•The post-PCV invasive disease potential of 25 pneumococcal serotypes was estimated.•The invasive disease potential of non-vaccine types, except 12F, are lower than 19A.•Age and disease presentation ...influence the invasive disease potential of serotypes.•Knowledge of invasive disease potential is valuable to assess and design vaccines.•Due to the diversity, surveillance of serotypes in carriage and IPD is critical.
Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV).
We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0–23, 24–29, and 0–59 months and by invasive clinical syndromes.
In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0–23 and 0–59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1–0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum.
There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.
•Pneumococcal conjugate vaccines have modestly reduced circulating vaccine serotypes in Soweto, South Africa.•There is a residual of vaccine serotypes.•Colonization by vaccine-serotype 19F remains ...high.•Co-colonization is higher in our setting than observed elsewhere.
Pneumococcal conjugate vaccines (PCVs) reduce pneumococcal-associated disease by reducing vaccine-serotype (VT) acquisition in vaccinated children, thereby interrupting VT transmission. The 7-valent-PCV was introduced in the South African immunization program in 2009 (13-valent-PCV since 2011) using a 2+1 schedule (at 6, 14, and 40 weeks of age). We aimed to evaluate temporal changes in VT and non-vaccine-serotype (NVT) colonization after 9 years of childhood PCV immunization in South Africa.
Nasopharyngeal swabs were collected from healthy children <60-month-old (n = 571) in 2018 (period-2) and compared with samples (n = 1135) collected during early PCV7-introduction (period-1, 2010-11) in an urban low-income setting (Soweto). Pneumococci were tested for using a multiplex quantitative-polymerase chain reaction serotyping reaction-set.
Overall pneumococcal colonization in period-2 (49.4%; 282/571) was 27.5% lower than period-1 (68.1%; 773/1135; adjusted odds ratio aOR: 0.66; 95% confidence interval CI: 0.54-0.88). Colonization by VT was reduced by 54.5% in period-2 (18.6%; 106/571) compared with period-1 (40.9%; 465/1135; aOR: 0.41; 95% CI: 0.3-0.56). Nevertheless, serotype 19F carriage prevalence was higher (8.1%; 46/571) in period-2 compared with period-1 (6.6%; 75/1135; aOR: 2.0; 95% CI: 1.09-3.56). NVT colonization prevalence was similar in period-2 and period-1 (37.8%; 216/571 and 42.4%; 481/1135).
There remains a high residual prevalence of VT, particularly 19F, colonization nine years post-introduction of PCV in the South African childhood immunization program.
Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing ...to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background.
Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%), Europe (19%), North America (12%), and South America (5%). These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage.
The combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction.
Penicillin and multidrug resistance were higher (p < .05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R2 = 0.27 p < .0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p < .05) of its antibiogram (mean misclassification error 0.28, SD ± 0.13).
We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed.
We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.
We evaluated pneumococcal colonization in children and adults between the time of 7-valent pneumococcal conjugate vaccine (PCV) introduction in the immunization program in 2009 to two years after ...transitioning to PCV13 in 2011.
Community-based carriage surveillance was undertaken between May-November 2013 (Period-3), with similar surveys in 2009 (Period-1) and 2011 (Period-2). Households with children below two years had a similar probability of being sampled in all surveys. Nasopharyngeal swabs were processed using standard methods and serotyped by Quellung.
In children>9-59 months old, overall pneumococcal colonization prevalence declined from 81.8% in Period-1 to 65.0% in Period-3 (p<0.001). Reductions of 70% (41.2% vs. 13.6%) in PCV7-serotypes colonization and 66% (15.3% vs. 4.4%) for the six additional PCV13-serotypes (PCV13-add6VT) were observed. There was, however, high residual colonization by PCV7-serotypes 19F (14.9% vs. 6.3%) and 23F (8.5% vs. 4.1%), despite reduction of 57% and 52%, respectively. Among individuals>12 years of age, there was 61% reduction in PCV7-serotype colonization (3.1% vs. 1.3%) and 75% decrease for PCV13-add6VT (2.1% vs. 0.6%) between Period-1 and Period-3.
The residual prevalence of serotypes 19F and 23F, four years after introducing PCV in the South Africa, suggests ongoing community transmission and transient vaccine effects.
Background. We investigated the impact of infant pneumococcal conjugate vaccine (PCV) immunization on pneumococcal colonization among human immunodeficiency virus (HIV)-infected and HIV-uninfected ...motherchild pairs. Methods. Pneumococcal colonization was assessed in May 2010-February 2011 (period 1; 7-valent PCV era) and May 2012-April 2013 (period 2; 13-valent PCV era). Standard microbiological methods were used for pneumococcus isolation and serotyping. Results. In children 0-12 years, PCV13-serotype colonization decreased from period 1 to period 2 among HIVuninfected (adjusted odds ratio OR, 0.32; 95% confidence interval CI, .25-.40) and HIV-infected children (adjusted OR, 0.37; 95% CI, .28-.49), while there was an increase in nonvaccine serotype colonization. Decreases in PCV13-serotype colonization were observed in HIV-uninfected women (adjusted OR, 0.44; 95% CI, .23-.81), with a similar trend in HIV-infected women. HIV-infected compared to -uninfected women had higher prevalence of overall (20.5% vs 9.7% in period 1; 13.8% vs 9.7% in period 2) and PCV 13-serotype colonization (8.7% vs 5.4% in period 1; 4.8% vs 2.0% in period 2), P<.04 for all observations. Conclusions. Targeted PCV vaccination of African infants in a setting with high HIV prevalence was associated with PCV 13-serotype colonization reduction, including among unvaccinated HIV-infected women.
A newly recognized pneumococcal serotype, 35D, which differs from the 35B polysaccharide in structure and serology by not binding to factor serum 35a, was recently reported. The genetic basis for ...this distinctive serology is due to the presence of an inactivating mutation in
, which encodes an O-acetyltransferase responsible for O-acetylation of a galactofuranose. Here, we assessed the genomic data of a worldwide pneumococcal collection to identify serotype 35D isolates and understand their geographical distribution, genetic background, and invasiveness potential. Of 21,980 pneumococcal isolates, 444 were originally typed as serotype 35B by PneumoCaT. Analysis of the
gene revealed 23 isolates from carriage (
= 4) and disease (
= 19) with partial or complete loss-of-function mutations, including mutations resulting in premature stop codons (
= 22) and an in-frame mutation (
= 1). These were selected for further analysis. The putative 35D isolates were geographically widespread, and 65.2% (15/23) of them was recovered after the introduction of pneumococcal conjugate vaccine 13 (PCV13). Compared with serotype 35B isolates, putative serotype 35D isolates have higher invasive disease potentials based on odds ratios (OR) (11.58; 95% confidence intervalCI, 1.42 to 94.19 versus 0.61; 95% CI, 0.40 to 0.92) and a higher prevalence of macrolide resistance mediated by
(26.1% versus 7.6%;
= 0.009). Using the Quellung reaction, 50% (10/20) of viable isolates were identified as serotype 35D, 25% (5/20) as serotype 35B, and 25% (5/20) as a mixture of 35B/35D. The discrepancy between phenotype and genotype requires further investigation. These findings illustrated a global distribution of an invasive serotype, 35D, among young children post-PCV13 introduction and underlined the invasive potential conferred by the loss of O-acetylation in the pneumococcal capsule.
The limited capability in most low- to middle-income countries to study the benefit of pneumococcal conjugate vaccine (PCV) in protecting against invasive pneumococcal disease (IPD) calls for ...alternate strategies to assess this. We used a mathematical model to predict the direct and indirect effectiveness of PCV by analyzing serotype-specific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005 to 2012 and colonization studies undertaken in human immunodeficiency virus (HIV)-uninfected and HIV-infected child-mother dyads from 2007 to 2009 (pre-PCV era), in 2010 (7-valent PCV era), and in 2012 (13-valent PCV era). We compared the model-predicted changes in IPD incidence with observed changes in IPD incidence, according to HIV status, in children aged 3 months-5 years and in women aged 18-45 years. We observed reductions in vaccine-serotype colonization and IPD due to vaccine serotypes among children and women after PCV introduction. Using the changes in vaccine-serotype colonization data, the model-predicted changes in vaccine-serotype IPD incidence rates were similar to the observed changes in PCV-unvaccinated children and adults, but not among children under age 24 months. Surveillance of colonization prior to and following PCV use can be used to impute the indirect protection afforded by PCV in unvaccinated age groups, including those in high-HIV-prevalence settings.
To assess the impact of immunization with pneumococcal conjugate vaccines on all-cause pneumonia hospitalizations among children in Soweto, South Africa.
We used data collected at the Chris Hani ...Baragwanath Hospital in Soweto between 2006 and 2014 - i.e. before and after April 2009, when a pneumococcal conjugate vaccine was first included in South Africa's routine immunization programme. Using a Bayesian generalized seasonal autoregressive moving-average model and the data collected in 2006-2008, we estimated the numbers of children that would have been hospitalized for pneumonia between 2010 and 2014 if no pneumococcal conjugate vaccines had been used. These estimates were then compared with the corresponding numbers of hospitalizations observed.
Between 2006 and 2014, 26 778 children younger than five years - including 3388 known to be infected with human immunodeficiency virus (HIV) - were admitted to the study hospital for pneumonia. We estimated that, for the children known to be infected with HIV and for the other children, pneumococcal conjugate vaccines reduced the numbers of hospitalizations for pneumonia in 2014 by 33% (50% credible interval, CrI: 6 to 52) and 39% (50% CrI: 24 to 50), respectively. In the study hospital in 2012-2014, as a result of immunizations with these vaccines, there were an estimated 3100 fewer pneumonia hospitalizations of children younger than five years.
In our study hospital, following the introduction of pneumococcal conjugate vaccines into the national immunization programme, there were significant reductions in pneumonia hospitalizations among children.
Pneumonia is a leading cause of child morbidity and death. Data on risk factors can guide prevention efforts. Within a study on pneumococcal conjugate vaccine effectiveness, we investigated risk ...factors for presumed bacterial pneumonia (PBP).
PBP cases were human immunodeficiency virus (HIV) uninfected children with lower respiratory tract infection and consolidation on chest radiograph or nonconsolidated infiltrate with C-reactive protein ≥40 mg/L hospitalized at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto. Age-matched community controls were identified using CHBAH birth records ±1 week of case birth date. Data were analyzed using conditional logistic regression.
A total of 889 PBP cases (median age 9 months) were matched to 2628 controls. Crowding was a significant risk factor among well-nourished children (adjusted odds ratio aOR: 2.29, 95% confidence interval CI: 1.89-2.78), but not in those with low weight-for-age. Malnutrition was associated with PBP; strength of association was highest in the absence of crowding (aOR: 6.68, 95% CI: 4.74-9.42). Exclusive breastfeeding was protective only among HIV-unexposed children (aOR: 0.65, 95% CI: 0.54-0.78). Self-reported maternal HIV infection was a risk factor among children exclusively breastfeed up to 4 months (aOR: 2.33, 95% CI: 1.53-3.55). Having indoor tap water was protective (aOR: 0.65, 95% CI: 0.54-0.78), whereas a primary care giver who smoked was a risk factor (aOR: 5.15, 95% CI: 2.94-9.03).
Our findings confirm several known pneumonia risk factors and highlight complex interactions between factors, including HIV exposure, breastfeeding, malnutrition and crowding. Improved housing, reduced secondhand smoke exposure and HIV prevention among women of reproductive age could lessen the child pneumonia burden.
Pneumococcal pneumonia has decreased significantly since the implementation of the pneumococcal conjugate vaccine (PCV), nevertheless, in many developing countries pneumonia mortality in infants ...remains high. We have undertaken a study of the nasopharyngeal (NP) microbiome during the first year of life in infants from The Philippines and South Africa. The study entailed the determination of the
sp. carriage using a
qPCR assay, whole metagenomic sequencing, and
serotyping of
, as well as 16S rRNA amplicon based community profiling. The
carriage in both populations increased with infant age and
+ samples ranged from 24 to 85% of the samples at each sampling time point. We next developed informatic tools for determining
community composition and pneumococcal serotype from metagenomic sequences derived from a subset of longitudinal
-positive
enrichment cultures from The Philippines (
= 26 infants, 50% vaccinated) and South African (
= 7 infants, 100% vaccinated). NP samples from infants were passaged in enrichment media, and metagenomic DNA was purified and sequenced.
capsular serotyping of these 51 metagenomic assemblies assigned known serotypes in 28 samples, and the co-occurrence of serotypes in 5 samples. Eighteen samples were not typeable using known serotypes but did encode for capsule biosynthetic cluster genes similar to non-encapsulated reference sequences. In addition, we performed metagenomic assembly and 16S rRNA amplicon profiling to understand co-colonization dynamics of
sp. and other NP genera, revealing the presence of multiple
species as well as potential respiratory pathogens in healthy infants. A range of virulence and drug resistant elements were identified as circulating in the NP microbiomes of these infants. This study revealed the frequent co-occurrence of multiple
strains along with
sp. and other potential pathogens such as
in the NP microbiome of these infants. In addition, the
serotype analysis proved powerful in determining the serotypes in
carriage, and may lead to developing better targeted vaccines to prevent invasive pneumococcal disease (IPD) in these countries. These findings suggest that NP colonization by
during the first years of life is a dynamic process involving multiple serotypes and species.
PDF
