Laboratory surveillance of invasive Haemophilus influenzae disease in Argentina, 2011-2019

Abstract The incorporation of Haemophilus influenzae type b (Hib) vaccine into the Argentine National Immunization Program in 1998 resulted in a dramatic decrease in the incidence of invasive disease due to this serotype. We assessed 1405 H. influenzae (Hi) isolates causing invasive infections referred to the National Reference Laboratory between 2011 and 2019. Non-encapsulated Hi were the most common strains (44.5%), followed by types b (41.1%) and a (10.0%). Significant increase in the proportion of type b was observed, from 31.2% in 2011, to 50% in 2015, correlating with the peak incidence rate, later decreasing to 33.6% by 2019. We compared the genetic relationship between clones circulating during the period of increased Hib incidence (2011-2015) and those of the prevaccination-transition period (1997-1998). Four pulsotypes predominated in both periods, G, M, P and K, G being the most common. Multilocus sequence typing revealed that the 4 pulsotypes belonged to ST6, or one of its simple or double locus variants. Isolates from fully vaccinated individuals did not differ from those of the rest of the population studied. After ruling out aspects associated with emergence of specific clones, we concluded that factors such as low booster coverage rates, delayed vaccination schedules and use of different vaccines may have contributed to the reemergence of Hib infections.

Resumen La introducción de la vacuna contra Haemophilus influenzae tipo b (Hib) en el Programa Nacional de Inmunización de Argentina en 1998 produjo una drástica disminución de la incidencia de enfermedad invasiva causada por este serotipo. En el Laboratorio Nacional de Referencia se estudiaron 1405 aislamientos de H. influenzae causantes de enfermedad invasiva recibidos en el período 2011-2019. H. influenzae no capsulado fue el más frecuente (44,5%), seguido por los tipos b (41,1%) y a (10,0%). Se observó un aumento significativo de la proporción del tipo b, de 31,2% en 2011 a 50% en 2015, que se correlacionó con un pico de incidencia en ese mismo año. Hacia 2019, descendió a 33,6%. Con el objetivo de evaluar los clones circulantes durante el incremento de la proporción de Hib y comparar con el período prevacunal-transición, se determinó la relación genética de una selección de aislamientos de los períodos 1997-1998 y 2011-2015. El análisis por PFGE mostró 4 pulsotipos predominantes en los 2 períodos, G, M, P y K, y el pulsotipo G fue mayoritario en ambos períodos. Por MLST se demostró que los 4 pulsotipos pertenecieron al ST6 o sus variantes (simple o doble locus). Entre los aislamientos de pacientes con vacunación completa no se hallaron clones diferentes respecto del resto de la población. Se postula que las coberturas de vacunación no satisfactorias en las dosis de refuerzo, los esquemas atrasados y el uso de diferentes vacunas pudieron haber contribuido a la reemergencia de Hib.

Laboratory surveillance of invasive Haemophilus influenzae disease in Argentina, 2011-2019.

The incorporation of Haemophilus influenzae type b (Hib) vaccine into the Argentine National Immunization Program in 1998 resulted in a dramatic decrease in the incidence of invasive disease due to this serotype. We assessed 1405 H. influenzae (Hi) isolates causing invasive infections referred to the National Reference Laboratory between 2011 and 2019. Non-encapsulated Hi were the most common strains (44.5%), followed by types b (41.1%) and a (10.0%). Significant increase in the proportion of type b was observed, from 31.2% in 2011, to 50% in 2015, correlating with the peak incidence rate, later decreasing to 33.6% by 2019. We compared the genetic relationship between clones circulating during the period of increased Hib incidence (2011-2015) and those of the prevaccination-transition period (1997-1998). Four pulsotypes predominated in both periods, G, M, P and K, G being the most common. Multi-locus sequence typing revealed that the 4 pulsotypes belonged to ST6, or one of its simple or double locus variants. Isolates from fully vaccinated individuals did not differ from those of the rest of the population studied. After ruling out aspects associated with emergence of specific clones, we concluded that factors such as low booster coverage rates, delayed vaccination schedules and use of different vaccines may have contributed to the reemergence of Hib infections.

Invasive Streptococcus pneumoniae isolates from pediatric population in Argentina for the period 2006-2019. Temporal progression of serotypes distribution and antibiotic resistance.

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. A total of 2908 pneumococcal isolates were analyzed between 2006 and 2019. Gold standard pneumococcal serotyping (the Neufeld-Quellung reaction) was performed to identify the serotypes associated with infection in children < 5 years in Argentina and agar dilution method was carried out to determine their profiles to 14 antimicrobial agents. In 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) was included in the National Immunization Program. In this work we have analyzed the local epidemiology of invasive pneumococcal diseases before and after the introduction of this vaccine in order to understand the epidemiological relevance and impact of PCV13. During the periods compared in the present study there was a significant increase in the proportion of non-PCV13 serotypes, serogroup 24 (246.7%) and 12F (85.7%), and a significant decrease in PCV13 serotypes, including serotypes 14 (91.2%), 5 (95.6%) and 1 (84.6%) among others. Another observation was that serotypes 3 (7.4%) and 19A (4.9%) still remain among the most frequent serotypes despite being part of the PCV13 formulation. Regarding antimicrobial resistance, in the present study we observed an increase in erythromycin resistance during the period of study mainly associated to serotype 14 in the pre-PCV13 period and to serogroup 24 in the post-PCV13 period, which also was the major NVT serotype associated with antimicrobial resistance and MDR. Serotypes 14, 24A/B/F and 19A were in the first three places among isolates resistant to all the antibiotics tested. Our data highlight the importance of continuous surveillance to assess the impact of pneumococcal vaccines and the use of antibiotics in the dynamic of pneumococcal serotypes.

Population genetic structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in children in Argentina.

Invasive disease caused by Streptococcus pneumoniae (IPD) is one of the leading causes of morbidity and mortality in young children worldwide. In Argentina, PCV13 was introduced into the childhood immunization programme nationwide in 2012 and PCV7 was available from 2000, but only in the private market. Since 1993 the National IPD Surveillance Programme, consisting of 150 hospitals, has conducted nationwide pneumococcal surveillance in Argentina in children under 6 years of age, as part of the SIREVA II-OPS network. A total of 1713 pneumococcal isolates characterized by serotype (Quellung) and antimicrobial resistance (agar dilution) to ten antibiotics, belonging to three study periods: pre-PCV7 era 1998-1999 (pre-PCV), before the introduction of PCV13 2010-2011 (PCV7) and after the introduction of PCV13 2012-2013 (PCV13), were available for inclusion. Fifty-four serotypes were identified in the entire collection and serotypes 14, 5 and 1 represented 50 % of the isolates. Resistance to penicillin was 34.9 %, cefotaxime 10.6 %, meropenem 4.9 %, cotrimoxazole 45 %, erythromycin 21.5 %, tetracycline 15.4 % and chloramphenicol 0.4 %. All the isolates were susceptible to levofloxacin, rifampin and vancomycin. Of 1713 isolates, 1061 (61.9 %) were non-susceptible to at least one antibiotic and 235(13.7 %) were multidrug resistant. A subset of 413 isolates was randomly selected and whole-genome sequenced as part of Global Pneumococcal Sequencing Project (GPS). The genome data was used to investigate the population structure of S. pneumoniae defining pneumococcal lineages using Global Pneumococcal Sequence Clusters (GPSCs), sequence types (STs) and clonal complexes (CCs), prevalent serotypes and their associated pneumococcal lineages and genomic inference of antimicrobial resistance. The collection showed a great diversity of strains. Among the 413 isolates, 73 known and 36 new STs were identified belonging to 38 CCs and 25 singletons, grouped into 52 GPSCs. Important changes were observed among vaccine types when pre-PCV and PCV13 periods were compared; a significant decrease in serotypes 14, 6B and 19F and a significant increase in 7F and 3. Among non-PCV13 types, serogroup 24 increased from 0 % in pre-PCV to 3.2 % in the PCV13 period. Our analysis showed that 66.1 % (273/413) of the isolates were predicted to be non-susceptible to at least one antibiotic and 11.9 % (49/413) were multidrug resistant. We found an agreement of 100 % when comparing the serotype determined by Quellung and WGS-based serotyping and 98.4 % of agreement in antimicrobial resistance. Continued surveillance of the pneumococcal population is needed to reveal the dynamics of pneumococcal isolates in Argentina in post-PCV13. This article contains data hosted by Microreact.

Oropharyngeal meningococcal carriage in children and adolescents, a single center study in Buenos Aires, Argentina.

BACKGROUND: Neisseria meningitidis (Nm) pharyngeal carriage is a necessary condition for invasive disease. We present the first carriage study in children in Buenos Aires, Argentina, considering 2017 as a transition year. Aims: to assess the rate of Nm carriage, to determine genogroup, clonal complex and outer membrane protein distribution, to determine carriage risk factors by age. METHODS: Cross-sectional study including children 1-17 yrs, at Ricardo Gutiérrez Children's Hospital in Buenos Aires 2017. Oro-pharyngeal swabs were taken and cultured within a short time after collection. Genogroup was determined by PCR and clonal complex by MLST. Categorical variables were analyzed. RESULTS: A total of 1,751 children were included. Group 1: 943 children 1-9 yrs, 38 Nm were isolated; overall carriage 4.0%. Genogroup distribution: B 26.3%, W 5.3%, Y 2.6%, Z 5.3%, other groups 7.9% and capsule null (cnl) 52.6%. Participating in extracurricular activities was the only independent predictor of Nm carriage. Group 2: 808 children 10-17 yrs, 76 Nm were isolated; overall carriage 9.4%. Genogroup distribution: B 19.7%, C 5.3%, W 7.9%, Y 9.2%, Z 5.3%, other groups 7.9% and cnl 44.7%. Independent predictors of carriage: attending pubs/night clubs and passive smoking (adjusted OR: 0.55, 95%CI = 0.32-0.93; p = 0.025). CONCLUSIONS: Overall carriage was higher in 10-17 yrs. The isolates presenting the cnl locus were prevalent in both age groups and genogroup B was the second most frequent.

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.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013-2017 / Distribución de los serotipos PCV13 y PPSV23 de Streptococcus pneumoniae en adultos argentinos con enfermedad invasiva, 2013-2017

Abstract Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18-64 and >65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sep-sis/bacteremia the most prevalent was serotype 8. In this work, for the 18-64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the >65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Resumen Streptococcus pneumoniae es una causa importante de enfermedad invasiva grave asociada con una alta mortalidad y morbilidad en todo el mundo. Para identificar los serotipos principales asociados con la infección en adultos en Argentina, 791 aislamientos de neumococo de 56 hospitales pertenecientes a 16 provincias y la ciudad de Buenos Aires fueron serotipificados. Los aislamientos fueron remitidos como parte del Programa Nacional de Vigilancia para la enfermedad neumocócica invasiva en adultos, que comenzó en 2013. Los serotipos 3, 8, 12F, 7F y 1 fueron los más prevalentes. Durante el período de estudio no hubo diferencias significativas en la distribución de serotipos entre los dos grupos de adultos estudiados (18-64 y >65 años), excepto para los serotipos 1, 3 y 23A. Los serotipos más prevalentes en casos de neumonía fueron 7F, 1, 12F, 8 y 3. Cuando el diagnóstico clínico fue meningitis, los serotipos 3 y 12F fueron los más prevalentes. Y el serotipo 8 fue el más prevalente en la sepsis/bacteriemia. En el grupo de 18-64 años, los serotipos PPSV23 y PCV13 representaron, respectivamente, el 74,56 y el 44,54% de los casos de enfermedad invasiva en el período estudiado. En el grupo de >65 años, estos serotipos representaron el 72,30 y 41,42%, respectivamente. Es importante conocer los serotipos causantes de infecciones neumocócicas invasivas en la población adulta en Argentina y detectar eventuales cambios en su distribución a lo largo del tiempo, para explorar la potencial cobertura de las vacunas utilizadas.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013-2017.

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18-64 and ≥65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sepsis/bacteremia the most prevalent was serotype 8. In this work, for the 18-64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the ≥65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Community acquired pneumonia incidence among children less than 5 years of age in Concordia, Argentina: vaccination impact.

OBJECTIVE: To measure the effectiveness of pneumococcal conjugated vaccine (PCV13) against Community Acquired Pneumonia (CAP) and invasive pneumococcal disease, 2 years after the vaccine (2+1) was included into the National Immunization Program of Argentina, and to describe variables associated with bacterial pneumonia and hospitalization. METHODS: This was a prospective, population-based surveillance study of CAP incidence (ambulatory and hospitalized) among children less than 5 years of age in the Department of Concordia (Entre Rios, Argentina) from April 2014 - March 2016. The diagnosis of probable bacterial pneumonia (PBP) was determined following the standardized WHO protocol. Incidence during the post-vaccine introduction period was compared with the results from a previous study that used similar methodology for the pre-PCV13 introduction period from 2002 - 2005. RESULTS: During the study period, 330 patients had a clinical diagnosis of CAP, of which 92 were PBP (6 with pleural effusion). S. pneumoniae was not isolated from any sample. No factors associated with PBP were found in multivariable analysis. The decrease in PBP and pleural effusion was significant in relation to the previous study: 63% (P < 0.0001) and 80.9% (P < 0.003), respectively. PCV13 uptake was 97.3% for the 1st dose and 84.8% for the booster dose. CONCLUSIONS: PCV13 was effective to reduce incidence of consolidated pneumonia and pleural effusion, among children less than 5 years of age in Concordia, Argentina. Vaccination is a very effective public health strategy for reducing vaccine preventable diseases, with impact on burden of disease and hospitalization.

Community acquired pneumonia incidence among children less than 5 years of age in Concordia, Argentina: vaccination impact / Incidencia de la neumonía extrahospitalaria en menores de 5 años en Concordia (Argentina): repercusión de la vacunación / Incidência de pneumonia adquirida na comunidade em crianças menores de 5 anos em Concordia, Argentina: impacto da vacinação

ABSTRACT Objective To measure the effectiveness of pneumococcal conjugated vaccine (PCV13) against Community Acquired Pneumonia (CAP) and invasive pneumococcal disease, 2 years after the vaccine (2+1) was included into the National Immunization Program of Argentina, and to describe variables associated with bacterial pneumonia and hospitalization. Methods This was a prospective, population-based surveillance study of CAP incidence (ambulatory and hospitalized) among children less than 5 years of age in the Department of Concordia (Entre Rios, Argentina) from April 2014 - March 2016. The diagnosis of probable bacterial pneumonia (PBP) was determined following the standardized WHO protocol. Incidence during the post-vaccine introduction period was compared with the results from a previous study that used similar methodology for the pre-PCV13 introduction period from 2002 - 2005. Results During the study period, 330 patients had a clinical diagnosis of CAP, of which 92 were PBP (6 with pleural effusion). S. pneumoniae was not isolated from any sample. No factors associated with PBP were found in multivariable analysis. The decrease in PBP and pleural effusion was significant in relation to the previous study: 63% (P < 0.0001) and 80.9% (P < 0.003), respectively. PCV13 uptake was 97.3% for the 1st dose and 84.8% for the booster dose. Conclusions PCV13 was effective to reduce incidence of consolidated pneumonia and pleural effusion, among children less than 5 years of age in Concordia, Argentina. Vaccination is a very effective public health strategy for reducing vaccine preventable diseases, with impact on burden of disease and hospitalization.

RESUMEN Objetivo Medir la efectividad de la vacuna antineumocócica conjugada (VNC13)contra la neumonía extrahospitalaria y las enfermedades neumocócicas invasoras, dos años después de que se incorporara la vacuna (2+1) en el Programa Nacional de Vacunación de Argentina, y describir las variables asociadas con la neumonía bacteriana y la hospitalización. Métodos Se llevó a cabo un estudio prospectivo de vigilancia poblacional de la incidencia de la neumonía extrahospitalaria (pacientes ambulatorios y hospitalizados) en menores de 5 años en el departamento Concordia (Entre Ríos, Argentina) desde abril del 2014 hasta marzo del 2016. Se determinó el diagnóstico de probable neumonía bacteriana según el protocolo estandarizado de la OMS. Se comparó la incidencia durante el período posterior a la incorporación de la vacuna con los resultados de un estudio anterior en el que se usó una metodología similar para el período previo a la incorporación de la VNC13 entre el 2002 y el 2005. Resultados Durante el estudio, 330 pacientes presentaron un diagnóstico clínico de neumonía extrahospitalaria, de los cuales 92 presentaron probable neumonía bacteriana (6 con derrame pleural). No se aisló ninguna muestra del S. pneumoniae. No se encontraron factores asociados con la neumonía bacteriana probable en el análisis multivariante. La disminución de la neumonía bacteriana probable y el derrame pleural fue significativa en relación con el estudio anterior: 63 % (P < 0,0001) y 80,9 % (P < 0,003), respectivamente. La absorción de la VNC13 fue de 97,3 % para la primera dosis y de 84,8 % para la dosis de refuerzo. Conclusiones La VNC13 fue efectiva para reducir la incidencia consolidada de derrame pleural y neumonía en menores de 5 años en Concordia (Argentina). La vacunación es una estrategia de salud pública muy efectiva para reducir las enfermedades prevenibles por vacunación, con repercusión en la carga de enfermedad y la hospitalización.

RESUMO Objetivo Avaliar a efetividade da vacina pneumocócica conjugada (PCV13) em prevenir pneumonia adquirida na comunidade (PAC) e doença pneumocócica invasiva (DPI) após 2 anos da incorporação da vacina (2 + 1) ao Programa Nacional de Vacinação da Argentina e descrever as variáveis associadas à ocorrência de pneumonia bacteriana e internação hospitalar. Métodos Estudo prospectivo de base populacional de vigilância da incidência de PAC (atendimento ambulatorial e em internação hospitalar) em crianças menores de 5 anos de idade realizado no Departamento de Concordia, Entre Rios, na Argentina, de abril de 2014 a março de 2016. O diagnóstico de provável pneumonia bacteriana foi determinado segundo o protocolo padronizado da OMS. A incidência no período pós-introdução da vacina foi comparada aos resultados de um estudo anterior realizado com metodologia semelhante no período pré-introdução da PCV13 de 2002 a 2005. Resultados No período de estudo, foi feito o diagnóstico clínico de PAC em 330 pacientes, dos quais 92 foram casos de provável pneumonia bacteriana (6 com derrame pleural). A bactéria Streptococcus pneumoniae não foi isolada em nenhuma amostra. Não foi observado nenhum fator associado à provável pneumonia bacteriana na análise multivariada. Houve uma redução significativa da ocorrência de provável pneumonia bacteriana e derrame pleural em relação ao estudo anterior: 63% (P < 0,0001) e 80,9% (P < 0,003), respectivamente. A cobertura vacinal de PCV13 foi de 97,3% para a primeira dose e 84,8% para a dose de reforço. Conclusões A PCV13 foi efetiva em reduzir a incidência de pneumonia com consolidação e derrame pleural em crianças menores de 5 anos em Concordia, na Argentina. A vacinação é uma estratégia de saúde pública muito efetiva para reduzir doenças que podem ser evitadas com vacina, com impacto na morbidade e nas internações hospitalares.

Characterization of Streptococcus pneumoniae invasive serotype 19A isolates from Argentina (1993-2014).

The aim of this study was to characterize Streptococcus pneumoniae serotype 19A isolates causing invasive pneumococcal disease in children, collected in Argentina between 1993 and 2014. A total of 176 isolates serotype 19A were analyzed. There was an increase in the proportion of serotype 19A isolates from 3% in 1993 to 6% in 2011, prior to the introduction of PCV13 in 2012, and from 2012 to 2014 its proportion gradually decreased. Penicillin resistance among serotype 19A isolates throughout the study period was 65.9%, but a significant increase was observed from 0% in 1993 to 87.5% in 2014. Genetic relationship of the isolates was determined by PFGE and selected strains were studied by MLST. Most of the isolates belonged to two clonal types: A (54.5%) and B (11.4%). Isolates of clonal type A were ST1131, a single locus variant of ST172 and accounted for 54% of the total collection. They were detected for the first time in our country in 1997 and most of them (93%) were penicillin non susceptible. Isolates of clonal type B were ST8121, a single locus variant of ST199, and were mainly susceptible to penicillin. These two clonal types are still in circulation and appear to be responsible for the dissemination of S. pneumoniae serotype 19A invasive isolates in our country.

[Infection by Bordetella pertussis and bordetella parapertussis in cases of suspected whooping cough (2011-2015) in Mar del Plata, Argentina]. / Infección por Bordetella pertussis y bordetella parapertussis en casos con sospecha de coqueluche (2011-2015). Mar del Plata, Argentina.

OBJECTIVES: . To classify the study population in the Argentinian National Health Surveillance System framework, determine the proportion of infection by Bordetella pertussis and Bordetella parapertussis, and identify factors associated with the cases of suspected whooping cough attended to in the city of Mar del Plata and its outskirts during the period 2011- 2015. MATERIALS AND METHODS: An observational and descriptive study was carried out. Clinical cases with suspicion of whooping cough were diagnosed by laboratory. The laboratory studies consisted of culture, PCR, and serology using the ELISA technique. RESULTS: A total of 572 cases were evaluated. The female sex was the most frequent (51.9%). The most frequent age range was 2 to 17 moths (51.1%; 290/568), which was also the group with the most confirmed cases. Only 47.8% (155/324) of the population studied had complete vaccination for their age. Whooping cough due to B. pertussis was confirmed in 15.5% (89/572) of cases and one case with B. parapertussis. Those cases that had contact with a coughing relative were significantly associated with the confirmation of Bordetella spp. by the laboratory (odds ratio: 3.3; 95% confidence interval: 1.9-5.4). CONCLUSIONS: The results show the need to suspect whooping cough and diagnose it early in children, adolescents, and adults in order to better control the disease. Likewise, continuing prevention and containment measures are fundamental in decreasing the circulation of the causal agent.

Infección por Bordetella pertussis y bordetella parapertussis en casos con sospecha de coqueluche (2011-2015). Mar del Plata, Argentina / Infection by Bordetella pertussis and bordetella parapertussis in cases of suspected whooping cough (2011-2015) in Mar del Plata, Argentina

RESUMEN Objetivos Caracterizar la población en estudio en el marco del Sistema Nacional de Vigilancia de Salud de la Argentina, determinar la proporción de infección por Bordetella pertussis y Bordetella parapertussis e identificar factores asociados de los casos con sospecha de coqueluche atendidos en la ciudad de Mar del Plata y alrededores durante el período 2011- 2015. Materiales y Métodos Se realizó un estudio observacional y descriptivo. Se diagnosticaron por laboratorio casos clínicos con sospecha de coqueluche. Los estudios de laboratorio consistieron en cultivo, PCR y serología por técnica de ELISA. Resultados Se evaluaron 572 casos. El sexo femenino fue el más frecuente con 51,9% (296/570), el rango etario más frecuente fue de 2 a 17 meses con 51,1% (290/568) que fue además el grupo con más casos confirmados. Solo el 47,8% (155/324) de la población estudiada tenía vacunación completa para su edad. Se confirmó coqueluche por Bordetella pertussis en el 15,5 % y un solo caso con Bordetella parapertussis. Hubo asociación entre tener un contacto familiar tosedor por más de dos semanas con la confirmación de Bordetella spp. (odds ratio [OR]: 3,3; [intervalo de confianza al 95%] IC 95%: 1,9 - 5,4). Conclusiones Existe la necesidad de realizar una evaluación oportuna de los casos sospechosos de coqueluche tanto en niños como en adolescentes y adultos para lograr un mejor control de la enfermedad. Asimismo, continuar con las medidas de prevención y de contención resulta fundamental para disminuir la circulación del agente causal.

ABSTRACT Objectives . To classify the study population in the Argentinian National Health Surveillance System framework, determine the proportion of infection by Bordetella pertussis and Bordetella parapertussis, and identify factors associated with the cases of suspected whooping cough attended to in the city of Mar del Plata and its outskirts during the period 2011- 2015. Materials and Methods An observational and descriptive study was carried out. Clinical cases with suspicion of whooping cough were diagnosed by laboratory. The laboratory studies consisted of culture, PCR, and serology using the ELISA technique. Results A total of 572 cases were evaluated. The female sex was the most frequent (51.9%). The most frequent age range was 2 to 17 moths (51.1%; 290/568), which was also the group with the most confirmed cases. Only 47.8% (155/324) of the population studied had complete vaccination for their age. Whooping cough due to B. pertussis was confirmed in 15.5% (89/572) of cases and one case with B. parapertussis. Those cases that had contact with a coughing relative were significantly associated with the confirmation of Bordetella spp. by the laboratory (odds ratio: 3.3; 95% confidence interval: 1.9-5.4). Conclusions The results show the need to suspect whooping cough and diagnose it early in children, adolescents, and adults in order to better control the disease. Likewise, continuing prevention and containment measures are fundamental in decreasing the circulation of the causal agent.

Meningococcal Disease in Children in Argentina A 3-year Active Sentinel Hospital Surveillance Study.

BACKGROUND: Meningococcal disease (MD) is a medical emergency and a serious public health problem. As new meningococcal vaccines become available, MD surveillance is crucial to provide baseline epidemiologic data before implementing preventive measures. We estimated MD incidence and epidemiology in Argentina using hospital-based surveillance. METHODS: Three-year prospective active surveillance in patients ≤15 years of age was conducted at 6 pediatric hospital sentinel units (March 2012 to February 2015). RESULTS: Of 184,360 hospitalized patients, 1444 (0.78%) had suspected meningitis or MD. Of these, 268 (19%) presented probable acute bacterial meningitis or MD, 168 (63%) were culture positive and 51 (30%) tested positive for Neisseria meningitidis. Of 100 culture-negative cases, 30 had positive meningococcal polymerase chain reaction. Thirteen patients presented other uncommon MD manifestations, resulting in a total of 94 MD cases and an annual incidence of 5.1/10 hospitalized patients [95% confidence interval (CI): 4-6]. Fifty-four (57%) patients were males, 48% were <1 year of age and the median age was 12.5 months (1 month to 15 years). Clinical presentations were the following: meningococcemia and meningitis (37%), meningitis (30%), meningococcemia (16%), arthritis (10%), bacteremia (5%) and pneumonia (2%). Twenty-eight percent had complications. Nine children died (case fatality rate: 10%), and 8 had sequelae. Serogroups were identified for 84 isolates. Serogroup W was associated with age <1 year (odds ratio: 3.18; 95% CI: 1.14-8.99); meningococcemia was associated with mortality (P = 0.0038). CONCLUSIONS: Highest rates of MD were observed among young infants. This study provides baseline data to estimate the impact of introducing meningococcal vaccines in Argentina.

[Pneumococcal meningitis in children under 15 years of age in Misiones (Argentina). Sixteen year's epidemiological surveillance]. / Meningitis neumocócica en niños menores de 15 años. Dieciséis años de vigilancia epidemiológica en Misiones, Argentina.

We report the results of pneumococcal meningitis surveillance conducted at the Provincial Pediatric Hospital of Posadas, Misiones (Argentina), before the conjugate vaccine was introduced into the national vaccination schedule. Between January 1994 and December 2009, 167 cases of Streptococcus pneumoniae meningitis were diagnosed in children aged 1 month to 15 years. The attack rate/100,000 children ranged from 19.2 (1997) to 4.3 (2009), with a mean of 10.6 and a tendency to decrease (y=-0.689x+16.52). The number of cases per 100,000 children decreased from 146.6 to 34.8 and particularly involved the group of children aged 1 to 11 months (94/167, 56%). Thirty point seven percent (30.7%) (46/150) of the isolates were resistant to penicillin whereas 16.7% (25/150) were non-susceptible to cefotaxime. ß-lactam resistance increased as from 1997 and began to decline in 2005. Nineteen serotypes were detected; type 14 was predominant and accounted for 32% (40/125). Eighty four point eight percent (84.8%) of the isolates were circumscribed to nine serotypes: 14, 5, 1, 7F, 18C, 6B, 9N, 9V and 4. Theoretical coverage for patients aged <2 years and >2 years was 84.1% (74/88) and 83.8% (31/37) for the 10-valent vaccine and 89.8 % (79/88) and 83.8% (31/37) for the 13-valent vaccine respectively. Penicillin resistance was restricted to 8 serotypes (14, 6B, 6A, 9V, 4, 23B, 19A1) and nonsusceptibility to cefotaxime was circumscribed to 3 serotypes (14, 9V and 1). This study will allow to evaluate the impact of the implementation of conjugate vaccines on our area.

Meningitis neumocócica en niños menores de 15 años: Dieciséis años de vigilancia epidemiológica en Misiones, Argentina / Pneumococcal meningitis in children under 15 years of age in Misiones (Argentina): Sixteen year's epidemiological surveillance

Se presentan en este trabajo los resultados de 16 años de vigilancia epidemiológica de meningitis neumocócica llevada a cabo en el Hospital Provincial de Pediatría de Misiones (Argentina), antes de la introducción de la vacuna conjugada al calendario nacional. En el período que va de enero de 1994 a diciembre de 2009 se diagnosticaron 167 casos de meningitis por Streptococcus pneumoniae en niños (1 mes-15 años). La tasa de ataque cada 100 000 niños varió entre 19,2 (1997) y 4,3 (2009), con una media de 10,6 y una tendencia en disminución (y = ""0,689x + 16,52). Esto fue a expensas del grupo de niños entre 1 y 11 meses (94/167, 56 %), en el que disminuyó de 146,6 a 34,8 casos cada 100 000 niños. El 30,7 % de los aislamientos (46/150) fueron resistentes a penicilina y el 16,7 % (25/150) no sensibles a cefotaxima. La resistencia a β-lactámicos se incrementó a partir de 1997 y comenzó a disminuir en 2005. Se detectaron 19 serotipos, predominó el 14 (32 %; 40/125). El 84,8 % de los aislamientos quedaron circunscriptos a nueve serotipos: 14, 5, 1, 7F, 18C, 6B, 9N, 9V y 4. La cobertura teórica en los niños < 2 años y > 2 años fue de 84,1 % (74/88) y 83,8 % (31/37) con la vacuna 10-valente, y de 89,8 % (79/88) y 83,8 % (31/37) con la vacuna 13-valente, respectivamente. La resistencia a penicilina estuvo circunscripta a 8 serotipos (14, 6B, 6A, 9V, 4, 23B, 1 y 19A), y la no sensibilidad a cefotaxima a 3 serotipos (14, 9V y 1), el más importante fue en ambos casos el serotipo 14. Este estudio permitirá evaluar el impacto de la implementación de las vacunas conjugadas en nuestra zona.

We report the results of pneumococcal meningitis surveillance conducted at the Provincial Pediatric Hospital of Posadas, Misiones (Argentina), before the conjugate vaccine was introduced into the national vaccination schedule. Between January 1994 and December 2009, 167 cases of Streptococcus pneumoniae meningitis were diagnosed in children aged 1 month to 15 years. The attack rate/100,000 children ranged from 19.2 (1997) to 4.3 (2009), with a mean of 10.6 and a tendency to decrease (y=""0.689x+16.52). The number of cases per 100,000 children decreased from 146.6 to 34.8 and particularly involved the group of children aged 1 to 11 months (94/167, 56%). Thirty point seven percent (30.7%) (46/150) of the isolates were resistant to penicillin whereas 16.7% (25/150) were non-susceptible to cefotaxime. β-lactam resistance increased as from 1997 and began to decline in 2005. Nineteen serotypes were detected; type 14 was predominant and accounted for 32% (40/125). Eighty four point eight percent (84.8%) of the isolates were circumscribed to nine serotypes: 14, 5, 1, 7F, 18C, 6B, 9N, 9V and 4. Theoretical coverage for patients aged <2 years and >2 years was 84.1% (74/88) and 83.8% (31/37) for the 10-valent vaccine and 89.8 % (79/88) and 83.8% (31/37) for the 13-valent vaccine respectively. Penicillin resistance was restricted to 8 serotypes (14, 6B, 6A, 9V, 4, 23B, 19A1) and nonsusceptibility to cefotaxime was circumscribed to 3 serotypes (14, 9V and 1). This study will allow to evaluate the impact of the implementation of conjugate vaccines on our area.

Vigilancia de serotipos en infecciones invasivas por Haemophilus influenzae en la Argentina en la era de la vacuna conjugada contra el serotipo b durante el período 2005-2010 / Surveillance of Haemophilus influenzae serotypes in Argentina from 2005 to 2010 during the Haemophilus influenzae type b conjugate vaccine era

La introducción de la vacuna contra Haemophilus influenzae tipo b en los programas de inmunización de muchos países produjo una reducción marcada en la incidencia de enfermedad invasiva causada por este serotipo y en su portación y un incremento de otros tipos capsulares y de aislamientos no capsulados. Se estudiaron 313 aislamientos de H. influenzae recuperados de sitio estéril, provenientes de pacientes pediátricos y adultos con enfermedad invasiva atendidos en 90 hospitales de la Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas durante el período 2005-2010. Las patologías más frecuentes fueron neumonía, 40,3 % (n = 126), meningitis, 30,0 % (n = 94) y bacteriemia, 26,5 % (n = 83). En los pacientes pediátricos (n = 279), la mayor frecuencia de aislamientos correspondió a menores de 2 años, 74,5 % (n = 208). Con respecto a la distribución de tipos, el 61,3 %, correspondió a H. influenzae no capsulados (n = 192); el 20,1 % al b (n = 63); 11,2 % al a (n = 35); 4,8 % al f y 2,6 % a otros. En meningitis predominaron H. influenzae capsulados mientras que en neumonía y bacteriemia resultaron dominantes los tipos no capsulados. Se determinó el biotipo en 306 aislamientos. Todos los aislamientos de tipo a correspondieron al biotipo II; el 66,7 % de los tipo b pertenecieron al biotipo I. Mediante las técnicas de aglutinación en lámina y PCR se estudiaron 220 aislamientos; la concordancia entre ambas fue de 0,982 (IC: 0,92-1,00). En el último año se encontró un aumento significativo del tipo b, lo cual indica la importancia de mantener la vigilancia clínica y laboratorial de la enfermedad invasiva por H. influenzae.

The introduction of the Haemophilus influenzae type b vaccine in the immunization programs of many countries has greatly reduced this invasive disease and the carriage caused by this serotype, also increasing other capsular types and non-capsular isolations. There were 313 isolations of H. influenzae under study, which were recovered from a sterile site coming from pediatric and adult patients carrying the invasive disease. Patients were treated at 90 different hospitals belonging to the Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas (National Lab Network for Meningitis and Acute Bacterial Respiratory Infections) from 2005 to 2010 for the following disorders: pneumonia, 40.3% (n = 126), meningitis, 30.0% (n = 94) and bacteremia, 26.5% (n = 83). In pediatric patients (n = 279), the highest frequency of isolations corresponded to children under the age of 2 years, 74.5% (n = 208). Regarding type distribution, 61.3% corresponded to non-capsular H. influenzae (n = 192), 20.1% to type b (n = 63), 11.2% to type a (n = 35), 4.8% to type f, and 2.6% to other types. Capsular H. influenzae was predominant in meningitis whereas non-capsular H. influenzae in pneumonia and bacteremia. The biotype was determined in 306 isolations. The totality (100%) of type a (n = 35) was biotype II whereas 66.7% of type b (n = 63) was biotype I. Slide agglutination and PCR tests were used in 220 isolations. There was a match of 0.982 (IC: 0.92-1.00) between them. During the last year, there was a great increase in type b, showing the importance of clinical and laboratory-based surveillance of the invasive disease caused by H. influenzae.

Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines.

A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AOM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

Phenotypic and genotypic characteristics of Neisseria meningitidis disease-causing strains in Argentina, 2010.

Phenotypic and genotypic characterization of 133 isolates of Neisseria meningitidis obtained from meningococcal disease cases in Argentina during 2010 were performed by the National Reference Laboratory as part of a project coordinated by the PAHO within the SIREVA II network. Serogroup, serotype, serosubtype and MLST characterization were performed. Minimum Inhibitory Concentration to penicillin, ampicillin, ceftriaxone, rifampin, chloramphenicol, tetracycline and ciprofloxacin were determined and interpreted according to CLSI guidelines. Almost 49% of isolates were W135, and two serotype:serosubtype combinations, W135:2a:P1.5,2:ST-11 and W135:2a:P1.2:ST-11 accounted for 78% of all W135 isolates. Serogroup B accounted for 42.1% of isolates, and was both phenotypically and genotypically diverse. Serogroup C isolates represented 5.3% of the dataset, and one isolate belonging to the ST-198 complex was non-groupable. Isolates belonged mainly to the ST-11 complex (48%) and to a lesser extent to the ST-865 (18%), ST-32 (9,8%) and the ST-35 complexes (9%). Intermediate resistance to penicillin and ampicillin was detected in 35.4% and 33.1% of isolates respectively. Two W135:2a:P1.5,2:ST-11:ST-11 isolates presented resistance to ciprofloxacin associated with a mutation in the QRDR of gyrA gene Thr91-Ile. These data show serogroup W135 was the first cause of disease in Argentina in 2010, and was strongly associated with the W135:2a:P1.5,2:ST-11 epidemic clone. Serogroup B was the second cause of disease and isolates belonging to this serogroup were phenotypically and genotypically diverse. The presence of isolates with intermediate resistance to penicillin and the presence of fluorquinolone-resistant isolates highlight the necessity and importance of maintaining and strengthening National Surveillance Programs.

Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines / Distribución de serotipos de neumococos aislados de pacientes pediátricos con otitis media aguda e infecciones invasivas y su cobertura potencial a través de vacunas conjugadas

A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AÜM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

Se realizó un estudio prospectivo descriptivo sobre la distribución de serotipos de neumococos aislados de niños con otitis media aguda (OMA) y con infecciones invasivas (INV) en un período de 16 meses. Se incluyeron 89 niños con INV neumocócicas y 324 con un primer episodio de OMA. Trescientos cuarenta y seis patógenos se aislaron de las secreciones de oído medio obtenidas de 250 pacientes. Se identificaron 30 serotipos y los más prevalentes fueron el 14, 19A, 9V, 3, 19F, 6A, 23F y 18C en OMA y el 14, 1, 19A, 5, 12F, 6B y 18C en INV. La cobertura potencial con la vacuna PCV10 sería de 46,5 % y 60,7 % para neumococos involucrados en OMA y en INV, respectivamente; con la PCV13, esta sería de 71,7 % y 73 %. La PCV10 conjugada con una proteína de Haemophilus tendría una cobertura inmunológica del 39,9 % para OMA, contra una cobertura del 18,5 % de la PCV13. Sin embargo, las diferencias en la prevención de INV fueron determinantes a la hora de considerar incorporarla al calendario nacional de vacunación para niños menores de 2 años en la Argentina.