Original articles ROSS RIVER VIRUS INFECTION SURVEILLANCE IN THE GREATER PERTH METROPOLITAN AREA – HAS THERE BEEN AN INCREASE IN CASES IN THE WINTER MONTHS? Linda A Selvey, Jenny A Donnelly, Michael D Lindsay, Sudha Pottumarthy Boddu, Victoria C D’Abrera, David W Smith Abstract Western Australian Notifiable Infectious Diseases An increase in off-season (June to September) Database (WANIDD). The serological component Ross River virus (RRV) notifications from the greater of the case definition is: RRV-IgG seroconversion Perth metropolitan area was observed from 2006 or a fourfold rise in RRV-IgG between acute and to 2009. We investigated the increase to determine convalescent samples; detection of RRV IgG and whether it is likely to have reflected a true increase IgM in a single sample; or detection of RRV-IgM in off-season cases. A single positive RRV IgM test without IgG when there is no detectable IgM to result is sufficient for RRV notification but where Barmah Forest virus (BFV). follow-up testing was performed, the positive pre- dictive value of an IgM test where IgG was nega- From 2006 onwards, all laboratories in Western tive was very low in the off-season and also in the Australia were legislatively required to directly notify season when using the only commercially available cases. Prior to that date, notifiable diseases were test kit. The increase in off-season notifications was notified by doctors based on clinical and/or labora- not associated with an increase in off-season test- tory diagnoses, and in the early 2000s by the only ing. Some Perth laboratories use more stringent public sector testing laboratory (PathWest Laboratory notification criteria than the nationally agreed RRV Medicine WA) and some private laboratories. case definition, and the geographical distribution of samples tested varies between laboratories. Local governments and the Environmental Health Our findings make a strong case to change the Directorate of WA Health undertake enhanced nationally agreed case definition for RRV to not surveillance of RRV cases notified by treating doc- accept a single IgM positive test result as labora- tors, to identify the most likely place of exposure tory definitive evidence where the IgG is negative. and date of onset of symptoms. This information is Our study also identified a range of challenges in recorded in the Mosquito Borne Disease Control interpreting changes in seasonal patterns and geo- (MBDC) database. graphical distribution of RRV. Any such observed changes should be investigated through further In the south-west of Western Australia, RRV data analysis and/or mosquito trapping and test- typically causes outbreaks of varying sizes between ing in order to assess validity. Commun Dis Intell October and May. In 2006 it was observed that the 2014;38(2):E115–E122. number of RRV notifications reported during the off-season (June to September) were higher than Keywords: Ross River virus, surveillance, expected in the Perth Metropolitan region and the notifications, serology Peel region immediately south of Perth (Figure 1). Introduction In Western Australia, RRV notifications are used to identify areas of high RRV activity to enable addi- Ross River virus (RRV) is a mosquito-borne tional mosquito control activity and public warnings. alphavirus infection that occurs throughout Notification data are complemented by mosquito Australia and the South Pacific.1,2 It causes an surveillance in areas of historically high activity over acute illness characterised by joint pain, arthritis, summer. A change in the distribution of RRV cases to fatigue and malaise, often accompanied by fever include the off-season in the south-west is potentially and a rash. While not life-threatening, RRV can very important as it could flag changes in the ecol- cause significant morbidity, with symptoms lasting ogy of vector mosquitoes and animal hosts. This has up to 6 months.1–3 implications for human health and for risk mitigation activities such as mosquito control. RRV is a nationally notifiable disease. Laboratories and treating doctors are required to report to the This study examined the notification data and Western Australian Department of Health (WA laboratory testing data, assessing whether the Health), all cases of RRV infection meeting the notifications reflected a real increase in off-season nationally agreed case definition.4 In Western RRV cases or an artefact of testing and/or notifica- Australia, notifications are recorded in the tion practices. CDI Vol 38 No 2 2014 E115 Original articles Methods published by the National Pathology Accreditation Advisory Council, and have been approved for This was a descriptive study. diagnostic use by the National Association of Testing Authorities. The sensitivity and specificity Notification rates of these tests is not known. Both tests are routinely performed on samples referred for RRV diagnosis. RRV notifications for the Perth Metropolitan and All but one laboratory (which refers their samples Peel regions by laboratory, month and year of to PathWest), including SJGP, use a commercial onset from 1 January 1990 to 30 June 2012 were enzyme immunoassay (EIA); Panbio® RRV IgM retrieved from WANIDD. Population data at ELISA and Panbio® RRV IgG ELISA (Alere, Statistical Local Area level were obtained from Sinnamon Park, Queensland Australia). The sen- the Australian Bureau of Statistics and aggre- sitivity and specificity of these tests was estimated gated into MBDC regions. Notification rates per in South Australia by testing samples taken in 1996 100,000 population were calculated by dividing the and 1997 using an HI test as the comparator. The number of notifications in that time period by the sensitivity of the PanBio ELISA kits was estimated estimated population for that year and multiplying to be 98.5% and 84.6% and the specificity 96.5% by 100,000, and were annualised by multiplying and 97.6% for IgM and IgG respectively.7 These the rate by 12 divided by the number of months. are the only commercial tests currently available in Australia. In response to a doctor’s request for RRV Enhanced surveillance data serology, all private laboratories test separately for IgM and IgG antibodies. Notification data by month and year of onset and region of acquisition as documented by enhanced PathWest routinely requests second samples where surveillance were retrieved from the MBDC the sample is IgM positive within 2 weeks of onset of database for the years 2006 to 2009 inclusive. illness independent of the HI test result. This allows The enhanced surveillance data were compared detection of seroconversion or a significant rise in with the notification data to assess whether hav- IgG using the HI tests to confirm acute infection. ing further information about the onset date and SJGP requests second samples where the initial IgM likely place of acquisition of infection changed the is positive but the IgG is negative in order to test proportion of off-season notifications in the Perth for seroconversion. The EIA tests do not quantify Metropolitan and Peel regions. results and cannot be routinely used to detect rises in IgG, but will detect seroconversion. Laboratory testing A more detailed analysis of positive IgM results was Laboratory testing data for the Perth Metropolitan carried out for patients from the Perth Metropolitan and Peel regions for the period from 1 January and Peel regions. Patients who had results for more 2002 to 31 August 2012 were obtained from than 1 sample were identified and the results were PathWest Laboratory Medicine WA (PathWest) used to assess the interpretation of the first IgM and St John of God Pathology (SJGP). PathWest positive sample for each patient. (Table 1). is the state reference laboratory. It uses an in-house immunofluorescence assay (IFA) for the detection Notification practices of the laboratories of IgM antibodies,5 and an in-house haemagglu- tination inhibition (HI) test.6 The latter detects The three private laboratories (SJGP and both IgG and IgM together and is less sensitive Laboratory B and C) and PathWest who, combined, than the IFA for detection of IgM.6 The in-house notify the majority of RRV cases, were contacted to assays have been validated according to guidelines ask about their notification practices for RRV. Table 1: Classification of Ross River virus IgM positive test results following follow-up testing Classification PathWest Private True positive Seroconversion from negative IgG (HI <40) to IgM with IgG seroconversion OR IgM and IgG positive OR HI ≥40 and a fourfold or greater rise in positive on initial and a later sample HI titre between acute and convalescent samples OR HI ≥40 on first and second samples False positive HI ≤40 on second sample seven or more days IgG negative on repeat testing seven or more days after the first test OR IgM becomes negative within after the first positive IgM test OR IgM becomes 6 months of the first test OR patient is known to negative within 6 months of the first test have past Ross River virus infection The positive predictive value of the test was calculated by the formula: true positive/(true positive + false positive). E116 CDI Vol 38 No 2 2014 CDI year and month regions, by Peel and Metropolitan Perth River, Ross rate Notification Figure 1: ( region Peel the for 59.6 vs 88.7 region; Metropolitan Perth the for 18.3 vs 23.4 of (mean years with other the compared 2006 2009 the to period for season the during rates notification in the difference significant no was ( region Peel the for 10.6 vs 37.6 region; Metropolitan Perth the for 2.4 vs 11.6 of (mean years other the to 20092006 compared and between years in the higher were regions Peel and Metropolitan in Perth off-season in the rates tion notifica 236,000. The was region Peel in the and people million 1.6 was in 2012 region Metropolitan Perth in the population The 2012.