Arboviral arthritides Michael Wehrhahn Microbiology registrar Centre for Infectious Diseases and Microbiology ICPMR Westmead Hospital
Arboviral arthritides
Michael Wehrhahn Microbiology registrar
Centre for Infectious Diseases and MicrobiologyICPMR
Westmead Hospital
Fever and arthropathy
Arboviruses in Australia
• Togaviridae - alphaviruses– Ross River virus
– Barmah Forest virus
– Sindbis
• Flaviviridae• Flaviviridae– Dengue
– Kunjin strain of West Nile
– Murray Valley Encephalitis
– Japanese Encephalitis
– Alfuy, Kokobera, Stratford, Edge Hill
• Bunyaviridae – GanGan, Trubanaman
Arboviruses overseas
that can cause arthritis
• Alphaviruses
– Chikungunya (Asia/Africa)
– O’nyong-nyong (Africa)
– Mayaro (Central/S America)– Mayaro (Central/S America)
– West Nile virus (Americas, Europe, Asia,
Africa)
Alphaviruses
• many have subclinical infection
• all ages; males/females affected equally
• incubation 2-15d
• typical symptoms:• typical symptoms:
– fever, headache, retro-orbital pain, myalgia,
malaise
– rash: maculopapular or morbilliform
– arthropathy
Alphavirus arthropathy
• joint manifestations typically commence early and often incapacitating– soon after fever
– coincident with onset of rash
• symmetrical• symmetrical
• polyarticular: predom small jts– hands, wrists, feet and ankles
– may be migratory
– morning stiffness
• Last weeks to months
• differentiating the different arboviruses based on clinical features let alone pattern of arthritis difficult
• Recent review:
Outhred, Kok, Dwyer. Viral arthritides. Expert Rev Anti Infect Ther. 2011
Virus Location Mosquito
Vector
Incubatio
n Period
(days)
Distinguishing
Clinical
Features
Laboratory
Diagnosis
Ross River
(alphavirus)
Australia (PNG,
Pacific)
Aedes sp. and
Culex sp.5-15
Epidemic
polyarthritis,
chronicity, rash
Serology
(NAT, culture)
Barmah ForestAustralia
Aedes sp. and 5-15
Epidemic
polyarthritis, rash Serology
Arboviruses (Australia) associated with arthritis and rash
Barmah Forest
(alphavirus)Australia
Aedes sp. and
Culex sp.5-15
polyarthritis, rash
more prominent
than RRv, myalgia
Serology
(NAT, culture)
Sindbis
(alphavirus)
Europe, Africa,
Asia, AustraliaCulex sp. <7 Rash, paraesthesiae
Serology
(culture)
Chikungunya
(alphavirus)
Africa, Indian
Ocean, South and
SE Asia
Aedes sp. 1-12Arthritis
predominant
Serology, NAT
(culture)
Dengue
(flavivirus)
Asia, Central and
South America,
Nth Queensland
Aedes sp. 4-7
Fever, rash,
arthralgias, DHS in
repeat infections
ICT, NS1
antigen, serology,
NAT, (culture)
(rarely Kunjin/WNV, Kokobera, Alfuy, Edge Hill, Stratford viruses, Gan gan, Trubanaman)
4%
56%
29%
Ross River virus
• “Epidemic polyarthritis” first described in 1928 at Narrandera and Hay NSW
• isolated from Aedes mosquitoes trapped at Ross River, Townsville 1959
• Isolated from humans during large outbreak in • Isolated from humans during large outbreak in South Pacific Islands 1981
• Australia, – PNG, Soloman Islands, E Indonesia, Fiji, Samoa,
New Caledonia
• active throughout year in Qld, usually after summer rains/spring rest of Australia
• Aedes/Cules spp
Arthritis in RRV
• Fever, arthritis, rash syndrome
• True arthritis in 40%
• Joints of the extremities
• Symmetrical (although pain may be asymmetric)• Symmetrical (although pain may be asymmetric)
• Effusions, tendinitis, plantar fasciitis less
commonly
• Persist for >6mths in about half (10% for BFV)
• Pathogenesis:
– Persistance of virus in synovial macrophages
Barmah Forest virus
Barmah Forest virus
• Barmah Forest on Murray, northern Victoria 1974
• pathogenicity established in 1988 in setting of RRV neg epidemic polyarthritissetting of RRV neg epidemic polyarthritis
• 10% of of epidemic polyarthritis
• seroprevalence 6% mid/far north coast NSW highest rates in Aust (68/100000)
• Culex/Culicoides/Aedes spp
• inc 7-10d
• acute polyarthritis/arthralgia– symmetrical, lg and small jts
– less severe than RRV– less severe than RRV
– 90% resolution by 6mths (compare RRv)
• myalgia, fever, HA
• rash (often pruritic) in 50% (- 100%) sometimes vesicular (~7d)
• symptoms may persist for months
Clinical features of
RRv and BFv
Ross River virusBarmah Forest
virus
Maculopapular rash ~100% 90%
Vesicular rash uncommon 10%
Joint pain >1 month 79-98% 49%
Flexman J et al Med J Aust 1998; 169:159-63
Joint pain >1 month 79-98% 49%
Joint pain >6 months 57% >10%
Joint swelling,
stiffness61-80% 30%
Myalgia 43-79% 70-80%
Lymphadenopathy 0.6-29% 7%
Fatigue 62-94% 80%
Fever 20-60% <50%
Sindbis
• Sindbis village, Nile delta, Egypt 1952– subsequently Africa, India, SEAsia
– Australia 1960s – widespread seropositivity• seroprevalence less than RR
• majority are subclinical (a few Aust cases in lit)• majority are subclinical (a few Aust cases in lit)
• fever + rash (often vesicular), headache, sore throat, arthralgia/arthritis, parasthaesia
• ‘biblical 7 yr intervals’
• more recently cause of Pogosta disease (Finland)
• Sindbis-like viruses: Ockelbo (Sweden); Karelian (Russia) and Whataroa (NZ)
86 pts with confirmed
infection
50% with joint symptoms for
>12 mths
Chikungunya
• 1958 DR Congo; then 1999– becoming widespread
• fever, rash
• arthralgia/arthritis (~100%)
• symmetrical, predom smaller joints :– fingers, wrists, toes, ankles
– also large joints
– swelling and tenosynovitis common
– often incapacitating
• weeks to months (compare dengue)
•“that which bends/contorts”
•2005-7: large outbreak in
Indian Ocean Islands
esp Reunion
•35% of inhabitants infected
O’nyong-nyong
• “weakening of the joints”
• antigenically related to Chikungunya– transmitted by Anopheles spp
• initially isolated in Uganda 1959• initially isolated in Uganda 1959• epidemic involving >2 million in 1960s
• 2nd epidemic in 1995-6: 400 people
• Chad in 2006
• fever, polyarthritis and rash– also eye/chest pain, lymphadenopathy,
• related virus: Igbo-Ora “disease that breaks your wings”
•2003: febrile rash illness amongst Liberian refugees
in Cote d’Ivoire
•consisted of:•consisted of:
fever 28/31 (90%),
pruritus (71%),
mac-pap rash (84%),
myalgias (71%),
arthralgias (58%).
•ONNV (PCR/serol)
Mayaro virus
• first isolated in Caribbean
in 1950s as cause of
epidemic of febrile rash
illness causing
arthropathyarthropathy
• epidemics in Bolivia and
Brazil
– more recently Venezuela
2010 >70 cases
• TM: Haemagogus spp
Dengue
• flavivirus: Swahili for “Break bone fever”
• biphasic illness: fever, rash,
• arthralgia in 60-80%
– “severe musculoskeletal/lumbar back pain”– “severe musculoskeletal/lumbar back pain”
• Widespread incl North Queensland
West Nile virus & Kunjin
• flavivirus of JE group– isolated in 1937 from N
Uganda
• caused 200 deaths amongst 3500 cases in amongst 3500 cases in US in 2002
• widespread incl Aust (Kunjin subtype: 1960 Aborig tribe in Qld)
• Culex spp
West Nile fever
• inc 2-14d
• sudden onset flu-like illness
– fever, headache, backache, myalgias
– arthralgias, retro-orbital pain– arthralgias, retro-orbital pain
– rash, conjunctivitis, lymphadenopathy
• indistinguishable from Dengue
• typically self limited within 10d
• Neurologic disease in <1% infected
Summary
Arboviral arthritides– predominantly alphaviruses (togaviridae)
– symmetrical, predominantly smaller joints
– often associated with rash– often associated with rash
– may be incapacitating
– consider esp in epidemic setting
– Australian vs returned travellers
– prevention: mosquito avoidance
– supportive treatment
Acknowledgements
• Dominic Dwyer for loan of some slides
• Jen Kok/Alex Outhred for proof of in press article:
– Viral arthritides. Expert Rev Anti Infect Ther. – Viral arthritides. Expert Rev Anti Infect Ther.
2011