Vaccine Reports
Safety of the Polish BCG-10 Vaccine During a Period of BCG
Vaccine Shortage: An Australian Experience
Nicole X. Wong, MBBS,*† Jim Buttery, PhD,‡§ Alissa McMinn, BN,† Zainul Azhar, MBBS,‡ and
Nigel W. Crawford, PhD*†
Abstract: Bacille Calmete-Guerin vaccine is widely administered to
reduce the risk of severe tuberculosis disease in children. Recent global
vaccine supply issues have led to the use of alternative products, which may
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vary in side effect profile. We report on the safety of the Polish (Moreau
strain) “Bacille Calmete-Guerin-10” vaccine in an Australian cohort. Using
active surveillance, we identified an adverse event rate of 54.6 per 10,000
doses (95% confidence interval: 38.5–75.2), which was comparable to that
reported with the Danish Sanofi-Pasteur and Connaught strains.
Key Words: adverse events following immunization, Bacille Calmete-
Guerin, vaccine safety
(Pediatr Infect Dis J 2020;39:e66–e68)
T he bacille Calmete-Guerin vaccine (BCG) is an attenuated
form of Mycobacterium bovis, administered to reduce the risk
of severe tuberculosis disease in children. In Australia, a country
with low tuberculosis disease incidence, BCG vaccine is recom-
mended for high-risk populations: children younger than 5 years
who are travelling to countries with high tuberculosis prevalence,
children of Aboriginal and Torres Strait Islander descent living in
communities with high disease incidence, and those with a family
history of leprosy.1
The BCG vaccine is very immunogenic, with potential for
localized and systemic reactions that may take weeks to months to
resolve.2 Common adverse events following immunization (AEFI)
with BCG include abscess formation and regional lymphadenitis.
While BCG is considered a relatively safe vaccine, disseminated
BCG disease and osteitis can occur. This is of particular concern in
immunocompromised children.3 Following initial development of
BCG, repeated subculture of the vaccine has led to multiple BCG
strains, which may vary in immunogenicity and side effect profile.4
Previous reviews of BCG safety have shown heterogeneity in the
side effect profile according to geographical region, BCG strain
used and the mode of administration.2,5
Since 2012, a worldwide shortage of the Danish Sanofi-
Pasteur BCG strain has led vaccine providers to utilize alternative
strains. In the Australian state of Victoria, the Polish “BCG-10”
vaccine derived from the Brazilian Moreau strain has recently been
utilized since February 2, 2016.
Accepted for publication January 30, 2020.
From the *Department of General Medicine, Royal Children’s Hospital, Mel-
bourne, Australia; †SAEFVIC, Murdoch Children’s Research Institute;
‡Department of Infection and Immunity, Monash Children’s Hospital,
Monash Health, Clayton, Australia; and §Department of Paediatrics, Monash
University, Clayton, Australia.
The authors have no funding or conflicts of interest to disclose.
Address for correspondence: Nicole X. Wong, MBBS, BMedSci, MBioeth,
Paediatric Registrar, General Medicine, Royal Children’s Hospital, 50 Flem-
ington Road, Parkville, Melbourne, Victoria 3052, Australia. E-mail: nico-
lexwong@gmail.com or nicole.wong@rch.org.au
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0891-3668/20/3906-0e66
DOI: 10.1097/INF.0000000000002630
e66 | www.pidj.com The Pediatric Infectious Disease Journal  •  Volume 39, Number 6, June 2020
Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
BCG-10 has been manufactured and utilized in Poland since
1955.6 However, there are limited reports of this strain’s safety.
Given suspected variation in BCG strain immunogenicity, we have
closely monitored AEFI patterns following the use of this vaccine
strain in Australia.
METHODS
In Australia, BCG vaccine provision is funded through state
programs. In the state of Victoria, BCG vaccine is largely adminis-
tered through the 2 tertiary pediatric hospitals, The Royal Children’s
Hospital (RCH) and Monash Children’s Hospital (MCH). Most vac-
cine recipients are younger than 12 months of age, though the vac-
cine is recommended in children up to 5 years of age in Australia. To
assess the safety of BCG-10, vaccine recipients were prospectively
monitored for AEFI. Children who received BCG vaccine at RCH
were reviewed via an email survey 6 months post BCG adminis-
tration. Children who received the vaccine via MCH were sent an
SMS 6 months postvaccination prompting families to report AEFI.
AEFI was then reported via Surveillance of Adverse Events Fol-
lowing Vaccinations in the Community (SAEFVIC), a state-wide
immunization safety service through which community members
and healthcare providers are able to report any reactions postvac-
cination. Additionally, a search of MCH records was performed to
identify any patients who had “BCG reaction” entered in their medi-
cal records. These records were reviewed to identify any children
who may have had AEFI that were not reported to SAEFVIC.
All RCH, MCH and SAEFVIC reports made during the
period of BCG-10 usage, from February 2016 to December 2018,
were reviewed. The SAEFVIC reports included those identified
through active follow-up of RCH and MCH vaccine recipients,
alongside a small number of external AEFI reports (children vac-
cinated in the community or overseas).
AEFI was defined according to Lotte’s classification,2 with
localized AEFI including abscess or necrosis. Lymphadenopathy
included enlarged lymph nodes that were fluctuant or adherent to
the skin. Redness at the injection site, nodule formation and skin
ulceration which resolved spontaneously were not considered an
AEFI, but rather an expected local reaction.7
The incidence of AEFI was calculated using the total num-
ber of vaccine doses administered through RCH and MCH as the
denominator. Statistical analysis was performed using SPSS.
RESULTS
During the study period, 6779 children received BCG vac-
cine (3484 at MCH and 3295 at RCH). There were 75 reported
side effects (21 identified through active surveillance at RCH, 47
via SAEFVIC and additional 5 from review of MCH records), as
shown in Figure 1. Children who received a different BCG vaccine
strain (ie, not BCG-10) and those assessed to have an expected,
local reaction were excluded. The remaining 37 were classified as
AEFI, an incidence of 54.6 AEFI per 10,000 doses (95% confi-
dence interval: 38.5–75.2). The median age of this group was 12.1
months (range 3.2–52 months).
The Pediatric Infectious Disease Journal  •  Volume 39, Number 6, June 2020 BCG-10 Safety: An Australian Experience

FIGURE 1.  Summary of adverse events identified following BCG-10 vaccination.

In this cohort, the most common AEFI was local abscess treatment was specified, cephalexin and flucloxacillin were
(25/37, 68%). Only one case required incision and drainage. administered). No children received antituberculous therapy.
Three children were treated with antibiotics (in cases where Potential risk factors in our cohort included eczema (7/37,

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Wong et al The Pediatric Infectious Disease Journal  •  Volume 39, Number 6, June 2020
18.9%) and immunosuppression (one child had known neutro-
penia).
DISCUSSION
This is the first profile of BCG-10 safety since its introduc-
tion in Australia. The only previous passive surveillance study of
this strain of BCG was from Poland reported an AEFI incidence
of 20–60 per 10,000 doses. The cohort in this Polish study also
appeared to have more severe AEFI, as a quarter of children with
AEFI required hospitalization, which may suggest more severe
reactions or differing hospitalization practices..6
The incidence of AEFI for this cohort of 54.6 per 10,000
doses is comparable to AEFI profiles of other BCG strains. An
Australia-wide study of BCG (Connaught or Denmark SSI) recipi-
ents from 2009 to 2014 reported an AEFI incidence of 33–68 per
10,000 doses.3 Another Victorian study of the same strains reported
a lower incidence of 11.6–15.4 per 10,000 doses.8 The spectrum
of AEFI in these studies was similar, with abscess, injection site
reaction and lymphadenopathy/lymphadenitis being the most com-
monly reported. The number of children with lymphadenopathy
was small, consistent with a previous review that suggested the
Brazilian Moreau strain was rarely associated with lymphadenitis5
The variable results of these studies show wide variation of
reported BCG effects, which may relate to variation in defining and
diagnosing AEFI. For example, the distinction between an expected
injection site reaction and abscess formation may vary between cli-
nicians. Additionally, technique with administration technique may
also influence rates of AEFI.9 Reporting patterns may also vary.
These factors introduce limitations into our study. During
this time period, vaccine providers and healthcare workers may
have been more likely to report reactions in the setting of a new
product. Additionally, the use of active follow-up for AEFI may
have resulted in more sensitive reporting, compared with previous
passive surveillance studies.
Finally, it is likely that additional doses of vaccine were
administered through private providers and travel clinics; hence,
the denominator used to calculate incidence is likely to be an under-
estimate. As BCG vaccine is not funded in Australia via the national
immunization program, there are no specific incentives for private
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providers to register BCG administration and BCG administra-
tion is rarely reported on the Australian Immunization Register. As
such, it is difficult to ascertain the true incidence of BCG-10 vac-
cine use. While we believe that adverse reactions sustained through
these providers would be captured via the SAFEVIC reporting sys-
tem, the number of total BCG vaccine doses administered state-
wide would be underestimated, resulting in an overestimated AEFI
incidence rate.
Despite these limitations, we believe our study provides a
reflection of the safety of BCG-10. The prospective nature of sur-
veillance and generous estimates of AEFI incidence have nonethe-
less shown a safety profile comparable to that documented with
previously used strains. In addition, the severity of AEFI in this
cohort was low, with few cases requiring intervention.
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