BCG-TB vaccination may be delayed for HIV-exposed infants

Veronica Hackethal
Aug. 17, 2014, 8:55 p.m.

Researchers have found no evidence that delayed administration of the bacillus Calmette-Guérin (BCG) vaccination for tuberculosis (TB) affects immune responses to the vaccine, according to a South African study published online August 8 in the Journal of Infectious Diseases.

"The immunogenicity of BCG vaccination in HIV-exposed, uninfected infants is not compromised when delayed until 8 weeks of age, and results in robust BCG-specific T cell responses at 14 weeks of age," write Christophe Toukam Tchakoute from the Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Department of Clinical Laboratory Sciences, University of Cape Town, South Africa, and colleagues.

In areas with endemic TB, infants routinely receive the BCG vaccine at birth to prevent disseminated TB. The World Health Organization, however, discourages this practice in HIV-infected infants, as it can result in severe disease and high mortality, the authors note. However, the HIV status of most infants is unknown at birth, and routine BCG administration continues in many countries.

To determine whether BCG administration can be safely delayed, Dr. Tchakoute and colleagues enrolled infants in the trial from a community health center in the Western Cape of South Africa between June 2010 and December 2012. This region has one of the highest rates of TB in the world, and maternal HIV prevalence hovers around 30%. In this area, pregnant women routinely receive HIV testing and counseling, and infants routinely receive HIV testing at 6 weeks, at 1 year, and at 6 weeks after stopping breast-feeding.

Of 149 HIV-exposed infants eligible for the study, researchers randomly assigned 28 HIV-uninfected infants to receive the BCG vaccine at birth and 28 to receive the BCG vaccine at 8 weeks. The authors analyzed whole blood at birth, 6, 8, and 14 weeks for immune responses to BCG.

The results suggest no significant differences between BCG-specific T-cell proliferation at 6 weeks postvaccination in the birth vs delayed vaccination groups. At 14 weeks, neither group showed significant differences regarding vaccine-specific responses in CD4+ (P = .968) and CD8+ T-cells (P = .672). Also at 14 weeks, the delayed group had significantly higher levels of interferon gamma–expressing CD4+ T cells, which are important for TB protection, and multifunctional BCG-specific T-cell cytokine responses, which indicate a strong immune response to the vaccine, compared with the birth group (P = .021 and P = .011, respectively). CD8+ T-cell analyses followed a similar pattern, suggesting the delayed group had improved T-cell secreting cytokine responses, which are crucial for generating TB immunity.

In a linked editorial, pediatrician Alexander W. Kay, MD, and assistant professor of medicine Catherine A. Blish, MD, PhD, from the Stanford University School of Medicine in California, suggest that delayed BCG immunization is not worse, and could even be better, than giving the vaccine at birth.

They also note that past studies have provided conflicting evidence on this issue. A previous South African study suggested that giving BCG at 10 weeks instead of at birth in HIV-unexposed infants resulted in improved immune responses, whereas a study in The Gambia found that delaying the vaccine until age 18 weeks resulted in decreased immune response. Environmental exposure to nontuberculous mycobacteria before receiving BCG could play a role in the discrepant results, Dr. Kay and Dr. Blish suggest. Exposure to nontuberculous mycobacteria has been linked to decreased immune responses to BCG, they explain. They propose that delayed vaccination be studied in various geographic areas with greater and lesser amounts of nontuberculous mycobacteria exposure.

Another concern, according Dr. Kay and Dr. Blish, could come from losses to follow-up with delayed vaccination. This could cause decreased vaccine coverage, ultimately leading to higher mortality from TB in HIV-exposed infants in TB-endemic regions.

"Tchakoute et al have established that BCG vaccination induces equal or enhanced Th1 cytokine responses in HIV-exposed infants when delayed until 8 weeks of age," the editorialists conclude.

"The possibility of improving the efficacy and safety of this important vaccination for all HIV-exposed infants should be investigated to the fullest extent."

The authors and editorialists have disclosed no relevant financial relationships.

J Infect Dis. Published online August 8, 2014. Article full text, Editorial full text

Source: Medscape