Increasing hepatitis virus screening uptake at worksites in Japan using nudge theory and full subsidies.

BACKGROUND: Despite the importance of hepatitis screening for decreasing liver cancer mortality, screening rates remain low in Japan. Previous studies show that full subsidies increase screening uptake, but full subsidies are costly and difficult to implement in low-resource settings. Alternatively, applying nudge theory to the message design could increase screening at lower costs. This study examined the effects of both methods in increasing hepatitis virus screening rates at worksites. METHODS: 1496 employees from a Japanese transportation company received client reminders for an optional hepatitis virus screening before their general health checkups. Groups A and B received a client reminder designed based on the principles of "Easy" and "Attractive," while the control group received a client reminder not developed using nudge theory. Additionally, hepatitis virus screening was offered to the control group and group A for a co-payment of JPY 612, but was fully subsidized for group B. The hepatitis virus screening rates among the groups were compared using a Chi-square test with Bonferroni correction, and the risk ratios of group A and group B to the control group were also calculated. To adjust for unobservable heterogeneity per cluster, the regression analysis was performed using generalized linear mixed models. RESULTS: The screening rate was 21.2%, 37.1%, and 86.3% for the control group, group A, and group B, respectively. And the risk ratio for group A was 1.75 (95% confidence interval [CI] 1.45-2.12) and that of group B was 4.08 (95% CI 3.44-4.83). The parameters of group A and group B also were significant when estimated using generalized linear mixed models. However, the cost-effectiveness (incremental cost-effectiveness ratio (ICER)) of the nudge-based reminder with the full subsidies was lower than that of only the nudge-based reminder. CONCLUSIONS: While fully subsidized screening led to the highest hepatitis screening rates, modifying client reminders using nudge theory significantly increased hepatitis screening uptake at lower costs per person.

Quantitative assessment of serum NV-F virus DNA concentrations in samples from patients coinfected with hepatitis B or C virus.

A novel hepatotropic virus, named NV-F virus, was recently identified. The clinical information for this virus is still scarce. Using PCR assay, NV-F viral DNA (NV-F-DNA) was detected in 12 of 50 (24%) hepatitis C virus (HCV)-infected patients (HCV-coinfected [HCVCI] group), 34 of 250 (13.6%) hepatitis B virus (HBV)-infected patients (HBV-coinfected [HBVCI] group), and 28 of 100 (28%) non-A-to-E (NAE) hepatitis patients. Basic clinical parameters were not significantly different among the three groups. By use of a PCR-based quantitative assay, the NV-F-DNA concentration was found to be above the detection limit (1.2 x 10(5) copies/ml) in 12/12 (100%) HCVCI patients, 14/34 (41.2%) HBVCI patients, and 4/28 (14.3%) NAE patients. The median serum NV-F-DNA concentration was 9.3 x 10(5) copies/ml in HCVCI patients, but it was below the detection limit in HBVCI and NAE patients (P values were 0.0045 and 0.0001, respectively). Stepwise multiple regression analysis identified the presence of anti-HCV as an independent factor for NV-F-DNA concentrations (beta = 6.2 x 10(9); P = 0.0245). In HBVCI patients, the NV-F-DNA concentration was inversely correlated with the HBV DNA concentration. The median NV-F-DNA concentration was below the detection limit in patients with HBV DNA concentrations above 1.4 x 10(5) copies/ml, but it was 1.58 x 10(6) copies/ml in patients with HBV DNA concentrations below 1.4 x 10(5) copies/ml (P = 0.030). In conclusion, NV-F-DNA concentrations were higher in HCVCI patients. A reciprocal relationship was found between NV-F-DNA and HBV DNA concentrations in HBVCI patients, indicating the presence of viral interference between these two DNA viruses.

Limitations of TaqMan PCR for detecting divergent viral pathogens illustrated by hepatitis A, B, C, and E viruses and human immunodeficiency virus.

Recent events illustrate the imperative to rapidly and accurately detect and identify pathogens during disease outbreaks, whether they are natural or engineered. Particularly for our primary goal of detecting bioterrorist releases, detection techniques must be both species-wide (capable of detecting all known strains of a given species) and species specific. Due to classification restrictions on the publication of data for species that may pose a bioterror threat, we illustrate the challenges of finding such assays using five nonthreat organisms that are nevertheless of public health concern: human immunodeficiency virus (HIV) and four species of hepatitis viruses. Fluorogenic probe-based PCR assays (TaqMan; Perkin-Elmer Corp., Applied Biosystems, Foster City, Calif.) may be sensitive, fast methods for the identification of species in which the genome is conserved among strains, such as hepatitis A virus. For species such as HIV, however, the strains are highly divergent. We use computational methods to show that nine TaqMan primer and probe sequences, or signatures, are needed to ensure that all strains will be detected, but this is an unfeasible number, considering the cost of TaqMan probes. Strains of hepatitis B, C, and E viruses show intermediate divergence, so that two to three TaqMan signatures are required to detect all strains of each virus. We conclude that for species such as hepatitis A virus with high levels of sequence conservation among strains, signatures can be found computationally for detection by the TaqMan assay, which is a sensitive, rapid, and cost-effective method. However, for species such as HIV with substantial genetic divergence among strains, the TaqMan assay becomes unfeasible and alternative detection methods may be required. We compare the TaqMan assay with some of the alternative nucleic acid-based detection techniques of microarray, chip, and bead technologies in terms of sensitivity, speed, and cost.

Yield and future issues of nucleic acid testing.

Despite the much lower actual yield than that estimated for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) nucleic acid testing (NAT)-only positives in the USA and Germany, look-back procedures have revealed that no HCV transmission has occurred in Germany since the introduction of NAT. This indicates sufficient sensitivity of the pool-PCR approach. The slow ramp-up of hepatitis B virus (HBV) however, may require a different approach. It has been shown in Germany that the pooling of samples followed by virus enrichment results in a significant yield. Single donation testing for HBV would not increase the yield, because virus enrichment from mini-pool results in a similar sensitivity to that of single donation testing. Both strategies may be useful for extending future NAT to HBV screening. New candidate viruses for NAT are Parvo B19 and hepatitis A virus (HAV) because of their extreme resistance to inactivation procedures. Their low pathogenicity and epidemiologic characteristics, however, make them candidate viruses only for pooled source plasma. The main future issues of NAT will be related to the automation of pooling, extraction and amplification as a single homogeneous process. Depending on the throughput, automated single donation NAT as demonstrated by the 'Tigris' system may be an option, as far as all transfusion-relevant viruses will be included. In the near future high throughput systems will rely on pooled donor samples, most probably in conjunction with efficient enrichment procedures. For these systems, automation of the extraction and amplification process will be one of the first steps. These procedures will also limitthe costs of NAT and keep it available for use with future candidate viruses.