RESUMEN
Meningococcus serogroup B (MenB), clonal complex 32 (cc 32), was the Brazilian epidemic strain of meningococcal disease (MD) in the 1990's. Currently, meningococcus serogroup C (MenC), cc 103, is responsible for most of the cases of the disease in Brazil. The aim of this study was to investigate the seroprevalence of bactericidal antibody (SBA) against representative epidemic strains of MenC, (N753/00 strain, C:23:P1.22,14-6, cc103) and MenB, (Cu385/83 strain, B:4,7:P1.15,19, cc32) in students and employees of a university hospital in the State of Rio Grande do Sul (RS, Brazil). A second MenC strain (N79/96, C:2b:P1.5-2,10, cc 8) was used as a prototype strain of Rio de Janeiro's outbreak that occurred in the 1990's. Our previous study showed a 9% rate of asymptomatic carriers in these same individuals. A second goal was to compare the SBA prevalence in meningococcal carriers and non-carriers. Fifty-nine percent of the studied population showed protective levels of SBA titers (log2≥2) against at least one of the three strains. About 40% of the individuals had protective levels of SBA against N753/00 and Cu385/83 strains. Nonetheless, only 22% of the individuals showed protective levels against N79/96 strain. Significantly higher antibody levels were seen in carriers compared to non-carriers (P≤0.009). This study showed that, similar to other States in Brazil, a MenC (23:P1.22,14-6, cc103) strain with epidemic potential is circulating in this hospital. Close control by the Epidemiological Surveillance Agency of RS of the number of cases of MD caused by MenC strains in the State is recommended to prevent a new disease outbreak.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Neisseria meningitidis Serogrupo B/inmunología , Neisseria meningitidis Serogrupo C/inmunología , Adulto , Brasil , Femenino , Hospitales Universitarios , Humanos , Immunoblotting/métodos , Masculino , Infecciones Meningocócicas/inmunología , Persona de Mediana Edad , Neisseria meningitidis Serogrupo B/aislamiento & purificación , Neisseria meningitidis Serogrupo C/aislamiento & purificación , Estudios Seroepidemiológicos , Serogrupo , Determinación de Anticuerpos Séricos Bactericidas , Estadísticas no Paramétricas , Adulto JovenRESUMEN
SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P<0·01], and residing <1 year in Rio Verde (mOR 7, 95% CI 1·11-43·9, P<0·02). Mass vaccination (>10 000 plant employees) stopped propagation in the plant, but not in the larger community.
Asunto(s)
Brotes de Enfermedades , Control de Infecciones/métodos , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/microbiología , Neisseria meningitidis Serogrupo C/aislamiento & purificación , Exposición Profesional , Adolescente , Adulto , Brasil/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/prevención & control , Femenino , Manipulación de Alimentos , Humanos , Lactante , Masculino , Vacunación Masiva/métodos , Infecciones Meningocócicas/mortalidad , Infecciones Meningocócicas/prevención & control , Persona de Mediana Edad , Vacunas Neumococicas/administración & dosificación , Análisis de Supervivencia , Adulto JovenRESUMEN
A mAb against the NadA protein from Neisseria meningitidis strain 3006 (serosubtype B : 2b : P1.2 : P5.2,8) demonstrated strong bactericidal activity against Brazilian epidemic serogroup B strain N44/89 (B : 4,7 : P1.19,15 : P5.5,7) and a serogroup C strain, IMC 2135 (C : 2a : P1.5,2), but not against another serogroup C strain, N1002/90 (C : 2b : P1.3 : P5.8). The immunogenicity of native NadA in an outer-membrane vesicle (OMV) preparation was also tested. Serum from mice immunized with OMV from serogroup B strain N44/89, which contains the NadA protein, showed bactericidal activity against serogroup B and C strains possessing NadA. In dot-blot analysis of 100 serogroup B and 100 serogroup C isolates from Brazilian patients, the mAb to NadA recognized about 60% of the samples from both serogroups. The molecular mass of the NadA protein from strain N44/89 determined by mass spectrometry was 37 971 Da and the peptide sequences were identical to those of NadA from N. meningitidis strain MC58.
Asunto(s)
Ratones , Neisseria meningitidis Serogrupo B/inmunología , Neisseria meningitidis Serogrupo C/inmunología , Vacunas Meningococicas/inmunología , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/metabolismo , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/química , BrasilRESUMEN
We evaluated the bactericidal antibody response to Neisseria meningitidis serogroup B in convalescent patients (n=65) from bacterial meningitis. Patients infected with B meningococci were stratified according to their vaccination status (Cuban BC vaccine) into group 1 (immunized) (n=12) and group 2 (non-immunized) (n=15). The results suggested that antibody titers > or =2 (log(2)) indicate a specific immune response to N. meningitidis. In group 1, 64% of patients had a significant antibody titer (> or =2) in their acute sera against a B:4:P1.15 strain, compared to only 21% of group 2 patients. All patients from group 1 without bactericidal antibodies in their acute sera had a significant increase (at least 2-fold increase in log(2) titers) in antibody titers in their convalescent sera, in contrast, to only 27% of patients from group 2 (P=0.06). Using mutant strains lacking OMP1 or OMP5, it was shown that OMP1 was an important antigen recognized by immunized patients but not by non-immunized patients.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Vacunas Bacterianas/inmunología , Meningitis Meningocócica/inmunología , Neisseria meningitidis/inmunología , Adolescente , Adulto , Proteínas de la Membrana Bacteriana Externa/inmunología , Niño , Preescolar , Humanos , Lactante , Meningitis Meningocócica/prevención & control , Vacunas Meningococicas , Persona de Mediana Edad , Neisseria meningitidis/clasificación , Serotipificación , VacunaciónRESUMEN
Neisseria meningitidis serogroup C polysaccharide (PS C) was conjugated to serogroup B outer membrane vesicles (OMV) in order to test the possibility of obtaining a bivalent group B and C meningococcus vaccine. The conjugate and controls were injected intraperitoneally into groups of ten mice with boosters on days 14 and 28 after the primary immunization. The following groups were used as control: (i) PS C; (ii) PS C plus OMV; (iii) OMV; and (iv) saline. The serum collected on days 0, 14, 28 and 42 were tested by enzyme-linked immunosorbent assay (ELISA) for PS C and OMV, and by complement mediated bactericidal assay against serogroups B and C. ELISA for PS C as well as bactericidal titres against serogroup C meningococci of the conjugated vaccine increased eight-fold (ELISA) and 32 fold (bactericidal) after 42 days in comparison with the PS C control group. ELISA for OMV and bactericidal titre against serogroup B meningococci of the conjugate showed no significant difference in comparison with the OMV containing controls. Furthermore, Western Blot assay of the conjugate immune serum did not bind OMV class four protein which is related to the complement dependent antibody suppressor. The results indicate that the PS C-OMV conjugate could be a candidate for a bivalent vaccine toward serogroups B and C meningococci.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Neisseria meningitidis/inmunología , Polisacáridos Bacterianos/inmunología , Animales , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/aislamiento & purificación , Proteínas de la Membrana Bacteriana Externa/aislamiento & purificación , Vacunas Bacterianas/química , Ensayo de Inmunoadsorción Enzimática , Immunoblotting , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/inmunología , Masculino , Vacunas Meningococicas , Ratones , Ratones Endogámicos C3H , Polisacáridos Bacterianos/aislamiento & purificación , Vacunas Conjugadas/química , Vacunas Conjugadas/inmunologíaRESUMEN
Pre- and postvaccination serum samples from 77 children aged 2 to 6 years, who received the Cuban BC vaccine (B:4:P1.15), were analyzed for bactericidal antibodies against a local B:4:P1.15 strain (N44/89). Sera from 16 individuals with bactericidal antibodies against the B:4:P1.15 strain were tested against 23 Brazilian isolates. These include B:4 strains of distinct serosubtypes: P1.15, P1.7,1, P1.3, P1.9, P1.nt, and a B:8,19,23:P1.16 strain. A Cuban B:4:P1.15 strain (Cu385/83) was also included in the study. The specificities of bactericidal antibodies were analyzed by using mutant strains lacking a class 1 protein (PorA protein) or a class 5 protein or both. The results indicated that PorA and class 5 proteins are the main targets recognized by the bactericidal antibodies of vaccinees. Nonetheless, a complex pattern of recognition by bactericidal antibodies was found, and vaccinees were grouped according to antibody specificity. Antibodies from some individuals recognized PorA of serosubtype P1.15. However, antibodies from these individuals could not kill all P1.15 strains tested. Antibodies from a second group recognized both PorA and class 5 proteins, and antibodies from a third group recognized an as yet unidentified target antigen. The results demonstrate the importance of determining the fine epitope specificity of bactericidal antibodies to improve the existing vaccines against B meningococci.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Especificidad de Anticuerpos , Proteínas de la Membrana Bacteriana Externa/uso terapéutico , Vacunas Bacterianas/uso terapéutico , Infecciones Meningocócicas/prevención & control , Vacunación , Brasil , Niño , Preescolar , Humanos , Infecciones Meningocócicas/inmunología , Vacunas Meningococicas , Datos de Secuencia Molecular , Mutación , Neisseria meningitidis/clasificación , Neisseria meningitidis/genética , Porinas/genética , SerotipificaciónRESUMEN
In the present study we report the results of an analysis, based on serotyping, multilocus enzyme electrophoresis (MEE), and ribotyping of N. meningitidis serogroup C strains isolated from patients with meningococcal disease (MD) in Rio Grande do Sul (RS) and Santa Catarina (SC) States, Brazil, as the Center of Epidemiology Control of Ministry of Health detected an increasing of MD cases due to this serogroup in the last two years (1992-1993). We have demonstrated that the MD due to N.meningitidis serogroup C strains in RS and SC States occurring in the last 4 years were caused mainly by one clone of strains (ET 40), with isolates indistinguishable by serogroup, serotype, subtype and even by ribotyping. One small number of cases that were not due to an ET 40 strains, represent closely related clones that probably are new lineages generated from the ET 40 clone referred as ET 11A complex. We have also analyzed N.meningitidis serogroup C strains isolated in the greater São Paulo in 1976 as representative of the first post epidemic year in that region. The ribotyping method, as well as MEE, could provide useful information about the clonal characteristics of those isolates and also of strains isolated in south Brazil. The strains from 1976 have more similarity with the actual endemic than epidemic strains, by the ribotyping, sulfonamide sensitivity, and MEE results. In conclusion, serotyping with monoclonal antibodies (C:2b:P1.3), MEE (ET 11 and ET 11A complex), and ribotyping by using ClaI restriction enzyme (Rb2), were useful to characterize these epidemic strains of N.meningitidis related to the increased incidence of MD in different States of south Brazil. It is mostly probable that these N.meningitidis serogroup C strains have poor or no genetic correlation with 1971-1975 epidemic serogroup C strains. The genetic similarity of members of the ET 11 and ET 11A complex were confirmed by the ribotyping method by using three restriction endonucleases.
Asunto(s)
Infecciones Meningocócicas/epidemiología , Neisseria meningitidis/genética , Técnicas de Tipificación Bacteriana , Brasil/epidemiología , Humanos , Neisseria meningitidis/clasificación , Neisseria meningitidis/aislamiento & purificaciónRESUMEN
Neisseria meningitidis are gram-negative diplococci responsible for cases of meningococcal disease all over the world. The epidemic potential of N. meningitidis serogroup B and C is clearly a function of their serotype antigens more than of their capsular polysaccharides. Until recently, hiperimmune sera were used to detect typing antigens on the bacteria. The advent of monoclonal antibodies (MAbs) offered the opportunity to eliminate many of the cross-reactions and have improved the accuracy and reproducibility of meningococcal serotyping. We have produced a MAb to the outer membrane protein of the already existent serotype 17 that have been detected by the use of hiperimmune rabbit sera. The prevalence of this serotype epitope is low in the Brazilian strains. By using the MAb 17 we could not decrease the percentage of nontypeable serogroup C strains. However, there were a decreasing in nontypeable strains to 13% into serogroup B strains and to 25% into the other serogroups.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Neisseria meningitidis/inmunología , Animales , Proteínas de la Membrana Bacteriana Externa/aislamiento & purificación , Brasil , Ratones , Ratones Endogámicos BALB C , Neisseria meningitidis/clasificación , SerotipificaciónRESUMEN
This investigation was carried out to evaluate the importance of individual meningococcal surface class 5 protein with respect to antibody induction and its functional activity. Two groups of mice were immunized with two vaccine preparations differing in the presence or absence of class 5 protein. The ELISA results show that both vaccines were immunogenic and elicited mainly IgG antibodies against the major classes of meningococcal surface proteins, and the absence of class 5 protein in the vaccine produced a significant change in the overall units ml-1 of antibodies against the homologous strain. The infant rat model and the bactericidal assay were used to evaluate the functional antibody activity. Our results showed that (1) even using two different challenge doses (10(6) and 10(7) bacteria/animal), mortality could not be detected when followed up at 48 h; (2) there was protection as determined by the infant rat model and bactericidal activity using sera from both vaccinated groups; (3) there were no differences in the bactericidal titres between these groups; (4) in the infant rat model there were no differences in the index of bacteraemia among the infected animals (counts ml-1 of blood); and (5) there were differences in the incidence of bacteraemia. This is the first evidence that some immunological differences in the vaccine response could be attributed to the absence of class 5 protein by using infant rat model but not by using the bactericidal assay.
Asunto(s)
Proteínas Bacterianas/inmunología , Vacunas Bacterianas/inmunología , Neisseria meningitidis/inmunología , Animales , Animales Recién Nacidos , Anticuerpos Monoclonales , Formación de Anticuerpos , Especificidad de Anticuerpos , Actividad Bactericida de la Sangre , Modelos Animales de Enfermedad , Humanos , Inmunización Pasiva , Ratones , RatasRESUMEN
Cerebrospinal fluid (CSF) samples from 2083 patients with acquired immunodeficiency syndrome (AIDS) and neurological complications were bacteriologically examined during a period of 7 years (1984-1990). The percentage of patients who had at least one bacterial agent cultured from the CSF was 6.2%. Mycobacterium tuberculosis was the most frequently isolated agent (4.3%), followed by Mycobacterium avium complex or MAC (0.7%), Pseudomonas spp (0.5%), Enterobacter spp (0.4%), and Staphylococcus aureus (0.3%). Among 130 culture positive patients, 89 (68.5%) had M. tuberculosis and 15 (11.6%) had MAC. The frequency of bacterial isolations increased from 1988 (5.2%) to 1990 (7.2%), partly due to the increase in MAC isolations. Bacterial agents were more frequently isolated from patients in the age group 21-30 years and from women (p < 0.05).
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/líquido cefalorraquídeo , Infecciones Bacterianas/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/microbiología , Adolescente , Adulto , Factores de Edad , Anciano , Infecciones Bacterianas/complicaciones , Enfermedades del Sistema Nervioso Central/complicaciones , Enfermedades del Sistema Nervioso Central/microbiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Factores SexualesRESUMEN
Epidemic strains of the Neisseria meningitidis C:2b:P1.3 electrophoretic type 11 complex were responsible for an outbreak in Curitiba, Parana State, Brazil, from 1990 to 1991. Strains of this complex were also isolated in other Brazilian states and were responsible for a meningococcal disease epidemic in São Paulo State in 1990. Serotyping both with monoclonal antibodies and by multilocus enzyme electrophoresis was useful for typing these epidemic strains related to the increased incidence of meningococcal disease. The genetic similarity of members of the electrophoretic type 11 complex was confirmed by the ribotyping method by using EcoRI or ClaI endonuclease restriction enzymes.
Asunto(s)
Infecciones Meningocócicas/microbiología , Neisseria meningitidis/clasificación , Técnicas de Tipificación Bacteriana , Brasil/epidemiología , ADN Ribosómico/análisis , Brotes de Enfermedades , Humanos , Infecciones Meningocócicas/epidemiología , Neisseria meningitidis/genéticaRESUMEN
In 1988, nine cases of human parasitism by Phagicola sp. were diagnosed in the municipality of Registro (São Paulo State, Brazil) by stool examinations, in patients who ate raw mullet (Mugil sp.). Six (66%) of the nine patients suffered from flatulence and four (44%) had diarrhoeal episodes; six (66%) showed slight eosinophilia. On the same occasion, 61 dogs and 11 cats from Registro were also submitted to stool examination. Only one dog (1.6%) showed Phagicola eggs in the stool. All patients were treated with a single dose of praziquantel (50 mg kg-1 body weight) and control stool tests performed on the 15th, 30th and 60th days post-treatment showed no trematode eggs.