Canine Rabies Elimination from the United States: an Epidemiological and Virological Perspective Canine Rabies Elimination from the United States: an Epidemiological and Virological Perspective Andrés Velasco Villa, Serena Reeder, Jesse Blanton,Lillian A Orciari and Charles E. Rupprecht Rabies Unit Poxvirus and Rabies Branch Division of Viral and Rickettsial Diseases Coordinating Center of Infectious Diseases Centers for Disease Control and Prevention The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agencies. Use of trade names and commercial sources are for identification only and do not imply endorsement by the US Department of Health and Human services.

Rabies is an acute viral encephalomyelitis caused by the members of the Lyssavirus genus and Rhabdoviridae family Disease definition Rabies causes more than 55, 000 human deaths, every year, throughout the world.

Rabies epizootiology RABIES RESERVOIRS URBAN RABIES WILD RABIES RABIES ASSOCIATED WITH TERRESTRIAL CARNIVORES SUSCEPTIBLE SPECIES (DEAD ENDS) Cats VECTORS Ferrets Perros Dogs Vampire bat Big brown bat Silver hair bat Red bat Free tail bat Mapaches Raccoons Gray foxes Stripped skunk Spotted skunk Arctic foxesCoyotes Mongooses RABIES ASSOCIATED WITH BATS Cows Goats and Sheep Humans and horses Pigs Beavers and woodchucks Raccoon dogs ENZOOTIC RABIES

Rabies status CityYear*Controlled EpizooticMemphis, TN EnzooticChicago, IL EnzooticPontiac, MI EnzooticSt Louis, MO & EnzooticLos Angeles, CA & EnzooticDallas, TX & EnzooticPhoenix, AZ & EnzooticHouston/Harris, TX Last dog rabies enzootics in the United States Rabies in Wild and Domestic Animals in the United States, History of rabies control and its elimination from the United States

1988 Major rabies enzootics in terrestrial carnivores and the last rabies outbreak that involved both dogs and coyotes in the United States FOX

Major Terrestrial RABV Biotypes: Geographic distribution in the US and Mexico. Major Terrestrial RABV Biotypes: Geographic distribution in the US and Mexico. Northcentral Skunk Southcentral Skunk Dog/ Coyote Raccoon CA Skunk Baja CA Skunk Red Fox Yucatan Skunk Yucatan Dog Chiapas Dog Guerrero-Oaxaca Dog Puebla -Tiaxcala Dog Estado de Mexico Dog Michoacan Dog US- MX Dog AZ Gray Fox Sinaloa- Durango Skunk North Central Mexico Skunk Puerto Rico Mongoose TX Gray Fox

To characterized, at genetic level, all RABV variants and lineages historically associated with enzootic rabies in dogs in the US in order to understand and follow up its elimination, evolution and re-emergence in wildlife canines. General and objective

Results

East Texas-Mex Border Dog-coyote D1 Yucatan Dog D10 Puebla-Tlaxcala Dog D3, D7, D8 Guerrero-Oaxaca Dog D9 Michoacan Dog D2, D4 Estado de Mexico Dog D5 and D6 Chiapas Dog West US-Mx border Dog-coyote D11 * Extinct dog rabies focus * * * * * Searching the origin of re emerging enzootic dog rabies in the US: the domestic dog/coyote case, part I ? Potentially, more cases during 2006 ?

Searching the origin of re emerging enzootic dog rabies in the US: the domestic dog/coyote case, part II

D5 E19 D13 E20 E17 A14 A15 G5 F6 B12 C8 D6 E14 C7 G3 H2 A16 C5 C12 D8 B19 H5 B13 D15 C3 C14 A8 B14 D13 A6 A9 C13 G4 B10 B2 E12 I6 H4 C9 A1 F17 C1 B17 I4 A4 H3 B20 B16 I5 F5 B5 D2 G1 A10 C21 B4 E11 E3 A13 A3 D1 H1 C19 B7 C2 F1 E8 I3 D4 F12 A12 I2 A18 C17 A5 F11 D14 A17 B1 D3 I1 B3 D16 G6 A2 E1 D17 B15 B11 B18 C11 C6 D7 F13 E10 G2 E7 E9 E2 F10 E5 D10 F14 E4 E16 F15 F3 F2 F4 E6 E15 D2 Michoacan Dog D3 Puebla Tlaxcala Dog D9 D6DFEdoMexDg D8PueTlxDg D7PueTlxDg D5EdoMexDg D4MichMorDg D10YucDg 3853 El Salvador, Central America Hm chisdg02 D11 West US-Mexico border dog foci “Sonora Dog variant” C16 C20 W6UScaliforniaSK7494 W7Yucunidentifiedreservoir W9MxBCSSk9002 W4732californiaSK W5USNorthcentralSk8498 WestCAnSK W2UsMxGrayfox Sonsk2003 W1SinDgoSk01 E13 D12 C15 C10 W3 US Texas gray fox D9 A11 E18 D11 B6 C18 C4 SD53304 SD55304 SD F SNP W11 US Southcentral Skunk B9 W12CanadaUSRaccoon W12 W13MxNorthcentralSk LCNA LCMx LCCi LBNA LMx LCi LANNA HTCi HTAg HTMx Mevcaluc9295 MCUS MCAzCAUSA8693 PipistrellusUSA EF1aCOUSA8502 EF1 71USA72EF1b AF394869ap93ca AF394868ap91ca MCiAg TdbrCidmtc EF2AZ EF2US TBCiAg Tadarida brasiliensis mexicana North America B8 Dr7 Dr6 Dr1 Dr2 Dr3 DrSA Dr4 Dr5 Duvenhage2 EBL W11 US Southcentral Skunk Tadarida brasiliensis mexicana North America D11 West Texas US Mexico border Dog “Sonora Dog” W3 US Texas gray fox Coyote/Dog East US- Mexico border Consensus amino acid change with respect Dog variants. Amino acid Serine change to Threonine in position 426. D2, D3 Puebla-Tlaxcala Michoacan Northcentral Skunk Southcentral Skunk Dog/Coyote Raccoon CA Skunk Red Fox Yucatan Dog Chiapas Dog Guerrero- Oaxaca Dog Puebla -Tlaxcala Dog Estado de Mexico Dog Michoacan Dog US- MX Dog AZ Gray Fox TX Gray Fox

1700Mxdfdg Mxdg02 575Mxtlxdg F 457Mxpuedg Mxpuepg Mxgtoct Mxpuedg02 67Mxtlxdg Mxgrodg99 657Mxdgosk Mxmxdg Mxpuebv Mxdfpg Mxdfhm Mxdffer Mxmichdk Mxmxdg Mxdfdg Mxmxdg Mxgrodg00 250Mxgrodg01 251Mxgrodg01 175Mxyucdg98 10Mxyucdg95 110Mxyucdg97 151Mxyuc98 428Mxyucct03 182Mxyucdg98 412Mxyucdg02 60Honddg Mxchisdg Mxmichct Mxmichbv Mxdgodg Mxchihbv Mxpuedg Mxpuepg Mxtlxgt Mxqrodg Puedg95 490Mxmichdg00 247Mxcoahcy Mxct02 B14Ustxcyken92 H2USTXWillcy98 E15USTXzavdg95 F2USTXlasallecy96 E14USTXhgocy95 G1USTXWebbcy97 B15UScyduv Mxsonbct 3140Mxsonbct Mxchihbct94 FluryLEP HEP-flury D9USTxdglub94 YC63China CVS11 PM1503 MRVChinahenan RAVNUCM61047 CVSFR AV01 RdfxEurope RacdgfxEastEu StepfxRdefxFareast RedfxMiddleast Africa1b Africa1a RCHLAB NiCEAB NishigaraAB BrdgV2 SADB19M31046 SRV9AF PuertoRico PrdgV1 2839PuertoRico 1629Mxbcssk Mxslpsk OrgTIndAY ArctfxPakistan U11734ontario24 U03769arctica1 AY352499ArctAK ArctfxSibCan 1500AFS Viverrid Viver African AF GUIAFR HAVAFR2 AsiandgInd-SriL AsiandgThai-Viet 2311Mxzacsk Mxslpsk RaccoonCAnUs SHBRVAY LC8 3901Mxmichbv Mxmichbv03 TB1 AF TB Salvhm Mxbvtamp verbv Mxhgoov Mxhgobv Mxslpbv04 AY573943flyfxGT7 U22845GT5 U22846GT D1 Coyote/Dog East US Mexico border D3 Dog Puebla-Tlaxcala D2 Michoacan W2 Arizona gray fox variant W3 Texas gray fox variant Vaccine strains related with CVS Flury LEP and HEP D11 Sonora Dog West US Mexico border Michoacan Chiapas and Central America D10 Yucatan D9 Guerrero Oaxaca D5 Estado de Mexico D4 Michoacan D6 Estado de Mexico D7 Dog Puebla Tlaxcala D8 Dog Puebla Tlaxcala Mexican dog lineages European and Middle east red fox African 1 dog SADB19 and Puerto Rico South American Dog variant Baja California Sur, skunk Arctic fox and arctic like variant African mongoose West African dog, Africa 2 Asian dog Vaccine strains red fox related North American Skunk and raccoon variants North American RV bat variants Outgroup, other Lyssavirus species Cosmopolitan dog variant Rabies associated with terrestrial carnivores Rabies associated with bats

Dog Rabies and Human Migrations Northcentral Skunk Southcentral Skunk Dog/ Coyote Raccoon CA Skunk Baja CA Skunk Red Fox Yucatan Dog Chiapas Dog Guerrero-Oaxaca Dog Puebla -Tiaxcala Dog Estado de Mexico Dog Michoacan Dog US- MX Dog AZ Gray Fox Puerto Rico Mongoose TX Gray Fox SAD B19 Puerto Rico Monngoose conection

We were able to detect historic movement patterns of major dog rabies enzootics which in turn are consistent with the demographics and immigration patterns of the Mexican and Central American populations described by the Sociologist Jorge Durand We also showed potential historic disseminations of enzootic dog rabies into wild life populations such as those illustrated by the phylogenetic analysis in gray foxes and coyotes in Texas. This findings stress out the importance of the historic follow up of rabies epizootics in order to assess future burdens for animal and public health. Final Remarks Our study showed that rabies virus associated with enzootics in dog populations has evolved over time, in discrete geographic lineages which may be translocated by human related activities.

To: Texas Department of Health, Austin, TX L. Zuckero P. Hunt S. Oertli L. Robinson National Zoonoses Program from the Ministry of Health, Mexico. Dr Fernando Vargas Pino and Rabies Laboratory at InDRE, from the Ministry of Health, Mexico. Acknowledgements