Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 M. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were >10 6 -fold. At the lowest concentration tested, 10 M, we observed >1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.Respiratory syncytial virus (RSV) is the most important viral cause of acute respiratory tract infection (ARI) in infancy and early childhood, with its greatest morbidity in infants (6,8,9). Throughout the world, RSV contributes significantly to annual hospital admissions due to ARI, especially during the epidemic season (18,23,27). In developing countries, malnutrition and deficiencies of micronutrients are associated with increased incidence and severity of ARI (25). Improvement in nutritional status might be a practical strategy for prevention of severe RSV disease in developing countries, if efficacious. At this time, however, we have a poor understanding of the role of micronutrients such as zinc in susceptibility to severe disease caused by RSV infection.Zinc supplementation in children in developing countries was demonstrated to cause a significant reduction in the prevalence of pneumonia (3,20). Zinc has been shown to mediate antiviral effects against certain viruses. Clinical studies showed that zinc significantly shortens the duration of symptoms during rhinovirus infection (17,19,28). Topical application of zinc sulfate also was found in one study to be effective in the treatment of herpes simplex virus (HSV) infection (26). The specific mechanism by which zinc mediated these clinical effects is unknown in most cases. Zinc also enhances the host response to ma...

The prevalence of group B streptococcal (GBS) colonization was studied in 136 pregnant women and their newborn infants by collecting vaginal and rectal swabs from the mothers and throat, rectal, and umbilical swabs from their infants. Maternal and infant colonization rates were 22% and 23%, respectively. One-third of infants born to colonized mothers and 15% of infants born to noncolonized mothers had GBS isolated. Of GBS-colonized infants, 50% remained colonized at the mean age of 2 months. Type V was the commonest serotype among GBS isolates from mothers and infants; type III strains were uncommon. The rarity of GBS disease in Gambian infants may be due to low rates of maternal carriage with the more virulent GBS serotypes.

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The prevalence of maternal respiratory syncytial virus (RSV)-neutralizing antibodies has been documented in developed countries, but there is little information from developing countries. We assessed the prevalence of RSV-neutralizing antibody in sera from Gambian women and their newborns and compared them with their American counterparts during a similar period. The geometric mean titers of maternal antibodies to RSV subgroup A in the two populations were similar, while titers of antibodies to RSV subgroup B in Gambian mothers were significantly higher (8.7 ؎ 1.4 versus 7.9 ؎ 1.3 [mean ؎ standard deviation], P < 0.001). The titers of neutralizing antibody in newborns in both populations correlated with the neutralizing-antibody titers of their mothers. Thus, the status of neutralizing antibody to both major RSV subgroups was comparable among infants and mothers in a developing country, The Gambia, and those in a developed country, the United States.

Neutralizing antibodies (Abs) are the principal protective mechanism against disease caused by reinfection with viruses. Ab-mediated neutralization of viruses is a complex process comprising multiple mechanisms. Every structural aspect of Abs is potentially capable of modulating the level of neutralizing activity or the mechanisms of neutralization. The focus of our laboratory is to understand the genetic and structural basis of Ab-mediated neutralization of human viral pathogens. We demonstrated the unexpected finding that virus antigen-binding fragments of Abs (Fabs) mediate potent virus neutralizing effects in vivo. This work has led to a broad investigation of the importance of the genetics, chemistry, and structure of the combining site to the neutralizing activity of antiviral Abs. Ongoing work in our laboratory reveals that effect or functions specified by the Ab isotype such as polymer formation, interactions with complement, interactions with Fc receptors, and the ability to transcytose mucosal epithelia, also modulate the mechanism and level of neutralizing effects mediated by antiviral Abs.