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Background: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya., Methods: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung., Results: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes., Conclusion: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Antimicrobial resistance is an emerging public health concern. Ten-valent pneumococcal vaccine (PCV10) was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule without catchup. From 2014 to 2018, children <2 years were randomly selected in two rural union councils of Matiari, Pakistan. Nasopharyngeal swabs were collected using standard WHO guidelines by trained staff and processed at Infectious Disease Research Laboratory at The Aga Khan University, Karachi using culture on sheep blood agar and Multiplex PCR methods described by CDC, USA. Pneumococcal isolates were identified by optochin sensitivity and bile solubility tests. Isolates were then tested for antimicrobial susceptibility by standard Kirby-Bauer disk-diffusion method on Mueller-Hinton Agar (MHA) with 5% sheep blood agar as per Clinical & Laboratory Standards Institute (CLSI) recommendations. Of 3140 children enrolled, pneumococcal isolates were detected in 2370 (75%). Vaccine coverage improved from 41% to 68.4%. Out of the 2370 isolates, 88.4%, 37.6% and 25% were resistant to cotrimoxazole, tetracycline and erythromycin, respectively. There was no resistance to penicillin, ceftriaxone, and vancomycin. For erythromycin, resistance increased from 20% in 2014/15 to 30.8% in 2017/18 and for tetracycline it increased from 34.9% to 41.8% both of which were explained by an increase in prevalence of serotype 19A. Pneumococcal isolates were susceptible to penicillin, ceftriaxone, and vancomycin. They were largely resistant to cotrimoxazole and tetracycline. There was an increase in erythromycin and tetracycline resistance attributed to increasing prevalence of serotype 19A. Pneumococcal isolates from carriage and invasive disease should be closely monitored for antimicrobial susceptibility. IMPORTANCE Antimicrobial resistance is an emerging public health concern particularly in low- and middle-income countries where there is poor regulation and easy availability of antibiotics. This is the first study from Pakistan to report antimicrobial resistance patterns of pneumococcus after vaccine introduction in the community. Pakistan was the first South-Asian country to introduce PCV10 in its Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule without catchup. In this study, we describe the PCV10 impact on antimicrobial resistance patterns of pneumococcal nasopharyngeal carriage in children younger than 2 years of age in a rural district in Pakistan after the introduction of the vaccine.

Background: Burkina Faso, a country in Africa's meningitis belt, introduced 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, with 3 primary doses given at 8, 12 and 16 weeks of age. To assess whether the new PCV13 program controlled pneumococcal carriage, we evaluated overall and serotype-specific colonization among children and adults during the first 3 years after introduction., Methods: We conducted 2 population-based, cross-sectional, age-stratified surveys in 2015 and 2017 in the city of Bobo-Dioulasso. We used standardized questionnaires to collect sociodemographic, epidemiologic, and vaccination data. Consenting eligible participants provided nasopharyngeal (all ages) and oropharyngeal (≥5 years only) swab specimens. Swab specimens were plated onto blood agar either directly (2015) or after broth enrichment (2017). Pneumococci were serotyped by conventional multiplex polymerase chain reaction. We assessed vaccine effect by comparing the proportion of vaccine-type (VT) carriage among colonized individuals from a published baseline survey (2008) with each post-PCV survey., Results: We recruited 992 (2015) and 1005 (2017) participants. Among children aged <5 years, 42.8% (2015) and 74.0% (2017) received ≥2 PCV13 doses. Among pneumococcal carriers aged <1 year, VT carriage declined from 55.8% in 2008 to 36.9% in 2017 (difference, 18.9%; 95% confidence interval, 1.9%-35.9%; P = .03); among carriers aged 1-4 years, VT carriage declined from 55.3% to 31.8% (difference, 23.5%; 6.8%-40.2%; P = .004); and among participants aged ≥5 years, no significant change was observed., Conclusion: Within 3 years of PCV13 implementation in Burkina Faso, we documented substantial reductions in the percentage of pneumococcal carriers with a VT among children aged <5 years, but not among persons aged ≥5 years. More time, a change in the PCV13 schedule, or both, may be needed to better control pneumococcal carriage in this setting., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Pneumococcal carriage is a precursor of invasive pneumococcal disease. Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in April 2013, using a 3-dose schedule without a booster. We evaluated PCV10 impact on pneumococcal carriage and colonization density by HIV status., Methods: We conducted 2 cross-sectional surveys (pre and post PCV10 introduction) among children 6 weeks to 59 months old. Participants included HIV-infected children presenting for routine care at outpatient clinics and a random sample of HIV-uninfected children from the community. We collected demographic data, vaccination history and nasopharyngeal swabs. Swabs were cultured and isolates serotyped by Quellung. We selected serotypes 11A, 19A and 19F for bacterial density analyses. We compared vaccine-type (VT) carriage prevalence from the pre-PCV10 with the post-PCV10 period by HIV status., Findings: Prevalence of VT carriage declined from 35.9% (110/306) pre already defined in the background. It should be pre-PCV (PCV) to 20.7% (36/174 fully vaccinated) post PCV (P < 0.001) in HIV-uninfected and from 34.8% (144/414) to 19.7% (27/137 fully vaccinated) (P = 0.002) in HIV-infected children. Colonization prevalence for the 3 serotypes (3, 6A, 19A) included in the 13-valent PCV but not in PCV10 increased from 12.4% (38/306) to 20.7% (36/174 fully vaccinated) (P = 0.009) among HIV- uninfected children, mainly driven by 19A; no significant increase was observed in HIV-infected children. VT carriage among unvaccinated children decreased by 30% (P = 0.005) in HIV-infected children, with no significant declines observed in HIV-uninfected children., Conclusion: Declines in VT carriage were observed in both HIV-uninfected and HIV-infected children after PCV10 introduction with an early signal of herd effect especially in HIV-infected children. Ongoing monitoring of increases in 19A carriage and disease is necessary.

Background: Pneumococcal colonization is a precursor to pneumonia, and pneumococcal conjugate vaccines (PCV) can decrease vaccine-type (VT) colonization. Pneumococcal colonization studies are traditionally done among healthy children in the community; however, VT colonization prevalence may differ between these children and those with pneumonia. We assessed overall and VT pneumococcal colonization and factors associated with colonization among children with and without pneumonia after Mozambique introduced 10-valent PCV (PCV10) in 2013., Methods: We used data from ongoing pneumonia surveillance in children aged <5 years and from cross-sectional nasopharyngeal colonization surveys conducted in October 2014 -April 2015 and October 2015 -May 2016. Pneumonia was defined using WHO standard criteria for radiologically confirmed pneumonia. Children with pneumonia enrolled from January 2014 -April 2016 were compared to children without pneumonia enrolled from the cross-sectional surveys. Clinical data and nasopharyngeal (NP) swabs were collected from each child. NP specimens were cultured for pneumococci, and culture-negative specimens from children with pneumonia underwent polymerase chain reaction (PCR)., Results: Of 778 and 927 children with and without pneumonia, 97.4% and 27.0% were exposed to antibiotics before swab collection, respectively. Based on culture, pneumococcal colonization was 45.1% for children with and 84.5% for children without pneumonia (P<0.001); VT pneumococcal colonization was 18.6% for children with and 23.4% for children without pneumonia (P = 0.02). The addition of PCR in children with pneumonia increased overall and VT-pneumococcal colonization to 79.2% and 31.1%, respectively. In multivariable analysis including PCR results, pneumonia was associated with VT pneumococcal colonization (adjusted OR: 1.4, 95%CI: 1.10-1.78)., Conclusion: Vaccine-type pneumococcal colonization remains common among children with and without pneumonia post-PCV10 introduction in Mozambique. In a population of children with high antibiotic exposure, the use of PCR for culture-negative NP swabs can improve assessment of pneumococcal colonization and circulating serotypes., Competing Interests: Dr. Beutel Sigauque currently works for John Snow, Inc with the Maternal and Child Survival Program in Mozambique. However, at the time this work was done, Dr. Sigauque was an employee of Fundação Manhiça / Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Moçambique. This change in affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other conflicts of interest to declare.

In 2014, an acute respiratory illness outbreak affected unaccompanied children from Central America entering the United States; 9% of 774 surveyed children were colonized with Streptococcus pneumoniae serotype 5. In our 2015 follow-up survey of 475 children, serotype 5 was not detected, and an interim recommendation to administer 13-valent pneumococcal conjugate vaccine to all unaccompanied children was discontinued.

With the accelerated introduction of new vaccines in low-income settings, understanding immunization program performance is critical. We sought to improve immunization history acquisition from Ministry of Health vaccination cards during a vaccine impact study of 10-valent pneumococcal conjugate vaccine on pneumococcal carriage among young children in Kenya in 2012 and 2013. We captured immunization history in a low proportion of study participants in 2012 using vaccination cards. To overcome this challenge, we implemented a household-based reminder system in 2013 using community health workers (CHWs), and increased the retrieval of vaccine cards from 62% in 2012 to 89% in 2013 (P < 0.001). The home-based reminder system using CHWs is an example of an approach that improved immunization history data quality in a resource-poor setting., (© The American Society of Tropical Medicine and Hygiene.)

Detection of pneumococcal carriage by multiple co-colonizing serotypes is important in assessing the benefits of pneumococcal conjugate vaccine (PCV). Various methods differing in sensitivity, cost and technical complexity have been employed to detect multiple serotypes of pneumococcus in respiratory specimens. We have developed an algorithmic method to detect all known serotypes that preserves the relative abundance of specific serotypes by using Quellung-guided molecular techniques. The method involves culturing respiratory swabs followed by serotyping of 100 colonies by either capsular (10 colonies) or PCR (90 colonies) reactions on 96-well plates. The method was evaluated using 102 nasal swabs from children carrying pneumococcus. Multiple serotypes were detected in 22% of carriers, compared to 3% by World Health Organization (WHO)-recommended morphology-based selection of 1 to 3 colonies. Our method, with a processing cost of $87, could detect subdominant strains making up as low as 1% of the population. The method is affordable, practical, and capable of detecting all known serotypes without false positive reactions or change in the native distribution of multiple serotypes., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine type (VT) pneumococci, an important driver of vaccine programs' overall benefits. The dosing schedule that best reduces carriage is unclear., Methods: We performed a systematic review of English language publications from 1994 to 2010 (supplemented post hoc with studies from 2011) reporting PCV effects on VT carriage to assess variability in effect by dosing schedule., Results: We identified 32 relevant studies (36 citations) from 12,980 citations reviewed. Twenty-one (66%) evaluated PCV7; none used PCV10 or PCV13. Five studies evaluated 2 primary doses and 13 three primary doses. After the first year of life, 14 evaluated 3-dose primary series with PCV booster (3+1), seven 3 doses plus 23-valent polysaccharide booster "3+1PPV23," five "3+0," four "2+1," three "2+1PPV23" and two "2+0." Four studies directly compared schedules. From these, 3 primary doses reduced VT carriage more than 2 doses at 1-7 months following the series (1 study significant; 2 borderline). In a study, the 2+1 schedule reduced VT carriage more than 2+0 at 18, but not at 24 months of age. One study of a 23-valent pneumococcal polysaccharide vaccine booster showed no effect. All 16 clinical trials with unvaccinated controls and 11 observational studies with before-after designs showed reduction in VT carriage., Conclusions: The available literature demonstrates VT-carriage reduction for 2+0, 2+1, 3+0 and 3+1 PCV schedules, but not for 23-valent pneumococcal polysaccharide vaccine booster. Comparisons between schedules show that 3 primary doses and a 2+1 schedule may reduce carriage more than 2 primary doses and a 2+0 schedule, respectively.

Background: To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical outcomes among nontargeted age groups., Methods: We systematically reviewed the English literature on infant PCV dosing schedules published from 1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5 years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP), vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia., Results: Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9 pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5 (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated reductions in incidence among young adult groups. Among syndromic pneumonia observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed significant indirect effect. The 1 study to directly compare between schedules was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings and parents of vaccinated children with either schedule., Conclusions: Indirect benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT-NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by data paucity on indirect effects, especially a lack of head-to-head studies and studies of PCV10 and PCV13.

Background: A second-generation 13-valent pneumococcal conjugate vaccine, PCV13, was recently licensed. Although PCV13 includes serotype 6A, the usefulness of that antigen may be limited by the emergence of a new serotype, 6C, which was identified among isolates initially characterized (Quellung reaction) as serotype 6A. The epidemiology of serotype 6C prior to and after 7-valent PCV (PCV7) introduction is incompletely understood., Methods: We analyzed conventionally serotyped 6A (CS6A) pneumococci from invasive disease case patients of all ages and carriage isolates from children and adults obtained in population-based studies among Navajo and White Mountain Apache communities during 1994-2009. Samples were tested by triplex polymerase chain reaction to resolve serotypes 6C and 6A., Results: A total of 74 invasive CS6A episodes occurred. All were retyped by polymerase chain reaction; 40 (54.1%) were serotype 6C. The mean annual incidence of serotype 6C invasive disease was 0.3 (95% confidence interval, 0.03-0.9), 0.7 (95% confidence interval, 0.2-1.3), and 1.5 (95% confidence interval, 1.0-2.1) cases per 100,000 population in the years prior to the PCV7 efficacy trial, during the time the PCV7 trial was conducted, and following PCV7 introduction and routine use, respectively (P = .01). In the routine vaccination era, 76% of invasive CS6As were serotype 6C; nearly all cases occurred in adults. The proportion of serotype 6C among CS6A carriage isolates increased from 42% to 61% to 94% in the prevaccine, early vaccine, and routine vaccination eras, respectively., Conclusion: In the PCV7 routine use era, virtually all serogroup 6 invasive pneumococcal disease and carriage strains among Navajo and White Mountain Apache communities are 6C. Monitoring and evaluation of this and other emerging serotypes among invasive disease and carriage isolates is warranted.

The measurement of pneumococcal carriage in the nasopharyngeal reservoir is subject to potential confounders that include low-density and multiple-strain colonization. To compare different methodologies, we picked a random sampling of 100 nasopharyngeal specimens recovered from infants less than 2 years of age who were previously assessed for pneumococcal carriage and serotypes by a conventional method that used direct plating from the transport/storage medium (50 specimens were culture negative and 50 specimens were culture positive for pneumococci). We used a broth enrichment approach and a conventional PCR approach (with and without broth enrichment) to determine pneumococcal carriage and serotypes, and the results were compared to the initial conventional culture-based results. Additionally, we used a lytA-targeted real-time PCR for pneumococcal detection. Broth enrichment for both the culture-based and the PCR-based methods enhanced the isolation of pneumococci and detection of serotype diversity, with the most effective serotype deduction method being one that used broth enrichment prior to sequential multiplex PCR. Similarly, we also found that broth enrichment followed by the lytA-specific real-time PCR was the most sensitive for the detection of apparent pneumococcal carriage. The broth enrichment, conventional multiplex PCR, and real-time PCR approaches used in this study were effective in detecting pneumococcal carriage in the 50 specimens that were negative by conventional direct plating from transport medium (range of numbers of positive specimens, 8/50 to 22/50 [16 to 44%]), and the three different serotyping approaches that used broth enrichment increased the number of serotype identifications from the 100 specimens (12 to 29 additional serotype identifications to be positive). A PCR-based approach that employed a broth enrichment step appeared to best enhance the detection of mixed serotypes and low-density pneumococcal carriage.

Objective: We describe an effort to reduce transmission of a multidrug-resistant Streptococcus pneumoniae (MDRSP) in a long-term-care facility (LTCF)., Design: Longitudinal cross-sectional study., Setting: An LTCF in New York City with ongoing disease due to an MDRSP strain among residents with AIDS since a 1995 outbreak. The MDRSP outbreak strain was susceptible to vancomycin but not to other antimicrobials tested, including fluoroquinolones., Participants: Residents and staff members of the LTCF during 1999 through 2001., Intervention: Implementing standard infection control measures, and developing and implementing "enhanced standard" infection control measures, modified respiratory droplet prevention measures to reduce inter-resident transmission., Results: Before the intervention, nasopharyngeal carriage of the MDRSP outbreak strain was detected in residents with AIDS and residents with tracheostomies who were not dependent on mechanical ventilation. The prevalence of nasopharyngeal carriage of the MDRSP outbreak strain was 7.8% among residents who had AIDS and 14.6% among residents with tracheostomies. After training sessions on standard and enhanced standard infection control measures, the staff appeared to have good knowledge and practice of the infection control measures. After the intervention, new transmission among residents with tracheostomies was prevented; however, these residents were prone to persistent tracheal carriage and needed ongoing enhanced standard infection control measures. Ongoing transmission among residents with AIDS, a socially active group, was documented, although fewer cases of disease due to the outbreak strain occurred., Conclusions: Infection control contributed to less transmission of MDRSP in the LTCE Additional strategies are needed to reduce transmission and carriage among certain resident populations.

Several studies have shown that nasopharyngeal sampling is more sensitive than oropharyngeal sampling for the detection of pneumococcal carriage in children. The data for adults are limited and conflicting. This study was part of a larger study of pneumococcal carriage on the Navajo and White Mountain Apache Reservation following a clinical trial of a seven-valent pneumococcal conjugate vaccine. Persons aged 18 years and older living in households with children enrolled in the vaccine trial were eligible. We collected both nasopharyngeal and oropharyngeal specimens by passing a flexible calcium alginate wire swab either nasally to the posterior nasopharynx or orally to the posterior oropharynx. Swabs were placed in skim milk-tryptone-glucose-glycerin medium and frozen at -70 degrees C. Pneumococcal isolation was performed by standard techniques. Analyses were based on specimens collected from 1,994 adults living in 1,054 households. Nasopharyngeal specimens (11.1%; 95% confidence interval [CI], 9.8 and 12.6%) were significantly more likely to grow pneumococci than were oropharyngeal specimens (5.8%; 95% CI, 4.8 to 6.9%) (P < 0.0001). Few persons had pneumococcal growth from both specimens (1.7%). Therefore, both tests together were more likely to identify pneumococcal carriage (15.2%; 95% CI, 13.7 to 16.9%) than either test alone. Although we found that nasopharyngeal sampling was more sensitive than oropharyngeal sampling, nasopharyngeal sampling alone would have underestimated the prevalence of pneumococcal carriage in this adult population. Sampling both sites may give more accurate results than sampling either site alone in studies of pneumococcal carriage in adults.

Background: Vancomycin is often added to therapy for meningitis caused by Streptococcus pneumoniae. Tolerant bacteria without classic resistance that escape killing by multiple antibiotics have been reported sporadically. We determined the prevalence of tolerance to vancomycin in pneumococci and its effect on the outcome of meningitis., Methods: Archival samples of 215 nasopharyngeal (NP) and 113 meningitis isolates were tested for the killing efficacy of vancomycin. Specific DNA sequence changes in a transporter locus were identified for tolerant isolates. Similar tests were conducted prospectively on 517 NP isolates from healthy children., Results: In archival isolates, tolerance to vancomycin was detected in 3.7% of NP and 10.6% of invasive isolates. Patients with meningitis caused by tolerant isolates had a worse estimated 30-day survival than did patients with meningitis caused by nontolerant isolates (49% vs. 86%; P = .048); 62.5% of tolerant archival NP isolates harbored a specific sequence change for pep27 and vex2 (P = .021). Prospective analysis of 517 carriage isolates indicated that 8.1% were tolerant to vancomycin and that 82.1% of tolerant isolates harbored the specified marker gene sequences (P = .001)., Conclusions: Tolerance to vancomycin exists in the population of pneumococci. Tolerant isolates are associated with meningitis of increased mortality, and these isolates can be tracked by specific marker sequences in 2 genes., (Copyright 2004 Infectious Diseases Society of America)