A 5-year-old, male English setter was diagnosed with heartworm disease.
A modified Knott's test was positive for circulating microfilariae. A point-of-care test for circulating Dirofilaria immitis antigens (IDEXX Snap) was positive for low-level antigenemia. Thoracic radiographs showed minimal evidence of pulmonary parenchymal inflammation and no enlargement of pulmonary arteries (Figure 1). A CBC and biochemical profiles were normal, except for eosinophilia (18 × 103/µl), slightly elevated total proteins (8.2 g/dl [reference range, 5.4 to 7.1]), and inversion of the albumin-to-globulin ratio (0.65 [reference range, 0.8 to 1.7]). An in-house ELISA revealed circulating antibodies against WSP. Urinalysis documented mild proteinuria (20 mg/dl).
ASK YOURSELF ...
There are several therapeutic protocols from which to choose for preadulticide/adulticide therapy in dogs with heartworm disease. Which of these protocols would be best for this patient?
A. Two injections of melarsomine dihydrochloride separated by a 24-hour interval (standard protocol)
B. A gradual, 2-stage elimination of worms using a 3-injection treatment protocol of 1 dose initially, followed in 4 to 6 weeks with a 2-dose treatment (alternative protocol)
C. Administration of a macrocyclic lactone before administration of alternative melarsomine
D. Administration of doxycycline and a macrocyclic lactone before administration of melarsomine with the standard protocol
Correct Answer: D
Administration of doxycycline and a macrocyclic lactone before administration of melarsomine with the standard protocol
According to the AHS guidelines for adulticide therapy in dogs, successful treatment is directly associated with risk for pulmonary thromboembolism; therefore, patients must be evaluated as having "low" or "high" risk for clinically important PTE. Furthermore, administration of a macrocyclic lactone immediately following diagnosis (for up to 6 months) has proven to be beneficial in preparing dogs for adulticide therapy by reducing circulating microfilariae and antigenic mass of adults. The most recent advance in therapy for filarial infections has targeted Wolbachia, bacteria that reside within D. immitis that are essential for worm fertility and survival. Additional treatment of patients with doxycycline is able to reduce Wolbachia (Figure 2), thereby potentially reducing strongly proinflammatory antigens released from the dead or dying worms.
Immediate adulticide therapy was not necessary in this case because:
• Detectable antigenemia was low, suggesting adult worm burden was low and that the patient would tolerate the standard adulticide protocol.
• Radiographic evidence of pulmonary inflammation was minimal, suggesting that this dog might benefit from preadulticide therapy (macrolide, doxycycline).
• Elevated total protein, mild proteinuria, and antiWSP antibodies were suggestive of the potential role of Wolbachia-associated, immune-mediated alterations that might have been minimized by pretreatment.
• Doxycycline pretreatment could potentially reduce levels of proinflammatory mediators like interleukin-8, whose release from canine neutrophils is triggered by Wolbachia.
• Microfilariae also harbor Wolbachia, and their elimination with a macrocyclic lactone, associated with doxycycline, may prove beneficial in reducing proinflammatory effects.
The dog was administered ivermectin at 6 µg/kg in a single dose and doxycycline at 10 mg/kg PO Q 24 H for 30 days before adulticide therapy. Routine blood analysis was repeated. Gamma globulin concentrations were decreased, associated with a decline in circulating antiWSP antibodies. Proteinuria also resolved. However, circulating microfilariae were still present, as was eosinophilia. Melarsomine dihydrochloride was administered according to the standard protocol (2.5 mg/kg). Exercise restriction was recommended for 4 weeks. No adverse effects of adulticide treatment were noted. Heartworm antigenic testing 6 months after treatment was negative.
• When the clinical presentation does not demand immediate intervention, heartworm-infected dogs may benefit from preadulticide therapy.
• Doxycycline treatment may help reduce inflammation and immune-mediated phenomena associated with Wolbachia.
• Macrocyclic lactones need to be administered for several consecutive months to eliminate circulating microfilariae.