your patient can make you sick – part 2 - toxoplasmosis

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Your Patient Can Make You Sick Part 1: Leptospirosis

Your Patient Can Make You Sick

Part 2: ToxoplasmosisJonathan M. Chapman, DVM, MPH, CPHSmall Animal Veterinarian Intern

VCA Arboretum View Animal HospitalVeterinary Technician Educational SeminarJanuary 12, 2016

Presentation outlineWhat is toxoplasmosis?Etiology and pathogenesisClinical findingsDiagnosisTreatmentZoonotic riskPreventionSummary and recommendations

What is toxoplasmosis?Toxoplasmosis is caused by Toxoplasma gondiiToxoplasma gondii has several characteristicsObligate intracellular coccidian protozoan parasiteInfects humans and warm-blooded animalsHas worldwide distribution

Etiology and pathogenesisFelids are the only definitive hosts ofT. gondiiWild and domestic cats serve as the main reservoir of infectionApproximately 30% of cats are serologically positive for infectionThere are three infectious stages ofT. gondiiTachyzoites (rapidly multiplying form)Bradyzoites (tissue cyst form)Sporozoites (in oocysts)T. gondiiis transmitted in several waysConsumption of infectious oocysts from cat fecesConsumption of tissue cysts in infected meatTransplacental transfer of tachyzoites from mother to fetus

Etiology and pathogenesisT. gondiigrowth cycle starts with enteroepithelial replicationAfter unexposed cats ingest uncooked meat containing tissue cysts Bradyzoites are released from tissue cystsAfter digestion in the stomach and small intestineBradyzoites invade intestinal epithelium and undergo sexual replicationRelease of oocysts in fecesOocysts are first noted in the feces at 3 days after infectionMay be released for as long as 20 days

Etiology and pathogenesisOocysts sporulate and become infectious outside the cat within 15 daysRemain viable in the environment for several monthsDepends on various factorsAerationEnvironmental temperatureCats usually shed oocysts only once in their lifetimeDevelop immunity toT gondiiafter the initial infectionOocysts are consumedUncooked meat containing tissue cysts (carnivores)Food or water contaminated with cat feces containing oocysts (all warm-blooded animals)T. gondiiinitiates extraintestinal replicationBradyzoites followed by sporozoites are released and infect intestinal epithelium

Etiology and pathogenesisTachyzoites emerge and disseminate via the bloodstream and lymphOccurs after several rounds of epithelial replicationTachyzoites infect tissues throughout the body and replicate intracellularlyCells rupture causing tissue necrosisYoung and immunocompromised animals may succumb to generalized toxoplasmosis at this stageOlder animals mount a powerful cell-mediated immune response to the tachyzoites to control infectionCauses tachyzoites to form into the tissue cysts or bradyzoites

Etiology and pathogenesisTissue cysts are usually seen in neurons, but also seen in other tissuesIndividual cysts are microscopicUp to 70 m in diameterMay enclose hundreds of bradyzoites in a strong and thin cyst wallMay remain viable in the host for many years or for the life of the host

Clinical findingsGeneral clinical signs of T. gondii infection include: PyrexiaLethargyAnorexiaWeight lossVomitingDiarrheaIcterusCoughingDyspneaOcular dischargePhotophobiaUveitisAtaxiaSeizuresDeath

Clinical findingsThe tachyzoite stage causes tissue damage and results in clinical signsClinical signs depend on several tachyzoite characteristicsThe number of tachyzoites releasedThe organs damaged by the tachyzoitesThe ability of the host immune system to limit tachyzoite spreadAdult immunocompetent animals control tachyzoite spread efficientlyToxoplasmosis is usually a subclinical illnessTachyzoites spread systemically in young animals, especially puppies, kittens, (and piglets) causing illnessTachyzoites may also spread to a fetusNecrosis in multiple fetal organsAcute generalized toxoplasmosis can developImmunocompromised adult animalsExample: Cats infected with feline immunodeficiency virus

DiagnosisStandard bloodwork, urinalysis, and thoracic and abdominal radiographs will not provide a definitive diagnosisThe following may be noted:CBCLeukopenia mainly characterized by a lymphopeniaNeutropenia with a degenerative left shiftLeukocytosis may occur during recoveryChemistryIncreased ALTIncreased ALPHypoalbuminemiaHyperbilirubinemiaMild hypocalcemiaUrinalysisMild proteinuriaBilirubinuriaThoracic radiographsInterstitial to alveolar lung patternPleural effusionAbdominal radiographsAbdominal effusionHepathomegaly

DiagnosisDefinitive diagnosis requires biologic, serologic, or histologic methods Clinical signs of toxoplasmosis are nonspecific and are not sufficient for a definite diagnosisAntemortem diagnosis Indirect hemagglutination assayIndirect fluorescent antibody assayLatex agglutination testELISA IgM antibodies appear faster after infection than IgG antibodiesIncreased IgM titers (>1:256) are consistent with recent infectionIgG antibodies appear by the fourth week after infectionIgM antibodies generally do not persist past 3 months after infectionIgG antibodies remain increased for years during subclinical infectionIgG titers must be measured in paired sera from the acute and convalescent stages (approx. 34 wk apart)Infection is indicated by an at least 4-fold increase in the titerCSF and aqueous humor may be analyzed Presence of tachyzoites or anti-T. gondiiantibodies indicates infection

DiagnosisPostmortem diagnosisTissue impression smearsTachyzoites may be noted Microscopic examination of tissue sections Tachyzoites or bradyzoites may be notedT. gondiiis morphologically similar to other protozoan parasitesSarcocystisspeciesNeospora caninum

DiagnosisOther diagnostic methodsFecalEvaluation with Sheathers sugar solutionSample may be diagnostic with visualization of oocystsFecal oocyst shedding rarely occurs during clinical diseaseCytologyT. gondii is rarely detected in body fluid during acute infectionBronchoalveolar lavage may be effective in identifying organisms when pulmonary signs are present

TreatmentTreatment for toxoplasmosis consists of oral medication and supportive careHowever, treatment is seldom warranted in animalsClindamycin12.5 mg/kg POBID x 14-28 daysTreatment of choice for dogs and catsPyrimethamine and sulfadiazinePyrimethamine : 0.25 0.5 mg/kg PO BID x 14-28 daysSulfadiazine: 30 mg/kg PO BID x 14-28 daysWidely used for treatment of toxoplasmosisDrugs act synergisticallyBeneficial if given in the acute stage of the diseaseActive multiplication of the parasiteUsually will not eradicate infectionLittle effect on the bradyzoite stage

TreatmentOther drugs used less commonlyDiaminodiphenylsulfone (dapsone)1 mg/kg PO q8h x 10 daysDo not use in catsCan cause hemolytic anemia or neurotoxicityAtovaquone13.3 mg/kg PO q8h x 10-21 days with a fatty mealSpiramycin 12.5-23.4 mg/kg PO q24h x 5-10 days

Zoonotic riskT. gondiiis an important zoonotic agentAs much as 60% of the human population in some areas of the world have serum IgG titers toT. gondiiExposure most likely occurs after ingestion of T. gondiiUndercooked meatOocysts from cat fecesThese people are likely to be persistently infectedToxoplasmosis is a major concern for people with immune system dysfunctionUsually presents as meningoencephalitisResults from the emergence ofT. gondiifrom tissue cysts located in the brainToxoplasmosis is also a concern for pregnant womenTachyzoites can migrate transplacentally and cause birth defects in human fetuses

PreventionThe stages ofT. gondiiin meat are killed by contact with soap and waterWash hands thoroughly with soap and waterWash all surfaces in contact with meat (Ex. Cutting boards, sink tops, knives, etc.)T. gondiiorganisms in meat can also be killed by exposure to extreme cold or heat or by gamma irradiationHeat meat throughout to 67C (152.6F) or cool to 13C (8.6F)Avoid tasting meat while cooking or while seasoning Tissue cysts are killed by exposure to 0.5 kilorads of gamma irradiation

PreventionWear gloves and wash hands thoroughly after working with soil or cat litterThoroughly wash vegetables or other foods in contact with soilPregnant women should avoid contact with possible contaminantsCat litterSoilRaw meatPet cats should be fed only dry or canned cat foods or properly cooked foods A cat litter box should be emptied dailyPreferably not by a pregnant womanNo vaccine is available for toxoplasmosis in animals or humans

Summary and recommendationsZoonotic diseaseMild to severe clinical signs occur including deathDefinitive diagnosis requires advanced testingTreatment is not always necessaryDisease prevention is importantClean cat litterboxes every dayAlways properly handle meat and other contaminantsPregnant women, youth, and immunocompromised individuals are most at risk

AcknowledgementsJoao Felipe de Brito Galvao, MV, MS, DACVIMKathleen Van Lanen, DVM, DACVECCElizabeth Norberg, CVT, BSThe entire staff at VCA Arboretum View Animal Hospital

Any questions?

ReferencesCenters for Disease Control and Prevention. "Toxoplasmosis. Parasites - Toxoplasmosis (Toxoplasma Infection). Centers for Disease Control and Prevention, 10 Jan. 2013. Web. 08 Jan. 2016.Lunn, Katharine F., BVMS, MS, PhD, MRCVS, DACVIM. "Overview of Toxoplasmosis."Merck Veterinary Manual. Merck Sharp & Dohme Corp., Apr. 2015. Web. 22 Dec. 2015.Plumb, Donald C. Plumb's Veterinary Drug Handbook. 8th ed. Hoboken, NJ: Wiley-Blackwell, 2015. Print.Tilley, Lawrence P. Toxoplasmosis."Blackwell's Five-minute Veterinary Consult: Canine and Feline. Oxford: Wiley-Blackwell, 2011. 1242-43. Print.