Abstract

BackgroundPeritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed.Methods and findingsWe investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%.ConclusionsThe analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.

Highlights

  • Tuberculosis (TB) is one of the world’s most lethal infectious diseases and peritoneal TB resulting from the growth of Mycobacterium tuberculosis complex bacteria in the peritoneum, is the sixth most frequent site of extra-pulmonary involvement

  • Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB

  • We report here on the diagnostic accuracy for rapid diagnosis of peritoneal TB of the percentages of IFN-γ-containing-CD4+ T lymphocytes after a short in vitro stimulation with purified protein derivative (PPD) or two different purified mycobacterial antigens, the heparin-binding haemagglutinin (HBHA) [11] and the early-secreted antigen target-6 (ESAT-6) [12]

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Summary

Introduction

Tuberculosis (TB) is one of the world’s most lethal infectious diseases and peritoneal TB resulting from the growth of Mycobacterium tuberculosis complex bacteria in the peritoneum, is the sixth most frequent site of extra-pulmonary involvement. TB peritonitis frequently occurs in patients with severe underlying medical conditions, such as end-stage renal or liver disease, further adding to the diagnostic difficulty [2,3]. Laboratory blood tests, such as a moderate inflammatory syndrome and elevated carbohydrate antigen-125 concentrations, provide unspecific results. More sensitive diagnosis depends on a highly invasive procedure, which is the peritoneal biopsy performed by laparoscopy providing a positive culture in 92% to 98% of cases [3] This procedure is associated with a significant risk for the patient, is costly and not available in resource-poor countries. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed

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