RESUMO
The development of immunization strategies to induce strong and multiepitopic T-cell responses against tumour antigens is needed for anti-tumour immunotherapy. However, a common finding after immunization with complex antigens is the preferential induction of immune responses against immunodominant epitopes. In this study, with the aim of inducing multiepitopic responses against several common tumour antigens, we have designed a minigene construct encoding four human leucocyte antigen (HLA)-A2-restricted epitopes belonging to tumour antigens CEA (CEA-691 and CEA-571), MAGE2 (MAGE2-157) and MAGE3 (MAGE3-112), as well as the universal PADRE epitope recognized by T helper lymphocytes. To optimize the activation of immune responses against these epitopes, we have used different antigen formats (short peptides encompassing individual epitopes and DNA plasmids or adenoviral constructs expressing the minigene) in single or combined immunization schedules. A single immunization with either DNA plasmid or recombinant adenovirus induced a monospecific immune response against the immunodominant epitope CEA-571, whereas immunization with the peptide pool induced responses against all epitopes. Combination of peptide priming followed by a boost with the plasmid and the recombinant adenovirus expressing the minigene induced stronger, multi-specific and long-lasting immune responses, overcoming the immunodominance imposed by the main T-cell epitope. Moreover, these combined immunization strategies were able to induce responses that were able to recognize Mel624 HLA-A2+ tumour cells expressing MAGE2. These results suggest that heterologous immunization strategies combining peptides and DNA or recombinant adenoviruses can be useful to broaden the specificity and enhance the efficacy of subunit vaccines.
Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Epitopos de Linfócito T , Peptídeos/imunologia , Vacinas de DNA/imunologia , Vacinas Sintéticas/imunologia , Adenoviridae/genética , Animais , Antígeno Carcinoembrionário/imunologia , Antígeno HLA-A2/imunologia , Humanos , Imunização , Camundongos , Proteínas de Neoplasias/imunologia , Plasmídeos , Linfócitos T Citotóxicos/imunologiaRESUMO
Introducción: La varicela es una enfermedad frecuente, muy contagiosa y por lo general benigna, pero con complicaciones potencialmente graves. Pacientes y métodos: Se revisan las historias clínicas de los niños hospitalizados por esta enfermedad entre 2001 y 2004 para evaluar las características clínicas y el coste que lleva consigo la hospitalización. Se excluyen los casos que presentaron varicela durante la hospitalización y que ingresaron por otros motivos. Resultados: De los 1.177 niños que fueron atendidos por varicela en urgencias, 101 fueron hospitalizados (8,6 %). La edad mediana fue de 3,2 años (21 días a 18,9 años). Veintiocho niños tenían enfermedad subyacente. Treinta y siete casos no presentaron complicaciones y el motivo de ingreso fue: a) riesgo de desarrollar varicela grave (21 niños con enfermedad de base y 3 neonatos), o b) tenían fiebre alta o afectación del estado general (13 niños). Los 64 niños restantes ingresaron por 66 complicaciones. La complicación más frecuente fue la infección de piel y tejidos blandos (33 casos) y su causa más habitual Streptococcus pyogenes (n = 13) y Streptococcus aureus (n = 10) que se aislaron en sangre o en el lugar de la infección. Otras fueron neumonía (13 niños), complicaciones neurológicas (9 niños con convulsiones febriles, dos meningoencefalitis, una encefalomielitis diseminada aguda, una cerebelitis), hematológicas (una neutropenia, una púrpura de Schönlein-Henoch y tres púrpuras trombocitopénicas) y osteoarticulares (una sinovitis, una artritis séptica). Una paciente falleció por insuficiencia multiorgánica. Durante el período de estudio el número de niños atendidos en urgencias por varicela se duplicó y el de ingresos por complicaciones se triplicó. La duración media de la hospitalización fue de 6,8 días (1-28 días) y el coste total asociado fue de 397.314,14 1, excluyendo el tratamiento sintomático. Conclusiones: La elevada morbilidad de la varicela y sus complicaciones y el elevado coste social apoyan la instauración universal de la vacuna, la cual reduciría el número total de casos, su gravedad, los gastos directos, generados por el cuidado médico y los gastos indirectos, relacionados con la enfermedad y hospitalización
Introduction: Varicella is a common, highly contagious disease. It is usually benign but has potentially serious complications. Patients and methods: To assess the clinical characteristics and the associated cost of varicella hospitalization, we reviewed the medical records of children hospitalized for varicella between 2001 and 2004. Children with coincidental varicella hospitalized for a different reason were excluded. Results: Of 1177 children with varicella attended at the emergency room, 101 (8.6 %) were hospitalized. The median age was 3.2 years (21 days to 18.9 years). Twenty-eight children had underlying disease. Thirty-seven children had no complications and the reason for admission was: a) risk of severe varicella (21 immunocompromised children, three neonates), and b) high fever or observation (13 cases). The 64 remaining children were admitted for 66 complications of varicella. The most common complications were skin/soft tissue infections (33 patients) and the leading cause was Streptococcus pyogenes (n = 13) and Staphylococcus aureus (n = 10) isolated in blood or the site of infection. Other complications were pneumonia (13 children), neurological (febrile seizures in nine, meningoencephalitis in two, acute disseminated encephalomyelitis in one, cerebellitis in one), hematological (neutropenia in one, Henoch-Schönlein purpura in one and thrombopenic purpura in three) and osteoarticular (synovitis in one and septic arthritis in one). One patient died of multiorgan failure. During the study period, the rate of emergency room visits due to varicella doubled and the number of admissions for complications tripled. The mean length of hospital stay was 6.8 days (range: 1-28 days) and the total associated cost was 397,314.14 3, excluding symptomatic treatment. Conclusions: The high morbidity associated with varicella and its complications, as well as the high social costs of this disease, support the implementation of routine varicella vaccination. This could reduce the total number of cases, their severity, direct costs, generated by medical care, and indirect costs, generated by the disease and hospitalization
Assuntos
Lactente , Criança , Adolescente , Humanos , Varicela/economia , Hospitalização/economia , Varicela/complicações , Varicela/epidemiologia , Varicela/prevenção & controle , Vacina contra Varicela , Efeitos Psicossociais da Doença , Hospitalização/estatística & dados numéricos , Morbidade , Espanha/epidemiologiaRESUMO
INTRODUCTION: The skin and soft tissue infections caused by Haemophilus influenzae type b (Hib) are usually mild but can be potentially serious due to the high probability of bacteremia. Prompt instauration of empiric intravenous antibiotic therapy according to the localization and characteristics of the lesion is mandatory to prevent severe complications. PATIENTS AND METHODS: Of 257 children admitted to the Children's Hospital of La Fe due to invasive Haemophilus influenzae type b disease (1973 to 2003), we reviewed 15 cases (5.8%) of skin and soft tissue infections, their outcome, complications and sequelae. RESULTS: Ten children (66.7%) were aged < 2 years old. In eight patients (53.3%) there was a history of upper respiratory tract infection. Localization was in the head in 9 children (60%) and blood culture was positive in 10 patients (66.7%). Meningitis was a complication in 2 children (13.3%) and limited mobility of the hand was a sequel in one child (6.6%). After the universal establishment of the Hib vaccine in 1997, 3 new patients were admitted; 2 children with an infected thyroglossal cyst and another with cellulitis in the left leg. Of these children, one had received only the three primary doses of the vaccine but not the booster dose, and the remaining two were unvaccinated immigrant children. CONCLUSION: Skin and soft tissue infections caused by Hib are potentially severe diseases with a risk of complications and sequelae. Due to the increase in unvaccinated immigrants and possible vaccine failures, universal immunization and epidemiological surveillance of carriers should be carried out to achieve total eradication.
Assuntos
Infecções por Haemophilus/epidemiologia , Haemophilus influenzae tipo b , Dermatopatias Bacterianas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Espanha/epidemiologiaRESUMO
INTRODUCTION: Varicella is a common, highly contagious disease. It is usually benign but has potentially serious complications. PATIENTS AND METHODS: To assess the clinical characteristics and the associated cost of varicella hospitalization, we reviewed the medical records of children hospitalized for varicella between 2001 and 2004. Children with coincidental varicella hospitalized for a different reason were excluded. RESULTS: Of 1177 children with varicella attended at the emergency room, 101 (8.6 %) were hospitalized. The median age was 3.2 years (21 days to 18.9 years). Twenty-eight children had underlying disease. Thirty-seven children had no complications and the reason for admission was: a) risk of severe varicella (21 immunocompromised children, three neonates), and b) high fever or observation (13 cases). The 64 remaining children were admitted for 66 complications of varicella. The most common complications were skin/soft tissue infections (33 patients) and the leading cause was Streptococcus pyogenes (n = 13) and Staphylococcus aureus (n = 10) isolated in blood or the site of infection. Other complications were pneumonia (13 children), neurological (febrile seizures in nine, meningoencephalitis in two, acute disseminated encephalomyelitis in one, cerebellitis in one), hematological (neutropenia in one, Henoch-Schönlein purpura in one and thrombopenic purpura in three) and osteoarticular (synovitis in one and septic arthritis in one). One patient died of multiorgan failure. During the study period, the rate of emergency room visits due to varicella doubled and the number of admissions for complications tripled. The mean length of hospital stay was 6.8 days (range: 1-28 days) and the total associated cost was 397,314.14 Euro, excluding symptomatic treatment. CONCLUSIONS: The high morbidity associated with varicella and its complications, as well as the high social costs of this disease, support the implementation of routine varicella vaccination. This could reduce the total number of cases, their severity, direct costs, generated by medical care, and indirect costs, generated by the disease and hospitalization.
Assuntos
Varicela/economia , Hospitalização/economia , Adolescente , Varicela/complicações , Varicela/epidemiologia , Varicela/prevenção & controle , Vacina contra Varicela , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Morbidade , Espanha/epidemiologiaRESUMO
Introducción. La infección de piel y tejidos blandos por Haemophilus influenzae tipo b (Hib) por lo general es leve pero potencialmente grave, debido a la elevada probabilidad de bacteriemia. Según la localización y las características de la lesión es fundamental la instauración precoz de antibioterapia empírica intravenosa, para evitar complicaciones graves. Pacientes y métodos. De 257 niños con enfermedad invasora por Hib ingresados en el Hospital infantil La Fe (1973-2003), se revisan 15 casos (5,8 %) de infección de piel y tejidos blandos, su evolución, complicaciones y secuelas. Resultados. Diez niños (66,7 %) eran menores de 2 años. En 8 casos (53,3 %) existían antecedentes de infección del tracto respiratorio superior. La localización fue en cabeza en 9 niños (60 %) y el hemocultivo fue positivo en 10 casos (66,7 %). Dos niños tuvieron meningitis como complicación (13,3 %) y otro tuvo como secuela limitación de la movilidad de la mano (6,6 %). Tras la vacunación universal frente a Hib (1997) ingresaron 3 casos: 2 niños con quistes del conducto tirogloso infectado y otro con celulitis en pierna izquierda. Uno de ellos sólo había recibido primovacunación, pero no la dosis de recuerdo y los otros dos eran inmigrantes no vacunados. Conclusiones. La infección de piel y tejidos blandos por Hib es una enfermedad potencialmente grave, con riesgo de complicaciones y secuelas importantes. Dado el incremento de población inmigrante no vacunada y los posibles de fallos vacunales, se debe insistir en la vacunación universal siguiendo una vigilancia epidemiológica de los portadores para su total erradicación
Introduction. The skin and soft tissue infections caused by Haemophilus influenzae type b (Hib) are usually mild but can be potentially serious due to the high probability of bacteremia. Prompt instauration of empiric intravenous antibiotic therapy according to the localization and characteristics of the lesion is mandatory to prevent severe complications. Patients and methods. Of 257 children admitted to the Children's Hospital of La Fe due to invasive Haemophilus influenzae type b disease (1973 to 2003), we reviewed 15 cases (5.8 %) of skin and soft tissue infections, their outcome, complications and sequelae. Results, Ten children (66.7 %) were aged < 2 years old. In eight patients (53.3 %) there was a history of upper respiratory tract infection. Localization was in the head in 9 children (60 %) and blood culture was positive in 10 patients (66.7 %). Meningitis was a complication in 2 children (13.3 %) and limited mobility of the hand was a sequel in one child (6.6 %). After the universal establishment of the Hib vaccine in 1997, 3 new patients were admitted; 2 children with an infected thyroglossal cyst and another with cellulitis in the left leg. Of these children, one had received only the three primary doses of the vaccine but not the booster dose, and the remaining two were unvaccinated immigrant children. Conclusion. Skin and soft tissue infections caused by Hib are potentially severe diseases with a risk of complications and sequelae. Due to the increase in unvaccinated immigrants and possible vaccine failures, universal immunization and epidemiological surveillance of carriers should be carried out to achieve total eradication
Assuntos
Lactente , Criança , Pré-Escolar , Humanos , Infecções por Haemophilus/epidemiologia , Dermatopatias Bacterianas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Haemophilus influenzae tipo b , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Espanha/epidemiologiaRESUMO
OBJECTIVE: Nocardiosis is a very rare, opportunistic infection caused by microorganisms of the genus Nocardia, and is associated with significant morbidity and mortality in kidney transplant patients receiving immunosuppressive therapy. MATERIAL AND METHODS: Since 1980, our Renal Transplant Unit has carried out 1239 kidney transplants, and five cases of Nocardia infection have occurred during this time. In this retrospective study, special consideration is given to clinical manifestations, treatment response (efficacy and side-effects) and the evolution of both the patient and the graft. Microbiological factors studied included biochemical profiles and antimicrobial sensitivity. RESULTS: Nocardiosis was observed in five men with a mean age of 49.2 years who had received immunosuppressive therapy (generally cyclosporin/azathioprine and prednisone) for a mean of 47.8 months (range 1-148 months). Four of the patients had good previous renal function. The clinical presentation of nocardiosis was as follows: pleuropulmonary pattern of infection, n = 3; subcutaneous abscess, n = 1; and fulminant multi-organ disseminated nocardiosis, n = 1. In all cases, direct observation using modified Ziehl-Neelsen staining proved positive, and in vitro culture revealed good sensitivity to trimethoprim-sulfamethoxazole and variable sensitivity to the other groups of antibiotics. Nocardia brasiliensis was isolated in two cases, and Nocardia asteroides in three. Two patients died, one due to multiple organ involvement and the other due to acute respiratory failure associated with severe hepatopathy caused by hepatitis C virus. The remaining cases improved. CONCLUSION: A low incidence of nocardiosis following kidney transplantation was observed. Fatal cases occurred in patients with bacteremia and serious comorbid medical conditions, in whom early diagnosis and specific treatment was required.
Assuntos
Antibacterianos/uso terapêutico , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/imunologia , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nocardia/efeitos dos fármacos , Nocardiose/imunologia , Estudos Retrospectivos , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoAssuntos
Escarlatina , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Cefalosporinas/uso terapêutico , Pré-Escolar , Quimioterapia Combinada/uso terapêutico , Feminino , Humanos , Lactente , Penicilinas/uso terapêutico , Recidiva , Escarlatina/diagnóstico , Escarlatina/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoAssuntos
Granuloma/etiologia , Dermatoses da Mão/etiologia , Linfangite/etiologia , Infecções por Mycobacterium/complicações , Dermatopatias Bacterianas/etiologia , Adulto , Biópsia , Granuloma/patologia , Dermatoses da Mão/patologia , Humanos , Linfangite/patologia , Masculino , Mycobacterium/isolamento & purificação , Infecções por Mycobacterium/patologia , Pele/patologia , PiscinasRESUMO
To assess and compare epidemiological factors, clinical and radiological signs, laboratory results and drug resistance in patients with tuberculosis (TB) with and without AIDS. Retrospective study of TB diagnosed bacteriologically between January 1993 and December 1996 at Hospital Universitario La Fe. Annual rates were 41.7, 47.1, 34.6 and 43.8 per 100,000 inhabitants in 1993 to 1996, respectively. AIDS was present in 22.4%. TB was pulmonary in 87% and 49.4% in patients without and with AIDS, respectively. Incidence was higher in the 25 to 34 age range. Prior contact with TB patients was established in 19.2% of cases. Pulmonary TB in patients with AIDS presented with normal lung X-rays in 30.1%; 16.2% of these had positive sputum cultures. Pulmonary cavitation was evident in 32.6% of TB patients without AIDS and 6.8% of those with AIDS. Pulmonary TB was diagnosed by culture of sputum taken at the time of admission in 25.9% of non AIDS patients and in 12.4% of patients with AIDS. Extrapulmonary TB was diagnosed by culture in most cases. Such forms predominated among TB plus AIDS patients, with most cases being ganglial and urogenital. Overall drug resistance was 8.3% (7.4% non-AIDS/11.5% AIDS). Primary resistance (PR) was 6.3% and 7.1%, PR to hydrazides was 5% and 5.4%, and secondary resistance was 32.4% and 33.3%. Drug resistance in non-AIDS and AIDS patients, was associated with a history of TB and past treatment (p < 0.009), prior contact with TB patients (p < 0.004) and pulmonary cavitatin (p < 0.02). TB with AIDS tends to occur in a younger population, is often extrapulmonary or with atypical lung involvement. Drug resistance is similar in patients with and without AIDS.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Tuberculose Pulmonar/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Análise de Variância , Feminino , Hospitais Universitários/estatística & dados numéricos , Humanos , Incidência , Masculino , Espanha/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/microbiologiaRESUMO
OBJECTIVE: The epidemiological and clinical characteristics, treatment and evolution of osteoarthritis by Haemophilus influenzae type b (HIB) are reviewed since there has been little published on this subject in our country. PATIENTS AND METHODS: The clinical histories of the 7 children with osteoarthritis due to Hib infection are reviewed. The diagnostic criteria included classical signs and symptoms of septic arthritis, radiological alterations compatible with joint infection and isolation of microorganisms in joint effusion and/or in the blood. RESULTS: During a 24-year period (1973-1996), 248 cases of invasive infection by Hib were documented. Seven cases (2.82%) had osteoarticular infections. The ages were between 5 and 7 years and there were more males than females (71.4% vs. 28.6%). Four children/58%) had previous upper respiratory infections (URI). The microorganism was isolated in the joint effusion in 5 children and in the blood sample of the other 2. C-reactive protein was high and radiology showed alterations in 100% of the cases. Surgical treatment with articular drainage was necessary in 5 children/71.4%). In 6 cases (85.7%) initial medical treatment was i.v. beta-lactam antibiotics for 2-3 weeks followed by oral antibiotic treatment for a minimum of 6 weeks. Three children (42.8%) had sequelae. CONCLUSIONS: Early diagnosis of bacterial osteoarthritis by Hib is difficult. Final therapeutical success depends on an early clinical diagnosis and aggressive multidisciplinary treatment. Drainage of the hip joint is mandatory for successful outcome. Currently, arthritis by Hib can be avoided and its sequelae prevented by vaccination.
Assuntos
Artrite Infecciosa/diagnóstico , Infecções por Haemophilus/diagnóstico , Haemophilus influenzae tipo b , Osteoartrite/diagnóstico , Artrite Infecciosa/microbiologia , Artrite Infecciosa/terapia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/terapia , Haemophilus influenzae tipo b/isolamento & purificação , Humanos , Lactente , Masculino , Osteoartrite/microbiologia , Osteoartrite/terapia , Estudos RetrospectivosAssuntos
Anisakis , Dermatite Alérgica de Contato/etiologia , Produtos Pesqueiros/efeitos adversos , Dermatoses da Mão/etiologia , Idoso , Animais , Dermatite Alérgica de Contato/diagnóstico , Feminino , Peixes/parasitologia , Dermatoses da Mão/diagnóstico , Humanos , Testes do Emplastro , Proteínas/efeitos adversosRESUMO
OBJECTIVE: Due to the higher incidence in invasive infections, the changes observed in the sensitivity of this microorganism during the last decade and the seriousness of pulmonary infections in children, the objective of this paper is to review the clinical and epidemiological characteristics of Haemophilus influenzae type b (Hib) pneumonia, as well as to give an update of treatment. PATIENTS AND METHODS: Twenty-four children diagnosed between 1973 and 1992 are reviewed using the following criteria: clinical manifestations of pneumonia, radiology and isolation of the microorganism. RESULTS: The annual average was 7.8 cases/100,000 children under 5 years of age. More females were affected (58.3% vs 41.6%). Of the cases studied, 58.3% of the children were under one year and 83.3% under 2 years of age. Fever was the most common clinical manifestation (95.8%). Blood cultures were positive in 21 cases (87.5%); pleural effusion culture contributed to the diagnosis in two other cases (8.3%) and deep bronchial aspirate in one other case. Of the Haemophilus influenzae type b strains 62.5% were resistant to ampicillin and 100% were sensitive to second and third generation cephalosporins. Three infants with chronic illness died (12.5%). CONCLUSIONS: Hib pneumonia is an infection usually affecting children younger than 2 years of age. Its clinical manifestations are indistinguishable from those of other microorganisms. Blood culture is the most useful technique to confirm the diagnosis. The increase in resistance to classical treatment (ampicillin) obliges us to consider amoxicillin-clavulanic as the selected empirical treatment. Second and third generation cephalosporins may be considered a good alternative. There is a high mortality in children with chronic illness.