Simar J, Belkhir L, Tombal B, André E
Microbiology Unit, Laboratory Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Infectious Diseases Unit, Department of Internal Medicine, Cliniques Universitaires Saint Luc, Brussels, Belgium.
BMC Res Notes. 2017 Jan 26;10(1):64. doi: 10.1186/s13104-017-2382-6.
Adjuvant therapy with bacillus Calmette-Guerin (BCG), a live attenuated strain of Mycobacterium bovis, has become the treatment of choice for low-risk superficial bladder carcinoma following transurethral resection of the bladder. Complications following vesical BCG instillations are uncommon but, in some cases, severe side-effects can occur such as sepsis or mycotic aneurysm. Besides usual laboratory techniques used for the diagnosis of Mycobacterium tuberculosis complex (MTBC) infections (smear microscopy and cultures), commercial immunochromatographic assays detecting MBP64, a 24 kDa M. tuberculosis complex-specific secretory protein, can rapidly distinguish MTBC and non-tuberculosis mycobacteria (NTM). MPB64 is found in M. tuberculosis, M. bovis and some but not all substrains of M.bovis BCG. Therefore, these immunochromatographic tests can lead to false negative results and delayed bacteriological diagnosis depending on the presence or absence of MPB64 protein in BCG substrains used for intravesical therapy.
We report the case of a 78-year-old male patient who was admitted to the hospital because of a 1-month history of unexplained fever, thrill, weight-loss and general malaise. His past medical history was marked by a non-muscle-invasive bladder carcinoma treated by transurethral resection followed by BCG instillations (Oncotice, Merck, USA). The patient was initially treated for a urinary tract infection but as fever persists after 72 h of antibiotherapy, urinary tract ultrasound was performed and revealed a large abdominal aortic aneurysm confirmed by computed tomography. Surgery was performed after multidisciplinary discussion. Direct smear of perioperative samples revealed acid-fast bacilli and both solid and liquid cultures were massively positive. Rapid identification of the positive mycobacterial culture was performed using an immunochromatographic assay based on the detection of the Mycobacterium tuberculosis MPB 64 antigen. The result was negative for Mycobacterium tuberculosis complex. After review of the medical record, a polymerase chain reaction (PCR) was performed and gave a positive result for M. tuberculosis complex. Anti-tuberculosis therapy was started immediately and the patient evolved favorably.
Through this case, we showed how the utilisation of MPB64 immunochromatographic assays can provide misleading information due to the variable presence of this protein among the different BCG strains. This case further illustrates the utility of rapid TB complex-specific PCR assays which provide a more reliable identification of all MTBC species.
卡介苗(BCG)是一种减毒活牛分枝杆菌,辅助治疗已成为经尿道膀胱切除术后低风险浅表性膀胱癌的首选治疗方法。膀胱内灌注卡介苗后的并发症并不常见,但在某些情况下,可能会出现严重的副作用,如败血症或霉菌性动脉瘤。除了用于诊断结核分枝杆菌复合群(MTBC)感染的常用实验室技术(涂片显微镜检查和培养)外,检测MPB64(一种24 kDa结核分枝杆菌复合群特异性分泌蛋白)的商业免疫色谱测定法可以快速区分MTBC和非结核分枝杆菌(NTM)。MPB64存在于结核分枝杆菌、牛分枝杆菌以及部分但并非所有的卡介苗牛分枝杆菌亚菌株中。因此,这些免疫色谱检测可能会导致假阴性结果,并根据膀胱内治疗所用卡介苗亚菌株中MPB64蛋白的有无导致细菌学诊断延迟。
我们报告了一例78岁男性患者,因1个月的不明原因发热、寒战、体重减轻和全身不适入院。他的既往病史以非肌层浸润性膀胱癌为特征,经尿道切除术后行卡介苗灌注治疗(Oncotice,美国默克公司)。患者最初因尿路感染接受治疗,但抗生素治疗72小时后仍持续发热,遂进行泌尿系统超声检查,发现一个大的腹主动脉瘤,计算机断层扫描证实了这一结果。经过多学科讨论后进行了手术。围手术期样本的直接涂片显示抗酸杆菌,固体和液体培养均大量阳性。使用基于检测结核分枝杆菌MPB 64抗原的免疫色谱测定法对阳性分枝杆菌培养物进行快速鉴定。结果显示结核分枝杆菌复合群为阴性。查阅病历后,进行了聚合酶链反应(PCR),结果显示结核分枝杆菌复合群为阳性。立即开始抗结核治疗,患者病情好转。
通过该病例,我们展示了由于不同卡介苗菌株中MPB64蛋白的存在情况不同,使用MPB64免疫色谱测定法如何会提供误导性信息。该病例进一步说明了快速结核复合群特异性PCR测定法的实用性,该方法能更可靠地鉴定所有MTBC菌种。