Ross river virus disease

Talk to your healthcare provider if you are sick and have recently traveled to an area where Ross River virus might be present. Your healthcare provider can order laboratory tests to diagnose Ross River virus infection.

There is no medicine to treat Ross River virus disease, but healthcare providers can treat the symptoms. In severe cases, some patients may need to be hospitalized and given intravenous fluids and other supportive care.

Keep mosquitoes out of your hotel room or lodging Choose a hotel or lodging with air conditioning or window and door screens. Use a mosquito net if you are unable to stay in a place with air conditioning or window and door screens or if you are sleeping outside. Sleep under a mosquito net Sleep under a mosquito net if you are outside or when screened rooms are not available.

Mosquitoes can live indoors and bite during the day and night. Buy a mosquito net at your local outdoor store or online before traveling overseas. Choose a mosquito net that is compact, white, rectangular, with holes per square inch, and long enough to tuck under the mattress.

Permethrin-treated mosquito nets provide more protection than untreated nets. Permethrin is an insecticide that kills mosquitoes and other insects. To determine if you can wash a treated mosquito net, follow the label instructions. Page last reviewed: February 26, Home Travelers Health. Most medically important arboviruses are transmitted to humans from other vertebrate species. The host is attractive to arthropod vectors and allows vectors to feed upon it.

The host is susceptible to virus infection, experiences low mortality from infection, and becomes viremic with a titer of sufficient magnitude and duration to infect susceptible blood-feeding vectors. The life history of the host proceeds in such a way that immunologically susceptible individuals enter the population at times of active transmission.

Host herd immunity remains low. To establish that a vertebrate is a reservoir host, the best evidence is frequent virus isolation from wild vertebrates. This is seldom possible because viremia is usually short-lived. Consequently, antibody prevalence is frequently used as an indicator of the prevalence of past infection.

However, laboratory studies of infection are needed to confirm the role of a vertebrate as a reservoir host, because this is the only means of establishing the level and duration of viremia Four criteria establish the vector competence of a mosquito species : i isolation of the disease-producing agent from wild-caught specimens, ii demonstration of its ability to become infected by feeding upon a viremic host, iii demonstration of its ability to transmit by bite, and iv field evidence confirming association of the infected arthropod with the vertebrate population in which the infection is occurring.

The overall risk for arbovirus disease in human populations is determined first by the presence of virus and vectors and second by the vector competence of the virus-vector system. Therefore, vector competence is central to the epidemiology of human arbovirus diseases.

These are now thought to have been due to RRV. Fifteen years later, during the Second World War, several outbreaks of arthralgia and arthritis were described in the Northern Territory, Queensland, and the Schouten Islands off the northern coast of Papua New Guinea 53 , 72 , 76 , 80 , , Fig.

In , Dowling 53 applied the name epidemic polyarthritis to the syndrome. Map showing cities, towns, and geographical features discussed in the text, areas where RRV is endemic, and the to South Pacific epidemic of RRV disease.

An epidemic occurred in the Murray Valley Fig. Because Chikungunya was known to be a group A arbovirus now the genus Alphavirus , Shope and Anderson sought serologic evidence that a group A arbovirus might be the cause of epidemic polyarthritis in Australia.

Sixteen pairs of acute and convalescent sera were tested, and six showed antibody to one or more of 10 group A arboviruses. Neutralization N testing for AMM and AMM now Getah viruses gave negative results for all acute-phase sera, but four convalescent-phase sera showed definite evidence of antibodies against one or both viruses.

Complement fixation CF testing of two pairs of sera was negative for all viruses except Getah virus, against which convalescent sera fixed complement. On the basis of this evidence, Shope and Anderson suggested that the cause of epidemic polyarthritis was an unknown group A arbovirus.

Next, Doherty et al. They tested sera from 20 patients with epidemic polyarthritis for antibodies against the virus, designated T48 T for Townsville and 48 for the mosquito pool number [R. Doherty, personal communication, ] as well as three other group A arboviruses Sindbis, Getah, and Bebaru.

Antibody titer to T48 was at least equal to that against the other viruses, and in most cases was higher. Seven patients had no significant antibody response to Getah or Bebaru virus. It was hypothesized that the virus causing epidemic polyarthritis was related to, or was, T48 The link between T48 and epidemic polyarthritis was further strengthened when Doherty et al.

Subsequently, the name Ross River virus was applied, and T48 became the type strain Finally in , RRV was isolated using IC inoculation of human serum into 1-to 2-day-old mice and subsequent serial passage after IC inoculation of brain suspension from any mice found sick or dead The serum used was from a 7-year-old aboriginal boy from Edward River, North Queensland, who had a headache and fever but no arthralgia or arthritis.

The child's nonspecific illness meant that the association between infection with RRV and the clinical entity known as epidemic polyarthritis remained conjectural Aaskov et al. The Pacific epidemic was the first occasion on which virus had been isolated from patients with symptoms of epidemic polyarthritis. Then, in , Aaskov et al. This was the first isolation of RRV from a patient with typical symptoms of polyarthritis in Australia. The genus Alphavirus contains small, enveloped viruses. The genome is single-stranded positive-sense RNA The genome of the T48 strain of RRV is 11, nucleotides in length and codes for four nonstructural proteins nsP1 to nsP4 , a capsid protein, and three envelope glycoproteins E1 to E3 The E3 glycoprotein is not incorporated in the virion T is the triangulation number, giving a multiplier of 60 that gives the number of subunits in the virus structure The E1 and E2 viral glycoproteins are embedded in the lipid bilayer to form the envelope Single E1 and E2 molecules associate to form heterodimers.

The E1-E2 heterodimers form one-to-one contacts between E2 and nucleocapsid monomers Alphavirus contains 24 registered members, all of which are arboviruses , and a 25th member, Trocara virus, has recently been added The genus Rubivirus contains only rubella virus On the basis of the nucleotide sequence of the nonstructural proteins, the genus Alphavirus segregates into New World American and Old World Eurasian-African-Australasian viruses An estimate of the time of divergence of the Old and New World alphaviruses was made on the basis of studies of the Venezuelan equine encephalitis virus VEE complex.

In a later study, phylogenetic analysis of the nsP1, nsP2, and nsP4 proteins was carried out. On the basis of the phylogeny and the estimate for the time of divergence of the New World EEE and VEE complexes, the Old and New World alphaviruses diverged as recently as 2, to 3, years ago On serologic criteria, RRV is classified in the SF antigenic complex of the genus Alphavirus , one of seven serologic complexes in the genus The relatively recent divergence of these three Old World alphaviruses from an ancestral virus in Australia, Africa, or Japan makes dispersal by birds seem likely.

Following the bite of an infected mosquito, RRV particles are inoculated and attach to a cell surface receptor, possibly an integrin The virus then penetrates and is uncoated within the cell Primary replication occurs in skeletal muscle 73 , 89 , , RRV then enters the blood, where clearance is mediated principally by neutralizing antibodies and type 1 interferon 86 , , At the time that symptoms commence, virus usually cannot be cultured from peripheral blood , so presumably it has been cleared by the mechanisms discussed above but has infected other tissues.

The most prominent and disabling symptom of RRV disease is arthralgia. Therefore, the following discussion is focused on joint infection and the pathogenesis of arthralgia and arthritis. Immune complexes are involved in the pathogenesis of some viral arthritides 65 , , but Fraser et al. Immune complexes deplete complement and attract neutrophils, but Fraser et al. Synovial effusions in acute RRV disease consist mainly of monocytes and activated macrophages 28 , 64 , 84 , which are attracted and activated by monocyte chemoattractant protein 1 MCP-1 , which is produced by RRV-infected synovial fibroblasts in vitro Thus, direct and indirect evidence argues against immune complexes as the cause of RRV arthralgia and arthritis.

Viable RRV has not been isolated from the joints of patients with chronic joint symptoms following RRV infection 28 , Viral antigen had been demonstrated in leukocytes from joint effusions, and viral RNA has been demonstrated by PCR testing of synovial biopsy specimens 64 , Human synovial cells can be productively infected with RRV in vitro 34 , La Linn and coworkers , showed that macrophages could be persistently and productively infected with RRV and suggested this might play a role in persistence through the phagocytosis of dying cells by other macrophages.

Neutralizing antibody cannot clear RRV from infected macrophages , Patients with RRV disease have a marked virus-specific T-lymphocyte proliferative response 3 , and cytotoxic T lymphocytes can clear RRV-infected macrophages , La Linn et al. This hypothesis fits well with earlier observations of Fraser and his group 62 , Human leukocyte antigen restriction of the ability to generate specific cytotoxic T lymphocytes and consequent persistent infection of joint macrophages or synovium may offer a mechanism for the persistence of symptoms , Interferon gamma, a cytokine produced by T lymphocytes, is elevated in synovial effusions of patients with RRV disease One or both of these substances may mediate inflammation in RRV-induced synovitis.

Synovial fibroblasts infected with RRV in vitro produce MCP-1, which has been implicated in the pathogenesis of some other viral arthritides and rheumatoid arthritis RRV arthritis is probably an infectious arthritis, possible inflammatory mediators have been identified, and an immunological mechanism for chronic symptoms occurring in some people has been suggested.

Virus isolation from humans is rarely achieved, probably because RRV does not persist beyond the early stages of disease. Diagnosis is usually made on serologic grounds Because of its production early in the course of Alphavirus infection and the fact that it usually does not persist at high titer 23 , 25 the detection of immunoglobulin M IgM in an acute-phase specimen provides a presumptive diagnosis of recent infection Sucrose gradient ultracentrifugation is required to separate IgM for HI testing, and only reference laboratories use the technique D.

False-positive ELISA results may be caused by BFV, rubella , Q fever , and noninfectious causes such as rheumatoid factor, although the last is normally controlled for in the testing procedure. A confirmed diagnosis cannot be made with a single serum specimen. Two sera obtained 10 to 14 days apart should be collected and tested in parallel by the same laboratory.

The acute-phase serum should be collected within 7 days, and the convalescent-phase serum within 8 to 28 days of onset of illness The standard for confirmed diagnosis of Alphavirus infections is a fourfold or greater increase or decrease in antibody titer determined by HI, CF, or N testing 23 , Kapeleris, PanBio, personal communication, Flexman et al.

Qiao, personal communication, The incubation period for most arboviruses in 5 to 15 days RRV usually incubates for 7 to 9 days, based on the experience of 20 patients who lived in areas of no risk, visited transmission zones, and developed symptoms with diagnosis confirmed by HI testing Incubation may be as long as 21 days or as short as 3 days. The first estimate is based on a questionnaire-survey of notified cases and the latter on a single case report RRV disease causes a characteristic syndrome, including constitutional effects, rash, and rheumatic manifestations Several less common presentations have also been described.

Fraser 60 described the clinical features of a series of 43 patients. At first he actively sought cases receiving medical or surgical care in the Murray Valley town of Echuca, Victoria, for any symptom that could be attributed to RRV or other viral infections. Later, cases were referred from the casualty department of the Royal Melbourne Hospital, rheumatologists, family practitioners, and infectious disease and other consultant physicians J.

Fraser, personal communication, Patients referred from rheumatologists and other consultant physicians might have been unusual. However, this description is still the best account of RRV disease and is especially useful because it was done by a single clinician with appropriate skills.

Unless otherwise specified, the description that follows is based on Fraser's observations. Joint symptoms and signs are usually symmetrical and acute in onset, ranging from tenderness with minor restriction of movement to extreme redness and swelling. Effusions are common and peripheral joints are predominantly involved.

The methods for case ascertainment differ, but the results clearly show that ankles, fingers, wrists, and knees are the joints most commonly affected. The metacarpophalangeal joints are also very frequently affected by pain The rash appears mainly on the limbs and trunk, but may also occur on the palms, soles, digits, face, and even the scalp.

Most commonly the skin eruption is maculopapular, but it may be vesicular or purpuric 60 , Fever affects from one third to one half of patients. Rash, fever, and arthralgia may occur in any sequence. Lymphadenopathy occurs quite often, sore throat and coryza less frequently, and diarrhea is rare 60 , In a small study, Bennett et al. Other manifestations reported include splenomegaly, hematuria, and glomerulonephritis 11 , 39 , 60 , 65 , Paresthesia may occur due to entrapment neuropathy.

Headache, neck stiffness, and photophobia may occur. So far there are only three case reports suggesting meningitis or encephalitis caused by RRV infection, indicating that these must be rare. None of the three cases were proven to be caused by RRV, and more effort should be made to isolate RRV from cerebrospinal fluid if future cases occur. Because of the serious nature of such manifestations, these cases are reviewed in detail, although the evidence that RRV infection caused these cases is not strong.

The first report was of a year-old man who died of encephalitis in Papua New Guinea during or the date of onset is not stated in the paper and had RRV antibody titers of 1 week after hospital admission.

No other cause of encephalitis could be found, but he did not have arthralgia or arthritis, RRV was not isolated, and autopsy could not be performed, so the evidence that RRV caused his death is weak Lucas and Qiao reported a year-old male who was admitted to the intensive care unit of the Alice Springs Fig. There was no rash or evidence of arthritis. Cerebrospinal fluid Gram stain, latex agglutination for bacterial capsular antigens, cryptococcal antigen, and India ink stain tests were negative.

There was no serologic evidence for other causes of acute and postinfectious meningoencephalitis. IgG was negative on both of these occasions, but became positive 90 days postadmission. The IgG seroconversion after 90 days was later than would be expected, even allowing for the slow seroconversion noted by Qiao ; M. Penna and Irving J. Penna and L. Irving, letter, Med. A year-old male developed headache and neck stiffness 1 week after onset of fever and arthralgia.

RRV IgM was detected in serum. Serologic tests for a number of other infectious causes of meningitis were negative. Recent estimates of the duration of symptoms with RRV disease have increased substantially compared with estimates made when the disease was first described. RRV disease has now become notorious in public discourse, with a reputation for inducing prolonged and disabling arthritis. Sibree found that 17 of 28 soldiers were able to carry on normal army duties. Eleven others were admitted to hospital, but eight of these resumed duties within 23 days.

Three remained in hospital for 60 to 70 days due to persistently painful joints. From the s, reports on the clinical features began to suggest that some patients developed chronic disease lasting for months to years. In a large New South Wales outbreak, Hawkes et al. Three recent studies suggested that an even longer duration of symptoms was typical. Westley-Wise et al. The validity of the last three studies is doubtful.

They involved mailed questionnaires sent to notified cases months or years after disease onset, and the calculations are based on the fraction who responded. In the study of Selden and Cameron, only of responded at 30 months This created a serious selection bias, as it is much more likely that those who were ill would respond, boosting estimated rates. Also, these studies used nonstandardized and nonvalidated questionnaires, lacked clinical review, did not exclude alternative diagnoses, and had no control groups.

A priori, we would not expect RRV disease morbidity to vary much. Evolution of the virus is slow 21 , and it remains genetically homogeneous over large geographic areas , This stability suggests that temporal or spatial changes in virulence are unlikely to occur. Methodological differences among the morbidity reports and substantial self-reporting bias in the three mailed questionnaire studies of the s 33 , , , together with cultural inflation of morbidity 88 over time, account for these differing estimates.

The so-called cultural inflation of morbidity 88 results from increasing health expectations on the part of the public and cultural pressures on health professionals to treat an ever-growing set of nonfatal diseases, leading to a paradoxical increase in demand for health services as mortality declines.

The lack of clinical review and exclusion of alternative diagnoses may be a threat to validity. An analogous situation exists with chronic Lyme disease in the United States and Canada and suggests that caution should be exercised in ascribing chronic symptoms to an infectious disease of which there is a high level of public awareness and concern.

Both infections have been implicated as causes of chronic rheumatic disease. In the case of Lyme disease, chronic illness directly attributable to Borrellia burgdorferi infection is considerably less common than previously thought. Burdge and O'Hanlon 20 , working in Canada, assessed 65 patients sent to a multidisciplinary referral center for Lyme disease. Only two patients were judged to have probable Lyme disease.

An American study of Lyme disease produced similar results Keary, Abstr. Thirty either had preexisting or subsequently developed another rheumatic disease. The prevalence of rheumatic symptoms in the community is high , It follows that prevalent symptoms not causally associated with RRV disease are likely to have been included in the results of the three s RRV symptom studies 33 , , , leading to an overestimate of symptom prevalence and duration.

Experience with Lyme disease and the study by Keary both suggest that it is unwise to assume that the symptoms reported in these studies have been caused by RRV infection. Until the natural history of RRV disease morbidity is better understood, the public health importance of this disease cannot be determined.

This requires repeated clinical assessments of a community-based inception cohort of symptomatic persons with confirmed incident RRV disease, using standard measures of morbidity, and comparing results to expected levels of morbidity for people of that age and sex. One of us D. The inception cohort was a group of 47 family practice patients diagnosed with RRV disease in and around Cairns Fig. One physician trained in rheumatological assessment D.

Harley reviewed all patients three times in their homes from 7 to days after diagnosis. The time course of symptoms and signs over approximately 7 months from onset is shown in the following table and graphs. There was a progressive diminution in symptom prevalence over time. The box plot Fig. The median number of painful joint groups decreased from four to one over the first 4 months and reached zero after 5 to 7 months. Of the four individuals who had abnormal findings in months 5 to 7, one was a year-old woman with severe preexisting osteoarthritis who had swelling of the ankle joint and proximal interphalangeal joints of the fingers and grade I tenderness of her knee joint.

These findings reflected her underlying disease rather than having been caused by RRV disease and therefore inflate the prevalence of joint abnormalities at this review. Number of joint types that were painful over 7 months of postinfection follow-up for 47 cases of RRV disease, Cairns, Prevalence of joint abnormality over 7 months of follow-up, RRV disease, Cairns, All analyses were linear regressions, with the study subject included as a random effect.

These are age- and sex-adjusted departures from the population standard for the Australian State of Queensland in standard deviation units, regressed against time since symptom onset. It is clear that the group returns to normal physically over 4 to 6 months and psychologically over 2 to 5 months. Physical dimensions of the SF, age and sex standardized to the Queensland population and regressed against time since symptom onset for RRV disease cases, Cairns, Psychological dimensions of the SF, age and sex standardized to the Queensland population and regressed against time since symptom onset for RRV disease cases, Cairns, The results of this study indicate that RRV disease does cause pain and suffering for several months in a substantial proportion of patients, but progressive resolution indicates that treating doctors are justified in taking an optimistic outlook regarding complete recovery over some months, whilst acknowledging the appreciable temporary disability that may result.

Recommendations on treatment for RRV disease are not based on clinical trials. Condon and Rouse 33 found that of patients, Physical interventions swimming, hydrotherapy, physiotherapy, or massage were the most beneficial for Some clinicians use oral corticosteroid therapy and have found that patients respond well D.

Harley, unpublished data , but it is doubtful whether steroids are needed, and the adverse effects should constrain their use. In theory, steroids could make RRV disease worse, but this has not been observed.

The available information is limited but suggests a stepwise approach would be best for treatment of RRV disease arthritis; first, a trial of rest and physical therapy, followed by simple analgesics, and then NSAIDs if necessary. Until more information is available, steroid treatment cannot be recommended. Theoretically, to establish the status of putative reservoir hosts, we require information on behavior, ecology, immunology, and reproductive cycles and the course of arbovirus infection.

In practice, most knowledge of the likely vertebrate reservoir hosts for arboviruses has come from antibody prevalence surveys and experimental studies of infection. This is true for RRV. Here we review knowledge of reservoir hosts for RRV, including the infrequent isolation of virus from vertebrates, extensive antibody prevalence surveys, the numerous experimental infection studies, and current thinking about reservoir hosts.

Even then, with only a small number of experimental infection studies performed on a small number of animals, it seems premature to rank vertebrate hosts for their importance as reservoirs. As outlined in the introduction to this section, many factors other than level and duration of viremia must be taken into account to determine reservoir status.

The antibody prevalence and laboratory infection and transmission data suggest significant roles for macropods as reservoir hosts. In , in a paper on arbovirus infections of mosquitoes and mammals at Mitchell River mission now Kowanyama on Cape York Peninsula in remote North Queensland, Doherty et al. Mackenzie et al. Before the white invasion of Australia, macropods may have been the reservoir for natural enzootic RRV transmission cycles, but it does not follow that they are the major reservoir for the large numbers of human infections that occur in Australia.

Macropods are rare in urban Australia, and they cannot be the usual source of metropolitan human infections, the main component of reported RRV disease. Other animals must be involved in urban areas. Antibody to RRV has been detected in brush tail possums, a common urban marsupial, albeit in very few animals. Given the large numbers of possums in many Australian cities, these animals warrant further investigation as potential reservoir hosts; indeed, recent experimental work at the Queensland Institute of Medical Research QIMR suggests they could be important reservoir hosts A.

Boyd, personal communication, Outbreaks in major metropolitan centers 9 , , , have led Mackenzie et al. RRV has been isolated from horses on two occasions 24 , Horses can experimentally infect Culex annulirostris a major vector of RRV They also develop relatively high-titered viremias 6.

These data indicate that horses may play a role as amplifying hosts when present in appreciable numbers. RRV is relatively homogeneous over large geographical areas, suggesting that humans or livestock transported by air or possibly flying foxes are able to transport the virus long distances , , , If birds act as reservoir hosts, they could also account for these observations.

Serologic surveys and virus isolations from mosquitoes trapped near flying fox camps suggest that flying foxes might be reservoir hosts 49 , 71 , 79 , However, experimentally infected gray-headed Pteropus poliocephalus and red Pteropus scapulatus flying foxes failed to develop detectable viremias Also, Ryan et al. RRV has been isolated frequently from mosquitoes collected at flying fox camps in Brisbane and Cairns 79 , Harley et al.

The number of positive pools from within 1 km of the camp was significantly greater than for mosquitoes trapped elsewhere, for all species trapped, and for the important vector species C.

The spectacled flying fox, P. Some people may heal within two to six weeks of infection, while others may still feel sick after three months. Symptoms of RRVB may persist for up to a year or more. A blood test can be used to confirm the presence of the Ross River virus.

Blood tests may examine levels of antibodies in the blood. It typically requires comparing blood taken in the early stages of the infection and another blood sample after two weeks later to confirm the virus. There are no available vaccines or medical cure for Ross River Virus Disease. Treatment options focus on easing pain in the joints and minimizing fatigue. Some people may get better with simple painkillers such as paracetamol and aspirin.

Others may require more potent medication to alleviate inflation. Stress management, gentle exercises, physiotherapy, and plenty of rest is necessary to treat the condition.

Emotional stress and physical exhaustion may exacerbate the symptoms or even prolong them. People with chronic symptoms require emotional support from family, friends, and caregivers. Most people who have been infected with the disease will not catch it again. Although in rare cases, people may experience one or more symptoms after it seems they have recovered.