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Fulltext Updates on Dengue Vaccine and Antiviral: Where Are We Heading?

Norshidah H, Vignesh R, Lai NS

Molecules, 2021 Nov 09;26(22).
PMID: 34833860 DOI: 10.3390/molecules26226768

Approximately 100-400 million people from more than 100 countries in the tropical and subtropical world are affected by dengue infections. Recent scientific breakthroughs have brought new insights into novel strategies for the production of dengue antivirals and vaccines. The search for specific dengue inhibitors is expanding, and the mechanisms for evaluating the efficacy of novel drugs are currently established, allowing for expedited translation into human trials. Furthermore, in the aftermath of the only FDA-approved vaccine, Dengvaxia, a safer and more effective dengue vaccine candidate is making its way through the clinical trials. Until an effective antiviral therapy and licensed vaccine are available, disease monitoring and vector population control will be the mainstays of dengue prevention. In this article, we highlighted recent advances made in the perspectives of efforts made recently, in dengue vaccine development and dengue antiviral drug.
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 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.
Fulltext Thalidomide as a Potential HIV Latency Reversal Agent: Is It the Right Time to Forget the Ancestral Sins?

Vignesh R, Shankar EM

EBioMedicine, 2017 Oct;24:20-21.
PMID: 28865747 DOI: 10.1016/j.ebiom.2017.08.025
Fulltext SARS-CoV-2 in Pregnant Women: Consequences of Vertical Transmission

Chaubey I, Vignesh R, Babu H, Wagoner I, Govindaraj S, Velu V

Front Cell Infect Microbiol, 2021;11:717104.
PMID: 34568094 DOI: 10.3389/fcimb.2021.717104
Fulltext Risk factors and frequency of tuberculosis-associated immune reconstitution inflammatory syndrome among HIV/Tuberculosis co-infected patients in Southern India

Vignesh R, Swathirajan CR, Solomon SS, Shankar EM, Murugavel KG

Indian J Med Microbiol, 2017 Apr-Jun;35(2):279-281.
PMID: 28681821 DOI: 10.4103/ijmm.IJMM_16_163

Immune reconstitution inflammatory syndrome (IRIS) continues to be a complication in HIV/tuberculosis (TB) co-infected patients initiating highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the risk factors associated with developing IRIS to identify a possible biomarker to predict or diagnose IRIS in patients initiating HAART. A total of 175 HIV/TB co-infected patients initiating HAART were followed up longitudinally during September 2010 to May 2013 attending a HIV care clinic in Chennai. Patients were followed up longitudinally after HAART initiation and baseline demographic, laboratory parameters and treatment characteristics between patients with IRIS events and those without IRIS events were compared. Chi-square or Fisher's exact test for categorical variables and a Wilcoxon rank-sum test for continuous variables were performed using SPSS, version 12.0 software. Patients with IRIS had a significantly lower median baseline CD4+ T-cell count (P = 0.0039). There were no differences in terms of sex, CD4 T-cell %, plasma viral load, time interval between initiating ATT and HAART between the IRIS and non-IRIS patients. Low CD4+ T-cell count (<100 cells/μL) could be used as a marker to screen and monitor patients initiating HAART.
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
Fulltext Recent advances targeting innate immunity-mediated therapies against HIV-1 infection

Shankar EM, Velu V, Vignesh R, Vijayaraghavalu S, Rukumani DV, Sabet NS

Microbiol. Immunol., 2012 Aug;56(8):497-505.
PMID: 22900503 DOI: 10.1111/j.1348-0421.2012.00485.x

Early defence mechanisms of innate immunity respond rapidly to infection against HIV-1 in the genital mucosa. Additionally, innate immunity optimises effective adaptive immune responses against persistent HIV infection. Recent research has highlighted the intrinsic roles of apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G, tripartite motif-containing protein 5, tetherin, sterile α-motif and histidine/aspartic acid domain-containing protein 1 in restricting HIV-1 replication. Likewise, certain endogenously secreted antimicrobial peptides, namely α/β/θ-defensins, lactoferrins, secretory leukocyte protease inhibitor, trappin-2/elafin and macrophage inflammatory protein-3α are reportedly protective. Whilst certain factors directly inhibit HIV, others can be permissive. Interferon-λ3 exerts an anti-HIV function by activating Janus kinase-signal transducer and activator of transcription-mediated innate responses. Morphine has been found to impair intracellular innate immunity, contributing to HIV establishment in macrophages. Interestingly, protegrin-1 could be used therapeutically to inhibit early HIV-1 establishment. Moreover, chloroquine inhibits plasmacytoid dendritic cell activation and improves effective T-cell responses. This minireview summarizes the recently identified targets for innate immunity-mediated therapies and outlines the challenges that lie ahead in improving treatment of HIV infection.
Recent advances on T-cell exhaustion in malaria infection

Shankar EM, Vignesh R, Dash AP

Med Microbiol Immunol, 2018 Aug;207(3-4):167-174.
PMID: 29936565 DOI: 10.1007/s00430-018-0547-0

T-cell exhaustion reportedly leads to dysfunctional immune responses of antigen-specific T cells. Investigations have revealed that T cells expand into functionally defective phenotypes with poor recall/memory abilities to parasitic antigens. The exploitation of co-inhibitory pathways represent a highly viable area of translational research that has very well been utilized against certain cancerous conditions. Malaria, at times, evolve into a sustained chronic state where T cells express several co-inhibitory molecules (negative immune checkpoints) facilitating parasite escape and sub-optimal protective responses. Experimental evidence suggests that blockade of co-inhibitory molecules on T cells in malaria could result in the sustenance of protective responses together with dramatic parasite clearance. The role of several co-inhibitory molecules in malaria infection largely remain unclear, and here we discussed the potential applicability of co-inhibitory molecules in the management of malaria with a view to harness protective host responses against chronic disease and associated consequences.
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.
Fulltext Plasma CXCL8 and MCP-1 as biomarkers of latent tuberculosis infection

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

medRxiv, 2023 Aug 09.
PMID: 37609153 DOI: 10.1101/2023.08.07.23293767

BACKGROUND: Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy.
METHODS: We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay.
RESULTS: 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.
CONCLUSIONS: We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.
Fulltext Performance of urinalysis tests in screening for significant bacteriuria among human immunodeficiency virus-infected subjects in South India

Vignesh R, Swathirajan CR, Solomon SS, Solomon S, Balakrishnan P

J Res Med Sci, 2017;22:77.
PMID: 28717374 DOI: 10.4103/jrms.JRMS_567_16
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.
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 Occurrence of enteric parasitic infections among HIV-infected individuals and its relation to CD4 T-cell counts with a special emphasis on coccidian parasites at a tertiary care centre in South India

Swathirajan CR, Vignesh R, Pradeep A, Solomon SS, Solomon S, Balakrishnan P

Indian J Med Microbiol, 2017 Jan-Mar;35(1):37-40.
PMID: 28303816 DOI: 10.4103/ijmm.IJMM_16_164

CONTEXT: Diarrhoea is one of the major complications occurring in over 90% of HIV-infected individuals in developing countries. Coccidian group of parasites, being opportunistic pathogens, have been implicated as the most common causative agents of diarrhoea among HIV-infected population.

AIMS: The aim was to study the magnitude of parasitic diarrhoea with special context to coccidian parasitic infections in HIV-infected individuals and their association with the patient's immunological status measured by CD4 T-cell counts.

SETTINGS AND DESIGN: This investigation was performed between January 2002 and December 2014 at a tertiary HIV care centre in Chennai, South India.

MATERIALS AND METHODS: Stool samples were collected and microscopically observed for parasites using direct, formal-ether-concentrated wet mounts and modified acid-fast staining for coccidian parasites. CD4 T-cell counts were done by FACScount.

STATISTICAL ANALYSIS USED: All statistical analyses were performed using GraphPad Prism software, version 5.0, andP < 0.05 was considered statistically significant.

RESULTS: Coccidian parasitic infection accounted for about 23.4% of parasitic infections, and of these, Cystoisospora belli was observed to be the most common cause of diarrhoea (88.8%), followed by Cryptosporidium spp. (9.9%) and Cyclospora spp. (1.3%). Trend analysis of coccidian aetiology during the study period revealed a significant rise in the positivity of C. belli and Cryptosporidium spp. (P = 0.001). Among the HIV patients with CD4+ T-cell counts <200 cells/μL, Cryptosporidium infection was most common (90%), followed by infection with C. belli(61.4%).

CONCLUSIONS: Coccidian parasites continue to be the most common aetiological agent of diarrhoea among patients with HIV. The increasing trend of positivity of both cystoisosporiasis and cryptosporidiosis over the study period and the high positivity of cryptosporidiosis in patients with lower CD4+ T-cell counts are issues of serious concern. The findings call for the need for the early diagnosis of coccidian parasites and appropriate intervention among HIV-infected patients.
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.
Isolation and genotyping of Toxoplasma gondii from free-range ducks in Malaysia

Puvanesuaran VR, Noordin R, Balakrishnan V

Avian Dis, 2013 Mar;57(1):128-32.
PMID: 23678741

Toxoplasma gondii is a parasitic protozoan that infects nearly one-third of humans. The present study was performed to isolate and genotype T. gondii from free-range ducks in Malaysia. Sera, heads, and hearts from 205 ducks were obtained from four states in Peninsular Malaysia, and 30 (14.63%) sera were found to be seropositive when assayed with the modified agglutination test (MAT > or = 1:6). All the positive samples were inoculated into mice, and T. gondii was successfully isolated from four individual duck samples (1.95%), which were initially found to be strongly seropositive (MAT > or = 1:24). The isolates were subjected to PCR-RFLP analysis, and two T. gondii strains were identified: type I and type II. This is the first reported study on the genetic characterization of T. gondii isolates from free-range farm animals in Southeast Asia.
Fulltext Is Herd Immunity Against SARS-CoV-2 a Silver Lining?

Vignesh R, Shankar EM, Velu V, Thyagarajan SP

Front Immunol, 2020;11:586781.
PMID: 33101320 DOI: 10.3389/fimmu.2020.586781
Fulltext Infectious risk assessment of unsafe handling practices and management of clinical solid waste

Hossain MS, Rahman NN, Balakrishnan V, Puvanesuaran VR, Sarker MZ, Kadir MO

Int J Environ Res Public Health, 2013 Jan 31;10(2):556-67.
PMID: 23435587 DOI: 10.3390/ijerph10020556

The present study was undertaken to determine the bacterial agents present in various clinical solid wastes, general waste and clinical sharp waste. The waste was collected from different wards/units in a healthcare facility in Penang Island, Malaysia. The presence of bacterial agents in clinical and general waste was determined using the conventional bacteria identification methods. Several pathogenic bacteria including opportunistic bacterial agent such as Pseudomonas aeruginosa, Salmonella spp., Klebsiella pneumoniae, Serratia marcescens, Acinetobacter baumannii, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes were detected in clinical solid wastes. The presence of specific pathogenic bacterial strains in clinical sharp waste was determined using 16s rDNA analysis. In this study, several nosocomial pathogenic bacteria strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Lysinibacillus sphaericus, Serratia marcescens, and Staphylococcus aureus were detected in clinical sharp waste. The present study suggests that waste generated from healthcare facilities should be sterilized at the point of generation in order to eliminate nosocomial infections from the general waste or either of the clinical wastes.

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