S I T M 420 REVIEWS Ross River Virus Disease in a Traveler to Australia Iqbal Hossain, MBBS, MRCP, Paul Anantharajah Tambyah, MD, and Annelies Wilder-Smith, MD,PhD,DTM&H Department of Medicine, National University of Singapore, Yong Loo Lin School of Medicine, Singapore Downloaded from https://academic.oup.com/jtm/article/16/6/420/1832822 by guest on 24 September 2021 DOI: 10.1111/j.1708-8305.2009.00345.x A 42-year-old Singaporean man was admitted to the transmission of chikungunya had not been reported in National University Hospital on November 29, 2005. 2005 either in Singapore or in Australia. Chikungunya He presented with a 2-day history of fever, myalgias, was only imported to Singapore in 2006 (three cases) severe arthralgias, and a rash. He had first noticed that and the first local transmission occurred in 2008. his left ankle was swollen and painful on movement. A Based on the positive Ross river virus (RRV) IgM that day later he developed a generalized non-pruritic rash. carries a sensitivity of 98.5% and specificity of 96.5%, There was no significant past medical history. He had combined with the recent travel history to Australia traveled to western Australia from November 14 to which is endemic for RRV disease, we therefore 20, 2005 where he had mainly visited lakes, parks, and made the diagnosis of RRV disease. He was treated rivers in and around Perth. There was no travel to any with nonsteroidal antiinflammatory medication and his developing country in the past 6 months. symptoms completely resolved after 2 weeks. This is On clinical examination his left ankle was swollen, the first reported case of RRV disease imported into erythematous with periarticular tenderness. There Singapore. was full range of movement. He had a generalized maculopapular rash which was more prominent over his lower limbs. Full blood count, urinalysis, liver Literature Review of Ross River Virus Disease enzymes, and serum creatinine were all normal. His C- RRV is an alphavirus and belongs to the family reactive protein (CRP) was raised to 17 mg/L (normal Togaviridae which comprises the genera alphavirus and value: less than 10 mg/L) and his ALT was raised Rubivirus.1 The virus is sustained mainly by mosquito- to 101 U/L (normal range: 5–60 IU/L), but all mammal cycles. Based on serological evidence and other liver parameters were normal. Dengue PCR and experimental infection studies, the main vertebrate hosts dengue serology were negative. Parvovirus and rubella are believed to be nonmigratory native macropods, serologies were negative. such as kangaroos and wallabies, all common to Because of his recent travel history to Australia and Australia.2 Other reservoir hosts, such as the new the triad of fever, arthritis, and rash, we considered Holland mouse and flying foxes have also been various arboviral diseases, and in particular, alpha virus implicated in the natural cycle of the virus.3–5 infections. Further screening for arboviral diseases was Horses are suspected to be amplifying hosts6–8 and performed by the Queensland Health Pathology and may transport the virus over wide areas. Possums Science Services in Brisbane, Australia. Ross River have also been shown to be efficient reservoirs and IgM [enzyme immunoassay (EIA)] was found to be may be involved in urban transmission cycles.2,8,9 reactive while Ross River IgG (EIA) was negative. All Dogs and cats have been exposed naturally to RRV other investigations including testing for Barmah Forest and can become infected but they are unlikely were negative. Unfortunately, chikungunya PCR was 10 not done routinely in 2005; however, chikungunya is to be important urban reservoirs of RRV. RRV has been recorded in 42 species of mosquitoes epidemiologically highly unlikely in this case as local representing seven genera.11 Different mosquito species are involved in different regions and varying seasonal Corresponding Author: Annelies Wilder-Smith, MD, PhD, and environmental conditions. In Australia, Aedes vigilax DTM&H Director, Travellers’ Screening and Vaccination and Aedes camptorhynchus are the main vectors in Clinic, Associate Professor, Department of Medicine, National the coastal regions, while Culex annulirostris is the University Singapore, Singapore, 5 Lower Kent Ridge Road, main vector further inland, and Aedes notoscriptus Singapore 119074. E-mail: epvws@pacific.net.sg is the predominant urban vector.11 RRV survives © 2009 International Society of Travel Medicine, 1195-1982 Journal of Travel Medicine 2009; Volume 16 (Issue 6): 420–423 Ross River Virus Disease 421 over winter and between epidemics by transovarial Table 1 Alpha viruses that cause the typical triad of rash, transmission.12,13 fever, and arthralgia, and their main geographical distribution Although the viremia in humans is thought to be Chikungunya Africa, Asia, Italy short lived, a man–mosquito–man cycle has been Ross River Australia described during explosive epidemics, such as those Barmah Forest Australia seen in western Pacific in 1979 and was suspected in O’nyong-nyong Africa Perth, western Australia in 1988/1989 and 1991/1992, Sindbis Mainly Africa 14–16 and in Brisbane, Queensland in 1992 and 1994. Mayaro South America Epidemics have emerged surrounding the Murray River in south eastern Australia after either high summer rainfalls or high winter rainfalls.17 Outbreaks between these diseases. However, clinical symptoms of RRV disease have been reported periodically may overlap and therefore, laboratory confirmation is Downloaded from https://academic.oup.com/jtm/article/16/6/420/1832822 by guest on 24 September 2021 throughout Australia.18 Putative environmental and always necessary. human risk factors are mosquito vectors, vertebrate The confirmatory diagnosis is based on virus hosts, natural and artificial topography vegetation, isolation, but this is rarely achieved probably because rainfall, temperature, tides, La Nina/EINi˜ no˜ climatic RRV does not persist beyond the early stages of phenomenon, age, sex, place of residence, population disease.35 Diagnosis is usually made serologically.35 immunity and density, migration, mobility, recreational The Haemagglutination Inhibition (HI) is less time activities, occupation, and vector/host competence of consuming to perform but also detects antibodies virus strains.18 directed against other closely related alphaviruses.35 The There are three major characteristics of RRV neutralization test (NT) is more sensitive and type- disease, namely severe arthralgias/arthritis, rash, and specific but requires the use of live RRV and is time fever, accompanied by constitutional symptoms such as consuming.35 Compliment fixation (CF) is useful as myalgia, fatigue, and headache.5 Incubation period is 5 the antibody used is produced later in an infection to 15 days but may be as long as 21 days or as short than NT and HI, and is relatively type-specific but it as 3 days. First symptoms are usually the involvement is short-lived.35 ELISA against RRV-specific IgG and of joints with pain only or with pain plus redness with IgM are often used.35 The Australian national notifiable swelling and tenderness. Joints usually involved are diseases case definition of confirmed cases requires wrists, knees, ankles, fingers, elbows, toes, and tarsal laboratory definitive evidence based either on isolation joints.1,19,20 Maculopapular or vesicular or purpuric rash of RRV, or detection of RRV by nested PCR, or IgG is observed in 50% to 70% of patients and affects mainly seroconversion or a significant increase in antibody the torso and the limbs but usually does not last for level or a fourfold or greater rise in titer to RRV, or more than 10 days.19,21 Myalgia affects around 60% of detection of RRV-specific IgM.36 RRV IgM ELISA patients. Fatigue is the most consistent constitutional test has a high sensitivity of 98.5% and specificity of symptom independent of any other manifestation.19 96.5%.37 Fever is also very common and does not necessarily There are still no evidence-based treatment guide- occur at the onset of symptoms.5 The duration of joint lines for RRV disease. Nonsteroidal antiinflammatory pain can last up to 3 to 6 months but can be as long as drugs can give dramatic symptomatic relief.38 Physical up to 1 year.20,22 interventions such as swimming, hydrotherapy, physio- For the typical presentation of ‘‘fever, severe therapy, or massage can be beneficial. An experimental arthralgia/arthritis, and rash,’’ the travel medicine vaccine is currently being investigated.39 practitioner needs to consider any of the following alpha virus infections that causes this triad, in particular Ross River Virus Disease and International chikungunya, RRV, Barmah Forest, Sindbis, O’nyong- Travelers nyong, and Mayaro, each associated with a typical geographical distribution (Table 1). A clue for RRV The overall age adjusted rate of RRV disease for tropical infection is a travel history to Australia, Papua New populations is four times higher than subtropical Guinea, Solomon Islands, American Samoa, Fiji, New populations.40 Seasonally, a higher number of cases Caledonia, or the Cook Islands.23–25 There are now are in summer and autumn with a definite decrease several case reports of RRV disease among international of cases in winter and spring.40 Outdoor activities, travelers to Australia and Fiji.26–28 particularly activities after sunset, living in tropical Other febrile viral diseases such as dengue and locations, and contact with animals are the greatest some rickettsial diseases may also present with fever, risks for RRV disease. Cases among international rash, and arthralgia, but usually the arthritis/arthralgia visitors to Queensland, Australia, have been described, is not so severe and prolonged as in alpha virus in particular in adults in the age group of 30 to 59 infections. Some typical clinical and laboratory features years and were highest among visitors from Japan of dengue, chikungunya, and Barmah Forest are and the UK/Ireland.40,41 In Queensland, the number summarized in Table 2 to help the clinician differentiate of RRV cases varied greatly across localities, with J Travel Med 2009; 16: 420–423 422 Hossain et al.