Raúl Ruvinsky

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis.

Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.

Invasive Streptococcus pneumoniae Infection in Latin American Children: Results of the Pan American Health Organization Surveillance Study

Protein-polysaccharide conjugate vaccines against Streptococcus pneumoniae promise to be an effective public health intervention for children, especially in an era of increasing antimicrobial resistance. To characterize the distribution of capsular types in Latin America, surveillance for invasive pneumococcal infection in children < or = 5 years of age was done in six countries between February 1993 and April 1996. Fifty percent of 1,649 sterile-site isolates were from children with pneumonia, and 52% were isolated from blood. The 15 most common of the capsular types prevalent throughout the region accounted for 87.7% of all isolates. Overall, 24.9% of isolates had diminished susceptibility to penicillin: 16.7% had intermediate resistance and 8.3% had high-level resistance. Three customized vaccine formulas containing 7, 12, and 15 capsular types were found to have regional coverages of 72%, 85%, and 88%, respectively. This study emphasizes the need for local surveillance for invasive pneumococcal disease prior to the development and evaluation of protein-polysaccharide conjugate vaccines for children.

Penicillin resistant pneumococcus and risk of treatment failure in pneumonia

Objective: To determine whether the presence of in vitro penicillin-resistant Streptococcus pneumoniae increases the risk of clinical failure in children hospitalised with severe pneumonia and treated with penicillin/ampicillin. Design: Multicentre, prospective, observational study. Setting: 12 tertiary-care centres in three countries in Latin America. Patients: 240 children aged 3–59 months, hospitalised with severe pneumonia and known in vitro susceptibility of S pneumoniae. Intervention: Patients were treated with intravenous penicillin/ampicillin after collection of blood and, when possible, pleural fluid for culture. The minimal inhibitory concentration (MIC) test was used to determine penicillin susceptibility of the pneumococcal strains isolated. Children were continuously monitored until discharge. Main outcome measures: The primary outcome was treatment failure (using clinical criteria). Results: Overall treatment failure was 21%. After allowing for different potential confounders, there was no evidence of association between treatment failure and in vitro resistance of S pneumoniae to penicillin according to the Clinical Laboratory Standards Institute (CLSI)/National Committee for Clinical Laboratory Standards (NCCLS) interpretative standards (adjRR = 1.03; 95%CI: 0.49–1.90 for resistant S pneumoniae). Conclusions: Intravenous penicillin/ampicillin remains the drug of choice for treating penicillin-resistant pneumococcal pneumonia in areas where the MIC does not exceed 2 μg/ml.

Antibiotic Resistance in Streptococcus pneumoniae in Six Latin American Countries: 1993-1999 Surveillance

The impact of invasive pneumococcal invasive disease is increased by the emergence of antibiotic resistance. We report regional and temporal variations in antibiotic resistance for 4,105 invasive Streptococcus pneumoniae isolates collected from Latin American children <5 years, between 1993 and 1999. Reduced susceptibility to penicillin was detected in 1,182 isolates (28.8%); 36% of these were resistant (> or = 2 microg/ml), including 12.6% with MIC > or = 4 microg/ml, occurring primarily in serotypes 14 and 23F. Reduced susceptibility to third-generation cephalosporins was detected in 12.1% of the collection. Mexico had the highest proportion of reduced susceptibility to penicillin (51.6%) and to third-generation cephalosporins (22%), whereas Brazil had the lowest at 20.9% and 0.7%, respectively. Isolates cultured from patients with pneumonia were more likely to have reduced susceptibility to third-generation cephalosporins than isolates from patients with meningitis (p < 0.0001). Susceptibility to trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, and vancomycin was tested by disk diffusion for 2.899 isolates. Reduced susceptibility was observed for 45.6%, 11.5%, 6.9%, and 0%, respectively. Thirty-one percent of the strains were resistant to > or = 2 drugs. High levels of antibiotic resistance in Latin America emphasize the need for the development of and adherence to rational antibiotic use guidelines. On-going surveillance will monitor the impact of these programs.

Impacto de Streptococcus pneumoniae en las neumonías del niño latinoamericano

La neumonia adquirida en la comunidad es una de las principales causas de morbilidad y mortalidad en la infancia. Estudios realizados en paises en desarrollo indican que los cuadros de neumonia mas graves se asocian a causas bacterianas, con predominio de Streptococcus pneumoniae, seguido por Haemophilus influenzae tipo b. El manejo de esas infecciones en los menores de 2 anos se ve dificultado por la carencia de vacunas apropiadas y por la disminucion de la susceptibilidad de S. pneumoniae a la penicilina y a otros antibioticos. En 1993, por iniciativa del Sistema Regional de Vacunas (SIREVA) de la Organizacion Panamericana de la Salud y con la financiacion de la Agencia Canadiense para el Desarrollo Internacional (Canadian International Development Agency: CIDA), se diseno un estudio para identificar los tipos capsulares de S. pneumoniae que causan enfermedad invasora en los ninos latinoamericanos menores de 5 anos, con el proposito de determinar tanto la composicion ideal de una vacuna conjugada que pudiera emplearse en la Region como la susceptibilidad a la penicilina de los aislados de S. pneumoniae. La iniciativa fue aceptada por Argentina, Brasil, Colombia, Chile, Mexico y Uruguay. En este informe se analiza la informacion sobre la neumonia por S. pneumoniae generada en los paises participantes. Se captaron 3 393 ninos con infecciones sistemicas por S. pneumoniae, de las cuales 1 578 correspondian a neumonias. El analisis se concentro en los 1 409 casos de neumonia de Argentina, Brasil, Colombia, Mexico y Uruguay. La distribucion por edades evidencio un franco predominio de los menores de 2 anos (63,8%). Se identificaron 12 tipos capsulares prevalentes, de los cuales los serotipos 14, 5 y 1 ocuparon los tres primeros lugares en la mayoria de los paises. En el periodo 1993-1998, la resistencia a la penicilina aumento en los cinco paises; al comienzo del estudio, los mayores porcentajes correspondieron a Mexico (47,0%) y los menores a Colombia (12,1%). La resistencia a la penicilina se asocio con un reducido numero de serotipos capsulares, fundamentalmente el 14 y el 23F, el primero resistente a la penicilina y a la trimetoprima-sulfametoxazol, y el segundo multirresistente. La frecuencia de la resistencia a la trimetoprima-sulfametoxazol fue elevada en todos los paises y el valor maximo correspondio a Argentina (58,0%). La disminucion de la susceptibilidad al cloranfenicol tuvo baja frecuencia, salvo en Colombia (23,4%). La resistencia a la eritromicina fue baja en todos los paises y todos los aislados fueron sensibles a la vancomicina.Community-acquired pneumonia is one of the leading causes of infant morbidity and mortality. Studies conducted in developing countries indicate that the most serious symptoms of pneumonia are associated with bacterial causes, mainly Streptococcus pneumoniae, followed by Haemophilus influenzae type b. Managing those infections in children under two years of age is hindered by the lack of appropriate vaccines and by the decreased susceptibility of S. pneumoniae to penicillin and other antibiotics. In 1993, at the initiative of the Regional System for Vaccines of the Pan American Health Organization, and with funding from the Canadian International Development Agency, a study was designed to identify the S. pneumoniae capsular types that cause invasive disease in Latin American children under 5 years of age. The objective of the study was to determine the ideal composition of a conjugate vaccine that could be used in Latin America, and the penicillin susceptibility of the S. pneumoniae isolates. The initiative was undertaken in Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. This report analyzes the information that the participating countries generated on pneumococcal pneumonia. A total of 3,393 children were found with systemic S. pneumoniae infections, of which 1,578 corresponded to pneumonias. The analysis focused on 1,409 cases of pneumonia in Argentina, Brazil, Colombia, Mexico, and Uruguay. Of the children, 63.8% of them were under two years of age. Twelve prevalent capsular types were identified, of which serotypes 14, 5, and 1 were the three most common in the majority of the countries. At the beginning of the study the highest level of penicillin resistance was found in Mexico (47.0%), and the lowest in Colombia (12.1%). Over the 1993-1998 period, resistance to penicillin increased in the five countries. Penicillin resistance was associated with a small number of capsular serotypes, mainly 14 and 23F. The first of those serotypes was resistant to penicillin and to trimethoprim-sulfamethoxazole, and the second was multiresistant. The frequency of resistance to trimethoprim-sulfamethoxazole was high in all of the countries; Argentina had the highest level, 58.0%. A decrease in susceptibility to chloramphenicol was uncommon, except in Colombia, where there was a resistance level of 23.4%. Resistance to erythromycin was low in all the countries, and all the isolates were susceptible to vancomycin.

Surveillance of invasive in Streptococcus pneumoniae in Argentina 1994–2007: Changes in serotype distribution, serotype coverage of pneumococcal conjugate vaccines and antibiotic resistance

Streptococcus pneumoniaeis a prevalent cause of invasive diseases in children, justifying continuous surveillance programs such as by the SIREVA group (Pan American Health Organization). The aim of this study was to determine the serotype distribution of S. pneumoniae causing invasive disease in children < 6 years old, the serotype coverage of the pneumococcal conjugate vaccine 7-valent (PCV7), 10-valent (PCV10) and 13-valent (PCV13), and antibiotic resistance, from 1994 to 2007. During this period, 2205 invasive S. pneumoniaewere included in the study. Although 49 different capsular types were identified, 12 serotypes accounted for 86% of all isolates. These were prevalent throughout the study period with serotype 14 predominating. Penicillin non-susceptible S. pneumoniaewas detected in 33.2% of all isolates. The coverage of PCV7, PCV10 and PCV13 from 2004 to 2007 for children < 2 years old was 51.7%, 72.4% and 84.5%, respectively. The data demonstrates a decline in serotype 14, and an increase in serotypes 1 and 19A in the study period. Resistance to penicillin and trimethoprim-sulfamethoxazole decreased, while resistance to erythromycin increased. These results demonstrate the need for the introduction of a conjugate pneumococcal vaccine and continuing surveillance to monitor changes in serotypes distribution and antimicrobial resistance.

Infecciones invasivas por Streptococcus pneumoniae: Estudio epidemiológico e importancia del desarrollo de un sistema de vigilancia

Las infecciones invasivas por streptococcus pnneumoniae(Spn)producen mortalidad elevada en paises en desarrollo,con tasa entre 4 y 100 veces mayores que las de Estados Unidos o Canada.Es el primer agente causal de neumonia en la infancia y de meningitis fuera de los brotes epidemicos po neisseria meningiditis.La OPS,a traves del grupo SIREVA,dedicado al desarrollo de vacunas en Latinoamerica,organizo un programa de vigilancia de infecciones invasivas por Spn en seis paises:argentina,Brasil,chile,colombia,Mexico y Uruguay iniciado en 1993 y que continua actualmente.En Argentina participan en la actualidad mas de 20 centros hospitalarios distribuidos en todas la areas geograficas del pais,actuando como Centro Nacional de referencia para la serotipificacion y determinacion de la resistencia a los antibioticos el Instituto ANLIS uDr.Carlos G Malbran.Objetivos.1)determinar los serotipos predominates,su resistencia a los antibioticos y los cambios temporales en infecciones invasivas por Spn de ninos menores de 5 anos de edad.2)Obtener informacion confiable para la formulacion de una vacuna conjugada adecuada para la region.Conclusiones.Un programa nacional de vigilancia de Spn invasivo fue desarrollado en Argentina y otros paises Latinoamericanos.Se identificaron por primera vez los serotipos predominantes en infecciones invasivas y se comprobo el incremento significativo de la resistencia a penicilina y otros antibioticos,similar a lo informado en casi todos los paises del mundo.Se obtuvo informacion epidemiologica valida para evaluar estrategias de prevencion en nuevas vacunas

Community Acquired Pneumonia Incidence Among Children Under 5 Years of Age in Concordia Argentina. Universal Vaccination Impact

Abstract Background In January 2012, Argentine introduced PCV-13 to the National Immunization Program. We performed an epidemiological study in order to describe consolidated pneumonia and pneumococcal disease incidence following PCV-13 routine vaccination. Methods Between April2014-March2016, a population-based surveillance study was carried out in Concordia. Clinical data, vaccination status and digital chest X-rays were recorded from children < 5 years old with pneumonia and pleural effusion. A pediatrician and a radiologist interpreted the images independently. A second reference radiologist arbitrated when discordances occurred. Bacterial etiology was investigated in blood and/or in pleural fluid. Probably bacterial pneumonia (PBP) was determined following WHO protocol. Results were compared with previous data (2002–2005) from the pre-PCV-13 vaccination era. Variables associated to consolidated pneumonia were evaluated by multivariate analysis using logistic regression Results 330 patients under 5 years old with pneumonia were assisted during the study period. Of these, 92 (27.9%-IC95% 23.2–33.1) were classified as PBP. Annual incidence rate, in pre and post vaccination period and impact of vaccination are described in table 1. Incidence of pneumococcal disease could not be estimated as pneumococcal isolation was negative in all cases. Multivariate analysis of post-PCV-13 vaccination era showed that incidence of consolidated pneumonia was significantly higher in hospitalized toddlers than outpatients OR: 2,97 (1,65–5,38). Table 1: PBP incidence (*100.000) by study period. Vaccination impact Final Classification Pre-vacccination period Post vaccination period Impact of 
vaccination N Population Incidence n Population Incidence Incidence Rate ratio (IC95%) Decrease P 
value Consolidated pneumonia 387 18.053 714,6 86 15.493 283.9 2.5 (1.8–3.6) 60.2% <0.001 Pneumonia with pleural effusion 72 18.053 132.9 6 15.493 19.4 6.7 (2.1–35.6) 85.4% 0.004 PBP (total) 459 18.053 847.5 92 15.493 296.9 2.8 (2–4) 64.9% <0.001 Conclusion A significant decline in consolidated pneumonia and pleural effusion incidence in <5 year old children was evidenced in Concordia after the introduction of PCV13 into national immunization program. Disclosures All authors: No reported disclosures.