Things your epidemiologist never told your about surveillance - Dr. Jeff Zimmerman, Veterinary Diagnostic Laboratory, Iowa State University, from the 2017 North American PRRS/National Swine Improvement Federation Joint Meeting, December 1‐3, 2017, Chicago, Illinois, USA. More presentations at http://www.swinecast.com/2017-north-american-prrs-nsif-joint-meeting

1. Challenges to Global Infectious Disease Surveillance
J Zimmerman, M Rotolo, C Wang, R Main

2. xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
Challenges to Global Infectious Disease Surveillance
J Zimmerman, M Rotolo, C Wang, R Main

3. Global Infectious Disease Surveillance -
Taking stock of our situation.

4. • Classical swine fever virus
identified in 1903.
• Benefit:cost ratio of CSFV
eradication in the U.S.
≥ $13.2 (USDA, 1981).
• 2017 - 32 of 181 (17.7%)
OIE-member countries free
of CSFV.
How are we doing?

5. • FMDV identified in 1897.
• 2013, 66 of 181 (36.5%) OIE
countries "FMD free where
vaccination is not practiced".
• Annual losses $6.5 to $21
billion dollars annually
(Knight-Jones, Rushton, 2013; Longjam et
al, 2011; OIE, 2017a).
How are we doing?

6. • PRRSV identified in 1991.
• U.S. pork producers' PRRSV
losses $664 million annually
(Holtkamp et al., 2013).
• European producers' losses
€126.79/sow/year and €3.77
per pig marketed in herds
with "slight" PRRS (Nathues et al.,
2017).
How are we doing?
https://www.prrscontrol.com/portal/prrscontrol/prrs-
knowledge/porcine-reproductive-and-respiratory-syndrome

7. Perfect storm … ?

8. FAOSTAT (2013) - Live pigs exported/imported

9. https://pbs.twimg.com/media/BnwxbIoIgAAVLkB.jpg

10. Challenges to Global Infectious
Disease Surveillance … where do we start?

11. Start with the end in mind:
• On-going surveillance for early
detection and rapid elimination.
• Risk-based surveillance?
• Syndromic surveillance?
• On-going sampling/testing?

12. Start with the end in mind:
• On-going surveillance for early
detection and rapid elimination.
• Ultimately, we rely on surveillance
sampling and diagnostic testing.
1. What is the best surveillance specimen?
2. Do we have the tests?
3. Statistically-based sampling methods?

13. 1. What is the best specimen?
https://www.flickr.com/photos/eufmd/8401462980
How about bleeding pigs?

15. We have options = aggregate samples
• Commonly used in environmental studies
• A sample collected from a specific location at a specific time
Apalachicola Bay, Florida Grab samples used in
environmental studies

16. Aggregate Samples
• Different than a pooled sample
• BY DEFINITION: “pooled sample” -
created by combining ≥ 2
specimens into one for testing
(Dorfman, 1943).
• Individual sample unit identity is
usually lost by pooling.

17. Aggregate Samples
• Examples
• Air samples, water samples
• Bulk tank milk samples
• Oral fluid samples (swine, bovine)
• Easy to collect
• Inexpensive, efficient surveillance
• Do we have assays for nucleic acid and
antibody detection?

18. Detection of pathogens in bulk tank milk samples
Pathogen* Method of Detection
Border disease virus PCR and ELISA
Bovine viral diarrhea virus PCR and ELISA
Coxiella burnetti PCR and ELISA
Foot-and-mouth disease virus PCR and ELISA
Mycobacterium avium subspp
paratuberculosis
Culture, PCR and ELISA
Mycoplasma bovis Culture, PCR and ELISA
Staphylococcus aureus Culture and PCR
Streptococcus agalactiae Culture and PCR
Schmallenberg virus ELISA
*Selected pathogens are of economic significance. List is not inclusive.
Citations available upon request.

19. Detection of pathogens in oral fluids
Pathogen* Method of Detection
African swine fever virus PCR and ELISA
Classical swine fever virus PCR
Foot-and-mouth disease virus PCR
Influenza A virus Isolation, PCR and ELISA
Porcine deltacoronavirus PCR
Porcine epidemic diarrhea virus PCR and ELISA
PRRSV Sequencing, PCR and ELISA
*Selected pathogens are of economic significance. List is not inclusive.
Citations available upon request.

20. How well do tests optimized for
aggregate samples work?

21. Within-pen
prevalence
One oral fluid sample
(rate of detection)
PCR | ELISA
No. serum samples to equal
the oral fluid detection rate
PCR | ELISA
5% 31% 17% 8 5
10% 79% 59% 11 7
15% 94% 85% 12 9
20% 98% 94% 13 10
25% 99% 97% 13 11
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxx Lopez & Osorio. 2004. Vet Immunol
Immunopath 102:155-163
Data from Olsen et al., 2013

22. Within-pen
prevalence
One oral fluid sample
(rate of detection)
PCR | ELISA
No. serum samples to equal
the oral fluid detection rate
PCR | ELISA
5% 31% 17% 8 5
10% 79% 59% 11 7
15% 94% 85% 12 9
20% 98% 94% 13 10
25% 99% 97% 13 11

23. Within-pen
prevalence
One oral fluid sample
(rate of detection)
PCR | ELISA
No. serum samples to equal
the oral fluid detection rate
PCR | ELISA
5% 31% 17% 8 5
10% 79% 59% 11 7
15% 94% 85% 12 9
20% 98% 94% 13 10
25% 99% 97% 13 11
Do you really want to bleed pigs?

24. Do we have enough information on tests
for aggregate samples?
(Do we have "validated" tests?)

25. Confusion in terminology …
• What is a validated test?
• Validation: "confirmation that the requirements for a specific
intended use are fulfilled"
• Validation parameters: accuracy, linearity, limit of detection,
limit of quantitation, range, recovery, repeatability,
reproducibility, ruggedness, diagnostic specificity/sensitivity,
analytic specificity/sensitivity.
• From: Glossary of Terms for Quality Assurance and Good Laboratory Practices.
2009. United Nations Office on Drugs and Crime. ISBN 978-92-1-148253-9

26. Annals of internal medicine. 1997 126:91-94.
xxxxxxxxxx
Lopez & Osorio. 2004. Vet Immunol
Immunopath 102:155-163

27. Lelie et al., 2002. Sensitivity of HCV RNA and HIV
RNA blood screening assays. Transfusion 42:527-536

28. Lelie et al., 2002. Sensitivity of HCV RNA and HIV
RNA blood screening assays. Transfusion 42:527-536
Lopez & Osorio. 2004. Vet Immunol
Immunopath 102:155-163

29. We need estimates of dx se / dx sp
to use tests in surveillance

30. Our Greatest Challenge:
Assume we have good samples
and tests. How to conduct
statistically-valid surveillance ?

31. Statistically-valid sampling for aggregate samples?
• Where?
• Abattoir? On-farm? At sites of concentration?
• On-farm sampling coordinated at the regional level?
• How frequently?
• How many?
The Old Answers do not apply to aggregate samples
or to contemporary animal production systems

32. WE NEED NEW ANSWERS … an example of the problem

33. How many marbles do
you need to sample in
order to include at least
one red?
100 marbles - 90 white, 10 red
prevalence = 10%

34. How many marbles to sample?
Population size x prevalence
= sample size

35. Assumption:
Binominal
distribution
How many marbles to sample?
Population size x prevalence
= sample size

36. Binomial distribution formula
Assumptions of binomal sampling?

37. How many pigs?
Population size x prevalence
= sample size
Assumption:
Binominal
distribution

38. Binomial distribution

39. Not binomial
distribution!

40. Today …
… spatial structure.

41. Spatial No spatial
autocorrelation autocorrelation
xxxxxxx

42. Further complications …
Spatial structure at the
barn level and at the
site level.

44. Traditional approach cannot work on modern farms ...
1. Sample size equations are based on
binomial or hypergeometric distributions.
2. These assume that results are independent.
3. This is generally true in "extensive" farms
but not in "intensive" farms.

45. Spatial sampling is better (than
random sampling) when there
is autocorrelation" Wang et al.
2012. Spatial Statistics 2:1-14.
Heikkinen, J. (2006). Assessment of
uncertainty in spatially systematic
sampling. Forest Inventory, 155.
Solutions? … work
in progress.

46. Summary

47. Start with the end in mind:
• We need on-going surveillance for early
detection and rapid elimination.
• Ultimately, we will rely on surveillance
sampling and diagnostic testing.
1. What is the best surveillance specimen?
2. Do we have the tests?
3. Statistically-based sampling methods?

48. Thank you!
jjzimm@iastate.edu