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.

Predictors for muscle invasion of upper tract urothelial carcinoma / 中华泌尿外科杂志

Objective:To explore the predictors of upper tract urothelial carcinoma (UTUC) invading muscle.Methods:The preoperative clinical data of 169 patients with UTUC who underwent radical nephroureterectomy (RNU) in the Department of Urology, Second Hospital of Tianjin Medical University from August 2019 to September 2021 were retrospectively collected. The average age of the patients was (67.7±8.3)years. There were 95 male cases (56.2%).15 cases (15.8%) were with diabetes, 46 cases (48.4%) with hypertension, 68 cases (71.6%) with hematuria, 44 cases (46.3%) with renal pelvis tumor, 74 cases (77.9%) with hydronephrosis and 8 cases (8.4%) with multifocality. There were 15 (20.3%), with diabetes, 40(54.1%) with hypertension, 58(78.4%)with hematuria, 32(43.2%) with renal pelvis tumor, 60(81.1%) with hydronephrosis and 2(2.7%) with multifocality among 74 female patients(43.8%), respectively. Patients’ body mass index (BMI) was (24.2±3.2) kg/m 2.The tumor diameter was (3.4±1.8) cm. The average count of neutrophil (NEU) was (4.2±1.7) ×10 9/L, with monocyte (MON) (0.4±0.2) ×10 9/L, platelet (PLT) (237.8±75.3) ×10 9/L and lymphocyte (LYM) (1.7±0.5) ×10 9/L. Neutrophil-to-lymphocyte ratio (NLR) was 2.7±1.4. Mmonocyte-to-lymphocyte ratio (MLR) was 0.3±0.1 and platelet-to-lymphocyte ratio (PLR) was 151.1±59.6. The concentrations of hemoglobin (Hb) and fibrinogen (FIB) were (127.1±18.3) g/L and(3.5±1.0) g/L. Univariate logistic regression analysis was performed on all preoperative data, and a nomogram was established to predict UTUC invading muscle by stepwise regression combined with multivariate logistic analysis. Concordance index (C-index) was used to evaluate the accuracy of the model, and Hosmer-Lemeshow test was used to check the fit. Using 1000 bootstrap resampling to validate the model and draw calibration plot. Receiver operating characteristics (ROC) curves were used to determine the most appropriate cut-off point of the model to predict tumor invasion and evaluate its sensitivity and specificity. Results:In this study, there were 169 cases. Postoperative pathological results showed that 18 cases (10.6%) were of low grade and 151 cases (89.4%) were of high grade. There were 2 patients (1.2%) with pT a stage, 44 patients (26.0%) with pT 1 stage, 37 patients (21.9%) with pT 2 stage, 81 patients (47.9%) with pT 3 stage and 5 patients (3.0%) with pT 4 stage. According to tumor stage, 46 patients were included into non-muscle invasive disease (NMID, pT a/T is/T 1) group and 123 patients were included into muscle invasive disease (MID, pT 2/T 3/T 4) group. Univariate analysis showed that hydronephrosis ( OR=2.919, 95% CI 1.332-6.387, P=0.007) was significantly correlated with MID. Tumor location in ureter ( OR=1.898, 95% CI 0.960-3.800, P=0.067), higher NLR value ( OR=1.313, 95% CI 0.9901.832, P=0.082) and FIB concentration ( OR=1.436, 95% CI 1.008-2.125, P=0.056) might have potential association with MID. Stepwise regression method was used to screen out PLT, FIB and hydronefrosis as the optimal combination for MID prediction. multivariate analysis suggested that PLT decreasing ( OR=0.727, 95% CI 0.548-0.955, P=0.023), FIB increasing ( OR=1.629, 95% CI 1.084-2.552, P=0.025) and hydronephrosis ( OR=2.500, 95% CI 1.111-5.601, P=0.026) were independent predictors of MID.The C-index of the model constructed by the three factors was 0.682, and the P-value of the goodness of fit was 0.778. The ROC curve showed that the optimal cut-off point for the prediction of high-risk MID by the nomogram was 0.627, achieving 39.1% specificity, 88.6% sensitivity and 0.682 area under the curve (AUC). Conclusions:Preoperative decrease of PLT, increase of FIB and hydronephrosis were independent factors for predicting UTUC invading muscle.

Enfermedades invasoras por Streptococcus pyogenes en población pediátrica. Caracterización clínico-molecular 2014-2020

Introducción: Streptococcuspyogenes (EGA) es agente de enfermedad invasora (EI); su alta morbimortalidad exige vigilancia epidemiológica. Objetivo: Describir características clínicas y epidemiológicas de niños hospitalizados con EI por EGA en un centro de referencia de Uruguay del 1/1/2014 al 31/12/2020 incluyendo el estudio de los factores de virulencia encontrados en las cepas aisladas. Materiales y Métodos: Descriptivo y retrospectivo. Definición de caso: aislamiento de EGA. en sitios estériles. Variables: epidemiológicas, clínicas, laboratorio, tratamiento y evolución. Se tipificó por secuenciación del gen emm. Se obtuvieron perfiles cromosómicos por digestión del ADN con la enzima SmaI. Presencia de los genes que codifican SpeB, SpeA, SpeC y Ssa, y susceptibilidad a antimicrobianos. Resultados: Tasa de admisiones: 3,98/10.000. Se incluyeron 22 pacientes; infección osteoarticular (n = 11), infección pleuropulmonar (n = 6), absceso no cutáneo (n = 4) y aislamiento en sangre (n = 1). Media de edad: 44 meses; 8 fueron graves, siendo su media de edad menor (16 meses) Todas los casos con neumonías fueron graves y un paciente falleció. Se secuenciaron 12 cepas: 5 emm1 (4 emm 1.29 y 1 emm 1) y 1 de cada uno de los siguientes: emm 6.4, emm 81, emm12, emm28, emm 22, emm 87, emm 11. Todas eran SpeB+. Perfiles de toxinas: SpeA+SpeC-Ssa-(5), SpeA-SpeC+Ssa-(4) SpeA-SpeC-Ssa-(2) y SpeA-SpeC+Ssa+ (2). Conclusiones: Este estudio permite dar continuidad a un estudio previo. Se logró mayor tipificación de EGA. que puede contribuir a su conocimiento clínico molecular. No hubo registro de pacientes con diagnóstico de SST ni de fascitis necrosante, a diferencia de la serie anterior.

Background: Streptococcus pyogenes (GAS) is an agent of invasive disease (ID); its high morbidity and mortality requires epidemiological surveillance. Aim: To describe the clinical and epidemiological characteristics of children hospitalized with ID due to GAS in a reference center in Uruguay from January 1-2014 to December 31-2020, including a study of virulence factors. Methods: Descriptive and retrospective. Case definition: Isolation of GAS in sterile sites. Variables: epidemiological, clinical, laboratory, treatment and evolution. Strains were typified by sequencing of the emm gene. Chromosomal profiles were obtained by digestion of the DNA. with the Smal enzyme. Presence of SpeB, SpeA and SpeC genes and susceptibility to antibiotics were performed. Results: Admissions rate: 3.98/10,000. 22 patients were included; osteoarticular infection (n = 11), pleuropulmonary infection (n = 6), non-cutaneous abscess (n = 4) and blood isolation (n = 1). Mean age: 44 months; 8 cases were severe, their mean age was lower (16 months). All pneumonia cases were severe and one patient died. Twelve strains were sequenced: 5 emm1 (4 emm1.29 and 1 emm1) and 1 of each: emm6.4, emm81, emm 12, emm28, emm 22, emm 87, emm 11. All were SpeB+. Toxin profiles: SpeA+SpeC-Ssa-(5), SpeA-SpeC+Ssa-(4) SpeA-SpeC-Ssa-(2) and SpeA-SpeC+Ssa+(2). Conclusions: This study allows to give continuity to a previous study. Greater typing of GAS was achieved, which may contribute to its molecular clinical knowledge. There was no record of patients diagnosed with TSS or necrotizing fascitis, unlike the previous series.

Whole-genome analysis of haemophilus influenzae invasive strains isolated from Campinas state University hospital. An epidemiological approach 2012 - 2019 and ancestor strains

Abstract Thirteen Haemophylus influenzae invasive strains isolated from patients at Clinical Hospital of State University of Campinas, from May 2013 through August 2019, was submitted to Illumina genome sequencing HiSeq platform. Further in silico analysis of serogroup and Multi Locus Sequence Typing (MLST) from whole DNA sequencing had demonstrated the actual clonal distribution in the Campinas Metropolitan region. Thus, results showed the existence of a new ST Haemophilus influenzae found in the Brazilian territory and an increase of strains belonging to serogroup a (three strains also belonging to ST23). In conclusion, we observed an increase of non-typable H. influenzae (NTHi) and a strain involved in invasive diseases in the Campinas - São Paulo region after frequent detection of those serotypes and genotypes in other Brazilian regions.

Streptococcal toxic shock syndrome / 中华实用儿科临床杂志

Streptococcal toxic shock syndrome (STSS) is a Group A Streptococcus (GAS) induced invasive infectious disease, which is characterized by abrupt onset and rapid progression with a high mortality rate.With the wide application of antimicrobial agents, the incidence of GAS infections has been substantially reduced.Nevertheless, STSS usually causes shock and multiple organ failure at the early stage of its clinical process, and the clinical symptoms are non-specific.Therefore, early identification, timely anti-infection and symptomatic treatment are particularly critical.Clinicians should pay high attention to the disease.

Priorización de nuevas vacunas e innovación al servicio de estrategias de vacunación / New vaccines prioritization and immunization-related innovation

La vacunación es el medio más efectivo para controlar la morbilidad y mortalidad relacionadas con enfermedades infecciosas. Para lograr esto, necesitamos vacunas inmunogénicas y seguras que faciliten y mejoren sus condiciones de transporte, almacenamiento y administración. Gracias a los avances en inmunología y bioinformática, es posible impulsar el descubrimiento de nuevas vacunas para enfrentar la tuberculosis, el virus respiratorio sincicial, el Streptococcus agalactiae, la enfermedad meningocócica invasora, entre otros. Así también, nuevas tecnologías, como la producción de vacunas utilizando plantas transgénicas y parches de microagujas, los cuales podrían facilitar la producción, disminuir los costos y efectos adversos. Sin embargo, no solo necesitamos las vacunas, sino que debemos conocer la epidemiología de las enfermedades prevenibles con vacuna para tomar decisiones fundadas, con el objetivo de planificar estrategias sanitarias, medir su impacto y evaluar la seguridad de su utilización, para alcanzar las metas de salud pública y la confianza de la población.

Vaccination is the most effective strategy to avoid morbidity and mortality related to infectious diseases. To achieve this, we need immunogenic and safe vaccines that facilitate and improve its transport, storage and administration conditions. Thanks to current advances in immunology and bioinformatics, it is possible to boost the discovery of new vaccines to deal with tuberculosis, the respiratory syncytial virus, Streptococcus agalactiae, meningococcal invasive disease, among others. In addition to new technologies such as the production of plant-based vaccines, and microneedles patches, which can facilitate its production, reducing costs and adverse effects. However, vaccines is not the only thing that we need, because we must know the epidemiology and burden of disease to take informed decisions to design optimal strategies, measuring their impact and assessing the safety of their use in order to achieve the goals health and population confidence.

Frecuencia de Streptococcus pneumoniae aislados de enfermedad invasiva en Paraguay, serotipos y perfil de sensibilidad (2010-2018) / Frequency of Streptococcus pneumoniae isolated from invasive disease in Paraguay, serotypes and sensitivity profile (2010-2018)

Streptococcus pneumoniae sigue siendo una de las causas más importantes de morbilidad y mortalidad en niños y adultos alrededor del mundo. El objetivo del estudio fue describir la frecuencia de aislamiento de S. pneumoniae en enfermedad invasiva, distribución de serotipos y sensibilidad antimicrobiana en Paraguay (2010-2018). Se estudiaron 793 cepas de S. pneumoniae aisladas de pacientes de todas las edades con enfermedad invasiva en Paraguay, provenientes de los diferentes centros centinelas y colaboradores en el marco de la vigilancia de meningitis y neumonías, durante el periodo 2010-2018. La frecuencia general según diagnóstico resultó 74.9% de neumonías (n=594), 18.4% de meningitis (n=146) y 6.7% de sepsis (n=53). El serotipo 14 fue más frecuente con 174 aislamientos (22.0%), seguido del serotipo 19A con 84 aislamientos (10.6%), el serotipo 3 con 66 aislamientos (8.3%) y el 6A con 37 aislamientos (4.7%). En meningitis se registró una frecuencia general de resistencia a penicilina del 32,2% y de ceftriaxona del 1,4%. En los casos de no meningitis la resistencia a penicilina fue del 0,8% y ceftriaxona del 0,3%. Los resultados de serotipos y sensibilidad antimicrobiana proporcionarán información necesaria para la implementación de estrategias de prevención y tratamiento de la enfermedad neumocócica en nuestro país, por lo que es necesaria una vigilancia continua para evaluar la carga de enfermedad, los serotipos circulantes y el aumento de la resistencia a los antibióticos

Streptococcus pneumoniae remains one of the most important causes of morbidity and mortality in children and adults worldwide. The objective of the study was to describe the frequency of isolation of S. pneumoniae in invasive disease, serotype distribution and antimicrobial susceptibility in Paraguay (2010-2018). We studied 793 strains of S. pneumoniae isolated from patients of all ages with invasive disease in Paraguay, from different sentinel centers and collaborators in the framework of meningitis and pneumonia surveillance during the period 2010-2018. The general frequency according to diagnosis was 74.9% of pneumonia (n = 594), 18.4% of meningitis (n = 146) and 6.7% of sepsis (n = 53). Serotype 14 was more frequent with 174 isolates (22.0%), followed by serotype 19A with 84 isolates (10.6%), serotype 3 with 66 isolates (8.3%) and 6A with 37 isolates (4.70%). In meningitis, there was a general frequency of penicillin resistance of 32.2% and ceftriaxone of 1.4%. In cases of non-meningitis, penicillin resistance was 0.8% and ceftriaxone 0.3%. The results of serotypes and antimicrobial sensitivity will provide necessary information for the implementation of prevention strategies and treatment of pneumococcal disease in our country, therefore it is necessary to continue monitoring in order to assess the burden of the disease, circulating serotypes and increased antibiotic resistance

Analysis of serotype and clinical manifestation of 80 children with invasive pneumococcal disease in Suzhou / 中国小儿急救医学

Objective To understand serotypes and clinical manifestation of children with invasive pneumococcal disease (IPD) in Suzhou,so as to find a better strategy for reducing the incidence and mortality of IPD. Methods Eighty children with IPD were enrolled into our study from January 2011 to December 2015. The data of epidemiology,serotype,clinical manifestation,laboratory results and prognosis were collected and analyzed. Results The mortality of 80 children with IPD was 17. 5%(14/80). Sixty percent of them were younger than 2 years old,and 78. 6% of 14 dead cases were younger than 2 years old,the median age of dead group 0. 68 (0. 45,2. 07) years was younger than 1. 61 (0. 85,3. 45) years of survival group ( P <0. 05). The incidence rates of hyperpyrexia,vomiting and somnolence in dead group were higher than those in survival group before admission ( P <0. 05), the incidence rates of shock, DIC, respiratory failure, AKI, seizure or coma in dead group were higher than those in survival group ( P<0. 05). The coincidence rate between choice of antibiotics before admission and drug sensitivity test was 15. 0%(12/80),the mortality of coincident group (coincidence between choice of antibiotics and drug sensitivity test) 8. 3% was lower than 16. 2% of non-coincident group with no statistical differences ( P>0. 05). The drug resistance rates of 80 pneumococcus to Erythromycin,Clindamycin,Tetracycline,Sulfamethoxazole,Penicillin,Cefotaxime,Amoxi-cillin,Chloramphenicol,Vancomycin and Levofloxacin were 100% (80/80),98. 8% (79/80),88. 8%(71/80),71. 3%(57/80),48. 8%(39/80),32. 5%(26/80),8. 8%(7/80),5. 0%(4/80),0(0/80) and 0(0/80) respectively. Eight serotypes of 80 IPD cases were listed in descending order:6B(25. 5%,20/80),14 (23. 8%,19/80),19F(15. 0%,12/80),19A(15. 0%,12/80),23F(8. 8%,7/80),20(5. 0%,4/80),9V (5. 0%,4/80) and 15B/C(2. 5%,2/80),and 6 serotypes of 14 dead cases were:6B(35. 7%,5/14),14 (28. 6%,4/14),19F(14. 3%,2/14),19A(7. 1%,1/14),23F(7. 1%,1/14) and 20(7. 1%,1/14); the coverage of IPD serotypes of 7-valent pneumococcal conjugate vaccine (PCV7) 77. 5%(62/80) was lower than 92. 5%(74/80) of 13-valent pneumococcal conjugate vaccine (P <0. 05). Conclusion Majority of dead cases of IPD is always younger than 2 years. The low coincidence rate of choices of antibiotics to inva-sive pneumococcus outpatient and low rate of PCV immunization in China are responsible for the high mortal-ity of IPD. Timely recognition of continuous hyperpyrexia, vomiting and somnolence in early stage and appropriate use of antibiotics is the key to improve the outcome of IPD. Thirteen-valent pneumococcal conju-gate vaccine immunization provides a robust strategy for reducing the incidence and mortality of IPD.

Serotipos de Streptococcus pneumoniae responsables de enfermedad invasiva en niños cubanos / Streptococcus pneumoniae serotypes responsible for invasive disease affecting Cuban children

Introducción: Streptococcus pneumoniae es causa importante de morbilidad y mortalidad a nivel mundial, fundamentalmente en niños < 5 años. En Cuba aún no se introdujo la vacunación antineumocócica, pero desde 2014, con el propósito de sentar las bases para la evaluación de su impacto, se lleva a cabo un protocolo de vigilancia centinela de la enfermedad neumocócica invasiva en niños ≤ 5 años. Objetivos: notificar los serotipos de S. pneumoniae responsables de enfermedad neumocócica invasiva en la población pediátrica cubana, y valorar la contribución de ese protocolo a la vigilancia. Métodos: se determinaron los serotipos de todos los aislamientos pediátricos invasivos y los recuperados de otitis media aguda, recibidos en el Laboratorio Nacional de Referencia de Neumococo, del Instituto de Medicina Tropical Pedro Kourí, entre 2013-2015. Se utilizó el método de hinchazón capsular empleando el juego de reactivos Pneumotest. Resultados: se notificaron 141 aislamientos invasivos en edad pediátrica. Predominaron los responsables de neumonías (76 vs. 49 aislamientos meníngeos) y la mayoría de estos fueron aportados por los hospitales involucrados en la vigilancia centinela (75 por ciento; 57/76). El 85,8 por ciento de los aislamientos quedaron contenidos en siete serotipos, que por orden de frecuencia fueron: 14, 19A, 6A, 19F, 6B, 3 y 23F. La cobertura serotípica de las diferentes vacunas neumocócicas multivalentes con posibilidades de ser empleadas se estimó entre 54 y 90 por ciento. Conclusiones: tras la introducción de la vacunación cabría esperar una reducción de la enfermedad neumocócica invasiva debida a los serotipos contenidos en las vacunas conjugadas disponibles, pero se insiste en la necesidad de fortalecer la vigilancia clínico-epidemiológica que se hace hoy de esta entidad en el país(AU)

Introduction: Streptococcus pneumoniae is a significant cause of morbidity and mortality worldwide mainly in children younger than 5 years. The pneumococcal vaccination has not been yet put into practice in Cuba; however, since 2014 a protocol of sentinel surveillance of the invasive pneumococcal disease in children aged 5 years or less is being implemented to lay the foundations for the evaluation of the impact of this vaccine. Objectives: to report on the S. pneumoniae serotypes responsible for the invasive pneumococcal disease in the Cuban pediatric population and to assess the contribution of this protocol to surveillance. Methods: the serotypes of all the invasive pediatric isolates and the recovered ones of acute otitis media were determined by the national laboratory of pneumococcal reference of Pedro Kourí Institute of Tropical Medicine from 2013 to 2015. The capsular swelling method was used with the Penumotest reagent set. Results: one hundred and forty one invasive isolates were reported at pediatric ages. The isolates causing pneumonia predominated (76 vs. 49 meningeal isolates) and most of them were provided by hospitals involved in the sentinel surveillance project (57 out of 76; 75 percent). In this regard, 85.8 percent of isolates belonged to seven serotypes that were in order of frequency the following: 14, 19A, 6A, 19F, 6B, 3 and 23F. The serotype coverage of the various multivalent pneumococcal vaccines of possible use was estimated at 54-90 percent. Conclusions: after the introduction of the vaccinations, one might expect that a reduction of the invasive pneumococcal disease occurs due to the serotypes included in the available conjugate vaccines, but emphasis is made on the need of strengthening at present the clinical and epidemiological surveillance system for this disease nationwide(AU)

Infección grave por Staphylococcus aureus meticilino sensible productor de leucocidina de Panton-Valentine: reportes de dos casos / Severe infection by methicillin sensitive Staphylococcus aureus producing Panton-Valentine leukocidin: reports of two cases

Staphylococcus aureus es uno de los principales agentes etiológicos de infecciones en niños provenientes de la comunidad y del ámbito hospitalario. La gravedad de estos cuadros se asocia a factores de virulencia, entre los que se encuentra la leucocidina de Panton-Valentine. Tanto Staphylococcus aureus resistente como sensible a la meticilina producen esta leucocidina, aunque con frecuencia variable. Presentamos a dos niños con infección grave por Staphylococcus aureus sensible a la meticilina productor de leucocidina de Panton-Valentine con complicaciones osteoarticulares y endovasculares. Es fundamental la sospecha diagnóstica, el tratamiento antibiótico adecuado y el manejo quirúrgico precoz para mejorar el abordaje de estas infecciones. Se debe mantener la vigilancia epidemiológica para detectar la frecuencia de las infecciones causadas por estas bacterias.

Staphylococcus aureus is a major etiologic agent of infections in children from the community and the hospital setting. The severity of these conditions is associated with virulence factors, including the Panton-Valentine leukocidin. Both methicillin resistant and sensitive Staphylococcus aureus produce this leukocidin although with varying frequency. We present two children with severe infection by sensitive Staphylococcus aureus producer of Panton-Valentine leukocidin with musculoskeletal and endovascular complications. It is essential the suspected diagnosis, appropriate antibiotic treatment and early surgical management to improve the approach of these infections. Epidemiological surveillance should be mantained to detect the frequency of infections caused by these bacteria.

Puesta al día en vacunación antineumocócica en adultos / Update on pneumococcal vaccination in adults

La enfermedad invasiva por Streptococcus pneumoniae constituye una importante causa de morbilidad y mortalidad, y es la primera causa de muerte prevenible mediante vacunación en el mundo, no solo en niños sino en todas las edades. Tanto la vacuna polisacárida como la vacuna conjugada antineumocócicas han demostrado reducción de las tasas de enfermedad invasiva en adultos. En los últimos años, a la luz de nueva evidencia disponible, los esquemas de vacunación antineumocócica para esta población han sufrido modificaciones. Este documento ofrece una actualización sobre las recomendaciones de vacunación a través de los fundamentos que han llevado a dicho cambio. (AU)

The Streptococcus pneumoniae invasive disease is a major cause of morbidity and mortality, being the leading cause of vaccine-preventable death in the world, not only in children but in all ages. Both the polysaccharide vaccine and pneumococcal conjugate vaccine have shown reduced rates of invasive disease in adults. In recent years, in light of new evidence available, schedules of pneumococcal vaccination for this population have changed. This document provides an update on vaccine recommendations through the rational that have led to this change. (AU)

Enfermedades invasoras por Streptococcus pyogenes 2005-2013: Hospital Pediátrico del Centro Hospitalario Pereira Rossell, Uruguay / Invasive Streptococcus pyogenes diseases 2005-2013: Pediatric Hospital Pereira Rossell Uruguay

Introduction: Streptococcus pyogenes infection causes a wide spectrum of clinical manifestations. Invasive disease (ID) is defined by the isolation of the microorganism from sterile sites. Objective: To analyze the clinical, epidemiological and molecular characteristics of ID by S.pyogenes in children hospitalized at Pediatric Hospital Pereira Rossell, from January 2005 to January 2013. Materials and Methods: A descriptive retrospective study was done in cases with isolation of S.pyogenes from sterile sites. Epidemiological variables, disease characteristics, laboratory parameters, treatment regimen received, hospitalization days and clinical outcome were analyzed. The presence of 4 genes encoding for virulence factors and chromosome profile studied by pulsed-field electrophoresis were done in the isolated strains. Results: A total of 42 cases (rate: 4.6 out of 10,000 admissions) were detected, from which 32 were analyzed. Average age was 44.7 months (14/32 < 2 years of age). In 5 cases, the portal of entry was identified. Clinical presentations were: osteoarticular infections (n = 15), shock (n = 6), skin and soft-tissue infections (n = 5), pneumonia (n = 3) and bacteremias (n = 3). Twenty cases required surgical procedures and 13 required intensive care admission. Average hospital stay was 17 days and one patient died. Molecular studies were performed in five strains; 4 different toxin profiles and pulsotypes were identified. Discussion: The incidence of ID at our hospital is similar to other series in the region. A better knowledge of clinical presentation and its relation with molecular characteristics represents a challenge.

Introducción: Streptococcus pyogenes, produce diversas manifestaciones clínicas. La enfermedad invasora (EI) se define por el aislamiento del microorganismo en sitios estériles. Objetivo: Analizar características clínico-epidemiológicas y moleculares de EI por S. pyogenes en niños hospitalizados en el HP-CHPR (1/1/05-31/1/13). Materiales y Métodos: Estudio descriptivo, retrospectivo, de casos con aislamiento de S. pyogenes de sitios estériles. Se analizaron variables epidemiológicas, características de la enfermedad, laboratorio, tratamientos, días de hospitalización y evolución. Se estudió la presencia de cuatro genes que codifican factores de virulencia y perfiles cromosómicos resueltos por electroforesis en campos pulsados. Resultados: Se detectó un total de 42 casos (tasa 4,6 cada 10.000 admisiones), se analizaron todas las variables en 32. Mediana de edad 44,7 meses (14 < 2 años). En cinco se identificó puerta de entrada. Formas de presentación: infección osteo-articular (n: 15), shock (n: 6), infección de piel y tejidos blandos (n: 5), neumonía (n: 3) y bacteriemia (n: 3). Veinte requirieron procedimientos quirúrgicos y 13 de cuidado intensivo. La media de estadía hospitalaria fue de 17 días. Hubo un fallecimiento. Se realizó estudios moleculares en cinco cepas, identificándose cuatro perfiles de toxinas y pulsotipos diferentes. Discusión: La incidencia de EI en nuestra institución coincide con otras series en la región. Profundizar el conocimiento de la presentación clínica y su relación con las características moleculares es un desafío.

Vigilancia de laboratorio de enfermedad meningocóccica invasora en Chile, 2006-2012 / Laboratory surveillance for invasive meningococcal disease in Chile, 2006-2012

Background: Laboratory surveillance of Invasive Meningococcal Disease (IMD) is performed by the Institute of Public Health of Chile. It confirms identification, classifies in serogroups and analyzes the genetic profiles of Neisseria meningitidis isolates from laboratories throughout the country. Aim: To show the results of this surveillance from 2006 to 2012. Methods: A descriptive data analysis of the confirmed cases of IMD and serological characterization, susceptibility and genetic profiles of the isolates. The analysis was disaggregated by serogroup, age and region. Results: From 2006 to 2012, 486 isolates of N. meningitidis were confirmed. In 2011 a rise in IMD rates was observed due to an increase in W serogroup cases, mainly affecting children aged 5 years or less. Serogroup W became the most prevalent during 2012 (58.3%), replacing the historically prevalent serogroup B. Predominating strains belonged to ST-32 complex/ET-5 complex (40, 4% of strains) and ST-41/44 complex/ Lineage 3 (45, 9% of strains). Conclusions: Laboratory surveillance has allowed the early detection of increasing IMD caused by serogroup W, which is emergent in Chile. This information has reinforced the daily monitoring of new cases, in collaboration with all the clinical laboratories of the country.

Introducción: La vigilancia de laboratorio de enfermedad meningocócica invasora (EMI) que realiza el Instituto de Salud Pública de Chile, confirma, seroagrupa y estudia el perfil genético de las cepas de Neisseria meningitidis provenientes de los laboratorios del país. Objetivo: En este artículo se muestra los resultados de esta vigilancia entre los años 2006 a 2012. Materiales y Métodos: Se realizó un análisis descriptivo de los casos confirmados de EMI, caracterización serológica, el análisis de susceptibilidad antimicrobiana y el estudio de subtipo genético de la cepa. El análisis se desagregó por serogrupo, edad y región. Resultados: En el período 2006-2012 fue confirmado un total de 486 cepas de N. meningitidis. A partir del año 2011 se observó un alza en la tasa de EMI dado por el número de casos del serogrupo W, afectando principalmente a niños bajo 5 años de edad. El W se transformó en el serogrupo prevalente el año 2012 (58,3%), desplazando al serogrupo B, el cual históricamente había sido prevalente. Predominaron principalmente las cepas pertenecientes al complejo clonal ST-32 complex/ET-5 complex (40,4% de las muestras) y el ST-41/44 complex/Lineage 3 (45,9% de las muestras). Conclusiones: El sistema de vigilancia de laboratorio ha permitido la identificación del serogrupo W, emergente en Chile. Esta información nos ha obligado a estar en permanente alerta y monitoreo de casos diarios, mediante la participación activa de todos los laboratorios clínicos del país.

Impacto del serotipo 5 en la enfermedad invasora por Streptococcus pneumoniae en la población pediátrica ingresada en el Hospital Materno Infantil José Domingo de Obaldía

La vigilancia de la enfermedad invasora por Streptococcus pneumoniae permite detectar los cambios geográficos y cronológicos en los serotipos circulantes y en la sensibilidad antimicrobiana, monitorizando además el impacto de las vacunas sobre la enfermedad. Objetivos: Describir los serotipos aislados y la sensibilidad antimicrobiana en los pacientes pediatrics hospitalizados con enfermedad invasora por Streptococcus pneumoniae. Describir la enfermedad invasora por Streptococcus pneumoniae y sus complicaciones clínicas asociadas. Metodología: Estudio retrospectivo, longitudinal, incluye pacientes pediátricos hospitalizados en el Hospital Materno Infantil José Domingo de Obaldía en el periodo de enero de 2010 a junio de 2011; los cuales se cursaron con enfermedad invasora por Streptococcus pneumoniae como etiología en este periodo. El diagnóstico microbiológico se realizó por coaglutinación en líquidos corporales y cultivo del microorganismo. La cepa se aisló en el laboratorio de microbiología y se tipificó en el Laboratorio Central. La enfermedad invasora fue definida por el cuadro clínico y el aislamiento de Streptococcus pneumoniae de un sitio previamente estéril. Variables analizadas: edad, sexo, procedencia, sitio de infección, complicaciones, tiempo hospitalario, mortalidad, ingreso a UCI, anemia, VIH , letalidad. Resultados: Se revisaron 25 expedientes de pacientes con enfermedad invasora y aislamiento de Streptococcus pneumoniae. Dos fueron excluidos. 20 pacientes fueron menores de 5 años y 3 mayores de 5 años. 11 varones y 12 niñas. El 91% fueron indigenas. El 60.8% procedía de la Comarca Ngöbe Buglé. Promedio hospitalario 25.3 días, rango 1-93 días. 60.8% ingresó con enfermedad grave a la UCIP; 92.8% ameritó ventilación mecánica y 78.5% presentó choque. 34%(8) cursó con compromiso de SNC y el 30% (7) bacteriemia. Se tipificaron 14 cepas , el (78.5%) fue serotipo 5. Todos los aislados fueron sensibles a penicilina. 31% (5) resistentes a TMP/SMX. El 74% de los casos tenia hemoglobina menor de 10 g y solamente 3 habían completado su vacunación con PCV-7. Todo fueron VIH negativo. 30% de los pacientes fallecieron. Conclusiones: En los caso evaluados encontramos un predominio del Streptococcus pneumoniae tipo 5 en el 78.5% de los casos. Los serotipos 24F, 18C y 4 fueron aislados en 1 caso cada uno; el 100% fue sensible a penicilina. La población más afectada fue la raza indígena y los menores de 5 años. El SNC y respiratorio fueron los sitios primarios de infección. El 61% ingreso con enfermedad grave y el 30% falleció.

The monitoring of the invading disease by S. pneumoniae allows detecting geographic and temporary changes in antimicrobial sensitivity, besides monitoring the impact of the vaccines on the disease. Objectives: To describe to the isolate serotypes and antimicrobial sensitivy of Streptococcus pneumoniae to associate invasive disease in the pediatric patients hospitalized. Besides clinical manifestations and complications. Methods: Retrospective, longitudinal study. Pediatrics patients hospitalized in the Maternal Hospital in January 2010 to June 2011; in which Streptococcus pneumoniae was isolated as etiology of invasive disease. The microbiological diagnosis for Streptococcus pneumoniae was realized with coaglutination and culture of body fluids. The strain was isolated in the microbiology laboratory and it was typified in the Central Laboratory in Panama City. An invasive disease was defined by clinical manifestations and the isolation of Streptococcus pneumoniae of a previously sterile site. Analyzes variables: age, sex, origins, site of infection, complications, hospital time, death, admission to UCI, anemia , HIV, lethality. Results: 25 files with Streptococcus pneumoniae isolation and invasive disease were reviewed. Two were excluded. 20 patients were younger than 5 years and 3 oldest of 5 years. 11 were boys and 12 girls. 91% were indigenous. 60.8% came from Comarca Ngöbe Bugle. Hospital average 25, 3 days with range 1-93 days. 60.8% had serious disease and went to the UCIP; 92.8% need mechanical ventilation and 78.5% suffering shock. 34% (8) presented with commitment respiratory and SNC simultaneously. 70% (20) patients with pneumonia presented pleural effusion. 21,7% pericardial effusion and 30% (7) bacteremia. 14 isolate were typified, serotype 5 (78.5%). All were sensible to penicillin; TMP/SMX resistant 31% (5). 74% had hemoglobin less than 10 g and only 3 had completed their vaccination with PCV-7. All were HIV negative. 30% lethality. Conclusions: Streptococcus pneumoniae serotype 5 were strains predominance in the 78.5%. Others as 24 F, 18C and 4, 1 case of each serotypes; 100% were sensible to penicillin. The people more affected was indigenous race and the younger than 5 years. The respiratory and SNC were the primary infections sites. 61% come with serious illness and 30% died.

Absceso hepático como presentación inicial de la enfermedad invasora por Streptococcus pneumoniae / Hepatic abscess as first manifestation of pneumococcal invasive disease

Pneumococcal invasive disease is an important cause of morbidity and mortality in different population groups. Most cases originate from an airway infection. We describe a patient with diabetes mellitus who presented a liver abscess as first manifestation of pneumococcal invasive disease, without respiratory symptoms. The patient was treated with percutaneous drainage and systemic antibiotics with good results. Streptococcus pneumoniae should be considered among the possible etiologies of hepatic abscess, even in absence of respiratory symptoms.

La enfermedad invasora por Streptococcus pneumoniae es una causa importante de morbi-mortalidad en diferentes grupos poblacionales. La mayor parte de los casos se origina a partir de un foco infeccioso primario de origen respiratorio. Se describe el caso de un paciente diabético en el cual esta grave enfermedad se presentó de manera inicial como un absceso hepático sin manifestaciones respiratorias asociadas. El enfermo respondió de manera apropiada al tratamiento quirúrgico percutáneo y a la administración de antimicrobianos sistémicos. Se propone la consideración de S. pneumoniae entre las etiologías posibles de los abscesos hepáticos en sujetos con factores de riesgo para enfermedad invasora por este microorganismo, aún en ausencia de síntomas respiratorios.

Declaración del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología acerca de la eficacia de la vacuna anti-neumocóccica 23 valente en el adulto mayor: Febrero 2010 / 23-Valent Pneumococcal Vaccine: Statement of the Consultive Committee of Immunizations on behalf of the Chilean Infectious Diseases Society: February 2010

The article summarizes the scientific evidence related with protection conferred by the 23 valent polysacchar-die vaccine against invasive pneumococcal disease, non bacteriemic pneumococcal pneumonia, and probable pneumococal pneumonia in the elderly. Eider patients with and without risk factors are considered. The impact of herd immunitty conferred by vaccination of children with conjugated pneumococcal vaccine in reduction of penumonia in adults is discussed. Based on this analysis, the Advisory Committee on Immunizations of the Chilean Infectious Disease Society makes recommendations on the most efficient vaccine strategy for reduction of pneumococcal pneumonia in the elderly.

El artículo resume los hallazgos de la evidencia científica en relación a la protección que confiere la vacuna neumocóccica polisacárida 23 valente contra la enfermedad neumocóccica invasora, las neumonías neumocóccicas no bacteriémicas y las neumonías probablemente de etiología neumocóccica en el adulto mayor, estableciendo una categorización entre adultos mayores con factores de riesgo y sin ellos. Se documenta a la vez, el impacto que ha tenido la vacuna neumocóccica conjugada en la población infantil, en reducir las neumonías en el adulto mayor. Basados en la información disponible, el Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología, realiza recomendaciones sobre cuál sería la mejor forma de prevenir las enfermedades neumocóccicas en el adulto mayor.

Economic burden of cervical cancer in Malaysia.

Cervical cancers form the second highest number of female cancers in Malaysia, imposing a substantial amount of cost burden on its management. However, an estimation of cost burden of abnormal smears, cervical pre-invasive and invasive diseases needs to be done to show how much spending has been allocated to the problem. An expert panel committee came up with the clinical pathway and management algorithm of cervical pre invasive and invasive diseases from July-December 2006 Malaysia. An activity based costing for each clinical pathway was done. Results were converted to USD. The cost of managing pre-invasive cervical cancers stage is USD 420,150 (Range: USD 197,158-879,679). Management of invasive cancer (new cases) costs USD 51,533,233.44 (Range: USD 32,405,399.69 - USD 129,014,768.40). The cost of managing existing cases is USD 17,005,966.87 (Range: USD 10,693,781.90 - USD 28,901,587.12). The total cost of managing cervical cancers by health care providers in a public setting is around USD 75,888,329.45 (Range: USD 48,083,804.60 - USD 48,083,804.60). The outcome of this study has shown that preventive modalities such as screening have only contributed to 10.3 % of the total management cost of cervical cancer. The major cost contribution (67%) came from treatment of invasive cancer especially at more advanced stages of cancer, followed by treatment of existing cases (22%) and lastly on pre-invasive disease (0.6%). This study revealed that proportion of preventive modality in this country was still low, and the major cost came from actual treatment cost of cervical cancer. Therefore, heightened public cervical cancer screening in the country is needed.

Aislamiento de distintos serotipos de Haemophilus influenzae en muestras profundas de pacientes pediátricos / Isolation of Haemophilus influenzae serotypes from sterile sites in sick children

Haemophilus influenzae (Hi) es responsable de diversas enfermedades humanas como sepsis, meningitis, celulitis y osteoartritis. En este trabajo se investigó la recuperación de distintos serotipos de Hi en muestras profundas de pacientes pediátricos. Se estudiaron 179 aislamientos de 146 niños durante el periodo 1996-2002 en el Laboratorio de Microbiología del Hospital de Niños Superiora Sor María Ludovica, Argentina. La distribución de los serotipos fue la siguiente: 1 a, 112 b, 1 c,1 d, 4 e, 3 f y 24 no tipificables. A partir del establecimiento de la estrategia de vacunación universal anti Hi b en 1998 se observa una disminución notable del serotipo b y un aumento relativo de otros y no tipificables.

Haemophilus influenzae (Hi) is the causative agent of several human diseases such as sepsis, meningitis, celulitis, and osteoarthritis. We investigated the isolation of Hi serotypes from sterile sites in sick children. One hundred and seventy nine strains from 146 patients were studied, period 1996-2002, at the Microbiology Laboratory, Hospital de Niños Superiora Sor María Ludovica, Argentina. The serotype distribution was:1 a, 112 b,1 c,1 d, 4 e, 3 f y 24 no typable. Since the beginning of universal Hi b vaccination in 1998, we have observed the fast decrease of serotype b and a relative increase of other serotypes.