Partial protection of baboons against Schistosoma mansoni using radiation-attenuated cryopreserved schistosomula.

Three groups of five baboons were vaccinated in Kenya using three doses of 10,000 viable cryopreserved schistosomula attenuated with either 10, 20 or 60 krad 60Co-irradiation prepared in England. Animals were vaccinated at four-week intervals, challenged after a further six weeks with 2,000 cercariae and perfused at 10 weeks after challenge. High antibody titres to schistosomula mediating in vitro cytoadherence with P 388D1 macrophage-like cells were demonstrated in all vaccinated animals but not in controls. Significant titres to soluble egg antigen (SEA) were also demonstrated by ELISA in the 10 and 20 krad vaccinated groups following the first vaccination. The subsequent vaccinations and the challenge boosted this response considerably. Mean anti-SEA titres were only elevated above background in the 60-krad group six weeks after the third vaccination and in the challenge controls six weeks after challenge. Peripheral eosinophil counts were slightly reduced and neutrophil counts slightly elevated before challenge while eosinophil and erythrocyte counts were elevated and neutrophil counts depressed after challenge. PCV values were erratic in all groups. Eggs appeared in the faeces from six weeks after challenge and excretion rates were higher in all three vaccinated groups than in the challenge controls by necropsy 10 weeks after challenge. Body-weights were depressed in all groups after challenge but subsequently rose in the 10 and 20 krad groups. The 60 krad and challenge control groups lost 12.4% and 7.9% of body-weight respectively after challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

The suitability of East African primates as animal models of visceral leishmaniasis.

The susceptibility of four East African primate species to experimental infection with Leishmania donovani was investigated. Vervet monkeys (Cercopithecus aethiops), Sykes monkeys (C. mitis) and baboons (Papio cynocephalus) all supported low grade infections for periods ranging between four and eight months and subsequently showed evidence of self-cure. Greater bushbabies (Galago crassicaudatus) remained completely refractory throughout the course of the experiment. The significance of hepatic histiocytic nodules in the infected primates, similar to those observed in asymptomatic human visceral leishmaniasis, and the susceptibility of Old World primates to experimental infection are discussed.

Marburg, Ebola and Rift Valley Fever virus antibodies in East African primates.

Sera from 464 primates held at four institutes in Kenya were tested by indirect immunofluorescence for the presence of antibodies against Marburg, Ebola, Congo haemorrhagic fever, Rift Valley fever and Lassa viruses. Four of 136 vervet monkeys were positive for Marburg virus antibodies and three of 184 baboons had antibodies against Ebola virus. One baboon was positive for Marburg virus antibodies. Two vervet monkeys, three baboons and one grivet monkey (of 56 tested) had antibodies against Rift Valley fever virus. No Congo or Lassa virus antibodies were detected. A sample of 88 sera of more arboreal primates (Sykes, blue and colobus monkeys) were negative against all five antigens, as were sera from 58 staff members of the institutes who worked with or near the animals.

Early implantation and embryonic development of the baboon: stages 5, 6 and 7.

Implantation stages of the olive baboon, Papio cynocephalus anubis, showing embryonic development equivalent to Carnegie stages 5, 6 and 7 of development, were collected by hysterotomy and examined histologically. The younger specimens (stage 5) consisted of a thick trophoblastic plate composed of cytotrophoblast and syncytiotrophoblast with multiple small clefts, and a bilaminar disk embryo with a small slit-like amniotic cavity. An epithelial plaque response was present in the uterine epithelium immediately peripheral to the implantation site, within an area of pronounced uterine edema. The bilaminar embryonic disk consisted of columnar epiblast cells underlying the amniotic cavity, and thickened visceral endodermal cells that form part of the yolk sac. The slightly further developed placenta (stage 6) consisted predominantly of cytotrophoblast including primary villi and syncytiotrophoblast lining large spaces containing maternal blood. Secondary placental villi were present in the oldest group (stage 7), and there was modest decidualization of the uterine stroma. An epithelial plaque response persisted, but varied in extent. The sequence of events in early development in the baboon is similar to that in the rhesus monkey insofar as blood space formation and endometrial responses are concerned. However, the plaque response is not so great as in the rhesus; there is no secondary placenta, and the decidual response is slightly more extensive.

The detection of ovulation and early pregnancy in the baboon by direct measurement of conjugated steroids in urine.

The pattern of excretion of urinary steroid metabolites in the olive baboon (Papio anubis) was examined during the menstrual cycle and in conception cycles in which embryos were surgically removed at intervals between day 11 and day 21 (day 0 = day of preovulatory estrogen peak). Conjugated estrone and pregnanediol-3α-glucuronide were measured in overnight urine samples by direct, nonextraction assays, and the levels were indexed by creatinine. Results showed that measurement of urinary conjugated estrone reflected preovulatory estrogen output and that pregnanediol-3α-glucuronide was an abundant urinary metabolite of progesterone. There was a defined postovulatory increase in the excretion of conjugated estrone during conception cycles in eight of ten animals. The timing of the increase ranged between day 13 and day 19 and was related to the appearance of elevated levels of urinary gonadotrophin. In four animals, increased estrogen excretion was first detected after the day of embryo removal, but this was most likely a response to chorionic gonadotrophin secreted before surgery. The findings demonstrate that measurement of conjugated estrone offers a rapid and practical approach for monitoring ovulation and implantation in the baboon by a single assay technique.

Reproduction in the vervet monkey (Cercopithecus aethiops): I. Testicular volume, testosterone, and seasonality.

To test whether the male could contribute to the birth peak seen in both wild and captive vervets, testicular volume and peripheral testosterone concentration were measured monthly in nine adults throughout a 14-month period. Volume was an average of 15% greater during the months of June to September, the period of natural breeding activity in the wild, than at other times of the year. Testosterone concentration rose throughout the time period but did not correlate with testicular volume. Quarterly biopsies of the right testis in animals either used for or withheld from breeding revealed the presence of spermatozoa and the existence of spermatogenesis throughout the year. There was no correlation of testicular volume with breeding status or biopsy. If these results from individually caged animals are representative of group-caged and wild animals, then such small seasonal changes are unlikely to affect year-round breeding. Therefore, a physiological contribution by the male to natural birth peaks seen in the wild and captivity is not readily apparent.

Reproduction in the vervet monkey (Cercopithecus aethiops): III. The menstrual cycle.

The menstrual cycles of 17 multiparous vervet monkeys were studied. Based on estradiol, progesterone, and LH profiles, ovulation is predicted to occur on day 13 of the 32.4-day menstrual cycle. Estradiol peaked on the day preceding the LH peak in 75% of cycles. Average luteal phase length (progesterone greater than 4 nmol/l) was 18 days, with progesterone rising above 4 nmol/l on the day of the LH peak. Vaginal cytology and perianal skin coloration exhibited too much within- and among-animal variability to be reliable indicators of menstrual cycle stages. Uterine biopsies of the proliferative phase were characterized by mild pseudostratification of the columnar epithelium and absence of glandular secretion; in contrast, those of the luteal phase had marked pseudostratification of the tall columnar epithelium with glandular secretions in the lumen. A few follicular-phase samples contained structures such as tortuous uterine glands with secretions. Such structures are more characteristic of the luteal phase. It is suggested that their presence can be explained by incomplete sloughing of the endometrium at menstruation, as this is known to be light or convert in this species.

Pregnancy outcome in free-ranging vervet monkeys (Cercopithecus aethiops).

A preliminary assessment of individual female differences in conception rate and fetal wastage has been determined for a population of wild vervet monkeys (Cercopithecus aethiops). One of three troops of vervet monkeys, the subjects of a long-term behavioral study, was trapped and blood was obtained for electrophoretic analysis. Pregnant females exhibited a distinctive serum aminopeptidase phenotype allowing a conclusive determination of pregnancy. Of the seven females diagnosed as pregnant, three later gave birth. Of the females that aborted, two were nulliparous and one was very old. Studies of captive animals have indicated that age and rank may affect a female's ability to carry a fetus to term. These factors, rather than the trapping procedure, may have been responsible for most of the fetal loss in the trapped troop. A comparison of all three troops for a 3-year period indicated that there were fluctuations in yearly birth success of individual females, as well as a relatively high miscarriage rate. The results of this study indicate the advantages of obtaining joint behavioral and biological data.

Reproduction in the vervet monkey (Cercopithecus aethiops): II. Annual menstrual patterns and seasonality.

Menstrual patterns and progesterone levels were monitored for 5 years from a cohort of 28 female vervet monkeys that were individually caged indoors. Three distinct cycle types (short, normal, and prolonged) were defined according to cycle length. Mean length of the normal cycle (32.5 days) and menses duration (4.8 days) are in agreement with previous reports. Prolonged cycles (> 50 days) contributed 20% of the total, with a decreased incidence during the natural peak breeding period. Weekly progesterone measurements indicated that many prolonged cycles were associated with an extended luteal phase, while others were probably due to lack of ovulation. From these data it would appear that the vervet monkey, although not strongly seasonal, does favor a particular time of year for breeding in a colony housed indoors.

Effects of ketamine anaesthesia, stress and repeated bleeding on the haematology of vervet monkeys.

Haematology values are presented for the vervet monkey (Cercopithecus aethiops), and the relative effects of high dose ketamine anaesthesia, stress of capture and repeated bleedings assessed. Anaesthesia resulted in decreased WBC and RBC values, attributed to depression of cardiovascular function. These effects were the reverse of those of alarm and strenuous exercise (leukocytosis and polycythaemia) during capture. Stress resulted in relatively high white and low red blood cell counts. Opposing effects of stress and anaesthesia led to comparable haematological values for trained, non-anaesthetized vervets and stressed, anaesthetized vervets. Effects of repeated bleedings were opposite in anaesthetized and non-anaesthetized animals. These effects, however, along with those of ketamine anaesthesia and stress, were relatively insignificant compared with the wide variation in haematological values found among individuals. The biological importance of these effects thus appeared to be slight. The concept of 'normal values' is discussed.

Tuberculosis in wild olive baboons, Papio cynocephalus anubis (Lesson), in Kenya.

Several wild olive baboons from a single troop in the Masai Mara Game Reserve, Kenya were observed to be lethargic and emaciated. Five were trapped and tuberculin tested by intradermal inoculation of 0.1 cc (100 IU) mammalian old tuberculin in the upper eyelid. Two of the five showed positive reaction at 72 hr and were examined at necropsy. Gross lesions in both animals consisted of multiple nodules with caseation in the lung, spleen and tracheobronchial lymph nodes. There were multiple granulomas throughout the lung, spleen and the lymph nodes. Tissues were cultured on Lowenstein-Jensen media with and without pyruvic acid. Isolates were typed as Mycobacterium bovis.

Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env.

Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4(+) T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV-1157ipd3, an extra NF-kappaB binding site was engineered into its 3' long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.

Captive propagation of vervet monkeys (Cercopithecus aethiops) in harems.

A small breeding colony of captive vervet monkeys (Cercopithecus aethiops), consisting of ten single male harem groups, was established in Kenya. Vervets were extremely prone to stress after capture and manipulative procedures led to high mortalities. Six weeks were required for partial habituation, after which routine handling was not too problematic. However, complete adjustment to captivity took a minimum of one year. Establishment of stable breeding groups from adult animals initially proved difficult because of fighting among females. Once harem groups stabilized, reproductive rate was high with just under 90% pregnancies and 85% livebirths annually. Births exhibited a seasonal pattern similar to that reported from wild populations in Kenya.