Maria Hortal

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999

BACKGROUND Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. METHODS The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. RESULTS By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. CONCLUSION These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.Background. Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. Methods. The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. Results. By June, 1999, 4105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. Conclusion. These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

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.

Three-Year Assessment of Methicillin-Resistant Staphylococcus aureus Clones in Latin America from 1996 to 1998

ABSTRACT Four hundred ninety-nine methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from 1996 to 1998 from 22 hospitals in five countries of Latin America—Argentina, Brazil, Chile, Uruguay and Mexico—were examined for antimicrobial susceptibility and clonal type in order to define the endemic clones in those hospitals. The hybridization of ClaI restriction digests with themecA- and Tn554-specific DNA probes combined with pulsed-field gel electrophoresis of chromosomal SmaI digests (ClaI-mecA::ClaI-Tn554::PFGE clonal types) documented not only the predominance and persistence of the Brazilian clone (XI::B::B) in Brazil (97%) and Argentina (86%) but also its massive dissemination to Uruguay (100%). Moreover, a close relative of the Brazilian clone (XI::κ::B) was highly represented in Chile (53%) together with a novel clone (47%) (II::E′::F) resistant to pencillin, oxacillin, ciprofloxacin, chloramphenicol, clindamycin, erythromycin, and gentamicin. A unique clonal type (I::NH::M) was detected in Mexico among pediatric isolates and was resistant to penicillin, oxacillin, and gentamicin only. This study clearly documented the very large capacity for geographic expansion and the persistence of the Brazilian clone, contributing not only to the increasing uniformity of the MRSA in South America but worldwide as well.

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.

Impact of Pneumococcal Conjugate Vaccines on the Incidence of Pneumonia in Hospitalized Children after Five Years of Its Introduction in Uruguay

Background Data on the burden of pneumococcal disease and the most frequent serotypes demonstrated that invasive disease and pneumonia were important manifestations affecting children under 5 years of age. Therefore, pneumococcal diseases prevention became a public health priority. Uruguay was the first Latin American country to incorporate PCV7 into its National Immunization Program. The aim of this study is to compare the incidence rates for hospitalized pneumonia in children from the pre PCV introduction period and the following five years of PCVs application in Uruguay. Methods and Findings Population-based surveillance of pneumonia hospitalization rates, in children, less than 14 years of age, had been performed prior pneumococcal vaccination, and continued following PCV7 introduction and PCV13 replacement, using the same methodology. Hospitalized children with pneumonia were enrolled from January 1, 2009 through December 31st, 2012. The study was carried out in an area with a population of 238,002 inhabitants of whom 18, 055 were under five years of age. Patients with acute lower respiratory infections for whom a chest radiograph was performed on admission were eligible. Digitalized radiographs were interpreted by a reference radiologist, using WHO criteria. Pneumonia was confirmed in 2,697 patients, 1,267 with consolidated and 1,430 with non consolidated pneumonia of which incidence decrease, between 2009 and 2012, was 27.3% and 46.4% respectively. 2001–2004 and 2009–2012 comparison showed a significant difference of 20.4% for consolidated pneumonia hospitalizations. A significant incidence decline was recorded among children 6 to 35 months of age. Conclusions An overall significant reduction in pneumonia hospitalizations was observed following the introduction of PCV7 and furthermore following the change to PCV13.

Ten-year review of invasive pneumococcal diseases in children and adults from Uruguay: clinical spectrum, serotypes, and antimicrobial resistance.

OBJECTIVES Since 1987, the Reference Laboratory of the Ministry of Health of Uruguay has been monitoring infections due to Streptococcus pneumoniae in patients under 5 years of age, in those between 5 to 14 years of age, and in adults. The purpose of the present study was to retrospectively analyze a 10-year collection of invasive S. pneumoniae isolates from children 5 to 14 years of age and adults. METHODS The Reference Childrens Hospital, Pasteur Hospital, and two private hospitals in Montevideo as well as four hospitals located in other representative areas of the country participated in the pneumococcal surveillance program. Based on the information available at the Microbiology Department of the Central Public Health Laboratory (demographic data, date and site of isolate, and clinical diagnosis), all patients with an invasive pneumococcal disease were recorded. Pneumonia was clinically and radiologically diagnosed and etiology was assessed by isolation of S. pneumoniae from blood or pleural fluid. All specimens were collected at the Emergency Service. Capsular serotyping and antimicrobial susceptibilities were determined for each isolate. RESULTS During the 10-year period, 228 invasive S. pneumoniae were identified and included in the study (blood, n = 129; cerebrospinal fluid [CSF], n = 73; pleural fluid, n = 20; peritoneal fluid, n = 3; synovial fluid, n = 1; pericardic fluid, n = 1; abscess, n = 1). The most frequent clinical presentations were pneumonia (n = 71) and meningitis (n = 69). Thirty-five adults had an underlying condition including, four with malignancies, four with lupus, two with human immunodeficiency virus (HIV)-infected, and two patients in hemodialysis among others. Eighteen of the 228 patients died (7.9% fatality rate), but only four of these had an underlying condition. Eleven fatal cases were attributable to meningitis (2 children, 9 and 11 years old; 9 adults, mean age, 59 y). Four patients with pneumonia and three with sepsis died, including a splenectomized woman. Nine different capsular serotypes (1, 5, 7, 9, 12, 15, 19A, 20, and 23A) were identified among the 18 fatal cases. Resistance to penicillin, generally combined with trimethoprim-sulfamethoxazole, fluctuated annually, not surpassing 10%. CONCLUSIONS The study results indicated that 96% of the serotypes involved in severe pneumococcal diseases were included in the 23-valent vaccine and that S. pneumoniae resistance to penicillin was moderate.

Etiology and severity of community acquired pneumonia in children from Uruguay: a 4-year study

The 4-year study (1987-1990) covered the major clinical-epidemiological characteristics of pneumonia in children as diagnosed at the emergency service of the Childrens Hospital, as well as etiologies, and factors involved in the most severe cases. Etiology was determined in 47.7% of the 541 pneumonia cases, involving 283 pathogens of which 38.6% were viruses and 12.6% bacteria. Viral and mixed etiologies were more frequent in children under 12 months of age. Bacteria predominated in ages between 6 and 23 months. Among the viruses, respiratory syncytial virus predominated (66%). The bacterial pneumonias accounted for 12.2% of the recognized etiologies. The most important bacterial agents were S. pneumoniae (64%) and H. influenzae (19%). H. influenzae and mixed infections had a relevant participation during the 1988 season, pointing to annual variations in the relative participation of pathogens and its possible implication in severity of diseases. Correlation of severity and increased percentage of etiological diagnosis was assessed: patients with respiratory rates over 70 rpm, or pleural effusion and/or extensive pulmonary parenchyma compromise yielded higher positive laboratory results. Various individual and family risk factors were recognized when comparing pneumonia children with healthy controls.

Evolution of an International External Quality Assurance Model To Support Laboratory Investigation of Streptococcus pneumoniae, Developed for the SIREVA Project in Latin America, from 1993 to 2005

ABSTRACT In 1993 the Pan American Health Organization initiated a laboratory-based surveillance system, called the SIREVA project, to learn about Streptococcus pneumoniae invasive disease in Latin American children. In 1994, National Laboratories in six countries were trained to perform serotyping and antibiotic susceptibility testing using broth microdilution to determine the MIC for specified antibiotics. An international External Quality Assurance (EQA) program was developed to monitor and support ongoing laboratory performance. The EQA program was coordinated by the National Centre for Streptococcus (NCS), Edmonton, Canada, and included external proficiency testing (EPT) and a validation process requiring regular submission of a sample of isolates from each laboratory to the NCS for verification of the serotype and MIC. In 1999, the EQA program was decentralized to use three of the original laboratories as regional quality control centers to address operational concerns and to accommodate the growth of the laboratory network to more than 20 countries including the Caribbean region. The overall EPT serotyping accuracies for phase I (1993 to 1998) and phase II (1999 to 2005) were 88.0 and 93.8%, respectively; the MIC correlations within ±1 log2 dilution of the expected result were 83.0 and 91.0% and the interpretive category agreements were 89.1 and 95.3%. Overall, the validation process serotyping accuracies for phases I and II were 81.9 and 88.1%, respectively, 80.4 and 90.5% for MIC agreement, and 85.8 and 94.3% for category agreement. These results indicate a high level of testing accuracy in participating National Laboratories and a sustained increase in EQA participation in Latin America and the Caribbean.

Dissemination of Streptococcus pneumoniae Clone Colombia5-19 in Latin America

ABSTRACT Streptococcus pneumoniae serotype 5 is the third most common capsular type causing invasive diseases in children younger than 5 years in Latin America. Preliminary data on Colombian serotype 5 isolates indicated a common clonal origin associated with resistance to tetracycline (TET) and chloramphenicol (CHL). We studied 172 S. pneumoniae serotype 5 invasive isolates from Argentina, Brazil, Colombia, Guatemala, Mexico, and Uruguay and confirmed the presence of the Colombia5-19 clone throughout Latin America. Fifteen subtypes of a pulsed-field gel electrophoresis pattern and 4 electrophoretic types (ET) were obtained. Most of the isolates from different geographical regions belonged to pattern A (34.3%), subtype A5 (41.9%), and ET1 (91.1%). The A pattern (n = 59) was resistant to TET and had variable resistance to CHL; it was present in Brazil (10.2%), Colombia (78%), Guatemala (8.5%), and Mexico (3.4%). Subtype A5 with variable susceptibility to TET and sensitive to CHL was found in Argentina (29.2%), Mexico (8.3%), and Uruguay (62.5%). Subtypes A1-A4, A7-A8, and A9-A11 (closely related to A) also shared ET1, while subtype A6 was assigned to ET1, ET2, and ET3. Eleven subtypes (n = 21) were found to be specific for one country each. In summary, the S. pneumoniae serotype 5 isolates from Latin American are genetically closely related but show different patterns of antibiotic resistance, probably as a result of horizontal transfer.

Resistencia a antibióticos no betalactámicos de aislamientos invasores de Streptococcus pneumoniae en niños latinoamericanos: SIREVA II, 2000-2005

OBJECTIVE To examine the development of resistance to erythromycin, chloramphenicol, trimethoprim-sulfamethoxazole (TMP-SMZ), and vancomycin of the invasive isolates of Streptococcus pneumoniae obtained from children in 10 Latin American/Caribbean countries during six years of surveillance. METHODS Analysis of 8 993 isolates of S. pneumoniae recovered in 2000-2005 from children with invasive infections, who were less than 6 years of age, and from Argentina, Brazil, Chile, Colombia, Cuba, Dominican Republic, Mexico, Paraguay, Uruguay, or Venezuela. Antibiotic susceptibility was determined through the methods established and standardized by the SIREVA project. Multidrug resistance was defined as: resistance to three or more antibiotics of the same class; to the non-beta-lactams analyzed by this study; or, to the beta-lactams evaluated by a previous study, in which 37.8% of these isolates showed decreased susceptibility to penicillin. RESULTS Some degree of resistance was found to TMP-SMZ and erythromycin (56.4% and 15.4% of the isolates studied, respectively), with 4.6% highly resistant to chloramphenicol. All isolates were susceptible to vancomycin. The highest prevalence of TMP-SMZ resistance was observed in the pneumonia isolates; and that of erythromycin, in cases of sepsis (61.6% and 25.5%, respectively; P < 0.01). The highest prevalence of TMP-SMZ resistance was found in Brazil (71.9%), and that of erythromycin, in Mexico (38.2%) and Venezuela (32.9%). The 14, 6B, 19F, and 23F serotypes were most often associated with resistance to the antibiotics in the study. CONCLUSIONS High and increasing rates of isolates resistant to TMP-SMZ and erythromycin were observed, as well as a decreasing percentage of isolates resistant to chloramphenicol. These trends highlight differences among the countries studied.