Childhood Intra-Thoracic Tuberculosis Clinical Presentation Determines Yield of Laboratory Diagnostic Assays

Abstract

Diagnosis of intra-thoracic tuberculosis (ITTB) in children is difficult due to the paucibacillary nature of the disease, the challenge in collecting appropriate specimens, and the low sensitivity of smear microscopy and culture. Culture and Xpert MTB/RIF provide higher diagnostic yield in presumptive TB in adults than in children. Current study was designed to understand poor yield of diagnostic assays in children. Children with presumptive ITTB were subjected to gastric aspirates and induced sputum twice. Samples were tested by Ziehl-Neelsen stain, Xpert MTB/RIF-assay, and MGIT-960 culture. Subjects were grouped as Confirmed, Unconfirmed, and Unlikely TB, and classified as progressive primary disease (PPD, lung parenchymal lesion), and primary pulmonary complex (PPC, hilar lymphadenopathy) on chest X-ray. Of children with culture-positive TB 51/394 (12.9%), culture-negative TB 305 (77.4%), and unlikely TB 38 (9.6%), 9 (2.3%) were smear positive, while 95 (24.1%) were Xpert-MTB/RIF positive. Xpert-MTB/RIF detected 40/51 culture confirmed cases (sensitivity 78.4% and NPV 96.3%). Culture was positive in more children presenting as PPD (p < 0.04). In culture-negative TB group, Xpert positivity was seen in 31% of those with PPD and 11.9% in those with PPC (p < 0.001).Conclusion: Xpert-MTB/RIF improved diagnosis by 2-fold and increased detection of MDR-TB. Both liquid culture and Xpert-MTB/RIF gave higher yield in children with lung parenchymal lesions. Children with hilar lymphadenopathy without active lung parenchymal lesions had poor diagnostic yield even with sensitive nucleic acid amplification tests, due to paucibacillary/localized disease, suggesting possible utility of invasively collected samples in early diagnosis and treatment.

Comparison of Characteristics and Clinical Outcomes of Children with Confirmed Tuberculosis and Unconfirmed Rapid Molecular Test Examination

“…Confirmed TB. [19] A study conducted by Swaminathan et al found symptoms of fever and cough for more than 2 weeks with or without respiratory tract infection as symptoms that are often found in bacteriologically confirmed TB. [11] Report of Rina Triasih et al complaints of fever and cough are the main complaints when a patient is diagnosed GeneXpert MTB/RIF rapid molecular test confirmed.…”

Multi-Centric Validation of Truenat MTB Rif Dx for Diagnosis of Extrapulmonary Tuberculosis

“…Microbiological Reference Standards (MRS) included LC, Smear and GX [8][9] . Results of TN were compared to MRS, Smear or Liquid Culture results taken together and to liquid culture alone as well.…”

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF

“…Microbiological reference standards (MRS) include LC, smear and GeneXpert MTB/RIF 1 , 8 . Truenat MTB-RIF Dx and GeneXpert MTB/RIF results were compared to MRS, smear or LC results taken together as well as to liquid culture alone in order to compare their performance.…”

“…Pulmonary and intra-thoracic tuberculosis (TB) in children is difficult to diagnose due to the pauci-bacillary nature of disease and varied presentation of involvement of the lungs. More often, younger children present with progressive primary disease (PPD, lung parenchymal lesion) while older children have mediastinal involvement and primary pulmonary complex (PPC, hilar-lymphadenopathy) on Chest X-ray 1 . Issues such as poor/inadequate sample and lower diagnostic yield of laboratory methods further leads to confusion in diagnosis and hence overuse of anti-tubercular treatment for presumptive TB cases.…”