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Cellular responses to Loa loa experimental infection in mandrills (Mandrillus sphinx) vaccinated with irradiated infective larvae.

In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days -60, -30 and -15. All animals were challenged with 100 intact L3 (day 0). Parasitological and immunological status were followed for 9 months. Vaccination delayed the appearance and mean peak of microfilaraemia. Five mandrills (Mf-) were never microfilaraemic (one V mandrill) or microfilaraemic on only one occasion (2 V and 2 NV), the other seven having stable microfilaraemia (Mf+). The cytokine response of peripheral blood mononuclear cells to L3 (L3 Ag) was Th2 dominated, while microfilariae (Mf Ag) elicited a Th0-like response. During vaccination, Th2 cytokine production significantly increased in V mandrills against L3 Ag, as well as Mf Ag, whereas Th1 cytokines decreased. On day 60 postinoculation, cellular proliferation was higher in V mandrills in response to L3 and Mf Ags and PHA-L mitogen. At the end of prepatency (on day 130), mandrills with delayed appearance of microfilaraemia exhibited a high, transient IL-2 and IL-4 secretion in response to L3 Ag. Finally, high anti-Mf Th2 cytokine levels characterized Mf-mandrills not only during prepatency, but also (for IL-5) before immunization. However, the presence of a balanced Th1 anti-L3 response during prepatency in the amicrofilaraemic mandrill suggests its importance in protective immunity. Taken together, our data suggest that Th2 cells and also Th1 components of the antifilarial response, especially to larval antigen, may contribute to parasite elimination.

Animals↗

Natural infection of wild-born mandrills (Mandrillus sphinx) with two different types of simian immunodeficiency virus.

We found a novel primate lentivirus in mandrill (Mandrillus sphinx). To clarify the evolutionary relationships and transmission patterns of human/simian immunodeficiency virus (HIV/SIV), we screened blood samples from 30 wild-born healthy Cameroonian mandrills. Five (16.7%) of them were seropositive for SIV. Three SIV strains were isolated from the five seropositive mandrills by cocultivation of their peripheral blood mononuclear cells (PBMCs) with PBMCs of rhesus macaques, a human T cell line (M8166), and/or a cynomolgus macaque T cell line (HSC-F). One of the newly isolated SIV strains was intravenously inoculated into two rhesus macaques and resulted in chronic infection. In the SIV-infected macaques at 45 weeks after inoculation, we observed a mild decline in the number of peripheral CD4(+) lymphocytes, lymphadenopathy, and blastic follicular dendritic cells with mild follicular hyperplasia in the peripheral lymph nodes. A phylogenetic analysis based on the pol sequence showed that the newly found SIVs from Cameroonian mandrills did not cluster with SIVmndGB1, which is the former representative strain of SIVmnd. The SIVmnds from Cameroon formed a new, independent lineage that branched before the root of the HIV-1/SIVcpz lineage with 996 of 1000 bootstrap replications. They clustered host specifically, and exhibited about 16.9% diversity at the level of nucleotide sequence among Cameroonian SIVmnd strains. These results indicate that the SIVmnds isolated in Cameroon are a novel type of SIVmnd and have infected Cameroonian mandrills for a long time. We therefore designated the Cameroonian SIVmnd as SIVmnd type 2 and redesignated SIVmndGB1 as SIVmnd type 1. To date, M. sphinx is the only primate species other than humans that is naturally infected with two different types of SIV.

Animals↗

Hematology and serum chemistry in the white-crowned mangabey (Cercocebus torquatus lunulatus) and in the mandrill (Mandrillus sphinx).

Reference values of some hematologic and plasma chemical parameters were established in two species of clinically normal Cercopithecidae. The following variables were studied in seven mandrills (Mandrillus sphinx) and nine white-crowned mangabeys (Cercocebus torquatus lunulatus): hematocrit, hemoglobin concentration, erythrocyte and leucocyte counts, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, glucose, urea, uric acid, cholesterol, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, gamma glutamyl transpeptidase, total serum proteins, albumin, globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total phosphorus, chloride, and serum osmolality. Few differences were observed when compared with human hematological data and with other species of Cercopithecidae Primates.

Animals↗

Simian T-cell lymphotropic virus type 1 from Mandrillus sphinx as a simian counterpart of human T-cell lymphotropic virus type 1 subtype D.

A recent serological and molecular survey of a semifree-ranging colony of mandrills (Mandrillus sphinx) living in Gabon, central Africa, indicated that 6 of 102 animals, all males, were infected with simian T-cell lymphotropic virus type 1 (STLV-1). These animals naturally live in the same forest area as do human inhabitants (mostly Pygmies) who are infected by the recently described human T-cell lymphotropic virus type 1 (HTLV-1) subtype D. We therefore investigated whether these mandrills were infected with an STLV-1 related to HTLV-1 subtype D. Nucleotide and/or amino acid sequence analyses of complete or partial long terminal repeat (LTR), env, and rex regions showed that HTLV-1 subtype D-specific mutations were found in three of four STLV-1-infected mandrills, while the remaining monkey was infected by a different STLV-1 subtype. Phylogenetic studies conducted on the LTR as well as on the env gp21 region showed that these three new STLV-1 strains from mandrills fall in the same monophyletic clade, supported by high bootstrap values, as do the sequences of HTLV-1 subtype D. These data show, for the first time, the presence of the same subtype of primate T-cell lymphotropic virus type 1 in humans and wild-caught monkeys originating from the same geographical area. This strongly supports the hypothesis that mandrills are the natural reservoir of HTLV-1 subtype D, although the possibility that another monkey species living in the same area could be the original reservoir of both human and mandrill viruses cannot be excluded. Due to the quasi-identity of both human and monkey viruses, interspecies transmission episodes leading to such a clade may have occurred recently.

Amino Acid Sequence↗

High levels of viral replication contrast with only transient changes in CD4(+) and CD8(+) cell numbers during the early phase of experimental infection with simian immunodeficiency virus SIVmnd-1 in Mandrillus sphinx.

Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four mandrills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected mandrill. Two noninfected control animals were monitored in parallel. Blood and lymph nodes were collected at three time points before infection, twice a week during the first month, and at days 60, 180, and 360 postinfection (p.i.). Anti-SIVmnd-1 antibodies were detected starting from days 28 to 32 p.i. Neither elevated temperature nor increased lymph node size were observed. The viral load in plasma peaked between days 7 to 10 p.i. (2 x 10(6) to 2 x 10(8) RNA equivalents/ml). Viremia then decreased 10- to 1,000-fold, reaching the viral set point between days 30 to 60 p.i. The levels during the chronic phase of infection were similar to that in the naturally infected donor mandrill (2 x 10(5) RNA equivalents/ml). The CD4(+) cell numbers and percentages in blood and lymph nodes decreased slightly (<10%) during primary infection, and CD8(+) cell numbers increased transiently. All values returned to preinfection infection levels by day 30 p.i. CD8(+) cell numbers or percentages, in peripheral blood and lymph nodes, did not increase during the 1 year of follow-up. In conclusion, SIVmnd-1 has the capacity for rapid and extensive replication in mandrills. Despite high levels of viremia, CD4(+) and CD8(+) cell numbers remained stable in the post-acute phase of infection, raising questions regarding the susceptibility of mandrill T cells to activation and/or cell death in response to SIVmnd-1 infection in vivo.

Animals↗

Sequences and timing of dental eruption in semi-free-ranging mandrills (Mandrillus sphinx).

The chronology of tooth emergence is often used to examine the growth and development of individuals and to compare life histories across species. Emergence patterns are also used to age animals and to infer life history influences for extinct species. However, comparative studies of primates are hindered by a lack of dental development data for many species. Here we describe the sequences and timing of tooth emergence for a large sample of semi-free-ranging mandrills (Mandrillus sphinx) and compare this with other life history variables for this species. Deciduous dentition emerged in the sequence i1 i2 c p3 p4. The augmented sequence (including information about variability in emergence sequence) was i1 i2 [c p3] p4 for the female maxilla and the male mandible, and i1 i2 c p3 p4 for the female mandible and the male maxilla. Deciduous dentition was complete by 5.0 months in females and 6.4 months in males. The permanent dentition began to emerge at 26 months, and complete adult dentition had emerged by 68 months for males and 85 months for females. Sex differences occurred in the augmented eruption sequences: females M1 I1 I2 [M2 C] P3 P4 M3, males M1 I1 [I2 M2] [P4 = P3 = C] M3. The order of tooth eruption and the occurrence of sequence polymorphisms were very similar to those observed for baboons and macaques. Comparison with life history variables showed that mandrills have complete deciduous dentition at weaning, females possess both adult incisors and M1 when they first reproduce, but still have deciduous canines and premolars, and that both sexes have full adult dentition before they attain their full adult stature and mass.

Age Factors↗

Comparison of spatial and orientational relationships as manifestations of divergent modes of social organization in captive groups of Mandrillus sphinx and Theropithecus gelada.

Recent theories of nonhuman primate social organization and behavior suggest the existence of two primary modes of attention. In centripetal social groups attention is directed inward toward the group, ultimately to the dominant male. In acentric social groups attention is directed outward toward the surrounding environment. Such fundamental differences in postulated attention structure promote extreme, but predictable, variability in spatial relationships and social organization between primates displaying opposing modes. This difference is tested in two species of Old World monkeys, Mandrillus sphinx and Theropithecus gelada (subfamily Cercopithecinae), and shown to be that individuals in strongly centripetal groups remain closer to their dominant males than individuals in weakly centripetal groups. Correlations with other socioecological factors, including visual attention and body orientation are also demonstrated.

Animals↗

Mammary gland adenocarcinoma in a mandrill (Mandrillus sphinix).

A 22-year-old female mandrill (Mandrillus sphinix) with continuously growing mass at the right mammary gland area was found dead, and a postmortem examination was performed. At necropsy, an elevated firm subcutaneous mass about 5 cm in diameter was present at the right mammary gland area. Axillary, mediastinal, and tracheobronchial lymph nodes were enlarged 2 to 4 times their normal sizes. Numerous metastatic foci 2 to 5 mm in diameter were scattered in the lung. Histologically, the tumor was diagnosed as mammary gland adenocarcinoma. Metastasis to the regional lymph nodes and lung was also confirmed. This is the first reported case of a mammary gland tumor in mandrill in Asia.

Adenocarcinoma↗

Use of polymerase chain reaction for accurate follow-up of Loa loa experimental infection in Mandrillus sphinx.

Mandrills (Mandrillus sphinx) experimentally infected with human Loa loa usually remain microfilaremic for a long period of time. Nevertheless some control their microfilaremia while still harboring adults worms, and therefore become occult-infected. A nested polymerase chain reaction (PCR) assay, targeted on the repeat 3 region of the gene coding for the L. loa 15-kD protein (15r3-PCR), has been evaluated in mandrills infected with third-stage larvae (L3) of L. loa. The results of this assay were negative during the prepatency period (4 months after inoculation), but became positive when microfilariae appeared in the blood, and remained positive in all mandrills, even in those that became amicrofilaremic. These results show that the positivity of the 15r3-PCR assay is linked to the appearance of microfilariae in peripheral blood and demonstrated that L. loa-specific DNA can be detected in blood from occult-infected mandrills.

Animals↗

Spontaneous diabetes mellitus in Macaca cyclopis and Mandrillus leucophaeus: case reports.

Spontaneous diabetes mellitus was reported in a Mandrillus leucophaeus (drill baboon) and a Mpacaca cyclopis (Formosan rock macaque). Each had hyperglycemia, impaired clearance of glucose during tolerance test, and reduced concentrations of immunoreactive insulin; the M cyclopis also had increased triglyceride and prebetalipoprotein concentrations. Both monkeys had extensive amyloid infiltration into the islets of Langerhans and loss of beta cells. Beta cell obliteration can account for the appearance of the diabetic syndrome in these and other nonhuman primate species.

Amyloidosis↗

Disseminated coccidioidomycosis in a mandrill baboon (Mandrillus sphinx): a case report.

A case of disseminated coccidioidomycosis caused by a dimorphic fungus Coccidioides immitis in a mandrill baboon (Mandrillus sphinx) was diagnosed following radiography, ultrasound-guided aspiration of thoracic lesions, and aspiration cytology of skeletal lesions of the left sixth rib. The diagnosis was confirmed by fungal culture and serum quantitative immunodiffusion for antibodies against C. immitis.

Animals↗

Signal content of red facial coloration in female mandrills (Mandrillus sphinx).

Studies of secondary sexual ornamentation and its maintenance by sexual selection tend to focus on males; however, females may also possess showy ornaments. For example, female mandrills possess facial coloration that ranges from black to bright pink. We used fortnightly photographs of 52 semi-free-ranging females aged above 3years over 19 months to evaluate whether colour conveys information concerning female competitive ability, reproductive quality, age or reproductive status. Colour was not related to female rank or quality (body mass index, age at first birth or mean inter-birth interval); however, colour did increase significantly with age and primiparous females were darker than multiparous females. Colour may therefore signal reproductive quality, as younger females are less fertile and produce smaller offspring. Colour was brighter during the follicular phase than during the luteal phase, suggesting that it may signal fertility. Colour also varied across gestation and peaked at four and eight weeks post-parturition, suggesting that it may signal approaching parturition and lactation. Future studies should examine the relationship between colour and the menstrual cycle in more detail, the hormonal basis of female colour, and determine experimentally whether mandrills of both sexes attend to differences in colour between and within females.

Aging↗

Primary simian immunodeficiency virus SIVmnd-2 infection in mandrills (Mandrillus sphinx).

Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10(7) to 10(8) RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10(5) to 10(6) RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10(5) to 10(6) DNA copies/10(6) cells) and stabilized at 10(3) to 10(4) DNA copies/10(6) cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.

Animals↗

Developmental variables and dominance rank in adolescent male mandrills (Mandrillus sphinx).

Previous research on semifree-ranging mandrills has shown that the degree of secondary sexual development differs among adult males. While some males are social, brightly colored, and have large testes and high levels of plasma testosterone, other males are peripheral or solitary, and lack fully developed secondary sexual features. In order to determine how these differences among males arise, and to investigate the influence of social factors, we examined the adolescent development of 13 semifree-ranging male mandrills of known age. Testicular volume began to increase markedly at 5.5 yr, and males began to develop secondary sexual adornments at the age of 6 yr. Males attained adult size and secondary sexual development at an average age of 9 yr. As males developed, they peripheralized, decreasing from 100% group-associated at 5 yr to 20% at 8 yr. At 9 yr some males reentered the social group and attained alpha rank, while others remained peripheral or solitary. Within this average development, there was marked variation among males in the timing of development. Adolescent males that were dominant for their age had higher testosterone levels, larger testes, and more advanced secondary sexual development than subordinate males. The implications of these findings are discussed in the light of differences that occur among adult males, male-male competition, and the evolution of secondary sexual adornments in this species.

Age Factors↗