The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children

Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg, 7505, South Africa.
Vaccine (Impact Factor: 3.62). 02/2007; 25(1):14-8. DOI: 10.1016/j.vaccine.2006.07.020
Source: PubMed


Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis vaccine, poses a risk to human immunodeficiency virus (HIV)-infected children; this risk has not been well quantified. We estimate the risk of disseminated BCG disease in HIV-infected children in a setting highly endemic for tuberculosis and HIV.
We conducted a prospective hospital-based surveillance study in the Western Cape Province, South Africa. Clinical and laboratory-confirmed cases of disseminated BCG disease in children<1 year of age from January 2002 to December 2004 at a referral hospital were used as numerator data. Denominator data for calculations of disseminated BCG risk were obtained through estimating the total number of HIV-infected infants receiving BCG based on the known vaccination coverage in the study setting, combined with population data on the total number of children<1 year of age, the known HIV prevalence amongst women attending public antenatal care facilities and different scenarios (5-15%) for the rate of vertical HIV transmission.
Nine cases of disseminated BCG disease were identified over the study period, seven of these were in HIV-infected infants. The estimated risk for HIV-infected infants to develop disseminated BCG disease, given a 95% BCG coverage and an HIV prevalence of 12.4-15.4% amongst women, were as follows for different scenarios of vertical HIV transmission: 329-417/100,000 vaccinees (assuming 5% vertical HIV transmission), 164-208/100,000 vaccinees (assuming 10% vertical HIV transmission) and 110-139/100,000 vaccinees (assuming 15% vertical HIV transmission).
The risk of disseminated BCG disease is increased several hundred fold in HIV-infected infants compared to the documented risk in HIV-uninfected infants. Data on the protective effect of BCG in HIV-exposed and infected children is lacking. Population- and hospital-based surveillance is vitally important to more accurately estimate the safety and benefits of BCG in HIV-exposed and infected infants.

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Available from: Ben Marais, Aug 27, 2014
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    • "There has been particular concern for the role of HIV infection in the safety of BCG vaccination [4]. A recent retrospective study documented a high frequency of BCG infection with complications in HIV-infected infants [5]. Current WHO vaccination policy does not recommend BCG vaccination of newborn infants with a known HIV-infection status, with or without infection symptoms [2]. "
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    ABSTRACT: Safety of individuals at risk of immune suppression is an important concern for live vaccines. The new-generation tuberculosis vaccine candidate MTBVAC, a genetically engineered doubly attenuated Mycobacterium tuberculosis mutant with deletions in phoP and fadD26 virulence genes has demonstrated comparable safety in different relevant animal models and superior protection in mice as compared to the only currently licensed tuberculosis vaccine Mycobacterium bovis BCG. Here we describe the construction of a highly attenuated MTBVAC-based live vaccine by an additional gene inactivation generated in erp of MTBVAC. The gene product of erp is an exported repeated protein (Erp), a virulence factor described to be involved in intracellular replication of M. tuberculosis. The resultant strain, MTBVAC erp(-), was tested in severe combined immunodeficiency (SCID) mouse model showing to be severely attenuated when compared to BCG and MTBVAC. Experiments conducted in immunocompetent mice revealed that the hyper-attenuated profile observed with MTBVAC erp(-) strain did not compromise its protective efficacy profile in comparison with BCG. These results postulate MTBVAC erp(-) as a potential tuberculosis vaccine candidate for use in high-risk populations of immune suppression (e.g., due to HIV infection), where the use of BCG is not recommended.
    Vaccine 07/2014; 32(40). DOI:10.1016/j.vaccine.2014.07.047 · 3.62 Impact Factor
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    • "However, it can cause severe disseminated disease, named BCG-osis, in patients affected by some primary immunodeficiency, such as severe combined immunodeficiency and chronic granulomatous disease [16]. Different studies revealed an increased risk of disseminated BCG disease in HIV-infected children, even if asymptomatic at time of vaccination [17,18]. Thus, WHO Global Advisory Committee on Vaccine Safety recommends that BGC should not be administered in HIV-infected patients [19]. "
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    ABSTRACT: one of the World Health Organization Millennium Development Goal is to reduce tuberculosis incidence by 2015. However, more of 8.5 million tuberculosis cases have been reported in 2011, with an increase of multidrug-resistant strains. Therefore, the World Health Organization target cannot be reach without the help of a vaccine able to limit the spread of tuberculosis. Nowadays, bacille Calmette-Guérin is the only vaccine available against tuberculosis. It prevents against meningeal and disseminated tuberculosis in children, but its effectiveness against pulmonary form in adolescents and adults is argued. a systematic review was performed by searches of Pubmed, references of the relevant articles and Aeras and websites. 100 articles were included in this review. Three viral vectored booster vaccines, five protein adjuvant booster vaccines, two priming vaccines and two therapeutic vaccines have been analyzed. Several vaccines are in the pipeline, but further studies on basic research, clinical trial and mass vaccination campaigns are needed to achieve the TB eradication target by 2050.
    BMC Infectious Diseases 01/2014; 14 Suppl 1(Suppl 1):S2. DOI:10.1186/1471-2334-14-S1-S2 · 2.61 Impact Factor
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    • "HIVinfected infants face a higher risk of TB infection [2], and pregnant women co-infected with HIV and TB are more likely to transmit both HIV and TB to their infants [2] [3]. The Bacille Calmette–Guérin (BCG) vaccine for prevention of TB infection can disseminate in HIV-infected infants with a case fatality of 75% [4]. The high morbidity and mortality associated with HIV and TB disease in infants underscore the urgent need for a safe neonatal vaccine to prevent pediatric HIV and TB infections. "
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    ABSTRACT: Mother-to-child-transmission of HIV by breast-feeding remains a major obstacle in the eradication of HIV infection. Compared to adults, HIV-infected infants have more rapid disease and show higher susceptibility to co-infections like tuberculosis (TB). Although the Bacille Calmette–Guérin vaccine can be administered at birth to protect against TB, BCG can disseminate in HIV-infected infants and increase mortality. Thus, a pediatric combination vaccine to stop both HIV and TB infection in infants is urgently needed. Towards the goal of developing a pediatric combination HIV-TB vaccine to prevent both oral HIV acquisition by breast-feeding and TB infection, we tested and optimized an immunization regimen using a novel live attenuated Mycobacterium tuberculosis vaccine engineered to express simian immunodeficiency (SIV) antigens followed by heterologous MVA-SIV boosting in the infant macaque model. A single oral dose of the attenuated Mtb-SIV vaccine strain mc26435 during the first week of life was sufficient to induce persistent TB-specific immune responses. SIV-specific immunity was induced at low but comparable magnitudes after oral or intradermal priming, and was enhanced following MVA-SIV boosts. T cell responses were most pronounced in intestinal tissues and oral lymph nodes. Importantly, in addition to plasma SIV-specific IgG and IgA antibodies, infant macaques developed mucosal SIV-specific IgA in saliva and intestinal IgA and IgG. While future SIV and Mtb challenge studies will be needed to determine the protective efficacy of the Mtb-SIV/MVA-SIV vaccine, infants at high risk for oral HIV acquisition by breast-feeding and TB infection could profoundly benefit from an effective combination vaccine.
    Trials in Vaccinology 12/2013; 2(1). DOI:10.1016/j.trivac.2013.09.005
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