[Show abstract][Hide abstract] ABSTRACT: Pulmonary tuberculosis continues to cause of mortality, particularly in developing countries. Despite modern anti-TB treatment, the elderly and immigrants from TB-endemic countries are at risk. Multidrug resistance has yet to be resolved..
To determine the mortality rate and predictors of mortality among patients hospitalized with TB in Israel.
We evaluated the medical records of 461 patients with active pulmonary TB who were hospitalized in the respiratory care department during the 5 year period 2000-2004. Data included demographic, clinical, laboratory and radiological findings, drug resistance as well as adverse reactions to anti-TB treatment.
Three main ethno-geographic groups were observed: 253 patients from the former USSR, 130 from Ethiopia, and 54 of Israeli origin (as well as 24 residents of other countries). Of the 461 patients 65 (13%) died in hospital. The factors that were best predictors of mortality were older age, ischemic heart disease, cachexia, prior corticosteroid treatment, hypoalbuminemia and pleural effusion (P < 0.005 for all). The ethno-geographic factor and the presence of multidrug-resistant bacteria had no significant effect on mortality in our study group.
The mortality rate in our study was relatively low, and there was no significant difference between the three ethno-geographic groups.
The Israel Medical Association journal: IMAJ 01/2008; 9(12):870-3. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.
To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.
The present study included (part 1): 39 patients with acute TB (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6 and IL-10 were measured in serum and in non-stimulated and PPD-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNgamma and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.
Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNgamma-SER, IFNgamma-PPD, IL-2R-SER, IL-10-SER, IL-10-NS and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNgamma were demonstrated in the second part of the study.
Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNgamma secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis.
The Israel Medical Association journal: IMAJ 07/2007; 9(6):479-83. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of TNFalpha blockers is associated with reactivation of tuberculosis. The Israeli Association of Rheumatology nominated a committee to determine guidelines for the prevention of tuberculosis in patients taking TNFalpha blockers. The risk of reactivation of tuberculosis is higher with monoclonal antibodies to TNFalpha (infliximab, adalimumab) in comparison with the soluble receptor of TNFalpha (etanercept). All patients who are candidates to receive TNFalpha blockers should be screened for active or latent tuberculosis. The screening includes: Tuberculin Skin Test (TST), chest X-ray and a questionnaire about possible exposure to tuberculosis. Two-step screening should be used as recommended by the Ministry of Health. The reaction elicited in the second test (if applied) should be used. In the general population latent tuberculosis is diagnosed when the TST response is 15 mm. or above; a reaction of 10 mm. or above is positive in populations with a history of definite or probable exposure to TB and 5 mm. is the threshold for populations who are immunosuppressed or if chest radiography reveals old tuberculosis without clear documentation of previous treatment. Patients with a TST less than 5 mm. should be questioned about prior exposure to tuberculosis. Latent tuberculosis should be treated with a 9 month course of isoniazid (300mg/d) or a 4 month course of rifampicin (600mg/d) or for 3 months with a combination of 300 mg. isoniazid and 600 mg. rifampicin daily. The committee recommends postponing treatment with TNFalpha blockers until completion of anti-tuberculosis therapy. If the clinical condition requires the urgent use of TNFalpha blockers, these may be initiated one month after starting treatment for latent tuberculosis.
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence of a wide array of auto-antibodies in patients with tuberculosis (TB) compared with healthy controls.
Forty-seven consecutive patients (age 47 +/- 21 years, 29 males) with recently diagnosed active pulmonary tuberculosis (PTB) and 39 healthy controls were enrolled. Data collected on a questionnaire included clinical features of the disease, duration of symptoms, presence of fever, cough, arthralgia, myalgia, sicca symptoms and others. Serum samples were collected from the patients' before initiating TB treatment, frozen at -20 degrees C and tested for antinuclear antibodies (ANA), anti-ds DNA, anti-Sm, anti-RNP, anti-Ro, anti-La, and anti-cardiolipin (ACA) (IgG and IgM).
Rheumatic symptoms were relatively rare: arthralgia (n = 2), myalgias (n = 2), and eye (n = 1) and mouth dryness (n = 4). The TB patients' mean serum levels of anti-ds DNA, anti-Sm, anti-RNP, anti-SSA (anti-Ro), and anti-ACA-IgM were significantly increased compared with controls (P < 0.05 for all). A significantly higher proportion of TB patients had increased pathological levels of anti-ds DNA (32% vs. 2.5%), anti-Sm (38% vs. 0%), anti-RNP (15% vs. 0%), anti-Ro (64% vs. 10%), anti-ACA-IgG (59% vs. 0%) and anti-ACA-IgM (47% vs. 7.7%) (P < 0.05 for all).
Patients with active TB have significantly increased titres of various auto-antibodies, including highly specific serological markers, such as anti-Sm.
Differential interpretation of serological studies of patients with systemic manifestations should consider the possibility of PTB.
The International Journal of Tuberculosis and Lung Disease 03/2007; 11(3):306-10. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence of anti-cyclic citrullinated proteins (anti-CCP) and IgM rheumatoid factor (RF) in sera of patients with TB compared with healthy controls.
47 consecutive patients with recently diagnosed active pulmonary TB and 39 healthy controls were studied. Data were collected by questionnaire on clinical features of the disease, duration of symptoms, fever, cough, arthralgia, myalgia, sicca symptoms. Serum samples were collected from patients before starting treatment for TB and frozen at -20 degrees C. Anti-CCP and IgM RF were evaluated by ELISA.
The mean (SD) duration of TB related symptoms was 4.4 (1.7) months, 73% had fever, 94% a cough. Rheumatic symptoms were relatively rare: arthralgia (4%), myalgias (4%), eye and mouth dryness (2% and 9%, respectively). Mean (SD) levels of anti-CCP were significantly increased in patients with TB compared with controls: 44.9 (51) IU v 20 (7.3) IU (p = 0.002). Serum levels >40 U were found in 15/47 (32%) patients compared with 1/39 (2.6%) controls (p = 0.002). Mean (SD) serum levels of IgM RF were significantly increased in patients with TB: 17.8 (19) v 4.3 (5) (p<0.0001). IgM RF was positive (>6 IU) in 29/47 (62%) patients v 1/39 (2.6%) controls (p<0.0001).
A significant proportion of patients with active TB have an increased titre of anti-CCP and IgM RF.
Annals of the Rheumatic Diseases 09/2006; 65(8):1110-2. DOI:10.1136/ard.2005.045229 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A previously diagnosed systemic lupus erythematosus patient presented with arthralgia, skin rash and muscular weakness. When treated with high-dose corticosteroids and methotrexate she improved, except for a persistent lesion in the hand which evolved into a profound ulcer, along with tender subcutaneous nodules in the calf. A skin biopsy disclosed necrotizing vasculitis with giant cell granuloma revealing acid fast positive bacteria on ziels nilsen staining. A chest X-ray disclosed miliary tuberculosis (TB). The patient was diagnosed as miliary TB with prominent cutaneous involvement and treated with four anti-tuberculous drugs with slow resolution of her systemic, pulmonary and skin signs.