RESUMEN
OBJECTIVES: To evaluate the clinical long-term course in patients with chronic granulomatous disease (CGD) with respect to different CGD subtypes and currently used antimicrobial prophylactic measures. STUDY DESIGN: The records of 39 patients with CGD who were monitored during a period of 22 years were reviewed. All infections, infectious complications, and clinical outcomes were documented for a total observation period of 610 patient-years and were stratified with respect to different CGD subtypes. RESULTS: Lymphadenitis, skin abscesses, and pneumonia occurred in 87%, 72%, and 59% of the patients, respectively. In 151 microbiologic isolates Staphylococcus aureus, Aspergillus species, Candida species, Pseudomonas species, and Salmonella species were the most frequently detected microorganisms. There were 167 severe infections requiring hospitalization and intravenous antimicrobial treatment, resulting in an incidence of 3.7 severe infections per 100 patient months (SI/100 PM). Long-term antibiotic prophylaxis significantly reduced the incidence of severe bacterial infections from 4.8 SI/100 PM to 1. 6 SI/100 PM (P =.0035). In contrast, fungal infections increased under antibiotic prophylaxis from a mean incidence of 0.2 SI/100 PM to 1.9 SI/100 PM (P =.04). We found a 50% survival rate through the fourth decade of life, with a plateau after the third decade of life. Patients with a complete absence of cytochrome b(558) showed an earlier manifestation of their disease and a higher incidence of infections and had significant lower survival than patients with only diminished cytochrome b(558) or autosomal recessive CGD. CONCLUSIONS: Infections with Aspergillus species have become the major cause of infectious complications and death in patients with CGD. Prophylactic and therapeutic measures are needed to further increase life expectancy and quality for patients with CGD.
Asunto(s)
Enfermedad Granulomatosa Crónica , Adolescente , Adulto , Edad de Inicio , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Niño , Preescolar , Estudios de Seguimiento , Enfermedad Granulomatosa Crónica/clasificación , Enfermedad Granulomatosa Crónica/mortalidad , Enfermedad Granulomatosa Crónica/fisiopatología , Enfermedad Granulomatosa Crónica/terapia , Humanos , Lactante , Itraconazol/uso terapéutico , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/prevención & control , Análisis de Supervivencia , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Método Doble Ciego , Epilepsia , Fiebre , Alemania , Humanos , Incidencia , Lactante , Estudios Prospectivos , Convulsiones , Espasmos Infantiles , Muerte Súbita del LactanteRESUMEN
In 26 infants and children with septicemia or bacterial meningitis, significantly elevated plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) were present at time of recognition of infection, even in those patients with neutropenia (range of reference values: 25 to 190 micrograms/L, n = 142; patients: 444 to 2049 micrograms/L, n = 26). After initiation of therapy, normalization of E-alpha 1-PI levels was observed in all patients who recovered from infection. In addition, 18 of 19 children with bacterial meningitis had increased cerebrospinal fluid concentrations of E-alpha 1-PI above the range of normal (range of reference values: 0 to 39 micrograms/L, n = 62; patients: 30 to 3490 micrograms/L, n = 19); concentrations of E-alpha 1-PI in bacterial meningitis were significantly increased when compared with those in aseptic meningitis (range 25 to 194 micrograms/L; n = 15). In 30 patients with local bacterial infections (pneumonia, urinary tract infections, etc.), E-alpha 1-PI was also elevated. These data suggest that E-alpha 1-PI is a sensitive indicator of systemic and local bacterial infection in childhood.