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
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.
Data collection and analysis
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
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
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.
Plain Language Summary
Bacillus Calmette-Guérin (BCG) is a widely used tuberculosis vaccine
derived from a non-infectious strain of the bovine tuberculosis bacillus
(Mycobacterium bovis) and mainly given to young children. Usually, the
only adverse reaction to the vaccine is an ulcer at the site of
injection, which may leave a small scar.
Very occasionally, however, especially in children with weakened immune
systems, the vaccine can cause more serious side effects. These can
include local infections at the injection site, which may spread to the
lymph nodes, causing lymphadenopathy, and the bones, and can even prove
life-threatening. These adverse reactions to the BCG vaccine are a
particular risk for children infected with the Human Immunodeficiency
Virus (HIV), where the condition is known as BCG immune reconstitution
inflammatory syndrome (BCG-IRIS).
In many cases, the infections resolve without any intervention, but
treatments can include oral antibiotics, needle aspiration, draining
abscesses, and surgically removing infected lymph nodes. This review was
conducted to try to determine the effectiveness of these different
The review found no evidence of any benefit of using oral antibiotics to
treat local or regional BCG-induced disease. In patients with
abscess-forming lymphadenopathy, the only intervention with proven
benefit was needle aspiration of the abscesses with or without local
injection of the antibiotic isoniazid.
Based on these findings, the review authors recommend a 'wait and see'
approach with follow-up visits for minor reactions and lymphadenopathy
without abscesses. For abscess-forming lymphadenopathy, which can cause
distress and discomfort, they advise needle aspiration. However, this
review is based on only five studies, all of which were assessed as
having a low or very low quality of evidence. As a consequence, the
authors conclude there is an urgent need for more and better studies on
ways to prevent and treat BCG-induced disease, especially BCG-IRIS.
Cuello-García, C.A.; Pérez-Gaxiola, G.; Jiménez Gutiérrez, C. Treating BCG-induced disease in children. Cochrane Database of Systematic Reviews (2013) (Issue 1) Art. No.: CD008300. [DOI: 10.1002/14651858.CD008300.pub2]
Treating BCG-induced disease in children.