Matthew Modansky, Melinda Erwin, John Elliot,. Richard R. Facklam, Anne ...... Galloway A, Deighton C, Deady J, Marticorena I, Efstratiou A. Type V group B ...
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Invasive Group B Streptococcal Disease: The Emergence of Serotype V Henry M. Blumberg, David S. Stephens, Matthew Modansky, Melinda Erwin, John Elliot, Richard R. Facklam, Anne Schuchat, Wendy Baughman, and Monica M. Farley
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine; VA Medical Center; and Centers for Disease Control and Prevention, Atlanta, GA.
Group B streptococci (GBS) cause invasive disease in neonates, pregnant adults, and nonpregnant adults with underlying or chronic disease. Previous studies found capsular serotypes la, Ib, II, and III cause invasive disease. Prospective population-based surveillance of invasive GBS disease was done from June 1992 to June 1993 in metropolitan Atlanta: 279 patients had invasive disease. Of these, 43% were ,;;;6 months old, and 57% were adults. The incidence among all adults was 7.7/ l00,OOO/year, 33% higher than in 1989-1990 (P < .01); the incidence in nonpregnant adults was 5.9/100,OOO/year, 37% higher than in 1989-1990 (P < .02). Serotyping of 178patient isolates revealed that 34% had GBS serotype la or Ia/c, 8% had Ib/c, 6% had II or Wc, 29% had III, 0% had IV, 21% had V, and 2% were nontypeable. Serotype V was recovered from all groups and was the most common serotype from nonpregnant adults. Serotype V isolates appeared to be highly related genetically. The increasing incidence of GBS disease in adults, the changing distribution of serotypes, and the emergence of serotype V will impact vaccine strategies.
Received 28 April 1995; revised 20 October 1995. Presented in part: Clinical Research Meeting, American Federation for Clinical Research, Baltimore, 2 May 1994 (abstract N-IN-0067). Human Investigation Committee approval for this study was received from the Emory University School of Medicine, the Georgia Department of Human Resources, and the Centers for Disease Control and Prevention. Financial support: Emory Medical Care Foundation, University Research Council of Emory University, National Vaccine Program, and Medical Research Service of the Department of Veterans Affairs. Reprints or correspondence: Dr. Henry M. Blumberg, Division of Infectious Diseases, Emory University School of Medicine, 69 Butler St., S.E., Atlanta, GA 30303. The Journal of Infectious Diseases 1996; 173:365-73 © 1996 by The University of Chicago. All rights reserved.
0022-1899/9617302-0012$01.00
Resistance to infection with GBS has been correlated with the presence of serum antibodies to type-specific determinants of capsular polysaccharides in both experimental animals and human neonates [10, 11]. Ongoing efforts to develop efficacious vaccines for the prevention of GBS disease in humans will require precise knowledge about serotype distribution and groups at risk for infection. Previous studies have reported a distribution of capsular serotypes Ia, Ib, II, and Ill, with few nontypeable isolates in neonates with early-onset disease (i.e., GBS disease occurring in the first week of life) and among pregnant women with vaginal GBS colonization [2,12-14]. Late-onset neonatal disease (i.e., disease occurring in newborns ~7 days of age) and meningitis among neonates is due primarily to serotype Ill, which accounts for 70% of such cases [15]. Little is known about serotype distribution or genetic relatedness of GBS isolates recovered from nonpregnant adults with invasive disease. Using prospective population-based surveillance, we explored the incidence of GBS disease among all age groups, the distribution of serotypes among GBS isolates recovered from those with invasive disease, including nonpregnant adults, and the molecular epidemiology of GBS disease in metropolitan Atlanta.
Materials and Methods Population-based surveillance. We did a prospective population-based surveillance of invasive GBS disease in the eight-county metropolitan Atlanta area from 1 June 1992 through 30 June 1993. The population of the surveillance area was 2,460,233 during the study period (Georgia Department of Human Resources, Atlanta). About 68% of the residents were white, 29% were black, and 3% were of other races or ethnic groups (1990 US census data). During the study period, there were 44,473 live births in the surveillance area (Georgia Department of Human Resources).
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Group B streptococci (Streptococcus agalactiae; GBS) are the leading cause of sepsis and meningitis in newborns in the United States and cause significant pregnancy-related morbidity affecting ~ 50,000 women each year in the United States [1-4]. Recently, it has been recognized that GBS are also an important cause of invasive disease in nonpregnant adults [5]. GBS disease in nonpregnant adults most commonly affects the elderly or those with chronic disease (e.g., diabetes mellitus, malignancy, and liver disease) and is often associated with a rate of high mortality [5, 6]. GBS are classified into serotypes on the basis of structural differences in capsular polysaccharides (Ia, Ib, and II- VI) and the presence or absence of protein antigen c [7]. Protein antigen c occurs in many serotype Ia and II strains, in all Ib strains, and in some serotype IV and VI strains [8]. Serotyping has been used traditionally to type GBS isolates; a currently used serotyping system consists of Ia, Ia/c, Ib/c, II, Il/c, III, IV, and V and of nontypeable isolates. The R and X protein antigens classify a few additional human strains but are most useful for serotyping bovine strains [9].
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used as a molecular size standard. PFGE banding patterns were compared visually; strains were considered distinguishable if PFGE patterns differed by ;,,3 bands [23]. Banding patterns were also compared by use of a computer-assisted system in which DNA typing gels were analyzed using Bio Image/Millipore whole band analyzer software (Bio Image, Ann Arbor, MI). Cluster analysis using the method ofunweighted pair-group average was done to calculate similarity or dissimilarity among GBS isolates. A significant difference was defined as a coefficient of similarity of 6 months of age, 5 [12%] of 43 from pregnant patients, and 10 [8%] of 110 from patients with early-onset neonatal disease) [15]. Many of the nontypeable isolates from that CDC project have recently been demonstrated to be serotype V isolates (unpublished data). In addition, a number of GBS isolates recovered from nonpregnant adult patients at Grady Memorial Hospital (Atlanta) in 1987-1988 that were nontypeable with antisera to serotypes Ia, lb, II, and III have recently been confirmed as serotype V (unpublished data). Molecular analyses of GBS using REAC and ribotyping or PFGE have proven to be useful subtyping methods and have provided the ability to discriminate among isolates of the same serotype [17, 48-50]. In our study, we noted 13 different ribotype patterns among the 170 isolates studied; 159 isolates were of six different ribotype patterns. As noted previously [17], these methods were very reproducible and REAC appeared to be a more sensitive typing method than ribotyping. PFGE also proved to be more sensitive than ribotyping, and because fewer bands are produced, it is much simpler than REAC to analyze. All serotype V isolates studied had the same ribotype (pattern 3) and the same or similar REAC patterns, and the 33 serotype V isolates studied by PFGE had the same or similar PFGE banding patterns (coefficient of similarity of >80%), suggesting that serotype V GBS isolates recovered from patients in our surveillance area are highly related. PFGE and REAC clearly differentiated between serotype V isolates and isolates of other serotypes (Ib/c and Il/c) that had ribotype hybridization banding pattern 3. Molecular analysis of serotype V isolates
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