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Displaying publications 1 - 20 of 27 in total

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Occult hepatitis B virus infection and current perspectives on global WHO 2030 eradication

Saravanan S, Shankar EM, Vignesh R, Ganesh PS, Sankar S, Velu V, et al.

J Viral Hepat, 2024 Apr 05.
PMID: 38578122 DOI: 10.1111/jvh.13928

The current World Health Organization (WHO) Hepatitis Elimination Strategy suffers from lack of a target for diagnosing or expunging occult HBV infection. A sizable segment of the global population has an undetected HBV infection, particularly the high-risk populations and those residing in countries like India with intermediate endemicity. There is growing proof that people with hidden HBV infection can infect others, and that these infections are linked to serious chronic hepatic complications, especially hepatocellular carcinoma. Given the current diagnostic infrastructure in low-resource settings, the WHO 2030 objective of obliterating hepatitis B appears to be undeniably challenging to accomplish. Given the molecular basis of occult HBV infection strongly linked to intrahepatic persistence, patients may inexplicably harbour HBV genomes for a prolonged duration without displaying any pronounced clinical or biochemical signs of liver disease, and present histological signs of moderate degree necro-inflammation, diffuse fibrosis, and hence the international strategy to eradicate viral hepatitis warrants inclusion of occult HBV infection.
Fulltext Ertapenem for multiple β-lactamases producing Gram-negative bacteria causing urinary tract infections in HIV patients

Kumar MRR, Arunagirinathan N, Vignesh R, Balakrishnan P, Solomon S, Sunil SS

J Res Med Sci, 2017;22:69.
PMID: 28616056 DOI: 10.4103/jrms.JRMS_884_16
Could rapid test reader maximize the benefits to the HIV self-tester?

Balakrishnan P, Girija ASS, Kannan I, Vignesh R, Shankar EM, Sucharitha ST

Indian J Med Microbiol, 2023;43:49-50.
PMID: 36280566 DOI: 10.1016/j.ijmmb.2022.10.004
Fulltext The Implementation of HIV Self-Testing in Resource-Limited Settings Where the HIV Disease Burden is High

Balakrishnan P, Smiline Girija AS, Shanmugam S, Kannan I, Vignesh R, Shankar EM, et al.

Int J Public Health, 2023;68:1605790.
PMID: 37266035 DOI: 10.3389/ijph.2023.1605790

In resource-limited settings, there is growing evidence that HIV testing is lacking among high-risk key populations such as men having sex with men, injection drug users, and transgenders largely due to stigma, discrimination, and lack of confidentiality. Findings from recent studies among high-risk key populations and the general population from various regions including resource-limited settings support the need for wider accessibility of HIV self-testing (HIV-ST) to reach those who may not otherwise have access to testing. Therefore, HIV-ST has untapped potential as a strategy to improve access to HIV testing and to increase testing frequency among key high-risk populations and their partners. Though HIV-ST has emerged as a safe, acceptable, and effective way to reach people, there are several roadblocks to implementing the HIV-ST policy, and fast-track policy implementation needs to be necessitated with newer or modified strategic plans.
Dissemination of Trimethoprim-Sulfamethoxazole Drug Resistance Genes Associated with Class 1 and Class 2 Integrons Among Gram-Negative Bacteria from HIV Patients in South India

Ramesh Kumar MR, Arunagirinathan N, Srivani S, Dhanasezhian A, Vijaykanth N, Manikandan N, et al.

Microb Drug Resist, 2017 Jul;23(5):602-608.
PMID: 27854149 DOI: 10.1089/mdr.2016.0034

The antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), is generally used for prophylaxis in HIV individuals to protect them from Pneumocystis jiroveci infection. Long-term use of TMP-SMX develops drug resistance among bacteria in HIV patients. The study was aimed to detect the TMP-SMX resistance genes among gram-negative bacteria from HIV patients. TMP-SMX-resistant isolates were detected by the Kirby-Bauer disc diffusion method. While TMP resistance genes such as dfrA1, dfrA5, dfrA7, and dfrA17 and SMX resistance genes such as sul1 and sul2 were detected by multiplex PCR, class 1 and class 2 integrons were detected by standard monoplex PCR. Of the 151 TMP-SMX-resistant bacterial isolates, 3 were positive for sul1 alone, 48 for sul2 alone, 11 for dfrA7 alone, 21 for sul1 and sul2, 1 for sul1 and dfrA7, 23 for sul2 and dfrA7, 2 for sul2 and dfrA5, 41 for sul1, sul2, and dfrA7, and 1 for sul2, dfrA5, and dfrA7. Of 60 TMP-SMX-resistant isolates positive for integrons, 44 had class 1 and 16 had class 2 integrons. It was found that the prevalence of sul genes (n = 202; p p p
Fulltext Do the clonally different Escherichia coli isolates causing different infections in a HIV positive patient affect the selection of antibiotics for their treatment?

Rameshkumar MR, Arunagirinathan N, Swathirajan CR, Vignesh R, Balakrishnan P, Solomon SS

Indian J Med Res, 2018 09;148(3):341-344.
PMID: 30425226 DOI: 10.4103/ijmr.IJMR_730_17
Fulltext Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+ T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control

Vimali J, Yong YK, Murugesan A, Vishnupriya K, Ashwin R, Daniel EA, et al.

Front Med (Lausanne), 2022;9:1019230.
PMID: 36405584 DOI: 10.3389/fmed.2022.1019230

Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1β, IL-8, and TNF-α, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log10 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log10 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the host's versatile immune armory against viral persistence.
Fulltext Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome-An Extempore Game of Misfiring with Defense Arsenals

Vignesh R, Balakrishnan P, Tan HY, Yong YK, Velu V, Larsson M, et al.

Pathogens, 2023 Jan 29;12(2).
PMID: 36839482 DOI: 10.3390/pathogens12020210

The lethal combination involving TB and HIV, known as "syndemic" diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART, eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although a significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic marker still remain a grey area of investigation. Here, we reviewed the latest research developments into IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.
Fulltext Surrogate Biomarkers of Disease Progression in Human Pegivirus Seropositive Human Immunodeficiency Virus-Infected Individuals

Vimali J, Yong YK, Murugesan A, Ashwin R, Balakrishnan P, Raju S, et al.

Viral Immunol, 2023 Jan;36(1):55-62.
PMID: 36355180 DOI: 10.1089/vim.2022.0144

Scientific observations indicate that an actively prevailing systemic condition could alleviate the pathology of another disease. Human pegivirus (HPgV), a highly ubiquitous flavivirus is believed to be associated with slow human immunodeficiency virus (HIV) disease progression, and has seldom been linked to hepatic pathology. In this study, we investigated whether HPgV seropositivity had any impact on surrogate markers of HIV disease progression in a cohort of HIV-infected HPgV seropositive (n = 28) and seronegative (n = 12) individuals who were prospectively evaluated for absolute CD4+ T cell counts, plasma viral load (PVL), liver enzymes, and plasma cytokine levels. The HIV PVL was relatively lower in HPgV seropositive than in HPgV seronegative HIV-infected subjects. Clinical markers of hepatic injury were significantly low among HPgV seropositive HIV-infected participants. HPgV seropositive individuals showed significantly higher levels of interleukin-7 (IL-7), and although not significant, the levels of IL-6 were lower among HPgV seropositive subjects. Spearman correlation analysis showed that the absolute CD4+T cell count was inversely correlated with HIV PVL. Exposure to HPgV appears to have a positive prognostic impact on the levels of surrogate biomarkers of HIV disease progression.
Fulltext Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors

Vimali J, Yong YK, Murugesan A, Tan HY, Zhang Y, Ashwin R, et al.

Front Biosci (Landmark Ed), 2024 Mar 22;29(3):128.
PMID: 38538288 DOI: 10.31083/j.fbl2903128

BACKGROUND: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells.
METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression.
RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL.
CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.
Fulltext Chronic viral infection compromises the quality of circulating mucosal-invariant T cells and follicular T helper cells via expression of both activating and inhibitory receptors

Vimali J, Yong YK, Murugesan A, Tan HY, Zhang Y, Ashwin R, et al.

Res Sq, 2023 Apr 27.
PMID: 37163092 DOI: 10.21203/rs.3.rs-2862719/v1

Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we investigated the role of immune activation and compared the quality of T-cell responses in chronic HBV, HCV, and HIV infections. Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and peripheral CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. The activation marker CD69 was significantly increased in CD4+ hi T cells, while CD8+ MAIT cells expressing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+ lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+ hi T cells, PD-1+CD8+ T cells, Ki67+CD4+ MAIT cells were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Chronic viral infection negatively impacts the quality of peripheral MAIT cells and TFH cells via expression of both activating and inhibitory receptors.
Fulltext Recent advances in HIV diagnostics: Point-of-care CD4 + T-cell count & viral load assays

Balakrishnan P, Saravanan S, Vignesh R, Shankar EM

Indian J Med Res, 2023 Nov 01;158(5&6):447-450.
PMID: 38063301 DOI: 10.4103/ijmr.ijmr_1616_23
Fulltext Plasma CXCL8 and MCP-1 as surrogate plasma biomarkers of latent tuberculosis infection among household contacts-A cross-sectional study

Selvavinayagam ST, Aswathy B, Yong YK, Frederick A, Murali L, Kalaivani V, et al.

PLOS Glob Public Health, 2023;3(11):e0002327.
PMID: 37992019 DOI: 10.1371/journal.pgph.0002327

Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.
Genomic surveillance of omicron B.1.1.529 SARS-CoV-2 and its variants between December 2021 and March 2023 in Tamil Nadu, India-A state-wide prospective longitudinal study

Selvavinayagam ST, Suvaithenamudhan S, Yong YK, Hemashree K, Rajeshkumar M, Kumaresan A, et al.

J Med Virol, 2024 Feb;96(2):e29456.
PMID: 38329187 DOI: 10.1002/jmv.29456

A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
Fulltext Emergence of SARS-CoV-2 Omicron Variant JN.1 in Tamil Nadu, India - Clinical Characteristics and Novel Mutations

Selvavinayagam ST, Sankar S, Yong YK, Murugesan A, Suvaithenamudhan S, Hemashree K, et al.

medRxiv, 2024 Apr 19.
PMID: 38699322 DOI: 10.1101/2024.04.16.24305882

In December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.
Fulltext Familial hemiplegic migraine in a child with seizure disorder: clinical history is the key to diagnosis

Balakrishnan P, Katakam PK, Hegde AP

BMJ Case Rep, 2019 Mar 25;12(3).
PMID: 30914414 DOI: 10.1136/bcr-2018-228687

Headache is a common presenting complaint in the paediatric population, with often migraine being a clinical diagnosis. Hemiplegic migraine is characterised by aura, sudden onset weakness of one side of the body which usually recovers without any residual neurological deficit. We report a child with a history of seizure disorder, well controlled and off medication for 3 years, who presented with a headache, aura and transient hemiplegia. Similar history in the patient's mother suggests the diagnosis of familial hemiplegic migraine. We would like to emphasise the importance of detailed history as an important aid in the diagnosis of neurological disorders in children.
Occurrence of extended-spectrum β-lactamase, AmpC, and carbapenemase-producing genes in gram-negative bacterial isolates from human immunodeficiency virus infected patients

Rameshkumar MR, Arunagirinathan N, Senthamilselvan B, Swathirajan CR, Solomon SS, Vignesh R, et al.

J Infect Public Health, 2021 Nov 10.
PMID: 34810142 DOI: 10.1016/j.jiph.2021.11.008

BACKGROUND: Progressive decline of immune response in HIV patients makes them susceptible to frequent bacterial infections. High usage of antibiotics influences the emergence of multidrug-resistant bacteria and worsens the clinical outcomes. In this study, the occurrence of drug-resistant genes in Gram-negative bacterial isolates from HIV patients in South India was analyzed.
METHODS: A total of 173 Gram-negative bacterial (GNB) isolates from HIV patients were screened for antibiotic susceptibility profile using the Kirby-Bauer diskdiffusion method. Positivity of drug-resistant genes was analyzed using polymerase chain reaction method.
RESULTS: In this study, 72.8% of bacterial isolates were obtained from urine specimens, and Escherichia coli (47.4%) was the predominantly isolated bacterium. Overall, 87.3% and 83.2% of GNB were resistant to 3rd generation cephalosporin antibiotics such as cefotaxime and ceftazidime, respectively, 56.6% were resistant to cephamycin (cefoxitin) and 43% to carbapenem (imipenem) antibiotics. Extended-spectrum β-lactamases (ESBL) production was noted among 79.5% of GNB isolates, followed by AmpC (57.1%) and Metallo β-lactamases (37.3%). Molecular analysis revealed that ESBL genes such as blaTEM (94.1%), blaCTX-M (89.2%), and blaSHV (24.2%) were detected at higher levels among GNB isolates. Carbapenemase-producing genes such as blaOXA-48 (20%), blaOXA-23 (2.6%), and both blaOXA-23 and blaOXA-51 like genes (2.6%) and AmpC producing genes such as blaCIT (26.7%), blaDHA (3.6%), and blaACC (1.8%) were detected at low-level.
CONCLUSIONS: This study concludes that ESBL producing genes are detected at high level among gram-negative bacterial isolates from HIV patients in South India.
Fulltext Retrospective Analysis of Antibiotic Resistance in Streptococcus spp. from HIV Patients (2012-2017) from Southern India

Swathirajan CR, Rameshkumar MR, Solomon SS, Vignesh R, Balakrishnan P

Adv Biomed Res, 2019;8:1.
PMID: 30775343 DOI: 10.4103/abr.abr_185_18
Performance of point-of-care Xpert HIV-1 plasma viral load assay at a tertiary HIV care centre in Southern India

Swathirajan CR, Vignesh R, Boobalan J, Solomon SS, Saravanan S, Balakrishnan P

J Med Microbiol, 2017 Oct;66(10):1379-1382.
PMID: 28901908 DOI: 10.1099/jmm.0.000514

BACKGROUND: Sustainable suppression of HIV replication forms the basis of anti-retroviral therapy (ART) medication. Thus, reliable quantification of HIV viral load has become an essential factor to monitor the effectiveness of the ART. Longer turnaround-time (TAT), batch testing and technical skills are major drawbacks of standard real-time PCR assays.
METHODS: The performance of the point-of-care Xpert HIV-1 viral load assay was evaluated against the Abbott RealTime PCR m2000rt system. A total of 96 plasma specimens ranging from 2.5 log10 copies ml-1 to 4.99 log10 copies ml-1 and proficiency testing panel specimens were used. Precision and accuracy were checked using the Pearson correlation co-efficient test and Bland-Altman analysis.
RESULTS: Compared to the Abbott RealTime PCR, the Xpert HIV-1 viral load assay showed a good correlation (Pearson r=0.81; P<0.0001) with a mean difference of 0.27 log10 copies ml-1 (95 % CI, -0.41 to 0.96 log10 copies ml-1; sd, 0.35 log10 copies ml-1).
CONCLUSION: Reliable and ease of testing individual specimens could make the Xpert HIV-1 viral load assay an efficient alternative method for ART monitoring in clinical management of HIV disease in resource-limited settings. The rapid test results (less than 2 h) could help in making an immediate clinical decision, which further strengthens patient care.
Changing drug resistance profile in Pseudomonas aeruginosa infection among HIV patients from 2010-2017: A retrospective study

Swathirajan CR, Rameshkumar MR, Solomon SS, Vignesh R, Balakrishnan P

J Glob Antimicrob Resist, 2019 03;16:274-277.
PMID: 30389636 DOI: 10.1016/j.jgar.2018.10.019

OBJECTIVES: Pseudomonas aeruginosa is an important aetiological agent causing pneumonia, urinary tract infections and bacteraemia. High antibiotic use in nosocomial settings and for immunocompromised conditions results in increasing multidrug resistance. This study analysed the antimicrobial resistance profile of P. aeruginosa isolates in an HIV setting.
METHODS: A total of 7386 clinical specimens were collected from HIV patients attending YRG CARE from 2010-2017. P. aeruginosa isolated from clinical specimens were identified conventionally, and antimicrobial susceptibility testing was performed by the Kirby-Bauer disk diffusion method.
RESULTS: A total of 260 P. aeruginosa strains were isolated, with 165 P. aeruginosa (63.5%) being isolated from hospitalised patients. A higher incidence of P. aeruginosa infection (25.8%) was observed in 2017, and most of the P. aeruginosa were isolated from sputum specimens (57.3%). A high level of resistance was noted to ceftazidime (49.6%), followed by ticarcillin (41.5%). Imipenem and meropenem resistance was observed in 15.0% and 16.9% of P. aeruginosa isolates, respectively. A high rate of imipenem resistance was noted in 2016 (46.2%) and a high rate of meropenem resistance was noted in 2017 (20.5%). An increasing resistance rate of P. aeruginosa was observed against aztreonam, cefepime, levofloxacin, meropenem, piperacillin, piperacillin/tazobactam, ticarcillin and tobramycin from 2010 to 2017.
CONCLUSION: A constant increase in drug-resistant P. aeruginosa isolates from HIV patients was observed from 2010 to 2017. Findings from this study urge the need for periodical monitoring and surveillance of the P. aeruginosa resistance profile, especially in hospitalised and immunocompromised patients in resource-limited settings.

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