Chikungunya Fever:
Re-emerging vectorborne disease
Margaret McLees, M.D., DTMH
Denver Public Health
January 17, 2014
Outline
 Case Presentation
 Epidemiology
 Presentation
 Diagnosis
 Treatment and Prevention
 Implications for our Travelers
Case
 65 yo female with fevers, rash, and arthralgias
 12-day trip to Bali, Indonesia, returned 2 days prior
 Day 12 developed severe arthralgias and arthritis
 Sick contact: landlord found down, dx’d with viral illness
 Traveled from Bali to Hong Kong
 Admitted in Hong Kong for 3 days
 Persistent severe arthralgias, 1 day diarrhea
 Rash
 Paracetamol, diclofenac, ranitidine
Case, continued
 Returned to Denver with ongoing rash and arthralgias,
resolution of fevers
 Medications: oral hormone replacement
 PMH: Migraines
 Social Hx: tourist activities while traveling, no bad habits,
+insect bites, no animal exposures, no freshwater/saltwater
exposures
 Afebrile on exam
 Conjunctival erythema
 Facial edema and rash
 Upper and lower extremity edema
Case: Rash
Case: Rash
Case: Laboratory data
 WBC 3.4, 8% bands, plt 109, AST 68
 Malaria smear negative
 Electrolytes, kidney, liver function, urinalysis normal
 Typhoid & paratyphoid by Widal test, Influenza A&B,
Dengue IgM, Brucella abortus Ag by Weil Felix,
respiratory virus panel negative
 CXR: blunted right costophrenic angle, no infiltrates or
consolidation
Clinical diagnosis:
Chikungunya Fever
 Serologies sent to CDC for arboviruses likely to be
present in SE Asia
 Ross River virus
 Dengue
 Chikungunya
 Japanese encephalitis virus
 IgM positive to multiple viruses on acute sample
 Chikungunya, Barmah Forest and Ross River Virus
 Chikungunya IgM, IgG positive on convalescent
samples in May
Chikungunya Virus (CHIKV):
Alphavirus
 “That which bends up” in
Swahili
 Togaviridae family
 Single strand RNA virus,
mosquito-transmitted
 New World: Fever, rash,
encephalitis
 Western equine encephalitis
 Eastern Equine encephalitis
 Old World: Fever, rash,
arthralgias
 Chikungunya
 Ross River Virus (Oceana)
 Barmah Forest Virus (AUS)
 O’nyong-nyong (Africa)
 Semliki Forest Virus (Africa)
 Mayoro (South America)
 Sindbis virus (AUS, Africa,
Europe, Asia minor)
www.cdc.gov/ncidod/dvbid/arbor/alphavir.htm
Mosquito Transmission:
Aedes aegypti and Aedes albopictus
Transmission: Aedes
mosquito
 Aedes aegypti





Urban mosquito
Needs standing water for larvae
Prefers cool, dark areas for resting
Feeds through the day, most active at dawn/dusk
Eggs do not survive winter in temperate climates
 Aedes albopictus: Asian Tiger Mosquito




Urban, periurban, rural habitats
Feeds through the day, most active dawn/afternoon
Eggs survive winter in temperate climates
Invasive- spreading in Europe and Americas
www.cdc.gov
CHIKV: Geographic
Distribution
As of January 6, 2014
www.cdc.gov
Aedes: Geographic distribution
and CHIKV imported cases
Soumahoro at al EID 2010
Transmission Cycle
 Africa
 Sylvatic transmission cycle
 Maintained in non-human primates, small mammals, Aedes
mosquitos
 Human reservoirs during epidemics without animal reservoirs
 Outbreaks usually associated with heavy rainful and increased
mosquito population
 Asia
 Human-mosquito cycle
 Urban epidemics
 Aedes aegypti and Aedes albopictus
Burt FJ et al. Lancet 2012; 379:662-71
www.cdc.gov
Transmission by corneal graft
 La Reunion Outbreak, Indian Ocean 2005-2007
 Implementation of screening of organ and tissue donors in
2005
 12 of 69 asymptomatic corneal donors were viremic or IgM
positive for CHIK
 4 of 12 corneas from these donors were infected with CHIK
(qRT-PCR)
 No correlation with systemic symptoms, viremia, or presence of
anti-CHIK IgM
 Mouse models showed ocular innoculation of CHIK produced
systemic infection
 Corneal collection and transplantation suspended
Couderc et al. JID 2012
Lumsden WH. Trans Roy Soc
Trop Med Hyg 1955;49:33-57
Clinical Findings
 Incubation period 1-12 days, average 2-4
 Abrupt onset fever, myalgias, headache and photophobia
 Rash: maculopapular, lasting 2-3 days



Aphthous ulcers
Vesiculobullous lesions with desquamation
Vasculitic lesions
 Diarrhea, nausea vomiting may occur
 Neurologic symptoms (up to 16%)



Encephalopathy, seizures, meningoencephalitis
Acute flacid paralysis
Guillan-Barre like syndrome
 Rarely: myocarditis, hepatitis, nephritis, anterior uveitis, retinitis, optic neuritis
Mahendradas et al. J Ophth Inflam Infec 2013; 3:35
Burt FJ et al. Lancet 2012; 379:662-71
Thiberville, SD et al. PLOS Neg Trop Dis. 2013
Clinical features: Day 1, 7, 25
Joint disease
 Severe Arthralgias
 Polyarticular, usually symmetric, small joints
 Swelling but no large effusions
 Some improvement in 1-2 weeks, but may persist for years
 Malaysia retrospective review
 Mean duration of arthralgia 3 months
 45% had arthralgias beyond 4 months
 22% with arthralgias beyond 1 year
 Réunion: Persistence at 36 months
 Risk increases with age >35 years old
 Presence of arthralgia at 4 months was predictor of chronic disease
 Mouse models suggest due to viral persistence in tissues
Zim MA et al. J Clin Virol. 2013; 56:141-45.
Thiberville, SD et al. PLOS Neg Trop Dis. 2013
Schilte et al. Plos Neg Trop Dis. 2013
Hawman et al. J. Virology 2013; 87:13878
Diagnosis
 Differential
 Dengue
 Ross River virus, O’nyong-nyong and other alphaviruses
 Leptospirosis, malaria, group A strep, rickettsia, rubella,
measles, parvovirus, enterovirus, adenovirus, rheumatologic
diseases
 Clinical findings, epidemiology, lab confirmation



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Viral culture in 1st 3 days of illness
RT-PCR for viral RNA in 1st 8 days
Serology for IgM and IgG by end of 1st week
Convalescent titers with four-fold increase in IgG
Samples to CDC through CDPHE
www.cdc.gov
Treatment and Prevention
 Acute Illness



Supportive care
NSAIDS
Case reports of short steroid courses for severe early disease
 Persistent arthralgias: no good data for treatment

Chloroquine, hydroxychloroquine
 No sig difference in efficacy for acute arthralgias between chloroquine and meloxicam in
509 indiv in India

Sulfasalazine, methotrexate, ribavirin, interferon-alpha
 Mosquito avoidance
 Vaccines in research, not licensed
 Monoclonal antibodies as prophylaxis effective in mouse models
 Mosquito avoidance on return home to prevent local transmission
Chopra et al. Arthritis and Rheum 2012. Accepted Article, doi:
10.1002/art.38221
Chopra et al. Arthritis and Rheum 2008;9:2921-2
Selvarajah et al. PLoS Neg Trop Dis 2013;7:e2423
Janu et al. J. Assoc. Phys India 2011; 59:83-6
CHIKV: re-emerging disease
 Initial descriptions in 1950s
 2006 Maldives
 2000 Epidemic in Kinshasa,
 2008 Singapore
DRC,
1st
in 39 years
 2001-2003 epidemic in
Indonesia,
1st
in 20 years
 2004 Coastal Kenya
 E226V mutation more
efficiently transmitted by
Aedes albopictus
 2005 Spread to Comoros
Islands
 2005-2007 Epidemic in
Réunion: 35% attack rate
 266,000 cases
 0.1% mortality
 2012 Rural Cambodia
 44.7% prevalence
 5.3% asymptomatic
 2012 Bhutan
 1st cases reported
 Index case recent travel from
India
 East/Central/South African
genotype
 2012 Papua New Guinea
 1st cases reported
MMWR 2012; 61: 737-40
www.cdc.gov/eid 2013 vol 19
CHIKV Epidemics
 2005-2006 Re-emergence in India after 32 years
 1.3 million cases in 13 states
 2007 Northern Italy: Emilia-Romagna
 254 locally acquired infections
 Index case just returned from India
 2010 French Riviera: Frejús, Nice
 Index case young girl with recent return from India
 December 2013 Carribbean isle of St. Martin
 Dec 6th: 2 cases of locally acquired chikungunya
 1st cases reported in the Americas
 Dec 10th: 2 confirmed, 4 probable, 20 suspected cases of
chikungunya reported to WHO
www.who.int/scr/don/2013_12_10a/en/index.html; accessed 1/12/14
Tomasello et al. Travel Med and Inf Dis 2013; 11, 274-284
CHIKV and US Travelers
 1995-2009: 109 lab-confirmed cases in US
 Adult travelers, mean age 48 yrs
 57% female
Gibney et al. CID 2011; 0:1-6
CHIKV and Travelers
 1995-2009: 109 lab-confirmed cases in US
 Adult travelers, mean age 48 yrs
 57% female
Gibney et al. CID 2011; 0:1-6
CHIKV Cases in the US
Gibney et al. CID 2011; 0:1-6
US Distribution of Imported
CHIKV
Gibney et al. CID 2011; 0:1-6
Travelers from Indian Ocean
Islands, 1997-2010
Savini et al., EID 2013; 19
Implications for Travelers
 Increased education regarding expanding geographic
distribution of vectors for chikungunya (and dengue)
virus, especially Europe and Caribbean
 Emphasis on need for mosquito avoidance in areas
that are not tropical or traditional risk areas
 Prompt evaluation of return travelers with fever and
awareness of CHIKV
 Avoidance of mosquitos after diagnosis of chikungunya
to decrease risk of local transmission