Evaluating the impact and cost-effectiveness of chlamydia management strategies in Hong Kong:A modeling study

OBJECTIVES: To illustrate the epidemiologic and cost-effectiveness impact of shifting the focus from population-based screening toward a targeted management approach for genital chlamydia infection. DESIGN: Modeling study, implementing an individual-based, stochastic, dynamic network model. SETTING: Hong Kong. POPULATION: A hypothetical sample network of 10,000 people with a partnership distribution based on Hong Kong's sexually active population of reproductive age (age 18–49 years). INTERVENTIONS: In this study, we present several scenarios with different implementations of universal vs. targeted screening (based on partner numbers). We also explored the impact of (1) screening only, (2) screening plus expedited partner therapy, and (3) screening plus partner testing. PRIMARY OUTCOME MEASURES: Change of chlamydia prevalence before and after implementing the different strategies. The cost-effectiveness analysis reports total direct cost from a health provider perspective, the QALYs gained, and incremental cost-effectiveness ratios (ICER). RESULTS: In comparing the effects of universal screening only and targeted screening of the high-risk population, the mean prevalence during the 10th year of intervention was 2.75 ± 0.30% and 2.35 ± 0.21%, respectively (compared with 3.24 ± 0.30% and 3.35 ± 0.21% before the interventions, respectively). The addition of contact tracing to the latter targeted screening scenario reduces the mean prevalence during the 10th year of intervention to 1.48 ± 0.13% (compared with 3.31 ± 0.33% at baseline) in the best-case of testing before treatment and maximal contact-tracing effectiveness (40%). Overall, the most effective scenarios were those for which interventions focused on the high-risk population defined by the number of partners, with contact tracing included. The ICER for targeted screening with contact tracing at 20% and 40% efficiency was $4,634 and$7,219 per QALY gained, respectively (10-year time horizon). Expedited partner therapy did not significantly impact overall chlamydia prevalence and caused overtreatment. CONCLUSIONS: Our study suggests that targeted screening with strengthened contact tracing efforts is the most cost-effective strategy to reduce the prevalence of chlamydia in Hong Kong

A tunable dual-input system for on-demand dynamic gene expression regulation

Cellular systems have evolved numerous mechanisms to adapt to environmental stimuli, underpinned by dynamic patterns of gene expression. In addition to gene transcription regulation, modulation of protein levels, dynamics and localization are essential checkpoints governing cell functions. The introduction of inducible promoters has allowed gene expression control using orthogonal molecules, facilitating its rapid and reversible manipulation to study gene function. However, differing protein stabilities hinder the generation of protein temporal profiles seen in vivo. Here, we improve the Tet-On system integrating conditional destabilising elements at the post-translational level and permitting simultaneous control of gene expression and protein stability. We show, in mammalian cells, that adding protein stability control allows faster response times, fully tunable and enhanced dynamic range, and improved in silico feedback control of gene expression. Finally, we highlight the effectiveness of our dual-input system to modulate levels of signalling pathway components in mouse Embryonic Stem Cells