Week 10

• Actinomyces spp. are part of the normal microbiota of the oral mucus membranes or tooth surfaces of mammals, including humans. Most Actinomyces infections are endogenous.
• Actinomyces spp.

  Gram-positive, club-shaped rods and filamentous branching bacteria

  Facultative or strict anaerobic, and capnophilic ( = require CO2)

  Non-spore forming and non-motile

  Microcolonies growing in the center of lesions, surrounded by macrophages ("sulphur granules")

  Outer zone of lesions has granulomatous characteristics (chronic infection)

  Commensals of the oral cavity, colonize nasopharyngeal and oral mucosae
• Pathogenesis of a chronic progressive pyogranulomatous disease

  1. Polymicrobial infection with oropharyngeal microbiota

  2. Disruption of oral mucosal barrier

  3. Spread by direct extension to bones (Lymphogenous and hematogenous spread also possible)

  4. Chronic infection with bone lysis
• Actinomyces bovis (Lumpy jaw in cattle)

  Pyogranulomatous osteomyelitis

  Localized, chronic and progressive granulomatous abscess involving the mandible, the maxillae and other bony tissues of the head

  Introduction of bacteria via penetrating wounds of the oral mucosa (e.g. wire, coarse hay, sticks)

  Bone infections result in facial distortion, loose teeth and dyspnea from swelling into nasal cavity

  Predisposition: trauma in the oral cavity!
• Actinomyces bovis (Lumpy jaw in cattle): diagnosis

  1. Clinical signs - swelling of jaw with fistulous tracts discharging purulent exudate

  2. Microscopic examination of crushed granules from aspirates of preferably unopened lesions

  3. Culture of purulent material (capnophilic)

  4. Radiography can be used to determine degree of bone destruction
• Actinomyces bovis (Lumpy jaw in cattle): treatment and control

  1. Treatment: Susceptible to penicillin G and iodine (toxicity), Long term treatment (3-12 months) with high dose penicillin, If lesions are small and circumscribed -> surgery with excision of foreign bodies and lesions

  Lesions are chronic, walled-off microcolonies - prolonged antimicrobial therapy may fail

  2. Control: Minimize risk of mechanical injury, Remove foreign bodies
• Dermatophilus spp.

  Gram-positive, filamentous branching bacteria

  Aerobic

  Motile asexual zoospores from which filamentous hyphae germinate

  Divides in two planes to give "tram-track" appearance and produce coccoid fragments which become motile zoospores

  Zoospores germinate to produce hyphae, which penetrate into the living epidermis and subsequently spread in all directions from the initial focus -> inflammation

  Normal protective skin barriers have to be reduced or deficient
• Sequence of events in Dermatophilus congolensis-infected skin

  1. Hyphae grow from cocci spreading into epidermis (Ag release)

  2. Immune response after second infection of normal healthy animal: Ab in exudate might prevent establishment of infection or accelerate lesion resolution (crusts evident by 7 days after infection)

  3. Non-resolution of lesions with repeated cycles of epidermal proliferation bacterial invasion release of exudate influx of neutrophils, accumulation of T cells and plasma cells in dermis
• Dermatophilus spp.

  Cause severe infections of traumatized and persistently wet skin with formation of scabs and crusts - Acute infection: 2-3 w, lesions heal spontaneously; Chronic infection: cornification of invaded epithelium -> scabs -> moisture enhances proliferation and release of zoospores from hyphae

  Cattle, sheep, goats, horses and less frequently pigs, dogs and cats

  Worldwide, but more prevalent in tropics (moisture!)

  Dermatophilosis can be transmitted from infected animals to humans through skin contact (use antibacterial soap and gloves!) ZOONOSIS
• Pathogenesis of dermatophilosis

  1. Filaments colonize hair follicles and penetrate skin layers

  2. Inflammatory cell layer is formed under infected epidermis and keratinizes -> scab and crust formation

  3. Accumulations of cutaneous keratinized material forming wart-like lesions and hair matted together
• Dermatophilosis can cause significant morbidity and mortality, loss of body condition, decreased milk production and increased somatic cell counts in the milk in some parts of the world
• Diagnosis of dermatophilosis

  Clinical appearance of lesions

  Detection of D. congolensis in stained smears or histologic sections from scabs

  Cytologic examination of fresh crusts stained with Giemsa stain
• Treatment of dermatophilosis

  1. Parenterally administered antibiotics (e.g. oxytetracycline)

  2. Topical treatments are less effective but may include 0.5% chlorhexidine and 4% iodine tincture
• Control measures for dermatophilosis

  1. Isolate and treat clinically affected animals

  2. Provide shelter during prolonged rainfall periods

  3. Clear grazing areas of thorny scrub

  4. Reduce tick infestation (e.g. dipping or spraying with acaricides, elimination of tick habitats)

  5. Prophylactic use of long-acting tetracyclines in endemic regions

  6. Control of intercurrent diseases

  7. Resistance through modification of skin microbiota?!
• Trueperella spp.

  • Gram-positive pleomorphic bacteria
  • Facultative anaerobic and capnophilic
  • Non-motile, non-spore forming and non-capsulated
  • Found on mucosal membranes of GI tract, respiratory and urogenital tract of cattle and swine (but survives in environment)
  • Opportunistic pathogens of cattle (and sheep & swine)
  • Pyolysin: haemolytic toxin, cytotoxic for neutrophils and macrophages, dermatonecrotic and lethal for laboratory animals
• Summer mastitis

  1. Synergistic action of Trueperella pyogenes, Peptostreptococcus indolicus and Streptococcus dysgalactiae

  2. Transmission of infection by the head fly (Hydrotea irritans)

  3. Affected quarter is swollen, hard, painful and hot with grossly enlarged teat. Udder secretion thick and clotted, like grains of rice, with green/yellow pus
• Diagnosis of Trueperella infections

  Smear and Gram stain of purulent material

  Necropsy and isolation of bacteria
• Treatment of Trueperella infections

  1. Penicillin G (but not for chronic infections!)

  2. Reports of resistance
• Prevention of Trueperella infections

  1. Prevent primary cause

  2. No efficient vaccine
• Actinobaculum suis

  • Gram positive rods
  • Anaerobes
  • Non-motile, non-spore forming
  • Commensal organism in preputial diverticulum of boars
  • NOT in urogenital tract of healthy sows
  • Transmitted at coitus
  • Potentially fatal due to renal failure
• Actinobaculum suis causes porcine cystitis and pyelonephritis 3-4 weeks post-coitus: anorexia, arching of the back, dysuria and haematuria
• Gram positive and Gram negative anaerobes

  • Gram positive: Clostridium spp. (spore-forming)
  • Gram negative: Fusobacterium necrophorum, Dichelobacter nodosus, Porphyromonas spp., Prevotella spp. (non spore-forming)
• Key bacterial characteristics of anaerobes

  • Causing abscesses, wound infections, aspiration pneumonia, intra-abdominal infections, bacteremia, enteric infections, toxaemia
  • Usually localized, often oral and GI tract associated
  • Spread by direct extension from mucosal surfaces
  • Transient bacteremia and secondary localization, especially on damaged heart valves
  • Polymicrobial infections and synergistic relationships
  • Anaerobic infections are mostly of endogenous origin
• Genus Clostridium

  Large Gram-positive rods, anaerobic, motile by flagella (except C. perfringens), rapid multiplication, endospore producing, widespread in soil, GI tract of animals and humans and in feces, powerful toxin producers
• Classification of clostridial pathogens by mode and site of action of their potent exotoxins

  • Neurotoxic clostridia (affect neuromuscular function without inducing observable tissue damage): C. tetani, C. botulinum
  • Histotoxic clostridia (localized lesions in muscle and liver, subsequently causing toxaemia): C. chauvoei, C. septicum, C. novyi type A and B, C. haemolyticum, C. sordelli
  • Enteropathogenic and enterotoxaemia-producing clostridia (interferes with protein synthesis in cells): C. perfringens type (A-E), C. difficile
• Necrosis is a common predisposing factor for and host response to clostridial infection

  provides initial opportunity for growth

  host response to many clostridial toxins

  facilitates rapid spread of infection through the body
• Species of veterinary importance

  • Clostridium tetani (causes tetanus in horses, humans, other species)
  • Clostridium botulinum (causes botulism in waterfowl, cattle, horses, sheep, mink, poultry, fish)
  • Clostridium chauvoei (causes blackleg in cattle, sheep)
  • Clostridium septicum (causes malignant oedema/gas gangrene in cattle, pigs, sheep; braxy/abomasitis in sheep)
  • Clostridium novyi type A and B (cause infectious necrotic hepatitis/black disease and gas gangrene in sheep)
• Clostridium tetani

  Acute, potentially fatal intoxication with neurotoxic clostridia causing spastic paralysis

  Reservoir: widespread in soil and feces

  Microscopy: Gram-positive anaerobic drumstick-shaped rods (produce terminal endospores)
• Tetanus pathogenesis

  1. Spores enter damaged tissue (wounds)

  2. Germinates under anaerobic conditions

  3. Multiplication & production of tetanospasmin (neurotoxin) and tetanolysin (tissue destruction)

  4. Tetanospasmin travels via blood and lymphatic system

  5. Tetanospasmin binds to motor neurons & travels along the axons to the spinal cord
• Ascending tetanus

  • Toxin travels from regional motor nerve in the limb -> tetanus in limbs then spread to other parts (less susceptible animals like dogs and cats)
• Tetanus diagnosis

  • Incubation period between 5 and 10 days
  • Latent tetanus: when wound at the site of infection is healed
  • Clinical signs: Stiffness ("rocking horse" stance) and lock-jaw, Localized spasms, Altered heart and respiratory rates, Dysphagia
  • Diagnosis: history & clinical signs; culture supportive (but can also be contamination!)
  • Animals that recover are not necessarily immune because toxin could have been below threshold required to stimulate the production of neutralizing antibodies
• Tetanus treatment

  1. Antitoxin: administered promptly to neutralize unbound toxin (intravenously or into subarachnoid space)

  2. Anti-tetanus equine serum (intramuscular or intravenously)

  3. Toxoid: inactive vaccine to promote active immune response (subcutaneously or intramuscular)

  4. Large doses of penicillin: kill toxin-producing vegetative cells of C. tetani in the lesions

  5. Surgical debridement of wounds and flush with hydrogen to produce aerobic conditions

  6. Supportive care: Reduce external stimuli, Sedatives, Muscle relaxants
• Tetanus control

  • Toxoid immunization (human, horses, small ruminants)
  • Post-exposure prophylaxis via a toxoid booster (human, horses)
  • Prompt wound management and rational antimicrobial therapy
  • Aseptic techniques while surgery
  • Proper sterilization of surgical instruments
• Clostridium botulinum

  Diverse group of neurotoxic clostridia (Toxin types A-G) that cause serious, potentially fatal intoxication by ingestion of pre-formed neurotoxin (Food intoxication) causing flaccid paralysis
• Clostridium botulinum reservoir: Germination of endospores with growth of vegetative cells and toxin production in rotting carcasses, decaying vegetation, contaminated canned foods, meat, fish, invertebrates
• Botulism pathogenesis

  1. Toxin absorbed from GI tract (intoxication)

  2. Occasional toxico-infectious wounds (spores germinate in wounds)

  3. Distribution of toxin in the bloodstream

  4. Toxin leaves circulatory system at neuromuscular junction

  5. Toxin prevents the fusion of synaptic vesicles of acetylcholine and thus release of acetylcholine at neuromuscular junction

  6. Flaccid paralysis

  Death: when nerves controlling respiratory system or heart (respiratory arrest)
• Binding of botulinum toxin is irreversible to the presynaptic membrane, only slowly releases. Nerve damage heals over time
• Botulism in humans

  • Foodborne botulism (rare but fatal; ingestion of toxins formed in contaminated foods)
  • Wound botulism (needles)
  • Infant botulism (spore-contaminated honey)
  • Inhalation botulism (rare and does not occur naturally > bioterrorism?!)
• Botulism: diagnosis

  1. Clinical signs develop 3 to 17 days after ingestion of toxin

  2. Clinical signs: Dilated pupils, Dry mucus membranes and decreased salvation, Tongue flaccidity and dysphagia, Paralysis of respiratory muscles > abdominal breathing

  3. Demonstration of toxin in serum of animal

  4. Demonstration of toxin in food and stomach contents
• Botulism: treatment & control

  1. Treatment: varied success with hydration, correcting electrolyte disturbances, antitoxin administration

  2. Toxoid vaccination of cattle in endemic regions in South Africa and Australia

  3. Routine vaccination of farmed mink and foxes

  4. Suspect foodstuffs should not be fed to domestic animals

  5. Avoid feeding and eating suspect foodstuff!

  6. Preparation and preservation of feed and food!

  7. Provide high quality feed and prevent water and soil contamination