Feng Ying C. Lin

The Efficacy of a Salmonella typhi Vi Conjugate Vaccine in Two-to-Five-Year-Old Children

BACKGROUND Typhoid fever is common in developing countries. The licensed typhoid vaccines confer only about 70 percent immunity, do not protect young children, and are not used for routine vaccination. A newly devised conjugate of the capsular polysaccharide of Salmonella typhi, Vi, bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A (rEPA), has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old. METHODS In a double-blind, randomized trial, we evaluated the safety, immunogenicity, and efficacy of the Vi-rEPA vaccine in children two to five years old in 16 communes in Dong Thap Province, Vietnam. Each of the 11,091 children received two injections six weeks apart of either Vi-rEPA or a saline placebo. Cases of typhoid, diagnosed by the isolation of S. typhi from blood cultures after 3 or more days of fever (a temperature of 37.5 degrees C or higher), were identified by active surveillance over a period of 27 months. We estimated efficacy by comparing the attack rate of typhoid in the vaccine group with that in the placebo group. RESULTS S. typhi was isolated from 4 of the 5525 children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children who received both injections of placebo (efficacy, 91.5 percent; 95 percent confidence interval, 77.1 to 96.6; P<0.001). Among the 771 children who received only one injection, there was 1 case of typhoid in the vaccine group and 8 cases in the placebo group. Cases were distributed evenly among all age groups and throughout the study period. No serious adverse reactions were observed. In all 36 children studied four weeks after the second injection of the vaccine, levels of serum IgG Vi antibodies had increased by a factor of 10 or more. CONCLUSIONS The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than 90 percent efficacy in children two to five years old. The antibody responses and the efficacy suggest that this vaccine should be at least as protective in persons who are more than five years old.

Level of Maternal IgG Anti-Group B Streptococcus Type III Antibody Correlated with Protection of Neonates against Early-Onset Disease Caused by This Pathogen

The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of > or = 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had > or = 10 microg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of < 2 microg/mL. A vaccine that induces IgG anti-GBS type III levels of > or = 10 microg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.

Population Structure of Invasive and Colonizing Strains of Streptococcus agalactiae from Neonates of Six U.S. Academic Centers from 1995 to 1999

ABSTRACT The purpose of this study was to describe the population structure of group B streptococci (GBS) isolated from infected and colonized neonates during a prospective active-surveillance study of early-onset disease in six centers in the United States from July 1995 to June 1999 and to examine its relationship to bovine strains of GBS. The phylogenetic lineage of each GBS isolate was determined by multilocus sequence typing, and isolates were clustered into clonal complexes (CCs) using the eBURST software program. A total of 899 neonatal GBS isolates were studied, of which 129 were associated with invasive disease. Serotype Ia, Ib, and V isolates were highly clonal, with 92% to 96% of serotype Ia, Ib, and V isolates being confined to single clonal clusters. In contrast, serotype II and III isolates were each comprised of two major clones, with 39% of serotype II and 41% of serotype III isolates in CC 17 and 41% of serotype II and 54% of serotype III isolates in CC 19. Further analysis demonstrates that the CC 17 serotype II and III GBS are closely related to a previously described “ancestral” lineage of bovine GBS. While 120 (93%) of invasive GBS were confined to the same lineages that colonized neonates, 9 (7%) of the invasive GBS isolates were from rare lineages that comprised only 2.7% of colonizing lineages. These results are consistent with those for other geographic regions that demonstrate the highly clonal nature of GBS infecting and colonizing human neonates.

Phylogenetic Lineages of Invasive and Colonizing Strains of Serotype III Group B Streptococci from Neonates: a Multicenter Prospective Study

ABSTRACT This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS.

Hypothesis: Neonatal respiratory distress may be related to asymptomatic colonization with group B streptococci.

Background: Phospholipids from the group B streptococcal (GBS) cell wall cause pulmonary hypertension in experimental animals. When exposed to penicillin, Streptococcus mutans releases phospholipids immediately. We hypothesize that newborns colonized with GBS receive bacterial phospholipids leading to pulmonary hypertension and respiratory distress, especially in the situation of newborns of penicillin-treated mothers. We examined clinical and epidemiologic data on these relations. Methods: We used data from a prospective multicenter GBS study conducted from 1995 to 1999 in which 1674 of 17,690 newborns cultured at 4 sites were colonized with GBS. Our analyses included 1610 colonized newborns ≥32 weeks gestation without early-onset disease. Clinical features were compared between 1003 lightly colonized (GBS positive at ≤2 sites) and 607 heavily colonized (positive at 3 or 4 sites) newborns. The rates of respiratory distress were compared between colonized newborns of penicillin-treated mothers and those of untreated mothers. Results: Of the 1610 colonized newborns, 8.8% had signs of respiratory distress within 48 hours after birth (cases). Oxygen supplementation was used in 60% of the cases, mechanical ventilation was required in 5% and persistent pulmonary hypertension was diagnosed in 2%. Compared with light colonization, heavy colonization increased the rate of respiratory distress 1.73-fold (95% CI, 1.26–2.38), a discharge diagnosis of respiratory disorder 2.02-fold (95% CI, 1.16–3.52), a blood/cerebrospinal fluid obtained for culture 1.54-fold (95% CI, 1.24–1.93) and antibiotic administration after birth 1.87-fold (95% CI, 1.34–2.61). Penicillin use during labor was associated with a 2.62-fold (95% CI, 1.79–3.83) increase in respiratory distress in the colonized newborn. Conclusions: Our findings support the association of neonatal respiratory distress with asymptomatic GBS colonization and with penicillin use during labor. These data require confirmation.

Antibiotic Susceptibility of Invasive Group B Streptococci from Neonates with Early-Onset Disease - A Multi Center Study 1995-97

Antibiotic Susceptibility of Invasive Group B Streptococci from Neonates with Early-Onset Disease - A Multi Center Study 1995-97

The Epidemiology of Infant Colonization and Early-Onset Group B Streptococcal(GBS) Disease in the U.S., a Multi-Center Study from 1995-97

The Epidemiology of Infant Colonization and Early-Onset Group B Streptococcal(GBS) Disease in the U.S., a Multi-Center Study from 1995-97

Determinants of Early-Onset Group B Streptococcal Disease - A Multi Center Case-Control Study

Determinants of Early-Onset Group B Streptococcal Disease - A Multi Center Case-Control Study