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Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides' immunogenic potential, which needs to be validated in different experimental systems. [ABSTRACT FROM AUTHOR]

Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute kidney injury and increased vascular permeability. Several species of orthohantaviruses were identified as causing infection, where Hantaan, Puumala, and Seoul viruses are most common. Orthohantaviruses are endemic to several Asian countries, such as China, South Korea, and Japan. Along with those countries, HFRS tops the list of zoonotic infections in the Far Eastern Federal District of Russia. Recently, orthohantavirus circulation was demonstrated in small mammals in Thailand and India, where orthohantavirus was not believed to be endemic. In this review, we summarized the current data on orthohantaviruses in Asia. We gave the synopsis of the history and diversity of orthohantaviruses in Asia. We also described the clinical presentation and current understanding of the pathogenesis of orthohantavirus infection. Additionally, conventional and novel approaches for preventing and treating orthohantavirus infection are discussed. [ABSTRACT FROM AUTHOR]

The article discusses worry and anxiety among people living with HIV (PLWH) in South India concerning COVID-19 infection, particularly focusing upon decreasing confidence in treatment options and effectiveness. The article attempts to validate adherence to antiretroviral (ART) medication amid state-instituted shelter-in-place, social distancing, and travel restrictions.

Abstract Background The massive scale-up of antiretroviral treatment (ART) access worldwide has brought tremendous benefit to populations affected by HIV/AIDS. Optimising HIV care in countries with diverse medical systems is critical; however data on best practices for HIV healthcare delivery in resource-constrained settings are limited. This study aimed to understand patient characteristics and treatment outcomes from different HIV healthcare settings in Bangalore, India. Methods Participants from public, private and public-private HIV healthcare settings were recruited between 2007 and 2009 and were administered structured interviews by trained staff. Self-reported adherence was measured using the visual analogue scale to capture adherence over the past month, and a history of treatment interruptions (defined as having missed medications for more than 48 hours in the past three months). In addition, CD4 count and viral load (VL) were measured; genotyping for drug resistance-associated mutations was performed on those who were in virological failure (VL > 1000 copies/ml). Results A total of 471 individuals were included in the analysis (263 from the public facility, 149 from the public-private facility and 59 from the private center). Private facility patients were more likely to be male, with higher education levels and incomes. More participants reported ≥ 95% adherence among public and public-private groups compared to private participants (public 97%; private 88%; public-private 93%, p < 0.05). Treatment interruptions were lowest among public participants (1%, 10%, 5% respectively, p < 0.001). Although longer clinic waiting times were experienced by more public participants (48%, compared to private 27%, public-private 19%, p < 0.001), adherence barriers were highest among private (31%) compared with public (10%) and public-private (17%, p < 0.001) participants. Viral load was detectable in 13% public, 22% private and 9% public-private participants (p < 0.05) suggesting fewer treatment failures among public and public-private settings. Drug resistance mutations were found more frequently among private facility patients (20%) compared to those from the public (9%) or public-private facility (8%, p < 0.05). Conclusions Adherence and treatment success was significantly higher among patients from public and public-private settings compared with patients from private facilities. These results suggest a possible benefit of the standardized care delivery system established in public and public-private health facilities where counselling by a multi-disciplinary team of workers is integral to provision of ART. Strengthening and increasing public-private partnerships can enhance the success of national ART programs.

Background: Estimate of prevalence of thyroid dysfunction in systemic lupus erythematosus (SLE) patients from India is scarce. The present study evaluated the prevalence of thyroid dysfunction and anti-thyroid peroxidase (TPO) antibodies in SLE patients, and the most prominent clinical features of thyroid dysfunction were noted. Materials and Methods: This descriptive, cross-sectional study involved 100 adult patients diagnosed with SLE at a tertiary teaching hospital, Bengaluru, India. The study excluded patients on medications that are known to cause thyroid dysfunctions, those with a history of thyroidectomy, and those with other systemic autoimmune diseases. Results: Among the 100 recruited patients, 99 were females, and most (47%) belonged to the age group of 20–30 years, the median duration of lupus was 24 months. Thyroid dysfunction was observed in 42% (n = 42), and hypothyroidism was the most common thyroid abnormality. None of the patients had hyperthyroidism. Among the patients with thyroid dysfunction, the corresponding number of patients with clinical hypothyroidism and subclinical hypothyroidism were 71% (n = 30) and 29% (n = 12). Of 25 patients with elevated anti-TPO, 48% (n = 12) had clinical hypothyroidism, 20% (n = 5) had subclinical hypothyroidism, and 32% (n = 8) had normal thyroid-stimulating hormone and free T4. Most of the patients with thyroid dysfunction were newly diagnosed, and the predominant symptoms noted were fatigue (75%), hair loss (75%), and joint pain (63%). Conclusions: The prevalence of thyroid dysfunction was found to be higher in SLE than previously published cohorts in India and the rest of the world. It does not affect lupus activity. [ABSTRACT FROM AUTHOR]

Introduction: Routine HIV viral load (VL) testing is not available in India. We compared test performance characteristics of immunologic failure (IF) against the gold standard of virologic failure (VF), examined evolution of drug resistance among those who stayed on a failing regimen because they did not meet criteria for IF and assessed implications for second-line therapy. Methods: Participants on first-line highly active antiretroviral therapy (HAART) in Bangalore, India, were monitored for 24 months at six-month intervals, with CD4 count, VL and genotype, if VL >1000 copies/ml. Standard WHO criteria were used to define IF; VF was defined as having two consecutive VL > 1000 copies/ml or one VL > 10,000 copies/ml. Resistance was assessed using standard International AIDS Society-USA (IAS-USA) recommendations. Results: Of 522 participants (67.6% male, mean age of 37.5; 85.1% on nevirapine- based and 40.4% on d4T-containing regimens), 57 (10.9%) had VF, 38 (7.3%) had IF and 13 (2.5%) had both VF and IF. The sensitivity of immunologic criteria to detect VF was 22.8%, specificity was 94.6% and positive predictive value was 34.2%. Forty-four participants with VF only continued on their failing first- line regimen; by the end of the study period, 90.9% had M184V, 63.6% had thymidine analogue mutations (TAMs), 34.1% had resistance to tenofovir, and 63.6% had resistance to etravirine. Conclusions: WHO IF criteria have low sensitivity for detecting VF, and the presence of IF poorly predicts VF. Relying on CD4 counts leads to unnecessary switches to second-line HAART and continuation of failing regimens, jeopardizing future therapeutic options. Universal access to VL monitoring would avoid costly switches to second-line HAART and preserve future treatment options. Keywords: virologic failure; immunologic failure; WHO criteria; genotype; resistance; India; resource-limited settings., Introduction An estimated 6.6 million HIV-infected individuals are receiving highly active antiretroviral therapy (HAART) in resource-limited settings [1]. In India alone, approximately 400,000 individuals have been started on HAART between [...]

Introduction: Rotaviruses cause Acute Gastroenteritis (AGE) in children. Characterisation of rotavirus VP7, VP4 and VP6 genes revealed novel genotypes circulating in the region. Aim: To characterise the circulating rotavirus genotypes in Central Kerala and compare the genotypes with vaccine components to assess the genetic variability. Materials and Methods: We analysed VP6, VP4 and VP7 genes of rotavirus strains from hospitalised children (January-December 2013) by amplification, sequencing and phylogenetic analysis. VP4 and VP7 antigenic epitopes of G1P8 strains were compared with vaccine strains to determine the genetic variations. Results: G1P8 was the predominant strain, G9P8, G1P6, G9P4 were also encountered in the study. VP6 gene analysis revealed that 91.30% of strains belonged to genotype I1 and 8.7% to genotype I2. G1 and G9 strains show low nucleotide and amino acid homology with corresponding vaccine strains. Comparison between the vaccine strain and G1 study strains, eight substitutions were observed in the VP7 epitope region. In the VP4 gene (VP8 region) 22 and 12 substitutions were observed compared to Rotarix with RotaTeq vaccine strains respectively. Conclusion: Study strains clustered closely with other Indian strains, indicating common ancestral link. G1P8 strains showed low homology with vaccine strains, suggesting genetic variability to escape vaccine-derived immune response. This study helped to identify the circulating rotavirus genotypes in the region and explored possibility of emergence of divergent strains. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B Virus (HBV) causes diverse clinical manifestations ranging from acute fulminant Hepatitis, Chronic Hepatitis (CHB) to liver cirrhosis and Haepatocellular Carcinoma (HCC). The HBV X gene (HBV-X) is a 154 amino acid multifunctional protein, mutates frequently and has a role in HBV related HCC. Aim: The current study was to explore the genetic variability and identify mutations of HBV-X in CHB patients from Central Kerala, India. Materials and Methods: The HBV-X sequences (n=39) from CHB (n=90) patients were analysed for nucleotide and amino acid diversity. Phylogenetic analyses were done using MEGA version 7.0.21 software to determine different genotypes. Results: Basal Core Promoter (BCP) mutations: A1762T/ G1764A (n=5) were found in HBeAg negative subjects (n=3, 60%). Bioinformatic analysis showed that the substitutions and mutations were HBV genotype/subgenotype specific. The predominant genotype detected was A1 (n=52, 57.77%) followed by genotype D (n=27, 30.00%). Nucleotide and amino acid diversities were more in genotype A1 than in D, which is responsible for transactivation (p<0.0001), those infected with this genotype may be at high risk for HCC. Conclusion: Genotype A1 isolates displayed most mutations/ substitutions in HBV-X, Further studies are necessary to understand its role in contributing to the development of HCC. The study represents the first formal investigation of HBV-X genetic variability in Kerala. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to determine the proportion of malaria, bacteraemia, scrub typhus, leptospirosis, chikungunya and dengue among hospitalized patients with acute undifferentiated fever in India, and to describe the performance of standard diagnostic methods.Methods: During April 2011-November 2012, 1564 patients aged ≥5 years with febrile illness for 2-14 days were consecutively included in an observational study at seven community hospitals in six states in India. Malaria microscopy, blood culture, Dengue rapid NS1 antigen and IgM Combo test, Leptospira IgM ELISA, Scrub typhus IgM ELISA and Chikungunya IgM ELISA were routinely performed at the hospitals. Second line testing, Dengue IgM capture ELISA (MAC-ELISA), Scrub typhus immunofluorescence (IFA), Leptospira Microscopic Agglutination Test (MAT), malaria PCR and malaria immunochromatographic rapid diagnostic test (RDT) Parahit Total™ were performed at the coordinating centre. Convalescence samples were not available. Case definitions were as follows: Leptospirosis: Positive ELISA and positive MAT. Scrub typhus: Positive ELISA and positive IFA. Dengue: Positive RDT and/or positive MAC-ELISA. Chikungunya: Positive ELISA. Bacteraemia: Growth in blood culture excluding those defined as contaminants. Malaria: Positive genus-specific PCR.Results: Malaria was diagnosed in 17% (268/1564) and among these 54% had P. falciparum. Dengue was diagnosed in 16% (244/1564). Bacteraemia was found in 8% (124/1564), and among these Salmonella typhi or S. paratyphi constituted 35%. Scrub typhus was diagnosed in 10%, leptospirosis in 7% and chikungunya in 6%. Fulfilling more than one case definition was common, most frequent in chikungunya where 26% (25/98) also had positive dengue test.Conclusions: Malaria and dengue were the most common causes of fever in this study. A high overlap between case definitions probably reflects high prevalence of prior infections, cross reactivity and subclinical infections, rather than high prevalence of coinfections. Low accuracy of routine diagnostic tests should be taken into consideration when approaching the patient with acute undifferentiated fever in India. [ABSTRACT FROM AUTHOR]

Introduction: Leptospirosis is a major public health problem in India. However, it has been underreported and under-diagnosed due to a lack of awareness of the disease, a functional surveillance system, and appropriate laboratory diagnostic facilities. Methodology: This multicenter study aimed to understand the Leptospira serovars causing leptospirosis in seven secondary-level hospitals in six states in India. Since early and accurate diagnosis of leptospirosis is one of the challenges faced by clinicians in India due to the poor specificity and sensitivity of commercially available diagnostic systems, an in-house indirect enzyme-linked immunosorbent assay (ELISA) was developed. Genomic DNA from L. interrogans serovar Canicola was used for polymerase chain reaction amplification, cloning, and expression of the lipL32 gene in E. coli to amplify, clone, and express the lipL32 gene. Results: Australis was the common serovar seen at all the study centers. Serovar Icterohaemorrhagiae was seen in samples from Tamil Nadu and Assam. In-house ELISA was standardized using the purified recombinant LipL32 polypeptide and was used to evaluate serum. Subsequently, acute serum samples from leptospirosis patients (n = 60) were screened. Compared to the gold standard, the microscopic agglutination test, sensitivity and specificity of the in-house ELISA was 95% and 90%, respectively. Conclusions: Understanding Leptospira serovars circulating in leptospirosis-endemic areas will help to formulate better vaccines. LipL32- based ELISA may serve as a valuable tool for early diagnosis of leptospirosis. [ABSTRACT FROM AUTHOR]

Background: Approximately one million malaria cases were reported in India in 2015, based on microscopy. This study aims to assess the malaria prevalence among hospitalised fever patients in India identified by PCR, and to evaluate the performance of routine diagnostic methods. Methods: During June 2011-December 2012, patients admitted with acute undifferentiated fever to seven secondary level community hospitals in Assam (Tezpur), Bihar (Raxaul), Chhattisgarh (Mungeli), Maharashtra (Ratnagiri), Andhra Pradesh (Anantapur) and Tamil Nadu (Oddanchatram and Ambur) were included. The malaria prevalence was assessed by polymerase chain reaction (PCR), routine microscopy, and a rapid diagnostic test (RDT) with PCR as a reference method. Results: The malaria prevalence by PCR was 19% (268/1412) ranging from 6% (Oddanchatram, South India) to 35% (Ratnagiri, West India). Among malaria positive patients P. falciparum single infection was detected in 46%, while 38% had P. vivax, 11% mixed infections with P. falciparum and P. vivax, and 5% P. malariae. Compared to PCR, microscopy had sensitivity of 29% and specificity of 98%, while the RDT had sensitivity of 24% and specificity of 99%. Conclusions: High malaria prevalence was identified by PCR in this cohort. Routine diagnostic methods had low sensitivity compared to PCR. The results suggest that malaria is underdiagnosed in rural India. However, low parasitaemia controlled by immunity may constitute a proportion of PCR positive cases, which calls for awareness of the fact that other pathogens could be responsible for the febrile disease in submicroscopic malaria. [ABSTRACT FROM AUTHOR]

Background: Short term efficacy of combination antiretroviral therapy (cART) in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings. Methodology/Principal Findings: A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression <100 copies/ml by their study baseline visit, were included and followed for two years. Blood samples were collected every six months for viral load and CD4 count. Drug resistance genotyping was performed when the viral load was >2000 copies/mL. Adherence and treatment interruptions (>48 h) were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs). Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations. Conclusion/Significance: Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines. [ABSTRACT FROM AUTHOR]

Context: Hand, foot, and mouth disease (HFMD) remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks. Aim: The aim of this study was to characterize HFMD-related isolates by molecular techniques. Settings and Design: Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC), Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot) were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease. Materials and Methods: Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD) cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE) in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR) and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST) algorithm. Statistical Analysis used: The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP). Results: Of the 30 suspected HFMD cases, only 17 (57%) were laboratory confirmed and Coxsackievirus A16 (CVA16) was identified as the etiological agent in all these cases. Conclusions: Coxsackievirus A16 (CVA16) was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the epidemiology of HFMD in India. [ABSTRACT FROM AUTHOR]

The article discusses the significance of reliable and valid adherence to study highly active antiretroviral therapy adherence in India. It indicates that consistent adherence to antiretroviral regimens is also important to evaluate the impact of adherence interventions. It notes that adherence must be brief and simple to administer in clinical settings in order to predict viral load.