Sindbis virus outbreak and evidence for geographical expansion in Finland, 2021

Sindbis virus (SINV) caused a large outbreak in Finland in 2021 with 566 laboratory-confirmed human cases and a notable geographical expansion. Compared with the last large outbreak in 2002, incidence was higher in several hospital districts but lower in traditionally endemic locations in eastern parts of the country. A high incidence is also expected in 2022. Awareness of SINV should be raised in Finland to increase recognition of the disease and prevent transmission through the promotion of control measures.

Sindbis virus (SINV) caused a large outbreak in Finland in 2021 with 566 laboratory-confirmed human cases and a notable geographical expansion. Compared with the last large outbreak in 2002, incidence was higher in several hospital districts but lower in traditionally endemic locations in eastern parts of the country. A high incidence is also expected in 2022. Awareness of SINV should be raised in Finland to increase recognition of the disease and prevent transmission through the promotion of control measures.
Sindbis virus (SINV) (Togaviridae family, Alphavirus genus) is the causative agent of Pogosta disease, a typically self-limited disease with common symptoms of rash, arthralgia, myalgia and fever [1,2]. In some cases, arthralgia and myalgia can persist from months to years and negatively affect quality of life [2,3]. While circulation of SINV has been reported in mosquitoes and birds globally, symptomatic human infection has almost exclusively been reported in Finland, Sweden, Russia and South Africa [4]. However, larger outbreaks and annual cases are reported only from Finland, where the SINV seroprevalence in the general population was 5.2% in the years 1999 to 2003 [5].
Laboratory diagnosis of Pogosta disease is done using ELISA, and paired samples are often needed because the antibody response against SINV develops slowly [6]. In Finland, SINV has been endemic since the 1960s, and the first epidemic occurred in 1974 [1,7]. A laboratory-confirmed case is defined as either detection of SINV IgM and IgG in a single serum specimen or seroconversion between paired specimens. The laboratory-confirmed cases have been notified to the National Infectious Diseases Register (NIDR) since its implementation in 1995 [8]. A total of 566 laboratoryconfirmed cases were notified in 2021, compared with an average of 158 annual cases between 1995 and 2021, making it a notable outbreak year. Similarly, high incidence had previously been reported in 2002 with 597 laboratory-confirmed cases.
The aim of this rapid communication is to increase awareness of an upcoming SINV epidemic in 2022. The high SINV incidence in 2021 may precede a larger epidemic.

Outbreak description
We retrieved laboratory-confirmed cases data for the years 2002 and 2021 from the NIDR. The data included date of specimen collection and place of residence at the time of diagnosis at hospital district level. Most of the SINV infections in 2021 were diagnosed in September (n = 309) and August (n = 175) ( Figure 1). A considerably smaller number of cases were reported in October (n = 49), November (n = 18), July (n = 8), December (n = 5) and June (n = 2).
Incidence rates of Pogosta disease in 2021 ranged in the different hospital districts from 0 (Åland Islands) to 40.6 (North Savo) per 100,000 residents ( Figure 2A). The hospital districts with the highest incidences were located in central, eastern and western Finland ( Figure  2B). In contrast, the lowest incidences were found in hospital districts in Lapland, along the southern coast and along the western coast southwards from Central Ostrobothnia.
Although some hospital districts reported large numbers of cases in both outbreaks (2002 and 2021), there were also clear differences ( Figure 2B). The SINV incidences in western and southern coastal hospital districts were lower in 2021 than in 2002 (by a range of 26-64%). The largest change in SINV infection incidence occurred in North Karelia (−71%), although SINV incidence rate in this hospital district remained high (23.3 per 100,000 inhabitants). Finally, SINV incidences were remarkably higher in several hospital districts in which not many SINV infection cases have typically been reported: Lapland, Länsi-Pohja, Kainuu, Central Ostrobothnia, North Ostrobothnia, Päijät-Häme, Kanta-Häme and Kymenlaakso (range: 71-471%) ( Figure 2B).

Discussion
The 2021 SINV outbreak was, to the best of our knowledge, the largest mosquito-borne viral disease outbreak in Europe that year. In comparison, West Nile virus caused 159 documented cases in the European Union and European Economic Area during the same mosquito season [9]. Pogosta disease cases peak in Finland typically between August and September, so it remains to be seen if there will be high case numbers this year. So far, the climatic conditions in 2022 have been favourable for mosquito abundance as in late winter, snow coverage was thick, generating a large amount of melting waters for the early season mosquitoes to breed in [10]. The grouse populations have also been increasing in Finland, providing more amplifying hosts for the SINV [11]. Also, larger numbers of mosquitoes have so far been observed, even though the mosquito season is still ongoing. All these factors create favourable prerequisites for enhanced SINV transmission in 2022.
The NIDR data for Pogosta disease cases allowed a comparison between different years by hospital district in Finland. However, the data were based on place of residence of the patient, which may not have reflected the location where the patient was infected. Despite this potential limitation, the available data suggested an expansion of the geographical range of Pogosta disease in 2021. We observed a considerably higher incidence in eight hospital districts compared with the previous outbreak in 2002. The positive change in incidence was highest in northern parts of the country and in four hospital districts with previously low incidence in southern Finland. The spatial pattern of highest incidences remained similar, which is in line with the spatial modelling results of the current SINV infection risk in Finland [12]. The typical peak in cases in August to September was also observed in the outbreaks of 2002 and 2021. In 2021, weather conditions were favourable for mosquito-borne transmission. The winter was snowy and the spring rainy, providing plenty of breeding grounds for the first mosquito generations. Furthermore, the summer was exceptionally warm, with record-high monthly mean air temperatures in June in southern and central parts of the country [13]. July was also warmer than the average [14]. Such conditions and high densities of the SINV mosquito vector and grouse population [12,15] have previously been associated with increased risk for Pogosta disease. Also, outdoor activities, which were especially popular in 2021 because of the coronavirus disease pandemic have been associated with the Pogosta disease risk [16].
The reasons for the observed geographical shift in the high incidence areas between the latest two Pogosta disease outbreaks are currently not known. The remaining immunity in the human population after the 2002 outbreak may have lowered the number of cases in the traditional endemic areas in 2021 but does not explain the spread to new areas. Further information would be needed on the factors affecting SINV emergence, including a possible effect of virus strain variation [17]. The longevity of the protective immunity after SINV infection also requires further investigation but re-infections have not been reported and for another mosquito-borne alphavirus, chikungunya virus, longlasting protective immunity has been shown [18,19].
Although the large outbreaks in 2002 and 2021 have probably increased awareness of the disease since then, it is likely that Pogosta disease is underdiagnosed in Finland, especially in areas where the disease is not common. The correct diagnosis of SINV patients is important because of the potential burden of persistent joint symptoms that can last for years. These symptoms have been reported in Finland in 24.5%, and more recently in Sweden up to 39%, of the diagnosed patients [20,21].

Conclusion
Sindbis virus caused the largest outbreak of mosquito-borne viral disease in the EU in 2021, with 566 diagnosed cases in a single country. The factors contributing and enabling SINV outbreaks are currently poorly understood. Raising public awareness of the disease and the ways of preventing mosquito bites would be important, especially in current high incidence and predicted risk areas in central, eastern and western Finland. One year after the 2002 outbreak year, elevated numbers of cases were reported in Finland and, therefore, we consider SINV transmission potential increased also for the 2022 mosquito season. The observed regional shift of reported cases to new areas poses challenges for the recognition of the disease and highlights the need for using virus-specific diagnostic testing of febrile patients with compatible symptoms.

Ethical statement
This research did not require ethical approval before implementation as Finnish law allows the Finnish Institute for Health and Welfare to conduct epidemiological research using surveillance data without further requirements.

Conflict of interest
None declared.