investments to support countries with greatest burden of viral hepatitis All heavily burdened countries to have fully funded elimination plans by 2019 Recognition of need to focus on high burden countries and support for national policy development (All) Funding for national elimination plans Creation of fiscal space for new programmes with costed investment programmes Adopt domestic innovative finance tools where appropriate Support national policy makers in their activity (WHO, UNITAID, NGOs) Provide international support for financing measures (UNITAID, GFATM, bilaterial donors) Prevention Ensure all WHO elimination targets addressed in plans Address operational challenges in delivery of birth dose HBV vaccine Ensure provision of harm reduction services and engage with marginalised group (e.g. prisoners, PWIDs). Ensure clear public health messages to encourage testing and treatment Support countries to decriminalise injecting drug use and ensure equitable access to services for all (NGOs, WHO, civil society) Ensure appropriate funding for HBV vaccine, including birth dose (GAVI, WHO) Support R&D into HCV vaccine development (Research funders and pharma) Testing and Models of Care Focus on substantially scaling up testing for HBV and HCV Create and evaluate simplified care pathways relevant to local setting, integrating with existing services. Promote task sharing and decentralisation of care through capacity building, training and removal of Support operational research into simplified pathways (Research funders, UNITAID) requirements for specialised prescribing Diagnostics Ensure testing is integrated into the wider healthcare system, rather than centralised facilties Ensure access to quality diagnostics through Essential Diagnostic List and prequalification (WHO, funders) Support implementation science for models of care and R&D into novel diagnostics suitable for decentralised settings. (Research funders, FIND, industry) Access to treatment Ensure all Essential Medicines for viral hepatitis are included in national programmes, with an emphasis on pan-genotypic regimens Apply comprehensive policy approach to promoting access, including compulsory licensing Ensure all essential medicines are pre-qualified and either available through voluntary licensing or Medicines Patent Pool (WHO, NGOs, civil society, funders) Support shared procurement mechanisms for treatment (PAHO) Monitor Progress National plans need clearly defined, measurable objectives Develop new indices of national progress Progress of individual countries needs to be closely monitored towards elimination goals (Polaris, WHO, Creation of Elimination Index) Develop greater capacity for advocacy in high burden regions (all) Viral hepatitis is one of the leading causes of death in the world. 96% of those deaths are due to hepatitis B and C, which are the focus of this commission. Unlike many other major diseases, the tools exist to eliminate viral hepatitis. A highly effective vaccine is available to prevent hepatitis B, and a revolution in HCV treat...
We are researchers who have published analyses of nucleic acid sequence variation of hepatitis C virus (HCV) and associated virological and clinical significance. We are concerned that our investigations are hampered by the lack of a consensus nomenclature for variants of HCV and that this leads to confusion when results from different laboratories are compared. Furthermore, because there are no consistently applied criteria by which new genotypes are defined, investigators assign new type descriptions to novel sequence variants on an ad hoc basis without agreement from
CD1 molecules are specialized in presenting lipids to T lymphocytes, but identification and isolation of CD1-restricted lipidspecific T cells has been hampered by the lack of reliable and sensitive techniques. We here report the construction of CD1d-glycolipid tetramers from fully denatured human CD1d molecules by using the technique of oxidative refolding chromatography. We demonstrate that chaperone-and foldase-assisted refolding of denatured CD1d molecules and 2-microglobulin in the presence of synthetic lipids is a rapid method for the generation of functional and specific CD1d tetramers, which unlike previously published protocols ensures isolation of CD1d tetramers loaded with a single lipid species. The use of human CD1d-␣-galactosylceramide tetramers for ex vivo staining of peripheral blood lymphocytes and intrahepatic T cells from patients with viral liver cirrhosis allowed for the first time simultaneous analysis of frequency and specificity of natural killer T cells in human clinical samples. Application of this protocol to other members of the CD1 family will provide powerful tools to investigate lipid-specific T cell immune responses in health and in disease.
Oral fluid testing is an effective alternative to serum antibody testing for surveillance of human immunodeficiency virus (HIV) and hepatitis B infections, and is being extended to hepatitis C infections. The objective of this study was to determine and compare the sensitivity and specificity of a modified commercial assay for the detection of antibody to hepatitis C virus (anti-HCV) in oral fluids collected by two different oral fluid collection devices (the Epitope OraSure trade mark and Sarstedt Salivette ) and in dried fingerprick blood spots. In this study, 253 anti-HCV seropositive patients and 394 blood donors (all anti-HCV negative) were recruited between August 2000 and January 2001. Each participant provided oral fluid specimens by OraSure and Salivette, and at least one dried blood spot. Serum specimens were collected from the patients whenever possible. For those injecting drug users who did not provide a serum specimen, HCV status was established on the basis of previous testing. All the nonserum samples were tested for the presence of anti-HCV, using a modified Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) protocol. The recommended preliminary cutoffs for the modified ELISA were suboptimal. Further, the sensitivity, specificity, and positive and negative predictive values could be improved by varying the cutoff and taking into account the likely prevalence of HCV in the population under investigation. For instance, given a population with a 50% prevalence of anti-HCV, the optimal sensitivities of the modified assay on OraSure, Salivette, and dried blood spots were 92%, 83%, and virtually 100%, respectively, in contrast to 83%, 59%, and 99% using the preliminary cutoffs. The respective optimal specificities were 99%, 93%, and 100%. In conclusion, oral fluids collected by the OraSure device provide an extremely useful method to conduct public health surveillance of not only HIV, but also hepatitis C, among injecting drug users. In addition, dried blood spot specimens may be useful for surveillance and could be employed as a first line diagnostic specimen.
Graphical abstract AuthorsHighlights Unusual genotypes (G1 non 1a/1b or G4 non 4a/4d) were common in African patients.11 previously unclassified HCV subtypes were represented including novel G1p.Patients with unusual G1 subtypes had a lower SVR rate than any other genotype.Failures were driven by patients treated with a first generation NS5A inhibitor.Background & Aims: HCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients. Methods:We identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen nextgeneration sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences. Results: Of 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%). Conclusions: Most individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination. Lay summary: Direct-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these geno-types. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b.
Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, V␣24/V11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls. Unlike V␣24/V11 NKT cells found in blood, those in the liver appeared to be recently activated.
First-line TDF is the most cost-effective treatment for patients with CHB at a £ 20,000 to £ 30,000/QALY ceiling ratio, costing £ 19,084/QALY gained compared with the next best alternative.
Hepatitis C virus (HCV) genotype 1a and 3a partial NS5B gene segment sequences obtained from 154 HCV-infected injection drug users were studied to determine the extent to which HCV transmission occurs between injection drug user communities in London, Edinburgh, Glasgow (United Kingdom), Marseilles (France), and Melbourne. Phylogenetic relationships between sequences were analyzed by conventional methods and by a recently developed method that numerically scores the extent of sequence segregation between groups through calculation of association indices. The association indices revealed that none of the cities sampled support an HCV population that is completely isolated from that circulating in the other cities. Sequences from Melbourne were most isolated, whereas those from London were most dispersed. This suggests that HCV transmission between these cities occurs, with London playing a pivotal role. The degree of city-specific segregation of HCV subtype 1a sequences was linearly related to that of subtype 3a, indicating that these subtypes have spread through similar transmission networks.
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