Investigations into an outbreak of suppurative lymphadenitis with BCG vaccine SSI® in Singapore

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

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“…Batch variability has been shown to affect the frequency of AEFI 20 . Each study site used two to three different batches.…”

Section: Discussionmentioning

confidence: 99%

Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

et al. 2022

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“…It is currently listed as a compulsory vaccine under the National Childhood Immunization Schedule (NCIP) in Singapore and is routinely administered at birth to all newborns since the mid-1950s. (MoH, 2017) Although the BCG vaccine is generally well-tolerated in the vast majority of children, local complications, such as abscesses, ulcers, or regional suppurative lymphadenitis may occur (Soh et al, 2014;Lee, 2015). The local incidence of suppurative lymphadenitis in Singapore from both active and passive surveillance data in Singapore was reported to be 3.16 per 1000 vaccinees in 2011.…”

Section: Introductionmentioning

confidence: 99%

“…The local incidence of suppurative lymphadenitis in Singapore from both active and passive surveillance data in Singapore was reported to be 3.16 per 1000 vaccinees in 2011. (Soh et al, 2014) The most severe complication includes a life-threatening disseminated BCG infection (BCGosis), with an estimated incidence of 1 to 3.4 per million, and is associated with a high case-fatality ratio. (Lee, 2015) Disseminated BCG infection should be regarded as an indicator of underlying immunodeficiency until proven otherwise, and should prompt further immunology evaluation.…”

Section: Introductionmentioning

confidence: 99%

Disseminated Bacillus-Calmette-Guérin Infections and Primary Immunodeficiency Disorders in Singapore: A Single Center 15-Year Retrospective Review

Ong

Chan

Chew

et al. 2020

International Journal of Infectious Diseases

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Background: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). Methods: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. Results: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 -7.4) months. All the patients had likely underlying PIDSfour with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. Conclusion: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.

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“…7 A study by Soh et al found that the sharp increase in BCG lymphadenitis might be related to the vaccine batch number, after excluding vaccine administration–related and host–related factors. 26 After the vaccine strain was switched, more BCG lymphadenitis cases were found in the United States, 9 Saudi Arabia, 27 South Korea, 12 and Gaza. 15 The Denmark II strain has been used in China since 1993.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological characteristics and trends of Bacillus Calmette–Guérin lymphadenitis in Shanghai, China from 2010 to 2019

Wang¹,

Zhou²,

Ming-bo³

et al. 2021

Human Vaccines & Immunotherapeutics

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Although the administration of the Bacillus Calmette-Guérin (BCG) vaccine is generally safe, lymphadenitis, the most common complication of BCG vaccination, can occur. Here, we describe the epidemiological characteristics and incidence trends of BCG lymphadenitis in Shanghai, China, among a population with a high burden of tuberculosis. A total of 56 cases of adverse events following immunization (AEFI) after BCG vaccination were reported in Shanghai, including 51 cases of BCG lymphadenitis (91.07%), from 2010 to 2019. The general incidence of BCG lymphadenitis was 173 per 1,000,000 doses in Shanghai from 2010 to 2019. A nonsignificant increase of 58.81% per year was observed between 2010 and 2012 (t = 0.93; p = .40), followed by a significant decline of 28.00% per year from 2012 to 2019 (t = −4.27; p < .01). Seven batches of BCG vaccines triggered three or more BCG lymphadenitis cases, for 27 (52.94%) cases in total. We identified two patients with immunodeficiency of chronic granulomatous disease, one of whom died four years later after BCG vaccination and another of whom was still being treated after two transplants. The average total care cost of the 47 recovered cases was 11,336 RMB (range: 2,637-33,861 RMB). Due to the high burden of BCG lymphadenitis, especially in children with immunodeficiency, it is suggested that government departments should strengthen healthcare provider training, assign specific nurses to perform BCG vaccination, monitor vaccinated individuals actively and timely detect abnormal signals so as to reduce the incidence of BCG lymphadenitis.

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Investigations into an outbreak of suppurative lymphadenitis with BCG vaccine SSI® in Singapore

Cited by 12 publications

References 12 publications

Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

Disseminated Bacillus-Calmette-Guérin Infections and Primary Immunodeficiency Disorders in Singapore: A Single Center 15-Year Retrospective Review

Epidemiological characteristics and trends of Bacillus Calmette–Guérin lymphadenitis in Shanghai, China from 2010 to 2019

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