Am. J. Trop. Med. Hyg., 77(3), 2007, pp. 504-506
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene
Echinococcus multilocularis Infection of Several Old World Monkey Species in a Breeding Enclosure
Dennis Tappe*,
Klaus Brehm,
Matthias Frosch,
Anja Blankenburg,
Annette Schrod,
Franz-Josef Kaup, AND
Kerstin Mätz-Rensing
Consiliary Laboratory for Echinococcosis, Institute of Hygiene and Microbiology, University of Würzburg, Germany; German Primate Center, Department of Infectious Pathology, Göttingen, Germany
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ABSTRACT
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Echinococcus multilocularis, the causative agent of alveolar echinococcosis, is spreading geographically in Europe, and prevalence rates in foxes, the final host, are increasing. Concomitantly, the rate of newly diagnosed human infections has already doubled in Germany. We report a cluster of alveolar echinococcosis in 24 animals of different Old World monkey species (15 cynomolgus monkeys, 5 rhesus monkeys, and 4 lion-tailed macaques) in northern Germany. The cluster described is the largest ever recorded in a single center. Cynomolgus monkeys were very susceptible and constituted the monkey species at highest risk, indicating that this species could act as a sentinel animal for the transmission of alveolar echinococcosis in zoological gardens or similar institutions.
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INTRODUCTION
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The fox-tapeworm Echinococcus multilocularis is widely distributed in the northern hemisphere1 and is the causative agent of alveolar echinococcosis (AE), one of the most dangerous zoonoses. The sylvatic life cycle involves red foxes (Vulpes vulpes) as final hosts and small rodents as intermediate hosts. Many mammal species, including humans and rarely nonhuman primates, can become intermediate hosts by accidental ingestion of eggs deposited with feces. AE develops subsequently with the metacestode stage of the parasite growing in the intermediate host. AE predominantly affects the liver and is often fatal. Recent reports from Switzerland2–4 and Japan5 indicate that the disease may be a threat for animals living in zoological gardens. We report the largest cluster of cases of AE recorded in a single center, affecting cynomolgus monkeys (Macaca fascicularis), rhesus monkeys (Macaca mulatta), and lion-tailed macaques (Macaca silenus) in a breeding facility in northern Germany, in the period from 1994 to 2006.
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STUDY
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The animals were kept in an open-air enclosure of the German Primate Center located at the edge of a forest in Lower Saxony, northern Germany. In 1994, the first rhesus monkey (M. mulatta) developed AE after the housing changed from entirely indoors to largely outdoors. The animal showed progressive abdominal enlargement, apathy, and anorexia and was euthanized. Hepatomegaly with fibrotic transformation and infiltrative cyst formation was noted at necropsy. Gross aspect and histopathological findings were consistent with infection by the metacestode stage of E. multilocularis. Since then, an additional three M. mulatta, five M. fascicularis, and three M. silenus have developed similar symptoms and died as a consequence of AE. The main pathologic findings in all 12 cases were severe hepatomegaly with fibrous transformation of the liver tissue, mainly in the right and middle lobes. Cystic metacestode tissue with a diameter up to 20 cm and a weight up to 4000 g could be demonstrated in the liver (Figure 1A
). A generalized subacute peritonitis was a concomitant finding in all animals investigated. The mesenteric lymph nodes appeared enlarged. Multilocular cysts were occasionally present in the lungs, the pancreas, and the heart (Table 1). These cysts were usually smaller than the total cystic mass present in the liver. Histologically, the liver parenchyma was destroyed by infiltrative growing cysts of different sizes. The cysts were surrounded by chronic inflammatory cell infiltration with foreign body-type giant cells. The cysts contained multiple protoscolices (Figure 1B).
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FIGURE 1. (A) Alveolar echinococcosis of a cynomolgus monkey (M. fascicularis). Large metacestode tissue infiltrating the liver; necropsy finding. (B) Budding echinococcal vesicle with protoscolices and calcareous corpuscles (magnification 40x). This figure appears in color at www.ajtmh.org.
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As many asymptomatic animals were suspected to be among the various monkey groups, sera of all animals that once lived in the enclosure were screened for anti-Echinococcus antibodies. Two different ELISAs were used in parallel: one using a crude larval antigen preparation from laboratory E. multilocularis and another using the recombinant EM10 antigen, an immunodominant E. multilocularis-specific cytoskeleton protein (sensitivity 93%, specificity 97–100%).6,7 Human sera of confirmed AE cases and sera of the deceased monkeys served as controls. Additionally, a commercially available western blot (LDBIO, Lyon, France) was used for the sera of the animals that tested positive in the ELISAs, confirming the results. A total of 130 rhesus monkeys (M. mulatta), 45 cynomolgus monkeys (M. fascicularis), 13 lion-tailed macaques (M. silenus), and 14 hamadryas baboons (Papio hamadryas) were tested, including the deceased animals. Among the entire population, 5 of the 130 rhesus monkeys (3.8%), 15 of the 45 cynomolgus monkeys (33.3%), and 4 of the 13 lion-tailed macaques (30.8%) were found to have positive serology at the end of the study period (March 2006). All monkeys that were initially seronegative were tested twice during the study period, and seroconversion was observed in 3 rhesus monkeys, 3 cynomolgus monkeys, and 1 lion-tailed macaque. Of the seropositive animals, 12 were still alive at the end of the study period and the developing hepatic AE lesions were controlled yearly by abdominal ultrasound. The animals were not treated and survived until today. The highest percentage of infection was found among the group of cynomolgus monkeys, the second highest among the lion-tailed macaques, and the lowest among the rhesus monkeys. In contrast, none of the baboons had a positive serology. There was no sex preference of seropositivity (male:female ratio, 1.3:1).
Wild foxes have been noticed frequently in the surroundings and on the Primate Center grounds. Direct contamination of the individual outdoor cages by entering foxes seems unlikely, as foxes cannot penetrate the cages’ fencings. However, shredded branches and mulch, which are used for environmental enrichment within the cages, have been stored outdoors on the Primate Center grounds and could have been fecally contaminated. Moreover, branches taken from the local woods have been used for environmental enrichment. Foxes might also have contaminated the direct surroundings of individual cages. As a preventive measure, collected branches were pre-cleaned using a high-pressure washer. Mulch and shredded branches were stored out of reach of foxes, and fox bait containing praziquantel were dispersed.
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DISCUSSION
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Many monkey species are susceptible to infection with E. multilocularis.2,8 In recently described smaller outbreaks of AE, only a few species were affected (five cynomolgus monkeys and two gorillas,2,9 12 cynomolgus monkeys,4 or 12 Japanese monkeys5). We describe the largest cluster of AE cases reported in captive monkeys, affecting 24 animals of three different Old World monkey species over a period of 12 years. Cynomolgus monkeys were the species at highest risk and presumably more susceptible to infection than other monkey species. The percentage of infected cynomolgus monkeys among colonies of captive primates was also high (>50%) in a report from Switzerland.3 In contrast, none of the baboons showed clinical signs of AE and no anti-Echinococcus antibodies were detectable either, although they had lived in the same enclosure for the same time period. Accordingly, no reports about AE in baboons have been published. As baboons are used to feeding on the ground, they would even have a higher risk of infection than the macaques. There were no differences observable in the behavior of the captive baboons compared with the macaques, e.g., no noticeable avoidance of branches or possibly contaminated soil. In contrast to AE, cases of cystic echinococcosis caused by the closely related E. granulosus have been described in baboons.10 However, baboons were shown to be relatively resistant to experimental E. granulosus infection,11 and a similar resistance to E. multilocularis infection can be assumed. The fact that E. granulosus is endemic in areas where wild baboons live, whereas E. multilocularis is not present in these regions, could also account for the lack of recorded AE cases in these monkeys.
The histologic patterns of infection in cynomolgus monkeys, rhesus monkeys, and lion-tailed macaques were shown to be similar to those found in the typical rodent intermediate host (e.g., presence of protoscolices, little necrosis). This report is the first description of AE in lion-tailed macaques. It confirms and expands previous data obtained from cynomolgus monkeys2,4 and a rhesus monkey.8 However, the findings contrast with AE cases in great apes, such as gorillas9,12 and orangutans,13 in whom pathologic changes resemble those found in humans (e.g., usually no protoscolices, widespread necrosis).
Since the 1990s, E. multilocularis has been spreading geographically, and increasing infection rates of red foxes have been noted in western and eastern European countries.1,14,15 For the last decade, fox population densities have been increasing drastically, and the raccoon dog, a neozootic, highly susceptible final host, has migrated from Asia to Germany and Poland.15 Today, E. multilocularis has been reported from Denmark, the Netherlands, Belgium, central France and Germany to Lithuania, Poland, Slovakia, Hungary and Northern Italy.15 The presence of the parasite in southeastern European countries is likely.1,15 In northern Germany, Denmark, and Poland, prevalence rates in foxes are usually < 5%,16 but focal areas of higher prevalence exist. In southern Germany and Switzerland, infection rates often exceed 50% and approach 100% locally.16 Animals in zoological gardens and in institutional colonies in the northern hemisphere are at risk, and AE must be considered as an emerging disease also in captive animals. Cynomolgus monkeys are very susceptible to AE and may thus indicate previously unknown areas of high transmission in zoos. In the scenario described, the increase of AE cases over the years in captive monkeys reflects the transition from sporadic cases to an endemic situation. Human caretakers for these animals are also at risk of infection via the same routes as the primates. With respect to the raised prevalence rates in foxes and an increase of fox population densities, an upsurge of human echinococcosis has already been noticed.17
Received May 3, 2007.
Accepted for publication May 20, 2007.
Acknowledgment: The authors thank Mechthild Schulze for carrying out the serology tests.
* Address correspondence to Dennis Tappe, Josef-Schneider-Str. 2, Würzburg, Bavaria, Germany. E-mail: dtappe{at}hygiene.uni-wuerzburg.de 
Authors’ addresses: Dennis Tappe, Klaus Brehm, and Matthias Frosch, Consiliary Laboratory for Echinococcosis, Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany, Telephone: +49-931-201-46036, Fax: +49-931-201-46445, E-mail: dtappe{at}hygiene.uni-wuerzburg.de. Anja Blankenburg, Annette Schrod, Franz-Josef Kaup, and Kerstin Mätz-Rensing, German Primate Center, Department of Infectious Pathology, Kellnerweg 4, 37077 Göttingen, Germany.
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ABSTRACT
INTRODUCTION
