Changing characteristics of invasive pneumococcal disease in Metropolitan Atlanta, Georgia, after introduction of a 7-valent pneumococcal conjugate vaccine.

BACKGROUND: The rate of invasive pneumococcal disease (IPD) has decreased among both immunized children and nonimmunized adults since the licensure of a heptavalent pneumococcal conjugate vaccine (PCV7) for use in infants in the United States in 2000. METHODS: Temporal trends in IPD incidence, clinical syndromes, and underlying conditions were analyzed using active laboratory- and population-based surveillance data from the Centers for Disease Control and Prevention-sponsored Georgia Emerging Infections Program for the 20-county Metropolitan Atlanta, Georgia, for the period of July 1997 through June 2004. P values were determined by test for trend. RESULTS: Since 2000, there have been significant decreases in the rates of invasive pneumococcal pneumonia (relative risk [RR], 0.80; P=.002) and meningitis (RR, 0.41; P=.003) in adults and for primary bacteremia, invasive pneumonia, and meningitis in children (RR, 0.16 [P<.001], 0.60 [P=.003], and 0.70 [P=.009], respectively). Among human immunodeficiency virus-infected persons, there were significant decreases in the overall rates of IPD (decrease of 43%; P<.001) and invasive pneumonia (decrease of 44%; P<.001) since 2000-2001, although the rate of IPD increased significantly (increase of 53%; P=.022) among patients with acquired immunodeficiency syndrome. There was a concurrent increase in the proportion of adults aged > or = 40 years with underlying comorbidities. Rates of non-PCV7 serotypes increased 1.61-fold and 1.28-fold from 2000-2001 to 2003-2004 in children and adults (P=.005 for both). CONCLUSIONS: The decreasing incidence of IPD in Atlanta since 2000-2001 was associated with decreases in cases of pneumonia and meningitis in adult and pediatric subjects and in cases of primary bacteremia in children. The burden of serotype-replacement disease remained small. Adults with comorbidities represent a growing proportion of patients with IPD.

Identification of serotype in culture negative pneumococcal meningitis using sequential multiplex PCR: implication for surveillance and vaccine design.

BACKGROUND: PCR-based serotyping of Streptococcus pneumoniae has been proposed as a simpler approach than conventional methods, but has not been applied to strains in Asia where serotypes are diverse and different from other part of the world. Furthermore, PCR has not been used to determine serotype distribution in culture-negative meningitis cases. METHODOLOGY: Thirty six serotype-specific primers, 7 newly designed and 29 previously published, were arranged in 7 multiplex PCR sets, each in new hierarchies designed for overall serotype distribution in Bangladesh, and specifically for meningitis and non-meningitis isolates. Culture-negative CSF specimens were then tested directly for serotype-specific sequences using the meningitis-specific set of primers. PCR-based serotyping of 367 strains of 56 known serotypes showed 100% concordance with quellung reaction test. The first 7 multiplex reactions revealed the serotype of 40% of all, and 31% and 48% non-meningitis and meningitis isolates, respectively. By redesigning the multiplex scheme specifically for non-meningitis or meningitis, the quellung reaction of 43% and 48% of respective isolates could be identified. Direct examination of 127 culture-negative CSF specimens, using the meningitis-specific set of primers, yielded serotype for 51 additional cases. CONCLUSIONS: This PCR approach, could improve ascertainment of pneumococcal serotype distributions, especially for meningitis in settings with high prior use of antibiotics.

Evaluating the costs of pneumococcal disease in selected Latin American countries.

OBJECTIVES: To estimate the costs of pneumococcal disease in Brazil, Chile and Uruguay, to describe how these costs vary between different patient groups, and to discuss factors that affect these cost variations. METHODS: The cost of pneumococcal disease was estimated from the health care perspective. For each country, baseline cost estimates were primarily developed using health resources information from patient-level data and facility-specific cost data. A regression model was constructed separately for four types of pneumococcal diseases. The skewness-kurtosis test and the Cook-Weisberg test were performed to test the normality of the residuals and the heteroscedasticity, respectively. RESULTS: The treatment of pneumococcal meningitis generated up to US$ 5 435 per child. The treatment costs of pneumococcal pneumonia were lower, ranging from US$ 372 per child to US$ 3 483 per child. Treatment of acute otitis media cost between US$ 20 per child and US$ 217 per child. The main source of treatment costs variations was level of service provided and country in which costs were incurred. However, the tendency of costs to change with these variables was not statistically significant at the 5% level for most pneumococcal disease models. CONCLUSIONS: Pneumococcal disease resulted in significant economic burden to selected health care systems in Latin America. The patterns of treatment cost of pneumococcal disease showed a great deal of variation.

Invasive pneumococcal infections in Canadian children, 1991-1998: implications for new vaccination strategies. Canadian Paediatric Society/Laboratory Centre for Disease Control Immunization Monitoring Program, Active (IMPACT).

We reviewed 2040 consecutive cases of invasive pneumococcal infection that were seen at 11 pediatric centers across Canada during 1991-1998 to determine if such infections could be prevented by new conjugate vaccines. Isolates from 1528 cases were serotyped. Most cases (61.5%) occurred in patients aged >2 years. Underlying medical conditions were present in 23.2% of case patients. Serotypes in the 7-valent conjugate vaccine matched isolates as follows: 85.8% of tested isolates from children aged 6 months to 5 years, but significantly fewer isolates in younger and older children; 72.9% of isolates from non-healthy children, but 83.9% of isolates from previously healthy children; and 95.4% of isolates with high-level penicillin resistance, but only 72.7% of those with intermediate-level resistance. Significant natural variation in the proportion of isolates matching 7-valent vaccines occurred from year to year and among centers. New conjugate vaccines have great potential but their effectiveness and limitations require ongoing study.

Evaluating the costs of pneumococcal disease in selected Latin American countries / Evaluación de los costos de la enfermedad neumocócica en países seleccionados de América Latina

OBJECTIVES: To estimate the costs of pneumococcal disease in Brazil, Chile and Uruguay, to describe how these costs vary between different patient groups, and to discuss factors that affect these cost variations. METHODS: The cost of pneumococcal disease was estimated from the health care perspective. For each country, baseline cost estimates were primarily developed using health resources information from patient-level data and facility-specific cost data. A regression model was constructed separately for four types of pneumococcal diseases. The skewness-kurtosis test and the Cook-Weisberg test were performed to test the normality of the residuals and the heteroscedasticity, respectively. RESULTS: The treatment of pneumococcal meningitis generated up to US$ 5 435 per child. The treatment costs of pneumococcal pneumonia were lower, ranging from US$ 372 per child to US$ 3 483 per child. Treatment of acute otitis media cost between US$ 20 per child and US$ 217 per child. The main source of treatment costs variations was level of service provided and country in which costs were incurred. However, the tendency of costs to change with these variables was not statistically significant at the 5 percent level for most pneumococcal disease models. CONCLUSIONS: Pneumococcal disease resulted in significant economic burden to selected health care systems in Latin America. The patterns of treatment cost of pneumococcal disease showed a great deal of variation.

OBJETIVOS: Estimar los costos de la enfermedad neumocócica en Brasil, Chile y Uruguay, describir cómo varían estos costos entre diferentes grupos de pacientes y discutir los factores que influyen en las variaciones de estos costos. MÉTODOS: El costo de la enfermedad neumocócica se estimó desde la perspectiva de la atención sanitaria. Inicialmente se establecieron estimados de referencia de los costos para cada país a partir de la información de los recursos sanitarios empleados, según los datos de cada paciente y los costos específicos de cada institución. Se construyeron modelos de regresión por separado para cuatro tipos de enfermedad neumocócica. Se realizaron las pruebas de asimetría-curtosis y de Cook-Weisberg para comprobar la normalidad de los residuos y la heterocedasticidad, respectivamente. RESULTADOS: El costo del tratamiento de la meningitis neumocócica fue de US$ 5 435 por cada niño, mientras el de la neumonía neumocócica fue menor, entre US$ 372 y US$ 3 483 por niño. El costo del tratamiento de la otitis media aguda fue de US$ 20 a US$ 217 por niño. La principal fuente de variación en los costos de tratamiento fue el nivel de servicio brindado y el país en que se generaron los costos. No obstante, la tendencia de los costos a variar no fue estadísticamente significativa (P > 0,05) en la mayoría de los modelos de la enfermedad neumocócica. CONCLUSIONES: La enfermedad neumocócica constituye una notable carga económica para los sistemas de salud seleccionados de América Latina. Los patrones del costo de tratamiento de la enfermedad neumocócica mostraron una gran variación.

Diagnosis of Streptococcus pneumoniae meningitis by polymerase chain reaction amplification of the gene for pneumolysin

Diagnosis of bacterial meningitis has long been based on classical methods of Gram stain, serological tests, and culture of cerebrospinal fluid (CSF). The performance of these methods, especially culture and direct smear, is thwarted by failure to detect bacteria following administration of antimicrobial agents and reluctance to performance lumbar punctures at admission. Indeed, patients with meningitis frequently receive antibiotics orally or by injection before the diagnosis is suspected or established. Thus an alternative method has become necessary to help clinicians and epidemiologists to management and control of bacterial meningitis. We evaluate the application of a polymerase chain reaction-based (PCR) assay for amplification of pneumolysin gene (ply) to diagnosis of Streptococcus pneumoniae meningitis. The PCR assay sensitivity for CSF was 96 percent (95 percent confidence interval, CI, 90-99 percent) compared to a sensitivity of 59 percent for culture (95 percent CI 49-69 percent), 66 percent for Gram stain (95 percent CI 56-74 percent), and 78 percent for latex agglutination test (95 percent CI 69-86 percent); PCR specificity was 100 percent (95 percent CI 83-100 percent). PCR results were available within 4 h of the start of the assay. This molecular approach proved to be reliable and useful to identify this bacterium compared with other classical laboratory methods for identification of bacterial meningitis pathogens.

Inmunización contra neumococos / Immunization against pneumococcus

Streptococus pneumoniae o neumococo, es una bacteria Gram-positiva considerada como uno de los principales agentes patógenos del aparato respiratorio en personas de todas las edades, particularmente aquellas de edad avanzada. En este último grupo de edad, la neumonía neumocócica sigue siendo una de las causas más importantes de morbilidad y mortalidad. Vacunas disponibles: el primer programa de vacunación antineumocócica se efectuó en 1911 en Africa del Sur en los trabajadores mineros, pues en ellos la incidencia de la enfermedad era muy alta y producía muchas defunciones. Al principio de la década de los 70 se usó la primera vacuna polisacarídica antineumocócica; en 1977 en los Estados Unidos se autorizó y en 1978 se inició la comercialización de la vacuna neumocócica de 14 serotipos, con 50 g. de polisacárido capsular. Hasta 1983 fue que se volvieron a autorizar cambios en la vacuna, ahora con 25 g. de cada polisacárido de 23 serotipos. Por lo que respecta a las vacunas en desarrollo se anota: desde su aparición, muchos se ha dicho sobre la antigenicidad y seguridad de la vacuna neumocócica. Aunque quedan por despejarse muchas dudas, lo que si está claro es que se necesita una vacuna más inmunogénica, especialmente para los niños menores de 2 años. Hasta el momento, lo más promisorio son las vacunas conjugadas a proteínas. Existen otras posibilidades de nuevas vacunas, las cuales se encuentran aún en estudio experimental e incluyen utilización de conjugados hexasacáridos y de anticuerpos monoclonales