Effect of coinfection with influenza virus and bacteria on host damage.

BACKGROUND: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. OBJECTIVE: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. METHOD: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. RESULTS: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. CONCLUSIONS: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

ANTECEDENTES: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. OBJETIVO: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. MÉTODO: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. RESULTADOS: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. CONCLUSIONES: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Effect of coinfection with influenza virus and bacteria on host damage / Efecto de la coinfección por virus de la influenza y bacterias en el daño al hospedero

Abstract Background: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. Objective: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Method: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Results: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. Conclusions: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

Resumen Antecedentes: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. Objetivo: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. Método: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. Resultados: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. Conclusiones: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Associação de meningite e pericardite na doença pneumocócica invasiva: um caso raro / Association of meningitis and pericarditis in invasive pneumococcal disease: a rare case

RESUMO Objetivo: Relatar um caso raro de uma criança com meningite associada a pericardite na doença pneumocócica invasiva. Descrição do caso: Este relato descreve uma evolução clínica desfavorável de um lactente feminino de 6 meses de idade, previamente hígido, que apresentou inicialmente sintomas respiratórios e febre. A radiografia de tórax revelou um aumento da área cardíaca sem alterações radiográficas nos pulmões. Após a identificação do derrame pericárdico, o paciente apresentou convulsões e entrou em coma. Pneumonia foi descartada durante a investigação clínica. Contudo, foi identificado Streptococcus pneumoniae nas culturas de líquor e sangue. O exame neurológico inicial foi compatível com morte encefálica, posteriormente confirmada pelo protocolo. Comentários: A pericardite purulenta tornou-se uma complicação rara da doença pneumocócica invasiva desde o advento da terapia antibiótica. Pacientes com pneumonia extensa são primariamente predispostos e, mesmo com tratamento adequado e precoce, estão sujeitos a altas taxas de mortalidade. A associação de meningite pneumocócica e pericardite é incomum e, portanto, de difícil diagnóstico. Por isso, uma alta suspeição diagnóstica é necessária para instituir o tratamento precoce e aumentar a sobrevida.

ABSTRACT Objective: To report a rare case of a child with invasive pneumococcal disease that presented meningitis associated with pericarditis. Case description: This report describes the unfavorable clinical course of a previously healthy 6-months-old female infant who initially presented symptoms of fever and respiratory problems. A chest X-ray revealed an increased cardiac area with no radiographic changes in the lungs. After identifying a pericardial effusion, the patient experienced seizures and went into coma. Pneumonia was excluded as a possibility during the clinical investigation. However, Streptococcus pneumoniae was identified in the cerebrospinal fluid and blood cultures. An initial neurological examination showed that the patient was brain dead, which was then later confirmed according to protocol. Comments: Purulent pericarditis has become a rare complication of invasive pneumococcal disease since the advent of antibiotic therapy. Patients with extensive pneumonia are primarily predisposed and, even with early and adequate treatment, are prone to high mortality rates. The association of pneumococcal meningitis and pericarditis is uncommon, and therefore difficult to diagnose. As such, diagnostic suspicion must be high in order to institute early treatment and increase survival.

ASSOCIATION OF MENINGITIS AND PERICARDITIS IN INVASIVE PNEUMOCOCCAL DISEASE: A RARE CASE. / ASSOCIAÇÃO DE MENINGITE E PERICARDITE NA DOENÇA PNEUMOCÓCICA INVASIVA: UM CASO RARO.

OBJECTIVE: To report a rare case of a child with invasive pneumococcal disease that presented meningitis associated with pericarditis. CASE DESCRIPTION: This report describes the unfavorable clinical course of a previously healthy 6-months-old female infant who initially presented symptoms of fever and respiratory problems. A chest X-ray revealed an increased cardiac area with no radiographic changes in the lungs. After identifying a pericardial effusion, the patient experienced seizures and went into coma. Pneumonia was excluded as a possibility during the clinical investigation. However, Streptococcus pneumoniae was identified in the cerebrospinal fluid and blood cultures. An initial neurological examination showed that the patient was brain dead, which was then later confirmed according to protocol. COMMENTS: Purulent pericarditis has become a rare complication of invasive pneumococcal disease since the advent of antibiotic therapy. Patients with extensive pneumonia are primarily predisposed and, even with early and adequate treatment, are prone to high mortality rates. The association of pneumococcal meningitis and pericarditis is uncommon, and therefore difficult to diagnose. As such, diagnostic suspicion must be high in order to institute early treatment and increase survival.

OBJETIVO: Relatar um caso raro de uma criança com meningite associada a pericardite na doença pneumocócica invasiva. DESCRIÇÃO DO CASO: Este relato descreve uma evolução clínica desfavorável de um lactente feminino de 6 meses de idade, previamente hígido, que apresentou inicialmente sintomas respiratórios e febre. A radiografia de tórax revelou um aumento da área cardíaca sem alterações radiográficas nos pulmões. Após a identificação do derrame pericárdico, o paciente apresentou convulsões e entrou em coma. Pneumonia foi descartada durante a investigação clínica. Contudo, foi identificado Streptococcus pneumoniae nas culturas de líquor e sangue. O exame neurológico inicial foi compatível com morte encefálica, posteriormente confirmada pelo protocolo. COMENTÁRIOS: A pericardite purulenta tornou-se uma complicação rara da doença pneumocócica invasiva desde o advento da terapia antibiótica. Pacientes com pneumonia extensa são primariamente predispostos e, mesmo com tratamento adequado e precoce, estão sujeitos a altas taxas de mortalidade. A associação de meningite pneumocócica e pericardite é incomum e, portanto, de difícil diagnóstico. Por isso, uma alta suspeição diagnóstica é necessária para instituir o tratamento precoce e aumentar a sobrevida.

Pneumococcal disease manifestation in children before and after vaccination: what's new?

Pneumococcal infections remain a relevant cause of morbidity and mortality in children, especially in countries where vaccination has not been introduced. In contrast to the common belief by many pediatricians, the most important pneumococcal infections are of the respiratory tract and not invasive diseases. The recent pandemic of the H1N1 virus prompted studies to better understand the interaction between the influenza virus, Streptococcus pneumoniae, and pneumonia outcomes. Radiological findings of bacteremic pneumonia have been well investigated and besides the typical alveolar consolidation, a broad spectrum of atypical patterns has been reported. Molecular techniques, such as real-time polymerase chain reaction (PCR), can improve the detection of S. pneumoniae in sterile fluids, mainly in regions where previous antibiotic therapy is a common practice. In the post vaccination era, new manifestations of pneumococcal invasive disease, such as hemolytic uremic syndrome, have increased in association with parapneumonic empyema. Moreover, serotypes not included in PCV7, particularly serotypes 1, 3, 5, 7F, and 19A, have been among the most common isolates in pneumococcal disease. In Latin America, pneumococcal primary peritonitis has been described as an important clinical syndrome in a growing proportion of patients, mainly in girls. The development of newer and more specific diagnostic markers to distinguish bacterial and viral pneumonia are urgently sought, and will be especially pertinent after the introduction of pneumococcal conjugate vaccines with expanded serotypes. Such markers would minimize inappropriate diagnosis of false positive cases and treatment with antibacterial agents, while increasing positive predictive values for diagnosis of bacterial pneumonia. The extension of serotype coverage with the new conjugate vaccines is promising for pneumococcal infections and coverage against antibiotic-resistant strains.

Estimation and comparison of EQ-5D health states' utility weights for pneumococcal and human papillomavirus diseases in Argentina, Chile, and the United Kingdom.

OBJECTIVES: To estimate and compare EuroQol instrument (EQ-5D) health states' values for pneumococcal and human papillomavirus (HPV) diseases in Argentina, Chile, and the United Kingdom. METHODS: Twelve vignettes were designed, pilot-tested, and administered to a convenience sample in a cross-sectional design to elicit descriptive EQ-5D state data. Country-specific EQ-5D time-trade-off-based weights were used to map these descriptive health states into local country preference weights. Descriptive analysis is reported and intercountry differences for each condition were compared using repeated measures analysis of variance. RESULTS: Seventy-three subjects completed the survey. Pneumococcal disease-related health states mean values ranged from -0.331 (sepsis, Chile) to 0.727 (auditive sequelae, Argentina). HPV-related conditions ranged from 0.152 (cervical cancer, United Kingdom) to 0.848 (cervical intraepithelial neoplasia 1, Argentina). Chile had consistently the lowest mean values in pneumococcal states and in one HPV state, whereas those of the United Kingdom were the lowest in most HPV states. Argentina had the highest mean values in both diseases. Differences in country-specific values for each health state were statistically (P < 0.001) significant except for six health states in which differences between Chilean and United Kingdom weights were nonsignificant. CONCLUSIONS: Utility values for most conditions differed statistically relevantly among analyzed countries, even though the same health states' descriptive set was valued for each. These results reflect the difference in social weights among different countries, which could be attributed to either different population values or valuation study methodologies. They stress the importance of using local preference weights for context-specific decision making.

Avances en el desarrollo de las vacunas neumocócicas conjugadas: [revisión] / Update on pneumococcal conjugate vaccines: [review]

El estreptococcus pneumoniae se encuentra entre los mayores patógenos causantes de infecciones invasoras y no invasoras en los dos extremos de la vida: en niños menores de 5 años y en personas mayores de 65 años de edad. Las principales manifestaciones asociadas a infecciones neumocócicas son: neumonía, bacteriemia febril, septicemia, otitis media y meningitis. Esta bacteria es uno de los principales agentes involucrados en la mortalidad infantil, con un estimado de 1000000 de muertes globales por año, en niños menores de 5 años de edad, la mayoría provenientes de países en vías de desarrollo, por lo que es considerada como un serio problema para la salud pública alrededor del mundo. En el 2000 se introdujo al mercado de los Estados Unidos de Norte América, la primera vacuna neumocócica conjugada, que a diferencia de la ya disponible vacuna neumocócica polisacárida, es capaz de proporcionar una respuesta inmune efectiva para la protección de niños menores de 2 años. La eficacia reportada para la vacuna conjugada heptavalente en los ensayos clínicos iniciales fue de un 97.4 por ciento contra la enfermedad neumocócica invasora producida por los serotipos incluidos en la vacuna, 4, 9V, 14, 19F, 23F, 18C y 6B. En la actualidad diferentes entidades regulatorias, incluyendo la Agencia Europea de Medicamentos, EMEA, han autorizado la comercialización de la vacuna conjugada 10-valente, en la que, además de los serotipos descritos para la vacuna 7-valente, se incluyen los serotipos 1, 5 y 7F; de estos diez serotipos, ocho se encuentran conjugados con la proteína transportadora D, un elemento que se encuentra en la porción externa del Haemophilus influenzae. La otra nueva vacuna conjugada que está en fase de análisis por diferentes entidades regulatorias, incluyendo la Administración de Alimentos y Drogas de los Estados Unidos...

Streptococcus pneumoniae is one of the major pathogens causing invasive and non invasive infections in children younger than 5 years as well as in the elderly. Primary clinical syndromesassociated with pneumococcal infections are pneumonia, bacteremia, acute otitis media andmeningitis. This microorganism contributes importantly to morbidity and mortality among children under 5years of age, it is estimated that 1,000, 000 deaths occurs per year in that age range alone, mostly from developing countries, thus becoming a serious public health problem around the globe. In year 2000 the first heptavalent conjugated pneumococcal vaccine was licensed in the United States of America, it differed from the already available polysaccharide pneumococcal vaccine,by its ability to provide an effective immune response for the protection of children under the age of 2. The efficacy of the heptavalent conjugated vaccine reported in initial clinical trials was 97,4% against invasive pneumococcal disease related to vaccine serotypes (4, 9V, 14, 19F, 23F, 18C and 6B). Different health authorities worldwide, including the European Medicines Agency(EMEA) had approved the introduction of a 10-valent formulation which includes all 7 PCV7 serotypes plus serotypes 1, 5 and 7F; 8 serotypes are conjugated with protein D as a novel carrier, an element found in the outer core of the non-typeable Haemophilus influenzae. Another new conjugated vaccine is being assessed by several regulatory entities such as the Food and Drug Administration (FDA) and EMEA and in Chile is already approved. This 13-valent formulation includes the 10 serotypes contained in the 10-valent vaccine plus serotypes 3, 6A and 19A, all conjugated to the carrier protein CRM197. These new formulations pretend to enhance vaccine coverage against S. pneumoniae including the frequent serotypes in developing countries (1 and 5) and emerging serotypes such as serotypes 3, 6A, 17F and 9A after a decade of PCV7 immunization.

TNF-alpha, IL-1beta, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae.

Bacterial meningitis caused by Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae, including sensory-motor deficits, seizures, and impairment of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, were shown to contribute to the development of brain injury in bacterial meningitis. Thus, the aim of this study was to verify the levels of the TNF-alpha, IL-1beta, IL-6, and CINC-1 in the rat brain after pneumococcal meningitis. The animals underwent a magna cistern tap receiving either 10 microL of sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration of 5x10(9) cfu/mL. The placebo group was killed immediately after the induction and the meningitis group at 0, 6, 12, 24, 48, and 96h after induction. The brains were removed followed by the isolation of the hippocampus and prefrontal cortex for determining TNF-alpha, IL-1beta, IL-6, and CINC-1 levels. In the hippocampus we found increased levels of the TNF-alpha only at 6h (p<0.01; F=3.777); CINC-1 levels increased at 6 and 24h (p<0.001; p<0.05; F=15.05); and IL-6 and IL-1beta levels were not altered. In the prefrontal cortex, the TNF-alpha levels were found to be increased only at 6h (p<0.05; F=4.921); IL-6 (p<0.05; F=11.69) and IL-1beta (p<0.001; F=132.0) levels were found to be increased only at 24h after meningitis induction; and CINC-1 levels were found to be increased at 6, 12, and 24h (p<0.01; p<0.01; p<0.01; F=16.86) after meningitis induction. Our data suggest that cytokine/chemokine levels can be putative biomarkers of brain damage in the first hours of the pneumococcal meningitis.

Clinical profile of pleural empyema and associated factors with prolonged hospitalization in paediatric tertiary centre in Angola, Luanda.

In a case series of 152 children aged from 2 to 132 months will pleural emphema from a paediatric tertiary hospital in Luanda, Angola between September 2004 and March 2005, the authors found a high prevalence of anaemia and malnutrition. The most prevalent bacteria in pleural fluid were: D pneumoniae, Haemophyllus and S aureus. The median for hospital stay was 25 days. The lethality was 7.8% and was not statistically associated with malnutrition, although this variable was associated, in multivariate analysis, with prolonged hospitalization time.

Optimized immune response elicited by a DNA vaccine expressing pneumococcal surface protein a is characterized by a balanced immunoglobulin G1 (IgG1)/IgG2a ratio and proinflammatory cytokine production.

We have previously shown that DNA immunization with PspA (pneumococcal surface protein A) DNA is able to elicit protection comparable to that elicited by immunization with PspA protein (with alum as adjuvant), even though the antibody levels elicited by DNA immunization are lower than those elicited by immunization with the protein. This work aims at characterizing the ability of sera to bind to the pneumococcal surface and to mediate complement deposition, using BALB/c wild-type and interleukin-4 knockout mice. We observed that higher anti-PspA levels correlated with intense antibody binding to the pneumococcal surface, while elevated complement deposition was observed with sera that presented balanced immunoglobulin G1 (IgG1)/IgG2a ratios, such as those from DNA-immunized mice. Furthermore, we demonstrated that gamma interferon and tumor necrosis factor alpha were strongly induced after intraperitoneal pneumococcal challenge only in mice immunized with the DNA vaccine. We therefore postulate that although both DNA and recombinant protein immunizations are able to protect mice against intraperitoneal pneumococcal challenge, an optimized response would be achieved by using a DNA vaccine and other strategies capable of inducing balanced Th1/Th2 responses.

[Streptococcus pneumoniae: serotype evolution and patterns of antimicrobial susceptibility in invasive isolates from 11 years surveillance (1994 -2004) in Colombia]. / Streptococcus pneumoniae: evolución de los serotipos y los patrones de susceptibilidad antimicrobiana en aislamientos invasores en 11 años de vigilancia en colombia (1994 -2004).

BACKGROUND: Streptococcus pneumoniae is an important cause of morbidity and mortality in children and adults in the world. OBJECTIVE: Analysis of data from laboratory surveillance of S. pneumoniae, invasive isolates recovered from 1994 to 2004. MATERIALS AND METHODS: Database of invasive isolates of S. pneumoniae, sent to the Microbiology Group through the national surveillance laboratory network of acute bacterial meningitis and acute respiratory infections, from 1994 to 2004. The isolates had epidemiological data, serotyping, antimicrobial susceptibility patterns and some of them molecular typing. RESULTS: The data of 2,022 isolates from 120 hospitals of different regions of the country were analyzed. The isolates were recovered mainly from blood cultures (50.7%) and cerebrospinal fluid (42%). The most important serotypes were 14, 6B, 23F, 1, 5, 6A, 19F, 18C y 9V, which account for 83.6% of isolates obtained from children under 6 years of age, 74% from the 6 -14 year age group and 61.4% from children over 14 years of age. Overall, 29.8% of isolates presented diminished susceptibility to penicillin (DSP), 44.3% to trimethoprim-sulphamethoxazole, 32.4% to tetracycline, 8.2% to chloramphenicol and 3.8% to erythromycin. All isolates were susceptible to vancomycin and 13% were multiresistant. Six hundred two DSP isolates were molecularly typed, 27 (4.5%), were related with the Spain23F-1 clone, 38 (6.3%) with the Spain6B-2, 301 (50%) with the Spain9V-3 and 75 (12.5%) with the Colombia23F-26 clone. Moreover, all 138 isolates with capsular type 5 were related to the Colombia5-19 clone. CONCLUSION: The results provide basic information necessary to design and implement strategies for prevention of pneumococcal disease.

Colonization capability of lactobacilli and pathogens in the respiratory tract of mice: microbiological, cytological, structural, and ultrastructural studies.

Respiratory tract infections are among the bacterial infections that affect humans with higher frequency. Those produced by Streptococcus pneumoniae are reported to have the highest incidence in the world, affecting both children and old people. As a 2001 report from the World Health Organization expressed it, the basic fight of children under 5 yr old is to survive. Five different conditions (acute respiratory infections, diarrhea, measles, palludism, and undernutrition) directly produce more than 50% of the deaths in this age group. Respiratory tract infections in the developing countries in the Americas are among the first three causes of death in children under 1 yr and between the first and second cause in children between 1 and 4 yr old. Pneumonia is responsible for 85 and 90% of deaths in children under 5 yr old (approx 150,000 annually), 95% of them occurring in the developing countries in the Americas. There is an increased worldwide tendency to use preventive measures and to consume products that help to maintain the health status of the individual. Thus the use of probiotics has increased systematically during the last decade, and the scientific literature trying to demonstrate the positive effect of such preparations has also increased. The term probiotic has been applied to products that (1) contain live microorganisms, freeze-dried or included in fermented products or (2) improve the health status of humans and animals, exerting effects in the mouth or gastrointestinal tract (included in foods or capsules), in the respiratory tract (as aerosols), or in the urogenital tract (by local application)Having in mind the high incidence of respiratory tract infections, and looking for preventive measures as well as the possible applications of probiotics, the aim of this chapter was to use mice as experimental models to determine whether members of the genus Lactobacillus were able to colonize and give protection from infections after inoculation by the intranasal route. To this end, the following procedures were carried out: 1. Screening of the predominant bacterial species in respiratory organs. 2. Study of the kinetics of colonization of the different groups of microorganisms from 15 d up to adult (2 mo). 3. Screening of the probiotic characteristics of all the isolated strains.

Influence of patient age on Streptococcus pneumoniae serotypes causing invasive disease.

All clinical S. pneumoniae specimens isolated from patients with invasive or sterile-site infections admitted to one regional general hospital in southern Chile were collected during a 5-year period (February 1994 to September 1999). A total of 247 strains belonging to 50 serotypes were isolated in this survey: 69 in patients under 5 years of age, 129 in patients 5 to 64 years old, and 49 from patients 65 years and older. Eight serotypes were identified in all age groups, while all other serotypes were found exclusively in one age group or in patients over 4 years of age. Serotype 3 was never found in patients under 5 years old, and serotype 14 was not found in patients >64 years of age. There was no difference in the serotypes causing infection in each one of the 5 years of the survey. Our results suggest that both bacterial virulence factors and host factors play an important role in the selection of S. pneumoniae serotypes causing invasive infection. Possible host factors include age-related differences in the immune response. Comparative studies with other areas of the world may help to further understanding of our observations in southern Chile.

Fisiopatología molecular de la infección por neumococo / Molecular pathophysiology in pneumococcal infection

El estudio del Streptococcus pneumoniae ha conducido a muchos avances en el conocimiento de la patogénesis de las infecciones bacterianas, entre ellos, el descubrimiento del papel de la pared celular y la respuesta inflamatoria del hospedero en el desarrollo de la enfermedad neumocócica, la importancia de los diferentes mecanismos de adherencia para aumentar su capacidad de condicionar daño tisular, además del descubrimiento del DNA, el desarrollo de la primer vacuna de polisacárido capsular y la alternativa en el tratamiento con moduladores de la respuesta inflamatoria. A continuación se hace una revisión de algunos de los detalles moleculares de la patogénesis del neumococo, incluyendo la identificación de los factores de virulencia desarrollados por avances genéticos recientes, que originan nuevos mecanismos en la activación de las infecciones por bacterias grampositivas y que son muy distintos a las vías conocidas para la endotoxina

Life-threatening infection in two children with hemoglobin S-beta-thalassemia.

Life-threatening infections with Streptococcus pneumoniae and parvovirus occurred in two patients with hemoglobin S-beta-thalassemia. We recommend that acute febrile illnesses in the presence of any hemoglobinopathy be considered potentially life threatening, and managed accordingly.

Spontaneous bacterial peritonitis in children with chronic liver disease: clinical features and etiologic factors.

We analyzed the clinical and bacteriologic features of 12 episodes of spontaneous bacterial peritonitis (SBP) in 11 children (four boys, median age 5.5 years) with chronic liver disease. All patients had cirrhosis and ascites; four had hypersplenism, and one was asplenic. Symptoms included increasing abdominal distention, pyrexia, abdominal pain, gastrointestinal disturbance, and encephalopathy. Nine had rebound tenderness on abdominal palpation, and 12 had reduced bowel sounds. The most frequent organisms isolated from culture of ascitic fluid were Streptococcus pneumoniae (nine). Klebsiella (two), and Haemophilus influenzae (one); blood cultures grew identical organisms in nine. Seven patients died despite intensive antibiotic therapy. In the 3 months prior to onset of SBP, defective yeast opsonization and reduced serum concentration of C4 were found in all nine children tested; eight had reduced concentration of C3. Functional deficiency of all complement components was present in four tested within 1 to 5 months of the onset. In contrast, only eight of 59 cirrhotic children without SBP had low C3, and eight had defective yeast opsonization, although 35 had low C4 values. Four of the patients with SBP and low C3 and C4 concentrations had normal concentrations at the time of diagnosis of liver disease 2 to 5 years previously. Opsonization of type III pneumococci was reduced in sera from three patients who subsequently developed pneumococcal peritonitis. The incidence of SBP in children with chronic liver disease is similar to that in adults, as are the clinical features. Our observations suggest that complement deficiency induced by chronic liver disease may be important in the pathogenesis of SBP.