Insight into diagnosis of female genital tuberculosis

ABSTRACT

Introduction

Female genital tuberculosis (TB) is a common form of extrapulmonary TB (EPTB) with varied clinical presentations, i.e. infertility, pelvic pain, and menstrual irregularities. Diagnosis of female genital TB is challenging predominantly due to paucibacillary nature of specimens and inconclusive results obtained by most of the routine laboratory tests.

Areas covered

This review has briefly summarized the epidemiology, clinical features, and transmission of female genital TB. Commonly used laboratory tests include bacteriological examination (smear/culture), tuberculin skin testing, interferon-γ release assays, imaging, laparoscopy/hysteroscopy, and histopathological/cytological observations. Furthermore, utility of nucleic acid amplification tests (NAATs), like loop-mediated isothermal amplification, PCR, multiplex-PCR, nested PCR, real-time PCR, and GeneXpert® could significantly improve the detection of female genital TB.

Expert opinion

Currently, there is no single test available for the efficient diagnosis of female genital TB, rather a combination of tests is being employed, which yields moderate diagnostic accuracy. The latest modalities developed for diagnosing pulmonary TB and other clinical EPTB forms, i.e. aptamer-linked immobilized sorbent assay, immuno-PCR (I-PCR), analysis of circulating cell-free DNA by NAATs, and identification of Mycobacterium tuberculosis biomarkers within extracellular vesicles of bodily fluids by I-PCR/nanoparticle-based I-PCR, may also be exploited to further improve the diagnosis of female genital TB.

KEYWORDS:

• Female genital TB
• diagnosis
• imaging
• histopathology
• IGRAs
• NAATs
• I-PCR
• ALISA
• cfDNA
• hysteroscopy/laparoscopy

Article highlights

• Female genital tuberculosis (TB) is difficult to diagnose primarily owing to atypical clinical presentations and paucibacillary nature of specimens.

• Routine laboratory tests including bacteriological examination (smear/culture) and histopathology yield low sensitivities. Mostly, female genital TB diagnosis relies on clinical suspicion, interferon-γ release assays (IGRAs), imaging, laparo-hysteroscopy, histopathology, and nucleic acid amplification tests (NAATs).

• Among several NAATs analyzed, TRC4 PCR and multiplex-PCR (M-PCR) targeting IS6110+hsp65+dnaJ revealed good diagnostic efficacy for diagnosing female genital TB.

• GeneXpert® MTB/RIF revealed a high specificity but low sensitivity, thus suggesting that Xpert could be used as an outstanding rule-in test but not as a promising rule-out test for detecting female genital TB cases.

• Markedly, there are abundant non-nucleic acid molecules (proteins, lipids, etc.) circulating within bodily fluids of genital TB patients, which remain unexploited. Recently developed immunological/molecular tools, i.e. aptamer-linked immobilized sorbent assay (ALISA), immuno-PCR (I-PCR) or real-time I-PCR utilized for diagnosing pulmonary TB (PTB) and other extrapulmonary TB (EPTB) types, can also be explored to detect those protein/lipid molecules and may assist in improving the female genital TB diagnosis.

• Detection of Mycobacterium tuberculosis (Mtb) biomarkers within extracellular vesicles (EVs) of bodily fluids of genital TB patients by I-PCR/nanoparticle-based I-PCR or ALISA could be another useful approach, which may translate into an attractive diagnostic kit.

• Detection of Mtb circulating cell-free DNA (cfDNA) by NAATs in easily accessible samples, i.e. urine/plasma of female genital TB cases may yield a good diagnostic efficacy that may develop into a point-of-care (POC) test.

Acknowledgments

The authors are sincerely thankful to Nisha Kapoor, QRG Super Speciality Hospital, Faridabad, India, for providing laparoscopic/hysteroscopic figures of female genital TB patients. PK Mehta acknowledges the Council of Scientific and Industrial Research, New Delhi for awarding the Emeritus Scientist Fellowship to pursue this study.

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

This paper was funded by the Indian Council of Medical Research (5/8/5/38/2014-ECD-I).