Optimal age targeting for pneumococcal vaccination in older adults; a modelling study.

Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.

Comparative performances of seven quantitative Reverse-Transcription Polymerase Chain Reaction assays (RT-qPCR) for detecting SARS-CoV-2 infection in samples from individuals suspected of COVID-19 in São Paulo, Brazil.

Introduction: Brazil is the second largest country with COVID-19 positive cases worldwide. Due to the potent spread of the virus and the scarcity of kits and supplies, the Brazilian Ministry of Health has granted authorization for the use of kits available during this emergency, without an accurate evaluation of their performance. This study compared the performance and cost-effectiveness of seven molecular assays/kits available in São Paulo, Brazil, for SARS-CoV-2 diagnosis. Materials and methods: A total of 205 nasopharyngeal/oropharyngeal samples from suspected cases of COVID-19, were tested using the following assays: (i) GeneFinder COVID-19 plus RealAmp kit; (ii) 2019-nCoV RNA PCR-Fluorescence Probing, Da An Gene Co.; (iii) in-house RT-qPCR SARS-CoV-2 IAL; (iv) 2019-nCoV kit, IDT; (v) molecular SARS-CoV-2 (E) kit, Bio-Manguinhos; (vi) Allplex 2019-nCoV modified Assay, Seegene Inc, and (vii) Biomol one-step COVID-19 kit, IBMP. The criteria for determining a SARS-CoV-2 true positive result included the cycle threshold cut-off values, the characteristics of exponential/linear curves, the gene target diversity, and a positive result in at least two assays. Results: The overall sensitivity of the assays listed were GeneFinder 83.6%, Da An Gene 100.0%, IAL 90.4%, IDT 94.6%, Bio-Manguinhos 87.7%, Allplex 97.3%, and IBMP 87.7%. The minor sensitive gene target was RdRP. Although all assays had a Cohen's Kappa index ≥0.893, the best tests used multiplex assays identifying N-gene and/or E-gene targets. Conclusion: All assays tested accurate for diagnosis, but considering cost-effectiveness (cost, time consumption, number of samples tested, and performance), the in-house IAL assay was ideal for COVID-19 diagnosis in São Paulo, Brazil.

The direct effect of pneumococcal conjugate vaccines on invasive pneumococcal disease in children in the Latin American and Caribbean region (SIREVA 2006-17): a multicentre, retrospective observational study.

BACKGROUND: Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease has been subjected to laboratory-based surveillance in Latin American and Caribbean countries since 1993. Invasive pneumococcal diseases remain a major cause of death and disability worldwide, particularly in children. We therefore aimed to assess the direct effect of pneumococcal conjugate vaccines (PCVs) on the distribution of pneumococcal serotypes causing invasive pneumococcal disease in children younger than 5 years before and after PCV introduction. METHODS: We did a multicentre, retrospective observational study in eight countries that had introduced PCV (ie, PCV countries) in the Latin American and Caribbean region: Argentina, Brazil, Chile, Colombia, Dominican Republic, Mexico, Paraguay, and Uruguay. Cuba and Venezuela were also included as non-PCV countries. Isolate data for Streptococcus pneumoniae were obtained between 2006 and 2017 from children younger than 5 years with an invasive pneumococcal disease from local laboratories or hospitals. Species' confirmation and capsular serotyping were done by the respective national reference laboratories. Databases from the Sistema Regional de Vacunas (SIREVA) participating countries were managed and cleaned in a unified database using Microsoft Excel 2016 and the program R (version 3.6.1). Analysis involved percentage change in vaccine serotypes between pre-PCV and post-PCV periods and the annual reporting rate of invasive pneumococcal diseases per 100 000 children younger than 5 years, which was used as a population reference to calculate percentage vaccine type reduction. FINDINGS: Between 2006 and 2017, 12 269 isolates of invasive pneumococcal disease were collected from children younger than 5 years in the ten Latin American and Caribbean countries. The ten serotypes included in ten-valent pneumococcal conjugate vaccine (PCV10) decreased significantly (p<0·0001) after any PCV introduction, except for the Dominican Republic. The percentage change for the ten vaccine serotypes in PCV10 countries was -91·6% in Brazil (530 [72·9%] of 727 before, 27 [6·1%] of 441 after); -85·0% in Chile (613 [72·6%] of 844 before, 44 [10·9%] of 404] after); -84·7% in Colombia (231 [63·1%] of 366 before, 34 [9·7%] of 352 after); and -73·8% in Paraguay (127 [77·0%] of 165 before, 22 [20·2%] of 109 after). In the 13-valent pneumococcal conjugate vaccine (PCV13) countries, the percentage change for the 13 vaccine serotypes was -59·6% in Argentina (853 [85·0%] of 1003 before, 149 [34·3%] of 434 after); -16·5% in the Dominican Republic (95 [80·5%] of 118 before, 39 [67·2%] of 58 after); -43·7% in Mexico (202 [73·2%] of 276 before, 63 [41·2%] of 153 after); and -45·9% in Uruguay (138 [80·7%] of 171 before, 38 [43·7%] of 87 after). Annual reporting rates showed a reduction from -82·5% (6·21 before vs 1·09 after per 100 000, 95% CI -61·6 to -92·0) to -94·7% (1·15 vs 0·06 per 100 000, -89·7 to -97·3) for PCV10 countries, and -58·8% (2·98 vs 1·23 per 100 000, -21·4 to -78·4) to -82·9% (7·80 vs 1·33 per 100 000, -76·9 to -87·4) for PCV13 countries. An increase in the amount of non-vaccine types was observed in the eight countries after PCV introduction together with an increase in their percentage in relation to total invasive strains in the post-PCV period. INTERPRETATION: SIREVA laboratory surveillance was able to confirm the effect of PCV vaccine on serotypes causing invasive pneumococcal disease in the eight PCV countries. Improved monitoring of the effect and trends in vaccine type as well as in non-vaccine type isolates is needed, as this information will be relevant for future decisions associated with new PCVs. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates.

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.

A mosaic tetracycline resistance gene tet(S/M) detected in an MDR pneumococcal CC230 lineage that underwent capsular switching in South Africa.

OBJECTIVES: We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions. METHODS: We whole-genome sequenced 12 254 pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth-death model. RESULTS: We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth-death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of ∼2.5. R declined to ∼1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage. CONCLUSIONS: The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era.

Nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in a Brazilian elderly cohort.

We aimed to investigate the nasopharyngeal colonization (NPC) by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in the elderly population and to assess the demographic factors associated with NPC. This was an observational cohort study in which outpatients aged ≥60 years were enrolled from April to August 2017, with a follow-up visit from September through December 2017. Nasopharyngeal (NP) swabs were collected, bacteria were detected and isolated, and isolates were subjected to phenotypic and molecular characterization using standard microbiological techniques. At enrolment, the rates of S. aureus, methicillin-resistant S. aureus (MRSA), H. influenzae, and S. pneumoniae among 776 elderly outpatients were 15.9%, 2.3%, 2.5%, and 2.2%, respectively. Toxin production was detected in 21.1% of methicillin-susceptible S. aureus, and three SCCmec types were identified: II/IIb, IVa, and VI. At the follow-up visit, all carriage rates were similar (p > 0.05) to the rates at enrolment. Most of S. pneumoniae serotypes were not included in pneumococcal conjugate vaccines (PCVs), except for 7F, 3, and 19A. All strains of H. influenzae were non-typeable. Previous use of antibiotics and 23-valent pneumococcal polysaccharide vaccination (p < 0.05) were risk factors for S. aureus and MRSA carriage; S. aureus colonization was also associated with chronic kidney disease (p = 0.021). S. pneumoniae carriage was associated with male gender (p = 0.032) and an absence of diabetes (p = 0.034), while not receiving an influenza vaccine (p = 0.049) and chronic obstructive pulmonary disease (p = 0.031) were risk factors for H. influenzae colonization. The frailty of study participants was not associated with colonization status. We found a higher S. aureus carriage rate compared with the S. pneumoniae- and H. influenzae-carriage rates in a well-attended population in a geriatric outpatient clinic. This is one of the few studies conducted in Brazil that can support future colonization studies among elderly individuals.

Expansion of the multidrug-resistant clonal complex 320 among invasive Streptococcus pneumoniae serotype 19A after the introduction of a ten-valent pneumococcal conjugate vaccine in Brazil.

BACKGROUND: In 2010, a ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in the routine infant national immunization program in Brazil. Invasive pneumococcal disease (IPD) caused by serotype 19A (Spn19A) increased after the introduction of PCVs in several countries. We compared the frequency, antimicrobial resistance and molecular patterns of invasive Spn19A strains before and after PCV10 introduction in Brazil using data from the national laboratory-based surveillance. METHODS: We analyzed invasive Spn19A strains isolated from 2005-2009 (pre-PCV10 period), 2011-2015 and 2016-2017 (post-PCV10 periods). Antimicrobial susceptibility was performed for all Spn19A strains, and multilocus sequence typing (MLST) was performed for strains isolated in the age groups <5 years and ≥50 years. RESULTS: Among the study period, a total of 9,852 invasive Spn strains were analyzed, and 673 (6.8%) belonged to serotype 19A. Overall, the proportion of Spn19A among the total number of IPD strains increased from 2.8% in 2005-2009 to 7.0% and 16.4% in 2011-2015 and 2016-2017, respectively. The relative increase in Spn19A was observed especially in children <5 years old (2005-2009: 3.2%; 2011-2015: 15.5%; 2016-2017: 31.2%). The percentage of penicillin resistance (MIC 2.0-4.0 µg/mL), erythromycin resistance and multidrug resistance (MDR) increased after PCV10 introduction due to the expansion of the MDR clonal complex CC320 (2005-2009: 8.6%; 2011-2015: 56.1%; 2016-2017: 66.5%). CONCLUSION: We observed an expansion of MDR-CC320 among invasive Spn19A strains after PCV10 introduction in Brazil, probably related to a combination of factors, such as vaccination and antimicrobial pressure. Continued surveillance of Spn19A strains is necessary to monitor the sustainability of this clonal complex in the Brazilian population.

Distribuição de sorotipos, perfil de suscetibilidade antimicrobiana e caracterização molecular de cepas de streptococcus pneumoniae isoladas de doença pneumocócica invasiva nos períodos pré e pós a introdução da vacina pneumocócica 10-valente no Brasil / Distribution of serotypes, antimicrobial susceptibility profile and molecular characterisation of strains of Streptococcus pneumoniae isolated from invasive pneumococcal disease in the periods before and after the introduction of the 10-valent pneumococcal vaccine in Brazil

A doença pneumocócica invasiva (DPI) é uma das principais causas de morbidade e letalidade afetando especialmente crianças e idosos, resultando em um problema de saúde pública. O Brasil introduziu a vacina pneumocócica conjugada 10-valente (PCV10) no programa nacional de imunização infantil em 2010. Os estudos de efetividade e de impacto da PCV10 no Brasil foram realizados 3 a 5 anos após a introdução da vacina e mostraram redução nos casos de DPI causada pelos sorotipos vacinais e aumento de sorotipos não incluídos na vacina. Portanto, estudos realizados em um período de tempo mais longo após vacinação são fundamentais para se observar a sustentabilidade do aumento dos sorotipos não vacinais ao longo dos anos. O objetivo deste estudo foi investigar as características de S.pneumoniae (distribuição de sorotipos, perfil de suscetibilidade aos antimicrobianos e identificação das linhagens genéticas dos sorotipos prevalentes) nos períodos pré-PCV10 (2005-2009), pós-PCV10-imediato (2010-2013) e pós-PCV10-tardio (2014-2017), sendo o período pósPCV10 composto de 7 anos de avaliação. Isolados de DPI foram obtidos através da vigilância laboratorial nacional para S. pneumoniae. Os isolados foram encaminhados ao Instituto Adolfo Lutz pelos LACENs e por outras instituições públicas e privadas. Os isolados foram sorotipados por Quellung, o perfil de suscetibilidade antimicrobiana foi determinado pelos testes de disco-difusão e concentração inibitória mínima por microdiluição e a caracterização molecular foi realizada por MLST. A %change foi utilizada para calcular as diferenças na prevalência dos sorotipos e da resistência antimicrobiana por período de estudo. As sequências-tipo foram determinadas na página da web MLST e os complexos clonais pelo programa eBURST. Um total de 11.136 isolados invasivos foi estudado fenotipicamente. Uma amostragem de 688 isolados foi selecionada para a identificação das linhagens genéticas. No período pós-PCV10-tardio foi observada uma redução de 69,6% de DPI pelos sorotipos vacinais e, em paralelo, um aumento de 105,8% dos sorotipos não incluídos na PCV10. O aumento dos sorotipos não-PCV10 foi relacionado principalmente aos sorotipos 3, 6C, 8, 12F e 19A. Detectamos uma elevação de 304,6% na resistência à eritromicina no período pósPCV10-tardio. O estudo molecular identificou 33 CC e 182 STs. No período pós-PCV10, clones internacionalmente disseminados foram identificados ST180 (Clone Holanda3 -31), ST53-12574 (Clone Holanda8 - 33) e ST218 (Clone Dinamarca12F-34)], e duas principais STs foram relacionadas à resistência aos antimicrobianos, a citar a ST320/19A, presente desde o pré-PCV10 e a ST386/6C detectada no pós-PCV10. O monitoramento das características de S. pneumoniae em um período de tempo longo após a introdução da PCV10 confirmou a proteção da vacina contra a DPI pelos sorotipos vacinais e detectou a alta prevalência de sorotipos não incluídos na PCV10. O estudo molecular identificou uma disseminação de clones internacionais no Brasil

Invasive pneumococcal disease (IPD) is one of the leading causes of morbidity and lethality affecting especially children and the elderly, resulting in a public health problem. Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the national program of childhood immunization in 2010. The effectiveness and impact studies of PCV10 in Brazil were carried out 3 to 5 years after the introduction of the vaccine and showed a reduction in cases of IPD caused by vaccine serotypes and increase in non-vaccine serotypes. Therefore, studies conducted over a longer period of time after vaccination is essential to observe the sustainability of the increase in non-vaccine serotypes over the years. The aim of this study was to investigate the characteristics of S. pneumoniae (distribution of serotypes, antimicrobial susceptibility profile and genetic lineages identification of prevalent serotypes) in the pre-PCV10 (2005-2009), immediate-postPCV10 (2010-2013) and late-post-PCV10 (2014-2017) periods, the postPCV10 period being composed of 7 years of evaluation. Isolated of DPI were obtained through national laboratory surveillance for S. pneumoniae. The isolates were sent to the Institute Adolfo Lutz by LACENs and other public and private institutions. The isolates were serotype by Quellung, the antimicrobial susceptibility profile was determined by disc-diffusion and minimum inhibitory concentration microdilution assays and the molecular characterization were performed by MLST. %change was used to calculate differences in the prevalence of serotypes and antimicrobial resistance per study period. The sequences-type were determined at MLST website and clonal complexes were defined by the program eBURST. A total of 11,136 invasive isolates were phenotipically studied. A sample of 688 isolates was selected for the identification of the genetic lineages. In the latepost-PCV10 period, a 69.6% reduction in IPD was observed by vaccine serotypes and, in parallel, a 105.8% increase in non-PCV10 serotypes. The increase in non-PCV10 serotypes was mainly related to serotypes 3, 6C, 8, 12F and 19A. We detected a 304.6% increase in resistance to erythromycin in the late-post-PCV10 period. The molecular study identified 33 CC and 182 STs. In the post-PCV10 period, internationally disseminated clones were identified [ST180 (Clone Netherlands3-31), ST53-12574 (Clone Netherlands8-33) and ST218 (Clone Denmark12F34)], and two major STs were related to antimicrobial resistance, to be cited the ST320/19A, present since the pre-PCV10 and the ST386/6C detected post-PCV10. Monitoring the characteristics of S. pneumoniae a long-term period after the introduction of PCV10 confirmed the protection of the vaccine against IPD by the vaccine serotypes and detected the high prevalence of non-PCV10 serotypes. The molecular study identified the great spread of international clones in Brazil

Distribution of Streptococcus pneumoniae serotypes in the northeast macro-region of São Paulo state/Brazil after the introduction of conjugate vaccine.

BACKGROUND: Infections caused by Streptococcus pneumoniae (Spn) still challenge health systems around the world, even with advances in vaccination programs. The present study evaluated the frequency of various Spn serotypes isolated in Regional Health Care Network 13 (RRAS 13), which includes the regional health departments (RHDs) of Araraquara, Barretos, Franca and Ribeirão Preto, especially after the introduction of 10-valent pneumococcal conjugate vaccine (PCV10) in 2010. METHODS: The analyzed Spn strains were isolated from patients with invasive pneumococcal diseases (IPDs) and then sent to Adolfo Lutz Institute (ALI) for further confirmative identification tests during the period from 1998 to 2013. The samples were from the cities in RRAS13, which is located in the Northeast region of São Paulo State, and totals 90 municipalities. RESULTS: We analyzed strains isolated from 796 patients. They were predominantly: men (58.9%); 20 to 60 years old (32.2%); evaluated from 2003 to 2010 (60.2%); and diagnosed with meningitis (45.7%) and pneumonia (45.0%), the most common invasive pneumococcal diseases. In 2010, serotypes 3, 19F, 1, 23F, 6A and 6B were among the most frequent, while serotypes 3, 12F, 14, 6A, 18C, 8 and 6B were more common after the introduction of PCV10. Serotypes 14, 19F and 3 were more frequent in meningitis, while serotypes 14, 3 and 1 prevailed in pneumonia. After 2010, there was a decrease in serotypes 14, 1, 23F and 5 and an increase in serotypes 3, 12F, 11A and 8, which were not present in the vaccine. CONCLUSIONS: The present study noted the increase in serotypes 3, 12F, 11A and 8 after vaccination. None of those serotypes are included in the available conjugate vaccines, which highlights the importance of continued monitoring of IPDs in order to measure the disease burden in the population in the long term and provide new epidemiological information to determine the impact of PCV10 in Brazil.

Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998-2013)

Abstract Introduction Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. Objective The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. Materials and methods This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital – Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. Results The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio = 4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio = 3.8) and when adjusted for comorbidity (Odds Ratio = 5.0) or age (Odds Ratio = 5.4). The same occurred with serotype 12F (respectively, Odds Ratio = 5.1, Odds Ratio = 5.0, and Odds Ratio = 4.7) Conclusion The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

Clinical and microbiological implications of invasive pneumococcal disease in hospitalized patients (1998-2013).

INTRODUCTION: Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. OBJECTIVE: The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. MATERIALS AND METHODS: This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital - Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. RESULTS: The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio=4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio=3.8) and when adjusted for comorbidity (Odds Ratio=5.0) or age (Odds Ratio=5.4). The same occurred with serotype 12F (respectively, Odds Ratio=5.1, Odds Ratio=5.0, and Odds Ratio=4.7) CONCLUSION: The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and adequacy of immunization.

Evaluating the impact of PCV-10 on invasive pneumococcal disease in Brazil: A time-series analysis.

Routine infant immunization with 10-valent pneumococcal conjugate vaccine (PCV-10) began in Brazil in 2010. The impact of the PCV-10 on rates of invasive pneumococcal disease (IPD) at the population level was not yet evaluated. Serotype-specific IPD changes after PCV-10 introduction is still to be determined. Data from national surveillance system for notifiable diseases (SINAN) and national reference laboratory for S. pneumoniae in Brazil (IAL) were linked to enhance case ascertainment of IPD. An interrupted time-series analysis was conducted to predict trends in the postvaccination IPD rates in the absence of PCV-10 vaccination, taking into consideration seasonality and secular trends. PCVs serotype-specific distribution were assessed before (2008-2009) and after (2011-2013) the introduction of PCV-10 in the immunization program. A total of 9,827 IPD cases were identified from 2008-2013 when combining SINAN and IAL databases. Overall, PCV-10 types decreased by 41.3% after PCV-10 vaccination period, mostly in children aged 2-23 months, while additional PCV-13 serotypes increased by 62.8% mainly in children under 5-year of age. For children aged 2-23 months, targeted by the immunization program, we observed a 44.2% (95%CI, 15.8-72.5%) reduction in IPD rates. In contrast, significant increase in IPD rates were observed for adults aged 18-39 y (18.9%, 95%CI 1.1-36.7%), 40-64 y (52.5%, 95%CI 24.8-80.3%), and elderly ≥ 65 y (79.3%, 95%CI 62.1-96.5%). This is the first report of a time-series analysis for PCV impact in IPD conducted at national level data in a developing country. We were able to show significant impact of PCV-10 on IPD for age groups targeted by vaccination in Brazil, 3 y after its introduction. No impact on other age groups was demonstrated.

Evaluation of Haemophilus influenzae type b carrier status among children 10 years after the introduction of Hib vaccine in Brazil.

The aim of the present study was to assess the prevalence of Haemophilus influenzae type b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Evaluation of Haemophilus influenzae type b carrier status among children 10 years after the introduction of Hib vaccine in Brazil

The aim of the present study was to assess the prevalence of Haemophilus influenzaetype b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Prevalence of pneumococcal serotypes and resistance to antimicrobial agents in patients with meningitis: ten-year analysis.

OBJECTIVES: To determine the prevalence of pneumococcal serotypes and antimicrobial susceptibility in patients with meningitis, and to evaluate the implications for vaccine coverage. METHODS: Pneumococcal strains obtained from normally sterile fluids from patients admitted with meningitis were isolated at the Hospital de Clínicas of the Universidade Federal de Uberlândia, Minas Gerais State, and sent to the Instituto Adolfo Lutz, city of São Paulo, São Paulo State, for further identification, serotyping, and antimicrobial susceptibility determination. RESULTS: From April 1999 to April 2009, 338 pneumococcal strains were isolated, and 72 obtained from patients with meningitis, were analyzed. Patients' ages varied from one month to 82.2 years (mean of 18.4 ± 22.9 years; median of 5.2 years) and 46 (63.9%) patients were male. Strains were isolated from cerebrospinal fluid [66 occasions (91.7%)] and blood [6 occasions (8.3%)]. The most commonly identified serotypes were 14, 19F, 3, 7F, 6A, 6B, 10A, 18C, 23F, 5, and 34. Of the 20 [27.8%] oxacillin-resistant strains, 17 [23.6%] were resistant to penicillin and nine [12.5%] to ceftriaxone, both resistance patterns being more common in children aged two years or less and during the 2005-2009 period. CONCLUSIONS: Resistance to penicillin and ceftriaxone was detected in 23.6% and 12.5% of the strains, respectively, and predominated in children aged two years or less and during the 2005-2009 period. There were 24 different serotypes of pneumococcus and 79.8% of the serotypes were represented in the 7-valent conjugated vaccine [PVC7].

Prevalence of pneumococcal serotypes and resistance to antimicrobial agents in patients with meningitis: ten-year analysis

OBJECTIVES: To determine the prevalence of pneumococcal serotypes and antimicrobial susceptibility in patients with meningitis, and to evaluate the implications for vaccine coverage. METHODS: Pneumococcal strains obtained from normally sterile fluids from patients admitted with meningitis were isolated at the Hospital de Clínicas of the Universidade Federal de Uberlândia, Minas Gerais State, and sent to the Instituto Adolfo Lutz, city of São Paulo, São Paulo State, for further identification, serotyping, and antimicrobial susceptibility determination. RESULTS: From April 1999 to April 2009, 338 pneumococcal strains were isolated, and 72 obtained from patients with meningitis, were analyzed. Patients' ages varied from one month to 82.2 years (mean of 18.4 ± 22.9 years; median of 5.2 years) and 46 (63.9 percent) patients were male. Strains were isolated from cerebrospinal fluid [66 occasions (91.7 percent)] and blood [6 occasions (8.3 percent)]. The most commonly identified serotypes were 14, 19F, 3, 7F, 6A, 6B, 10A, 18C, 23F, 5, and 34. Of the 20 [27.8 percent] oxacillin-resistant strains, 17 [23.6 percent] were resistant to penicillin and nine [12.5 percent] to ceftriaxone, both resistance patterns being more common in children aged two years or less and during the 2005-2009 period. CONCLUSIONS: Resistance to penicillin and ceftriaxone was detected in 23.6 percent and 12.5 percent of the strains, respectively, and predominated in children aged two years or less and during the 2005-2009 period. There were 24 different serotypes of pneumococcus and 79.8 percent of the serotypes were represented in the 7-valent conjugated vaccine [PVC7].

Prevalência de sorotipos e resistência antimicrobiana de cepas invasivas do pneumococo em crianças: análise de 9 anos / Prevalence of serotypes and antimicrobial resistance of invasive strains of pneumococcus in children: analysis of 9 years

OBJETIVO: Avaliar o perfil de sorotipos e a sensibilidade aos antimicrobianos de cepas de pneumococo obtidas de crianças e as implicações na formulação de vacinas pneumocócicas. MÉTODOS: Cepas de pneumococo isoladas no Hospital de Clínicas da Universidade Federal de Uberlândia, Uberlândia (MG), a partir de pacientes com doença invasiva, foram enviadas ao Instituto Adolfo Lutz, São Paulo (SP), para confirmação da identificação, sorotipagem e determinação da sensibilidade aos antimicrobianos. RESULTADOS: De abril de 1999 a dezembro de 2008, foram avaliadas 142 cepas de pneumococo obtidas de crianças de até 5 anos de idade. Setenta e cinco (52,8 por cento) eram de pacientes do sexo masculino, e a idade variou de 1 a 60 meses (média de 19±15,4 meses e mediana de 15 meses). Os diagnósticos clínicos mais comuns foram pneumonia [92 casos (64,8 por cento)] e meningite [33 casos (23,2 por cento)], e as principais fontes de recuperação foram sangue [61 amostras (43 por cento)], líquido pleural [52 (36,6 por cento)] e liquor [28 (19,7 por cento)]. Os sorotipos mais comuns foram o 14, 5, 6B, 1, 6A, 18C, 19A, 3, 9V, 19F, 23F, 9N e 10A. Foram detectadas 14 (9,9 por cento) cepas penicilina-resistentes, restritas aos sorotipos 14, 6B, 19F, 19A e 23F e predominantes no período de 2004 a 2008 (p = 0,000). Foi detectada sensibilidade diminuída ao cotrimoxazol (79,5 por cento), à eritromicina e à clindamicina (11,3 por cento cada) e à ceftriaxona (5,6 por cento). CONCLUSÕES: A resistência à penicilina foi detectada em 9,9 por cento das cepas e predominou no período de 2004 a 2008. Foram identificados 20 diferentes sorotipos de pneumococo, e a cifra de cobertura pela vacina 7-valente atualmente disponível (PN CRM7) é de 71,9 por cento.

OBJECTIVE: To determine the prevalence of serotypes and antimicrobial susceptibility of strains of pneumococcus in children and to evaluate the implications for vaccine formulation. METHODS: Strains of pneumococcus obtained from children admitted with invasive diseases were isolated at Hospital de Clínicas of Universidade Federal de Uberlândia, Uberlândia, Brazil, and sent to Instituto Adolfo Lutz, São Paulo, Brazil, for further identification, serotyping, and determination of antimicrobial susceptibility. RESULTS: From April 1999 to December 2008, 142 strains of pneumococcus, obtained from children under 5 years of age, were analyzed. Seventy-five (52.8 percent) patients were male, and the age ranged from 1 to 60 months (mean age = 19±15.4 months; median = 15 months). The most common diagnoses were pneumonia [92 cases (64.8 percent)] and meningitis [33 cases (23.2 percent)]. The strains were mostly isolated from blood [61 samples (43 percent)], pleural fluid [52 samples (36.6 percent)], and cerebrospinal fluid [28 samples (19.7 percent)]. The most common serotypes were 14, 5, 6B, 1, 6A, 18C, 19A, 3, 9V, 19F, 23F, 9N, and 10A. There were 14 [9.9 percent] penicillin-resistant strains, which was detected only in the following serotypes: 14, 6B, 19F, 19A, and 23F, being predominant from 2004 to 2008 (p = 0.000). There was reduced susceptibility to co-trimoxazole (79.5 percent), erythromycin and clindamycin (11.3 percent each), and ceftriaxone (5.6 percent). CONCLUSIONS: Penicillin resistance was detected in 9.9 percent of the strains, being predominant from 2004 to 2008. Twenty different pneumococcal serotypes were identified, and 71.9 percent of the serotypes were represented in the 7-valent conjugate vaccine (PN CRM7) currently available.

New susceptibility breakpoints in antimicrobial resistance rates of invasive pneumococcal strains.

OBJECTIVE: To evaluate the impact of new penicillin susceptibility breakpoints on resistance rates of pneumococcal strains collected from children with pneumonia. METHODS: Pneumococcal strains collected from patients admitted with pneumonia were isolated at the clinical analysis lab of Hospital de Clínicas de Uberlândia, Uberlândia, Brazil, and sent to Instituto Adolfo Lutz, São Paulo, Brazil, for further identification, serotyping and determination of antimicrobial susceptibility. RESULTS: From April 1999 to December 2008, 330 strains of pneumococcus were sent to Instituto Adolfo Lutz; of these, 195 (59%) were collected from patients with pneumonia. One hundred strains collected from patients < or = 12 years old were analyzed. The patients' age ranged from 1 to 12.6 years old (with mean age of 2.4 and median of 1.7 years). Forty-seven patients were male. The strains were isolated from blood (42%) and pleural fluid (58%). There were 35 oxacillin-resistant strains: according to the criteria defined by the Clinical and Laboratory Standards Institute (CLSI) in 2007 [minimum inhibitory concentration (MIC) < or = 0.06 microg/mL for susceptibility (S), 0.12 to 1 microg/mL for intermediate resistance (IR), and > or = 2 microg/mL for full resistance (FR)], 22 strains had IR and 11 strains had FR. According to the current breakpoints defined by the CLSI in 2008 (< or = 2 microg/mL for S, 4 microg/mL for IR and > or = 8 microg/mL for FR), only one strain had IR to penicillin. There was resistance to co-trimoxazole (80%), tetracycline (21%), erythromycin (13%), clindamycin (13%), and ceftriaxone (one strain simultaneously resistant to penicillin). CONCLUSIONS: When the new breakpoints for in vitro susceptibility were applied, penicillin resistance rates dropped 97%, from 33 to 1%.