Chesson strain Plasmodium vivax in Saimiri sciureus boliviensis monkeys

Nine Saimiri sciureus boliviensis monkeys were inoculated with sporozoites of Plasmodium vivax (Chesson strain) dissected from Anopheles stephensi mosquitoes infected by feeding on blood from infected chimpanzees. The animals were splenectomized 7 days after inoculation. Seven animals developed infections with prepatent periods ranging from 12 to 43 days (mean of 19.6 days). Parasitemias were low during the first 50 days. Maximum parasitemias in 5 animals in which the strain adapted ranged from 10,000 to 46,800 per mm3. Anopheles freeborni mosquitoes were infected by feeding on 4 of the monkeys.     

The Uganda I/CDC strain of Plasmodium malariae in Aotus lemurinus griseimembra monkeys

Two lines of the Uganda I/CDC strain of Plasmodium malariae were studied in splenectomized Aotus lemurinus griseimembra monkeys. A line initially adapted to these monkeys from an infected chimpanzee failed to produce high-level parasite counts or mosquito infection in 13 of this type of monkey during 16 linear passages. Another line, originally adapted from the chimpanzee to Aotus azarae boliviensis, after 7 linear passages in 3 different types of Aotus was then passaged to 14 splenectomized A. lemurinus griseimembra. Geometric mean maximum parasitemia in these monkeys was 18,400/mm3. Mosquito infections were readily obtained during the period just after the parasite count rose above 1,000/mm3. Anopheles freeborni, An. stephensi, An. dirus, and 2 strains of An. gambiae supported the development of the parasite to the presence of sporozoites in the salivary glands. Two attempts to transmit the strain to other splenectomized A. lemurinus griseimembra by sporozoite inoculation were unsuccessful.     

The Peruvian III strain of Plasmodium brasilianum in Saimiri sciureus boliviensis monkeys

A strain of Plasmodium brasilianum was isolated from a naturally infected Saimiri monkey from Peru and subsequently passaged to 21 splenectomized Saimiri sciureus boliviensis monkeys. Nine of 12 attempts to transmit infection by sporozoite inoculation were successful with prepatent periods ranging from 23 to 41 days. Gametocytes were infective to Anopheles freeborni, Anopheles stephensi, Anopheles dirus, Anopheles maculatus, and Anopheles gambiae mosquitoes. The strain demonstrated a high level of resistance to cure with chloroquine.     

Sporozoite-induced infections of the Salvador I strain of Plasmodium vivax in Saimiri sciureus boliviensis monkeys

Twenty Saimiri sciureus boliviensis monkeys from Bolivia were inoculated intravenously with sporozoites of the Salvador I strain of Plasmodium vivax. All animals were splenectomized 7 days after inoculation. Inoculation of 100,000 sporozoites resulted in prepatent periods averaging 16.6 days; all monkeys developed high-level parasitemias with an average maximum of 103,000 per mm3. Inoculation of 10,000 sporozoites resulted in average prepatent periods of 19.4 days; one of the resulting infections produced a transient low-level parasitemia. Of 5 monkeys inoculated with 1,000 sporozoites, 4 had prepatent periods of from 24 to 35 days and 1 failed to demonstrate any parasitemia; 1 monkey supported a low-level transient parasitemia, whereas the other 3 monkeys had high-level parasitemias. It is proposed that by using a minimum inoculum of 10,000 sporozoites, the model system may be useful in the testing of anti-sporozoite vaccines directed against P. vivax.     

Transmission of the OS strain of Plasmodium inui to Saimiri sciureus boliviensis and Aotus azarae boliviensis monkeys by Anopheles dirus mosquitoes

Eight Saimiri and 7 Aotus monkeys were exposed to infection with the OS strain of Plasmodium inui via the bites of from 2 to 7 Anopheles dirus mosquitoes. All Saimiri monkeys developed high-level infections of from 152,000 to 500,000/mm3 after prepatent periods of from 14 to 17 days. Only 1 Aotus monkey developed a patent infection after a period of 28 days. Feeding on these animals failed to result in infection of An. dirus mosquitoes.     

A PCR-based marker to simply identify Saimiri sciureus and S. boliviensis boliviensis

Squirrel monkeys, mainly Saimiri sciureus and S. boliviensis, are common in zoos and widely used in biomedical research. However, an exact species identification based on morphological characteristics is difficult. Hence, several molecular methods were proposed, but all of them are expensive and require extensive laboratory work. In contrast, we describe an Alu integration, which is present in S. boliviensis boliviensis and absent in S. sciureus. Among analyzed S. b. peruviensis specimens various presence/absence patterns of the integration were detected indicating that this study population might have originated from a natural hybrid zone. Based on the size of the Alu element ( approximately 300 bp), the presence/absence pattern of the integration can easily be traced by PCR and followed by agarose gel electrophoresis.     

Studies of the Sal I strain of Plasmodium vivax in the squirrel monkey (Saimiri sciureus)

The Sal I strain of Plasmodium vivax was successfully adapted to three phenotypes of the squirrel monkey, Saimiri sciureus. Through five linear blood passages, parasitemias in excess of 200,000/mm3 blood were attained; Bolivian phenotype Saimiri appear to develop higher peak parasitemias. Sporozoites of the Sal I strain inoculated intravenously produced patent parasitemias in all five squirrel monkeys challenged, with prepatent periods ranging from 21 to 38 days. Anopheles freeborni and An. gambiae were the most susceptible of eight anopheline species fed on infected squirrel monkeys. As a model for in vivo studies of P. vivax the Sal I strain in Saimiri has great potential.     

Infection of Saimiri boliviensis monkeys with Plasmodium coatneyi

Abundant, apparently normally developing, liver-stage parasites of Plasmodium coatneyi were demonstrated following injection of sporozoites dissected from the salivary glands of Anopheles dirus mosquitoes. Erythrocytic development was not demonstrated.     

Plasmodium falciparum: genetic stability of the Uganda Palo Alto strain propagated in the squirrel monkey (Saimiri sciureus).

The Uganda Palo Alto strain of Plasmodium falciparum has been extensively used in several laboratories to infect Saimiri monkeys. In the study reported here three distinct lines derived by parallel serial blood transfers from a single 10-year-old passage of the Palo Alto strain were examined for genetic diversity using the polymerase chain reaction and restriction mapping techniques. A comparison of the PF 11.1, P190, MSA2, S-Ag, and KAHRP genes indicates that these parasite lines are apparently homogeneous and stable. Nevertheless, microheterogeneity was observed with molecular probes which are known to easily detect restriction fragment length polymorphisms (rep 20 and telomeric probes). These data show that the genetic characters of the strain can be considered monomorphic and are conserved after multiple passages in the squirrel monkey.     

Captive breeding of squirrel monkeys,Saimiri sciureus and Saimiri boliviensis: The problem of hybrid groups

The electrophoretic variability of blood proteins coding for up to 32 genetic loci was analyzed in 108 squirrel monkeys (Saimiri sciureus, Saimiri boliviensis, hybrids) from two captive colonies. Twelve polymorphic loci with 31 alleles are reported. The biallelic Ada* locus, G-statistics and Hardy-Weinberg genotype equilibria are useful for recognizing hybrids between S. sciureus and S. boliviensis. Backcrosses in hybrid stocks and gene flow in a natural hybrid belt, however, complicate the taxonomic diagnosis of captive specimens: S. sciureus phenotypes imported from Peru possessed the allele Ada*132, which generally characterizes S. boliviensis (or species hybrids). The complex taxonomy of Saimiri spp. Requires careful planning of captive breeding. We suggest a genetic analysis of the founder individuals before their inclusion in the European studbook population and to breed S. sciureus from Guyana separately from Peruvian imports, because the latter bear a greater risk of being taxonomically heterogeneous. Zoo Biol 17:95–109, 1998. © 1998 Wiley-Liss, Inc.     

Elevation in plasma glucagon levels in response to stress in squirrel monkeys: comparisons of two subspecies (Saimiri sciureus boliviensis and Saimiri sciureus sciureus)

Bolivian (Bo) and Brazilian (Br) squirrel monkeys (SMs) were captured and restrained to determine patterns of glucagon and glucose response. In both subspecies, plasma glucagon and glucose levels rose rapidly in response to restraint procedures; glucagon levels in BrSMs and glucose levels in both subspecies returned to basal values in 15 minutes. The magnitude of the glucagon and glucose responses differed significantly between BoSMs and BrSMs.     

Neonatal activity and state control differences among three squirrel monkey subspecies (Saimiri sciureus sciureus,S. boliviensis boliviensis,and S. boliviensis peruviensis)

Squirrel monkeys are a long-standing biomedical model, with multiple species and subspecies housed in research facilities. Few studies have examined the developmental differences between these subspecies, which may affect research outcomes. The primate neonatal neurobehavioral assessment was completed at 2 weeks of age with 279 dam-reared squirrel monkeys (188 Saimiri boliviensis boliviensis, 45 S. b. peruviensis, and 46 Saimiri. sciureus sciureus). Activity, orientation to stimuli, state control, and motor maturity scores, as well as startle responses and number of vocalizations were compared across subspecies and sex using factorial analysis of covariance (ANCOVAs) controlling for birthweight. There were no differences in orientation or motor maturity scores (p > .05) among the three subspecies or between sexes; however, there were significant subspecies differences in motor activity and state control scores. Of the three subspecies, S. s. sciureus has the lowest state control and activity scores (p < .05). They also had the most exaggerated startle response/aversion to a sudden loud noise, vocalized significantly less, and were less likely to resist restraint during the assessment (p < .05). The three subspecies of squirrel monkeys did not differ in motor development and attention to external stimuli but were significantly different in state control and activity levels. Overall S. s. sciureus were less active, agitated, irritable, and easier to console compared to S. b. boliviensis and S. b. peruviensis. This supports field research on socioecology which documented different social structure and behavior in wild populations of S. s. sciureus compared to S. b. boliviensis and S. b. peruviensis.     

The susceptibility of the Indonesian I/CDC strain of Plasmodium vivax to chloroquine.

A strain of Plasmodium vivax from Indonesia was adapted to splenectomized Aotus and Saimiri monkeys and tested for its susceptibility to chloroquine. Animals were infected by intravenous inoculation of heparinized parasitized blood and subsequently treated with 8 or 15 mg (base) of chloroquine by oral intubation. Recrudescence of infection occurred in 4 of 4 Aotus and 5 of 6 Saimiri monkeys treated with 15 mg base of chloroquine, indicating a level of resistance between that of the standard Chesson strain of P. vivax and the recently reported resistant strains from Papua New Guinea.     

Male behavior through the breeding season in Saimiri boliviensis boliviensis

The Bolivian squirrel monkey (Saimiri boliviensis boliviensis) is a seasonal breeder. Male squirrel monkeys show distinct morphological and behavioral changes prior to and during the breeding season. A “fatting syndrome” includes increased body weight, increased levels of androgens, and in the Bolivian subspecies, an increasingly active role in the social organization of the group. In this study, the behavior of ten adult male Bolivian squirrel monkeys was analyzed over a 6-month period prior to, during, and after the breeding season. Each was housed as the only adult male in a breeding unit with six to ten adult females and one juvenile male. Employing a principle components method, 11 behavioral clusters were generated from 27 responses. Their activity clusters were identified as follows: sexual activity that showed a peak around the time of peak conceptions; excitatory activity that was initially high but decreased throughout the breeding season; and maintenance activity that did not change across the breeding season. The changing social behavior of the male squirrel monkey parallels physiological changes and is correlated with changing androgen levels.     

Experimental Plasmodium falciparum cerebral malaria in the squirrel monkey Saimiri sciureus.

Infection of the squirrel monkey, Saimiri sciureus, with several strains of Plasmodium falciparum leads in a proportion of animals to neurological symptoms with a fatal outcome. This first simian model for human cerebral malaria was studied with three strains of parasites, the uncloned Palo Alto(FUP-1) strain, the Palo AltoPLF3 clone MHB11, and the recently monkey-adapted P. falciparum strain IPC/RAY. Cerebral malaria could develop during primo infection of monkeys, whether the animals had been splenectomized or not. It did not occur in all animals and the appearance of neurological symptoms could not be predicted, as it was not related to the degree of parasitemia or duration of parasite infections.     

Growth of skeletal components in the young squirrel monkey (Saimiri sciureus boliviensis): a longitudinal experiment

A functional skeletal criterion, as an extension of the van der Klaauw's cranial theory, was adopted in the present study. The null hypothesis tested was: "The major skeletal components of the platyrrhine body grow linearly, regardless of their functional dependence to different demands." The acceptance of the hypothesis will imply that all Saimiri skeletal growth may be satisfactorily explained by independent variables in a single equation. The rejection will suggest that such skeletal growth patterns have to be explained by variables in several different equations, and perhaps these equations may vary with the effect of sex and undernutrition. Control and undernourished squirrel monkeys were radiographed monthly for 2 years; they were also measured; and their volumetric and morphometric neurocranial, facial, and pelvic indices were calculated. The curves that best described each of the 24-point sequences were obtained. Three main growth patterns were observed: 1) Simple linear (femur length for all groups, and pelvic index for control and undernourished females), for which the simple regression equation explained more than 95% of the variation; 2) Complex linear (pelvic index for control and undernourished males, and neurocranial and facial indices for all of the groups), for which more than 95% of the variation was explained by one of the four four-function type equations; and 3) Noncorrelated with age (neurofacial index for undernourished males, and pelviofemoral index for control females and undernourished males and females), which showed nonsignificant correlations with respect to age. The food intake and the oscillations of the environmental temperature might help to explain the undulating growth trajectory observed in the complex linear components.     

Cortisol metabolism in the Bolivian squirrel monkey (Saimiri boliviensis boliviensis)

New World squirrel monkeys (Saimiri spp.) have high circulating cortisol levels but normal electrolytes and blood pressures. The goal of the present study was to gain insight into adaptive mechanisms used by Bolivian squirrel monkeys to minimize the effects of high cortisol on mineralocorticoid receptor (MR) activity and electrolyte and water balance. Aldosterone levels in serum from 10 squirrel monkeys were 17.7 +/- 3.4 ng/dl (normal range in humans, 4 to 31 ng/dl), suggesting that squirrel monkeys do not exhibit a compensatory increase in aldosterone. The squirrel monkey MR was cloned and expressed in COS-7 cells and found to have similar responsiveness to cortisol and aldosterone as human MR, suggesting that squirrel monkey MR is not inherently less responsive to cortisol. To determine whether altered metabolism of cortisol might contribute to MR protection in squirrel monkeys, serum and urinary cortisol and cortisone were measured, and a comprehensive urinary corticosteroid metabolite profile was performed in samples from anesthetized and awake squirrel monkeys. The levels of cortisone exceeded those of cortisol in serum and urine, suggesting increased peripheral 11beta-hydroxysteroid dehydrogenase 2 activity in squirrel monkeys. In addition, a significant fraction (approximately 20%) of total corticosteroids excreted in the urine of squirrel monkeys appeared as 6beta-hydroxycortisol, compared with that in man (1%). Therefore, changes in cortisol metabolism likely contribute to adaptive mechanisms used by Bolivian squirrel monkeys to minimize effects of high cortisol.     

Adaptation of the Plasmodium falciparum FCB strain for in vitro and in vivo analysis in squirrel monkeys (Saimiri sciureus)

The asexual blood stages of the Plasmodium falciparum parasite are responsible for inducing the clinical symptoms and the most severe presentations of malaria infection that causes frequent mortality and morbidity in tropical and subtropical areas of the world, making the blood stages of infection a key target of new malaria treatment and prevention strategies. Progress towards the development of more effective treatment and prevention strategies has been hindered by the limited availability of infection models that permit the sequential analysis of blood stage parasites in vitro followed by in vivo analysis to confirm therapeutic benefits. To advance a model for in vitro and in vivo analysis of blood stage parasites, we examined nine laboratory strains of P. falciparum to determine which strains could adapt to growth in vivo in splenectomized squirrel monkeys (Saimiri sciureus). Only one of the nine laboratory strains tested, the FCB strain, adapted to in vivo growth. Morphological analysis show that the adapted ring-stage parasites have a different morphology from original parasites cultured in vitro, and more often they were found to localize at the edge of the infected red blood cell. No remarkable differences were observed for both trophozoites and schizonts. The adapted strain can be cultured back in vitro similar to the original parasite, indicating that the adapted parasite can develop both in vitro and in vivo. This squirrel monkey-adapted P. falciparum parasite is expected to be suitable and is advantageous for the research and development of vaccines and antimalarial drugs.