Short communicationThe risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children
Introduction
Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis strain vaccine, is routinely given to infants at birth or shortly thereafter, in regions where tuberculosis is endemic. The World Health Organization (WHO) currently recommends that BCG be given to all asymptomatic infants, irrespective of human immunodeficiency virus (HIV) exposure [1]. This policy has practical limitations, as most HIV-exposed infants are infected perinatally, and are therefore asymptomatic at birth. Vaccination with BCG has remained the standard of care for tuberculosis prevention in most developing countries because of its documented efficacy in preventing life-threatening forms of disease in HIV-uninfected infants and young children. It is the only currently available vaccine, is inexpensive and requires only one encounter with an infant [2].
In the absence of HIV infection, BCG-associated adverse events in children include injection-site lesions, adenitis, suppurative adenitis and very rarely, disseminated disease. Adverse events vary with vaccine strain type, physical–chemical properties, bacillary load, administration method and host immune characteristics [3]. The reported frequency of disseminated BCG disease has traditionally been less than five per one million vaccinees and is mainly associated with congenital cellular immunodeficiency [4]. Despite several case reports of local and disseminated BCG disease in HIV-infected infants [5], [6], [7], [8], [9], the risk of disseminated BCG disease in children vertically infected with HIV remains poorly quantified, partly due to a lack of surveillance and adequate population-based data in HIV-endemic settings.
Disseminated BCG disease in HIV-infected children is likely to be underreported, especially in settings highly endemic for tuberculosis and HIV, where diagnostic facilities are often limited [10]. Even where mycobacterial culture is available, disseminated BCG disease may be misdiagnosed as tuberculosis in HIV-infected children, in the absence of accurate Mycobacterium tuberculosis complex speciation [11]. This preliminary reports aims to estimate the risk of disseminated BCG disease in HIV-infected infants in a setting highly endemic for tuberculosis and HIV, using available paediatric population data and known BCG coverage rates and analyzing different hypothetical scenarios for vertical transmission of HIV combined with known maternal antenatal HIV prevalence in the public health sector.
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Study setting
This study was conducted from January 2002 to December 2004 at the Tygerberg Children's Hospital, Western Cape Province, South Africa, which drains 30–50% of provincial tertiary paediatric referrals. The adult tuberculosis incidence in the province was 678/100,000 in 2003, the incidence of tuberculosis in children <13 years of age was 407/100,000 and the HIV prevalence among women attending public antenatal care facilities was 15.4% (95% CI: 12.5–18.2%) in 2004 [12], [13], [14]. Current South
Results
Nine children were diagnosed with disseminated BCG disease over the study period. All these children had immune deficiencies. Seven children were HIV-infected; all had advanced HIV disease and were <1 year of age; the mortality was 85.7% (6/7). The two HIV-uninfected children with disseminated BCG disease, both had primary immune deficiencies including one child with severe combined immunodeficiency and a second with an unidentified T-cell deficiency. Detailed data on the clinical presentation,
Discussion
We have demonstrated that neonatal BCG vaccination may pose a considerable risk of distant or disseminated BCG disease to infants vertically infected with HIV, even when they are asymptomatic when vaccinated at birth. The estimated risk of disseminated BCG disease in HIV-infected children was increased several hundred fold compared to that historically described in HIV-negative children. Further surveillance of BCG safety is critically important to more accurately estimate the risk of BCG
Acknowledgements
The authors would like to thank Robin Warren, DST/NRF Centre of Excellence and Department of Medical Biochemistry, Faculty of Health Sciences, Stellenbosch University for PCR speciation, Wendy Brittle for mycobacterial culture, Cape Town City Health (Pren Naidoo and Ivan Toms), the Western Cape Province Department of Health (Keith Cloete and Fawzia Desai) for advice on immunization and HIV surveillance data and the South African Actuarial Society (Leigh Johnson and Keith Dorrington), for use
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