Scholarly article on topic 'OL-035 Tuberculosis disease burden in Southeast Asia'

OL-035 Tuberculosis disease burden in Southeast Asia Academic research paper on "Clinical medicine"

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Academic research paper on topic "OL-035 Tuberculosis disease burden in Southeast Asia"


Abstracts, 5th DICID

source for most antibiotics on the market today, including the first-line and salvage TB regimens, including rifampin, streptomycin, amikacin and etc. A set of Microbial Natural Product Library (MNPL) containing secondary metabolites from a unique collection of actinomycetes and fungal strains from un- or under-explored ecological niches in China has been constructed. A pilot screen for potential anti-TB compounds was conducted with a selection of 5,000 extracts samples from this MNPL, utilizing a GFP labeled M. bovis BCG based HTS model (Z'-factor 0.8, CV< 15%, throughput 60,000 wells/day). 80 out of the 5,000 extracts showed >90% inhibition against logarithmically growing BCG were further evaluated on M. tb H37Rv strains at Broad Institute, as a dilution series ranging from 1x to 1/128x. The results showed that 46 extracts demonstrated anti-H37Rv activity, with 8 showing activity at 1/16x, and 1 showing activity at 1/128x. The following large scale fermentation and bioactivity guided compound isolation work lead to the discovery of diversified class of anti-TB compounds, including actinomycins (MIC 'Mug/ml), quinomycins (MIC 0.5ug/ml), nanaomycins (MIC 8ug/ml), cyclopeptides (MIC 2-8ug/ml), anthraquinones (MIC 4-8ug/ml), oligomycins, part of which were new compounds (not listed).

|OL-033| Etambutol-mediated changes in rat liver

cytochrome P-450 isoforms expression and DNA-fragmentation processes

S. Anisimova1 *, G. Shayakhmetova1, L. Bondarenko1, V. Kovalenko1. 1SI "institute of Pharmacology & Toxicology" National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine

Objectives: Etambutol is one of first-line antitubercular drugs in current therapeutic regimens. Its main disadvantage is wide spectrum of adverse effects which can lead to therapeutic failure. The aim of present study was to investigate etambutol effects on rat liver cytochrome P-450 isoforms expression and DNA-fragmentation processes. Methods: Wistar albino male rats (160-200g b.w.) were divided into two groups: I - received etambutol per os at a dose of 155 mg/kg b.w./day, II - control. After 60 days of the experiment, rats were sacrificed via cervical dislocation. Expression of rat liver CYP2E1, CYP3A2 and CYP2C23 were studied by RT-PCR methods. DNA fragmentation was investigated electrophoretically.

Results: Our data demonstrated etambutol-mediated quantitative and qualitative changes in male rat DNA fragmentation and expression of CYP2E1, CYP3A2 and CYP2C23 in comparison with control. CYP2E1 and CYP3A2 expression increasing was accompanied with CYP2C23 expression inhibition. DNA fragmentation processes were also greatly intensified at etambutol treatment. Its introduction caused appearance of new fractions with longer DNA-fragments (above 1000 b.p., 1000-800 b.p. and 800-600 b.p.). Among shorter DNA-fragments main fraction contained chains with 20-30 b.p.

Conclusion: Thus etambutol treatment caused adverse effects in organisms on the level of cytochrome P-450 isoforms expression and DNA-fragmentation processes. Extensive investigation of etambutol and cytochrome P-450 system interactions allowed to prevent or correct this antitubercular agent adverse effects.

|OL-Q34| A comparison study of extrapulmonary and pulmonary tuberculosis in Hong Kong

S.S. Lamb1*, I.F. Hung1, K.K. To1. 1 Queen Mary Hospital, Hong Kong SAR, China

Background: This study examines the differences between culture positive extrapulmonary and pulmonary tuberculosis

(TB) patients. It correlates these findings with the current

understanding of extrapulmonary TB. It looks at how these

factors affect mortality at six months and at the role of

underlying diseases in drug resistance.

Method: This is a two year retrospective study comparing

115 extrapulmonary TB patients with 115 pulmonary TB


Results: Extrapulmonary patients were younger than pulmonary patients with a median age of 53 years versus 73 years (p< 0.001). They presented more commonly with lymphadenopathy (p<0.001). More extrapulmonary patients had chronic renal failure (p< 0.002) and Human Immunodeficiency Virus (HIV) infection (p = 0.005). They had a higher median erythrocyte sedimentation rate (61 mm/h vs. 48mm/h, p = 0.017), and lactate dehydrogenase level (309U/L vs. 197U/L, p = 0.006). They had a lower median hemoglobin (10.7g/dL vs. 11.7g/dL, p = 0.002), white blood cell count (7.4x 109/L vs. 8.5x109/L, p = 0.039), and lymphocyte count (0.9x 109/L vs. 1.1 x109/L, p = 0.051). There was no difference in mortality between extrapulmonary and pulmonary groups. Multivariate analysis identified age >60 years (Odds Ratio [OR] 2.4, 95% Confidence interval [95% CI] 0.98-5.77, p = 0.054), presentation with decreased general condition (OR 3.5, 95% CI 1.46-8.34, p = 0.005), hypertension (OR 2.7, 95% CI 1.16-6.38, p = 0.021), radiological old TB (OR 2.6, 95% CI 1.25-5.52, p = 0.014), and pleural effusion (OR 3.2, 95%CI 1.45-7.03, p = 0.004) as independent risk factors for mortality.

9.1% of all cases had culture evidence of drug resistance. HIV infection (p = 0.001) and intravenous drug usage (p = 0.001) were the two risk factors identified. Conclusion: There are important differences in demographics, clinical presentation and risk factors for extrapulmonary compared with pulmonary TB. Mortality is related to age and co-morbidity.

|OL-Q35| Tuberculosis disease burden in Southeast Asia D.S. Bais1*, R.C. Tripathi2, W. Hassan3, V.P. Singh4. 1Tongji

Medical College of HUST, China, 2Base Hospital, Army

Medical Corps, India, 3Huazhong Agriculture University,

4Lioning Medical University, China

Objectives: Tuberculosis, MTB or TB is the seventh leading

frequent cause of death worldwide among infectious

diseases. It is important to evaluate the current burden of disease, to know how this has been changing over time.

Method: Review of current literature. Result: According to the WHO, an estimated about 9.2 million (139/100,000 population) new cases of TB occurred in 2006. Of these cases, 4.1 million (62/100,000 population)

were new smear positive cases. There were 14.4 million (219/100,000 population) prevalent cases. There are 22 high-burden countries, but the majority of patients with TB live in the eight country of Asia; India, China, Indonesia, Bangladesh, Pakistan, Philippines, Vietnam and Afghanistan. India is the highest TB burden country in the world and accounts for nearly one-fifth (20%) of global burden of tuberculosis. In India, TB affects adults in the most productive age group (15-54 years). More than 80% of TB cases are in this group. TB kills almost 0.37 million Indian people every year with mortality rate of about 28/100,000 population. Globally, the case detection rate by DOTS programs increased almost linearly from 11% in 1995 to 28% in 2000, and then accelerated to 45% in 2003. The recent acceleration has been mostly due to rapid implementation in India, where case detection increased from 1.7% in 1998 to 47% in 2003, and in China, where it increased from 30% in 2002 to 43% in 2003. India and China together accounted for

Free Paper Presentation 5: Tuberculosis

63% of the increase in case notification by DOTS programs between 2002 and 2003.

Conclusions: Without DOTS and Public awareness program, it is highly unlikely that countries will be able to develop effective and sustainable tuberculosis program. With the introduction of DOTS, achieving the global targets for tuberculosis control has now become a realistic proposition.

|OL-Q36| Incidence of multi drug resistant tuberculosis (MDR-TB) in extrapulmonary tuberculosis cases in Northern India A.K. Maurya1*, S. Kant1, V.L. Nag2, R.A.S. Kushwaha1, M. Kumar2, S. Jain2, T.N. Dhole2. 1 Department of Pulmonary Medicine, Chhatrapati Shahuji Maharaj Medical University (Erstwhile King George Medical University) Lucknow, India, 2Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Background: The importance of extrapulmonary tuberculosis (EPTB) among all forms of tuberculosis has not yet been ascertained in developing countries. Multi drug resistant tuberculosis (MDR-TB) is an increasing worldwide problem aswell as in India. The transmission of resistance strains is increasing day-by-day because of the rising load of MDR-TB patients. The aim of the study to know incidence of MDR-TB in extra pulmonary tuberculosis cases in tertiary care hospitals in Northern India.

Materials and Methods: A total of 789 specimens from patients of EPTB cases with varied presentation were studied. All the samples were processed for ZNStaining for Acid Fast bacilli and radiometric BACTEC culture for Mycobacteria. Identification of M. tuberculosis complex (MTBC) was done by BACTEC NAP (p-nitro-a-acetylamino-b-hydroxy propiophenone) differentiation test. All M. tuberculosis isolates were recovered for radiometric based drug susceptibility pattern against streptomycin, isoniazid, rifampicin and ethambutol (SHRE) using the proportion method.

Results: 165 (20.7%) of 797 patients clinically suspected to have extra pulmonary tuberculosis were BACTEC culture positive for mycobacteria. Out of 165 cases, 127 (77%) were newly diagnosed and 38 (23%) previous treated cases. On Biochemical characterization, 123 (74.5%) of the 164 isolates were identified as Mycobacterium tuberculosis complex by NAP Test. A total of 123 (74.5%) M. tuberculosis isolates for firstline antitubercular drug susceptibility pattern. We observed that MDR strains (resistance to rifampicin and isoniazid) were found in 15 (12.1%) of 123 isolates. Overall results shown that incidence of MDRTB in EPTB case was 12.1%.

Conclusion: M. tuberculosis was present in 20.7 percent samples. The maximum numbers of M. tuberculosis were isolated from lymph node aspiration. Our study originates that multi drug resistant tuberculosis is gradually increased in extrapulmonary tuberculosis cases.

|OL-Q37| Analysis of microRNA expression profiling

identifies two microRNAs as potential diagnostic markers for active tuberculosis J. Wu1*, C.Y. Lu1, W.H. Zhang1. 1 Department of infectious disease, Huashan Hospital, Fudan University, China

Background: The biological behaviors and disease relevance of microRNAs in the development of active tuberculosis (ATB) are still unknown.

Methods: The expression profile of microRNA under the challenge of mycobacterium tuberculosis PPD was first measured using microarray in PBMCs isolated from

ATB patients and health controls (HC). The remarkably reactive microRNAs were further validated in other cohorts by quantitative real-time PCR (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive microRNAs.

Result: It turned out that 14 out of 866 human microRNAs showed significantly higher increased expression after PPD stimulation in ATB than in HC groups. The qRT-PCR study validated the findings from microarray-based screen, in which, upon PPD stimulation, miR-155 had fold change of 1.4 in HC group and 3.7 in ATB group (p< 0.0001); miR-155* had 1.9 in HC and 4.6 in ATB group (p< 0.005). In ROC plots, area under the curve (AUC) was 0.8972 for miR-155 and 0.7945 for miR-155*.

Conclusion: MiR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens.

|OL-Q38| Efficiency of RD-1 antigen-specific interferon-"/ release assays (IGRAs) blood-based tests for the diagnosis of Mycobacterium tuberculosis infection in Pott's disease at a tertiary care hospital

M. Kumar1 *, R. Kumar2, V.L. Nag3, N. Krishnani4, U. Singh5,

T.N. Dhole3, A.K. Maurya3, S.G. Babu1. 1 Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India, 2Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, 3Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, 4Department of Pathalogy, Sanjay Gandhi

Postgraduate Institute of Medical Sciences, Lucknow, India,

5Department of Biostastic, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Objective: QuantiFERON-TBGold (QFT-G) test is a recent method in the diagnosis of latent or active tuberculosis and shows better results. This assay based on the detection of interferon-gamma; produced by stimulated T lymphocytes with tuberculosis specific antigens. In this study we evaluate the degree of usefulness of this method in detecting the Pott's disease.

Methods: A total of 83 cases were included in this study. Among them few were confirmed tuberculosis patients as evidenced by the traditional clinical techniques like Ziehl Nelsen smear, BACTEC culture, PCR IS6110 gene and histopathology as well as they undergone surgery for treatment. In this study nonsurgical cases were also included, their confirmation was done with the TB ELISA. The above all cases were compared with the recent QFT-G assay for its efficacy, sensitivity and specificity in confirming the cases of both suspected and confirmed tuberculosis. Results: The study comprised of 83 cases, however 5cases were excluded in this as they were found to be malignant. Among the 52 surgical cases, it was found that 39 were tested to be tuberculosis and 13 were found to be negative by the traditional clinical techniques. However, the QFT-G assay gives the result that among the 39 active tuberculosis samples only 24 found to be positive. Interestingly, 1 has given tuberculosis positive from the samples observed to be negative by the traditional tests. Then, the sensitivity and specificity was 62% and 92%, (p value = 0.001), 56% and 100%, (p value = 0.009) surgical and nonsurgical patient correspondingly. The overall 60% sensitivity and 95% specificity (p value <0.001).

Conclusion: By analyzing the obtained results we can say that the specificity of QFT-G was high but its sensitivity