Investigation of a combination of amiodarone and itraconazole for treatment of American trypanosomiasis (Chagas disease) in dogs

被引:21
作者
Madigan, Roy [1 ]
Majoy, Sean [2 ]
Ritter, Kristine [2 ]
Luis Concepcion, Juan [3 ]
Elizabeth Marquez, Maria [3 ]
Caribay Silva, Sasha [3 ]
Zao, Chih-Ling [4 ]
Perez Alvarez, Alexandra [5 ]
Rodriguez-Morales, Alfonso J. [6 ]
Mogollon-Mendoza, Adriana C. [5 ,7 ]
Estep, J. Scot [1 ]
Benaim, Gustavo [8 ,9 ]
Paniz-Mondolfi, Alberto E. [3 ,5 ,8 ,10 ,11 ]
机构
[1] Anim Hosp Smithson Valley, 286 Singing Oaks,Ste 113, Spring Branch, TX 78070 USA
[2] LTC Daniel E Holland Mil Working Dog Hosp, 1219 Knight St, Lackland AFB, TX 78236 USA
[3] Univ Los Andes, Fac Ciencias, Lab Enzimol Parasitos, Merida 5101, Venezuela
[4] VRL Labs, 7540 Louis Pasteur,Ste 250, San Antonio, TX 78229 USA
[5] Venezuelan Sci Incubator & Zoonosis & Emerging Pa, Infect Dis Res Branch, Av Intercomunal Barquisimeto Acarigua, Cabudare 3023, Lara, Venezuela
[6] Univ Tecnol Pereira, Fac Ciencias Salud, Grp Invest Salud Publ & Infecc, Sect Julita, Pereira 660003, Risaralda, Colombia
[7] Univ Ctr Lisandro Alvarado, Escuela Med, Ciencias Salud, Barquisimeto 3001, Lara, Venezuela
[8] Inst Estudios Avanzados, Carretera Nacl Hoyo Puerta, Lab Senalizac Celular & Bioquim Parasitos, Caracas 1015A, Venezuela
[9] Cent Univ Venezuela, Fac Ciencias, Inst Expt Biol, Caracas 1041A, Venezuela
[10] IDB Biomed Res Inst, Av Intercomunal Barquisimeto Acarigua, Cabudare 3023, Lara, Venezuela
[11] Inst Venezolano Seguros Sociales, Direcc Salud, Direcc Nacl Docencia & Invest, Edif Sede, Caracas 1010, Venezuela
来源
JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION | 2019年 / 255卷 / 03期
关键词
ETIOLOGIC TREATMENT; RANDOMIZED-TRIAL; CRUZI INFECTION; BENZNIDAZOLE; CHEMOTHERAPY; INHIBITORS; CARDIOMYOPATHY; SUSCEPTIBILITY; TRANSMISSION; POSACONAZOLE;
D O I
10.2460/javma.255.3.317
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
OBJECTIVE To evaluate clinical, serologic, parasitological, and histologic outcomes of dogs with naturally occurring Trypanosoma cruzi infection treated for 12 months with amiodarone and itraconazole. ANIMALS 121 dogs from southern Texas and southern Louisiana. PROCEDURES Treatment group dogs (n = 105) received a combination of amiodarone hydrochloride (approx 7.5 mg/kg [3.4 mg/lb], PO, q 24 h, with or without a loading dosage protocol) and itraconazole (approx 10 mg/kg [4.5 mg/lb], PO, q 24 h, adjusted to maintain a plasma concentration of 1 to 2 mu g/mL) for 12 months. Control group dogs (n = 16) received no antitrypanosomal medications. Serologic assays for anti-T cruzi antibodies, PCR assays for T cruzi DNA in blood, and physical evaluations were performed 1, 6, 9, 12, and 24 months after study initiation. Adverse events were recorded. Outcomes of interest were recorded and compared between groups. RESULTS 86 of 105 treatment group dogs and 8 of 16 control group dogs survived and completed the study (5/19 and 6/7 deaths of treatment and control group dogs, respectively, were attributed to T cruzi infection). Mean survival time until death attributed to T cruzi was longer (23.19 vs 15.64 months) for the treatment group. Results of PCR assays were negative for all (n = 92) tested treatment group dogs (except for 1 dog at 1 time point) from 6 to 24 months after study initiation. Clinical improvement in >= 1 clinical sign was observed in 53 of 54 and 0 of 10 treatment and control group dogs, respectively; adverse drug events were minor and reversible. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested efficacy of this trypanocidal drug combination for the treatment of T cruzi infection in dogs.
引用
收藏
页码:317 / 329
页数:13
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