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Shriram A.N.,Medical Port | Krishnamoorthy K.,Vector Control Research Center Indian Council of Medical Research | Saha B.P.,Directorate of Health Services | Kumaraswami V.,Tuberculosis Research Center Indian Council of Medical Research | And 3 more authors.
Parasitology Research | Year: 2011

The elimination of lymphatic filariasis in the Andaman and Nicobar Islands provides unique opportunities and challenges at the same time. Since these islands are remote, are sparsely populated, and have poor transport networks, mass drug administration programs are likely to be difficult to implement. Diurnally subperiodic Wuchereria bancrofti vectored by Downsiomyia nivea was considered for the scope of vector control options. Considering the bioecology of this mosquito, vector control including personal protection measures may not be feasible. However, since these islands are covered by separate administrative machinery which also plays an important role in regulating the food supply, the use of diethylcarbamazine (DEC)-fortified salt as a tool for the interruption of transmission is appealing. DEC-fortified salt has been successfully pilot tested in India and elsewhere, operationally used by China for eliminating lymphatic filariasis. Administration of DEC-fortified salt though simple, rapid, safe, and cost-effective, challenges are to be tackled for translating this precept into action by evolving operationally feasible strategy. Although the use of DEC-fortified salt is conceptually simple, it requires commitment of all sections of the society, an elaborate distribution mechanism that ensures the use of DEC-fortified salt only in the endemic communities, and a vigorous monitoring mechanism. Here, we examine the inbuilt administrative mechanisms to serve the tribal people, health infrastructure, and public distribution system and discuss the prospects of putting in place an operationally feasible strategy for its elimination. © 2011 Springer-Verlag.


Suhadev M.,Tuberculosis Research Center Indian Council of Medical Research | Mahadevan U.,Loyola College | Dilip M.,Tuberculosis Research Center Indian Council of Medical Research | Suryanarayanan D.,Tuberculosis Research Center Indian Council of Medical Research | And 2 more authors.
Journal of the International Association of Physicians in AIDS Care | Year: 2011

Most studies have described the outcome of HIV status disclosure rather than the process of disclosure. Hence, a study was conducted among 201 women who accompanied their spouses and children to 3 hospitals at Chennai and Vellore, Tamil Nadu, India, during January to June 2007. Majority of the respondents were sero-positive (69%) and marriage was the only risk factor for them. Of 201 women, 49% did not know the reason for their husbands' HIV infection. Confidentiality of the patient was often breached during disclosure as family members were drawn into the process without consulting the patient. Only for 117 (50%) respondents, HIV diagnosis was disclosed directly by the health providers. There was a considerable delay for men in disclosing their HIV status to their spouses. Apart from the spouses, 122 (61%) shared their diagnosis with other family members. Disgrace to self and family (54%), fear of discrimination (27%), and fear of rejection (9%) were reported for nondisclosure. © The Author(s) 2011.


Senbagavalli P.,National Institutes of Health | Anuradha R.,National Institutes of Health | Ramanathan V.D.,Tuberculosis Research Center Indian Council of Medical Research | Kumaraswami V.,Tuberculosis Research Center | And 2 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2011

The presence of circulating immune complexes (CICs) is a characteristic feature of human lymphatic filariasis. However, the role of CICs in modulating granulocyte function and complement functional activity in filarial infection is unknown. The levels of CICs in association with complement activation in clinically asymptomatic, filarial-infected patients (INF); filarial-infected patients with overt lymphatic pathologic changes (CPDT); and uninfected controls (EN) were examined. Significantly increased levels of CICs and enhanced functional efficiency of the classical and mannose-binding lectin pathways of the complement system was observed in INF compared with CPDT and EN. Polyethylene glycol - precipitated CICs from INF and CPDT induced significantly increased granulocyte activation compared with those from EN, determined by the increased production of neutrophil granular proteins and a variety of pro-inflammatory cytokines. Thus, CIC-mediated enhanced granulocyte activation and modulation of complement function are important features of filarial infection and disease. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene.


Subramanyam B.,Tuberculosis Research Center Indian Council of Medical Research | Kumar V.,Tuberculosis Research Center Indian Council of Medical Research | Perumal V.,Tuberculosis Research Center Indian Council of Medical Research | Nagamiah S.,Tuberculosis Research Center Indian Council of Medical Research
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2010

The overgrowth of normal flora escaping the action of sputum processing chemicals is the major problem in broth-based tuberculosis (TB) detection systems. The use of phages to control the overgrowth of normal flora in processed sputum samples has already been established. Phage lysin and its supplementation to phagebiotics for the effective control of normal flora in sputum specimens were evaluated. Crude lysin was prepared from phage host mixture using standard procedures. About 120 sputum samples processed with 4% NaOH were collected and used to evaluate the effect of lysin, phagebiotics and phagebiotics supplemented with lysin on the overgrowth of normal flora. The effect of phagebiotics and lysin on the growth and retrieval of Mycobacterium tuberculosis was studied by conventional methods and the luciferase reporter phage (LRP) assay. Lysin alone and phagebiotics supplemented with lysin arrested the growth of normal flora in a significantly greater number of samples than phagebiotics alone. Lysin and phagebiotics did not show any inhibitory activity on M. tuberculosis. The use of antibiotics can be replaced by lysin or phagebiotics supplemented with lysin to control the overgrowth of normal flora in processed sputum samples without hampering the viability of M. tuberculosis. © 2010 Springer-Verlag.


Kumar A.K.H.,Tuberculosis Research Center Indian Council of Medical Research | Sudha V.,Tuberculosis Research Center Indian Council of Medical Research | Srinivasan R.,Tuberculosis Research Center Indian Council of Medical Research | Ramachandran G.,Tuberculosis Research Center Indian Council of Medical Research
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2011

A high performance liquid chromatographic method for determination of moxifloxacin in human saliva was developed. The method involved deproteinisation of the sample with perchloric acid and analysis of the supernatant using a reversed-phase C18 column (150 mm) and fluorescence detection at an excitation wavelength of 290 nm and an emission wavelength of 460 nm. The assay was specific for moxifloxacin and linear from 0.25 to 10.0. μg/ml. The relative standard deviation of intra- and inter-day assays was lower than 10%. The average recovery of moxifloxacin from saliva was 101%. Due to its simplicity, the assay can be used for pharmacokinetic studies of moxifloxacin. © 2011 Elsevier B.V.


PubMed | Tuberculosis Research Center Indian Council of Medical Research
Type: Journal Article | Journal: Bioinformation | Year: 2011

Mycobacteriophage genome database (MGDB) is an exclusive repository of the 64 completely sequenced mycobacteriophages with annotated information. It is a comprehensive compilation of the various gene parameters captured from several databases pooled together to empower mycobacteriophage researchers. The MGDB (Version No.1.0) comprises of 6086 genes from 64 mycobacteriophages classified into 72 families based on ACLAME database. Manual curation was aided by information available from public databases which was enriched further by analysis. Its web interface allows browsing as well as querying the classification. The main objective is to collect and organize the complexity inherent to mycobacteriophage protein classification in a rational way. The other objective is to browse the existing and new genomes and describe their functional annotation.The database is available for free at http://mpgdb.ibioinformatics.org/mpgdb.php.


PubMed | Tuberculosis Research Center Indian Council of Medical Research
Type: Evaluation Studies | Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases | Year: 2012

Phage lysin was evaluated as a substitute for antibiotics in sputum samples processed by a modified Petroffs method for the detection of Mycobacterium tuberculosis with the MGIT 960 system. One hundred and fifty sputum samples were processed, inoculated onto two slopes of Lowenstein-Jensen medium, and divided in to two aliquots of 0.5mL each. One aliquot was added to 7mL of MGIT medium containing polymyxin B, amphotericin B, nalidixic acid, trimethoprim and azlocillin (PANTA) (MGIT-PANTA) and the other was added to 7mL of MGIT medium containing 0.8mL of lysin (MGIT-Lysin). The samples were randomized and incubated at 37C in the MGIT 960 system. The sensitivity and specificity of MGIT-Lysin were 97% and 88%, respectively, as compared with MGIT-PANTA. The average times to detection with MGIT-Lysin and MGIT-PANTA were 9.3 and 8.6 days, respectively. The rate of contamination with MGIT-PANTA and MGIT-Lysin were 16% and 7.3%, respectively. Phage lysin can be substituted for antibiotics in processed sputum samples for the detection of M. tuberculosis.


PubMed | Tuberculosis Research Center Indian Council of Medical Research
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2011

Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression.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.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.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.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.


PubMed | Tuberculosis Research Center Indian Council of Medical Research
Type: Journal Article | Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences | Year: 2011

A high performance liquid chromatographic method for determination of moxifloxacin in human saliva was developed. The method involved deproteinisation of the sample with perchloric acid and analysis of the supernatant using a reversed-phase C18 column (150 mm) and fluorescence detection at an excitation wavelength of 290 nm and an emission wavelength of 460 nm. The assay was specific for moxifloxacin and linear from 0.25 to 10.0 g/ml. The relative standard deviation of intra- and inter-day assays was lower than 10%. The average recovery of moxifloxacin from saliva was 101%. Due to its simplicity, the assay can be used for pharmacokinetic studies of moxifloxacin.


PubMed | Tuberculosis Research Center Indian Council of Medical Research
Type: Journal Article | Journal: Indian journal of pediatrics | Year: 2011

Tuberculosis (TB) is among the top 10 causes of death among children worldwide. Recent reports suggest that the currently recommended dosages of first-line anti-TB drugs are not adequate in children, particularly younger children. The objective of this review was to synthesize available pharmacokinetic data of anti-TB drugs in children from different settings that would help determine optimal doses of anti-TB drugs, in order to provide evidence-based recommendations. A PubMed database was searched from 1970 to present using the terms rifampicin, isoniazid, pyrazinamide, ethambutol, pharmacokinetics, HIV, TB, nutrition and children. References from identified articles were also reviewed and abstract from recent meetings were included. Available pharmacokinetic data from different settings suggest that age, nutritional status, HIV infection and gene polymorphisms in drug metabolising enzymes could significantly influence the pharmacokinetics of first-line anti-TB drugs. However, most of the pharmacokinetic studies conducted so far in children have failed to associate drug concentrations with treatment outcomes. Hence, more studies to examine the relationship between drug pharmacokinetics and response to anti-TB treatment are required. Studies to examine the impact of nutritional status and HIV infection on the pharmacokinetics of anti-TB drugs in children are needed.

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