Wilder-Smith, A. | Search bioRxiv

bioRxiv2018

Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure

The tetravalent dengue vaccine CYD-TDV (Dengvaxia(R)) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 30-year timeframe. Under a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on the sensitivity of serological screening in high-transmission settings and on a combination of sensitivity and specificity in low-transmission settings. Reducing risk from an individual perspective required high specificity, no less than 0.8. Cost-effectiveness could be achievable from the perspective of a public payer provided that screening sensitivity for prior DENV exposure and the value of a disability-adjusted life-year were both high. Cost-effectiveness was also achievable from an individual perspective, particularly with high screening specificity and low coverage. Whereas the results of this analysis offer general guidelines about CYD-TDV vaccination, decisions in specific contexts would benefit from additional, more context-specific modeling analyses. In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in certain epidemiological settings, provided that screening is highly specific, at least moderately sensitive, and inexpensive.

epidemiology↗

bioRxiv2018

Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis

Background Zika virus (ZIKV) emerged in Latin America & the Caribbean (LAC) region in 2013, and has had serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and a lack of a comprehensive collation of data from affected countries.\n\nMethods Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 91 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vector capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.\n\nResults There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p<0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.\n\nConclusions The findings suggest that the ZIKV epidemic is by and large over, with incidence projected to be low in most cities in LAC in 2018. Local low levels of transmission are probable but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

epidemiology↗