Recent updates in diagnosis of abdominal tuberculosis with emphasis on nucleic acid amplification tests

ABSTRACT

Introduction

Abdominal tuberculosis (TB) is a common epitome of extrapulmonary TB (EPTB), wherein peritoneal and intestinal TB are the most prevalent forms. Diagnosis of abdominal TB is a daunting challenge owing to variable anatomical locations, paucibacillary nature of specimens and atypical clinical presentations that mimic other abdominal diseases, such as Crohn’s disease and malignancies. In this review, we made a comprehensive study on the diagnosis of abdominal TB.

Area covered

Various modalities employed for abdominal TB diagnosis include clinical features, imaging, bacteriological tests (smear/culture), histopathological/cytological observations, interferon-gamma release assays and nucleic acid amplification tests (NAATs). Among NAATs, loop-mediated isothermal amplification assay, PCR, multiplex-PCR, nested PCR, real-time PCR and GeneXpert® MTB/RIF were discussed. Identification of circulating Mycobacterium tuberculosis cell-free DNA by real-time PCR within ascitic fluids is another useful approach.

Expert opinion

Several novel molecular/immunological methods, such as GeneXpert Ultra, aptamer-linked immobilized sorbent assay, immuno-PCR (I-PCR) and nanoparticle-based I-PCR have recently been developed for detecting pulmonary TB and several EPTB types, which may also be explored for abdominal TB diagnosis. Precise and prompt diagnosis of abdominal TB may initiate an early therapy so as to reduce the complications, i.e. abdominal pain, ascites, abdominal distension, intestinal obstruction/perforation, etc., and avoid surgical involvement.

Plain Language Summary

Abdominal tuberculosis (TB) is a manifestation of extrapulmonary TB (EPTB), where peritoneal and intestinal TB are two major forms. Diagnosis of abdominal TB is difficult owing to low bacterial load present in clinical samples and non-specific clinical presentations as it mimics other diseases such as inflammatory bowel diseases, abdominal malignancies, etc. Bacteriological tests (smear/culture) almost fail owing to poor sensitivities and it is not always possible to get representative tissue samples for histopathological and cytological observations. In recent years, molecular tests i.e. nucleic acid amplification tests (NAATs), such as PCR/multiplex-PCR (M-PCR), nested PCR and GeneXpert are widely employed. Markedly, PCR/M-PCR and nested PCR exhibited reasonable good sensitivities/specificities, while GeneXpert revealed low sensitivity in most of the studies but high specificity, thus it could assist in differential diagnosis of intestinal TB and Crohn’s disease. Further, novel molecular/immunological tests employed for pulmonary TB and other EPTB types were described and those tests can also be utilized to diagnose abdominal TB. Reliable and rapid diagnosis of abdominal TB would initiate an early start of anti-tubercular therapy and reduce the severe complications.

KEYWORDS:

• Abdominal TB
• peritoneal TB
• intestinal TB
• diagnosis
• imaging
• histopathology
• colonoscopy
• laparoscopy
• NAATs
• I-PCR

Article highlights

• Diagnosis of abdominal tuberculosis (TB) is challenging due to sparse bacterial load in specimens, non-specific clinical presentations, and their close resemblance to other abdominal diseases, such as Crohn’s disease, malignancies, and lymphomas.

• Routine laboratory and bacteriological (smear/culture) tests mostly remain inconclusive as they yield low sensitivities/specificities, thus diagnosis mainly relies on clinical suspicion, histopathological examination (HPE), imaging, and nucleic acid amplification tests (NAATs).

• Among various NAATs, IS6110 nested PCR, M-PCR targeting mpt64+IS6110 and mpt64+IS6110+pstS1 showed promising results. Further, multi-targeted LAMP (using mpt64 and IS6110) exhibited high sensitivity/specificity.

• GeneXpert® MTB/RIF revealed a high specificity but low sensitivity for abdominal TB diagnosis, thus suggesting its role as an excellent rule-in test but not as good rule-out test.

• Detection of circulating cell-free DNA (cfDNA) by real-time PCR within ascitic fluids of abdominal TB cases showed a significantly higher sensitivity than GeneXpert, though high specificity was attained with both the techniques. Identification of circulating cfDNA within easily accessible samples, i.e. plasma/urine of abdominal TB patients may yield a good diagnostic accuracy and develop into a point-of-care (POC) test.

• Several novel molecular/immunological tools, e.g. GeneXpert Ultra, aptamer-linked immobilized sorbent assay (ALISA), immuno-PCR (I-PCR)/real-time I-PCR and nanoparticle-based I-PCR have recently been developed to diagnose pulmonary TB and other extrapulmonary TB (EPTB) types, which can also be utilized for efficient diagnosis of abdominal TB, thus an early start of anti-tubercular therapy (ATT) is initiated that would reduce the complications associated with disease.

Declaration of interests

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This article received financial support from the Indian Council of Medical Research, [5/8/5/38/2014-ECD-I], New Delhi. PK Mehta acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi for awarding the Emeritus Scientist Fellowship to pursue this study. PM acknowledges ICMR and MDU, Rohtak for providing Junior Research Fellowship and University Research Scholarship. BD acknowledges CSIR, New Delhi for providing Research Associate Fellowship.