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The aim of this study was to analyze the population dynamics of Streptococcus pneumoniae in a remotely living African Pygmy population. The same pygmy population (Gabon) was prospectively screened for nasopharyngeal S. pneumoniae colonization in 2011 (n = 103), 2013 (n = 104) and 2017 (n = 107). Non-duplicate isolates (n = 126) were serotyped and tested for antimicrobial resistance (broth microdilution). At the three sampling time points, resistance rates were highest for tetracycline (36–58%), followed by penicillin (parenteral, meningitis-breakpoints, 6–39%) and chloramphenicol (3–15%). The majority of isolates was non-typeable (NT, n = 18/126, 14.3%) followed by serotype 6B (n = 17/126, 13.5%), 21 and 15A (n = 9/126, 7.1%, each). The distribution of serotypes was highly dynamic as only three serotypes (14, 17F, NT) were detected during all three visits. Resistance rates and serotypes of nasopharyngeal S. pneumoniae markedly changed in the remote Babongo population. This rapid change in serotypes could challenge the selection of pneumococcal vaccine.

Pneumococcal disease is an important cause of morbidity and mortality worldwide with a significant financial burden. Pneumococcal vaccines are available and recommended in many countries for at-risk populations including young children, the elderly and those with underlying medical conditions. The Hajj and Umrah mass gatherings attract millions of Muslim pilgrims to the Kingdom of Saudi Arabia each year. These events increase the risk of pneumococcal disease especially among the large number of elderly pilgrims with co-morbidities. However, there is no unified official policy for vaccination against pneumococcal disease for pilgrims attending Hajj and Umrah, largely due to the lack of a strong evidence-base in the context of these events. Here we review knowledge gaps regarding pneumococcal disease during Hajj and Umrah and highlight important research agendas to strengthen the evidence-base to inform pneumococcal vaccination policy for pilgrims. Available data indicates that the true clinical and financial burdens of pneumococcal disease at Hajj and Umrah are still not determined. There is limited information on antimicrobial resistance among S. pneumoniae isolated from diseased pilgrims and no information on the serotypes involved. Finally, the efficacy and effectiveness of the current vaccines in the context of Hajj and Umrah have not been studied. Research agendas proposed in this article would help fill knowledge gaps regarding pneumococcal disease at Hajj and Umrah and would constitute a strong basis for an informed and potentially unified policy regarding pneumococcal vaccination for these events.

Young children – the main asymptomatic carriers of pneumococcus – are often the source of pneumococcal infections. PCV13 replaced PCV7 in 2010 in Hungary and it became a mandatory vaccine in 2014. In this work we surveyed the effect of vaccination in three groups: in healthy children under 7 years; in children of the same age but infected with pneumococcus (P1); in older patients (P2) who were very likely not vaccinated. Nasal swabs were taken from 522 healthy children to screen pneumococcal carriage between March 2015 and May 2016. In the same time period, 146 clinical isolates were collected, mainly from mucosal infections. Serotypes, antibiotic susceptibility and clonality of the isolates was determined and compared. The carriage rate was 39.1%. Regarding carriage, the serotype distribution showed the total disappearance of serotypes 3 and 6A compared to former Hungarian studies. The prevalence of PCV13 serotypes was only 5.8% represented by three serotypes (19F, 19A, 9V). Of note, serotype 19A (a very resistant and invasive type) also decreased significantly. In the patient groups, PCV13 prevalence was higher: 17.5% (P1) and 32.6% (P2). Although serotype 3 was present in P1 (7.9%), the leading serotype was 23B (22.2%), a non-vaccine type (NVT). P2 showed the most diverse serotype distribution, but serotype 3 was predominant here (15.7%). Pneumococcal isolates from the patients were more resistant towards the tested antibiotics compared to those from carriers. PCV13 seems to be highly successful in reducing the prevalence of vaccine serotypes. The serotype-rearrangement can be seen also among clinical isolates, albeit somewhat later in time. Fortunately, the replacing serotypes are less invasive and less resistant, but, most worrisome, serotype 19F can be found again with increased frequency among carriage isolates and mucosal infections. Further surveillance is needed to carefully monitor such successful, antibiotic resistant “refugees”.

Objective To identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany. Methods Active surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group, serotypes, site of infection, and relative incidence reduction compared to pre-vaccination period (1997–2001) at nadir and for the most recent season are reported. We calculated vaccine coverage at the age of 24 months using health insurance claims data. Results 96–97% of children had received at least two doses of PCV since 2009. The maximum impact on overall IPD incidence was achieved in 2012/13 (−48% [95% CI: −55%; −39%]) with a rebound to −26% [95% CI: −36%; −16%] in 2015/16. Non-PCV13 serotypes accounted for 84.1% of the IPD cases in 2015/16. The most frequent non-PCV serotypes in IPD in 2014/15 and 2015/16 were 10A, 24F, 15C, 12F, 38, 22F, 23B, and 15B. The impact at nadir was highest in children 0–1 years of age both in meningitis and non-meningitis cases, whereas the impact for other age groups was higher for meningitis cases. The rebound mainly pertained to non-meningitis cases. Conclusion The maximum impact of pneumococcal conjugate vaccination has been attained and signs of a rebound are apparent. Sustained surveillance for IPD in children is warranted to assess whether these trends will continue. There may be a need for vaccines using antigens common to all serotypes.

Streptococcus ( S .) agalactiae represents a significant pathogen for humans and animals. However, there are only a few elderly reports on S . agalactiae infections in wild and zoo elephants even though this pathogen has been isolated comparatively frequently in these endangered animal species. Consequently, between 2004 and 2015, we collected S. agalactiae isolates from African and Asian elephants (n = 23) living in four different zoos in Germany. These isolates were characterised and compared with isolates from other animal species (n = 20 isolates) and humans (n = 3). We found that the isolates from elephants can be readily identified by classical biochemistry and MALDI-TOF mass spectrometry. Further characterisations for epidemiological issues were achieved using Fourier transform-infrared spectroscopy, capsule typing and molecular fingerprinting (PFGE, RAPD PCR). We could demonstrate that our elephant isolate collection contained at least six different lineages that were representative for their source of origin. Despite generally broad antimicrobial susceptibility of S. agalactiae , many showed tetracycline resistance in vitro . S. agalactiae plays an important role in bacterial infections not only in cattle and humans, but also in elephants. Comparative studies were able to differentiate S. agalactiae isolates from elephants into different infectious clusters based on their epidemiological background.

Streptococcus pneumoniae is a rare cause of urinary tract infection. Between January 2010 and December 2014, 26 urine samples from 18 different patients contained S. pneumoniae at the Department for Infectious Diseases, University Hospital of Heidelberg. Patient age varied between three and 72 years. 13 patients were male and five were female. Past medical histories of 16 patients were available. Eight patients had a past medical history of renal transplant and four patients had other renal dysfunctions. Further analyses of the isolates revealed that the aspect of colonies is more resembling S. mitis than invasive isolates of S. pneumoniae. Optochin disk diameters tend to be 14 mm or smaller. Identification using MALDI-TOF or VITEK2 identification cards was accurate. Only 2 isolates showed a decreased susceptibility towards penicillin (MIC = 0.5 mg/L). Eight different serotypes were identified using a PCR approach as well Neufeld-Quellungs reaction.

Summary Background The annual Muslim pilgrimage attracts over two million pilgrims who gather in a limited time and space. The pilgrimage carries the potential risk of increase risk of the acquisition of Streptococcus pneumonia. In this cohort study, we evaluate the effect of the Hajj on the prevalence of pneumococcal serotype nasopharyngeal carriage in the Hajj pilgrim population. The secondary objective is to evaluate the effects of the mass gathering on carriage of invasive pneumococcal serotypes. Methods This is a prospective cohort study with two data collection periods: at the beginning and at the end of the Hajj. Nasopharyngeal samples were taken via a standardized swabbing method. Results A total of 1175 pilgrims were enrolled at the beginning of the study and 1155 (98.3%) were included at the second part of the study. The pre-Hajj samples were obtained at a mean of 0 days and the post-Hajj sampling occurred at a mean of 15 days after arrival to Saudi Arabia. The overall carriage rate of Streptococcus pneumoniae in the pre- and post-Hajj was 1.8% and 7.1% (P = 0.0016). The potential coverage of the 7-valent pneumococcal conjugate vaccine (PCV7), PCV10 and PCV13 were 15.5%, 19.1%; and 35.5%, respectively. The coverage for the 23-valent pneumococcal polysaccharide vaccine (PPV23) was 40%. Conclusion Although there was an increase in the acquisition of S. pneumoniae, its magnitude is low which does not support public health recommendations for general pneumococcal vaccination of pilgrims except those at risk.

To assess the vaccine effectiveness (VE) of PCV13 for invasive pneumococcal disease (IPD) regarding the extra six serotypes with a 3+1 schedule in Germany.Active surveillance for IPD in children16 years eligible for PCV13 vaccination. We used the Broome method and logistic regression to estimate VE.Data on 164/304 reported IPD cases were informative and met the inclusion criteria. VE for the extra six serotypes was 88% [95% confidence interval (CI): 73; 95] and 83% [56; 94] for at least one and for at least two doses respectively. VE for the complete 3+1 vaccination schedule was not conclusive because of a wide 95% CI. For serotype 3 VE appeared to be zero with an even wider 95% CI.PCV13 VE against the extra six serotypes with the 3+1 schedule in Germany was only marginally higher compared to previously published data for the 2+1 schedule.

Background The antihypertensives reserpine and verapamil are also inhibitors of pneumococcal efflux pumps. We addressed the following questions: (i) Do verapamil and reserpine influence the mutation ratio of pneumococci in the presence of ciprofloxacin? (ii) At which concentrations does this occur? (iii) Is this limited to isolates with efflux phenotype? Methods 14 clinical isolates, nested in 6 genetically similar clusters, were used, 7 strains with efflux and 7 without. The mutation ratio in the presence of ciprofloxacin (3× MIC) and increasing concentrations of reserpine and verapamil was determined and the quinolone-resistance determining regions (QRDR) of selected mutants were sequenced. Analysis of the efficacy was performed using a mixed linear model, supported by descriptive statistics. Results Reserpine and verapamil reduced the mutation ratio of QRDR in the presence of ciprofloxacin with the required concentration for a reduction ≥50% of 1 mg/l for reserpine and 50 mg/l for verapamil. The mutation prevention effect is not limited to, but is more pronounced in efflux positive phenotypes. Conclusion Reserpine and verapamil can prevent the selection of ciprofloxacin resistant isolates by reduction of the mutation ratio, particularly in strain with an efflux phenotype. However, the required concentrations are too toxic for clinical use.

Introduction Vaccination with pneumococcal conjugate vaccine (PCV) for all children

Efficacy of 7-valent pneumococcal conjugate vaccination has been shown in randomized controlled trials using 4 dose vaccination schedules in children under 2 years of age. A case-control study from the US showed considerable protection from IPD for reduced vaccination schedules and even some protection from only one dose. In Germany, delayed and incomplete vaccination is a major issue. We assessed efficacy of PCV7 using data on cases of IPD from active surveillance and applying the indirect cohort design proposed by Broome, comparing cases of IPD with a vaccine serotype with cases with a non-vaccine serotype. Efficacy of at least one dose of PCV7 was estimated to be 88.3% (95% CI: 64.0-96.6). Estimates of efficacy for one, two, and three doses in the first 7 months of life were 78.1% (3.4-96.1), 89.8% (20.6-100.0), and 94.6% (69.7-99.5) respectively. Our study adds to evidence of good protection from IPD by reduced vaccination schedules with PCV7, e.g. with two doses as primary series, in a setting where a high proportion of children receives vaccination delayed.

Continuous nationwide surveillance of invasive pneumococcal disease has been conducted in Germany for more than 15 years. In this study, 3724 isolates were included. A total of 2065 isolates were obtained from children under 16 years of age from 1997 to 2006, and 1659 isolates were obtained from adults aged 16 years and older between 2002 and 2006. Results were classified to federal states, and supra-regional trends were illustrated by classifying the federal states into the regions ‘North-West’, ‘North-East’ and ‘South’. Among childhood isolates, the most common serotypes were 14 (26.4%), 6B (7.7%), 23F (7.4%), 19F (7.1%), 1 (7.0%), 18C (6.2%), and 7F (5.6%). Serotype coverage for the 7-valent conjugate vaccine was 62.3%. For the 10-valent and 13-valent vaccines (both in development) the coverage was 75.5% and 84.8%, respectively. The 23-valent polysaccharide vaccine had a coverage of 87.3%. The coverage varies considerably among the federal states. Penicillin G resistance was observed in 7.4% of meningitis cases. In the non-meningitis group, no intermediate resistant or resistant strains were detected. Among adults, the most common serotypes were 14 (16.9%), 3 (9.2%), 4 (7.8%), 7F (7.5%), 1 (6.8%), and 9V (6.1%). Serotype coverage for the 7-valent conjugate vaccine was 46.5%. For the pneumococcal conjugate vaccines in development, the coverage was 61.1% (10-valent) and 76.3% (13-valent). The 23-valent polysaccharide vaccine had a coverage of 88.7%. Penicillin G resistance was observed in 6.4% of meningitis cases. Among these, considerably higher rates of resistance were observed in the North-East region (13.0%) than in the North-West (7.1%) and South (1.8%) regions.

Mutations in the transpeptidase domain of penicillin-binding protein 2x (PBP2x) of Streptococcus pneumoniae that reduce the affinity to beta-lactams are important determinants of resistance to these antibiotics. We have now analyzed in vitro and in vivo properties of PBP2x variants from cefotaxime-resistant laboratory mutants and a clinical isolate. The patterns of two to four resistance-specific mutations present in each of the proteins, all of which are placed between 6.6 and 24 A around the active site, fall into three categories according to their positions in the three-dimensional structure. The first PBP2x group is characterized by mutations at the end of helix α11 and carries the well-known T550A change and/or one mutation on the surface of the penicillin-binding domain in close contact with the C-terminal domain. All group I proteins display very low acylation efficiencies, ≤ 1700 M − 1 s − 1 , for cefotaxime. The second class represented by PBP2x of the mutant C505 shows acylation efficiencies below 100 M − 1 s − 1 for both cefotaxime and benzylpenicillin and contains the mutation L403F at a critical site close to the active serine. PBP2x of the clinical isolate 669 reveals a third mutational pathway where at least the two mutations Q552E and S389L are important for resistance, and acylation efficiency is reduced for both beta-lactams to around 10,000 M − 1 s − 1 . In each group, at least one mutation is located in close vicinity to the active site and mediates a resistance phenotype in vivo alone, whereas other mutations might exhibit secondary effects only in context with other alterations.

Based on active prospective surveillance, we report the incidence and serotype distribution for invasive pneumococcal disease in German children between 1997 and 2003. While incidence of meningitis cases was stable over time, there was an increase in non-meningitis cases. In absence of a general pneumococcal conjugate vaccination program, there were considerable and significant changes in serotype distribution over time. These should be considered when discussing the effect of vaccination programs and related changes in serotype distribution.