Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-Resistant<i>Mycobacterium tuberculosis</i>M and Ra Strains

Geffner, Laura; Yokobori, Noemí; Basile, Juan I.; Schierloh, Pablo; Balboa, Luciana; Romero, M. Carolina; Ritacco, Viviana; Vescovo, Marisa; Montaner, Pablo González; López, Beatriz; Barrera, Lucía; Alemán, Mercedes; Abatte, Eduardo; Sasiain, María C.; Barrera, Silvia de la

doi:10.1128/iai.00224-09

Cited by 65 publications

(70 citation statements)

References 54 publications

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“…The disease indications for transplantation included hepatitis B virus with or without hepatocellular carcinoma (HCC; 92), hepatitis C virus infection with or without HCC (25), primary biliary cirrhosis (12), alcoholic cirrhosis (8), hepatitis B virus and hepatitis C virus with or without HCC (6), Wilson's disease (4), and other (5).…”

Section: Resultsmentioning

confidence: 99%

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Solitary pulmonary nodule in the liver transplant candidate: Importance of diagnosis and treatment

et al. 2010

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Our objectives were to define the incidence and etiology of solitary pulmonary nodules (SPNs) in patients undergoing living donor liver transplantation (LDLT), describe a diagnostic approach to the management of SPNs in LDLT, and define the impact of SPNs on the overall survival of adult LDLT recipients. Nine patients (9/152, 5.9%) were diagnosed with an SPN on the basis of chest radiography findings during the pretransplant survey. All were male. The mean age was 52 years. All the patients had hepatitis B virus-related cirrhosis with hepatocellular carcinoma. All were asymptomatic for the lung lesion. All underwent contrast-enhanced chest computed tomography (CT) to verify the presence and possible etiology of the SPNs. In 3 cases, CT was used to definitely determine that there was no pulmonary nodule; in 2, CT led to a definite diagnosis of pulmonary tuberculosis. In 4, CT led to a definite identification of an SPN but not to an etiological diagnosis. Two patients underwent outright thoracoscopy and biopsy of their SPNs. Biopsy showed cryptococcosis in both patients. One received a therapeutic trial of an antituberculosis treatment, and repeat CT after 1 month showed a regression in the size of the SPN. A diagnosis of tuberculosis was made. One patient had an inconclusive whole body positron emission tomography scan and subsequently underwent thoracoscopy where biopsy showed tuberculosis. A concomitant malignancy, either primary lung cancer or metastasis from the liver tumor, was not identified. All patients were surviving with their original grafts and were lung infection-free. The overall mean posttransplant follow-up was 54 months (range ¼ 33-96 months). Patients undergoing transplantation require a thorough clinical evaluation to exclude overt and occult malignancies that would preclude the planned procedure. This is important because routine immunosuppression use after transplantation may often result in the body's loss of immunoregulatory functions and thus in a myriad of problems, including oncological and infectious processes. Occult infections may manifest as fulminant, life-threatening sepsis after transplantation.Indeterminate pulmonary nodules in transplant candidates pose both diagnostic and therapeutic

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Section: Resultsmentioning

confidence: 99%

“…Furthermore, experimental T regulatory cell depletion decreases interferon-gamma expression and cytotoxic T lymphocyte activity in TB patients. 25 If it is unchecked post-transplant, the range of clinical diseases extends to extrapulmonary diseases, particularly in the bones, joints, and gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Solitary pulmonary nodule in the liver transplant candidate: Importance of diagnosis and treatment

et al. 2010

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“…89–91 Using an in-vitro killing assay, we showed that depletion of peripheral blood CD4+/FOXP3+ regulatory T cells in patients with drug-sensitive 92 and drug-resistant (unpublished) tuberculosis augmented mycobacterial containment, suggesting an important subversive biological role for these cells. This finding suggests that immunomodulation by manipulation of regulatory T cells (eg, targeting of antagonists for interleukin 2 receptors, autologous transfusion after expansion, infusion of mesenchymal stromal cells, 93 or blocking of other regulatory T-cell functions) 94 might affect disease progression.…”

Section: Pathogenesis and Mechanisms Of Drug-resistant Tuberculosismentioning

confidence: 95%

Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis

Dheda

Gumbo

Gandhi

et al. 2014

The Lancet Respiratory Medicine

258

205

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Extensively drug-resistant tuberculosis is a burgeoning global health crisis mainly affecting economically active young adults, and has high mortality irrespective of HIV status. In some countries such as South Africa, drug-resistant tuberculosis represents less than 3% of all cases but consumes more than a third of the total national budget for tuberculosis, which is unsustainable and threatens to destabilise national tuberculosis programmes. However, concern about drug-resistant tuberculosis has been eclipsed by that of totally and extremely drug-resistant tuberculosis—ie, resistance to all or nearly all conventional first-line and second-line antituberculosis drugs. In this Review, we discuss the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medicolegal aspects of extensively drug-resistant tuberculosis and other resistant strains. Finally, we discuss the emerging problem of functionally untreatable tuberculosis, and the issues and challenges that it poses to public health and clinical practice. The emergence and growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis—and increased funding to strengthen global control efforts, research, and advocacy—even more pressing.

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“…Though early, non-randomised trials indicated potential efficacy as a HDT in multidrugresistant (MDR)-TB [150,151], a subsequent randomised trial involving 110 patients with pansensitive pulmonary TB found no effect [148]. However, as Geffner et al [152] demonstrate in a study including 25 MDR and 20 pansensitive TB patients, MDR strains induce greater Th2 and decreased Th1 responses when compared to pansensitive strains. Thus the mechanism of action of recombinant IL-2 may render it a uniquely efficacious HDT for the treatment of MDR-TB rather than pansensitive disease.…”

Section: Cytokine Modulationmentioning

confidence: 84%

Sharpening nature's tools for efficient tuberculosis control: A review of the potential role and development of host-directed therapies and strategies for targeted respiratory delivery

O'Connor

Gleeson

Fagan-Murphy

et al. 2016

Advanced Drug Delivery Reviews

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Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-ResistantMycobacterium tuberculosisM and Ra Strains

Cited by 65 publications

References 54 publications

Solitary pulmonary nodule in the liver transplant candidate: Importance of diagnosis and treatment

Solitary pulmonary nodule in the liver transplant candidate: Importance of diagnosis and treatment

Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis

Sharpening nature's tools for efficient tuberculosis control: A review of the potential role and development of host-directed therapies and strategies for targeted respiratory delivery

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