United States Department of Agriculture
Animal and Plant Health Inspection Service
Compendium for Coxiella burnetiiAmerican Sheep Industry Association
January 24, 2012
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Katherine Marshall, DVM MSC
Centers for Epidemiology and Animal Health,
Fort Collins, CO
United States Department of Agriculture
Animal and Plant Health Inspection Service
Q fever in the US
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United States Department of Agriculture
Animal and Plant Health Inspection Service
Why is CDC Interested in Q fever?
• Category B bioterrorism agent
- need to understand background levels
before a BT event takes place
• Current numbers of cases are under-reported
- true level of disease unknown
- level of serious disease (endocarditis) unknown
- economic burden of Q fever in humans and
animals is poorly assessed
- in Australia, considered the most
economically important zoonosis
CDC slide
United States Department of Agriculture
Animal and Plant Health Inspection Service
Ruminant shedding• Milk, fecal, placental fluids, fetal tissues, vaginal mucus,
urine
• Ruminant species variation
Cattle shed more in milk and for longer periods1,2
Vaginal mucus shedding limited in time
Sheep/Goats shed periparturiently (wks - months post partuition)2
Caprine
Milk main route
Vaginal mucus and feces less common
Ovine
Feces, milk, and vaginal mucus shedding
Most shed by all routes simultaneously
United States Department of Agriculture
Animal and Plant Health Inspection Service
Why the interest? Netherlands outbreak in 2007- 2009
• Began with abortions on goat farms 2005 – 2007
• 15 dairy goat farms, 1 dairy sheep farm
• In 2007, there were 168 human cases
• In 2008, there were 1,000 human cases
• In 2009, there were 2,357 human cases
What happened?
Increase in goat populations (10 fold increase from 1998 – 2008), naïve human population, good conditions for aerosol spread, other?
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United States Department of Agriculture
Animal and Plant Health Inspection Service
More on Netherlands• Human cases
• Increased from 0 – 32 from 1975 – 1986
• Fluctuated within same range 1986-2006
• Animals
• Cattle – 1981 ~36% herds positive
• Sheep – 1986 3-5% animals positive
• Goats – 1986 – 2.6% animals positive
• Change in small ruminant notification requirement 2008
• Required for small ruminants kept for milk production
United States Department of Agriculture
Animal and Plant Health Inspection Service
Control measures - 2009 Mandatory national management protocol for dairy
goat and sheep operations
~250,000 small ruminants vaccinated (prohibited prior to October 2008)
Mandatory movement restrictions
Educational campaign – veterinarians, physicians, public
Bulk milk tank monitoring of farms with >50 dairy sheep or goats
Pregnant sheep and goats on positive farms culled -~50,000
Could it happen here??
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United States Department of Agriculture
Animal and Plant Health Inspection Service
Goat-Associated Outbreak, 2011
Abortion storm among goats at Farm A in Washington Stillbirths noted by owners Dec 2010 – Jan 2011
Veterinarian consulted; multiple tests negative
Veterinarian assisted in C-section for goat; 2 stillborn kids (late March)
Placenta sent to local veterinary lab Washington Animal Disease Diagnostic Lab (WADDL) detected C.
burnetii by immunohistochemistry (late April 2011)
Reporting chain commences: WADDL
Washington State Department of Agriculture (WSDA)
Washington State Department of Health (WA DOH)
“County A” Health Department
WA DOH slide
United States Department of Agriculture
Animal and Plant Health Inspection Service
Multi-State Summary
Traced goats from Farm A to 20 additional farms
Included WA, MT, and OR
17 of 21 total farms participated in investigation
Detected C. burnetii in herds at 16 of 17 farms
Identified 20 human infections (11 WA; 9 MT)
15 (75%) were symptomatic
4 hospitalized; no deaths
Genetic analysis identified same strain (type 8) in 3 specimens
Index goat placenta, MT goat, WA environmental swab
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WA DOH slide
United States Department of Agriculture
Animal and Plant Health Inspection Service
Needs • Consistent reporting requirements across states
• Unknown prevalence of acute cases in livestock
• Consistent response to positive herds / flocks
• Considers not only human health risks
• Needs of the producers as they continue management of their flocks/herds
• Increased producer education on Q fever the risks to humans and ways to reduce risk
• Viable control and prevention options for producers
Potential for Genetic Tools
• Up to 3-fold differential human Q fever depending on sheep breed exposure (De Lange et al 2013)
• Suggests one or more genetic elements present in sheep with major roles in amount of C. burnetii shedding
• Consistent with genetic observations in other species, like cattle and mice
Goal: Marker-Assisted Breeding
• Genetic marker-assisted breeding has been successfully used for classical sheep scrapie
• Multiple genetic marker tools for OPPV, etc.
• Selective breeding of low C. burnetii shedding sheep would have benefit for reduced transmission to sheep, other livestock, and humans
Approach: Find and Prioritize Genes
• Genome-wide association scan (GWAS)
• Systematic search along all chromosomes for gene regions harboring the most important genetic variants
• Phenotype: C. burnetii shedding– Ideal case would be to find sheep that do not shed
– Low shedding sheep also beneficial
– Quantitative measure of shedding accomplishes search for both
Shedding Assays for C. burnetii
• Some standardization of serological testing and simple PCR
• Little standardization for quantitative shedding measures– Literally dozens of quantitative PCR assays in use,
published and unpublished
• Testing more than a dozen published qPCRdiagnostic assays– First test is to replicate reported lab results
Incorporating New Sequence Data Into Diagnostic Selection
• First complete genome sequence for C. burnetiipublished in 2003 (Seshadi et al 2003)
• Sequences for more C. burnetii strains from around world published recently
• While some qPCR tests have good representation of target sequences in most or all known Coxiellastrains, other tests are less robust
• Best tests are robust to strain differences
– Incorporating such tests into sampling
Current Project Goal
• GWAS output is a prioritized list of all such gene regions with important genetic variants
• This is the critical first step to developing genetic breeding tools
• Thank You: National Sheep Industry Improvement Center
– Project: “Identification of Genetic Regions Associated with Shedding of Coxiella burnetii (Q Fever) in Sheep”
Future Directions• Work to convert such regions to useful genetic
markers for breeding
• Vaccine development – goal reduce/eliminate shedding transmission to environment and other hosts
• Are learning from vaccine development in other countries
Future Directions• Further work can convert such regions to useful
genetic markers for breeding
• Fine mapping & Validation– Produce genetic markers useful beyond discovery
flocks
• Assess potential for correlated responses to selection– Make sure breeding based on genetic markers does
not hinder other production objectives
• Develop similar tools for other species
