Effect of coinfection with influenza virus and bacteria on host damage / Efecto de la coinfección por virus de la influenza y bacterias en el daño al hospedero

Abstract Background: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. Objective: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Method: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Results: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. Conclusions: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

Resumen Antecedentes: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. Objetivo: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. Método: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. Resultados: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. Conclusiones: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Hemolytic uremic syndrome associated with streptococcus pneumoniae in pediatrics: a case series / Síndrome hemolítico-urêmica associada com streptococcus pneumoniae em pediatria: série de casos

ABSTRACT Objective: To describe a case series of four (4) patients with hemolytic uremic syndrome due to Streptococcus pneumoniae in a level four complexity institution in the city of Bogotá, D.C., Colombia. Cases description: We describe cases of four patients who presented respiratory symptoms and fever. All four patients were in regular conditions on hospital admission, after which they required intensive care and ventilatory support. Upon admission, three cases showed evidence of pleuropulmonary complication. Penicillin-sensitive Streptococcus pneumoniae was isolated in all cases. All patients presented anemia, severe thrombocytopenia, schistocytes on peripheral blood smear, and hyperazotemia. They required blood transfusion and renal replacement therapy during their hospitalization. The patients were diagnosed with hemolytic uremic syndrome due to S. pneumoniae. Three of the four patients had a progressive recovery of the renal function and were discharged after an average of 36 days of hospital stay. The remaining patient had two amputations in the extremities due to thrombotic vascular complications and was discharged after 99 days of hospital stay, requiring hemodialysis every other day. Comments: Hemolytic uremic syndrome due to Streptococcus pneumoniae is a rare but severe complication of invasive pneumococcal disease. Complicated pneumonia is the main condition associated with this entity. It is noteworthy the short period in which these cases were presented, considering the low annual incidence of the disease.

RESUMO Objetivo: Descrever uma série de casos de quatro pacientes com síndrome hemolítico-urêmica por pneumococo em uma instituição de referência em Bogotá, Colômbia. Descrição dos casos: Descrevemos os casos de quatro pacientes que apresentaram sintomas respiratórios e febre. Todos estavam em estado geral regular à admissão hospitalar e necessitaram de cuidados intensivos e suporte ventilatório. Na admissão, em três dos casos foi evidenciada a complicação pleuropulmonar. Isolamento de Streptococcus pneumoniae sensível à penicilina foi realizado em todos os casos. Os quatro pacientes precisaram de transfusão sanguínea e terapia de reposição renal durante a hospitalização. Nos testes laboratoriais, observou-se anemia, trombocitopenia grave, presença de esquizócitos em esfregaço de sangue periférico e hiperazotemia. Com esse quadro, o diagnóstico foi de síndrome hemolítico-urêmica associada à infecção por S. pneumoniae. Houve recuperação progressiva da função renal em três dos quatro pacientes, que tiveram alta após 36 dias de internação hospitalar, em média. Um paciente teve complicações vasculares trombóticas, resultando em duas amputações nas extremidades, e teve alta após 99 dias de internação, com necessidade de hemodiálise em dias alternados. Comentários: A síndrome hemolítico-urêmica por Streptococcus pneumoniae é uma complicação rara, mas grave, da doença invasiva pneumocócica. A pneumonia complicada é a principal condição associada a essa entidade. Destaca-se o curto período em que esses casos foram apresentados, levando em conta a baixa incidência anual de síndrome hemolítico-urêmica.

Infecciones invasivas por serotipos no vacunales de Streptococcus pneumoniae: una amenaza creciente / Invasive infections by non-vaccine serotypes of Streptococcus pneumoniae: a growing threat

Resumen Introducción: En México, cuando se inició la aplicación de la vacuna PCV13 (neumocócica conjugada), se cubría el 70.6% de los serotipos causantes de enfermedad invasiva por neumococo en menores de 5 años. Después de varios años, los casos de enfermedad causada por los serotipos incluidos en la vacuna han disminuido; sin embargo, se ha producido un reemplazo por los serotipos no incluidos en la vacuna. Caso clínico: Se presentan tres casos de pacientes pediátricos que desarrollaron enfermedad invasiva por serotipos no incluidos en la PCV13: uno con meningitis y bacteriemia (serotipo 15C) y dos con neumonía, uno de ellos complicado con derrame (serotipo 35B). Los pacientes fueron atendidos en un hospital pediátrico en Saltillo, Coahuila, durante el periodo de 2015 a 2018. Conclusiones: Resulta alarmante que se presenten tres casos graves por serotipos de Streptococcus pneumoniae no incluidos en la PCV13 en un solo hospital pediátrico en el norte del país. Este es un fenómeno que esta sucediendo a escala nacional e internacional: un incremento de casos de enfermedad invasiva por serotipos de neumococo no incluidos en la vacuna utilizada actualmente.

Abstract Background: In Mexico, 70.6% of serotypes causing invasive pneumococcal disease were covered since the application of the PCV13 vaccine in children under 5 years of age. After several years of immunization, cases of disease caused by the serotypes included in the vaccine have decreased. However, a replacement due to serotypes not included in the vaccine has been observed. Case report: Three cases of pediatric patients who developed invasive disease due to serotypes not included in PCV13 are described: one with meningitis and bacteremia (serotype 15C), and two with pneumonia, of which one complicated with effusion (serotype 35B). Patients were treated in a pediatric hospital in Saltillo, Coahuila, from 2015 to 2018. Conclusions: Three serious cases due to serotypes of Streptococcus pneumoniae not included in PCV13 were reported in a single pediatric hospital in a northern state of Mexico. This phenomenon is taking place nationwide and worldwide: an increase of cases of invasive disease due to pneumococcal serotypes not included in the vaccine currently used.

Antimicrobial susceptibility and fluctuations in clonal complexes of serogroup 6 Streptococcus pneumoniae isolates collected from children in Beijing, China, between 1997 and 2016

ABSTRACT This study examined the antimicrobial susceptibility patterns and clonal complex (CC) characteristics of serogroup 6 Streptococcus pneumoniae isolates collected from children in Beijing, China, between 1997 and 2016. Serotypes were determined using the Quellung reaction, and the antimicrobial susceptibility profiles of the isolates were determined using the disc-diffusion method or by E-test. Sequence types (STs) were assigned based on multilocus sequence typing. A total of 250 isolates were examined, with 55.2%, 30.0%, 12.8%, and 2.0% of isolates identified as serotypes 6A, 6B, 6C, and 6D, respectively. All of the isolates were susceptible to levofloxacin and vancomycin, and the non-suceptibitility rate to penicillin was 41.6%. Eighty-two distinct STs, assigned to 13 CCs and 28 singletons, were identified. CC982 was the most prevalent CC amongst serotype 6A isolates (34%), followed by CC9789 and CC3173. Amongst serotype 6B isolates, CC90 and CC4542 were the most common, accounting for 25.3% and 14.7% of isolates respectively. Over the study period, the prevalence of CC982, CC4542, and CC4536 isolates showing susceptibility to penicillin and cefuroxime decreased, and the proportion of CC3173, CC9789, CC855, and CC902 isolates showing non-susceptibility to these two antibiotics increased.

Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital / Cobertura vacinal pneumocócica teórica: análise de sorotipos isolados de pacientes internados em hospital terciário

ABSTRACT Objective: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). Methods: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. Results: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. Conclusions: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.

RESUMO Objetivo: Avaliar os sorotipos de Streptococcus pneumoniae isolados de uma população internada em um hospital terciário para verificar a cobertura vacinal teórica das vacinas conjugada pneumocócica 13-valente (VCP13) e pneumocócica polissacarídica 23-valente (VPP23). Métodos: Estudo transversal envolvendo 118 pacientes internados no Hospital São Lucas, na cidade de Porto Alegre (RS), cujas amostras de cultura de sangue, líquor ou outro líquido estéril apresentaram isolados de pneumococos entre janeiro de 2005 e dezembro de 2016. A cobertura vacinal teórica foi estudada em relação aos sorotipos observados na amostra e sua relação com os contidos nas vacinas pneumocócicas disponíveis no Brasil. Resultados: A maioria da população era masculina (n = 66; 55,9%), com mediana de idade de 57 anos (intervalo interquartil: 33-72 anos). O agravo mais frequente foi pneumonia, e o pneumococo foi mais frequentemente isolado em hemocultura. Mais de um quarto da população estudada tinha algum grau de imunossupressão (n = 34; 28,8%). Na amostra geral, 39 pacientes (33,1%) foram a óbito. Não houve associações significativas do número de óbitos com o tipo de comorbidades, internação em UTI ou necessidade de ventilação mecânica. A cobertura vacinal teórica da VPP23 e da combinação VCP13 + VPP23 foi de 31,4% e 50,8%, respectivamente. Conclusões: Nesta amostra, se os pacientes tivessem sido previamente vacinados com a combinação VCP13 seguida de VPP23, teoricamente, 50,8% dos casos de doença pneumocócica invasiva que necessitaram de internação hospitalar poderiam ter sido prevenidos potencialmente. Essa doença deve ser prevenida com a vacinação não só de crianças e idosos, mas também de adultos em idade economicamente ativa, para reduzir o custo socioeconômico, a morbidade e a mortalidade ainda associados à doença, especialmente em países subdesenvolvidos.

Enfermedad neumocócica invasiva por serotipo 38, reporte de caso clínico / Invasive pneumococcal disease by serotype 38, a clinical case report

La enfermedad neumocócica invasiva (ENI) es causa de morbimortalidad prevenible en pediatría. Con la introducción de vacunas antineumocócicas conjugadas disminuyó la prevalencia de ENI en 61,9% en los menores de 2 años, y se produjo un cambio en la distribución de serotipos y un aumento de ENI por serotipos no vaccinales. En este contexto, es relevante la vigilancia epidemiológica de los serotipos emergentes causantes de ENI en la población. Se presentará el caso de una lactante de 11 meses con diagnóstico de meningitis causada por neumococo serotipo 38, su evolución y consecuencias clínicas, y se realiza un análisis de la situación epidemiológica actual.

In pediatrics,invasive pneumococcal disease is a preventable cause ofmorbidity andmortality.The introduction of conjugated pneumococcal vaccines has reduced the prevalence of invasive pneumococcal disease by 61.9% in the under two's and has brought about a change in the distribution of serotypes and a rise in invasive pneumococcal disease caused by non-vaccine serotypes.This being the case,itis very importanttomonitorthe epidemiology ofthe emerging serotypes causing the disease in the population.We presentthe case of an 11 month old infant diagnosed with meningitis caused by serotype 38, describing his clinical course andclinical consequences; andweperforman analysis ofthepresent epidemiologica lsituation

Molecular characterization of non-vaccine Streptococcus pneumoniae serotypes 11A, 15 B/C and 23A recovered from invasive isolates in Colombia / Caracterización molecular de los serotipos no vacunales 11A, 15 B/C y 23A de Streptococcus pneumoniae recuperados de aislamientos invasivos en Colombia

Resumen Introduction: A total of 192 invasive Streptococcus pneumoniae isolates, from serotypes 11A, 15B/C and 23A (not included in the conjugated vaccines), were collected in Colombia between 1994 and 2014 as part of the activities of the Network surveillance system for the causative agents of pneumonia and meningitis (SIREVA II). Objective: To determine the molecular characteristics ofinvasive S. pneumoniaeisolates from serotypes 11A, 15B/C and 23A in Colombia from 1994 to 2014. Materials and methods: The molecular characterization of the isolates was carried out through Pulse-Field Gel Electrophoresis (PFGE) and Multilocus Sequence Typing (MLST). Results: Serotype 11A showed one clonal group represented by ST62. Serotype 15B/C was composed of three groups associated with Netherlands15B-37 ST199 (28.75%), ST8495 (18.75%), and SLV (Single-Locus Variant) of ST193 (21.25%). Isolates from serotype 23A were gathered in three clonal groups, with70.21% closely related toST42, 17.02% to Colombia23F-ST338, and6.38% to Netherlands15B-37 ST199. Conclusion: Clones Colombia23F-ST338 andNetherlands15B-ST199 covered more serotypes than those previously found by other authors, including serotype 23A. These analyses reveal the importance of capsular switching in the spreading of successful clones among non-vaccine serotypes causing invasive pneumococcal disease.

Abstract Introducción. En Colombia se recolectaron 192 aislamientos invasivos de Streptococcus pneumoniae de los serotipos 11A, 15B/C y 23A (no incluidos en las vacunas conjugadas) entre 1994 y 2014, como parte de las actividades del Sistema de Redes de Vigilancia de los Agentes Responsables de Neumonías y MeningitisBacterianas (SIREVA II). Objetivo. Determinar las características moleculares de aislamientosinvasivos de los serotipos11A, 15B/C y 23A de S. pneumoniae recolectados en Colombia entre 1994 y 2014. Materiales y métodos. La caracterización molecular de los aislamientos se hizo medianteelectroforesis en gel de campo pulsado (Pulse-Field Gel Electrophoresis, PFGE) y por tipificación de secuencias multilocus (Multilocus Sequence Typing, MLST). Resultados. El serotipo 11A mostró un grupo clonal representadopor el ST62, en tanto que el serotipo15B/C se distribuyó en tres grupos asociados conlos clones Netherlands15B-37 ST199 (28,75 %), ST8495 (18,75 %) y SLV (variante en un solo locus) de ST193 (21,25 %). Los aislamientos con serotipo 23A se agruparon en tres gruposclonales; 70,21 % de ellos estaban estrechamente relacionadoscon elST42, 17,02 % con elColombia23F-ST338, y 6,38 % con el Netherlands15B-37 ST199. Conclusión. Los clones Colombia23F-ST338 y Netherlands15B-ST199 encontrados en este estudio abarcaronmás serotipos de los reportados previamente por otros autores, incluido el serotipo23A. Estos análisis revelan laimportancia de la conmutación(switching) capsular en la expansión de clones exitosos entre los serotipos no vacunales como causa de enfermedad invasiva neumocócica.

Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria

Abstract The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011-2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p < 0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin - 46.5%, trimethoprim-sulfamethoxazole - 45.4%, erythromycin - 43.9%, tetracycline - 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions.

The virulence of Streptococcus pneumoniae partially depends on dprA

Abstract Streptococcus pneumoniae is one of the most frequent opportunistic pathogens worldwide. DNA processing protein A (DprA) is an important factor involved in bacterial uptake and DNA integration into bacterial genome, but its role in S. pneumoniae virulence remains unclear. The aim of this study was to characterize the effects of the pneumococcal dprA gene on the pathogenesis of S. pneumoniae. To construct a dprA-deficient pneumococcal strain, the dprA gene of the S. pneumoniae strain D39 was inactivated. The virulence of this dprA-deficient strain, designated ΔD39, was compared with that of the wild-type strain by evaluating their respective capabilities to adhere to human pulmonary epithelial cells (PEC-A549) and by analyzing their choline-binding protein expression levels. In addition, the expression profiles of genes associated with virulence and host survival assays were also conducted with the mutant and the wild-type strain. Our results indicate that the capability of ΔD39 to adhere to the PEC-A549 airway cells was significantly lower (p < 0.01) compared with D39. Additionally, the 100-KD choline-binding protein was not detected in ΔD39. The addition of competence-stimulating peptide (CSP) lead to a significantly reduction of psaA mRNA expression in the dprA-deficient mutant and an increased level of psaA transcripts in the wild-type strain (p < 0.01). The median survival time of mice intraperitoneally infected with ΔD39 was significantly higher (p < 0.01) than that of mice infected with D39. The results of this study suggest that DprA has a significant effect on virulence characteristics of S. pneumoniae by influencing the expression of choline-binding protein and PsaA.

Bacteriemia oculta en niños atendidos en el Complejo Asistencial Dr. Sótero del Río: experiencia post vacuna neumocóccica conjugada / Occult bacteremia in Sótero del Río Hospital: experience after pneumococcal conjugated vaccine

Background: Occult bacteremia (OB) is one of the possible diagnoses of children younger than 3 years with fever without source in the emergency room. Objective: describe OB in the era after introduction of pneumococcal vaccine in Chile. Patients and Methods: Prospective descriptive review of data of children with possible OB diagnosis, referred from the emergency department between 2010-2013. Results: Possible OB was diagnosed on 391 patients. 233 had focus, mainly respiratory virus and urinary tract infection. On 158 patients, probable BO was diagnosed, 20 had proven OB from which 15 had positive blood culture for Streptococcus pneumoniae. From these, 7 were fully or partially vaccinated. The serotype was identified on 14 cases: 6 were PCV10 vaccine serotypes (none of them vaccinated), 2 were serotype related (both partially vaccinated) and 6 were non vaccine serotypes (partially or totally vaccinated). Discussion: It is necessary to improve diagnostic methods for respiratory viruses and urinary tract infections and try to expand coverage of pneumococcal conjugated vaccines in the pediatric population in order to reduce the risk of invasive pneumococcal disease in Chile.

Introducción: La bacteriemia oculta (BO) es uno de los diagnósticos que se plantean en los niños bajo 3 años de edad que se presentan con fiebre sin foco en el servicio de urgencia. Objetivo: Describir el diagnóstico de BO luego de la introducción de la vacunación universal para Streptococcus pneumoniae en Chile. Materiales y Métodos: Revisión descriptiva de seguimiento prospectivo de datos de niños con diagnóstico de BO posible derivados del SU entre 2010 y 2013. Resultados: Se diagnosticó BO posible en 391 pacientes. En 233 pacientes se encontró foco, siendo infecciones respiratorias virales e infección urinaria las más frecuentes. En 158 pacientes se diagnosticó BO probable, en 20 BO probada y 15 tuvieron hemocultivos positivos para S. pneumoniae. De estos últimos 7 estaban total o parcialmente vacunados. Se identificó serotipo en 14 casos: 6 serotipos vaccinales incluidos en PCV10 (ninguno vacunado), 2 serotipos relacionados (ambos parcialmente protegido) y 6 serotipos no vaccinales (parcial o totalmente vacunados). Discusión: Es necesario mejorar las técnicas diagnósticas de infecciones respiratorias virales e infección urinaria e intentar ampliar la cobertura de las vacunas neumocóccicas conjugadas en la población pediátrica, para reducir el riesgo de enfermedades neumocóccicas invasoras en Chile.

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.

Endocardite pneumocócica em válvula aórtica nativa - apresentação fulminante / Native aortic valve pneumococcal endocarditis - fulminant presentation

RESUMO A endocardite pneumocócica é uma entidade rara, cuja incidência se situa entre 1% e 3% dos casos de endocardite de válvula nativa. Esta patologia tem um prognóstico naturalmente adverso, com elevada mortalidade. Relata-se predileção pela válvula aórtica, de forma que é frequente que se apresente com insuficiência cardíaca. Apresentamos o caso de uma paciente do sexo feminino com 60 anos de idade e história pregressa de sinusite, admitida com diagnóstico de pneumonia. Após rápida deterioração, com sinais de choque séptico, ela foi transferida para a unidade de terapia intensiva. O ecocardiograma transesofágico revelou grave refluxo aórtico, devido à presença de vegetações valvares. As hemoculturas foram positivas para Streptococcus pneumoniae. A paciente foi submetida à cirurgia cardíaca e apresentou múltiplas complicações pós-operatórias. Apesar disso, apresentou lenta, porém completa recuperação. A endocardite infecciosa deve ser afastada em caso do surgimento de qualquer suspeita, e a ecocardiografia deve ser realizada precocemente nos pacientes com resposta insuficiente aos vasopressores e inotrópicos. Pacientes com endocardite pneumocócica se beneficiam de uma abordagem agressiva, com realização precoce da intervenção cirúrgica.

ABSTRACT Pneumococcal endocarditis is a rare entity, corresponding to 1 to 3% of native valve endocarditis cases. It has a typically adverse prognosis, with high mortality. There is a reported predilection for the aortic valve; thus, a common presentation is acute left heart failure. We present a case of a 60-year-old woman with a history of sinusitis, who was admitted with the diagnosis of pneumonia. She rapidly deteriorated with signs of septic shock and was transferred to the critical care unit. The transesophageal echocardiogram revealed severe aortic regurgitation due to valve vegetations. Blood cultures were positive for Streptococcus pneumoniae. She underwent cardiac surgery and had multiple postoperative complications. Nonetheless, the patient made a slow and complete recovery. Infectious endocarditis should be ruled out if any suspicion arises, and echocardiography should be performed in an early stage in patients with poor response to vasopressors and inotropes. Patients with pneumococcal endocarditis benefit from an aggressive approach, with performance of early surgery.

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing noninvasive diseases in a Children's Hospital, Shanghai

Background: Streptococcus pneumoniae, which cause noninvasive pneumococcal diseases, severely impair children's health. This study analyzed serotype distribution and antimicrobial resistance of S. pneumoniae from January 2012 to December 2012 in a Children's Hospital, Shanghai. Methods: A total of 328 pneumococcal isolates were serotyped by multiplex sequential PCR and/or capsule-quellung reaction. The minimum inhibitory concentrations for 11 antimi- crobial agents were determined by broth microdilution method. Results: Among 328 strains, 19F (36.3%), 19A (13.4%), 6A (11.9%), 23F (11.0%), 14 (5.8%), 6B (5.2%), and 15B/C (4.3%) were the most common serotypes. The coverage rates of 7-, 10-, and 13-valent conjugate vaccines (PCV7, PCV10, and PCV13) were 58.2%, 58.2%, and 84.1%, respectively. Out of the isolates, 26 (7.9%) strains were penicillin resistant. Most of the strains displayed high resistance rate to macrolides (98.5% to erythromycin, 97.9% to azithromycin, and 97.0% to clindamycin). Conclusions: The potential coverage of PCV13 is higher than PCV7 and PCV10 because of the emergence of 19A and there should be long-term and systematic surveillance for non-vaccine serotypes. .

Infección invasiva por Streptococcus pneumoniae: reporte de caso de un paciente con síndrome de Austrian / Invasive Streptococcus pneumoniae infection (Austrian syndrome): a case report

Descrito inicialmente en 1957 por Robert Austrian, el síndrome que lleva su nombre se define como la tríada de neumonía, endocarditis y meningitis secundarias a una infección invasiva por Streptococcus pneumoniae . Desde entonces, y debido a su infrecuencia, se han reportado muy pocos casos en la literatura científica. A continuación se presenta el caso de un paciente de 61 años de edad con un cuadro inicial de meningitis bacteriana por S. pneumoniae , acompañado de neumonía bacteriana e insuficiencia mitral grave asociada a cuatro vegetaciones sobre la cara auricular de la valva posterior, con ruptura y prolapso de su festón central posterior. Se aisló S. pneumoniae , serotipo 18C, en líquido cefalorraquídeo y en dos hemocultivos. El paciente recibió antibióticos de amplio espectro y fue sometido a reemplazo valvular temprano con un resultado clínico satisfactorio. El principal factor pronóstico de esta condición lo determina el daño valvular subsecuente, sobre todo en pacientes con compromiso de la válvula aórtica, por lo que es necesario identificar tempranamente la extensión del compromiso valvular y definir oportunamente el tratamiento quirúrgico y antibiótico del paciente. En casos menos frecuentes, en los que solo hay compromiso de la válvula mitral, la evolución clínica es menos aguda y, por lo general, el tratamiento antibiótico dirigido y las medidas de soporte avanzado suelen ser suficientes para su control.

Austrian syndrome is defined as the triad consisting of pneumonia, endocarditis and meningitis due to invasive Streptococcus pneumoniae infection. Few case reports have been reported since its first description in 1975 by Robert Austrian, mainly because it is rarely observed. Below we report the case of a 61 year-old male patient who presented with bacterial meningitis due S. pneumoniae followed by bacterial pneumonia and severe mitral regurgitation, associated with four vegetations on the atrial surface of the posterior mitral leaflet; in addition, there was rupture and prolapse of its middle scallop. The S. pneumoniae bacterium was isolated from cerebrospinal fluid and blood cultures. In consequence, the patient was given broad-spectrum antibiotic therapy and had an early valve replacement performed, obtaining a good clinical outcome. The key prognostic factor of the Austrian syndrome is determined by the damage of cardiac valves, particularly in patients with a compromised aortic valve; hence, it is necessary to identify the degree of valve injury and define surgical and antibiotic treatment on a timely fashion. However, in subacute, less frequent clinical cases where the mitral valve is the main valve compromised, usually a directed antibiotic therapy associated with advanced support measures are sufficient to control this infection.

Detection of the Efflux-Mediated Erythromycin Resistance Transposon in Streptococcus pneumoniae

BACKGROUND: The present analysis focuses on phenotypic and genotypic characterizations of efflux-mediated erythromycin resistance in Streptococcus pneumoniae due to an increase in macrolide resistance in S. pneumoniae worldwide. METHODS: We investigated the prevalence of efflux-mediated erythromycin resistance and its relevant genetic elements from 186 specimens of S. pneumonia isolated from clinical and normal flora from Tehran, Iran. The presence of erythromycin resistance genes was tested by PCR with two sets of primers, specific for erm(B) and mef(A/E), and their genetic elements with tetM, xis, and int genes. Isolates were typed with the BOX PCR method and tested for resistance to six antibiotics. RESULTS: Antibiotic susceptibility tests revealed that 100% and 47% isolates were resistant to tetracycline and erythromycin, respectively. The erythromycin and clindamycin double-disc diffusion test for macrolide-lincosamide-streptograminB (MLSB) resistance phenotype showed 74 (84%) isolates with the constitutive MLSB phenotype and the remaining with the M phenotype. BOX PCR demonstrated the presence of 7 types in pneumococci with the M phenotype. Fourteen (16%) isolates with the M phenotype harbored mef(A/E), tetM, xis, and int genes. CONCLUSIONS: The present results suggest dissemination of polyclonal groups of S. pneumoniae with the M phenotype carrying resistance genes attributed to transposon 2009.

Infecciones invasivas con bacteriemia por Streptococcus pneumoniae en niños: ¿qué pasó en los últimos 5 años? / Invasive infections with bacteremia due to Streptococcus pneumoniae in children: What has happened over the past 5 years?

Introducción: Las infecciones por Streptococcus pneumoniae (Spn) constituyen enfermedades de alta prevalencia y representan una de las principales causas de morbimortalidad en pediatría. La resistencia antibiótica de S. pneumoniae es variable según las características del huésped, serotipos predominantes y la circulación de clones determinados. El objetivo del estudio fue evaluar las características de los niños con infecciones invasivas con bacteriemia por Spn, la sensibilidad a los antibióticos betalactámicos (penicilina y ceftriaxona) de las cepas, los serotipos identificados y la frecuencia de los serotipos en el período pre-vacunación universal para neumococo (2008 ­ 2011) versus pos vacunal (2012 ­ 2013). Material y métodos: estudio prospectivo. Se incluyeron todos los <18 años internados con documentación de Spn en hemocultivos en el Hospital de Pediatría J. P. Garrahan en el periodo 2008-2013.Se utilizó el programa Epi info versión 3.2.2 (Epi Info 7).Resultados: se incluyeron 171 pacientes, con 52,6% de varones, mediana de edad de 31 meses (RIC 12-61); 116 niños tenían co-morbilidad asociada (67,8%). Las formas clínicas de infección más frecuentes fueron neumonía (n: 68; 39,8%), supuración pleuropulmonar en 12,3% (n:21) y fiebre sin foco clínico en 18,7% (n: 32). La mortalidad fue del 8,2% (n: 14). Todos los aislamientos de Spn fueron sensibles a la penicilina y a las cefalosporinas de tercera generación. No se identificaron Spn con sensibilidad disminuida a los betalactámicos. Los serotipos predominantes fueron el 14, 1, 6A, 7F, 12F, 19A y 23F. Se identificaron serotipos incluidos en la vacuna neumocóccica 13­ V (VNC13) en el período pre vacunal en el 71.1% (n:74) versus 59.7% (n:40) en el período pos vacunal; dicha diferencia no fue estadísticamente significativa. Conclusiones: la mayoría de los pacientes con infecciones invasivas por Spn incluidos en este estudio presentaban enfermedades subyacentes. En el periodo observado no se identificaron cepas de Spn con sensibilidad disminuida a los beta- lactámicos. Aunque la incorporación de la vacuna VNC13 es reciente, la frecuencia de identificación de serotipos incluidos en la VNC-13 disminuyó un 11,4% en relación al periodo pre vacunal (71,1% vs 59,7%) (AU)

Introduction: Infections due to Streptococcus pneumoniae (Spn) are highly prevalent diseases that account for one of the main causes of morbidity and mortality in pediatrics. Resistance to antibiotics of S. pneumoniae is variable according to host characteristics, predominant serotypes, and circulation of dominant clones. The aim of this study was to assess the characteristics of children with invasive infections and bacteremia due to Spn, sensitivity of the strains to beta-lactam antibiotics (penicillin and ceftriaxone), the identified serotypes, and the incidence of serotypes in the pre-universal vaccination for pneumococcus period (2008 ­ 2011) versus the post-vaccination period (2012 ­ 2013). Material and methods: A prospective study. All children <18 years of age with documented Spn in hemocultures admitted to the Pediatric Hospital J. P. Garrahan between 2008 and 2013 were included. Epi info 3.2.2 (Epi Info 7) was used for statistical analysis. Results: We included 171 patients, 52.6% of whom were boys, with a mean age of 31 months (IQR 12-61); 116 children had associated comorbidities (67.8%). The most common clinical manifestations of infection were pneumonia (n: 68; 39.8%), inflammatory-purulent pleuropulmonary disease (n:21; 12.3%), and fever without a clinical focus (n: 32; 18.7%). Mortality was 8.2% (n: 14). All Spn isolates were sensitive to penicillin and third-generation cephalosporins. No Spn with reduced sensitivity to beta-lactams were found. Predominant serotypes were 14, 1, 6A, 7F, 12F, 19ª, and 23F. Serotypes included in the pneumococcal vaccine 13­ V (VNC13) were identified in the pre-vaccination period in 71.1% (n:74) versus 59.7% (n:40) in the post-vaccination period; this difference was not statistically significant. Conclusions: The majority of patients with invasive infections due to Spn included in this study had underlying diseases. In the study period no strains of Spn with diminished sensitivity to beta-lactams were observed. Although the VNC13 vaccine has been recently incorporated, the incidence of identification of serotypes included in the VNC-13 vaccine has decreased 11.4% compared to the pre-vaccine period (71.1% vs 59.7%)

Vigilancia de laboratorio de Streptococcus pneumoniae procedente de enfermedad invasora, Chile 2007-2012 / Laboratory surveillance of Streptococcus pneumoniae from invasive disease, Chile 2007-2012

Background: 10-valent pneumococcal vaccine (PCV-10) was introduced in 2011 to the National Immunization Program in Chile. It was administered in 4 doses, but in 2012 it was modified to a 3 dose program. This article shows the results of the Laboratory Surveillance System for Streptococcus pneumoniae isolated of invasive disease from 2007 to 2012 and compares the incidence of invasive pneumococcal disease (IPD) by age groups in the prevaccinal (2007-2010) and postvaccinal period (2012). Methods: Descriptive study of S. pneumoniae surveillance in invasive diseases cases confirmed at the National Reference Laboratory of the Institute of Public Health of Chile from 2007 to 2012. Results: Global incidence of laboratory confirmed IPD cases decreased 27.8% from 2007 to 2012 and showed a lower risk for IPD in 2012 compared with 2007. Incidence in children aged 1 year or less decreased from 56.1 to 16.3 per 100,000 and from 42.0 to 19.9 per 100,000 in children aged 12 to 23 months in the same period. Highest decreases were observed in IPD cases caused by serotypes 4 (100%), 19F (93.3%), 23F (90.9%), 14 (81.1%), 6B (70%), 18C (58.3%) and 1(81.8%) in children aged 2 years or less. Conclusion: Surveillance System detects S.pneumoniae isolated from invasive diseases, contributing with information about laboratory confirmed IPD trends, prevalent serotypes and replacement effects. These results can be used as evidence in healthcare decision making for pneumococcal vaccines.

Introducción: La vacuna neumocóccica 10 valente fue incorporada al Programa Nacional de Inmunizaciones (PNI) desde enero de 2011 para lactantes mediante un esquema de cuatro dosis, y desde 2012, con un esquema de tres dosis. El objetivo de esta publicación es dar a conocer el resultado de la vigilancia de laboratorio de Streptococcus pneumoniae aislado de enfermedad invasora (ENI) desde el año 2007 al 2012 y comparar la incidencia de esta enfermedad según grupos de edades en un período prevacunal (2007-2010) con el postvacunal (2012). Materiales y Métodos: Estudio descriptivo de los resultados de la vigilancia de S. pneumoniae en los casos de ENI confirmados microbiológicamente en Chile, en el Laboratorio Biomédico Nacional de Referencia del Instituto de Salud Pública de Chile (ISP) durante los años 2007 a 2012. Resultados: La evolución de la incidencia global de S. pneumoniae en casos de ENI muestra un menor riesgo en los años estudiados (OR 2011 vs 2007-2010: 0,82 (IC 95%: 0,75-0,89); OR 2012 vs 2007-2010: 0,76 (IC 95%: 0,70-0,82)). En niños bajo un año de edad, la incidencia disminuyó desde 56,1 a 16,3 por 100.000 y en niños de 12 meses a 23 meses desde 42,0 a 19,9 por 100.000, en el mismo período. Los mayores porcentajes de disminución en los menores de 2 años se observaron en los casos de ENI producidos por los serotipos 4 (100%), 19F (93,3%), 23F (90,9%), 14 (81,1%), 6B (70%), 18C (58,3%) y 1(81,8%). Conclusión: El sistema de vigilancia permite detectar cepas de S. pneumoniae aisladas de enfermedad invasora en nuestro país, lo que aporta información respecto de la tendencia de la ENI confirmada microbiológicamente en Chile, los serotipos prevalentes y el posible efecto de reemplazo de ellos descrito en otros países, aportando a la autoridad de salud una herramienta adicional para la toma de decisiones respecto del tipo de vacuna a usar en el PNI con la mejor evidencia disponible.

Differentiation of Haemonchus placei from Haemonchus contortus by PCR and by morphometrics of adult parasites and third stage larvae / Identificação de Haemonchus placei e Haemonchus contortus por PCR e por análise morfológica de parasitas adultos e larvas infectantes

Molecular and morphological methods were evaluated to distinguish between Haemonchus contortus and Haemonchus placei species. A total of 141 H. contortus and 89 H. placei male adult specimens collected from artificially infected lambs were identified individually by PCR analysis, using a species-specific primer pair. These PCR results were used as gold standard for Haemonchus spp. identification. Haemonchus placei presented higher mean spicule and barb lengths than H. contortus (P<0.05). However, some measurements overlapped. For this reason, a discriminate function did not allow the correct identification of 13 H. contortus and one H. placei specimen. The sheath tail length of the third stage larvae (L3), which comprises the distance between the tip of the larval tail and the end of the sheath tail, were measured. Only three of the 485 H. placei larvae (0.619%) had a sheath tail shorter than 85 µm, while only four of the 500 H. contortus larvae (0.8%) presented a sheath tail longer than 85 µm. The results indicated that 6.09% of the male adult specimens would be misclassified based on the discriminate function, while only 0.71% of infective larvae would be misclassified. Therefore, identification of L3 can be used as the first method to indicate the presence of H. placei and/or H. contortus in a population of domestic ruminants.

Métodos moleculares e morfológicos foram avaliados para a identificação de Haemonchus contortus e Haemonchus placei. No total, 141 H. contortus e 89 H. placei machos adultos, obtidos de cordeiros artificialmente infectados, foram identificados individualmente por PCR com o emprego de um par de “primers” espécie-específico. Esses resultados da análise por PCR foram considerados como padrão para a identificação das espécies de Haemonchus. Haemonchus placei apresentou valores médios de espículos e ganchos superiores aos de H. contortus (P<0,05). Entretanto, houve sobreposição de alguns valores. Por essa razão, a função discriminante não permitiu a identificação correta de 13 exemplares de H. contortus e de um, de H. placei. Foi medida a cauda da bainha de larvas infectantes (L3), que compreende a distância entre a ponta da cauda da larva e a ponta da cauda da bainha. Apenas três das 485 L3 de H. placei (0,619%) apresentaram a cauda da bainha com medida inferior a 85 µm e somente em quatro das 500 L3 de H. contortus (0,8%) essa medida foi superior a 85 µm. Os resultados demonstraram que 6,09% dos machos adultos seriam identificados erroneamente com base na função discriminante, enquanto a identificação incorreta de L3 seria de apenas 0,71%. Portanto, a identificação de L3 pode ser utilizada como método inicial para indicar a presença de H. placei e/ou H. contortus em uma população de ruminantes domésticos.

Antimicrobial resistance in streptococcus pneumoniae: mechanisms and current epidemiology

Infections caused by Streptococcus pneumoniae are a worrisome public health problem worldwide. Young children and the elderly are the main age groups affected and the highest burden of the disease is found in developing countries. Pneumococcal infections cause 11% of the total infant deaths, representing the leading cause of child death currently preventable by vaccination. Epidemiologic information about pneumococci in Brazil is somehow restricted, but available data reinforce the worrisome occurrence of pneumococcal diseases, which are commonly treated empirically. Limitations in the diagnostic methods, along with the severity of disease contribute to this behavior. Thus, surveillance studies are crucial to define the prevalence of resistant strains both globally and in a particular region, as these strains may compromise empirical therapeutic choices. However, although different clones of penicillin non-susceptible pneumococci are internationally distributed, and considering diseases other than meningitis, the prevalence of resistance to penicillin is quite low, making this old, safe, and inexpensive drug an attractive first choice to treat pneumococcal infections. The widespread use of conjugate vaccines among children, influencing the circulation of resistant clones and the distribution of serotypes reinforces the need of surveillance studies to define the prevalence of resistance