Experimental and Toxicologic Pathology 66 (2014) 263–265
Contents lists available at ScienceDirect
Experimental and Toxicologic Pathology journal homepage: www.elsevier.de/etp
Short Communication
Cerebral Baylisascaris larva migrans in a cynomolgus macaque (Macaca fascicularis) Ahmed Shoieb a,∗ , Zaher A. Radi b a b
Pfizer Drug Safety Research and Development, 455 Eastern Point Road, MS 8274-1221, Building 274, Office 1703F, Groton, CT 06340, USA Pfizer Worldwide Research and Development, Drug Safety R&D, Andover, MA, USA
a r t i c l e
i n f o
Article history: Received 1 March 2014 Accepted 28 March 2014 Keywords: Cynomolgus macaque Baylisascaris spp. Histopathology
a b s t r a c t An incidental, asymptomatic, focal inflammatory lesion was detected in brain cerebrum of an approximately 6-year-old, female cynomolgus macaque from a chronic toxicology study. No gross lesions were noted at necropsy. Microscopically, the lesion contained a cross-section of larvae approximately 70–80 m in diameter, a centrally located intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. Mixed inflammatory cells of eosinophils, macrophages, and lymphocytes admixed with abundant connective tissue stroma and necrosis surrounded the larvae. Histochemical stains for trichrome revealed significant amount of fibrous connective tissue. The morphology of the larvae was compatible with Baylisascaris spp. Based on the microscopic and histochemical examination, a diagnosis of neural Baylisascaris spp. larva migrans was made. © 2014 Elsevier GmbH. All rights reserved.
1. Introduction Cynomolgus monkeys are used in preclinical testing of novel small molecule pharmaceutical agents in toxicology studies. In addition, cynomolgus monkeys are used in neuroscience and toxicology studies of novel antibody therapies because of their similarity with humans in biochemical responses, similar pharmacological distribution and behavior of the target proteins, comparable absorption, metabolic, pharmacokinetic, and distribution profiles for some chemicals, and the structural and functional brain similarity with humans (Fitzsimmons et al., 2007; Schein et al., 1970; Sibal and Samson, 2001). Baylisascariasis is caused by common intestinal ascarid nematodes Baylisascaris spp. which include Baylisascaris procyonis of raccoons and Baylisascaris columnaris of skunks (final hosts) (Hernandez et al., 2013; Kazacos, 2001). The larvae migrate throughout the body of the intermediate/paratenic hosts including many species of mammals (including humans), rodents, domestic and wild animals, and birds and this larvae migrations results in visceral larva migrans (VLM), and subsequent invasion of the central nervous system (CNS) tissue (neural larva migrans), or the eye (ocular larva migrans). Invasion of the
∗ Corresponding author. Tel.: +1 860 441 3614; fax: +1 860 686 0557. E-mail addresses: [email protected], ahmed.shoieb@pfizer.com (A. Shoieb), Zaher.Radi@Pfizer.com (Z.A. Radi). http://dx.doi.org/10.1016/j.etp.2014.03.004 0940-2993/© 2014 Elsevier GmbH. All rights reserved.
brain seems to be particularly common in rodents, rabbits, and birds (Bauer, 2013; Furuoka et al., 2003; Kazacos, 1991; Richardson et al., 1980; Van Andel et al., 1995). In nonhuman primates, few reported cases of CNS and/or visceral Baylisascariasis have been described in a spider monkey (Garlick et al., 1996), orangutan (Pongo pygmaeus) (Hanley et al., 2006), Japanese macaques (Macaca fuscata fuscata) (Sato et al., 2005), lemurs (Varecia variegata variegata) (Campbell et al., 1997), white-handed gibbon (Ball et al., 1998), and rhesus macaques (Macaca mulatta) (Gozalo et al., 2008). However, no reports of Baylisascariasis have been described in brain cerebrum in cynomolgus monkeys used in toxicology studies. This report documents the first, to the best of our knowledge, spontaneous case of brain larval migration of Baylisascaris spp. in a cynomolgus monkey (Macaca fascicularis).
2. Materials and methods The animal in this case was a 6 years-old, 4 kg, female cynomolgus monkey used in a 1-month toxicology study. This toxicology study was conducted in accordance with the current guidelines for animal welfare (National Research Council for the Care and Use of Laboratory Animals, 2011; Animal Welfare Act (AWA), 1966). The procedures used in this study have been reviewed and approved by the Institutional Animal Care and Use Committee (IACUC). Animals used in this study were specific pathogen free for B virus (Macacine herpesvirus 1), Simian T-lymphotropic virus 1
264
A. Shoieb, Z.A. Radi / Experimental and Toxicologic Pathology 66 (2014) 263–265
Fig. 1. Cerebrum: a focal inflammatory lesion composed of a mixed of inflammatory cells and fibrosis. 150×, H&E stain.
(STLV-1), Simian Immunodeficiency Virus (SIV) and Simian Retrovirus Type D (SRV) 1–5 and periodically tested and found to be negative for tuberculosis. Animal procedures were IACUCapproved and conformed to the Guide for the Care and Use of Laboratory Animals. Purpose bred cynomolgus macaques (Macaca fascicularis) were housed at an AAALAC-accredited Pfizer facility. The animal in this case survived to its scheduled euthanasia and there were there were no clinical signs, changes in organ weights, or necropsy findings. No significant abnormalities were seen in any blood samples from this animal as hematology, serum chemistry, and liver function tests were within normal limits. Complete necropsy and tissue collection and evaluation were performed on this animal, and representative samples of all organs including the brain were fixed in 10% neutral buffered formalin. Paraffin embedded tissue blocks were sectioned to 4–5 um and stained with hematoxylin and eosin (H&E). In addition, phosphotungstic acid hematoxylin (PTAH) and Masson’s Trichrome Stains were used to facilitate distinguishing cells from the surrounding connective tissue and fibrin deposits in the lesion. 3. Results By light microscopy, a small focal inflammatory lesion was noted in the cerebrum of the brain and was characterized a mixed leukocytic cell infiltrate including mononuclear cells (mainly macrophages, and a few lymphocytes) and eosinophils intermingled with irregular areas of fibrosis) (Fig. 1). No causative agent was noted in the submitted brain sections. Because this monkey was from a test article-dosed group, upon preliminary light microscopic assessment of the lesion a differential diagnosis of thrombus was suspected, and special PTAH and trichrome histochemical stains were performed to better characterize the lesion. The PTAH stain was negative and the trichrome stain. Furthermore, deeper H&E sections revealed the presence of a necrotic focus and significant amount of fibrosis in addition to the mixed inflammatory infiltrates (Figs. 2 and 3). In addition, a parasitic larva was noted with morphologic features compatible with Baylisascaris spp. (Fig. 2). The morphologic features of the parasite included an average cross sectional diameter of 70–80 m, single prominent lateral ala on each side, and conically shaped lateral columns which were smaller than the centrally placed intestines. These morphologic features were diagnostic for Baylisascaris spp. larvae (Figs. 2 and 3). Only one larva was seen in multiple sections of brain tissue.
Fig. 2. Cerebrum: deep section and high power magnification of the inflammatory lesion in Fig. 1, containing a cross sectional single prominent lateral ala on each side, and the conical shape of the lateral columns which were smaller than the central intestines of consistent with Baylisascaris spp. within a core of necrosis and surrounded by fibrosis and inflammation. 200×, H&E stain.
4. Discussion The natural host of Baylisascaris spp. is the raccoon found in northern temperate regions of North America, adult parasites live in the small intestine (Hernandez et al., 2013; Kazacos, 2001). Skunks carry Baylisascaris columnaris, a similar species to B. Procyonis; however, it is not as prevalent as B. Procyonis (Kazacos, 2001). Baylisascaris spp. can cause a serious public health concern (zoonotic disease) since infection with Baylisascaris spp. via oral ingestion with infective Baylisascaris eggs produced serious CNS disease in man (Sorvillo et al., 2002; Wise et al., 2005) and in a variety of bird and mammals resulted from lesions including inflammation, and degenerative alterations associated with the larvae migration in the brain and spinal cord (Bauer, 2013; Furuoka et al., 2003; Kazacos et al., 1981; Kazacos, 1991; Richardson et al., 1980; Van Andel et al., 1995; Wolff, 1993). Despite lack of neurologic signs in the history of this cynomolgus macaque monkey in this report and no gross lesions were detected during the necropsy; the morphology of larva in its brain sections were diagnostic for Baylisascaris spp. infection of the midbrain. Although Baylisascariasis has been reported in the CNS of in some strains of nonhuman primates (Ball et al., 1998; Campbell et al., 1997; Gozalo et al., 2008; Garlick et al., 1996; Hanley et al., 2006; Sato et al., 2005); to the best of our knowledge, not in cynomolgus macaque.
Fig. 3. Cerebrum: Baylisascaris spp. larvae within extensive area of necrosis and surrounded by significant fibrosis and inflammation. 200×, Trichrome stain.
A. Shoieb, Z.A. Radi / Experimental and Toxicologic Pathology 66 (2014) 263–265
Because of the diversity of clinical neurologic changes that may result from clinical neural larva migrans, such CNS disturbances presenting in nonhuman primates in toxicity studies can sometimes be difficult to differentiate from possible effects of test articles when there is only a small number of animals in each individual study. Furthermore, published data on this topic in nonhuman primates are scarce. It is hoped, therefore, that this report will help by providing example of the sort of neural larva migrans background findings in cynomolgus macaques that are not test article-related, along with a framework for defining the diagnosis of low-level or covert Baylisascaris infection with no clinical CNS disease. This incidental lesion should not be mistaken with other non-neoplastic, e.g., thrombotic or test article-related lesions in nonhuman primates used for biopharmaceutical safety studies as it may result in falsely attributing a safety signal on a drug candidate particularly if it is coupled with clinical signs. References Ball RL, Dryden M, Wilson S, Veatch J. Cerebrospinal nematodiasis in a whitehanded gibbon (Hylobates lar) due to Baylisascaris sp. J Zoo Wildl Med 1998;29: 221–4. Bauer C. Baylisascariosis – infections of animals and humans with ‘unusual roundworms’. Vet Parasitol 2013;193:404–12. Campbell GA, Hoover JP, Russell WC, Breazile JE. Naturally occurring cerebral nematodiasis due to Baylisascaris larval migration in two black-and-white ruffed lemurs (Varecia variegata variegata) and suspected cases in three emus (Dromaius novaehollandiae). J Zoo Wildl Med 1997;28:204–7. Fitzsimmons NA, Drake W, Hanson TL, Lebedev MA, Nicolelis MA. Primate reaching cued by multichannel spatiotemporal cortical microstimulation. J Neurosci 2007;27:5593–602. Furuoka H, Sato H, Kubo M, Owaki S, Kobayashi Y, Matsui T, et al. Neuropathological observation of rabbits (Oryctolagus cuniculus) affected with raccoon roundworm (Baylisascaris procyonis) larva migrans in Japan. J Vet Med Sci 2003;65:695–9.
265
Garlick DS, Marcus LC, Pokras M, Schelling SH. Baylisascaris larva migrans in a spider monkey (Ateles sp.). J Med Primatol 1996;25:133–6. Gozalo AS, Cheng LI, Elkins WR, Kazacos KR, Maximova OA, Montali RJ, et al. Visceral and neural larva migrans in rhesus macaques. J Am Assoc Lab Anim Sci 2008;47(4):64–7, ISSN: 1559-6109, E-ISSN: 1559-6109. Hanley CS, Simmons HA, Wallace RS, Clyde VL. Visceral and presumptive neural Baylisascariasis in an orangutan (Pongo pygmaeus). J Zoo Wildl Med 2006;37:553–7. Hernandez SM, Galbreath B, Riddle DF, Moore AP, Palamar MB, Levy MG, et al. Baylisascaris procyonis in raccoons (Procyon lotor) from North Carolina and current status of the parasite in the USA. Parasitol Res 2013;112:693–8. Kazacos KR. Visceral and ocular larva migrans. Semin Vet Med Surg (Small Anim) 1991;6:227–35. Kazacos KR. Baylisascaris procyonis and related species. In: Samuel WM, Pybus MJ, Kocan AA, editors. Parasitic diseases of wild mammals. 2nd ed. Ames, IA: Iowa State Univ. Press; 2001. p. 304–41. Kazacos KR, Wirtz WL, Burger PP, Christmas CS. Raccoon ascarid larvae as a cause of fatal central nervous system disease in subhuman primates. J Am Vet Med Assoc 1981;179:1089–94. Richardson JA, Kazacos KR, Thacker HL, Dhillon AS, Winterfield RW. Verminous encephalitis in commercial chickens. Avian Dis 1980;24:498–503. Sato H, Une Y, Kawakami S, Saito E, Kamiya H, Akao N, et al. Fatal Baylisascaris larva migrans in a colony of Japanese macaques kept by a safari-style zoo in Japan. J Parasitol 2005;91:716–9. Schein PS, Davis RD, Carter S, Newman J, Schein DR, Rall DP. The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man. Clin Pharmacol Ther 1970;11:3–40. Sibal LR, Samson KJ. Nonhuman primates: a critical role in current disease research. ILAR J 2001;42:74–84. Sorvillo F, Ash LR, Berlin OG, Morse SA. Baylisascaris procyonis: an emerging helminthic zoonosis. Emerg Infect Dis 2002;8:355–9. Van Andel RA, Franklin CL, Besch-Williford C, Riley LK, Hook RR Jr, Kazacos KR. Cerebrospinal larva migrans due to Baylisascaris procyonis in a guinea pig colony. Lab Anim Sci 1995;45:27–30. Wise ME, Sorvillo FJ, Shafir SC, Ash LR, Berlin OG. Severe and fatal central nervous system disease in humans caused by Baylisascaris procyonis, the common roundworm of raccoons: a review of current literature. Microbes Infect 2005;7:317–23. Wolff PL. Parasites of new world primates. In: Fowler ME, editor. Zoo and wild animal medicine, current therapy 3. Philadelphia, PA: W.B. Saunders Co.; 1993. p. 378–89.
Contents lists available at ScienceDirect
Experimental and Toxicologic Pathology journal homepage: www.elsevier.de/etp
Short Communication
Cerebral Baylisascaris larva migrans in a cynomolgus macaque (Macaca fascicularis) Ahmed Shoieb a,∗ , Zaher A. Radi b a b
Pfizer Drug Safety Research and Development, 455 Eastern Point Road, MS 8274-1221, Building 274, Office 1703F, Groton, CT 06340, USA Pfizer Worldwide Research and Development, Drug Safety R&D, Andover, MA, USA
a r t i c l e
i n f o
Article history: Received 1 March 2014 Accepted 28 March 2014 Keywords: Cynomolgus macaque Baylisascaris spp. Histopathology
a b s t r a c t An incidental, asymptomatic, focal inflammatory lesion was detected in brain cerebrum of an approximately 6-year-old, female cynomolgus macaque from a chronic toxicology study. No gross lesions were noted at necropsy. Microscopically, the lesion contained a cross-section of larvae approximately 70–80 m in diameter, a centrally located intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. Mixed inflammatory cells of eosinophils, macrophages, and lymphocytes admixed with abundant connective tissue stroma and necrosis surrounded the larvae. Histochemical stains for trichrome revealed significant amount of fibrous connective tissue. The morphology of the larvae was compatible with Baylisascaris spp. Based on the microscopic and histochemical examination, a diagnosis of neural Baylisascaris spp. larva migrans was made. © 2014 Elsevier GmbH. All rights reserved.
1. Introduction Cynomolgus monkeys are used in preclinical testing of novel small molecule pharmaceutical agents in toxicology studies. In addition, cynomolgus monkeys are used in neuroscience and toxicology studies of novel antibody therapies because of their similarity with humans in biochemical responses, similar pharmacological distribution and behavior of the target proteins, comparable absorption, metabolic, pharmacokinetic, and distribution profiles for some chemicals, and the structural and functional brain similarity with humans (Fitzsimmons et al., 2007; Schein et al., 1970; Sibal and Samson, 2001). Baylisascariasis is caused by common intestinal ascarid nematodes Baylisascaris spp. which include Baylisascaris procyonis of raccoons and Baylisascaris columnaris of skunks (final hosts) (Hernandez et al., 2013; Kazacos, 2001). The larvae migrate throughout the body of the intermediate/paratenic hosts including many species of mammals (including humans), rodents, domestic and wild animals, and birds and this larvae migrations results in visceral larva migrans (VLM), and subsequent invasion of the central nervous system (CNS) tissue (neural larva migrans), or the eye (ocular larva migrans). Invasion of the
∗ Corresponding author. Tel.: +1 860 441 3614; fax: +1 860 686 0557. E-mail addresses: [email protected], ahmed.shoieb@pfizer.com (A. Shoieb), Zaher.Radi@Pfizer.com (Z.A. Radi). http://dx.doi.org/10.1016/j.etp.2014.03.004 0940-2993/© 2014 Elsevier GmbH. All rights reserved.
brain seems to be particularly common in rodents, rabbits, and birds (Bauer, 2013; Furuoka et al., 2003; Kazacos, 1991; Richardson et al., 1980; Van Andel et al., 1995). In nonhuman primates, few reported cases of CNS and/or visceral Baylisascariasis have been described in a spider monkey (Garlick et al., 1996), orangutan (Pongo pygmaeus) (Hanley et al., 2006), Japanese macaques (Macaca fuscata fuscata) (Sato et al., 2005), lemurs (Varecia variegata variegata) (Campbell et al., 1997), white-handed gibbon (Ball et al., 1998), and rhesus macaques (Macaca mulatta) (Gozalo et al., 2008). However, no reports of Baylisascariasis have been described in brain cerebrum in cynomolgus monkeys used in toxicology studies. This report documents the first, to the best of our knowledge, spontaneous case of brain larval migration of Baylisascaris spp. in a cynomolgus monkey (Macaca fascicularis).
2. Materials and methods The animal in this case was a 6 years-old, 4 kg, female cynomolgus monkey used in a 1-month toxicology study. This toxicology study was conducted in accordance with the current guidelines for animal welfare (National Research Council for the Care and Use of Laboratory Animals, 2011; Animal Welfare Act (AWA), 1966). The procedures used in this study have been reviewed and approved by the Institutional Animal Care and Use Committee (IACUC). Animals used in this study were specific pathogen free for B virus (Macacine herpesvirus 1), Simian T-lymphotropic virus 1
264
A. Shoieb, Z.A. Radi / Experimental and Toxicologic Pathology 66 (2014) 263–265
Fig. 1. Cerebrum: a focal inflammatory lesion composed of a mixed of inflammatory cells and fibrosis. 150×, H&E stain.
(STLV-1), Simian Immunodeficiency Virus (SIV) and Simian Retrovirus Type D (SRV) 1–5 and periodically tested and found to be negative for tuberculosis. Animal procedures were IACUCapproved and conformed to the Guide for the Care and Use of Laboratory Animals. Purpose bred cynomolgus macaques (Macaca fascicularis) were housed at an AAALAC-accredited Pfizer facility. The animal in this case survived to its scheduled euthanasia and there were there were no clinical signs, changes in organ weights, or necropsy findings. No significant abnormalities were seen in any blood samples from this animal as hematology, serum chemistry, and liver function tests were within normal limits. Complete necropsy and tissue collection and evaluation were performed on this animal, and representative samples of all organs including the brain were fixed in 10% neutral buffered formalin. Paraffin embedded tissue blocks were sectioned to 4–5 um and stained with hematoxylin and eosin (H&E). In addition, phosphotungstic acid hematoxylin (PTAH) and Masson’s Trichrome Stains were used to facilitate distinguishing cells from the surrounding connective tissue and fibrin deposits in the lesion. 3. Results By light microscopy, a small focal inflammatory lesion was noted in the cerebrum of the brain and was characterized a mixed leukocytic cell infiltrate including mononuclear cells (mainly macrophages, and a few lymphocytes) and eosinophils intermingled with irregular areas of fibrosis) (Fig. 1). No causative agent was noted in the submitted brain sections. Because this monkey was from a test article-dosed group, upon preliminary light microscopic assessment of the lesion a differential diagnosis of thrombus was suspected, and special PTAH and trichrome histochemical stains were performed to better characterize the lesion. The PTAH stain was negative and the trichrome stain. Furthermore, deeper H&E sections revealed the presence of a necrotic focus and significant amount of fibrosis in addition to the mixed inflammatory infiltrates (Figs. 2 and 3). In addition, a parasitic larva was noted with morphologic features compatible with Baylisascaris spp. (Fig. 2). The morphologic features of the parasite included an average cross sectional diameter of 70–80 m, single prominent lateral ala on each side, and conically shaped lateral columns which were smaller than the centrally placed intestines. These morphologic features were diagnostic for Baylisascaris spp. larvae (Figs. 2 and 3). Only one larva was seen in multiple sections of brain tissue.
Fig. 2. Cerebrum: deep section and high power magnification of the inflammatory lesion in Fig. 1, containing a cross sectional single prominent lateral ala on each side, and the conical shape of the lateral columns which were smaller than the central intestines of consistent with Baylisascaris spp. within a core of necrosis and surrounded by fibrosis and inflammation. 200×, H&E stain.
4. Discussion The natural host of Baylisascaris spp. is the raccoon found in northern temperate regions of North America, adult parasites live in the small intestine (Hernandez et al., 2013; Kazacos, 2001). Skunks carry Baylisascaris columnaris, a similar species to B. Procyonis; however, it is not as prevalent as B. Procyonis (Kazacos, 2001). Baylisascaris spp. can cause a serious public health concern (zoonotic disease) since infection with Baylisascaris spp. via oral ingestion with infective Baylisascaris eggs produced serious CNS disease in man (Sorvillo et al., 2002; Wise et al., 2005) and in a variety of bird and mammals resulted from lesions including inflammation, and degenerative alterations associated with the larvae migration in the brain and spinal cord (Bauer, 2013; Furuoka et al., 2003; Kazacos et al., 1981; Kazacos, 1991; Richardson et al., 1980; Van Andel et al., 1995; Wolff, 1993). Despite lack of neurologic signs in the history of this cynomolgus macaque monkey in this report and no gross lesions were detected during the necropsy; the morphology of larva in its brain sections were diagnostic for Baylisascaris spp. infection of the midbrain. Although Baylisascariasis has been reported in the CNS of in some strains of nonhuman primates (Ball et al., 1998; Campbell et al., 1997; Gozalo et al., 2008; Garlick et al., 1996; Hanley et al., 2006; Sato et al., 2005); to the best of our knowledge, not in cynomolgus macaque.
Fig. 3. Cerebrum: Baylisascaris spp. larvae within extensive area of necrosis and surrounded by significant fibrosis and inflammation. 200×, Trichrome stain.
A. Shoieb, Z.A. Radi / Experimental and Toxicologic Pathology 66 (2014) 263–265
Because of the diversity of clinical neurologic changes that may result from clinical neural larva migrans, such CNS disturbances presenting in nonhuman primates in toxicity studies can sometimes be difficult to differentiate from possible effects of test articles when there is only a small number of animals in each individual study. Furthermore, published data on this topic in nonhuman primates are scarce. It is hoped, therefore, that this report will help by providing example of the sort of neural larva migrans background findings in cynomolgus macaques that are not test article-related, along with a framework for defining the diagnosis of low-level or covert Baylisascaris infection with no clinical CNS disease. This incidental lesion should not be mistaken with other non-neoplastic, e.g., thrombotic or test article-related lesions in nonhuman primates used for biopharmaceutical safety studies as it may result in falsely attributing a safety signal on a drug candidate particularly if it is coupled with clinical signs. References Ball RL, Dryden M, Wilson S, Veatch J. Cerebrospinal nematodiasis in a whitehanded gibbon (Hylobates lar) due to Baylisascaris sp. J Zoo Wildl Med 1998;29: 221–4. Bauer C. Baylisascariosis – infections of animals and humans with ‘unusual roundworms’. Vet Parasitol 2013;193:404–12. Campbell GA, Hoover JP, Russell WC, Breazile JE. Naturally occurring cerebral nematodiasis due to Baylisascaris larval migration in two black-and-white ruffed lemurs (Varecia variegata variegata) and suspected cases in three emus (Dromaius novaehollandiae). J Zoo Wildl Med 1997;28:204–7. Fitzsimmons NA, Drake W, Hanson TL, Lebedev MA, Nicolelis MA. Primate reaching cued by multichannel spatiotemporal cortical microstimulation. J Neurosci 2007;27:5593–602. Furuoka H, Sato H, Kubo M, Owaki S, Kobayashi Y, Matsui T, et al. Neuropathological observation of rabbits (Oryctolagus cuniculus) affected with raccoon roundworm (Baylisascaris procyonis) larva migrans in Japan. J Vet Med Sci 2003;65:695–9.
265
Garlick DS, Marcus LC, Pokras M, Schelling SH. Baylisascaris larva migrans in a spider monkey (Ateles sp.). J Med Primatol 1996;25:133–6. Gozalo AS, Cheng LI, Elkins WR, Kazacos KR, Maximova OA, Montali RJ, et al. Visceral and neural larva migrans in rhesus macaques. J Am Assoc Lab Anim Sci 2008;47(4):64–7, ISSN: 1559-6109, E-ISSN: 1559-6109. Hanley CS, Simmons HA, Wallace RS, Clyde VL. Visceral and presumptive neural Baylisascariasis in an orangutan (Pongo pygmaeus). J Zoo Wildl Med 2006;37:553–7. Hernandez SM, Galbreath B, Riddle DF, Moore AP, Palamar MB, Levy MG, et al. Baylisascaris procyonis in raccoons (Procyon lotor) from North Carolina and current status of the parasite in the USA. Parasitol Res 2013;112:693–8. Kazacos KR. Visceral and ocular larva migrans. Semin Vet Med Surg (Small Anim) 1991;6:227–35. Kazacos KR. Baylisascaris procyonis and related species. In: Samuel WM, Pybus MJ, Kocan AA, editors. Parasitic diseases of wild mammals. 2nd ed. Ames, IA: Iowa State Univ. Press; 2001. p. 304–41. Kazacos KR, Wirtz WL, Burger PP, Christmas CS. Raccoon ascarid larvae as a cause of fatal central nervous system disease in subhuman primates. J Am Vet Med Assoc 1981;179:1089–94. Richardson JA, Kazacos KR, Thacker HL, Dhillon AS, Winterfield RW. Verminous encephalitis in commercial chickens. Avian Dis 1980;24:498–503. Sato H, Une Y, Kawakami S, Saito E, Kamiya H, Akao N, et al. Fatal Baylisascaris larva migrans in a colony of Japanese macaques kept by a safari-style zoo in Japan. J Parasitol 2005;91:716–9. Schein PS, Davis RD, Carter S, Newman J, Schein DR, Rall DP. The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in man. Clin Pharmacol Ther 1970;11:3–40. Sibal LR, Samson KJ. Nonhuman primates: a critical role in current disease research. ILAR J 2001;42:74–84. Sorvillo F, Ash LR, Berlin OG, Morse SA. Baylisascaris procyonis: an emerging helminthic zoonosis. Emerg Infect Dis 2002;8:355–9. Van Andel RA, Franklin CL, Besch-Williford C, Riley LK, Hook RR Jr, Kazacos KR. Cerebrospinal larva migrans due to Baylisascaris procyonis in a guinea pig colony. Lab Anim Sci 1995;45:27–30. Wise ME, Sorvillo FJ, Shafir SC, Ash LR, Berlin OG. Severe and fatal central nervous system disease in humans caused by Baylisascaris procyonis, the common roundworm of raccoons: a review of current literature. Microbes Infect 2005;7:317–23. Wolff PL. Parasites of new world primates. In: Fowler ME, editor. Zoo and wild animal medicine, current therapy 3. Philadelphia, PA: W.B. Saunders Co.; 1993. p. 378–89.
