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.

Evolutionary dynamics of respiratory syncytial virus in Buenos Aires: Viral diversity, migration, and subgroup replacement.

Globally, the human respiratory syncytial virus (RSV) is one of the major causes of lower respiratory tract infections (LRTIs) in children. The scarcity of complete genome data limits our understanding of RSV spatiotemporal distribution, evolution, and viral variant emergence. Nasopharyngeal samples collected from hospitalized pediatric patients from Buenos Aires tested positive for RSV LRTI during four consecutive outbreaks (2014-2017) were randomly subsampled for RSV complete genome sequencing. Phylodynamic studies and viral population characterization of genomic variability, diversity, and migration of viruses to and from Argentina during the study period were performed. Our sequencing effort resulted in one of the largest collections of RSV genomes from a given location (141 RSV-A and 135 RSV-B) published so far. RSV-B was dominant during the 2014-2016 outbreaks (60 per cent of cases) but was abruptly replaced by RSV-A in 2017, with RSV-A accounting for 90 per cent of sequenced samples. A significant decrease in RSV genomic diversity-represented by both a reduction in genetic lineages detected and the predominance of viral variants defined by signature amino acids-was observed in Buenos Aires in 2016, the year prior to the RSV subgroup predominance replacement. Multiple introductions to Buenos Aires were detected, some with persistent detection over seasons, and also, RSV was observed to migrate from Buenos Aires to other countries. Our results suggest that the decrease in viral diversity may have allowed the dramatic predominance switch from RSV-B to RSV-A in 2017. The immune pressure generated against circulating viruses with limited diversity during a given outbreak may have created a fertile ground for an antigenically divergent RSV variant to be introduced and successfully spread in the subsequent outbreak. Overall, our RSV genomic analysis of intra- and inter-outbreak diversity provides an opportunity to better understand the epochal evolutionary dynamics of RSV.

Role of Noroviruses in Sporadic Acute Gastroenteritis Cases from Children Attending a Large Referral Children's Hospital in Buenos Aires City, Argentina.

BACKGROUND: Noroviruses (NVs) are recognized as the leading cause of sporadic and epidemic acute gastroenteritis worldwide, in all age groups. Although there is increasing knowledge that NVs are responsible for many acute gastroenteritis outbreaks in Argentina, studies to estimate prevalence in sporadic cases are scarce. METHODS: A descriptive, observational and cross-sectional study was conducted with children under 5 years with acute gastroenteritis attending the outpatient department at the "Ricardo Gutiérrez" Children's Hospital (RGCH) in Buenos Aires City between June 2017 and June 2021. Sociodemographic, clinical and epidemiologic data were recorded. Stool samples were tested and genotyped for norovirus. Association between norovirus detection and demographic and clinical variables was assessed. RESULTS: A total of 350 children with acute diarrhea were included, of which stool samples were collected for 332 (94.9%). Norovirus was detected in 81 cases (24.4%). Vomiting and moderate/severe diarrhea were more frequent in norovirus-positive than norovirus-negative children. However, the presence of watery diarrhea and a history of rotavirus vaccination were significantly associated with norovirus etiology. GII and GII.4 were the most frequently detected genogroup and genotype, respectively. CONCLUSIONS: NVs were detected with high frequency, mostly in children between 6 months and 2 years old, reinforcing the hypothesis of a newly updated scenario of norovirus predominance over rotavirus. Watery diarrhea, complete vaccination against rotavirus and vomiting are 3 key parameters that should raise suspicion of possible norovirus gastroenteritis. Continuous and active norovirus surveillance in this age group is important because children represent a priority group for norovirus vaccine design and development.

Comparison of Epidemiologic and Clinical COVID-19 Profiles in Children in Argentina, During Circulation of Original and Variant (Alpha, Gamma and Lambda) Strains.

BACKGROUND: Information on the impact of the different variants in children in Latin America is scarce. The objective of this study was to describe epidemiologic and clinical features of COVID-19 infection in children under 18 years of age in Argentina, comparing the periods before and after the circulation of new variants. METHODS: Observational, cross-sectional, multicentric, analytical study. All patients under 18 years of age with confirmed SARS-CoV-2 infection admitted at 22 healthcare centers were included. Two study periods were established: Period 1 (EW10-2020 to EW12-2021) for the Wuhan strain; Period 2 (EW13 to EW35 2021) for Alpha, Gamma, Delta and Lambda variants. FINDINGS: A total of 6330 confirmed cases were included. Period 1: 3575 (56.5%), period 2: 2755 (43.5%). During period 2, a lower number of asymptomatic cases was observed, while general, respiratory and neurologic signs and symptoms increased in all age groups. Oxygen therapy requirement was higher during the first period (36.7% vs 19.1%; P < 0.001). No significant differences were observed in the rates of severe or critical cases (6.3% vs 5,4%; P = 0.102), intensive care admission (2.1% vs 2%; P < 0.656) or case fatality (0.3% vs 0.5 %; P < 0.229). MIS-C cases occurred more frequently during the first period (1.9% vs 1.1%; P = 0.009). INTERPRETATION: The clinical spectrum of COVID-19 in Argentina has evolved. With the emergence of new variants, although the number of asymptomatic cases declined, numbers of severe and critical cases, as well as case fatality rates in children, remained unchanged.

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

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

COVID-19 in Children: Correlation Between Epidemiologic, Clinical Characteristics, and RT-qPCR Cycle Threshold Values.

BACKGROUND: Initially, the impact of SARS-CoV-2 infection on children was unknown. Standard COVID-19 diagnosis is confirmed using real-time qPCR. Cycle threshold (Ct) values of RT-qPCR are inversely proportional to viral load and the test indirectly quantifies viral RNA copy numbers. The objective of this study was to determine the correlation between epidemiology, clinical characteristics, severity of confirmed COVID-19 cases, and Ct values. METHODS: An observational, analytical, cross-sectional study. All children with COVID-19 under 18 years old admitted to the Ricardo Gutiérrez Children's Hospital between March 1, 2020, and February 28, 2021, were included. SARS-CoV-2 infection was confirmed using RT-qPCR. RESULTS: Median age of patients was 7 years. Ct values were estimated in 419 cases, median Ct value was 23.5 [interquartile range (IQR): 18.9-30.9]. Levels were significantly lower in symptomatic than asymptomatic patients (Ct: 22.1; IQR: 18.4-22.1), in children <2 years of age (Ct: 20.6; IQR: 17.3-27.3) and when sample collection was <4 days after symptom onset (Ct: 21.1; IQR: 18.1-27.5). In children >2 years of age, Ct values were significantly lower in symptomatic (Ct: 22.6; IQR: 18.7-29.3) than asymptomatic (Ct: 31.2; IQR: 24.5-33.3) patients. CONCLUSIONS: Children younger than 2 years with COVID-19 have lower values of Ct-as a proxy for higher viral load-than older children. Symptomatic children over 2 years of age had lower Ct values compared with asymptomatic children.

Estudio multicéntrico de casos confirmados de COVID-19: datos preliminares de 2690 pacientes pediátricos en Argentina durante el primer año de la pandemia / A multicenter study of confirmed COVID-19 cases: preliminary data on 2690 pediatric patients in Argentina during the first year of the pandemic

Introducción. La evidencia actual indica que la gravedad de la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés) es menor en la población pediátrica, los datos locales aún son limitados. Objetivo: caracterizar los aspectos clínicos y epidemiológicos de la infección por COVID-19 en menores de 18 años en Argentina. Población y métodos. Estudio transversal, observacional y analítico de casos confirmados de COVID-19 entre 0 y 18 años asistidos entre marzo de 2020 y marzo de 2021 en 19 centros pediátricos de referencia de Argentina. Se realizó un análisis multivariado para identificar las variables predictoras de cuadros graves. Resultados. Se incluyeron 2690 casos de COVID-19: 77,7 % residentes del área metropolitana de Buenos Aires, 50,1 % de sexo masculino, mediana de edad de 5,6 años. El 90 % ocurrió entre las semanas epidemiológicas 20-47 del 2020; 60,4 % con antecedente de contacto con personas con COVID-19; y 96,6 % en el entorno familiar. El 51,4 % presentó síntomas respiratorios; 61,6 % síntomas generales; 18,8 % síntomas gastrointestinales; 17,1 % síntomas neurológicos; 7,2 % otros y 21,5 % fueron asintomáticos. El 59,4 % fue hospitalizado; 7,4 fueron graves o críticos. Se registraron 57 casos de síndrome inflamatorio multisistémico. El antecedente de asma, displasia broncopulmonar, cardiopatía congénita, desnutrición moderada a grave, obesidad, enfermedad neurológica crónica y/o edad menor de 6 meses resultaron predictores independientes de gravedad. Residir en barrios vulnerables resultó protector. Conclusiones. Más de la mitad de los casos refirieron antecedente de contacto con personas con COVID-19 en el entorno familiar. La hospitalización no respondió a criterios clínicos de gravedad. La gravedad se encuentra asociada a la existencia de ciertas comorbilidades.

Introduction. The current evidence indicates that the severity of the coronavirus disease 2019 (COVID-19) is lower in the pediatric population but local data are still limited. Objective: To characterize the clinical and epidemiological aspects of COVID-19 infection in patients younger than 18 years in Argentina. Population and methods. Cross-sectional, observational, and analytical study of confirmed COVID-19 patients aged 0-18 years seen between March 2020 and March 2021 at 19 referral children's hospitals of Argentina. A multivariate analysis was done to identify predictors of severe cases. Results. A total of 2690 COVID-19 cases were included: 77.7% lived in the Metropolitan Area of Buenos Aires; 50.1% were males; patients' median age was 5.6 years. Of them, 90% were seen during epidemiological weeks 20-47 of 2020; 60.4% had a history of contact with COVID-19 patients; and 96.6% in their family setting. Also, 51.4% had respiratory symptoms; 61.6%, general symptoms; 18.8%, gastrointestinal symptoms; 17.1%, neurological symptoms; 7.2%, other symptoms; and 21.5% were asymptomatic. In addition, 59.4% of patients were hospitalized and 7.4% had a severe or critical course. A total of 57 patients developed multisystem inflammatory syndrome. A history of asthma, bronchopulmonary dysplasia, congenital heart disease, moderate to severe malnutrition, obesity, chronic neurological disease and/or age younger than 6 months were independent predictors of severity.Livinginavulnerableneighborhoodwas a protective factor. Conclusions. More than half of cases referred a history of contact with COVID-19 patients in the family setting. Hospitalization was not based on clinical criteria of severity. Severity was associated with the presence of certain comorbidities

A multicenter study of confirmed COVID-19 cases: preliminary data on 2690 pediatric patients in Argentina during the first year of the pandemic. / Estudio multicéntrico de casos confirmados de COVID-19: datos preliminares de 2690 pacientes pediátricos en Argentina durante el primer año de la pandemia.

INTRODUCTION: The current evidence indicates that the severity of the coronavirus disease 2019 (COVID-19) is lower in the pediatric population but local data are still limited. Objective: To characterize the clinical and epidemiological aspects of COVID-19 infection in patients younger than 18 years in Argentina. POPULATION AND METHODS: Cross-sectional, observational, and analytical study of confirmed COVID-19 patients aged 0-18 years seen between March 2020 and March 2021 at 19 referral children's hospitals of Argentina. A multivariate analysis was done to identify predictors of severe cases. RESULTS: A total of 2690 COVID-19 cases were included: 77.7% lived in the Metropolitan Area of Buenos Aires; 50.1% were males; patients' median age was 5.6 years. Of them, 90% were seen during epidemiological weeks 20-47 of 2020; 60.4% had a history of contact with COVID-19 patients; and 96.6% in their family setting. Also, 51.4% had respiratory symptoms; 61.6%, general symptoms; 18.8%, gastrointestinal symptoms; 17.1%, neurological symptoms; 7.2%, other symptoms; and 21.5% were asymptomatic. In addition, 59.4% of patients were hospitalized and 7.4% had a severe or critical course. A total of 57 patients developed multisystem inflammatory syndrome. A history of asthma, bronchopulmonary dysplasia, congenital heart disease, moderate to severe malnutrition, obesity, chronic neurological disease and/or age younger than 6 months were independent predictors of severity. Living in a vulnerable neighborhood was a protective factor. CONCLUSIONS: More than half of cases referred a history of contact with COVID-19 patients in the family setting. Hospitalization was not based on clinical criteria of severity. Severity was associated with the presence of certain comorbidities.

Introducción. La evidencia actual indica que la gravedad de la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés) es menor en la población pediátrica, los datos locales aún son limitados. OBJETIVO: caracterizar los aspectos clínicos y epidemiológicos de la infección por COVID-19 en menores de 18 años en Argentina. Población y métodos. Estudio transversal, observacional y analítico de casos confirmados de COVID-19 entre 0 y 18 años asistidos entre marzo de 2020 y marzo de 2021 en 19 centros pediátricos de referencia de Argentina. Se realizó un análisis multivariado para identificar las variables predictoras de cuadros graves. RESULTADOS: Se incluyeron 2690 casos de COVID-19: 77,7 % residentes del área metropolitana de Buenos Aires, 50,1 % de sexo masculino, mediana de edad de 5,6 años. El 90 % ocurrió entre las semanas epidemiológicas 2047 del 2020; 60,4 % con antecedente de contacto con personas con COVID-19; y 96,6 % en el entorno familiar. El 51,4 % presentó síntomas respiratorios; 61,6 % síntomas generales; 18,8 % síntomas gastrointestinales; 17,1 % síntomas neurológicos; 7,2 % otros y 21,5 % fueron asintomáticos. El 59,4 % fue hospitalizado; 7,4 % fueron graves o críticos. Se registraron 57 casos de síndrome inflamatorio multisistémico. El antecedente de asma, displasia broncopulmonar, cardiopatía congénita, desnutrición moderada a grave, obesidad, enfermedad neurológica crónica y/o edad menor de 6 meses resultaron predictores independientes de gravedad. Residir en barrios vulnerables resultó protector. CONCLUSIONES: Más de la mitad de los casos refirieron antecedente de contacto con personas con COVID-19 en el entorno familiar. La hospitalización no respondió a criterios clínicos de gravedad. La gravedad se encuentra asociada a la existencia de ciertas comorbilidades.

Impact of varicella vaccine on nosocomial outbreaks and management of post exposure prophylaxis following in a paediatric hospital.

INTRODUCTION: In 2015, varicella vaccine was introduced to the National Immunization Programme in a one-dose regimen for infants aged 15 months. The aim of this study was to describe and compare the epidemiologic characteristics, management strategies and costs of varicella outbreaks in Ricardo Gutierrez Children's Hospital (HNRG) from 2000 to 2019, before (PreV period) and after (PostV period) the introduction of the varicella vaccine. METHODS: A retrospective, analytic study of the impact of nosocomial varicella outbreaks at the HNRG, based on active epidemiologic surveillance. We compared nosocomial varicella outbreaks rates (per 10,000 discharges) between PreV and PostV, excluding the intervention year (2015). RESULTS: During PreV, an average of 15.87 (13.91-18.02) outbreaks per year was observed and in PostV 5.5 per year (3.44-8.32). Outbreaks adjusted by all cause discharges showed a reduction of 59.13% (-36.68%, -73.62%) after vaccine introduction. Considering that in PreV the average of susceptible cases per outbreak was 5.0 and in PostV 7.8, with a cost per susceptible of AR$ $6,522 (80.27 USD) PreV and 6,708 PostV the economic impact on the reduction of outbreaks after the introduction of the vaccine, showed an estimated average savings per year of AR$ -252,128 AR$ (-3,103.11 USD). CONCLUSIONS: The number of annual varicella hospital outbreaks at the HNRG decreased significantly after varicella vaccine was introduced to NIP in Argentina with a relevant reduction in terms of costs.

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

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

Virus sincicial respiratorio en niños nacidos prematuros: 19 años de vigilancia epidemiológica activa en un hospital pediátrico / Respiratory syncytial virus in preterm infants: 19 years of active epidemiological surveillance in a children's hospital

Introducción. El virus sincicial respiratorio (VSR) es el principal agente causal de la infección respiratoria aguda baja (IRAB) en pediatría. Los niños prematuros tienen mayor riesgo de complicaciones asociadas con esta infección. Los objetivos fueron describir y comparar las características clínicas y epidemiológicas asociadas a IRAB por VSR en niños/as nacidos pretérmino y a término, y establecer predictores de letalidad en los prematuros.Métodos. Estudio prospectivo, transversal, de pacientes ingresados por IRAB, en el período 2000-2018. El diagnóstico virológico se realizó mediante inmunofluorescencia indirecta o reacción en cadena de la polimerasa con transcriptasa inversa de aspirados nasofaríngeos. Se registraron las características clínico-epidemiológicas. Se desarrolló un modelo de regresión logística múltiple para establecer los predictores de letalidad en prematuros.Resultados. Se incluyeron 16 018 casos de IRAB; 13 545 (el 84,6 %) fueron estudiados; 6047 (el 45 %) positivos; VSR predominó en el 81,1 % (4907); mostró un patrón epidémico estacional; el 14 % (686) fueron prematuros.Los prematuros mostraron mayor frecuencia de comorbilidades, antecedentes respiratorios perinatales, cardiopatía congénita, desnutrición, enfermedad respiratoria crónica, displasia broncopulmonar, hospitalización previa por IRAB y enfermedad neurológica crónica (p < 0,001); requirieron más cuidados intensivos, mayor tiempo de internación y mayor tasa de letalidad (p < 0,01). La cardiopatía congénita fue predictor independiente de letalidad por VSR en prematuros [OR 3,67 (1,25-10,8), p = 0,01].Conclusión. VSR mostró un patrón epidémico, afectó a prematuros con ciertas comorbilidades con mayor morbimortalidad que los de término. La letalidad por VSR en prematuros se asoció con la cardiopatía congénita.

Introduction. Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (ALRTI) in pediatrics. Preterm infants are at a higher risk for complications. We aimed to describe and compare the clinical and epidemiological characteristics associated with ALRTI due to RSV in preterm and term infants and to establish the predictors of fatality among preterm infants.Methods. Prospective, cross-sectional study of patients admitted due to ALRTI in the 2000-2018 period. Viral diagnosis was done by indirect immunofluorescence or reverse transcription polymerase chain reaction in nasopharyngeal aspirates. Clinical and epidemiological characteristics were recorded. A multiple logistic regression model established the predictors of fatality among preterm infants.Results. A total of 16 018 ALRTI cases were included; 13 545 (84.6 %) were tested; 6047 (45 %) were positive; RSV was prevalent in 81.1 % (4907), with a seasonal epidemic pattern; 14 % (686) were preterm infants.Comorbidities, perinatal respiratory history, congenital heart disease, malnutrition, chronic respiratory disease, bronchopulmonary dysplasia, prior hospitalization due to ALRTI, and chronic neurological disease (p < 0.001) were more common among preterm infants; they required more intensive care and a longer length of stay, and had a higher fatality rate (p < 0.01). Congenital heart disease was an independent predictor of fatality due to RSV among preterm infants (OR: 3.67 [1.25-10.8], p = 0.01).Conclusion. RSV showed an epidemic pattern and affected more preterm infants with certain comorbidities, with a higher morbidity and mortality, compared to term infants. RSV fatality among preterm infants was associated with congenital heart disease.

Respiratory syncytial virus in preterm infants: 19 years of active epidemiological surveillance in a children's hospital. / Virus sincicial respiratorio en niños nacidos prematuros: 19 años de vigilancia epidemiológica activa en un hospital pediátrico.

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (ALRTI) in pediatrics. Preterm infants are at a higher risk for complications. We aimed to describe and compare the clinical and epidemiological characteristics associated with ALRTI due to RSV in preterm and term infants and to establish the predictors of fatality among preterm infants. METHODS: Prospective, cross-sectional study of patients admitted due to ALRTI in the 2000-2018 period. Viral diagnosis was done by indirect immunofluorescence or reverse transcription polymerase chain reaction in nasopharyngeal aspirates. Clinical and epidemiological characteristics were recorded. A multiple logistic regression model established the predictors of fatality among preterm infants. RESULTS: A total of 16 018 ALRTI cases were included; 13 545 (84.6 %) were tested; 6047 (45 %) were positive; RSV was prevalent in 81.1 % (4907), with a seasonal epidemic pattern; 14 % (686) were preterm infants. Comorbidities, perinatal respiratory history, congenital heart disease, malnutrition, chronic respiratory disease, bronchopulmonary dysplasia, prior hospitalization due to ALRTI, and chronic neurological disease (p < 0.001) were more common among preterm infants; they required more intensive care and a longer length of stay, and had a higher fatality rate (p < 0.01). Congenital heart disease was an independent predictor of fatality due to RSV among preterm infants (OR: 3.67 [1.25-10.8], p = 0.01). CONCLUSION: RSV showed an epidemic pattern and affected more preterm infants with certain comorbidities, with a higher morbidity and mortality, compared to term infants. RSV fatality among preterm infants was associated with congenital heart disease.

Introducción. El virus sincicial respiratorio (VSR) es el principal agente causal de la infección respiratoria aguda baja (IRAB) en pediatría. Los niños prematuros tienen mayor riesgo de complicaciones asociadas con esta infección. Los objetivos fueron describir y comparar las características clínicas y epidemiológicas asociadas a IRAB por VSR en niños/as nacidos pretérmino y a término, y establecer predictores de letalidad en los prematuros. Métodos. Estudio prospectivo, transversal, de pacientes ingresados por IRAB, en el período 2000-2018. El diagnóstico virológico se realizó mediante inmunofluorescencia indirecta o reacción en cadena de la polimerasa con transcriptasa inversa de aspirados nasofaríngeos. Se registraron las características clínicoepidemiológicas. Se desarrolló un modelo de regresión logística múltiple para establecer los predictores de letalidad en prematuros. Resultados. Se incluyeron 16 018 casos de IRAB; 13 545 (el 84,6 %) fueron estudiados; 6047 (el 45 %) positivos; VSR predominó en el 81,1 % (4907); mostró un patrón epidémico estacional; el 14 % (686) fueron prematuros. Los prematuros mostraron mayor frecuencia de comorbilidades, antecedentes respiratorios perinatales, cardiopatía congénita, desnutrición, enfermedad respiratoria crónica, displasia broncopulmonar, hospitalización previa por IRAB y enfermedad neurológica crónica (p < 0,001); requirieron más cuidados intensivos, mayor tiempo de internación y mayor tasa de letalidad (p < 0,01). La cardiopatía congénita fue predictor independiente de letalidad por VSR en prematuros [OR 3,67 (1,25-10,8), p = 0,01]. Conclusión. VSR mostró un patrón epidémico, afectó a prematuros con ciertas comorbilidades con mayor morbimortalidad que los de término. La letalidad por VSR en prematuros se asoció con la cardiopatía congénita.

Maternal Vaccination in Argentina: Tetanus, Diphtheria, and Acellular Pertussis Vaccine Effectiveness During Pregnancy in Preventing Pertussis in Infants <2 Months of Age.

BACKGROUND: In 2011, Argentina experienced its highest pertussis incidence and mortality rates of the last decade; 60% of deaths were among infants aged <2 months. In response, a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was recommended for all pregnant women at ≥20 weeks of gestation. Although recent studies suggest that maternal Tdap vaccination is effective at preventing infant disease, no data have come from low- or middle-income countries, nor from ones using whole-cell pertussis vaccines for primary immunization. METHODS: We conducted a matched case-control evaluation to assess the effectiveness of maternal Tdap vaccination in preventing pertussis among infants aged <2 months in Argentina. Pertussis case patients identified from September 2012 to March 2016 at 6 hospital sites and confirmed by polymerase chain reaction testing were included. Five randomly selected controls were matched to each case patient by hospital site and mother's health district. We used multivariable conditional logistic regression to calculate odds ratios (ORs). Vaccine effectiveness (VE) was estimated as (1 - OR) × 100%. RESULTS: Seventy-one case patients and 300 controls were included in the analysis. Forty-nine percent of case patients and 78% of controls had mothers who were vaccinated during pregnancy. Overall Tdap VE was estimated at 80.7% (95% confidence interval, 52.1%-92.2%). We found similar VE whether Tdap was administered during the second or third trimester. CONCLUSIONS: Tdap vaccination during pregnancy is effective in preventing pertussis in infants aged <2 months in Argentina, with similar effectiveness whether administered during the second or third trimester of pregnancy.

Burden of Respiratory Syncytial Virus Disease and Mortality Risk Factors in Argentina: 18 Years of Active Surveillance in a Children's Hospital.

BACKGROUND: Respiratory syncytial virus is the leading cause of acute lower respiratory infection in children. We aimed to describe the clinical-epidemiologic pattern and risk factors for mortality associated with RSV infection. METHODS: This is a prospective, cross-sectional study of acute lower respiratory infection in children admitted to the Children's Hospital during 2000 to 2017. Viral diagnosis was made by fluorescent antibody techniques or real-time-polymerase chain reaction. We compared clinical-epidemiologic characteristics of RSV infection in nonfatal versus fatal cases. Multiple logistic regression was used to identify independent predictors of mortality. RESULTS: Of 15,451 patients with acute lower respiratory infection, 13,033 were tested for respiratory viruses and 5831 (45%) were positive: RSV 81.3% (4738), influenza 7.6% (440), parainfluenza 6.9% (402) and adenovirus 4.3% (251). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV cases show a case fatality rate of 1.7% (82/4687). Fatal cases had a higher proportion of prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurologic disease (P < 0.01) and pneumonia at clinical presentation (P = 0.014). No significant difference between genders was observed. Most deaths occurred among children who had complications: respiratory distress (80.5%), nosocomial infections (45.7%), sepsis (31.7%) and atelectasis (13.4%). Independent predictors of RSV mortality were moderate-to-severe malnourishment, odds ratio (OR): 3.69 [95% confidence interval (CI): 1.98-6.87; P < 0.0001]; chronic neurologic disease, OR: 4.14 (95% CI: 2.12-8.08; P < 0.0001); congenital heart disease, OR: 4.18 (95% CI: 2.39-7.32; P< 0.0001); and the age less than 6 months, OR: 1.99 (95% CI: 1.24-3.18; P = 0.004). CONCLUSIONS: RSV showed an epidemic pattern affecting mostly young children. Malnourishment, chronic neurologic disease, congenital heart disease and the age less than 6 months were the independent risk factors for RSV mortality.

[Assessment of the use in adults of four vaccines: a population survey in Argentina]. / Evaluación del uso en adultos de cuatro vacunas: una encuesta poblacional en Argentina.

Vaccination is one of the most effective strategies for disease prevention. Argentina initiated the transition from child vaccination to family vaccination through the incorporation of an adult schedule. One of the difficulties with this last group is to assess the percentage of use (PU) of the vaccines. With the aim of determining the PU of adult vaccines in Argentina, a vaccination module was included in the National Survey of Risk Factors carried out in 2013 by the National Ministry of Health. The sampling had a stratified multistage design. A total of 32 365 people = 18 year-old were surveyed about the use of four vaccines included in the National Vaccination Calendar: hepatitis B, tetanus, influenza, and pneumococcus. The entire population was surveyed for tetanus and hepatitis B while certain groups at risk were evaluated for influenza and pneumococcus, according to current recommendations. PU varied according to the vaccine analyzed: tetanus 49.8%, hepatitis B 21.7%, influenza 51.6% and pneumococcus 16.2%. The main information sources on adult vaccination were media (television, internet, etc.) followed by health personnel (70.8% and 27.9%, respectively). The survey is a suitable tool to assess the use of vaccines by adults, identify low coverage populations, and to plan and implement strategies to improve coverage.

Bordetella pertussis (Bp) disease: Before (2003-2011) and after (2013-2016) maternal immunization strategy in a pediatric hospital.

INTRODUCTION: Whooping cough continues to be a major cause of morbidity and mortality in infants younger than 1 year. In 2012, Argentina introduced Tdap in pregnancy to prevent infant mortality. The aim of this study is to describe the impact of maternal immunization on the hospitalization and mortality rates of confirmed Bordetella pertussis (Bp) cases by comparing pre- and post-Tdap vaccine recommendation periods. MATERIAL AND METHODS: All PCR-confirmed Bp cases from "R. Gutierrez" Children's Hospital identified between December 2003 and December 2016 were included in. Analysis was performed comparing hospitalization rates (per 10,000 discharges) between pre-vaccination (PreV) 2003-2011 and post-vaccination (PostV) 2013-2016 time periods, excluding the intervention year (2012). RESULTS: During the study time frame, there were 1046 suspected Bp cases, of which 337 (32.2%) were confirmed. Three-hundred eight cases were analyzed (excluding year 2012): 237 in PreV and 71 in PostV. In comparison with PreV, PostV cases were older (3 vs 9 months; p < 0.001), and required less hospitalization (86.9% vs 67.6%; p < 0.001). Bp hospitalization rate (HR) decreased (22.3 vs 11.6; p < 0.001). The mortality rate in PreV 5.9% (14 cases); there were not deaths during PostV (p = 0.036). CONCLUSIONS: Confirmed cases were among infants younger than 1 year In PostV, Bp cases were older and there was a significant decrease in the hospitalization rate. There were no fatal cases in our center after the pregnancy Tdap recommendation was implemented.

Actualización sobre enfermedad meningocócica y su prevención / Update on meningococcal disease and its prevention

En Argentina la enfermedad meningocócica (EM) tiene un comportamiento endemo-epidémico y los niños <5 años son los más afectados, la letalidad es del 10%, con mayor impacto en <1 año. Históricamente los serogrupos predominantes fueron B y C y en la actualidad prevalecen los serogrupos W y B. En 2017 Argentina incorporó la vacunación meningocócica (Resolución 10/2015) con un esquema de 2+1 (3 meses-5 meses-15/18 meses) de la vacuna conjugada cuadrivalente ACWY-CRM197-Menveo®. La estrategia incluye una única dosis de vacuna a los 11 años, con el objetivo de disminuir la portación orofaríngea y así contribuir a la disminución de la incidencia de EM en el grupo más vulnerable. El programa también provee la vacunación para huéspedes especiales. También se encuentran disponibles la vacuna cuadrivalente ACWY conjugada con toxoide diftérico (MenACYW-D)-Menactra®, licenciada para niños ≥9 meses hasta los 55 años, y la vacuna meningocócica B multicomponente recombinante (MenB-4C)-Bexsero®. Esta última aprobada en 2015 para su uso en ≥2 meses de vida. Estudios post licencia demostraron un alto nivel de protección y de seguridad de la vacuna. Es por el momento una vacuna de indicación individual que se está analizando en la esfera de Salud Pública

Meningococcal disease (MD) is endemoepidemic in Argentina, where most cases occur in children <5 years of age, and the fatality rate is 10% with the highest impact among infants <1 year of age. Historically, the predominant serogroups were B and C, and the serogroups W and B prevail at present. In 2017, the meningococcal vaccine was introduced in the Argentine National Immunization Program with a two-dose plus a booster schedule (3 months-5 months-15/18 months) of the quadrivalent meningococcal conjugate vaccine MenACWY-CRM197 (Menveo®). The strategy includes a single dose of the vaccine at 11 years of age, with the aim of reducing oropharyngeal carriage, thus contributing to the reduction of the MD incidence in the most vulnerable group. The program also provides vaccination for special hosts. There are also other vaccines available privately, such as the quadrivalent meningococcal conjugate vaccine MenACWY-D (Menactra®), licensed for children ≥9 months of age up to 55 years of age, and the multicomponent meningococcal serogroup B vaccine 4CMenB (Bexsero®). This vaccine was approved in 2015 for use in ≥2 months of age. Post-license studies demonstrated its strong protection and safety. It is, for the time being, a vaccine of individual indication that is being analyzed in the Public Health area

Inmunización materna ¿Por qué vacunar a las embarazadas? / Maternal immuniza on: why should pregnant women be vaccinated?

La inmunización materna representa una oportunidad excepcional para proteger a las mujeres embarazadas y a sus hijos en los primeros meses de vida de enfermedades que causan una morbilidad y mortalidad considerables tales como las producidas por B. pertussis, virus sincicial respiratorio o influenza. La protección de los infantes se logra mediante la transmisión transplacentaria de elevadas concentraciones de anticuerpos protectores. Se estima que el 40% de las defunciones infantiles a nivel mundial ocurren en el período neonatal, y muchas de estas muertes se deben a infecciones que podrían prevenirse mediante vacunas maternas existentes o futuras. El siguiente artículo tiene como objetivo remarcar la importancia de la vacunación en el embarazo y actualizar el calendario de vacunación durante el mismo en la Argentina, resaltando la necesidad por parte del personal de Salud de conocerlo para no perder oportunidades de vacunación en este grupo

Maternal immunization is an exceptional opportunity for protecting pregnant women and their children in their first months of life against diseases that cause considerable morbidity and mortality, such as those caused by B. pertussis, respiratory syncytial virus or influenza. Infant protection is achieved through transplacental transmission of high concentrations of protective antibodies. It is estimated that 40% of infant deaths worldwide occur in the neonatal period, and many of these deaths are due to infections that could be prevented by existing or future maternal vaccines. The following article aims to highlight the importance of vaccination in pregnancy and to update the vaccination schedule during it in Argentina, underlining the need for health personnel to know it so as not to miss vaccination opportunities in this group

Enfermedad por Bordetella pertussis ¿Qué hacer ante una sospecha de coqueluche? / Bordetella pertussis disease. What to do when whooping cough is suspected

Coqueluche o tos convulsa es una enfermedad infecciosa, de presentación aguda, causada por la bacteria Bordetella pertussis. Hay evidencia de una alta carga de enfermedad en los países en desarrollo en los cuales sigue siendo una de las principales causas de muertes prevenibles por vacunación. La adecuada vigilancia epidemiológica, la detección precoz de casos, el manejo adecuado de brotes y el mantenimiento de altas coberturas de vacunación son los pilares de la prevención. El objetivo de este artículo es describir las normas vigentes para el manejo de los casos de Coqueluche y sus contactos

Pertussis or whooping cough is an infectious disease, of acute presentation, caused by the Bordetella pertussis bacterium. There is evidence of a high burden of disease in developing countries where it continues to be one of the leading causes of vaccine-preventable deaths. Adequate epidemiological surveillance, the early detection of cases, the proper management of outbreaks and the maintenance of high vaccination coverage are the pillars of prevention. The aim of this article is to describe the current guides for the management of cases of whooping cough and its contacts

Impacto de la vacunación para Rotavirus, ¿cuál es el rol de los Calicivirus humanos? / Impact of Rotavirus vaccination: what is the role of human Caliciviruses?

Las enfermedades infecciosas constituyen la segunda causa de mortalidad en los menores de 5 años. La diarrea aguda y la neumonía son las que generan la mayor carga de enfermedad. Argentina introdujo la vacunación sistemática contra rotavirus en el año 2015. El objetivo de este trabajo es describir el cambio epidemiológico de las diarreas agudas luego de la implementación de la vacuna rotavirus en Argentina, así como la eventual aparición de otros virus como nuevos agentes causales de esta patología y los desafíos para su diagnóstico. Para lograr el objetivo se realizó una revisión bibliográfica. En Argentina dos años después del inicio de la estrategia de vacunación con coberturas entre 61-75% se evidenció un descenso de 10% de las diarreas agudas globalmente y de 50% en las diarreas causadas por rotavirus. También se observó un desplazamiento de la estacionalidad en la ocurrencia de diarreas agudas de 10 semanas respecto a la etapa pre vacunación. A nivel mundial se ha descripto posterior a la introducción de la vacunación contra rotavirus una mayor relevancia de otros agentes (calicivirus humano) como causa de diarrea aguda, con un comportamiento diferencial en cuanto a la morbimortalidad, manejo clínico y diagnóstico. Se requiere un sistema de vigilancia continua e integrada para comprender la epidemiología y la evolución de estos agentes virales para ajustar medidas de prevención y control de la enfermedad

Infectious diseases are the second cause of mortality in children under 5 years of age. Acute diarrhea and pneumonia cause the greatest burden of disease. Argentina introduced routine rotavirus vaccination in 2015. The aim was to describe epidemiological changes in acute diarrhea after the implementation of rotavirus immunization in Argentina, as well as the possible appearance of other viruses as new causative agents and the challenges for its diagnosis. To achieve the objective, a bibliographic review was carried out. Argentina achieved coverage between 61-75% two years after the introduction in the national calendar. A decrease in acute diarrhea (10%) and diarrhea caused by rotavirus (50%) was observed. There was also change in the acute diarrhea seasonality, showing a delay in the occurrence of 10 weeks compared to the pre-vaccination stage. After the introduction of rotavirus vaccination a greater relevance of other agents (human calicivirus) has been described worldwide causing acute diarrhea, with a differential behavior in terms of morbidity, mortality, clinical management and diagnosis. A continuous and integrated surveillance system is required to understand the epidemiology and evolution of these viral agents to adjust measures for the prevention and control of the disease