Blue Peter Public Health and Research Center

Cherlapally, India

Blue Peter Public Health and Research Center

Cherlapally, India
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Jonnalagada S.,Blue Peter Public Health and Research Center | Harries A.D.,International Union Against Tuberculosis and Lung Disease The Union | Harries A.D.,London School of Hygiene and Tropical Medicine | Zachariah R.,Médecins Sans Frontières | And 6 more authors.
BMC Public Health | Year: 2011

Background: India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TB-related deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with "early" death, occurring in the initial 8 weeks of treatment. Methods. This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results: There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with "early death". Conclusion: In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed. © 2011 Jonnalagada et al.; licensee BioMed Central Ltd.

Pydi S.S.,Blue Peter Public Health and Research Center | Sunder S.R.,Blue Peter Public Health and Research Center | Venkatasubramanian S.,University of Texas Health Science Center at Tyler | Kovvali S.,Southern Regional Center | And 2 more authors.
Human Immunology | Year: 2013

NK cells are vital components of innate immune system and are the first cells which come into picture mediating resistance against intracellular pathogens. NK cell cytotoxicity is modulated by a wide variety of cell surface receptors that recognize and respond towards infected cells. Activation of NK cells are controlled by both inhibitory and activating receptors, encoded by KIR genes and bind to HLA ligands. Not much is known about KIR genes and their influence on the pathogenesis with M. tuberculosis infection. Our study aimed at detecting the presence of 14 KIR genes, their distribution and their association with tuberculosis. Total 77 different genotype combinations were observed which belonged to B-haplotype. Fifteen genotypes were similar to those reported in other world populations while remaining 62 were unique to this study group. Inhibitory genes KIR3DL1, KIR2DL3 and activating genes KIR2DS1, KIR2DS5 conferred susceptibility towards TB either individually or in haplotype combinations. The complimentary MHC ligands need to be tested for the functional relevance of the associated genes. © 2012 American Society for Histocompatibility and Immunogenetics.

Dittrich N.,Charité - Medical University of Berlin | Berrocal-Almanza L.C.,Charité - Medical University of Berlin | Thada S.,Charité - Medical University of Berlin | Thada S.,Bhagwan Mahavir Medical Research Center | And 12 more authors.
Tuberculosis | Year: 2015

Background Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (MTB) infection, is still a global public health problem. TB susceptibility varies greatly in infected individuals, and mycobacterial recognition by the innate immune system likely affects disease course and outcome. This research describes a single nucleotide polymorphism in the Toll-like receptor (TLR) 1 gene that functionally alters the innate immune response to MTB and is associated with TB susceptibility in India. Methods 206 TB patients and 239 healthy controls from Hyderabad, India were analyzed for SNPs in the TLR1 and TLR2 genes, which were subsequently correlated to TB susceptibility. To test individual responses to MTB lysates, we stimulated PBMCs from genotyped healthy German individuals, as well as HEK cells transfected with TLR1/2 variants. TNF production and NF-kB activation were assessed respectively. Results Cohort analysis associated the TLR1-248N SNP (RS4833095) with TB protection. TLR1-248N expressing PBMCs from healthy controls exhibited an increased TNF response to MTB lysates. In addition to this, functional studies using HEK cell lines transfected with TLR1-248N and stimulated with MTB showed an increased NF-kB activation. Conclusion SNP TLR1-248N is associated with TB protection in an Indian population and exhibits an increased immune response to MTB lysate in vitro. © 2015 Elsevier Ltd.

Shinde V.,Blue Peter Public Health and Research Center | Marcinek P.,University of Tübingen | Rani D.S.,CSIR - Central Electrochemical Research Institute | Sunder S.R.,Blue Peter Public Health and Research Center | And 6 more authors.
Human Immunology | Year: 2013

The heterodimeric transporter associated with antigen processing (. TAP) gene loci is known to play a vital role in immune surveillance. We investigated a possible association of gene polymorphisms both in TAP1 and TAP2 in a cohort of clinically classified leprosy patients (. n=. 222) and in ethnically matched controls (. n=. 223). The TAP1 and TAP2 genes were genotyped for four single nucleotide polymorphisms TAP1 (rs1057141 Iso333Val and rs1135216 Asp637Gly) and TAP2 (rs2228396 Ala565Thr and rs241447 Ala665Thr) by direct sequencing and ARMS-PCR. The minor allele of TAP1 637G contributes to an increased risk to leprosy compared to controls (OR: 1.68, 95% CI 1.2-2.36, P=. 0.0057). An increased risk for the variant minor allele of the TAP1 637G to multibacillary (BL. +. LL) or paucibacillary (BT. +. TT) infections was also observed [multibacillary vs. controls (OR: 1.56, 95% CI 1.07-2.28, P=. 0.054); paucibacillary vs. controls (OR: 1.92, 95% CI 1.21-3.01, P=. 0.013)]. In the dominant model, the genotypes of the TAP1 rs1135216AG. +. GG additionally contributed to an increased risk. Overall our findings demonstrate that the TAP1 gene variant (rs1135216 Asp637Gly) influences the susceptibility to clinically classified leprosy patients in Indian population. © 2013 American Society for Histocompatibility and Immunogenetics.

Li W.,Colorado State University | Sakamuri R.M.,Colorado State University | Lyons D.E.,Colorado State University | Orcullo F.M.,Leonard Wood Memorial Center for Leprosy Research | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Drug resistance surveillance identified six untreated leprosy patients in the Philippines with Mycobacterium leprae folP1 mutations which confer dapsone resistance. Five patients share a village of residence; four who carried the mutation, Thr53Val, were also linked by M. leprae variable-number tandem repeat (VNTR) strain types. In India, folP1 mutations were detected in two relapse patients with a history of dapsone treatment. Mutations were not found in the rifampin target gene rpoB. These findings indicate that dapsone resistance is being transmitted. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Visser L.H.,St Elisabeth hospital | Jain S.,CODEWEL Nireekshana ACET | Lokesh B.,Narayana Medical College | Suneetha S.,CODEWEL Nireekshana ACET | Subbanna J.,Blue Peter Public Health and Research Center
Muscle and Nerve | Year: 2012

Introduction: From histopathological studies of peripheral nerves in leprosy, it is known that the epineurium can be thickened. We measured the epineurial thickness of the ulnar nerve by high resolution sonography (HRUS). Methods: The epineurium of the ulnar nerve was measured above the elbow on transverse scan in 25 healthy controls and 26 leprosy patients. Results: The mean epineurial thickness was 0.77 mm (95% confidence interval [CI] 0.66-0.88) in symptomatic ulnar nerves (n = 20), 0.58 mm (CI 0.51-0.65) in asymptomatic nerves (n = 30), and 0.49 mm (CI 0.44-0.54) in healthy controls (n = 25) (P = 0.0001). This thickening was related to the cross-sectional area of the ulnar nerve, but not with increased blood flow. Conclusions: The epineurium of the ulnar nerve can be measured with the use of HRUS, and it is often strikingly thickened in leprosy patients, especially in those with ulnar involvement. © 2012 Wiley Periodicals, Inc.

Joshi L.,Bhagwan Mahavir Medical Research Center | Ponnana M.,Bhagwan Mahavir Medical Research Center | Sivangala R.,Bhagwan Mahavir Medical Research Center | Chelluri L.K.,Global Hospital | And 5 more authors.
PLoS ONE | Year: 2015

Background Household contacts of diagnostically established tuberculosis (TB) patients are highly susceptible to disease development. It is surmised that cytokines perhaps play a synergistic and a prognostic role in the activation of the otherwise latent infection in these house hold contacts. Evaluation of the cytokines and any of their inherent polymorphisms might provide a useful diagnostic tool in evaluating the immune regulation and the progression of the disease. The cytokines thus released in a paracrine manner in serum may also provide an indirect measure of the cytokine function. Objective The present study was aimed to evaluate the levels of TNF-α, IL-10 & IL-6 cytokines and their correlation with genotype variants amongst tuberculosis patients and their household contacts. Methods The cytokine levels were estimated in serum by enzyme-linked immunosorbent assay (ELISA) and their polymorphisms were studied by amplification refractory mutation system polymerase chain reaction (ARMs PCR) in active pulmonary tuberculosis patients (APTB = 150), household contacts (HHC = 190), and healthy controls (HC = 150). Results The median values of TNF-α cytokine were significantly high among APTB and HHC compared to HCs (P< 0.0001 and 0.0001). IL-6 levels also were elevated among APTB compared to HHC and HC, and a significant difference was observed between APTB and HHC at P<0.0001; APTB & HC at P< 0.04; HHC & HC at P< 0.01. The IL-10 levels were low in APTB compared to HHC and HCs and no significant difference was observed. TNF-α/IL-10 ratio was significant and indicated Th1 predominance in APTB and HHC. IL-6/IL-10 showed pronounced Th1 expression in APTB and Th2 in HHC and HC. The ROC analysis indicated that both IL-10 and IL-6 can be used to decide the risk of exposed individual to a disease. The results of multivariate analysis indicate that IL-10 (-1082) GA genotype was significantly associated with p<0.028 in APTB. No significant association was observed between genotypes, other serum cytokine levels and clinical characteristics between APTB, HHC and HCs. Conclusion Large sample size with follow-up at different time points may further illuminate the role of IL-10 and IL-6 cytokines as a prognostic marker in house hold contacts. © 2015 Joshi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Marcinek P.,University of Tübingen | Jha A.N.,CSIR - Central Electrochemical Research Institute | Shinde V.,Blue Peter Public Health and Research Center | Sundaramoorthy A.,Bharathiar University | And 8 more authors.
PLoS ONE | Year: 2013

In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae. © 2013 Marcinek et al.

Benjamin R.,University of Hyderabad | Banerjee A.,University of Hyderabad | Sunder S.R.,Blue Peter Public Health and Research Center | Gaddam S.,Bhagawan Mahavir Medical Research Center | And 2 more authors.
PLoS ONE | Year: 2013

Background:Cytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy.Methodology/Principal Findings:We analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio.Conclusion/Significance:With these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse. © 2013 Benjamin et al.

Pydi S.S.,Blue Peter Public Health and Research Center | Bandaru A.R.,Blue Peter Public Health and Research Center | Venkatasubramanian S.,Blue Peter Public Health and Research Center | Jonnalagada S.,Blue Peter Public Health and Research Center | Valluri V.L.,Blue Peter Public Health and Research Center
Tuberculosis | Year: 2011

IFN-γ is the most commonly measured cytokine released by the cells to define the cellular immune responses induced by the vaccine candidates for tuberculosis. IL-15 acts as a co-stimulator in IFN-γ production by NK cells and may therefore be important in the control of Mycobacterium tuberculosis that requires IFN-γ for clearance. The aim of the study is to determine whether Ag85A can also stimulate the innate immune response through the expression of IL-15, a cytokine that bridges the innate and adaptive immune systems. The expression of IL-15 was up regulated by about 4 fold in PPD+ healthy controls as compared with TB patients. Significantly higher expression of IL-15 mRNA in the Ag85A stimulated cells not only in PPD+ healthy controls but also in TB patients substantiates the use of Ag85A as a vaccine candidate over ESAT-6. © 2010 Published by Elsevier Ltd.

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