Japanese monkey (Macaca fuscata) with alveolar echinococcosis after treatment with albendazole for 10 years: serodiagnosis and determination of albendazole metabolites

Abstract

In 1997, an outbreak of alveolar echinococcosis in Japanese monkeys (Macaca fuscata) occurred in a zoo in Hokkaido, Japan. Twelve infected monkeys from a colony (n = 57) were diagnosed serologically by Western blotting, and ultrasonography showed the presence of tumor-like tissue in the livers of nine monkeys. The 12 infected monkeys have been treated with albendazole for 10 years without surgical resection. Ten of these monkeys have died so far; diagnoses were confirmed histopathologically through autopsy. Two of these monkeys are still alive. Recently, a significant difference between the two living monkeys was recognized. A difference in curative effect was demonstrated between the two living monkeys by radiography, contrast enhanced computed tomography, and contrast ultrasound. One showed metastasis to various organs, and the other appeared to be almost cured, as demonstrated by size reduction and calcification of the lesion after albendazole treatment for 10 years. This time, serological reexamination was performed to corroborate this apparent difference. The serological tests supported the preliminary imaging findings. In addition, the presence of albendazole metabolites in sera was confirmed by high-performance liquid chromatography. In this study, it was demonstrated that tests which have been used in human cases were also effective for diagnosing alveolar echinococcosis and for assessing curative effects in nonhuman primates such as M. fuscata.

Respiratory System Diseases of Nonhuman Primates

“…Additional cases of hydatid disease have been seen in a thick-tailed galago (Otolemur crassicaudatus), a ringtailed lemur (Lemur catta), and rhesus macaques, one of which had a primary lung cyst with subsequent spread to the abdomen (Palotay and Uno, 1975). Several cases of "alveolar echinococcosis" due to E. multilocularis also have been reported in nonhuman primates, most of which had either primary or concurrent pulmonary involvement (Garcia et al, 2002;Yamano et al, 2009). Long-term albendazole was efficacious in treatment of some of the Japanese macaques in the outbreak described by Yamano et al (2009).…”

“…Several cases of "alveolar echinococcosis" due to E. multilocularis also have been reported in nonhuman primates, most of which had either primary or concurrent pulmonary involvement (Garcia et al, 2002;Yamano et al, 2009). Long-term albendazole was efficacious in treatment of some of the Japanese macaques in the outbreak described by Yamano et al (2009). A detailed account of imaging studies performed on two of these macaques was described by Kishimoto et al (2009), which demonstrated mineralization of many of the lesions.…”

Aspects of albendazole metabolism in western lowland gorillas (Gorilla gorilla gorilla) compared to humans and other species assessed by HPLC, LC‐MS, and chiral electrokinetic chromatography

“…This, however, was not validated, but would make sense if the pharmacokinetics is similar to what was described for sheep [14]. For Japanese monkeys, no ABZSO 2 but significant plasma levels of ABZSO and ABZSO 2 ‐NH 2 were reported [32]. This finding is difficult to comprehend because ABZSO 2 ‐NH 2 is a metabolite of ABZSO 2 (Figure 1).…”

“…A similar HPLC pattern was monitored in sera of Japanese monkeys ( Macaca fuscata ) with alveolar echinococcosis that were treated with ABZ. In this work, the two ABZ metabolite peaks were assigned to ABZSO and ABZSO 2 ‐NH 2 [32]. No scientific article about the metabolism of ABZ in gorillas was found in the literature.…”

Time course of the antibody response in humans compared with rats experimentally infected with hepatic alveolar echinococcosis

“…In particular, the antibody response time course in the postoperative stage offers information about curative effects (Fujimoto et al , 2005). In non-human primates such as the Japanese monkey ( Macaca fuscata ), we previously diagnosed AE by serodiagnosis and ultrasonography (Sato et al , 2005) and showed it to be almost cured after treatment with albendazole for 10 years, by imaging analysis and the disappearance of the 18 kDa band in a WB test (Kishimoto et al , 2009; Yamano et al , 2009c).…”