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