Eur J Clin Microbiol Infect Dis DOI 10.1007/s10096-014-2283-8
ARTICLE
Recent trends in epidemiology of invasive pneumococcal disease in Poland A. Skoczyńska & A. Kuch & E. Sadowy & I. Waśko & M. Markowska & P. Ronkiewicz & B. Matynia & A. Bojarska & K. Wasiak & A. Gołębiewska & M. van der Linden & W. Hryniewicz & Participants of a laboratory-based surveillance of community acquired invasive bacterial infections (BINet)
Received: 30 September 2014 / Accepted: 5 November 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract The objectives of this study were to assess the current incidence of invasive pneumococcal disease (IPD) in Poland (2011–2013), where mass vaccination has not been implemented, and to characterize the Streptococcus pneumoniae isolates responsible for invasive infections by determining their serotype distribution and antimicrobial resistance patterns. For all isolates identification, serotyping and antimicrobial minimal inhibitory concentrations determination were performed based on routine techniques. The highest incidence rates were observed among adults older than 85 years old (4.62/100,000) and children under 1 year of age (4.28/100,000). The general case fatality ratio (CFR) was 25.4 %, with the highest CFR in the age group ≥85 years old (59.7 %). The most common serotypes were 3, 14, 19A, 4, 9V, 19F, 1, and 23 F (61.3 % of all isolates). The 10- and 13valent pneumococcal conjugated vaccines (PCV) covered
Anna Skoczyńska and Alicja Kuch contributed equally to this work. A. Skoczyńska (*) : A. Kuch : I. Waśko : M. Markowska : P. Ronkiewicz : B. Matynia : A. Gołębiewska : W. Hryniewicz National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland e-mail: [email protected] E. Sadowy : A. Bojarska Department of Molecular Microbiology, National Medicines Institute, Warsaw, Poland M. van der Linden German National Reference Center for Streptococci, Department of Medical Microbiology University Hospital RWTH Aachen, Aachen, Germany Present Address: K. Wasiak Department of Microbiology, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
46.0 and 71.8 % of all IPD cases, 61.4 and 79.5 % of cases in children under two years, and 60.4 and 78.6 % of cases involving children under five years of age, respectively. The PCV13 and 23-valent polysaccharide vaccine covered 68.7 and 86.0 % of cases in adults >65 years old, respectively. Decreased susceptibility was noted for penicillin (24.8 %), cefotaxime (10.0 %), meropenem (5.0 %), rifampicin (0.8 %), chloramphenicol (4.3 %), erythromycin (29.7 %) and clindamycin (25.6 %). Multi-drug resistance characterized 21.6 % of the pneumococci tested. Despite deficiencies in the Polish surveillance system and strong underestimation of IPD cases, results of the study showed good theoretical coverage of PCV, which should encourage inclusion of anti-pneumococcal conjugate vaccine into the national immunization program.
Introduction Despite development of anti-pneumococcal vaccines, Streptococcus pneumoniae (pneumococcus) remains the major cause of severe invasive infections worldwide, including predominantly bacteremic pneumonia, sepsis and meningitis. These invasive diseases are associated with high morbidity and mortality, especially among the very young and the elderly. Pneumococcus is also a global cause of less serious but more frequent respiratory tract infections, such as otitis media, sinusitis and non-bacteremic pneumonia [1–3]. Introduction of antipneumococcal conjugate vaccines into national immunization programs resulted in a dramatic decrease in the number of invasive infections in those countries implementing the PCV and had a positive influence on the level or severity of non-invasive infection. However,
Eur J Clin Microbiol Infect Dis
the fight against pneumococcal disease is hampered by antigenic diversity of the pneumococcal capsule, a major virulence factor of these bacteria and a target of all current commercially available vaccines. There are at least 94 capsule types (serotypes) that differ by invasiveness, disease severity, antibiotic resistance profiles and case fatality ratio. Consequently, differences in serotype distribution among continents and countries lead to diverse vaccine coverage, as well as antibiotic resistance levels [2, 4, 5]. Therefore, since the currently available vaccines provide protection only against a limited number of serotypes their distribution and characteristics warrant careful continuous monitoring. Poland is one of the few European countries where mass vaccination against pneumococcal diseases has not been introduced, although currently both vaccines, PCV10 and PCV13, are available [6, http://vaccineschedule.ecdc.europa.eu/Pages/Scheduler.aspx]. PCV7 was registered in Poland in 2001 (available since 2005), PCV10 in 2009 and PCV13 in 2010. As yet, the anti-pneumococcal conjugated vaccines are free of charge for children from some risk groups and the PCVs are highly recommended for children from two months to five years old. Additionally, PCV13 is recommended for everyone from the second month of life onward, and PPV23 for persons more than two years old, according to the Summary of Product Characteristics [6]. There are also some local initiatives, as in Kielce city, where the authorities decided to offer free vaccination for all children under two years of age, living within the city borders [7]. Moreover, according to the data provided by the National Institute of Public Health–National Institute of Hygiene, every year the number of parents who decide to vaccinate their children has increased, namely, 139,039 in 2010, 159,166 in 2011 and 173,248 in 2012, children below 15 years old completed their vaccination programs (primary or reinforcing) [8–10]. Based on these recent data vaccine coverage could be estimated as approximately 15 %. In Poland, cases of IPD are identified through two independent surveillance systems, a hospital-based surveillance system run by the National Institute of Public Health–National Institute of Hygiene (NIPH-NIH) and a laboratory-confirmed surveillance system performed in the National Reference Centre for Bacterial Meningitis (NRCBM), described elsewhere [11, 12]. The latter system provides phenotypic and genotypic characteristics of isolates, together with epidemiological data. Here, we report results from the Polish laboratory-based invasive pneumococcal disease (IPD) surveillance for 2011 through 2013, including the incidence, case fatality ratio, serotype distribution, and antimicrobial resistance patterns of isolates.
Material and methods Country background At the end of 2012, the Polish population of 38,533,299 included 775,364 (2.0 %) and 2,056,255 (5.3 %) children under two and five years of age, respectively [13, 14]. The birth cohort in 2012 was 386,257 [14]. As the denominator for the calculation of annual incidence estimates we used Polish demographic data for the 31st of December of each study year. There were no data available for 2013 yet, therefore the demographic data from 2012 were used. Case definition A case of IPD was defined as the recovery of an isolate of S. pneumoniae from a normally sterile site, such as blood, cerebrospinal fluid (CSF), pleural fluid, joint aspirate, pericardial fluid, or peritoneal fluid. Pneumococcal meningitis was defined by an isolation of S. pneumoniae from CSF or the clinical diagnosis of meningitis with pneumococci isolated from blood. Only one isolate from each IPD case was included in the study. For the assessment of incidence rate, cases where the pneumolysin and autolysin genes were detected by PCR in the normally sterile materials listed above were also included [15, 16]. Identification and serotyping All isolates were identified based on typical morphology, Gram stain, susceptibility to optochin (bioMerieux, Marcy l’Etoile, France), and bile solubility [17]. Serotypes of S. pneumoniae were determined by a Pneumotest-Latex kit (Statens Serum Institut, Copenhagen, Denmark) and PCR in the NRCBM [18–20]. Serotypes not identified by the above methods were subjected to the Neufeld Quellung test in the National Reference Center for Streptococci in Aachen, Germany, as previously described [21]. Susceptibility testing Minimal inhibitory concentrations (MICs) for penicillin, cefotaxime, rifampicin, meropenem, chloramphenicol, and vancomycin were determined by the Etest (AB Biodisk, Solna, Sweden) or MICEvaluators (Oxoid) according to manufacturers’ instructions. Susceptibility to erythromycin and clindamycin was established on the basis of the double disc test, and resistant isolates were assigned to specific phenotypes, including constitutive MLSB (cMLSB), inducible MLSB (iMLSB) and efflux-mediated resistance (M-phenotype). The results were interpreted according to the current EUCAST guidelines [22]. An isolate was characterized as multidrug-resistant (MDR) when non-susceptible to at least
Eur J Clin Microbiol Infect Dis
one agent in ≥3 antimicrobial categories [23]. The quality control strain was S. pneumoniae ATCC 49619.
was similar to the general CFR of this study but was much higher for septic pneumonia (37.0 %) in comparison to bacteremic pneumonia (18.6 %, p=0.0005).
Statistical analysis Serotypes of S. pneumoniae and vaccine coverage Chi-square test and Fisher’s exact test were used to analyse the differences in frequencies (http://www.vassarstats.net/tab2x2. html); p-values ≤0.05 were considered to be significant.
Results Isolate collection trends and incidence rates From 2011 to the end of 2013, the NRCBM provided laboratory confirmation of 1,190 IPD cases, including 1,138 (95.6 %) positive cultures and 52 PCR-based confirmations. The number of cases identified per year increased over the study period from 355 in 2011 to 474 in 2013. The incidence rates of IPD by age group in specific years are shown in Table 1. The highest incidence was observed among adults older than 85 years old (4.62/100,000), followed by children under one year of age (4.28/100,000) (Table 1). Pneumococci were isolated from patients in hospitals located in all 16 regions of Poland, but isolate submissions to the NRCBM differed considerably among the regions (from 13 to 209 isolates) and as a consequence the incidence rates of IPD were also affected (Fig. 1). Of 1,190S. pneumoniae, 834 (70.1 %) were recovered from blood, 337 (28.3 %) from CSF, and 1.6 % from other sterile material, such as pleural (n=15), peritoneal (n=3), and pericardial (n=1) fluids. Among all the patients, 25.5 % were diagnosed as having meningitis, 29.3 % bacteremic/septic pneumonia, 18.7 % sepsis, 8.3 % meningitis with sepsis, and the remaining 18.2 % with other manifestations or unspecified IPD. Age data were available for 1,183 cases (99.4 %) and the patient ages ranged from one day to 96 years (median, 56 years). Among 1,189 patients with gender reported, 60.2 % were male. Meningitis was most frequent in children under one year of age (57.1 %) in comparison to other patients (32.9 %; p= 0.03). Bacteremic/septic pneumonia was the most common form of IPD among patients ≥80 (43.4 %), in comparison to children
ARTICLE
Recent trends in epidemiology of invasive pneumococcal disease in Poland A. Skoczyńska & A. Kuch & E. Sadowy & I. Waśko & M. Markowska & P. Ronkiewicz & B. Matynia & A. Bojarska & K. Wasiak & A. Gołębiewska & M. van der Linden & W. Hryniewicz & Participants of a laboratory-based surveillance of community acquired invasive bacterial infections (BINet)
Received: 30 September 2014 / Accepted: 5 November 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract The objectives of this study were to assess the current incidence of invasive pneumococcal disease (IPD) in Poland (2011–2013), where mass vaccination has not been implemented, and to characterize the Streptococcus pneumoniae isolates responsible for invasive infections by determining their serotype distribution and antimicrobial resistance patterns. For all isolates identification, serotyping and antimicrobial minimal inhibitory concentrations determination were performed based on routine techniques. The highest incidence rates were observed among adults older than 85 years old (4.62/100,000) and children under 1 year of age (4.28/100,000). The general case fatality ratio (CFR) was 25.4 %, with the highest CFR in the age group ≥85 years old (59.7 %). The most common serotypes were 3, 14, 19A, 4, 9V, 19F, 1, and 23 F (61.3 % of all isolates). The 10- and 13valent pneumococcal conjugated vaccines (PCV) covered
Anna Skoczyńska and Alicja Kuch contributed equally to this work. A. Skoczyńska (*) : A. Kuch : I. Waśko : M. Markowska : P. Ronkiewicz : B. Matynia : A. Gołębiewska : W. Hryniewicz National Reference Centre for Bacterial Meningitis, Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland e-mail: [email protected] E. Sadowy : A. Bojarska Department of Molecular Microbiology, National Medicines Institute, Warsaw, Poland M. van der Linden German National Reference Center for Streptococci, Department of Medical Microbiology University Hospital RWTH Aachen, Aachen, Germany Present Address: K. Wasiak Department of Microbiology, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
46.0 and 71.8 % of all IPD cases, 61.4 and 79.5 % of cases in children under two years, and 60.4 and 78.6 % of cases involving children under five years of age, respectively. The PCV13 and 23-valent polysaccharide vaccine covered 68.7 and 86.0 % of cases in adults >65 years old, respectively. Decreased susceptibility was noted for penicillin (24.8 %), cefotaxime (10.0 %), meropenem (5.0 %), rifampicin (0.8 %), chloramphenicol (4.3 %), erythromycin (29.7 %) and clindamycin (25.6 %). Multi-drug resistance characterized 21.6 % of the pneumococci tested. Despite deficiencies in the Polish surveillance system and strong underestimation of IPD cases, results of the study showed good theoretical coverage of PCV, which should encourage inclusion of anti-pneumococcal conjugate vaccine into the national immunization program.
Introduction Despite development of anti-pneumococcal vaccines, Streptococcus pneumoniae (pneumococcus) remains the major cause of severe invasive infections worldwide, including predominantly bacteremic pneumonia, sepsis and meningitis. These invasive diseases are associated with high morbidity and mortality, especially among the very young and the elderly. Pneumococcus is also a global cause of less serious but more frequent respiratory tract infections, such as otitis media, sinusitis and non-bacteremic pneumonia [1–3]. Introduction of antipneumococcal conjugate vaccines into national immunization programs resulted in a dramatic decrease in the number of invasive infections in those countries implementing the PCV and had a positive influence on the level or severity of non-invasive infection. However,
Eur J Clin Microbiol Infect Dis
the fight against pneumococcal disease is hampered by antigenic diversity of the pneumococcal capsule, a major virulence factor of these bacteria and a target of all current commercially available vaccines. There are at least 94 capsule types (serotypes) that differ by invasiveness, disease severity, antibiotic resistance profiles and case fatality ratio. Consequently, differences in serotype distribution among continents and countries lead to diverse vaccine coverage, as well as antibiotic resistance levels [2, 4, 5]. Therefore, since the currently available vaccines provide protection only against a limited number of serotypes their distribution and characteristics warrant careful continuous monitoring. Poland is one of the few European countries where mass vaccination against pneumococcal diseases has not been introduced, although currently both vaccines, PCV10 and PCV13, are available [6, http://vaccineschedule.ecdc.europa.eu/Pages/Scheduler.aspx]. PCV7 was registered in Poland in 2001 (available since 2005), PCV10 in 2009 and PCV13 in 2010. As yet, the anti-pneumococcal conjugated vaccines are free of charge for children from some risk groups and the PCVs are highly recommended for children from two months to five years old. Additionally, PCV13 is recommended for everyone from the second month of life onward, and PPV23 for persons more than two years old, according to the Summary of Product Characteristics [6]. There are also some local initiatives, as in Kielce city, where the authorities decided to offer free vaccination for all children under two years of age, living within the city borders [7]. Moreover, according to the data provided by the National Institute of Public Health–National Institute of Hygiene, every year the number of parents who decide to vaccinate their children has increased, namely, 139,039 in 2010, 159,166 in 2011 and 173,248 in 2012, children below 15 years old completed their vaccination programs (primary or reinforcing) [8–10]. Based on these recent data vaccine coverage could be estimated as approximately 15 %. In Poland, cases of IPD are identified through two independent surveillance systems, a hospital-based surveillance system run by the National Institute of Public Health–National Institute of Hygiene (NIPH-NIH) and a laboratory-confirmed surveillance system performed in the National Reference Centre for Bacterial Meningitis (NRCBM), described elsewhere [11, 12]. The latter system provides phenotypic and genotypic characteristics of isolates, together with epidemiological data. Here, we report results from the Polish laboratory-based invasive pneumococcal disease (IPD) surveillance for 2011 through 2013, including the incidence, case fatality ratio, serotype distribution, and antimicrobial resistance patterns of isolates.
Material and methods Country background At the end of 2012, the Polish population of 38,533,299 included 775,364 (2.0 %) and 2,056,255 (5.3 %) children under two and five years of age, respectively [13, 14]. The birth cohort in 2012 was 386,257 [14]. As the denominator for the calculation of annual incidence estimates we used Polish demographic data for the 31st of December of each study year. There were no data available for 2013 yet, therefore the demographic data from 2012 were used. Case definition A case of IPD was defined as the recovery of an isolate of S. pneumoniae from a normally sterile site, such as blood, cerebrospinal fluid (CSF), pleural fluid, joint aspirate, pericardial fluid, or peritoneal fluid. Pneumococcal meningitis was defined by an isolation of S. pneumoniae from CSF or the clinical diagnosis of meningitis with pneumococci isolated from blood. Only one isolate from each IPD case was included in the study. For the assessment of incidence rate, cases where the pneumolysin and autolysin genes were detected by PCR in the normally sterile materials listed above were also included [15, 16]. Identification and serotyping All isolates were identified based on typical morphology, Gram stain, susceptibility to optochin (bioMerieux, Marcy l’Etoile, France), and bile solubility [17]. Serotypes of S. pneumoniae were determined by a Pneumotest-Latex kit (Statens Serum Institut, Copenhagen, Denmark) and PCR in the NRCBM [18–20]. Serotypes not identified by the above methods were subjected to the Neufeld Quellung test in the National Reference Center for Streptococci in Aachen, Germany, as previously described [21]. Susceptibility testing Minimal inhibitory concentrations (MICs) for penicillin, cefotaxime, rifampicin, meropenem, chloramphenicol, and vancomycin were determined by the Etest (AB Biodisk, Solna, Sweden) or MICEvaluators (Oxoid) according to manufacturers’ instructions. Susceptibility to erythromycin and clindamycin was established on the basis of the double disc test, and resistant isolates were assigned to specific phenotypes, including constitutive MLSB (cMLSB), inducible MLSB (iMLSB) and efflux-mediated resistance (M-phenotype). The results were interpreted according to the current EUCAST guidelines [22]. An isolate was characterized as multidrug-resistant (MDR) when non-susceptible to at least
Eur J Clin Microbiol Infect Dis
one agent in ≥3 antimicrobial categories [23]. The quality control strain was S. pneumoniae ATCC 49619.
was similar to the general CFR of this study but was much higher for septic pneumonia (37.0 %) in comparison to bacteremic pneumonia (18.6 %, p=0.0005).
Statistical analysis Serotypes of S. pneumoniae and vaccine coverage Chi-square test and Fisher’s exact test were used to analyse the differences in frequencies (http://www.vassarstats.net/tab2x2. html); p-values ≤0.05 were considered to be significant.
Results Isolate collection trends and incidence rates From 2011 to the end of 2013, the NRCBM provided laboratory confirmation of 1,190 IPD cases, including 1,138 (95.6 %) positive cultures and 52 PCR-based confirmations. The number of cases identified per year increased over the study period from 355 in 2011 to 474 in 2013. The incidence rates of IPD by age group in specific years are shown in Table 1. The highest incidence was observed among adults older than 85 years old (4.62/100,000), followed by children under one year of age (4.28/100,000) (Table 1). Pneumococci were isolated from patients in hospitals located in all 16 regions of Poland, but isolate submissions to the NRCBM differed considerably among the regions (from 13 to 209 isolates) and as a consequence the incidence rates of IPD were also affected (Fig. 1). Of 1,190S. pneumoniae, 834 (70.1 %) were recovered from blood, 337 (28.3 %) from CSF, and 1.6 % from other sterile material, such as pleural (n=15), peritoneal (n=3), and pericardial (n=1) fluids. Among all the patients, 25.5 % were diagnosed as having meningitis, 29.3 % bacteremic/septic pneumonia, 18.7 % sepsis, 8.3 % meningitis with sepsis, and the remaining 18.2 % with other manifestations or unspecified IPD. Age data were available for 1,183 cases (99.4 %) and the patient ages ranged from one day to 96 years (median, 56 years). Among 1,189 patients with gender reported, 60.2 % were male. Meningitis was most frequent in children under one year of age (57.1 %) in comparison to other patients (32.9 %; p= 0.03). Bacteremic/septic pneumonia was the most common form of IPD among patients ≥80 (43.4 %), in comparison to children
