The native capsular polysaccharide of type III group B Streptococcus elicits a specific antibody response in only 60% of nonimmune human subjects. To enhance the immunogenicity of this polysaccharide, we coupled the type III polysaccharide to tetanus toxoid. Prior to coupling, aldehyde groups were introduced on the polysaccharide by controlled periodate oxidation, resulting in the conversion of 25% of the sialic acid residues of the polysaccharide to residues of the 8-carbon analogue of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. Tetanus toxoid was conjugated to the polysaccharide by reductive amination, via the free aldehyde groups present on the partially oxidized sialic acid residues. Rabbits vaccinated with the conjugate vaccine produced IgG antibodies that reacted with the native type III group B streptococcal polysaccharide (3/3 rabbits), while rabbits immunized with the unconjugated type III polysaccharide failed to respond (0/3 rabbits). Sera from animals receiving conjugate vaccine opsonized type III group B streptococci for phagocytic killing by human peripheral blood leukocytes, and protected mice against lethal challenge with live type III group B streptococci. The results suggest that this method of conjugation to a carrier protein may be a useful strategy to improve the immunogenicity of the type III group B Streptococcus polysaccharide in human sub-

These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

In this study, previous use of penicillin or ampicillin and private medical coverage were associated with having DRSP. Children with nonmeningeal invasive disease responded equally well to penicillin regardless of the penicillin susceptibility of their pneumococcal isolate.

A laboratory surveillance study was developed in Brazil in 1993 to determine capsular types and antimicrobial susceptibility of Streptococcus pneumoniae strains. By studying 360 strains isolated from children with invasive infections in three different cities, 8 out of 34 types were identified as being the most prevalent and considered as the reference group for further analyses. This group comprised 77.7% of all strains studied, and includes the types 1, 5, 6A/B, 9V, 14, 19F, 19A, and 23F. The prevalence of this reference group was significantly higher among strains isolated from children with pneumonia than meningitis. Similarly, this group was more prevalent among strains isolated from children 3 to 6 years of age than from children under 2 years of age. Most strains (78.6%) were found to be susceptible to penicillin and only 1.4% showed high resistance to this antibiotic. However, intermediate resistance to penicillin was detected in 20% of the strains. This laboratory surveillance will be maintained and extended to other cities of Brazil to better define and monitor the trends of pneumococcal infections for proper control and prevention.

The Pan American Health Organization (PAHO) has conducted a study of Streptococcus pneumoniae in six Latin-American countries: Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. Sterile site isolates from children aged < or =5 years showing clinical symptoms of pneumonia (as defined by the clinical criteria of WHO), meningitis, sepsis or bacteremia (without infectious foci), arthritis, and peritonitis were the source of most of the invasive pneumococcal isolates collected between the end of 1993 and 1996 in the six participating countries. Partial characterization of these isolates (antibiotic resistance and serotyping) have already been described (Microbial Drug Resistance 3:(2):131-163, 1997). In the next phase of the study, 326 S. pneumoniae isolates with reduced penicillin susceptibility were transferred to the Laboratory of Microbiology at The Rockefeller University for molecular characterization, and a summary and overview of the findings is described in this article. Some of the most interesting findings were as follows: (1) There was a surprisingly high representation of two internationally spread clones, which made up >80% of the strains with penicillin MIC of 1 microg/ml or higher; most of these isolates were recovered in large cities, supporting the likelihood that the source of these clones is through international travel. (2) The frequency of resistance to trimethoprim/sulfamethoxazole was extremely high (present in 85% of all isolates with decreased penicillin susceptibility). (3) None of these isolates was resistant to ofloxacin, and macrolide resistance was rare (present in 6.4% of the isolates). (4) There was an apparent inverse relationship between level of penicillin resistance and genetic diversity. (5) There were striking differences in the "microbiologic profiles" of the six different Latin-American countries.