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| AMERICAN HEARTWORM SOCIETY'S HEARTWORM HOTLINE Benefits of Anti-Wolbachia Therapy UÊReduces ability of parasite to reproduce UÊReduces infectivity UÊPotential adulticidal therapy and/or enhancement of slow- or soft-kill efficacy UÊReduces microfilarial burdens more effec- tively, safely, and rapidly UÊReduces reaction to worm death, both spontaneous (presumably) and postadulticide UÊKills or impairs developing larvae Wolbachia are necessary for the parasite (in this case, Dirofilaria immitis) to develop, thrive, reproduce, and maintain infectivity. Doxycycline has been used to (presumably) rid the parasite of Wolbachia organisms; therefore, D immitis organisms do not thrive, may deteriorate and die, and have reduced reproductive potential, which helps manage HWD in infected dogs and reduces potential for infection in other dogs. Potential and realized benefits derived from anti-Wolba- chia therapy include: 1. Reduced Ability of Parasite to Reproduce Ê ÌÊ h>ÃÊ LiinÊ ÃhoÜnÊ Ìh>ÌÊ ÌhiÊ Wolbachia organism is suppressed (killed) by doxycycline and the result- ing, negative effects on the heartworm reproductive system renders the parasite infertile or less fertile (temporarily?), with reduced microfilarial numbers.1,2,3 2. Reduced Infectivity Ê nÊ`oÝÞVÞVlini-ÌÀi>Ìi`Ê`o}Ã]ÊiÛinÊivÊmiVÀovil>Ài>iÊ>ÀiÊ produced and ingested in a mosquito's blood meal, the resultant L3 are incapable of producing infection, reducing the spread of HWD.1,2,3 3. Potentiate Adulticidal Therapy and/or Enhancement of Slow- or Soft-kill Efficacy Most agree that Wolbachia is an obligatory symbi- ont for D immitis, which gives hope that Wolbachia eradication with antibiotics would result in the nema- tode's demise. Unfortunately, prolonged doxycycline therapy does not kill heartworms because they are not sufficiently bound to their bacterial symbionts.4 Nevertheless, 2 studies3,5 doxycycline shortens the time until worm death when administered chronically with ivermectin/pyrantel at preventive dosages, but with a decreased dosing inter- val:3,5 Study 1: Using surgically transplanted worms, it was shown that a combination of: UÊWeekly ivermectin (at the monthly preventive dos- age of 6 mcg/kg PO) and UÊDaily doxycycline (10 mg/kg PO Q 24 H for 24 weeks of a 36-week study) reduced heartworm bur- den by 78% after 9 months of therapy as compared to control dogs.3 Study 2: Using echocardiography, this study evalu- ated the effect of: 42 Today's Veterinary Practice July/August 2012 UÊDaily doxycycline (10 mg/kg PO Q 24 H for 30 days) and UÊIvermectin/pyrantel (6–14 mcg/kg PO every 15 days for 180 days; then monthly) on microfilariemia, heartworm antigenemia, and «>À>ÃiÌiÊlo>`°Ê nÊn>ÌÕÀ>llÞ-inviVÌi`Ê`o}ÃÊ vÀomÊ >nÊ in`imiVÊ Ài}ionÊ ovÊ negative for circulating microfilariae by day 90 and 73% became antigen negative by day 300.5 The results of these studies suggest that the combi- nation of doxycycline and ivermectin is (slowly) adul- ticidal in dogs with D immitis, which indicates that doxycycline enhances therapy for the soft- or slow-kill method. 4. Effective, Safe, & Rapid Reduction of Microfilarial Burdens Ê nÊÌhiÊÌÀ>nël>nÌi`ÊÜoÀmÊmo`ilÊminÌioni`ÊinÊ-ÌÕ`ÞÊ 1, it was shown that a combination of weekly ivermec- tin (6 mcg/kg) and daily doxycycline (10 mg/kg Q 24 H) eliminated microfilariae over 8 to 12 weeks.3 This elimination is relatively fast, but not so rapid that therapy results in the adverse, shock-like reac- tions seen with rapid destruction of large numbers of miVÀovil>Ài>i°Ê nÊ>``iÌion]ÊÃÕL>VÕÌiÊÀimoÛ>lÊovÊmiVÀo- filariae lessens the chance of macrocyclic lactone resistance, especially when the practitioner is forced to use the slow-kill method due to owner finances or difficulty attaining adulticide (ie, melarsomine). 5. Reduced Lung Reaction to Worm Death (Spontaneous & Postadulticide) Study 1 also showed that the combination of weekly ivermectin (6 mcg/kg PO) and daily doxycycline (10 mg/kg PO Q 24 H) significantly reduced lung lesions after melarsomine therapy.3,6 6. Developing Larva Eliminated Recently, McCall, et al, demonstrated that, while doxy- cycline (even with ivermectin) does not have rapid adulticidal efficacy, doxycycline monotherapy does stop the progression of infective larvae to adulthood when administered for the first 30 days of infection at 10 mg/kg PO Q 24 H.7 UÊ vÊÌhiÊÎäÊ`>ÞÃÊovÊ>`miniÃÌÀ>ÌionÊLi}inÊonÊ`>ÞÊ{äÊovÊ infection, however, the effect is partially lost, with have demonstrated that Should We Worry About Resistance? Concern has been raised about the potential devel- opment of bacterial resistance if doxycycline is administered in all cases of HWD. In my opinion, this concern is worth considering as doxycycline is widely used and valuable to our profession (and physicians) for treatment of a variety of infectious processes. On the other hand, concerns for resis- tance generally occur when drugs are used at sub- optimal dosages and durations of therapy. Neither of these result from the current treatment recommen- dations for HWD. Ì>lÞ]Ê >llÊ `o}ÃÊ LiV>miÊ