Chikungunya Fever: Re-emerging vector borne 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

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      Viral culture in 1 st 3 days of illness RT-PCR for viral RNA in 1 st 8 days Serology for IgM and IgG by end of 1 st 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 2000 Epidemic in Kinshasa, DRC, 1 st in 39 years  2001-2003 epidemic in Indonesia, 1 st 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  1 st cases reported  Index case recent travel from India  East/Central/South African genotype  2012 Papua New Guinea  1 st 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 6 th : 2 cases of locally acquired chikungunya 1 st cases reported in the Americas Dec 10 th : 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