California Bovine Tuberculosis USAHA October California Department of Food and Agriculture Animal Health Branch

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California Bovine Tuberculosis USAHA October 2014 California Department of Food and Agriculture Animal Health Branch

California Bovine TB: 1999-2014 1999: Gain Bovine TB Free Status April 2003: Downgraded to Mod. Accredited Advanced (MAA) - bovine TB in 3 dairy herds April 2005: Regained Free Status Sept 2008: Downgraded to MAA - bovine TB in 3 dairy herds Jan 2009: 4 th affected dairy herd Eligible for Free in 2012 but 2011-12: 3 affected dairy herds Feb 2013: 1 affected dairy herd Eligible for Free July 2016 11 affected dairy herds in 11 years

Location of the 11 Affected Dairy Herds in California 7 in Central Valley Mycobacterium bovis in California dairies: A case series of 2002 2013 outbreaks B. McCluskey et al J Pre Vet Med April 2014 4 in Chino milk shed

Eleven Bovine Tuberculosis Affected Herds Detected in California in Eleven Years ~35,000 Dairy Cows in TB-Affected Herds Premises Dairy A Tulare Co. Dairy B Tulare Co. Dairy C Kings Co. Date Herd Detected How Detected Approximate Herd Size # Infected Animals May 2002 Slaughter trace 3,600 adults 53 October 2002 December 2002 Traces into and out of Dairy A (owner also a dealer) 2,000 adults 1 Slaughter trace 400 adults 35 Resolution Epidemiology Strain Depopulated ~6,500 in November 2002; restocked Depopulated ~5,000 in March 2003; restocked Depopulated ~600 in 2003; restocked April Unknown source; bulls from local breeders; replacements from out of state Exposed to Dairy A Unknown source; purebred herd, imported ~60% of cattle from "TB Free" states New strain type Genotype matched Dairy A New strain type Dairy D Fresno Co. December 2007 Slaughter trace 2,600 adults 5 Depopulated ~5,000 in August 2008; restocked Unknown source; purebred herd, few trace-ins New strain type Dairy E Fresno Co. May 2008 Trace out of Dairy D 400 adults 1 Depopulated ~1,000 in August 2008; restocked on different premises Infected cow moved from Dairy D (infected animal was CFT negative) Genotype matched Dairy D Dairy F Fresno Co. May 2008 Trace into Dairy D 2,500 on one premises and 9,500 at another 1 Test and removal program; released from quarantine December 2009 Unknown source; purebred herd, very few trace-ins New strain type Dairy G San Bernardino Co. January 2009 Trace out of Dairy F 1,300 adults 1 Test and removal program; released from quarantine June 2010 Unknown source New strain type Dairy H San Bernardino Co. April 2011 Slaughter trace 6,000 (total) 9 Test and removal program; released from quarantine February 2013 Unknown source New strain type Dairy I San Bernardino Co. October 2011 Slaughter trace 1,500 adults 65 Depopulated ~3,300 in 2012; not restocked June Unknown source; shared equipment with M-branded cattle in the past New strain type Dairy J San Bernardino Co. December 2011 Contact with Dairy I 2,000 (total) 1 Test and removal program; released from quarantine November 2012 Exposed to Dairy I Genotype matched Dairy I Dairy K Tulare Co. February 2013 Slaughter trace 2,200 adults 14 Test and removal program; released from quarantine July 2014 Potentially exposed to Dairy A Genotype matched Dairy A

11 Affected Dairy Herds in 11 years 6 detected by slaughter surveillance 5 detected by trace testing: 2 were new strains why? 7 different M. bovis strain types = 7 introductions of bovine TB in California s dairies Never found source of the 7 introductions Minimal spread from herds (4 w/same strain-type) CA is only MAA State in nation How is M. bovis entering CA dairies? Direct: Cattle (legal/illegal), wildlife, people, etc? Fomite: Foodborne, airborne, environment, etc? How can we mitigate these introductions?

Bovine TB Surveillance in California A. Slaughter Surveillance Had four of top 40 US adult packing plants (95% of adults) Submit granulomas to CA lab (FY13-14) = 1,070 total Now all split samples to NVLS for PCR Adults slaughtered in CA (FY13-14) = 777,468 Rate = 2.75 submissions per 2,000 adults Fat cattle slaughtered in CA (FY13-14) = 702,273 B. Live Cattle TB Surveillance FY 13-14 Private Veterinarians: 120,491 CFTs (1,264 accessions) Suspects = 1,420 Response Rate 1.18% Regulatory Veterinarians: 75,351 CFTs (58 herds) Suspects = 1,302 Response Rate 1.73%

February 2013 TB-Affected Herd Granuloma at AZ packing plant September 2012 NVSL not compatible : M. bovis cultured October 2012 Trace: No individual ID collected, 1 of 151 rebranded cattle, 117 from CA (72 CA herds) 34 from other states Breed DNA = Holstein, female (62 CA herds), sire? M. bovis genotype matched strain from 2002 CA herd Focus trace & 2002 related affected herd 2,200 cow dairy: Test & removal plan (USDA model) 14 TB-infected cattle removed (on first two tests) Released July 2014 (after 5 whole herd tests) Annual tests for 5 years after release quarantine

Investigation of 2013 Affected Herd 5 years of records: brand + sale-yard + private sales 11 dairy herds assoc. at calf ranch Trace ~4,400 cattle sold 2008-2013 Epi investigated 99 herds Examined 36 herds for brands from affected herd Tested 65 trace herds (approx 106,000 cows) No spread of bovine TB detected Wildlife surveillance: Negative Two USDA/APHIS/VS IMT assisted investigation Public Health and OSHA oversight of dairy personnel Infection hidden from surveillance for 10 yrs

April 2013: Slaughter Trace Granuloma at California plant PCR positive; M. bovis cultured Inadequate ID to confidently trace Breed DNA: Jersey female Most likely: 3 yr old cow From dispersed 500 cow San Diego Co dairy To California Jan 2012 from Pennsylvania dealer (origin untraceable) M. bovis genotype: Unique strain (8 th ) Most closely resembles Mexican steer in TX in 2001 (26 SNPs difference) Investigations complete

September 2013: Slaughter Trace Granuloma at California plant (during TB-review) PCR positive; M. bovis cultured M. bovis genotype: Same strain as April 2013 cow Trace (backtag not sub): 12 year-old home raised beef cow Granuloma DNA matched to ½ sibling in herd Herd ~150 pairs quarantined: TB tested neg. twice - released Retest herd in 12 months Contacts & wildlife tested neg Herd was exposed to dairy (source of April 2013 sample) Irrigate with reclaimed water Which infected first dairy or beef?

November 2013: Slaughter Trace M. bovis cultured Dec 26, 2013 Granuloma collected at California plant Nov 2013 Trace: Utah backtag, but hair DNA not match TBtissue DNA Female, Holstein M. bovis genotype: Unique strain (9 th ) Test: Herds of origin of index and cattle on either side on packing-plant rail Utah tested 3 most likely herds: Neg California tested 4 herds: Neg Additional herd scheduled: AZ next

Is There an M. bovis Reservoir in California? Mexican Origin Cattle? 435 M. bovis infected cattle in US from slaughter surveillance FY 2001 June 30, 2014 87 US or unknown origin fed cattle: 20% 52 Adults: 12% 295 Mexican origin fed cattle: 68% Genotyping indicates that these Mexican cattle were not the source of infection for California s recent dairy cases

Human TB Cases Attributable to M. bovis by Age Group California, 2003-2012 120 70-100 cases each year, ~50% of total US cases! <15 yrs 15-64 yrs 65+ yrs % M.bovis 7 100 6 Count 80 60 40 5 4 3 2 % M. bovis 20 1 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 0

Percentage of Human TB Cases Attributable to M. bovis, California, 2003-2011 M. tuberculosis and M. bovis disease in people: Clinically, radiographically, and pathologically indistinguishable M. bovis accounts for ~4.5% of all culturepositive TB cases in CA, compared to 1-2% nationally 1 About 25% of childhood TB in US is due to M. bovis Del Norte San Francisco San Mateo Santa Cruz Trinity Lake Solano Contra Costa Santa Clara Siskiyo u Tehama Glenn Yolo Shasta Butte Modoc Lassen Plum as Sierra Nevada Placer El Dorado Alpine Tuolumne Mariposa Merced San Luis Obispo Santa Barbara In San Diego, 10% of TB cases are due to M. bovis Madera Fresno Kings Ventura Amador Mono Tulare Kern Los Angeles Inyo San Diego Legend Dark Brown: 4 percent Medium Brown: 2-4 percent Light Brown: 0.1-3.9 percent Gray: No M. bovis cases Cases: Occurred in 32 counties, concentrated in southern California San Bernardino Riverside Imperial Cases: >80% Hispanic ~64% have extrapulmonary lesions 1 Hlavsa, Clin Infect Disease, 2008

Spoligotype and 24 MIRU-VNTR Genotyping Results Year Cattle M. bovis Case # Cattle Isolates Genotyped # CA People with Same Genotype Any Epi Links? 2007 Dairy D: Fresno 6 5 0 reside in affected counties, 2 recent US arrivals, 2/3 interviewed/no link accurint search neg 2007 Dairy F: Fresno 1 3 2009 2011 2011 2011 2011 * 1-off MIRU-VNTR Dairy G: San Bernardino Dairy H: San Bernardino Dairy H: San Bernardino Dairy I: San Bernardino Dairy I: San Bernardino 0 reside in county, 2 interviewed, no epi link accurint search neg 1 4 Accurint search neg 4 2 0 reside in county, accurint and DMV searches, no links 1* 0 NA 23 0 NA 1* 2 0 reside in county, accurint and DMV searches, no links 16 people infected with strains that match 5 herd strains

Goals Whole Genome Sequencing Project Plan M. bovis Isolates from People in California Better characterize M. bovis isolates in North America Build database to guide US cattle disease control policies Determine if US sporadic cattle TB strains also infect people Assist Mexico s cattle TB program Identify source herds infecting people Reduced M. bovis in people Comments CA Dept Public Health (CDPH) hold patient information Project will not interfere with CDPH genotyping (spoligo/miru) NVSL will report results to CDPH CDFA hold cattle herd information If isolates from cattle and people match - CDFA and CDPH discuss

Potential TB Source Mexican Origin Cattle Domestic Cattle People Wildlife Cattle Feed/water Non-traditional species Potential Sources and Mitigation of Risk of Bovine Tuberculosis to California s Cattle Mitigate Risk Support Mexico control programs, entry requirements, surveillance, traceability Keep separate from replacement stock Prevent illegal entry (dairy calves/cheese/etc) Surveillance, traceability, and diagnostic tests Pasteurize waste milk/colostrum Biosecurity/management practices Educate workers to reduce risk: prevention, testing, treatment, sanitation Support TB-control/education programs for Mexicans Determine if herds with human sanitation problems should be TB-tested Ensure biosolids/reclaimed water adequately treated before use Prevent cattle from contact with sewage wastewater (wildlife component?) Surveillance; biosecurity to control contact Waste water management; feed source biosecurity, imported feeds? Surveillance, prevent contact

Take-home Messages 1. New M. bovis strains continue in US cattle with no definitive source: 32 unexplained US herds since 2000 (>5 SNP to fed case) {Suelee} 2. Need active surveillance of adult and fed cattle 3. Lack of individual cattle identification hinders tracing 4. Need rapid accurate tests to detect infection 5. Over 50% of US M. bovis cases in people occur in California 6. Genotyping is helping to determine disease relationships 7. Determine what makes a herd high risk for disease 8. Mitigate the risk of introducing disease from many potential sources