Babu B.V.,Health Systems Research Division |
Babu G.R.,National Institute of Virology
Transactions of the Royal Society of Tropical Medicine and Hygiene | Year: 2014
India's mass drug administration (MDA) programme to eliminate lymphatic filariasis (PELF) covers all 250 endemic districts, but compliance with treatment is not adequate for the programme to succeed in eradicating this neglected tropical disease. The objective of our study was to systematically review published studies on the coverage of and compliance with MDA under the PELF in India. We searched several databases-PubMed/Medline, Google Scholar, CINAHL/EBSCO, Web of Knowledge (including Web of Science) and OVID-and by applying selection criteria identified a total of 36 papers to include in the review.Overall MDA coverage rates varied between 48.8% and 98.8%, while compliance rates ranged from 20.8% to 93.7%. The coverage-compliance gap is large in many MDA programmes. The effective level of compliance, ≥65%, was reported in only 10 of a total of 31 MDAs (5 of 20 MDAs in rural areas and 2 of 12 MDAs in urban areas). The review has identified a gap between coverage and compliance, and potentially correctable causes of this gap. These causes need to be addressed if the Indian programme is to advance towards elimination of lymphatic filariasis. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved.
Kumar S.,National Institute of Virology |
Arankalle V.A.,National Institute of Virology
PLoS ONE | Year: 2010
Background: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55-75% mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated. Methods and Findings: Efficacy of synthetic short interfering RNA (siRNA) or short hairpin RNA (shRNA) in protecting mice from CHPV infection was assessed. The target genes were P and M genes primarily because important role of the former in viral replication and lethal nature of the latter. Real time one step RT-PCR and plaque assay were used for the assessment of gene silencing. Using pAcGFP1N1-CHPV-P, we showed that P-2 siRNA was most efficient in reducing the expression of P gene in-vitro. Both quantitative assays documented 2logs reduction in the virus titer when P-2, M-5 or M-6 siRNAs were transfected 2hr post infection (PI). Use of these siRNAs in combination did not result in enhanced efficiency. P-2 siRNA was found to tolerate four mismatches in the center. As compared to five different shRNAs, P-2 siRNA was most effective in inhibiting CHPV replication. An extended survival was noted when mice infected intracranially with 100 LD 50 CHPV were treated with cationic lipid complexed 5 μg P-2 siRNA simultaneously. Infection with 10LD 50 and treatment with two doses of siRNA first, simultaneously and second 24 hr PI, resulted in 70% survival. Surviving mice showed 4logs less CHPV titers in brain without histopathological changes or antibody response. Gene expression profiles of P-2 siRNA treated mice showed no interferon response. First dose of siRNA at 2hr or 4hr PI with second dose at 24hr resulted in 40% and 20% survival respectively suggesting potential application in therapy. Conclusions: The results highlight therapeutic potential of siRNA in treating rapid and fatal Chandipura encephalitis. © 2010 Kumar, Arankalle.
Arora R.,National Institute of Virology |
Chitambar S.D.,National Institute of Virology
Infection, Genetics and Evolution | Year: 2011
Rotavirus G1P strains are the most predominant cause of rotavirus diarrhea, worldwide and are an important component of currently licensed RotaTeq and Rotarix vaccines. Despite a significant contribution of these strains in causing diarrhea in Indian children, none of them has been characterized completely, to date. This issue was addressed in the present study by sequencing and phylogenetic analysis of complete genomes of 3 Indian rotavirus strains (06361, 0613158 and 061060) of G1P specificity. Genotype of G1P I1R1C1M1A1N1T1E1H1 respectively, for the VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 genes was assigned to all of the three strains. The sequence analysis of structural and nonstructural genes indicated genetic relatedness (94-99.5%) with recently circulating strains and divergence (2.4-15.6%) with old prototype strains. Phylogenetic analysis revealed that new strains (Western Indian rotavirus strains and recently isolated strains - Dhaka16-03 (G1P), Dhaka25-02 (G12P), Matlab13-03 (G12P), B3458 (G9P), Matlab36-03 (G11P), and B4633-03 (G12P) and old prototype strains (KU and Wa) clustered in the same lineages of VP1, VP2, VP3, NSP2 and NSP4 genes however, grouped separately in VP6, NSP1 and NSP5 genes with 10-11%, 15.6-16.7% and 6.3-7.5% nucleotide sequence divergence, respectively. These results suggest that the rotavirus VP6, NSP1 and NSP5 genes of Wa-like rotaviruses are more prone to temporal mutations. Both structural and nonstructural genes of the Western Indian rotavirus strains shared nucleotide and amino acid substitutions with the Bangladeshi strain, Dhaka16-03 (G1P) in the year 2003. This study documents for the first time the phylogenetic and evolutionary relationships of Indian G1P rotavirus strains with the rotavirus strains from other parts of world and provides data useful for the evaluation of rotavirus vaccine programs. © 2011 Elsevier B.V.
Association of polymorphisms in the promoter regions of TNF-α (-308) with susceptibility to hepatitis e virus and TNF-α (-1031) and IFN-γ (+874) genes with clinical outcome of hepatitis e infection in India
Mishra N.,National Institute of Virology |
Arankalle V.A.,National Institute of Virology
Journal of Hepatology | Year: 2011
Background & Aims: Hepatitis E virus (HEV) is the predominant cause of acute viral hepatitis (AVH-E) and acute liver failure (ALF-E) among adults from developing countries. Pathogenesis of hepatitis E is poorly understood. Earlier, we showed association of elevated serum levels of TNF-α, IFN-γ, and IL-12 with ALF-E. The role of TNF-α and IFN-γ gene promoter polymorphisms with disease severity was investigated. Methods: The study population included 374 anti-HEV negative apparently healthy controls, 136 subclinical hepatitis E, 353 AVH-E, and 25 ALF-E patients. Polymorphisms at promoter regions of TNF-α-308G/A, TNF-α-1031T/C, and IFN-γ+874T/A were investigated employing allelic discrimination/ SNaPshot™ methods. Results: ALF-E patients were younger with significantly higher ALT levels when compared to other categories. Genotype TNF-α-308AA frequency was significantly higher among subclinical and clinical hepatitis E than the controls (p = 0.03, 0.0007). No significant difference was observed among AVH-E/ALF-E groups. The -308A allele was significantly higher in HEV-infected individuals; fatal ALF patients showed higher frequency than the recovered (p = 0.024). TNF-α-1031CC, IFN-γ+874TT, and IFN-γ+874TA genotypes were significantly associated with clinical disease. With respect to the controls, genotype +874TA was more frequent in subclinical infection (p = 0.005) while +874AA frequency was lower in the AVH-E category (p = 0.003). Conclusions: The data reveal association of TNF-α-308AA genotype with susceptibility to HEV and that of TNF-α-1031CC and IFN-γ+874TT and TA with clinical disease, irrespective of the outcome. Higher -308A allele frequency was associated with susceptibility to HEV and the fatal outcome of ALF-E. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Verma V.,National Institute of Virology |
Arankalle V.A.,National Institute of Virology
Journal of Applied Microbiology | Year: 2010
Aims: The prevalence of enteric viruses in drinking and river water samples collected from Pune, India was assessed. During an outbreak of HEV in a small town near pune, water samples were screened for enteric viruses. Methods and Results: The water samples were subjected to adsorption-elution-based virus concentration protocol followed by multiplex nested PCR. Among 64 Mutha river samples, 49 (76·56%) were positive for Hepatitis A Virus, 36 (56·25%) were positive for Rotavirus, 33 (51·56%) were positive for Enterovirus and 16 (25%) were positive for Hepatitis E Virus RNA. Only enterovirus RNA was detected in 2/662 (0·3%) drinking water samples, and the samples from the city's water reservoir tested negative for all four viruses. HEV RNA was detected in three out of four river water samples during HEV outbreak and partial sequences from patients and water sample were identical. Conclusions: The study suggests absence of enteric viruses both in the source and in the purified water samples from Pune city, not allowing evaluation of the purification system and documents high prevalence of enteric viruses in river water, posing threat to the community. Significance and Impact of the Study: The rapid, sensitive and relatively inexpensive protocol developed for virological evaluation of water seems extremely useful and should be adapted for evaluating viral contamination of water for human consumption. This will lead to development of adequate control measures thereby reducing disease burden because of enteric viruses. © 2009 The Society for Applied Microbiology.