Point mutations and multiple variants across the "a" determinant can destroy the antigenicity and immunogenicity of hepatitis B virus (HBV) leading to false negative assay and vaccine escape. In this study, the presence of surface gene variants of HBV was investigated among patients clinically diagnosed with chronic hepatitis B and positive for HBV DNA from 2002 to 2009. Sequence analysis of the surface gene of HBV showed that 23 (43%) of the 53 isolates had variations. Out of the 23 isolates, 15 (65%) exhibited single or multiple substitutions, which resulted to specific amino acid changes. The remaining 8 (35%) isolates had silent mutations. The amino acid substitution M133T which was associated with failure of HBsAg detection was found in one isolate (7%, 1/15), while the amino acid substitution D144A which was associated with vaccine escape was observed in one isolate (7%, 1/15). No G145R mutation was observed. Of the 15 isolates with identified single or multiple substitutions, 6 (40%) were found to have unique sequences which caused changes in the hydrophobicity profile in the protein. Unique sequence variants at amino acid positions M103I, L109P, S117R, F134I, and S136L found in this study have not yet been reported. These data should be taken into account when developing next generation HBV assays to detect both common and unique variants, and when new HBV vaccines will be designed.
The first shotgun genome sequence of a microbial pathogen from the Philippines is reported. Yersinia enterocolitica subsp. palearctica strain PhRBD_Ye1 is the first Y. enterocolitica strain sequenced from an animal source, swine, which is a natural source of yersiniosis. The closest phylogenetic match is a human clinical isolate from Germany.
Background: After five years of development and formal evaluation, the Health Protection Agency in England deployed a national web-based system for communicable disease control in January 2010. HPZone is now used in all 26 local health protection units covering 9 regions and the national centre for infections. Various challenges were encountered during the rollout and included standards, governance, workflows, integration with other software suites and IT infrastructure. Crucial to the deployment was winning the hearts and minds of users.Methods: HPZone was developed bottom-up with the users in mind from the start and began with the development of a structured risk assessment. The implementation included the collection of national contextual data sets, procedures for improved security of access, direct import of laboratory data and implementation of recent notification legislation, together with systems for enhanced software flexibility, server resilience and reliability. Nominated disease boards were tasked to populate workflow templates consisting of conditioned actions for cases (possible, probable, confirmed), enquiries and outbreaks.Results: HPZone was successfully deployed across 26 HPUs from December 2009 to March 2010. Laboratory data from across the country has been linked directly to HPZone. From January 2010 to mid-February 2012, 136,487 confirmed cases have been recorded (including Food poisoning: 102,031, Mumps: 20,166, Measles: 8,358), 13,112 outbreaks and 108,970 enquiries. 4,409 schools and 3,531 care homes have been affected. Lessons have been learned in respect of clinical and surveillance issues, integration with laboratory data and notifications, case and outbreak management, and enhanced IT infrastructure resilience and scalability. Coincidence and threshold alerts were implemented and facilities for automated notifications developed realising the enter-once-use-many paradigm.Conclusion: HPZone has enabled decision support without replacing professional judgment and provided improved detection, surveillance and control. It has facilitated transparency underpinning national resource allocation. HPZone has enabled targeted support and training, and provided opportunities to capture and share best practice. With a national award received in November 2011, HPZone has been recognised as an innovative web-based decision support system for harnessing infectious disease data, information and knowledge management and for improving service quality and public health outcomes.
Background: Hepatitis B virus (HBV) mutations conveying resistance to antivirals are a major health concern worldwide in the treatment of chronic hepatitis B infection. The availability of a sensitive assay that can detect emerging HBV antiviral resistance mutations is important for individualized monitoring of response to standard of care treatment. The risk of developing lamivudine (LAM) resistance is 14% to 70% after 1 to 5 years of treatment, which is sufficiently high to justify HBV antiviral resistance mutation testing. On the other hand, resistance to adefovir (ADV) is slow to emerge, ranging from 3% to 29% following 1 to 5 years of treatment. Mutation analysis helps in decision-making for clinical management of chronic HBV infection and molecular epidemiological studies as well. This study seeks to determine the presence of LAM and ADV resistance mutations among Filipino patients clinically diagnosed with chronic hepatitis B from July 2008 to December 2011.Methods: A total of fourteen samples were examined for the presence of antiviral resistance mutations using line probe assay, INNO-LiPA HBV DR v2. There were 9 (64%) males and 5 (36%) females with ages ranging from 17 to 69 years old.Results: Among the fourteen samples, 5 (36%) had wild-type, 4 (28%) had HBV mutant strain DNA not detected, and 5 (36%) had HBV DNA mutations. Out of the 5 HBV DNA mutant strains, one or 20% had one-drug resistance mutation detected (rtA181T for ADV). Three or 60% had 3-drug resistance mutations pattern detected. The first patient had rtG173L for LAM compensatory mutation, rtL180M for LAM, and rtM204V for LAM. The second patient had rtL80I for LAM compensatory mutation, rtL180M for LAM, and rtM204I for LAM, telbivudine (TBV). The third patient had L180L/A181T upcoming resistance for ADV, M204I upcoming resistance for LAM, emtricitabine, TBV, and N236T upcoming resistance for ADV. The remaining one or 20% had 4 drug-resistance mutations detected (rtA181T for ADV, rtL180M for LAM, rtM204V for LAM, and rtM204I for LAM, TBV).Conclusion: The most frequently encountered LAM-resistant mutant was rtM204V/I. Overall, the line probe assay provides a useful tool for the detection of lamivudine and adefovir resistance mutations among HBV-infected Filipino patients. http://dx.
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