Current updates in diagnosis of male urogenital tuberculosis

ABSTRACT

Introduction: Urogenital tuberculosis (UGTB) is a common manifestation of extrapulmonary TB (EPTB), which affects both men and women in a ratio of 2:1. Similar to other EPTB types, diagnosis of UGTB is quite challenging owing to atypical clinical presentation and paucibacillary nature of specimens. This review is primarily focused on the current updates developed in the diagnosis of male UGTB.

Area covered: Smear/culture, imaging, histopathology, and interferon-γ release assays are the main modalities employed for detecting male UGTB cases. Moreover, we described the utility of nucleic acid amplification tests (NAATs), including loop-mediated isothermal amplification, PCR, nested-PCR, and GeneXpert (MTB/RIF) assays. The possibility of using other novel modalities, such as immuno-PCR (I-PCR), aptamer-linked immobilized sorbent assay (ALISA), and identification of circulating cell-free DNA (cfDNA) by NAATs were also discussed.

Expert opinion: The current methods used for the diagnosis of male UGTB are not adequate. Therefore, the latest molecular/immunological tools, i.e. Xpert Ultra, Truenat MTB^TM, I-PCR, ALISA, and cfDNA detection employed for the diagnosis of other EPTB forms and pulmonary TB may also be exploited for UGTB diagnosis. Reliable and timely diagnosis of male UGTB may initiate an early start of anti-tubercular therapy that would reduce infertility and other complications associated with disease.

KEYWORDS:

• Male UGTB
• M. tuberculosis
• Renal failure
• Infertility
• IGRAs
• NAATs
• Immuno-PCR
• ALISA
• cfDNA

Article Highlights

• Urogenital TB (UGTB) comprising renal and genital TB, is the second most prevalent form of extrapulmonary TB in developing countries and the third most prevalent form in developed countries.

• Male UGTB is often difficult to diagnose owing to paucibacillary nature of specimens and atypical presentation of disease.

• Diagnosis of male UGTB mostly depends on clinical findings and imaging, though bacteriological tests (smear/culture) almost fail. However, NAATs, such as PCR and GeneXpert are employed as adjunct tests for diagnosing male UGTB.

• GeneXpert is a major innovation in TB diagnostics which simultaneously detects Mtb and rifampin resistance within 2 h. However, Xpert revealed a moderate sensitivity but high specificity in male UGTB cases, thus Xpert could be used as an excellent rule-in test but not as a promising rule-out test for male UGTB diagnosis. Implementation of Xpert Ultra for male UGTB diagnosis may further enhance the sensitivity.

• Notably, there are abundant non-nucleic acid molecules (proteins/lipids, etc.) circulating in bodily fluids of male UGTB patients, which may be detected by novel ultrasensitive techniques, like immuno-PCR (I-PCR) or aptamer-linked immobilized sorbent assay (ALISA).

• Detection of circulating Mtbcell-free DNA (cfDNA) by NAATs in easily accessible samples, i.e. blood/urine of male UGTB cases could be another useful approach, which may develop into apoint-of-care (POC) test.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The financial support provided by ICMR(5/8/5/38/2014-ECD-I), New Delhi, India is being acknowledged. PKM acknowledges CSIR, New Delhi, India for awarding the Emeritus Scientist Fellowship to pursue this study. EK also acknowledges CSIR, New Delhi, India for providing the Junior/Senior Research Fellowship.