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PubMed1985

Mice varying in resistance to African trypanosomiasis respond differently to treatments with variant surface glycoprotein.

A comparative analysis of responses between resistant and susceptible hosts revealed that DBA/2 mice, after treatment with variant surface coat glycoprotein (VSG) from virulent or avirulent African trypanosomes, developed splenomegaly as the result of a near-doubling of the splenic cell population, had less polyclonal activation of B cells and were protected upon challenge with homologous trypanosomes. The susceptible C3H/Anf and C3H/HeJ mice on the other hand increased their splenic cell population by only 12%, had about twice the production of unelicited antibodies and were not immunized by the VSG treatments. This indicated that (a) proliferation of spleen cells during African trypanosomiasis may reflect an attempt to generate a specific and protective immune response and is not merely the result of polyclonal activation of lymphocytes; (b) production of unelicited antibodies is not merely a "bystander reaction" to the generation of antigen-specific responses; and (c) polyclonal antibody production in response to VSG is not linked to the LPS gene. Nonspecific immunosuppression as measured in mitogen assays was not elicited by VSG in either resistant or susceptible mice, indicating that polyclonal lymphocyte activation and nonspecific immunosuppression are unlinked phenomena. Mice injected with VSG from either virulent or avirulent isolates at levels normally encountered by hosts during severe, acute infection developed the same degree of splenomegaly and production of unelicited (polyclonal) antibodies. Therefore, any differences in polyclonal activation of lymphocytes measured between mice with acute vs. chronic African trypanosomiasis can be attributed to quantitative and not qualitative differences in VSG.

Animals↗
PubMed1989

Bovine trypanosomiasis in southern Tanzania: investigation into the incidence of infection and duration of chemoprophylaxis.

Before implementing chemoprophylaxis to control bovine trypanosomiasis it is essential to have epidemiological data upon which to base control regimes. A study was conducted under natural tsetse challenge with two groups each of 12 calves grazing their first season. Group 1 received isometamidium treatments prophylactically at intervals during the rainy season and calves in group 2 were treated individually with diminazene as they become infected with trypanosomes. Infections were first detected in the unprotected calves and indicated that the onset of challenge was approximately four weeks after the rainy season began. Trypanosoma vivax accounted for 21 of the 30 infections detected in blood smears, and although one infection remained unspeciated, the remaining eight were T. congolense. It was concluded that a prophylactic regime beginning one month after the start of the rains with repeat treatments of isometamidium at 1 mg/kg at intervals of 10 weeks could be expected to give good control of trypanosomiasis at this location.

Age Factors↗
PubMed1981

Pig trypanosomiasis: effects of infection on feed intake, liveweight gain and carcass traits.

Forty growing pigs were used in an experiment to determine the probable cause of retarded growth or weight loss in animals suffering from trypanosomiasis caused by Trypanosoma brucei, T. congolense or T. simiae. Animals infected with T. brucei or T. congolense had mild or symptomless infections with no significant effect on packed cell volume (PCV), voluntary feed intake, mean liveweight gain, feed conversion efficiency, carcass traits or feed cost per unit of weight gain. Uninfected pigs gained slightly more and required slightly less feed per unit of weight gain than pigs infected with T. brucei or T. congolense but the differences were non-significant. Pigs infected with T. simiae showed a marked drop in PCV and a significantly poor performance which was reflected in curtailment of feed intake, impaired feed conversion efficiency, growth failure, poor carcass traits and extremely high and uneconomical feed cost per unit of weight gain. Growth failure or weight loss in trypanosomiasis would appear to be due largely to the combined effect of reduced feed intake and impaired efficiency of feed conversion.

Animal Feed↗
PubMed1993

Pharmacology of existing drugs for animal trypanosomiasis.

Lack of much interest by the pharmaceutical industry to venture into development of new antitrypanosomal drugs has been a major stimulus to an intensification of research into the few existing drugs. Those indicated for animal trypanosomiasis include: isometamidium, homidium and diminazene, used primarily against Trypanosoma congolense, T. vivax and T. brucei; and quinapyramine, mainly indicated for use against T. evansi infections. A great deal of research effort has focused on development of pharmacological and parasitological methodologies, which have considerably advanced our understanding on the efficacy, resistance, disposition and toxicological mechanisms of these drugs. While a clinical breakthrough has been made in the recent past, in the field of chemotherapy of T. evansi infections by the introduction of a new arsenic compound, melarsenoxide cysteamine, chemotherapy of T. simiae infections in pigs still remains a major challenge because the existing drugs are either ineffective or too toxic for economic use. Further research into the existing drugs is a prerequisite for their optimal usage in the overall effort of improving animal health and productivity through control of trypanosomiasis.

Animals↗
PubMed1994

Delayed recovery of adrenocortical and testicular function after chemotherapy of human trypanosomiasis.

The following indicators of pituitary, adreno-cortical and testicular function were measured in 58 male African trypanosomiasis patients from Western Kenya; plasma cortisol, luteinizing hormone (LH) and testosterone levels. The measurements were carried out by specific radioimmunoassay methods in early and late stage infected patients on admission to hospital and in both groups of patients after one month of chemotherapy. Packed cell volume (PCV) and hemoglobin levels were also measured in all the patients to determine the extent of their anaemia and success of recovery. High parasitaemia, anaemia and clinical symptoms of human trypanosomiasis were found in the infected patients and were eliminated with chemotherapy in the infected/treated patients. Increased levels of cortisol and decreased concentrations of testosterone without significant changes in LH levels were evident in the infected patients; this condition remained unchanged even after one month of chemotherapy. Evidence is thus provided of persistent hormonal perturbations which probably indicate residual endocrine organ damage.

Adolescent↗
PubMed1985

Catalytic irreversible inhibition of Trypanosoma brucei brucei ornithine decarboxylase by substrate and product analogs and their effects on murine trypanosomiasis.

Ornithine decarboxylase from Trypanosoma brucei brucei was inhibited by several substrate (ornithine) and product (putrescine) analogs both in vitro and in vivo. Since alpha-difluoromethylornithine is effective for the treatment of experimental and clinical African trypanosomiasis, it was possible that the more potent ornithine and putrescine analogs might be more active in treating the disease. However, only alpha-monofluoromethyldehydroornithine methyl ester was more potent than alpha-difluromethylornithine against mouse trypanosomiasis and warrants further study in model infections.

Animals↗
PubMed1991

Galactocerebrosides are antigens for immunoglobulins in sera of an experimental model of trypanosomiasis in sheep.

In an experimental model of human African trypanosomiasis in sheep inoculated with Trypanosoma brucei brucei, we report an immunoglobulin reactivity towards central nervous system (CNS) glycolipids. Immunocharacterization of the glycolipid antigens was performed on thin-layer chromatography using peroxidase-labelled second antibody. An immunoreactivity against galactocerebroside antigens was observed in inoculated animals up to a dilution of 1:600 and was suppressed after immunoadsorption of sera on pure galactocerebrosides. As galactocerebroside antigen is responsible for demyelination in several experimental models, the relation between the important glycolipid immunoreactivity in inoculated sheep sera and the pathogenesis of CNS demyelination in African trypanosomiasis is suggested.

Animals↗
PubMed1987

Comparison between bloodstream and procyclic form trypanosomes for serological diagnosis of African human trypanosomiasis.

Trypanosoma brucei brucei MiTat 1.2 bloodstream and corresponding procyclic forms, as well as procyclics of T. b. gambiense and T. b. rhodesiense, were fixed, in suspension, using a mixture of 80% acetone and 0.25% (v/v) formalin in saline and used as antigens for diagnosis of African human trypanosomiasis by the indirect immunofluorescent antibody test. T. b. brucei bloodstream forms detected 41/42 and 37/41 parasitologically diagnosed cases of T. b. rhodesiense and T. b. gambiense trypanosomiasis, respectively, while the procyclic stages detected the same number (41/42) of T. b. rhodesiense, but fewer (29/41) T. b. gambiense infections.

Animals↗
PubMedDate not supplied

Serum lipid and lipoprotein abnormalities in human African trypanosomiasis.

We have studied the serum lipoprotein system in human African trypanosomiasis (Trypanosoma brucei gambiense infection). The study was carried out on 74 Congolense patients suffering from sleeping sickness and 34 Congolense control subjects living in the endemic region of Boko Songho. We have determined the serum concentrations of lipids (triglycerides, cholesterol, phospholipids) and apolipoproteins (apolipoprotein A-I and B), and the separation of serum lipoproteins by electrophoresis. For the patients infected with T. b. gambiense, in comparison with control subjects, the results have shown (i) a significant increase in triglyceride concentration and a decrease in cholesterol concentration; (ii) a significant rise in apolipoprotein B concentration and a significant reduction in apolipoprotein A-I concentration; and (iii) an increase in low density lipoproteins and a decrease in high density lipoproteins. We conclude, therefore, that human African trypanosomiasis is associated with marked alterations in the composition and levels of host lipoproteins.

Adolescent↗
PubMed1992

Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis.

CD-1 mice infected with the protozoan parasite Trypanosoma brucei brucei developed few signs of central nervous system pathology associated with the invasion of the central nervous system by these parasites and did not survive beyond 5-6 weeks with deaths common before this time point. However, use of the trypanocidal drug diminazene aceturate (40 mg/kg), which fails to cross the blood-brain barrier, on day 21 post-infection led to the development of central nervous system pathology similar to that seen in the fatal post-treatment reactive encephalopathies that can occur in human African trypanosomiasis. Enzyme-linked immunosorbent assays were used to measure autoantibody titres to double-stranded DNA, myelin basic protein and to the myelin-specific galactocerebrosides and gangliosides in groups of infected mice, with or without the post-treatment reaction, on day 30 post-infection and compared with uninfected controls. Infection with T. brucei brucei raised the titres of all of these autoantibodies. Treatment of infected mice with diminazene aceturate resulted in elevated levels of all of these autoantibodies compared to the untreated animals. There was a strong positive correlation between the central nervous system pathology and the levels of autoantibodies to myelin basic protein, galactocerebrosides and gangliosides, but not to double-stranded DNA. The elevated titres observed may be a consequence of the polyclonal B cell activation that is believed to occur in African trypanosomiasis, parasite epitopes that are cross-reactive with these central nervous system (CNS)-specific antigens or result from the CNS damage associated with sub-curative chemotherapy.

Animals↗
PubMed1991

Towards more efficacious chemotherapy of trypanosomiasis: combination of alpha-difluoromethylornithine (DFMO) with reactive oxygen generating drugs.

Trypanosomiasis (whether African sleeping sickness, or American Chaga's disease) is caused by an infection with a protozoan parasite, i.e. the trypanosome. This carries fatal sequences in the untreated host. Currently available chemotherapeutic drugs (some of which cure by involving reactive oxygen species (ROS] are not optimally adequate. They are toxic as well, and may also be carcinogenic. It is therefore desirable to devise better chemotherapeutic regimens. ROS destroy the parasite, but excess ROS damage host tissue and are potentially carcinogenic. Alpha-difluoromethylornithine (DFMO) inhibits ornithine decarboxylase and so lowers the levels of spermine and spermidine. This singular effect in the parasite inhibits its multiplication, whereas in the host tissue it prevents carcinogenesis by preventing cell proliferation. Thus, combination of ROS-generating drugs with DFMO would be very effective against trypanosomiasis, and would be without cancer risk too. The combination is therefore advocated for chemotherapy of trypanosoma infections. This necessities experimental investigations specifically directed towards establishing the optimally efficacious combination of DFMO with the drugs.

Drug Therapy, Combination↗
PubMed2005

Clinical assessment of the entry into neurological state in rat experimental African trypanosomiasis.

Human African trypanosomiasis, caused by Trypanosoma brucei (T.b.) gambiense or rhodesiense, evolves in two stages: haemolymphatic stage and meningo-encephalitic stages, the latter featuring numerous neurological disorders. In experimental models infected with diverse T.b. sub-species, body weight (BW) loss, drop in food intake (FI), and hypo-activity after an asymptomatic period suggest the occurrence of a similar two-stage organization. In addition to daily measurement of BW and FI, body core temperature (T(co)) and spontaneous activity (SA) were recorded by telemetry in T.b. brucei-infected rats. After a 10--12-day symptom-free period, a complex clinical syndrome occurred suddenly. If the animal survived the access, the syndrome re-occurred at approximately 5-day intervals until death. The syndrome was made of a drop in FI and BW, a sharp decrease in T(co) and a loss of SA, suggesting a brisk alteration of the central nervous system functioning. Such events confirm the existence of a two-stage disease development in experimental trypanosomiasis. The entry into the second stage is marked by the occurrence of the first access, BW follow-up being essential and often sufficient its determination.

Animals↗
PubMed2006

Interest of tumor necrosis factor-alpha -308 G/A and interleukin-10 -592 C/A polymorphisms in human African trypanosomiasis.

This study aimed to determine whether single nucleotide polymorphisms (SNPs) within tumour necrosis factor-alpha (TNF) and interleukin-10 (IL10) promoters and genes are associated with human African trypanosomiasis (HAT). The polymorphisms used in the analysis were TNF(-308G/A), TNF(-238G/A), TNF(-1031T/C), TNF(+488G/A), IL10(-1082G/A) and IL10(-592C/A). A familial case-control sample of 277 individuals (102 cases and 175 parents) and a matched case-control group of 225 subjects (88 cases and 137 unrelated controls) were gathered together in this study. A conditional logistic regression was used to test for association. We carried out this analysis in the overall population and after stratification by time of exposure, age and ethnic group. Our results show that in the overall population, and after stratification by time of exposure, the IL10(-592A) allele is associated with a lower risk of disease, suggesting the possibility of a protective effect. After stratification by time of exposure, individuals homozygous for the SNP located in the TNF(-308) promoter were shown to present a higher risk of developing the disease early after exposure. Our study shows that TNF(-308G/A) and IL10(-592C/A) SNPs are polymorphisms of interest in the investigation of the genetic susceptibility to human African trypanosomiasis. Larger studies are currently underway to confirm these results.

Adult↗
PubMed2005

The vervet monkey (Chlorocebus aethiops) as an experimental model for Trypanosoma brucei gambiense human African trypanosomiasis: a clinical, biological and pathological study.

It has long been known that the vervet monkey, Chlorocebus (C.) aethiops, can be infected with Trypanosoma rhodesiense, but this model has not been described for T. gambiense. In this study, we report the development of such a model for human African trypanosomiasis. Twelve vervet monkeys infected with T. gambiense developed chronic disease. The duration of the disease ranged between 23 and 612 days (median 89 days) in five untreated animals. Trypanosomes were detected in the blood within the first 10 days post-infection and in the cerebrospinal fluid, with a median delay of 120 days (n = 4, range 28-348 days). Clinical changes included loss of weight, adenopathy, and in some cases eyelid oedema and lethargy. Haematological alterations included decreases in haemoglobin level and transitory decreases in platelet count. Biological modifications included increased gamma globulins and total proteins and decreased albumin. Pathological features of the infection were presence of Mott's cells, inflammatory infiltration of either mononuclear cells or lymphocytes and plasma cells in the brain parenchyma, and astrocytosis. These observations indicate that the development of the disease in vervet monkeys is similar to human T. gambiense infection. We conclude that C. aethiops is a promising experimental primate model for the study of T. gambiense trypanosomiasis.

Animals↗
PubMed2006

Trypanosomiasis by Trypanosoma vivax in cattle in the Brazilian semiarid: Description of an outbreak and lesions in the nervous system.

An outbreak of trypanosomiasis by Trypanosoma vivax is reported in the semiarid of Paraíba, Northeastern Brazil from May to August 2002. Sixty-four cows out of 130 were affected; 11 died and the other recovered after treatment with diminazene aceturate. Affected animals had fever, anemia, weight loss, hypoglycemia, increased serum levels of aspartate aminotransferase and, in nine cows, nervous signs. All cows with nervous signs died; six of them recovered after treatment, but the disease relapsed. Six cows aborted and one delivered a calf that died immediately after parturition. Thirty-two out of 100 calves were affected and five died. Nervous signs were not observed in the calves. Gross lesions were thickening of the meninges, enlarged lymph nodes and prominent white pulp of the spleen. The main histological lesion was meningoencephalitis and malacia in the brain of cows with nervous signs. No antibodies against trypanosomes were found in 33 blood samples collected before the outbreak in the affected farm and in 29 samples collected at the same time in two other neighbor farms. Until January 2003, all 89 animals tested had antibodies against T. vivax, suggesting the occurrence of sub clinical infections in cattle without clinical signs. Only two out of 85 serum samples collected on April 2004 were positive for T. vivax antibodies. Data obtained suggested that the semiarid region is non-endemic for trypanosomiasis and that disease occurred due to introduction of the parasite in a susceptible population after an apparent rise in the Tabanus spp. population.

Abortion, Veterinary↗
PubMed2000

Preliminary evaluation of LATEX/T. b. gambiense and alternative versions of CATT/T. b. gambiense for the serodiagnosis of human african trypanosomiasis of a population at risk in Côte d'Ivoire: considerations for mass-screening.

A study was conducted to compare classical card agglutination test for trypanosomiasis (CATT)/T. b. gambiense with CATT-EDTA and LATEX/T. b. gambiense as alternative field tests for serodiagnosis of Human African Trypanosomiasis. The tests were performed on freshly collected blood in an endemic and a low prevalence area in Côte d'Ivoire. Diagnostic performance of each test was assessed using Quantitative Buffy Coat as the parasitological reference and immune trypanolysis as the serological reference test. According to the parasitological data, CATT-EDTA on 10 microl and LATEX/T. b. gambiense on blood diluted 1:4, detecting all confirmed cases with good specificity (respectively 94.6% and 98.1%) yielded better results than the classical CATT did (one false negative and 92.5% specific). However, when immune trypanolysis data and feasibility are taken into account, the classical CATT remains the test of choice for mass screening under the given field conditions.

Agglutination Tests↗
PubMedDate not supplied

Diagnosis of human trypanosomiasis, due to Trypanosoma brucei gambiense in central Africa, by the polymerase chain reaction.

During a mass screening of sleeping sickness conducted in 1998 and 1999, and involving 27,932 persons in Cameroon and the Central African Republic, we tested the polymerase chain reaction (PCR) on whole blood for the diagnosis of human African trypanosomiasis due to Trypanosoma brucei gambiense. The 1858 samples obtained were from 4 groups: 155 infected patients, 1432 serological suspects detected by the card agglutination test for trypanosomiasis (CATT), 222 negative controls living in the prospected area (negative with the CATT and parasitological methods), and 49 negative controls (CATT and parasitological methods) and unexposed to the disease (Europeans). The technique of DNA extraction used made it possible to preserve the blood samples in the field. The primers used were specific for T. brucei s.l. Only 1 patient was PCR negative, and 3 of the negative controls, exposed to the disease, were PCR positive. Among the 1432 serological suspects, only 50 were PCR positive. During the 6-month follow-up after the surveys, the 3 negative controls, who were initially positive by PCR, were found to be negative. These initial positive PCR results are unlikely to have been due to a cross-reaction with T. brucei brucei, which is non-pathogenic for man, but are more likely to have resulted from a mislabelling of sample tubes. All control individuals, exposed or not to the disease, were negative by PCR. The PCR-negative patient was possibly a registration error. Among 50 PCR positive serological suspects, 39 of them were re-examined. Five were found to be positive by the kit for in-vitro isolation of trypanosomes, representing an increase in patients of almost 13%. At the end of the study, 160 patients were diagnosed, and the PCR was positive for 159 of them (99.4%). Moreover, the PCR made it possible to reduce the number of suspects to be re-examined (50 instead of 1432; a reduction of 96.5%).

Agglutination Tests↗
PubMed2002

Epidemiology and diagnosis of African trypanosomiasis using DNA probes.

The accurate identification of trypanosome species has been a challenging problem in the epidemiology of African trypanosomiasis, both human and animal. The last 10 years have seen great progress through the application of deoxyribonucleic acid (DNA) probe technology, although this has also revealed greater complexity than supposed. While a single repetitive DNA probe can identify all members of the subgenus Trypanosoma (Trypanozoon), including the human pathogens T. brucei gambiense and T. b. rhodesiense as well as the non-tsetse-transmitted trypanosomes T. evansi and T. equiperdum, at least 6 probes are needed to distinguish members of the subgenus Nannomonas, in which only 2 species, T. congolense and T. simiae, were previously recognized. Similarly, the subgenus Duttonella appears to consist of more than one species. Use of this battery of DNA probes to identify the trypanosomes carried by tsetse flies in the field has yielded some surprises about the accuracy (or inaccuracy) of previous identification methods. An unexpectedly high prevalence of mixed infections has been found in all the field studies carried out so far. The large number of infections that remain unidentified by the available probes suggests the existence of other, as yet unknown, trypanosome species. Limited use of the polymerase chain reaction has been made for diagnosis of human and animal trypanosomiasis, due to its high cost.

Animals↗