CVRS, lymph and muscle protozoa

CVRS, lymph and muscle protozoa

1) Babesia

2) Leish-mania

3) Sarco-cystis

Babesia taxonomy

Phylum: Apicomplexa

Order: Piroplasma

Bovine babesiosis (UK and Ireland)

• Death

• Reduced milk

• Vet costs

(more severe burden in the tropics)

Babesiosis alternative names

Redwater fever (see clinical signs) or Texas fever

Babesiosis diagnosis

Staining of blood smear → merozoite in RBCs

• Dif-quik or Giemsa stain

Merozoite replicates inside RBC
damage RBC as emerge and leave

leads to release of haemoglobin

causes red-coloured urine = haemoglobinuria→ hence redwater fever

Small V large Babesia species

Small (B. divergens) → more pathogenic in UK

Large (B. major) → nonpathogenic, sheep and goats

pleomorphism exists

Babesia life cycle

tick → cow → tick

Tick = final host

• sexual rep → tick intestine

• asexual rep → various tissues → vermi-cules (asexual + worm-like)

  • enter tick ovary and eggs → transovarial transmission → passed onto next tick gen

    • much lower transmissionrate to nymph

      • lower rate of trans-stadial transmission

      • cattle babesia tick disease → usually one host tick

      • It molts to the next stage while still attached to the same animal.

      • many opportunities for tick to infect SAME cow

  • OR vermicules migrate to salivary gland → feeds on cows and transmits infection

  • sporozoites → shizogony in various tissues

cattle = intermediate host → asexual repro in cow RBCs

Babesia lifecycle in diagram form

Babesia Life Cycle (e.g., Babesia bovis)

1. Tick feeds on infected vertebrate host (e.g., cow)
   → Ingests Babesia-infected red blood cells (RBCs) containing merozoites.

2. Sexual reproduction in tick gut
   → Merozoites develop into gametes, which fuse to form zygotes.

3. Asexual repro in various tissues

4. Vermicule stage that multiplies (not linked to zygote stage)

5. Zygotes invade tick tissues
   → Migrate to salivary glands (and ovaries in transovarial species).

6. Sporogony in salivary glands OR in tick ovary and eggs
   → Zygotes produce sporozoites (infective stage for vertebrates).

7. Tick bites new host
   → Sporozoites injected into host bloodstream.

8. Asexual reproduction in CowRBCs
   → Sporozoites enter RBCs → become trophozoites → divide to form merozoites.

9. Merozoites lyse RBCs and infect new RBCs
   → Causes clinical signs of babesiosis (e.g., fever, anemia).

10. Cycle repeats when another tick feeds on this host.

Babesiosis pathogenesis

• Babesia schizogony (from sporozoite) infects RBC

• merozoites (last stage schizogony) inside RBC → infection

• Merozoites produce proteinaceous waste product → antigen

• Antigen trapped in RBC builds up, causing cell lysis

• Antigen released from lysed cell, sticks to other uninfected RBCs → immune system detects foreign antigen and attacks uninfected RBCs

• Freed merozoites continue cycle

Babesiosis clinical signs

• Fever

• Anaemia

• Haemoglobinuria

• Continuous diarrhoea

  • need to continually defecate even when no faeces left

• Neurological signs seen in some species but not in UK

Babesiosis graph

• Parasitaemia (merozoite in blood)

• Lag phase → parasite replicating and detectable

• PCV decreases due to RBC lysis (antigen binding, rapid merozoite reproduction)

  • Crisis level PCV slightly after parasite peak → can be fatal

• End of lag phase → immune response causes rapid parasitaemia decrease

  • blood highly accessible to immune system → parasites quickly destroyed

• If host survives, PCV rises again

Consequences

• Death

• Convalescence (recovery)

• Carrier state

Babesia divergens epidemiology

• Endemic areas (hotspots)

• Sporadic with sudden disease storms

  • Usually spring and autumn

• Determined by tick pressure and host susceptibility

Risk factors for clinical babesiosis [4]

1. Hill grazing

2. >2 years old

3. Newly purchased

4. Stressed

Tick pressure- definition

Number of ticks present and ability to transmit disease

Factors influencing tick pressure [4]

• Species present (Ixodes main vector)

  • Scotland

  • Wales

  • West of England

• Population size

• Location of tick habitats

  • foliage, humid, damp

  • damp = ireland and wales

• Proportion of ticks infected

Determinants of Babesia host susceptibility

• Refractory (infected but unlikely to be clinically sick) → calves <9 months

• Adults susceptible until infected

• Immunity develops rapidly but wanes overtime

• Carrier state → premunity → animal constantly getting infected

• Stress → transport, calving etc

Why are calves <9 months refractory for Babesiosis?

• Higher numbers of NK and gamma delta T cells

  • Release IFN-g to kill Babesia

  • less effective at targeting antigen coating RBCs

  • Retain higher RBC levels

• Older animals have fewer or less effective cells

  • acute disease in non-immune older animals

Babesiosis enzootic stability

• Ticks frequently have Babesia

• Continual reinfection

• Consistently high level of herd immunity → disease rare due to enzootic stability

Youth resistance → infection but no disease → partial immunity → disease still cycles with minimal clinical signs

Babesiosis enzootic instability

• Fewer ticks or low levels of ticks with Babesia

• Infrequent reinfection → low immunity in herd

• Clinical cases with more severe diseases → enzootic instability

Bovine babesiosis control

• Chemotherapy/ chemoprophylaxis

  • Imido-carb

    • Strict use → kills parasite but long withdrawal period

      • Meat → 213 days

      • Milk → 21 days

Bovine babesiosis vaccination (not UK)

• Deliberate infection and treatment with attenuated strain

• Recombinant vax not on the market

Best means to control Babesiosis

control the ticks

Other Babesia species

• Large → B. canis (dog)

• Small → B. gib-soni (horse)

• Virulence varies with species and strain

• Can be subclinical in immune dogs

Canine babesiosis

• Not endemic in UK → no British dog immunity

• Death reported from travelling abroad after return to UK

• Prevent tick bites

Canine babesiosis vaccines

• Not available in UK

• Nobi-vac Piro → B. canis

  • Reduces pathology, not infection

  • WIthdrawn in EU

Leishmania

• intracellular pathogen → replicates in macrophages

  • replicating in macrophage = a-mas-ti-gote

• Closely related to trypanosomes (African sleeping sickness → Tsetse fly)

• Disease in humans, dogs, wild animals

• Common in S. America, S. Europe, Africa, Asia

Leishmania Life cycle

Digenetic life cycle → 2 stages

1. Leishmania amastigote ingested by blood feeding sandfly (intermediate host)

   • Phlebotomus (old world)

   • (US → Lutzomyia)

2. Transformation into promastigote and multiplication in fly gut

3. Migration to fly proboscis

4. Fly inoculates vertebrate when feeding on blood

5. Transformation into amastigote in macrophage

   

Pathogenesis- Leishmania

• Foci of proliferating Leishmania

  • Skin → cutaneous Leishmaniosis

  • Internal organs → visceral Leishmaniosis

• Long incubation period → months to years for clinical signs to arise

• Many infected dogs asymptomatic

Cutaneous leishmaniosis → clinical signs

• Shallow skin ulcers

  • lip

  • eyelid

  • ear pinna

Visceral leishmaniosis → clinical signs

• More common

• Chronic wasting conditions

• Generalised eczema

  • hair loss around eyes → spectacles

  • hair loss → more chance of being bitten by fly

• Intermittent fever

• Generalised lymphadenopathy (LN swelling) → immune system persistently alert

Leishmania epidemiology and primary species

• Primarily L. infantum

• Disease dependent on sandfly distribution

  • Inland foci in S. Europe

  • Present in most of S and Central America, most of Africa, lots of Asia

• UK disease occurence

  • normally rare because cold (esp N UK)

  • most common in south → high population density

  • people travel from mainland Europe (France, Italy)

Leishmania infection reservoirs

Wild animals esp rodents, dogs

Leishmania mechanism of transmission

• Sandfly bite mainly

• Direct contact but some transmission where no flies are

• Suggested alternative transmission routes

  • Vertical transmission possible

  • Venereal

  • Blood products

  • Dog licking ear of other dog → past case

British dog Leishmaniosis

• Little to no immunity

• Susceptible in endemic areas abroad

• Other hosts → foxes, horses, cats

Leishmania diagnosis [3]

• Look for Leishmania → amastigotes

  • Skin smears and scrapings

  • Lymph node and marrow biopsies

• Serology

• PCR

Leishmania Treatment and control

• Chemotherapy

  • but expensive, needs prolonged treatment, only suppresses infection

• Prevent sandfly bites

  • Collars and sprays containing insecticide with repellent effect

• Vaccination

  • Leishmania naive animals

  • Does not prevent infection as usual

• Culling of stray/feral dogs

Leishmania vaccinations [3]

1. CaniLeish (Virbac)

   • Purified protein secreted/excreted by L. infantum

   • Withdrawn in many regions

2. Leti-fend

   • L. infantum recombinant proteins

3. Neoleish

   • Plasmid DNA containing L. infantum LACK gene

Vaccine could be used both preventatively and for treatment

Sarcocystis spp. taxonomy

• Apicomplexa (as usual)

• Cyst forming coccidian (budget toxoplasma)

• Several species

Sarcocystis species

• S. hominis

• S. sui-hominis

Both use humans as final host

Sarcocystis life cycle

Obligate heteroxenous → must have multiple hosts to complete life cycle

1. Oocyst sporulates internally (in human intestine) like cryptosporidium and is egested

2. 2 -cyte ×4 -zoites (like toxo & neo)

3. Thin oocyst wall → sporocysts shed into environment and ingested by intermediate host (cow and pig)

4. Schizonts → merozoites in capillary epithelium

5. Merozoites infect cardiac/skeletal muscle

6. Merozoites form sarcocysts containing thousands of bradyzoites

7. Meat poorly cooked, eaten by person

8. Bradyzoites released and invade intestinal epithelium enterocytes

9. Bradyzoites → gametocytes in enterocytes

10. Gametocytes → zygote → oocyst

Sarcocystis general facts

• Difficult to detect microscopically

• Tissue cysts common in ducks in UK → rice grain disease in breast muscle in duck

• Thick cyst wall containing bradyzoites

  • Primarily in cardiac and skeletal muscle

  • Compartmentalised (septa) cysts

Sarcocystis epidemiology- general transmission

Predator-prey relationship → FH eats (omnivorous/herbivorous) IH

• Fox/dog FH → deer IH

• Weasel FH → rodent IH

• Raptor FH → rodent IH

• Snake FH → rodent IH

Sarcocystis in dogs

• Prevalence in Belgian minced beef (S. cruzi)

• Other intermediate hosts:

  • pig

  • horse

  • deer

  • camelid

Sarco-cysti-osis in final host

• Low pathogenicity, usually no clinical signs

  • exception S. suihominis → causes severe intestinal sarco-cysti-osis in humans

    • Extraintestinal form → cysts in cardiac and striated muscles

Sarco-cysti-osis in intermediate hosts

• Pathogenic

• Acute sarcocystiosis

  • Only seen after massive infection

  • Fever, apathy, anaemia, CNS disorders, coagulopathy, haemorrhages, death, abortion

Sarcocystis cyst properties

• Large, grossly seen in abattoir meat → meat inspection importance

• Not killed by refridgeration

• Infectious for 2-3 weeks

• Killed by cooking thoroughly for 10 minutes or freezing for 3 days

Sarcocystis neurona

• Causes EPM (equine protozoan myelo-encephalitis)

  • necrotising encephalo-mye-litis

• Coinfection implicated

• IH unknown, suspected armadillo, raccoon, skunk

• FH suspected opossum

S. neurona in horse

DEAD END HOST

Neurological symptoms

• Unilateral paralysis

• Gluteal atrophy

• Tongue prolapse - abnormal protrusion

• Ataxia

• Depression :(

Why more CVRS dog parasites in north

climate change

north now warmer

bring parasite to naive host pop (from mainland europe)

because naive pop → large outbreak potential