Infectious Diseases MSK.pdf

Infectious Diseases of the Musculoskeletal System Dr. Clare Ryan ([email protected]) Dr. Mary Hondalus ([email protected]) Dr. Cassan Pulaski ([email protected]) September 4, 2024 Lecture Outline 1. Viral pathogen 1. CAEV 2. Bacterial pathogens 1. Actinomyces...

Infectious Diseases of the Musculoskeletal System Dr. Clare Ryan ([email protected]) Dr. Mary Hondalus ([email protected]) Dr. Cassan Pulaski ([email protected]) September 4, 2024 Lecture Outline 1. Viral pathogen 1. CAEV 2. Bacterial pathogens 1. Actinomyces spp., 2. Clostridium spp., 3. Borrelia spp. 3. Parasitic pathogens 1. Tissue-cyst forming coccidia 2. Hepatozoonosis 3. Trichinellosis Learning Objectives Recognize route(s) of transmission for CAEV Describe the pathophysiology of CAEV- associated polysynovitis/arthritis Recognize approximate ages at which arthritis and encephalitis caused by CAEV occur Describe testing and management practices utilized to reduce transmission of CAEV within a herd  Caprine Arthritis and Encephalitis Virus (CAEV) Lentivirus- lifelong infection NO vaccine available https://www.intechopen.com/chapters/43276  Caprine Arthritis Encephalitis Virus (CAEV) Primarily a goat pathogen (also sheep) Common in dairy goats, in industrialized countries https://stepladdercreamery.com/blogs/blog/meet-our-top-10-milking-goats  CAEV: Transmission From dam to kid through colostrum/milk, close contact Possible horizontal transfer via fomites  CAEV: Clinical signs Most (~70-80%) goats asymptomatic A small number develop symptoms Arthritis, Encephalitis (more common in kids) Pneumonia Mastitis Weight loss  CAEV: Pathophysiology of arthritis Polysynovitis-arthritis Goats > 6 months DOI:10.4314/ovj.v7i1. Immune complexes 5 Non-neutralizing antibodies, PLUS Virus-infected macrophages https://doi.org/10.1177/104063871143550 Managing the herd: CAEV Testing Serology: Serological monitoring 2x/year Challenging, as animals can shed virus PRIOR to seroconversion start to produce antibodies PCR: Less commonly utilized https://www.goatbiology.com/caetestagid.html Could test: milk, blood, joint fluid/synovium Many herds will cull positive animals Managing the Herd: CAEV Pasteurize milk/colostrum (45 °C for 1 hour) Restrict pooling of colostrum Separate/cull any affected animals New animals: Quarantine Test twice at ≥60-day interval  Bonus info: Impact of genetics Goats that carry one or both of these two MHC alleles are more likely to develop arthritis or encephalitis: Be1 Be14 Goats carrying the Be7 allele are LESS likely to be symptomatic Learning Objectives  State the Gram stain characteristics and typical morphology of Actinomyces spp., Clostridium spp. and Borrelia spp. and the species of medical importance  State where Actinomyces spp., Clostridium spp. and Borrelia spp. organisms reside and how transmission of disease caused by these organism occurs  Describe the pathogenesis and main clinical presentations of Lumpy Jaw, Black Leg, Malignant Edema and Lyme Disease in the various hosts and aspects of diagnosis / disease control and prevention.  Where appropriate, be able to describe the bacterial, host or environmental / management factors that contribute to development of the aforementioned diseases Actinomyces spp. (general) group  Gram-positive, pleomorphic filamentous branching, rod.  Normal flora of oropharynx, GI tract and urogenital tract.  Relevant pathogenic species include A. bovis, A. viscosus. dogs Characteristic pleomorphic shape of Actinomyces species.  Actinomyces: Transmission all times Carrying  Endogenous. Trauma to oral mucous membranes allows infection, which is usually locally invasive and rarely may disseminate.  Clinical Disease: Actinomycosis Actinomyces bovis  Normal flora of mouth of cattle.  Causes actinomycosis or “Lumpy jaw” in cattle, which is pyogranulomatous osteomyelitis and soft tissue infection of face and jaw (tumor-like). Fistulas develop and Draintooutside drain. Sinuses may be involved  Occurs following injury to oral mucosa by sharp pieces of feed or Actinomycosis: “Lumpy Jaw” foreign body. May enter dental alveoli when teeth are erupting (age 2-3 years) Clinical Disease: Actinomycosis A. bovis (con’t):  Initially painless, hard boney swelling (bilateral or unilateral). Usually enlarges slowly, becomes painful, open to outside and draining  May cause difficulty chewing, tooth loss.  Local expansion into soft tissue  Not contagious  Infection / disease more common Bilateral boney swelling in beef breeds. Less common in of actinomycosis (Lumpy Jaw) other animal species  Actinomycosis- A. bovis (con’t): Diagnosis: Clinical signs, cytology and culture of exudate. Treatment:  Surgical debridement  Antibacterial therapy particularly iodides +/- penicillin  Early treatment improves prognosis Chronic granuloma Prevention:Enviroside Δ  avoid feeding course stemmy hay.  Clostridium spp. (general):  Gram-positive, anaerobic, rods  Several species commonly found in the soil and in the intestine.  ***Clostridial diseases are toxin- based.  Clostridium spp. are classified as histotoxic (toxins damage host cells), neurotoxic, or enterotoxic depending on activity of toxins Clostridium with endospores produced  Produce *spores.  Spores are dormant and resistant bacterial form that preserves the genetic material during times of extreme environmental stress. Allows survival in soil and intestine.  Numerous Clostridium species of veterinary importance.  Clostridium chauvoei  Spores present in soil and intestinal tract of normal ruminants especially cattle. growing  Vegetative bacteria produce a group of histiotoxins that cause emphysematous necrotic myositis and systemic toxemia.  Muscle trauma likely, but most often no overt wound present. necrotic muscle of C. chauvoei infection  Risk factors are rapidly growing animal on high plane of nutrition (well fed cattle).  Clinical disease called (Blackleg) is manifest by sudden onset of muscle inflammation with necrosis. Usually multiple cattle affected. Disease can also occur in sheep.  Transmission of Blackleg Ingestion of spores in soil or endogenous in intestine Spores enter blood/lymph from intestinal tract Spores seed muscle Unknown stimulus triggers germination of spore (but can be any local anoxic condition causing bruising). Toxin production. fever, lameness, or rapid death or sudden death without signs. Postmortem: necrotic, edematous, emphysematous muscle  Blackleg -C. chauvoei Acute lameness, stiff gait, skin normal. Sudden death common Necrotic muscle (gangrenous). Often lesion confined to part of one limb. Sometimes multiple lesions.  Clostridium chauvoei (con’t)  Diagnosis: sporulated Gram- positive rods can be found in muscle. PCR of muscle tissue. Also, fluorescent antibody (FA) test for organisms in tissue can provide definitive diagnosis. C. chauvoei (arrows) Culture not often done (difficult to in affected muscle recover bacteria).  Treatment –antibiotics (penicillin) but often not successful.  Prevention- vaccination (bacterin) wholeby  Clostridium septicum:  Organism/spores found in soil and GI tract.  Enters muscle via wounds- shearing, tail docking, lambing, castrations, i.m. injection.  Histiotoxic toxins produced at site cause host muscle cell death. Disease is Malignant Edema, a gangrenous myonecrosis with edema, subcutaneous emphysema and systemic toxemia (rapid Drainage of abscess caused shock-like syndrome). by Clostridium spp. following i.m. Banamine injection  All domestic animals- horse, cattle, sheep, and pigs.  Typically sporadic cases, affecting individual animals.  Malignant Edema (con’t)  Acute onset fever, toxemia, pain over affected area, subcutaneous emphysema.  ***May sometimes be caused by other clostridium species i.e. C. perfringens, C. chauvoei, C. sordellii, C. novyi and mixed infections also occur. Drainage for treatment of Malignant Edema following  Diagnosis: Clinical signs. Culture/PCR of i.m. Banamine injection muscle. FA on muscle for Clostridial organisms.  Treatment: antibiotics, incision and drainage of wound and supportive care.  Control: Good hygiene. Multivalent Clostridial bacterin or toxoid for ruminants will prevent.  Borrelia  Gram-negative, spirochete.  Most significant pathogen is B. burgdorferi, causative agent of Lyme disease  Requires host or tick vector for survival. Are not free-living in B. burgdorferi the environment.  Borrelia: Pathogenic Features:  OspA protein (outer surface protein A) mediates attachment to tick gut.  Other Osp proteins mediate attachment to mammalian hosts (including attachment B. burgdorferi to mammalian host collagen).  Antigenic variation: Changing expression pattern of Osp proteins expressed in host interferes with antibody clearance.  Borrelia Transmission:  Requires reservoir hosts (white footed mouse, birds, chipmunks, white-tailed deer).  Transmitted by deer ticks (genus Ixodes scapularis Ixodes). (deer tick).  Tick larvae and nymphs acquire the infection by feeding on reservoir hosts.  Domestic animals and humans infected by tick bite (nymphs and adult ticks). Peromyscus leucopus White-footed mouse.  Borrelia Transmission (con’t):  Infected tick bites host, spirochetes in gut of tick migrate to salivary gland, are secreted into saliva and then into host.  Tick must be attached for @ 36 – L to R: Ixodes scapularis 48 hr for transmission to occur. Adult female, adult male nymph, larva.  Binds in dermis layer and then spreads systemically.  Infected reservoir hosts are asymptomatic. White-tailed deer, reservoir host.  B. burgdorferi Clinical Disease: Lyme Borreliosis: Humans  Called “Lyme Disease”.  Occurs primarily in northeast USA, in Mid-west and Pacific Coast.  Humans infected by nymph or adult tick bite, usually in spring or Female and male. I scapularis summer. (Size comparison to pin).  Acute and chronic disease forms. Acute: “flu-like” symptoms i.e. fever, headache, malaise, myalgia, and erythema migrans (EM) (bull’s eye lesion at site of tick bite). Erythema migrans  B. burgdorferi Clinical Disease: Lyme Borreliosis: Humans  Most cases show EM, which occurs 3 to 30 days post bite.  Chronic disease: arthritis, cardiac disease and neurological manifestations are typical.  Diagnosis: serology for antibody; PCR for antigen in blood and synovial fluid  Clinically normal people may have strong antibody titers.  Human vaccine currently in clinical trials Erythema migrans  Lyme Borreliosis: Dogs  95% of exposed (serologically positive) dogs are asymptomatic. Most infections subclinical.  If clinical signs occur, primary manifestation is arthritis. One or more joints may be involved (shifting leg lameness). Joints are swollen, I. scapularis nymph hot, painful. Signs due to host inflammatory Smaller than dog tick. response.  Lameness occurs generally 2-5 months post bite.  EM is rare in dog. Chronic disease primarily includes recurring polyarthritis, nephritis, cardiac disease (arrhythmias), neurological Ixodes scapularis signs (seizures, aggression).  Lyme Borreliosis: Dogs (con’t).  Diagnosis: Very difficult to confirm. History of exposure, clinical signs, positive serology (ELISA), SNAP 3Dx; 4Dx Test, and response to treatment. Organism difficult to isolate / culture.  SNAP test can discriminate infection from vaccination. Detects antibody to a surface antigen that is expressed (C6 peptide) in animal host. Vaccine does not contain C6 peptide.  Like humans, clinically normal dogs (and other animals) may have high antibody titers.  Lyme Borreliosis: Dogs (con’t). Treatment: -long term (> 30days) antibiotic therapy (i.e. doxycycline) is often effective if administered early. Shifting Leg lameness Due to Lyme Disease  Lyme Borreliosis: Dogs (con’t). Prevention: 1. Remove attached tick. 2. Tick control: keeping lawns mowed, & application of anti-tick medication to dog. 3. +/- Vaccination: recommended if in affected region. -Recombitek Lyme: (recombinant OspA protein) -Duramune Lyme: (killed whole bacteria vaccine, multiple Osps) -Duramune Lyme /Leptovax4 – combination Borrelia bacterin plus subunit (proteins) from four strains of Leptospira  Lyme Borreliosis: Horse and Cow:  Majority of sero-positive horses and cattle show no clinical signs.  Stiffness, lameness, joint pain, fever, most commonly reported signs. Rarely neurological signs and cardiac disease. Decreased milk production in cow. Transmission of B. burgdorferi  Diagnosis: Signs and serology  Treatment: antibiotics i.e. tetracyclines. And coming to a clinic near you… Learning Objectives  Become familiar with major parasites that cause musculoskeletal disease/pathology, including important features of life cycle  Describe the pathogenesis and main clinical presentations of each parasite in the various hosts  Describe diagnostics and management of each parasite, including control/prevention  Parasites Helminths Protozoa Arthropods Nematodes Flatworms Insects Arachnids (Roundworms) Flies Ticks Cestodes (Tapeworms) Fleas Mites Trematodes Lice (Flukes) Protozoan Parasites Hemoflagellates Mucoflagellates Protozoa  Apicomplexa: Eimeriorina Coccidians Eimeriidae: Direct LC, intestinal Piroplasms cells, host-specific Cryptosporidiidae: Direct LC, Trematodes intestinal cells, less specificity Cestodes Sarcocystiidae: “tissue-cyst Helminths forming”, indirect LC (asexual: Nematodes intermediate, sexual: final) Acanthocephalans Neospora sp. Sarcocystis sp. Ticks Toxoplasma sp. Mites Arthropods  Apicomplexa: Adeleorina Lice Hepatozoon sp.: indirect LC Fleas (sexual stage in tick!) Flies Helminth Parasites (nematode) Hemoflagellates Mucoflagellates Protozoa  Nematoda: Enoplida Coccidians Piroplasms Trichocephalida: Trichinella sp. Trematodes Cestodes At least one stage of life Helminths cycle develops in cells or Nematodes tissues in this order Acanthocephalans Smallest human Ticks nematode, largest of the Mites intracellular parasites Arthropods Lice Fleas Flies For each parasite, can you recognize:  Basic taxonomy – Protozoan? Nematode?  General life cycle features – Direct? Indirect? What is the infective stage? Where is the parasite in host?  Clinical Importance – Presentation? Severity? Zoonotic concerns?  Basic diagnosis and management Morphological vs Molecular? Treatment available? Prevention available? Neospora caninum  Tissue-cyst forming coccidian with worldwide distribution  Indirect life cycle: DH: canids, sexual stage in intestinal epithelium; IH: most mammals (cattle, ungulates), asexual stage in tissue- cysts Neospora caninum  Infectious inflammatory myopathy in dogs Most clinical cases in dogs < 1 year Meningoencephalitis, polymyositis, polyradiculoneuritis https://www.youtube.com/watch?v=TqRG2CuMlAg  Major cause of abortion in cattle  Vertical transmission important in dogs & cattle  DX: serology, ID or PCR in biopsy, aspirate, CSF, blood  Prevention: no raw meat diets! Sarcocystis neurona  Tissue-cyst forming coccidian and causative agent of EPM  Indirect life cycle: DH: opossum, sexual stage in intestinal epithelium; IH: variety of mammals, asexual stage in tissue- cysts Horses are aberrant host  More to come…  Clinical Presentation in Horses aka Equine Protozoal Myeloencephalitis (EPM)  Remember the 3 As Asymmetry = a symptom that is worse on one side of the body than on the opposite side Atrophy = muscle deterioration Ataxia = inability to coordinate movement Most frequent sign is gait abnormality related to CNS disease AAEP EPM Guidelines Toxoplasma gondii  Zoonotic, tissue-cyst forming coccidian with worldwide distribution  Indirect life cycle: DH: felids only; asexual & sexual reproduction in enterocytes IH: So. Many.  Major cause of abortion in small ruminants, significant morbidity in marsupials, and ocular disease in humans  More to come… Congenitally infected kittens can be Zoonotic Clinical Hepatozoon americanum  Arthropod-borne intracellular protozoan  Indirect life cycle: DH: TICKS; IH: multiple, including dogs  American canine hepatozoonosis (ACH) Severe to fatal disease  GulfCoast I ck Hepatozoon americanum  CS: fever, mucopurulent ocular discharge, muscle atrophy, muscle & bone pain, lameness, recumbency Inflammation in striated muscle tissue, proliferation “onion skin cysts” Bony proliferation along periosteum of long bones  DX: clinical signs & radiographic findings Muscle biopsy and/or PCR on blood for confirmation  Tick control!  Tick is definitive host  Dog is intermediate host, infected: Ingestion of tick Ingestion of paratenic host (that ate tick) https://www.youtube.com/watch?v=YlV0ygGy-iU  Ornate Scutum Inornate Scutum Short Mouthparts Dermacentor sp. Rhipicephalus sp. Long Mouthparts Amblyomma sp. Ixodes sp.  distal over p Case Example – Enjoy  Trichinella spiralis  Zoonotic nematode that occurs in carnivores & omnivores  Indirect and weird life cycle Among non-human animals by predation or carrion consumption Domestic cycle: pigs & rodents Sylvatic cycle: wild/feral mammals Nurse cells, encapsulated larvae in striated muscle  Risks: wild game meat, pigs raised outdoors  Not common in production swine in USA Questions?