Facts about Sindbis fever
Sindbis virus (SINV) is an enveloped RNA virus of the genus Alphavirus in the virus family Togaviridae. Sindbis virus is related to Chikungunya alphavirus.
Sindbis virus was first isolated from Culex mosquitoes in 1952 in the Nile river delta in Egypt. The first human cases were described in Uganda in 1961, South Africa in 1963, and Australia in 1967. The virus was subsequently acknowledged as the causative agent of a rash-arthritis syndrome.
The clinical disease caused by SINV infection is known as Pogosta disease (Finland), Ockelbo disease (Sweden), and Karelian fever (Russia).
The incubation period of SINV infection is often less than seven days, but has not been established. Maculopapular and often itchy exanthema over the trunk and limbs, mild fever, and joint symptoms, particularly in wrists, hips, knees, and ankles, are the hallmarks of acute SINV infection, sometimes accompanied by nausea, general malaise, headache, and muscle pain. Infectious and basic blood parameters are typically within normal range. In children, the clinical disease is usually mild, and can present without joint symptoms. Asymptomatic infections are not uncommon. Fatal infections have not been reported.
Extra-articular symptoms usually diminish within 1–2 weeks, but in a considerable proportion of patients SINV infection leads to persistent joint manifestations that can continue for months or years, and in rare cases can even result in chronic arthritis.
Sindbis virus is widely and continuously found in insects (the main vectors are Culex and Culiseta mosquitoes) and vertebrates in Eurasia, Africa, and Oceania. However, clinical SINV infection in humans has almost exclusively been reported in Northern Europe where it is endemic and where large outbreaks occur intermittently. Cases are occasionally reported in Australia, China, and South Africa.
Sindbis virus or antibodies to SINV have been identified in wildlife in the following countries: Austria, Belarus, Bulgaria, Czech Republic, Estonia, Finland, Germany, Hungary, Italy, Moldova, Norway, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Spain, Sweden, Ukraine, and also in the UK.
Outbreaks have been reported in Finland and Sweden. In Finland, cases are reported every year, but larger outbreaks have occurred every seven years; during the 2002 outbreak in the highly endemic region of North Karelia, the incidence rate (counting serodiagnosed infections) was 81 cases/100 000 population. The proportion of subclinical and mild cases is probably high, but the available evidence is too limited to be able to quantify it.
The hypothesis is that SINV cycles between ornithophilic mosquito species and birds. Birds might be involved in the natural cycle of SINV as important reservoirs, but spillover to other vertebrates may occur. Grouse and passerines are probable amplifying hosts for SINV. The close relationship of South African and Northern European SINV strains suggests that migratory birds may carry the virus over long distances.
Mosquitoes of genera Culex and Culiseta are considered the primary vectors to transmit SINV to humans, but the virus has been also isolated from Aedes and Anopheles mosquitoes. In Northern Europe, practically all human infections take place in August and September, when the primary vector species are prevalent. The current understanding is that SINV infection provides a lifelong immunity against repeat infections. There is no evidence of human-to-human transmission. No evidence is available regarding risk of blood donation, but it cannot be excluded. Nevertheless, the viraemic window in SINV infection is narrower and with lower titres than in Chikungunya virus infection, suggesting a probably low risk of transmission through blood donation. This is also highlighted by the considerable difficulty in detecting virus or viral nucleic acid from acutely ill patients.
All persons who are not immune to SINV and are exposed to vector mosquitoes may become infected. In endemic areas the incidence rates are highest in those aged 30–69 years. Symptomatic infection occurs equally in males and females.
No vaccine or prophylactic medication is available for SINV infection. Prevention is based on protective measures against mosquitoes in areas with known SINV circulation, including appropriate clothing (long sleeves and trousers) and the application of insect repellent on exposed skin.
A clinically suspected SINV infection requires laboratory confirmation. The laboratory diagnosis of acute SINV infection is based on detection of SINV immunoglobulin M (IgM) antibodies or IgG seroconversion between paired samples taken two weeks apart, usually using enzyme-linked immunosorbent assay (ELISA) platform. Antibodies can also be detected with immunofluorescence and hemagglutination inhibition techniques. Diagnostic tests are performed only in specialised laboratories using in-house assays.
Immunoglobulin M antibodies become detectable within eight days, and IgG antibodies within 11 days from onset of symptoms. More than one-third of the patients show IgM antibodies even six months after infection, which may be related to persisting symptoms. Immunoglobulin G antibodies remain detectable for life. A positive IgG with a negative IgM test result is a sign of previous immunity. Molecular diagnostic techniques (e.g., RT-PCR) are not presently applicable for routine laboratory diagnostics of SINV infection. Parvovirus B19, rubellavirus, and measles can be considered in the differential diagnosis.
Management and treatment
No specific antiviral treatment is available for SINV infection. Treatment is symptomatic: antihistamins can be used for itching rash, and non-salicylate analgesics for joint pain. Intra-articular corticosteroids are sometimes used for persisting joint symptoms, but there is little evidence on their effectiveness.
Key areas of uncertainty
- Lack of vaccine or antiviral treatment
- Vastly unknown epidemiology
- Virus circulation in nature
- Range of possible viral hosts
- Range of possible vector mosquitoes
- Host response mechanisms in relation to susceptibility to symptomatic infection
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