Blood Borne Infections 2025 PDF

Blood Borne Infections AMBER HARRIS, DVM, DACVIM (SAIM) VETM5291 – CRH II 1/13/25 Objectives Understand routes, modes of transmission, and prevention for each disease. Be able to describe cytology findings for each disease. Understand and recognize the clinical syndromes associated with...

Blood Borne Infections AMBER HARRIS, DVM, DACVIM (SAIM) VETM5291 – CRH II 1/13/25 Objectives Understand routes, modes of transmission, and prevention for each disease. Be able to describe cytology findings for each disease. Understand and recognize the clinical syndromes associated with each disease. Understand screening and diagnostic tests for each infection; understand the limitations of each testing method; design a diagnostic plan. Understand treatment recommendations for each disease. Outline Primary mode of transmission: Tick borne Ehrlichiosis Anaplasmosis Rickettsiosis Cytauxzoonosis Multiple modes Mycoplasmosis Babesiosis Eating the host Tularemia Readings Greene’s Infectious Diseases of the Dog and Cat, 5th edition ◦ Available online through UGA Library ◦ Chapters: 44, 45, 46, 58, 74, 97, 98 TICK BORNE TRANSMISSION Ehrlichiosis 3 species: Ehrlichia canis*, ewingii*, chaffeensis Intracellular, gram-negative bacteria Within family Anaplasmataceae Includes Anaplasma platys and Anaplasma phagocytophilum E. canis – canine monocytic ehrlichiosis Geographic distribution: E. canis – worldwide but esp. tropical and subtropical regions E. ewingii – south central and southeastern USA E. chaffeensis – southern and south-central USA, Africa Ehrlichiosis cont’ Mode of transmission: Tickborne: Rhipicephalus sanguineus (Brown Dog tick) – E. canis Amblyomma americanum (Lone Star tick) – E. ewingii and chaffeensis Amblyomma maculatum (Gulf Coast tick) – E. chaffeensis Major CS: E. canis: fever, lethargy, inappetence, weight loss, cutaneous/mucosal petechia/ecchymotic hemorrhages, lymphadenomegaly, splenomegaly, uveitis Cats: fever, lethargy, inappetence, weight loss, hyperesthesia, joint pain E. ewingii: fever, lethargy, inappetence, polyarthritis Can infect and cause disease in humans Ehrlichiosis cont’ Form morulae w/in phagosomes of circulating leukocytes: E. canis – monocytes, macrophages, >> lymphocytes Canine monocytic ehrlichiosis (CMD) E. ewingii – granulocytes Canine granulocytic ehrlichiosis E. chaffeensis – human monocytic ehrlichiosis (HME) Ehrlichiosis cont’ E. canis – Canine monocytic ehrlichiosis (CME) Acute, subclinical, and chronic phases Thrombocytopenia most commonly seen (1-4 wks post infection) >90% of acute infections +/- morulae w/in circulating monocytes in acute infection Ehrlichiosis cont’ E. canis – diagnosis Serology: IFA (gold standard) Abs detected 7-28 days infection False negative w/acute infection ELISA (e.g. SNAP 4Dx Plus, IDEXX) - antibodies Western immunoblotting (primarily research) PCR (whole blood) Helpful for acute infection Ehrlichiosis cont’ E. canis – diagnosis Ideal: Serology + PCR Positive serum ab titer may reflect previous exposure vs active infection Retest 2-3 wks later Interpret in light of dog’s clinical signs! High titers do NOT correlate w/severity of hyperglobulinmia, disease, or duration of illness Cross-reactivity w/E. chaffeensis > E. ewingii, A. phagocytophilum Ehrlichiosis cont’ E. canis – treatment Supportive care Antibiotics! Doxycycline – high blood, tissue, and intracellular concentration Dose??? 10mg/kg/d x 28 days? 5 mg/kg q12 x 14 days? 16-23 days? 21 to 28 days? 6 wks? Current recommendation: 10 mg/kg/d, PO x 21-28 days for acute infection Minocycline 10 mg/kg, PO, q12 x 28 days Ehrlichiosis cont’ E. canis – treatment Clinical improvement w/in 24-48 hours Platelets w/in ref range w/in 10-14 days post starting treatment Dogs can be reinfected! Titers decline and become negative w/in 6-9 mos post treatment Ehrlichiosis cont’ E. chaffeensis Experimentally infected dogs: fever, thrombocytopenia, leukopenia Possible persistent carrier state in dogs (bone marrow, spleen, liver, LN, lungs, kidneys, brain) Diagnosis: Serology – detectable ab titers 7-23 d post infection; cross reactivity w/other Ehrlichia spp RT-PCR Tx: antibiotics - doxycycline Ehrlichiosis cont’ E. ewingii Infected dogs can serve as reservoir host Replicates in neutrophils Usually subclinical Acute disease (2-3 wks post infection): fever, lethargy, anorexia, lameness (neutrophilic polyarthritis), possibly neurologic manifestations Diagnosis: Morulae prior to seroconversion or CS Thrombocytopenia (43%), anemia, mild to moderate neutrophilic leukocytosis w/left shift Serology – abs present ~1 month post inoculation ELISA, cross-reacts w/other Ehrlichia spp False negative in acute illness PCR – positive as early as 4 days post inoculation TX: doxycycline Rapid clinical improvement w/in 24-48 hrs Anaplasmosis 2 species: Anaplasma platys – canine thrombocytotropic anaplasmosis Anaplasma phagocytophilum – canine granulocytic anaplasmosis Obligate intracellular, gram-negative pleomorphic bacteria; obligate aerobes; lack cell wall Within the family Anaplasmataceae Geographic distribution: A. phagocytophilum – upper midwestern, northeastern, western states A. platys – throughout Americas Anaplasmosis Transmission: Ixodes ricinus-persulcatus complex – A. phagocytophilum (Ixodes scapularis – Blacklegged tick; I. pacificus - Western Blacklegged tick) Rhipicephalus sanguineus (Brown Dog tick) – A. platys Major CS: A. phagocytophilum – fever, lethargy, inappetence, lameness (polyarthritis) A. platys – maybe fever, lethargy Causes human granulocytic anaplasmosis (A. phagocytophilum) Dogs = sentinels Anaplasmosis Anaplasma phagocytophilum – canine granulocytic anaplasmosis Tropic for granulocytes, esp. neutrophils – forms morulae w/in Tick must attach for 24-48 hrs for transmission to occur Mild to moderate, occasionally severe, thrombocytopenia (~90%) (+/- other cytopenias) – immune-mediated mechanism? Self-limiting in many infected dogs/cats Anaplasmosis Anaplasma phagocytophilum – canine granulocytic anaplasmosis Diagnosis: Morulae w/in granulocytes – as early as 4 days post inoculation Acute and convalescent serology (titers)/ELISA for antibodies PCR – for acute infection w/o morulae Treatment: Doxycycline! 5 mg/kg PO q12 x 28 days? 14 days? Clinical improvement w/in 24-48 hrs of treatment Platelet counts normalize w/in 2-14 days of treatment initiation Anaplasmosis Anaplasma platys – infectious canine cyclic thrombocytopenia (ICCT) platelet tropism Thrombocytopenia +/- mild, nonregenerative anemia Cycles of thrombocytopenia q1-2 weeks Diagnosis: Morulae in platelets after 7—19 days post infection Serology – cross reacts w/other Anaplasma spp ELISA – false negative in acute infection Paired titers PCR Treatment: Doxycycline! 10 mg/kg PO q24 x 21 days; 28+ days in more severe variants Rickettsia rickettsii Rickettsia rickettsii – Rocky Mountain Spotted Fever (RMSF) Gram-negative, obligately intracellular bacteria Infects endothelial cells Affects humans and dogs Part of the family Rickettsiaceae Major CS: acute, febrile illness; vasculitis; fever, vomiting, ocular signs (retinal hemorrhage, uveitis, episcleral injection), lymphadenomegaly, splenomegaly, peripheral edema, cutaneous hyperemia and necrosis, polyarthritis, neurologic signs Rickettsia rickettsii Geographic distribution: North, Central, South America Mode of transmission: Ticks - Dermacentor variabilis (American dog tick), andersoni (Rocky Mountain wood tick), Amblyomma americanum (lone star tick), cajennense sensu lato (Cayenne tick), aureolatum (yellow dog tick), Rhipicephalus sanguineus (brown dog tick) Rickettsia rickettsii Young and purebred dogs overrepresented? English Springer Spaniels w/phosphofructokinase (PFK) deficiency GSDs Endotheliotropic → disseminated vasculitis Spreads through lymphatics or directly into bloodstream to small capillaries Primarily infects endothelial cells; smooth muscles and monocytes can be infected Primarily an acute disease Rickettsia rickettsii Diagnosis: Acute CS + PCR or IHC → active infection Seroconversion Positive titer only indicates exposure Acute and convalescent titers needed (4-fold change to confirm infection) PCR – especially in acute phase False negatives d/t low numbers of organisms; transient circulation; antibiotic therapy Rickettsia rickettsii Thrombocytopenia common (vasculitis and immune-mediated platelet destruction) Treatment: Should be started before confirmed diagnosis Doxycycline! 7 days usually adequate – 5 mg/kg PO q12 x 7-14 days Rapid clinical response (24-48 hrs) Possible lifelong immunity to reinfection  Cytauxzoonosis Cytauxzoon felis Hematoprotozoal parasite Two distinct forms: Nonerythrocytic – schizont Erythrocytic – piroplasm Bobcat reservoir host Arthropod vectors: Amblyomma Americanum (lone star tick) > Dermacentor variabilis (American dog tick)  Cytauxzoonosis Geographic distribution: Midwest, south- central, south-eastern, mid-Atlantic states Expanded with expansion of A. americanum range Transmission: the feeding of vector ticks No human health significance Cytauxzoonosis Infected bobcat Amblyomma (uninfected tick) Infected tick Uninfected domestic cat Subclinical carrier Death Clinically ill cat Greene’s Infectious Disease 4th ed., p. 766  Cytauxzoonosis Clinical disease: 1-3 weeks after infection Rapid clinical course – death within days Major CS: rapidly progressive febrile illness (up to 107F), icterus, pallor, lymphadenomegaly, splenomegaly, hepatomegaly, seizures  Diagnosis of Cytauxzoonosis ID RBC parasites on blood smear Piroplasms shaped as “signet rings” within RBCs Distinguish from M. haemofelis Epicellular cocci/rods/rings PCR May remain positive in recovered cats Diagnosis of Cytauxzoonosis Schizonts within mononuclear cells Schizont-laden macrophages on FNA (LN, spleen, liver) 20 µm Treatment of Cytauxzoonosis Supportive, intensive care IV fluids Red blood cell transfusion for severe anemia Heparin for clot formation associated with DIC Careful if already bleeding! Antiprotozoal therapy Imidocarb – may lack efficacy Atovaquone and azithromycin Improved survival rate compared to imidocarb → 60% vs 26% No vaccine; prevent tick bite MULTIPLE MODES Hemotropic mycoplasmas Gram-negative, obligate epierythrocytic bacteria; wall-less bacteria; non-acid fast Formerly “Haemobartonella” and “Eperythrozoon” Includes: Dogs: Mycoplasma haemocanis, “Candidatus Mycoplasma haematoparvum” Cats: Mycoplasma haemofelis, “Candidatus Mycoplasma haemominutum,” “Candidatus Mycoplasma turicensis” Geographic distributions: worldwide Hemotropic mycoplasmas Mode of transmission: Ticks (Rhipicephalus sanguineus) – M. haemocanis Other arthropods (fleas? Mosquitoes?) Biting/aggressive interactions Vertical transmission Ingestion/injection of infected blood Major clinical signs (CS): fever, lethargy, inappetence, weakness, pallor, dehydration Possible zoonotic infections  Hemotropic Mycoplasmas in Cats M. haemofelis, “Candidatus Mycoplasma haemominutum,” and “Candidatus Mycoplasma turicensis” Blood film: small, dark, blue-staining rods, cocci, or slightly larger ring forms “Candidatus M. haemominutum” – rarely seen in blood films May see loss of normal appearance and shape Eclinpath.com: M. haemofelis (left), M. haemominutum (center); Greene’s, pg. 311 (right) – EM M. haemofelis Hemotropic Mycoplasmas in Cats Exact prevalence difficult to determine Clinical disease appears most associated w/M. haemofelis: severe hemolytic anemia Macrocytic, hypochromic Regenerative (pronounced reticulocytosis not always evident) Positive Coombs (esp. cold agglutinins); autoagglutination – acute phase FIV/FeLV positive* Hemotropic Mycoplasmas in Cats: M. haemofelis CS w/in 2-34 days post infection Anemia lasting 18-30 days M. haemofelis blood organism numbers fluctuate greatly Chronic infection not usually associated w/signif anemia Hemotropic Mycoplasmas in Cats “Candidatus M. haemominutum” No clinical illness or significant anemia Carrier status common Occasional reports of only recognizable cause of anemia in some naturally infected cats (usually co-infection required) Risk factors: Older age Outdoor exposure Cutaneous SCC Stomatitis FIV and/or FeLV positive “Candidatus M. turicensis” Moderate to severe hemolytic anemia Hemotropic Mycoplasmas in Dogs: M. haemocanis Experimental transmission via Rhipicephalus sanguineus (brown dog tick) Blood transfusions Prepatent period: 1 or 2 d to 2+ weeks Some w/rapidly progressive anemia and death w/in ~ 1 m post infection Gradual anemia w/repetitive parasitemic episodes Hemolytic anemia +/- positive Coomb’s test ~1-2 mo required for HCT to drop to minimum and 1-2 mo to recovery Splenectomy!!  Hemotropic Mycoplasmas in Dogs M. haemocanis (formerly Haemobartonella canis) Different strain of M. haemofelis vs. its own species More commonly forms chains on surface of RBC; can see small cocci, rods, rings “Candidatus Mycoplasma haematoparvum” – novel, small hemoplasma Greene’s, pg. 695, Fig. 58.3 Canditatus M. Greene’s, pg. 695, Fig. 58.2 M. haemocanis haematoparvum Diagnosis: Direct cytologic examination Stained blood smears: ~50% (acute phase) – M. haemofelis, “Ca, M. haemominutum;” M. haemocanis PCR-based assays – highly sensitive Can have subclinical carrier state Interpret positive results in light of CS Culture - unsuccessful Therapy and Prevention Supportive care Antimicrobial therapy Does NOT predictably clear organism from body! Doxycycline – 10 mg/kg PO q24 or 5 mg/kg PO q12 x 2-4 wks! Marbofloxacin – 2-5.5 mg/kg PO q24 x 2-4 wks Pradofloxacin and enrofloxacin = second-line Therapy and Prevention Treatment protocol for clearance of chronic M. haemofelis: Doxycycline 5 mg/kg PO q12 x 4 wks, then Marbofloxacin 2 mg/kg PO q24 x 2 wks Clinical improvement w/in 2-3 days starting treatment Prevention: Flea/tick preventatives Screen blood donors (PCR preferred)  Canine Babesiosis Intraerythrocytic protozoan parasite Many Babesia species: Dogs: Babesia canis, rossi, vogeli, gibsoni, conradae, vulpes, negevi sp. Nov. Cats: Babesia felis, canis, gibsoni, cati, lengau Multiple other unnamed species Geographic distribution: worldwide; species specific geographic distribution Major CS: lethargy, pallor, splenomegaly; subclinical No human health concerns Transmission - Babesiosis B. canis (vogeli) Rhipicephalus sanguineus (Brown Dog Tick) Most commonly southern US Prevalence from 3.8-59% Greyhounds B. gibsoni NON-VECTOR most common Dog fighting wounds (Haemaphysalis spp., Rhipicephalus sanguineus) Transplacental Babesia in Greyhounds and APBTs Greyhounds: B. canis Reported rates of positive carriers = 20-60% Risk considered to be low for clinical disease Risk increases to other dogs if in kennel situation Know the seropositive status of adopted greyhounds! Pit Bull Terriers: B. gibsoni Most cases in US reported in this breed Other dog breed positive - has the dog been in a fight with an APBT? History is important! Canine Babesiosis – Pathogenesis Infected RBCs have parasite antigens on their surface Induce host-opsonizing antibodies ➔ removal of infected erythrocytes by mononuclear-phagocyte system Hosts develop anti-RBC membrane antibodies against self antigens ➔ immune-mediated anemia Thrombocytopenia due to consumption of platelets +/- immune mediated HEMOLYTIC ANEMIA and THROMBOCYTOPENIA Anemia initially mild, normocytic, normochromic Then macrocytic, hypochromic, and regenerative Splenectomy makes parasitemia and anemia more severe Diagnosis of Babesiosis Microscopic identification Large spp. 3-7 um in length – e.g. B. canis, vogeli, rossi Small spp. 1-3 um in length – e.g. B. gibsoni, conradae, vulpes Serologic testing IFA Convalescent titers Nucleic acid-based detection PCR – required for accurate species identification No “perfect” test Parasite Visualization Capillary blood = ear tip or nailbed Negative slide exam does not rule it out! Poor sensitivity Babesia canis on blood smear Babesia gibsoni on blood smear Treatment of Babesiosis Imidocarb dipropionate Side effects = pain, autonomic signs Likely curative for B. canis, vogeli, rossi Reduces morbidity and mortality for B. gibsoni Does not cure these! Atovaquone and Azithromycin combination therapy More effective treatment for B. gibsoni, conradae Use liquid suspension of atovaquone Clindamycin, metronidazole, and doxycycline combination therapy For B. gibsoni if fail atovaquone/azithromycin Minimum 3 months Uncertain efficacy EAT THE HOST Tularemia Francisella tularensis – gram-negative coccobacillus, facultative intracellular bacteria, aerobic Mode of transmission – inoculation, skin/mucosal contact, aerosol inhalation, ingestion, vector transmission Major vectors: Ticks: Dermacenter andrsoni, variabilis, Amblyomma American (eastern USA) Biting flies (western USA) Tularemia Geographic distribution: Northern hemisphere (between 30 degrees and 71 degrees of latitude); virulent strains prevalent in USA Major CS: fever, lethargy, inappetence, lymphadenopathy, SC abscesses, splenomegaly, hepatomegaly, GI signs Young adult cats and dogs; cats more susceptible Reportable disease in USA  Tularemia Survives in macrophages Incubation period of 1-5 days in dogs/cats Thrombocytopenia (moderate) Diagnosis: Culture – requires BSL3 level labs (not recommended) PCR Serology – acute and convalescent titers (fourfold increase) False negatives possible in acute phase Single positive titers alone not diagnostic Direct IFA of tissue Tularemia - treatment Supportive care Antibiotics: Humans: initial drug of choice = parenteral aminoglycosides (e.g. gentamicin); doxycycline also used but higher relapse rate in humans; fluoroquinolones also used but also relapse Cats/dogs: Gentamicin 5-8 mg/kg IV,IM,SC q24 x 14 d Preferred for initial 72 hours of treatment when possible → minimizes caregiver exposure Doxycycline 5 mg/kg PO q12 x 2-3 wks Marbofloxacin 2.75-5.5 mg/kg PO q24 x 2-3 wks Protective against reinfection if survive Questions?