Arboviruses are increasingly impacting Europe, in part due to the effects of climate change. This emphasizes the need for improving preparedness for emerging arboviral infections that often co-circulate and may have overlapping clinical syndromes. Therefore, we aimed to strengthen surveillance networks for four clinically relevant arboviruses in southeast Europe.
This study reports secondary objectives of a prospective observational study in adults hospitalized with an arbovirus-compatible disease syndrome in 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (1 May 2016 - 31 October 2019). The main objectives of the study - describing the prevalence, clinical management, and outcomes of four arboviruses endemic to southeast Europe - are reported elsewhere. In this study, given the challenges in arbovirus diagnostics, we developed a diagnostic interpretation algorithm taking into account the (serological) outcomes and sample timing to study arbovirus prevalence in southeast Europe. We used enzyme-linked immunosorbent assay (ELISA) and custom-printed protein microarrays to simultaneously detect serum antibodies against Crimean-Congo haemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), Toscana virus (TOSV) and West Nile virus (WNV), followed by confirmation assays (virus neutralization test (VNT) or Indirect immunofluorescence test (IIFT)). Patients were sampled on day 0, 7, 28 and 60 post-hospital admission. Descriptive analysis was performed for virus reactive cases by geography and year, and possible associated factors (age, gender and insect bites) were analyzed by statistical analysis (t-test, chi-square test, Fisher’s exact test).
Of 2896 individuals screened, 913 were eligible for inclusion, of whom 863 had samples sent to the study reference laboratories for molecular and serological analyses. Serum sampling was often incomplete (samples missing from one or more timepoints or no data on time since symptom onset) (602/863 patients, 69.8%) with heterogeneous timing after symptom onset up to 40 days (median delayed collection of 5-6 days), impacting ability to diagnose arbovirus infection by serology. Using an interpretation table incorporating timing and completeness of sampling, 1 (0.1 %), 10 (1.2%), 40 (4.6%), and 52 (6.0%) out of 863 patients tested positive for confirmed recent infection, for CCHFV, TBEV, TOSV and WNV respectively. Most of TOSV acute confirmed cases were found in Albania (25/40, 62.5%), whereas WNV was primarily identified in Romania (36/52, 69.2%). Albania also had the highest overall TOSV seropositivity (168/282, 59.6%), mainly explained by confirmed (previously) exposed individuals (104/168, 61.9%). Older age was significantly associated with WNV and TOSV (sero)positivity (p <0.0001), as well as higher odds of TOSV reactivity in males (OR: 1.56; CI: 1.15-2.11; p-value: 0.0055), WNV reactivity with mosquito bites (OR: 2.47; CI: 1.54-3.97; p-value: 0.00023) and TBEV reactivity with tick bites (OR: 2.21; CI: 1.19-4.11; p-value: 0.018).
More details see our preprint here preprint; the accepted version on Lancet Infectious Disease is to be appear.
Authors: Louella M.R. Kasbergen, E. De Bruin, Felicity Chandler, Louise Sigfrid, Xin Hui Chan, L. Hookham, Jia Wei, Siyu Chen, Corine H. GeurtsvanKessel et al. *PREPARE MERMAIDS ARBO investigator group.