Application of whole-genome sequencing in a case study of renal tuberculosis in a child

Abstract

Background: Urogenital tuberculosis (TB) is rare in children and usually develops due to reactivation of the foci in the genitourinary tract after the latency period following initial infection. Urogenital TB in children has no pathognomonic clinical features that can result in overlooking or misdiagnosing this clinical entity. Here, we report important findings regarding the pathogenesis and transmission of TB by using genotyping and whole-genome sequencing (WGS) in a study of renal TB case in a child.

Case presentation: A 13-year-old boy was admitted to the hospital because of high fever, severe dry cough, flank pain and painful urination. Abdominal ultrasonography and CT revealed an 8 mm calculus in the kidney, and clinical findings were initially interpreted as nephrolithiasis. Nevertheless, due to the atypical clinical presentation of kidney stone disease, additional investigations for possible TB were performed. The QuantiFERON®-TB Gold Plus test was positive, and the Mantoux test resulted in 15 mm of induration, confirming infection with Mycobacterium tuberculosis (Mtb). Chest X-ray was normal. Chest CT revealed calcified intrathoracic lymph nodes. The urine sample tested positive for acid-fast bacilli, and Mtb cultures were obtained from urine and bronchial aspirate samples, resulting in a final diagnosis of intrathoracic lymph node and renal TB. Contact investigation revealed that the child's father was diagnosed with TB when the child was 1 year old. Genotyping and WGS analysis of Mtb isolates of the child and his father confirmed the epidemiological link and pointed to the latency of infection in the child.

Conclusions: This case report confirmed the development of active TB from calcified lesions in adolescent after 12 years of exposure, demonstrated the absence of microevolutionary changes in the Mtb genome during the period of latency, and proved the importance of appropriate evaluation and management to prevent the progression of TB infection to active TB disease. The use of WGS provided the ultimate resolution for the detection of TB transmission and reactivation events.

Keywords: Childhood tuberculosis; Genotyping; Urogenital tuberculosis; Whole-genome sequencing.

Fig. 1

Pathological and genotyping findings. a: Abdominal computed tomography. A calculus in left kidney is shown (arrow). b: Chest X-ray. c, d: Chest computed tomography. Calcified intrathoracic lymph nodes in subcarinal and left bronchopulmonary lymph node groups (arrow). e: Spoligotyping analysis of Mtb isolates. Lane 1: urine sample, child (September 5, 2016); Lane 2: urine sample, child (September 6, 2016); Lane 3: bronchial aspirate sample, child (September 9, 2016); Lane 4: sputum sample, father (February 2, 2004). F: IS 6110 RFLP analysis of Mtb isolates. Lane 1: urine sample, child (September 5, 2016); Lane 2: urine sample, child (September 6, 2016); Lane 3: bronchial aspirate sample, child (September 9, 2016); Lane 4: sputum sample, father (February 2, 2004)