Bacillus Calmette-Guérin (BCG) Infections at High Frequency in Both AR-CGD and X-CGD Patients Following BCG Vaccination

Abstract

Background Patients with chronic granulomatous disease (CGD) develop severe infections, including Bacillus Calmette-Guérin (BCG). Although the autosomal recessive CGD (AR-CGD) patients should hypothetically develop relatively fewer infections compared to the X-linked CGD (X-CGD) patients due to more residual reactive oxygen intermediates, the impacts of BCG vaccination on AR-CGD and X-CGD patients are unclear. Herein, we demonstrated the clinical features of BCG infections, treatments, and genetic factors in CGD patients after BCG vaccination under the Japanese immunization program. Methods We collected data retrospectively from 43 patients with CGD and assessed their history of initial infection, age at diagnosis of CGD, BCG vaccination history, clinical course, treatment for BCG infections, and genetic mutations associated with CGD. Results Fourteen CGD patients avoided BCG vaccination because of other preceding infections and family history. Of 29 patients with CGD who received BCG vaccination, 20 patients developed BCG infections. Although the age at onset of initial infection in X-CGD patients was significantly younger than that in AR-CGD patients (P<0.01), the onset and frequency of BCG infections were similar in X-CGD and AR-CGD patients. In X-CGD patients, BCG infections equally developed in the patients carrying missense, insertion, deletion, nonsense, and splice mutations of CYBB. All CGD patients with BCG infections were successfully treated with anti-tuberculous drugs. Conclusions Although X-CGD patients develop severe infections at a younger age than AR-CGD patients, our data suggested that BCG infections develop at high frequency in both AR-CGD and X-CGD patients, regardless of genotype and mutant forms.

Mesenteric abscess caused by coinfection with Bacillus Calmette-Guérin and Phialemonium sp. in chronic granulomatous disease

“…In CGD patients, differences in residual ROS production due to the genotype or the type of inheritance affects the development of severe infections [8] . In X-CGD patients, the mutations in CYBB other than missense mutations have fewer ROS production than missense mutations in CYBB and would cause more severe infections.…”

“…In X-CGD patients, the mutations in CYBB other than missense mutations have fewer ROS production than missense mutations in CYBB and would cause more severe infections. However, the development of BCG infections has been reported to be independent of genotype or mutant forms [3] , [8] , [9] . Under the Japanese vaccination program, children generally receive BCG vaccination before 1 year old.…”

“…Under the Japanese vaccination program, children generally receive BCG vaccination before 1 year old. Approximately 67% of CGD patients receive BCG vaccination before a CGD diagnosis [8] . BCG-osis, the most fatal reaction after BCG vaccination, is highly observed in approximately 30% of BCG-vaccinated CGD patients.…”