Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial.

BACKGROUND: The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. METHODS AND FINDINGS: This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. CONCLUSIONS: Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00466947.

A multi-country study of intussusception in children under 2 years of age in Latin America: analysis of prospective surveillance data.

BACKGROUND: Intussusception (IS) is a form of acute intestinal obstruction that occurs mainly in infants and is usually of unknown cause. An association between IS and the first licensed rotavirus vaccine, a reassortant-tetravalent, rhesus-based rotavirus vaccine (RRV-TV), led to the withdrawal of the vaccine. New rotavirus vaccines have now been developed and extensively studied for their potential association with IS. This study aimed to describe the epidemiology and to estimate the incidence of IS in Latin American infants prior to new vaccine introduction. METHODS: Children under 2 years of age representing potential IS cases were enrolled in 16 centers in 11 Latin American countries from January 2003 to May 2005. IS cases were classified as definite, probable, possible or suspected as stated on the Brighton Collaboration Working Group guidelines. RESULTS: From 517 potential cases identified, 476 (92%) cases were classified as definite, 21 probable, 10 possible and 10 suspected for intussusception. Among the 476 definite IS cases, the median age at presentation was 6.4 months with 89% of cases aged <1 year. The male to female ratio was 1.5:1. The incidence of definite IS per 100,000 subject-years ranged from 1.9 in Brazil to 62.4 in Argentina for children <2 years of age, and from 3.8 in Brazil to 105.3 in Argentina for children aged <1 year. Median hospital stay was 4 days with a high prevalence of surgery as the primary treatment (65%). Most cases (88%) made a complete recovery, but 13 (3%) died. No clear seasonal pattern of IS cases emerged. CONCLUSIONS: This study describes the epidemiology and estimates the incidence of IS in Latin American infants prior to the introduction of new rotavirus vaccines. The incidence of IS was found to vary between different countries, as observed in previous studies. TRIAL REGISTRATION: Clinical study identifier 999910/204 (SERO-EPI-IS-204).

Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study.

BACKGROUND: Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. METHODS: 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). FINDINGS: 897 infants were excluded from the according-to-protocol analysis. Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. INTERPRETATION: Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). RESULTS: The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). CONCLUSIONS: Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)

[Clinical- epidemiological characteristics and predictors of coronary complications in children of Argentina with Kawasaki disease]. / Características clínico-epidemiológicas y predictores de complicaciones coronarias en niños de Argentina con enfermedad de Kawasaki.

BACKGROUND: Kawasaki disease (EK) is an acute systemic vasculitis with a risk of developing coronary aneurysms. AIM: To describe the clinical and epidemiological characteristics of children with EK in Argentina and to analyse the risk factors for the development of coronary's complications (CC). METHODS: Multicenter, retrospective, cross-sectional, observational and analytical study. It included patients younger than 18 years of age diagnosed with EK in hospitals in Argentina, between January the 1st, 2010 and December the 31th, 2013. RESULTS: N = 193 subjects. Age: medium: 29 months. Total incidence 5 cases / 10,000 hospital discharges. CC was observed in 15.5% of patients. Increased risk factors for CC: Elevated number of days with fever at the time of treatment placement (p = 0.0033); Increased of: heart frequency (p = 0.0021), erythrosedimentation (ESR) (p = 0.005), C-reactive protein (CRP) (p < 0.0001), leukocytes (p = 0.0006), neutrophils (p = 0.0021); Decreased of hematocrit (p = 0.0007) and hemoglobin (p < 0.0001).Association with CC: non-coronary cardiological alterations (OR = 10,818); PCR greater than 68 mg /L (OR = 11,596); leukocytes greater than 20,000 / mm3 (OR = 4.316); and ESR greater than 64 mm / 1 hour (OR = 4.267). CONCLUSION: The most frequent form of presentation was complete EK, the risk of CC was higher in males, younger than 5 years old, the risk factors (clinical and laboratory) were similar to those described in the literature.

PCV13 vaccination impact: A multicenter study of pneumonia in 10 pediatric hospitals in Argentina.

INTRODUCTION: In 2012, PCV13 was introduced into the National Immunization Program in Argentina, 2+1 schedule for children <2 years. Coverage rates for 1st and 3rd doses were 69% and 41.0% in 2012, 98% and 86% in 2013; 99% and 89% in 2014, respectively. The aims of this study were to evaluate impact of PCV13 on Consolidated Pneumonia (CP) and Pneumococcal Pneumonia (PP) burden, and to describe epidemiological-clinical pattern of PP during the three-year period following vaccine introduction. METHODS: Hospital-based study at 10 pediatric surveillance units in Argentina. CP and PP discharge rates per 10,000 hospital discharges were compared between the pre-vaccination period 2007-2011 (preVp), the year of intervention (2012) and the post-vaccination period 2013-2014 (postVp). RESULTS: Significant reduction in CP and PP discharge rates was observed in patients <5 years [% reduction (95%CI)]: 10.2% (6.3; 14.0) in 2012 and 24.8% (21.3; 28.2) in postVp for CP discharge rate; 59.5% (48.0; 68.5) in 2012 and 68.8% (58.3; 76.6) in postVp for PP discharge rate. Significant changes were also observed in children ≥5 years, mainly in PP discharge rate. A total of 297 PP cases were studied; 59.3% male; 31.3% <2 years; 42.9% had received PCV13 in 2012 and 84.5% in posVp. Case fatality rate was 3.4%. PCV13 serotypes decreased from 83.0% (39/47) in 2012 to 64.2% (52/81) in postVp, p = 0.039. CONCLUSIONS: After PCV13 introduction, significant reduction in CP and PP discharge rates was observed in hospitalized children <5 years. In patients ≥5 years, PP discharge rate also decreased significantly.

Community-acquired methicillin-resistant Staphylococcus aureus infections: hospitalization and case fatality risk in 10 pediatric facilities in Argentina. / Infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad: hospitalización y riesgo de letalidad en 10 centros pediátricos de Argentina.

INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are prevalent both in Argentina and worldwide, and they may have a severe clinical course. OBJECTIVES: To estimate the hospitalization rate and case fatality risk factors of CA-MRSA infection. METHODS: Cross-sectional, analytical study. All patients < 15 years old with community-acquired Staphylococcus aureus (CA-SA) infections admitted to 10 pediatric facilities between January 2012 and December 2014 were included. RESULTS: Out of 1141 patients with CA-SA, 904 (79.2%) had CA-MRSA. The rate of hospitalization of CA-MRSA cases (per 10 000 discharges) among patients < 5 years old was 27.6 in 2012, 35.2 in 2013, and 42.7 in 2014 (p = 0.0002). The 2-4-year-old group was the most affected one: 32.2, 49.4, and 54.4, respectively (p = 0.0057). The clinical presentations included skin and soft tissue infections: 66.2%, pneumonia: 11.5%, sepsis/bacteremia: 8.5%, osteomyelitis: 5.5%, arthritis: 5.2%, psoas abscess: 1.0%, pericarditis/endocarditis: 0.8%, meningitis: 0.6%, and other: 0.7%. In terms of antibiotic resistance, 11.1% had resistance to erythromycin; 8.4%, to gentamicin; and 0.6%, to trimethoprim-sulfamethoxazole. All strains were susceptible to vancomycin. The case fatality rate was 2.2% and associated risk factors were (odds ratio [95% confidence interval]) age > 8 years (2.78, 1.05-7.37), pneumonia (6.37, 2.3717.09), meningitis (19.53, 2.40-127.87), and sepsis/bacteremia (39.65, 11.94-145.55). CONCLUSIONS: The rate of CA-MRSA infection was high; the rate of hospitalization increased in the 2013-2014 period; the 2-4-year-old group was the most affected one. A higher case fatality risk was observed among patients > 8 years old and those with the clinical presentations of pneumonia, meningitis, and sepsis.

INTRODUCCIÓN: Las infecciones por Staphylococcus aureusmeticilino resistente adquirido en la comunidad (SAMR-C) son prevalentes en Argentina y el mundo; pueden tener evolución grave. OBJETIVOS: Estimar tasa de hospitalización y factores de riesgo de letalidad de la infección por SAMR-C. MÉTODOS: Estudio analítico transversal. Se incluyeron todos los pacientes < 15 años con infección por Staphylococcus aureusadquirido en la comunidad (SA-C) hospitalizados en 10 centros pediátricos, entre enero/2012-diciembre/2014. RESULTADOS: Del total de 1141 pacientes con infección por SA-C, 904 (79,2%) fueron SAMR-C. La tasa de hospitalización de casos de SAMR-C (por 10 000 egresos) en < 5 años fue 27,6 en 2012, 35,2 en 2013 y 42,7 en 2014 (p= 0,0002). El grupo de 2-4 años fue el más afectado: 32,2, 49,4 y 54,4, respectivamente (p= 0,0057). Las presentaciones clínicas fueron infección de piel y partes blandas (IPPB): 66,2%; neumonía:11,5%; sepsis/bacteriemia: 8,5%; osteomielitis: 5,5%; artritis: 5,2%; absceso de psoas: 1,0%; pericarditis/endocarditis: 0,8%; meningitis: 0,6%; otras: 0,7%. La resistencia antibiótica fue, para eritromicina, 11,1%; clindamicina, 11,0%; gentamicina, 8,4%; trimetoprima-sulfametoxazol: 0,6%. Todas las cepas fueron sensibles a vancomicina. La letalidad fue 2,2% y los factores de riesgo asociados fueron [OR (IC 95%)] edad > 8 años (2,78; 1,05-7,37), neumonía (6,37; 2,37-17,09), meningitis (19,53; 2,40-127,87) y sepsis/bacteriemia (39,65; 11,94-145,55). CONCLUSIONES: La tasa de infección por SAMR-C fue alta; la tasa de hospitalización aumentó en 2013-14; el grupo de 2-4 años fue el más afectado. Presentaron mayor riesgo de letalidad los > 8 años y las clínicas de neumonía, meningitis y sepsis.

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

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

A new challenge for the world: the eradication of polio. / Un nuevo desafío para el mundo: la erradicación de la poliomielitis.

Poliovirus infects 100% of susceptible individuals and causes acute flaccid paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type 2 has been eradicated worldwide; and type 3 is close to being eradicated. In this region, the last case of wild poliovirus occurred in Peru in 1991. There are still two endemic countries: Afghanistan and Pakistan, but countries where there is no circulation of the wild poliovirus have also reported imported cases of polio. In May 2012, the World Health Assembly declared the polio eradication a programmatic emergency for global public health and, as a result, developed the Polio Eradication and Endgame Strategic Plan 2013-2018. The Plan has four objectives: 1) Detect and interrupt all poliovirus transmission and maintain surveillance of acute flaccid paralysis in children < 15 years. 2) Strengthen immunization systems and withdraw oral polio vaccine by the first trimester of 2016. Replace the trivalent oral polio vaccine with the bivalent oral vaccine, containing serotypes 1 and 3, and introduce the inactivated polio vaccine in all immunization schedules to maintain immunity against poliovirus type 2. 3) Contain poliovirus and certify interruption of transmission. 4) Plan the exploitation of the fight against polio and its impact on public health. The plan is expected to reach its goals by 2018; all use of the oral polio vaccine will be interrupted thereafter. Change in immunization schedules will require pediatricians to provide advice and guidance to families depending on the varied situations of everyday practice.

El poliovirus infecta al 100% de las personas susceptibles y produce parálisis flácida aguda en un caso cada 200 infecciones. El tipo 1 causa poliomielitis epidémica; el tipo 2 está erradicado a nivel mundial; y el tipo 3, al borde de la erradicación. En la región, el último caso de enfermedad por virus salvaje fue en Perú, en 1991. Quedan dos países endémicos: Afganistán y Pakistán, pero países sin circulación de virus salvaje notificaron casos importados de poliomielitis. En mayo de 2012, la Asamblea Mundial de la Salud declaró que la erradicación del poliovirus era una emergencia programática para la salud pública mundial y, en respuesta, se elaboró el Plan Estratégico para la Erradicación de la Poliomielitis y la fase final 2013-2018. Los objetivos son los siguientes: 1) Detectar e interrumpir la transmisión de poliovirus y mantener la vigilancia de parálisis flácida aguda en < 15 años. 2) Fortalecer los sistemas de inmunización y retirar la vacuna antipoliomielítica oral hasta el primer trimestre de 2016. Cambiar la vacuna trivalente oral por bivalente oral, que contiene poliovirus tipo 1 y 3, e introducir la vacuna inactivada en todos los programas de vacunación para mantener la inmunidad contra poliovirus 2. 3) Contener los poliovirus y certificar la interrupción de su transmisión. 4) Planificar el aprovechamiento de esta lucha y su impacto en la salud pública. Este plan espera alcanzar su objetivo en 2018, después de lo cual todo el uso de la vacuna antipoliomielítica oral será detenido. El cambio en los esquemas de vacunación necesitará del pediatra que aconseje y oriente a las familias en las diferentes situaciones de la práctica diaria.

Nineteen-years of pneumococcal invasive disease surveillance in a children's hospital in Mendoza, Argentina.

Five hundred and thirty-seven children admitted to Hospital Dr. Notti and diagnosed with invasive pneumococcal disease between 1993 and 2011 were studied. Their median age was 19 months (range= 0-192 months); 34.82% were <1 year old and 23.46%, >60 months old. Pneumonia with or without effusion (48.04%) and meningitis (29.05%) were the most predominant conditions, with a case fatality rate of 6.14%. Identified serotypes corresponded to 14, 5 and 1 in56.86% of cases. Sensitivity to penicillin was observed in99.74% of non-meningeal strains, while sensitivity to ceftriaxone was found in 98.08% ofmeningeal strains. Risk factors inpneumonia with effusionwere associated to age >60 months old, RR: 1.47 (1.06-2.04), p= 0.02, to serotype 5, RR: 2.57 (1.71-3.87), p= 0.0001, and to serotype 1, RR: 1.86 (1.17-2.96), p= 0.014; in the case of meningitis, risk factors were mainly associated to age <1 year old, RR: 2.35 (1.87-3.06), p= 0.0000, and to serotype 18C, RR: 2.19 (1.3-3.7), p= 0.024. Conclusion. Streptococcus pneumonia was a major problem in infants younger than one year old, who predominantly developed meningitis which caused half of deaths, and in children older than 60 months old, who had a prevalence of pneumonia with effusion. Most cases were sensitive to penicillin and ceftriaxone.

Características clínico-epidemiológicas y predictores de complicaciones coronarias en niños de Argentina con enfermedad de Kawasaki / Clinical- epidemiological characteristics and predictors of coronary complications in children of Argentina with Kawasaki disease

Resumen Introducción: La enfermedad de Kawasaki (EK) es una vasculitis sistémica aguda con riesgo de desarrollar aneurismas coronarios. Objetivos: Describir características clínico-epidemiológicas en niños con diagnóstico de EK en Argentina. Analizar factores de riesgo para el desarrollo de complicaciones coronarias (CC). Población y Métodos: Estudio multicéntrico, retrospectivo, transversal, observacional y analítico. Incluyó pacientes bajo 18 años de edad, con diagnóstico de EK en hospitales de Argentina, entre el 1 de enero de 2010 y el 31 de diciembre de 2013. Resultados: N = 193 sujetos. Edad: mediana: 29 meses. Tasa promedio total país 5 casos/10.000 egresos hospitalarios. Presentaron CC 15,5%. Mayor riesgo de CC: Mayor cantidad de días de fiebre al momento de colocación del tratamiento (p = 0,0033); Aumento de: frecuencia cardíaca (p = 0,0021), eritrosedimentación (VSG) (p = 0,005), proteína C reactiva (PCR) (p < 0,0001), leucocitosis (p = 0,0006), neutrofilia (p = 0,0021); Disminución de hematocrito (p = 0,0007) y hemoglobina (p < 0,0001). Asociación con CC: alteraciones cardiológicas no coronarias (ORv10.818); PCR mayor de 68 mg/L (OR = 11.596); leucocitos mayores a 20.000/mm3 (OR= 4.316); y VSG mayor de 64 mm/1° hora (OR = 4.267). Conclusión: La forma de presentación más frecuente fue EK completa, el riesgo de CC fue mayor en varones, menores de 5 años de edad, los factores de riesgo (clínicos y de laboratorio) fueron semejantes a los descritos en la bibliografía.

Background: Kawasaki disease (EK) is an acute systemic vasculitis with a risk of developing coronary aneurysms. Aim: To describe the clinical and epidemiological characteristics of children with EK in Argentina and to analyse the risk factors for the development of coronary's complications (CC). Methods: Multicenter, retrospective, cross-sectional, observational and analytical study. It included patients younger than 18 years of age diagnosed with EK in hospitals in Argentina, between January the 1st, 2010 and December the 31th, 2013. Results: N = 193 subjects. Age: medium: 29 months. Total incidence 5 cases / 10,000 hospital discharges. CC was observed in 15.5% of patients. Increased risk factors for CC: Elevated number of days with fever at the time of treatment placement (p = 0.0033); Increased of: heart frequency (p = 0.0021), erythrosedimentation (ESR) (p = 0.005), C-reactive protein (CRP) (p < 0.0001), leukocytes (p = 0.0006), neutrophils (p = 0.0021); Decreased of hematocrit (p = 0.0007) and hemoglobin (p < 0.0001).Association with CC: non-coronary cardiological alterations (OR = 10,818); PCR greater than 68 mg /L (OR = 11,596); leukocytes greater than 20,000 / mm3 (OR = 4.316); and ESR greater than 64 mm / 1 hour (OR = 4.267). Conclusion: The most frequent form of presentation was complete EK, the risk of CC was higher in males, younger than 5 years old, the risk factors (clinical and laboratory) were similar to those described in the literature.

[Influenza A pH1N1 meningoencephalitis: a case report]. / Meningoencefalitis por influenza A pH1N1. Presentación de un caso clínico.

The influenza virus causes epidemics and pandemics with high morbidity and mortality. According to the World Health Organization, this virus causes 3-5 million cases of severe illness and 250,000 to 500,000 deaths each year. The disease is mainly respiratory and the most common complications are pneumonia, exacerbation of underlying diseases and less frequently respiratory complications. We report a 6-year-old patient with meningoencephalitis due to a new influenza A (IA), strain pH1N1, with viral documentation in cerebrospinal fluid (CSF). We provide detailed clinical, laboratory and imaging of the case, which responded favorably to sequels. Knowledge of this form of presentation is of great clinical and epidemiological significance due to the limited scientific evidence published internationally.

Infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad: hospitalización y riesgo de letalidad en 10 centros pediátricos de Argentina / Community-acquired methicillin-resistant Staphylococcus aureus infections: hospitalization and case fatality risk in 10 pediatric facilities in Argentina

Introducción. Las infecciones por Staphylococcus aureusmeticilino resistente adquirido en la comunidad (SAMR-C) son prevalentes en Argentina y el mundo; pueden tener evolución grave. Objetivos: Estimar tasa de hospitalización y factores de riesgo de letalidad de la infección por SAMR-C. Métodos. Estudio analítico transversal. Se incluyeron todos los pacientes < 15 años con infección por Staphylococcus aureusadquirido en la comunidad (SA-C) hospitalizados en 10 centros pediátricos, entre enero/2012-diciembre/2014. Resultados. Del total de 1141 pacientes con infección por SA-C, 904 (79,2%) fueron SAMR-C. La tasa de hospitalización de casos de SAMR-C (por 10 000 egresos) en < 5 años fue 27,6 en 2012, 35,2 en 2013 y 42,7 en 2014 (p= 0,0002). El grupo de 2-4 años fue el más afectado: 32,2, 49,4 y 54,4, respectivamente (p= 0,0057). Las presentaciones clínicas fueron infección de piel y partes blandas (IPPB): 66,2%; neumonía:11,5%; sepsis/bacteriemia: 8,5%; osteomielitis: 5,5%; artritis: 5,2%; absceso de psoas: 1,0%; pericarditis/endocarditis: 0,8%; meningitis: 0,6%; otras: 0,7%. La resistencia antibiótica fue, para eritromicina, 11,1%; clindamicina, 11,0%; gentamicina, 8,4%; trimetoprima-sulfametoxazol: 0,6%. Todas las cepas fueron sensibles a vancomicina. La letalidad fue 2,2% y los factores de riesgo asociados fueron --#91;OR (IC 95%)--#93; edad > 8 años (2,78; 1,05-7,37), neumonía (6,37; 2,37-17,09), meningitis (19,53; 2,40-127,87) y sepsis/bacteriemia (39,65; 11,94-145,55). Conclusiones. La tasa de infección por SAMR-C fue alta; la tasa de hospitalización aumentó en 2013-14; el grupo de 2-4 años fue el más afectado. Presentaron mayor riesgo de letalidad los > 8 años y las clínicas de neumonía, meningitis y sepsis.

Introduction. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are prevalent both in Argentina and worldwide, and they may have a severe clinical course. Objectives: To estimate the hospitalization rate and case fatality risk factors of CA-MRSA infection. Methods. Cross-sectional, analytical study. All patients < 15 years old with community-acquired Staphylococcus aureus (CA-SA) infections admitted to 10 pediatric facilities between January 2012 and December 2014 were included. Results. Out of 1141 patients with CA-SA, 904 (79.2%) had CA-MRSA. The rate of hospitalization of CA-MRSA cases (per 10 000 discharges) among patients < 5 years old was 27.6 in 2012, 35.2 in 2013, and 42.7 in 2014 (p = 0.0002). The 2-4-year-old group was the most affected one: 32.2, 49.4, and 54.4, respectively (p = 0.0057). The clinical presentations included skin and soft tissue infections: 66.2%, pneumonia: 11.5%, sepsis/bacteremia: 8.5%, osteomyelitis: 5.5%, arthritis: 5.2%, psoas abscess: 1.0%, pericarditis/endocarditis: 0.8%, meningitis: 0.6%, and other: 0.7%. In terms of antibiotic resistance, 11.1% had resistance to erythromycin; 8.4%, to gentamicin; and 0.6%, to trimethoprim-sulfamethoxazole. All strains were susceptible to vancomycin. The case fatality rate was 2.2% and associated risk factors were (odds ratio --#91;95% confidence interval--#93;) age > 8 years (2.78, 1.05-7.37), pneumonia (6.37, 2.3717.09), meningitis (19.53, 2.40-127.87), and sepsis/bacteremia (39.65, 11.94-145.55). Conclusions. The rate of CA-MRSA infection was high; the rate of hospitalization increased in the 2013-2014 period; the 2-4-year-old group was the most affected one. A higher case fatality risk was observed among patients > 8 years old and those with the clinical presentations of pneumonia, meningitis, and sepsis.

[Delayed vaccine schedule and missed opportunities for vaccination in children up to 24 months. A multicenter study]. / Esquemas atrasados de vacunación y oportunidades perdidas de vacunación en niños de hasta 24 meses: estudio multicéntrico.

INTRODUCTION: Delayed vaccine schedule (DVS) and missed opportunities of vaccination (MOV) are some of the main causes of low coverage in children ≤24 month in Argentina. OBJECTIVES: To determine the prevalence of DVS and the rate of MOV during the frst 24 months of life and risk factors for their occurrence. POPULATION AND METHODS: We conducted a survey among children ≤24 month's caregivers at five hospitals in different departments, between August-December/2008. RESULTS: Total enrolled: 1591 children; 54.2% male, median of age 8 months (0-24 months). Eighty percent concurred with vaccine-card, 75.9% consulted by pathology. Overall DVS rate: 39.7%. Most common DVS reason: the current mild disease: 38.5%. Overall MOV rate: 19.8%. Most common MOV reason: no detection of the need to vaccinate 47.8%. DTPHib and OPV vaccines had a higher risk of DVS and MOV. DVS independent predictors: age ≥6 months, administration for additionally recommended vaccines and prolonged waiting in the last vaccination. MOV independent predictors were: age ≥6 months, no compliance with prior care, and not asking for vaccines. CONCLUSION: We found a high proportion of MOV and mainly of DVS; they were associated mostly to false contraindications, lack of questioning on vaccines and difficulties in the quality of care provided to parents.

Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

BACKGROUND: The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. METHODS: Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. RESULTS: During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: <0-100) and 80.6% (95% CI: 51.4-93.2) against the pooled non-G1 rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. CONCLUSION: RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

Diecinueve años de vigilancia de enfermedad invasiva neumocócica en un hospital pediátrico de Mendoza, Argentina / Nineteen-years of pneumococcal invasive disease surveillance in a children’s hospital in Mendoza, Argentina

Estudiamos 537 niños internados en el Hospital Dr. Notti, entre 1993 y 2011, con enfermedad invasiva neumocócica. La mediana de edad fue 19 meses (R = 0-192 m); 34,82% fueron < 1 año y 23,46%, t 60 meses. Predominaron neumonía con y sin derrame (48,04%) y meningitis (29,05%), con una letalidad de 6,14%. El 56,86% de los serotipos identificados fueron 14, 5 y 1. Mostraron sensibilidad a la penicilina el 99,74% de cepas no meníngeas y a la ceftriaxona, el 98,08% de cepas meníngeas. Los factores de riesgo en neumonía con derrame se asociaron a la edad t 60 meses, RR 1,47 (1,06-2,04), p 0,02, serotipos 5, RR 2,57 (1,71-3,87), p 0,0001 y 1 RR 1,86 (1,17-2,96), p 0,014 y en las meningitis, principalmente a < 1 año, RR 2,35 (1,87-3,06), p 0,0000 y serotipo 18C, RR 2,19 (1,3-3,7), p 0,024. Conclusión. El Streptococcus pneumoniae representó un problema importante en menores de un año, en quienes predominó la meningitis y causó más de la mitad de las muertes, y en mayores de 60 meses, en los que prevalecieron neumonías con derrame. La mayoría fueron sensibles a la penicilina y a la ceftriaxona.

Five hundred and thirty-seven children admitted to Hospital Dr. Notti and diagnosed with invasive pneumococcal disease between 1993 and 2011 were studied. Their median age was 19 months (range= 0-192 months); 34.82% were <1 year old and 23.46%, ≥60 months old. Pneumonia with or without effusion (48.04%) and meningitis (29.05%) were the most predominant conditions, with a case fatality rate of 6.14%. Identified serotypes corresponded to 14, 5 and 1 in 56.86% of cases. Sensitivity to penicillin was observed in 99.74% of non-meningeal strains, while sensitivity to ceftriaxone was found in 98.08% of meningeal strains. Risk factors in pneumonia with effusion were associated to age ≥60 months old, RR: 1.47 (1.06-2.04), p= 0.02, to serotype 5, RR: 2.57 (1.71-3.87), p= 0.0001, and to serotype 1, RR: 1.86 (1.17-2.96), p= 0.014; in the case of meningitis, risk factors were mainly associated to age <1 year old, RR: 2.35 (1.87-3.06), p= 0.0000, and to serotype 18C, RR: 2.19 (1.3-3.7), p= 0.024. Conclusion. Streptococcus pneumonia was a major problem in infants younger than one year old, who predominantly developed meningitis which caused half of deaths, and in children older than 60 months old, who had a prevalence of pneumonia with effusion. Most cases were sensitive to penicillin and ceftriaxone

Meningoencefalitis por influenza A pH1N1: Presentación de un caso clínico / Influenza A pH1N1 meningoencephalitis: A case report

El virus influenza produce epidemias y pandemias con alta morbilidad-mortalidad. Según datos de la Organización Mundial de la Salud, causa 3-5 millones de casos de enfermedad grave y 250 000 a 500 000 muertes cada año. La enfermedad es fundamentalmente respiratoria y las complicaciones más frecuentes son: neumonía, descompensación de enfermedades subyacentes y, menos frecuentemente, complicaciones no respiratorias. Se presenta un paciente de 6 años con meningoencefalitis por la nueva cepa influenza A (IA) pH1N1, con documentación viral en líquido cefalorraquídeo (LCR). Se detallan hallazgos clínicos, de laboratorio e imágenes del caso, el cual evolucionó favorablemente con secuelas. Resulta de gran importancia clínica y epidemiológica el conocimiento de esta forma de presentación, debido a la escasa evidencia científica publicada internacionalmente.

The influenza virus causes epidemics and pandemics with high morbidity and mortality. According to the World Health Organization, this virus causes 3-5 million cases of severe illness and 250,000 to 500,000 deaths each year. The disease is mainly respiratory and the most common complications are pneumonia, exacerbation of underlying diseases and less frequently respiratory complications. We report a 6-year-old patient with meningoencephalitis due to a new influenza A (IA), strain pH1N1, with viral documentation in cerebrospinal fluid (CSF). We provide detailed clinical, laboratory and imaging of the case, which responded favorably to sequels. Knowledge of this form of presentation is of great clinical and epidemiological significance due to the limited scientific evidence published internationally.

Esquemas atrasados de vacunacion y oportunidades perdidas de vacunacion en niños de hasta 24 meses: estudio multicentrico / Delayed vaccine schedule and missed opportunities for vaccination in children up to 24 months: a multicenter study

Introduccion. Los esquemas atrasados de vacunacion (EAV) y las oportunidades perdidas de vacunacion (OPV) en niños constituyen algunas de las principales causas de baja cobertura. Objetivos: Determinar tasas de EAV y OPV en niños menor o igual 24 meses y los factores asociados a su ocurrencia. Poblacion y metodos. Encuesta a los cuidadores de niños menor o igual 24 meses a la salida de los consultorios de clinica pediatrica y de guardia en 5 hospitales de diferentes provincias, entre agosto diciembre de 2008. Resultados. Total enrolado: 1591 niños; 54,2 por ciento varones, mediana de edad 8 meses (0-24); 80,1 por ciento tenia carnet; 75,9 por ciento consultaba por patologia. Tasa global EAV: 39,7 por ciento. Motivo mas frecuente de atraso: enfermedad actual leve: 38,5 por ciento. Tasa global OPV: 19,8 por ciento. Motivo mas frecuente de OPV: no deteccion de la necesidad de vacunar: 47,8 por ciento. Cuadruple y Sabin presentaron mayor riesgo de EAV y OPV. Predictores independientes de EAV: edad mayor o igual 6 meses, administracion de vacunas fuera de calendario y espera prolongadaen la ultima vacunacion; y de OPV: edad mayor o igual 6 meses, no conformidad con la atencion previa, falta de interrogatorio por vacunas. Conclusiones. Se hallo una proporcion importante de OPV y principalmente de EAV; estas se vincularon, en su mayor parte, a falsas contraindicaciones,falta de interrogatorio por vacunas y a dificultades en la calidad de atencion brindada a los padres.

Introduction. Delayed vaccine schedule (DVS) and missed opportunities of vaccination (MOV) are some of the main causes of low coverage in children /6 months, no compliance with prior care, and not asking for vaccines.Conclusion. We found a high proportion of MOV and mainly of DVS; they were associated mostly to false contraindications, lack of questioning onvaccines and difficulties in the quality of care provided to parents.

Aspectos clínicos y epidemiológicos de la invaginación intestinal en niños menores de 2 años, de la provincia de Mendoza, Argentina / Clinical and epidemiological aspects of intestinal intussusception in children younger than two years old, in Mendoza, Argentina

Introducción. La invaginación intestinal es una enfermedadgrave, generalmente idiopática. Constituyela principal causa de obstrucción intestinal enniños, en especial en menores de 1 año. El objetivoes describir características clínicas y epidemiológicasde la invaginación intestinal y calcular su incidenciaanual en menores de 1 y 2 años de edad.Población, material y método. Estudio descriptivo,observacional. Se analizaron las historias clínicasde menores de 2 años, internados con diagnósticode invaginación, entre el 1/01/2003 y el 31/12/2005 en la provincia de Mendoza. Se evaluó edad, sexo, mes de diagnóstico, enfermedad previa, clínica, localización, tratamiento, complicaciones, tiempo de internación. Se calculó incidencia anual por edad y por año.Resultados. Se enrolaron 77 sujetos, rango de edad:1 a 22 meses, mediana: 6 meses. Menores de 1 año:88 por ciento. El mayor número de casos se presentó entreoctubre y marzo (68 por ciento). Veintinueve refirieron enfermedad previa (respiratoria 69 por ciento, diarrea 17 por ciento). Manifestaciones abdominales más frecuentes: vómitos 87 por ciento, dolor abdominal 79 por ciento, deposiciones con sangre 67 por ciento. La localización más frecuente fue ileocecoapendiculocólica en 30 (39 por ciento). Se indicó tratamiento quirúrgico en 72 pacientes (93,5 por ciento). La incidencia en menores de 1 año fue 0,77, 0,82 y 0,67/1.000 y en menores de 2 años; 0,41, 0,51 y 0,39/1.000, para los años 2003, 2004 y 2005, respectivamente.Conclusiones. La mayor incidencia se observó enmenores de 1 año y la localización leocecoapendiculocólicafue la más frecuente. Más del 90 por ciento de lospacientes requirió cirugía, con buena evolución