Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.

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.

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.

Impact of varicella vaccination in Argentina: Seroprevalence in children and adults in a pediatric hospital.

BACKGROUND: Varicella is the primary infection caused by varicella-zoster virus (VZV). In Argentina, the varicella vaccine was introduced in the National Immunization Programme in 2015 as a single dose scheduled at 15 months of age. OBJECTIVES: To estimate VZV seroprevalence in a healthy hospital based population before and after vaccine introduction to the NIP. MATERIAL Y METHODS: Cross-sectional, observational, analytic study. Healthy subjects 1-40 years of age were included between June and December 2019 and tested for VZV-antibodies. Results were compared to data from a similar prevaccination study. RESULTS: Out of 599 samples, 11 indeterminate results were excluded, 424 were positive; overall seroprevalence rate was 72.1% (95 %CI = 68,3-75,8%). No differences were observed between pre and post vaccination studies for overall prevalence or between age groups, except for vaccinated children aged 11-15 (p = 0,005). Rates increased in both periods in subjects aged 6 years or older. Primary vaccine failures were 21%; in subjects <5 years 83% seropositive cases had been vaccinated, in >5 year-olds >90% seropositive cases were associated with a history of infection (OR: 10,4; IC95%: 6,4-16,8; p < 0,001) or household contact (OR:4,8; IC95%: 3,1-7,6; p < 0,001). Vaccination protected against disease (OR: 0.25; 95 %CI: 0.09-0.68; p = 0.004). CONCLUSION: seroprevalence was high in all age groups except in unvaccinated 12 to 15-month infants. Seropositivity was due to vaccination in 15 months to 5 year-old children and to infection in older children.

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.

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.

Influenza virus: 16 years' experience of clinical epidemiologic patterns and associated infection factors in hospitalized children in Argentina.

BACKGROUND: Influenza is an important cause of acute lower respiratory tract infection (aLRTI), hospitalization, and mortality in children. This study aimed to describe the clinical and epidemiologic patterns and infection factors associated with influenza, and compare case features of influenza A and B. METHODS: In a prospective, cross-sectional study, patients admitted for aLRTI, between 2000 and 2015, were tested for respiratory syncytial virus, adenovirus, influenza, or parainfluenza, and confirmed by fluorescent antibody (FA) or real-time polymerase chain reaction (RT-PCR) assay of nasopharyngeal aspirates. RESULTS: Of 14,044 patients, 37.7% (5290) had FA- or RT-PCR-confirmed samples that identified influenza in 2.8% (394/14,044; 91.4% [360] influenza A, 8.6% [34] influenza B) of cases. Influenza frequency followed a seasonal epidemic pattern (May-July, the lowest average temperature months). The median age of cases was 12 months (interquartile range: 6-21 months); 56.1% (221/394) of cases were male. Consolidated pneumonia was the most frequent clinical presentation (56.9%; 224/394). Roughly half (49.7%; 196/394) of all cases had previous respiratory admissions; 9.4% (37/394) were re-admissions; 61.5% (241/392) had comorbidities; 26.2% (102/389) had complications; 7.8% (30/384) had nosocomial infections. The average case fatality rate was 2.1% (8/389). Chronic neurologic disease was significantly higher in influenza B cases compared to influenza A cases (p = 0.030). The independent predictors for influenza were: age ≥6 months, odds ratio (OR): 1.88 (95% confidence interval [CI]: 1.44-2.45); p<0.001; presence of chronic neurologic disease, OR: 1.48 (95% CI: 1.01-2.17); p = 0.041; previous respiratory admissions, OR: 1.71 (95% CI: 1.36-2.14); p<0.001; re-admissions, OR: 1.71 (95% CI: 1.17-2.51); p = 0.006; clinical pneumonia, OR: 1.50 (95% CI: 1.21-1.87); p<0.001; immunodeficiency, OR: 1.87 (95% CI: 1.15-3.05); p = 0.011; cystic fibrosis, OR: 4.42 (95% CI: 1.29-15.14); p = 0.018. CONCLUSION: Influenza showed an epidemic seasonal pattern (May-July), with higher risk in children ≥6 months, or with pneumonia, previous respiratory admissions, or certain comorbidities.

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.

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

Recomendaciones ante exposición a varicela en el ámbito hospitalario / Recommendations concerning exposure to chickenpox in hospital settings

La varicela es una infección viral aguda, con elevada transmisibilidad. Si bien en la mayor parte de los casos cursa como una infección benigna, puede presentar complicaciones en ciertos grupos de riesgo fundamentalmente en el ámbito hospitalario. El siguiente artículo resume los aspectos más importantes del abordaje de los pacientes expuestos a varicela, focalizando en el manejo epidemiológico de los contactos susceptibles en el ámbito de los servicios de salud

Chickenpox is an acute viral infection, with high transmissibility. Although, in most cases, it is a benign infection, it can cause complications in certain risk groups, mainly in the hospital setting. The following article summarizes the most important aspects of the management of patients exposed to varicella, focusing on the epidemiological management of susceptible contacts in the field of health care services

VSR: un futuro promisorio en vacunas / RSV: a promising future for vaccines

Las Infecciones Respiratorias Agudas Bajas (IRAB) persisten como una de las mayores causas de morbilidad y mortalidad en los países en vías de desarrollo, siendo el virus sincicial respiratorio (VSR) la principal causa de IRAB en bebés y niños pequeños a nivel mundial. Hasta el momento no existe terapia antiviral disponible ni vacuna eficaz aprobada para su prevención. El único método de profilaxis contra VSR disponible es el Palivizumab, un anticuerpo monoclonal humanizado contra la glicoproteína F que puede ser utilizado para prevenir la enfermedad severa en los grupos de alto riesgo, pero su alto costo y la necesidad de varias administraciones dificulta su uso. Hay aproximadamente un total de 60 estrategias entre vacunas y anticuerpos monoclonales humanizados contra el VSR en desarrollo, de las cuales 16 están en ensayos de Fase 1-3. El objetivo de esta revisión es describir las principales líneas de investigación vigentes

Acute lower respiratory infections (ALRI) are one of the main causes of morbidity and mortality in developing countries, with the respiratory syncytial virus (RSV) being the most important cause of ALRI in infants and young children worldwide. So far there is no available antiviral therapy or effective vaccine approved for its prevention. The only available method of prophylaxis against RSV is Palivizumab, a humanized monoclonal antibody against the F glycoprotein that can be used to prevent the severe disease in high-risk groups, but its high cost and the need for several administrations make its use difficult. Approximately 60 strategies between vaccines and humanized monoclonal antibodies against RSV are being developed, of which 16 are in Phase 1-3 trials. The aim of this review is to describe the main current lines of research in the field

Influencia de los virus respiratorios en la evaluación de la efectividad de la vacuna neumocócica de 13 serotipos en menores de 5 años: estudio de series temporales 2001-2013 / Influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in children under 5 years old: A time-series study for the 2001-2013 period

Introducción. Streptococcus pneumoniae es el principal agente de las neumonías consolidantes de causa bacteriana. En 2012, se introdujo la vacuna contra neumococo de 13 serotipos al Calendario Nacional en Argentina para niños inmunocompetentes a partir de los dos meses de edad (2 + 1). Objetivo. Analizar la influencia de los virus respiratorios en la evaluación de la efectividad de la vacuna conjugada contra el neumococo de 13 serotipos en relación con el número de hospitalizaciones por neumonías consolidantes confirmadas por radiología (NCCR). Métodos. Estudio observacional analítico de series temporales. Se incluyeron todos los niños internados con diagnóstico de NCCR según criterios de la Organización Mundial de la Salud, marzo-noviembre de 2001-2013. El diagnóstico viral (virus sincicial respiratorio, adenovirus, influenza y parainfluenza) se realizó por inmunofluorescencia indirecta de aspirados nasofaríngeos o por reacción en cadena de la polimerasa con transcriptasa inversa. Se desarrollaron series temporales que compararon los períodos prevacunación 20012011 y posvacunación 2012-2013. Resultados. De un total de 11 306 niños menores de 5 años con infecciones respiratorias agudas bajas, se incluyeron 4974 con NCCR. Promedio anual de internación por NCCR: 394,8 prevacunación; 315,5 posvacunación (reducción del 20,1%; IC 95% 13,13-26,49%; p <0,001). Promedio anual de internación por NCCR no viral: 255,5 prevacunación; 183 posvacunación (reducción del 28,4%; IC 95% 20,5-35,78%; p <0,001). Promedio anual de internación por NCCR viral: 139,2 prevacunación; 132 posvacunación (reducción del 4,8%; IC 95% 8,38-16,49%; p= 0,4758). La proporción de NCCR con diagnóstico viral positivo fue 35,3% prevacunación y 42% posvacunación (p= 0,001). Conclusiones. Se observó un descenso significativo de las internaciones por NCCR en forma global luego de la introducción de la vacuna contra neumococo de 13 serotipos, particularmente en aquellas de etiología no viral. Es fundamental continuar la vigilancia epidemiológica para evaluar el impacto de esta medida y el comportamiento viral en relación con las NCCR.

Introduction. S treptococcus pneumoniae is the main agent in bacterial consolidated pneumonias. In 2012, the 13-valent pneumococcal conjugate vaccine was introduced in the Argentine national immunization schedule for immunocompetent children as of two months old with a two-dose schedule plus a booster. Objective.To analyze the influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in relation to the number of hospitalizations for radiologically-confirmed consolidated pneumonias (RCCP). Methods. Observational, analytical, time-series study. All children hospitalized with a diagnosis of RCCP as per the World Health Organization's criteria between March and November throughout the2001-2013period were included. Viral diagnosis (respiratory syncytial virus, adenovirus, influenza and parainfluenza) was performed by indirect immunofluorescence using nasopharyngeal aspirates or by reverse transcription polymerase chain reaction. Time-series were developed to compare preimmunization 2001-2011 and post-immunization 2012-2013 periods. Results. Out of a total of 11,306 children under 5 years old with acute lower respiratory tract infections, 4974 with RCCP were included. Annual average number of hospitalizations for RCCP: 394.8 pre-immunization, 315.5 post-immunization (reduction of 20.1%, 95% confidence interval --CI--: 13.13-26.49%, p < 0.001). Annual average number of hospitalizations for non-viral RCCP: 255.5 pre-immunization, 183 post-immunization (reduction of 28.4%, 95% CI: 20.5-35.78%, p < 0.001). Annual average number of hospitalizations for viral RCCP: 139.2 pre-immunization, 132 post-immunization (reduction of 4.8%, 95% CI: 8.38-16.49%, p= 0.4758). The proportion of RCCP with positive viral diagnosis was 35.3 % pre-immunization and 42% post-immunization (p= 0.001). Conclusions. An overall significant reduction in the number of hospitalizations for RCCP was observed following the introduction of the 13-valent pneumococcal conjugate vaccine, especially in the case of non-viral pneumonias. It is critical to continue with the epidemiological surveillance to evaluate the impact of this intervention and viral behavior in relation to RCCP.

Influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in children under 5 years old: A time-series study for the 2001-2013 period.

INTRODUCTION: S treptococcus pneumoniae is the main agent in bacterial consolidated pneumonias. In 2012, the 13-valent pneumococcal conjugate vaccine was introduced in the Argentine national immunization schedule for immunocompetent children as of two months old with a two-dose schedule plus a booster. OBJECTIVE: To analyze the influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in relation to the number of hospitalizations for radiologically-confirmed consolidated pneumonias (RCCP). METHODS: Observational, analytical, time-series study. All children hospitalized with a diagnosis of RCCP as per the World Health Organization's criteria between March and November throughout the2001-2013period were included. Viral diagnosis (respiratory syncytial virus, adenovirus, influenza and parainfluenza) was performed by indirect immunofluorescence using nasopharyngeal aspirates or by reverse transcription polymerase chain reaction. Time-series were developed to compare preimmunization 2001-2011 and post-immunization 2012-2013 periods. RESULTS: Out of a total of 11,306 children under 5 years old with acute lower respiratory tract infections, 4974 with RCCP were included. Annual average number of hospitalizations for RCCP: 394.8 pre-immunization, 315.5 post-immunization (reduction of 20.1%, 95% confidence interval |-CI-|: 13.13-26.49%, p < 0.001). Annual average number of hospitalizations for non-viral RCCP: 255.5 pre-immunization, 183 post-immunization (reduction of 28.4%, 95% CI: 20.5-35.78%, p < 0.001). Annual average number of hospitalizations for viral RCCP: 139.2 pre-immunization, 132 post-immunization (reduction of 4.8%, 95% CI: 8.38-16.49%, p= 0.4758). The proportion of RCCP with positive viral diagnosis was 35.3 % pre-immunization and 42% post-immunization (p= 0.001). CONCLUSIONS: An overall significant reduction in the number of hospitalizations for RCCP was observed following the introduction of the 13-valent pneumococcal conjugate vaccine, especially in the case of non-viral pneumonias. It is critical to continue with the epidemiological surveillance to evaluate the impact of this intervention and viral behavior in relation to RCCP.

Virus respiratorio sincicial: Patrón clínico epidemiológico en niños internados en un hospital pediátrico durante los años 2000-2013 / Respiratory syncytial virus: Clinical and epidemiological pattern in pediatric patients admitted to a children's hospital between 2000 and 2013

Introducción. El virus respiratorio sincicial (VRS) es el principal agente asociado a infección respiratoria aguda baja en niños. El objetivo de este estudio fue describir el patrón clínico-epidemiológico e identificar los factores de riesgo de infección por VRS. Población y métodos. Estudio prospectivo de cohorte de pacientes internados por infección respiratoria aguda baja en el Hospital de Niños Ricardo Gutiérrez, marzo-noviembre, 20002013. El diagnóstico viral para VRS, adenovirus, influenza y parainfluenza se realizó por inmunofluorescencia indirecta de aspirados nasofaríngeos. Resultados. Se incluyeron 12 555 niños; 38,2% (4798) presentaron rescate viral; el VRS representó el 81,8% (3924/4798) sin variaciones anuales significativas (71,2-88,1), con patrón epidémico estacional (mayo-julio); fue seguido por influenza (7,6%), parainfluenza (5,9%) y adenovirus (4,7%). Los casos con rescate de VRS (3924) tuvieron una mediana de edad de 7 meses (0-214 meses); 74,2% eran menores de 1 año; 43,1%, menores de 6 meses; 56,5%, varones; y la manifestación clínica más frecuente fue bronquiolitis (60,7%). El 41,6% tenía comorbilidades; las más frecuentes, enfermedad respiratoria crónica (74%), cardiopatías congénitas (14%) y enfermedad neurológica crónica (10,2%). El 25% presentó complicaciones. La letalidad fue 1,9% (74/3888). Los predictores independientes de infección por VRS fueron la edad < 3 meses OR 2,8 (2,14-3,67), p < 0,01 , la bronquiolitis como presentación clínica OR 1,54 (1,32-1,79), p < 0,01 y la presencia de hipoxemia al momento del ingreso OR 1,84 (1,42-2,37), p < 0,01 . Conclusiones. La infección por VRS presentó un patrón epidémico estacional y se asoció más a niños pequeños menores de tres meses con bronquiolitis e hipoxemia al momento del ingreso.

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Virus respiratorio sincicial: Patrón clínico epidemiológico en niños internados en un hospital pediátrico durante los años 2000-2013 / Respiratory syncytial virus: Clinical and epidemiological pattern in pediatric patients admitted to a childrens hospital between 2000 and 2013

Introducción. El virus respiratorio sincicial (VRS) es el principal agente asociado a infección respiratoria aguda baja en niños. El objetivo de este estudio fue describir el patrón clínico-epidemiológico e identificar los factores de riesgo de infección por VRS. Población y métodos. Estudio prospectivo de cohorte de pacientes internados por infección respiratoria aguda baja en el Hospital de Niños Ricardo Gutiérrez, marzo-noviembre, 20002013. El diagnóstico viral para VRS, adenovirus, influenza y parainfluenza se realizó por inmunofluorescencia indirecta de aspirados nasofaríngeos. Resultados. Se incluyeron 12 555 niños; 38,2% (4798) presentaron rescate viral; el VRS representó el 81,8% (3924/4798) sin variaciones anuales significativas (71,2-88,1), con patrón epidémico estacional (mayo-julio); fue seguido por influenza (7,6%), parainfluenza (5,9%) y adenovirus (4,7%). Los casos con rescate de VRS (3924) tuvieron una mediana de edad de 7 meses (0-214 meses); 74,2% eran menores de 1 año; 43,1%, menores de 6 meses; 56,5%, varones; y la manifestación clínica más frecuente fue bronquiolitis (60,7%). El 41,6% tenía comorbilidades; las más frecuentes, enfermedad respiratoria crónica (74%), cardiopatías congénitas (14%) y enfermedad neurológica crónica (10,2%). El 25% presentó complicaciones. La letalidad fue 1,9% (74/3888). Los predictores independientes de infección por VRS fueron la edad < 3 meses OR 2,8 (2,14-3,67), p < 0,01 , la bronquiolitis como presentación clínica OR 1,54 (1,32-1,79), p < 0,01 y la presencia de hipoxemia al momento del ingreso OR 1,84 (1,42-2,37), p < 0,01 . Conclusiones. La infección por VRS presentó un patrón epidémico estacional y se asoció más a niños pequeños menores de tres meses con bronquiolitis e hipoxemia al momento del ingreso.(AU)

.(AU)

Respiratory syncytial virus: clinical and epidemiological pattern in pediatric patients admitted to a children's hospital between 2000 and 2013.

INTRODUCTION: Respiratory syncytial virus (RSV) is the major causative organism associated with acute lower respiratory tract infections in children.The objective of this study was to describe the clinical and epidemiological pattern of RSV and identify risk factors for RSV infection. POPULATION AND METHODS: Prospective, cohort study on patients hospitalized due to acute lower respiratory tract infection at Hospital de Niños Ricardo Gutiérrez between March and November throughout the 2000-2013 period. The virological diagnosis of RSV, adenovirus, influenza and parainfluenza was performed by indirect immunofluorescence using nasopharyngeal aspirates. RESULTS: A total of 12,555 children were included, 38.2% (4798) had virus rescued from samples. RSV accounted for 81.8% of cases (3924/4798) with no significant annual variations (71.2- 88.1) and with an epidemic seasonal pattern(May through July); RSV was followed by influenza (7.6%), parainfluenza (5.9%), and adenovirus (4.7%).The median age of patients with RSV rescue (3924) was 7 months old (0- 214 months old), while 74.2% were younger than 1 year old, 43.1% were younger than 6 months old, 56.5% were males and the most common clinical presentation was bronchiolitis (60.7%). Comorbidities were observed in 41.6% of cases. The most common comorbidities were chronic respiratory disease (74%), congenital heart disease (14%), and chronic neurological disease (10.2%).Complications occurred in 25%of cases. The case fatality rate was 1.9% (74/3888). Independent predictors of RSV infection were age <3 months old (OR: 2.8 [2.14-3.67], p < 0.01),clinical presentation of bronchiolitis (OR: 1.54 [1.32-1.79], p < 0.01), and hypoxemia at the time of admission (OR: 1.84 [1.42-2.37], p < 0.01). CONCLUSIONS: RSV infection displayed a seasonal pattern and was associated with infants younger than 3 months old with bronchiolitis and hypoxemia at the time of admission.

Epidemiology of Bordetella pertussis in a children's hospital.

INTRODUCTION: Pertussis or whooping cough continues to be a major cause of morbidity and mortality in infants younger than 1 year old. OBJECTIVES: To describe the clinical and epidemiological profile of Bordetella pertussis and to analyze the factors associated with confirmation by PCR and case fatality rate. MATERIAL AND METHODS: Prospective, cohort study conducted between December 2003 and December 2011. The study included children seen at the Hospital de Niños Ricardo Gutiérrez suspected of pertussis. The factors associated with confirmation by PCR and the case fatality rate by relative risk (RR) with a 95% confidence interval were studied. RESULTS: Six hundred and twenty patients with a 38% of positive cases (236/620) were included, 3 cases were confirmed by epidemiological link. Confirmed cases (239) showed a seasonal pattern from September through February, a median age of 3 months old, and 89% had received less than three vaccine doses. Eighty six percent of patients were hospitalized: their median length of stay was 7 days. A total of 99% of patients were eu-trophic, 98% were immunocompetent and 17.5% required intensive care. The clinical presentation was analyzed in 480 patients. Of them, 38% (184) had a positive PCR result and their symptoms were: 96.2%, cough; 76.5%, paroxysmal cough; 57.9% cyanosis; 55.7%, respiratory distress; 29%, fever; 22.4%, apnea; 21.9%, vomiting after coughing. A multivariate analysis identified the following as independent predictors associated with confirmation of pertussis by PCR: paroxysmal cough (OR 2.52: 1.50-4.22; p= 0.000) and leukocytosis upon admission >20 000 white blood cells/mm3 (OR 7.96: 4.82-13.17; p= 0.000); having developed fever reduced the chance of having a positive PCR result (OR 0.47: 0.29-0.77; p= 0.003). The case fatality rate for hospitalized patients was 6.8%. Leukocytosis >30 000 white blood cells/mm3 was a predictor of fatality (RR 6.7: 1.88-23.9; p= 0.001). CONCLUSIONS: Confirmed cases were mostly infants younger than 1 year old who were healthy before and who had not completed their primary immunization schedule. Paroxysmal cough and leukocytosis were associated with PCR diagnosis, while leukocytosis was a predictor of mortality.

Epidemiología de Bordetella pertussis en un hospital pediátrico / Epidemiology of Bordetella pertussis in a children's hospital

Introducción. La tos ferina o coqueluche continúa siendo una importante causa de morbimortalidad en los menores de un año. Objetivos. Describir el perfil clínico-epidemiológico de Bordetella pertussis, y analizar los factores asociados a la confrmación por PCR y la letalidad. Materiales y métodos. Estudio prospectivo de cohorte realizado entre diciembre de 2003 y diciembre de 2011. Se incluyeron niños asistidos en el Hospital de Niños Ricardo Gutiérrez con sospecha de padecer la enfermedad. Se estudiaron los factores asociados a confrmación por PCR y letalidad mediante riesgo relativo (RR) con intervalo del 95%. Resultados. Se incluyeron 620 pacientes con una positividad del 38% (236/620), 3 casos se confrmaron por nexo. Los confrmados (239) presentaron un patrón estacional de septiembre a febrero, una mediana de edad de 3 meses, y 89%, menos de tres dosis de vacuna. El 86% se internaron: la mediana de estadía fue de 7 días. Un 99% de los pacientes eran eutrófcos, 98% inmunocompetentes y 17,5% requirieron cuidados intensivos. Se analizó la clínica en 480 pacientes. El 38% (184) tuvieron PCR positiva y presentaron: 96,2% tos, 76,5% tos paroxística, 57,9% cianosis, 55,7% difcultad respiratoria, 29% febre, 22,4% apnea, 21,9% vómitos postusígenos. El análisis multivariado identifcó, como predictores independientes asociados a la confrmación de coqueluche por PCR: tos paroxística (OR 2,52: 1,50 a 4,22; p= 0,000) y leucocitosis al ingre s a r ≥20 000 glóbulos blancos/ mm³ (OR 7,96: 4,82 a 13,17; p= 0,000); haber presentado febre disminuyó la probabilidad de obtener un resultado de PCR positivo (OR 0,47: 0,29 a 0,77; p = 0,003). La letalidad en los pacientes internados fue de 6,8%. Una leucocitosis ≥ 30 000 glóbulos blancos/mm³ fue un predictor de letalidad (RR 6,7: 1,88 a 23,9; p= 0,001). Conclusiones. Los casos confirmados correspondieron, en su mayoría, a menores de un año antes sanos y que no habían completado el esquema de vacunación primario. La tos paroxística y la leucocitosis se asociaron al diagnóstico por PCR, mientras que la leucocitosis fue un predictor de mortalidad.

Introduction. Pertussis or whooping cough continues to be a major cause of morbidity and mortality in infants younger than 1 year old. Objectives. To describe the clinical and epidemiological profle of Bordetella pertussis and to analyze the factors associated with confrmation by PCR and case fatality rate. Material and Methods. Prospective, cohort study conducted between December 2003 and December 2011. The study included children seen at the Hospital de Niños Ricardo Gutiérrez suspected of pertussis. The factors associated with confrmation by PCR and the case fatality rate by relative risk (RR) with a 95% confdence interval were studied. Results. Six hundred and twenty patients with a 38% of positive cases (236/620) were included, 3 cases were confrmed by epidemiological link. Confrmed cases (239) showed a seasonal pattern from September through February, a median age of 3 months old, and 89% had received less than three vaccine doses. Eighty six percent of patients were hospitalized: their median length of stay was 7 days. A total of 99% of patients were eu-trophic, 98% were immunocompetent and 17.5% required intensive care. The clinical presentation was analyzed in 480 patients. Of them, 38% (184) had a positive PCR result and their symptoms were: 96.2%, cough; 76.5%, paroxysmal cough; 57.9% cyanosis; 55.7%, respiratory distress; 29%, fever; 22.4%, apnea; 21.9%, vomiting after coughing. A multivariate analysis identifed the following as independent predictors associated with confrmation of pertussis by PCR: paroxysmal cough (OR 2.52: 1.50-4.22; p= 0.000) and leu-kocytosis upon admission >20 000 white blood cells/mm³ (OR 7.96: 4.82-13.17; p= 0.000); having developed fever reduced the chance of having a positive PCR result (OR 0.47: 0.29-0.77; p= 0.003). The case fatality rate for hospitalized patients was 6.8%. Leukocytosis >30 000 white blood cells/mm3 was a predictor of fatality (RR 6.7: 1.88-23.9; p= 0.001). Conclusions. Confrmed cases were mostly infants younger than 1 year old who were healthy before and who had not completed their primary immunization schedule. Paroxysmal cough and leukocytosis were associated with PCR diagnosis, while leukocytosis was a predictor of mortality.

Epidemiología de Bordetella pertussis en un hospital pediátrico / Epidemiology of Bordetella pertussis in a childrens hospital

Introducción. La tos ferina o coqueluche continúa siendo una importante causa de morbimortalidad en los menores de un año. Objetivos. Describir el perfil clínico-epidemiológico de Bordetella pertussis, y analizar los factores asociados a la confrmación por PCR y la letalidad. Materiales y métodos. Estudio prospectivo de cohorte realizado entre diciembre de 2003 y diciembre de 2011. Se incluyeron niños asistidos en el Hospital de Niños Ricardo Gutiérrez con sospecha de padecer la enfermedad. Se estudiaron los factores asociados a confrmación por PCR y letalidad mediante riesgo relativo (RR) con intervalo del 95%. Resultados. Se incluyeron 620 pacientes con una positividad del 38% (236/620), 3 casos se confrmaron por nexo. Los confrmados (239) presentaron un patrón estacional de septiembre a febrero, una mediana de edad de 3 meses, y 89%, menos de tres dosis de vacuna. El 86% se internaron: la mediana de estadía fue de 7 días. Un 99% de los pacientes eran eutrófcos, 98% inmunocompetentes y 17,5% requirieron cuidados intensivos. Se analizó la clínica en 480 pacientes. El 38% (184) tuvieron PCR positiva y presentaron: 96,2% tos, 76,5% tos paroxística, 57,9% cianosis, 55,7% difcultad respiratoria, 29% febre, 22,4% apnea, 21,9% vómitos postusígenos. El análisis multivariado identifcó, como predictores independientes asociados a la confrmación de coqueluche por PCR: tos paroxística (OR 2,52: 1,50 a 4,22; p= 0,000) y leucocitosis al ingre s a r ≥20 000 glóbulos blancos/ mm³ (OR 7,96: 4,82 a 13,17; p= 0,000); haber presentado febre disminuyó la probabilidad de obtener un resultado de PCR positivo (OR 0,47: 0,29 a 0,77; p = 0,003). La letalidad en los pacientes internados fue de 6,8%. Una leucocitosis ≥ 30 000 glóbulos blancos/mm³ fue un predictor de letalidad (RR 6,7: 1,88 a 23,9; p= 0,001). Conclusiones. Los casos confirmados correspondieron, en su mayoría, a menores de un año antes sanos y que no habían completado el esquema de vacunación primario. La tos paroxística y la leucocitosis se asociaron al diagnóstico por PCR, mientras que la leucocitosis fue un predictor de mortalidad.(AU)

Introduction. Pertussis or whooping cough continues to be a major cause of morbidity and mortality in infants younger than 1 year old. Objectives. To describe the clinical and epidemiological profle of Bordetella pertussis and to analyze the factors associated with confrmation by PCR and case fatality rate. Material and Methods. Prospective, cohort study conducted between December 2003 and December 2011. The study included children seen at the Hospital de Niños Ricardo Gutiérrez suspected of pertussis. The factors associated with confrmation by PCR and the case fatality rate by relative risk (RR) with a 95% confdence interval were studied. Results. Six hundred and twenty patients with a 38% of positive cases (236/620) were included, 3 cases were confrmed by epidemiological link. Confrmed cases (239) showed a seasonal pattern from September through February, a median age of 3 months old, and 89% had received less than three vaccine doses. Eighty six percent of patients were hospitalized: their median length of stay was 7 days. A total of 99% of patients were eu-trophic, 98% were immunocompetent and 17.5% required intensive care. The clinical presentation was analyzed in 480 patients. Of them, 38% (184) had a positive PCR result and their symptoms were: 96.2%, cough; 76.5%, paroxysmal cough; 57.9% cyanosis; 55.7%, respiratory distress; 29%, fever; 22.4%, apnea; 21.9%, vomiting after coughing. A multivariate analysis identifed the following as independent predictors associated with confrmation of pertussis by PCR: paroxysmal cough (OR 2.52: 1.50-4.22; p= 0.000) and leu-kocytosis upon admission >20 000 white blood cells/mm³ (OR 7.96: 4.82-13.17; p= 0.000); having developed fever reduced the chance of having a positive PCR result (OR 0.47: 0.29-0.77; p= 0.003). The case fatality rate for hospitalized patients was 6.8%. Leukocytosis >30 000 white blood cells/mm3 was a predictor of fatality (RR 6.7: 1.88-23.9; p= 0.001). Conclusions. Confrmed cases were mostly infants younger than 1 year old who were healthy before and who had not completed their primary immunization schedule. Paroxysmal cough and leukocytosis were associated with PCR diagnosis, while leukocytosis was a predictor of mortality.(AU)