L16-17 - Heartworm Infections and Disease

What’s the scientific name for canine HW?

Dirofilaria immitis

Dirofilaria immitis

Life cycle of Dirofilaria immitis

• Viviparous → gives birth to live young (microfilaria)

• Mosquitoes → larvae migrate in SQ tissue → colonize pulmonary artery after about 100 days → become reproducing adult worm

• Microfilaria akes about 14 days to become infective stage in mosquito → as long as >57 F

What is the morphology of Dirofilaria immitis?

Males → coiled tail

Otherwise unremarkable

What does the L3/L4 migrating larvae of Dirofilaria immitis secrete?

Extracellular vesciles (ESVs) → responsible for downregulating host immunity and allows for them to migrate

What conditions are needed for infective larvae development of Dirofilaria immitis?

• > 57 F and sufficient precipitation

• Depends on having infected microfilaria animals for mosquitoes to feed on

Describe the pathogenesis of Dirofilaria immitis

• Worms live in pulmonary arteries and R side of heart

• Immune system stimulation

• Obstructive fibrosis, pulmonary endothelial damage and narrowing of vasculature bed with impaired blood flow → reduced CO

• Pulmonary hypertension

What is occuring in this image?

• Pulmonary hypertension

• Right side of heart is enlarged → hypertrophy

• Reversed “D” profile of heart

• Enlarged, thickened pulmonary artery

• Pulmonary infiltrates in caudal lung lobes

How can Dirofilaria immitis affect the kidneys?

• Glomeruli obstruction with Ab-Ag or microfilaria

• Endosymbiotic gram-negative bacteria (Wolbachia pipientis) that have been given via arthropod vectors → trasmitted to microfilariae by adult worms

What is caval syndrome?

• Large number of Dirofilaria immitis worms push through right atrium into vena cava → obstruction of blood flow and interferes with tricuspid valve

• Hemolysis of blood that does pass through

• Causes liver failure

• Fatal if not surgically removed

What is DIC?

• Disseminated intravascular coagulation

• Disorder that is caused by consumption of coagulation proteins → causes uncontrolled hemorrhaging

• Facilitating Factor : HW induced pulmonary thromboembolism

What’s the most important factor responsible for transmission of canine heartworm disease?

The occurence of microfilaremic hosts in the area

How can Dirofilaria immitis be prevented and what is the mechanism of action?

• Ivermectin → monthly administration, targets L3/L4

  • High affinity for GluCls → flaccid paralysis of somatic musculature (can’t stay in place), paralytic effect on paryngeal pump (starves)

• Macrocyclic Lactones

  • High affinity for GluCls → prevents reproduction

  • Inhibit ability to secrete ESVs → exposes paratistes to host immune system → leukocyte binding

Heartworm preventatives

• Do not prevent HW infection! → kills L3/L4 by facilitating host’s immune respose

• Chewable, topical and 6 or 12 month injectable

What are the Multi-Modal prophylactic programs against HW?

• K9 Advantix → just prevents mosquitoes from landing on animal, must use in conjunction with HW prophylaxis

• Vectra 3D → mosquito repellency + kill mosquitoes, protect against HW

• Simparica Trio → Isoxazoline and Macrocyclic lactone → true repellent and killing of mosquitoes, protect against CHW

How can Dirofilaria immitis be drug resistant?

• Over expression of the P-glycoproteins (MDR1 gene)

• ATP-dependent drug efflux pump → decreases drug accumulation on GluCl channels

  • HeartGard Plus and Interceptor

• Moxidectin doesn’t efflux as readily → still effective against HW

• Mostly in Mississippi river delta dogs

How do most cases of HW diseases of animals on prophylactic programs occur?

Owners not complying to montly administration → NOT due to drug resistance

How does monthly administration of macroclyclic lactone prophylactic drugs (Ivermectin, Milbemycin, Moxidectin) prevent canine HW disease?

• Drugs kill migrating larvae acquired 30 days before treatment by interfering with their ES metabolism and expose them to host immunity

Symptoms of Dirofilaria immitis

• Exercise intolerant

• Trouble breathing when extra effort is required of heart

How is Dirofilaria immitis diagnosed?

• Filter Test

• Knott’s Test

• Serologic Testing → ELISA for female uterine antigen

Size must be >300 um

Dirofilaria immitis → microfilaria

• Tapered head and straight tail

Dirofilaria immitis → microfilaria

• Tapered head and straight tail

Acanthocheilonema reconditum (Dipetalonema)

• Similiar to HW

• Smaller

• Head is blunt like broomstick

• Hooked tail

Why is antigen testing being used for HW test?

• Can miss microfilariae

• Antigen testing is most sensitive method

• However, microfilariae detection is being used to recognize drug-resistant isolates

What defines the accuracy of serologic testing for heartworm?

Sensitivity → ability of test to detect subjects with infections

• Affected by: # of worms, sex ratio, maturity

Specificity → ability to detect those without infection

• Affected by: false color development, poor discrimination b/w color vs. non-color, poor washing technique, cross reaction with other parasitic species

What occurs if HW tests have poor sensitivity?

Many false negatives!

What occurs if HW tests have poor specificity?

Many false positives!

How is predictive value calculated in HW tests? What do high/low values mean?

Function of sensitivity, specificity and prevalence of infection in the population

• Low prevalence = poor positive predictive value (too many false positives)

• High prevalence = greater positive predictive value

What is the HW susceptibility gap?

• Negative antigen test b/c larvae are too young

• Not susceptible to drugs → become infected

What is predictive value? What do low and high values mean?

Probability that the tests correctly discriminate between those with an infection and those without one

• Low → poor positive predictive value (excessive false positives)

• High → higher prevalence of disease

What justifies the HW prevalence being 1%?

• Low natural prevelanence in animals tha tare well cared for

• Monthly medications lowers microfilaremia

• Minimal reservoir of infected dogs nearby

What’s the significance of Ag-Ab complexes in the diagnosis of canine HW? How is this problem solved?

• Significantly ill animals will intiate a large antibody immune response → Ab-Ag complexes form and take up all the HW antigens → no antigens left for test to detect!

• Heat treatment → breaks complexes and test will show positive