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Despite the introduction of the pneumococcal vaccine, Streptococcus pneumoniae remains a cause of invasive diseases in Brazil. This study provides the distribution of serotypes and antimicrobial susceptibility patterns for pneumococcal isolates before and during the years of the COVID-19 pandemic in two age groups, <5 and ≥50 years. This is a national laboratory-based surveillance study that uses data from the Brazilian national laboratory for invasive S. pneumoniae from the pre-COVID-19 (January 2016 to January 2020) and COVID-19 (February 2020 to May 2022) periods. Antimicrobial resistance was evaluated by disk diffusion and minimum inhibitory concentration. The year 2020 was marked by a 44.6% reduction in isolates received and was followed by an upward trend from 2021 onwards, which became evident in 2022. No differences were observed in serotypes distribution between the studied periods. The COVID-19 period was marked by the high prevalence of serotypes 19A, 3, and 6C in both age groups. Serotypes 19A and 6C were related to non-antimicrobial susceptibility. We observed a reduction in S. pneumoniae, without changes in serotypes distribution and epidemiological capsular switch during the COVID-19 period. We observed elevated resistance rates, mainly to penicillin and ceftriaxone for non-meningitis cases in children under 5 years of age.

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BACKGROUND: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. METHODS: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. CONCLUSION: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

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ABSTRACT Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others Results: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

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Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly. Keywords: Antimicrobial resistance; Chronic diseases; Comorbidity; Invasive pneumococcal diseases; Pneumococcal conjugate vaccine; Pneumococcal serotypes; Pneumococcal vaccine.

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In 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) into the national children's immunization programme. This study describes the genetic characteristics of invasive Streptococcus pneumoniae isolates before and after PCV10 introduction. A subset of 466 [pre-PCV10 (2008-2009): n=232, post-PCV10 (2012-2013): n=234;<5 years old: n=310, ≥5 years old: n=156] pneumococcal isolates, collected through national laboratory surveillance, were whole-genome sequenced (WGS) to determine serotype, pilus locus, antimicrobial resistance and genetic lineages. Following PCV10 introduction, in the <5 years age group, non-vaccine serotypes (NVT) serotype 3 and serotype 19A were the most frequent, and serotypes 12F, 8 and 9 N in the ≥5 years old group. The study identified 65 Global Pneumococcal Sequence Clusters (GPSCs): 49 (88 %) were GPSCs previously described and 16 (12 %) were Brazilian clusters. In total, 36 GPSCs (55 %) were NVT lineages, 18 (28 %) vaccine serotypes (VT) and 11 (17 %) were both VT and NVT lineages. In both sampling periods, the most frequent lineage was GPSC6 (CC156, serotypes 14/9V). In the <5 years old group, a decrease in penicillin (P=0.0123) and cotrimoxazole (P<0.0001) resistance and an increase in tetracycline (P=0.019) were observed. Penicillin nonsusceptibility was predicted in 40 % of the isolates; 127 PBP combinations were identified (51 predicted MIC≥0.125 mg l-1); cotrimoxazole (folA and/or folP alterations), macrolide (mef and/or ermB) and tetracycline (tetM, tetO or tetS/M) resistance were predicted in 63, 13 and 21.6 % of pneumococci studied, respectively. The main lineages associated with multidrug resistance in the post-PCV10 period were composed of NVT, GPSC1 (CC320, serotype 19A), and GPSC47 (ST386, serotype 6C). The study provides a baseline for future comparisons and identified important NVT lineages in the post-PCV10 period in Brazil.

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BACKGROUND: Brazil introduced 10-valent pneumococcal conjugate vaccine (PCV10) into its immunization program in 2010. We assessed antimicrobial susceptibility of Streptococcus pneumoniae (Spn) obtained from a national surveillance system for invasive pneumococcal diseases (IPD) before/after PCV10 introduction. METHODS: Antimicrobial non-susceptible isolates were defined as intermediate or resistant. Minimum inhibitory concentrations (MICs) to penicillin and ceftriaxone were analyzed by year. Antimicrobial susceptibility rates were assessed for each three-year-period using the pre-PCV10-period as reference. Susceptibility of vaccine-types was evaluated for 2017-2019. RESULTS: 11,380 isolates were studied. Spn with penicillin ≥ 0.125 mg/L and ceftriaxone ≥ 1.0 mg/L decreased in the three-years after PCV10 introduction (2011-2013: penicillin, 28.1-22.5%; ceftriaxone, 11.3%-7.6%) versus pre-PCV10-years (2007-2009: penicillin, 33.8-38.1%; ceftriaxone, 17.2%-15.6%). After 2013, the proportion of Spn with those MICs to penicillin and ceftriaxone increased to 39.4% and 19.7% in 2019, respectively. Non-susceptibility to penicillin and ceftriaxone increased in 2014-2016, and again in 2017-2019 especially among children < 5 years with meningitis (penicillin, 53.9%; ceftriaxone, 28.0%); multidrug-resistance reached 25% in 2017-2019. Serotypes 19A, 6C and 23A were most associated with antimicrobial non-susceptibility. CONCLUSIONS: Antimicrobial non-susceptible Spn decreased in the three-years after vaccination but subsequently increased and was associated with non-PCV10-types. Antimicrobial susceptibility surveillance is fundamental for guiding antibiotic therapy policies.

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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.

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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.

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Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013. METHOD: The carriage survey was conducted among 531 children, aged 12 months to <24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only. RESULTS: No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p < 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8-1.8%) and 95.5% (19.8-0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6-44.8%) and 185% (19.6-55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2-0.6%, p < 0.001) and increase in serotype 19A (1.8-6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC ≥ 2.0 mg/L) and cefotaxime (MIC ≥ 1.0 mg/L) values. CONCLUSION: After 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.

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