Group B Streptococcus (GBS) carriage by pregnant women is the primary risk factor for early-onset GBS neonatal sepsis. Intrapartum antibiotic prophylaxis (IAP) can prevent this transmission route, and two main approaches are recommended to base the selection of pregnant women to be submitted to IAP: the risk-based and the culture-based strategies. In Brazil, compliance to such recommendations is poor, and not much is known about GBS carriage. In the present study, 3,647 pregnant women living in Rio de Janeiro State, Brazil, were screened for GBS anogenital colonization, over a period of 8 years (2008–2015). GBS was detected in 956 (26.2%) of them, and presence of vaginal discharge was the only trait associated with a higher risk for GBS colonization. Serotypes Ia (257; 37.3%) and II (137; 19.9%) were the most frequent among 689 (72.1% of the total) GBS isolates evaluated, followed by NT isolates (84; 12.1%), serotype Ib (77; 11.1%), V (63; 9.1%), III (47; 6.8%) and IV (24; 3.5%). Estimated coverage of major serotype-based GBS vaccines currently under clinical trials would vary from 65.2% to 84.3%. All 689 isolates tested were susceptible to ampicillin and vancomycin. Resistance to chloramphenicol, clindamycin, erythromycin, levofloxacin, and tetracycline was observed in 5% (35), 2% (14), 14% (97), 5% (35) and 86% (592) of the isolates, respectively. No significant fluctuations in colonization rates, serotype distribution and antimicrobial susceptibility profiles were observed throughout the period of time investigated. The culture-based approach for IAP recommendation showed to be the best choice for the population investigated when compared to the risk-based, since the first did not increase the number of pregnant women submitted to antibiotic therapy and covered a larger number of women who were actually colonized by GBS. The fact the not all isolates were available for additional characterization, and serotype IX antiserum was not available for testing represent limitations of this study. Nevertheless, to the best of our knowledge, this is the largest investigation on GBS carriage among pregnant women in Brazil up to date, and results are useful for improving GBS prevention and treatment strategies.
Citation: Botelho ACN, Oliveira JG, Damasco AP, Santos KTB, Ferreira AFM, Rocha GT, et al. (2018) Streptococcus agalactiae carriage among pregnant women living in Rio de Janeiro, Brazil, over a period of eight years. PLoS ONE 13(5): e0196925. https://doi.org/10.1371/journal.pone.0196925
Editor: Jose Melo-Cristino, Universidade de Lisboa Faculdade de Medicina, PORTUGAL
Received: November 16, 2017; Accepted: April 23, 2018; Published: May 11, 2018
Copyright: © 2018 Botelho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information file.
Funding: This work was supported in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Brazil. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Streptococcus agalactiae (Group B Streptococcus, GBS) remains as a major cause of morbidity and mortality among newborns in many countries . Pregnant women asymptomatically colonized by GBS in the genitourinary and/or gastrointestinal tracts are the main reservoir of this microorganism, and early-onset GBS neonatal sepsis (EONS), which represents nearly 80% of all GBS neonatal syndromes, is usually a consequence of vertical transmission during labor [1, 2, 3]. Intrapartum antibiotic prophylaxis (IAP) can prevent this transmission route, and two main approaches are available to select pregnant women that will be submitted to IAP: the risk-based and the culture-based strategies. The Centers for Disease Control and Prevention  recommends that all pregnant women in the USA between the 35th and 37th gestational weeks should be screened for vaginal-rectal GBS colonization, and those with positive cultures should be submitted to IAP. In other countries, such as the United Kingdom and the Netherlands, IAP is administered based on the presence of clinical risk factors (such as preterm labor, premature or prolonged rupture of membranes, GBS bacteriuria, previous infant with GBS disease) . The Brazilian Society for Pediatrics [6, 7] recommends the culture-based policy since 2011, but adhesion to these guidelines seems to be very low (around 20%) in Brazil .
GBS serotyping is based on antigenic differences of the polysaccharide capsule . Currently, ten different capsular types are recognized, including Ia, Ib, II-IX . The classification in serotypes is widely used for epidemiological purposes and pathogenicity studies and constitutes a valuable tool to predict the impact of putative polysaccharide-based GBS vaccines. Main serotype-based vaccine candidates currently under clinical trials comprise up to five of the ten capsular types described to date .
S. agalactiae is still considered uniformly susceptible to penicillin, although isolates with reduced susceptibility to this drug have been sporadically reported since 2008 . The use of clindamycin or erythromycin was recommended as alternatives in IAP for penicillin-allergic women with high risk of anaphylaxis or when therapeutic failure is suspected . However, increasing rates of clindamycin and erythromycin resistance have been detected in several regions of the world, including Europe [12, 13], Asia [11, 14], North America [15, 16] and South America [17–19]; for this reason, clindamycin does no longer constitute an empiric reliable alternative .
In general, data on the occurrence of GBS colonization and distribution of GBS serotypes and antimicrobial susceptibility profiles among pregnant women living in different Brazilian locations are still largely unknown, as the information available is usually related to small groups of patients and short-term observations. In the present study, we evaluated the occurrence, serotype distribution and antimicrobial susceptibility profiling of GBS isolates recovered from pregnant women seeking medical assistance at a public maternity in Rio de Janeiro State, Brazil, during a period of 8 years, and analyzed the association of clinical, social and demographic aspects with GBS colonization.
Material and methods
Population included in the study
A total of 3,647 pregnant women between the 35th and 37th gestational weeks, seeking medical attention at a public maternity in Rio de Janeiro State between March 2008 and December 2015, were enrolled in the present study. The maternity is located in a major metropolitan area of Rio de Janeiro State, in the Southeastern region of Brazil. Rio de Janeiro is the third most populated state in the country, and it can be considered as representative of the ethnic, social and economic diversity of the Brazilian population due to the historic high flow of immigration [20, 21]. Clinical and socio-demographic information about the patients was gathered by the hospital medical staff as part of the regular procedures for patient assistance. Clinical aspects investigated included presence of vaginal discharge, preterm birth, urinary tract infections, use of antibiotics during pregnancy, maternal pathology, history of previous neonatal death, history of previous neonatal GBS infection and allergy to penicillin. Socio-demographic data included ethnicity, marital status, scholarship level and place of birth. Written informed consent was obtained from each participant. This study was approved by the research Ethical Committee from University Hospital Clementino Fraga Filho of the Federal University of Rio de Janeiro (UFRJ) under number 219/05.
Collection of clinical specimens and detection of GBS
A single ano-vaginal specimen was collected from each patient by an attending physician. Either a sterile conventional cotton swab or a flocked swab (Copan Diagnostics Inc., Murrieta, CA, USA) was initially introduced in the middle third of vaginal region and later in the rectum through the anal sphincter, according to CDC recommendations (2010). Each swab was then inoculated in 3 ml of selective Todd-Hewitt broth (sTHB; Plast Labor, Rio de Janeiro, RJ, Brazil) supplemented with nalidixic acid (15 μg/mL; Sigma-Aldrich, St. Louis, MO, USA) and gentamicin (8 μg/mL; Sigma-Aldrich) . After incubation for 18–48 h at 36°C under aerobic atmosphere, an aliquot of each sTHB culture was sub-cultured on 5% sheep blood agar plates (Plast Labor) and incubated for 18–24 h under the same conditions. Colonies with expected morphological and hemolytic patterns on 5% sheep blood agar plates were submitted to identification by conventional procedures, including Gram staining, catalase and CAMP production testing . Serological grouping was performed by using a commercial latex agglutination test (Slidex Strepto Kit, bioMerieux, France), according to the manufacturer’s instructions.
Determination of capsular types
Serotypes were determined by the Ouchterlony double immunodiffusion method, after HCl extraction of capsular polysaccharides, and using specific antisera (gently provided by the Centers for Disease Control and Prevention, CDC, GA, USA) against types Ia-VIII [8, 9].
Antimicrobial susceptibility testing
The isolates were tested for susceptibility to ampicillin, chloramphenicol, clindamycin, erythromycin, levofloxacin, tetracycline and vancomycin (Oxoid, Basingstoke, United Kingdom) by the disk diffusion method, according to the CLSI guidelines and interpretative criteria . MLSB phenotypes were determined by the double-disk diffusion test.
GBS colonization was detected in 956 (26.2%) of the 3,647 pregnant women evaluated, and no significant fluctuations in the colonization rates were observed throughout the period of time investigated (Fig 1; p = 0.0693).
The red line indicates relative percentages in each period and the black line represents the tendency line.
The distribution of clinical, social and demographic characteristics among the population investigated, according to the presence or absence of GBS colonization, is shown in Table 1. These data are related to those pregnant women from whom all the specified information was available (a total of 3,369 out of the 3,647 pregnant women enrolled in the present study). The age of the participants ranged from 12 to 48 years old with a mean of 28.26 (standard deviation of ± 6.2). Cephalexin and nitrofurantoin were the antimicrobials most commonly used during pregnancy for treatment of different conditions, followed by penicillin and ceftriaxone. Arterial hypertension and gestational diabetes were the most frequent maternal pathologies observed. Concomitant infections, such as HIV, syphilis, toxoplasmosis and HPV, were also reported. Eight patients reported previous neonatal death due to GBS infections, and three of them were colonized by GBS in the current pregnancy. Among clinical, social and demographic aspects evaluated, presence of vaginal discharge was the only characteristic statistically associated with GBS colonization (p = 0.003), although a trend for an association between white ethnicity and lower GBS colonization rates was observed (p = 0.057). One-hundred twenty-six (13.7%) of the 956 colonized women did not present any clinical risk factor associated with GBS carriage, including previous infant with GBS infection, GBS bacteriuria, premature or prolonged rupture of membranes and premature labor.
Among the 956 GBS isolates recovered throughout the period of study, 689 (72.1%) were available for serotyping and antimicrobial susceptibility testing (the remaining 267 were lost or became non-viable), and they represented 49.8 to 100.0% of the isolates recovered in each two-year period of time evaluated (Table 2).
Overall, 257 (37.3%) out of 689 isolates belonged to serotype Ia, 77 (11.2%) to serotype Ib, 137 (19.9%) to serotype II, 47 (6.8%) to serotype III, 24 (3.5%) to serotype IV and 63 (9.2%) to serotype V. Eighty-four (12.1%) isolates were nontypeable (NT). Serotypes VI, VII and VIII were not detected. The distribution of serotypes throughout the period of time included in the study is shown in Fig 2. No significant fluctuations on the frequencies of serotypes were detected throughout the period of investigation, except for serotypes Ia and Ib, which slightly decreased and increased, respectively, from 2010 onwards.
All 689 GBS isolates evaluated were susceptible to ampicillin and vancomycin. Resistance to chloramphenicol and levofloxacin was observed in thirty-five (5%) isolates. Five hundred and ninety-two (86%) isolates showed resistance to tetracycline. Resistance to erythromycin and clindamycin was observed in ninety-seven (14%), and fourteen (2%) isolates, respectively. The distribution of antimicrobial resistance profiles among GBS isolates throughout the period of study did not show any significant fluctuations (Fig 3). Most of the erythromycin-resistant isolates (74/97) presented the M phenotype, while fourteen showed the constitutive MLSB phenotype (cMLSB) and nine had the induced phenotype (iMLSB). No evident association between antimicrobial susceptibility profile and serotype was detected (Table 3). Characteristics of 689 GBS isolates analyzed for serotyping and antimicrobial susceptibility are presented in the Supplementary S1 Table.
Chl-R, Chloramphenicol-resistant isolates; Cli-R, Clindamycin-resistant isolates; Ery-R, Erythromycin-resistant isolates; Lev-R, Levofloxacin-resistant isolates; Tet-R, Tetracycline-resistant isolates.
In the present study, GBS colonization was detected in 26.2% of the pregnant women attending a maternity located in a major urban area in the State of Rio de Janeiro, Brazil, over a period of 8 years. GBS colonization rates may vary according to the geographic area. Different studies indicate that around 20% of pregnant women are colonized by GBS in the USA [15, 23–25]. In Europe, colonization rates range from 19% to 29% in the Eastern region, from 11% to 21% in the Western region, and from 6% to 32% in the Southern region . In Thailand  and South Africa , 12% and 21% of pregnant women, respectively, are found to carry this microorganism. Studies performed in different Brazilian locations show the occurrence of GBS colonization among pregnant women at rates ranging from 10% to 29% [29–32]. The first report available from Rio de Janeiro, in 1982, showed a GBS colonization rate of 25.2% among pregnant women , while a more recent study, conducted with HIV-positive pregnant women in 2011, revealed a rate of 32.2% . Compared to the rate found in the present study, these data indicate that GBS colonization rates in Rio de Janeiro did not fluctuated significantly over the last thirty-five years.
Certain clinical, social and demographic aspects have been previously associated with a higher risk of GBS carriage and development of EONS. In the present study, presence of vaginal discharge was the only characteristic statistically associated with a higher occurrence of GBS colonization, although a strong trend between white pregnant women and lower occurrence of GBS colonization was also seen. Likewise, in a study performed in Santa Catarina, a state located in the South region of Brazil, presence of vaginal discharge and Afro-American ethnicity were characteristics associated with higher prevalence of GBS colonization among pregnant women . In addition, in a study conducted in Ceará, a state located in the Northeast region of Brazil, belonging to white ethnicity was the only characteristic associated with lower prevalence of GBS colonization among 213 pregnant women investigated from 2008 to 2010 .
Currently, there is no international consensus as to whether IAP is best achieved through risk-based or culture-based approaches. Reasons why the risk-based strategy is implemented in some places include that culture-based method might not be affordable and/or that risk-based strategy might lead to a lower number of pregnant women exposed to widespread use of antibiotics . If the risk-based approach was considered solely in the present study, a similar percentage of pregnant women would have been submitted to IAP (830/3,369; 24.6%). However, nearly 14% of women known to be colonized by GBS by the culture-based approach would have been excluded from IAP recommendation. These observations suggest that, at least regarding the population analyzed in the present study, the culture-based method seemed to be superior in preventing GBS neonatal diseases since it would not significantly increase the number of pregnant women submitted to antibiotic therapy and would cover a larger number of women who were actually colonized by GBS.
The capsular polysaccharide is a major S. agalactiae virulence factor, allowing the bacteria to evade the host immune system , besides being the target of the major vaccine proposals currently being evaluated [1, 37]. The most common capsular types in this study were Ia and II, together accounting for 57.2% of 689 GBS isolates investigated, while serotypes Ib, III, IV and V were represented in lower percentages ranging from 3.5 to 11.1%. The distribution of serotypes may vary according to several factors, including the geographic region, clinical source of GBS strain, and period of time. Serotypes Ia, III and V are usually the most common in the United States, Europe and Australia [1, 5, 38]. In the present study, the distribution of serotypes was consistent with results of previous reports from Brazil [18, 39], indicating that serotype Ia is the most frequent among GBS isolates recovered from colonization or infection cases in individuals of different ages, occurring at rates of 23 to 38%, followed by serotype II with rates around 15%. Serotype IV was the least frequent in the present study, as it has also been observed in other Brazilian studies [40, 41], with rates ranging from 1 to 5%. Only in Paraná State, in the South of Brazil, this serotype is commonly detected, being described as the third most prevalent . Regarding other serotypes, including Ib, III and V, and non-typeable (NT) isolates, the rates found in the present study are in accordance with previous reports from Brazil [18, 39–41]. Nevertheless, some of the NT isolates in the present study might actually represent encapsulated strains that were not properly detected, not only because serotype IX antiserum was not available for testing, but also because genotyping methods for determining the capsular type were not available.
Moreover, considering the panorama of serotype distribution in the present study, estimated coverage of the main serotype-based GBS vaccines currently under clinical trials would be of 65.2% for the trivalent CRM197 conjugate vaccine (targeting serotypes Ia, Ib and III; Novartis)  and 84.3% for pentavalent vaccine (targeting Ia, Ib, II, III, and V; Pfizer). Therefore, monitoring the distribution of capsular types among strains circulating in different areas is important not only for elucidating the biology and epidemiology of S. agalactiae but also for evaluating the potential impact of vaccine strategies according to the peculiarities of each geographic area. This is of particular importance when serotypes not included in vaccine schemes tend to emerge after vaccine introduction; this was the case for pneumococcal conjugate vaccines and for the Haemophilus influenza vaccine worldwide [43, 44].
The uniform susceptibility of GBS to beta-lactam antibiotics detected in the present study is in agreement with previous findings from different locations [11, 14, 15, 18, 19, 39–41]. However, reduced susceptibility has been sporadically reported elsewhere , underscoring the importance of continuous surveillance of this characteristic among GBS isolates. The rates of resistance to erythromycin (14%) and clindamycin (2%) found in this study are, in general, in accordance with those observed in previous studies conducted in Brazil and in other Latin American countries [17, 18, 39, 41]. Moreover, antimicrobial resistance rates were shown to have no fluctuations over the period of eight years investigated. On the other hand, increasingly higher erythromycin resistance rates have been detected in Asia, Europe, United States and Canada in the last years [11, 13–16]. Our data suggest that, despite of the relatively low resistance rates still detected in Brazil, use of erythromycin and clindamycin as alternative drugs for treating GBS infections in individuals with penicillin allergy should be supported by routine susceptibility testing.
As a limitation of the study, results regarding serotype distribution and antimicrobial susceptibility profiling were obtained from 689 of the 956 GBS isolates recovered from pregnant women. Since characterization of the isolates was not performed in parallel with isolation from clinical samples and preliminary identification, some GBS strains were lost during storage period, especially those isolated in the first years of the study (2008–2011). Nevertheless, the fraction analyzed represented more than 70% of the total number of isolates, and at least nearly 50% of the isolates in each two-year period, being almost fully representative of all isolates during the last four years included in the study (2012–2015).
In conclusion, the present report provides unprecedented volume of data on GBS characteristics among a large population of pregnant women living in Brazil during a long-term period, serving as a basis for assessment of the potential coverage of upcoming vaccines and for improving prevention and treatment strategies that effectively decrease GBS colonization at the moment of labor and, consequently, occurrence of neonatal diseases.
We thank Filomena Soares Pereira da Rocha and Jaqueline Martins Morais for their technical assistance.
- 1. Doare KL, Heath PT. An overview of global GBS epidemiology. Vaccine. 2013; 31,7–12.
- 2. Schuchat A, Wenger JD. Epidemiology of group B streptococcal disease. Risk factors, prevention strategies, and vaccine development. Epidemiol Rev. 1994; 16(2):374–402. pmid:7713185.
- 3. Schrag SJ, Verani JR. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine. 2013; 31 Suppl 4:D20–D26.
- 4. Verani JR, McGee L, Schrag SJ, Division of Bacterial Diseases NCfI, Respiratory Diseases CfDC, Prevention. Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports. 2010; 59(RR-10):1–36. pmid:21088663
- 5. Le Doare K, O’Driscoll M, Turner K, Seedat F, Russell NJ, Seale AC, et al. Intrapartum antibiotic chemoprophylaxis policies for the prevention of group B streptococcal disease worldwide: systematic review. Clin Infect Dis. 2017; 65: S143–S151. pmid:29117324
- 6. Sociedade Brasileira de Pediatria (SBP), 2018. http://www.sbp.com.br/publicacoes/
- 7. Costa H. Prevenção da doença perinatal pelo estreptococco do grupo B. Manual da Sociedade Brasileira de Pediatria; 2011; 1–18.
- 8. Lancefield RCA. Sorological differentiation of specific types of bovine hemolytic streptococci (Group B). J Exp Med. 1934; 59:441–458. pmid:19870257
- 9. Spellerberg B, Brandt C. Streptococcus. In: Jorgensen JH et al, editors. Manual of Clinical Microbiology, Vol 1: American Society for Microbiology; 2015. pp. 383–402.
- 10. Lin SM, Zhi Y, Ahn KB, Lim S, Seo HS. Status of group B streptococcal vaccine development. Clin Exp Vaccine Res. 2018; 7: 76–81. pmid:29399583
- 11. Kimura K, Nagano N, Nagano Y, Suzuki S, Wachino J, Shibayama K, et al. High frequency of fluoroquinolone- and macrolide-resistant streptococci among clinically isolated group B streptococci with reduced penicillin susceptibility. J Antimicrob Chemother. 2013; 68:539–542. pmid:23111853
- 12. De Francesco MA, Caracciolo S, Gargiulo F, Manca N. Phenotypes, genotypes, serotypes and molecular epidemiology of erythromycin-resistant Streptococcus agalactiae in Italy. Eur J Clin Microbiol Infect Dis. 2012; 32:1741–1747.
- 13. Fröhlicher S, Reichen-Fahrni G, Müller M, Surbek D, Droz S, Spellerberg B, et al. Serotype distribution and antimicrobial susceptibility of group B streptococci in pregnant women: results from a Swiss tertiary centre. Swiss Med Wkly. 2014; 20:144.
- 14. Khan MA, Faiz A, Ashshi AM. Maternal colonization of group B streptococcus: prevalence, associated factors and antimicrobial resistance. Ann Saudi Med. 2015; 35:423–427. pmid:26657224
- 15. Back EE, O’Grady EJ, Back JD. High rates of perinatal group B Streptococcus clindamycin and erythromycin resistance in an upstate New York hospital. Antimicrob Agents Chemother. 2012; 56:739–742. pmid:22143529
- 16. Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005. JAMA. 2008; 299:2056–2065. pmid:18460666
- 17. Abarzúa F, Argomedo C, Meissner A, Díaz T, Garrido P, Fariña S, et al. Prevalence of anal-vaginal colonization of Streptococcus agalactiae in third trimester of pregnancy and susceptibility to macrolides and lincosamides, in pregnant women controlled at Clínica Alemana Temuco, Southern Chile. Rev Chilena Infectol. 2014; 31:305–308. pmid:25146205
- 18. Dutra VG, Alves VM, Olendzki AN, Dias CA, de Bastos AF, Santos GO, et al. Streptococcus agalactiae in Brazil: serotype distribution, virulence determinants and antimicrobial susceptibility. BMC Infect Dis. 2014; 14:323–332. pmid:24919844
- 19. Melo SC, Santos NC, Oliveira M, Scodro RB, Cardoso RF, Pádua RA, et al. Antimicrobial susceptibility of Streptococcus agalactiae isolated from pregnant women. Rev Inst Med Trop Sao Paulo. 2016; 58:83–86. pmid:27828624
- 20. Instituto Brasileiro de Geografia e Estatística (IBGE), 2016. https://cidades.ibge.gov.br/v4/brasil/rj/panorama
- 21. Pesquisa Nacional por Amostras de Domicílios (PNAD), 2015. https://biblioteca.ibge.gov.br/visualizacao/livros/liv99054.pdf
- 22. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 27th Edition. CLSI supplement M100-S27, Wayne PA: CLSI; 2017.
- 23. Campbell JR, Hillier SL, Krohn MA, Ferrieri P, Zaleznik DF, Baker CJ. Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery. Obstet Gynecol. 2000; 96:498–503. pmid:11004347
- 24. Lin FY, Weisman LE, Azimi P, Young AE, Chang K, Cielo M, et al. Assessment of intrapartum antibiotic prophylaxis for the prevention of early-onset group B streptococcal disease. Pediatr Infect Dis J. 2011; 30:759–763. pmid:21540758
- 25. Nobbs AH, Lamont RJ, Jenkinson HF. Streptococcus adherence and colonization. Microbiol Mol Biol Rev. 2009; 73:407–450. pmid:19721085
- 26. Barcaite E, Bartusevicius A, Tameliene R, Kliucinskas M, Maleckiene L, Nadisauskiene R. Prevalence of maternal group B streptococcal colonisation in European countries. Acta Obst. Gynecol. Scand. 2008; 87:260–271.
- 27. Turner C, Turner P, Po L, Maner N, De Zoysa A, Afshar B, et al. Group B streptococcal carriage, serotype distribution and antibiotic susceptibilities in pregnant women at the time of delivery in a refugee population on the Thai-Myanmar border. BMC Infect Dis. 2012; 8:12–34.
- 28. Madziyhandila M, Adrian PV, Cutland CL, Kuwanda L, Schrag SJ, Madhi AS, et al. Serotype distribution and invasive potential of group B Streptococcus isolates causing disease in infants and colonizing maternal-newborn dyads. PLoS One. 2011; 21:178–181.
- 29. Função JM, Narchi NZ. A study of group B Streptococcus in pregnant women of eastern São Paulo Rev Esc Enferm USP. 2013; 47:22–29. pmid:23515799
- 30. Marconi C, Rocchetti TL, Rall VL, Carvalho LR, Borges VT, Silva MG. Detection of Streptococcus agalactiae colonization in pregnant women by using combined swab cultures: cross-sectional prevalence study. São Paulo Med J. 2010; 128:60–62. pmid:20676570
- 31. Rocchetti TT, Marconi C, Rall VL, Borges VT, Corrente JE, da Silva MG. Group B streptococci colonization in pregnant women: risk factors and evaluation of the vaginal flora. Arch Gynecol Obstet. 2011; 283:717–721. pmid:20349243
- 32. Simões JA, Alves VM, Fracalanzza SE, de Camargo RP, Mathias L, Milanez HM, et al. Phenotypical characteristics of group B Streptococcus in parturients. Braz J Infect Dis. 2007; 11:261–266. pmid:17625774
- 33. Benchetrit LC, Fracalanzza SEL, Peregrino H, Camelo AA, Sanches LA, et al. Carriage of Streptococcus agalactiae in women and neonates and distribution of serological types: a study in Brazil. J Clin Microbiol. 1982; 15:787–790. pmid:7047552
- 34. João EC, Gouvêa MI, Menezes JA, Matos H, Cruz ML, Rodrigues CA, et al. Group B Streptococcus in a cohort of HIV-infected pregnant women: prevalence of colonization, identification and antimicrobial susceptibility profile. Scand J Infect Dis. 2011; 43: 742–746. pmid:21671824
- 35. Kruk CR, Feuerschuette OH, Silveira SK, Trapani Cordazo M Júnior, et al. Epidemiologic profile of Streptococcus agalactiae colonization in pregnant women attending prenatal care in a city of southern of Brazil. Braz J Infect Dis. 2013; 17:722–723. pmid:24120829
- 36. Linhares JJ, Cavalcante Neto PG, Vasconcelos JL, Saraiva TV, Ribeiro AM, Siqueira TM, et al. Prevalence of the colonization by Streptococcus agalactiae in pregnant women from a maternity in Ceará, Brazil, correlating with perinatal outcomes. Rev Bras Ginecol Obstet. 2011; 33:395–400. pmid:22282027
- 37. Heath PT. Status of vaccine research and development of vaccines for GBS. Vaccine. 2016; 34: 2876–2879. pmid:26988258
- 38. Johri AK, Paoletti LC, Glaser P, Dua M, Sharma PK, Grandi G, et al. Group B Streptococcus: global incidence and vaccine development. Nat Rev Microbiol. 2006; 4: 932–942. pmid:17088932
- 39. Palmeiro JK, Dalla-Costa LM, Fracalanzza SEL, Botelho ACN, Nogueira KS, Scheffer MC, et al. Phenotypic and genotypic characterization of group B streptococcal isolates in Southern Brazil. J Clin Microbiol. 2010; 48:4397–4403. pmid:20881175
- 40. Otaguiri ES, Morguette AE, Tavares ER, dos Santos PM, Morey AT, Cardoso JD, et al. Streptococcus agalactiae isolated from patients seen at University Hospital of Londrina, Paraná, Brazil: capsular types, genotyping, antimicrobial susceptibility and virulence determinants. BMC Microbiol. 2013; 13: 297–306.
- 41. Pinto TC, Costa NS, Vianna Souza AR, Silva LG, Corrêa AB, Fernandes FG, et al. Distribution of serotypes and evaluation of antimicrobial susceptibility among human and bovine Streptococcus agalactiae strains isolated in Brazil between 1980 and 2006. Braz J Infect Dis. 2013; 17: 131–136. pmid:23453948
- 42. Madhi SA, Koen A, Cutland CL, Jose L, Govender N, Wittke F, et al. Antibody kinetics and response to routine vaccinations in infants born to women who received an investigational trivalent group B Streptococcus polysaccharide CRM197-conjugate vaccine during pregnancy. Clin Infect Dis. 2017; 65:1897–1904. pmid:29029127
- 43. Soeters HM, Blain A, Pondo T, Doman B, Farley MM, Harrison LH, et al. Current epidemiology and trends in invasive Haemophilus influenzae disease-United States, 2009–2015. Clin Infect Dis. 2018; pmid:29509834
- 44. Principi N, Di Cara G, Bizzarri I, Isidori C, Borgia P, Mignini C, et al. Prevention of invasive pneumococcal disease: problems emerged after some years of the 13-valent pneumococcal conjugate vaccine use. Curr Infect Dis Rep. 2018; 24:1–8.