Tick-borne viral diseases in the United States
Tick-borne viral diseases in the United States J. Erin Staples Arboviral Diseases Branch Centers for Disease Control and Prevention Fort Collins, CO March 31, 2015 National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-borne Diseases Disclosure The Association of Public Health Laboratories adheres to established standards regarding industry support of continuing education for healthcare professionals. The following disclosures of personal financial relationships with commercial interests within the last 12 months as relative to this presentation have been made by the speaker(s): J. Erin Staples, MD, PhD - Nothing to disclose. 2 Objectives Describe geographic distribution and clinical features of tick-borne viral diseases Understand role of molecular and serologic diagnostic testing in confirming tick-borne viral infections 3 Colorado tick fever 4 Colorado tick fever (CTF) virus Double-stranded RNA virus Family: Reoviridae; Genus: Coltivirus Transmitted primarily by Dermacentor andersoni (Rocky Mountain wood tick) Small rodents are primary reservoir 5 Ecology of CTF virus 6 CTF epidemiology Endemic to mountainous regions (elevation of 4,000-10,000 feet) of western U.S. and southwestern Canada CTF is currently reportable in six states Arizona, Colorado, Montana, Oregon, Utah, and Wyoming Up to 90% of cases recall tick exposure Blood-borne and laboratory transmission rare 7 Approximate geographic distribution of Dermacentor andersoni and counties of residence for CTF cases, United States – 2002-2012 * All cases were acquired in states where local transmission of CTF virus has been reported previously. **Derived from James AM, Freier JE, Keirans JE, Durden LA, et al. Distribution, seasonality, and hosts of the Rocky Mountain wood tick in the United States. J Med Entomol 2006; 43:17–24. 8 Number of CTF cases by year, United States – 1987-2012 Median 55 cases/year Median 5 cases/year 120 Number of cases 100 80 60 40 20 0 9 Month of illness onset for CTF cases, United States – 2002-2012 30 Number of cases 25 20 15 10 5 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Month of illness onset 10 Demographics of CTF cases, United States – 2002-2012 Characteristic N=75 n (%) Sex Male Age (years) 0-19 20-39 40-59 ≥60 Unknown 47 (63) 11 13 30 19 2 (15) (17) (40) (25) (3) 11 Clinical features of CTF Incubation period 2-3 days (range 1-14 days) Sudden onset of fever; can be bi-phasic Other symptoms include chills, headache, myalgia, and malaise Rare reports of meningitis, encephalitis, hepatitis, pericarditis, pneumonia, coma 15-30% of cases hospitalized 12 Clinical laboratory findings of CTF Some findings secondary to CTF virus infecting hematopoietic progenitor cells Leukopenia with relative lymphocytosis Atypical lymphocytes Moderate thrombocytopenia 13 Treatment and outcome for CTF No specific treatment; supportive therapy Illness duration 7-10 days but malaise can last for weeks Death is rare 14 Diagnostic testing for CTF virus infection Testing is available at Focus Diagnostics, Montana Public Health Laboratory, and CDC CTFV infects red blood cells; leads to prolonged viremia and delayed antibody production RT-PCR is most sensitive for acute samples; also can culture virus IFA or neutralization testing for antibodies may not be positive until 2-3 weeks post infection IHC also available for tissues 15 Number and proportion of samples positive for CTF virus infection by days post onset and assay Days post illness onset 0-6 RNA No. pos/ No. tested (%) 14/14 (100) Neutralizing antibodies No. pos/ (%) No. tested 0/12 (0) IgG antibodies No. pos/ (%) No. tested 1/8 (13) 7-13 8/8 (100) 1/2 (50) 1/2 (50) 14-20 1/1 (100) 2/4 (50) 5/6 (83) ≥21 0/0 (0) 16/16 (100) 3/3 (100) 16 Summary of CTF virus and disease Likely under-recognized cause of febrile illness in spring and early summer in Western U.S. Majority of cases recall tick exposure Samples collected in first 14 days of illness should be tested for viral RNA Antibody testing not reliably positive until 3 weeks after illness onset Defer blood donors for 6 months 17 References for CTF Yendell SJ, Fischer M, Staples JE. Colorado tick fever in the United States, 20022012. Vector Borne Zoonotic Dis 2015; in press. Brackney MM, Marfin AA, Staples JE, et al. Epidemiology of Colorado tick fever in Montana, Utah, and Wyoming, 1995-2003. Vector Borne Zoonotic Dis 2010;10:381-5. Eisen L, Ibarra-Juarez LA, Eisen RJ, Piesman J. Indicators for elevated risk of human exposure to host-seeking adults of the Rocky Mountain wood tick (Dermacentor andersoni) in Colorado. J Vector Ecol 2008;33:117-28. CDC. Transmission of Colorado tick fever virus by blood transfusion -- Montana. Morb Mortal Wkly Rep 1975;24:422-7. Romero JR, Simonsen KA. Powassan encephalitis and Colorado tick fever. Infect Dis Clin North Am 2008;22:545-59. Lambert AJ, Kosoy O, Velez JO, Russell BJ, Lanciotti RS. Detection of Colorado tick fever viral RNA in acute human serum samples by a quantitative real-time RT-PCR assay. J Virol Methods 2007;140:43-8. Marfin A, Campbell G. Colorado tick fever and related Coltivirus infections. In: Goodman J, ed. Tick-Borne Diseases of Humans. Washington, D.C.: ASM Press; 2005:143-9. Attoui H, Jaafar FM, de Micco P, de Lamballerie X. Coltiviruses and Seadornaviruses in North America, Europe, and Asia. Emerging Infectious Diseases 2005;11:1673-9. 18 Powassan (POW) virus Single-stranded RNA virus with two lineages POW virus or Lineage I POW virus Deer tick virus (DTV) or Lineage II POW virus Family: Flaviviridae; Genus: Flavivirus Member of tick-borne encephalitis group Transmitted primarily by Ixodes spp. Lineage I: I. cookei, I. marxi, and I. spinipalpus Lineage II: I. scapularis, I. dammini; D. andersoni Small to medium mammals (rodent, woodchucks, skunks) are main reservoirs 19 POW virus disease epidemiology Endemic primarily in northeastern states and Great Lake region POWV disease is nationally notifiable No other modes of transmission documented Theoretical risk for blood and in utero transmission Tick-borne encephalitis virus transmitted via ingestion of milk from infected ungulates 20 Geographic distribution of POW virus neuroinvasive disease cases, United States – 2004-2013 21 Number of POW virus disease cases by year, United States – 1970-2013 Median 0 cases; Northeast US 18 Median 6 cases; NE and North Central US Number of cases 16 14 12 10 8 6 4 2 0 Year 22 Month of illness onset for POW virus disease cases, United States – 2004-2013 20 18 Number of cases 16 14 12 10 8 6 4 2 0 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Month of illness onset 23 Demographics of POW virus disease cases, United States – 2004-2013 Characteristic N=65 n (%) Sex Male Age (years) 0-19 20-39 40-59 ≥60 48 (74) 10 8 15 32 (15) (12) (23) (49) 24 Clinical features of POW virus disease Incubation period range 8-34 days Asymptomatic or mild disease may occur Fever, headache, vomiting, and weakness are initial symptoms of neuroinvasive disease Progresses to altered mental status, aphasia, paresis, movement disorders, nerve palsies 88% of cases hospitalized 25 Clinical laboratory and imaging findings of POW virus disease CSF with lymphocyte pleocytosis though neutrophils can predominate early Normal or mildly elevated CSF protein Normal CSF glucose Brain MRI with demyelinating disease or microvascular ischemia in parietal or temporal lobes 26 Treatment and outcome for POW virus disease No specific treatment; supportive therapy Roughly half of cases have long-term neurologic sequelae 10-20% of cases are fatal 27 Diagnostic testing for POW virus infections Testing is available at Minnesota and New York state public health laboratories and CDC Viremia rarely detected early in illness and usually only with nested RT-PCR Antibody measured by IgM and IgG EIA and neutralization testing Cross-reactivity can occur in EIA with related flaviviruses Antibody testing can not differentiate between lineages IHC also available for tissues 28 Summary of POW virus and disease Likely under-recognized cause of neuroinvasive disease during tick season Occurs predominantly in northeastern and north central United States Neutralizing antibody testing needed to confirm diagnosis due to flavivirus cross-reactivity 29 References for POWV Lindsey NP, Lehman JA, Staples JE, Fischer M. West Nile virus and other arboviral diseases -- United States, 2013. MMWR 2014;63(24):521-526. Dupuis AP, Peters RJ, Pruinski MA et al. Isolation of deer tick virus (Powassan virus, lineage II) from Ixodes scapularis and detection of antibody in vertebrate hosts sampled in the Hudson Valley, New York State. Parasites & Vectors. 2013;6:185. Brackney DE, Nofchissey RA, Fitzpatrick KA, Brown IK, Ebel GD. Stable prevalence of Powassan virus in Ixodes scapularis in a northern Wisconsin focus. Am J Trop Med Hyg. 2008;79(6):971-973. Ebel GD. Update on Powassan virus: emergence of a North American tick-borne flavivirus. Annu Rev Entomol. 2010;55:95-110. Ebel GD, Spielman A, Telford SR, 3rd. Phylogeny of North American Powassan virus. J Gen Virol. Jul 2001;82(Pt 7):1657-1665. Hinten SR, Beckett GA, Gensheimer KF, et al. Increased recognition of Powassan encephalitis in the United States, 1999-2005. Vector Borne Zoonotic Dis. 2008;8(6):733-740. Johnson DK, Staples JE, Sotir MJ, Warshauer DM, Davis JP. Tickborne Powassan virus infections among Wisconsin residents. Wis Med J. 2010;109(2):91-7. Tavakoli NP, Wang H, Dupuis M, et al. Fatal case of deer tick virus encephalitis. N Engl J Med. 2009;360(20):2099-2107. 30 Initial Heartland virus disease cases In June 2009, two adult males seen at hospitals in northwestern Missouri Both relatively healthy; one reported recent diagnosis of Type II diabetes mellitus Symptoms and signs were similar for both Fever, fatigue, anorexia, and diarrhea Leukopenia and thrombocytopenia 31 Exposures for initial cases Both farmers who resided and worked land Both reported multiple tick exposures prior to their illness onset No recent travel, vaccinations, or other recent illnesses 32 Hospital course for initial cases Both were admitted and received doxycycline for presumptive ehrlichiosis Failed to improve and laboratory parameters worsened during hospitalization Thrombocytopenia became more significant Moderately elevated liver transaminases developed Both patients discharged home after 10-12 days Laboratory testing for etiology was negative 33 Identification of novel virus Acute samples were sent to CDC to culture for Ehrlichia chaffeensis Both showed cytopathic effects Characteristic morulae were not seen Electron microscopy performed identified bunyavirus-like particles In 2011, next generation sequencing identified virus as novel phlebovirus, Heartland virus 34 Entomologic evaluation Ticks and mosquitoes collected from farmers’ residences and local areas to test for HRTV Heartland virus recovered in 10 Amblyomma americanum (Lone star tick) pools Amblyomma americanum likely vector 35 Identification of additional Heartland virus disease cases Epidemiologic investigation implemented with MO Dept of Health and Senior Services in 2012 Prospect study with participants enrolled in 7 medical facilities throughout MO Enrollment criteria includes fever, leukopenia, and thromobocytopenia Excludes non-infectious etiologies In 2013, cases tested from other locations 36 Epidemiology of Heartland virus disease cases From 2012-2013, 6 additional cases identified from Missouri and Tennessee All patients were males Median age is 58 years (range: 50-80 years) Illness onset was in May (n=3), July (1), and September (2) 37 Clinical features and outcome of Heartland virus disease Of 5 patients where symptoms were collected, all reported fatigue and anorexia Other symptoms included headache, nausea, myalgia, or arthralgia Four (67%) of 6 patients were hospitalized One (17%) died 38 Reported exposures for Heartland virus disease cases (N=6) All patients reported spending >1 hour per day outside 5 (83%) reported tick bites in 14 days prior to illness onset 39 Diagnostics testing for Heartland virus infections Testing currently available at CDC; several academic centers performing RT-PCR RT-PCR on acute serum is often positive for Heartland viral RNA Neutralization test used for determining antibody titers in acute and convalescent samples IgM MIA and IFA and IgG MIA and ELISA have been developed but need further validation IHC available to test tissues 40 Summary of Heartland virus and disease Previously unrecognized human pathogen, likely transmitted by A. americanum Clinically similar to ehrlichiosis/anaplasmosis Consider diagnosis in patients with fever, leukopenia, and thrombocytopenia who test negative for tick-borne pathogen or do not improve on doxycycline Serologic and molecular testing can be used to diagnosis Heartland virus infections 41 References for Heartland virus McMullan LK, Folk SM, Kelly AJ, et al. A new phlebovirus associated with severe febrile illness in Missouri. N Engl J Med 2012;367:834-841. Savage HM, Godsey MS Jr, Lambert A, et al. First detection of heartland virus (Bunyaviridae: Phlebovirus) from field collected arthropods. Am J Trop Med Hyg 2013;89:445-452. Pastula DM, Turabelidze G, Yates KF, et al. Notes from the field: Heartland virus disease - United States, 2012-2013. Morb Mortal Wkly Rep 2014;63:270-271. Muehlenbachs A, Fata CR, Lambert AJ, et al. Heartland virus-associated death in Tennessee. Clin Infect Dis 2014;59:845-850. 42 Prevention of tick-borne viral diseases No vaccines to prevent tick-borne viral diseases in United States Tick-borne encephalitis vaccine available in Canada and Europe Avoid tick bites Use insect repellent Wear long sleeves and pants Avoided wooded or bushy areas with high grass Perform thorough tick checks after spending time outdoors to remove ticks before they attach 43 CDC websites and downloadable information on tick-borne diseases Colorado tick fever http://www.cdc.gov/coloradotickfever/ Powassan virus disease http://www.cdc.gov/powassan/ Heartland virus disease http://www.cdc.gov/ncezid/dvbd/heartland/index.html General tick-borne disease information http://www.cdc.gov/ticks/index.html Tickborne Diseases of the United States: A Reference Manual for Health Care Providers, Second Edition http://www.cdc.gov/lyme/resources/TickborneDiseases.pdf Free app in Apple App store (“cdc tickborne”); android version anticipated by May 2015 44 Questions For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone: 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: [email protected] Web: http://www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases Division of Vector-borne Diseases
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