Reply to Thysen et al

TO THE EDITOR—We thank Thysen et al for their cautionary perspective on BCG vaccination policy changes. Although we found improved immunogenicity of BCG vaccine in human immunodeficiency virus (HIV)–exposed infants vaccinated at 8 weeks of age, compared with immu-nogenicity among those vaccinated at birth [1], we do not recommend changes to vaccine-delivery services on the basis of these data. Nonetheless, our study contributes valuable data indicating that the immunogenicity of BCG vaccination is not negatively affected by delaying administration until 8 weeks of age, which is much needed in regions of high HIV prevalence where new tuberculosis vaccination strategies are undergoing clinical evaluation [2]. As highlighted by Thysen et al, previous trials have shown that BCG vaccination can improve all-cause mortality in West African children [3, 4], and in some cases, can improve innate and adaptive immunity to unrelated antigens [5, 6]. However, it is important to note the context in which these studies were performed. Gambia and Guinea-Bissau have poor healthcare infrastructures, high infant mortality [7], and considerably lower HIV infection and tuberculosis incidences than South Africa, where our trial was conducted. In such settings, the benefits associated with early BCG vaccination could outweigh any risks posed to HIV-infected infants, and delaying BCG vaccination could be detrimental to child survival. In settings with good integration of routine infant vaccination services, programs to prevent and treat tuberculosis, and services to prevent mother-to-child transmission of HIV, where infrastructure could support selectively delayed BCG vaccination for HIV-exposed infants, the risks due to delaying BCG vaccination would be lower. Additional points to consider are that in the prior studies from Guinea-Bissau, BCG vaccination was combined with other interventions, including vitamin A administration, and the randomized trials studied delayed BCG vaccination in low-birth-weight infants only, in whom mortality is high and immunity less mature [3, 4]. In West Africa, routine infant immunization coverage is relatively low, and data on the causes of infant mortality in these studies are limited [8]. A recent systematic review of studies performed elsewhere did not show any clear evidence of beneficial nonspecific effects associated with BCG vaccination [9], which may be setting specific. Furthermore, it is unclear whether there are any nonspecific protective effects from BCG vaccination in HIV-exposed infants, who have altered adaptive and innate immunity [10, 11]. One of the suggested mechanisms by which BCG vaccination improves immunity to pathogens other than the agents of tuberculosis is …