Bartonella quintana in cynomolgus monkey (Macaca fascicularis)

We identified a Bartonella quintana strain by polymerase chain reaction amplification, cloning, and sequencing of DNA extracted from lysed erythrocytes and cultured colonies grown from peripheral blood collected from a captive-bred cynomolgus monkey (Macaca fascicularis). This report describes naturally acquired B. quintana infection in a nonhuman primate.     

Treatment with antibiotics reduces plasma equol concentration in cynomolgus monkeys (Macaca fascicularis)

To explore the importance of equol on health outcomes in future studies, it was necessary to develop a method to reduce equol production. Female monkeys (n = 22) fed a soy diet were treated twice daily with vehicle (control; n = 4), doxycycline (2.5 mg/kg; n = 4), metronidazole (125 mg/d; n = 3), kanamycin (1000 mg/d; n = 4), vancomycin (100 mg/d; n = 3) or kanamycin+vancomycin (n = 4). Plasma samples were collected 4 h postfeeding at baseline, after 4 wk of treatment and 8 wk after the end of treatment and analyzed for isoflavonoid concentrations. Fecal swabs were collected at baseline and at the end of antibiotic treatment for analysis of Gram(+) and Gram(-) bacterial growth. Equol concentrations were reduced (P < 0.05) compared with baseline by 80, 93, 98 and 99% after treatment with metronidazole (955 +/- 164 vs. 193 +/- 53 nmol/L), kanamycin (545 +/- 211 vs. 37.1 +/- 17.6 nmol/L), vancomycin (607 +/- 163 vs. 8.9 +/- 8.2 nmol/L) and kanamycin+vancomycin (721 +/- 169 vs. 17.4 +/- 17.3 nmol/L), respectively. Daidzein concentrations were increased (P < 0.05) compared with baseline by treatment with doxycycline (336 +/- 87 vs. 576 +/- 76 nmol/L), kanamycin (168 +/- 67 vs. 374 +/- 15 nmol/L), and kanamycin+vancomycin (166 +/- 35 vs. 384 +/- 78 nmol/L). Similar increases (P < 0.05) in dihydrodaidzein were observed after treatment with kanamycin (31.2 +/- 6.2 vs. 479 +/- 188 nmol/L) and metronidazole (56.0 +/- 27.9 vs. 414 +/- 212 nmol/L). Isoflavonoid concentrations returned to baseline values after antibiotic treatment was terminated. Gram(+) bacterial growth was reduced by all treatments, including Control, compared with baseline. In conclusion, treatment with antibiotics resulted in a marked reduction in plasma equol concentrations and altered plasma isoflavonoid patterns in cynomolgus monkeys.     

Dietary soy protein containing isoflavonoids does not adversely affect the reproductive tract of male cynomolgus macaques (Macaca fascicularis)

Short-term dietary studies of soy-protein-derived isoflavonoids, using rodent and nonhuman primate models, have documented variable effects on the reproductive tract. Long-term effects of dietary soy and/or isoflavonoids on the reproductive tract of nonhuman primates have not been determined. The objective of this study was to assess the effects of long-term consumption of dietary soy isoflavonoids on histomorphology of the mammary glands and prostate gland, testis, and sperm counts in adult male cynomolgus macaques. Ninety-one adult male cynomolgus macaques (Macaca fascicularis) were fed diets for 3 y differing only in protein source: 1) a soy-free, casein-lactalbumin-based diet or 2) a low-soy isoflavonoid diet ( approximately 6 mg . kg(-1) . d(-1)) or 3) a high-soy isoflavonoid diet ( approximately 12 mg . kg(-1) . d(-1)). Serum isoflavonoids were measured by liquid chromatographic-photodiode array electrospray MS. Mammary gland, prostate gland, and testes were obtained at postmortem and evaluated histopathologically and histomorphometrically. Epididymal and testicular sperm counts were performed. Serum isoflavonoid concentrations at 4 h postfeeding differed among all groups (P < 0.001) and were (means +/- SEM) 67 +/- 23 (soy-free diet), 799 +/- 44 (low-soy isoflavonoid diet), and 1458 +/- 80 nmol . L(-1) (high-soy isoflavonoid diet). Diet did not alter serum estradiol and testosterone concentrations or epididymal and testicular sperm counts. Organ weights and histologic indices did not differ among treatment groups. Mammary gland histopathologic and histomorphometric analysis revealed no abnormalities and no indication of gynecomastia. We found no evidence of an adverse effect of soy isoflavonoids at physiologically relevant doses within the reproductive organs of adult male macaques.     

Alteration in bone marrow RNA of vitamin E-deficient monkey, Macaca fascicularis.

In anemic crab-eating monkeys, Macaca fascicularis, there is an alteration in the bone marrow RNA species resulting from early vitamin E deficiency, when compared with those from normal simian bone marrow or from phenylhydrazine-induced anemic bone marrow of rabbit. Anemia of vitamin E deficiency is specifically associated with a reduction in the ribosomal RNA content.     

Prevention of hypercholesterolemia in monkeys (Macaca fascicularis) by digitonin.

Digitonin mixed in the diet was well tolerated by rats and cynomolgus monkeys (Macaca fascicularis), and prevented the expected rise in plasma cholesterol in monkeys fed a diet containing butter and cholesterol. Both digitonin and mildly hydrolyzed digitonin precipitated cholesterol dispersed in micellar suspensions and decreased intestinal absorption of cholesterol in rats, but only digitonin bound cholesterol in vitro. The hypocholesterolemic effect of digitonin may be secondary to decreased intestinal absorption of cholesterol associated with a disturbance in the micellar suspension of cholesterol in the intestinal content. Modification of other mechanisms that may be involved in membrane transport of cholesterol through the intestinal epithelium is not ruled out by the present findings.     

Effect of oxytocin on plasma testosterone levels in the male macaques (Macaca fascicularis)

The effect of oxytocin on testicular function was examined in the adult male long-tailed macaques (Macaca fascicularis). The monkeys were either infused with increasing concentrations of synthetic oxytocin (16-128 m.i.u./min for 3 h) or injected daily for a week with the same hormone (20 i.u., i.v.) and the plasma testosterone levels measured. The results of the present study show that acute infusion or chronic injection of oxytocin does not significantly affect the plasma testosterone levels, suggesting that systemic control of testicular endocrine function by oxytocin may be unimportant.     

Tickborne encephalitis in naturally exposed monkey (Macaca sylvanus)

We describe tickborne encephalitis (TBE) in a monkey (Macaca sylvanus) after natural exposure in an area at risk for TBE. TBE virus was present in the brain and could be identified as closely related to the European subtype, strain Neudoerfl.     

The effect of the anti-progestin RU 486 on early pregnancy in the long-tailed macaque (Macaca fascicularis)

The efficacy of various doses of RU 486 in terminating pregnancy before and after the luteal-placental shift (LPS) in the long-tailed macaque (Macaca fascicularis) was assessed through sonographic examination and measurements of steroid hormones and their metabolites. Intramuscular injection of 1.0, 2.5, 12.5, or 25.0 mg/kg was administered either from gestational day (GD) 15-18 (Group 1; N = 11) or GD 23-26 (Group 2; N = 9). The timing of treatment was determined by the detection of the preovulatory estrogen peak via daily urinary estrone conjugate (E1C) measurements. In Group 1, a 90.9% pregnancy loss was observed (10/11); seven animals aborted during GD 15-20, two animals indicated early embryonic death with retained gestational sacs, one animal aborted on GD 56, and one pregnancy was maintained. In Group 2, an 88.9% pregnancy loss was observed (8/9); eight animals aborted between GD 26-29, and one pregnancy was unaffected. Hormone profiles appeared to fall secondarily to the loss of trophoblast function. These results indicate: (a) RU 486 was more effective after the LPS; and (b) the primary effect of RU 486 appeared to be at the level of the products of conception.     

A critical analysis of the cynomolgus macaque,Macaca fascicularis,as a model to test HIV-1/SIV vaccine efficacy

The use of a number of non-rhesus macaque species, but especially cynomolgus macaques as a model for HIV-1 vaccine development has increased in recent years. Cynomolgus macaques have been used in the United Kingdom, Europe, Canada and Australia as a model for HIV vaccine development for many years. Unlike rhesus macaques, cynomolgus macaques infected with SIV show a pattern of disease pathogenesis that more closely resembles that of human HIV-1 infection, exhibiting lower peak and set-point viral loads and slower progression to disease with more typical AIDS defining illnesses. Several advances have been made recently in the use of the cynomolgus macaque SIV challenge model that allow the demonstration of vaccine efficacy using attenuated viruses and vectors that are both viral and non-viral in origin. This review aims to probe the details of various vaccination trials carried out in cynomolgus macaques in the context of our modern understanding of the highly diverse immunogenetics of this species with a view to understanding the species-specific immune correlates of protection and the efficacy of vectors that have been used to design vaccines.     

Plasma carotenoids of monkeys (Macaca fascicularis and Saimiri sciureus) fed a nonpurified diet

The major carotenoid pigments in the plasma and in a common, nonpurified diet of two species of monkeys (Macaca fascicularis and Saimiri sciureus) were measured. The xanthophylls, lutein, zeaxanthin, alpha-cryptoxanthin, and beta-cryptoxanthin, were the principal carotenoids in both the diet and the plasma. Lutein and zeaxanthin were abundant in the all-trans, the 9-cis, and the 13-cis geometrical isomers in the diet, but the 9-cis form was rarely measurable in plasma. However, the 13-cis isomers of lutein and zeaxanthin were found in higher proportions in plasma than in the diet. For both the monohydroxy-xanthophylls, alpha-cryptoxanthin and beta-cryptoxanthin, and the dihydroxy-xanthophylls, lutein and zeaxanthin, the beta, beta structural isomer (beta-cryptoxanthin or zeaxanthin) is less abundant than the beta, epsilon isomer in plasma than in the diet. These results indicate substantial specificity in the absorption or retention of closely related carotenoid isomers in primates. The proportions of different geometrical isomers of lutein and zeaxanthin in the plasma of both species of monkeys were nearly identical and were similar to human values. The hydrocarbon carotenoids, alpha-carotene, beta-carotene and lycopene were usually undetectable in monkey plasma. The monkeys appear to be like humans in their utilization of lutein and zeaxanthin but distinctly different in some other aspects of carotenoid utilization.     

Contraceptive potentiality of STS-557--a feasibility study in male bonnet monkey (Macaca radiata)

STS-557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9(10)-diene-3-one) was administered (i.m.) to two groups (4 in each group) of adult male bonnet monkeys at a daily dose of 10 mg/monkey for 12 weeks (first group) and 5 mg/monkey for 14 weeks (second group). Treatment with the 10 mg dose resulted in a significant decline in the count, motility, acrosin and hyaluronidase activities and the fertilizing ability (zona-free hamster egg penetration assay) of spermatozoa by the 6th week of initiation of treatment. The circulating level of STS-557 was low after one week and increased from the 2nd week of treatment when the serum level of testosterone was significantly reduced. Complete recovery was observed by the 11th week after withdrawal of treatment. The treatment with the 5 mg dose had minor and inconsistent effect on the motility, hyaluronidase and acrosin activity, and the fertilizing ability of spermatozoa in addition to the blood level of testosterone. STS-557 may have the potentiality to be used as a chemical contraceptive in the male but compensation for the reduced level of blood testosterone may be necessary.     

Effects of lead exposure on peripheral nerve in the cynomolgus monkey

The relationship between blood lead concentration and nerve conduction velocity has been examined, using the cynomolgus monkey as a model for human lead poisoning, with lead dose and blood lead concentration maintained under controlled conditions, to determine whether nerve conduction velocity could be used as an objective measure of the effects of lead on the nervous system at subclinical concentrations. Five cynomolgus monkeys were maintained at a blood lead concentration of 90-100 micrograms Pb/100 ml for nine months by daily oral dosing with lead acetate (12-15 mg Pb/kg body weight). Motor nerve conduction velocity in the ulnar nerve was measured, together with blood lead concentrations. Blood lead concentrations were proportional to lead intake, reaching a stable level within one to two weeks. Lead did not accumulate in the blood, and blood lead concentrations were found to decrease to a maintained plateau from initial high concentrations during the first seven days of dosing. The animals showed no clinical or behavioural evidence of lead poisoning at any time during the study, although there was a progressive decrease in blood packed cell volume, haemoglobin concentration, and erythrocyte concentration. The maximal motor nerve conduction velocity of the ulnar nerve remained constant throughout the study, although changes were observed in the conduction velocity of slowly conducting nerve fibres. At termination, intranuclear inclusions were found in the renal tubular cells of all animals as were focal areas of myelin degeneration in the ulnar and sciatic nerves.     

Molecular detection and prevalence of Giardia duodenalis and Cryptosporidium spp. among long-tailed macaques (Macaca fascicularis) in Thailand

Giardia duodenalis and Cryptosporidium spp. are divergent protozoal intestinal parasites that infect human beings and other animals, including non-human primates. Although long-tailed macaques (Macaca fascicularis) reside in human communities in Thailand, the prevalence of Giardia spp. and Cryptosporidium spp. in these primates has not been previously investigated. The objective of this study was to evaluate long-tailed macaques living near human communities as possible hosts of these intestinal parasites. In 2014, 200 fecal samples were randomly collected from long-tailed macaques living in different areas of Lopburi province, Thailand, and tested with a panel of PCR assays for Giardia spp. and Cryptosporidium spp. G. duodenalis assemblage B was most frequently detected (6%), while assemblage A and an inconclusive assemblage were detected in single samples, for a total G. duodenalis infection rate of 7%. Two samples (1%) tested positive for Cryptosporidium spp., which were both classified as monkey genotypes. No significant associations were found between G. duodenalis infection and sex or location of macaques. This study indicates that long-tailed macaques can carry G. duodenalis and, to a lesser extent, Cryptosporidium spp. monkey genotype. These results warrant education of residents and tourists to limit contact with long-tailed macaques and to take hygienic precautions to mitigate risk of zoonotic and anthroponotic transmission of these parasites between people and macaques.     

Termination of pregnancy in macaques (Macaca radiata) using monkey antiserum to ovine luteinizing hormone.

The ability of a monkey antiserum to ovine LH to interrupt gestation in monkeys has been established. The antiserum has been shown to neutralize monkey pituitary LH by a number of criteria. The significant increase in serum progesterone level on day 23 of the cycle shown by mated monkeys has been used as an index of pregnancy. Injection of LH antiserum during the first week of missed menses (day 29–31 of cycle or day 18–20 of gestation) causes significant reduction in serum levels of progesterone followed by onset of bleeding which is interpreted as the termination of gestation. The same dose of non-immune serum given to monkeys during the same period does not have any deleterious effect on the progress of pregnancy. The antiserum-treated animals after the termination of gestation, resume cyclicity. Injection of antiserum after day 25 of gestation does not bring about termination of pregnancy. It is suggested that by using antisera raised in humans to ovine LH, this method may be developed as a fertility control measure in humans.     

Effects of lead exposure on peripheral nerve in the cynomolgus monkey.

The relationship between blood lead concentration and nerve conduction velocity has been examined, using the cynomolgus monkey as a model for human lead poisoning, with lead dose and blood lead concentration maintained under controlled conditions, to determine whether nerve conduction velocity could be used as an objective measure of the effects of lead on the nervous system at subclinical concentrations. Five cynomolgus monkeys were maintained at a blood lead concentration of 90-100 micrograms Pb/100 ml for nine months by daily oral dosing with lead acetate (12-15 mg Pb/kg body weight). Motor nerve conduction velocity in the ulnar nerve was measured, together with blood lead concentrations. Blood lead concentrations were proportional to lead intake, reaching a stable level within one to two weeks. Lead did not accumulate in the blood, and blood lead concentrations were found to decrease to a maintained plateau from initial high concentrations during the first seven days of dosing. The animals showed no clinical or behavioural evidence of lead poisoning at any time during the study, although there was a progressive decrease in blood packed cell volume, haemoglobin concentration, and erythrocyte concentration. The maximal motor nerve conduction velocity of the ulnar nerve remained constant throughout the study, although changes were observed in the conduction velocity of slowly conducting nerve fibres. At termination, intranuclear inclusions were found in the renal tubular cells of all animals as were focal areas of myelin degeneration in the ulnar and sciatic nerves.     

Indel-informed Bayesian analysis suggests cryptic population structure between Plasmodium knowlesi of humans and long-tailed macaques (Macaca fascicularis) in Malaysian Borneo

Plasmodium knowlesi is an important causative agent of malaria in humans of Southeast Asia. Macaques are natural hosts for this parasite, but little is conclusively known about its patterns of transmission within and between these hosts. Here, we apply a comprehensive phylogenetic approach to test for patterns of cryptic population genetic structure between P. knowlesi isolated from humans and long-tailed macaques from the state of Sarawak in Malaysian Borneo. Our approach differs from previous investigations through our exhaustive use of archival 18S Small Subunit rRNA (18S) gene sequences from Plasmodium and Hepatocystis species, our inclusion of insertion and deletion information during phylogenetic inference, and our application of Bayesian phylogenetic inference to this problem. We report distinct clades of P. knowlesi that predominantly contained sequences from either human or macaque hosts for paralogous A-type and S-type 18S gene loci. We report significant partitioning of sequence distances between host species across both types of loci, and confirmed that sequences of the same locus type showed significantly biased assortment into different clades depending on their host species. Our results support the zoonotic potential of Plasmodium knowlesi, but also suggest that humans may be preferentially infected with certain strains of this parasite. Broadly, such patterns could arise through preferential zoonotic transmission of some parasite lineages or a disposition of parasites to transmit within, rather than between, human and macaque hosts. Available data are insufficient to address these hypotheses. Our results suggest that the epidemiology of P. knowlesi may be more complicated than previously assumed, and highlight the need for renewed and more vigorous explorations of transmission patterns in the fifth human malarial parasite.     

Polychlorinated biphenyl toxicity in the pregnant cynomolgus monkey: A pilot study

Three pregnant cynomolgus monkeys (Macaca fascicularis) were dosed with 100 or 400 g/kg/day of Aroclor^® 1254 from approximately 60 days of gestation. One additional pregnant monkey was given dose vehicle only. The two monkeys dosed with 100 g/kg/day delivered stillborn infants and the 400 g/kg/day dosed monkey delivered a term infant that had impaired immunologic function compared with the control infant, and died at 139 days post partum. The three dams also had impaired immunologic capacity assessed at approximately 50 days post partum (148 days treatment). With the exception of loss of fingernails in two monkeys, no overt clinical signs of toxicity were observed in the adults. Polychlorinated biphenyl (PCB) concentrations and peak ratios in breast milk and tissues are reported.