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Chikungunya Fever: Re-emerging vector-borne disease

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.

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Chikungunya Fever: Re-emerging vector-borne disease

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  1. Chikungunya Fever:Re-emerging vector-borne disease Margaret McLees, M.D., DTMH Denver Public Health January 17, 2014

  2. Outline • Case Presentation • Epidemiology • Presentation • Diagnosis • Treatment and Prevention • Implications for our Travelers

  3. 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

  4. 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

  5. Case: Rash

  6. Case: Rash

  7. 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

  8. 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

  9. 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

  10. Mosquito Transmission: Aedes aegypti and Aedes albopictus

  11. 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

  12. CHIKV: Geographic Distribution As of January 6, 2014 www.cdc.gov

  13. Aedes: Geographic distribution and CHIKV imported cases Soumahoro at al EID 2010

  14. 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

  15. 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

  16. Lumsden WH. Trans Roy Soc Trop Med Hyg 1955;49:33-57

  17. 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

  18. Clinical features: Day 1, 7, 25 Thiberville, SD et al. PLOS Neg Trop Dis. 2013

  19. 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

  20. 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 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

  21. 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

  22. 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: 737-40 www.cdc.gov/eid 2013 vol 19

  23. 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

  24. 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

  25. 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

  26. CHIKV Cases in the US Gibney et al. CID 2011; 0:1-6

  27. US Distribution of Imported CHIKV Gibney et al. CID 2011; 0:1-6

  28. Travelers from Indian Ocean Islands, 1997-2010 Savini et al., EID 2013; 19

  29. 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

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