Chikungunya Fever:Re-emerging vector-

borne diseaseMargaret McLees, M.D., DTMH

Denver Public HealthJanuary 17, 2014

OutlineCase Presentation

Epidemiology

Presentation

Diagnosis

Treatment and Prevention

Implications for our Travelers

Case65 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, continuedReturned 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 dataWBC 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 AsiaRoss River virusDengueChikungunya Japanese encephalitis virus

IgM positive to multiple viruses on acute sampleChikungunya, 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

www.cdc.gov/ncidod/dvbid/arbor/alphavir.htm

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)

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 CycleAfrica

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; 379:662-71www.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; 3:35Burt FJ et al. Lancet 2012; 379:662-71

Clinical features: Day 1, 7, 25

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20

13

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 tissuesZim MA et al. J Clin Virol. 2013; 56:141-45.Thiberville, SD et al. PLOS Neg Trop Dis. 2013Schilte et al. Plos Neg Trop Dis. 2013Hawman et al. J. Virology 2013; 87:13878

DiagnosisDifferential

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 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;9:2921-2Selvarajah et al. PLoS Neg Trop Dis 2013;7:e2423Janu et al. J. Assoc. Phys India 2011; 59:83-6

CHIKV: re-emerging disease

Initial descriptions in 1950s

2000 Epidemic in Kinshasa, 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

2006 Maldives

2008 Singapore

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: 737-40www.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 1/12/14Tomasello et al. Travel Med and Inf Dis 2013; 11, 274-284

CHIKV and US Travelers1995-2009: 109 lab-confirmed cases in US

Adult travelers, mean age 48 yrs57% female

Gibney et al. CID 2011; 0:1-6

CHIKV and Travelers1995-2009: 109 lab-confirmed cases in US

Adult travelers, mean age 48 yrs57% 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