Prevalence and serotype distribution of group B Streptococcus in León, Nicaragua

Summary

While under-five mortality has steadily declined since 1990, declines in neonatal mortality are less pronounced. Group B Streptococcus (GBS) disease is the most common cause of infant sepsis and meningitis, causing approximately 90,000 deaths and 56,000 stillbirths globally in 2015. Mothers with rectovaginal GBS colonization can vertically transmit GBS to infants during labour, causing early-onset GBS disease (EOD). To prevent EOD, 60 countries have instituted national policies to provide intrapartum antibiotic prophylaxis (IAP) to women with GBS colonization or who meet certain GBS risk criteria. However, lack of universal GBS screening, particularly in low- and middle-income countries (LMIC) complicates EOD prevention. Further, late-onset GBS disease (LOD) can occur with horizontal mother-infant GBS transmission after the first week of life, and cannot be prevented with IAP. A prophylactic GBS vaccine administered late in pregnancy could prevent infant GBS infection.

Investigational GBS vaccines have shown safety and immunogenicity in Phase 2 trials. However, GBS serotype distribution in LMIC are largely unknown. We propose a study in León, Nicaragua, to guide serotype-specific GBS prevention strategies. We will first collect rectovaginal samples from pregnant women to characterize GBS serotype distribution and serotype coverage of candidate pentavalent and hexavalent GBS vaccines. Next, we will describe the frequency and patterns of co-colonization with multiple GBS serotypes in colonized women. This data will improve estimates of serotype-specific GBS vaccine effectiveness, providing evidence-based guidance for GBS vaccine development and policy-making.

Project outcomes

Rectovaginal colonization with group B Streptococcus (GBS) is the primary cause of neonatal sepsis globally. To inform maternal GBS vaccine development, we present preliminary results from an ongoing study of GBS colonization in pregnant women in León, Nicaragua. 

We recruited pregnant women at public health clinics in León between 35-37 weeks gestation. We collected one vaginal and one rectal sample from each woman, and transported them to the study lab in modified Stuart’s transport medium. Samples were processed and cultured within 24 hours of collection using three methods: direct plating onto chromogenic agar for presumptive identification of GBS (CHROM); direct plating onto Columbia nalidixic acid (CNA) agar; and incubation in Todd Hewitt w/CAN (LIM) broth followed by plating onto CNA. Suspected GBS colonies underwent Gram stain, catalase test, CAMP test, and latex agglutination serology to confirm GBS. Positive serology was considered definitive for GBS colonization regardless of the culture method, and women with positive serology from either anatomical site were considered colonized with GBS.

We observed moderate agreement between culture methods: LIM versus CNA, k=0.47; LIM versus CHROM, k=0.44. Compared to serology as the gold standard, CNA culture was 30% sensitive for GBS detection; LIM was 56% sensitive; and CHROM was 76% sensitive. Based on serology, 62 women (20%) were colonized with GBS in the vagina, rectum, or both, based on bacterial culture. Thirty-six women were colonized at a single anatomical site, where as 26 women were colonized at both sites. In two-thirds of women who were colonized with GBS, isolates were resistant to penicillin, the first-line drug for intrapartum antibiotic prophylaxis to prevent infant GBS infection.

Three colonies from each sample were randomly selected to undergo typing for any of the 10 known GBS serotypes. We identified a preponderance of types Ia (30%), II (29%), and III (19%), as well as 3 instance of co-colonization with multiple serotypes: Ib + III (n=2) and Ib + V (n=1). The distribution of GBS serotypes is consistent with regional and global estimates suggesting that types I-V account for the majority of rectovaginal colonization among pregnant women. Furthermore, all of the types detected in our study are included in candidate pentavalent and hexavalent GBS vaccines. If these vaccines are proven safe and efficacious, they could serve as a preferred alternative to penicillin-based GBS prevention, and could greatly reduce the burden of GBS colonization and subsequent infant GBS disease in Nicaragua.

 

Nadja VielotDr Nadja Alexandra Vielot Postdoctoral Research Associate
Family Medicine, University of North Carolina at Chapel Hill (USA)


Collaborators:
Professor Samuel Vilchez, National University of Nicaragua, León (Nicaragua)

Professor Neil French, University of Liverpool (UK)