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Background: In view of the importance of chronic HBV (CHB) infection and the global burden of non-alcoholic fatty liver disease (NAFLD), it is imperative to understand the potential interplay between the two diseases. Methods: Here, we retrospectively investigated the association between NAFLD and CHB infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between year 2013 and 2016, we studied 449 subjects in the current investigation. Findings: CAP and LSM scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the HBV viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. Interpretations: Together, we found that there was a high concurrence of NAFLD among patients with CHB. The presence of metabolic syndrome and chronic inflammation in CHB patients were two independent factors that led to progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components. Plasma markers of liver steatosis and fibrosis progression are key to development of cell-targeted therapies exploiting specific molecular pathways. Funding Statement: This work was supported by a grant from the Frontier Research Grant (FRG), FG019-17AFR to Mohamed Rosmawati and Xiamen University Malaysia Research Funding (XMUMRF), XMUMRF/2018-C2/ILAB/0001. Marie Larsson is supported by the Swedish Research Council, the Swedish Physicians against AIDS Research Foundation; VINNMER for Vinnova, Linkoping University Hospital Research Fund, ALF Grants Region Ostergotland, FORSS. Declaration of Interests: The authors declare no conflicts interest. Ethics Approval Statement: The medical records of patients were extracted from the hospital database using patients’ unique hospital registration number. This study was approved by the Medical Ethics Committee of the University Malaya Medical Centre (MEC-938.42).

Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.

Colony morphology variation is a characteristic of Burkholderia pseudomallei primary clinical isolates, associated with variations in expression of virulence factors. Here, we performed comparative investigations on adhesion, invasion, plaque-forming abilities and protein profiles of B. pseudomallei wild-type (WT) and a small colony variant (SCV). The percentage of SCV adherence to A549 cells was significantly higher (2.73%) than WT (1.91%). In contrast, WT was significantly more efficient (0.63%) than SCV (0.31%) in invasiveness and in inducing cellular damage. Using 2-DE and MALDI TOF/TOF, 263 and 258 protein spots were detected in WT and SCV, respectively. Comparatively, 49 proteins were differentially expressed in SCV when compared with WT. Of these, 31 proteins were up-regulated, namely, nucleoside diphosphate kinase (Ndk), phosphoglycerate kinase (Pgk), thioredoxin (TrxA), putative ferritin DPS-family DNA-binding protein (DPS) and oxidoreductase (AhpC) that are known to be involved in adhesion, intracellular survival and persistence. However, among the 18 down-regulated proteins, enolase (Eno), elongation factor (EF-Tu) and universal stress-related proteins were associated with invasion and virulence. Differences observed in these protein profiles provide ample clues to their association with the morphotypic and phenotypic characteristics of colony variants, providing additional insights into the potential association of B. pseudomallei colony morphotypes with disease pathogenesis. Biological significance Comparative analyses were performed on the ability of wild-type and small colony variant of B. pseudomallei to adhere, invade and form plaques on human epithelial cells. In addition, proteomic analysis of these different colony morphotypes was also carried out. This research provides insights into the virulence and pathogenesis attributes of B. pseudomallei and contributes to better understand the pathogenesis of melioidosis.

The mechanisms behind certain co-morbid conditions associated with chronic HIV disease still remain elusive. HIV-associated peripheral neuropathy is one among those rarely studied manifestations in HIV-1 infection. Numerous underlying factors associated with peripheral neuropathy have been described in HIV disease. Herein, we hypothesized certain heretofore undescribed potential mechanisms that lead to HIV associated neuropathy. Being a multifactoral manifestation, HIV-associated neuropathy is presumed to have an association with physiological factors namely, adrenal inadequacy/steroid resistance and lipodystrophy-induced cushion-effect loss in peripheral nerves. Therefore, management of the adrenals with steroids at the time-point of high inflammatory burden thereby preventing lipodystrophy by selecting the optimum treatment regimen could markedly alleviate the severity of HIV-associated neuropathic manifestations.

Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory manifestation that occurs subsequent to initiation of highly active antiretroviral therapy in terminal (HAART) HIV infection, mainly due to the restoration of robust immune responses directed against latent microbial antigens. IRIS is believed to be multifactorial and less studied. Herein, we postulate that hypothalamo–pituitary–adrenal (HPA) dysregulation, a well-documented manifestation in HIV/AIDS, could possibly disturb the balance between pro-inflammatory and anti-inflammatory cytokines leading to clinical IRIS. Drugs, opportunistic infections, stress and numerous intrinsic and extrinsic factors have been described to be the possible causes of IRIS in HIV illness.

SummaryObjectiveThe role of oxidative stress in disease progression has been shown to be more complicated in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) compared to those who remain treatment-naïve. This study examined the changes in the antioxidant profile of HIV-infected subjects who remained HAART-naïve due to a high CD4 cell count and HIV-negative controls, over a 12-month follow-up period at YRG CARE, a tertiary HIV referral centre in southern India.MethodsWe prospectively studied 35 HIV-infected participants (18 on d4T+3TC+EFV (stavudine+lamivudine+efavirenz), eight on AZT+3TC+EFV (zidovudine+lamivudine+efavirenz), and nine who were antiretroviral therapy-naïve) and 20 HIV-negative controls. Antioxidant profile (total antioxidant status, glutathione reductase, glutathione peroxidase, uric acid, ceruloplasmin, zinc, and albumin), CD4 cell count, plasma viral load, dietary intake, and history of smoking and alcohol use were determined at baseline and at twelve months.ResultsAt 12 months, participants on HAART showed a significant increase in glutathione peroxidase (baseline: 1765 vs. 12 months: 2850U/l; p

Summary Objectives The prevalence of hepatitis B virus (HBV) is reportedly the main cause of hepatocellular carcinoma (HCC) in India, where hepatitis C virus (HCV)-associated HCC is believed to be relatively less prevalent. We verified the usefulness of alpha-fetoprotein (AFP) as a tumor marker and analyzed the influence of viral etiology on AFP levels in HCC. Methods Of a total of 1012 cases with liver disease, 202 were investigated for the presence of AFP (142 HCC cases, 30 cirrhosis cases, and 30 chronic liver disease (CLD) cases). In addition, serum samples from 30 healthy patients, 30 hepatitis B surface antigen (HBsAg) carriers, and 30 acute viral hepatitis cases were included as controls. AFP was quantitatively determined using a commercial ELISA (Quorum Diagnostics, Canada). Out of the 142 HCC cases screened for AFP, aflatoxin B1 (AFB1) detection was carried out in 38 HCC cases using an in-house immunoperoxidase test. Results In HBV and HCV co-infected HCC cases, the AFP positivity was 85.7%. In HBV alone-associated HCC, the positivity was 62.9%, and 54.5% of AFB1 positive HCC cases showed AFP positivity. In HBV and HCV negative HCC cases, the positivity was 20.5%, and in HCV-associated HCC it was 17.6%. The HBV/HCV co-infected group and HBV alone positive HCC cases had significantly elevated levels of AFP. When AFP positivity was analyzed based on the marker profile of HBV, 89.7% of AFP positive cases were HBV-DNA positive. Conclusions The overall positivity pattern of AFP in HCC does indicate that higher levels of AFP are observed with hepatitis virus positivity, especially with HBV. Further studies must be carried out to correlate the serum levels of AFP with the size, number, and degree of differentiation of HCC nodules.

Background We established the biochemical and hematological reference intervals among a south Indian healthy adult population attending an HIV referral centre in Chennai, southern India. Methods In a cross sectional study, 213 study subjects (129 male and 84 female) were studied between March and August 2005. All of the parameters were analyzed using standard hematological and biochemical techniques. Results Certain biochemical (viz. total bilirubin, alanine transaminase, albumin, creatinine, total protein, lipid profile, creatine phospokinase, uric acid and lactate) and hematological (mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and lymphocyte levels) parameters presented higher upper limits. In addition, the upper limits of white blood cell count, platelet count, hematocrit, red blood cell count and hemoglobin level were low in comparison to the currently reported ranges. Conclusion Ethnic variation in reference intervals was observed in certain biochemical and hematological analytes in a south Indian adult population.

Summary Background The true seroepidemiology of acute Mycoplasma pneumoniae infection in HIV infected individuals is ambiguous. Methods This study examined the serosurveillance of IgM antibodies to M. pneumoniae in HIV infected patients presenting with pulmonary symptoms at a tertiary AIDS care center in Chennai, Southern India, using cold-haemagglutination test and commercial enzyme linked immunosorbent assay in acute serum specimens. Results One hundred HIV infected patients had enrolled in the study; 21 (21%) were positive for M. pneumoniae IgM antibodies by ELISA and 34 (34%) showed evidence of cold hemagglutinins. Conclusion This serosurveillance study reports a 21% prevalence of M. pneumoniae IgM antibody among HIV infected patients with pulmonary symptoms by ELISA and non-specific diagnosis was confirmed in 34% of the cases screened. Determination of cold agglutination titer could be used as a substitute to other expensive procedures in limited resource settings and third-world nations to diagnose M. pneumoniae infections for prompt initiation of therapy, as CAT has been found to be 100% sensitive and 84% specific in the diagnosis of M. pneumoniae infection.

Background Foot infections are a frequent complication of patients with diabetes mellitus, accounting for up to 20% of diabetes-related hospital admissions. Infectious agents are associated with the worst outcomes, which may ultimately lead to amputation of the infected foot unless prompt treatment strategies are ensued. The present study sought to reveal the bacterial etiology of diabetic foot ulcers in South India, the diabetic capital of India. Methods A 10-month-long descriptive study was carried out to analyse the aerobic and anaerobic bacterial isolates of all patients admitted with diabetic foot infections presenting with Wagner grade 2–5 ulcers. Bacteriological diagnosis and antibiotic sensitivity profiles were carried out and analysed using standard procedures. Results Diabetic polyneuropathy was found to be common (56.8%) and gram-negative bacteria (57.6%) were isolated more often than gram-positive ones (42.3%) in the patients screened. The most frequent bacterial isolates were Pseudomonas aeruginosa , Staphylococcus aureus , coagulase-negative staphylococci (CONS), and Enterobacteriaceaes. Forty-nine cultures (68%) showed polymicrobial involvement. About 44% of P. aeruginosa were multi-drug-resistant, and MRSA was recovered on eight occasions (10.3%). Bacteroides spp. and Peptostreptococcus spp. were the major anaerobic isolates. Conclusions Our study supports the viewpoint put forth by previous South Indian authors that the distribution of gram-negative bacteria (57.6%) is more common than that of gram-positive ones (42.3%) and it is contrary to the viewpoint that diabetic foot infections are frequently monomicrobial. Furthermore, recovery of multi-drug-resistant P. aeruginosa isolates is of serious concern, as almost no one has reported the same from the South Indian milieu.

Studies have shown that the more iron in a given population, the more that population is vulnerable to intracellular opportunistic infections (OIs) in AIDS, mainly because these microbes make use of the intracellular iron to proliferate, and could render infections deadly. In contrast, macrophages that lack iron are effective in preventing an establishment of infection. We propose that reduction in total body iron could be a valuable treatment option for some intracellular infections, including OIs. We suggest two options to deprive pathogens of using intracellular iron (i) to practice regular blood-letting, an ancient treatment option, and (ii) to down-regulate hepcidin, the key hormone involved in the regulation of iron balance and recycling. This could also deprive transformed cells of metabolizing iron for survival. Whether or these methods serve to curb the onset of OIs/cancers to prolong HIV disease progression remains to be investigated.

BACKGROUND: The co-factors underlying abnormal lactate level remains to be determined in resource-limited settings. In a cross-sectional study conducted between January 2004 and July 2006 we determined the proportion of HIV-infected persons with abnormal lactate levels and correlated the association of certain co-factors of abnormal lactate levels at a tertiary HIV care centre in Chennai Southern India. METHODS: Lactate was estimated by the enzymatic method using an Olympus AU 400 autoanalyzer. Absolute CD4+T lymphocyte count was determined by the Guava personal cell analyser (Guava Technologies Inc. Hayward CA USA). Subjects were classified to have normal or abnormal values of lactate based on the reference interval (0.3-2.2 mmol/L). A p value 0.05 was considered statistically significant. RESULTS: A total of 225 HIV-infected individuals (HAART experienced 213 (95%) and HAART naive (5%)) were included in the analysis. Mean age was 34+/-8 and 36+/-9 years for the individuals with normal and abnormal lactate levels respectively. Of these 185 (82%) had normal (0.3-2.2 mmol/L) and 40 (18%) had abnormal (>2.2 mmol/L) lactate levels. Significant difference in relation to female gender was observed between the normal and abnormal groups (p=0.03). Among the abnormal group 39 (97.5%) subjects were HAART experienced compared to 174 (94.1%) normal group. Among the abnormal group 24 (60%) individuals had a CD4 count of

Background: A great deal of effort has been devoted to understanding the role of AIDSassociated mycoplasmas in recent years. However, the role of Mycoplasma pneumoniae in HIV disease remains unclear. Methods: We studied 300 adult HIV infected persons (200 with community-acquired pneumonia (CAP) and 100 with no respiratory illness) and 75 HIV uninfected persons with CAP and analysed the prevalence of respiratory pathogens. Results: Prevalence of M. pneumoniae was 17% by induced sputum and 11.3% by throat swab culture in HIV positive subjects. Seroprevalence of anti-M. pneumoniae IgM was 11.7% by ELISA and 14.3% by gelatin microparticle agglutination test. Prevalence of M. pneumoniae among HIV negative cases was relatively low. Streptococcus pneumoniaewas predominant (28%) among subjects with lower respiratory disease, whereas Staphylococcus aureus (15%) was more common among cases with upper respiratory illness. Rales (P=0.001), pharyngeal erythema (P=0.02), cervical adenopathy (P=0.004) and crepitations (P=0.001) showed significance in relation to M. pneumoniae positivity. Statistical significance was observed with regard to total lymphocyte count (P=0.02) and erythrocyte sedimentation rate (P=0.04), and M. pneumoniae positivity. Conclusion: The prevalence of M. pneumoniae in HIV infected subjects was relatively higher than HIV uninfected subjects with respiratory disease.

This letter to the editor describes a study which investigated the profile of tuberculosis (TB) and the nature of drug resistance pattern among 176 HIV-positive subjects suspected of TB based on the clinical grounds attending a tertiary AIDS care center in Chennai South India. It states that anti-TB drug susceptibility testing should be performed for all patients who are culture positive for M. tuberculosis and concludes that there is a need for strengthening collaboration between TB and AIDS control programs to counteract the impact of HIV on TB.