Exam 2 - Lecture 18

Question 1

Briefly Explain The Phases for Treatment

Answer 1

-3 Phases:

1) Pre‐adulticide clinical evaluation and treatment:
-Clinical evaluation
-Removal of HW larvae & Wolbachia

2) Adulticide treatment:
-Melarsomine dyhydrochloride to kill adult worms ≥ 100 days post‐infection in pulmonary artery (2 or 3 injection protocols available)
- “Slow Kill” alternatives (not endorsed by AHS, CAPC or FDA labeled)

3) Post‐adulticide evaluation and treatment to eliminate microfilaria if necessary:
-Antigen testing to verify treatment effectiveness
-Microfilaria testing & treatment

Question 2

Early Treatment Diagnosis (Day 0) to Day 30

Answer 2

-Pre‐adulticide clinical evaluation (@ Diagnosis):
* Classify Patient: Symptomatic for clinical disease or Asymptomatic
* Blood chemistry panel (kidney function, liver enzymes)
* Radiographic evaluation
* Blood examination for microfilariae!

-1st treatment to remove migrating Heartworm larvae acquired within last 30 to 45 days prior to diagnosis:
* Any monthly prophylactic acceptable (prefer drug w/ low microfilaricidal activity)
* Ivermectin, Selamectin, Milbemycin, or Moxidectin

-Treatment to remove the Wolbachia:
* Doxycycline @ 10mg/kg BID, 4 weeks
* Reduce risk of thromboembolic complications
* Enhance the killing activity of the adulticide drug on worms in heart
* Render the microfilariae un‐infective to mosquitos

-2nd monthly prophylactic treatment (@ Day 30)

Question 3

Adulticidal Treatment Day 60 to Day 90

Answer 3

-Removal of adult worms in pulmonary artery/ right ventricle:
* Immiticide, Diroban (Melarsomine Dihydrochloride)
* Safe, highly efficacious (90 to 98%)
* Only effective against adult worms in pulmonary artery @ ~100 days post‐infection
* Expedient, full course of treatment in ~ 60 to 90 days
* Low risk of hepatotoxicity
* Pulmonary thromboembolism risk

-Immiticide Treatment Regimens
* Classic FDA labeled (2 injection) for Stabilized Class 1 and Class 2
* 2.5mg/kg, IM deep epaxial lumbar, SID, 24 hours apart
-AHS/CAPC Recommended; 3 total injections w/out regard to HWD Class
* 2.5mg/kg, deep epaxial lumbar, SID, once @ Day 60 following initial
diagnosis;
* Repeat (x2) @ 24 intervals , Day 90 & 91 post‐initial diagnosis

-Treated animal on cage rest & leash walk for 6 to 8 weeks: efficacy is 90 to 98%;

Question 4

“Slow Kill” Adulticidal Treatments

Answer 4

-Removal of adult worms in pulmonary artery/ right ventricle:
-Original “Slow Kill” Ivermectin
-Efficacious over extended period of time (71% when given over 24 months, 95 % @ 29 months)
-Pulmonary thromboembolism risk
-HW associated inflammatory disease still on‐going

-New “Slow Kill” regimen:
-Ivermectin 6 to 8μg/kg, SID q 15 day intervals for 6 months
- *Doxycycline 10mg/kg SID for 30 days
-Efficacy 78% @ 36 weeks post‐initial treatment
-Killed microfilariae by 12 weeks

-Moxi‐Doxy:
-Advantage Multi (Imidicloprid + Moxidectin) monthly for 10 months
- *Doxycycline 10 mg/kg BID for 30 days
-Efficacy 95.9% elimination of adult heartworms
-Killed microfilariae by 21 days
7

• Likely associated w/ reduced risk of PTR

Question 5

Adulticidal Treatment

Answer 5

-Concerns:
-Post‐adulticidal risk of thromboembolisim
-Dead, dying, deteriorating worms in vascular circulation
-True in all treatment regimens but natural part of disease clearing process
-Mitigated by exercise restriction
-Corticosteroids recommended to suppress the inflammatory response of host

-Recent paper suggest revaluation:
* Dogs receiving prednisone appeared to have higher risk of thromboembolism
-Aggravation of intimal disease, act as pro‐coagulants, and reduce pulmonary blood flow necessary to clear deteriorating worms and debris

-Reduction of inflammatory response & complications
-Treatment of Wolbachia w/ Doxycycline appears to mitigate this concern

Question 6

Adulticidal Treatment - Considerations:

Answer 6

• Adulticidal treatment is expensive (88% cost of prevention)
• AHS/CAPC recommended regimen requires multiple hospital visits over
  90+ days (single Tx, followed by 2 Tx @ 24 hr)
• Certainly warranted for animals with clinically complicated HW disease,
  altered blood chemistry, radiographic changes, evidence suggestive of “large” HW burden
• FDA (2 injection) regimen has demonstrated history (since 1995) of efficacy (~96% cases cleared w/out issue)
• Warranted for animals diagnosed asymptomatic on routine annual screen, normal blood chemistry, no radiographic anomalies, no evidence to suggest HW burden of more than small number of worms
• Original “Slow Kill” premise rejected because of prolonged course of therapy, on‐going pathology/disease process
• Also said to facilitate “emerging drug resistance”
• New “Slow Kill” w/ Doxycycline demonstrated to reduce adverse effect of
  Wolbachia in the disease process; also shown to render microfilaria un‐infective to mosquitos
• Moxi‐Doxy looks promising as “alternative Tx”, mitigates pathogenic effects of Wolbachia; killed microfilariae by 21 days

Question 7

Adulticidal Treatments

Answer 7

-All treatment regimens have pros & cons with efficacy and safety:

-Melarsomine is the only FDA approved adulticidal treatment

-Moxi‐Doxy looks promising and may gain favor as a legitimate alternative; Not endorsed by AHS or CAPC

-*All treatment effects enhanced w/ Doxycycline:
-Reduction of inflammatory biomarkers, mitigate pathologic changes, renders microfilariae non‐infective to mosquitos

-License to practice veterinary medicine based on your
scientific knowledge & skills

-Keep in mind all are recommendations for you to consider and apply in the best interest of your patient and client