Ross River virus

Ross River virus disease also called Ross River Fever or epidemic polyarthritis, is a nationally notifiable disease in Australia caused by the Ross River virus which is a zoonotic alphavirus that is spread by the bite of an infected female mosquito ¹. Ross River virus was first isolated in 1959 from Aedes vigilax mosquitoes collected near Ross River in Townsville and the causative role of Ross River virus disease was confirmed in 1971 by isolation of the virus from the blood of an Indigenous child with the disease. Some Aedes species of mosquitoes have recently been renamed Ochlerotatus spp.

Ross River virus disease occurs widely in Australia, accounting for the highest number of human mosquito-borne virus infections (arbovirus or arthropod-borne virus). In northern and central Queensland, cases of Ross River virus occur throughout the year, but most cases occur between February and May. On average there are 4800 cases of Ross River virus notified per year Australia-wide, with the majority from Queensland ². There are occasional large outbreaks of Ross River virus involving a significantly higher number of human cases. In 2015, there were 9800 notifications of Ross River virus – almost double the national average, 6192 of which were reported from Queensland. In 2017, an outbreak occurred in Victoria, with some 1200 notifications reported in January and February alone, exceeding the state counts for the previous four years combined ².

Ross River virus infection in humans is largely a biological accident as humans are not preferred host for the virus. Common hosts for the virus are wallabies, kangaroos, possums, wombats and occasionally dogs, horses, cattle, pigs and humans.

Most cases of Ross River virus infections occur in coastal regions which have salt-marsh habitats with large populations of the mosquitoes that can carry the Ross River virus but cases are occasionally reported in inland areas of Australia. In northern and central Queensland, Ross River virus is active throughout the year, in other states, disease presence follows spring and summer rains because carrier mosquitoes are more likely to breed under wet conditions.

Ross River Virus symptoms:

• Some people will have flu-like symptoms that include fever, chills, headache and aches and pains in the muscles and joints.
• Some joints can become swollen, and joint stiffness may be particularly noticeable in the morning.
• Sometimes a rash occurs on the body, arms or legs. The rash usually disappears after 7 to 10 days.
• A general feeling of being unwell, tired or weak may also occur at times during the illness.
• Symptoms usually develop about 7-10 days after being bitten by an infected mosquito.
• The majority of people recover completely in a few weeks. Others may experience symptoms such as joint pain and tiredness for many months.

Ross River Virus is not usually fatal ³. About 55%–75% of people who are infected with Ross River virus do not feel sick. For those who do feel sick, symptoms of Ross River virus include multiple joint pain and swelling (polyarthritis), muscle pain (myalgia), fever, tiredness, headache, fatigue and rash. The fever may be mild and go unnoticed. The rash involves the chest, back and limbs. The joints of legs and hands are most commonly affected and back pain is also relatively common. Most patients recover within a few weeks, but some people experience joint pain, joint stiffness, or tiredness for many months ⁴. At least half of patients with the disease are well enough to return to work within a month of the onset of symptoms but about one in ten may be still suffering with joint pain after three months. The illness tends to subside over time with occasional relapses of joint pain and fatigue. The good news is that the virus does not cause permanent damage to joints and that eventually the symptoms will stop.

It is generally considered that infection with Ross River virus results in long-term immunity to the disease. However, two distinct genetic types of virus exist; one predominates in eastern Australia and the other in Western Australia.

Presently, there is no specific treatment or commercially available vaccine for Ross River virus; patients are usually given supportive care and prescribed general analgesics and anti-inflammatory agents to treat symptoms ⁵. The best means to reduce the risk of infection is through mosquito control and avoidance of mosquito bites ⁴.

Figure 1. Ross River virus rash

Who is at risk of Ross River virus?

Ross River virus occurs in Australia and Papua New Guinea. People who are in contact with known mosquito habitats and who live in warm, humid climates near bodies of water will be most at risk of Ross River virus infection. Ross River virus infections are the most common mosquito-borne infection in Australia, and infections occurs in many rural areas in New South Wales. Infections are uncommon in major cities and towns. Outbreaks can occur when local conditions of rainfall, tides and temperature promote mosquito breeding. Ross River virus cannot be transmitted from person to person.

What can travelers do to prevent Ross River virus disease?

Travelers who go to Australia and Papua New Guinea are at risk for Ross River virus disease. Travelers who plan to spend a lot of time outdoors or who will be in areas with a lot of mosquitoes are at increased risk of Ross River virus disease. Disease risk is lower during the colder winter months. Ross River virus infection is the most common mosquito-related infection in Australia.

Can I pass Ross River virus disease to other people?

No, Ross River virus disease is thought to be only passed through the mosquito bite rather than human-to-human contacts, although one case of transfusion transmitted infection was reported recently.

Infection with the Ross River virus confers lifelong immunity.

Is there a cure for Ross River virus?

There is no known cure for Ross River virus infections. However there are many treatments available to relieve the symptoms and most people will recover with time. Protection against mosquito bites is the best way to avoid infection.

Is there a vaccine for Ross River virus disease?

No, but researchers are attempting to develop a Ross River vaccine.

Ross River virus transmission

Ross River virus is spread by certain types of female mosquitoes.

• Female mosquitoes feed on animals and people. If they feed on the blood of an infected animal, the mosquito may become infected. The virus then multiplies within the mosquito and is passed to other animals or people when the mosquito feeds again.
• The number of infections tends to peak in the summer and autumn months.
• Ross River virus is not spread directly from one person to another.

Ross River virus infection cannot be spread from human to human. Ross River virus is spread from animals to humans by a number of different types of mosquitoes. More than 40 species of mosquitoes have yielded isolates of Ross River virus ⁶, although many are likely to only have a minor role in Ross River virus transmission. Species most commonly associated with Ross River virus transmission include salt marsh mosquitoes Aedes camptorhychus, presenting in southern Australia and is replaced by Aedes vigilax north of its range, and the freshwater mosquito (Culex annulirostris) that is present throughout Australia, excluding Tasmania and Aedes notoscriptus ⁴. Aedes vigilax breeds in salty pools in mangroves and salt marshes after flooding by spring tides and heavy rains. Culex annulirostris breeds in permanent bodies of fresh water while Aedes notoscriptus breeds in containers close to homes and other human activity such as bird baths, pot plant saucers and backyard rubbish holding water.

A definitive description of the host-vector relationships in the transmission cycle of Ross River virus is currently not available. Non-human reservoirs of Ross River virus are thought to play a significant role in Ross River virus endemicity ⁷. While several authors have suggested that human-mosquito-human transmission of Ross River virus may occur during epidemics ⁸, such transmission is not believed to be sufficient to account for the total number of reported cases each year in Australia ⁶, nor to be responsible for the long-term persistence of Ross River virus.

Marsupials are generally considered better reservoirs of Ross River virus than placental mammals, which in turn are better reservoirs than birds ⁹. This hypothesis first appeared in the literature in 1971 ¹⁰ following epidemiological studies in northern Queensland where high rates of Ross River virus seropositivity were detected in macropods (kangaroos and wallabies). However, the hypothesis deserves critical re-evaluation because there is evidence that Ross River virus circulates in countries in the Pacific, where marsupials are absent ¹¹.

Ross River virus is maintained in a primary mosquito–mammal cycle involving macropods (particularly the western grey kangaroo), and possibly other marsupials and wild rodents. A human–mosquito cycle may occur in explosive outbreaks. Horses can act as amplifier hosts, and appear to develop joint and nervous system disease after infection with Ross River virus. Fruit bats might act as vertebrate hosts in some areas. Vertical transmission in desiccation-resistant eggs of Ochlerotatus spp. mosquitoes may be a mechanism to enable the virus to persist in the environment for long periods. This could explain the rapid appearance of cases of Ross River virus disease after heavy rains. Ross River virus is endemic throughout Australia, Papua New Guinea, adjacent Indonesia and Solomon Islands.

Ross River virus prevention

No vaccine or medicine can prevent Ross River virus disease. The most effective way to prevent Ross River virus infection is to protect yourself from mosquito bites while both indoors and outdoors as well as reduce opportunities for mosquito breeding near homes.

• Cover exposed skin by wearing long-sleeved shirts, long pants, and hats.
• Use an appropriate insect repellent as directed.
• Higher percentages of active ingredient provide longer protection. Use products with the following active ingredients:
  • DEET (Products containing DEET include Off!, Cutter, Sawyer, and Ultrathon)
  • Picaridin (also known as KBR 3023, Bayrepel, and icaridin products containing picaridin include Cutter Advanced, Skin So Soft Bug Guard Plus, and Autan [outside the US])
  • Oil of lemon eucalyptus (OLE) or PMD (Products containing OLE include Repel and Off! Botanicals)
  • IR3535 (Products containing IR3535 include Skin So Soft Bug Guard Plus Expedition and SkinSmart)
• Always follow product directions and reapply as directed:
• If you are also using sunscreen, apply sunscreen first and insect repellent second.
• Follow package directions when applying repellent on children. Avoid applying repellent to their hands, eyes, and mouth.
• Use permethrin-treated clothing and gear (such as boots, pants, socks, and tents). You can buy pre-treated clothing and gear or treat them yourself:
• Treated clothing remains protective after multiple washings. See the product information to find out how long the protection will last.
• If treating items yourself, follow the product instructions carefully.
• Do not use permethrin directly on skin.
• Stay and sleep in screened or air conditioned rooms.
• Use a bed net if the area where you are sleeping is exposed to the outdoors.

If you feel sick and think you may have Ross River virus disease:

• Talk to your doctor or nurse if you feel seriously ill, especially if you have a fever. Tell him or her about your travel.

Ross River virus symptoms

Many people who are infected with Ross River virus will never develop symptoms.

Ross River virus symptoms and their severity vary from person to person but can include:

• painful and/or swollen joints (the most commonly affected joints are the wrists, knees, ankles, fingers, elbows, shoulders and jaw). Pain usually develops quickly and may be intense and more severe in different joints at different times. Joint pain is much more common than swelling
• sore muscles
• aching tendons
• skin rashes (although these tend to be more common to Barmah Forest virus disease)
• fever
• tiredness
• headaches
• swollen lymph nodes.

Less common symptoms include:

• sore eyes
• sore throat
• nausea
• tingling in the palms of the hands or soles of the feet.

Symptoms tend to be milder in children and the illness often doesn’t last as long.

Ross River virus causes inflammation and pain in multiple joints (epidemic polyarthritis). While there are a wide range of Ross River virus disease symptoms, they typically include arthritic joint pain, usually of the peripheral joints, which affects 83%–98% of patients; fatigue and a raised red rash affecting mainly the trunk and limbs (one to ten days after the fever with joint pain and swelling), both of which affect over 50% of patients; and fever, which affects 20%–60% of patients ⁵. The severity of symptoms varies, as does their duration, which can range from a few weeks to several months ¹². Some people, especially children, may become infected without showing any symptoms. The rash usually lasts for one to ten days and may or may not be accompanied by a fever. The joint pain can be severe and usually lasts two to six weeks. Several studies indicate that chronic joint pain affects over 50% of Ross River virus disease patients, which can persist for years after diagnosis ⁵.

Most people become unwell within three to 11 days after being bitten by an infectious mosquito.

Ross River virus diagnosis

Ross River virus isolation from humans is rarely achieved, probably because Ross River virus does not persist beyond the early stages of disease. Diagnosis is usually made on serologic grounds ¹³.

Laboratory evidence requires one of the following:

• isolation of Ross River virus
• detection of Ross River virus by nucleic acid testing
• IgG seroconversion, a significant increase in antibody level, or a fourfold or greater rise in titre to Ross River virus
• detection of Ross River virus-specific immunoglobulin M (IgM) in the absence of IgM to Barmah Forest virus unless Ross River virus immunoglobulin G (IgG) is also detected
• detection of Ross River virus-specific IgM in the presence of Ross River virus IgG.

Because of its production early in the course of Alphavirus infection and the fact that it usually does not persist at high titer ¹⁴ the detection of immunoglobulin M (IgM) in an acute-phase specimen provides a presumptive diagnosis of recent infection ¹⁵. Sucrose gradient ultracentrifugation is required to separate IgM for hemagglutination inhibition testing, and only reference laboratories use the technique ¹⁶. In most laboratories hemagglutination inhibition cannot distinguish IgM and IgG. Enzyme-linked immunosorbent assay (ELISA) allows measurement of IgG and IgM separately, enabling presumptive diagnosis by a single IgM-positive specimen ¹⁷. False-positive ELISA results may be caused by Barmah Forest virus, rubella ¹⁸, Q fever ¹⁹, 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 ¹⁵. The standard for confirmed diagnosis of Alphavirus infections is a fourfold or greater increase or decrease in antibody titer determined by hemagglutination inhibition, complement fixation or nucleocapsid testing ¹⁵.

Until 1999, most testing for Ross River virus infection in Australia was done using indirect ELISA with a kit manufactured by PanBio; a second kit manufactured by Biocene is also now available. Flexman et al. ²⁰ suggest that IgG seroconversion, that is, an IgG-negative acute and IgG-positive convalescent specimen on ELISA testing, confirms the diagnosis. Based on ELISA testing of 124 HI-positive patients infected in South Australia from 1996 to 1997, the sensitivity of the PanBio ELISA kit is 98.5 and 84.6% and the specificity is 96.5 and 97.6% for IgM and IgG, respectively ²¹.

Ross River virus blood test

Suspected Ross River virus cases are confirmed by blood tests measuring two classes of antibodies, immunoglobulin G (IgG) and immunoglobulin M (IgM).

Diagnosis can only be regarded as conclusive if you seroconvert for IgG (go from negative IgG test to positive result) or if you have a four-fold rise in IgG antibody titer is detected in two blood samples taken at least two weeks apart, one at the beginning of illness and the second one two to four weeks later.

IgM antibody is a class of antibodies which are often used as indicators of recent infection. However, it is important to remember that in the Ross River disease this class of antibodies may be detected for long periods of time after the infection (18 to 48 months) and false-positive results with some test systems are not uncommon, particularly in individuals with autoimmune disease or who are infected with another agent such as Barmah Forest Virus, rubella or Q fever. When clinically important, it may be useful to have positive IgM antibody results verified by a reference laboratory. Ross River virus can also be detected by polymerase chain reaction (PCR), however, the usefulness of this test is limited by the short duration of viremia that follows infection. Testing for Ross River viral nucleic acid (RNA) can also be performed by reference laboratories but its use is limited to early in the disease course.

Diagnostic laboratories are required by law to report all positive cases to local public health units.

Ross River virus treatment

There is no specific drug treatment for Ross River virus infection. Treatment involves managing the symptoms that develop. Your doctor will advise on treatment for joint and muscle pains. Symptoms of joint pain and fever can be treated with painkillers such as paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) can help relieve the symptoms. A combination of plenty of rest and gentle exercise are important to keep joints moving and to prevent overtiredness, but medication may sometimes be necessary.

No treatment has been shown to shorten the duration or alter the course of Ross River virus. In one study, 36% of patients reported that NSAIDS provided the most effective relief, while 16% found over-the-counter analgesics (aspirin or paracetamol) to be most effective ²². Swimming, hydrotherapy, physiotherapy or massage was the most effective treatment for 10% of patients, while one-quarter found that rest provided the only relief. Eighteen percent found no relief from any form of treatment. Another study found that 58% of patients took NSAIDS at some stage of their illness and were largely satisfied with their effectiveness ²³. Corticosteroids have been used in some patients ²⁴, however, these is no evidence to support their effectiveness and they are not recommended.

Living with Ross River virus

Many people who are infected with the Ross River virus will never develop symptoms.

Ross River virus disease can cause incapacity and inability to work for 2–3 months. However, most people recover completely from these viruses, although recovery can take a few weeks to a few months. Arthralgias resolved for the majority of patients by 5–7 months, with the median number of painful joint groups decreasing from four to one over 4 months, and then to zero by 5–7 months. Psychological and physical functioning returned to normal by 2–5 months and 4–6 months respectively. During this time you may find that your symptoms are worse some days and better other days. You may also need some form of treatment, usually medicines, while symptoms are present to help control joint pain and swelling. For some people, symptoms persist or come and go for a year or more, although this is rare. Ross River virus does not cause any permanent damage to the joints and your joints will recover fully over time. Once you have had the Ross River virus, you are protected from the disease for the rest of your life.

Premorbid and concurrent conditions may influence the course of Ross River virus disease. One study ²³ found that at 6 months after diagnosis nearly half of patients had a comorbid condition, with rheumatologic conditions and depression being the most common. While the prevalence of these conditions was not greater than expected in the Ross River virus disease cohort, the impact on clinical outcome was significant. Among patients with Ross River virus disease alone, the majority had almost completely recovered their physical and mental health by 6 months, whereas those with a comorbid condition had significant illness up to 12 months after diagnosis. Only one of 60 patients had persisting symptoms at 12 months in the absence of any diagnosis other than Ross River virus disease. Another study ²⁵ evaluated the association between Ross River virus and chronic fatigue syndrome and followed 250 patients for 12 months following a diagnosis of Ross River virus, Ebstein-Barr virus or Q fever. The incidence of chronic fatigue was 12% at 6 months and 9% at 12 months, and did not differ between infective agents. Its onset was predicted only by the severity of the acute illness and not by premorbid psychiatric or medical disorders.

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