WHO, 2016. Global Tuberculosis Report 2016. Geneva, Switzerland: World Health Organization.
Harries AD, Hargreaves NJ, Kemp J, Jindani A, Enarson DA, Maher D, Salaniponi FM, 2001. Deaths from tuberculosis in sub-Saharan African countries with a high prevalence of HIV-1. Lancet 357: 1519–1523.
Harries AD, Nyirenda TE, Banerjee A, Boeree MJ, Salaniponi FM, 1999. Treatment outcome of patients with smear-negative and smear-positive pulmonary tuberculosis in the National Tuberculosis Control Programme, Malawi. Trans R Soc Trop Med Hyg 93: 443–446.
Macpherson P et al. 2011. Risk factors for mortality in smear-negative tuberculosis suspects: a cohort study in Harare, Zimbabwe. Int J Tuberc Lung Dis 15: 1390–1396.
Perez-Velez CM, Marais BJ, 2012. Tuberculosis in children. N Engl J Med 367: 348–361.
Gupta RK, Lucas SB, Fielding KL, Lawn SD, 2015. Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS 29: 1987–2002.
WHO, 2015. Global Tuberculosis Report. Geneva, Switzerland: World Health Organization.
Small PM, Pai M, 2010. Tuberculosis diagnosis–time for a game change. N Engl J Med 363: 1070–1071.
Detjen AK, DiNardo AR, Leyden J, Steingart KR, Menzies D, Schiller I, Dendukuri N, Mandalakas AM, 2015. Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis. Lancet Respir Med 3: 451–461.
Aryan E, Makvandi M, Farajzadeh A, Huygen K, Alvandi AH, Gouya MM, Sadrizadeh A, Romano M, 2013. Clinical value of IS6110-based loop-mediated isothermal amplification for detection of Mycobacterium tuberculosis complex in respiratory specimens. J Infect 66: 487–493.
Jeanes C, O’Grady J, 2016. Diagnosing tuberculosis in the 21st century—dawn of a genomics revolution? Int J Mycobacteriol 5: 384–391.
Pholwat S, Stroup S, Foongladda S, Houpt E, 2013. Digital PCR to detect and quantify heteroresistance in drug resistant Mycobacterium tuberculosis. PLoS One 8: e57238.
Steingart KR, Sohn H, Schiller I, Kloda LA, Boehme CC, Pai M, Dendukuri N, 2013. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 1: CD009593.
Ulmar D, Ornstein OG, 1933. Gastric examination in pulmonary tuberculosis with negative sputum: diagnostic importance. JAMA 101: 835–836.
Alonso JM, 2008. Immunity and pathophysiology of respiratory tract infections. Med Mal Infect 38: 433–437.
DiNardo AR, Hahn A, Leyden J, Stager C, Baron EJ, Graviss EA, Mandalakas AM, Guy E, 2015. Use of string test and stool specimens to diagnose pulmonary tuberculosis. Int J Infect Dis 41: 50–52.
Wolf H et al. 2008. Diagnosis of pediatric pulmonary tuberculosis by stool PCR. Am J Trop Med Hyg 79: 893–898.
Kokuto H, Sasaki Y, Yoshimatsu S, Mizuno K, Yi L, Mitarai S, 2015. Detection of Mycobacterium tuberculosis (MTB) in fecal specimens from adults diagnosed with pulmonary tuberculosis using the Xpert MTB/rifampicin test. Open Forum Infect Dis 2: ofv074.
Nicol MP, Spiers K, Workman L, Isaacs W, Munro J, Black F, Zemanay W, Zar HJ, 2013. Xpert MTB/RIF testing of stool samples for the diagnosis of pulmonary tuberculosis in children. Clin Infect Dis 57: e18–e21.
Marcy O et al. 2016. Performance of Xpert MTB/RIF and alternative specimen collection methods for the diagnosis of tuberculosis in HIV-infected children. Clin Infect Dis 62: 1161–1168.
Walters E et al. 2017. Xpert MTB/RIF on stool is useful for the rapid diagnosis of tuberculosis in young children with severe pulmonary disease. Pediatr Infect Dis J 36: 837–843.
Taylor N, Gaur RL, Baron EJ, Banaei N, 2012. Can a simple flotation method lower the limit of detection of Mycobacterium tuberculosis in extrapulmonary samples analyzed by the GeneXpert MTB/RIF assay? J Clin Microbiol 50: 2272–2276.
Banada PP, Naidoo U, Deshpande S, Karim F, Flynn JL, O’Malley M, Jones M, Nanassy O, Jeena P, Alland D, 2016. A novel sample processing method for rapid detection of tuberculosis in the stool of pediatric patients using the Xpert MTB/RIF assay. PLoS One 11: e0151980.
Nahid P et al. 2016. Executive summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis 63: 853–867.
Detjen AKDA, Leyden J, Steingart KR, Menzies D, Schiller I, Dendukuri N, Mandalakas AM, 2013. Systematic Review and Meta-Analysis: Xpert MTB/RIF for the Diagnosis of Pulmonary Tuberculosis, Peripheral Lymph Node TB and TB meningitis in Children. WHO Expert Group Meeting on Use of Xpert MTB/RIF in TB control in low and middle-income settings. WHO Expert Meeting, May 20–21, 2013, Vevrier Du-Lac, France.
Malherbe ST et al. 2016. Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat Med 22: 1094–1100.
Shenai S et al. 2016. Bacterial loads measured by the Xpert MTB/RIF assay as markers of culture conversion and bacteriological cure in pulmonary TB. PLoS One 11: e0160062.
Barletta F, Vandelannoote K, Collantes J, Evans CA, Arevalo J, Rigouts L, 2014. Standardization of a TaqMan-based real-time PCR for the detection of Mycobacterium tuberculosis-complex in human sputum. Am J Trop Med Hyg 91: 709–714.
Graham SM et al. 2012. Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel. J Infect Dis 205 (Suppl 2): S199–S208.
Mejia R, Vicuna Y, Broncano N, Sandoval C, Vaca M, Chico M, Cooper PJ, Nutman TB, 2013. A novel, multi-parallel, real-time polymerase chain reaction approach for eight gastrointestinal parasites provides improved diagnostic capabilities to resource-limited at-risk populations. Am J Trop Med Hyg 88: 1041–1047.
Cepheid, 2015. Xpert MTB/RIF Package Insert. Available at: http://www.cepheid.com/us/mtbrif-pi. Accessed April 27, 2018.
Van Rie A, 2013. Xpert MTB/RIF: a game changer for the diagnosis of pulmonary tuberculosis in children? Lancet Glob Health 1: e60–e61.
Desjardin LE et al. 1999. Measurement of sputum Mycobacterium tuberculosis messenger RNA as a surrogate for response to chemotherapy. Am J Respir Crit Care Med 160: 203–210.
Foley JA, Andosca JB, 1943. The value of the examination of gastric contents for tubercle bacilli. Ann Intern Med 19: 629–633.
Walters E, Gie RP, Hesseling AC, Friedrich SO, Diacon AH, Gie RP, 2012. Rapid diagnosis of pediatric intrathoracic tuberculosis from stool samples using the Xpert MTB/RIF Assay: a pilot study. Pediatr Infect Dis J 31: 1316.
Lok KH, Benjamin WH Jr., Kimerling ME, Pruitt V, Lathan M, Razeq J, Hooper N, Cronin W, Dunlap NE, 2002. Molecular differentiation of Mycobacterium tuberculosis strains without IS6110 insertions. Emerg Infect Dis 8: 1310–1313.
|Past two years||Past Year||Past 30 Days|
|Full Text Views||1027||286||7|
A quantifiable, stool-based, Mycobacterium tuberculosis (Mtb) test has potential complementary value to respiratory specimens. Limit of detection (LOD) was determined by spiking control stool. Clinical test performance was evaluated in a cohort with pulmonary tuberculosis (TB) (N = 166) and asymptomatic household TB child contacts (N = 105). Stool-quantitative polymerase chain reaction (qPCR) results were compared with sputum acid-fast bacilli (AFB) microscopy, GeneXpert MTB/RIF (Xpert MTB/RIF), and cultures. In Mtb stool-spiking studies, the LOD was 96 colony-forming units/50 mg of stool (95% confidence interval [CI]: 84.8–105.6). Among specimens collected within 72 hours of antituberculosis treatment (ATT) initiation, stool qPCR detected 22 of 23 (95%) of culture-positive cases. Among clinically diagnosed cases that were Xpert MTB/RIF and culture negative, stool qPCR detected an additional 8% (3/37). Among asymptomatic, recently TB-exposed participants, stool PCR detected Mtb in two of 105 (1.9%) patients. Two months after ATT, the Mtb quantitative burden in femtogram per microliters decreased (Wilcoxon signed-rank P < 0.001) and persistent positive stool PCR was associated with treatment failure or drug resistance (relative risk 2.8, CI: 1.2–6.5; P = 0.012). Stool-based qPCR is a promising complementary technique to sputum-based diagnosis. It detects and quantifies low levels of stool Mtb DNA, thereby supporting adjunct diagnosis and treatment monitoring in pulmonary TB.
Financial support: This work was supported by Early Career Grants by ASTMH/ Burroughs Wellcome Fund and the Thrasher Research Fund (A. R. D.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. R. M. reports grants and other from Romark Laboratories outside the submitted work.
Conflicts of interest: The authors do not have a commercial or other association that would be a conflict of interest. Aspect of these data was presented at the International Union Conference of Tuberculosis and Lung Disease, Liverpool, United Kingdom, 2016. No authors have changed address since completion of the study.
Authors’ addresses: Andrew R. DiNardo, Department of Global and Immigrant Health, Baylor College of Medicine, Houston, TX, E-mail: email@example.com. Alexander W. Kay, Celia Fung, and Pilar Ustero, Global TB department, The Baylor-Swaziland Children’s Foundation, Mbabane, Swaziland, E-mails: firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org. Gugu Maphalala and Sindisiwe Dlamini, National Reference Laboratory, Swaziland Ministry of Health, Mbabane, Swaziland, E-mails: email@example.com and firstname.lastname@example.org. Nadine M. Harris, Internal Medicine-Infectious Diseases, Baylor College of Medicine, Houston, TX, E-mail: email@example.com. Godwin Mtetwa, Global TB Department, Baylor-Swaziland Children’s Foundation, Mbabane, Swaziland, E-mail: firstname.lastname@example.org. Ngan Ha and Edward A. Graviss, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, TX, E-mails: email@example.com and firstname.lastname@example.org. Rojelio Mejia, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, E-mail: email@example.com. Anna M. Mandalakas, Global TB Program, Baylor College of Medicine, Houston, TX, E-mail: firstname.lastname@example.org.
Reprint requests: Patricia Dorman, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates St., Houston, TX 77030, E-mail: email@example.com, Phone: 832-822-133, Fax: 832-825-1281.
These authors contributed equally to this work.