Objective: To describe the natural history, treatment and cost of Ross River virus‐induced epidemic polyarthritis (RRV disease). Design: Questionnaire‐based longitudinal prospective study. Participants and setting: Patients in the greater Brisbane area, Queensland, diagnosed with RRV disease by their general practitioners based on clinical symptoms and paired serological tests between November 1997 and April 1999. Main outcome measures: Scores on two validated quality‐of‐life questionnaires (Clinical Health Assessment Questionnaire and Medical Outcomes Study Short Form 36) were obtained soon after diagnosis and one, two, three, six and 12 months thereafter. Scores were compared between patients diagnosed with RRV disease alone and those with RRV disease plus other conditions. Results: 67 patients were enrolled. Most patients with RRV disease alone had severe acute symptoms, but followed a consistent path to recovery within three to six months. Other conditions, often chronic rheumatic diseases or depression, were identified in half the cohort; their quality‐of‐life scores suggested stable chronic illness between six and 12 months after diagnosis. Non‐steroidal anti‐inflammatory drugs (NSAIDs) were taken by 58% of patients (average use, 7.6 weeks; range, 2–22 weeks). Time off work averaged 1.9 days, and direct cost to the community was estimated as $A1018 per patient. Conclusions: Symptom duration and frequency of long‐term symptoms may have been overestimated by previous studies of RRV disease. Disease persisting six to 12 months after RRV diagnosis was largely attributable to other conditions, highlighting the need to seek other diagnoses in RRV patients with persistent symptoms.

The pharmacokinetics of primaquine have been well defined in male volunteers, but there is little data on the disposition of the drug in women. We compared the kinetics of primaquine in nine male and nine female healthy Australian volunteers after the administration of a single oral dose (30 mg base) of primaquine. No statistical differences were observed in the following kinetic parameters of primaquine between men and women, respectively: maximum plasma concentration (93 +/- 26 and 115 +/- 38 ng/mL; 95% confidence interval [CI] of the mean difference: -55 to 10 ng/mL; P = 0.16), area under the curve (1.1 +/- 0.5 and 1.2 +/- 0.4 microg x h/mL; 95% CI: -0.6 to 0.3 microg x h/mL; P = 0.54), and clearance (0.34 +/- 0.12 and 0.39 +/- 0.14 L/h/kg; 95% CI: -0.17 to 0.08 L/h/kg; P = 0.46). The clinical relevance of such findings would suggest that sex does not have to be taken into account as a factor when prescribing primaquine for radical cure or terminal prophylaxis of Plasmodium vivax malaria.

Two outbreaks of epidemic polyarthritis occurred among Australian Defence Force personnel during and following short military exercises in the Shoalwater Bay Training Area, northeastern Australia, in 2016 and 2017. Ross River virus (RRV) IgM was detected in acute-phase serum samples from most patients (28/28 in 2016 and 25/31 in 2017), and RRV was recovered from 4/38 serum samples assayed (1/21 in 2016 and 3/17 in 2017). Phylogenetic analyses of RRV envelope glycoprotein E2 and nonstructural protein nsP3 nucleotide sequences segregated the RRV isolates obtained in 2016 and 2017 outbreaks into 2 distinct sublineages, suggesting that each outbreak was caused by a different strain of RRV. The spatiotemporal characteristics of the 2016 outbreak suggested that some of the infections involved human-mosquito-human transmission without any intermediate host. These outbreaks highlight the importance of personal protective measures in preventing vectorborne diseases for which no vaccine or specific prophylaxis exists.

W ith ≈15,000 laboratory-confirmed cases over the last decade, Barmah Forest virus (BFV) is the second most common cause of human arboviral disease in Australia, after Ross River virus (RRV) (1). BFV is a positive-sense, single-strand, enveloped RNA virus of genus Alphavirus, family Togaviridae. Other viruses in this genus include chikungunya virus, RRV, Sindbis virus, and Eastern and Western equine encephalitis viruses. BFV was first isolated in 1974 from Culex annulirostris mosquitoes trapped near Barmah Forest, northern Victoria, Australia (2); the first case of a clinical BFV infection in humans was reported in 1986 (3). Since then, BFV has been reported throughout mainland Australia and Papua New Guinea (4,5). Clinical signs and symptoms of BFV infection, including polyarthritis, arthralgia, and myalgia, are similar to but milder than those of RRV infection (6-7). Through phylogenetic analyses of the nucleotide sequences of complete E2 envelope protein genes and of the 3′ untranslated region (3′ UTR), we identified 3 BFV lineages. However, we found only 1 example of 2 of the lineages (5,8). RRV caused epidemic polyarthritis outbreaks in military personnel in Australia during and after short military exercises in the Shoalwater Bay Training Area in northeastern Australia in 2016 and 2017 (9). The soldier in this study was among personnel who sought treatment during the 2017 outbreak with a suspected RRV infection. Signs and symptoms included rash on the face and body, nausea, headache, fatigue, lethargy, and joint and muscle pain. This retrospective study was approved by the Australian Department of Defence and Department of Veterans' Affairs Human Research Ethics Committee (DDVA HREC), Joint Health Command Low-Risk Ethical Review Panel (no. 16-021). We obtained formal written consent from the soldier. During a retrospective investigation of the outbreak, using PanBio ELISA kits (Abbott, https://www.abbott. com), we detected BFV IgG and IgM, but not RRV IgG and IgM, in convalescent serum samples collected 23, 28, and 38 days after onset of symptoms in the patient. After inoculating 100 µL of the serum into cultures of C6/36 mosquito cells and 2 subsequent passages in this cell line, we did not detect infectious virus in the acutephase serum sample collected on the day of symptom onset. However, we detected BFV RNA, but not RRV RNA, using a quantitative reverse-transcription PCR assay of RNA extracted from 140 µL of the acute-phase sample using a QiaAMP Viral RNA Mini Kit (QIA-GEN, https://www.qiagen.com). BFV E2 RNA was present at 4.2 ×10 6 copies/mL, with a forward primer 8985F (5′-AGTGTGGCAGTACAACTCCCAAT-3′) corresponding to genome position 8985-9006 and a reverse primer (5′-AAGGCACATGGATCTTTCCTTTC-3′) corresponding to genome position 9036-9058. For sequencing, we amplified the E2 and 3′ UTR genes by reverse transcription PCR using primers E2 forward 8205F 5′-GCTGTCTGACCACTACTACCA-3′ and E2 reverse 9833R 5′-GACTTAATCACTACTA-AAGATAGCG-3′, and 3′ UTR forward 10923F 5′-TC-CATCCATCTCTACTACCG-3′ and reverse poly-T