Rodent Pathogens. Judy Hickman-Davis, DVM, PhD, DACLAM. Associate Professor, VPM

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1 A Review of Common Rodent Pathogens Judy Hickman-Davis, DVM, PhD, DACLAM Clinical Veterinarian, ULAR Associate Professor, VPM

2 Purpose of Sentinel Rodents To monitor the health status t in each colony animal room, isolator, and quarantine group.

3 OSU Rodent Health Monitoring Dirty bedding Endo- and Ectoparasites Quarterly all rodents Viral and bacterial pathogens Serology quarterly Microbiology on sterile rodents semiannually PCR Helicobacter semiannually

4 Rodent Health Surveillance Viral and Bacterial Pathogens RAT Sendai PVM SDAV KRV H-1 RPV RMV NS-1 REO GDVII RAT LCMV MAV1&2 Hantan M. pulmonis E. cuniculus Carbacillus MOUSE Sendaid i MOUSE EDIM PVM ECTRO MHV MAV1&2 MVM MCMV MPV1 K MPV2 POLY NS-1 1 Hantan GDVII M. pulmonis REO E. cuniculus LCMV Carbacillus Pasturella MTLV Pseudomonas H. hepaticus H. bilis

5 OSU Sentinel Program Since 2006 Current rodent sentinel program 247 PIs 13 Facilities ~4000 serology tests per year ~1650 necropsy tests per year

6 OSU Rodent Health Monitoring Room Entry Housing requirements Disease Status sterile, ventilated micro-isolator Negative for viral & bacterial agents, 1 cages, hood, sterile supplies parasitology and Helicobacter 2 3 sterile, ventilated micro-isolator cages, hood, sterile supplies barrier ventilated micro-isolator or static cages, hood Negative for viral & bacterial agents, parasitology; Helicobacter positive Negative for viral agents and Helicobacter barrier ventilated micro-isolator or Negative for viral agents, unknown 4 static ti cages, hood Helicobacter status t 5 conventional housing & techniques Negative for viral agents, unknown Helicobacter status 6 Housing varies as listed in room Positive for viral, bacterial agent or parasitology

7 MPV/ MVM MHV Helicobacter Nematodes Acariasis i

8 Parvovirus Mouse Parvovirus (MPV) Minute Virus of Mice (MVM) Both are just 2 different serotypes of parvovirus Rat Parvovirus, Kilham Rat Virus (RPV, KRV) Common viral agents almost never associated with disease or lesions (asymptomatic)

9 Parvovirus Virus is naked and hydrophilic Resistant to environmental conditions Heat resistant Dry resistant Solvent (alcohol, chloroform, ether) resistant

10 Parvovirus RPV/ KRV Rat only natural host Excreted in feces, urine, milk & nasal secretions Most common contaminant in transplantable tumors MVM Mouse only natural host Excreted in feces, urine & nasal secretions Most common contaminant in transplantable tumors MPV Mouse only natural host Fecal-oral transmission (respiratory?) Most common contaminant in transplantable tumors

11 Diagnosis ELISA PCR for viral surface proteins Treatment MVM-burnout MPV-rederivation RPV-replace or rederive

12 MHV MPV/MVM Helicobacter Nematodes Acariasis i

13 Mouse Hepatitis Virus RNA virus, enveloped Family: Coronaviridae Lipophilic Heat resistant Solvent and disinfectant sensitive

14 Transmission Aerosol fine mist or spray Fomites-an inanimate object or substance capable of carrying infections organisms Direct contact Highly Contagious! Contaminates cell lines and transplantable tumors

15 Clinical signs Diarrhea, wasting & death in naive infants and immunocompromised Asymptomatic in immunocompetent mice Expression of the disease depends on Age Genotype Experimental status Virulence of viral strain Young mice are protected by maternal antibodies up to weaning

16 Diagnosis In immunocompetent animals: Serology In immunodeficient i animals: Identification of virus in feces Histopathology after observation of lesions

17 Prevention All biological products of animal origin should be tested before being inoculated into mice

18 Treatment Depopulation Euthanasia of all non-essential animals Quarantine Rederive infected colonies Burn out

19 Helicobacter MPV/MVM MHV Nematodes Acariasis i

20 Helicobacter Common infection of lab mice Gram negative Microaerophilic Curved/spiralshape

21 Helicobacter Mice, rats, hamsters, gerbils, woodchucks Colonization Cecum and colon Stomach, gall bladder, liver Fecal oral contact Helicobacter free hamsters and gerbils difficult to obtain commercially

22 Helicobacter H. hepaticus: Hepatitis in immunocompetent strains H. bilis Hepatitis in immunocompetent strains Liver and colon cancer in susceptible strains

23 Characteristic Lesions Gross Enlarged edematous cecum and colon +/- rectal prolapse p Enlarged mesenteric lymph nodes Hepatic p necrosis with multifocal pale to white foci

24 Diagnosis Gross and Histological lesions Warthin-Starry or Steiner silver stains Culture (difficult and nonspecific) Serology ELISA (false negatives) PCR (test of choice)

25 Eradication Antibiotic therapy Amoxicillin or tetracycline + metronidazole and bismuth (triple therapy) Medicated diet: Labdiet 5001 grain based rodent diet (Amoxicillin, metronidazole and bacon flavored bismuth) Medicated wafers (amoxicillin, clarithromycin, metronidazole and omeprazole) Labor intensive, $$, and not curative

26 Eradication Husbandry and colony maintenance Rederivation ($$) Cross fostering Not an option for hamsters Transplacental transfer possible

27 Nematodes MPV/MVM MHV Helicobacter Acariasis i

28 Syphacia obvelata Pin Worms Common mouse pinworm Rat, gerbil, and hamster can be infected Eggs are flattened on one side and have pointed ends. Direct life cycle Infection often occurs in combination with Aspicularis i tetraptera Adult mice tend to be more resistant

29 Pin Worms Aspicularis p tetraptera Eggs are ellipsoidal Heaviest infestation is expected at 5-6 wks. Direct life cycle Immune expulsion of parasites and resistance to reinfection are hallmarks of A. tetraptera infection

30 Diagnosis Syphacia obvelata (mouse pinworm) infestation Tape test eggs in the perianal area; adult worms in the cecum or large intestine; ELISA to detect serum antibodies Aspicularis tetraptera (mouse pinworm) infection Detect eggs in the feces; adult worm in the large intestine

31 Pin Worms Clinical Signs Rectal prolapse, intussusception, enteritis, and fecal impaction Treatment Fenbendazole diet X 6 weeks

32 Acariasis MPV/MVM MHV Helicobacter Nematodes

33 Furmites Mites are arthropods with 8 legs, more similar to spiders than insects Host specific (no Zoonotic concern) Spend the majority of their live on the host (vs. Fleas) as a surface dweller Prefer locations that are most isolated from grooming actions Transmission is through direct contact

34 Clinical Signs Mouse strain and mite dependent, in some may not be clinically apparent while black mice are considered particularly sensitive Clinical Signs: Pruritis Scruffiness or unkempt fur Patchy hair loss Ulceration Pyderma

35 Diagnostics Hair Pluck Plucking hairs from the pelt and examining under a dissecting microscope may reveal the eggs (laid on the hair shaft) or the mites

36 Diagnostics Direct Examine If the pelt from a recently killed mouse is cooled to room temperature, the mites will crawl up to the tips of the hairs, looking like white specks

37 Diagnostics Tape Test Stick with cellophane tape in areas of interest, place on a microscope slide and examine under 40x (mites or mite eggs)

38 Acariasis = infestation with mites Myocoptes musculinus Most common Myobia musculi Thermotactic, they crawl to the end of hair shafts on dead hosts Radfordia affinis Closely resembles Myobia and may occur as a mixed infestation

39 Treatment Options Atgard dichlorvos Cholinesterase inhibitor Effective in killing adults and eggs by placing granules in bedding every week for 2-3 weeks, less labor intensive, cost effective for large groups

40 OUTBREAK MPV/MVM MHV Helicobacter Nematodes Acariasis

41 How do we find them?? Diagnostic challenges Indirect contact best for transmission? (sentinel program relies on contact with dirty bedding) Labor intensive Test 20% of cages during an outbreak Diagnostics are not 100% Few positives = smaller likelihood we can pick them up

42 Environmental Contamination Microisolator cages provide a barrier to spread Remember direct contact is required for some pathogens Use of appropriate PPE Remove prior to leaving room Biosafety hood technique!!! Minimize contamination of work space, spread from cage to cage (eggs in bedding, on gloves, etc) Use disinfecant i (Spor-Klenz) to clean surfaces, gloves, cages, etc Change gloves after handling known positive cages or rack to rack!!

43 Treatment?! Determination of who to treat Prophylactic treatment of quarantine groups from suspect colonies (pinworms, furmites ) In the face of an outbreak, cages vs. groups vs. racks vs. rooms Research or health affect of treatment vs. disease in colony Treatment options? Cost, labor, effectiveness, safety

44 Test Yourself

45 Test Yourself Aspicularis tetraptera belongs to the group (Phylum) of parasites called? A. Cestodes B. Nomads C. Hematodes D. Nematodes E. True toads

46 Test Yourself True or False MPV is a bacteria that can be eradicated using the technique known as burn out. FALSE MHV is highly contagious and can cause serious disease in young and immunocompromised animals. TRUE

47 Syphacia obvelata

48 Aspicularis tetraptera

49 QUESTIONS??

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