Effect of vegetable oils on the experimental infection of mice with Trypanosoma congolense.

Vegetable oils are frequently used as solvents for lipophilic materials; accordingly, the effects of their components should be considered in animal experiments. In this study, the effects of various vegetable oils on the course of Trypanosoma congolense infection were examined in mice. C57BL/6J mice were orally administered four kinds of oils (i.e., coconut oil, olive oil, high oleic safflower oil, and high linoleic safflower oil) with different fatty acid compositions and infected with T. congolense IL-3000. Oil-treated mice infected with T. congolense showed significantly higher survival rates and lower parasitemia than those of control mice. Notably, coconut oil, which mainly consists of saturated fatty acids, delayed the development of parasitemia at the early stage of infection. These results indicated that vegetable oil intake could affect T. congolense infection in mice. These findings have important practical implications; for example, they suggest the potential effectiveness of vegetable oils as a part of the regular animal diet for controlling tropical diseases and indicate that vegetable oils are not suitable solvents for studies of the efficacy of lipophilic agents against T. congolense.

Comparative insecticidal activity of cypermethrin and cypermethrin-mix applications against stomoxyine vectors.

Stomoxyines are mechanical vectors of several pathogens of livestock with severe consequences such as low productivity from constant irritation and disturbance. In vitro and in vivo bioassays were conducted to confirm the efficacy of cypermethrin analogues on stomoxyines. Cattle treated with cypermethrin (Pantex 30 g l-1) and cypermethrin-mix (cypermethrin + oil from Senna occidentalis locally prepared by Fulani herdsmen) were compared using the restricted insecticidal application (RAP) method and a local Fulani application approach (FAA), while untreated cattle serve as control. A total of 550 speciated-fed Stomoxys niger were exposed to graded concentration of cypermethrin (Group A-D) at 30 µg/ml, 20 µg/ml, 10 µg/ml, 5 µg/ml, 1 µg/ml and 0.5 µg/ml. After 48 h, the flies were assessed for mortality. In vivo bioassay of behavioural responses to stomoxyines showed greater mean percentage repellence using RAP (94.6%) of cypermethrin when compared with FAA (46.3%). The sigmoidal non-linear regression model curve of in vitro bioassay showed cypermethrin (Pantex®-group A) to be most effective with LC50 of 1.52 µg/mL and it is significantly more effective than cypermethrin (Ectopouron®-group B) and cypermethrin-mix (Fulani cypermethrin mixture-group C) at 22.62 µg/ml and 20.62 µg/ml concentration, respectively. In this study, Pantex® demonstrated excellent stomoxyine repellence using RAP method with significant insecticidal effect. Therefore, the appropriate use of cypermethrin insecticides using RAP method is recommended for vector control to prevent African animal trypanosomiasis in Nigeria.

How can tsetse population genetics contribute to African trypanosomiasis control?

In sub-Saharan Africa, tsetse transmitted Trypanosomiases have an enormous impact on human health and economic development. Both the World Health Organisation and African countries through the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) have recently asserted their determination to rid the sub-continent of these diseases, and it is increasingly recognised that vector control should play an important role. This review mainly focuses on population genetics of tsetse of the palpalis group, the main vectors of sleeping sickness, and reports recent results on tsetse population structure and on measures of gene flow between populations. Implications of these studies for large-scale tsetse control programmes being undertaken in West Africa are important, particularly regarding control strategies (suppression or eradication).

Protective effect of humus extract against Trypanosoma brucei infection in mice.

Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms are present. Oral administration of humus extract to mice successfully induced effective protection against experimental challenge by the two subspecies, Trypanosoma brucei brucei and T. brucei gambiense. Mortality was most reduced among mice who received a 3% humus extract for 21 days in drinking water ad libitum. Spleen cells from humus-administered mice exhibited significant non-specific cytotoxic activity against L1210 mouse leukemia target cells. Also, spleen cells produced significantly higher amounts of Interferon-gamma when stimulated in vitro with Concanavalin A than cells from normal controls. These results clearly show that administration to mice of humus extract induced effective resistance against Trypanosoma infection. Enhancement of the innate immune system may be involved in host defense against trypanosomiasis.

Alkaloids from Cassytha filiformis and related aporphines: antitrypanosomal activity, cytotoxicity, and interaction with DNA and topoisomerases.

Cassytha filiformis (Lauraceae), a widely distributed parasitic plant, contains several aporphine alkaloids and is often used in African folk medicine to treat cancer, African trypanosomiasis and other diseases. In a previous investigation, we showed that the alkaloid plant extract and the isolated aporphines possessed in vitro cytotoxic properties. In this paper, we evaluated the in vitro activity of the alkaloid extract (IC50 = 2.2 microg/mL) and its three major aporphine alkaloids (actinodaphnine, cassythine, and dicentrine) on Trypanosoma brucei brucei as well as four related commercially available aporphines (bulbocapnine, glaucine, isocorydine, boldine). Only the three alkaloids from Cassytha filiformis were active on the trypanosomes in vitro (IC50 = 3-15 microM). Additionally, we compared the cytotoxicity of these seven compounds on HeLa cells. Glaucine was the most cytotoxic compound on HeLa cells (IC50 = 8.2 microM) in the series. In order to elucidate their mechanism of action, the binding mode of these molecules to DNA was studied by UV absorption, circular and linear dichroism spectroscopy. The results of the optical measurements indicated that all seven aporphines effectively bind to DNA and behave as typical intercalating agents. Biochemical experiments showed that actinodaphnine, cassythine and dicentrine also interfere with the catalytic activity of topoisomerases in contrast to the four other aporphines. These interactions with DNA may explain, at least in part, the effects observed on cancer cells and on trypanosomes.

[Human African trypanosomiasis: present and future treatment ]. / La trypanosomose humaine africaine: propos sur le traitement actuel et les perspectives.

During his life General Lapeyssonnie coped with the hazards linked to the therapeutics of the human African trypanosomiasis (HAT), sometimes with passion and disappointment, sometimes with revolt and hope. Because of a lack of political and financial concern during the past decades, a real global policy against the disease and a drug research against HAT didn't emerge. Today, some changes seem to take place. They are the result of the frightening spread of the disease and of the moral obligation that forces pharmaceutical companies to intervene. Drug research needs to be increased. New drugs should present no toxicity and should be able to cross through the blood-brain barrier with efficient cerebrospinal fluid concentrations. Moreover, new drugs should be easy to synthesize, easy to use and at a low cost. Today, megazol is the only one product in preclinical development, which seems to reach each of these goals.

Prophylactic effects of isometamidium- and ethidium-sustained release devices against Trypanosoma congolense in cattle.

Two successive experiments were carried out in which three cows were treated by intramuscular injection of either 0.5 mg/kg isometamidium or 1 mg/kg ethidium and compared with another group of three cows which received a subcutaneously implanted sustained release device (SRD) containing the same dose of drug. The prophylactic effect of both drug formulations was evaluated by exposing the animals at monthly intervals to Glossina morsitans morsitans infected with Trypanosoma congolense. The average protection period using the isometamidium- and the ethidium-SRD was extended by a factor of 3.2 and 2.8, respectively in comparison with the intramuscular injection of the drugs. In the analysis of isometamidium concentrations in the serum of the animals using a competitive drug-ELISA the drugs remained present for much longer periods in the sera of the implanted animals than in those of the intramuscularly treated cattle. The animals were still protected, however, a long time after the disappearance of detectable drug levels in the serum. No difference in drug sensitivity could be observed, when breakthrough isolates were compared from animals which received the ethidium-SRD and those treated intramuscularly, although a slight loss sensitivity occurred in the breakthrough isolates as compared to the parent trypanosome population.

Comparative evaluation of the prophylactic effect of slow release devices containing homidium bromide and isometamidium on Trypanosoma congolense in rabbits.

Two consecutive experiments were carried out to evaluate the prophylactic effect of biodegradable slow release devices (SRD), containing either isometamidium or homidium bromide. Rabbits subcutaneously implanted with SRD, were challenged with different Trypanosoma congolense stocks at regular intervals between 1 and 6.5 months after treatment. In a first experiment the efficacy of two types of isometamidium-SRD (poly(D,L-lactide) and poly(D,L-lactide-co-glycolide)) was compared with the classical intramuscular (i.m.) injection of the drug. Since the former polymer gave an average protection period, which was much longer than the other isometamidium formulation, a second experiment was carried out to evaluate the prophylactic effect of poly(D,L-lactide) SRD, containing either isometamidium or homidium bromide, with that of the i.m. injections of the same drugs at a dose of 1 mg kg-1. The average protection period of the homidium bromide SRD was significantly longer than that of the i.m. injected drug (112 vs. 49 days). No significant difference was obtained, however, when isometamidium was administered either as a SRD or as an i.m. injection. The average protection periods were, respectively, 106 +/- 37 days and 84 +/- 18 days. When breakthrough isolates derived from SRD-treated animals were compared with the original stocks of T. congolense, the former showed some loss of sensitivity to homidium bromide. No difference in sensitivity was observed, however, for isometamidium.

Chemotherapeutic effects of Annona senegalensis in Trypanosoma brucei brucei.

Mice infected with Trypanosoma brucei brucei 8/18 strain were treated orally and intramuscularly (im) with aqueous root extracts of Annona senegalensis, in doses of 27.8 mg kg-1 and 9.5 mg kg-1 respectively, for four consecutive days commencing 72 hours after the mice were infected. At these dosages the parasites were cleared from the circulation and no relapse was recorded over 60 days. The plant extract, however, had no effect on the trypanosomes when therapy was initiated at the late stages of infection, that is, about the sixth day when the parasitaemia level was 0.9 x 10(6); and all the animals died a day or two later. The herbal extracts also did not show any prophylactic action when given prior to infection. The root extract possesses different margins of safety in the mice depending on the route of administration. The therapeutic index for oral administration was 5.13, and that for im administration was 1.8. Chemical tests revealed that the plant extract contains alkaloids, saponins and tannins. Adverse reactions, especially to doses of 2.3-5.76 mg kg-1, were noted in animals that received the drug parenterally, but not when the drug was administered orally. However, A. senegalensis is shown to be therapeutically effective against T. b. brucei in mice, which agrees with the claims of Nigerian practitioners of Traditional Medicine that it is effective against trypanosomiasis in man.

[A community battle against a tropical endemic disease: supernatural beliefs and tsetse fly traps in the Congo]. / La lutte communautaire contre une endémie tropicale: croyances surnaturelles et pièges à tsétsé au Congo.

Community participation in the control of tropical diseases is of major importance nowadays, particularly for sleeping sickness (Gambian trypanosomiasis). Indeed, the authoritarian measures used with success to control this disease during the colonial period are difficult to apply now. Moreover, in the Congo, cultural and financial restrictions are such that patients sometimes refuse treatment. Thus, it has become highly desirable for vector control to be carried out at the same time as the treatment of patients. Trapping tsetse flies (or Glossina) is an ingenious and effective anti-vectorial method which has been tested in 55 villages of the Congo. The blue-black pyramid trap used does not require insecticide impregnation, and is hung in the branches by means of a capture-bag containing diesel oil. These trials, conducted in the sleeping sickness focus of the Niari river, have demonstrated the feasibility of local communities taking over the responsibility for the traps, while at the same time revealing certain obstacles. Indeed, the efficacy of this method depends on the optimization of trapping. This involves the determination of strategic capture sites by periodically harvesting the flies and moving the traps in order to catch the maximum number of flies. It also involves regular maintenance of the traps (i.e. repairs, checking the capture bag, clearing vegetation...). However, although these activities would appear to be feasible at community level, they are not always carried out satisfactorily. This results in the insufficient viability of the traps and finally to the reinvasion of the treated area by the tsetse. This study presents aspects of the present-day Congolese socio-cultural environment characterized by the revitalization of traditional Bantou mysticism and religious worship. The possessors of the 'Vital Force' or Kundu (sorcerers and healers) are confronted at night in an 'over-reality' consisting of the visible reality together with innumberable beings and objects existing specifically in the invisible state. This nocturnal confrontation may modify the local balance of power and relationships, and is also thought to cause certain symptoms of sleeping sickness and other diseases. During the colonial period, Kundu was prohibited. Under the influence of the Christian church, and because of the progress of modern medicine, the power of the sorcerers and healers gradually decreased. Then, in the 1960s, the eruption of Marxism as an anti-religious theory, modified the balance of power once more.(ABSTRACT TRUNCATED AT 400 WORDS)

[The flexibility of an integrated health service in the campaign against Trypanosoma brucei gambiense trypanosomiasis]. / Réflexions sur la flexibilité d'un service de santé integré dans la lutte contre la trypanosomiase à Trypanosoma brucei gambiense.

The difficulties encountered by the vertical control programme of the gambiense human african trypanosomiasis in various countries, and the achievements of the primary health care policies on the other hand, justify the consideration of an alternative operational management model for this disease. The alternative model presented here is the integrated model. The authors define the concept of integration, discuss its justifications and describe the operational model. Integration is not a goal in itself and could be completed by a vertical approach of the problem in function of the local situations. Integration appears both as a rational response from the health care service to the needs of the population and as a research instrument aiming at answering more adequately the sleeping sickness problem.

[Socio-entomologic survey in human trypanosomiasis focus of Yamba (Peoples Republic of Congo)]. / Enquête socio-entomologique dans le foyer de trypanosomiase humaine de Yamba (République populaire du Congo).

A study carried out at villagers level in a focus infected by human trypanosomiasis (Yamba, Bouenza region, Congo, Mikengue ethnic group) revealed that modern medicin is recognized by them as the sole possibility to treat the sleeping sickness. The witch doctor, if he cannot transmit the sickness, is perfectly able to aggravate it. He is considered as the responsible for any fatal issue. Tsetse flies are charged of transmitting the sickness as well as other biting insects (black flies, ceratopogonidae). The elders give an historical role to pigs in spreading the sickness. Villagers seem very determined to assume themselves fighting against the tsetse fly by trapping, but impregnation of traps by an insecticide got some problems (technical know-how, equipment) which have been solved by a new model of trap designed by the ORSTOM Center in Brazzaville.

Maternally derived immunity in young mice to infection with Trypanosoma brucei and its potentiation by Berenil chemotherapy.

Young mice which were allowed to suckle, from birth, a mother infected with Trypanosoma brucei, or a mother whose infection had been cured before parturition with Berenil chemotherapy, were themselves immune to homologous trypanosome challenge. This immunity extended until approximately 25 days of age, and was transmitted in the colostrum/milk of the mother. Mice born of infected mothers, but transferred at birth to normal foster mothers, were susceptible to trypanosome infection. Drug prophylaxis in normal newborn mice was also effective for approximately 25 days, but in mice which, in addition, received colostral antibody from the mother, combined immunochemoprophylaxis protected the offspring for 40-50 days. Since the combination of protective strategies continued to resist challenge beyond the stage when, on its own, each component's efficacy had decayed, it may be of practical value as an approach to improved disease control under certain field conditions where trypanosomiasis prevails.

Effect of copper on growth and serum constituents of immunized and non-immunized rabbits infected with Trypanosoma brucei.

Seventy-two five-week-old New Zealand White rabbits were divided into three groups and fed a basal diet containing 0, 125 or 250 ppm supplemental Cu for 4 weeks before each Cu-group was further subdivided into three lots of 8 rabbits each. One subgroup was immunized with Trypanosoma brucei before being infected with the same parasite, another subgroup was infected without immunization while the third subgroup was neither immunized nor infected. Parasitemia slightly depressed growth and efficiency of feed utilization while supplemental Cu at 125 and 250 ppm improved both parameters in rabbits. Immunization conferred slight protection on body weight losses by the infected rabbits while supplemental Cu at 250 ppm alone or in combination with immunization completely obliterated the effects of infection on growth performance. Infection depressed haematocrit, haemoglobin, and serum glucose, while the alkaline phosphatase activity was increased. Supplemental Cu significantly increased both haemoglobin and serum glucose levels. Supplemental Cu reversed the effects of parasite infection on blood constituents. The study indicates that Cu may not only promote growth but will also suppress the effects of parasitemia on performance and serum profile of rabbits infected with trypanosomes.