High impact of molecular surveillance on hepatitis A outbreak case detection in Sweden: a retrospective study, 2009 to 2018

BACKGROUND: Swedish hepatitis A surveillance includes sequence-based typing, but its contribution to outbreak detection in relation to epidemiological investigations has not been fully evaluated. AIM: To evaluate the role of sequence-based typing in hepatitis A outbreak detection and to describe the hepatitis A epidemiology in Sweden to improve surveillance. METHODS: We retrospectively investigated hepatitis A virus sequences of 447 cases notified in Sweden 2009–18. We performed a phylogenetic analysis of evolutionary distances to identify cases with similar virus sequences (≥ 459/460 identical nt in the VP1/P2A junction). Unique sequences, dyads and sequence-based clusters (SBCs) were identified. We linked non-sequenced cases by epidemiological information and retrospectively assessed the value of typing for outbreak identification. RESULTS: Fifty-five percent (n = 542/990) of the notified hepatitis A cases were referred to the Public Health Agency of Sweden for typing and 447 (45%) were sequenced successfully. Subgenotypes included IA (42.5%, n = 190), IB (42.7%, n = 191) and IIIA (14.8%, n = 66). Phylogenetic analysis identified 154 unique sequences, 33 dyads (66 cases) and 34 SBCs (227 cases). The combination of molecular and epidemiological data revealed 23 potential outbreaks comprising 201 cases. Cases were linked by sequence (59%, n = 118), epidemiological data (11%, n = 23) or both (30%, n = 60). Typing was needed to identify 15 of 23 potential outbreak signals. CONCLUSION: Sequence-based typing contributed substantially to detecting clustering cases and identifying outbreaks in Sweden. The results show routine sequence-based typing detects outbreaks, promotes timely outbreak investigations and facilitates international collaboration.