Dengue pre-vaccination screening based on serostatus: rapid tests and implementation strategies
January 14-16, 2019 - Les Pensieres Center for Global Health, Veyrier-du-Lac (France)
Dengue is a major public health problem with more than 3.6 billion people at risk for dengue virus (DENV) infection and an estimated 390 million infections annually in over 120 tropical and sub-tropical countries.
In the absence of truly effective and sustainable vector control measures, a dengue vaccine is urgently needed. The first dengue vaccine was licensed in 2015; the live attenuated recombinant tetravalent vaccine CYD-TDV. However, new evidence highlighted the serostatus-dependent vaccine performance of CYD-TDV; a retrospective analysis of clinical trial data, stratifying participants according to their dengue serostatus before the first vaccine dose, revealed an excess risk of severe dengue in seronegative vaccine recipients, while in seropositive vaccine recipients, the vaccine was efficacious and safe. Whether this serostatus-dependent vaccine performance will also be observed for the second-generation dengue vaccines is currently unknown. However, a differential performance based on baseline serostatus is theoretically possible for all live dengue vaccines.
SAGE provided revised recommendations in April 2018 on how best to use this vaccine in populations at risk: Countries considering the introduction of CYD-TDV should only do so if the minimization of the risk in seronegative individuals can be assured. The pre-vaccination screening is the preferred strategy as with such a strategy predominantly persons with evidence of a past dengue infection would be vaccinated (based on an antibody test, or on a laboratory confirmed dengue infection in the past).
To support a pre-vaccination screening strategy, WHO and many expert panels highlighted the urgent need for rapid diagnostic tests (RDT) to determine serostatus. To date, no RDT has been licensed for the indication of determining dengue serostatus, eg past dengue infection. Pre-vaccination screening strategies will require RDTs that can be done at point of care, provide rapid test results, are sensitive and specific, as well as inexpensive for use in a population wide programme.
In addition to target product profiles for such RDTs, policy-makers need to think through the risk-benefit of diagnostic tests, given that there will always be a certain trade off between sensitivity and specificity. What level of sensitivity and specificity is good enough, which trade-offs are acceptable by communities and governments, how much evidence is needed, and does one need standardized risk classification? Public acceptance of a certain level of specificity will depend on background seroprevalence, co-circulation of other flaviviruses, and the epidemiological situation of dengue in any given country. Optimal age targeting is another aspect that will differ from country to country depending on the peak of hospitalizations seen. Furthermore, both the pre-vaccination screening require careful planning around communication, implementation strategies, acceptability to stakeholders and communities, and cost-effectiveness studies.
NITAG experts, EPI managers, policy-makers with experience in vaccine introduction, front-line academic and public health scientists with expertise in vaccine introduction and mass vaccination, industry, diagnostics manufacturers, leaders of laboratory networks, regulatory authorities; WHO; CDC.
Objectives of the meeting
Assess rapid diagnostic tests (RDT) for screening for past dengue infection
- Discuss the target product profile for RDTs to support a pre-vaccination screening strategy
- Present a landscape analysis on RDT characteristics, and their sensitivity and specificity in different flavivirus endemic settings
- Elaborate on population level benefit versus individual risk
- Address policy-makers` perceptions and views on risk-benefit assessment of an RDT as a pre-vaccination screening tool under different scenarios (high versus low seroprevalence)
Discuss implementation strategies for pre-vaccination screening programmes for dengue vaccines
- Discuss practical issues for programmatic roll-out
- Address the optimal age for vaccine introduction
- Discuss communication strategies with regards to vaccine confidence, both for policy makers, the medical community and the lay public
- Elaborate on school based campaigns versus other facility-based programs
- Cassandra Kelly, Foundation for Innovative New Diagnostics (FIND)
- May C. Chu, Department of Epidemiology, Colorado School of Public Health, University of Colorado, Anschutz Medical Center, Aurora
- Anna Durbin, The Anna Durbin Lab; Johns Hopkins University School of Medicine
- Duane J. Gubler, Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore
- Annelies Wilder-Smith, Partnership for Dengue Control; Lee Kong Chian School of Medicine, Singapore; Institute of Public Health, University of Heidelberg; Department of Global Health and Epidemiology, University of Umea
- In Kyu Yoon, International Vaccine Institute