Tuberculosis Reactivation In Patients Research Articles

Reactivation of Tuberculosis in Patients with Ankylosing Spondylitis on Tofacitinib Therapy

Reactivation of Tuberculosis in Patients with Ankylosing Spondylitis on Tofacitinib Therapy

57-Year-Old Man With Headache, Vomiting, and Gait Instability

57-Year-Old Man With Headache, Vomiting, and Gait Instability

Mini Review: Reactivation of Tuberculosis in Patients with Solid Cancer

Mini Review: Reactivation of Tuberculosis in Patients with Solid Cancer

Lack of reactivation of tuberculosis in patients with psoriasis treated with secukinumab in a real-world setting of latent tuberculosis infection

Background Some biologics for psoriasis, especially anti-tumor necrosis factor (TNF)-α therapies, may re-activate latent tuberculosis (TBC) infection with consequent morbidity and mortality. However, there is a low reported incidence of conversion to positive TBC status among patients with psoriasis treated with second-generation biologic therapies, particularly anti-interleukin (IL)-17 therapies such as secukinumab. Objectives To evaluate the safety profile of secukinumab in psoriasis patients with latent TBC infection. Methods Real-life data were collected by retrospective chart review on patients with moderate-to-severe psoriasis who showed positivity for TBC screening at baseline and underwent secukinumab treatment for psoriasis at six Italian centers. Patients received secukinumab 300 mg at week 0/1/2/3/4, then every 4 weeks. Results Fifty-nine patients were enrolled; 30.5% also had psoriatic arthritis and other comorbidities were common. At baseline, the mean psoriasis duration was 14.5 years. Ten (17%) patients did not undergo prophylaxis before starting secukinumab. Conversely, isoniazid ± rifampicin or rifampicin alone prophylaxis was administered in 49/59 (83.1%) patients. After a mean treatment duration of 84 weeks, there were no cases of TBC reactivation and no unexpected safety signals. Conclusions Secukinumab use over an extended period was safe in psoriasis patients with latent TBC, even in patients who did not receive chemoprophylaxis.

High Burden of Adverse Drug Reactions to Isoniazid Preventive Therapy in People Living With HIV at 3 Tertiary Hospitals in Uganda: Associated Factors.

HIV is one of the most important risk factors of tuberculosis (TB)-related morbidity and mortality. Isoniazid preventive therapy (IPT) is recommended to prevent latent TB reactivation in patients with HIV. However, due to multiple therapies and comorbidities, these patients are predisposed to adverse drug reactions (ADRs) that lead to increased morbidity and mortality. The aim of this study was to determine the prevalence and associated factors of suspected IPT-linked ADRs in HIV-positive patients using IPT. A cross-sectional study was conducted between February and March 2020 at 3 regional referral hospitals (RRHs) in central Uganda. We sampled 660 HIV-positive patients aged 10 years or older who received IPT between July and December 2019 inclusive. Patients were interviewed using a pretested structured questionnaire, and their treatment records were reviewed. A modified Poisson regression model with clustered robust standard errors was used to identify factors associated with suspected IPT-linked ADRs. The prevalence of the suspected ADRs was 51% (334 of the 660; 95% confidence interval [CI]: 18% to 83%). Patients self-reported 7-fold the number of suspected ADRs documented in the clinical files by the health care workers. Musculoskeletal symptoms were the most frequently experienced reaction (14%), followed by dizziness (13%) and peripheral neuropathy (11%). Serious suspected ADRs were experienced by 12% of the study participants; the most common were hepatotoxicity (26%), dizziness (23%), and neuropathy (17%). Female sex (aPR [adjusted prevalence ratio]: 0.92, 95% CI: = 0.88 to 0.95), study site (aPR: 1.09, 95% CI: = 1.09 to 1.18), level of education (aPR: 0.94, 95% CI: = 0.94 to 0.99), history of TB (aPR: 0.93, 95% CI: = 0.87 to 0.99), good IPT adherence (aPR: 1.16, 95% CI: = 1.05 to 1.29), and use of protease inhibitor (PI)-based antiretroviral therapy (aPR: 1.01, 95% CI: = 1.00 to 1.02) were significantly associated with suspected IPT-linked ADRs. The prevalence of suspected IPT-linked ADRs is high, and hepatotoxicity is the most commonly reported serious suspected ADR. Patients self-reported more suspected ADRs than those documented in clinical files by health care workers. Patient engagement could improve ADR detection and potentially strengthen the pharmacovigilance system. Patients with a high risk of ADR ought to be monitored regularly to enable early detection and management.

Analyzing Tuberculosis Reactivation in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis Treated with Biological Therapy Using Machine Learning Methods

This study is based on the consideration that the patients with rheumatoid arthritis and ankylosing spondylitis undergoing biological therapy have a higher risk of developing tuberculosis. The QuantiFERON-TB Gold test result was the output of the models and a series of features related to the patients and their treatments were chosen as inputs. A distribution of patients by gender and biological therapy, followed at the time of inclusion in the study, and at the end of the study, is made for both rheumatoid arthritis and ankylosing spondylitis. A series of classification algorithms (random forest, nearest neighbor, k-nearest neighbors, C4.5 decision trees, non-nested generalized exemplars, and support vector machines) and attribute selection algorithms (ReliefF, InfoGain, and correlation-based feature selection) were successfully applied. Useful information was obtained regarding the influence of biological and classical treatments on tuberculosis risk, and most of them agreed with medical studies.

ACTIVE TB AFTER THE USE OF TOCILIZUMAB FOR COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Tocilizumab is a humanized anti-IL-6 receptor antibody and inhibits the binding of IL-6 to its receptors, associated with Th17 and Th22 cell differentiation which is critical for anti-mycobacterial activity. It is commonly used in patients with active rheumatoid arthritis. During the COVID-19 pandemic, tocilizumab has been widely used in severe COVID-19 infection with elevated markers of systemic inflammation. We report a case of active tuberculosis after the use of tocilizumab for COVID-19 pneumonia. CASE PRESENTATION: An 80-year-old Asian female with hypertension, coronary artery disease presented to the emergency department(ED) due to a one-day duration of fever, cough, and altered mental status. About three months prior to presentation, she had COVID-19 pneumonia requiring prolong hospitalization which was complicated by acute respiratory distress syndrome. She received tocilizumab, remdesivir, steroids and hydroxychloroquine for COVID-19 infection. Following the hospital stay, she was discharged to a long-term acute care facility, and then went home. She is originally from China and moved to the United States 50 years ago. In the ED she was febrile (100.4°F) and hypoxemic, subsequently placed on 4L of nasal cannula. The laboratory data was remarkable for leukocytosis and lactic acidosis. The chest radiograph showed bilateral reticular nodular patchy opacities. The patient was admitted and empiric antibiotics were started for possible pneumonia. Despite this treatment, her respiratory status deteriorated and she was intubated on day 4, with CT chest (figure1) revealing innumerable bilateral micronodules with centrilobular distribution and tree-in-bud opacities. There were also 2 large cavitary lesions in the right upper lobe. The sputum specimen was sent, which returned positive for Acid-Fast Bacillus. In addition, Mycobacterium tuberculosis PCR on sputum was positive. Therefore, the first-line anti-tuberculosis agents including rifampin, isoniazid, pyrazinamide, and ethambutol were started. The Mycobacterium tuberculosis Complex was isolated on sputum 3 weeks later. DISCUSSION: The data from clinical trials indicate that the use of tocilizumab is associated with a very low or absent risk of tuberculosis reactivation. However, this case highlights the judicious use of tocilizumab in patients who are at high risk of exposure or reactivation such as immigrants from endemic regions, IV drug users and health care workers, etc. In our case, the patient had other factors including severe COVID-18 infection, use of steroids, prolonged hospital stay, and malnutrition which might compromise the immune system, and predispose to active tuberculosis. CONCLUSIONS: We suggest that tests be performed to rule out latent tuberculosis in selected patients prior to tocilizumab use and monitor all patients for active tuberculosis during treatment. REFERENCE #1: Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180(3):1962-70. REFERENCE #2: Cantini F, Nannini C, Niccoli L, Petrone L, Ippolito G, Goletti D. Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics. Mediators Inflamm. 2017;2017:8909834. REFERENCE #3: Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis. 2011;70(12):2148-51. DISCLOSURES: No relevant relationships by Goutham Dronavalli, source=Web Response No relevant relationships by Sungryong Noh, source=Web Response

1636. Risk of Latent Tuberculosis Reactivation in Patients Treated with Checkpoint Inhibitors Immunotherapy Compared to Other Anti-Cancer Therapies including Hematopoietic Cell Transplantation

BackgroundThe risk of latent tuberculosis infection (LTBI) reactivation in cancer patients during checkpoint inhibitor immunotherapy (CPI) remains largely unknown. We sought to evaluate LTBI therapy and outcomes between cancer patients receiving CPI versus conventional chemotherapy (CC) and hematopoietic cell transplantation (HCT) recipients.MethodsWe conducted a retrospective cohort study of adult patients with LTBI (positive T-SPOT TB test) at MD Anderson Cancer Center between April 2016 and May 2020, who received CPI or combined with other conventional chemotherapy. Thereafter we compared each group to patients treated with other anti-cancer therapies including CC alone or HCT.ResultsWe identified 106 patients with LTBI, who were analyzed into 3 distinct groups: CPI (32 patients, 30%) CC alone (37 patients, 35%), and HCT (37 patients, 35% (7 autologous versus 30 allogeneic). The majority of patients in the CPI group (97%) had solid tumors compared to 54% in the CC group. Nivolumab was the most commonly used CPI agent in 13 patients (40%), followed by pembrolizumab 10 pts (31%). In the CPI group, 20 pts (62%) received LTBI therapy that included Isoniazid (INH), versus 18 patients (49%) in the HCT group and 16 patients (43%) in the CC group (p=0.26). Only 3 patients (CC group) had TB reactivations (8%; p=0.11). None of these 3 patients had received LTBI therapy or corticosteroids prior to the diagnosis. Immune-related adverse effect (IrAEs) were reported in 11 pts (34%) patients, and 9 (82%) of them received corticosteroids. Out of 20 of CPI patients whom received INH, 4 (20%) developed possible INH-induced liver toxicities leading to interruption of medication versus 1 (6%) patient which had mild hepatitis in CC group versus none of HCT patients (p=0.09).ConclusionOur data suggest that latent tuberculosis reactivation remains rare, especially in the severely immunocompromised patients on CPI, CC and steroids. However, hepatotoxicity is relatively common in patients treated with CPI and INH. Therefore, caution and close laboratory and clinical monitoring is required to avoid significant hepatic injury and interruption of LTBI therapy and lifesaving oncological therapy.Disclosures Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

Association of Secukinumab Treatment With Tuberculosis Reactivation in Patients With Psoriasis, Psoriatic Arthritis, or Ankylosing Spondylitis

Approximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics. To assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. This pooled cohort study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018. Reporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years). A total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported. This study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.

No reactivation of tuberculosis in patients with latent tuberculosis infection receiving ixekizumab: A report from 16 clinical studies of patients with psoriasis or psoriatic arthritis

No reactivation of tuberculosis in patients with latent tuberculosis infection receiving ixekizumab: A report from 16 clinical studies of patients with psoriasis or psoriatic arthritis

Risk of tuberculosis reactivation during interleukin-17 inhibitor therapy for psoriasis: a systematic review.

Immunosuppressive therapies, effective in treating inflammatory disorders such as psoriasis, increase the risk of serious infections, such as tuberculosis (TB). For example, tumour necrosis factor (TNF)-alpha inhibitors significantly increase the risk of TB reactivation in patients with latent TB infection (LTBI), which has led clinicians to routinely test for TB prior to initiation of these medications. This protocol has since extended to other, newer immunomodulatory therapies for psoriasis, such as interleukin (IL)-17 inhibitors, including secukinumab, ixekizumab and brodalumab. We conducted a systematic review to examine whether there is any evidence that IL-17 inhibitor therapy for psoriasis increases the risk of TB reactivation. Using PubMed and EMBASE, our literature search resulted in 139 total articles. After manually reviewing each article for the discussion of IL-17 inhibitors for psoriasis, with data originating from clinical trials, and assessment for incidence of TB reactivation, 23 articles met the full inclusion criteria for our review. Overall, we found no cases of TB reactivation in patients treated with IL-17 inhibitors for psoriasis. This suggests that IL-17 inhibitors may be safely used in psoriasis patients with LTBI who receive appropriate LTBI treatment. However, long-term real-world studies are warranted to further evaluate this risk.

Genitourinary Tract Infection Due to Mycobacterium avium intracellulare Complex Infection in Pretransplant Setting With Recurrence Following Transplant: A Case Report

Genitourinary (GU) tract infection with Mycobacterium avium intracellulare complex (MAI) is very rare and, to our knowledge, has never been reported in the solid organ transplant literature. Case DescriptionA 61-year-old Somali-born woman had a history of liver cirrhosis due to chronic hepatitis C infection. She was diagnosed as having and treated for latent tuberculosis infection and GU tract infection due to MAI. She received a total of 17 months antimycobacterial therapy consisting of azithromycin, ethambutol, and moxifloxacin. Within 5 months of the initiation of antimicrobial therapy, there was documented sterilization of urine mycobacterial cultures. Liver and kidney transplant was performed 3 months after finishing the treatment course. One year following transplant, GU tract infection due to MAI recurred. She declined further diagnostic testing as well as mycobacterial therapy. She died 15 months following transplant for reasons not related to infections. ConclusionThe treatment of MAI infection in solid organ transplant candidates and recipients is challenging, and the duration of therapy in this population is not known. The recurrence of infection following transplant in this case may argue in favor of a duration that extends beyond the date of transplant. The combination of a fluoroquinolone and ethambutol may successfully prevent reactivation of tuberculosis in patients with history of latent tuberculosis infection and deserves further evaluation.

Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics.

Tuberculosis (TB) still represents an important issue for public health in underdeveloped countries, but the use of antitumor necrosis factor agents (anti-TNF) for the treatment of inflammatory rheumatic disorders has reopened the problem also in countries with low TB incidence, due to the increased risk of TB reactivation in subjects with latent tuberculosis infection (LTBI). Over the last 5 years, several non-anti-TNF-targeted biologics have been licensed for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. We reviewed the epidemiology of TB, the role of different cytokines and of the immune system cells involved in the immune response against TB infection, the methods to detect LTBI, and the risk of TB reactivation in patients exposed to non-anti-TNF-targeted biologics. Given the limited role exerted by the cytokines different from TNF, as expected, data from controlled trials, national registries of biologics, and postmarketing surveillance show that the risk of TB reactivation in patients receiving non-anti-TNF-targeted biologics is negligible, hence raising the question whether the screening procedures for LTBI would be necessary.

Latent tuberculosis infection in patients with chronic plaque psoriasis who are candidates for biological therapy.

Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to biological therapy. To investigate the prevalence of LTBI in patients with psoriasis who are candidates for biological therapy. LTBI was investigated in patients with moderate-to-severe psoriasis (n = 243), Crohn disease (n = 64) or rheumatoid arthritis (RA) (n = 56) and in healthcare workers (n = 1683). LTBI diagnosis was based on positive QuantiFERON-B Gold In-Tube (QFT-GIT) in vitro assay without any clinical, radiological or microbiological evidence of active tuberculosis. LTBI was diagnosed in 8.2% of patients with psoriasis, 7% with Crohn disease and 9% with RA, and in 8.8% of healthcare workers (P = 0.9). Patients with psoriasis who also had LTBI (n = 20) received a 9-month prophylaxis with isoniazid (5 mg kg(-1) daily). None of these patients developed active tuberculosis infection after receiving biological therapy (etanercept, adalimumab, infliximab or ustekinumab) for 37 ± 32 weeks (mean ± SD). All patients with psoriasis were retested for LTBI after 31 ± 1.7 months. Five of the 20 patients with LTBI presented QFT-GIT reversion and two patients out of 243 (0.8%) had QFT-GIT conversion and received antibiotic prophylaxis. The prevalence of LTBI in patients with psoriasis is similar to that in patients with Crohn disease or RA and in healthcare workers. Prophylaxis with isoniazid is effective in preventing tuberculosis reactivation in patients with LTBI receiving biological therapy.

Lactobacillus Rhamnosus Sepsis in an Immunosuppressed Patient with Tuberculous Meningitis and Myeloradiculitis

Portugal has reduced the incidence of the disease in last year’s, but has an incidence that surpasses the average in Europe. The risk of reactivation of latent tuberculosis in patients about to undergo immunosuppressive and immunomodulatory therapy is high, and therefore, screening and treatment is mandatory in order to avoid the evolution of the disease from latent to active, with severe forms often difficult to treat. We report a case of a 37 years old female, previously medicated with prednisolone and mycophenolate mofetil for a bullous pemphigus until the diagnosis of disseminated tuberculosis. In the course of the disease, a central venous catheter was placed for total parenteral nutrition due suspicion of poor absorption of antituberculous drugs. The patient had an endocarditis and septic thrombophlebitis with bacteremia due to Lactobacillus rhamnosus and difficult to treat tuberculosis complicated with meningomyeloradiculitis, which resulted in paraplegia associated with a neurogenic bladder.

Diagnosis of tuberculosis in patients with psoriasis: the need for a modified approach

To the Editors: We read with interest the TBNET consensus statement on the diagnosis and treatment of tuberculosis (TB) in patients screened for tumour necrosis factor (TNF)-α antagonist therapy [1]. Admittedly, accumulated evidence during the last decade demonstrates that adherence to such guidelines has minimised the risk of TB reactivation in patients receiving immunosuppressive regimens, including anti-TNF-α therapy. For TNF-α antagonists specifically, targeted preventive chemotherapy prior to the onset of therapy has significantly reduced the risk of progression of latent TB infection (LTBI) to overt disease, yet at the cost of increased risk for significant treatment-associated toxicity. Thus, in an effort to avoid possible over-treatment prior to treatment with TNF-α antagonists and to accurately identify patients who would benefit from anti-TB treatment, patient cohorts inherently predisposed to overdiagnosis of LTBI should be identified. In the TBNET consensus statement, the author panel concludes: “Screening for latent infection and preventive chemotherapy against TB should not be different for patients with different underlying disease […] who are candidates for …

How tumour necrosis factor blockers interfere with tuberculosis immunity

Tumour necrosis factor (TNF) is a potent inflammatory cytokine that plays an important role in immunity to numerous bacterial infections, including Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) in humans. Infliximab, adalimumab, certolizumab pegol and etanercept are anti-TNF agents used to treat a range of inflammatory/autoimmune diseases, such as rheumatoid arthritis. The use of some of these drugs has been linked to reactivation TB. In addition to blocking TNF-mediated immune responses, some anti-TNF drugs have been found to interfere with innate immune responses, such as phagolysosomal maturation and monocyte apoptosis, as well as cell-mediated responses, including interferon-gamma secretion by memory T cells, complement-mediated lysis of Mtb-reactive CD8+ T cells and increased regulatory T cell activity. This review summarizes some of the reported effects of TNF blockers on immune cell responses in the context of the observed clinical data on TB reactivation in patients on anti-TNF therapy.

Reactivation of pulmonary tuberculosis in malignancy.

Deterioration of immunity due to local or systemic effects of the tumor itself and/or administered chemotherapeutics or radiotherapy may play roles in the reactivation of tuberculosis, increasing the mortality in patients with various malignancies. In a country with a high prevalence of tuberculosis such as Turkey, most people have inactive tuberculous lesions and tuberculin test positivity. Therefore, a prospective study was carried out to investigate the frequency of tuberculosis reactivation in patients with a malignancy. Seventy-three patients with a malignancy and undergoing diagnostic fiberoptic bronchoscopy were enrolled in the study during a 2-year period (1993-1995). Bronchoscopic biopsies and cytologic materials were obtained. Bronchoalveolar lavage fluids, bronchial washings, and pre- and postbronchoscopic sputum specimens were also evaluated for acid-fast bacilli. A diagnosis of tuberculosis was based on smear and/or culture positivity for acid-fast bacilli. The mean age of the patients was 56.2 +/- 13.6 years, with a male/female ratio of 69/4. The biopsy proven malignancies were as follows: primary lung carcinoma (n = 66, 90.4%), lymphoma (n = 5, 6.8%), metastatic breast adenocarcinoma (n = 1, 1.4%), and acute myelocytic leukemia (n = 1, 1.4%). Thirty-one of all patients had findings compatible with tuberculosis on radiology. The sputa and bronchial washing specimens were smear negative in all patients. Acid-fast bacilli were grown on culture in 6 patients (8%) (primary lung cancer, n = 5; non-Hodgkin lymphoma, n = 1). Four of these 6 patients had positive radiology for tuberculosis. These subjects were treated with a three- or four-drug anti-tuberculosis regimen. Two months later, smears remained acid-fast bacilli negative, or no bacilli were grown on culture. The possibility of coexisting tuberculosis should be kept in mind in patients with a malignancy, especially those with lung carcinoma in countries with a high prevalence of tuberculosis. Pulmonary infections encountered in such patients should raise the suspicion of tuberculosis reactivation, and in addition to direct microscopic evaluation, sputum specimens and materials obtained by fiberoptic bronchoscopy should be cultivated for tuberculosis. Three-four-drug anti-tuberculosis regimens should be given, especially in countries with high drug-resistance rates for eradicating tuberculosis.

Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis.

Infliximab is a chimeric monoclonal antibody that binds to tumour necrosis factor-alpha (TNFalpha) and neutralises its effects. TNFalpha plays an important role in the development of both Crohn's disease and rheumatoid arthritis. In a large, double-blind, randomised study involving patients with active, refractory Crohn's disease, significantly more recipients of intravenous infliximab, compared with placebo, achieved a clinical response after 4 weeks' follow-up. Moreover, infliximab administration was associated with a rapid improvement in endoscopic and histological findings in clinical trials involving patients with active, refractory Crohn's disease. The results of the A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen (ACCENT) I study showed that maintenance infliximab therapy prolonged response and remission in patients with moderate to severe Crohn's disease. In patients with enterocutaneous fistulae associated with Crohn's disease who were involved in a double-blind, randomised study, significantly more patients who received multiple infusions of infliximab, compared with placebo, experienced a > or=50% reduction from baseline in the number of draining fistulae at > or =2 consecutive study visits. In patients with active rheumatoid arthritis refractory to treatment with methotrexate who were enrolled in a large, double-blind, randomised study [the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study], American College of Rheumatology (ACR) 20, 50 and 70% response rates were seen in significantly more patients who received multiple infusions of infliximab plus methotrexate, compared with methotrexate plus placebo, after 30 and 54 weeks' treatment. Moreover, the ACR 20% response rate was maintained after 102 weeks' treatment. In addition, significantly less radiographic progression was seen in infliximab plus methotrexate, compared with methotrexate plus placebo, recipients after 54 weeks' treatment. Infliximab therapy was also associated with improvements in health-related quality of life in patients with Crohn's disease or rheumatoid arthritis. Infliximab was generally well tolerated in clinical trials with the most common adverse events including upper respiratory tract infection, headache, nausea, coughing, sinusitis and diarrhoea. Infliximab therapy may be associated with an increased risk of reactivation of tuberculosis in patients with latent disease. In conclusion, infliximab is an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in patients with Crohn's disease who have fistulae. Moreover, infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying antirheumatic drugs, in terms of reducing symptoms and signs, improving physical function and delaying the progression of structural damage.

Exogenous Reinfection with Tuberculosis on a European Island with a Moderate Incidence of Disease

The frequency and determinants of exogenous reinfection and of endogenous reactivation of tuberculosis in patients previously treated are poorly understood. In Gran Canaria Island, Spain, between 1991 and 1996, 962 tuberculosis cases were confirmed by culture. Drug susceptibility testing was performed on available bacterial isolates and IS6110-based RFLP genotyping was carried out. Twenty-three patients (2.4%) had two positive cultures separated by at least 12 mo, 18 of whom had bacterial DNA available for genotypic analysis. The initial and final isolates from eight (44%) were different genotypes, indicating exogenous reinfection. Six of them were retreated after cure and two retreated after default. Six were HIV seronegative and two were HIV seropositive. Endogenous reactivation was seen in the remaining 10 patients of whom eight were retreated after default and two after cure. Three of the eight (38%) being retreated after default developed multidrug resistance. One genotype was responsible for a second episode of tuberculosis in five cases, three exogenous reinfections and two endogenous reactivations. In the context of a moderate incidence of tuberculosis, exogenous reinfection is an important cause of TB recurrence, even in HIV-seronegative patients.