RESUMEN
Since 2006, meningococcal serogroup C (MenC) conjugate (MCC) vaccines have been supplied by the Brazilian government for HIV-infected children under 13 years old. For measuring protection against MenC, the serum bactericidal antibody (SBA) assay is the method of choice. The characterization of T follicular helper cells (TFH) cells has been an area of intensive study because of their significance in multiple human diseases and in vaccinology. The objective of this study was to characterize the phenotype of peripheral TFH cells and B cells and how they associated with each other and with SBA levels induced by vaccination as well as with serum cytokine levels of HIV-infected and non-infected children and adolescents. We found that CD27-IgD-CD21-CD38+ (exhausted B cells) as well as short-lived plasmablasts (CD27+IgD-CD21-CD38+) are increased in cART treated HIV patients and negatively associated with MCC vaccine induced SBA levels. Baseline frequency of activated peripheral TFH cells was a negative correlate for SBA response to MCC vaccine but positively correlated with circulating plasmablast frequency. Baseline IL4-levels positively associated with SBA response but showed a negative correlation with activated peripheral TFH cells frequency. The increased frequency of activated peripheral TFH cells found in non-responders to the vaccine implies that higher activation/differentiation of CD4 T cells within the lymph node is not necessarily associated with induction of vaccine responses.
Asunto(s)
Linfocitos B/inmunología , Infecciones por VIH/inmunología , VIH-1/fisiología , Meningitis Bacterianas/inmunología , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo C/fisiología , Linfocitos T Colaboradores-Inductores/inmunología , Adolescente , Anticuerpos Antibacterianos/sangre , Circulación Sanguínea , Niño , Preescolar , Estudios de Cohortes , Resistencia a la Enfermedad , Femenino , Centro Germinal/inmunología , Humanos , Interleucina-4/sangre , Activación de Linfocitos , Masculino , Estudios Prospectivos , VacunaciónRESUMEN
Streptococcus pneumoniae remains an important cause of disease with high mortality and morbidity, especially in children and in the elderly. The widespread use of the polysaccharide conjugate vaccines in some countries has led to a significant decrease in invasive disease caused by vaccine serotypes, but an increase in disease caused by non-vaccine serotypes has impacted on the overall efficacy of these vaccines on pneumococcal disease. The obvious solution to overcome such shortcomings would be the development of new formulations that provide serotype-independent immunity. This review focuses on the most promising approaches, including protein antigens, whole cell pneumococcal vaccines, and recombinant bacteria expressing pneumococcal antigens. The protective capacity of these vaccine candidates against the different stages of pneumococcal infection, including colonization, mucosal disease, and invasive disease in animal models is reviewed. Some of the human trials that have already been performed or that are currently ongoing are presented. Finally, the feasibility and the possible shortcomings of these candidates in relation to an ideal vaccine against pneumococcal infections are discussed.
Asunto(s)
Meningitis Bacterianas/inmunología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/uso terapéutico , Animales , Antígenos/inmunología , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Humanos , Meningitis Bacterianas/microbiología , Ratones , Membrana Mucosa/inmunología , Infecciones Neumocócicas/microbiología , Proteínas Recombinantes/inmunología , Serotipificación , Streptococcus pneumoniae , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/uso terapéuticoRESUMEN
BACKGROUND: The kynurenine (KYN) pathway has been shown to be altered in several diseases which compromise the central nervous system (CNS) including infectious diseases such as bacterial meningitis (BM). The aim of this study was to assess single nucleotide polymorphisms (SNPs) in four genes of KYN pathway in patients with meningitis and their correlation with markers of immune response in BM. METHODS: One hundred and one individuals were enrolled in this study to investigate SNPs in the following genes: indoleamine-2,3-dioxygenase (IDO1 gene), kynureninase (KYNU gene), kynurenine aminotransferase I (CCBL1 gene), and kynurenine aminotransferase II (AADAT gene). SNP analyses were performed by primer-introduced restriction analysis-PCR (PIRA-PCR) followed by RFLP. Cytokines were measured using multiplex bead assay while immunoglobulins (IG) by immunodiffusion plates and NF-kappaB and c-Jun by dot blot assay. RESULTS: The variant allele of SNP AADAT+401C/T showed prevalent frequency in patients with BM. A significant decrease (p < 0.05) in TNF-α, IL-1ß, IL-6, MIP-1αCCL3 and MIP-1ß/CCL4 levels was observed in BM patients homozygous (TT) to the SNP AADAT+401C/T. Furthermore, a significant (p < 0.05) decrease in cell count was observed in cerebrospinal fluid (CSF) from patients with TT genotype. In addition, an increase in the IgG level in adults (p < 0.05) was observed. The variant allele for KYNU+715G/A was found with low frequency in the groups, and the SNPs in IDO1+434T/G, KYNU+693G/A, CCBL1+164T/C, and AADAT+650C/T had no frequency in this population. CONCLUSIONS: This study is the first report of an association of SNP AADAT+401C/T with the host immune response to BM, suggesting that this SNP may affect the host ability in recruitment of leukocytes to the infection site. This finding may contribute to identifying potential targets for pharmacological intervention as adjuvant therapy for BM.
Asunto(s)
Meningitis Bacterianas/enzimología , Meningitis Bacterianas/inmunología , Polimorfismo de Nucleótido Simple , Transaminasas/genética , Adolescente , Adulto , Alelos , Secuencia de Bases , Estudios de Casos y Controles , Quimiocinas/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Cartilla de ADN/genética , Femenino , Frecuencia de los Genes , Humanos , Hidrolasas/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Masculino , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/genética , Persona de Mediana Edad , Adulto JovenRESUMEN
This article analyzes the entrepreneurial cooperation between Cuba and Brazil in health biotechnology. It looks at the strategies applied and the main impacts. The respective government/political wills and the corresponding South-South collaboration policies are discussed, as well as the steps taken to materialize collaboration programs, including joint production of a meningitis vaccine for Africa. This cooperation is a good example of how South-South collaboration can be a useful tool to promote capacity building and provide cost-effective health solutions for developing countries.
Asunto(s)
Biotecnología , Cooperación Internacional , Vacunas Bacterianas/biosíntesis , Brasil , Cuba , Meningitis Bacterianas/inmunología , Meningitis Bacterianas/prevención & control , Formulación de Políticas , Política , Transferencia de TecnologíaRESUMEN
BACKGROUND: Over recent decades, a resurgence of invasive group A streptococcal (GAS) infections has been observed; GAS remains a rare cause of pyogenic meningitis. We report herein population-based findings of long-term surveillance for GAS meningitis in Salvador, Brazil, and estimate the overall burden of invasive GAS infections. METHODS: From February 1996 to February 2007 we conducted active surveillance for GAS meningitis in the state reference hospital for infectious diseases in Salvador, Brazil. Data on clinical presentation, laboratory records, and outcome were collected through interviews and chart review. GAS isolates were evaluated for antimicrobial susceptibility and emm type. RESULTS: We identified 20 cases of GAS meningitis, which accounted for 0.9% of all culture-proven bacterial meningitis in the study period. The mean annual incidence of GAS meningitis was 0.03 cases per 100,000 population in metropolitan Salvador and peaked in children <1 year of age (0.67 cases per 100,000 population). Among 17 cases with clinical information available, 41% required intensive care unit support and 25% died. Tested isolates were susceptible to penicillin and exhibited large emm type diversity. Based on the incidence of GAS meningitis, we estimate that the annual incidence of GAS infection is 3 cases per 100,000 population in metropolitan Salvador. CONCLUSIONS: Although rare, GAS is a life-threatening cause of bacterial meningitis. Knowledge of the incidence and emm type variability of the disease is necessary for planning immunization strategies.
Asunto(s)
Meningitis Bacterianas/epidemiología , Infecciones Estreptocócicas/epidemiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Brasil/epidemiología , Niño , Costo de Enfermedad , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Meningitis Bacterianas/inmunología , Meningitis Bacterianas/mortalidad , Persona de Mediana Edad , Infecciones Estreptocócicas/economía , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/mortalidad , Streptococcus agalactiaeRESUMEN
ntroducción. Las meningoencefalitis son una de las enfermedades más temidas en la infancia, tanto por su mortalidadcomo por sus posibles secuelas. Sin embargo, conocer tempranamente si su origen es bacteriano o vírico e instauraruna terapéutica adecuada resulta muy beneficioso para el paciente y el médico de asistencia. El índice haptoglobina/IgG y la escala de Boyer se han utilizado con estos fines. Pacientes y métodos. Se estudiaron 39 pacientes en edad pediátrica con eldiagnóstico de meningoencefalitis: 14 que sufrían meningoencefalitis bacterianas y 25 meningoencefalitis víricas. Se calculó el índice haptoglobina/IgG y se le aplicó la escala de Boyer para conocer su utilidad en el diagnóstico diferencial de las meningoencefalitis. La relevancia clínica del índice haptoglobina/IgG y la escala de Boyer se compararon a través de las curvas ROC. Resultados. La escala de Boyer no presentó asociación estadísticamente significativa con el origen de las meningoencefalitis.La sensibilidad y especificidad del índice haptoglobina/IgG fueron del 71,4 y el 64 por ciento, respectivamente, para iguales parámetros en la escala de Boyer del 28 y el 100 por ciento. El índice haptoglobina/IgG presentó mayor precisión para el diagnósticodiferencial de las meningitis bacterianas y víricas que la escala de Boyer a través del área bajo la curvas ROC. Conclusiones. El índice haptoglobina/IgG mostró su superioridad diagnóstica con relación a la escala de Boyer para establecer el origen de las meningoencefalitis(AU)
INTRODUCTION: The meningitis is one of the most severe diseases in children due to its mortality or sequels. However, timely knowledge of whether the infection is bacterial or viral in origin and applied a specific therapeutic would be beneficial for the patients and clinician. The haptoglobin/IgG index and Boyer's score have been use in this purpose. PATIENTS AND METHODS: 39 pediatric patients, 14 suffering from viral meningoencephalitis and 25 from bacterial meningoencephalitis were study. Boyer's score and Hp/IgG index were applied in order to evaluate its diagnostic accuracy. The clinical relevance of haptoglobin/IgG index and Boyer's score were compared by the analysis of the receiver-operating characteristic (ROC) curves. RESULTS: There were no association between Boyer's score and the cause of the meningitis. The sensitivity and specificity of haptoglobin/IgG index were de 71.4 and 64 percent, respectively. The same parametric to Boyer's score were de 28 and 100 percent. Increased haptoglobin/IgG index presents bigger precision for the differential diagnostic of the bacterial and viral meningitis than the scale of Boyer according to the curves ROC. CONCLUSION: The index haptoglobin/IgG showed its diagnostic superiority with relationship to the scale of Boyer to establish the origin of the meningoencephalitis(AU)
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Haptoglobinas , Inmunoglobulina G , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/inmunología , Meningitis Viral/diagnóstico , Meningitis Viral/inmunología , Estudios RetrospectivosRESUMEN
Se realizó un estudio exploratorio transversal descriptivo . La muestra se seleccionó entre los pacientes que ingresaron en la Unidad de Cuidados Intensivos del Hospital Pediátrico Juan Manuel Márquez de La Habana y los que asistieron a la Unidad de Emergencias del Hospital Pediátrico de Matanzas en el período comprendido entre los meses de marzo y agosto del año 2003. Se determinó la concentración de IL6 en el líquido cefalorraquídeo y el suero con el uso de un ensayo tipo ELISA. Nuestros resultados muestran que este mediador alcanza concentraciones significativamente superiores en el líquido cefalorraquídeo de pacientes portadores de meningitis bacteriana. Teniendo en cuenta estas observaciones, la IL-6 dosificada en líquido cefalorraquídeo pudiera ser una variable discriminatoria en la meningitis(AU)
A descriptive exploratory study was carried out among children with meningitis. The sample was chosen among the patients who were admitted in the Intensive Care Unit of the Pediatric Hospital Juan Manuel Marquez in Havana City and among those who attended the Emergency Unit of Matanzas Pediatric Hospital in the period between March and August 2003. The concentration of IL- 6 in cephalorachideal liquids and in serum was determined by using an ELISA test. Our results show that this mediator reaches higher level concentrations in the cephalorachideal liquids of patients carrying bacterial meningitis. Taking into account these observations the IL-6 dosage in cephalorachideal liquids could be a discriminating variable in meningitis(AU)
Asunto(s)
Humanos , Niño , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Meningitis Bacterianas/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Unidades de Cuidado Intensivo PediátricoRESUMEN
We investigated whether monocyte-derived dendritic cells (MDDCs) generated in vitro from bacteria-infected MS patients modified autoreactive T cells activation patterns. T cell clones (TCCs) stimulated with MDDCs from infected MS patients responded with maximal proliferation, inducing IL-12, IL-17 and IFN-gamma secretion, at concentrations significantly lower than after incubation with MDDCs isolated from uninfected individuals and bacterial meningitis (BM) patients. Moreover, infected MDDCs promoted TCCs survival, and secreted more IL-12, IL-18, and IL-23. Finally, MDDCs from infected MS subjects showed higher expression of myeloid differentiation factor 88 (MyD88), as well as of HLA-DR, CD1a, CD80, CD86, CD273, CD40, CD83 and CCR7 when compared to MDDCs from uninfected MS individuals, and BM patients. Thus, activation of the innate immune system by microbial products in MS patients affects the generation MDDCs and their ability to modify autoreactive T cell activation patterns, which may be linked to MS relapse induction during bacterial infections.
Asunto(s)
Infecciones Bacterianas/inmunología , Células Dendríticas/inmunología , Monocitos/inmunología , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/inmunología , Linfocitos T/inmunología , Adulto , Antígenos de Superficie/inmunología , Infecciones Bacterianas/fisiopatología , Proliferación Celular , Células Cultivadas , Quimiocinas/inmunología , Quimiocinas/metabolismo , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/microbiología , Femenino , Humanos , Inmunidad Innata/inmunología , Activación de Linfocitos/inmunología , Masculino , Meningitis Bacterianas/inmunología , Meningitis Bacterianas/fisiopatología , Persona de Mediana Edad , Monocitos/microbiología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Factor 88 de Diferenciación Mieloide/inmunología , Estudios ProspectivosRESUMEN
Se describen algunos aspectos epidemiológicos de las meningoencefalitis bacterianas (MEB) en Cuba entre 1998 y el año 2000, según los datos de la Vigilancia Nacional de las MEB (VNMEB) disponibles. Se reportaron un total de 530 casos en menores de 15 años en todo el país durante el período. El grupo de edad más afectado resultó el de menos de 5 años. Los agentes más frecuentemente identificados fueron Haemophilus influenzae tipo b (Hib), Streptococcus pneumoniae (Spn) y Neisseria meningitidis (Nm). La incidencia de Hib disminuyó 4 veces por el efecto de la vacunación masiva, especialmente en los menores de 5 años, a partir del año 2000 Spn es el principal agente causante de MEB y el más letal en Cuba. La letalidad general se incrementó de 10,6 a 20,4 (por ciento), y fue el grupo de los de menos de 1 año uno de los más afectados. Futuros estudios permitirán profundizar en la epidemiología de estas infecciones y monitorear los cambios que ocurran como consecuencia de intervenciones(AU)
Asunto(s)
Humanos , Niño , Adolescente , Meningoencefalitis/epidemiología , Meningoencefalitis/inmunología , Monitoreo Epidemiológico , Vacunas Bacterianas , Niño , Meningitis Bacterianas/epidemiología , Meningitis Bacterianas/inmunologíaRESUMEN
INTRODUCTION: Dynamics of the immune response in Central Nervous System (CSN) is different from the well-known switch of IgM synthesis to IgG synthesis in blood. OBJECTIVE: Broadcast the behavior and the factors involved in the dynamics of the intrathecal immune response in infectious neurological disorders. DEVELOPMENT: The lack of a switch from IgM class response to IgG response could be more related to regulation-modulation mechanisms of the CNS immune response than differs from blood in a different cytokines composition, and the possibility of chemokines synthesis during the neuroinflammatory process, and the neuroimmune-endocrine mechanisms. The immune pattern can be stable like neuroborreliosis, and can be modify like in herpes simplex meningoencephalitis. It could have a typical pattern like in Neisseria meningitidis meningoencephalitis and neurotuberculosis. Also the pattern could be still detectable for many years after sufficient treatment and complete recovery of the symptom-free patients like in neurosyphilis or an advanced precocious response during the childhood. In HIV encephalopathy the pattern remains the same during the evolution but in other virus infections, like Echo 6 or Coxsackie B5, depends on the biological agent. CONCLUSIONS: In order to know the acuity of the disease, we have to know the physiopathologic characteristics of the biological agents, time courses, locations of the pathological processes, and the host age. The main signs in cerebrospinal fluid of an acute, active disease of CNS are the increased of cerebrospinal fluid cell count and the increased of albumin ratio.
Asunto(s)
Encefalitis por Herpes Simple/inmunología , Región de Cambio de la Inmunoglobulina , Inmunoglobulinas/líquido cefalorraquídeo , Meningitis Bacterianas/inmunología , Complejo SIDA Demencia/líquido cefalorraquídeo , Complejo SIDA Demencia/inmunología , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/inmunología , Inmunoglobulina M/líquido cefalorraquídeo , Inmunoglobulina M/inmunología , Inmunoglobulinas/inmunología , Meningitis Bacterianas/líquido cefalorraquídeoRESUMEN
The diagnosis of human neurobrucellosis usually relies on the detection of antibodies to Brucella lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) by agglutination tests or enzyme-linked immunosorbent assay (ELISA). Here we describe the detection of immunoglobulin G (IgG) to cytoplasmic proteins (CP) of Brucella spp. by ELISA and Western blotting in seven CSF samples from five patients with neurobrucellosis. While IgG to CP (titers of 200 to 12, 800) and IgG to LPS (800 to 6,400) were found in the CSF of these patients, these antibodies were not detected in CSF samples from two patients who had systemic brucellosis without neurological involvement. The latter, however, had serum IgG and IgM to both LPS and CP. No reactivity to these antigens was found in CSF samples from 14 and 20 patients suffering from nonbrucellar meningitis and noninfectious diseases, respectively. These findings suggest that, in addition to its usefulness in the serological diagnosis of human systemic brucellosis, the ELISA with CP antigen can be used for the specific diagnosis of human neurobrucellosis.
Asunto(s)
Brucella/inmunología , Brucelosis/diagnóstico , Brucelosis/inmunología , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/inmunología , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/líquido cefalorraquídeo , Antígenos Bacterianos/sangre , Antígenos Bacterianos/líquido cefalorraquídeo , Antígenos Bacterianos/inmunología , Brucelosis/líquido cefalorraquídeo , Enfermedad Crónica , Citoplasma/química , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/análisis , Lipopolisacáridos , Masculino , Meningitis Bacterianas/líquido cefalorraquídeo , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/diagnóstico , Meningoencefalitis/inmunologíaRESUMEN
Levels of interleukin-6 and tumor necrosis factor alpha were measured in cerebrospinal fluids from patients with meningitis. Interleukin-6 was increased in aseptic and bacterial meningitis, whereas tumor necrosis factor alpha was increased only in bacterial meningitis. We concluded that measurement of cytokines in cerebrospinal fluid may be useful for the rapid diagnosis of meningitis.
Asunto(s)
Interleucina-6/líquido cefalorraquídeo , Meningitis Aséptica/líquido cefalorraquídeo , Meningitis Aséptica/inmunología , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/inmunología , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Estudios de Casos y Controles , Líquido Cefalorraquídeo/citología , Niño , Preescolar , Diagnóstico Diferencial , Humanos , Lactante , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: The effect of nationwide vaccination in The Netherlands with conjugate Haemophilus influenzae type b vaccine on the incidence of H. influenzae meningitis was assessed in the first 3 years after the introduction of vaccination to the birth cohort at 3 months of age. STUDY DESIGN: Children in The Netherlands born after April 1, 1993, were vaccinated at the age of 3, 4, 5, and 11 months. Children older than 3 months at the inception of the H. influenzae type b vaccination program were not immunized. The number of cases among the vaccine cohort was compared with the number in a historical control group of children born in the period April 1, 1990, and April 1, 1993. RESULTS: The total number of patients with meningitis caused by H. influenzae type b reached a low, but constant level, that was expected for absence of herd immunity. Among children in the vaccine era group 22 cases occurred, whereas among the historical control group (prevaccine era) 342 cases were found. In the vaccine era cohort, 2 patients with H. influenzae type b meningitis had been vaccinated three times, 13 received one or no vaccine dose because of their age, and 7 were not vaccinated for religious or logistic reasons. The number of cases among nonvaccinated children older than 3 years and the number of H. influenzae meningitis cases caused by strains other than type b did not change. CONCLUSIONS: Conjugate H. influenzae type b vaccine prevents H. influenzae type b meningitis very effectively (99.4%) in children vaccinated twice or more. To reach rapid prevention of all H. influenzae type b disease simultaneous introduction of H. influenzae type b vaccination of children at various ages is recommended.
Asunto(s)
Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/administración & dosificación , Meningitis Bacterianas/prevención & control , Estudios de Cohortes , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/inmunología , Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b , Humanos , Inmunidad Innata , Incidencia , Lactante , Meningitis Bacterianas/epidemiología , Meningitis Bacterianas/inmunología , Países Bajos/epidemiologíaRESUMEN
INTRODUCTION: Between 1985 and 1995, 3,860 cerebrospinal fluid (CSF) samples from patients with mycotic meningitis were analyzed. METHODS: Direct examination, cultures, complement fixation (CF) and immunodiffusion (ID) with Histoplasma capsulatum were carried out. RESULTS: Seventy four samples from 31 patients (three of them with AIDS) were reactive at the immunological assays. Cultures were positive in five patients. In 26 patients the clinical diagnosis together with positive CSF assays gave indirect evidence of meningeal histoplasmosis. ID and CF reactivity were 93.5% and 100% respectively. For 23 patients who had simultaneous examination of blood and CSF the double positivity was 78.2%. CONCLUSIONS: Because of the direct isolation of Histoplasma capsulatum is a difficult one, the diagnosis of subacute or chronic meningeal histoplasmosis may be confirmed by indirect immunological assays.
Asunto(s)
Histoplasmosis/microbiología , Meningitis Bacterianas/inmunología , Meningitis Bacterianas/microbiología , Adolescente , Adulto , Anciano , Ventriculografía Cerebral , Líquido Cefalorraquídeo/microbiología , Preescolar , Enfermedad Crónica , Femenino , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/diagnóstico por imagen , Masculino , Meningitis Bacterianas/complicaciones , Meningitis Bacterianas/diagnóstico , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Factor I deficiency causes a permanent, uncontrolled activation of the alternative pathway resulting in an increased turnover of C3 and consumption of factor B, factor H and properdin. Factor I deficiency is clinically associated with recurrent bacterial infections already in early infancy, mainly affecting the upper and lower respiratory tract, or presenting as meningitis or septicemia. We here report on a Brazilian family (n = 9) with known consanguinity, where in 3/7 children, suffering from chronic otitis, meningitis, and respiratory infections, a complete factor I deficiency was recognized. One of the patients died after fulminant sepsis. Hemolytic activity of the alternative pathway was not detectable in the patients' sera due to decreased plasma concentrations of C3, factor B and properdin. As a consequence of factor I deficiency, C3b could not be metabolized with the result that no C3-derived split products (C3dg/C3d) were detectable in the patients' sera. In vitro reconstitution with purified factor I restored the regulatory function in the patients' sera with the subsequent cleavage of C3b to C3c and C3dg. Factor H levels were decreased in all patients' sera and found to be tightly complexed with C3b resulting in a modified electrophoretic mobility. Upon factor I reconstitution, factor H was released from C3b regaining its beta 1 electrophoretic mobility. Complement-mediated biological functions like opsonization of bacteria, chemotactic activity and phagocytosis in these patients were impaired. The parents (cousins, 2nd degree) and 3/4 siblings had significantly reduced factor I plasma levels without further alteration in their complement profile. 3 of these obviously heterozygously deficient family members suffered from recurrent bacterial infections of different frequency and severity.
Asunto(s)
Infecciones Bacterianas/inmunología , Factor I de Complemento/deficiencia , Meningitis Bacterianas/inmunología , Otitis Media/inmunología , Infecciones del Sistema Respiratorio/inmunología , Adolescente , Adulto , Brasil , Niño , Preescolar , Activación de Complemento/inmunología , Complemento C3/inmunología , Complemento C3/metabolismo , Factor B del Complemento/inmunología , Factor B del Complemento/metabolismo , Factor H de Complemento/inmunología , Factor H de Complemento/metabolismo , Factor I de Complemento/inmunología , Consanguinidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Properdina/inmunología , Properdina/metabolismo , Sepsis/inmunologíaRESUMEN
The accuracy of the latex particle agglutination test (LPAT) was assessed in blood stained cerebrospinal fluid (CSF) specimens from 166 paediatric patients, aged from three months to 13 years. A commercial LPAT kit was used to detect Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis A, B, and C soluble antigens. Culture of CSF specimens was used as the standard and all laboratory procedures were performed blind. The mean CSF erythrocyte count was 66,406 cells/mm3 in the cases and 11,560 cells/mm3 in the controls. The sensitivity and the specificity of LPAT were 83.8 and 94.0%, respectively, suggesting that LPAT is a useful diagnostic tool even in blood stained CSF specimens.
Asunto(s)
Antígenos Bacterianos/líquido cefalorraquídeo , Pruebas de Fijación de Látex , Meningitis Bacterianas/líquido cefalorraquídeo , Adolescente , Niño , Preescolar , Recuento de Eritrocitos , Estudios de Evaluación como Asunto , Reacciones Falso Positivas , Femenino , Haemophilus influenzae/inmunología , Humanos , Lactante , Masculino , Meningitis Bacterianas/inmunología , Neisseria meningitidis/inmunología , Valor Predictivo de las Pruebas , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Streptococcus pneumoniae/inmunologíaRESUMEN
Aspectos gerais relacionados ao quadro clinico, bacterias mais frequentemente observadas nas diferentes idades, procedimentos laboratoriais e sua interpretacao, tratamento e profilaxia das meningites bacterianas agudas da crianca sao apresentados.