Heart and Lungworms in Dogs and Cats (Week 1, Mod 10)

Describe Dirofilaria immitis, generally… what type of parasite?  Final host?  Intermediate hosts?  Distribution?

A nematode (roundworm) parasite

• Final host: dog, wild dogs, cat, ferret, sea lion, (human, accidental FH)

• Intermediate host (IMH): mosquito

• Site: cardiovascular system

  • right ventricle, posterior vena cava, pulmonary artery

• Distribution: USA, warm temperate zones (Europe), tropics  

• Not endemic in UK – identified in pets travelled or imported from Southern and Eastern Europe

What is the lifecycle of D. immitis?

Adult worms in heart → eggs hatch INSIDE adult; releases L1 (microfilariae) into blood → mf ingested by mosquito → L1 to L3 in mosquito within 10-14 days → L3 transmitted to final host by feeding mosquito

L3 → L4 in subq tissue of host → juvenile adult migrates to heart → Become adults in the heart

Describe the pathogenesis of D. Immitis in dogs… what does it depend on? What does it cause systemically?

Depends on worm burden

• Low numbers, little apparent ill effect

• High numbers, lots of problems

Pathology associated with adults in heart

• Impede blood flow

  • Giving rise to chronic congested right-sided heart failure

  • Pulmonary embolism

    • Adults blocking vessels

    • Important if treat to kill adult worms

  • Vena cava syndrome (blocked)

  • Endocarditis in valves, pulmonary endarteritis

    • Local inflammatory response

  • Glomerulonephritis

    • Deposition of immune complexes in kidney

What are the clinical signs of a D. immitis infection? (hint: there are 4, one major one)

• Cardiovascular dysfunction

• Listless/gradual loss of condition

• Exercise intolerance!!!

• Chronic soft cough

What are 3 main ways to diagnose for a D. immitis infection?

• Radiography or Echocardiography

• Detection of Mf in blood

  • Wet blood film

  • Stain dry blood film

• Detection of circulating antigen by ELISA

  • Immunochromatographic test

  • Referred to as SNAP test (10 mins)

  • Detects Ag released from female adult worms  

What are some of the factors that come with using an ELISA test to diagnose for heart worm? How effective are they?

• Antigen tests can detect a single female but not a male worm

  • Antigen is secreted by adult female worm

• Start testing by 6-7 months of age (PPP ~ 6 months)

• More sensitive than Mf detection, particularly if animal on prophylaxis

  • Mf can be concentrated from blood to help detection

• Some dogs have occult infections (adults but no Mf)

• And ~7% dogs have Mf but no Ag- so best to use both tests

Describe the distribution of heart worm…

• Major pathogen in USA 

• Spread rapidly over last two decades

• Present in Southern & Eastern Europe

• Only ever found in UK in imported/travelled dogs 

• Mosquitoes present in UK that can transmit infection (but rarely warm enough to develop)

What are 5 different factors that can affect the epidemiology of D. immitis in dogs?

• Density of dogs

• Numbers of strays & wild canids

• Mf can be present for long periods

• Poor immunity

• Poor owner compliance for prophylaxis

How is the mosquito essential to the epidemiology of D. immitis?

• Distribution and spread of susceptible vectors

  • Environmental change/urban ‘heat islands’

  • Introduction/spread of new vector species 

  • Capacity for rapid population increase

• Short developmental period Mf-L3, 10-14 days

  • Temperature dependent development

  • Stop development if <14^oC (57⁰F)

• Some mosquitoes can survive for months

• Infection rates can vary 2-19%

  • But can be much higher in vicinity of infected dogs

How do we approach prophylactic control to heart worm?

Controlling prophylactically is better and easier than treatment!

• Recommended to treat all year round no matter where you live; better owner compliance that way

What are two options for prophylactic treatments?  What are some of the cons of these treatments?

Macrocyclic lactones (e.g. ivermectin/milbemycin-orally or selamectin/moxidectin topically) monthly

• kill L3 and L4 up to ~6 weeks p.i.

DEC (diethylcarbamazine) daily (not widely used)

Cons:

• Prophylactic drugs do not kill adult worms

• MLs may have sterilising effect on female worms

• But some evidence of treatment failures:

  • Potential drug resistance

  • Potential anaphylactic reactions if microfilariae count is high (more dead worms -> body has a hypersensitivity reaction)

In general, what life stage do prophylactic treatments target?

Targets the L3 → L4 life stages

• Ideally dogs should be Mf-ve pre-treatment

• Combine with mosquito repellent/ectoparasiticide

What is the other “parasite” that heart worm carries, and how can we utilize it for treatment against adult worms?

Wolbachia

• Bacterial endosymbiont

• Killing Wolbachia with doxycycline sterilizes female- eventual death of adult worms

• Combination of IVM and doxycycline kills adult D. immitis*

  • Need to monitor canines under treatment with ivermectin and doxycycline combination… adult worms will release an antigen that can again result in an anaphylactic reaction

What is the CURRENT recommended treatment for dogs with heart worm?

Macrocytic Lactones + doxycycline combo (Moxy-Doxy treatment)

• ML clears Mf and prevents new infections 

• Dox reduces pathology associated with dead adults, shrinks the worm mass

• Followed by melarsomine (Immiticide®) to kill adult worms

  • Not licensed in UK

  • Exercise must be restricted

Describe a D. immitis infection in CATS…

• Not well adapted to cats; reduced susceptibility, however very pathogenic in cats

• Adult worms live for shorter period of time compared to dog

• Mf are transient

• Prevalence generally 5-15% of that in local dog population

Mainly effects the LUNGS of the cat; no approved treatment, is very complex

• pathology comes from the inflammatory response to the worms, unlike in dogs, which comes from biomass of adults

How do we treat and control D. immitis in cats?

• Pathology in cats relates to the inflammatory response to worms/worm death

• If no clinical signs, can allow spontaneous recovery, with monitoring

• Melarsomine is very toxic in cats

• Chemoprophylaxis using ML compounds

What is the Angiostrongylus vasorum parasite?

Dog lungworm

• Final host: dog, fox

• Intermediate host: molluscs

• Migration site: right ventricle + pulmonary artery

• Are small and brown

What is the lifecycle of A. vasorum?

Adults in heart → females RELEASE EGGS → eggs hatch in pulmonary capillaries → L1 break into alveoli and migrate up the lungs → L1 are coughed up and swallowed; shed in feces

Mollusc eats L1 → L1 to L3 in mollusc → L3 released from intermediate host when definitie host consumes them → L4 to adult in final host → Adult migrates to the R side of the heart

Describe the pathogenesis of A. vasorum…

Part infection, part hosts’ own immune response

• Pathology comes from a chronic infection

  • Associated with adults in large vessels and eggs in the pulmonary capillaries

• Fibrosis can be seen in arteries as part of the immune response

• Leads to chronic congestive cardiac failure

Will also see:

• lung mottling from penetrating L1s

• EXCESSIVE BLEEDING BIG SIGN

  • Infection causes lower fibrinogen levels

What are the clinical signs of an A. vasorum infection?

Early on - asymptomatic

Later - increased respiratory rate/ cough on exercise

• Heavy worm burden, symptoms in resting dog

  • fainting

  • s.c. haematoma

• Can be associated with brain and spinal cord haemorrhage

• Sub-cutaneous haematomas

• Parasite excretory/secretory products interfere with blood clotting

• Can be confused with warfarin (rat poison) poisoning due to excessive bleeding and clotting troubles

What are the ways to diagnose an A. vasorum infection?

• Diagnosis Baermann on faecal sample

• But sporadic, so should sample on 3 days to ensure detection

• L1, characteristic tail with small spine

• PCR

• Ag test (IDEXX)

  • Detects antigen in the blood stream of the infected dog 

  • Not compromised by intermittent shedding of larvae in faeces 

  • And a PCR test (but only used in research)