The prevalence of antibody to hepatitis C virus (HCV) was estimated in 3 tropical populations using 2 screening ELISAs to detect antibody to the c100-3 antigen and 2 supplementary assays designed to test the specificity of these tests. Two hundred and eighty-six of 385 (74.2%) sera from Kiribati, 17 of 138 (12.3%) sera from Vanuatu, and 39 of 173 (22.5%) sera from Zaire were reactive in the initial screening assay. The proportion of reactive sera which were also reactive in the second screening ELISA varied between populations (55.1% in Kiribati, 85.1% in Vanuatu, and 39.2% from Zaire). Reactive sera were selected at random for confirmatory testing. Only 3 of 49 (6.12%) of sera from Kiribati and 1 of 14 (4.76%) of sera from Vanuatu positive in the initial ELISA were reactive in the confirmatory assays. The proportion of confirmed positive sera from Zaire was higher 8 of 28 (28.5%). Based on the results of these supplementary assays the estimated prevalence of anti-HCV in these populations is 4.8% in Kiribati, less than 1% in Vanuatu, and 6.4% in Zaire. Reliance on a single screening ELISA to estimate the prevalence of anti-HCV in stored sera from tropical communities may lead to a gross over-estimate of the true prevalence in these populations.
We report the development of three rapid, fully automated immunoassays allowing the differential diagnosis of acute viral hepatitis. These assays detect HBsAg, IgM antibody to hepatitis B core antigen (IgM anti-HBc) and IgM antibody to hepatitis A virus (IgM anti-HAV) using the IMx instrument system. All IMx assays were run in less than 45 minutes and all steps were fully automated including specimen dilution steps. Specimens from blood donors, diagnostic and hospital patients, and individuals with a variety of infectious and immune diseases were tested for IgM anti-HAV (n = 1473) or for IgM anti-HBc (n = 1606) or for HBsAg (n = 9700) by the IMx and commercially available EIA and RIA. Each IMx assay showed 99.8% agreement with current EIA. Reproducibility in all hepatitis IMx assays was significantly better than that observed with manual or semiautomated assays; within-run and between-run % CV ranged from 2.2 to 4.8 and 3.5 to 10.3 respectively. In 29 acute hepatitis B patients studied, HBsAg and IgM anti-HBc were detected in the first available patient bleed collected from 0 to 4 week from the onset of symptoms. IgM anti-HBc persisted at reactive levels in the IMx assay for 1 to 24 weeks (mean 12.1 +/- 5.3 weeks) after the patient presented with symptoms. In individuals exposed to hepatitis A, IgM anti-HAV was detectable by IMx by 40 days post exposure (average 33.5 days) and IgM had declined to unreactive levels in IMx for all patients by from 3 to 6 months post exposure. These data demonstrate the use of these rapid IMx assays for differentiation of acute hepatitis A and B.
Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures.
FDA has been regulating diagnostic tests (including biomarkers) since passage of the Medical Device Amendments of 1976. Although always of interest as diagnostic tools, biomarkers (particularly genetic/genomic) have become of increased interest because of their potential impact on the development and personalized use of drugs. Unfortunately, there seem to be uncertainties among translational researchers as to the specifi c analytical and clinical measurement criteria needed for the approval of these novel biomarkers. This meeting presentation describes the current FDA perspective and major requirements and data for the validation/approval of an in vitro diagnostic device (IVD) based on a biomarker. The approval process for an IVD based on a biomarker used in the identifi cation of a disease or condition (diagnosing, screening, monitoring) is well established, and is essentially identical to the process to generate suffi cient analytical and clinical data for the approval of regular diagnostic devices. On the contrary, approvals for IVDs based on biomarker which may be designed to evaluate the effi cacy or answer safety questions for new drug entities are less streamlined. The clinical studies are more complex, resulting in higher ethical standards, increased costs and requiring complex statistical evaluation. There is a small but growing literature on new models for co-development of drugs and diagnostics which will be discussed. Regulators like the FDA develop and bring a fl exible regulatory toolbox to the table and are committed to assuring that scientifi c and regulatory thresholds are tempered to assure rapid access to new technologies while protecting public health.
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