Acute symptoms and sequelae of Ross River virus infection in South-Western Australia: A follow-up study

doi:10.1016/S0928-0197(94)00043-3

Clinical and Diagnostic Virology

Volume 3, Issue 3, March 1995, Pages 273-284

Clinical and Diagnos...

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Abstract

Background

Unusually high tides along the south-west coast of Western Australia (WA) during the spring and summer of 1988-89 provided ideal breeding conditions for mosquito vectors of Ross River virus (RRV). This was followed by the biggest outbreak of RRV infection ever documented in WA (330 notified cases).

Objectives

To describe the nature and duration of symptoms of RRV infection in WA, and associated functional disability; to determine the perceived effectiveness of treatments; to determine the usefulness of available information on RRV infection.

Study design

A retrospective study of all cases of RRV infection reported from South West WA during the 1988-89 outbreak, using a self-administered patient questionnaire.

Results

The most common symptoms were arthralgia, tiredness and lethargy, and joint stiffness and swelling. In patients with joint manifestations, the knees, wrists and ankles were almost always affected. Non-steroidal anti-inflammatory agents, rest, simple analgesics and hydrotherapy were subjectively the most helpful treatments. Only 27% of patients had recovered completely within 6 months of onset of symptoms. Three years after the outbreak, up to 57% still experienced at least intermittent joint symptoms. Less than one-third of people reported that the available information adequately explained the consequences of RRV infection.

Conclusions

Compared with patients elsewhere in Australia, people infected with RRV in the South West of WA experience a slightly different spectrum of clinical symptoms, with a longer period of disability. This may be related to the presence of a different topotype of the virus to that found elsewhere in Australia. Better information for doctors and patients on the likely course of the illness is needed. Future studies should examine the economic cost associated with RRV infection, and evaluate treatments to shorten the period of disability.

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The relationship between rheumatic autoimmune diseases and alphaviruses infections is a theme already present in the literature that raises a series of questions, whose answers are still not easy to understand. Hypotheses that associate autoimmune diseases such as rheumatoid arthritis (RA) in patients after infection by alphavirus are reinforced by comparative results of cellular responses, profile of circulating cytokines, reported cases, in addition to predictive studies. In this way, we present a compilation of this information that approximates the infections of chikungunya virus (CHIKV), O’nyong-nyong virus (ONNV), Ross River virus (RRV), Barmah Forest virus (BFV), Mayaro virus (MAYV), and Sindbis virus (SINV) with the particularities seen in rheumatic autoimmune diseases like RA. However, all considerations about arthritogenic alphaviruses must be taken with care, and generalizations must be avoided in order to avoid speculation.
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Moreover, RRV infection has been identified as a possible emerging infectious disease across the world in the future (Yuen and Bielefeldt-Ohmann, 2021). RRV infection is characterized by rash, fever, arthralgia and rheumatic manifestations (Condon and Rouse, 1995; Harley et al., 2001). In the long term, RRV causes non-fatal polyarthritis that ranges from mild to severe and debilitating in some patients (Flaxman et al., 1998).
Ross River virus (RRV) infection is one of the emerging and prevalent arboviral diseases in Australia and the Pacific Islands. Although many studies have been conducted to establish the relationship between temperature and RRV infection, there has been no comprehensive review of the association so far. In this study, we performed a systematic review and meta-analysis to assess the effect of temperature on RRV transmission. We searched PubMed, Scopus, Embase, and Web of Science with additional lateral searches from references. The quality and strength of evidence from the included studies were evaluated following the Navigation Guide framework. We have qualitatively synthesized the evidence and conducted a meta-analysis to pool the relative risks (RRs) of RRV infection per 1 °C increase in temperature. Subgroup analyses were performed by climate zones, temperature metrics, and lag periods. A total of 17 studies met the inclusion criteria, of which six were included in the meta-analysis The meta-analysis revealed that the overall RR for the association between temperature and the risk of RRV infection was 1.09 (95% confidence interval (CI): 1.02, 1.17). Subgroup analyses by climate zones showed an increase in RRV infection per 1 °C increase in temperature in humid subtropical and cold semi-arid climate zones. The overall quality of evidence was "moderate" and we rated the strength of evidence to be "limited", warranting additional evidence to reduce uncertainty. The results showed that the risk of RRV infection is positively associated with temperature. However, the risk varies across different climate zones, temperature metrics and lag periods. These findings indicate that future studies on the association between temperature and RRV infection should consider local and regional climate, socio-demographic, and environmental factors to explore vulnerability at local and regional levels.
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Other non-specific signs and symptoms include arthralgia, myalgia, maculopapular rash, fever, fatigue (chronic fatigue), and lethargy or headache, or both.8 Although most of these symptoms are self-limiting (for less than 6 days91), debilitating arthritis can persist for up to 6 months,8,91–94 and clinical infection is rare (and usually mild) in children. BFV shares the standard symptoms of fever, rash, myalgia, and polyarthritis or polyarthralgia that are common to most arthritogenic alphaviruses, and as such, cannot readily be distinguished on the basis of the clinical symptoms alone.2,38
Mosquito-borne viruses, or arboviruses, have been part of the infectious disease landscape for centuries, and are often, but not exclusively, endemic to equatorial and subtropical regions of the world. The past two decades saw the re-emergence of arthritogenic alphaviruses, a genus of arboviruses that includes several members that cause severe arthritic disease. Recent outbreaks further highlight the substantial public health burden caused by these viruses. Arthritogenic alphaviruses are often reported in the context of focused outbreaks in specific regions (eg, Caribbean, southeast Asia, and Indian Ocean) and cause debilitating acute disease that can extend to chronic manifestations for years after infection. These viruses are classified among several antigenic complexes, span a range of hosts and mosquito vectors, and can be distributed along specific geographical locations. In this Review, we highlight key features of alphaviruses that are known to cause arthritic disease in humans and outline the present findings pertaining to classification, immunogenicity, pathogenesis, and experimental approaches aimed at limiting disease manifestations. Although the most prominent alphavirus outbreaks in the past 15 years featured chikungunya virus, and a large body of work has been dedicated to understanding chikungunya disease mechanisms, this Review will instead focus on other arthritogenic alphaviruses that have been identified globally and provide a comprehensive appraisal of present and future research directions.
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In a larger study of 255 RRVD patients, NSAIDs provided the “best and most effective relief” in 36.4% of cases, 16.4% found aspirin or paracetamol was the most effective and physical intervention (hydrotherapy, physiotherapy, or massage) was most beneficial for 10.3% of patients. Rest was the only relief for 24.1% of patients and 18.5% found no effective treatment for the symptoms of RRVD [14]. The use of etanercept, an anti-tumuor necrosis factor, and methotrexate, a disease-modifying antirheumatic drug, have both proven to be effective for the treatment of rheumatoid arthritis [54].
Ross River virus (RRV) is an arthitogenic alphavirus capable of causing outbreaks of debilitating musculoskeletal inflammatory disease in humans. RRV is the most common mosquito-borne disease in Australia, with outbreaks of RRV generally occurring during seasonal wet and warm conditions. Patients with Ross River virus disease (RRVD) typically present with fever, polyarthralgia, myalgia and a maculopapular erythematous rash. Treatment of the disease is usually palliative with no licensed vaccines or antiviral therapies currently available. In an effort to better inform therapeutic design, much progress has been made to understand the pathogenesis of RRVD. Progress has been largely driven by clinical evaluations supported by research using established murine models of RRVD, able to accurately replicate human disease. In this review we describe RRVD pathogenesis and the role of the host immune response, with particular focus on insights from studying animal models. We also discuss prospects for effective vaccines, preclinical development of therapeutic strategies and raise important questions for future RRV research.
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There are also no reported clinical trials for therapeutic management of horses or humans affected by RRV. Surveillance of human patients affected by RRV found that one half of affected people surveyed reported pain relief to be the most effective management of joint pain (36.4% reported NSAIDs provided the most relief, whereas 16.4% reported aspirin or paracetamol as providing the most effective relief) [14]. Rest was cited by 24.1% of human patients as their main source of relief.
Ross River virus (RRV), a mosquito-transmitted alphavirus prevalent in Australia, is believed to cause poor performance, lethargy, and muscle stiffness in Australian horses. However, disease progression and management is poorly documented. A better understanding of disease presentation, acute therapy, and long-term management is required. The aim of the study was to describe clinical presentation, diagnosis, acute treatment, and long-term management of RRV infection in horses. This study is a series of retrospective case reports. Clinical and diagnostic data were obtained from both veterinary records, and owner interviews for five performance horses that presented with acute poor performance coupled with serologic evidence of RRV exposure. Clinical and owner reports were evaluated from the time of presentation until the horses appeared asymptomatic and had returned to normal performance. Ross River virus was suspected to be the cause of generalized muscle stiffness and poor performance in five performance horses located in southeast Queensland between 2011 and 2015. Clinical symptoms included pyrexia, tachypnea, exercise intolerance, generalized muscle stiffness, synovial effusion, and edema of the lower limbs. Serologic investigations (ELISA and/or virus neutralization assay) detected antibody responses to RRV. Horses were treated with nonsteroidal anti-inflammatory drugs (n = 5) and disease-modifying osteoarthritis drugs (n = 2). Most horses returned to previous athletic capabilities between 7 and 12 months after the onset of symptoms. Not all horses in the study had preclinical serology or submitted paired blood samples for serology, meaning assumption of acute infection in those horses was made based on clinical signs coupled with positive serology. Ross River virus is a significant but poorly understood cause of poor performance in Australian horses. This report is the only one to document longitudinal management of performance horses affected by RRV infection. Much more research is needed to gain a better understanding of this infection in horses.
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No known locally acquired human mosquito-borne diseases have occurred in New Zealand, and reported cases of arboviral infections have been diagnosed exclusively in travellers. In this paper, we review the epidemiology of Ross River virus cases (RRV) in New Zealand and discuss the potential risk of local disease transmission.
Cases of RRV reported to the Notifiable Disease Surveillance system from 1997 to 2009 were analysed. Available data included demographics, travel history and mosquito avoidance behaviour. A total of 22 cases of RRV were reported, and included New Zealand residents returning home from overseas (20 cases, 14 to Australia, 5 to Fiji, 1 unknown destination) as well as international visitors (2 from Australia).
Reported cases of RRV confirm that New Zealand is vulnerable to virus importation. With several potential mosquito vectors, it is theoretically possible for a local “virgin soil” epidemic to occur. It is important for travellers, medical practitioners, and public health authorities to be aware of this threat, and take appropriate precautions to reduce the risk of a local epidemic. Protecting travellers from RRV is important from a travel medicine perspective, but also has potentially significant public health benefits for the general population.

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Acute symptoms and sequelae of Ross River virus infection in South-Western Australia: A follow-up study

Background

Objectives

Study design

Results

Conclusions

Clin. Rheum. Dis.

Epidemic polyarthritis in northeastern Australia, 1978–1979

Med. J. Aust.

I've suffered 11 years

Subiaco Post

Arbovirus infections in humans in New South Wales

Med. J. Aust.

Antigenic relationships of alphaviruses by a simple micro-culture cross-neutralisation method

J. Gen. Virol.

Annually recurrent epidemic polyarthritis and Ross River virus activity in a coastal area of New South Wales. I. Occurrence of the disease

Am. J. Trop. Med. Hyg.

A Review of Notifiable Infectious Diseases in Western Australia, 1985–89

Epi Info, Version 5.01b: a word processing, database and statistics program for epidemiology on microcomputers

Annually recurrent epidemic polyarthritis and Ross River virus activity in a coastal area of New South Wales. II. Mosquitoes, wildlife and viruses

Am. J. Trop. Med. Hyg.

A major outbreak of epidemic polyarthritis in New South Wales during the summer of 1983/84

Med. J. Aust.

Epidemiology in Medicine

Ross River virus (epidemic polyarthritis)