Trypanosoma brucei gambiense infection in vervet monkeys: a potential model for early-stage disease.

BACKGROUND: Non-human primates are important experimental models for human African trypanosomiasis. METHODS: Six monkeys were intravenously inoculated with 10(5) trypanosomes of Trypanosoma brucei gambiense IL 3253. They were monitored for 180 days for parasitemia, hematology, clinical and biochemical profiles. RESULTS: The pre-patent period was 2-3 days. From 33 to 123 dpi, the parasitemia was low and only detectable by the hematocrit centrifugation technique. Thereafter, to the end of the experimental period, the parasitemia was undetectable by parasitological methods. Clinical signs observed were lymphadenopathy and splenomegaly. Hematological changes included a decline in hemoglobin occurring between 14 and 56 dpi and a significant decline in platelet counts after infection. The levels of total protein, albumin and globulins increased from 26 dpi for the rest of the experimental period. No parasites were detected in cerebrospinal spinal fluid, and no brain pathology was observed. CONCLUSION: This vervet monkey model can only be used for early-stage disease Gambian sleeping sickness.

Lipid metabolism and other metabolic changes in vervet monkeys experimentally infected with Trypanosoma brucei rhodesiense.

BACKGROUND: Human African trypanosomiasis is associated with metabolic changes which have not been well characterized. METHODS: Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and late-stage disease induced at 28 days post-infection. Ear prick blood for glucose determination and blood samples were obtained at weekly intervals for 56 days. Analysis was carried out using dry chemistry analysis. RESULTS: In early infection, there was a significant increase in creatine kinase, while during early and transitional stage of infection there was a significant decrease in glucose and high-density lipoprotein and an increase in triglyceride levels. In the late stage, there was a significant increase in both total cholesterol and LDL levels. CONCLUSIONS: Further investigations should focus on levels of total cholesterol during the follow-up period in curatively treated vervet monkeys. Apart from their importance in disease staging, the changes in lipids levels may also affect the pharmacokinetics of some trypanocides.

Hematological changes in vervet monkeys (Chlorocebus aethiops) during eight months' adaptation to captivity.

This study investigated fluctuations in hematological values of 50 wild-caught vervet monkeys (African green monkeys, grivets, Chlorocebus aethiops) during habituation to captivity. The monkeys were categorized into four groups according to age and sex viz adult males, adult females, juvenile males, and juvenile females. The erythrocyte values were significantly higher (P<0.05) in the adult males than in the other animals. There was an increase in most of the erythrocyte parameters studied during the monitoring period with the most significant being hemoglobin, hematocrit, and mean corpuscular volume. However, the red cell distribution widths, which were higher in adult females, declined. The total white blood cell (WBC) counts, which were higher in adult females than in the other animals, were closely correlated with granulocytes counts. The WBC levels decreased in all the animals throughout the 8 months study, indicating gradually decreasing stress, but they were relatively stable in males. The platelet counts declined significantly (P<0.05) and at 8 months post capture the counts were higher in females than in males. The juvenile female platelet counts were relatively stable during the monitoring period. The maintenance of the monkeys on an improved stable diet and in environment-controlled housing combined with progressing psycho-physiological adaptation may be important factors for the gradual improvements of the hematological values recorded. There were wide variations in these between individual animals emphasizing the need for long adaptation combined with establishment of individual baseline values before experimental studies.

The activity of aminoglycoside antibiotics against Trypanosoma brucei.

The trypanocidal activity of four aminoglycosides was determined against Trypanosoma brucei in vitro. The drug activity in descending order, was as follows; paromomycin kanamycin>gentamycin > neomycin. Paromomycin bad the highest activity and the concentration that inhibited 50% of trypanosome growth (IC50) was 11.4microM. The effect of paromomycin on the causative agents of the East African form of sleeping sickness - T.b. rhodesiense KETRI 265, 2285, 2545, 2562 and EATRO 110,112, 1152 was subsequently assessed. Variations sensitivities between the trypanosome populations were observed and IC50 values ranging from 13.01 to 43.06 microM recorded. However, when paromomycin was administered intraperitoneally (i.p) at 500 mg/kg, it was not effective in curing mice infected with T. b. rhodesienseKETRI 2545 the most drug-sensitive isolate in vitro. Lack of in vivo activity may be because the trypanosome is an extracellular parasite. The pharmacokinetics of paromomycin in the mouse model need to be determined.