Government Hospital of Thoracic Medicine

Chennai, India

Government Hospital of Thoracic Medicine

Chennai, India
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Myerson R.,Institute for Health Metrics and Evaluation | Makela S.M.,Institute for Health Metrics and Evaluation | Chandrasekhar C.,Government Hospital of Thoracic Medicine | Mathew S.,International Training and Education Center for Health chnology Arogyaan | Chakraborty S.,International Training and Education Center for Health chnology Arogyaan
BMC Health Services Research | Year: 2012

Background: HIV voluntary counselling and testing was a key HIV prevention strategy brought to scale by India's National AIDS Control Organization. Condom uptake is an essential metric of intervention impact given the expansion of the epidemic into an increasingly diverse population. With only 20% of first-time counselling and testing clients at the largest HIV treatment hospital in south India reporting previous condom use, the question of intervention impact on condom use deserves investigation. In this study, we track intervention impact across various demographic groups and identify the added value of more thorough counselling. Methods. Data were collected from 8,865 individuals who attended counselling multiple times at the Tamil Nadu Government Hospital of Thoracic Medicine over the years 2004-2009. Counsellors recorded client demographic characteristics, HIV risk behaviours reported, and counselling services provided after each counselling session. Matching and regression methods were used to determine the probability of condom uptake by serostatus, gender, and receipt of personalized risk reduction counselling while controlling for other characteristics. Results: HIV counselling and testing was associated with condom uptake among 29.2% of HIV positive women (CI 24.5-34.4%), 31.7% of HIV positive men (CI 27.8-35.4%), 15.5% of HIV negative women (CI 11.2-20.8%), and only 3.6% of HIV negative men (CI 1.9-5.9%) who had previously never used condoms. Personalized risk reduction counselling increased impact in some groups; for example an additional 18% of HIV negative women (CI 11.3-24.4%) and 17% of HIV positive men (CI 10.9-23.4%) started using condoms. The number of sexual partners was not associated with the impact of counselling completeness. Conclusions: Because the components of testing and counselling impact the condom use habits of men and women differently, understanding the dynamics of condom use negotiation between partners is essential to optimizing impact on Indian couples. Clients' predicted condom uptake ranged between 4% and 47% depending on factors like gender, serostatus, and services provided. Personalized risk reduction counselling is associated with increased chance of condom use, with larger gains in HIV negative women and HIV positive men. HIV negative men are least likely to start using condoms and least impacted by additional counselling. © 2012 Myerson et al; licensee BioMed Central Ltd.

Parasa V.R.R.,National Institute for Research in Tuberculosis ICMR | Sikhamani R.,Government Hospital of Thoracic Medicine | Raja A.,National Institute for Research in Tuberculosis ICMR
PLoS ONE | Year: 2012

Background: NK cells express several specialized receptors through which they recognize and discriminate virally-infected/tumor cells efficiently from healthy cells and kill them. This ability to lyse is regulated by an array of inhibitory or activating receptors. The present study investigated the frequency of various NK receptors expressed by NK cell subsets from HIV-infected TB patients. The effect of IL-15+IL-12 stimulation on the expression of NK receptors was also studied. Methodology/Principal Findings: The study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals and patients with HIV and tuberculosis co-infection. The expression of NK cell receptors was analyzed on two NK cell subsets within the peripheral blood: CD16+CD3- and CD56+CD3- using flow cytometry. The expression of inhibitory receptors (CD158a, CD158b, KIRp70, CD85j and NKG2A) on NK subsets was increased in HIV, when compared to NHS. But the response in HIV-TB was not uniform. Stimulation with IL-15+IL-12 dropped (p<0.05) the expression of CD85j and NKG2A in HIV. The basal expression of natural cytotoxicity receptors (NKp30 and NKp46) on NK cell subsets was lowered (p<0.05) in HIV and HIV-TB as compared to NHS. However, the expression of NKp44 and NKG2D was elevated in HIV. Enhanced NKp46 and NKG2D expression was observed in HIV with IL-15+IL-12 stimulation. The coreceptor NKp80 was found to be expressed in higher numbers on NK subsets from HIV compared to NHS, which elevated with IL-15+IL-12 stimulation. The expression of NK receptors and response to stimulation was primarily on CD56+CD3- subset. Conclusions/Significance: IL-15+IL-12 has an immunomodulatory effect on NK cell subsets from HIV-infected individuals viz down-regulation of iNKRs, elevation of activatory receptors NKp46 and NKG2D, and induction of coreceptor NKp80. IL-15+IL-12 is not likely to be of value when co-infected with TB probably due to the influence of tuberculosis. © 2012 Parasa et al.

PubMed | University of Madras, Bharath University and Government Hospital of Thoracic Medicine
Type: | Journal: Journal of pathogens | Year: 2016

Extended Spectrum -Lactamases (ESBLs) confer resistance to third-generation cephalosporins and CTX-M types have emerged as the most prominent ESBLs worldwide. This study was designed to determine the prevalence of CTX-M positive ESBL-producing urinary E. coli isolates from HIV patients and to establish the association of multidrug resistance, phylogeny, and virulence profile with CTX-M production. A total of 57 ESBL producers identified among 76 E. coli strains isolated from HIV patients from South India were screened for bla CTX-M, AmpC production, multidrug resistance, and nine virulence associated genes (VAGs), fimH, pap, afa/dra, sfa/foc, iutA, fyuA, iroN, usp, and kpsMII. The majority (70.2%) of the ESBL producers harbored bla CTX-M and were AmpC coproducers. Among the CTX-M producers, 47.5% were found to be UPEC, 10% harbored as many as 7 VAGs, and 45% possessed kpsMII. Multidrug resistance (CIP(R)SXT(R)GEN(R)) was significantly more common among the CTX-M producers compared to the nonproducers (70% versus 41.2%). However, 71.4% of the multidrug resistant CTX-M producers exhibited susceptibility to nitrofurantoin thereby making it an effective alternative to cephalosporins/fluoroquinolones. The emergence of CTX-M-producing highly virulent, multidrug resistant uropathogenic E. coli is of significant public health concern in countries like India with a high burden of HIV/AIDS.

Rewari B.B.,Ministry of Health and Family Welfare | Bachani D.,Ministry of Health and Family Welfare | Rajasekaran S.,Government Hospital of Thoracic Medicine | Deshpande A.,Sir Jj Hospital | And 3 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2010

Background: The identification and management of first-line antiretroviral therapy (ART) failure is a key challenge for HIV programs in resource-limited settings. In 2008, the National AIDS Control Organisation, India piloted a national strategy to provide second-line ART. We assessed the National AIDS Control Organisation second-line ART evaluation algorithm. Methods: Adult patients who had received 6 months or more of standard first-line ART were referred for second-line ART evaluation if they demonstrated CD4 decline to pre-ART values, CD4 drop to less than 50% of peak on-treatment value, failure to achieve CD4 greater than 100 c/mm, or development of a new World Health Organization Stage 3 or 4 AIDS-defining illness. Patients received HIV RNA testing, and those with HIV RNA 10,000 c/mL or greater qualified to switch to second-line ART. World Health Organization-defined clinical and CD4 criteria for ART failure were compared against virologic failure criteria. Results: Between January and June 2008, 154 patients met criteria for evaluation. Of 122 (79%) patients who had HIV RNA testing, 87 (71%) had viral load 10,000 c/mL or greater and were recommended to start second-line ART, 29 (24%) had viral load less than 400 c/mL, and six (5%) had viral load between 400 and 10,000 c/mL. The positive predictive value of World Health Organization clinical/immunologic criteria to detect virologic failure was 71% (95% confidence interval, 63% to 79%). Conclusions: Second-line ART was initiated in the public sector in India using an approach combining clinical and immunologic evaluation with confirmation of virologic failure. Almost 25% of patients who met clinical/immunologic failure criteria demonstrated virologic suppression. Inclusion of targeted HIV RNA testing in the evaluation of treatment failure can prevent unnecessary switches to second-line ART. © 2010 by Lippincott Williams & Wilkins.

Ramachandran G.,National Institute for Research in Tuberculosis | Kumar A.K.H.,National Institute for Research in Tuberculosis | Bhavani P.K.,National Institute for Research in Tuberculosis | Kannan T.,National Institute for Research in Tuberculosis | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (Cmax) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median Cmax and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC0-8]) of INH (Cmax, 2.5 versus 5.1 -g/ml, respectively [P = 0.016]; AUC0-8, 11.1 versus 22.0 -g/ml • h, respectively [P = 0.047[) and PZA (Cmax, 34.1 versus 42.3 -g/ml, respectively [P = 0.055]; AUC0-8, 177.9 versus 221.7 -g/ml • h, respectively [P = 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median Cmax of RMP (1.0 versus 2.8 μg/ml, respectively; P = 0.002) and PZA (31.9 versus 44.4 μg/ml, respectively; P = 0.045) were significantly lower. Among all factors studied, the PZA Cmax influenced TB treatment outcome (P = 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP Cmax. The PZA Cmax significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized. © 2015 American Society for Microbiology. All Rights Reserved.

Swaminathan S.,Tuberculosis Research Center | Ramachandran G.,Tuberculosis Research Center | Kupparam H.K.A.,Tuberculosis Research Center | Mahalingam V.,Tuberculosis Research Center | And 6 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2011

Background: Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression. Objectives: To study the influence of age, drug dose and formulation type, nutritional status and CYP2B6 516G>T polymorphism on blood concentrations of nevirapine in children treated with generic antiretroviral drugs. Methods: A multicentre study was conducted at four sites in India. HIV-infected children receiving generic nevirapine-based fixed-dose combinations were recruited. Trough and 2 h nevirapine plasma concentrations were determined by HPLC. Characterization of the CYP2B6 gene polymorphism was performed using direct sequencing. Clinical and nutritional status was recorded. Groups were compared using the Mann-Whitney U-test and multivariable logistic regression analysis was performed to identify factors contributing to low drug levels. Results: Ninety-four children of median age 78 months were studied; 60% were undernourished or stunted. Stunted children had a significantly lower 2 h nevirapine concentration compared with non-stunted children (P<0.05); there were no significant differences in trough concentrations between different nutritional groups. Nevirapine levels were significantly higher in children with TT compared with GG and GT CYP2B6 genotypes (P<0.01). Children ≤3 years had a 3.2 (95% confidence interval 1.07-9.45) times higher risk of having sub-therapeutic nevirapine concentrations. Conclusions: Nevirapine blood concentrations are affected by many factors, most notably age ≤3 years; a combination of young age, stunting and CYP2B6 GG or GT genotype could potentially result in sub-therapeutic nevirapine concentrations. Dosing recommendations for children should be reviewed in the light of these findings. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Syed Ahamed Kabeer B.,Tuberculosis Research Center | Sikhamani R.,Government Hospital of Thoracic Medicine | Raja A.,Tuberculosis Research Center
Diagnostic Microbiology and Infectious Disease | Year: 2011

We aimed to compare the positivity of the QuantiFERON TB gold in-tube (QFT-IT antigens) specific interferon gamma (IFN-γ/QFT-IT) and IFN-γ-inducible protein-10 (IP-10/QFT-IT) assays with tuberculin skin test (TST) among human immunodeficiency virus (HIV)-infected individuals in a TB endemic setting. A total of 180 HIV-infected subjects, with no evidence of active TB, were recruited. IFN-γ and IP-10 levels specific to QFT-IT antigens were measured in plasma from QFT-IT tubes. The overall positivity of TST at the 5-mm cut-off point (19%) was significantly lower when compared to IFN-γ/QFT-IT (38%) and IP-10/QFT-IT (45%) assays. The positivity of IP-10/QFT-IT was significantly higher than that of IFN-γ/QFT-IT (P = 0.038). Indeterminate results for IFN-γ/QFT-IT and IP-10/QFT-IT were more frequent in subjects with CD4 count <100 cells/μL than in those with >100 cells/μL. IFN-γ/QFT-IT (9%) yielded significantly higher number of indeterminate results than IP-10/QFT-IT (5%). The frequency of these responses is higher than the proportion of individuals with positive TST results. However, 6 IFN-γ/QFT-IT- or IP-10/QFT-IT-negative subjects were positive for TST at the 5-mm cut-off point. Prospective and prognostic studies are required to clarify the significance of these data. © 2011 Elsevier Inc.

Ramana Rao P.V.,Tuberculosis Research Center | Rajasekaran S.,Government Hospital of Thoracic Medicine | Raja A.,Tuberculosis Research Center
Journal of Interferon and Cytokine Research | Year: 2010

Natural killer (NK) cells control Mycobacterium tuberculosis infection mainly through secreted cytokines. Cytokine dysregulation among HIV may cause rapid disease progression. Our objective was to examine whether impaired production of innate cytokines are responsible for cytokine dysregulation during HIV infection. The study included 30 subjects each of normal healthy subjects (NHS), pulmonary tuberculosis patients (TB), HIV-infected individuals (HIV), and HIV-TB co-infected patients (HIV-TB). Intracellular cytokine staining method was used to enumerate the cytokine-positive NK cells. Unlike NHS (100%), only 27% of HIV-TB and 57% of HIV infected patients have detectable plasma interleukin (IL)-15 levels that signify impaired rather than decreased IL-15 production. Basal type 1 cytokine (IL-2, interferon- [IFN-], and tumor necrosis factor- [TNF-])-secreting NK cells (NK1 cytokines) were decreased significantly (P < 0.05) in TB, HIV, and HIV-TB, when compared with NHS. Stimulation with M. tuberculosis H37Rv enhanced the NK1 cytokines in NHS (P < 0.05), but not in other groups. With IL-15+IL-12 stimulation, we found increased NK1 cytokines (IL-2 and IFN-) in HIV (P < 0.05), but not in HIV-TB, when compared to unstimulated condition. Supplementing IL-15+IL-12 has potential in improving the frequency of NK1 cytokines for HIV, but not HIV-TB, suggesting that TB influences cytokine response during HIV infection. © Mary Ann Liebert, Inc.

Kabeer B.S.A.,Tuberculosis Research Center | Sikhamani R.,Government Hospital of Thoracic Medicine | Raja A.,Tuberculosis Research Center
AIDS | Year: 2010

Interferon gamma (IFNγ)-based in-vitro assays have suboptimal sensitivity, especially in immunocompromised individuals, which emphasizes the need for alternative markers for tuberculosis (TB) diagnosis. We compared TB antigens-specific IFNγ and IFNγ-inducible protein-10 levels in culture of whole blood samples from HIV-TB patients. We report that IFNγ-inducible protein-10 detects a greater number of HIV-TB cases than IFNγ and suggest that IFNγ-inducible protein-10 may be a better alternative marker for latent TB infection diagnosis among immunocompromised individuals. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Ramachandran G.,National Institute for Research in Tuberculosis | Hemanth Kumar A.K.,National Institute for Research in Tuberculosis | Bhavani P.K.,National Institute for Research in Tuberculosis | Poorana Gangadevi N.,National Institute for Research in Tuberculosis | And 7 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2013

SETTING: The currently recommended dosages of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol in children are extrapolated from adult pharmacokinetic studies, and have not been adequately evaluated in children. OBJECTIVE: To describe the pharmacokinetics of RMP, INH and PZA given thrice weekly in children with tuberculosis (TB), and to relate pharmacokinetics to treatment outcomes. METHODS: Eighty-four human immunodeficiency virus negative children with TB aged 1-12 years in Chennai and Madurai, India, were recruited. Phenotypic INH acetylator status was determined. Nutritional status was assessed using Z scores. During the intensive phase of anti-tuberculosis treatment, a complete pharmacokinetic study was performed after directly observed administration of drugs. At 2 and 6 months, drug levels were measured 2 h post-dose. Drug concentrations were measured using high performance liquid chromatography and pharmacokinetic variables were calculated. Multi-variable regression analysis was performed to explore factors impacting drug levels and treatment outcomes. RESULTS AND CONCLUSIONS: Children aged <3 years had significantly lower RMP, INH and PZA concentrations than older children, and 90% of all children had sub-therapeutic RMP Cmax (<8 μg/ml). Age, nutritional status and INH acetylator status influenced drug levels. Peak RMP and INH concentrations were important determinants of treatment outcome. Recommendations for anti-tuberculosis treatment in children should take these factors into consideration. © 2013 The Union.

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