reactions, including local, regional, distant and disseminated manifestations that may cause parental distress. Rarely, it can cause serious illness and even death. Among those patients with immunocompromised conditions, such as the human immunodeficiency virus (HIV) infection, the complication rate is even higher.
To assess the effects of different interventions for treating BCG-induced disease in children.
The following databases were searched: the Cochrane Infectious Diseases Group Specialized Register and Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (The Cochrane Library 2012, Issue 4); MEDLINE (1966 to November 2012); EMBASE (1947 to November 2012); and LILACS (1980 to November 2012). The metaRegister of Controlled Trials (mRCT) and the WHO trials search portal. Conference proceedings for relevant abstracts and experts were also contacted to identify studies. No language restrictions were applied.
Randomized controlled trials (RCTs) comparing any medical or surgical treatment modality for BCG-induced disease in children.
Two authors independently evaluated titles, applied inclusion criteria, and assessed the risk of bias of studies. The primary outcomes were the failure rate of therapies for all types of BCG vaccine-induced complications and the time to resolution of illness measured in months. The secondary outcomes were death from BCG vaccine-induced disease and the all-cause mortality. Risk ratios (RRs) were used as measure of effect for dichotomous outcomes and mean differences for continuous outcomes.
Five RCTs analysing 341 children addressed the primary outcomes and were included. Four arms compared oral antibiotics to no intervention or placebo, one arm evaluated needle aspiration compared to no intervention, and another evaluated the use of locally instilled isoniazid versus oral erythromycin.Two small studies evaluated oral isoniazid; we are uncertain of whether this intervention has an effect on clinical failure (RR 1.48; 95% Confidence Interval (CI) 0.79 to 2.78; 54 participants, two studies, very low quality evidence). Similarly, for oral erythromycin, we are uncertain if there is an effect (clinical failure RR 1.03; 95% CI 0.70 to 1.53; 148 participants, three studies, very low quality evidence), and for oral isoniazid plus rifampicin (clinical failure, RR 1.20; 95% CI 0.51 to 2.83; 35 participants, one study, very low quality evidence).In patients with lymphadenitis abscess, needle aspiration may reduce clinically persistent BCG-induced disease at 6 to 9 months of follow-up (RR 0.13; 95% CI 0.03 to 0.55; 77 participants, one study, low quality evidence). In another study of patients with the same condition, aspiration plus local instillation of isoniazid reduces time to clinical cure compared to aspiration plus oral erythromycin (mean difference 1.49 months less; 95% CI 0.82 to 2.15 less; 27 participants, one study).No RCTs of HIV-infected infants with a BCG-induced disease evaluated the use of antibiotics or other therapies for reducing the rate of clinical failure or the time to clinical resolution. No data on mortality secondary to the interventions for treating BCG-induced disease were reported.
It is unclear if oral antibiotics (isoniazid, erythromycin, or a combination of isoniazid plus rifampicin) are effective for the resolution of BCG-induced disease. Most non-suppurated lymphadenitis will resolve without treatment in 4 to 6 months. Patients with lymphadenitis abscess might benefit from needle aspiration and possibly local instillation of isoniazid could shorten recovery time. Included studies were generally small and could be better conducted. Further research should evaluate the use of needle aspiration and local instillation of isoniazid in fluctuant nodes. Therapeutic and preventive measures in HIV-infected infants could be important given the higher risk of negative outcomes in this group.

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    • "Local and regional adverse reactions occur most frequently and the majority are self-limiting [4] [17]. However, many clinicians advocate treatment, including use of antimicrobials, needle aspiration and/or surgery [4] [11] [17] and practice is likely to vary substantially across sites. Here we describe our experience of BCG vaccine-associated adverse reactions in children referred to two large hospitals in London, United Kingdom. "
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    ABSTRACT: Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. Injection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain. Copyright © 2015. Published by Elsevier Ltd.
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    ABSTRACT: Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine is widely administered to prevent tuberculosis. Vaccine complications are rare. However, when BCG-related adverse reactions arise there is a need to rapidly and reliably identify BCG from other members of the Mycobacterium tuberculosis complex (TBC). PCR assays based on the detection of the regions of difference (RD), in particular RD1 and RD9, have been invaluable in the identification of BCG. Prior to this study, specimens were identified through HPLC analysis at a local reference laboratory taking up to 2 weeks for a result. We sought to expedite the identification process by validating a RD1, RD9 and hsp65 PCR assay for the identification and differentiation of BCG from TBC. In last past 3 years, we validated the RD1, RD9 and hsp65 PCR assay for 16 mycobacterial isolates obtained from children who had experienced adverse reactions to BCG vaccination. In these cases, the clinician required a definitive identification of the isolate. The RD1 and RD9 PCR profiles indicated that all 16 isolates were BCG whilst amplification of the hsp65 target functioned as a PCR positive control. When tested against clinical M. tuberculosis (MTB), reference and non-tuberculous mycobacteria the PCR assay demonstrated 100% sensitivity and specificity. The RD1, RD9 and hsp65 PCR assay is a useful tool for the rapid and reliable identification of BCG. Its ease of use has allowed it to be implemented in our clinical microbiology laboratory.
    Full-text · Article · Oct 2013 · BMC Research Notes
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    Preview · Article · Nov 2013 · Archives of Disease in Childhood - Education and Practice
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