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Jamestown Canyon Virus Revisited: Are We Neglecting and Under Recognized Mosquito-Borne Disease ______

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Jamestown Canyon Virus Revisited: Are We Neglecting and Under Recognized Mosquito-Borne Disease ______ ______________________________________ Jamestown Canyon Virus Revisited: Are We Neglecting and Under Recognized Mosquito-Borne Disease ________________________________________________ Theodore G. Andreadis, PhD Center for Vector Biology & Zoonotic Diseases and Northeast Regional Center for Excellence in Vector-Borne Diseases The Connecticut Agricultural Experiment Station New Haven, CT JAMESTOWN CANYON VIRUS • Mosquito-borne Orthobunyavirus (ss-RNA) found 1 2 1 38 throughout much of temperate North America 1 7 94 6 8 1 1 2 1 1 1 1 • First isolated in 1961 from Culiseta inornata in CO 2 1 1 • Human cases are comparatively rare but appear to be 2 1 on the rise (166 cases from 2004 – 2018) 3 • Mostly in Midwestern and Northeastern states Distribution Human Cases 2000-18 CDC ArboNet • Sero-prevalence = 6.7% - 48.2% - “Under Recognized” 80 • Causes acute febrile illness, fever, meningitis, or 70 Human cases = 166 meningoencephalitis Range = 10 – 84 yrs 60 Median = 48 yrs • Infects a variety of free ranging ungulates - deer, moose, 50 bison, elk (sero-prevalence: 21% in CT, 77% in WI) 40 • White-tailed deer recognized as principal amplification 30 hosts (experimental infections and prevalence of Ab) 20 • Isolated from 26 mosquito species, mostly boreal Aedes 10 • Vertically transmitted in mosquitoes 0 04 06 08 10 12 14 16 18 Matkovic et al (2019), Am. J. Trop. Med. Hyg., 100: 445–451 Enhanced Arboviral Surveillance to Increase Detection of Jamestown Canyon Virus Infections, Wisconsin, 2011–2016 Clinical manifestations of patients with Probable cases JCV disease Confirmed cases Fever 83% N = 30 General weakness 70% Headache 66% Nausea 37% Neck rigidity 30% Altered mental status 23% Dizziness 16% Photophobia 13% Tremors 13% Arthralgia 13% Seizures 6% Matkovic et al (2019), Am. J. Trop. Med. Hyg., 100: 445–451 Enhanced Arboviral Surveillance to Increase Detection of Jamestown Canyon Virus Infections, Wisconsin, 2011–2016 Characteristics of patients with JCV Probable cases disease Confirmed cases N = 30 Age Range 10-84 yrs. Median age = 54 yrs Median Age 54 yrs. Males 56% Outdoor exposure 73% History of mosquito bite 56% No travel out of state 80% Hospitalized 47% Neuroinvasive 50% Fatality 3% OBJECTIVES Examine the spatial and temporal patterns of Jamestown Canyon virus activity in the Connecticut as a function of: • Vector mosquito abundance and distribution with identification of key vectors • Land use characteristics Agriculture/Grass Forest Developed Wetland 80 70 • Distribution and abundance of white-tailed 60 deer, Odocoileus virginianus, reservoir 50 vertebrate host 40 30 - Exponential increase with reforestation 20 throughout the northeastern US since 1900 10 Deer Abundance Thousands / Abundance Deer 0 1880 1900 1920 1940 1960 1980 2000 2020 Mosquito Collection and Arbovirus Isolation Methods • Data gleaned from our State-wide Mosquito/Arbovirus Surveillance Program • 20 year period: 1997 to 2017 • Conducted from June - October • 92 permanent trapping stations (trap weekly) • CO2-baited CDC light trap and gravid traps • Mosquitoes identified to species (45 species) • Pooled by species and site (Maximum of 50) • Virus isolation in Vero cell cultures (BSL 3) • Virus identification by real time PCR or RT-PCR Jamestown Canyon Virus – Spatial Geographic Distribution • Virus detected in 84 of 91 sites (92%) 1997-2017 • Equally distributed throughout urban, suburban and rural locales 1 2 3 5 • No significant association with any 4 land cover categories (r = 0.17) • No significant relationship to white- 6 9 tailed deer abundance 10 7 8 12 140 r = 0.09 11 P = 0.80 11 120 11 100 12 12 No. virus isolations 80 Agric/Soil/Grass 1 - 5 Forest 6 - 10 60 Developed/Urban Deep Water 6 11 - 30 40 Wetland 3 No. VirusIsolations 3 11 1-12 Deer Management Zones No virus detected 20 9 7 4 7 4 5 0 2 5 8 0 5 10 15 20 25 30 35 No. Deer / sq. mile Jamestown Canyon Virus – Isolations from Mosquitoes 1997 - 2017 • 478 virus isolations from 25 of 45 (55%) mosquito species Ae. canadensis collected 112 isolations 120 43 sites 20 years • Mostly Aedes and Anopheles 110 100 • 5 species incriminated as most Ae. communis 90 Ae. sollicitans important vectors based on: Ae. thibaulti 80 Ae. cantator Ae. triseriatus An. quadrimaculatus − Number of years detected 70 An. walker Cs. melanura 60 Ae. abserratus An. punctipennis Cs. morsitans − Number of sites detected Cx. restuans 50 Cx. salinarius Ae. aurifer Ps. ferox − Number of virus isolations 40 No. virus isolations virus No. 50 • Aedes canadensis* 30 Ae. sticticus Cq. perturbans 20 40 • Aedes cantator Ae. vexans Ae. stimulans 10 Ae. excrucians Ae. trivittatus 30 • Aedes abserratus 0 Ae. provocans Ae. cinereus 20 • Anopheles punctipennis* 20 Ae. taeniorynchus 15 10 • Aedes aurifer 10 No. sites detected No. years detected 5 0 * Competent lab vector 0 Andreadis et al. VBZD 8: 2008 Aedes canadensis • Among the most abundant and widely distributed species in the state • Larvae develop in a variety of freshwater habitats Aedes canadensis − Temporary leaf-lined pools in wooded areas − Roadside ditches − Vernal pools in open fields − Permanent swamps • Univoltine – peak populations in June - July • Feed on a variety of animals but mostly mammals (98%) including humans (Molaei et al JME 2008) 80 JCV + • White-tailed deer - 95% of mammalian blood meals JCV - 60 Aedes • Competent vector of JCV canadensis (Heard et al JAMCA 1991) 40 20 Mean no. mosquitoes / light trap light / Mean mosquitoes no. 0 Jun Jul Aug Sept Jamestown Canyon Virus – Yearly Activity 1997 - 2017 • Consistently detected every year 70 350 • Infection rates range from 0.05 - No. virus isolations 60 No. mosquitoes 300 0.36 (MLE/1000) mean = 0.16 • Yearly virus activity is directly 50 250 related to overall mosquito abundance 40 200 70 60 r = 0.75 30 150 P < 0.001 50 No. Virus IsolationsNo. Virus 20 100 No. Mosquitoes (x1000) 40 30 10 50 No. VirusIsolations 20 10 0 0 0 199797 1998 98 1999 99 2000 00 2001 01 2002 02 2003 03 2004 04 2005 05 2006 06 2007 07 2008 08 2009 09 2010 10 2011 11 2012 12 2013 13 2014 14 2015 15 2016 16 2017 17 0 50 100 150 200 250 300 350 YEAR No. Mosquitoes Andreadis et al. VBZD 8: 2008 Jamestown Canyon Virus – Seasonal Prevalence • Infected mosquitoes detected from June through September 100 350 • Virus isolations parallel 0.5 Virus isolations Mosquitoes overall mosquito abundance 300 MLE = 0.5 - 0.02 80 • Greatest number of virus 250 isolations: mid - June through mid – July 60 200 • Correspondingly high infection rates (MLE) during 150 same time (0.5) 40 • Consistent with vertical No. virus isolations 100 transmission 20 Mean no. mosquitoes / light trap light / mosquitoes no. Mean 50 0.02 0 0 Jun Jul Aug Sept Andreadis et al. VBZD 8: 2008 Am. J. Trop. Med. Hyg., 77(6), 2007, pp. 1157–1162 Genetic Relationships of Jamestown Canyon Virus Strains Infecting Mosquitoes Collected in Connecticut Philip M. Armstrong and Theodore G. Andreadis 1966 - 2006 • Sequenced 56 JCV isolates from Connecticut 1966 - 2006 • Analysis of nucleotide sequences from the S segment (nucleocapsid) (maximum likelihood) • Two Major Lineages in Connecticut 1998 - 2004 - Lineage A 1966 - 2006 - Lineages B1 and B2 1998 - 2004 • Lineages did not group by year of 2000 - 2003 isolation or mosquito species • Very little change over time Distribution of Jamestown Canyon Virus Lineages in Connecticut • Geographically structured - Lineage A (west) - Lineage B (east) • Both lineages in some sites • Long term maintenance of local populations of JCV suggests local overwintering and persistence of virus • JCV appears to be evolving slowly by random mutation (genetic drift) Connecticut • No evidence for genetic River reassortment among lineages A and B (genetic shift) Armstrong & Andreadis AJTMH 79 : 2007 Summary • JCV is widely distributed in CT and consistently amplifies each year • Activity occurs from June to September with peak from late June through mid July • Activity is a function of mosquito abundance • Vectors are largely univoltine woodland species • Aedes canadensis appears to be principal vector • The virus is very stable suggesting local overwintering in mosquitoes via transovarial transmission with long 100 350 Virus isolations term persistence Mosquitoes 300 80 • Human exposure is likely to be moderate to high 250 60 200 • Clinicians should consider JCV infection in differential 150 40 diagnosis when an arboviral infection is suspected to be 100 20 causing febrile neurological illness and WNV testing is 50 0.02 inconclusive or negative 0 0 Jun Jul Aug Sept CAES Center for Vector Biology & Zoonotic Diseases NE Regional Center for Excellence in Vector-Borne Diseases Dr. Philip Armstrong Dr. John Anderson John Shepard Angela Bransfield Michael Micensik Tanya Pertruff Funding Sources • USDA NIFA • State of Connecticut • Hatch CONH00768 • Connecticut Department • CDC of Public Health • ELC cooperative agreement Questions? Alexander Skochkov “Old Mosquito”.
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