The document summarizes presentations from a conference call on selected zoonotic diseases from December 2, 2009. It includes the following summaries: 1) An update on hantavirus pulmonary syndrome in the United States, which has caused over 500 cases and a 35% fatality rate, mostly in southwestern states. Special Pathogens is developing a new website and maps with more data. 2) Details on four rare cases of pediatric hantavirus pulmonary syndrome in 2009 in Colorado, Washington, and Arizona. Environmental investigations found rodent exposures in each case. 3) A study demonstrating that a canine adenovirus recombinant rabies vaccine administered orally protected raccoons and skunks against rabies

1. 1 Selected Zoonotic Diseases Conference Call December 2, 2009

2. Adam Macneil, PhD Special Pathogens Branch (SPB), CDC 404-639-4651 amacneil1@cdc.gov Barbara Knust, DVM, MPH SPB, CDC 404-639-1104 bknust@cdc.gov Hantavirus in the United States Selected Zoonotic Diseases Conference Call December 2 ,2009

3. Update: Epidemiology of Hantavirus Pulmonary Syndrome in the United States Adam MacNeil, PhD, MPH Barbara Knust, DVM, MPH Special Pathogens Branch, CDC The findings and conclusions in this presentation are those of the author(s) and do not necessarily represent the views of the Centers for Disease Control and Prevention.

4. Hantavirus Pulmonary Syndrome (HPS) Severe respiratory infection, high fatality Febrile illness, acute thrombocytopenia Rapid onset: Bilateral pulmonary edema / Acute respiratory distress syndrome Caused by new world hantaviruses Rodent reservoir Multiple hantavirus species, reservoirs US: mostly Sin Nombre virus, associated the deer mouse (Peromyscus maniculatus)

5. HPS in the United States Discovered in 1993: Outbreak in Four Corners region of US ‘Retrospective’ diagnosis of prior cases (serologic evidence back to 1959) HPS Registry Maintained by Special Pathogens Branch, CDC Systematically collect data on all confirmed HPS cases in the US Additional data fields (clinical, outcome, laboratory testing) to National Notifiable Diseases Surveillance System

6. HPS registry data sources 1. Diagnostic samples submitted to CDC, case report form included 2. Case report forms submitted by states (diagnosis made at state or private lab) 3. National Notifiable Diseases Surveillance System Recently attempted to acquire forms for all cases from 2006 onward Contact state HD, acquire case report form Thank you to state HD personnel who assisted

7. HPS Registry 534 cases 36.5% case fatality Infections occurred in 31 states Majority of cases in southwestern US 63% cases male 78% white, 19% N. America / American Indian Pediatric (16 years or less) cases rare: 7%

13. Deer mouse (Sin Nombre virus) White-footed mouse (New York virus) Hispid cotton rat (Black Creek Canal virus) Rice rat (Bayou virus) Distribution of hantavirus reservoirs From: Mills et al, Vector-Borne and Zoonotic Diseases 2009: Epub ahead of print

14. Summary Over 500 HPS cases documented >35% case fatality HPS continues to occur Majority of cases in southwestern US Cases and reservoirs do exist across entire US Special Pathogens in the process of rolling out new website and maps http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/epislides/episls.htm Please contact with questions, data clarification, consultations

15. Pediatric Hantavirus Pulmonary Syndrome, 2009 Case 1 (CO) 6 year old male Presented to hospital: 5/16/09 Case 2 (WA) 14 year old male Presented to hospital: 6/8/09 Case 3 (CO) 6 year old male Presented to hospital: 7/12/09 Case 4 (AZ) 9 year old female Presented to hospital: 7/12/09

16. Clinical Findings

17. Environmental Assessment– Rodent Exposures Case 1: Rodent feces in child’s room and play areas Case 2: Hand-grinding corn contaminated with rodent feces 8 days prior to illness Case 3: Bitten by mouse 10 days prior to illness Case 4: Rodent feces and nesting materials in home and play areas

18. Acknowledgements Craig Levy, Arizona DHS Dr. Elisabeth Lawaczek & Bill Ray, Colorado DPHE Nicola Marsden-Haug, Washington State DPH State & Territorial Epidemiologists NNDSS SPB staff: Pierre Rollin, Jim Mills, Andy Comer, Craig Manning, Arie Manangan, Julie Pierzchala

19. Brian F. Allan, PhD Postdoctoral Fellow, Tyson Research Center, Washington University in Saint Louis 314-935-8443 ballan@biology2.wustl.edu Research on integrated pest management approaches to preventing lone star tick bites and ehrlichiosis Selected Zoonotic Diseases Conference Call December 2, 2009

20. William H. Wunner, PhDProfessor and Director of Outreach Education and Technology Training The WistarInstitute 215-898-3854 wunner@wistar.org Deborah J. Briggs, PhD Adjunct Professor, College of Veterinary Medicine, Kansas State University briggs@vet.k-state.edu Overview of special collections on papers on rabies appearing in the journals Vaccine and PLoS NTD Selected Zoonotic Diseases Conference Call December 2, 2009

21. Heather Henderson, DVM, MPH Georgia Department of Community Health 706-845-4035 ext. 235 hihenderson@dhr.state.ga.us Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine Selected Zoonotic Diseases Conference Call December 2, 2009

22. Oral immunization of raccoons and skunks with a canine adenovirus recombinant rabies vaccine Heather Henderson, DVM, MPH Epidemiologist II, District 4 Public Health Georgia Department of Community Health

23. Background Oral vaccination of wildlife is an important part of rabies control Attenuated (ERA/SAD/SAG) and recombinant vaccinia (V-RG) vaccines have been used successfully in raccoons, foxes, coyotes Concerns about residual pathogenicity and human contact with baits No licensed oral vaccine effective in skunks Need for oral vaccine with efficacy in majority of terrestrial reservoir species

24. Background VNA produced against rabies virus glycoprotein (RVG) RVG gene can be inserted into a viral vector to produce recombinant vaccine Vector must be able to replicate on mucosal surfaces, have minimal safety concerns Canine adenovirus serotype 2 (CAV2) is associated with mild upper respiratory infections in dogs Modified-live CAV2 vaccines used to prevent disease from CAV1 and CAV2 with excellent safety and efficacy Human and canine-derived adenovirus vectors induce potent cellular, humoral, and mucosal immunity CAV2-RVG previously constructed, effective against lethal challenge in mice when administered IM or IN

25. Methods 14 raccoons 7 experimental group (CAV2-RVG) 7 control group (placebo), 1 animal died on day 21 Challenge with rabies virus day 28 post-vaccination 23 skunks 6 negative control (CAV2 parent virus) 5 experimental group 1 (CAV2-RVG, 1x108 TCID) 6 experimental group 2 (CAV2-RVG, 10-fold dilution) 6 positive control (recombinant virus SPBNGAS-GAS) Challenge with rabies virus day 35 post-vaccination All treatments administered PO Animals euthanized at first clinical signs of rabies, brain tissue tested by DFA to confirm rabies

26. Results All animals seronegative at start of study No adverse effects noted in animals receiving CAV2-RVG after >500 animal-days observation

27. Results Raccoons Control group 6 / 6 seronegative 7 days after challenge All succumbed to rabies Experimental group 6 / 7 seroconverted by day 21 after vaccination; 1 seroconverted within 7 days after challenge (day 35) All survived challenge

28. Results Skunks Negative control group 6 / 6 seronegative 7 days after challenge 4 / 6 succumbed to rabies Experimental groups 1 and 2 10 / 11 seroconverted by day 21; 1 seroconverted by day 35 All survived challenge Positive control group 5 / 6 seroconverted and survived challenge 1 remained seronegative and succumbed to rabies

29. Discussion CAV2 virus meets many criteria for an ideal recombinant rabies vaccine vector Concerns include potential for inhibition by naturally occurring antibodies in target population and induced pathology in target or non-target species More work needed to assess importance of excretion of live recombinant virus in feces; establish safety and efficacy in other species; determine optimal effective dose Safe, effective, and affordable oral vaccine for free-roaming dogs in canine rabies-endemic countries will be essential for elimination of canine rabies—responsible for >99% of human rabies

30. Co-authors Felix Jackson (CDC) Kayla Bean (CDC) Brian Panasuk (CDC) Michael Niezgoda (CDC) Dennis Slate (USDA/APHIS/WS) Jianwei Li (Thomas Jefferson Univ.) Bernard Dietzschold (Thomas Jefferson Univ.) Jeff Mattis (CDC) Charles E. Rupprecht (CDC)

31. 31 Selected Zoonotic Diseases Conference Call December 2, 2009