An overview of molecular epidemiology of hepatitis B virus (HBV) in India

Hepatitis B virus (HBV) is one of the major global public health problems. In India, HBsAg prevalence among general population ranges from 2% to 8%, placing India in intermediate HBV endemicity zone and the number of HBV carriers is estimated to be 50 million, forming the second largest global pool of chronic HBV infections. India is a vast country, comprised of multiracial communities with wide variations in ethnicity and cultural patterns, which is attributable to its geographical location, gene influx due to invasion and/or anthropological migrations in the past. Moreover, recent increase in trade, trafficking and use of illicit drugs has also considerably influenced the epidemiology of HBV, specifically in the eastern and north eastern parts of India. However, data on the molecular epidemiology of HBV in India is scanty. HBV genotypes A and D have been well documented from different parts of mainland India. Interestingly, in addition to genotypes A and D, genotype C having high nucleotide similarity with south East Asian subgenotype Cs/C1 strain, have been detected exclusively from eastern Indian HBV carriers, suggesting a recent introduction. Thus, compared to other parts of India, the molecular epidemiology of HBV is naturally distinct in eastern India. Very recently, taking the advantage of circulation of three distinct HBV genotypes within the population of eastern India, different aspects of HBV molecular epidemiology was studied that revealed very interesting results. In this study, the clinical significance of HBV genotypes, core promoter and precore mutations, possible routes of introduction of HBV genotype C in eastern India, the clinical implications of x gene variability, prevalence of the AFB1 induced p53 gene codon 249 mutation, the transmission potentiality of HBV among asymptomatic/inactive or occult HBV carriers and the genetic variability of HBV persisting in the PBL was investigated. In this manuscript, the information available on the molecular epidemiology of HBV in India has been reviewed and the results of studies among the eastern Indian population have been summarised

Microbiological Research and Applied Sciences in the North Eastern Region of India

The northeastern part of India (NE India) is an important biodiversity hotspots and is blessed with a huge diversity of flora and fauna along with other natural resources. Being quite distinct in natural features from rest of the country, NE India has its own unique challenges and opportunities. This part of India is geographically isolated from China by Eastern Himalayas, while tropical forests separate this region from Myanmar and Bangladesh. The armed forces deployed in the NE region have to operate in a wide variety of environments ranging from high altitudes, to tropical rain forests, which pose several operational challenges

Agroterrorism in Indian Context

In the context of change in global scenario of terrorism and economic competition, the risk of deliberate attack on agriculture is increasing. In a country, like India, whose economy is largely dependent on agriculture produce and exports, any such malicious attack can grossly destabilise the socio-economic structure. Additionally, an attack on major food crops can lead to potential threat to food security, subsequently, leading to destabilised law and order situation of a state. It is therefore very important to understand the risks and threats of agroterrorism for a given country in order to be prepared for any such circumstance. In this review we discuss different aspects of agroterrorism, its history, possibilities of such incidences in Indian scenario and mitigation strategies, which can be achieved through regular surveillance of pathogens in vulnerable crop ecosystems. We also describe a recent episode of outbreak of cotton leaf curl disease in the Northwest Indian cotton growing region and discuss it from the perspective of a possible threat on one of the most important economic crops of our country

Study on Air Bacteria at Different Altitudinal Locations in Tezpur to Tawang Axis

Microflora plays an important role in modulating environmental quality. Among microflora, bacteria are omnipresent in the environment. Pathogenic bacteria, present in air, are known to affect significantly the health and well-being of human, animal or plant populations. Air bacteria monitoring is thus essential for surveillance of pathogenic microorganisms from public health perspective besides its significant implications in detection and mitigation of biothreat related issues. Despite the geo-politically strategic importance of northeast India, there is scarcity of data on human health and disease surveillance. Considering these facts, we, for the first time studied the bacterial diversity of air at six important sites adjacent to the international border in the northeast region of India, having an altitude range of 73 m (Tezpur) to 4170 m (Sela Pass) above sea level. Standard microbiological techniques, such as Tryptone Soya Agar, Mannitol salt and McConkey agar strips and plates were used for air bacterial load assessment and culture for subsequent analysis using biochemical and molecular techniques. Following RFLP study, twenty six different bacterial colonies were isolated. Subsequently, bacteria identification was carried out by examining the substrate utilisation patterns, sequencing 16S rRNA gene and phylogenetic analysis. Results of the study reveal that the isolates mostly belong to two genera Bacillus and Staphylococcus (eleven in each genus), along with Micrococcus, Pseduomonas and Acinetobacter. Based on significant match of our sequences with that of medically important bacterial 16S rRNA sequences available at 16SpathDB 2.0 and review of available literature, we found that a number of these bacterial species have the pathogenic potential. In this manuscript we report our results and discuss the importance of air bacterial surveillance from the perspective of human health, hygiene and biothreat mitigation

Potential Application of Bacteriophage in Decontaminating Biothreat Agents

Multidrug resistant bacterial infections have become a potent risk, globally and there is an urgent need to phage and phage-derived enzymes as a therapeutic agent. The risk is more prominent in underdeveloped nations, where high population density, poor drinking water, inadequate sanitary and health care facilities ease the spread of infection. Bacteriophages (or ‘phages’) are abundant in nature and highly specific in their infection and pathogenicity, allowing their isolation, enrichment and use against specific bacteria. Employing bacteriophages as a tool for neutralizing potential biological threat agents can thus be an effective approach towards preparedness for biothreat mitigation. Unlike chemical antibiotics, phages are self-propagating, i.e., starting with a small number they can sustain their population, do not affect non-target/ beneficial bacterial populations. The tremendous potential of bacteriophages has recently been shown in treating multidrug resistant bacterial infections in terminally ill human subjects with unprecedented success. The natural anti-bacterial properties can be harnessed for decontamination of food, water, crops and for many other purposes including pathogen reduction in wastewater etc. Additionally, with the advancement in genetic engineering, deliberate use of such engineered multidrug resistant bacteria by state/non-state players has also become a reality. Owing to their resistance to several of the available antibiotics, control and mitigation of emerging pathogens is going to be great challenge. In this context, bacteriophages could be of potential use, since these viruses specifically infect bacterial hosts, often leading to their destruction

Drug Trafficking Routes and Hepatitis B in Injection Drug Users, Manipur, India

Prevalence of hepatitis B genotype C in injection drug users in the northeastern Indian state of Manipur, neighboring the "Golden Triangle," correlates well with overland drug-trafficking routes, the injection drug use epidemic, and the spread of HIV. Further spread to other regions of India through mobile populations is possible

Distribution of hepatitis B virus genotypes: Phylogenetic analysis and virological characteristics of Genotype C circulating among HBV carriers in Kolkata, Eastern India

Aim: To evaluate the genotype distribution of hepatitis B virus (HBV) in Eastern India and to clarify the phylogenetic origin and virological characteristics of the recently identified genotype C in this region. Methods: Genotype determination, T1762/A1764 mutation in the basal core promoter (BCP) and A1896 mutation in the precore region of 230 subjects were determined by restriction fragment length polymorphism method (RFLP) and the result was confirmed by direct sequencing. Results: The predominant genotypes D (HBV/D) and A (HBV/A) were detected in 131/230 (57%) and 57/230 (25%) samples. In addition, genotype C (HBV/C) was detected in 42/230 (18%) isolates. Surface gene region was sequenced from 45 isolates (27 HBV/C, 9 HBV/A and 9 HBV/D). Phylogenetic analysis revealed that all of the HBV/C sequences clustered with South East Asian subgenotype (HBV/Cs). The sequence data showed remarkable similarity with a Thai strain (AF068756) (99.5% ± 0.4% nucleotide identities) in 90% of the genotype C strains analyzed. T1762/A1764 mutation in BCP region, associated with high ALT was significantly higher in HBeAg negative isolates than HBeAg positive isolates. Frequency of A1896 mutation leading to HBeAg negativity was low. Conclusion: The present study reports the genotypic distribution and the characteristics of partial genome sequences of HBV/C isolates from Eastern India. Low genetic diversity and confinement of HBV/C in Eastern India possibly indicate a recent, limited, spread in this region. Genotype C with T1762/A1764 mutation has been reported to increase the risk for hepatocellular carcinoma; therefore genotype C carriers in Eastern India should be carefully monitored

Anti-hepatitis B core antigen testing with detection and characterization of occult hepatitis B virus by an in-house nucleic acid testing among blood donors in Behrampur, Ganjam, Orissa in southeastern India: implications for transfusion

<p>Abstract</p> <p>Background</p> <p>Occult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India.</p> <p>Methods</p> <p>A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing.</p> <p>Results</p> <p>A total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples.</p> <p>Conclusion</p> <p>Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.</p

Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in Huh-7 cells with a defective Jak-Stat pathway

<p>Abstract</p> <p>Background</p> <p>The sustained virological response to interferon-alpha (IFN-α) in individuals infected with hepatitis C virus (HCV) genotype 1 is only 50%, but is about 80% in patients infected with genotype 2-6 viruses. The molecular mechanisms explaining the differences in IFN-α responsiveness between HCV 1 and other genotypes have not been elucidated.</p> <p>Results</p> <p>Virus and host cellular factors contributing to IFN responsiveness were analyzed using a green fluorescence protein (GFP) based replication system of HCV 2a and Huh-7 cell clones that either possesses or lack a functional Jak-Stat pathway. The GFP gene was inserted into the C-terminal non-structural protein 5A of HCV 2a full-length and sub-genomic clones. Both HCV clones replicated to a high level in Huh-7 cells and could be visualized by either fluorescence microscopy or flow cytometric analysis. Huh-7 cells transfected with the GFP tagged HCV 2a genome produced infectious virus particles and the replication of fluorescence virus particles was demonstrated in naïve Huh-7.5 cells after infection. IFN-α effectively inhibited the replication of full-length as well as sub-genomic HCV 2a clones in Huh-7 cells with a functional Jak-Stat pathway. However, the antiviral effect of IFN-α against HCV 2a virus was not observed in Huh-7 cell clones with a defect in Jak-Stat signaling. HCV infection or replication did not alter IFN-α induced Stat phosphorylation or ISRE promoter-luciferase activity in both the sensitive and resistant Huh-7 cell clones.</p> <p>Conclusions</p> <p>The cellular Jak-Stat pathway is critical for a successful IFN-α antiviral response against HCV 2a. HCV infection or replication did not alter signaling by the Jak-Stat pathway. GFP labeled JFH1 2a replicon based stable cell lines with IFN sensitive and IFN resistant phenotypes can be used to develop new strategies to overcome IFN-resistance against hepatitis C.</p