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In a cluster-randomized trial conducted in Gambian villages, Anna Roca and colleagues find that vaccination of children with pneumococcal conjugate vaccines reduced vaccine-type pneumococcal carriage even among nonvaccinated older children and adults.

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

Editors' Summary

Background

The prevention of pneumococcal disease, especially in children in developing countries, is a major international public health priority. Despite all the international attention on the UN's Millennium Development Goal 4—to reduce deaths in children under five years by two-thirds between 1990 and 2015—pneumonia, sepsis, and meningitis together compose more than 25% of the 10 million deaths occurring in children less than five years of age. Streptococcus pneumoniae is a leading bacterial cause of these diseases, and the World Health Organization estimates that approximately 800,000 children die each year of invasive pneumococcal disease.

Pneumococcal conjugate vaccines are currently available and protect against the serotypes that most commonly cause invasive pneumococcal disease in young children in North America and Europe. Such vaccines have been highly successful in reducing the incidence of invasive pneumococcal disease in both vaccinated children and in the non-vaccinated older population by reducing nasopharyngeal carriage (presence of pneumococcal bacteria in the back of the nose) in vaccinated infants, resulting in decreased transmission to contacts—the so-called herd effect. However, few countries with the highest burden of invasive pneumococcal disease, especially those in sub-Saharan Africa, have introduced the vaccine into their national immunization programs.

Why Was This Study Done?

The features of pneumococcal nasopharyngeal carriage and invasive pneumococcal disease in sub-Saharan Africa are different than in other regions. Therefore, careful evaluation of the immune effects of vaccination requires long-term, longitudinal studies. As an alternative to such long-term observational studies, and to anticipate the potential long-term effects of the introduction of pneumococcal conjugate vaccination in sub-Saharan Africa, the researchers conducted a cluster-randomized (by village) trial in The Gambia in which the whole populations of some villages were immunized with the vaccine PCV-7, and other villages received a control.

What Did the Researchers Do and Find?

With full consent from communities, the researchers randomized 21 similar villages in a rural region of western Gambia to receive pneumococcal conjugate vaccine or a control—meningococcal serogroup C conjugated vaccine, which is unlikely to affect pneumococcal carriage rates. For ethical reasons, the researchers only randomized residents aged over 30 months—all young infants received PCV-7, as a similar vaccine had already been shown to be effective in young infants. Before immunization began, the researchers took nasopharyngeal swabs from a random selection of village residents to determine the baseline pneumococcal carriage rates of both the serotypes of pneumococci covered by the vaccine (vaccine types, VTs) and the serotypes of pneumococci not covered in the vaccine (non-vaccine types, NVTs). The researchers then took nasopharyngeal swabs from a random sample of 1,200 of village residents in both groups of villages in cross-sectional surveys at 4–6, 12, and 22 months after vaccination. Villagers and laboratory staff were unaware of which vaccine was which (that is, they were blinded).

Before immunization, the overall prevalence of pneumococcal carriage in both groups was high, at 71.1%, and decreased with age. After vaccination, the overall prevalence of pneumococcal carriage in all three surveys was similar between vaccinated and control villages, showing a marked fall. However, the prevalence of carriage of VT pneumococci was significantly lower in vaccinated than in control villages in all surveys for all age groups. The prevalence of carriage of NVT pneumococci was similar in vaccinated and in control villages, except for a slightly higher prevalence of NVT pneumococci among vaccinated communities in adults at 4–6 months after vaccination. The researchers also found that the overall prevalence of pneumococcal carriage fell markedly after vaccination and reached minimum levels at 12 months in both study arms and in all age groups.

What Do These Findings Mean?

These findings show that vaccination of young Gambian children reduced carriage of VT pneumococci in vaccinated children but also in vaccinated and non-vaccinated older children and adults, revealing a potential herd effect from vaccination of young children. Furthermore, the immunological pressure induced by vaccinating whole communities did not lead to a community-wide increase in carriage of NVT pneumococci during a two-year period after vaccination. The researchers plan to conduct more long-term follow-up studies to determine nasopharyngeal carriage in these communities.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001107.

The World Health Organization has information about pneumococcus

The US Centers for Disease Control and Prevention provides information about pneumococcal conjugate vaccination

This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.

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

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

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

To determine the prevalence of carriage of respiratory bacterial pathogens, and the risk factors for and serotype distribution of pneumococcal carriage in an Australian Aboriginal population.

Methods

Surveys of nasopharyngeal carriage of Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxella catarrhalis were conducted among adults (≥16 years) and children (2 to 15 years) in four rural communities in 2002 and 2004. Infant seven-valent pneumococcal conjugate vaccine (7PCV) with booster 23-valent pneumococcal polysaccharide vaccine was introduced in 2001. Standard microbiological methods were used.

Results

At the time of the 2002 survey, 94% of eligible children had received catch-up pneumococcal vaccination. 324 adults (538 examinations) and 218 children (350 examinations) were enrolled. Pneumococcal carriage prevalence was 26% (95% CI, 22-30) among adults and 67% (95% CI, 62-72) among children. Carriage of non-typeable H. influenzae among adults and children was 23% (95% CI, 19-27) and 57% (95% CI, 52-63) respectively and for M. catarrhalis, 17% (95% CI, 14-21) and 74% (95% CI, 69-78) respectively. Adult pneumococcal carriage was associated with increasing age (p = 0.0005 test of trend), concurrent carriage of non-typeable H. influenzae (Odds ratio [OR] 6.74; 95% CI, 4.06-11.2) or M. catarrhalis (OR 3.27; 95% CI, 1.97-5.45), male sex (OR 2.21; 95% CI, 1.31-3.73), rhinorrhoea (OR 1.66; 95% CI, 1.05-2.64), and frequent exposure to outside fires (OR 6.89; 95% CI, 1.87-25.4). Among children, pneumococcal carriage was associated with decreasing age (p < 0.0001 test of trend), and carriage of non-typeable H. influenzae (OR 9.34; 95% CI, 4.71-18.5) or M. catarrhalis (OR 2.67; 95% CI, 1.34-5.33). Excluding an outbreak of serotype 1 in children, the percentages of serotypes included in 7, 10, and 13PCV were 23%, 23%, and 29% (adults) and 22%, 24%, and 40% (2-15 years). Dominance of serotype 16F, and persistent 19F and 6B carriage three years after initiation of 7PCV is noteworthy.

Conclusions

Population-based carriage of S. pneumoniae, non-typeable H. influenzae, and M. catarrhalis was high in this Australian Aboriginal population. Reducing smoke exposure may reduce pneumococcal carriage. The indirect effects of 10 or 13PCV, above those of 7PCV, among adults in this population may be limited.

To confirm the effect of 7-valent pneumococcal conjugate vaccine (PCV7), pneumococcal nasopharyngeal (NP) carriage was compared between vaccinated (3 + 1 doses PCV7) and non-vaccinated children. Vaccinated subjects were recruited from highly vaccinated regions (≥ 60%), Seoul and Incheon whereas control subjects were recruited from Jeju Island where vaccination rates are low (< 15%). NP swabs were obtained from 400 children aged 18-59 months. Serotype and antibiotic susceptibility was analyzed. Pneumococcal carriage rate was 18.0% (36/200) and 31.5% (63/200) for the vaccinated and control group, respectively. Among those vaccinated, 41.7% (15/36) of the serotypes were vaccine-related type (VRT: 6A, 6C, 19A) with the most common serotype 6C. The next common type was non-typable/non-capsule 30.6% (11/36) followed by non-vaccine type 16.7% (6/36) and vaccine type (VT) serotypes were found in only 11.1% (4/36). In contrast, 52.4% (33/63) of the isolates in the control group were VT. Resistance rates for penicillin and erythromycin were lower in the vaccine group (vaccine vs control; penicillin 45.2% vs 71.4%, erythromycin 74.2% vs 90.5%, P < 0.05). Multi-drug resistance was also lower in vaccinated subjects (vaccine vs control; 45.2% vs 69.8%, P < 0.05). PCV7 reduces carriage in VT which leads to replacement of pneumococci by antibiotic susceptible VRT or non-vaccine type strains.

Background

We sought to measure trends in Streptococcus pneumoniae (SP) carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13).

Methods

We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008–9 and compared with to similar studies performed in 2001, 2003–4, and 2006–7. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006–07 and 2008–09) were evaluated.

Results

We collected nasopharyngeal specimens from 1,011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008–09, newly-targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin non-susceptible S. pneumoniae (PNSP). In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with PNSP carriage.

Conclusions

Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted.

In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes.

Background

Simultaneous carriage of more than one strain of Streptococcus pneumoniae promotes horizontal gene transfer events and may lead to capsule switch and acquisition of antibiotic resistance. We studied the epidemiology of cocolonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal vaccine (PCV7).

Methodology

Nasopharyngeal swabs (n 1120) were collected from outpatients between 2004 and 2009 within an ongoing nationwide surveillance program. Cocolonization was detected directly from swabs by restriction fragment length polymorphism (RFLP) analysis. Serotypes were identified by agglutination, multiplex PCR and microarray.

Principal Findings

Rate of multiple colonization remained stable up to three years after PCV7 introduction. Cocolonization was associated with serotypes of low carriage prevalence in the prevaccine era. Pneumococcal colonization density was higher in cocolonized samples and cocolonizing strains were present in a balanced ratio (median 1.38). Other characteristics of cocolonization were a higher frequency at young age, but no association with recurrent acute otitis media, recent antibiotic exposure, day care usage and PCV7 vaccination status.

Conclusions

Pneumococcal cocolonization is dominated by serotypes of low carriage prevalence in the prevaccine era, which coexist in the nasopharynx. Emergence of such previously rare serotypes under vaccine selection pressure may promote cocolonization in the future.

This study determined the serotype-specific acquisition rates for pneumococcal colonization in a cohort of 1404 newborn infants followed intensively for 3 months. By observing pneumococcal carriage in family members, we were able to determine serotype-specific transmission probabilities between relatives.

Background. Herd protection and serotype replacement disease following introduction of pneumococcal conjugate vaccine (PCV) are attributable to the vaccine's impact on colonization. Prior to vaccine introduction in Kenya, we did an epidemiological study to estimate the rate of pneumococcal acquisition, by serotype, in an uncolonized population.

Methods. Nasopharyngeal swab specimens were taken from newborns aged ≤7 days and weekly thereafter for 13 weeks. Parents, and siblings aged <10 years, were swabbed at monthly intervals. Swabs were transported in skim milk-tryptone-glucose-glycerin and cultured on gentamicin blood agar. Pneumococci were serotyped by the Quellung reaction. We used survival analysis and Cox regression analysis to examine serotype-specific acquisition rates and risk factors and calculated transmission probabilities from the pattern of acquisitions within the family.

Results. Of 1404 infants recruited, 887 were colonized by 3 months of age, with the earliest acquisition detected on the first day of life. The median time to acquisition was 38.5 days. The pneumococcal acquisition rate was 0.0189 acquisitions/day (95% confidence interval, .0177–.0202 acquisitions/day). Serotype-specific acquisition rates varied from 0.00002–0.0025 acquisitions/day among 49 different serotypes. Season, coryza, and exposure to cigarettes, cooking fumes, and other children in the home were each significant risk factors for acquisition. The transmission probability per 30-day duration of contact with a carrier was 0.23 (95% CI, .20–.26).

Conclusions. Newborn infants in Kilifi have high rates of nasopharyngeal acquisition of pneumococci. Half of these acquisitions involve serotypes not included in any current vaccine. Several risk factors are modifiable through intervention. Newborns represent a consistent population of pneumococcus-naive individuals in which to estimate the impact of PCV on transmission.

Background

After the implementation of 7-valent pneumococcal conjugate vaccine (PCV7), in several countries, serotype 19A is now the serotype most frequently involved in pneumococcal diseases and carriage. To determine factors potentially related to 19A nasopharyngeal (NP) carriage we analyzed data from an ongoing prospective French national surveillance study of pneumococcal NP carriage in young children.

Methods

NP swabs were obtained from children aged 6 to 24 months, either during routine check-ups with normal findings, or when they presented with acute otitis media (AOM). The swabs were sent for analysis to the French National Reference Centre for Pneumococci. Factors influencing pneumococcal carriage and carriage of penicillin non-susceptible (PNSP), 19A and PNS-19A were investigated by multivariate logistic regression.

Results

From 2006 to 2009, 66 practitioners enrolled 3507 children (mean age 13.6 months), of whom, 98.3% of children had been vaccinated with PCV7 and 33.4% of children attended daycare centres (DCC). Serotype 19A was found in 10.4% of the overall population, 20.5% of S. pneumoniae carriers (n = 1780) and 40.8% of PNSP carriers (n = 799). Among 19A strains, 10.7% were penicillin-susceptible, 80% intermediate and 9.3% fully resistant. Logistic regression analysis showed that the main factors associated with PNSP carriage were AOM (OR = 3.09, 95% CI [2.39;3.98]), DCC (OR = 1.70, 95% CI [1.42;2.03]), and recent antibiotic use (OR = 1.24, 95% CI [1.05;1.47]. The main factors predictive of 19A carriage were recent antibiotic use (OR = 1.81, 95% CI [1.42;2.30]), AOM (OR = 1.67, 95% CI [1.11;2.49]), DCC (OR = 1.56, 95% CI [1.21;2.2] and young age, <12 months (OR = 1.51, 95% CI [1.16;1.97]).

Conclusion

In a population of children aged from 6 to 24 months with a high rate of PCV7 vaccination coverage, we found that antibiotic exposure, DCC attendance and AOM were linked to 19A carriage.

Background

Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs).

Methodology

In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction.

Principal Findings

S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively.

Conclusions

This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.

Background

Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents.

Methodology/Principal Findings

This study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1∶1∶1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n = 336), 2+1-doses (336) or no dose (n = 333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p = 0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38–0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52–0.88).

Conclusions/Significance

PCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted.

Trial Registration

ClinicalTrials.gov NCT00189020

Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n = 173), unvaccinated children of the vaccine era (n = 169), and fully vaccinated children (4 doses; n = 150). Co-colonization, serotype identification, and relative serotype abundance were detected by analysis of DNA of the total bacterial growth of the primary culture plate using the plyNCR-RFLP method and a molecular serotyping microarray-based strategy. The plyNCR-RFLP method detected an overall co-colonization rate of 20.1%. Microarray analysis confirmed the plyNCR-RFLP results. Vaccination status was the only factor found to be significantly associated with co-colonization: co-colonization rates were significantly lower (p = 0.004; Fisher's exact test) among fully vaccinated children (8.0%) than among children from the pre-PCV7 era (17.3%) or unvaccinated children of the PCV7 era (18.3%). In the PCV7 era there were significantly less non-vaccine type (NVT) co-colonization events than would be expected based on the NVT distribution observed in the pre-PCV7 era (p = 0.024). In conclusion, vaccination with PCV7 resulted in a lower co-colonization rate due to an asymmetric distribution between NVTs found in single and co-colonized samples. We propose that some NVTs prevalent in the PCV7 era are more competitive than others, hampering their co-existence in the same niche. This result may have important implications since a decrease in co-colonization events is expected to translate in decreased opportunities for horizontal gene transfer, hindering pneumococcal evolution events such as acquisition of antibiotic resistance determinants or capsular switch. This might represent a novel potential benefit of conjugate vaccines.

Background

Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France.

Methods

Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies.

Results

We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001).

Conclusion

The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.

To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in 329 prebooster 11-month-old children, 330 fully vaccinated 24-month-old children, and 324 parents with age-matched pre-PCV7 (unvaccinated) controls (ages 12 and 24 months, n = 319 and n = 321, respectively) and 296 of their parents. PCV7 serotype prevalences before and after PCV7 implementation, respectively, were 38% and 8% among 11-month-old children, 36% and 4% among 24-month-old children, and 8% and 1% among parents. Non-PCV7 serotype prevalences were 29% and 39% among 11-month-old children, 30% and 45% among 24-month-old children, and 8% and 15% among parents, respectively; serotypes 11A and 19A were most frequently isolated. PCV7 serotypes were largely replaced by non-PCV7 serotypes. Disappearance of PCV7 serotypes in parents suggests strong transmission reduction through vaccination.

The 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine type Streptococcus pneumoniae but leads to replacement by nonvaccine serotypes and may affect carriage of other respiratory pathogens. We investigated nasopharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian infants participating in a pneumococcal vaccine trial using quantitative PCR. Vaccination did not affect pathogen carriage rates or densities, whereas significant differences between the two major ethnic groups were observed.

Aims: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years.

Methods: Non-randomised, unblinded controlled study of 2–5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls. Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls). The swabs were cultured and serotyped for Streptococcus pneumoniae.

Results: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups.

Conclusions: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2–5 years of age.

Background

In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule.

Methods

We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs) in 2003 and 2005. Nasal secretions were collected and processed according to published methods.

Results

902 children (mean age 25 months) living in 29 communities in 2003 and 818 children (mean age 35 months) in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order) 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL) strains (15% overall) was detected in serotypes (descending order) 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL) strains (5% overall), was detected in serotypes (descending order) 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C.

Conclusion

Pneumococcal carriage remains high (~80%) in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined years were 16F, 19A, 11A, 6C and 23B. Antimicrobial non-susceptibility was detected in these and 17 additional serotypes. Shifts in serotype-specific carriage suggest a need more research to clarify the association between pneumococcal vaccination and carriage at the serotype level.

Background

The CRM197-conjugated 7-valent pneumococcal vaccine (PCV7) is protective against vaccine serotype disease and nasopharyngeal carriage. Data on PCV7-induced mucosal antibodies in relation to systemic or natural anticapsular antibodies are scarce.

Methods

In a randomized controlled setting, children received PCV7 at age 2 and 4 months (2-dose group), at age 2, 4 and 11 months (2+1-dose group) or no PCV7 (control group). From 188 children paired saliva samples were collected at 12 and 24 months of age. From a subgroup of 15 immunized children also serum samples were collected. IgG and IgA antibody-levels were measured by multiplex immunoassay.

Results

At 12 months, both vaccine groups showed higher serum and saliva IgG-levels against vaccine serotypes compared with controls which sustained until 24 months for most serotypes. Salivary IgG-levels were 10–20-fold lower compared to serum IgG, however, serum and saliva IgG-levels were highly correlated. Serum and salivary IgA-levels were higher in both vaccine groups at 12 months compared with controls, except for serotype 19F. Higher salivary IgA levels remained present for most serotypes in the 2+1-dose group until 24 months, but not in the 2-dose group. Salivary IgA more than IgG, increased after documented carriage of serotypes 6B, 19F and 23F In contrast to IgG, salivary IgA-levels were comparable with serum, suggesting local IgA-production.

Conclusions

PCV7 vaccination results in significant increases in salivary IgG and IgA-levels, which are more pronounced for IgG when compared to controls. In contrast, salivary anticapsular IgA-levels seemed to respond more to natural boosting. Salivary IgG and IgA-levels correlate well with systemic antibodies, suggesting saliva might be useful as potential future surveillance tool.

A cross sectional study by Stefan Flasche and coworkers document the serotype replacement of Streptococcus pneumoniae that has occurred in England since the introduction of PCV7 vaccination.

Background

We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines.

Methods and Findings

Nasopharyngeal swabs were taken from children <5 y old and family members (n = 400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case∶carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76–1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence.

Conclusion

Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Pneumococcal diseases—major causes of illness and death in children and adults worldwide—are caused by Streptococcus pneumoniae, a bacterium that often colonizes the nasopharynx (the area of the throat behind the nose). Carriage of S. pneumoniae bacteria does not necessarily cause disease. However, these bacteria can cause local, noninvasive diseases such as ear infections and sinusitis and, more rarely, they can spread into the lungs, the bloodstream, or the covering of the brain, where they cause pneumonia, septicemia, and meningitis, respectively. Although these invasive pneumococcal diseases (IPDs) can be successfully treated if administered early, they can be fatal. Consequently, it is better to protect people against IPDs through vaccination than risk infection. Vaccination primes the immune system to recognize and attack disease-causing organisms (pathogens) rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules (antigens) that it recognizes as foreign.

Why Was This Study Done?

There are more than 90 S. pneumoniae variants or “serotypes” characterized by different polysaccharide (complex sugar) coats, which trigger the immune response against S. pneumoniae and determine each serotype's propensity to cause IPD. The pneumococcal conjugate vaccine PCV7 contains polysaccharides (linked to a protein carrier) from the seven serotypes mainly responsible for IPD in the US in 2000 when routine childhood PCV7 vaccination was introduced in that country. PCV7 prevents both IPD caused by the serotypes it contains and carriage of these serotypes, which means that, after vaccination, previously uncommon, nonvaccine serotypes can colonize the nasopharynx. If these serotypes have a high invasiveness potential, then “serotype replacement” could reduce the benefits of vaccination. In this cross-sectional study (a study that investigates the relationship between a disease and an intervention in a population at one time point), the researchers investigate the effect of the UK PCV7 vaccination program (which began in 2006) on serotype-specific carriage and IPD in England to understand the role of PCV7 in serotype replacement and to predict the likely impact of vaccines containing additional serotypes (higher valency vaccines).

What Did the Researchers Do and Find?

The researchers examined nasopharyngeal swabs taken from PCV7-vaccinated children and their families for S. pneumoniae, determined the serotype of any bacteria they found, and compared the proportion of people carrying S. pneumoniae (carrier prevalence) and the distribution of serotypes in this study population and in a similar population that was studied in 2000/2001, before the PCV vaccination program began. Overall, there was no statistically significant change in carrier prevalence, but carriage of vaccine serotypes decreased in vaccinated children and their contacts whereas carriage of nonvaccine serotypes increased. The serotype-specific case-to-carrier ratios (CCRs; a measure of serotype invasiveness that was estimated using national IPD data) of the replacing serotypes were generally lower than those of the original serotypes, which resulted in a net reduction in IPD in children. Moreover, before PCV7 vaccination began, PCV7-included serotypes were responsible for similar proportions of pneumococcal carriage and disease; afterwards, the additional serotypes present in the higher valency vaccines PVC10 and PVC13 were responsible for a higher proportion of disease than carriage. Finally, three serotypes not present in the higher valency vaccines with outstandingly high CCRs (high invasiveness potential) are identified.

What Do These Findings Mean?

These findings document the serotype replacement of S. pneumoniae that has occurred in England since the introduction of PCV7 vaccination and highlight the importance of assessing the effects of pneumococcal vaccines on carriage as well as on IPDs. Because the additional serotypes included in PCV10 and PCV13 have high CCRs but low carriage prevalence and because most of the potential replacement serotypes have low CCRs, these findings suggest that the introduction of higher valency vaccines should further reduce the occurrence of invasive disease with limited risk of additional serotype replacement. However, the emergence of a few serotypes that have high CCRs but are not included in PCV10 and PCV13 might mitigate the benefits of higher valency vaccines. In other words, although the recent introduction of PCV13 into UK vaccination schedules is likely to have an incremental benefit on the reduction of IPD compared to PCV7, this benefit might be offset by increases in the carriage of some high CCR serotypes. These serotypes should be considered for inclusion in future vaccines.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001017.

The US Centers for Disease Control and Prevention provides information for patients and health professionals on all aspects of pneumococcal disease and pneumococcal vaccination

The US National Foundation for Infectious Diseases has a fact sheet on pneumococcal diseases

The UK Health Protection Agency provides information on pneumococcal disease and on pneumococcal vaccines

The World Health Organization also provides information on pneumococcal vaccines

MedlinePlus has links to further information about pneumococcal infections (in English and Spanish)

This study evaluated effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiDCV) compared with the 7-valent vaccine on nasopharyngeal bacterial colonization, specifically nontypeable Haemophilus influenzae (NTHi). PHiD-CV had no differential effect on nasopharyngeal NTHi colonization.

Background. This study evaluated the effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D–conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal conjugate vaccine (7vCRM) in young children.

Methods. A randomized controlled trial in the Netherlands, initiated 2 years after 7vCRM introduction, was conducted between 1 April 2008 and 1 December 2010. Infants (N = 780) received either PHiD-CV or 7vCRM (2:1) at 2, 3, 4, and 11–13 months of age. Nasopharyngeal samples taken at 5, 11, 14, 18, and 24 months of age were cultured to detect Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae and S. pneumoniae and confirmed H. influenzae as nontypeable (NTHi). Primary outcome measure was vaccine efficacy (VE) against NTHi colonization.

Results. In both groups, NTHi colonization increased with age from 33% in 5-month-olds to 65% in 24-month-olds. Three months postbooster, VE against colonization was 0.5% (95% confidence interval [CI], −21.8% to 18.4%) and VE against acquisition 10.9% (95% CI, −31.3% to 38.9%). At each sampling moment, no differences between groups in either NTHi prevalence or H. influenzae density were detected. Streptococcus pneumoniae (range, 39%–57%), M. catarrhalis (range, 63%­–69%), and S. aureus (range, 9%–30%) colonization patterns were similar between groups.

Conclusions. PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or H. influenzae density in healthy Dutch children up to 2 years of age, implying that herd effects for NTHi are not to be expected. Other bacterial colonization patterns were also similar.

Clinical Trials Registration NCT00652951.

Introduction

England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether.

Methods

A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13.

Results

Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether.

Conclusion

Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch.

Background

The development of optimal vaccination strategies for pneumococcal conjugate vaccines requires serotype-specific data on disease incidence and carriage prevalence. This information is lacking for the African meningitis belt.

Methods

We conducted hospital-based surveillance of acute bacterial meningitis in an urban and rural population of Burkina Faso during 2007–09. Cerebrospinal fluid was evaluated by polymerase chain reaction for species and serotype. In 2008, nasopharyngeal swabs were obtained from a representative population sample (1 month to 39 years; N = 519) and additional oropharyngeal swabs from 145 participants. Swabs were evaluated by culture.

Results

Annual pneumococcal meningitis incidence rates were highest among <6-month-old (58/100,000) and 15- to 19-year-old persons (15/100,000). Annual serotype 1 incidence was around 5/100,000 in all age groups. Pneumococcal carriage prevalence in nasopharyngeal swabs was 63% among <5-year-old children and 22% among ≥5-year-old persons, but adding oropharyngeal to nasopharyngeal swabs increased the estimated carriage prevalence by 60%. Serotype 1 showed high propensity for invasive disease, particularly among persons aged ≥5 years.

Conclusions

Serotype 1 causes the majority of cases with a relatively constant age-specific incidence. Pneumococcal carriage is common in all age groups including adults. Vaccination programs in this region may need to include older target age groups for optimal impact on disease burden.