Cellular Immune responses during latent tuberculosis : immunodiagnosis and correlates of protection
Leyten, E.M.S.
Citation
Leyten, E. M. S. (2008, October 8). Cellular Immune responses during latent tuberculosis : immunodiagnosis and correlates of protection. Retrieved from https://hdl.handle.net/1887/13137
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/13137
Note: To cite this publication please use the final published version (if applicable).
Chapter 7
A patient with de novo
tuberculosis during anti-TNF-α therapy illustrating diagnostic
pitfalls and paradoxical response to treatment
Sandra M. Arend1, Eliane M.S. Leyten1, Willeke P.J. Franken1, Erik M. Huisman2, Jaap T. van Dissel1
1Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands 2Municipal Health Service (GGD), The Hague, The Netherlands
Clinical Infectious Diseases 2007;45(11):1470-5
ABSTRACT
In 2005, a 24-y-old man with Crohn’s disease who was treated with infliximab since several months was exposed to a case of smear-positive tuberculosis (TB). Soon after exposure he complained of malaise, dry cough and weight loss. Despite a normal chest radiography and negative tuberculin skin test, TB disease was considered the most likely diagnosis. Quantiferon-TB Gold in-tube assay was positive. Acid fast staining and PCR on broncho-alveolar lavage fluid were negative but M. tuberculosis was cultured. After initiation of four antitubercular drugs and discontinuation of infliximab, the patient developed an immune reconstitution syndrome accompanied by enlarged mediastinal lymph nodes and multiple intrapulmonary miliary lesions. This case of de novo TB dur- ing anti-TNF-α treatment illustrates the uncharacteristic presentation, elusiveness of the diagnosis and that discontinuation of anti-TNF-α treatment can be accompanied by an immune reconstitution syndrome similar to that observed in HIV-infected individuals with TB.
Chapter 7 INTRODUCTION
Treatment with antagonists of tumour necrosis factor α (anti-TNF) have made a major impact on the treatment of several disabling inflammatory disorders such as rheumatoid arthritis (RA) and Crohn’s disease. In 2001 it was first reported that these drugs impor- tantly increase the risk of reactivation tuberculosis (TB) [1, 2]. TB can be difficult to diag- nose in that setting and the response to treatment can be unpredictable [3, 4]. Therefore, screening for the presence of latent TB infection is now routinely done before starting such treatment [5-7]. Nevertheless, TB continues to be reported in patients during anti- TNF treatment [8]. In part, this may be related to the limited sensitivity of the tuberculin skin test in patients who are already immunosuppressed by previous treatment [7, 9].
In addition, de novo infection can occur which obviously cannot be prevented through screening. This case report illustrates various clinical pitfalls and complications that can be encountered in patients with TB during anti-TNF treatment.
CASE REPORT
July 2005, a 24-y-old man with Crohn’s disease since 1998 was referred to our hospital (Patient A). He was born in the Netherlands of Capeverdian parents. He had been treated with azathioprine since several years, intermittently in combination with prednisone in varying dosages. After negative screening with a tuberculin skin test (TST) and chest radiography in August 2004 he received four dosages of TNF-α blocking agent infliximab (Remicade®) between August 2004 and May 2005, in combination with prednisone 10 mg daily. On July 11th 2005 he visited the Municipal Health Service as part of a contact in- vestigation because a Capeverdian colleague (Patient B) had been diagnosed with smear- positive (Bronckhorst +5) pulmonary TB. They had car-pooled to work for one hour every working day during the previous two weeks. The chest radiography was reported as
‘normal’ and unchanged compared to before starting anti-TNF treatment. The TST was not done as it was considered unreliable because he used immunosuppressive drugs and the patient was referred to our hospital for expert consultation.
The patient reported fatigue, night sweats and dry cough since several weeks and had noted weight loss of 3 kg, but no fever. On physical examination he appeared moderately ill and had a dry cough. Laboratory results showed an elevated erythrocyte sedimention rate (ESR) of 114 mm/first h, moderate anemia (hemoglobin 7.8 mmol/L) and elevated lactacte dehydrogenase of 569 IU/L (normal <450). Because anti-TNF is known to mask clinical symptoms and signs of infections, TB disease was strongly suspected despite the negative radiographic findings. The TST was performed resulting in 0 mm induration but the QuantiFERON-TB Gold in tube assay (Cellestis Ltd., Carnegy, Australia), an in-vitro
1 3 4
July 2005 AugustSeptAugust 2004
Infliximab Exposure Colleague smear +5 TB They had travelleddaily in the same car
2 HRZE azathioprine150 mg fever Bronchoscopy/BAL ZN-PCR- Culture: MTB+ after 2 weeks
M. Crohn since 1998 QuantiFERONTB Gold POSITIVE: 3.48 IU/mL
Exposure?
weight loss dry cough Clinical course Prolonged but finally successful treatment of TB Persistent radiographic abnormalities remained
Screening TST: 0 mm X-chest: normal No LTBI
10 HR Immune reconstitution syndrome Cough & weight loss Elevated liver enzymes X-chest: mediastinalLymphadenopathy CT: idem plus miliaryintrapulmonary lesions
Clinical work-up ESR: 114 mm TST:0 mm X-chest: unchanged Before anti-TNF22-07-200523-08-2005
2006 5
2
prednisone 10 mg* #
* 6 Figure 1. Time line of clinical course. * Indicates intermittent episodes of glucocorticosteroid treatment. # Boxed numbers indicate clinical features representing the learning points of the case: (1) Screening for latent TB infection may be insensitive in patients already using immunosuppressive drugs and are ineffective with regard to future TB exposure. (2) Primary infection in patients during anti-TNF treatment carries a high risk of immediate progressive and disseminated TB. (3) Radiographic features and skin testing may be false negative in this setting. (4) A novel blood-based TB specific in vitro assay was positive, thus helped to detect TB infection. These tests can be false nega- tive, however, and if positive cannot differentiate between TB disease and latent TB infection. (5) Direct results of broncho-alveolar lavage may be negative, yet culture can be positive. (6) Treatment of TB in association with discontinuation of anti-TNF treatment may lead to severe immune reconstitution disease with clinical and radiographic features. Abbreviations: BAL; broncho-alveolar lavage, HRZE; isoniazide (H), rifampin (R), pyrazinamide (Z), ethambutol (E), LTBI; latent TB infection, MTB; Mycobacterium tuberculosis, TB; tuberculosis, TST; tuberculin skin test, ZN; Ziehl-Neelsen staining.
Chapter 7 whole blood assay for detection of interferon-γ production in response to Mycobacte-
rium tuberculosis specific antigens, was positive (3.48 IU interferon-γ/mL). Acid-fast staining and PCR for M. tuberculosis complex on broncho-alveolar lavage fluid were negative. The clinical course is shown in Figure 1. Awaiting culture results, treatment for TB with four drugs was started while infliximab was withheld. After three weeks, the BACTEC MGIT 960 (BD Biosciences, Sparks, Md) culture (fluid medium) became positive for fully susceptible M. tuberculosis with an identical IS6110 restriction fragment length polymorphism (RFLP) fingerprint pattern as that of the isolate obtained from his colleague (Figure 2), indicating primary progressive or de novo TB infection.
Several days after starting TB treatment, his fatigue increased and he now for the first time developed a fever up to 39 ºC. Two weeks into treatment the fever had subsided but his weight had further decreased to 49 kg while his weight before this episode had been 56 kg, the dry cough was now continuous and he noticed chest pain on inspiration.
Serum transaminases were normal at that time. Chest radiography now revealed medi- astinal lymphadenopathy while a CT scan in addition showed multiple intrapulmonary miliary nodules. One month after starting treatment for TB, three sputa were auramine positive, with +1 in Ziehl-Neelsen, and became culture positive with still fully susceptible M. tuberculosis. No other infection was diagnosed and the clinical deterioration was at- tributed to an immune reconstitution syndrome. January 2006, the cough had finally stopped. After a prolonged illness the clinical course was favorable but a chest radiograph still showed abnormalities with persistent hilar lymphadenopathy and intrapulmonary nodules at the end of 12 months treatment. These had improved but not yet completely resolved one year later. Limited activity of Crohn’s disease allowed gradual discontinua- tion of all immunosuppressive drugs and thus far there has been no need for restarting anti-TNF treatment.
NLA000501283 NLA000501299
Colleague (patient B) Patient A
Figure 2. RFLP fingerprint pattern of M. tuberculosis isolates.
IS6110 restriction fragment length polymorphism genotype of Patient A and his colleague (patient B) showing identical patterns
DISCUSSION
This report illustrates several remarkable and clinically relevant aspects of TB occurring during treatment with TNF antagonists. It demonstrates the occurrence of de novo TB after starting TNF antagonists, potentially rapid progression to active TB following ex- posure, negative radiographic features despite disseminated lung disease, the finding of a false-negative TST result in association with a positive result of a TB-specific whole blood assay and finally a paradoxical response to antitubercular agents.
Limitations of screening before starting TNF antagonists
Reactivation TB during treatment with TNF antagonists is a now well-recognized clinical entity and the implementation of recommendations regarding the management of latent TB infection has importantly decreased the TB rate among anti-TNF treated patients despite the well-known limitations of the TST [10]. However, even optimal screening and treatment for latent TB before starting anti-TNF does not prevent the occurrence of de novo TB following exposure at any later time point. In that regard, it has been suggested to perform annual TSTs [11]. The prevalence of positive TST results in native Dutch individuals in our patient’s age category is around one percent, indicating that the popu- lation risk of exposure is generally low. In certain settings such as among immigrants, homeless persons, drug abusers, prison inmates or those who have contact with any of these groups, the risk of TB exposure is higher. Our patient was infected by a colleague and the exposure could have been neither foreseen nor prevented. Genetic fingerprinting of the M. tuberculosis isolate provided conclusive evidence of the recent transmission.
Empirical treatment of latent TB infection in patients receiving anti-TNF treatment and who have been in close contact with a proven smear-positive case of TB would carry the risk of treating subclinical TB disease with monotherapy and subsequent development of drug resistance. A thorough clinical evaluation is therefore warranted in this setting.
Rapid progression to active TB following exposure
Differentiation between primary and reactivation TB should take into account variables such as time between anti-TNF and development of TB disease or recognized exposure to a case of smear-positive TB as was clearly the case in our patient. The clinical course in our patient underscores that TNF antagonists can predispose for early and rapid progres- sion following TB exposure. The absolute risk of TB disease following primary exposure during TNF antagonists is not known but is most likely very high. In persons without im- mune defects, the lifetime risk of TB disease is thought to be ten percent with the majority of the cases occurring within one year following infection. Available data on the risk of TB disease in immunocompromised patients all refer to the risk of reactivation TB, thus encompass relative risks compared to subjects without immunosuppression [12, 13]. In
Chapter 7 patients with HIV infection and a positive TST the risk of reactivation TB is as high as
ten percent per year [14]. Solid organ transplant recipients have a relative risk of TB re- activation that is 20-74 times higher than that of the general population [15]. Wolfe et al.
reported that the risk of TB among RA patients not treated with anti-TNF agents was not different from the rate in the general US population [13] while a study in Korea, that has an intermediate TB burden, demonstrated a higher rate of TB among RA patients [16]. In the former study, infliximab increased the risk of TB in patients with rheumatoid arthritis from 6.2 cases (95% CI 1.6-34.4) per 100,000 patients to 52.5 cases (95% CI 14.3-134.4) per 100,000 patients patient-years of exposure and a similar fold increase was found in the Korean study. No cases occurred in persons with preventive therapy. However, it must be realized that these Figures were derived from unselected RA patients and the risk of TB reactivation is most likely manifold higher among RA patients using infliximab who actually harbour latent TB infection and have not received preventive treatment.
The critical role of TNF to maintain latent TB infection has been studied in mice [17, 18]. In another study, mice first received anti-TNF treatment and were subsequently in- fected with M. tuberculosis, thus mimicking primary exposure similar to what occurred in our patient. All animals developed almost immediate and rapidly fatal disease [19].
The risk of immediate progression to TB disease in humans following exposure during use of anti-TNF agents is not precisely known but can be assumed to be high.
Clinical features of TB during TNF antagonists
In the initial report by Keane of 70 cases of TB during infliximab, extrapulmonary and disseminated TB occurred in resp 57% and 24% of patients, which is considerably more frequent than is generally observed [1]. This is pathogenetically understandable in the light of the central role of TNF in the development and maintenance of intact granulomas [20]. Apart from the extent of infection, the clinical presentation of TB occurring dur- ing treatment with TNF antagonists can be uncharacteristic. In our patient, the chest radiograph did not show abnormalities while the patient had pulmonary symptoms and M. tuberculosis was isolated from the broncho-alveolar lavage fluid. This is similar to findings in HIV infected subjects, with normal chest radiographs in 10% of patients with pulmonary TB mostly in association with low CD4+ cell counts [21, 22]. The lack of symptoms or objective signs of infection can be explained by the fact that symptoms and signs are often caused by the host immune response and not directly by the infectious agent. Thus, when the clinical suspicion of TB is high, diagnostic procedures should be performed despite the absence of radiographic abnormalities. A case of post-mortem diagnosis of TB despite a large number of diagnostic procedures with negative findings has been reported [4]. Early empirical treatment for presumed TB disease without any proof is, however, not the answer because many other opportunistic or common bacterial infections can occur in patients using TNF antagonists [11, 23-25].
Diagnostic value of the TST and of M. tuberculosis-specific in vitro assays The TST is based on delayed type hypersensitivity to tuberculin and is therefore less reli- able in patients using drugs that affect the cellular immune system or in patients with extensive TB and T cell anergy. The false negative TST in our patient obtained after expo- sure and during immune suppression with prednisone, azathioprine as well as infliximab was therefore not surprising. Novel blood tests have become available that detect inter- feron gamma production in response to specific antigens of M. tuberculosis [26-28]. In our patient, the whole blood assay QuantiFERON TB Gold in-tube was strongly positive, which strengthened the decision for empirical treatment of TB awaiting results of micro- biological diagnostic tests. In our patient, the blood test was apparently less affected by immuno-suppressive drugs than was the TST. This is in agreement with studies indicat- ing that in vitro interferon gamma release assays perform well in HIV infected individuals [29-32]. However, a limited sensitivity of QuantiFERON TB Gold for TB disease has also been reported and a negative blood test result does not exclude TB disease [33, 34]. In a clinical setting including many immunocompromised patients, QuantiFERON TB Gold more frequently produced indeterminate results due to failure of response to the positive control antigen than did T-SPOT.TB (Oxford Immunotec Ltd, Abingdon, UK), which is another TB-specific blood test based on the ELISPOT technique using incubation of a defined number of isolated white blood cells and therefore is not dependent on the white blood cell count [35]. A recent study evaluated in-house ELISPOT and other assay formats based on TB-specific antigens for screening of patients before the use of anti-TNF agents.
The finding that some blood tests had better sensitivity as well as better specificity than the TST for detection of latent TB infection is promising [36]. Further studies are needed to better define the potential role of blood tests for screening before starting anti-TNF or the work-up of immunocompromised patients with suspected TB.
Paradoxical response to antituberculosis drugs or immune reconstitution disease
It has been previously been suggested that TNF antagonists should ideally be discontin- ued for the duration of active TB therapy [11, 37]. However, our report showed that an immune reconstitution syndrome can occur that is analogous to that observed during infections in patients co-infected with HIV and who are treated with highly active anti- retroviral therapy [38]. The syndrome is caused by a restoring cellular immune system in the presence of an infection, illustrating the important role of the host immune response in the development of symptoms. The occurrence of an immune reconstition syndrome in patients who developed TB during treatment with TNF antagonists has previously been reported [3, 39]. In all cases, anti-TNF treatment had been stopped at the time TB was diagnosed. Thus, both continuing and stopping anti-TNF treatment carry the risk of an adverse clinical course and at present it is not clear whether anti-TNF treatment can be
Chapter 7 safely continued or restarted in patient with active TB disease. In that regard, Matsumoto
et al report on a patient in whom infliximab was discontinued when TB was diagnosed and restarted after 9 months of TB treatment, first in combination with 3 months of isoniazid and rifampin followed by continued use of isoniazid [40]. The authors stated that infliximab may be considered in patients recovered from TB and in whom anti-TB therapy can be maintained. TNF is a two-sided sword, however, as it is not only essential for the containment of latent TB infection but is also responsible for the weight loss and constitutional symptoms of TB disease. In that regard, a study in HIV-1 associated TB suggested that adjunctive etanercept as immunotherapy is safe during TB treatment and could even be beneficial, while corticosteroids were effective but caused severe side effects [41, 42]. The benefits and risks of TNF antagonists during active TB could depend on pharmacodynamic differences between etanercept and neutralizing antibodies such as infliximab [43].
In HIV infected patients the treatment of immune reconstitution symptoms with pred- nisone can be effective and, provided that mycobacterial resistance or other infections as a cause of clinical deterioration are ruled out, this could be considered in patients treated with TNF antagonists as well. While steroids are considered useful, the necessary dose and duration of treatment remain unclear. In that regard, it is of note that our pa- tient developed immune reconstitution symptoms during use of 10 mg prednisone daily.
However, the effective dose was probably lower due to the enzyme induction as a result of rifampin use and could have been too low to exert a beneficial effect on the immune reconstitution symptoms.
In conclusion, this report illustrates several striking clinical features of TB during treat- ment with TNF antagonists. Optimal screening for latent TB infection cannot prevent all TB in patients treated with TNF antagonists, primary TB infection may rapidly progress to severe disease, clinical signs of TB can be unreliable or masked during anti-TNF and a normal chest radiograph does not rule out TB lung disease. The TST may be falsely nega- tive as was the case in our patient, but a true positive would have been helpful. A specific blood tests for TB was positive before culture results became available. The occurrence of a severe immune reconstitution syndrome in our patient suggests that the discontinu- ation of a TNF antagonist is not without risk. As many opportunistic infections as well as common infections have also been described during use of TNF antagonists, the dif- ferential diagnosis and clinical work-up demand an open mind at all stages.
REFERENCE LIST
(1) Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor a-neutralizing agent. N Engl J Med 2001; 345(15):1098-104.
(2) Keane J. TNF-blocking agents and tuberculosis: new drugs illuminate an old topic. Rheumatology (Oxford) 2005; 44(6):714-20.
(3) Garcia VC, Rodriguez FS, Martinez LJ, et al. Paradoxical response to antituberculous therapy in infliximab-treated patients with disseminated tuberculosis. Clin Infect Dis 2005; 40(5):756-9.
(4) Vonkeman HE, van der Valk PD, Mulder L, van de Laar MA. Fatal extrapulmonary tuberculosis during treatment with the immunosuppressive infliximab [Fatale miliaire tuberculose tijdens behandeling met infliximab]. Ned Tijdschr Geneeskd 2002; 146(25):1196-9.
(5) Arend SM, Breedveld FC, van Dissel JT. TNF-a blockade and tuberculosis: better look before you leap.
Neth J Med 2003; 61(4):111-9.
(6) Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatoid arthritis and other immune mediated inflammatory diseases (May 2003). Ann Rheum Dis 2003; 62(Suppl 2):ii2-ii9.
(7) British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment. Thorax 2005; 60(10):800-5.
(8) Sichletidis L, Settas L, Spyratos D, Chloros D, Patakas D. Tuberculosis in patients receiving anti-TNF agents despite chemoprophylaxis. Int J Tuberc Lung Dis 2006; 10(10):1127-32.
(9) Huebner RE, Schein MF, Bass Jr JB. The tuberculin skin test. Clin Infect Dis 1993; 17:968-75.
(10) Carmona L, Gomez-Reino JJ, Rodriguez-Valverde V, et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists.
Arthritis Rheum 2005; 52(6):1766-72.
(11) Crum NF, Lederman ER, Wallace MR. Infections associated with tumor necrosis factor-alpha antago- nists. Medicine (Baltimore) 2005; 84(5):291-302.
(12) Rose DN. Benefits of screening for latent Mycobacterium tuberculosis infection. Arch Intern Med 2000;
160:1513-21.
(13) Wolfe F, Michaud K, Anderson J, Urbansky K. Tuberculosis infection in patients with rheumatoid ar- thritis and the effect of infliximab therapy. Arthritis Rheum 2004; 50(2):372-9.
(14) Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000; 161:S221-S247.
(15) Munoz P, Rodriguez C, Bouza E. Mycobacterium tuberculosis infection in recipients of solid organ transplants. Clin Infect Dis 2005; 40(4):581-7.
(16) Seong SS, Choi CB, Woo JH, et al. Incidence of tuberculosis in Korean patients with rheumatoid arthri- tis (RA): effects of RA itself and of tumor necrosis factor blockers. J Rheumatol 2007; 34(4):706-11.
(17) Flynn JL, Goldstein MM, Chan J, et al. Tumor necrosis factor-alpha is required in the protective im- mune response against Mycobacterium tuberculosis in mice. Immunity 1995; 2(6):561-72.
(18) Botha T, Ryffel B. Reactivation of latent tuberculosis infection in TNF-deficient mice. J Immunol 2003;
171(6):31103118.
(19) Mohan VP, Scanga CA, Yu K, et al. Effects of tumor necrosis factor alpha on host immune re- sponse in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun 2001;
69(3):1847-55.
(20) Algood HM, Lin PL, Flynn JL. Tumor necrosis factor and chemokine interactions in the formation and maintenance of granulomas in tuberculosis. Clin Infect Dis 2005; 41(Suppl 3):S189-S193.
(21) Sharma SK, Mohan A, Sharma A, Mitra DK. Miliary tuberculosis: new insights into an old disease.
Lancet Infect Dis 2005; 5(7):415-30.
(22) Palmieri F, Girardi E, Pellicelli AM, et al. Pulmonary tuberculosis in HIV-infected patients presenting with normal chest radiograph and negative sputum smear. Infection 2002; 30(2):68-74.
(23) Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004; 38(9):1261-5.
(24) Listing J, Strangfeld A, Kary S, et al. Infections in patients with rheumatoid arthritis treated with bio- logic agents. Arthritis Rheum 2005; 52(11):3403-12.
Chapter 7 (25) Dixon WG, Watson K, Lunt M, Hyrich KL, Silman AJ, Symmons DP. Rates of serious infection, includ-
ing site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti- tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register.
Arthritis Rheum 2006; 54(8):2368-76.
(26) Pai M, Riley LW, Colford JM, Jr. Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect Dis 2004; 4(12):761-76.
(27) Pai M, Kalantri S, Dheda K. New tools and emerging technologies for the diagnosis of tuberculosis: part I. Latent tuberculosis. Expert Rev Mol Diagn 2006; 6(3):413-22.
(28) Pai M, Menzies D. Interferon-g release assays: what is their role in the diagnosis of active tuberculosis?
Clin Infect Dis 2007; 44(1):74-7.
(29) Chapman AL, Munkanta M, Wilkinson KA, et al. Rapid detection of active and latent tuberculosis infection in HIV- positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells.
AIDS 2002; 16(17):2285-93.
(30) Dheda K, Lalvani A, Miller RF, et al. Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count. AIDS 2005; 19(17):2038-41.
(31) Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Ravn P. Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test. Respir Res 2006; 7:56.
(32) Rangaka MX, Wilkinson KA, Seldon R, et al. Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection. Am J Respir Crit Care Med 2007; 175(5):514-20.
(33) Dewan PK, Grinsdale J, Kawamura LM. Low sensitivity of a whole-blood interferon-g release assay for detection of active tuberculosis. Clin Infect Dis 2007; 44(1):69-73.
(34) Sood A, Schuyler M. Finally, a perfect diagnostic test for pulmonary tuberculosis--or is it? Am J Respir Crit Care Med 2006; 174(9):963-4.
(35) Ferrara G, Losi M, D’Amico R, et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet 2006;
367(9519):1328-34.
(36) Sellam J, Hamdi H, Roy C, et al. Comparison of in vitro-specific blood tests with tuberculin skin test for diagnosis of latent tuberculosis before anti-TNF therapy. Ann Rheum Dis 2007; Epub ahead of print:doi:10.1136/ard.2007.069799.
(37) Centers for Disease Control and Prevention. Tuberculosis associated with blocking agents against tu- mor necrosis factor-alpha--California, 2002-2003. Morb Mortal Wkly Rep 2004; 53(30):683-6.
(38) Shelburne SA, Visnegarwala F, Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005; 19(4):399-406.
(39) Belknap R, Reves R, Burman W. Immune reconstitution to Mycobacterium tuberculosis after discon- tinuing infliximab. Int J Tuberc Lung Dis 2005; 9(9):1057-8.
(40) Matsumoto T, Tanaka T, Kawase I. Infliximab for rheumatoid arthritis in a patient with tuberculosis. N Engl J Med 2006; 355(7):740-1.
(41) Wallis RS, Kyambadde P, Johnson JL, et al. A study of the safety, immunology, virology, and microbiol- ogy of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS 2004; 18(2):257-64.
(42) Wallis RS. Reconsidering adjuvant immunotherapy for tuberculosis. Clin Infect Dis 2005;
41(2):201-8.
(43) Dinarello CA. Differences between anti-tumor necrosis factor-alpha monoclonal antibodies and soluble TNF receptors in host defense impairment. J Rheumatol Suppl 2005; 74:40-7.
