Pneumococcal bacteraemia in adults over a 10-year period (2011-2020): a clinical and serotype analysis.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal tract coloniser responsible for invasive pneumococcal disease, which is largely vaccine preventable. Vaccination is recommended from birth for all, and through adulthood for those with risk conditions. AIMS: To describe the clinical and serotype analysis of pneumococcus bacteraemia over a 10-year period. METHODS: A 10-year (February 2011-December 2020) retrospective review was performed on all adult (age ≥18 years) pneumococcus bacteraemia presenting to the four public hospitals in Western Sydney, Australia. Comorbidities and risk factors were recorded. RESULTS: Three hundred unique episodes of S. pneumoniae bloodstream infection (SPBI) were identified during the study period. The median age for SPBI was 63 years with 31.7% aged 70 years or older. A 94.7% had one or more risks factors for SPBI. Pneumonia was reported in 80% of all SPBI, whereas meningitis was reported in 6% and infective endocarditis in <1%. Asplenia was noted in 2.4%. Seven- and 30-day mortality was 6.6% and 11.9%, with a higher 30-day mortality in those aged ≥70 years (24.4%). The serotype distribution showed 7-valent conjugate vaccine covered 11.0% of all isolates, whereas 13-valent conjugate vaccine (13vPCV) and a 23-valent polysaccharide vaccine (23vPPV) covered 41.7% and 69.0% respectively. Immunisation details were available for 110 individuals, of whom, only 7.3% had received pneumococcal vaccination. CONCLUSIONS: Most patients with pneumococcal bacteraemia had age- or comorbidity-related risk factors but were not vaccinated. Two-thirds of cases occurred in people aged <70 years. 13vPCV and 23vPPV covered 41.7% and 69.0% of bacteraemic isolates.

Real world impact of 13vPCV in preventing invasive pneumococcal pneumonia in Australian children: A national study.

BACKGROUND: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia. METHODS: Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were sampled from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status. RESULTS: From February 2015 to September 2018, we enrolled 1,168 children with pneumonia; 779 were 13vPCV-eligible and were individually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6-1.0) among IPP cases compared to matched controls. CONCLUSION: We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3.

Immunogenicity and Efficacy of Pneumococcal Conjugate Vaccine (Prevenar13®) in Preventing Acquisition of Carriage of Pneumococcal Vaccine Serotypes in Tanzanian Children With HIV/AIDS.

In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] -6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.

Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia.

BACKGROUND: Empyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program. METHODS: For bacterial pneumonia and empyema hospitalisations, we ascertained incidence rates (IRs) using the National Hospital Morbidity Database International Statistical Classification of Disease discharge codes and relevant population denominators, and calculated incidence rate ratios (IRR) comparing the 13vPCV period (June 2012-May 2017) with the 7vPCV period (June 2007-May 2011). Blood and pleural fluid (PF) cultures and PF PCR of 401 children with empyema from 11 Australian hospitals during the 13vPCV period were compared with our previous study in the 7vPCV period. FINDINGS: Across 7vPCV and 13vPCV periods, IRs per million children (95% CIs) were 1605 (1588 to 1621) and 1272 (1259 to 1285) for bacterial pneumonia, and 14.23 (12.67 to 15.79) and 17.89 (16.37 to 19.42) for empyema hospitalisations. IRRs were 0.79 (0.78 to 0.80) for bacterial pneumonia and 1.25 (1.09 to 1.44) for empyema. Of 161 empyema cases with SP serotypes, 147 (91.3%) were vaccine types. ST3 accounted for 76.4% of identified serotypes in the 13vPCV period, more than double than the 7vPCV period (p<0.001); ST19A decreased from 36.4% to 12.4%. No cases of ST1 empyema were identified in the 13vPCV period versus 14.5% in the 7vPCV period. INTERPRETATION: 13vPCV resulted in a significant reduction in all-cause hospitalisations for bacterial pneumonia but empyema hospitalisations significantly increased, with emergence of pneumococcal ST3 as the dominant serotype in empyema. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry ACTRN 12614000354684.

Genome-wide analysis of Streptococcus pneumoniae serogroup 19 in the decade after the introduction of pneumococcal conjugate vaccines in Australia.

The decline in invasive pneumococcal disease (IPD), following the introduction of the 7-valent pneumococcal conjugate vaccination (PCV-7), was tempered by emergence of non-vaccine serotypes, particularly 19A. In Australia, three years after PCV-7 was replaced by PCV-13, containing 19A and 19F antigens, serogroup 19 was still a prominent cause of IPD in children under five. In this study we examined the evolution of serogroup 19 before and after introduction of paediatric vaccines in New South Wales (NSW), Australia. Genomes of 124 serogroup 19 IPD isolates collected before (2004) and after introduction of PCV-7 (2008) and PCV-13 (2014), from children under five in NSW, were analysed. Eleven core genome sequence clusters (cgSC) and 35 multilocus sequence types (ST) were identified. The majority (78/124) of the isolates belonged to four cgSCs: cgSC7 (ST199), cgSC11 (ST320), cgSC8 (ST63) and cgSC9 (ST2345). ST63 and ST2345 were exclusively serotype 19A and accounted for its predominantly intermediate penicillin resistance; these two clusters first appeared in 2008 and largely disappeared after introduction of PCV-13. Serogroup 19 was responsible for the highest proportion of vaccine failures in NSW. Relatively low immunogenicity of serogroup 19 antigens and Australia's three-dose vaccine schedule could affect the population dynamics of this serogroup.

Using a practical molecular capsular serotype prediction strategy to investigate Streptococcus pneumoniae serotype distribution and antimicrobial resistance in Chinese local hospitalized children.

BACKGROUND: China is one of ten countries with the highest prevalence rate of pneumococcal infections. However, there is limited serotype surveillance data for Streptococcus pneumoniae, especially from the community or rural regions, partly due to limited serotyping capacity because Quellung serotyping is only available in few centers in China. The aim of this study was to develop a simple, practical and economic pneumococcal serotype prediction strategy suitable for future serotype surveillance in China. METHODS: In this study, 193 S. pneumoniae isolates were collected from hospitalized children, 96.9 % of whom were < 5 years old. The cpsB sequetyping, complemented by selective and modified USA CDC sequential multiplex-PCR, was performed on all the isolates, and serotypes 6A-6D specific PCRs were done on all serogroup 6 isolates. Based on systematic analysis of available GenBank cpsB sequences, we established a more comprehensive cpsB sequence database than originally published for cpsB sequetyping. Antibiotic susceptibility of all isolates was determined using the disk diffusion or E-test assays. RESULTS: We built up a comprehensive S. pneumoniae serotype cpsB sequetyping database for all the 95 described serotypes first, and then developed a simple strategy for serotype prediction based on the improved cpsB sequetyping and selective multiplex-PCR. Using the developed serotype prediction strategy, 191 of 193 isolates were successfully "serotyped", and only two isolates were "non-serotypeable". Sixteen serotypes were identified among the 191 "serotypeable" isolates. The serotype distribution of the isolates from high to low was: 19 F (34.7 %), 23 F (17.1 %), 19A (11.9 %), 14 (7.3 %), 15B/15C (6.7 %), 6B (6.7 %), 6A (6.2 %), 9 V/9A (1.6 %); serotypes 6C, 3, 15 F/15A, 23A and 20 (each 1.1 %); serotypes 10B, 28 F/28A and 34 (each 0.5 %). The prevalence of parenteral penicillin resistance was 1.0 % in the non-meningitis isolates and 88.6 % in meningitis isolates. The total rate of multidrug resistance was 86.8 %. CONCLUSIONS: The integrated cpsB sequetyping supplemented with selective mPCR and serotypes 6A-6D specific PCRs "cocktail" strategy is practical, simple and cost-effective for use in pneumococcal infection serotype surveillance in China. For hospitalized children with non-meningitis penicillin-susceptible pneumococcal infections, clinicians still can use narrow-spectrum and cheaper penicillin, using the parenteral route, rather than using broader-spectrum and more expensive antimicrobials.

Nasopharyngeal carriage of Streptococcus pneumoniae: prevalence and risk factors in HIV-positive children in Tanzania.

BACKGROUND: Pneumococcal colonization of the nasopharynx is especially common in young children and is a pre-requisite for pneumococcal disease. Those with immunosuppression, such as HIV, are at higher risk of colonization and disease, especially at older ages. Currently, vaccination schedules are only offered to children under 6 months of age, despite the large impact of pneumococcal disease in older unvaccinated children with HIV. We conducted a study to assess the prevalence of, and risk factors for, pneumococcal carriage in HIV-positive children aged <15 years. METHODS: We collected a single nasopharyngeal swab from 142 HIV-infected children aged 1-14 years over a 2-month period. To detect carriage of pneumococcus, these samples were cultured and serotyped; PCR was performed on negative samples. We also collected epidemiological data via survey and medical records. RESULTS: The overall carriage rate was 81% and was at least 76% in those aged 5-14 years. The 7-, 10-, and 13-valent pneumococcal vaccines would cover 37%, 37%, and 49% of children with carriage, respectively. In the multivariate analysis, we identified increase in weight since last visit (p=0.028) and the existence of care-givers who had respiratory symptoms in the past week (p=0.022) as risk factors for carriage. Weight gain was also significantly associated with antiretroviral use (p=0.002). CONCLUSIONS: These data illuminate the little known area of pneumococcal carriage in older HIV-infected children as well as finding novel risk factors for pneumococcal carriage, namely the association with household members who have respiratory symptoms and with an increase in the child's weight prior to swabbing. Weight gain may be due to an increase in health enabling more mobility and increasing the risk of acquiring carriage. The carriage rate observed (81%) is one of the highest recorded. Further research should address whether vaccination can prevent the acquisition of carriage and so protect against disease.

Molecular epidemiology of Streptococcus pneumoniae serogroup 6 isolates from Fijian children, including newly identified serotypes 6C and 6D.

Multilocus sequence typing (MLST) was applied to all unique serotype 6C and 6D isolates and a random selection of serotype 6B and 6A isolates from nasopharyngeal swabs from Fijian children enrolled in a recent vaccine trial. The results suggest that Fijian serotype 6D has arisen independently from both serotypes 6A/C and 6B.

Identification of newly described Streptococcus pneumoniae serotype 6D by use of the Quellung reaction and PCR.

We tested 121 pneumococcal serogroup 6 isolates (including 30 serotype 6C and 24 serotype 6D isolates) by serotype-specific PCR and the Quellung reaction, using "old" and "new" pool B, factor 6b, and new factor 6d antisera. In combination with group B and other factor antisera, factor 6d antiserum can reliably identify the newly described serotype 6D.

Distribution of serotypes, genotypes, and resistance determinants among macrolide-resistant Streptococcus pneumoniae isolates.

Macrolide resistance in Streptococcus pneumoniae has emerged as an important clinical problem worldwide over the past decade. The aim of this study was to analyze the phenotypes (serotype and antibiotic susceptibility), genotypes (multilocus sequence type [MLST] and antibiotic resistance gene/transposon profiles) among the 31% (102/328) of invasive isolates from children in New South Wales, Australia, in 2005 that were resistant to erythromycin. Three serotypes--19F (47 isolates [46%]), 14 (27 isolates [26%]), and 6B (12 isolates [12%])--accounted for 86 (84%) of these 102 isolates. Seventy four (73%) isolates had the macrolide-lincosamide-streptogramin B (MLS(B)) resistance phenotype and carried Tn916 transposons (most commonly Tn6002); of these, 73 (99%) contained the erythromycin ribosomal methylase gene [erm(B)], 34 (47%) also carried the macrolide efflux gene [mef(E)], and 41 (55%) belonged to serotype 19F. Of 28 (27%) isolates with the M phenotype, 22 (79%) carried mef(A), including 16 (57%) belonging to serotype 14, and only six (19%) carried Tn916 transposons. Most (84%) isolates which contained mef also contained one of the msr(A) homologues, mel or msr(D); 38 of 40 (95%) isolates with mef(E) (on mega) carried mel, and of 28 (39%) isolates with mef(A), 10 (39%) carried mel and another 11(39%) carried msr(D), on Tn1207.1. Two predominant macrolide-resistant S. pneumoniae clonal clusters (CCs) were identified in this population. CC-271 contained 44% of isolates, most of which belonged to serotype 19F, had the MLS(B) phenotype, were multidrug resistant, and carried transposons of the Tn916 family; CC-15 contained 23% of isolates, most of which were serotype 14, had the M phenotype, and carried mef(A) on Tn1207.1. Erythromycin resistance among S. pneumoniae isolates in New South Wales is mainly due to the dissemination of multidrug-resistant S. pneumoniae strains or horizontal spread of the Tn916 family of transposons.

First report of putative Streptococcus pneumoniae serotype 6D among nasopharyngeal isolates from Fijian children.

BACKGROUND: A putative Streptococcus pneumoniae serotype, 6D, resulting from the introduction of wciN(beta) into serotype 6B has been proposed. METHODS: We studied 98 unique serogroup 6 isolates from Fijian children, two-thirds of whom had received at least 1 dose of 7-valent pneumococcal conjugate vaccine, and 51 invasive isolates from Australian children. We used a polymerase chain reaction (PCR) system that targets both wciN(beta) and the single-nucleotide polymorphism that differentiates serotypes 6A and 6B-wciP584g (6A) and wciP584a (6B). RESULTS: Two (9%) of 22 Australian isolates and 24 (38%) of 64 Fijian isolates previously identified as 6A by the Quellung reaction and wciP584g PCR contained wciN(beta) and were designated as 6C; 14 (41%) of 34 Fijian isolates previously identified as 6B by the Quellung reaction and wciP584a PCR contained wciN(beta) and were designated as the new putative serotype 6D. A significantly smaller proportion of children from whom serotype 6D was isolated (2/14 [14%]) had not received PCV-7, compared with the proportion of those from whom serotype 6B was isolated (11/20 [55%]) (P < .05). CONCLUSION: This is the first report of naturally occurring S. pneumoniae serotype 6D.

Simple, accurate, serotype-specific PCR assay to differentiate Streptococcus pneumoniae serotypes 6A, 6B, and 6C.

In this study, we developed a simple, reliable, serotype-specific PCR method to differentiate Streptococcus pneumoniae serotypes 6A, 6B, and 6C. It was more efficient and practical than the assays currently being used to identify serotypes 6A, 6B, and 6C. Of 120 selected serogroup 6 isolates from subjects with invasive (n = 101) and noninvasive (n = 19) pneumococcal disease, most of which were collected after 2003 in New South Wales, 45 had been identified as 6A and 75 had been identified as 6B by the Quellung reaction. PCR analysis confirmed the results for serotype 6B isolates and identified two different subtypes. Fourteen of 45 isolates that had been identified as serotype 6A actually belonged to serotype 6C.