Given the diagnostic delay inherent in the sole reliance on sputum and urine culture for suspected miliary tuberculosis1 clinicians should, in future, consider adjunctive use of molecular strategies2–6 either to prove that miliary pulmonary shadowing is attributable to mycobacterial bacteraemia or to raise the index of suspicion for other culprit pathogens in the event of nondiagnostic molecular results. In a study which enrolled 32 adults with proven tuberculosis (either localized or disseminated), Mycobacterium tuberculosis DNA was detected in the peripheral blood by polymerase chain reaction (PCR) in 82% of human immunodeficiency virus (HIV)-positive subjects and in 33% of HIV-negative subjects.2 Furthermore, PCR was positive in all cases of disseminated disease in both HIV-positive (six cases) and HIV-negative subjects (two cases).2 Urine-based molecular detection of M. tuberculosis is an alternative diagnostic strategy,3 given the fact that the kidneys serve as a filter to trap M. tuberculosis bacilli in those with mycobacteremia.4 In a study which enrolled patients with pulmonary tuberculosis, others with extrapulmonary tuberculosis, but none with disseminated tuberculosis, urine-based nested PCR generated an overall sensitivity of 29.6% and specificity of 72.6%, for the diagnosis of tuberculosis, with no significant difference between HIV-positive and HIV-negative subjects.3 Another urine-based strategy is the quantification of lipoarabinomannan, a breakdown product of the M. tuberculosis cell wall.5 Among HIV-negative subjects this test had a sensitivity of 20% and specificity of 100% for diagnosing definite disseminated tuberculosis.5 Diagnostic rates are improved by combining urine-based PCR with evaluation of urinary lipoarabinomannan.6 In a study which exclusively enrolled HIV-positive subjects, 88% of patients with blood culture-positive M. tuberculosis also tested positive with this twin urine-based diagnostic strategy.6 Mimics of miliary tuberculosis include disseminated cryptococcosis, even in HIV-negative subjects.7 Exceptionally, miliary tuberculosis may coexist with pulmonary cryptococcosis.8 Conflict of interest: None declared. References 1 Matsuura H, Nakatsu M. Miliary tuberculosis. QJM 2017; 110: 683. Google Scholar CrossRef Search ADS PubMed 2 Folgueira L, Delgado R, Palenque E, Aguado JM, Noriega AR. Rapid diagnosis of Mycobacterium tuberculosis bacteremia by PCR. J Clin Microbiol 1996; 34: 512– 5. Google Scholar PubMed 3 Makiani MJ, Davoodian P, Baghershiroodi M, Nejatizadeh AA, Fakkhar F, Zangeneh M, et al. Urine-based nested PCR for the diagnosis of Mycobacterium tuberculosis; A comparative study between HIV-positive and HIV-negative patients. Jundishapur J Microbiol 2016; 9: e35634. Google Scholar PubMed 4 Lawn SDS, Kerkhoff AD. Rapid diagnosis of TB in HIV-positive in patients with M. tuberculosis bacteremia in Sub-Saharan Africa. Int J Tuberc Lung Dis 2015; 19: 1557– 9. Google Scholar CrossRef Search ADS PubMed 5 Suwanpimolkul G, Kawkitinarong K, Manosuthi W, Sophonphan J, Gatechompol S, Ohata PJ, et al. Utility of urine lipoarabinomannan(LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: a prospective TB cohort from Thailand Big City TB Research Network International. J Infect Dis 2017; 59: 96– 102. 6 Kerkhoff AD, Barr AD, Schutz C, Burton R, Nicol MP, Lawn SD, et al. Disseminated tuberculosis among hospitalised HIV patients in South Africa: a common condition that can be rapidly diagnosed using urine-based assays. Sci Rep 2017; 7: 10931. Google Scholar CrossRef Search ADS PubMed 7 Severo C, Bruno RM, Oliviera FDM, Teixeria PZ, Hochhegger B, Severo LC. A case of miliary pulmonary cryptococcosis and review of literature. Mycopathologia 2015; 179: 313– 5. Google Scholar CrossRef Search ADS PubMed 8 Kakeya H, Izumikawa K, Yamada K, Obata Y, Nishino T, Takazono T, et al. Three cases of concurrent infection with Mycobacterium tuberculosis and Cryptococcus neoformans. Intern Med 2014; 53: 1685– 92. Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: email@example.com
QJM: An International Journal of Medicine – Oxford University Press
Published: Mar 1, 2018
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