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PubMed2001

Absence of a cysteine protease effect on bacterial virulence in two murine models of human invasive group A streptococcal infection.

The cysteine protease of group A streptococci has been suggested to contribute to the pathogenesis of invasive infection through degradation of host tissue, activation of the host inflammatory response, release of protective molecules from the bacterial cell surface, or other mechanisms. However, studies of the effects on virulence of inactivating the cysteine protease gene speB have yielded conflicting results. In some reports, a speB mutant was relatively avirulent in mouse models of invasive infection whereas little or no attenuation of virulence was observed in other studies of similar mutant strains. Possible reasons for these discordant results include differences in the streptococcal strains from which the speB mutants were derived, differences in the infection models employed, or unintended effects on another virulence determinant(s) that arose during the derivation of a speB mutant. We attempted to clarify these issues by characterizing the phenotypic properties and relative virulence in mice of two speB mutant strains, both derived from wild-type strain AM3: speB mutant AM3speB, which has been shown to be markedly attenuated in virulence in mice after intraperitoneal or subcutaneous challenge, and AM3speBOmega, a new mutant strain derived for this investigation. Both mutant strains were negative for protease activity, as expected, and both produced wild-type amounts of type 3 M protein and streptolysin O. However, AM3speB produced significantly less cell-associated hyaluronic acid capsule than did parent strain AM3 or strain AM3speBOmega. Compared to wild-type strain AM3, AM3speB was more sensitive to opsonophagocytic killing in vitro and was significantly less virulent in mice after intraperitoneal challenge. By contrast, AM3speBOmega was fully resistant to phagocytosis and did not differ significantly from the wild-type strain in mouse virulence after an intraperitoneal or subcutaneous challenge. We concluded that previous reports attributing loss of virulence in strain AM3speB to inactivation of speB are in error. Within the limitations of the models used, we found no effect of cysteine protease on invasive streptococcal infection.

Animals↗
PubMedDate not supplied

Potential use of intravenous immune globulin for group B streptococcal infection.

Several lines of evidence suggest that passive immunization as adjunctive therapy for or prevention of group B streptococcal (GBS) sepsis in neonates will require the use of preparations of human intravenous immune globulin (IVIG) that are hyperimmune for protective antibodies to GBS. Results from both in vitro and in vivo experiments utilizing commercially available IVIG preparations suggest that the doses necessary for achieving levels of pathogen-specific antibody capable of promoting efficient opsonization and phagocytosis of GBS may be prohibitive. Several laboratories have reported that standard IVIG preparations contain only modest levels of antibodies to the four capsular polysaccharides of GBS (the protective moieties), are variable in their effect on in vitro opsonophagocytosis by dose and method of preparation, and are significantly less protective in animal models than is IVIG prepared from adults immunized with GBS polysaccharide vaccines. Further, when we gave a single infusion of standard IVIG at a dose of either 500 or 750 mg/kg to 10 premature neonates during the first week of life, opsonophagocytosis of type III GBS by their sera and adult neutrophils was observed only when high levels of specific antibody were achieved, levels only transiently achieved in nonimmune infants. Commercial preparation of human immune globulin hyperimmune for GBS will be required for optimal adjunctive therapy in patients with sepsis due to GBS and for the possible prevention of late-onset infant disease.

Antibodies, Bacterial↗
PubMedDate not supplied

Comparison of prevention strategies for neonatal group B streptococcal infection. A population-based economic analysis.

BACKGROUND: Intrapartum antibiotics can prevent early-onset neonatal group B streptococcal (GBS) disease but have not been widely used. Obstacles include difficulty in implementing screening for GBS colonization and uncertainty about cost-effectiveness. The GBS vaccines for disease prevention are now being developed. METHODS: We developed a decision analysis model and used standard cost-effectiveness and cost-benefit analysis methods. We compared the outcomes and costs of the recent practice of no intervention with those expected for three prevention strategies: (1) intrapartum antibiotics administered to colonized women with labor complications, (2) an alternative strategy that does not require screening but uses epidemiologic criteria and labor complications to target intrapartum antibiotics, and (3) maternal vaccination. We used data from multistate population-based surveillance to estimate the potential impact of each strategy on disease and costs in the United States. RESULTS: Intrapartum antibiotic prophylaxis of high-risk women identified by screening could prevent approximately 3300 cases (47% of neonatal disease) annually in the United States and could save approximately $16 million in direct medical costs. Chemoprophylaxis of high-risk women identified using epidemiologic criteria could potentially be equally effective (3200 cases prevented) and would avoid the logistical difficulties of screening; the net savings would be approximately $66 million. Vaccinating 80% of pregnant women with a vaccine that prevents 80% of cases among infants born at or after 34 weeks of gestation would prevent approximately 4100 neonatal cases annually with a net savings of $131 million. CONCLUSIONS: Universal prenatal screening for GBS and chemoprophylaxis of colonized women with labor complications is likely to be cost-beneficial in the United States. Development of alternative strategies should be further explored for populations in which GBS screening is impractical. Continued development of a GBS vaccine is an important public health priority.

Anti-Bacterial Agents↗