Academic journal article Bulletin of the World Health Organization

BCG Vaccination of Full-Term Infants with Chronic Intrauterine Malnutrition: Influence of Immunization Age on Development of Post-Vaccination, Delayed Tuberculin Hypersensitivity

Academic journal article Bulletin of the World Health Organization

BCG Vaccination of Full-Term Infants with Chronic Intrauterine Malnutrition: Influence of Immunization Age on Development of Post-Vaccination, Delayed Tuberculin Hypersensitivity

Article excerpt

Introduction

Intrauterine growth retardation (IUGR) is a major public health problem in developing countries. As many as 2 million infants with low birth weight that is secondary to chronic fetal malnutrition are born every year in Latin America, where the incidence of low-birth-weight infants can be as high as 30%.[1] Growth-retarded infants represent a highly heterogeneous group in terms of etiology, severity, and body proportions. The most prevalent type of IUGR in developing countries, symmetric or proportionate IUGR, probably results from a long-term growth-retarding process that begins early in gestation and may be caused by inhibition of cellular mitosis. Infants with symmetric IUGR are characterized by proportional reductions in weight, length, and head circumference.[2] Asymmetric inhibition of fetal growth results from interference with growth later in gestation, and infants with this type of growth retardation typically have visceral wasting and decreased birth weight but relative preservation of length and of head circumference. A multiplicity of socioeconomic and other factors, chronic malnutrition, poor education, and poverty are strongly associated with the incidence of IUGR among the underprivileged populations of developing countries.[3]

Globally, tuberculosis is a serious and highly prevalent infectious disease and remains a significant problem despite public health control efforts. In the developing countries of Africa, Asia and Oceania, the incidence of pulmonary tuberculosis is as high as 300 per 100 000. Also, reported rates for countries in South America range as high as 225 per 100 000 (in Bolivia), while 70 per 100 000 is more typical.[4] In such countries, the factors associated with acquiring the infection and of developing tuberculosis are similar to those associated with the high rate of IUGR.

BCG vaccination is the mainstay of tuberculosis control programmes in most countries. Because BCG is effective in preventing the severe forms of childhood tuberculosis, e.g., meningitis and miliary tuberculosis,[5] WHO recommends that BCG vaccine be administered as early as possible to children in countries where the disease has a high prevalence.[6] Based on recommendations by the WHO Expanded Programme on Immunization (EPI),[7] developing countries have adopted the policy of vaccinating children as newborns and young infants.

BCG vaccination of infants who have IUGR is not contraindicated according to EPI recommendations.[8] In most countries where BCG vaccine is routinely used, infants are vaccinated soon after birth, without regard to their intrauterine growth status. It is not known, however, whether the vaccine is as immunogenic or protective in infants who have IUGR compared with those whose intrauterine growth is normal. There are only few data about the immune response of infants with IUGR to BCG vaccination, but the findings suggest that their immunogenicity may be poor. Studies of BCG vaccination of full-term newborns with severe IUGR in India reported that the cell-mediated immune response to the tuberculin protein is deficient if the vaccine is administered within 48 hours of delivery or at 1 month of age.[9, 10] Other studies of the immunocompetence of newborn infants with IUGR have reported conflicting results about their ability, compared with infants whose intrauterine growth is normal, to respond to antigens in lymphoproliferative assays.[11-13]

The long-term morbidity and mortality rates for infants with IUGR are high[14] and are partly accounted for by their greater risk of developing serious infections, including tuberculosis. Because of the absence of data about the immunogenicity of BCG in infants with IUGR, it is not known whether current vaccination programmes in developing countries decrease the risk of serious tuberculosis among such infants. We have evaluated the immunogenicity of BCG vaccination at different ages for a group of full-term infants with symmetric or proportionate IUGR and a group of full-term infants with normal intrauterine growth in an urban Brazilian population, using skin testing and lymphocyte transformation tests to tuberculin antigen. …

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