Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an extremely successful pathogen that adapts to survive within the host. During the latency phase of infection, M. tuberculosis employs a range of effector proteins to be cloud the host immune system and shapes its lifestyle to reside in granulomas, sophisticated, and organized structures of immune cells that are established by the host in response to persistent infection. While normally being restrained in immunocompetent hosts, M. tuberculosis within granulomas can cause the recrudescence of TB when host immunity is compromised. Aside from causing TB, accumulating evidence suggests that M. tuberculosis is also associated with multiple other human diseases, such as pulmonary complications, autoimmune diseases, and metabolic syndromes. Furthermore, it has been recently appreciated that M. tuberculosis infection can also reciprocally interact with the human microbiome, which has a strong link to immune balance and health. In this review, we highlight the adaptive survival of M. tuberculosis within the host and provide an overview for regulatory mechanisms underlying interactions between M. tuberculosis infection and multiple important human diseases. A better understanding of how M. tuberculosis regulates the host immune system to cause TB and reciprocally regulates other human diseases is critical for developing rational treatments to better control TB and help alleviate its associated comorbidities.

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Mycobacterium tuberculosis: An Adaptable Pathogen Associated With Multiple Human Diseases

Diagnosing abdominal tuberculosis remains a great challenge even for experienced clinicians. It is a great mimicker that has unusual presentations. A high index of suspicion is essential for reaching its diagnosis. Clinical and radiological findings of abdominal tuberculosis are non-specific. Herein, we report the lessons we have learned over the last 30 years stemming from our own mistakes in diagnosing abdominal tuberculosis supported by illustrative challenging clinical cases. Furthermore, we report our diagnostic algorithm for abdominal tuberculosis. This diagnostic algorithm will help in reaching the proper diagnosis by histopathology or microbiology. Our diagnostic workup depends on categorizing the clinical and radiological findings of abdominal tuberculosis into five different categories including (1) gastrointestinal, (2) solid organ lesions, (3) lymphadenopathy, (4) wet peritonitis, and (5) dry/fixed peritonitis. The diagnosis in gastrointestinal tuberculosis and dry peritonitis can be reached by endoscopy. The diagnosis in solid organ lesions can be reached by ultrasound-guided aspiration. The diagnosis in wet peritonitis and lymphadenopathy can be reached by ultrasound-guided aspiration followed by laparoscopy if needed. Diagnostic laparotomy should be kept as the last option for achieving a histological diagnosis. Capsule endoscopy and enteroscopy were not included in the diagnostic algorithm because of the limited data of using these modalities in abdominal tuberculosis. They need special expertise, and rarely used in low- and middle-income countries. Furthermore, capsule endoscopy may cause complete intestinal obstruction in small bowel strictures. A definite diagnosis can be reached in only 80% of the patients. Therapeutic diagnosis should be tried in the remaining 20%.

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Diagnosis of abdominal tuberculosis: lessons learned over 30 years: pectoral assay

Background
Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six-month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six-month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers.

Objectives
To compare six-month versus longer drug regimens to treat people that have abdominal TB.

Search methods
We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists.

Selection criteria
We included randomized controlled trials (RCTs) that compared six-month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six-month follow-up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT.

Data collection and analysis
Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta-analyses. We assessed the quality of the evidence using the GRADE approach.

Main results
We included three RCTs, with 328 participants, that compared six-month regimens with nine-month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co-morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow-up after completion of treatment was between 12 and 39 months.

Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens (very low quality evidence). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six-month and nine-month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence). For death, there were 2/150 (1.3%) in the six-month group and 4/144 (2.8%) in the nine-month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence). Only one trial reported on adherence to treatment, with only one participant allocated to the nine-month regimen presenting poor adherence to treatment. We do not know whether six-month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence).

Authors' conclusions
We found no evidence to suggest that six-month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine-month regimens regarding relapse at the end of follow-up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six-month treatment for people with abdominal TB. Larger studies that include HIV-positive people, with long follow-up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question.

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Six‐month therapy for abdominal tuberculosis

Objective
To describe characteristics, presentation, time to diagnosis and diagnostic findings of patients with intestinal tuberculosis (ITB) in a low-burden country.

Method
Retrospective study of 61 consecutive ITB patients diagnosed between 2008-2014 at a large East London hospital.

Results
40 of 61 patients were male. Mean age was 34.6 years. 93% of patients were born abroad, mostly from TB-endemic areas (Indian subcontinent: 88%, Africa: 9%). 25% had concomitant pulmonary TB. Median time from symptom onset to ITB diagnosis was 13 weeks (IQR 3-26 weeks). Ten patients were initially treated for IBD, although patients had ITB. The main sites of ITB involvement were the ileocaecum (44%) or small bowel (34%). Five patients had isolated perianal disease. Colonoscopy confirmed a diagnosis of ITB in 77% of those performed. 42 of 61 patients had a diagnosis of ITB confirmed on positive histology and/or microbiology .

Conclusion
Diagnosis of ITB is often delayed, which may result in significant morbidity. ITB should be excluded in patients with abdominal complaints who come from TB-endemic areas to establish prompt diagnosis and treatment. Diagnosis is challenging but aided by axial imaging, colonoscopy and tissue biopsy for TB culture and histology.

This article is protected by copyright. All rights reserved.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/tmi.12908

Intestinal Tuberculosis: A Diagnostic Challenge

Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12 years in Southeastern Korea. A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB. The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study. Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

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Clinical features and outcomes of abdominal tuberculosis in southeastern Korea: 12 years of experience

Abdominal tuberculosis is an increasingly common disease that poses diagnostic challenge, as the nonspecific features of the disease which may lead to diagnostic delays and development of complications. This condition is regarded as a great mimicker of other abdominal pathology. A high index of suspicion is an important factor in early diagnosis. Abdominal involvement may occur in the gastrointestinal tract, peritoneum, lymphnodes or solid viscera. Various investigative methods have been used to aid in the diagnosis of abdominal tuberculosis. Early diagnosis and initiation of antituberculous therapy and surgical treatment are essential to prevent morbidity and mortality. Most of the patients respond very well to standard antitubercular therapy and surgery is required only in a minority of cases. Imaging plays an important role in diagnosis of abdominal tuberculosis because early recognition of this condition is important. We reviewed our experience with the findings on various imaging modalities for diagnosis of this potentially treatable disease.

Vasudevan Ravisankar

Papers

Abdominal tuberculosis of the gastrointestinal tract: Revisited