Washington State Departments of Agriculture and Health

Q Fever in North Central WashingtonJacqueline Dawson, PhDPublic Health EpidemiologistChelan, Douglas, Grant, Kittitas and Okanogan Counties509-886-6428Jacqueline.Dawson@cdhd.wa.govJeff Ketchel, MA, RS; Lois Swenson, RN & Amber McCoy, RSGrant County Health DistrictBen Smith, DVMWashington State Department of Agriculture

1History1935 Queensland, Australia Montana 2012Worldwide OutbreaksMilitary troopsCities and townsDownwind from farmsNext to roads traveled by animalswww.cfsph.iastate.edu

2Q Query fever was first reported in Brisbane, Queensland, Australia, in 1935 by Derrick, who described outbreaks of febrile illness in abattoir workers. Burnet and his associate Freeman successfully isolated the organism and investigated the epidemiology of the disease. Concurrently, a similar agent (initially called the Nine Mile agent) was isolated from ticks in Montana by Davis and Cox and was subsequently found to be the same organism as that found in Queensland. In 1938 the organism was named Coxiella burnetii in honor of Cox and Burnet. In 1944 there were outbreaks among British and American troops stationed in the Mediterranean (Italy); outbreaks also occurred during World War II and during the Persian Gulf. Outbreaks have similarly been reported among persons residing in cities and towns downwind from sites where infected animals are kept.The OrganismCoxiella burnetiiBacteriaGrows inside cellsSpore-like Stable and resistant-Category B bioterrorism agent:long-term environmental stability =weeks to years resistance to heat and dryingextremely low infectious dose (1 bacteria)aerosol infectious route Killed by pasteurization

3Coxiella burnetii is a obligate intracellular gram-negative pathogen. It was previously identified as a rickettsial agent, but has been recently reclassified as Proteobacteria, the same group that contains bacteria such as Legionella. It replicates in host monocytes and macrophages. It has tremendous stability and can reach high concentrations in animal environments. Because it forms unusual spore-like structures it is highly resistant to environmental conditions and many disinfectants. Coxiella burnetii can survive 7 to 10 days on wool at room temperature, 1 month on fresh meat in cold storage, 120 days in dust and more than 40 months in skim milk. The organism is killed by pasteurization. Coxiella burnetii exists in two antigenic phases. This is important in the diagnosis of Q fever. Phase I is pathogenic and found in infected animals or in nature. Phase II is less pathogenic and is recovered only after multiple lab passages in eggs or cell cultures. Increased antibodies to phase II antigens indicate acute infection while a rise in phase I reflects a chronic infection of Q fever. TransmissionAerosolPlacenta and birth fluidsUrine, feces, milk Direct contactSurfacesIngestionTicksHuman-to-human extremely rareIngestion (mainly drinking raw milk) is probably a minor factor in the transmission of C. burnetii and a point of controversy. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88923/

4Aerosolization is the primary mode of transmission in humans and domestic ruminants represent the most frequent source of infection. Organisms can be found in airborne droplets or dust contaminated by placental tissues, birth fluids, or excreta of infected animals. Shedding of C. burnetii into the environment occurs mainly during parturition; over 109 bacteria per gram of placenta are released at the time of delivery. Aerosol or direct transmission can occur when infected animals are processed as meat, during necropsies, or while assisting deliveries.

Due to persistence of the organism in the environment, dried infective material can contaminate water, dust, and soil; C. burnetii has been isolated downwind up to mile or more from a known source. Fomites (i.e., newborn animals, wool, bedding, clothing) can also be contaminated and serve as a source of infection. Shedding in the milk occurs due to infected mammary glands, but pasteurization kills this organism.

C. burnetii has been naturally and experimentally isolated from a variety of arthropods, (mainly ticks but also cockroaches, beetles, flies, fleas, lice, mites). Over 40 tick species are naturally infected with C. burnetii, and transovarial (mother to offspring) and transstadial (between developmental life stages) transmission has been documented. Feces of infected arthropods can serve as a source of C. burnetii infection and can remain infective for at least 19 months.

Animals typically acquire Q fever through exposure to other infected animals, either through direct contact with contaminated material or aerosol exposure.Animal DiseaseSheep, cattle, goats, cats, dogs, some wild animals (including rodents), birds and ticks. Localizes in: mammary glandssupramammary lymph nodesplacenta uterus, from which it may be shed in subsequent parturitions and lactationsMay be asymptomaticReproductive failureAbortionsStillbirthsRetained placentaInfertilityWeak newbornsLow birth weightsCarrier state

5Sheep, cattle, and goats are the most common reservoirs of Q fever. The incubation period for animals is variable. Affected animals may be asymptomatic; when clinical disease occurs, reproductive failure is usually the only symptom seen. This may include abortions, stillbirths, retained placentas, infertility, weak newborns, and mastitis in dairy cattle. Lambs born following Coxiella abortions may be carried to term. However, ewes can remain chronically infected and continue to shed organisms. Organisms may be shed in milk and feces for several days after parturition.Acute InfectionThe bacteria can cause a sudden onset of: High fever (104 F) with shaking chills (night sweats)Vomiting, diarrhea, abdominal pain and chest painMuscle and joint painsSevere headache (often behind the eyes) Extreme fatigueFlu-like symptoms that usually last for 2-6 weeks Pneumonia (30 to 50%)Hepatitis (33%)= liver inflammation Skin rash (10%)Other signs (< 1%)Myocarditis, meningoencephalitis, pericarditisDeath: 1 to 2%

6Symptoms of acute disease can vary in severity and duration; a self-limited febrile or flu-like illness often occurs. Signs include fever, chills, sweats, retrobulbar headache, fatigue, anorexia, malaise, myalgia, and chest pain. Illness typically lasts from one to three weeks. 30 to 50% of patients with symptomatic illness will develop pneumonia. In more severe cases, a nonproductive cough with pneumonitis may develop. Radiographs of patients with pneumonia resemble those of patients with viral pneumonia etiologies. Multiple rounded opacities of both lungs on x-ray may be noted, and pleural effusion may also be seen. Additionally, many clinically ill patients will have abnormal liver enzymes, and some will develop hepatitis although jaundice is rare. Exanthema (rash) occurs in about 10% of cases. Rarely meningoencephalitis or pericarditis may occur with acute infection. Only 2% of acute infections require hospitalization and a similar percentage result in death. Chronic Disease1 to 5% of those infectedPrior heart diseasepregnant women Immunocompromised (ex: Cancer therapy)Endocarditis (infection of a heart valve)Poor liver functionBone infection50% relapse rate after antibiotic therapy7Chronic Q fever (infection greater than six months in duration) occurs in 1 to 5% of those infected and is relatively uncommon. It typically develops in persons with pre-existing cardiac valvular disease. Immunocompromised persons and pregnant women are also at great risk for the chronic form. Endocarditis is the major clinical presentation and accounts for 60 to 70% of all chronic Q fever cases. Infection can also affect the liver causing granulomatous hepatitis or cirrhosis. Kupffer cells are considered to be target cells for C. burnetii. Involvement in bone and arteries has also been reported. Patients who have had acute Q fever may also develop the chronic form as soon as 1 year or as long as 20 years after initial infection.Risk to Pregnant Women

Most asymptomaticTransplacental transmissionReported complicationsIn-utero deathPremature birthLow birth weight8Pregnant women who become infected by C. burnetii are typically asymptomatic. However, the organism can be transplacentally transmitted. Depending on the timing of infection abortion, neonatal death, premature birth, low birth weight, or placentitis may occur. The greatest risk is during the first trimester. Pregnant women are also at a greater risk of developing chronic Q fever infection. Pregnant women with Q fever may pose a degree of risk to medical staff.Where is it?The true incidence is unknown in the Pacific Northwest. WSU is currently conducting a study to determine the geographic distribution and goat herd prevalence.

EpidemiologyOccupational and environmental hazardFarmersLivestock producersVeterinarians and techniciansMeat processors/ abattoir workersLaboratory workers

10Q fever is an occupational hazard for persons in contact with domestic animals, such as cattle, sheep and goats. Persons at risk include farmers, livestock producers, veterinarians, abattoir workers, those in contact with dairy products, and laboratory personnel performing culture and diagnostics. There has been an increase in reports of sporadic cases in people living in urban areas after occasional contact with farm animals or after contact with infected pets, such as dogs and cats. Treatment GOATS Treatment: Oral tetracycline at the therapeutic dose may be given for 2-4 wk. In known infected herds administering tetracycline (8 mg/kg/day) prophylactically in the water supply prior to parturition may reduce spread of the organism. Merck Veterinary Manual

HUMANSTreatment DoxycyclineChronic disease long course2 to 3 years of medicationImmunityLong lasting (possibly lifelong)11The antibiotic treatment of choice is doxycycline. Antibiotic treatment is most effective when initiated within the first three days of illness. For chronic disease, treatment may be necessary for 2 to 3 years. Doxycycline and quinolones are contraindicated in pregnant women but long term therapy with co-trimoxazole (trimethoprim/sulfamethoxazole combination) has prevented fetal death in some cases. Persons recovering from Q fever are thought to develop long-lasting (possibly lifelong) immunity.

Lab testing for Q feverSerology = CF or ELISADetects antibodies produced against bacteria

LIVE bugs?= Culture at CDCRisk to laboratory personnel

PCR = polymerase chain reaction Detects and amplifies the bacteria (LIVE or DEAD)

12Polymerase Chain Reaction = PCR

Phase I vs II AntibodiesDuring the course of the infection, the outer membrane of the organism undergoes changes in its lipopolysaccharide structure, called phase variation. Acute: Higher Phase II antibody titers Not very infectiousChronic: Higher Phase I antibody titersHighly infectious http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88923/

Q fever in Washington, 2011Producer wanted to know the source of abortions in goat herdPlacenta sent to WSU by local Vet Producer assisted with tracing herd sales in WA, OR and MT

Coxiella burnetii organisms (red) within infected placenta cells (blue)

Washington State Study Humans: 61 samples were collected from Producers/family and Agriculture personnelGoats were tested from 13 farms in 7 counties: Adams, Chelan, Clark, Franklin, Grant (N=6), Pend Oreille & ThurstonSamples were collected by WSDA & USDA Vets:326 Blood samples312 Vaginal swabs108 Fecal swabs37 Milk samples

Environmental samples were taken from a few farms

Results From All Washington FarmsPEOPLE:11 / 61 (18%) had positive serum samples7 / 11 (64%) people were sick4 / 11 (36%) people were not sickAll Vets and Extension service personnel were negativeMost Producers were negative, even on goat positive farms5 / 11 Grant County: 4+ (3 ill) in a family with meat goats since 2007All goats PCR negative (including goat from Farm A); 9% ELISA +1 + recently moved to WA: raised goats, sheep and cattle whole lifeBought dog from Farm A; goats and sheep from other farmsGOATS:8% goats were ELISA + 10% fecal swabs (males) were PCR +31% of vaginal swabs were PCR +All whole blood samples were PCR negativeAll 19 + milk samples were from one non-milk producing farm

Animal Tracing ?3 positive does on one farm were not from Farm AOne positive had never been off of the farmDoes bred at Farm A were ELISA and PCR negativeQ fever is ubiquitous, so positive animals should be found throughout the stateWSU conducting study of goats around WAFarm AFarm X

2011 Environmental ResultsCDC isolated live Coxiella burnetii from the WA goat placenta and a vaginal swab taken from a Montana goat. The 2 isolates and a WA environmental sample are in the same genetic group (sequence type 8). Type 8 was previously seen in a chronic human Q fever case in Washington State with no connection to goats. Type 8 has also been found in several other goats and chronic human cases in the US.

Presence of Coxiella burnetii DNA in the Environment of the United States, 2006 to 2008 http://aem.asm.org/content/76/13/4469.full.pdf+html CDC found Q fever bacteria in environmental samples from post offices, stores, schools, farms, dairies and fairgrounds Rocky Mountains- 45%South Central 36%Upper Midwest 25%Deep South 16%West Coast 14%East Coast 6%Some areas had up to 50% positive samplesBest Practices to Control Q FeverNational seroprevalence:41.6% of sheep 16.5% of goats3.4% of cattle

http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/52000.htm

Prevention and Control Eradication not practicalToo many reservoirsConstant exposureStability of agent in environment

WSDA: Best Practices to Control Q Feverhttp://agr.wa.gov/FoodAnimal/AnimalHealth/Diseases/QFeverManagementPractices.pdf

When is the most risk ? 2 weeks prior to one month after birthLactationAbortions PlacentasBirth fluidsKidding/lambing/calving barns

Where is the most risk? Highest risk is due to contact with birth products such as placentas, birth fluids, etc.Use disposable glovesBarn only clothesMask to reduce airborne bacteria in dustRemove any dead fetuses and placentas as soon as you can in plastic bags and burn or bury at least 3 feetCompost and spread on fieldsRisk of selling manure

Immediately clean birthing areas then apply 10% Bleach, 5% Hydrogen Peroxide, or 1% Lysol30 minute contact timeKeep down dust

Farm BiosecurityLimit access for visitorsPeople with high risk to contract it are immune compromised, pregnant women, and heart valve patientsWash hands and arms after animal contactKeep barn clothes out of the houseClean and disinfect boots

Farm BiosecurityMaintain good records of animal movementsIf your animal aborts, contact local veterinarian and save everything you can, especially placenta, for diagnostic evaluationCulling of animals based on blood tests is not recommended and wont ensure a negative herd.

2 Kidding SeasonsC. burnetii infection in goats seems to be limited to two kidding seasons. Natural History of Q Fever in GoatsTodd HatchetteThe Department of Medicine, Dalhousie University, Halifax, Nova ScotiaNancy Campbell, Robert Hudson, Didier Raoult, Thomas J. MarrieMarch 2003, Vol. 3, No. 1, Pages 11-15 Posted online on July 9, 2004.ConclusionQ fever is everywhere. Individual antibody test of little value.Q fever can not be traced to any one source with any reliability.All farms had multiple sources of animals or bred animals at multiple farms.The number of antibody positive animals in this investigation (8%) was lower than that of previous studies. ResourcesMany links on our website www.agr.wa.gov Sublinks to CDC and university websites on:CompostingManure and animalsDisinfectionBasics of different products and what they will work onBoot cleaning Hand washing

AcknowledgementsCenters for Disease Control and PreventionCenter for Food Security and Public Health at Iowa State UniversityUSDA- veterinarians and laboratoriansWSU- Field Disease Investigative Unit, Extension Service and LabLocal county health jurisdictionsQuestions?