Elvina Karyadi

Increased Production of Interleukin 4 by CD4+ and CD8+ T Cells from Patients with Tuberculosis Is Related to the Presence of Pulmonary Cavities

In tuberculosis, cellular immunity is considered to be responsible for the eradication of infection but also for damage of host tissues. In animal models, the balance between Th1-type cytokines, especially interferon (IFN)-gamma, and Th2-type cytokines, primarily interleukin (IL)-4, seems crucial for these effects. Reports on Th1-type and Th2-type cytokines in human tuberculosis are conflicting, and little is known about their role in tissue damage. Flow-cytometric assessment of cytokine responses was performed in human immunodeficiency virus (HIV)-seronegative patients with active tuberculosis and in healthy controls. Patients and controls showed no significant difference in expression of IFN-gamma. However, patients showed a striking increase in production of IL-4 in CD4+ as well as CD8+ T cells. Most remarkably, the expression of IL-4 was especially elevated in patients with cavitary tuberculosis. The Th2-type response with increased production of IL-4 in patients with tuberculosis may antagonize host defense and lead to tissue necrosis.

Zinc and vitamin A supplementation fails to reduce sputum conversion time in severely malnourished pulmonary tuberculosis patients in Indonesia

BackgroundA previous study showed that combination of zinc and vitamin A reduced sputum conversion time in pulmonary tuberculosis (TB) patients.ObjectiveWe studied the efficacy of which single micronutrient contributed more to the sputum conversion time.MethodsIn a double-blind randomized community trial, newly sputum smear positive pulmonary TB patients were assigned randomly to receive zinc, vitamin A, zinc + vitamin A or placebo on top of TB treatment. Patients were asked to deliver their sputum on weekly basis to measure positivity of the bacteria. Nutritional status, chest x-ray, hemoglobin, C-reactive protein (CRP), retinol and zinc level were examined prior to, after 2 and 6 months of treatment.ResultsInitially, 300 patients were enrolled, and 255 finished the treatment. Most patients were severely malnourished (mean BMI 16.5 ± 2.2 Kg/m2). Patients in the zinc + vitamin A group showed earlier sputum conversion time (mean 1.9 weeks) compared with that in the other groups; however the difference was not significant. Also, no benefit could be demonstrated of any of the used supplementations on clinical, nutritional, chest x-ray, or laboratory findings.ConclusionsThis study among severely malnourished TB patients, did not confirm that single or combined supplementation of zinc and vitamin A significantly reduced sputum conversion time or had other significant benefit.

Vitamin A deficiency and other factors associated with severe tuberculosis in Timor and Rote Islands, East Nusa Tenggara Province, Indonesia

Background:Plasma zinc and vitamin A concentrations have been reported to be low in tuberculosis (TB) patients in some studies, although it is not clear whether this constitutes a risk for a more severe clinical presentation among TB patients. The acute phase reaction may also deplete zinc and vitamin A in the plasma. Therefore, we further studied these associations.Methods:We carried out a cross-sectional study among newly diagnosed sputum smear-positive TB patients in East Nusa Tenggara. The patients were categorized as either mild TB when Karnofsky Score (KS) ⩾80 or severe TB (KS <80). Body mass index (BMI), mid upper arm circumference (MUAC), chest radiograph, and the results of hemoglobin, erythrocyte sedimentation rate, albumin, C-reactive protein (CRP), zinc and vitamin A in plasma were correlated with TB category.Results:A total of 300 TB patients participated in the study (63% male and 37% female), and were categorized as mild TB (53%) or severe TB (47%). Vitamin A, hemoglobin and plasma albumin were significantly lower, and CRP was significantly higher, in severe TB than in mild TB, and the active lesion area on the chest radiograph was greater among severe TB patients. In a multiple regression analysis, after adjustment for CRP, low vitamin A (β=3.2, 95%CI (confidence interval) 1.6–4.9, P=0.000) but not zinc, correlated with the severity of TB. MUAC was better than BMI as a predictor of TB severity (β=1.3, 95%CI 0.6–6.2, P=0.000).Conclusions:Severe TB was associated with vitamin A deficiency. MUAC can be applied as a measure of TB severity.

Effectiveness of the Bacillus Calmette-Guerin vaccine in an Indonesian population with D543N NRAMP1 polymorphism

INTRODUCTION Bacille Calmette-Guerin (BCG) vaccination remains a routine immunization in primary care in tuberculosis (TB)-endemic areas, though several studies found that its efficacy was inconclusive. Natural resistance-asociated machrophage protein 1 (NRAMP1) polymorphism has been shown to result in higher susceptibility to TB. Information on genetic susceptibility in populations will be useful in planning the application of the BCG vaccine. The present study explored BCG efficacy in a rural Timor population with specific NRAMP1 polymorphism in a TB-endemic region of eastern Indonesia. METHODOLOGY A case-control study with 64 newly diagnosed pulmonary TB patients and 65 healthy controls was performed. BCG scars were examined by a physician. NRAMP1 polymorphism was evaluated using molecular methods. RESULTS Half of the subjects (65; 50.4%) had a clear presenting BCG scar on the upper arm, suggesting a successful BCG vaccination. Among the subjects, D543N NRAMP1 polymorphism, history of contact with TB patients, and not having a clear BCG scar on the upper arm tended to be significantly association with active TB. The significant differences were more profound when subjects were divided based on presenting BCG scar. Subjects without clear BCG scars had significant association with developing TB disease (p = 0.014). In multivariate analysis, history of previous contact with TB patients and unclear presenting BCG scar were associated with active TB (OR 9.2; 2.0-43.8 95% CI, OR 4.8; 2.1-11.0 95% CI, respectively). CONCLUSIONS BCG vaccination in our population was effective for TB protection, especially in highly endemic areas of TB, regardless genetic susceptibility.