Search

Background: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence., Methods: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time., Findings: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49)., Interpretation: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses., Funding: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd., Competing Interests: Declaration of interests RA was employed by GlaxoSmithKline Vaccines and received grant awards from WHO, Gavi, and the Bill & Melinda Gates Foundation whilst employed at MRC Gambia. MK, SH, and BG received grants from the Bill & Melinda Gates Foundation. MK received grants from Gavi, Merck, and Pfizer, and personal fees from Pfizer. All other authors declare no competing interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence., Methods: We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2-59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia., Findings: We investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2-11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7-36) in 2014-15. In the 12-23 month age group, radiological pneumonia decreased from 15·3 to 10·9 cases per 1000 person-years (29% decline, 12-42). In children aged 2-4 years, incidence fell from 5·2 to 4·1 cases per 1000 person-years (22% decline, 1-39). Incidence of all clinical pneumonia increased by 4% (-1 to 8), but hospitalised cases declined by 8% (3-13). Pneumococcal pneumonia declined from 2·9 to 1·2 cases per 1000 person-years (58% decline, 22-77) in children aged 2-11 months and from 2·6 to 0·7 cases per 1000 person-years (75% decline, 47-88) in children aged 12-23 months. Hypoxic pneumonia fell from 13·1 to 5·7 cases per 1000 person-years (57% decline, 42-67) in children aged 2-11 months and from 6·8 to 1·9 cases per 1000 person-years (72% decline, 58-82) in children aged 12-23 months. In the case-control study, the best estimate of the effectiveness of three doses of PCV13 against radiological pneumonia was an adjusted odds ratio of 0·57 (0·30-1·08) in children aged 3-11 months and vaccine effectiveness increased with greater numbers of doses (p=0·026). The analysis in children aged 12 months and older was underpowered because there were few unvaccinated cases and controls., Interpretation: The introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia., Funding: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011., Methods: We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008-May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013-Dec 31, 2014), adjusting for changes in case ascertainment over time., Findings: We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30-71) in the 2-23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64-91) reduction in serotypes covered by the PCV13 vaccine. In the 2-4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25-75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39-83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2-59 months increased by 47% (-21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time., Interpretation: The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2-59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2-4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease., Funding: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council., (Copyright © 2016 Mackenzie et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide. A heptavalent polysaccharide-protein conjugate vaccine (PCV) has proven highly effective in preventing pneumococcal disease in industrialized countries. Two higher-valent pneumococcal conjugate vaccines are now widely available, even in the poorest countries. These differ from each other in the number of serotypes and carrier proteins used for their conjugation. Some have assumed that the only meaningful clinical difference between PCV formulations is a function of the number of serotypes each contains. A careful review of recent clinical data with these and several unlicensed PCV formulations points to important similarities but also that some key properties of each vaccine likely differ from one another.

Background: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era., Methods: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region., Results: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes., Conclusion: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination.

Background: Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies., Methods: Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2-30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study., Results: 57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26-0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87-1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50-0.92], p = 0.013 in control villages and HR 0.31 [0.19-0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06-2.06], p = 0.022) and (HR 1.52 [1.11-2.10], p = 0.010 respectively) were significantly higher., Conclusion: PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring., Trial Registration: ISRCTN Register 51695599.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

Background: A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3-4 years after primary vaccination., Methodology/principal Findings: We recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9 serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a median age of 45 months (range, 38-52 months); 138 had received 3 doses of PCV-9 in infancy and 144 were controls. Before receiving PCV-7, a high proportion of children had antibody concentrations >0.35 µg/mL to most of the serotypes in PCV-9 (average of 75% in the PCV-9 and 66% in the control group respectively). The geometric mean antibody concentrations in the vaccinated group were significantly higher compared to controls for serotypes 6B, 14, and 23F. Antibody concentrations were significantly increased to serotypes in the PCV-7 vaccine both 6-8 weeks and 16-18 months after PCV-7. Antibodies to serotypes 6B, 9V and 23F were higher in the PCV-9 group than in the control group 6-8 weeks after PCV-7, but only the 6B difference was sustained at 16-18 months. There was no significant difference in nasopharyngeal carriage between the two groups., Conclusions/significance: Pneumococcal antibody concentrations in Gambian children were high 34-48 months after a 3-dose primary infant vaccination series of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly higher than in control children for 3 of the 9 serotypes. Antibody concentrations increased after PCV-7 and remained raised for at least 18 months.

Background: A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes., Methods: A single-blind, cluster-randomized (by village) trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group); in 10 control villages only children <30 months old or those born during the study received PCV-7. Subjects over the age of 30 months resident in vaccine villages received a single dose of PCV-7 whilst those in control villages received a single dose of a serogroup C meningococcal conjugate vaccine. Serum antibody concentrations against specific pneumococcal polysaccharides were measured in approximately 200 age-stratified subjects before, 4-6, 12 and 24 months following vaccination., Results: Baseline pneumococcal antibody concentrations were generally high and increased with age up to 10 years. One dose of PCV-7 increased geometric mean antibody concentrations (GMC) in vaccinated versus control villages for vaccine serotypes 6B and 18C, and 4 and 18C, in the young (under 5 years) and older age groups (5+ years) respectively. There were significantly higher proportions of subjects in the vaccinated than in the control communities with an antibody concentration believed to protect against carriage (>5.0 µg/mL) for all but serotype 9V of the PCV-7 serotypes in the older group, but not in the younger age group., Conclusion: Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities., Trial Registration: Controlled-Trials.com ISRCTN51695599 51695599.

Background: Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria., Methods: This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST)., Results: The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage., Conclusions: Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for impact assessment following vaccine introduction in Nigeria.

Background: Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia., Methods and Findings: A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively). A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04-0.57] and OR = 0.32 [95% CI 0.10-0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small., Conclusions: Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a "herd effect" in non-vaccinated older children and adults. No significant serotype replacement was detected. Please see later in the article for the Editors' Summary.

The immunogenicity and impact on carriage of fewer doses of pneumococcal conjugate vaccine (PCV7) followed by booster with pneumococcal polysaccharide vaccine (PPV) were investigated. 684 infants were assigned randomly to one of the three groups that received one (A), two (B) or three (C) doses of PCV7 between 2 and 4 months of age, plus PPV at 10 months. Following primary vaccination protective antibody titers of >0.35 μg/ml against the PCV7 serotypes combined increased significantly with the number of PCV7 doses, 44% vs. 77% vs. 94% (p<0.001), and correlated positively with the opsonophagocytic indices, but negatively with nasopharyngeal carriage of pneumococcus. The differences in antibody responses and pneumococcal carriage between the groups diminished following booster with PPV, implying that administration of one or two doses of PCV7, with a booster dose of PPV might lower the cost of protection against IPD in young children in resource poor countries., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Nasopharyngeal carriage of Streptococcus pneumoniae is extremely prevalent in The Gambia. We studied the effects of vaccination with pneumococcal conjugate vaccines on the carriage of individual serotypes and on antimicrobial resistance in vaccinated children and their younger siblings., Methods: A longitudinal study of a subsample of children (n=2342) who participated in a randomized, placebo controlled trial of a 9-valent pneumococcal conjugate vaccines (PCV-9) in The Gambia, and a cross-sectional study of non-PCV-9-vaccinated younger siblings (n=675)., Results: Recipients of PCV-9 were less likely to carry vaccine serotypes 4, 6B, 9V, 14, 19F, and 23F but more likely to carry vaccine-associated 19A and 9 nonvaccine serotypes at approximately 6 months postvaccination (age, 12 months) than were controls (each P<0.05). At approximately 16 months postvaccination, carriage of vaccine-associated-serotype 6A was also significantly reduced (P<0.01) while 3 other nonvaccine serotypes were more prevalent in the PCV-9 recipients (each P<0.05). At 16 months, but not 6 months, postvaccination PCV-9 recipients had lower rate of carrying isolates resistant to tetracycline and trimethoprim-sulfamethoxazole (TMP-SMZ) than controls (risk ratio: 0.90 and 0.95, respectively; each P<0.05). There was no difference in patterns of carriage of pneumococci in younger siblings of PCV-9 or placebo recipients., Conclusions: The effects of 9-valent pneumococcal conjugate vaccines on carriage of pneumococci persisted for at least 16 months postvaccination in Gambian children. Vaccination had no indirect effect on carriage in younger siblings and there was limited impact on antibiotic resistance.

Background: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children, Methods: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST., Results: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618., Conclusion: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia.

Objective: To determine the value of C-reactive protein (CRP) and procalcitonin in the evaluation of the efficacy of a pneumococcal conjugate vaccine in Gambian children., Methods: The investigation was done as a substudy of a phase III pneumococcal conjugate vaccine trial. A pilot study (n = 120) to compare CRP and procalcitonin concentrations in children with pneumonia was undertaken, followed by a larger study of CRP concentrations (n = 1868) obtained from a subsample of children with clinical pneumonia seen during the trial., Results: In the pilot study, CRP had a higher sensitivity and specificity for the detection of primary endpoint (radiographic) pneumonia than procalcitonin. In the subsequent study of 1868 episodes of clinical pneumonia, CRP showed moderate sensitivity but poor positive predictive value in identifying primary endpoint pneumonia or pneumococcal bacteraemia. Addition of CRP thresholds of 40, 60 or 120 mg/l to the diagnosis of clinical pneumonia did not give higher estimates of vaccine efficacy or vaccine attributable reduction in incidence than primary endpoint pneumonia., Conclusion: A combination of a raised CRP concentration with a clinical diagnosis of pneumonia is a more specific endpoint than clinical pneumonia alone but less appropriate than primary endpoint pneumonia as a measure of the impact of a pneumococcal vaccine in a Gambian setting.

Prevention of nasopharyngeal colonization may reduce the burden of pneumococcal infection during infancy. Colostrum obtained from Gambian mothers who had been vaccinated with either Pneumovax II or Mengivax A&C (n=8 per group) during pregnancy was examined for inhibition of adherence of Streptococcus pneumoniae serotypes 6B and 14 to pharyngeal epithelial cells in vitro. Pneumococcal adherence was significantly reduced in the presence of breast milk (P< or =.0001 for S. pneumoniae serotype 14; P=.036 for serotype 6B), independent of the concentration of secretory IgA antibodies. Maternal vaccination with polyvalent pneumococcal polysaccharide vaccine boosts the capacity of colostrum to inhibit adherence of pneumococci to pharyngeal epithelial cells. In breast-feeding populations, maternal vaccination might prevent pneumococcal disease in young infants.

Background: In breast-feeding populations, immunization during pregnancy with pneumococcal polysaccharide offers a potentially useful approach to preventing pneumococcal disease in young infants., Methods: Breast milk samples were collected at 0, 2, 4 and 6 months after delivery from Gambian women vaccinated during pregnancy (24-32 weeks gestation) with Pneumovax II (n = 56) or Mengivax A&C (n = 57). Specimens were examined for secretory immunoglobulin A (s-IgA) concentration, subclass distribution and avidity specific to pneumococcal serotypes 4, 6B, 14, 19F and 23F and the antigen mixture in Pneumovax II by enzyme-linked immunosorbent assay. Colostral s-IgA and IgG concentrations in paired maternal sera were compared., Results: Colostral s-IgA concentrations specific to all pneumococcal polysaccharide antigens investigated were significantly higher (P < 0.05) among Pneumovax II vaccinees. Titers specific to serotypes 4, 6B and 14 and the vaccine formula remained significantly higher during 6 months, and those for 19F were higher during 4 months. Significantly higher concentrations of vaccine antigen-specific s-IgA antibody were sustained for 6 months after delivery (P = 0.011). Comparison of colostral s-IgA and IgG in serum revealed a significant correlation only among Mengivax A&C vaccinees for pneumococcal polysaccharide 23F (rs= 0.68; P < or = 0.0001). Vaccination elicited trends toward increased s-IgA2, reaching significance for serotype 14 and the vaccine formula. Immunization elicited significantly higher s-IgA avidities specific to all pneumococcal polysaccharide antigens studied during 6 months., Conclusions: The public health value of immunization during pregnancy with pneumococcal polysaccharide vaccine in breast-feeding populations warrants further evaluation, particularly in populations with a high incidence of pneumococcal disease in early infancy.

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. [ABSTRACT FROM AUTHOR]

Background: A village-randomized trial of a seven-valent pneumococcal-conjugate-vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT) and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage of pneumococci two years after vaccination. Here, we report findings four years after vaccination. Methods: PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages. Villages were randomized (older children and adults) to receive PCV-7 (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine (partly vaccinated villages). Cross-sectional surveys (CSS) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8 partly vaccinated) participated in a CSS conducted four years after vaccination started. Results: Four years after vaccination, the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [6.4% versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001). Prevalence of NVT four years after vaccination was similar between study groups [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre-vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype 19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found. Conclusions: The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms. No significant serotype replacement was detected. Trial Registration: ClinicalTrials.gov ISRCTN51695599 [ABSTRACT FROM AUTHOR]

Background. To prepare for national introduction of a pneumococcal vaccine of restricted valency, we studied the pattern of nasopharyngeal carriage of Streptococcus pneumoniae and its transmission in Gambian villages over time. Methods. We collected nasopharyngeal swab specimens every 2 weeks from 158 villagers in 19 households in 2 villages over 1 year. We studied the prevalence and duration of S. pneumoniae carriage, the effect of household size and composition on carriage, and sequence type-specific carriage within and between households. Results. Ninety-seven percent of children and 85% of adults carried S. pneumoniae at some time. Fifty-three serotypes were represented among 1522 isolates. Carriage was more common among children than adults for all serotypes studied except 9V. There was an overall trend toward shorter carriage with increasing age (Pp.043) and significant differences in carriage duration between serotypes. For most serotypes, the odds of being a carrier were greater if there were other carriers in the household. The prevalence of carriage varied by serotype. Most notably, serotype 5 carriage occurred in only 1 village and was transient. Multilocus sequence typing of serotype 6B isolates from 1 village revealed 8 different sequence types and strong evidence of nonrandom distribution among households (P!.001). Study by sequence type suggested household spread starting most commonly in children, followed by spread to adults. Conclusions. This longitudinal carriage study in Gambian villages provides unique information on the pattern of spread of S. pneumoniae in rural Africa and a baseline for evaluating the impact of the introduction of pneumococcal conjugate vaccine into the region. [ABSTRACT FROM AUTHOR]

Background. Streptococcus pneumoniae is a leading cause of vaccine-preventable disease worldwide. Pneumococcal protein antigens are currently under study as components of potential vaccines that offer protection against multiple serotypes. We have therefore characterized T cell pneumococcal immunity acquired through asymptomatic carriage. Methods. Peripheral blood mononuclear cells from 40 healthy Gambian adults were stimulated with supernatants derived from S. pneumoniae strain (D39), 2 isogenic mutant strains lacking either pneumolysin or choline binding protein A, and recombinant pneumolysin. Immune responses were measured by cellular proliferation and by interleukin-10 (IL-10) and interferon-γ (IFN-γ) enzyme-linked immunosorbent spot and bioplex cytokine assays. Nasopharyngeal swabs were cultured to determine carriage rates. Results. S. pneumoniae nasopharyngeal carriage was detected in 60% of individuals. Both effector and resting (or central) CD4+ T cell memory were frequently present to a range of pneumococcal antigens. However, the level of the effector memory response did not relate to current nasopharyngeal carriage. Pneumolysin was not immunodominant in these T cell responses but induced a distinct proinflammatory profile (high IFN-γ, IL-12[p40], and L-17 levels and low IL-10 and IL-13 levels). Conclusions. In this population, T cell-mediated immunological memory potentially capable of pathogen clearance and immune surveillance is common but is not associated with the absolute interruption of pneumococcal carriage. How this naturally acquired immune memory influences pneumococcal vaccine efficacy remains to be determined. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. To prepare for the introduction of a pneumococcal conjugate vaccine of restricted valency, we studied the nasopharyngeal carriage of Streptococcus pneumoniae in Gambian villagers. Methods. A cross-sectional survey was conducted in 21 villages after a census. We recorded demographic characteristics, information on medical history, and data on possible risk factors for carriage from subjects. We collected a nasopharyngeal swab specimen from each subject for isolation and serotyping of S. pneumoniae and for antibiotic susceptibility testing. Results. The prevalence of S. pneumoniae carriage among 2872 villagers was 72%. It was highest among infants (i.e., children aged <1 year; 97%); the rate was 93% among babies aged <1 month and decreased with increasing age (P < .001). Prevalence of carriage was linked to proximity to another village. Sixty-three percent of isolates recovered from children aged <5 years were covered by the 7-valent vaccine or were of a vaccine-related serotype, compared with 43% of isolates overall. Forty-three isolates (14.3%) tested were initially penicillin resistant; none had high-level resistance, and 4 had intermediate resistance. The rates of resistance to other antibiotics were as follows: trimethoprim-sulfamethoxazole, 39%; tetracycline, 32.3%; chloramphenicol, 6.3%; cefotaxime, 0.3%; and erythromycin, 0%. The rates were highest for isolates of vaccine serotypes. Conclusions. Pneumococcal carriage rates among Gambian villagers are very high. A pneumococcal conjugate vaccine of restricted valency should reduce the pool of antibiotic-resistant pneumococci. The large reservoir of pneumococci of nonvaccine serotypes will require close monitoring when the vaccine is introduced. [ABSTRACT FROM AUTHOR]