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Intestinal tuberculosis [keywords]
- Comparative Functional Genomics and the Bovine Macrophage Response to Strains of the Mycobacterium Genus. [REVIEW]
- Front Immunol 2014.:536.
Mycobacterial infections are major causes of morbidity and mortality in cattle and are also potential zoonotic agents with implications for human health. Despite the implementation of comprehensive animal surveillance programs, many mycobacterial diseases have remained recalcitrant to eradication in several industrialized countries. Two major mycobacterial pathogens of cattle are Mycobacterium bovis and Mycobacterium avium subspecies paratuberculosis (MAP), the causative agents of bovine tuberculosis (BTB) and Johne's disease (JD), respectively. BTB is a chronic, granulomatous disease of the respiratory tract that is spread via aerosol transmission, while JD is a chronic granulomatous disease of the intestines that is transmitted via the fecal-oral route. Although these diseases exhibit differential tissue tropism and distinct complex etiologies, both M. bovis and MAP infect, reside, and replicate in host macrophages - the key host innate immune cell that encounters mycobacterial pathogens after initial exposure and mediates the subsequent immune response. The persistence of M. bovis and MAP in macrophages relies on a diverse series of immunomodulatory mechanisms, including the inhibition of phagosome maturation and apoptosis, generation of cytokine-induced necrosis enabling dissemination of infection through the host, local pathology, and ultimately shedding of the pathogen. Here, we review the bovine macrophage response to infection with M. bovis and MAP. In particular, we describe how recent advances in functional genomics are shedding light on the host macrophage-pathogen interactions that underlie different mycobacterial diseases. To illustrate this, we present new analyses of previously published bovine macrophage transcriptomics data following in vitro infection with virulent M. bovis, the attenuated vaccine strain M. bovis BCG, and MAP, and discuss our findings with respect to the differing etiologies of BTB and JD.
- Tuberculosis in pregnancy:a challenging differential diagnosisfor inflammatory bowel disease. [JOURNAL ARTICLE]
- Ceska Gynekol 2014; 79(4):305-308.
Objective: To describe a case of tuberculosis with intestinal variant in a pregnant woman in the 17th week of pregnancy.Design: Case report.Setting: Department of Obstetrics, Federal University of São Paulo (UNIFESP), São Paulo-SP, Brazil.Conclusion: Tuberculosis is a public health problem that concerns many countries in the world. It was declareda public emergency by the World Health Organization in 2005. Its presence during pregnancy brings maternal risk and fetal impairment if not treated quickly and properly. The intestinal variant is not the most common form of the disease and may be confused with inflammatory bowel diseases, especially Crohns disease. Knowledge of the specific characteristics, combined with a detailed medical history and appropriate diagnostic methods can make all the difference in gestational prognosis. We report the case of a pregnant woman who wrongly underwent treatment for inflammatory bowel disease at another service. After admission to our university hospital, fruitful diagnostic clarification was achieved and the patient was diagnosed and treated for tuberculosis. We describe the details of the investigation and, in particular, review the main characteristics in the literature for differentiating the two diseases.Keywords: tuberculosis, pregnancy, X-ray, colonoscopy, microscopy.
- Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India. [Journal Article]
- United European Gastroenterol J 2014 Oct; 2(5):397-405.
Current methods to establish the diagnosis of intestinal tuberculosis are inadequate.We aimed to determine the clinical features of intestinal tuberculosis and evaluate inflammatory biomarkers in intestinal as well as pulmonary tuberculosis.We recruited 38 intestinal tuberculosis patients, 119 pulmonary tuberculosis patients and 91 controls with functional gastrointestinal disorders between October 2009 and July 2012 for the investigation of clinical features, C-reactive protein (CRP), faecal and serum calprotectin. Faecal calprotectin ≥200 µg/g was used as a cut-off to determine intestinal inflammation of clinical significance. Three patient categories were established: (a) pulmonary tuberculosis and faecal calprotectin <200 µg/g (isolated pulmonary tuberculosis); (b) pulmonary tuberculosis and faecal calprotectin ≥200 µg/g (combined pulmonary and intestinal tuberculosis); (c) isolated intestinal tuberculosis.Common clinical features of intestinal tuberculosis were abdominal pain, fatigue, weight loss and watery diarrhoea. Intestinal tuberculosis patients had elevated median CRP (10.7 mg/l), faecal calprotectin (320 µg/g) and serum calprotectin (5.7 µg/ml). Complete normalisation of CRP (1.0 mg/L), faecal calprotectin (16 µg/g) and serum calprotectin (1.4 µg/ml)) was seen upon clinical remission. Patients with combined pulmonary and intestinal tuberculosis had the highest levels of CRP (53.8 mg/l) and serum calprotectin (6.5 µg/ml) and presented with signs of more severe disease.Calprotectin analysis reveals intestinal tuberculosis in patients with pulmonary tuberculosis and pinpoints those in need of rigorous follow-up.
- Severity of bovine tuberculosis is associated with co-infection with common pathogens in wild boar. [Journal Article]
- PLoS One 2014; 9(10):e110123.
Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under controlled conditions. Furthermore, more research including other important pathogens, such as gastro-intestinal nematodes, will be necessary to complete this picture.
- Visceral fat as a useful parameter in the differential diagnosis of Crohn's disease and intestinal tuberculosis. [Journal Article]
- Intestinal Res 2014 Jan; 12(1):42-7.
Because of the similarities in the clinical presentations of Crohn's disease (CD) and intestinal tuberculosis (ITB), differential diagnosis is critical. Mesenteric adipose tissue hypertrophy and creeping fat are characteristic features of CD. The purpose of this study was to assess the usefulness of visceral fat for the differential diagnosis of CD and ITB.We conducted a retrospective review of 50 patients with findings of CD or ITB between January 2005 and July 2008. Abdominal computed tomography (CT) was performed on all subjects during their first evaluation. The abdominal fat area was assessed using quantitative abdominal CT.The ratio of visceral fat to total fat (VF/TF) was significantly higher in male CD patients than in male ITB patients. The ratio of visceral fat to subcutaneous fat (VF/SF) was also higher in CD patients than in patients with ITB. For a VF/TF cut-off value of 0.46, the sensitivity and specificity for the diagnosis of CD were 42.1% and 93.3% respectively, with positive and negative predictive values of 88.9% and 56.0%, respectively.Measurement of the abdominal fat area using CT can be clinically useful for the differential diagnosis of CD and ITB.
- Intestinal tuberculosis in a child living in a country with a low incidence of tuberculosis: a case report. [Journal Article]
- BMC Res Notes 2014.:762.
Relatively common in adults, intestinal tuberculosis is considered rare in children and adolescents. The protean manifestations of intestinal tuberculosis mean that the diagnosis is often delayed (sometimes even for years), thus leading to increased mortality and unnecessary surgery. The main diagnostic dilemma is to differentiate intestinal tuberculosis and Crohn's disease because a misdiagnosis can have dramatic consequences.A 13-year-old Caucasian, Italian female adolescent attended the Emergency Department complaining of abdominal pain, a fever of up to 38°C, night sweats, diarrhea with blood in stool, and a weight loss of about three kilograms over the previous two months. Physical examination revealed a marked skin pallor and considerable abdominal distension with relevant discomfort in all the abdominal quadrant. Laboratory tests revealed a decreased white blood cell count with anemia and increased C-reactive protein levels. The Mantoux tuberculin skin test was negative. A chest X-ray and an abdominal ultrasonography did not reveal any significant findings. The patient underwent colonoscopy that showed diffuse mucosal congestion and significant blood loss, and laparatomy showed small bowel and colon loops with a whitish appearance. A biopsy of the ileal mucosa revealed inflammation with noncaseating granulomas possibly due to bacterial infection. Given the suspicion of an opportunistic bacterial infection in a child with chronic inflammatory bowel disease (possibly Crohn's disease), treatment with a third-generation cephalosporin was started. However, the abdominal pain, fever and poor general condition persisted and so, after 11 days, the patient underwent total body computed tomography and magnetic resonance imaging of the brain. On the basis of the radiological findings, miliary tuberculosis was suspected and bronchoscopy was performed and resulted positive for Mycobacterium tuberculosis. Miliary tuberculosis was confirmed and an effective treatment with four drugs was started.This case shows that the manifestations of intestinal tuberculosis can be very difficult to diagnose and mimic those of Chron's disease. Total body computed tomography and laparotomy with an intestinal biopsy for the detection of Mycobacterium tuberculosis are the means of avoid the risks of a misdiagnosis in children with unexplained chronic abdominal problems.
- Screening for Imported Diseases in an Immigrant Population: Experience from a Teaching Hospital in Barcelona, Spain. [JOURNAL ARTICLE]
- Am J Trop Med Hyg 2014 Oct 20.
The objective of this study was to describe the screening for imported diseases among an immigrant population. This retrospective observational study was of all of adult immigrants attended at the Tropical Medicine Unit of the Vall d'Hebron Teaching Hospital from September of 2007 to March of 2010. The screening strategy was adjusted by symptoms, country of origin, and length of residence in Europe. Overall, 927 patients were included. The median age was 34.5 years, and 42.1% of patients were male. A diagnosis was made in 419 (45.2%) patients. The most frequent diagnoses were Chagas disease, anemia, latent tuberculosis infection, intestinal parasitosis, hepatitis B virus (HBV) infection, and human immunodeficiency virus (HIV) infection. After screening, more diseases were identified in immigrants from sub-Saharan Africa (new diagnoses in 56.6% of patients) than patients from other geographic areas. The geographic origin and length of residence in a developed country determine the prevalence of diseases; hence, screening protocols must be based on this information.
- Carboxymefloquine, the major metabolite of antimalarial drug mefloquine, induces drug metabolizing enzyme and transporter expression by activation of pregnane X receptor. [JOURNAL ARTICLE]
- Antimicrob Agents Chemother 2014 Oct 13.
Malaria patients are frequently co-infected with HIV and mycobacteria causing tuberculosis, which increases the co-administration of drugs and thereby enhances the risk of pharmacokinetic drug-drug interactions. Activation of pregnane X receptor (PXR) by xenobiotics, including many drugs, induces drug metabolism and transport, thereby possibly resulting in attenuation or loss of the therapeutic response of drugs being co-administered. While several artemisinin-type antimalarial drugs have been shown to activate PXR, data on non-artemisinin-type antimalarials are still missing. Therefore this study aims to elucidate the potential of non-artemisinin antimalarial drugs and drug metabolites to activate PXR. The screening of 16 clinically used antimalarial drugs and six major drug metabolites for binding to PXR, using the two-hybrid PXR ligand binding domain assembly assay, identified carboxymefloquine, the major and pharmacological inactive metabolite of the antimalarial drug mefloquine, as a potential PXR ligand. Two-hybrid PXR-coactivator and -corepressor interaction assays, as well as PXR-dependent promoter reporter gene assays, confirmed carboxymefloquine as a novel PXR agonist, which specifically activated the human receptor. In the PXR-expressing intestinal LS174T cells and in primary human hepatocytes, carboxymefloquine induced the expression of drug metabolizing enzymes and transporters on the mRNA and protein level. The crucial role of PXR for carboxymefloquine-dependent induction of gene expression was confirmed by siRNA-mediated knock-down of the receptor. Thus, the clinical use of mefloquine may result in pharmacokinetic drug-drug interactions by means of its metabolite carboxymefloquine. Whether these in vitro finding are of in vivo relevance has to be addressed in future clinical drug-drug interaction studies.
- Confluent Granulomas and Ulcers Lined by Epithelioid Histiocytes: New Ideal Method for Differentiation of ITB and CD? A Meta Analysis. [Journal Article]
- PLoS One 2014; 9(10):e103303.
There are few widely accepted criteria other than caseation, which has low sensitivity, for differentiating intestinal tuberculosis (ITB) and Crohn's disease (CD).We performed a meta-analysis to evaluate the use of confluent granulomas and ulcers lined by epithelioid histiocytes as histological methods for differentiating ITB and CD, compared with that of caseation.We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library and Chinese Biomedicine Database for all relevant studies on the histological differentiation of ITB and CD. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Study quality and heterogeneity were assessed. Meta-regression analysis and sensitivity analyses were performed.Ten randomized trials involving 316 ITB and 376 CD patients were included. The results showed that analysis of caseation showed an overall weighted area under the curve (AUC) of 0.9966, overall sensitivity and specificity were 0.21 and 1.00, respectively, with a positive likelihood ratio (+LR) of 10.79, negative likelihood ratio(-LR) of 0.82 and DOR of 13.74. Confluent granulomas had a lower overall weighted AUC of 0.9381, sensitivity and specificity were 0.38 and 0.99, respectively, with a +LR of 16.29, -LR of 0.65 and DOR of 26.52. Overall weighted AUC for ulcers lined by epithelioid histiocytes was 0.9017, sensitivity and specificity were 0.41 and 0.94, respectively, with a +LR of 6.46, -LR of 0.54 and DOR of 13.17. Significant heterogeneity was noted for the studies. Meta-regression analysis showed that study source, publication year, size, design and quality did not affect heterogeneity.Confluent granulomas and ulcers lined by epithelioid histiocytes are helpful in distinguishing ITB from CD, which may provide a new method, other than caseating granulomas and acid-fast bacilli, to differentiate ITB and CD in mucosal biopsies.
- [A case of esophageal and intestinal tuberculosis that occurred during treatment of rheumatoid arthritis with etanercept]. [English Abstract, Journal Article]
- Kekkaku 2014 Aug; 89(8):711-6.
An 88-year-old woman with rheumatoid arthritis who had started etanercept treatment in July 2011 was referred to our hospital in February 2012 for right-sided pleural effusion. Chest computed tomography showed right pleural effusion, partial swelling of a calcified mediastinal lymph node, and mid-esophageal thickening of the mucosal wall. Gastroendoscopy showed mid-esophageal ulceration. Histological examination of biopsy specimens from this ulceration revealed noncaseating granulomas with Langhans giant cells. Ziehl-Neelsen staining of this section was positive for acid-fast bacilli. Polymerase chain reaction analysis of gastric juice was positive for Mycobacterium tuberculosis; we therefore diagnosed the patient with esophageal tuberculosis. However, since abdominal computed tomography showed swelling of mesenteric lymph nodes, we also suspected intestinal tuberculosis. Colonoscopy showed multiple ileal erosions; histological analyses of biopsied specimens revealed granulomas with Langhans giant cells, similar to the esophageal findings. We finally diagnosed the patient with both esophageal and intestinal tuberculosis. After anti-tuberculosis treatment, the right pleural effusion disappeared and the abdominal lesions improved. Although mycobacterial involvement of both the esophagus and intestine is rare in immunocompromised and immunocompetent hosts, differential diagnosis of these diseases is likely to become more important.