Dirofilaria immitis: Diethylcarbamazine-induced anaphylactoid reactions in infected dogs

Rg, Hamilton; Wagner, Edward K.; April, Milton; Winkelstein, JA; Sobotka, AK; Bleeker, E; Nf, Adkinson

doi:10.1016/0014-4894(86)90197-9

Cited by 14 publications

(5 citation statements)

References 20 publications

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“…Mf products fix complement (Staniunas & Hammerberg, 1982) and the release of large quantities of antigen on parasite death may generate the post-DEC hypersensitivity syndrome. Studies by Hamilton et al (1986) support this explanation. Normal uninfected dogs, when injected with a somatic extract of D. immitis, undergo a similar shock syndrome (complement depletion, release of mast cell mediators, vasoconstriction and drop in blood pressure) to that seen on DEC treatment of an infected dog.…”

Section: Immunological Side-effects Of Dec Administrationmentioning

confidence: 87%

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Maizels¹,

Denham

1992

Parasitology

134

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Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals. It may also account for the inconsistencies in the effects of DEC against different filariae in different host species. In addition, we discuss the significant side-effects often associated with treatment of heavily infected patients, and the longer-term changes in T-cell reactivity and the host-parasite relationship which follow successful treatment with DEC.

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Section: Immunological Side-effects Of Dec Administrationmentioning

confidence: 87%

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Maizels¹,

Denham

1992

Parasitology

134

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“…In fact, evidence that MLs rely on the host’s immune response to ‘exposed’ filarial worms is not surprising, as the concept that the ultimate activity of an anthelmintic drug is the result of an immunologic process is not new. Diethylcarbamazine (DEC) employs a different mechanism than that of MLs, but it still targets filarial worms by facilitating an enhanced stimulation of the innate immune response [42, 121–123]. …”

Section: Discussionmentioning

confidence: 99%

Examining the role of macrolides and host immunity in combatting filarial parasites

Carithers

2017

Parasites Vectors

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Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also thought to be the ML mode of action against filarial nematodes, but researchers have not been able to validate these characteristic effects of immobilization/starvation of MLs in vitro, even at higher doses than are possible in vivo. Relatively recently, ML receptor sites exclusively located proximate to the excretory-secretory (ES) apparatus were identified in Brugia malayi microfilaria and an ML-induced suppression of secretory protein release by B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that suppression of these ES proteins prevents the filarial worm from interfering with the host’s complement cascade, reducing the ability of the parasite to evade the immune system. Live microfilariae and/or larvae, thus exposed, are attacked and presented to the host’s innate immune mechanisms and are ultimately killed by the immune response, not the ML drug. These live, exposed filarial worms stimulate development of innate, cellular and humoral immune responses that when properly stimulated, are capable of clearing all larvae or microfilariae present in the host, regardless of their individual sensitivity to MLs. Additional research in this area can be expected to improve our understanding of the relationships among filarial worms, MLs, and the host immune system, which likely would have implications in filarial disease management in humans and animals.

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“…4,8,15 Alternatively, they may have concerns for anaphylactic reactions secondary to microfilarial death following administration of macrocyclic lactones or with historical diethylcarbamazine administration. 8,16 The findings of this study reveal an opportunity to increase awareness of the value of heartworm preventive therapy as part of HWD treatment protocols, and raise awareness of strategies to mitigate the risk of anaphylactic reactions, among practicing veterinarians.…”

Section: Hwd Cases With Clinical Signsmentioning

confidence: 87%

Approaches to Canine Heartworm Disease Treatment Among Alumni of a Single College of Veterinary Medicine

Dixon-Jimenez¹,

Coleman²,

Rapoport

et al. 2018

Journal of the American Animal Hospital Association

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This descriptive study was designed to ascertain the current heartworm treatment strategies employed by veterinary graduates of a single college of veterinary medicine, to assess the frequency with which each of these treatment strategies is prescribed, and to report the motivation behind the use of these treatment strategies. A survey containing a combination of multiple-choice and open-ended questions was distributed via e-mail with an online link during 2013 to graduates of the University of Georgia College of Veterinary Medicine. Demographic data and opinions regarding treatment for cases of canine heartworm disease (HWD) were obtained, and motivation for recommending different treatment strategies was assessed. Nearly all 170 respondents (99%) indicated that they recommend melarsomine dihydrochloride for first-line treatment of canine HWD. Exercise restriction (80%) and monthly heartworm preventive (75%) were components of the treatment approach to HWD with no clinical signs. The majority of respondents (74%) indicated that when first-line treatment recommendations were declined, they endorsed long-term administration of ivermectin (i.e., "slow-kill" method) despite current American Heartworm Society guidelines that recommend against the use of long-term macrocyclic lactone administration for the monotherapy treatment of canine HWD. Respondents also indicated that owners' financial concerns frequently result in modification of HWD treatment. Routine inclusion of exercise restriction is commonly, but not universally, utilized and may represent an opportunity for improvement in the management of this disease. In addition, when first-line recommendations for heartworm disease treatment are declined, a two-dose melarsomine protocol instead of the slow-kill method should be considered.

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Dirofilaria immitis: Diethylcarbamazine-induced anaphylactoid reactions in infected dogs

Cited by 14 publications

References 20 publications

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Examining the role of macrolides and host immunity in combatting filarial parasites

Approaches to Canine Heartworm Disease Treatment Among Alumni of a Single College of Veterinary Medicine

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