SummaryBackgroundThe indirect effects of pneumococcal conjugate vaccines (PCVs) are mediated through reductions in carriage of vaccine serotypes. Data on PCVs in Asia and the Pacific are scarce. Fiji introduced the ten-valent PCV (PCV10) in 2012, with a schedule consisting of three priming doses at 6, 10, and 14 weeks of age and no booster dose (3 + 0 schedule) without catch-up. We investigated the effects of PCV10 introduction using cross-sectional nasopharyngeal carriage surveys.MethodsWe did four annual carriage surveys (one pre-PCV10 and three post-PCV10) in the greater Suva area in Fiji, during 2012–15, of 5–8-week-old infants, 12–23-month-old children, 2–6-year-old children, and their caregivers (total of 8109 participants). Eligible participants were of appropriate age, had axillary temperature lower than 37°C, and had lived in the community for at least 3 consecutive months. We used purposive quota sampling to ensure a proper representation of the Fiji population. Pneumococci were detected by real-time quantitative PCR, and molecular serotyping was done with microarray.Findings3 years after PCV10 introduction, vaccine-serotype carriage prevalence declined, with adjusted prevalences (2015 vs 2012) of 0·56 (95% CI 0·34–0·93) in 5–8-week-old infants, 0·34 (0·23–0·49) in 12–23-month-olds, 0·47 (0·34–0·66) in 2–6-year-olds, and 0·43 (0·13–1·42) in caregivers. Reductions in PCV10 serotype carriage were evident in both main ethnic groups in Fiji; however, carriage of non-PCV10 serotypes increased in Indigenous Fijian infants and children. Density of PCV10 serotypes and non-PCV10 serotypes was lower in PCV10-vaccinated children aged 12–23 months than in PCV10-unvaccinated children of the same age group (PCV10 serotypes −0·56 [95% CI −0·98 to −0·15], p=0·0077; non-PCV10 serotypes −0·29 [–0·57 to −0·02], p=0·0334).InterpretationDirect and indirect effects on pneumococcal carriage post-PCV10 are likely to result in reductions in pneumococcal disease, including in infants too young to be vaccinated. Serotype replacement in carriage in Fijian children, particularly Indigenous children, warrants further monitoring. Observed changes in pneumococcal density might be temporal rather than vaccine related.FundingDepartment of Foreign Affairs and Trade of the Australian Government through the Fiji Health Sector Support Program; Victorian Government's Operational Infrastructure Support Program; Bill & Melinda Gates Foundation.

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This study describes predictors of pneumococcal nasopharyngeal carriage and density in Fiji. We used data from four annual (2012-2015) cross-sectional surveys, pre-and postintroduction of ten-valent pneumococcal conjugate vaccine (PCV10) in October 2012. Infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and their caregivers participated. Pneumococci were detected and quantified using lytA qPCR, with molecular serotyping by microarray. Logistic and quantile regression were used to determine predictors of pneumococcal carriage and density, respectively. There were 8,109 participants. Pneumococcal carriage was negatively associated with years post-PCV10 introduction (global P<0.001), and positively associated with indigenous iTaukei ethnicity (aOR 2.74 [95% CI 2.17-3.45] P<0.001); young age (infant, toddler, and child compared with caregiver participant groups) (global P<0.001); urban residence (aOR 1.45 [95% CI 1.30-2.57] P<0.001); living with �2 children <5 years of age (aOR 1.42 [95% CI 1.27-1.59] P<0.001); low family income (aOR 1.44 [95% CI 1.28-1.62] P<0.001); and upper respiratory tract infection (URTI) symptoms (aOR 1.77 [95% CI 1.57-2.01] P<0.001). Predictors were similar for PCV10 and non-PCV10 carriage, except PCV10 carriage was negatively associated with PCV10 vaccination (0.58 [95% CI 0.41-0.82] P = 0.002) and positively associated with exposure to household cigarette smoke (aOR 1.21 [95% CI 1.02-1.43] P = 0.031), while there was no association between years post-PCV10 introduction and non-PCV10 carriage. Pneumococcal density was positively associated with URTI symptoms (adjusted median difference 0.28 [95% CI 0.16, 0.40] P<0.001) and toddler and child, compared with caregiver, participant groups (global P = 0.008). Predictors were similar for PCV10 and non-PCV10 density, except infant, toddler, and child participant groups were not associated with PCV10 density. PCV10 introduction was associated with reduced the odds of overall and PCV10 pneumococcal carriage in Fiji. However, after adjustment iTaukei ethnicity was positively

Background Streptococcus pneumoniae is a significant global pathogen that colonises the nasopharynx of healthy children. Pneumococcal conjugate vaccines, which reduce nasopharyngeal colonisation of vaccine-type S. pneumoniae , may have broader effects on the nasopharyngeal microbiota; however, data are limited. In Fiji, nasopharyngeal carriage prevalence of S. pneumoniae and other colonising species differ between the two main ethnic groups. Here, we examined the association between the 7-valent pneumococcal conjugate vaccine (PCV7) and the nasopharyngeal microbiota of children in Fiji, including for each of the two main ethnic groups—indigenous Fijians (iTaukei) and Fijians of Indian descent (FID). Method The nasopharyngeal microbiota of 132 Fijian children was examined using nasopharyngeal swabs collected from 12-month-old iTaukei and FID children who were vaccinated (3 doses PCV7) or unvaccinated in infancy as part of a phase II randomised controlled trial. Microbiota composition was determined by sequencing the V4 region of the 16S rRNA gene. Species-specific carriage of S. pneumoniae , Haemophilus influenzae , Moraxella catarrhalis and Staphylococcus aureus was determined using real-time quantitative PCR. Associations between microbiota composition and other host and environmental factors were considered in the analysis. Results PCV7 had no overall impact on microbial diversity or composition. However, ethnic differences were observed in both diversity and composition with iTaukei children having higher relative abundance of Moraxella ( p = 0.004) and Haemophilus ( p = 0.004) and lower relative abundance of Staphylococcus ( p = 0.026), Dolosigranulum ( p = 0.004) and Corynebacterium ( p = 0.003) compared with FID children. Further, when we stratified by ethnicity, associations with PCV7 could be detected: vaccinated iTaukei children had a lower relative abundance of Streptococcus and Haemophilus compared with unvaccinated iTaukei children ( p = 0.022 and p = 0.043, respectively); and vaccinated FID children had a higher relative abundance of Dolosigranulum compared with unvaccinated FID children ( p = 0.037). Children with symptoms of an upper respiratory tract infection (URTI) had a significantly different microbiota composition to children without symptoms. The microbiota composition of iTaukei children without URTI symptoms was most...

Streptococcus pneumoniae (the pneumococcus) carriage is commonly used to measure effects of pneumococcal vaccines. Based on findings from culture-based studies, the World Health Organization recommends both nasopharyngeal (NP) and oropharyngeal (OP) sampling for detecting adult carriage. Given evidence of potential confounding by other streptococci, we evaluated molecular methods for pneumococcal identification and serotyping from 250 OP samples collected from adults in Fiji, using paired NP samples for comparison. Samples were screened using lytA quantitative PCR (qPCR), as well as pneumococcal identification and serotyping conducted by DNA microarray. A subset of OP samples were characterized by latex sweep agglutination and multiplex PCR. Alternate qPCR assays (piaB and bguR) for pneumococcal identification were evaluated. The lytA qPCR was less specific and had poor positive predictive value (PPV) in OP samples (88% and 26%, respectively) compared with NP samples (95% and 64%, respectively). Using additional targets piaB and/or bguR improved qPCR specificity in OP, although the PPV (42 to 53%) was still poor. Using microarray, we found that 102/107 (95%) of OP samples contained nonpneumococcal streptococci with partial or divergent complements of pneumococcal capsule genes. We explored 91 colonies isolated from 11 OP samples using various techniques, including multiplex PCR, latex agglutination, and microarray. We found that nonpneumococcal streptococci contribute to false positives in pneumococcal serotyping and may also contribute to spurious identification by qPCR. Our results highlight that molecular approaches should include multiple loci to minimize false-positive results when testing OP samples. Regardless of method, pneumococcal identification and serotyping results from OP samples should be interpreted with caution. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is a significant global pathogen. Accurate identification and serotyping are vital. In contrast with World Health Organization recommendations based on culture methods, we demonstrate that pneumococcal identification and serotyping with molecular methods are affected by sample type. Results from oropharyngeal samples from adults were often inaccurate. This is particularly important for assessment of vaccine impact using carriage studies, particularly in low- and middle-income countries where there are significant barriers for disease surveillance.