Invasive Pneumococcal Disease Surveillance Research Articles

Genomic differences among carriage and invasive nontypeable pneumococci circulating in South Africa.

Most pneumococci express a polysaccharide capsule, a key virulence factor and target for pneumococcal vaccines. However, pneumococci showing no serological evidence of capsule expression [nontypeable pneumococci (NTPn)] are more frequently isolated from carriage studies than in invasive disease. Limited data exist about the population structure of carriage NTPn from the African continent. We aimed to characterize carriage NTPn and compare them to previously described invasive NTPn. Carriage and invasive NTPn isolates were obtained from South African cross-sectional studies (2009 and 2012) and laboratory-based surveillance for invasive pneumococcal disease (2003–2013), respectively. Isolates were characterized by capsular locus sequence analysis, multilocus sequence typing, antimicrobial non-susceptibility patterns and phylogenetic analysis. NTPn represented 3.7 % (137/3721) of carriage isolates compared to 0.1 % (39/32 824) of invasive isolates (P<0.001), and 24 % (33/137) of individuals were co-colonized with encapsulated pneumococci. Non-susceptibility to cotrimoxazole [84 % (112/133) vs 44 % (17/39)], penicillin [77 % (102/133) vs 36 % (14/39)], erythromycin [53 % (70/133) vs 31 % (12/39)] and clindamycin [36 % (48/133) vs 18 % (7/39)] was higher (P=0.03) among carriage than invasive NTPn. Ninety-one per cent (124/137) of carriage NTPn had complete deletion of the capsular locus and 9 % (13/137) had capsule genes, compared to 44 % (17/39) and 56 % (22/39) of invasive NTPn, respectively. Carriage NTPn were slightly less diverse [Simpson’s diversity index (D)=0.92] compared to invasive NTPn [D=0.97]. Sixty-seven per cent (92/137) of carriage NTPn belonged to a lineage exclusive to NTPn strains compared to 23 % (9/39) of invasive NTPn. We identified 293 and 275 genes that were significantly associated with carriage and invasive NTPn, respectively. NTPn isolates detected in carriage differed from those causing invasive disease, which may explain their success in colonisation or in causing invasive disease.

Invasive Pneumococcal Disease Surveillance, 1 July to 30 September 2017.

The number of notified cases of invasive pneumococcal disease (IPD) in the third quarter of 2019 was higher than in the previous quarter, but lower than in the third quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.

Streptococcus pneumoniae serotype 3 is masking PCV13-mediated herd immunity in Canadian adults hospitalized with community acquired pneumonia: A study from the Serious Outcomes Surveillance (SOS) Network of the Canadian immunization research Network (CIRN)

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. MethodsActive surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. ResultsOf 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. ConclusionHerd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

Effectiveness of the seven-valent and thirteen-valent pneumococcal conjugate vaccines in England: The indirect cohort design, 2006–2018

BackgroundThe 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the UK childhood immunisation programme in 2006 and replaced with a 13-valent vaccine (PCV13) in 2010. Both vaccines led to rapid declines in vaccine-serotype invasive pneumococcal disease (IPD). Here, we assessed the long-term vaccine-effectiveness (VE) of both vaccines in England. MethodsPublic Health England conducts enhanced national surveillance of IPD in England. VE against IPD was estimated using vaccine-serotype IPD cases and non-vaccine serotype IPD controls among vaccine-eligible children from September 2006 to June 2018 (the Broome method). ResultsVaccine history was available for 3421 IPD cases, including 1299 due to the additional PCV13 serotypes and the PCV13-related serotype 6C, 274 PCV7 serotypes and 1848 non-PCV13 serotypes. For the complete 2 + 1 schedule, both PCV7 and PCV13 showed high effectiveness against PCV7 serotypes with a combined VE of 92.0% (95%CI, 81.7–96.7). For the 2 + 1 schedule, PCV13 VE against the additional PCV13 serotypes plus 6C was 73.7% (31.1–89.9) compared to 90.0% (75.3 – 96.0) for PCV7 against PCV7 serotypes, although PCV13 VE increased to 84.8% (58.7–94.4) if serotype 3 was excluded; all 36 eligible serotype 3 IPD cases were fully-vaccinated with PCV13. Case numbers were low in older ages but there was evidence of waning, which was significant for serotype 19A for which there were sufficient numbers of cases for analysis. ConclusionsPCVs are highly effective in preventing vaccine-serotype IPD except for serotype 3 which has been increasing in incidence. Serotype 19A IPD has also persisted, likely due to a slightly lower VE and/or more rapid waning of protection.

Serotype distribution and antibiotic resistance among invasive Streptococcus pneumoniae from Oman post 13-valent vaccine introduction

ObjectiveThis study was undertaken to determine the serotype distribution and drug susceptibility patterns in pneumococcal isolates recovered from patients with invasive pneumococcal disease (IPD). MethodsAll invasive pneumococcal isolates received between June 2014 and June 2016 were included in the study as part of a national laboratory-based IPD surveillance program. Isolates recovered from clinical specimens of normally sterile body sites were included. ResultsA total of 41 different serotypes were identified among the 132 pneumococcal isolates included in this study. The most prevalent serotypes/serogroups were 12 (8.3%), 15 (8.3%), 19F (7.6%), 3 (6.1%), and 19A (6.1%);. It was observed that overall vaccine coverage rates for pneumococcal conjugate vaccines (PCV), PCV7, PCV10 and PCV13 were 15.9%, 24.2% and 37.1% respectively. 56.8% (n=75) of the isolates were non-susceptible to at least one antibiotic and 40.9% (n=54) of the isolates were resistant to PEN (M). 18.9% (n=25) of the isolates were multi-drug resistant (MDR).The case fatality rate was 15.9%. ConclusionOur study results call for broader vaccine coverage, emphasizes the need to introduce the conjugate pneumococcal vaccine for the high risk adult population and stress the importance of continuous surveillance of serotypes and antimicrobial resistance to guide vaccine development and antimicrobial stewardship activities.

Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study

SummaryBackgroundTen-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2–11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12–59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County.MethodsThis study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999–Dec 31, 2010) and postvaccine (Jan 1, 2012–Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016.FindingsSurveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03–0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17–0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5–14 years [adjusted IRR 0·26, 95% CI 0·11–0·59], and ≥15 years [0·19, 0·07–0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19–0·35) and non-PCV10-type carriage increased (1·71, 1·47–1·99).InterpretationIntroduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa.FundingGavi, The Vaccine Alliance and The Wellcome Trust of Great Britain.

Pneumococcal Conjugate Vaccine Rollout in India: Expectations and Challenges

AbstractIndia is one among the four Asian countries with the greatest number of deaths due to pneumococcal infection among children under 5 years. pneumococcal conjugate vaccine (PCV) has been introduced in a phased manner in five major Indian states. Ambiguity remains in choosing the appropriate type of PCV and optimum schedule with maximum effectiveness specific for each country. Here, we discuss the evidences with respect to serotype coverage, immunogenicity, reactogenicity and dosage schedule for introduction of PCV13 in India. In addition, the expected PCV impact and the challenges are detailed. PCV13 is expected to provide >75% serotype coverage for invasive pneumococcal disease (IPD) serotypes in Indian children combined with the replacement by nonvaccine serotypes which is unpredictable due to lack of complete data. Nasopharyngeal (NP) surveillance is easy, feasible and can replace IPD surveillance in resource-poor settings. Continuous IPD as well as NP surveillance in all the regions are necessary to assess the impact of PCV in India.

Epidemiological and clinical features of invasive pneumococcal disease caused by serotype 12F in adults, Japan.

Enhanced surveillance of invasive pneumococcal disease (IPD) in adults was conducted during April 2013–March 2018 in 10 of 47 prefectures in Japan, and a total of 1277 IPD patients were enrolled. An emergence of IPD caused by serotype 12F was identified during May 2015–March 2018 through this surveillance. 12F isolates were composed of four related sequence types. In total, 120 patients with 12F IPD were reported during this period. To characterize the clinical features of 12F IPD, the disease characteristics of these patients were compared with those of 1157 patients with non-12F IPD. Compared with the non-12F IPD patients, a significantly lower proportion of 12F IPD patients was aged 65 years or older (55% vs. 70%), vaccinated with 23-valent pneumococcal polysaccharide (4% vs. 14%), had comorbid illness (65% vs. 77%), or were immunocompromised (19% vs. 30%; all P < 0.05). No significant difference in the proportion of case fatalities was found between the two groups. The proportions of those aged 65 years or older (53% vs. 69%) and with bacteremic pneumonia (35% vs. 69%) were significantly lower in 17 patients who died from 12F IPD than in 205 patients who died from non-12F IPD (all P < 0.05). Differences in clinical features were similarly found between 12F IPD patients and patients in low- or intermediate-level invasive potential serogroups. Our data demonstrated that serotype 12F was associated with IPD in younger adults and a lower proportion of comorbid illness, including immunocompromised conditions, in adult IPD, suggesting the high invasive potential of the serotype 12F. In addition, patients who died from 12F IPD were younger and had proportionately more bacteremia without focus. These findings may provide new insight into the pathogenesis of IPD in adults caused by 12F serotype with a high invasive potential.

Invasive Pneumococcal Disease Surveillance, 1 October to 31 December 2017

The number of notified cases of invasive pneumococcal disease (IPD) in the fourth quarter of 2017 was substantially less than the previous quarter, but slightly greater than the fourth quarter of 2016. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional 6 serotypes covered by the 13vPCV across all age groups, however in 2017 this decline is no longer evident. Additionally, over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV) and also those serotypes not covered by any available vaccine has been increasing steadily across all age groups (Figure 1).

Invasive pneumococcal diseases in children and adults before and after introduction of the 10-valent pneumococcal conjugate vaccine into the Austrian national immunization program.

BackgroundIn February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study.MethodsThe study period was divided into pre- (2009–2011) and post-period (2013–2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5–49 and ≥50 years old. Additionally, for the 5–49 and ≥50 years old, and the 50–59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression.ResultsThe PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5–49 years old.ConclusionsOur study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time.

Spatial Distribution of Invasive Pneumococcal Serotypes in West Africa: A Retrospective Analysis to Inform Immunization in Persons with Sickle Cell Disease

Background: Susceptibility to invasive pneumococcal disease (IPD) is high in children with sickle cell disease (SCD). National guidelines in many countries recommend a combined schedule of 13-valent pneumococcal conjugate vaccine (PCV13) beginning after birth followed by the 23-valent polysaccharide vaccine (PPSV23) beginning at age 2 years. In Africa, where the burden of SCD is greatest, PPSV23 is generally unavailable and not routinely administered to children with SCD. To help inform optimal immunization regimens for children with SCD in West Africa, we sought to determine the prevalence and spatial distribution of IPD in the region. We focused specifically on the 24 combined pneumococcus strains covered by PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and PPSV23 (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F). This analysis also explored the epidemiology of IPD-associated serotypes after the introduction of routine PCV13 immunization in countries in West Africa.Methods: We conducted a systematic review of published literature between 1990 and January 2017 using BIOSIS Previews, Embase, and Ovid MEDLINE. Inclusion criteria were all investigations that reported estimates of prevalence or incidence and the specific serotype distribution profile of invasive Streptococcus pneumoniae (including bacteremia, meningitis, osteomyelitis, or pneumonia) in children and adults in ECOWAS-defined West Africa: Benin, Burkina Faso, Cape Verde, Cote d'Ivoire, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone, and Togo. The search strategy utilized various combinations of relevant keywords and MeSH headings. Timing of the introduction of routine PCV13 immunization into study countries was determined through WHO national immunization coverage surveillance data. We generated maps of the spatial distribution of pneumococcal serotypes in countries with available data using R (version 3.3.3).Results: The search yielded 540 unique studies. We excluded 395 papers based on title and abstract. The remaining 145 studies underwent full text review. Twenty papers (representing 20 datasets and 1980 isolates) met inclusion criteria. Gambia had the most datasets (5); no data were available from six countries (Benin, Cape Verde, Cote d'Ivoire, Guinea, Liberia, and Sierra Leone); and at least one dataset was available from each of the remaining 8 countries. The most frequent invasive serotypes reported across countries were 1, 5, 6A, 12F, 14, and 23F; together, these represented 79.7% of all serotypes identified in IPD in children and adults in West Africa. Most (89.2%) of the serotypes identified are included in PCV13. However, serotypes 2 and 12F, which are covered only by PPSV23, represented 3.3% and 4.8% of identified IPD serotypes, respectively, across the 9 countries studied. These serotypes also accounted for up to 10% of isolates found in individual countries. PCV13 was introduced into all countries with datasets analyzed between 2011 and 2015. Only 1 dataset identified in the literature search (Ghana) was obtained after the introduction of routine pneumococcal vaccination, which precluded analysis of the impact of vaccination on temporal trends in serotype incidence.Conclusions: To our knowledge this is the first attempt to aggregate IPD serotype data across West Africa. While the majority of serotypes identified are included in PCV13, two serotypes exclusive to PPSV23 (2 and 12F) together accounted for 8.1% of the total IPD burden. Moreover, in some countries, the proportion of strains included in PPSV23 and not PCV13 is higher. Immunizing persons with SCD in West Africa with PPSV23 therefore may be warranted to optimize protection from IPD. Furthermore, as PCV13 vaccination coverage increases, it is possible that the epidemiology of IPD may shift to more strains exclusively covered by PPSV23. This analysis is limited by its retrospective nature and the paucity of data available after introduction of routine pneumococcal vaccination. Further work, including dynamic IPD surveillance and disease modeling, is needed to better understand the epidemiology of pneumococcus in West Africa with the aim of keeping vulnerable populations, such as those with SCD, safe from IPD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

2401. Risk Factors for Antimicrobial Resistance in Invasive Pneumococcal disease (IPD) in Toronto, Canada, 2012–2017

BackgroundSeveral studies have documented factors predictive of antimicrobial resistance (AMR) in invasive pneumococcal disease(IPD). However, the implementation of routine pediatric PCV programs, antimicrobial stewardship, and increasing immunocompromised in populating might be expected to change such factors. We report on predictive factors for AMR in IPD from 2012 to 2017.MethodsTIBDN performs population-based surveillance for IPD in Toronto/Peel (pop 4.5M). IPD cases are reported to a central office and one isolate/case is serotyped and has antimicrobial susceptibility testing performed by broth microdilution to CLSI standards.Results2459 cases of IPD were identified from January 2012 to December 2017. Overall rates of resistance to penicillin, macrolides, fluoroquinolones, and TMP-SMX were relatively stable over the course were stable over the study. Risk factors for infection with resistant to penicillin at meningitis breakpoints as opposed to penicillin- susceptible pneumococci were current residence at nursing home (odds ratio [OR], 2.30; P < 0.001), immune compromised status (OR, 1.41; P = 0.012), HIV infection (OR 2.13, P = 0.016), history of receiving PPV23 vaccine (OR 1.38; P = 0.007). Infection with TMP-SMX-resistant pneumococci was associated with HIV infection (OR, 3.2; P = 0.001) and current residence in a nursing home (OR 2.4, P = 0.002). Infection with macrolide-resistant isolates was associated with any use of macrolide 3 months prior to infection (OR, 3.24; P < 0.001), or macrolide treatment failure of the current episode (OR, 6.64; P = 0.003). Infection with levofloxacin-resistant pneumococci was associated with current residence in a nursing home (OR, 13.7; P < .001), and fluorquinolone treatment failure of the current episode (OR 49.4, P = 0.0034).ConclusionPrevious same class antibiotic exposure remains a major predictive factor for macrolide resistance. History of treatment failure is a predictive factor for macrolide and fluoroquinolone failure. HIV infection and immune compromise are risk factors for IPD infection with penicillin resistant pneumococci. Hospital acquisition of infection is no longer a risk factor for fluoroquinolone resistance.Disclosures All authors: No reported disclosures.

The choice of analytical methodology can alter conclusions regarding herd effects of paediatric pneumococcal vaccination programmes

BackgroundEstimation of the magnitude of the herd effect on invasive pneumococcal disease (IPD) is important when evaluating health benefits and cost-effectiveness of paediatric pneumococcal conjugate vaccine (PCV) programmes and may influence policy makers’ decisions on PCV use. Several epidemiological, programmatic, and immunological factors can affect the magnitude of the PCV herd effect. We investigated to what extent the choice of analytical methodology may also influence herd effect estimates. MethodsTo estimate the magnitude of the herd effect from paediatric PCV programmes, we examined overall IPD incidence rates in ≥65-year-olds from Finland, Australia, England/Wales, and the United States under different analytical scenarios. We used two different statistical methods: before/after comparison of average IPD incidence rates and interrupted time series (ITS) analysis accounting for underlying time trends. We also investigated how varying the length of the pre- and post-PCV analysis periods influenced the outcomes. ResultsThe estimated impact of paediatric PCV programmes on IPD incidence rates in adults ≥65 years varied substantially across the different scenarios within each country. The choice of statistical method and analysis periods contributed to this variation, and their influence varied by setting. For the datasets from England/Wales and the United States, the different scenarios produced relatively minor variation in estimated impact. For the Australian and Finnish datasets, differences were more prominent. In particular, for Finland, opposite conclusions could be drawn depending on the methodology: while no estimated herd effect was seen with the before/after method, a herd effect was evident with the ITS method. ConclusionsThe choice of statistical method and analysis periods can substantially influence the magnitude of estimated herd effects from paediatric PCV programmes. It is important to consider the reliability and presence of pre-PCV patterns in the IPD surveillance data used for analysis, the methodology and associated assumptions used to estimate herd effects.

Invasive Pneumococcal Disease in UK Children

Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013-2016. There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks' gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%-8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants.

Characteristics of Children With Invasive Pneumococcal Disease After the Introduction of the 13-valent Pneumococcal Conjugate Vaccine in England and Wales, 2010-2016.

In England and Wales, replacement of childhood 7-valent pneumococcal conjugate vaccine (PCV7) with a 13-valent vaccine (PCV13) in 2010 was associated with a significant reduction in PCV13-serotype invasive pneumococcal disease (IPD), with a small increase in IPD due to non-vaccine serotypes. Here, we describe the clinical presentation, comorbidity prevalence, serotype distribution and outcomes of childhood IPD during the first 6 years after PCV13 introduction. Public Health England conducts enhanced IPD surveillance in England and Wales, with detailed information requested from general practitioners for all cases in children <5 years of age. Invasive isolates are routinely serotyped at the Public Health England reference laboratory. From April 2010 to March 2016, 1280 IPD episodes were confirmed in 1255 children 3-59 months of age; 84.3% (1059/1255) isolates were serotyped. Clinical presentation with meningitis was most prevalent in 3- to 11-month olds (45.8%, 209/456) and lower respiratory tract infection in 24- to 59-month olds (46.7%, 133/285). Overall, 259 (20.6%) children had 292 comorbidities, particularly immunosuppression (31.6%, 92/292). Twenty-one children (1.8%) had recurrent IPD. The case fatality rate was 5.1% (64/1255; 95% confidence interval [CI]: 3.9%-6.5%) and independently associated with meningitis (aOR 3.53; 95% CI: 1.62-7.70) and presence of comorbidity (aOR, 2.41; 95% CI: 1.25-4.64). In 2015/2016, PCV13 serotypes were responsible for 10.8% (25/232) of serotyped cases; the most prevalent non-PCV13 serotypes were 12F (18%), 10A (12%), 23B (10%), 33F (10%), 15B/C (10%) and 8 (8%). Most childhood IPD cases are now due to non-PCV13 serotypes. A higher proportion of children with IPD have underlying comorbidity, but, reassuringly, the risk of recurrent IPD or death remains low.

The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: A systematic review and meta-analysis

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.

Invasive pneumococcal disease in Indian adults: 11 years' experience.

To investigate the epidemiology of invasive pneumococcal disease (IPD), prevalent serotypes, and pattern of antimicrobial resistance (AMR) in Indian adults. Prospective laboratory based surveillance of IPD was carried out in >18 years age group between January 2007 and July 2017, from a tertiary care hospital in South India. All Streptococcus pneumoniae culture positives from blood, CSF and sterile body fluids were characterized to identify the serotypes and AMR. A total of 408 IPD cases were characterized in this study. The overall case fatality rate in this study was 17.8% (95% confidence interval (CI): 14.1, 22.4). Pneumonia (39%), meningitis (24.3%), and septicaemia (18.4%) were the most common clinical conditions associated with IPD. Serotypes 1, 3, 5, 19F, 8, 14, 23F, 4, 19A and 6B were the predominant serotypes in this study. Penicillin non-susceptibility was low with 6.4% CONCLUSION: Serotype data from this study helped in accurate estimation of pneumococcal conjugate vaccine-13 and pneumococcal polysaccharide vaccine-23 protective coverage against serotypes causing IPD in India as 58.7% (95% CI: 53.8, 63.4) and 67.4% (95% CI: 62.7, 71.8) respectively. Penicillin non-susceptibility in meningeal IPD cases is 27.4%. Empirical therapy for meningeal IPD must be cephalosporin in combination with vancomycin since cefotaxime non-susceptibility in meningeal IPD is 9.9.

Increased carriage of non-vaccine serotypes with low invasive disease potential four years after switching to the 10-valent pneumococcal conjugate vaccine in The Netherlands.

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in The Netherlands in 2006 and was replaced by PHiD-CV10 in 2011. Data on carriage prevalence of S. pneumoniae serotypes in children and invasive pneumococcal disease (IPD) in children and older adults were collected to examine the impact of PCVs on carriage and IPD in The Netherlands. Pneumococcal carriage prevalence was determined by conventional culture of nasopharyngeal swabs in 24-month-old children in 2015/2016. Data were compared to similar carriage studies in 2005 (pre-PCV7 introduction), 2009, 2010/2011 and 2012/2013. Invasive pneumococcal disease isolates from hospitalized children <5 years and adults >65 years (2004–2016) were obtained by sentinel surveillance. All isolates were serotyped by Quellung. Serotype invasive disease potential was calculated using carriage and nationwide IPD data in children. The overall pneumococcal carriage rate was 48% in 2015/2016, lower than in 2010/2011 (64%) and pre-vaccination in 2005 (66%). Carriage of the previously dominant non-vaccine serotypes 19A and 11A has declined since 2010/2011, from 14.2% to 4.6% and 4.2% to 2.7%, respectively, whereas carriage of serotypes 6C and 23B has increased (4.2% to 6.7% and 3.9% to 7.3%), making serotypes 6C and 23B the most prevalent carriage serotypes. IPD incidence declined in children (20/100,000 cases in 2004/2006 to 6/100,000 cases in 2015/2016) as well as in older adults (63/100,000 cases to 51/100,000 cases). Serotypes 6C, 23B and 11A have high carriage prevalence in children, but show low invasive disease potential. Serotype 8 is the main causative agent for IPD in older adults (11.3%). In conclusion, 10 years after the introduction of pneumococcal vaccination in children in The Netherlands shifts in carriage and disease serotypes are still ongoing. Surveillance of both carriage and IPD is important to assess PCV impact and to predict necessary future vaccination strategies in both children and older adults.

Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study

Pneumococcal conjugate vaccines (PCVs) have substantially reduced the incidence of invasive pneumococcal disease caused by vaccine serotypes; however, replacement disease with non-PCV serotypes remains a concern. We describe the population effect of the seven-valent and 13-valent PCVs (PCV7 and PCV13) on invasive pneumococcal disease in England and Wales. Using national invasive pneumococcal disease surveillance data for 2016/17, we compared incidence rate ratios (IRRs) against pre-PCV13 (2008/09-2009/10) and pre-PCV7 (2000/01-2005/06) baselines. We also estimated the number of invasive pneumococcal disease cases prevented since the introduction of PCVs. In 2016/17, overall invasive pneumococcal disease incidence (9·87 cases per 100 000; 5450 cases) across all age groups was 37% lower (IRR 0·63, 95% CI 0·60-0·65) than pre-PCV7 incidence (14·79 per 100 000; 8167 cases) and 7% lower (0·93; 0·89-0·97) than pre-PCV13 incidence (10·13 per 100 000; 5595 cases). By 2016/17, PCV7-type invasive pneumococcal disease incidence across all age groups had decreased by 97% (0·24 per 100 000; 0·03, 0·02-0·04) compared with the pre-PCV7 period, whereas additional PCV13-type invasive pneumococcal disease decreased by 64% (1·66 per 100 000; 0·36, 0·32-0·40) since the introduction of PCV13. Invasive pneumococcal disease incidence due to non-PCV13 serotypes doubled (7·97 per 100 000; 1·97, 1·86-2·09) since the introduction of PCV7, and accelerated since 2013/14-especially serotypes 8, 12F, and 9N, which were responsible for more than 40% of invasive pneumococcal disease cases by 2016/17. Invasive pneumococcal disease incidence in children younger than 5 years remained stable since 2013/14, with nearly all replacement disease occurring in adults. We estimated 38 366 invasive pneumococcal disease cases were prevented in the 11 years since the introduction of PCV7. Both PCV7 and PCV13 have had a major effect in reducing the burden of invasive pneumococcal disease in England and Wales; however, rapid increases in some non-PCV13 serotypes are compromising the benefits of the programme. Public Health England.

Invasive Disease Caused Simultaneously by Dual Serotypes of Streptococcus pneumoniae.

There are at least 98 known pneumococcal serotypes. Invasive pneumococcal disease (IPD) is usually caused by a single serotype, and dual-serotype IPD is rare. To assess factors associated with dual-serotype IPD, patient information obtained through laboratory-based surveillance for IPD from 2005 through 2014 in South Africa was reviewed. Genomes of isolate pairs from coinfected individuals were sequenced to determine their molecular characteristics. For 30 (91%) of 33 patients with dual serotypes, one or both isolates were a pneumococcal conjugate vaccine (PCV13) serotype. Dual-serotype IPD was associated with children <5 years of age (adjusted odds ratio [aOR], 4.7; 95% confidence interval [95% CI], 1.8 to 11.7), underlying illness (other than HIV) (aOR, 2.8; 95% CI, 1.1 to 6.6) and death (aOR, 2.5; 95% CI, 1.08 to 6.09). For each coinfecting pair, isolates were genotypically unrelated, and their genotypes were common among isolates of the same serotype in South Africa. Of 701 accessory genes identified among dual-serotype IPD isolates, four were common between isolate pairs. Coinfecting isolate pairs had different genotypic backgrounds. The association of dual serotypes with death warrants increased awareness of IPD coinfection caused by two or more serotypes.