# Ross River Virus Antibody Prevalence, Fiji Islands, 2013–2015

Maite Aubry, Mike Kama, Jessica Vanhomwegen, Anita Teissier, Teheipuaura Mariteragi-Helle, Stéphane Hue, Martin L Hibberd, Jean-Claude Manuguerra, Ketan Christi, Conall Watson, et al.

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To cite this version:

Maite Aubry, Mike Kama, Jessica Vanhomwegen, Anita Teissier, Teheipuaura Mariteragi-Helle, et al. Ross River Virus Antibody Prevalence, Fiji Islands, 2013–2015. Emerging Infectious Diseases, 2019, 25 (4), pp.827-830. 10.3201/eid2504.180694. hal-02263771

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Distributed under a Creative Commons Attribution 4.0 International License
nos. MG808405-MG808410). BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi) and phylogenetic analyses of the segment 2 sequences showed that the EHDV recently isolated in cattle in Israel belongs to serotype 1 and is closely related to the IbAr22619 strain from Nigeria, with which it shares 95.72%–95.76% identity (Figure).

Retrospective analysis of clinical signs in EHDV-1-infected cattle enabled us to conclude that in many farms EHDV infection was asymptomatic or subclinical; milk-yield reduction, fever, and recumbency were the only prominent clinical signs observed during the outbreak. However, animals with BTV and EHDV co-infections showed more severe clinical signs, including fever, abortion, lameness, subcutaneous emphysema, and death.

During recent years, several new arboviruses have been detected in Israel that were not identified previously. BTV serotype 3 was first identified in 2016 but probably was present in Israel since at least 2013 (9), EHDV serotype 6 was identified in 2015 (6), EHDV serotype 1 was found in 2016, and Shuni virus was detected in 2014 (10). These findings showed that new introductions of arthropodborne viral infections into the Middle East region had occurred. Molecular epidemiologic data indicate the viruses originated in Africa, as ours and other studies (5,6) have shown. Molecular diagnostics, vector-control strategies, and epidemiologic studies should be implemented in Israel to mitigate potential risk for future outbreaks.

## About the Authors

Drs. Golender and Bumbarov are virologists in the Virology Department of the Kimron Veterinary Institute, Beit Dagan, Israel. Their primary research interests include the investigation of arboviral infections caused by viruses of the *Reoviridae* (Orbiviruses) family and the *Peribunyaviridae* (Orthobunyavirus, Simbu serogroup viruses) family, which affect ruminant populations, and developing diagnostic methods to detect these viruses.

## References

1. Savini G, Afonso A, Mellor P, Aradaib I, Yadin H, Sanaa M, et al. Epizootic haemorrhagic disease. Res Vet Sci. 2011;91:1–17. http://dx.doi.org/10.1016/j.rvsc.2011.05.004

2. Weir RP, Harmsen MB, Hunt NT, Blacksell SD, Lunt RA, Pritchard LI, et al. EHDV-1, a new Australian serotype of epizootic haemorrhagic disease virus isolated from sentinel cattle in the Northern Territory. Vet Microbiol. 1997;58:135–43. http://dx.doi.org/10.1016/S0378-1135(97)00155-7

3. Cêtre-Sossah C, Roger M, Sailleau C, Rieau L, Zientara S, Bréard E, et al. Epizootic haemorrhagic disease virus in Reunion Island: evidence for the circulation of a new serotype and associated risk factors. Vet Microbiol. 2014;170:383–90. http://dx.doi.org/10.1016/j.vetmic.2014.02.007

4. Subramaniam K, Lednicky JA, Loeb J, Sayler KA, Wisely SM, Waltzek TB. Genomic sequences of epizootic hemorrhagic disease viruses isolated from Florida white-tailed deer. Genome Announc. 2017;5:e01174-17. http://dx.doi.org/10.1128/genomeA.01174-17

5. Yadin H, Brenner J, Bumbarov V, Oved Z, Stram Y, Klement E, et al. Epizootic haemorrhagic disease virus type 7 infection in cattle in Israel. Vet Rec. 2008;162:53–6. http://dx.doi.org/10.1136/vr.162.2.53

6. Golender N, Khinich Y, Gorohov A, Abramovitz I, Bumbarov V. Epizootic hemorrhagic disease virus serotype 6 outbreak in Israeli cattle in 2015. J Vet Diagn Invest. 2017;29:885–8. http://dx.doi.org/10.1177/1040638717726826

7. Golender N, Bumbarov VY, Erster O, Beer M, Khinich Y, Wernike K. Development and validation of a universal S-segment-based real-time RT-PCR assay for the detection of Simbu serogroup viruses. J Virol Methods. 2018;261:80–5. http://dx.doi.org/10.1016/j.jviromet.2018.08.008

8. Kumar S, Stecher G, Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33:1870–4. http://dx.doi.org/10.1093/molbev/msw054

9. Golender N, Eldar A, Khinich Y, Kenigswald G, Bumbarov V. Novel topotypes of bluetongue serotype 3 viruses in the Mediterranean Basin. In: Abstracts of the 11th EPIZONE Annual Meeting, Paris, France, 2017 Sep 19–21. Abstract C1; p. 26.

10. Golender N, Brenner J, Valdman M, Khinich Y, Bumbarov V, Panshin A, et al. Malformations caused by Shuni virus in ruminants, Israel, 2014–2015. Emerg Infect Dis. 2015;21:2267–8. http://dx.doi.org/10.3201/eid2112.150804

Address for correspondence: Natalia Golender, Kimron Veterinary Institute, Beit Dagan 50250, POB 12, Israel; email: golendern@moag.gov.il

# Ross River Virus Antibody Prevalence, Fiji Islands, 2013–2015

Maite Aubry, Mike Kama, Jessica Vanhomwegen, Anita Teissier, Teheipuaura Mariteragi-Helle, Stephane Hue, Martin L. Hibberd, Jean-Claude Manuguerra, Ketan Christi, Conall H. Watson, Eric J. Nilles, Colleen L. Lau, John Aaskov, Didier Musso, Adam J. Kucharski, Van-Mai Cao-Lormeau

Author affiliations: Institut Louis Malardé, Papeete, French Polynesia (M. Aubry, A. Teissier, T. Mariteragi-Helle, D. Musso, V.-M. Cao-Lormeau); Fiji Centre for Communicable Disease Control, Suva, Fiji (M. Kama); The University of the South Pacific, Suva (M. Kama, K. Christi); Institut Pasteur, Paris, France (J. Vanhomwegen, J.-C. Manuguerra); London School of Hygiene and Tropical Medicine, London, UK (S. Hue, M.L. Hibberd, C.H. Watson, A.J. Kucharski); World Health Organization Division of Pacific Technical Support, Suva (E.J. Nilles); Harvard Medical School and Brigham and Women's Hospital, Boston,
Massachusetts, USA (E.J. Nilles); Harvard Humanitarian Initiative, Cambridge, Massachusetts (E.J. Nilles); Queensland University of Technology, Brisbane, Queensland, Australia (J. Aaskov); Australian National University, Canberra, Australian Capital Territory, Australia (C.L. Lau); Aix Marseille Université, IRD, AP-HM, SSA, VITROME, IHU-Méditerranée Infection, Marseille, France (D. Musso)

DOI: https://doi.org/10.3201/eid2504.180694

A unique outbreak of Ross River virus (RRV) infection was reported in Fiji in 1979. In 2013, RRV seroprevalence among residents was 46.5% (362/778). Of the residents who were seronegative in 2013 and retested in 2015, 10.9% (21/192) had seroconverted to RRV, suggesting ongoing endemic circulation of RRV in Fiji.

Ross River virus (RRV) is an *Alphavirus* of the family *Togaviridae* and is transmitted to humans by *Aedes* and *Culex* mosquitoes (1). Marsupials are considered important reservoirs of RRV (1). Clinical manifestations of RRV infections include fever, rash, and arthralgia. RRV is endemic to Australia, where it causes ≈5,000 cases of epidemic polyarthritis annually (1). Outbreaks of RRV infection were reported during 1979–1980 in Fiji, the Cook Islands, American Samoa, New Caledonia, and Wallis and Futuna (1–3). Subsequently, RRV infections were detected in travelers returning from Fiji during 1997–2009 (3) and in patients with suspected dengue in Fiji in 2005 (4).

The Republic of the Fiji Islands comprises 322 islands distributed among 4 administrative divisions (Central, Western, Eastern, and Northern) and has a population of

≈830,000. Apart from RRV, the 4 serotypes of dengue virus were the only mosquitoborne viruses known to circulate in Fiji until the recent emergence of Zika and chikungunya viruses (5). We report evidence of endemic RRV circulation in Fiji on the basis of serologic analysis of blood samples collected in 2013 and 2015.

Our study included 778 participants recruited during September–November 2013 from the Central, Western, and Northern divisions for a community-based serosurvey for leptospirosis and typhoid (6). Among the residents from the Central division who had participated in the 2013 survey, 333 had blood drawn again during October–November 2015, including 311 whose serum sample collected in 2013 was available for testing. We tested all blood samples for RRV IgG by using a recombinant antigen-based microsphere immunoassay (7). We analyzed the data with GraphPad Prism 6.03 using the Fisher or χ² test. We considered p values <0.05 to be significant.

The prevalence of RRV antibodies among participants in 2013 was 46.5% and was lower in the Central (38.1%) than the Western (58.6%; p<0.0001) and Northern (55.9%; p = 0.0108) divisions (Table). The prevalence of RRV antibodies among the participants sampled in the Central division in 2015 (37.2%) was similar to results from this division in 2013 (38.1%). In 2013, a total of 37.4% of the participants born after 1982 (postoutbreak) had RRV antibodies, and this rate in 2015 (26.9%) was not significantly different (p = 0.0685). The prevalence of RRV antibodies increased with age (p<0.0001 in 2013, p = 0.0020 in 2015) and was higher in rural than in urban (p<0.0001 in 2013, p = 0.0197 in 2015) and periurban areas (p = 0.0060 in 2013). No difference by sex was observed. Among the 311 participants with available serum

<table><caption>**Table.** Prevalence of Ross River virus antibodies in a representative subset of the population of Fiji sampled during September–November 2013 (n = 778) and October–November 2015 (n = 333)*</caption><thead><tr><th rowspan="2">Variable</th><th colspan="2">No. seropositive/mo. tested (% [95% CI])</th></tr><tr><th>2013</th><th>2015</th></tr></thead><tbody><tr><td>Birth year</td><td></td><td></td></tr><tr><td>&lt;1982</td><td>197/336 (58.6 [53.4–63.9])</td><td>68/144 (47.2 [39.6–55.7])</td></tr><tr><td>&gt;1982</td><td>165/441 (37.4 [32.9–42.1])</td><td>56/189 (29.6 [23.2–36.7])</td></tr><tr><td>1982–1990</td><td>58/117 (49.6 [41.1–58.9])</td><td>17/38 (44.7 [31.4–61.4])</td></tr><tr><td>1991–2000</td><td>66/146 (45.2 [37.7–53.6])</td><td>20/66 (30.3 [21.3–42.9])</td></tr><tr><td>2001–2010</td><td>40/170 (23.5 [18.1–30.7])</td><td>19/83 (22.9 [15.8–33.5])</td></tr><tr><td>&gt;2011</td><td>1/8 (12.5 [0.3–52.7])</td><td>0/2 (0.0 [0.0–84.2])</td></tr><tr><td>Sex</td><td></td><td></td></tr><tr><td>F</td><td>195/423 (46.1 [41.5–51.0])</td><td>73/190 (38.4 [32.1–45.8])</td></tr><tr><td>M</td><td>167/354 (47.5 [42.2–52.5])</td><td>51/143 (35.7 [28.6–44.1])</td></tr><tr><td>Division</td><td></td><td></td></tr><tr><td>Central</td><td>172/451 (38.1 [33.9–42.8])</td><td>124/333 (37.2 [32.4–42.7])</td></tr><tr><td>Northern</td><td>33/59 (55.9 [44.1–68.7])</td><td>ND</td></tr><tr><td>Western</td><td>157/268 (58.6 [52.8–64.5])</td><td>ND</td></tr><tr><td>Zone</td><td></td><td></td></tr><tr><td>Rural</td><td>189/344 (54.9 [49.8–60.3])</td><td>52/113 (46.0 [37.5–55.6])</td></tr><tr><td>Periurban</td><td>55/135 (40.7 [33.2–49.5])</td><td>27/77 (35.1 [26.0–46.8])</td></tr><tr><td>Urban</td><td>117/298 (39.3 [34.1–45.1])</td><td>45/143 (31.5 [24.8–39.8])</td></tr><tr><td>Total</td><td>362/778† (46.5 [43.1–50.1])</td><td>124/333 (37.2 [32.4–42.7])</td></tr></tbody></table>

<footnote>*ND, no data (participants were not recruited from the Northern and Western divisions in 2015).</footnote>

<footnote>†For 1 participant, information about age and sex were not available; for another participant, information about the zone of residence was not available.</footnote>
samples collected in both 2013 and 2015, a total of 21 (10.9%) of the 192 participants who had no detectable RRV antibodies in 2013 had seroconverted to RRV by 2015 (data not shown).

A serosurvey conducted after the RRV outbreak in Fiji in 1979 detected RRV antibodies in 92% of the participants from the Western division (2). In our study, which was conducted in 2013, RRV antibody prevalence in the Western, Central, and Northern divisions ranged from 38.1% to 58.6%, and 37.4% of persons born after 1982 had RRV antibodies, suggesting that RRV circulated in all 3 divisions after the 1979 outbreak. The report of RRV infection in travelers or inhabitants from Fiji during 1997–2009 (3,4), the observations that 10.9% of the sero-negative participants in our study seroconverted to RRV during 2013–2015, and the increase in the prevalence of RRV antibodies with age, strongly suggest endemic RRV transmission in Fiji.

The finding that RRV seroprevalence was higher in rural than in urban and periurban environments suggests increased transmission risks in the rural areas, potentially because of higher-risk occupations of rural residents (including farming and outdoor work), greater exposure related to rural housing or other environmental factors, greater animal reservoir density, the possibility that non-domestic mosquito species in Fiji such as *Aedes vigilax*, *Ae. polynesiensis*, *Ae. pseudoscutellaris*, *Ae. albopictus*, and *Culex annulirostris* might be more competent vectors of RRV than peridomestic mosquito species such as *Ae. aegypti* (8).

Serosurveys conducted in American Samoa in 2010 (1), in French Polynesia during 2011–2013 (9) and 2014–2015 (7), and our study in Fiji during 2013–2015 suggest that endemic circulation of RRV in the Pacific region continued, or recommenced, after 1979–1980. These data provide further evidence for endemic transmission of RRV in areas where marsupials are absent (10). Because of extensive travel between Australia and the Pacific Islands, it is plausible that RRV is repeatedly seeded into the Pacific region. Whether this plays an important role in perpetuating local transmission in the Pacific Islands is unknown. As previously illustrated with Zika and chikungunya viruses, a risk exists for emerging arboviruses to be imported from the Pacific to other parts of the world, and RRV could be the next unexpected threat.

This work was part of ISID-Pacific and R-ZERO Pacific programs funded by the French Ministry for Europe and Foreign Affairs (Pacific Funds nos. 06314-09/04/14, 12115-02/09/15, 03016-20/05/16, and 04917-19/07/17). The study also received support from the Embassy of France in the Republic of the Fiji Islands. The study was supported by the French Government's Investissement d'Avenir Program (Labex IBEID no.

ANR-10-LABX-62-IBEID). C.L.L. was supported by an Australian National Health and Medical Research Council Fellowship (no. 1109035). Fieldwork in 2013 was funded by the World Health Organization Western Pacific Region and by the Chadwick Trust. C.H.W. was supported by the UK Medical Research Council (grant no. MR/J003999/1). A.J.K. was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (grant no. 206250/Z/17/Z).

The study was approved by the Fiji National Health Research Ethics Review Committee (FNRER/no. 2015.114.NW and FNRER/no. 2015.45.MC), the University of the South Pacific (FSTER/2015/10/Research Proposal Approval), and the London School of Hygiene and Tropical Medicine Observational Research Ethics Committee (approval nos. 6344 and 10207).

## About the Author

Dr. Aubry is a research scientist at the Institut Louis Malardé, Papeete, French Polynesia. Her research interests include the prevalence, epidemiology, and genetic evolution in the Pacific region of various arboviruses, such as dengue, Zika, chikungunya, and Ross River viruses.

## References

1. Lau C, Aubry M, Musso D, Teissier A, Paulous S, Desprès P, et al. New evidence for endemic circulation of Ross River virus in the Pacific Islands and the potential for emergence. Int J Infect Dis. 2017;57:73–6. http://dx.doi.org/10.1016/j.ijid.2017.01.041

2. Aaskov JG, Mataika JU, Lawrence GW, Rabukawaqa V, Tucker MM, Miles JA, et al. An epidemic of Ross River virus infection in Fiji, 1979. Am J Trop Med Hyg. 1981;30:1053–9. http://dx.doi.org/10.4269/ajtmh.1981.30.1053

3. Lau C, Weinstein P, Slaney D. Imported cases of Ross River virus disease in New Zealand—a travel medicine perspective. Travel Med Infect Dis. 2012;10:129–34. http://dx.doi.org/10.1016/j.tmaid.2012.04.001

4. Ngwe Tun MM, Inoue S, Thant KZ, Talemaitoga N, Aryati A, Dimaano EM, et al. Retrospective seroepidemiological study of chikungunya infection in South Asia, Southeast Asia and the Pacific region. Epidemiol Infect. 2016;144:2268–75. http://dx.doi.org/10.1017/S095026881600056X

5. Cao-Lormeau V-M, Musso D. Emerging arboviruses in the Pacific. Lancet. 2014;384:1571–2. http://dx.doi.org/10.1016/S0140-6736(14)61977-2

6. Lau CL, Watson CH, Lowry JH, David MC, Craig SB, Wynwood SJ, et al. Human leptospirosis infection in Fiji: an eco-epidemiological approach to identifying risk factors and environmental drivers for transmission. PLoS Negl Trop Dis. 2016;10:e0004405. http://dx.doi.org/10.1371/journal.pntd.0004405

7. Aubry M, Teissier A, Huart M, Merceron S, Vanhomwegen J, Roche C, et al. Ross River virus seroprevalence, French Polynesia, 2014–2015. Emerg Infect Dis. 2017;23:1751–3. http://dx.doi.org/10.3201/eid2310.170583

8. Mitchell CJ, Teissier DJ. Vector competence of geographic strains of *Aedes albopictus* and *Aedes polynesiensis* and certain other *Aedes* (*Stegomyia*) mosquitoes for Ross River virus. J Am Mosq Control Assoc. 1987;3:142–7.
9. Aubry M, Finke J, Teissier A, Roche C, Broult J, Paulous S, et al. Silent circulation of Ross River virus in French Polynesia. Int J Infect Dis. 2015;37:19–24. http://dx.doi.org/10.1016/j.ijid.2015.06.005

10. Stephenson EB, Peel AJ, Reid SA, Jansen CC, McCallum H. The non-human reservoirs of Ross River virus: a systematic review of the evidence. Parasit Vectors. 2018;11:188. http://dx.doi.org/10.1186/s13071-018-2733-8

Address for correspondence: Van-Mai Cao-Lormeau, Institut Louis Malardé, PO Box 30, 98713 Papeete, Tahiti, French Polynesia; email: mlormeau@ilm.pf

# Malignant Aspergillus flavus Otitis Externa with Jugular Thrombosis

Maxime Moniot, Marion Montava, Stéphane Ranque, Ugo Scemama, Carole Cassagne, Varoquaux Arthur

Author affiliations: Aix-Marseille University, Marseille, France (M. Moniot, S. Ranque, C. Cassagne); La Conception University Hospital, Marseille (M. Montava, U. Scemama, V. Arthur)

DOI: https://doi.org/10.3201/eid2504.180710

We report a case of malignant otitis externa with jugular vein thrombosis caused by *Aspergillus flavus*. Magnetic resonance imaging revealed an unusual ink smudge pattern deep in a cervical abscess. The pattern was consistent with mycetoma and may be important for diagnosing these life-threatening infections.

A 73-year-old male patient sought care from the otolaryngology department at University Hospital, Marseille, France. He had a 5-month history of malignant otitis externa (MOE), which was worsening despite 4 months of treatment with intravenous ceftazidime, oral ciprofloxacin, and topical neomycin, polymyxin B, dexamethasone, and thiomersal combination. The patient had a history of high blood pressure, treated with perindopril and nicardipine, and diabetes mellitus, inadequately controlled (hemoglobin A1c 7.7%) with metformin and sitagliptin.

The patient was admitted, and otoscopic examination found otorrhea, inflammation, and stenosis of the right

external auditory canal; we could not see the tympanic membrane. Examination of the cranial nerve was normal. Pure-tone audiogram showed a right mixed hearing loss with air-bone gap at 15 dB and symmetric bone curve by presbycusis. Laboratory testing showed elevated erythrocyte sedimentation level (42 mm at 1 h, 82 mm at 2 h) and leukocytosis (11 g/L); C-reactive protein results were within reference range. A computed tomography (CT) scan of the head showed thickening of the ear skin; focal tympanal bone osteolysis; partial right mastoid air cells and middle-ear cavity opacification; and osteolysis of the occipital, styloid, and mastoid bones consistent with MOE (Appendix Figure, https://wwwnc.cdc.gov/EID/article/25/4/18-0710-App1.pdf). Magnetic resonance imaging (MRI) with contrast media confirmed skull base osteomyelitis, evidenced by bone lysis and marrow enhancement of the clivus (Figure, panels A–C). Both MRI and CT showed a right jugular vein thrombosis and cellulitis and abscess in the carotid and perivertebral spaces. Abscess content had an unusual aspect: T2-weighted imaging signal void foci surrounded by a hypersignal rim.

We treated the right jugular vein thrombosis with enoxaparin. The patient underwent surgical debridement with facial nerve monitoring; we collected transmastoid biopsy samples and pus for microbiological analysis and inserted a transtympanic aerator. Direct microscopic examination of the samples showed hyaline septate hyphae consistent with hyalohyphomycosis. Biopsy samples grew 2 bacteria, *Corynebacterium striatum* and *Enterococcus faecalis*, and 1 filamentous fungus, *Aspergillus flavus*, that we identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Microflex LT, https://www.bruker.com) against an in-house database described by Normand et al. (1). Etest antifungal susceptibility testing (bioMérieux, https://www.biomerieux.com) showed that the *A. flavus* strain was sensitive to voriconazole (MIC 0.380 mg/L) and resistant to amphotericin B (MIC 12 mg/L). We stopped administration of auricular drops, continued intravenous ceftazidime (1.5 g/d) and oral ciprofloxacin (1.5 g/d), and started voriconazole therapy (6 mg/kg/12 h intravenously, followed by 400 mg/d orally). Otalgia, otorrhea, and inflammatory external auditory canal symptoms were relieved, and the patient recovered after 6 weeks. No further follow-up was available.

Fungi cause ≈10% of MOE (2). The 3 leading species, by decreasing frequency, are *A. fumigatus*, *A. flavus*, and *A. niger* (3). *A. flavus* is more frequently involved in MOE than is *A. niger* (3,4).

Jugular vein thrombosis (JVT) was previously reported in MOE (5) and other conditions such as Lemierre syndrome, invasive fungal infection, or any inflammatory process including otitis media. Various pathogens can cause JVT, especially *Fusobacterium necrophorum* and zygomycetes.