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.
Infective larvae of Brugia malayi subperiodic obtained by dissection of infected Aedes togoi were injected subcutaneously into the scrotal region of Mastomys natalensis. From altogether 58 infected male M. natalensis 81% showed consistently or intermittently detectable microfilaraemia, whereas in 19% of the animals no microfilaraemia could be detected at any stage. The mean prepatent period was 136 days; the microfilarial density varied from 1 to 535 per 20 c. mm blood. In those animlas with consistently detectable and in general higher microfilaraemia an average of 13.1 live adult worms were found, against an average of 6.4 adult worms in animals with intermittent detectable and in general lower microfilaraemia. An average of 1.5 worms was found in animals which at no stage showed detectable microfilaraemia. A correlation between worm burden and prepatent period could be observed in the individual groups. From the total of 520 live adult worms recovered at necropsy, 37% were found in the lungs, 29% in the parenchyma of the testes and 34% in the lymphatic system. 47% of live fertile female worms were found in the lymphatic system, whereas the majority, i.e; 52% of infertile female worms were detected in the lungs. In addition, 380 encapsulated dead worms were found, most of them (98%) in the lymphatic system. 61% of a total of 900 live and dead worms were found in the region of the lymphatic system.
The chemoprophylactic use of diethylcarbamazine citrate at total oral doses of 15--180 mg/kg body weight was tested against subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos). A total dose of 45 mg/kg body weight given over 9 days killed all developing infective larvae. Similarly, a total dose of 35 mg/kg body weight given over 7 days killed all fourth stage larvae. The minimum effective dose that prevents infection would be 5 mg/kg body weight daily for 7 days every month.
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.
R. sabanus and R. muelleri are very common in the lowland forests of Malaysia. In nature they are infected with Breinlia sp. and D. ramachandrani. In an attempt to determine whether they are also susceptible to subperiodic B. malayi and thereby being potential reservoirs of infection of the disease, 24 R. muelleri and 17 R. sabanus were experimentally infected with the parasite. Results show that although they can support the full development of the parasite, they are poor hosts. This confirms the observation that in Malaysia natural infection of Rattus spp. with the parasite has not been seen. These rats therefore are probably not important in the zoonotic transmission of subperiodic B. malayi in Malaysia.
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.