Human parapoxvirus infections – a field investigation evaluating clinical, epidemiologic and molecular aspects

1. Human parapoxvirus infections – a field investigation evaluating clinical, epidemiologic and molecular aspects E. Lederman, MD LCDR MC USN Poxvirus and Rabies Branch, DVRD/NCZVED

2. Objectives • Identify routes of transmission of parapoxviruses from animals to humans • Identify current diagnostic techniques available for confirmation of parapoxvirus infection • Distinguish between human parapoxvirus infections and cutaneous anthrax using clinical and historical information

3. Overview • Background on Parapoxviridae • focus on orf and pseudocowpox • Background on Investigation • Field • Laboratory • Investigation results • Conclusions • Limitations

4. Parapoxviruses • Orf virus • Pseudocowpox virus • Bovine papular stomatitis virus • Sealpox virus

5. Clinical manifestations - ruminants Orf stomatitis Pseudocowpox mastitis • Common diseases of ruminants – endemic worldwide • Infections via animal or environmental contact or vaccine (orf) • 40% of flocks in US infected with orf in the past 3 years • 4% of operations use the live orf vaccine* • Most common in spring (coinciding with livestock births) * NAHMS Sheep Survey, 2001

6. Zoonotic disease Orf virus Pseudocowpox virus • Incidence in humans is UNKNOWN • Not reportable, rural areas, occupational/avocational, self-limited • Similarity in manifestation  “barnyard parapoxvirus” • Last 4-8 weeks, may be painful, may become superinfected • EM and serology can not distinguish; need molecular diagnostics

7. Clinical manifestations – humans with immune compromise extensive lesions - require medical and/or surgical therapy Lederman, Green, DeGroot et al. CID 2007 in press

8. Impetus for investigation • 4 human cases of parapoxvirus infections in Missouri residents from Feb-May 2006 • 2 were initially diagnosed as cutaneous anthrax • Expending limited public health resources • 1 child was barred from school because of communicability concerns • A need to improve clinician recognition • Fair season will begin in one month • Is the general public at risk?

9. Objectives of the investigation* • Incidence unknownbut previous 2 years MO had reported 1 case to CDC • True increase in disease vs. increase in reporting? • Common source ? (e.g. sale barn or orf vaccine) • Lingering risk to humans (infected animals)? • Health messages to minimize risk? • 2 cases misdiagnosed as cutaneous anthrax • Potential educational messages for primary care providers? *initiated 19 June 06

10. Methods

11. Investigation methods - surveys • Standardized survey tools • Cases • Livestock handlers • Local veterinarians • Photographic aids • Livestock handlers

12. Field Investigation – surveys of community farmers • History of infections and risk factors • at neighboring farms and at county/state fairs (livestock exhibitors) • Questions regarding: • Demographics, occupation, animal exposure (# and activities), parapoxvirus infx in their animals, personal history of parapox infection, glove use, use of the orf vaccine

13. Field investigation – survey of local veterinarians • Veterinary experience with animal and human parapoxvirus infections, and use of the orf vaccine (live, unattenuated)

14. Investigation methods - animal and environmental sampling Obtained oral swabs of ill and asymptomatic animals, and swabs/sample of animal environments

15. molecular analysis of specimens • parapoxvirus real time assays • genus • species specific *DNA polymerase gene-based primer

16. Results

17. Case finding and risk assessment– case farms and neighboring farms

18. Field investigation - cases • Demographics • M:F 2:2, ages 10-41 • Risk factors • 4/4 infected on family farm • 3/4 bottle feeding; 1/4 shearing • 3/4 caring for ill animals at the time of infection • Gloves were not worn by any case when handling ill animals • Animal movement • 3/4 fairs only (no new animals on operation), 1/4 animals from sale barns/other farms (raised calves) • No animals had overt parapox infx at the time of our investigation • Orf vaccine use • None • No additional cases were identified at case farms

19. Field investigation - cases • However - • Two cases (above) at neighboring farm; confirmed by serology • Both were bottle feeding sick kids • No evidence linking these to the primary cases

20. Field investigation – infected livestock • 3 / 5 neighboring farms had overtly infected animals • State Fair did not have any overtly infected animals* *reported by state public health veterinarian, Dr. Howard Pue

21. Livestock handler survey results • 16/97 (16.5%) reported h/o parapox infx • Compared* individuals with and without a report of parapoxvirus infections • Male sex (OR 5.1 [1.5-17.2]) • Observation of infected animals in their herd/flock (OR 7.6 [1.0-61.1]) *Chi square or Fishers exact test, SAS 9.0

22. Burden of disease estimate • In our survey population rate of parapoxvirus infection: 5.8 infx / 1,000 PY (farm years) • If an average farmer works for 30 years, then 18% of all exposed farmers have a lifetime risk of parapoxvirus infection

23. Veterinarian survey results* • 46% consulted for human orf at one time, 11% for pseudocowpox • 36% were aware of orf vaccine use in local flocks *Response rate of 63%

24. Laboratory - results • Animal and environmental sampling • At case farms • Specimens taken during on site visit – all negative • 1 ( + ) calf specimen (obtained soon after human case) • Genetic match with human • At neighboring farms and state fair • 100% of animals with clinical disease (sheep and goats) ( + ) by PCR • 22% of asymptomatic animals • Artificial nipple – weakly positive

25. Conclusions

26. Conclusions • Parapoxvirus infections are common in MO livestock (target species) and their handlers (16%) • Educate the target human population • FAQ sheet • May be confused with alarming clinical entities (e.g. anthrax) • Focused education for PCPs/PHPs is warranted

27. Educational materials for target population • FAQ sheet geared towards industry • Coauthored by CDC and APHIS • 3 industry newsletters • Readership ~100,000 • CDC website • APHIS website http://www.cdc.gov/ncidod/dvrd/orf_virus/

28. Parapox vs. cutaneous anthrax:two key points • Health of the animals • Asymptomatic or minimal disease – NOT ANTHRAX • Anthrax kills animals – deaths within 24-48 hr • Geographic distribution • B. anthracis is NOT routinely found in all U.S. soil • In soil where previously infected animals have died • Major epizootics in the previous 50 years: ND, SD, MN, TX • Other states: NM, NV, CA, MT

29. Conclusions • Parapoxvirus infections on these three case farms do not appear to have a common source • Reporting more likely b/c of confusion with anthrax AND • Release of MMWR

30. Conclusions • Veterinarians may be consulted for human disease • May contribute to underrecognition • Transmission to humans • “nurser’s nodule” – bottle/tube feeding and general care of juveniles appears to be the route of transmission now (5/6 cases)

31. Conclusions • Fomites • Common feed troughs/nipples may be important in animal-animal transmission • Asymptomatic animals appear to shed virus • Orf vaccine • Although used in this community, the orf vaccine does not appear to be related to these human cases

32. Study Limitations • Information bias • Recall, accuracy of diagnosis • Convenience sampling • Not generalizable • Lack of a reliable culture system • Proof of viable virus (and thus infectivity to humans)

33. Missouri DHSS Howard Pue BaoPing Zhu Lisa Sitler Ralph Horne APHIS-USDA Katherine Marshall California State Lab, Virology David Schnurr CDC DVRD – Poxvirus Program Everyone! NCHS Min Tao DVRD-OD Abbigail Tumpey Dana Haberling DFBMD Sean Shadomy Acknowledgements Partners Disclaimer: The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy.

34. Thank you !