Persistent and Emerging Pneumococcal Carriage Serotypes in a Rural Gambian Community After 10 Years of Pneumococcal Conjugate Vaccine Pressure.

BACKGROUND: The continuing impact of pneumococcal conjugate vaccines (PCVs) in regions with high pneumococcal transmission is threatened by the persistence of vaccine serotypes (VTs) and the emergence of nonvaccine serotypes (NVTs). METHODS: In 2016, we conducted a cross-sectional carriage survey (CSS5) in a community where PCV7 was first introduced in 2006 during a cluster-randomized trial conducted before nationwide introduction of PCV7 (2009) and PCV13 (2011). We estimated prevalence of PCV13 VT and NVT by age and compared these with earlier surveys before (CSS0), during (CSS1-3), and after the trial but before PCV13 (CSS4). Genomic analysis was conducted for the nontypeable pneumococci. RESULTS: Prevalence of PCV13 VT carriage decreased during the 10 years between CSS0 and CSS5 across all age groups (67.6% to 13.5%, P < .001; 59.8% to 14.4%, P < .001; 43.1% to 17.9%, P < .001; and 24.0% to 5.1%, P < .001, in <2, 2-4, 5-14, and ≥15 years, respectively). However, there was no difference between CSS4 and CSS5 in children ≥2 years and adults (children <2 years, no data). The prevalence of PCV13 NVT increased between CSS0 and CSS5 for children <2 years but decreased in older children and adults. In CSS5, serotypes 3, 6A, and 19F were the most common VT and nontypeable isolates were the most common NVT. Among nontypeable isolates, 73.0% lost the ability to express a capsule. Of these, 70.8% were from a VT background. CONCLUSIONS: The decrease in PCV13 VT that has occurred since the introduction of PCV13 appears to have plateaued. Significant carriage of these serotypes remains in all age groups.

Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia.

BACKGROUND: The widespread use of pneumococcal conjugate vaccine (PCV) has brought about a dramatic decrease in pneumococci of vaccine serotypes (VTs) but nonvaccine serotypes (NVTs) have emerged. METHODS: We conducted a cross-sectional survey (CSS) among infants who received 3 doses of 13-valent PCV (PCV13) and their mothers 5 years (CSS3) after PCV13 introduction. Nasopharyngeal swab samples were collected and cultured for isolation of Streptococcus pneumoniae. Whole-genome sequencing of the nontypeable strains was performed. Data were compared with those from 2 previous surveys conducted before PCV13 introduction (CSS1) and 1 year later (CSS2). RESULTS: Among infants, VT carriage decreased from 33.3% (113/339) in CSS1 to 11.4% (40/351) in CSS3 (P = .001) while NVTs increased from 53.1% (180/339) in CSS1 to 74.4% (261/351) in CSS3 (P < .001). Among mothers, there was a significant decrease in VTs between CSS2 8.4% (29/347) and CSS3 5.6% (19/342) (P = .006). NVTs increased from 16.6% (55/331) in CSS1 to 32.2% (110/342) in CSS3 (P < .001). In CSS3, the most prevalent VTs were 7F in infants and 3 in mothers, and the most prevalent NVTs were serogroup 16 and nontypeables, respectively. Genomic analysis showed that VTs were more likely than NVTs to lose their ability to express the capsule. CONCLUSIONS: Five years after PCV13 introduction, we show both direct (infants) and indirect effects (mothers) of the vaccine, while NVT replacement has occurred in both groups. Ongoing circulation of VTs warrants further study of their relevance in any consideration of a reduced dose schedule.

Long-term Impact of Oral Azithromycin Taken by Gambian Women During Labor on Prevalence and Antibiotic Susceptibility of Streptococcus pneumoniae and Staphylococcus aureus in Their Infants: Follow-up of a Randomized Clinical Trial.

Background: Oral azithromycin given to women in labor decreases maternal and neonatal bacterial carriage but increases azithromycin-resistant bacteria during at least 4 weeks following the intervention. We assessed the prevalence of bacterial carriage and azithromycin resistance 12 months after treatment among study infants. Methods: Nasopharyngeal swabs (NPSs) were collected between November 2014 and May 2015 from children aged 11-13 months whose mothers had received azithromycin or placebo during labor. Streptococcus pneumoniae and Staphylococcus aureus were isolated using conventional microbiological methods. Antibiotic susceptibility was determined by disk diffusion and confirmed by Etest or VITEK-2. Results: NPSs were collected from 461 children. The prevalence of S. pneumoniae and S. aureus was similar between children from the azithromycin and placebo arms (85.0% vs 82.1%; odds ratio [OR], 1.23 [95% confidence interval {CI}, .73-2.08] for S. pneumoniae and 21.7% vs 21.3%; OR, 1.02 [95% CI, .64-1.64] for S. aureus). Prevalence of azithromycin-resistant S. pneumoniae was similar in both arms (1.8% vs 0.9% in children from the azithromycin and placebo arms, respectively; OR, 2.10 [95% CI, .30-23.38]); resistance to other antibiotics was also similar between arms. For S. aureus, there was no difference in azithromycin resistance between children in the azithromycin (3.1%) and placebo (2.6%) arms (OR, 1.22 [95% CI, .35-4.47]) or resistance to any other antibiotics. Conclusions: The higher prevalence of S. aureus azithromycin resistance observed among women treated during labor and their babies 4 weeks after treatment had waned 12 months after delivery. Azithromycin intervention did not induce other antibiotic resistance to S. pneumoniae or S. aureus. Clinical Trials Registration: NCT01800942.

Short-term increase in the carriage of azithromycin-resistant Escherichia coli and Klebsiella pneumoniae in mothers and their newborns following intra-partum azithromycin: a post hoc analysis of a double-blind randomized trial.

OBJECTIVES: To evaluate the impact of one oral dose of intrapartum azithromycin (2 g) on the carriage and antibiotic resistance of Escherichia coli and Klebsiella pneumoniae in the nasopharynx, breast milk and vaginal swabs of mothers and K. pneumoniae in the nasopharynx of their newborns. METHODS: We performed a post hoc analysis of a double-blind, placebo-controlled randomized-trial (ratio 1:1) conducted in The Gambia. Breast milk (BM) and vaginal swabs (VS) from mothers and nasopharyngeal swabs (NPS) from mother-newborn pairs were collected at different timepoints during the 4 week follow-up. Samples were processed using standard microbiological procedures. For BM and NPS post-intervention results were combined for analysis. RESULTS: In the original trial 829 mothers were randomized. In this analysis, complete sample sets were available for 630 mothers for E. coli analysis (76.0%) and 564 mother-newborn pairs for K. pneumoniae analysis (68.0%). For E. coli, carriage prevalence in BM and VS was similar in both arms but resistance was higher in the azithromycin arm in VS (2.6% versus 0%, P = 0.004). For K. pneumoniae, carriage prevalence was higher in the azithromycin arm for BM (13.8% versus 8.7%, P = 0.055) but not for VS or NPS. Prevalence of azithromycin resistant K. pneumoniae was higher in the azithromycin arm for BM (3.6% versus 1.0%, P = 0.050) and VS (1.5% versus 0% P = 0.057). CONCLUSIONS: Oral intrapartum azithromycin did not reduce carriage of E. coli and K. pneumoniae and was associated with an increase in the prevalence of azithromycin-resistant E. coli and K. pneumoniae isolates in BM and VS.