Colour cues for leaf food selection by long-tailed macaques (Macaca fascicularis) with a new suggestion for the evolution of trichromatic colour vision.

Leaf colour, size and toughness were investigated in five plant species important in the diet of Macaca fascicularis in Singapore. Leaf colour and size were examined as potential visual cues for food selection, whereas toughness mirrored fibre content, the inverse of food quality. As leaves matured, they changed colour and toughened. Leaf lightness and yellowness were strongly negatively correlated with toughness, but variation in both the red-green axis of the CIE Lab colour space and leaf size were not. Leaves selected as food by the macaques were distinguished by being very light, yellow to slightly green. Some leaves were dappled with red. The literature suggests that these leaves are relatively rich in protein without being tough and therefore would be sought after by primates. We argue that leaf colour is an important indicator of the nutritive value of leaves. Trichromatic vision is an important advantage in finding those palatable leaves that are dappled red. These would appear dark to dichromatic primates and be deceptive by making leaves look older (lower in quality) than they actually are. This would decrease the perceived window of feeding opportunity for such primates who would be at a disadvantage in trying to find these leaves. It is possible that trichromatic vision in catarrhine primates may have originally evolved for the detection of red coloration in the leaves of shade-tolerant tropical plants, enabling the better exploitation of a food resource.

Chemotherapeutic effect of CGI 18041 against subperiodic Brugia malayi infection in Presbytis cristata.

CGI 18041, an adduct of benzothiazol isothiocyanate N-methyl piperazine, was evaluated for its antifilarial properties in subperiodic Brugia malayi infected Presbytis cristata. Animals experimentally infected with 200-400 subperiodic Brugia malayi infective larvae, were matched according to microfilaria density, infective dose, and duration of infection. They were then randomly assigned to various treatment and control groups. The compound was suspended in 1% Tween 20 in distilled water, sonicated, and then fed to monkeys using a stomach tube. Control animals received an equivalent volume of drug diluent. CGI 18041 at a single oral dose of 50 mg/kg had complete adulticidal and microfilaricidal activities against subperiodic B. malayi in P. cristata. It was also extremely effective at a single dose of 25 mg/kg, the final geometric mean microfilaria count being 1.6% of initial level, and only 1.0% of the infective dose was recovered as live adult worms at autopsy 6 weeks post-treatment. In control animals, these were 226.9% and 5.56% respectively.

Hematological changes in subperiodic Brugia malayi infection of the leaf-monkey, Presbytis cristata.

Hematological changes were monitored in the leaf-monkey, Presbytis cristata, infected experimentally with 200 subperiodic Brugia malayi infective larvae. Prepatent periods were 54-86 days and peak microfilarial geometric mean counts (GMCs) were 1324 per ml blood. Total leukocyte and differential counts were measured at pre-infection, and then at weakly intervals before and during patency. Blood eosinophil level increased to about thrice the initial level at 3 weeks post-infection and this was maintained for the next 13 weeks before it started to rise again, increasing to more than 5 times the initial level at 20 weeks post-infection. The observed pattern of eosinophilia is probably related to the level of microfilaremia and the destruction of microfilariae in the spleen. There was no significant change in the total leukocyte counts during the period of observation.

Biochemical studies in Presbytis cristata infected with subperiodic Brugia malayi.

The Presbytis cristata--Brugia malayi model, now established as a reliable non-human primate model for the experimental screening of potential filaricides, was monitored at monthly intervals for changes in the liver and renal function tests and also for alkaline phosphatase levels during infection. Animals infected with 200-400 infective larvae became patient at 50-90 days post-infection and geometric mean microfilarial counts were above 1000 per ml from the fourth month onwards. There were no significant changes in the biochemical parameters monitored throughout the period of observation. This is an important observation as any changes seen in these parameters during experimental drug studies can be attributed to drug reaction or toxicity and this will be invaluable in decision making as to drug safety.

Antifilarial activity of intravenous suramin and oral diethylcarbamazine citrate on subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata.

The known filaricides, suramin and diethylcarbamazine citrate, were tested against subperiodic Brugia malayi infection in the leaf-monkey, Presbytis cristata. As expected, intravenous suramin at 10 mg/kg daily x 5 days or 17 mg/kg weekly x 5 weeks, did not show any microfilaricidal activity, but substantially reduced the recovery of live adult worms to 50.6% and 13.6% of controls respectively. Oral diethylcarbamazine citrate at 6 mg/kg daily x 6 or 10 days reduced final microfilarial counts to 30% of initial counts four weeks post-treatment and adult worm recovery was reduced to 4.5% and 0% of controls respectively. Although the antifilarial activity of these drugs against the infection in this non-human primate model appears to be similar to that seen in man, these results have to be confirmed using larger groups of animals.

Experimental infection of the leaf-monkeys, Presbytis cristata and Presbytis melalophos with subperiodic Brugia malayi.

The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.

Antifilarial activity of CGP 20376 against subperiodic Brugia malayi in the leaf-monkey Presbytis cristata.

CGP 20376, a 5-methoxyl-6-dithiocarbamic-S- (2-carboxy-ethyl) ester derivative of benzothiazole was evaluated for its antifilarial properties and shown to be extremely effective against subperiodic Brugia malayi in the leaf-monkey, Presbytis cristata at oral doses of 20-100 mg/kg. The compound and/or its metabolites had complete micro- and microfilaricidal activities even when given at a single dose of 20 mg/kg. Lower doses had incomplete filaricidal action.

Experimental infection of the leaf-monkey, Presbytis cristata, with subperiodic Brugia malayi.

Presbytis cristata monkeys infected through the inoculation of between 200 and 400 subperiodic Brugia malayi infective larvae (L3) in the right thigh, in both thighs or in the dorsum of the right foot were followed up for varying periods of up to about 8 months after infection. All 148 inoculated animals became patent, with mean prepatent periods being between 66 and 76 days. In animals injected in the thigh, the patterns of microfilaraemia were similar, there being a rapid rise in the geometric mean counts (GMCs) of microfilariae during the first 10-12 weeks of patency, which then plateaued at levels of greater than 1000/ml. Adult worm recovery, expressed as the percentage of the infective dose, was significantly higher in animals injected with 100 L3 in each thigh, being 9.4% as compared with 2.8%-4.8% in other groups. It is therefore recommended that animals should be injected with 100 L3 in each thigh and that the testing of potential filaricides in this model be carried out during the phase of rapid increase in microfilaraemia to ensure that any microfilaricidal effect can easily be detected.