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Fulltext Chromogenic agar medium for rapid detection of extended-spectrum β-lactamases and Klebsiella pneumoniae carbapenemases producing bacteria from human immunodeficiency virus patients

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

J Res Med Sci, 2015 Dec;20(12):1219-20.
PMID: 26958061 DOI: 10.4103/1735-1995.172994
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
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.
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.
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
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
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 Detection of blaNDM-1 and blaNDM-5 genes among Gram-negative bacteria isolated from human immunodeficiency virus patients in South India

Rameshkumar MR, Arunagirinathan N, Indu P, Swathirajan CR, Solomon SS, Vignesh R, et al.

J Res Med Sci, 2018;23:112.
PMID: 30774691 DOI: 10.4103/jrms.JRMS_627_18
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.
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.
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 Bacterial etiology and antibiotic resistance profile of bloodstream infections in human immunodeficiency virus patients from Southern India

Swathirajan CR, Rameshkumar MR, Solomon SS, Pradeep A, Chithra DA, Balakrishnan R, et al.

J Res Med Sci, 2019;24:82.
PMID: 31620181 DOI: 10.4103/jrms.JRMS_55_19
Fulltext Could Perturbation of Gut Microbiota Possibly Exacerbate the Severity of COVID-19 via Cytokine Storm?

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

Front Immunol, 2020;11:607734.
PMID: 33569053 DOI: 10.3389/fimmu.2020.607734
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 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 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 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 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.
A Tête-à-tête with ChatGPT on the impact of artificial intelligence in medical education

Vignesh R, Pradeep P, Balakrishnan P

Med J Malaysia, 2023 Jul;78(4):547-549.
PMID: 37518931

Chat Generative Pre-Trained Transformer (ChatGPT) is an artificial intelligence (AI) language model developed by OpenAI. It is trained to process vast amounts of text and engage in human-like conversational interaction with users. Being accessible by all, it is widely used and its capabilities range from language translation, summarising long texts and creative writing. This article explores the potential role of ChatGPT in medical education and the possible concerns about the misuse of this technology through a conversation with ChatGPT itself via text prompts. The implications of this technology in medical education as told by ChatGPT are interesting and seemingly helpful for both the students and the tutors. However, this could be a double-edged sword considering the risks of compromised students' integrity and concerns of over-reliance. This also calls for counter strategies and policies in place to mitigate these risks.
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

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