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Ross River Disease in a Traveler to

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 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 . 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 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 Disease enzymes, and serum creatinine were all normal. His C- RRV is an 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 - 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 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 Health Pathology and may transport the virus over wide areas. Possums Science Services in , 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 are the main vectors in Clinic, Associate Professor, Department of Medicine, National the coastal regions, while is the University Singapore, Singapore, 5 Lower Kent Ridge Road, main 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 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 virus strains.18 directed against other closely related .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 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 , , New populations.40 Seasonally, a higher number of cases Caledonia, or the .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.

Table 2 Clinical features for Ross River virus disease, disease, chikungunya, and

Ross River Barmah Forest virus disease virus disease Chikungunya Dengue References

Incubation period 5–15 d 7–10 d 1–12 d 3–14 d 29–34 Arthritis Polyarthritis, small and Similar to RRV Similar to RRV Milder arthralgia, usually large joints without arthritis; often myalgias, retro-orbital pain, and headache Hemorrhagic None None Most likely none Petechiae, epistaxis, rarely manifestations severe bleeding such as gastrointestinal or

intracerebral bleeding Downloaded from https://academic.oup.com/jtm/article/16/6/420/1832822 by guest on 24 September 2021 Fever Up to 10 d or longer Similar to RRV 7–10 d Usually defervesence by day 5–7 Duration of Arthralgia/arthritis for 6 Similar to RRV Lasting from weeks to Short-lived, usually less arthralgia mo, sometimes longer often months, than 10 d sometimes up to 1 yr Geographic Australia, west Pacific Australia South and east Asia, Tropical and subtropical 29,32,34 distribution Africa, Pacific, Italy countries worldwide Frequency in Most common arboviral Less common Mainly imported Mainly in northern Australia disease Queensland and northern territories the highest being in and Brisbane.40 RRV References disease in fact had a significant impact on tourism and industry, as well as on residents of affected areas in 1. Johnston RE, Peters CJ. Alphavirus. Fields virology. Queensland.41 Camping increased the risk eightfold Chapter 28. Philadelphia, PA: Lippincott-Raven Pub- for RRV disease in tropical Australia. Mosquito coils, lishers, 1996. 2. Boyd AM, Hall RA, Gemmell RT, Kay BH. Experimental repellents, and citronella candles each decreased the risk infection of Australian brushtail possums, trichosurus by at least twofold, with a dose-response for the number valpecula (Phalangeridae: Marsupialia), with Ross River of protective measures used. Light-colored clothing and Barmah Forest viruses by use of a natural mosquito 42 decreased the risk threefold. vector system. Am J Trop Med Hyg 2001; 65(6): The risk of importation of RRV disease via travelers 777–782. to countries where there are receptive mosquitoes 3. Gard G, Marshall ID, Woodroofe GM. Annually such as Singapore exists, but is likely to be small as recurrent epidemic polyarthritis and Ross River virus viremia is short-lived and animal reservoirs such as activity in a coastal area of New South Wales: II. Mos- kangaroos and wallabies are not present. However, quitoes, virus and wildlife. Am J Trop Med Hyg 1973; 22(4):551–560. the disease has meanwhile expanded from Australia 4. Ryan PA, Martin L, Mackenzie JS, Kay BH. Investi- to the nearby Pacific Islands, and this was likely gation of gray-headed flying foxes, Pteropus poliocephalus to be due to a combination of viremic travelers, (Megachiroptera: Pteropodidae) and mosquitoes in the expansion of mosquitoes, and possibly animal reservoirs. ecology of Ross River virus in Australia. Am J Trop Med Ever increasing human movements, ecologic changes, Hyg 1997; 57(4):476–482. changing human behavior, and insecticide resistant 5. Mackenzie JS, Lindsay MD, Coelen RJ, et al. mosquitoes may potentially contribute to the further causing human disease in the Australasian zoogeographic spread of this disease. Therefore, travel medicine region. Arch Virol 1994; 136(3–4):447–467. specialists, infectious diseases specialists, and healthcare 6. Amin J, Hueston L, Dwyer DE, Capon A. Ross River virus infections in the north-west outskirts of the Sydney providers should be familiar with the clinical features 23,24,29 basin. Commun Dis Intell 1998; 22(6):101–102. of RRV disease. Travelers to endemic countries 7. Azoulas JK. Arboviral diseases of horses and possums. need to receive pre-travel advice about the risk, Res Aust 1997; 7:75–77. symptoms, and preventive measures with regards to 8. Azoulas JK. Ross River virus disease of horses. Aust RRV disease. Equine Vet 1998; 16:56–58. 9. Boyd AM, Kay BH. Assessment of the potential of dogs and cats as urban reservoirs of Ross River and Barmah Forest viruses. Aust Vet J 2002; 80(1–2):83–86. Declaration of Interests 10. Russell RC. Ross River virus: ecology and distribution. Annu Rev Entomol 2002; 47:1–31. 11. Broom AK, Wright AE, Mackenzie JS, et al. Isola- The authors state they have no conflicts of interest to tion of Murray Valley encephalitis and Ross River declare. viruses from Aedes normanensis (Diptera: Culcidae)

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