Fatal familial insomnia is a prion disease with a mutation in codon 178 of the PrP gene, but the disease phenotype seems to differ from that of previously described kindreds with the same point mutation.

An enzyme-linked immunosorbent assay (ELISA) and a rapid immunochromatographic test for detection of immunoglobulin G (IgG) antibodies in severe acute respiratory syndrome (SARS) patients were developed by utilizing the well-characterized recombinant proteins Gst-N and Gst-U274. The ELISA detected IgG antibodies to SARS-CoV in all 74 convalescent-phase samples from SARS patients while weakly cross-reacting to only 1 of the 210 control sera from healthy donors. This finding thus led to a kit sensitivity, specificity, and accuracy of 100, 99.5, and 99.6%, respectively. The test thus provided a positive predictive value (PPV) of 98.7% and a negative predictive value (NPV) of 100%. In addition, the ELISA gave a positive delta of 5.4 and a negative delta of 3.6, indicating an excellent differentiation between positives and negatives. The same recombinant proteins were also applied to a newly developed platform for the development of a 15-min rapid test. The resulting rapid test has an excellent agreement of 99.6%, with a kappa value of 1.00, with the ELISA. Again, this rapid test was able to detect 100% of the samples tested (n ‫؍‬ 42) while maintaining a specificity of 99.0% (n ‫؍‬ 210). The PPV and NPV for the rapid test thus reached 95.3 and 100%, respectively.

A new double-antigen sandwich-based enzyme-linked immunosorbent assay (ELISA) for the detection of total antibodies (immunoglobulin G [IgG] and IgM) specific for hepatitis E virus (HEV) was developed by utilizing well-characterized recombinant protein ET2.1 and its peroxidase-labeled counterpart. Our study showed that the ELISA detected all the positive patient samples (n ‫؍‬ 265) regardless of whether they contained IgM or IgG antibodies, or both, while it maintained an excellent specificity of 98.8% with samples from various patient or healthy control groups (total number of samples, 424). The test had a detection limit for anti-HEV IgG antibodies that was equivalent to 62 mIU/ml of the international reference. Compared with the serological status of the specimens determined on the basis of tests performed at the individual collection sites, the testing outcome generated by the new ELISA had a good agreement of 99.3%, with a kappa value of 0.985. The positive predictive value and the negative predictive value for the new test reached 98.1% and 100%, respectively. This ELISA had a positive delta value of 4.836 and a negative delta value of 3.314 (where delta is a measure of the number of standard deviations by which the cutoff is separated from the mean of the sample groups) (N. Crofts, W. Maskill, and I. D. Gust, J. Virol. Methods 22:51-59, 1988), indicating that it had an excellent ability to differentiate the infected and noninfected cohorts. Furthermore, the new design enables the detection of antibodies not only in human samples but also in pig samples. Our preliminary data showed that the ELISA could detect seroconversion in samples from pigs at as early as 14 days postinoculation. The potential utility of detecting specific antibodies in pigs will be an added advantage for managing the disease, with suggested zoonotic implications.

An immunochromatographic test for rapid detection of IgM antibodies in patients with acute hepatitis E infection was developed utilizing the well-characterized recombinant protein EP2.1 and monoclonal antibody 4B2. The new rapid test based on a novel reverse-flow technology was able to generate a positive result within 2 to 3 min. Our study showed that this test was able to detect anti-HEV IgM antibodies in 96.7% of the patient samples tested (n ‫؍‬ 151) while maintaining an excellent specificity of 98.6% with samples from various patient or healthy control groups (total n ‫؍‬ 208). Furthermore, this rapid test gave a good specificity of 90.9% when tested with rheumatoid factor (RF)-positive sera (RF value of <850 IU/ml; n ‫؍‬ 11) although a higher concentration of RF in samples might cause cross-reactivity. The new test has a good agreement of 97.2% with a kappa value of 0.943 when compared with a reference enzyme-linked immunosorbent assay. The positive predictive value and the negative predictive value for the rapid test thus reached 98.0 and 97.6%, respectively. This is the first rapid, point-of-care test for hepatitis E and will be especially useful for the diagnosis of acute hepatitis E virus infection in field and emergency settings and in resource-poor countries.Hepatitis E is known as enterically transmitted non-A non-B hepatitis, and the etiological agent for this disease has been well established as an nonenveloped, positive-sense, singlestranded RNA virus named hepatitis E virus (HEV) (16,18,9). Although the disease is a self-limited one with a mortality rate of 1 to 3% in general adult populations, hepatitis E infection in pregnant women can take more severe forms, with a case fatality rate up to 20%, especially during the third trimester (10). Because the causative HEV is excreted in the feces of infected individuals, contaminated water and food supplies can provoke major outbreaks and are assumed to be the primary source for infections. It is therefore not surprising that epidemics of this waterborne hepatitis have occurred frequently in Central and South Asia, North and West Africa, the Middle East, and Mexico, in geographic areas where fecal contamination of drinking water is common. However, increasing evidence suggests that sporadic infections have occurred in areas where traditionally the disease is nonendemic, including the Untied States, Japan, and Europe, and thus the disease might be more widespread than previously recognized (3). Furthermore, existing studies showed that the prevalence of immunoglobulin G (IgG) antibodies to HEV were much lower than expected in areas of endemicity but higher than anticipated in regions where the disease is nonendemic (4). Many individuals are therefore susceptible to the infection. In this respect, hepatitis E is increasingly an important public health concern of global significance (20).The recent outbreaks of HEV in Chad and Sudan provide a reminder of this concern (http://www.who.int/csr/don/2004_09 _28/en/print.html and http://www.who.int/csr/don/200...