65 results on '"Kannangai, Rajesh"'
Search Results
2. HPV and molecular mimicry in systemic lupus erythematosus and an impact of compiling B-cell epitopes and MHC-class II binding profiles with in silico evidence.
- Author
-
Calvin, D. John Dickson, Steve, Runal John, Kannangai, Rajesh, Abraham, Priya, Udhaya Kumar, S., Balasundaram, Ambritha, George Priya Doss, C., Thomas, Vinotha, Thomas, Anitha, Danda, Debashish, and Fletcher, John Gnanadurai
- Published
- 2023
- Full Text
- View/download PDF
3. Diagnostic study of human papillomavirus DNA detection in cervical and vaginal samples using the filter paper card.
- Author
-
Ramesan, Chiyancheri Koroth, Calvin, John Dickson, Thomas, Anitha, Fletcher, John, Kannangai, Rajesh, Abraham, Priya, and Peedicayil, Abraham
- Published
- 2023
- Full Text
- View/download PDF
4. Challenges and Pragmatic Solutions for Assessing the Reliability of HIV-1 Viral Load Monitoring in Resource-Constrained Settings
- Author
-
Demosthenes, John Paul, Ghale, Ben Chirag, Alex, Diviya, Ramalingam, Veena Vadhini, Fletcher, Gnanadurai John, Abraham, Priya, and Kannangai, Rajesh
- Abstract
Introduction:HIV-1 RNA detection is the most reliable method for monitoring treatment response among people living with HIV. Effective quality control measures that include internal quality control (IQC) are challenging in resource-constrained settings. Methods:We ascertained the utility of the kit low positive control (LPC) as an effective IQC to monitor the reliability of the HIV-1 viral load assay. Variations in LPC values were measured for 390 different runs over 10 years (2011–2021) and compared to in-house IQC data using Levey-Jennings control chart. Results:Overall, the Levey-Jennings analysis showed minimal variation (±0.5 log) for both the LPC and IQC data. The mean LPC value for first 20 runs (20 days) was 2.91. The mean LPC value for the 390 runs comprising 35 different lots was 3.01 ± 0.1 log. Conclusion:Our decadal data reveal that Abbott RealTime HIV-1 assay (Abbott Molecular Inc., IL, USA) LPC exhibited no significant biological variation over 390 runs distributed over 10 years. Hence, assay LPC can supplant the IQC for monitoring assay trends as a stable and commutable material in resource-constrained settings.
- Published
- 2023
- Full Text
- View/download PDF
5. The impact of human papilloma virus on human reproductive health and the effect on male infertility: An updated review.
- Author
-
Das, Soumik, Doss C, George Priya, Fletcher, John, Kannangai, Rajesh, Abraham, Priya, and Ramanathan, Gnanasambandan
- Subjects
MALE infertility ,HUMAN papillomavirus ,REPRODUCTIVE health ,MALE reproductive health ,SEXUALLY transmitted diseases ,YOUNG adults - Abstract
It is believed that human papilloma virus infection (HPV), which is caused by the DNA virus, is the most prominent factor contributing to sexually transmitted disease (STD) in the world, with males having a prevalence rate of 3.5%–45% while that women are 2%–44%. Infertility is a rising problem on a global basis, affecting anywhere from 10% to 30% of couples who have reached reproductive age. This study aims to investigate the existing research on HPV, its connection to male infertility, and how it could be a helpful tool for medical professionals managing HPV in the context of reproductive health care. Infection with HPV has been identified as a risk factor for several spontaneous abortions; however, there is a lack of evidence on how HPV influences individuals undergoing assisted reproductive technology (ART) in terms of live births. The significance of the immune response to HPV‐infected male reproductive system cells and its effect on embryos, as well as the oxidative stress generated by high‐risk HPV DNA damage and genomic instability, is discussed in this review. Further, the association between male individuals infected with HPV and asthenozoospermia should provide a compelling case for vaccinating young people against HPV. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Longitudinal assessment of HCV core antigen kinetics to monitor therapeutic response in the age of DAAs.
- Author
-
Ponnuvel, Suresh, Prakash, Arul, Steve, Runal John, Doss, George Priya, Goel, Ashish, Zachariah, Uday George, Eapen, Chundamannil Eapen, Rebekah, Grace, Kannangai, Rajesh, Fletcher, Gnanadurai John, and Abraham, Priya
- Subjects
BIOMARKERS ,DISCOURSE markers ,ANTIVIRAL agents ,ANTIGENS ,VIRAL replication - Abstract
Background: In the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response. Methods: In this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years. Results: After the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05). Conclusions: It is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Indian microbiology EQAS registered laboratory’s capacity building and infection control practices during the COVID-19 pandemic in India: Lessons learnt and gaps identified
- Author
-
Murugesan, Malathi, Raveendran, Reena, Kannangai, Rajesh, Ramasamy, Jagadish, Ray, Pallab, Gope, Mallika, Natarajan, Venkateswaran, Walia, Kamini, Wattal, Chand, and Veeraraghavan, Balaji
- Abstract
The COVID-19 pandemic was unique in the history of outbreaks because of the massive scaling up of resources related to diagnostics, treatment modalities, and vaccines. To understand the impact of the pandemic among laboratory professionals, we aimed to conduct a survey to assess the improvement in the lab capacity post-covid in terms of infrastructure and accreditation status across various levels of hospitals and to determine the changes in the practice of infection control precautions during the pandemic.
- Published
- 2023
- Full Text
- View/download PDF
8. Age‐stratified adeno‐associated virus serotype 3 neutralizing and total antibody prevalence in hemophilia A patients from India.
- Author
-
Daniel, Hubert D.‐J, Kumar, Sanjay, Kannangai, Rajesh, J., Farzana, Joel, Joseph N., Abraham, Aby, Lakshmi, Kavitha M., Agbandje‐McKenna, Mavis, Coleman, Kirsten E., Srivastava, Arun, Srivastava, Alok, and Abraham, Asha M.
- Subjects
HEMOPHILIACS ,ADENO-associated virus ,ENZYME-linked immunosorbent assay ,HEMOPHILIA ,GENE therapy - Abstract
Gene therapy using an adeno‐associated virus (AAV) vector offers a new treatment option for individuals with monogenetic disorders. The major bottleneck is the presence of pre‐existing anti‐AAV antibodies, which impacts its use. Even very low titers of neutralizing antibodies (NAb) to capsids from natural AAV infections have been reported to inhibit the transduction of intravenously administered AAV in animal models and are associated with limited efficacy in human trials. Assessing the level of pre‐existing NAb is important for determining the primary eligibility of patients for AAV vector‐based gene therapy clinical trials. Techniques used to screen AAV‐antibodies include AAV capsid enzyme‐linked immunosorbent assay (ELISA) and transduction inhibition assay (TIA) for detecting total capsid‐binding (TAb) and Nab, respectively. In this study, we screened 521 individuals with hemophilia A from India for TAb and NAb using ELISA and TIA, respectively. The prevalence of TAb and NAb in hemophilia A patients from India were 96% and 77.5%, respectively. There was a significant increase in anti‐AAV3 NAb prevalence with age in the hemophilia A patient group from India. There was a trend in anti‐AAV3 TAb positivity between the pediatric age group (94.4%) and the adult age group (97.4%). [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. Internal quality control for HIV testing of blood donors - Dried tube specimen as a cost-effective alternative.
- Author
-
Dhoot, Ashish, Mammen, Joy, Mathews, Nitty, Kannangai, Rajesh, Daniel, Dolly, and Prasannakumar, S
- Subjects
DIAGNOSIS of HIV infections ,BLOOD chemical analysis ,BLOOD banks ,MEDICAL screening ,BLOOD collection ,QUALITY assurance ,COST analysis ,ENZYME-linked immunosorbent assay ,DESCRIPTIVE statistics ,DATA analysis software - Abstract
BACKGROUND: An important aspect of ensuring blood safety is the performance of mandatory serological testing for transfusion transmissible infections. The practice of internal quality control (IQC) in blood banks in India is nonuniform, especially the use of third-party materials. Cited reasons are cost, lack of access to control materials, and need for deep-freezers for storage, if prepared in-house. OBJECTIVE: Validation of dried tube specimen (DTS) from HIV-positive plasma as a low-cost, stable material for use as IQC material in blood banks. METHODS: Fresh-frozen plasma (FFP) prepared from four HIV-positive blood-donors were pooled. Equal numbers of seronegative FFPs were pooled. Twenty microlitre aliquots of plasma were made in micro-centrifuge tubes and air-dried overnight at room-temperature. These were stored in 2–8°C refrigerators and tested once weekly for 6 months on multiple platforms with different detection principles: Rapid tests, second-generation enzyme-linked immunosorbent assay (ELISA), fourth-generation ELISA, and fourth-generation Chemiluminescence immunoassay. The protocol was sustained over the next 6 months with decreased testing frequency to study the extended stability of DTS. RESULTS: A total of 139 positive-DTS and 139 negative-DTS were tested with 100% samples showing consistent results on all platforms over 1 year. There was mild deterioration in reaction strengths, which did not interfere in result interpretations. CONCLUSION: Plasma in form of DTS maintained stability when stored at 2–8°C for 1 year. This provides evidence that DTS can be a modality for the production of cost-effective, stable, in-house control material for resource-restricted countries. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. The CCR5 Gene Edited CD34+CD90+ Hematopoietic Stem Cell Population Serves as an Optimal Graft Source for HIV Gene Therapy.
- Author
-
Karuppusamy, Karthik V., Demosthenes, John Paul, Venkatesan, Vigneshwaran, Christopher, Abisha Crystal, Babu, Prathibha, Azhagiri, Manojkumar K., Jacob, Annlin, Ramalingam, Veena Vadhini, Rangaraj, Sumathi, Murugesan, Mohankumar Kumarasamypet, Marepally, Srujan Kumar, Varghese, George M., Srivastava, Alok, Kannangai, Rajesh, and Thangavel, Saravanabhavan
- Subjects
HEMATOPOIETIC stem cells ,GENOME editing ,GENE therapy ,CHEMOKINE receptors ,CELL populations - Abstract
Transplantation of allogenic hematopoietic stem and progenitor cells (HSPCs) with C-C chemokine receptor type 5 (CCR5) Δ32 genotype generates HIV-1 resistant immune cells. CCR5 gene edited autologous HSPCs can be a potential alternative to hematopoietic stem cell transplantation (HSCT) from HLA-matched CCR5 null donor. However, the clinical application of gene edited autologous HSPCs is critically limited by the quality of the graft, as HIV also infects the HSPCs. In this study, by using mobilized HSPCs from healthy donors, we show that the CD34
+ CD90+ hematopoietic stem cells (HSCs) express 7-fold lower CD4/CCR5 HIV receptors, higher levels of SAMHD1 anti-viral restriction factor, and possess lower susceptibility to HIV infection than the CD34+ CD90- hematopoietic progenitor cells. Further, the treatment with small molecule cocktail of Resveratrol, UM729 and SR1(RUS) improved the in vivo engraftment potential of CD34+ CD90+ HSCs. To demonstrate that CD34+ CD90+ HSC population as an ideal graft for HIV gene therapy, we sort purified CD34+ CD90+ HSCs, treated with RUS and then gene edited the CCR5 with single sgRNA. On transplantation, 100,000 CD34+ CD90+ HSCs were sufficient for long-term repopulation of the entire bone marrow of NBSGW mice. Importantly, the gene editing efficiency of ~90% in the infused product was maintained in vivo , facilitating the generation of CCR5 null immune cells, resistant to HIV infection. Altogether, CCR5 gene editing of CD34+ CD90+ HSCs provide an ideal gene manipulation strategy for autologous HSCT based gene therapy for HIV infection. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
11. Prevalence of Adeno-Associated Virus 3 Capsid Binding and Neutralizing Antibodies in Healthy and Hemophilia B Individuals from India.
- Author
-
Daniel, Hubert D.-J., Kumar, Sanjay, Kannangai, Rajesh, Lakshmi, Kavitha M., Agbandje-Mckenna, Mavis, Coleman, Kirsten, Srivastava, Arun, Srivastava, Alok, and Abraham, Asha Mary
- Published
- 2021
- Full Text
- View/download PDF
12. Chronic Immune Activation Among Treatment Naïve HIV/ HBV Coinfected Individuals From Southern India
- Author
-
Demosthenes, John P., Fletcher, Gnanadurai John, Zachariah, Uday George, Varghese, George Mannil, Pulimood, Susanne Alexander, Abraham, Priya, and Kannangai, Rajesh
- Abstract
Background: Chronic immune activation is one of the most widely recognized hallmarks of HIV infection. T-cells that express CD38+ and HLA-DR+ show poor proliferative potential, signal transduction, and increased apoptotic potential. This affects HIV pathogenesis and its outcome and further complicates with a coinfection like HBV. Methods: Study Design: cross-sectional. Blood samples were collected and analyzed for virological markers using ELISA for HBeAg and RT-PCR for HIV Viral load. Chronic immune activation markers of CD8+ and CD4+ T cells were measured by Flow cytometry for both HIV and HBV. Results: There was a significant increase in HBV replication shown by higher HBV DNA (p=0.002), a higher proportion of HBeAg (p=0.0049), and lower CD4 counts (p=0.04) among HIV/HBV coinfected individuals, compared to the monoinfected groups. The frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ in the HIV/HBV coinfection were significantly higher than HBV monoinfected group (P< 0.0001) and in the HIV monoinfected group (P < 0.0001). The Liver fibrosis score APRI and FIB-4, were higher in the coinfected group compared with HBV monoinfected group (0.67 vs. 0.25, p = 0.0085; 3.48 vs. 0.98, p = 0.0026) respectively. The cytokine levels of IL-17, Fas-L,TNF -α, IL-10, IL-2 and Granzyme B were also measured and compared among the study groups. Conclusion: Our data suggest that HIV probably influences immune activation of CD4+ and CD8+ T cells and this may play a significant role in accelerating the disease outcome among HIV/HBV coinfected individuals.
- Published
- 2021
- Full Text
- View/download PDF
13. Autoantibodies Among HIV-1 Infected Individuals and the Effect of Anti-Retroviral Therapy (ART) on It
- Author
-
Steve, Runal J., Alex, Diviya, Yesudhason, Binesh Lal, Prakash, John A. J., Mathews, Nitty Skariah, Daniel, Dolly, Ramalingam, Veena Vadhini, Demosthenes, John Paul, Ghale, Ben Chirag, Anantharam, Raghavendran, Rebekah, Grace, Rupali, Priscilla, Varghese, George Mannil, and Kannangai, Rajesh
- Abstract
Background: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies. Methods: It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board. Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity for anti-cardiolipin antibody was 15% among ART naïve while none of the ART experienced or controls were positive (p<0.05). IgM β2 glycoprotein-1 were 4%, 1% and 3% among ART naïve, treated and controls, respectively (p<0.05). IgG β2 glycoprotein-1 was 2% among ART naïve while none of the treated and controls were positive (p<0.05). The mean total IgG level among ART naïve, experienced, and controls were 21.82 (SD 6.67), 16.91 (SD 3.38), 13.70 (SD 2.24) grams/Litre, respectively (p<0.05). Conclusion: ART has a significant effect on IgG anti-cardiolipin antibody and total IgG but only a marginal effect on ANA, IgM, and IgG β2 glycoprotein-1 antibodies.
- Published
- 2021
- Full Text
- View/download PDF
14. Evaluating the PGMY-Centre Hospitalier Universitaire Vaudois Assay as a Cost-effective Tool for Human Papillomavirus Genotyping in HIV-infected Women
- Author
-
Baliga, Pallavi Ravindra, Anantharam, Raghavendran, Thomas, Vinotha, Rupali, Priscilla, Chopra, Manu, Pulimood, Susanne, Lionel, Jessie, Peedicayil, Abraham, Kannangai, Rajesh, Gnanamony, Manu, and Abraham, Priya
- Abstract
Aims:Cervical cancer is one of the leading causes of cancer among women, worldwide. HIV-positive women tend to have persistent infection and infection with multiple human papillomavirus (HPV) types. There is a need for affordable HPV DNA tests as viable alternatives to the existing costly commercial assays. The aim of the study was to establish PGMY-CHUV reverse hybridization assay as a cost-effective tool for HPV genotyping. Study Design:This was a prospective study conducted in a tertiary care centre from March 2011 to July 2012. Subjects and Methods:Fifty cervical brush samples from HIV-infected women and 43 WHO reference samples were tested by both the CHUV assay and linear array (LA). Results:The CHUV assay in comparison to the LA showed a sensitivity of 91%, specificity of 52% and a moderate agreement for all samples that were compared. However, most high-risk HPV types were identified amongst the clinical samples, and the entire range of genotypes in the WHO reference panel was detected. Statistical Analysis:The accuracy indices such as sensitivity, specificity, positive predictive value and negative predictive value were calculated. The level of agreement (kappa value) between the two assays was also calculated. Conclusion:The CHUV assay had an acceptable sensitivity, but it lacked specificity for HPV detection. Despite the lower rates of detection of multiple infections from clinical samples, better results were obtained with the WHO reference samples and the ability of the assay to identify the entire range of genotypes suggests that it can be an efficient tool for genotyping.
- Published
- 2019
- Full Text
- View/download PDF
15. Interaction of Human Immunodeficiency Virus-1 and Human Immunodeficiency Virus-2 Capsid Amino Acid Variants with Human Tripartite Motif 5αProtein SPRY Domain and its Association with Pathogenesis
- Author
-
Ramalingam, Veena Vadhini, Subramanian, Suganya, Fletcher, G.John, Rupali, Priscilla, Varghese, George, Pulimood, Susanne, Jeyaseelan, Lakshmanan, Nandagopal, Balaji, Sridharan, Gopalan, and Kannangai, Rajesh
- Abstract
Purpose:The sequence variation of human immunodeficiency virus (HIV) capsid region may influence and alter the susceptibility to human tripartite motif 5αprotein (huTRIM5α). Materials and Methods:Molecular docking was carried out with huTRIM5αSPRY domain by the use of ClusPro and Hex docking program for HIV-1 and HIV-2 capsid sequences. Results:The sequence analysis on HIV-1 and HIV-2 capsid gag gene identified 35 (19.7%) single-nucleotide polymorphisms (SNPs) in HIV-1 and 8 (4.5%) SNPs in HIV-2. The variations observed in the HIV-2 capsid region were significantly lower than HIV-1 (P< 0.001). The molecular docking analysis showed that HIV-1 wild type used V1 loop, while HIV-2 used V3 loop of huTRIM5αfor interaction. HIV-1 with A116T SNP and HIV-2 with V81A SNP use V3 and V1 loop of huTRIM5α for interaction respectively. The reduced huTRIM5αinhibition may lead to a faster progression of disease among HIV-1-infected individuals. However, in case of HIV-2, increased inhibition by huTRIM5αslows down the disease progression. Conclusion:Polymorphisms in the capsid protein with both HIV-1- and HIV-2-monoinfected individuals showed the difference in the docking energy from the wild type. This is the first study which documents the difference in the usage of loop between the two HIV types for interaction with huTRIM5α. Variations in the capsid protein result in alteration in the binding to the restriction factor huTRIM5α.
- Published
- 2019
- Full Text
- View/download PDF
16. Risk factors for active tuberculosis in human immunodeficiency virus-infected individuals.
- Author
-
Turaka, Vijay, Nair, Roshini, Sebastian, Tunny, Kannangai, Rajesh, Michael, Joy, and Varghese, George
- Published
- 2019
- Full Text
- View/download PDF
17. Will an innovative connected AideSmart! app-based multiplex, point-of-care screening strategy for HIV and related coinfections affect timely quality antenatal screening of rural Indian women? Results from a cross-sectional study in India.
- Author
-
Pai, Nitika Pant, Daher, Jana, Prashanth, H. R., Shetty, Achal, Sahni, Rani Diana, Kannangai, Rajesh, Abraham, Priya, Isaac, Rita, and Pant Pai, Nitika
- Subjects
PREVENTION of communicable diseases ,DIAGNOSIS of HIV infections ,HIV prevention ,PREVENTION of pregnancy complications ,SEXUALLY transmitted disease diagnosis ,PREVENTION of sexually transmitted diseases ,DIAGNOSIS of syphilis ,SYPHILIS prevention ,VERTICAL transmission (Communicable diseases) ,CLINICAL medicine ,COMMUNICABLE diseases ,COMPARATIVE studies ,MEDICAL databases ,INFORMATION storage & retrieval systems ,RESEARCH methodology ,MEDICAL cooperation ,PREGNANCY complications ,PRENATAL care ,PRENATAL diagnosis ,RESEARCH ,RURAL population ,TRICHOMONIASIS ,EVALUATION research ,CROSS-sectional method ,MOBILE apps ,MIXED infections ,PREVENTION - Abstract
Objectives: In rural pregnant Indian women, multiple missed antenatal screening opportunities due to inadequate public health facility-based screening result in undiagnosed HIV and sexually transmitted bloodborne infections (STBBIs) and conditions (anaemia). Untreated infections complicate pregnancy management, precipitate adverse outcomes and risk mother-to-child transmission. Additionally, a shortage of trained doctors, rural women's preference for home delivery and health illiteracy affect health service delivery. To address these issues, we developed AideSmart!, an innovative, app-based, cloud-connected, rapid screening strategy that offers multiplex screening for STBBIs and anaemia at the point of care. It offers connectivity, integration, expedited communications and linkages to clinical care throughout pregnancy.Methods: In a cross-sectional study, we evaluated the AideSmart! strategy for feasibility, acceptability, preference and impact. We trained 15 healthcare professionals (HCPs) to offer the AideSmart! strategy to 510 pregnant women presenting for care to outreach rural service units of Christian Medical College, Vellore, India.Results: With the AideSmart! screening strategy, we recorded an acceptability of 100% (510/510), feasibility (completion rate) of 91.6% (466/510) and preference of 73%. We detected 239 infections/conditions (239/510, 46.8%) at the point-of-care, of which 168 (168/239; 70%) were lab confirmed, staged and treated rapidly. Of the 168 confirmed infections/conditions, 127 were anaemia, 11 Trichomonas and 30 hepatitis B virus (HBV) (25 resolved naturally, 5 active infections). Four infants (4/5; 80%) were prophylaxed for HBV and were declared disease-free at 9 months. Recruited participants were young; mean age was 24 years (range: 17-40) and 74% (376/510) were in their second trimester. Furthermore, 95% of the participants were retained throughout their pregnancy.Conclusion: The AideSmart! strategy was deemed feasible to operationalise by HCPs. It was accepted and preferred by participants, resulting in timely screening and treatment of HIV/STIs and anaemia, preventing mother-to-child transmission. The strategy could be reverse-innovated to any context to maximise its health impact. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
18. Treponema pallidum Immunohistochemistry is positive in human intestinal Spirochetosis.
- Author
-
Graham, Rondell P., Naini, Bita V., Shah, Sejal S., Arnold, Christina A., Kannangai, Rajesh, Torbenson, Michael S., and Lam-Himlin, Dora M.
- Subjects
TREPONEMA pallidum ,TREPONEMATOSES ,SPIROCHAETOSIS ,DIAGNOSTIC immunohistochemistry ,DIAGNOSTIC specimens ,GENETICS ,DIAGNOSIS - Abstract
Background: Human intestinal spirochetosis (IS) has been recognized for decades, but whether it represents commensalism or a pathogenic process remains controversial. IS is diagnosed on routine stains with confirmation by silver stains but these stains are labor intensive and slow to read. We evaluated the Treponema pallidum immunostain as a diagnostic adjunct for IS. Methods: We retrieved biopsies from 33 patients with IS for this study. Each case was tested by Warthin-Starry (WS) and T. pallidum immunohistochemistry (IHC). Species specific genotyping was performed in 3 cases. Results: Patients with IS ranged from 22 to 82 years without gender predilection. IS involved normal (n = 15), and inflamed (n = 5) mucosa and colonic polyps (n = 13). Warthin-Starry and T. pallidum IHC were positive in all cases including both species of Brachyspira. Six (18%) symptomatic patients were treated for IS, and experienced resolution. In patients diagnosed with incidental IS on cancer screening (n = 5), follow up biopsies, without therapy, were negative for IS. T. pallidum IHC required 75 min less hands-on time than WS for performance and was faster to interpret. Conclusions: T. pallidum IHC can be used to confirm the diagnosis of IS and is easier to perform and faster to interpret than WS. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
19. Application of viromics: a new approach to the understanding of viral infections in humans.
- Author
-
Ramamurthy, Mageshbabu, Sankar, Sathish, Kannangai, Rajesh, Nandagopal, Balaji, and Sridharan, Gopalan
- Published
- 2017
- Full Text
- View/download PDF
20. Characteristics of Treatment-naïve HBV-Infected Individuals with HIV-1 Coinfection: A Cross-sectional Study from South India
- Author
-
Demosthenes, John Paul, Sachithanandham, Jaiprasath, Fletcher, Gnanadurai John, Zachariah, Uday George, Varghese, George Mathew, John Daniel, Hubert Darius, Jeyaseelan, Lakshmanan, Abraham, Priya, and Kannangai, Rajesh
- Abstract
Purpose:Human immunodeficiency virus-1 (HIV-1) and hepatitis B virus (HBV) coinfection has become a major health problem across the globe. The increased life expectancy of HIV-1 patients due to antiretroviral therapy has led to the emergence of liver disease as a major mortality factor among them. The purpose of the study was to examine the baseline characteristics of HBV in treatment-naïve HBV/HIV coinfection from southern India compared to monoinfected individuals. Materials and Methods:The study was cross sectional in design, and samples were examined from 80 HIV-1, 70 HBV and 35 HBV/HIV-coinfected individuals using chemiluminescent microparticle immunoassay, real-time polymerase chain reaction and flow cytometry assays. Results:There was a significant increase in HBV DNA (P= 0.0001), higher hepatitis B e antigen percentage difference (P= 0.027) and lower CD4 counts (P= 0.01) among the HBV/HIV-coinfected individuals, but no difference in the HIV-1 viral load compared to HIV-1-monoinfected individuals. Also, the aspartate aminotransferase levels, prothrombin time and the international normalised ratio were significantly high among coinfected individuals. Conclusion:These findings conclude that HIV-1 coinfection can have serious implications on the outcome of HBV-related liver disease. To the contrary, HBV infection had no consequence on the progression of HIV-1 disease but distinctly lowered CD4+ T-cells.
- Published
- 2019
- Full Text
- View/download PDF
21. Performance of a Modified In-House HIV-1 Avidity Assay among a Cohort of Newly Diagnosed HIV-1 Infected Individuals and the Effect of ART on the Maturation of HIV-1 Specific Antibodies
- Author
-
Alex, Diviya, Williams, Tennison I. Raj, Sachithanandham, Jaiprasath, Prasannakumar, Swaminathan, Demosthenes, John Paul, Ramalingam, Veena Vadhini, Victor, Punitha John, Rupali, Priscilla, Fletcher, Gnanadurai John, and Kannangai, Rajesh
- Abstract
Background: Viral kinetics impact humoral immune response to HIV; antibody avidity testing helps distinguish recent (<6 months) and long-term HIV infection. This study aims to determine the frequency of recent HIV-1 infection among clients attending ICTC (Integrated Counselling and Testing Centre) using a commercial EIA, to correlate it with a modified in-house avidity assay and to study the impact of ART on anti-HIV-1 antibody maturation. Methods: Commercial LAg Avidity EIA was used to detect antibody avidity among 117 treatment naïve HIV-1 infected individuals. A second-generation HIV ELISA was modified for in-house antibody avidity testing and cutoff was set based on Receiver Operating Characteristic (ROC) analysis. Archived paired samples from 25 HIV-1 infected individuals before ART and after successful ART; samples from 7 individuals responding to ART and during virological failure were also tested by LAg Avidity EIA. Results: Six individuals (5.1%) were identified as recently infected by a combination of LAg avidity assay and HIV-1 viral load testing. The modified in-house avidity assay demonstrated sensitivity and specificity of 100% and 98.2%, respectively, at AI=0.69 by ROC analysis. Median ODn values of individuals when responding to ART were significantly lower than pre-ART [4.136 (IQR 3.437– 4.827) vs 4.455 (IQR 3.748–5.120), p=0.006] whereas ODn values were higher during virological failure [4.260 (IQR 3.665 – 4.515) vs 2.868 (IQR 2.247 – 3.921), p=0.16]. Conclusion: This modified in-house antibody avidity assay is an inexpensive method to detect recent HIV-1 infection. ART demonstrated significant effect on HIV-1 antibody avidity owing to changes in viral kinetics.
- Published
- 2019
- Full Text
- View/download PDF
22. Will an innovative connected AideSmart! app-based multiplex, point-of-care screening strategy for HIV and related coinfections affect timely quality antenatal screening of rural Indian women? Results from a cross-sectional study in India
- Author
-
Pant Pai, Nitika, Daher, Jana, Prashanth, HR, Shetty, Achal, Sahni, Rani Diana, Kannangai, Rajesh, Abraham, Priya, and Isaac, Rita
- Abstract
ObjectivesIn rural pregnant Indian women, multiple missed antenatal screening opportunities due to inadequate public health facility-based screening result in undiagnosed HIV and sexually transmitted bloodborne infections (STBBIs) and conditions (anaemia). Untreated infections complicate pregnancy management, precipitate adverse outcomes and risk mother-to-child transmission. Additionally, a shortage of trained doctors, rural women’s preference for home delivery and health illiteracy affect health service delivery. To address these issues, we developed AideSmart!, an innovative, app-based, cloud-connected, rapid screening strategy that offers multiplex screening for STBBIs and anaemia at the point of care. It offers connectivity, integration, expedited communications and linkages to clinical care throughout pregnancy.MethodsIn a cross-sectional study, we evaluated the AideSmart! strategy for feasibility, acceptability, preference and impact. We trained 15 healthcare professionals (HCPs) to offer the AideSmart! strategy to 510 pregnant women presenting for care to outreach rural service units of Christian Medical College, Vellore, India.ResultsWith the AideSmart! screening strategy, we recorded an acceptability of 100% (510/510), feasibility (completion rate) of 91.6% (466/510) and preference of 73%. We detected 239 infections/conditions (239/510, 46.8%) at the point-of-care, of which 168 (168/239; 70%) were lab confirmed, staged and treated rapidly. Of the 168 confirmed infections/conditions, 127 were anaemia, 11 Trichomonas and 30 hepatitis B virus (HBV) (25 resolved naturally, 5 active infections). Four infants (4/5; 80%) were prophylaxed for HBV and were declared disease-free at 9 months. Recruited participants were young; mean age was 24 years (range: 17–40) and 74% (376/510) were in their second trimester. Furthermore, 95% of the participants were retained throughout their pregnancy.ConclusionThe AideSmart! strategy was deemed feasible to operationalise by HCPs. It was accepted and preferred by participants, resulting in timely screening and treatment of HIV/STIs and anaemia, preventing mother-to-child transmission. The strategy could be reverse-innovated to any context to maximise its health impact.
- Published
- 2019
- Full Text
- View/download PDF
23. Genital Human Papillomavirus Infection in Indian HIV-Seropositive Men Who Have Sex With Men.
- Author
-
Raghavendran, Anantharam, Hernandez, Alexandra L., Lensing, Shelly, Gnanamony, Manu, Karthik, Rajiv, Sivasubramanian, Murgesan, Kannangai, Rajesh, Abraham, Priya, Mathai, Dilip, and Palefsky, Joel M.
- Published
- 2017
- Full Text
- View/download PDF
24. Performance of an In-House Real-Time PCR Assay for Detecting Cytomegalovirus Infection among Transplant Patients from a Tertiary Care Centre
- Author
-
Duraisamy, Santhosh Kumar, Mammen, Shoba, Lakshminarayan, Sasi Kumar Reddy, Verghese, Susan, Moorthy, Mahesh, George, Biju, Kannangai, Rajesh, Varghese, Santosh, Srivastava, Alok, and Abraham, Asha Mary
- Abstract
Background:Quantitative Cytomegalovirus (CMV) polymerase chain reactions are increasingly being used for monitoring CMV DNAemia in haematopoietic stem cell transplants and solid organ transplants. Objective:In this study, a commercial CMV viral load assay was compared with an in-house viral load assay. Materials and Methods:A total of 176 whole-blood samples were tested for CMV DNAemia using both assays. Results:Our evaluation showed a difference of 1 log10copies/ml between the two assay systems in determining CMV viral loads in the clinical samples. Conclusion:The in-house viral load assay had a better correlation with clinical findings compared to the commercial assay. Quality assessment of these assays was done by the United Kingdom National External Quality Assessment Scheme (UKNEQAS), an external proficiency testing programme, and by the National Institute for Biological Standard and Control (NIBSC) standard. For UKNEQAS and NIBSC standards, the bias between the assays was 0.73 log10and 0.85 log10, respectively. This difference is well within the acceptable range already reported in the literature.
- Published
- 2018
- Full Text
- View/download PDF
25. BK Virus Characterisation among HIV-1-Infected Individuals and Its Association with Immunosuppression
- Author
-
Jagannath, Subha, Sachithanandham, Jaiprasath, Ramalingam, Veena V., Demosthenes, John Paul, Abraham, Asha M., Zachariah, Anand, Varghese, George M., and Kannangai, Rajesh
- Abstract
Purpose:BK virus (BKV) is an opportunistic pathogen which causes significant morbidity and mortality in individuals who are immunodeficient. We aimed to quantitate and characterise BKV and to correlate with the degree of immunosuppression among human immunodeficiency virus (HIV)-1-infected individuals. Methods:BKV DNA detection was carried out using an in-house quantitative real-time polymerase chain reaction on paired whole-blood and urine samples collected from 187 antiretroviral therapy (ART)-naïve HIV-1-infected individuals and 93 healthy individuals who served as controls. Sequencing was performed for a proportion of high BK viral load (VL) samples to observe non-coding control region (NCCR) rearrangements. Results:BKV positivity in urine was 25.6% among HIV-infected individuals and 10.7% in control individuals (P= 0.03). The BK VL showed a significant negative correlation with CD4+ T-cell counts, a positive correlation with WHO clinical staging and no significant correlation with HIV-1 VL. Of 42 BKVs from urine samples sequenced, two showed rearrangements without clinically severe disease or high VL. Their NCCR and VP1 sequence-based genotyping revealed genotype I. In a small subset of individuals (n= 8) on ART who were being followed up, six individuals showed either decrease or complete clearance of virus with ART. Conclusion:There was a higher frequency of BK viruria in HIV-1-infected individuals than among healthy controls and the positivity correlated with the degree of immunosuppression. There was no association of high VL with NCCR rearrangements in urine.
- Published
- 2018
- Full Text
- View/download PDF
26. Effect of Interleukin-28B Polymorphism on Interleukin-28 Expression and Immunological Recovery amongst HIV-1-Infected Individuals Following Antiretroviral Therapy
- Author
-
Srinidhi, B.V., Fletcher, G.John, Sachidanantham, Jaiprasath, Rupali, Priscilla, Ramalingam, Veena Vadhini, Demosthenes, J.P., Abraham, O.C., Pulimood, Susanne A., Rebekah, Grace, and Kannangai, Rajesh
- Abstract
Purpose:Type III interferon is well known to have diverse antiviral and immunomodulatory activities. Studies describing the association of interleukin (IL)-28 polymorphisms in treatment-experienced HIV participants are limited. This study was aimed to determine the association of IL-28B gene polymorphisms with immunological recovery in HIV patients on 6–9 months of antiretroviral therapy (ART). Methods:Eighty treatment-naive HIV patients were recruited, of which 48 patients were followed up after 6–9 months of ART. Whole blood samples were collected before and after 6–9 months of ART. CD4, CD8 and CD3 counts were enumerated flow cytometry. IL-28B polymorphisms (rs12979860 and rs8099917) were profiled by polymerase chain reaction (PCR)-restriction fragment length polymorphism. The IL-28 mRNA and plasma HIV-1 viral load were estimated using real-time PCR and plasma IL-28 level by ELISA. Results:The CD4, CD4/CD3%, IL-28 mRNA and reversal of CD4/CD8 ratio were significantly increased following 6–9 months of ART (P< 0.01). The rs12979860 CC genotype and rs12979860:rs8099917 (CC: TT) haplotype showed significant association with higher CD4+ T-cell count amongst treatment-naive HIV-infected individuals (P< 0.05). In addition, there was a significant association of rs12979860 CC genotype with increase in CD4/CD3% following 6–9 months of ART. IL-28 mRNA showed correlation with the HIV-1 viral load, and there was a significant increase in the IL-28 mRNA expression following 6–9 months of ART. Conclusion:Our preliminary findings suggest that IL-28 polymorphisms could influence both immunological recovery and therapeutic response in HIV infection. Hence, functional studies are warranted to understand the mechanistic basis of IL-28-mediated host genetic influence on HIV therapeutic response.
- Published
- 2017
- Full Text
- View/download PDF
27. The performance of reverse transcriptase assay for the estimation of the plasma viral load in HIV-1 and HIV-2 infections.
- Author
-
Padaki, Priyadarshini A., Sachithanandham, Jaiprasath, Isaac, Rita, Ramalingam, Veena V., Abraham, Ooriapadickal C., Pulimood, Susanne A., and Kannangai, Rajesh
- Abstract
Viral load testing for human immunodeficiency virus 1 (HIV-1) in resource-poor settings continues to be a challenge. Although antiretroviral therapy (ART) is being made available in developing countries, monitoring of viral load is not being done on a regular basis. The purpose of this study was to assess the utility of Cavidi version 3.0, which measures the plasma reverse transcriptase (RT) activity and compare its performance with molecular HIV viral load assays. In all, 125 HIV-1 and 13 HIV-2 positive samples were analyzed. The overall sensitivity of the assay was 86.8% and 94.1% for viral load >1000 copies/ml measured by Qiagen Artus HIV-1 RG RT PCR and Abbott RealTime HIV-1 PCR assays, respectively. Compared with the routine molecular viral load assays, Cavidi version 3.0 is inexpensive, user-friendly, the expenditure on infrastructure is minimal, and it can be used for monitoring of both HIV types. [ABSTRACT FROM PUBLISHER]
- Published
- 2016
- Full Text
- View/download PDF
28. Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India.
- Author
-
Hernandez, Alexandra L., Karthik, Rajiv, Sivasubramanian, Murugesan, Raghavendran, Anantharam, Gnanamony, Manu, Lensing, Shelly, Lee, Jeannette Y., Kannangai, Rajesh, Abraham, Priya, Mathai, Dilip, and Palefsky, Joel M.
- Published
- 2016
- Full Text
- View/download PDF
29. Early detection, reactivation of cytomegalovirus DNA & immediate early (IE)-mRNA expression in a hemetopoitic stem cell-transplant patient
- Author
-
Thomas, Sangeeta, Duraisamy, Santhosh Kumar, Ahmed, Rayaz, Abraham, Aby, Vishwabandhya, Auro, Mathews, Vikram, Srivastava, Alok, Prasanna, Kannangai, Rajesh, Abraham, O.C., George, Biju, and Abraham, Asha Mary
- Abstract
Human cytomegalovirus (HCMV) reactivation is a major cause of morbidity and mortality among stem cell transplant recipients post-transplantation.
- Published
- 2023
- Full Text
- View/download PDF
30. Performance of LigAmp Assay for Sensitive Detection of Drug-Resistant Hepatitis B Virus Minor Variants in Comparison with Standard Nucleotide Sequencing.
- Author
-
Ismail, Ashrafali, Sachithanandham, Jaiprasath, Eapen, Chundmannil, Kannangai, Rajesh, and Abraham, Priya
- Subjects
DRUG resistance ,HEPATITIS B virus ,NUCLEOTIDE sequence ,REVERSE transcriptase ,VIROLOGY ,GENETIC mutation - Abstract
Background and Objectives: A virus population often exists as a complex mixture of genetic populations. Antiviral-resistant mutants could be circulating as minority variants in the mixed virus population that are not detected by standard sequencing methods. The role of minor drug-resistant variants and clinical outcome is slowly evolving and there is a need to employ sensitive methods for detection of minority variants that emerge as dominant species and subsequently affect the antiviral efficacy. This study was intended to develop a technique called the ligation amplification assay (LigAmp) to identify minor drug-resistant variants of hepatitis B virus (HBV). Methods: A LigAmp HBV assay was developed and clinical samples were tested from chronic hepatitis B subjects on antiviral treatment. Nucleotide sequencing of HBV reverse transcriptase (rt) region was performed and the results were compared with LigAmp assay. The performance of LigAmp assay was validated by clonal sequencing. Virological response was measured using HBV DNA levels and the results were correlated with antiviral-resistant mutations detected by sequencing and LigAmp assays. Results: A total of 80 reactions of LigAmp assay were performed for rtM204V and rtM204I (ATT) mutant detection. Samples were obtained from 40 chronic hepatitis B subjects. Among these subjects, rtM204V and rtM204I (ATT) mutations were identified by standard sequencing in 10 (25 %) and 12 (30 %) subjects, respectively. LigAmp detected both rtM204V and rtM204I (ATT) mutations in 13 (32.5 %) subjects, rtM204I mutation in 12 (30 %) subjects and rtM204V mutation in 1 (2.5 %) subject, respectively. LigAmp detected primary resistant mutants in 69.4 % of lamivudine non-responders while sequencing detected resistant mutations in only 55.6 % subjects ( p < 0.001). Conclusions: This data shows significantly higher sensitivity of LigAmp for detection of minority rtM204V and rtM204I (ATT) mutations over standard sequencing. Therefore, LigAmp has potential clinical utility for appropriate monitoring and tailoring of HBV therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
31. Lamivudine Monotherapy in Chronic Hepatitis B Patients from the Indian Subcontinent: Antiviral Resistance Mutations and Predictive Factors of Treatment Response.
- Author
-
Ismail, Ashrafali, Samuel, Prasanna, Ramachandran, Jeyamani, Eapen, Chundamannil, Kannangai, Rajesh, and Abraham, Priya
- Subjects
CHRONIC hepatitis B ,HEPATITIS B virus ,DISEASE management ,LAMIVUDINE ,ANTIVIRAL agents ,DRUG resistance in microorganisms ,GENETIC mutation ,INDIGENOUS peoples of the Americas ,PATIENTS ,THERAPEUTICS - Abstract
Background and objective: Management of chronic hepatitis B is a global public health challenge. There are several updated guidelines proposed based on treatment outcome data from the respective study populations. In this study, we aim to characterize the antiviral resistance mutations to lamivudine monotherapy in patients diagnosed with chronic hepatitis B from the Indian subcontinent. Methods: A total of 147 lamivudine-treated patients with a median treatment duration of 13 (interquartile range 8-24) months were studied. Virological response was measured by hepatitis B virus (HBV) DNA levels. Antiviral resistance mutations were identified by sequencing HBV reverse transcriptase domains. Factors associated with virological response and antiviral resistance mutations were analyzed. Results: Virological response was observed in 50 (35 %) patients while 84 (57 %) were non-responders. The virological response for the remaining 13 (9 %) patients was undetermined. Forty patients (27 %) developed lamivudine-resistant mutations. HBV genotypes, subgenotypes and hepatitis B surface antigen subtypes did not show significant association with virological response or lamivudine-resistant mutations. High HBV DNA levels and increased treatment duration were strongly associated with the development of lamivudine-resistant mutations ( p = 0.002 and p < 0.001). Patients who continued to be positive for hepatitis B e antigen have an increased risk for treatment failure ( p = 0.010). High baseline aspartate transaminase levels were significantly associated with subsequent lamivudine response ( p = 0.037). Conclusion: Considering the limited potency and high resistance rates to lamivudine therapy, our study emphasizes the use of more potent drugs in the management of chronic hepatitis B in the Indian subcontinent. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
32. Role of polymerase chain reaction in the diagnosis of Trichomonas vaginalis infection in human immunodeficiency virus-infected individuals from India (South).
- Author
-
Paul, Hema, Peter, Dincy, Pulimood, Susanne A., Abraham, Oriapadickal Cherian, Mathai, Elezabeth, Prasad, Jasmine H., and Kannangai, Rajesh
- Subjects
POLYMERASE chain reaction ,TRICHOMONAS vaginalis ,HIV-positive persons ,HIV infection risk factors ,DIAGNOSIS ,HEALTH - Abstract
Background: Trichomonas vaginalis is a protozoan parasite and an etiological agent for trichomoniasis, a sexually transmitted infection (STI). Fifty to eighty percentage of women with trichomoniasis are asymptomatic and in the absence of treatment the infection persists longer. Aim: To evaluate the role of polymerase chain reaction (PCR) in the diagnosis of trichomoniasis and also to look at the frequency of infection among human immunodeficiency virus (HIV) infected women. Methods: A non-nested PCR was standardized to detect 102 bp size amplified product of the adhesin gene of T. vaginalis. The real time performance of this assay was performed with vaginal swab samples from 198 HIV-seropositive women who attended the infectious disease clinic and compared with wet mount and culture in Diamond's modified media. Results: Among the prospectively studied 198 HIV-infected women, 1 (0.51%) was positive by wet mount, 6 (3.03%) were positive by culture and 10 (5.02%) were positive by the PCR. There was a significant observed agreement between the PCR and culture (κ=0.74, Z=10.7, P<0.0000). Conclusion: Our study showed that the PCR assay for the amplification of adhesion gene is a highly sensitive method to screen the high risk group individuals like HIV-positive women for Trichomonas vaginalis compared to the culture. Testing algorithm should be, wet mount and if negative, test by PCR as it is rapid compared to culture which takes 7 days. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
33. Fibrolamellar carcinomas are positive for CD68.
- Author
-
Ross, Hillary M, Daniel, Hubert D J, Vivekanandan, Perumal, Kannangai, Rajesh, Yeh, Matthew M, Wu, Tsung-Teh, Makhlouf, Hala R, and Torbenson, Michael
- Published
- 2011
- Full Text
- View/download PDF
34. HIV-1 with Predicted CXCR4 Genotype Identified in Clade C from India.
- Author
-
Kandathil, Abraham Joseph, Kannangai, Rajesh, Abraham, Oriapadickal Cherian, Pulimood, Susanne Alexander, Jensen, Mark A., and Sridharan, Gopalan
- Subjects
HIV ,HIV infections ,ANTIRETROVIRAL agents ,AMINO acids - Abstract
Background and objective: HIV-1 uses co-receptors CCR5 and CXCR4 in addition to CD4 for viral entry into cells. CCR5 is used in the early stages of HIV-1 infection, but viruses that utilize CXCR4 for viral entry emerge in the later stages. This is not common among clade Cstrains, with previous data from India showing the absence of the emergence of CXCR4-using strains. Sequence analysis has demonstrated that the V3 loop plays a very important role in determining the syncytium-inducing (SI) phenotype. The V3 region of the SI variants were observed to have positively charged amino acids at positions 11 and/or 25 and also a overall higher charge. This study looked at co-receptor usage among HIV-1 strains in India from individuals who were antiretroviral therapy (ART) naïve and those not responding to ART. Methods: Amplification and sequencing of the HIV-1 env gp120 V3 region was done on 40 ART-naïve individuals, who were selected for the study based on their CD4 counts, and eight patients who had not responded to ART. The sequences were submitted to Geno2Pheno and Web PSSM. The pol gene sequences of these strains were submitted to the REGA HIV-1 subtyping tool. Results: Forty-seven strains were identified as clade C and one strain as clade A1. Geno2Pheno identified three CXCR4-using strains, and the Web PSSM clade C matrix identified two. Conclusion: We report, for the first time, CXCR4-using strains among HIV-1 clade C strains circulating in India. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
35. Frequency of Transmitted Drug Resistance Mutations Among Treatment-Naïve HIV-1-Infected Individuals at a Tertiary Care Centre in South India.
- Author
-
Kannangai, Rajesh, David, Shoba, Sundaresan, Vijayanand, Sachithanandham, Jaiprasath, Mani, Monika, Abraham, Ooriapadickal, Pulimood, Susanne, Rupali, Priscilla, and Sridharan, Gopalan
- Subjects
DRUG resistance ,HIV infections ,THERAPEUTICS ,ANTIRETROVIRAL agents ,TERTIARY care ,GENETIC mutation ,DEATH rate ,DISEASE prevalence - Abstract
Introduction: Morbidity and mortality among HIV-1-infected individuals has been dramatically reduced by the implementation of combinational antiretroviral therapy (ART). However, the efficiency of these therapies is compromised due to HIV-1 transmitted drug resistance mutations (TDRMs). Methods: We collected a total of 127 samples from ART-naïve HIV-infected individuals and sequenced the pol gene and analysed for drug resistance mutations using the Calibrated Population Resistance (CPR) tool in the Stanford database. Results: All the 127 clinical samples (100 %) were identified as HIV-1 subtype C. Based on the CPR tool, three strains (2.4 %) had TDRMs, and these were K101E, Y181C and G190A. Our findings correlated well with the WHO surveys conducted in Asia, including India, which consistently reported <5 % TDRM among the specific populations assessed. Conclusion: In countries like India, regular monitoring of TDRMs will provide better information for clinical practice improvement and policy making. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
36. Comprehensive Genetic and Epigenetic Analysis of Occult Hepatitis B from Liver Tissue Samples.
- Author
-
Vivekanandan, Perumal, Kannangai, Rajesh, Ray, Stuart C., Thomas, David L., and Torbenson, Michael
- Subjects
MEDICAL sciences ,MEDICAL research ,LIVER diseases ,HEPATITIS B virus ,VIRAL hepatitis ,METHYLATION ,GENETIC polymorphisms ,EPITOPES ,DNA - Abstract
Background. Occult infection with hepatitis B virus (HBV) is a type of chronic HBV infection that is characterized by the absence of a detectable hepatitis B surface antigen in the blood and by very low levels of HBV DNA in the blood and liver. The mechanisms leading to occult HBV infection remain poorly understood but include possible genetic mutations and deletions. Recently, it has been shown that HBV has CpG islands that are methylated, raising the possibility that epigenetic changes may also be important. Methods. The full-length genomes of isolates from 5 cases of occult HBV infection were cloned and analyzed for mutations and deletions. Additional studies were performed to examine for APOBEC3G (1 member of a family of deaminating proteins that are part of the innate immune system's defense against viral infection) hyperediting and methylation of viral DNA. Results. Numerous mutations and deletions were found in the genomes of occult HBV. However, similar types and locations of polymorphisms were also noted in the genome sequences of HBV isolated from control liver tissue samples obtained from individuals with nonoccult HBV infection. Evidence of APOBEC3G hyperediting was found in 1 case of occult HBV infection, but hyperedited sequences made up only a small proportion of the viral sequences. Methylation of HBV CpG islands 1 and 2 was evident in both occult and nonoccult HBV sequences, with island 2 more densely methylated in occult HBV sequences and island 1 more densely methylated in nonoccult HBV sequences. Conclusion. Deletions and mutations are common in occult HBV but are also found in control nonoccult HBV, and no unique genetic signature for occult HBV was found. Methylation patterns differ between cases of occult and nonoccult HBV infection, suggesting that epigenetic changes may be relevant to occult HBV. Together, these findings suggest that multiple mechanisms can contribute to occult HBV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
37. Fibrolamellar carcinomas show overexpression of genes in the RAS, MAPK, PIK3, and xenobiotic degradation pathways.
- Author
-
Kannangai, Rajesh, Vivekanandan, Perumal, Martinez-Murillo, Francisco, Choti, Michael, and Torbenson, Michael
- Subjects
LIVER cancer ,GENE expression ,POLYMERASE chain reaction ,PATHOLOGY - Abstract
Summary: Fibrolamellar carcinomas (FLC) are a rare type of primary hepatocellular carcinoma found in younger individuals. FLC are known to have relatively few consistent chromosomal alterations, although a gain of chromosome 1q has been reported. The gene expression of 4 FLC (2 primary FLC and 2 metastatic deposits) were studied using Affymetrix DNA microarray technology (Santa Clara, CA). Selected genes were confirmed by real-time polymerase chain reaction. Relatively few genes were significantly overexpressed—447 genes, case 1; 1298 genes, case 2—corresponding to approximately 0.8% and 2.3%, respectively, of the 56000 transcripts present in the arrays. Of these, 155 genes were overexpressed simultaneously by both tumors. The number of significantly overexpressed genes more than doubled in the 2 metastatic deposits (2777 and 2855 genes compared with 1298 in the primary tumor). Proteins involved in the RAS, MAPK, PIK3, and xenobiotic degradation pathways were commonly overexpressed. Because chromosome 1q is thought to contain an important oncogene, additional attention was focused on this region. Of 114 total genes found overexpressed in common among all primary and metastatic tumors, 11 of 114 genes were located on chromosome 1q: ARF1, CD46, CNIH4, ENSA, FH, NICE-3, PSMB4, RGS2, RGS5, TIMM17A, and UFC1. Primary FLC show overexpression of genes involved in the RAS, MAPK, PIK3, and xenobiotic degradation pathways. Eleven common genes were consistently overexpressed on chromosome 1q among all tumors and metastases and warrant further study as potential oncogenes. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
38. EGFR is phosphorylated at Ty845 in hepatocellular carcinoma.
- Author
-
Kannangai, Rajesh, Sahin, Fikret, and Torbenson, Michael S.
- Published
- 2006
- Full Text
- View/download PDF
39. Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile.
- Author
-
Kannangai, Rajesh, Diehl, Anna Mae, Sicklick, Jason, Rojkind, Marcus, Thomas, David, and Torbenson, Michael
- Subjects
LIVER cancer ,KUPFFER cells ,GENE expression ,RENAL cell carcinoma ,TRANSFORMING growth factors ,SMOOTH muscle ,DIAGNOSTIC use of polymerase chain reaction - Abstract
Summary: Background and Aims: Angiomyolipomas (AMLs) of the liver are rare neoplasms composed of large epithelioid cells with intermixed fat and blood vessels. Hepatic AMLs have no clear normal-cell counterpart in the liver. However, AMLs and stellate cells both are positive for neural crest–derived markers including HMB-45 antigen. Methods: To further explore the similarities between hepatic AMLs and stellate cells, gene expression of a hepatic AML was studied by cDNA microarray. Real-time polymerase chain reaction was used to confirm gene expression. Hepatic stellate cells can be quiescent, activated, or have a myofibroblastic phenotype depending on their state of activation. Expression of known markers of activated stellate cells was compared between the AML, activated primary mouse stellate cells, and stellate cell lines with activated and myofibroblastic phenotypes. Next, 5 novel genes from the AML were selected because they were not previously known to be markers of stellate cells and mRNA expression measured in the activated mouse stellate cells and in myofibroblastic stellate cell lines. Finally, expression levels of 10 novel genes were determined in 5 cirrhotic and 5 noncirrhotic human livers. Results: Overexpression of known markers of activated stellate cells including transforming growth factor β (TGF-β), smooth muscle actin, and collagen was found in the hepatic AML. Three of 5 novel markers that were identified in the AML, RRAD (Ras-related associated with diabetes), CTSK (cathepsin K), and NIBAN were also found to be overexpressed in activated stellate cells compared with quiescent or myofibroblastic stellate cells. In addition, 9 of 10 novel genes overexpressed in AML were also overexpressed in cirrhotic human livers versus noncirrhotic livers. Conclusions: Hepatic AMLs share a similar gene expression profile and may differentiate toward activated stellate cells. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
40. Survivin overexpression in hepatocellular carcinoma is associated with p53 dysregulation.
- Author
-
Kannangai, Rajesh, Wang, Jianzhou, Liu, Qiong, Sahin, Fikret, and Torbenson, Michael
- Abstract
Background: Survivin is a recently described anti-apoptotic protein that is suppressed by wild-type p53 and is overexpressed in 41–70% of hepatocellular carcinomas from Asia. Two alternatively spliced transcripts have also been described: anti-apoptotic survivin-ΔEx3 and non—anti-apoptotic survivin-2B. Survivin splice variant expression has not been studied in HCC, and little is known about survivin expression in hepatocellular carcinomas arising in other parts of the world, where risk factors are often different than they are in Asia. Aim of the Study: We studied survivin mRNA and protein expression in a United States cohort of hepatocellular carcinomas and correlated the findings with p53 immunopositivity. Methods: RT-PCR was performed for survivin, survivin-2B, and survivin-ΔEx3 in 20 HCCs and one intrahepatic cholangiocarcinoma. Expression levels of total survivin were evaluated with real-time PCR. Protein expression was examined by immunohistochemistry. Results: Survivin was the major transcript, and all transcripts were present in all normal and neoplastic tissues; 11/20 (55%) HCCs and the one cholangiocarcinoma showed twofold or greater overexpression of survivin. Next, we examined survivin and p53 protein expression by immunohistochemistry on a separate series of 79 HCC, 13 fibrolamellar carcinomas, and 15 hepatic adenomas; 14/79 (17%) HCC, but none of the fibrolamellar carcinomas or hepatic adenomas, showed survivin protein overexpression, and 25/79 HCC (32%) showed abnormal nuclear accumulation of p53, which correlated with increased survivin expression. Conclusions: All three survivin transcripts are present in normal liver and HCC. Survivin is the dominant transcript in HCC and is overexpressed in 55% of cases. Survivin protein overexpression is associated with aberrant p53 nuclear positivity. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
41. FHIT mRNA and protein expression in hepatocellular carcinoma.
- Author
-
Kannangai, Rajesh, Sahin, Fikret, Adegbola, Onikepe, Ashfaq, Raheela, Su, Gloria H., and Torbenson, Michael
- Published
- 2004
- Full Text
- View/download PDF
42. High prevalence of occult hepatitis B in Baltimore injection drug users.
- Author
-
Torbenson, Michael, Kannangai, Rajesh, Astemborski, Jacquie, Strathdee, Steffanie A., Vlahov, David, and Thomas, David L.
- Published
- 2004
- Full Text
- View/download PDF
43. HIV-2 Subtype Circulating in India (South).
- Author
-
Kannangai, Rajesh, Shaji, Ramachandran V., Ramalingam, Sandeep, Jesudason, Mary V., Abraham, Oriapadickal C., George, Renu, Shanmugam, Arvindh P., Schwartz, David H., and Sridharan, Gopalan
- Published
- 2003
- Full Text
- View/download PDF
44. Vaccinia reactive antibodies in a south Indian population.
- Author
-
Kannangai, Rajesh, Finny, G. Joseph, John, T. Jacob, Sridharan, Gopalan, and Gopal, Robin
- Published
- 2000
- Full Text
- View/download PDF
45. Association of Neurotropic Viruses in HIV-Infected Individuals Who Died of Secondary Complications of Tuberculosis, Cryptococcosis, or Toxoplasmosis in South India
- Author
-
Kannangai, Rajesh, Sachithanandham, Jaiprasath, Mahadevan, Anita, Abraham, Asha Mary, Sridharan, Gopalan, Desai, Anita, Ravi, Vasanthapuram, and Shankar, Susarla Krishna
- Abstract
ABSTRACTThe frequencies of 10 opportunistic DNA viruses were determined by multiplex real-time PCR in paired cerebrospinal fluid (CSF) and brain tissue of HIV-infected individuals. In the CSF, viruses were detectable in 45/55 cases: JC virus (JCV) in 62%, Epstein-Barr virus (EBV) in 44%, cytomegalovirus (CMV) in 25%, varicella-zoster virus (VZV) in 3.6%, herpes simplex virus 1 (HSV-1) in 1.8%, and human herpesvirus 6 (HHV-6) in 1.8% of cases. A single virus was detectable in 20 cases, 19 cases had coinfection with two viruses, and 6 cases were positive for three viruses. JCV was detectable in the CSF of 62% of cases and in 42% of brain tissues, with higher loads in progressive multifocal leukoencephalopathy (PML) (P< 0.05).
- Published
- 2013
- Full Text
- View/download PDF
46. Daily Quality Control in CD3+and CD4+T Cell Estimation by the FACSCount System at a Tertiary Care Center in South India
- Author
-
Ramalingam, Veena V., Mani, Monika, Sundaresan, Vijayanand C., Karunaiya, Ramesh J., Sachithanandham, Jaiprasath, and Kannangai, Rajesh
- Abstract
ABSTRACTCD4+T cell count estimations are subject to high variations; hence, in this study, the previous day's tested samples were included routinely as the internal quality controls. The percentages of variation of the 2-day values were analyzed for 280 observations and the mean variation for CD4+and CD3+T cell counts ranged from 5.21% to 9.66%. This method is a good internal quality control (IQC) procedure for the estimation of CD3+and CD4+T cell counts in resource-poor settings.
- Published
- 2012
- Full Text
- View/download PDF
47. Viral Infections in Immunocompromised Hosts
- Author
-
Ramamurthy, Mageshbabu, Kannangai, Rajesh, Abraham, Asha, and Sridharan, Gopalan
- Abstract
Abstract: Several viral infections have been shown to occur in immunocompromised hosts like tumour bearing hosts, transplant recipients and human immunodeficiency virus (HIV) infected individuals. In these categories of patients they cause severe morbidity and disseminated fatal infections if untreated. The viruses that are significantly associated with disease in immunocompromised hosts are the members of family Herpesviridae, others include Adenoviruses (Adenoviridae), JC virus and BK virus family (Papovaviridae) and certain members of Paramyxoviridae like Respiratory Syncitial Virus, metapneumovirus and parainfluenza viruses. Infections could be seen in individuals when their HIV disease is asymptomatic and more fatal infections are seen when HIV disease is symptomatic. Infections with Hepatitis A virus and Hepatitis E virus could be seen as community acquired infections among immunosuppressed patients. Early and specific detection of opportunistic viruses is possible today by using certain new techniques like real-time multiplex polymerase chain reaction. It is possible to intervene with antivirals which reduce morbidity and mortality if the diagnosis is achieved early in the course of disease.
- Published
- 2012
- Full Text
- View/download PDF
48. Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis
- Author
-
Sicklick, Jason K., Li, Yin-Xiong, Jayaraman, Aruna, Kannangai, Rajesh, Qi, Yi, Vivekanandan, Perumal, Ludlow, John W., Owzar, Kouros, Chen, Wei, Torbenson, Michael S., and Diehl, Anna Mae
- Abstract
Hedgehog (Hh) pathway activation promotes tumors in several endodermally derived tissues, but its role in the pathogenesis of hepatocellular carcinoma (HCC) is unknown. Although normal hepatocytes lack Hh signaling, activation of the Hh pathway in endodermal progenitors is required for liver development. Thus, we hypothesized that hepatocarcinogenesis may involve regulation of Hh signaling. This pathway is activated when Hh ligand binds to its receptor, Patched (PTC). In an unoccupied state, PTC normally functions as a tumor suppressor that inhibits Smoothened (SMO), a proto-oncoprotein, from activating downstream components and transcription of target genes. Here we show that in HCCs, overexpression of the Smo proto-oncogene, as well as an increase in the stoichiometric ratio of Smo to Ptc mRNA levels, correlated with tumor size, a prognostic indicator in HCC biology. In one tumor we identified a novel Smo mutation in an evolutionarily conserved residue. We also demonstrated that HCC cell lines (HepG2 and Hep3B) expressed Hh pathway components and activated Hh transcriptional targets. In Hep3B cells, cyclopamine, an inhibitor of wild-type SMO, had no effect, but KAAD-cyclopamine, a blocker of oncogenic SMO, inhibited Hh signaling activity by 50%, decreased expression of the hepatocarcinogenic oncogene, c-myc, by 8-fold, and inhibited the growth rate of Hep3B cells by 94%. These data support our hypothesis that Hh signaling is dysregulated in human hepatocarcinogenesis. We demonstrate that overexpression and/or tumorigenic activation of the Smo proto-oncogene mediates c-myc overexpression which plays a critical role in hepatocarcinogenesis and suggests that Smo is a prognostic factor in HCC tumorigenesis.
- Published
- 2006
- Full Text
- View/download PDF
49. Concurrent evaluation of p53, beta-catenin, and alpha-fetoprotein expression in human hepatocellular carcinoma.
- Author
-
Torbenson, Michael, Kannangai, Rajesh, Abraham, Susan, Sahin, Fikret, Choti, Michael, and Wang, Jianzhou
- Abstract
Recent models suggest that hepatocellular carcinoma (HCC) develops through several independent pathways marked by key mutations in the beta-catenin or p53 gene. An additional pathway potentially is marked by aberrant expression of a-fetoprotein (AFP). To see whether these potential markers are expressed independently, we immunostained sequential sections from 55 HCCs. Of the cases, 30 (55%) were positive for 1 or more proteins: AFP, 19 cases (35%); p53, 12 cases (22%); and beta-catenin, 9 cases (16%). Seven tumors (13%) were positive for more than 1 protein, with 4 of 7 positive in the same area of tumor and 3 of 7 positive in different areas of the carcinomas. By statistical analysis, expression of the markers was independent of one another and of tumor size. Concurrent evaluation of p53, beta-catenin, and AFP protein expression showed no associations, supporting models in which these proteins might serve as markers of independent pathways in the development of HCC.
- Published
- 2004
- Full Text
- View/download PDF
50. Colonic spirochetosis in children and adults.
- Author
-
Koteish, Ayman, Kannangai, Rajesh, Abraham, Susan C, and Torbenson, Michael
- Abstract
We undertook a retrospective analysis of colonic spirochetosis in 14 cases: females, 3; males, 11; children, 4; adults, 10. Two men had HIV infections. All children and both HIV-infected men had abdominal complaints, diarrhea, or both. Most other adults underwent colonoscopy for polyp screening (n = 4) or follow-up of Crohn disease (n = 1) or had other indications (n = 2) or diarrhea (n = 1). Histologically, spirochetosis was identified in all parts of the colon and was not strongly associated with active inflammation, mucosal injury, or changes of chronicity. Genotype analysis of 13 cases showed that 11 resulted from Brachyspira aalborgi and 2 from Brachyspira pilosicoli infections. Only 2 patients were treated specifically with antibiotics, with complete resolution of abdominal symptoms in 1 patient with follow-up. Follow-up biopsy result were available for 2 patients who did not receive treatment; one showed persistent spirochetosis, and the other was negative. Spirochetosis in this series had a male predominance, was generally caused by B aalborgi, and occurred in 2 distinct clinical settings: children who often have abdominal symptoms and adults who typically are asymptomatic. While treatment information remains limited, treatment can lead to resolution of symptoms in some cases.
- Published
- 2003
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.