Lang Alois B, Rüdeberg Anna, Schöni Martin H, Que John U, Fürer Emil, Schaad Urs B
Research Immunology, Berna Biotech, Ltd., Bern, Switzerland.
Pediatr Infect Dis J. 2004 Jun;23(6):504-10. doi: 10.1097/01.inf.0000129688.50588.ac.
Cystic fibrosis (CF) almost always leads to chronic airway infection with Pseudomonas aeruginosa. Despite advances in antibiotic therapy, after chronic infection rapid deterioration in lung function occurs, increasing morbidity and mortality. Prevention of infection by vaccination is desirable, but earlier trials produced disappointing results. The promising short term immunogenicity and safety of a new P. aeruginosa vaccine prompted us to evaluate its long term efficacy. We conducted a 10-year retrospective analysis of outcomes in a group of vaccinated patients.
In 1989-1990, 30 young children with CF, mean age 7 years, with no prior history of infection with P. aeruginosa, were vaccinated against P. aeruginosa with a polyvalent conjugate vaccine. We report the follow-up of 26 of these patients from 1989 to 2001. The patients were given yearly vaccine boosters. Comparisons were made with a CF patient control group matched for gender, age and, where possible, genetic mutation. Vaccinated patients and controls were attending a single CF clinic and received the same clinical management throughout the study period. Main outcomes were time to infection, proportion of patients infected, development of P. aeruginosa mucoid phenotype, lung function and body weight.
The time to infection with P. aeruginosa was longer in the vaccination group than in the control group, and fewer vaccinated patients than controls became chronically infected (32% versus 72%; P < 0.001). The proportion of mucoid infections was higher in the control group (44%) than in the vaccinated group (25%). Patients >/=18 years of age at the end of the study had a lower mean forced expiratory volume at 1 s (FEV1) than did those 13-17 years of age, but this difference was small in the vaccinated group (73.6% versus 83.7%) compared with the controls (48.0% versus 78.7%). In the >/=18 year age category the mean FEV1% at 10 years was 73.6% (vaccinated) and 48.0% (controls) (P < 0.05). In the vaccinated group only 11 (44%) of 25 patients were underweight at the 10-year follow-up compared with 18 (72%) of 25 at the beginning of the study. In the control group 17 (68%) of 25 patients were underweight at 10-year follow-up compared with 16 (64%) of 25 at the beginning of the study.
Regular vaccination of young CF patients for a period of 10 years with a polyvalent conjugate vaccine reduced the frequency of chronic infection with P. aeruginosa. This was associated with better preservation of lung function. Vaccinated patients gained more weight during the study period, a possible indication of an improved overall health status.
囊性纤维化(CF)几乎总会导致铜绿假单胞菌慢性气道感染。尽管抗生素治疗取得了进展,但慢性感染后肺功能会迅速恶化,发病率和死亡率不断上升。通过接种疫苗预防感染是可取的,但早期试验结果令人失望。一种新型铜绿假单胞菌疫苗颇具前景的短期免疫原性和安全性促使我们评估其长期疗效。我们对一组接种疫苗患者的结局进行了为期10年的回顾性分析。
1989年至1990年,30名平均年龄7岁、既往无铜绿假单胞菌感染史的CF幼儿接种了一种多价结合疫苗以预防铜绿假单胞菌感染。我们报告了其中26名患者从1989年至2001年的随访情况。这些患者每年接受疫苗加强接种。与按性别、年龄以及在可能情况下按基因突变匹配的CF患者对照组进行比较。接种疫苗的患者和对照组均在一家CF诊所就诊,在整个研究期间接受相同的临床管理。主要结局指标为感染时间、感染患者比例、铜绿假单胞菌黏液样表型的出现、肺功能和体重。
接种疫苗组感染铜绿假单胞菌的时间比对照组更长,接种疫苗的患者中发生慢性感染的人数少于对照组(32%对72%;P<0.001)。对照组黏液样感染的比例(44%)高于接种疫苗组(25%)。研究结束时年龄≥18岁的患者1秒用力呼气量(FEV1)的平均值低于13至17岁的患者,但与对照组(48.0%对78.7%)相比,接种疫苗组的这一差异较小(73.6%对83.7%)。在≥18岁年龄组中,10年时FEV1%的平均值在接种疫苗组为73.6%,在对照组为48.0%(P<0.05)。在接种疫苗组中,25名患者在10年随访时有11名(44%)体重过轻,而研究开始时25名中有18名(72%)体重过轻。在对照组中,25名患者在10年随访时有17名(68%)体重过轻,而研究开始时25名中有16名(64%)体重过轻。
对CF幼儿定期接种多价结合疫苗10年可降低铜绿假单胞菌慢性感染的频率。这与肺功能的更好保存相关。接种疫苗的患者在研究期间体重增加更多,这可能表明整体健康状况有所改善。