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

Abstract

The tetravalent dengue vaccine CYD-TDV (Dengvaxia®) 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. We used an agent-based model to simulate DENV transmission over a 30-year timeframe, with and without vaccination. We considered 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. We evaluated the cost-effectiveness of screening and vaccination under economic scenarios 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. Costeffectiveness 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. 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.. CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/367060 doi: bioRxiv preprint first posted online Jul. 11, 2018; 2 INTRODUCTION A safe and effective dengue vaccine could have a major public health impact, as dengue causes approximately 9,000 deaths and between 50-100 million clinically apparent cases worldwide every year [1,2], with increasing geographic distribution [3]. The first licensed dengue vaccine, CYD-TDV (Dengvaxia®), is a tetravalent, live-attenuated vaccine that was licensed in multiple countries after demonstrating efficacy against symptomatic disease in phase-III trials [4,5]. Protection has been hypothesized to derive primarily from the vaccine functioning as a "silent infection" [6]. Following their first natural infection subsequent to vaccination, this mechanism would result in vaccinees with prior dengue v...

IgG Antibody Responses to the Aedes albopictus 34k2 Salivary Protein as Novel Candidate Marker of Human Exposure to the Tiger Mosquito

“…Importantly, there are currently no specific anti-viral drugs to treat these diseases. A dengue vaccine has been approved by FDA in 2019 but its use appears to have some limitations (CDC, 2019 ; Espana et al, 2019 ), and despite the availability of a safe and effective vaccine for yellow fever, the disease is still endemic in Africa and in Central-South America (WHO, 2019 ). In this scenario, vector monitoring and control, along with the prevention of human-mosquito contact, still represent the main methods to contain the transmission of these arboviral diseases.…”

Hidden heterogeneity and its influence on dengue vaccination impact

“…(2017) H Proportion of time spent in community of residence (travel, no travel) 0.975, 1 Assumed β h Transmission coefficient (travel, no travel) 0.253, 0.245 Calibrated β l Transmission coefficient (travel, no travel) 0.127, 0.175 Calibrated Average intervention coverage across communities h and l 0.5 Assumed Intervention coverage in community c 0–1 Varied Sensitivity of pre-vaccination screening 0.95 España et al. (2019) Specificity of pre-vaccination screening 0.85 España et al. (2019) γ Rate of recovery from infection 0.25 Meltzer et al.…”

“…The background death rate, δ t,a , was assumed to adequately capture the small proportion of DENV infections that resulted in death. Although our model was not designed with a specific population in mind, we used birth and death rates from Brazil ( United NationsDepartment of Economic et al., 2017 ) given that it is a large, dengue-endemic country that has been the subject of CYD-TDV modeling before ( España et al., 2019 ; Flasche et al., 2016 ). To ground our analysis in contemporary demographic rates, we assumed that CYD-TDV vaccination began in 2020, meaning that the model burn-in period began in 1960 and that vaccination impacts were tracked until 2050.…”

“…Following previous work ( España et al., 2019 ; Flasche et al., 2016 ), we used the proportion of symptomatic cases averted to quantify the impacts of CYD-TDV vaccination from a public health perspective. Negative values indicated an increase in cases, while positive values indicated a decrease.…”

“…Second, it is also important that screening have high sensitivity to ensure that seropositive individuals benefit from vaccination, particularly in areas with high baseline seroprevalence ( Flasche & Smith, 2019 ). Third, an assay for serological screening with a given sensitivity and specificity is expected to have greater impact in an area with higher baseline seroprevalence, due to the higher proportion of seropositive individuals and the greater benefits of herd immunity in these settings ( España et al., 2019 ). For these reasons, baseline seroprevalence could influence decisions about which screening assay is most appropriate in a given setting, or whether vaccination with CYD-TDV is appropriate in the first place.…”