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The search for a chronic experimental model for human African trypanosomiasis (HAT) in animals with cerebral lesions and neurological disorders has been difficult. Models with meningo-encephalitis have been proposed using Trypanosoma brucei gambiense or T. b. rhodesiense. Meningo-encephalitis is rare in infection with T. b. brucei. It has been shown that the treatment of mice infected with T. b. brucei with diminazene aceturate (Berenyl) led to development of a rapid meningo-encephalitis. In this study, we report the development of a chronic experimental model of HAT in mice infected with T. b. brucei AnTat 1.1E. To obtain a chronic evolution of the infection, on Day 21 postinfection, mice were treated with a dose of suramin (Moranyl) at 20 mg x kg(-1) body weight, a dose which failed to eliminate trypanosomes in the central nervous system (CNS). This treatment, repeated after each parasitemic relapse in the blood, allowed animals to survive more than 300 days postinfection. After a few weeks of infection, mice displayed neurological signs. Histological studies showed the appearance of increasing inflammatory lesions, from meningitis to meningo-encephalitis, with progression of lesions throughout the perivascular spaces in cerebral and cerebellum parenchyma. No demyelination or neuronal alteration were observed except in the necrotic spaces. Trypanosomes were observed in different structures in CNS. An immunohistochemical study of glial fibrillary acidic protein (GFAP) showed an increasing astrocytosis according to the duration of the infection. This model reproduces neurological and histological pathology observed in the human disease and can be useful for further immunopathological, neurohistological and therapeutic studies on this condition.

Two acute phase proteins; C-reactive protein and acid alpha 1-glycoprotein and three nutritional markers; prealbumin, retinol binding protein and transferrin have been evaluated in 8 patients suffering from trypanosomiasis in meningoencephalitic state and compared to those obtained from 15 normal control subjects. Findings show a markly decrease of nutritional markers without change of sera acute phase proteins. We concluded that in meningo-encephalitic state of human african trypanosomiasis, denutrition was a major biological or clinical feature in association with lymphoid cells stimulation as revealed by beta 2-M levels.

During a period of six years (1/1/89-12/31/94), seven children with trypanosomiasis were admitted to the Department of Pediatrics of Owendo Pediatric Hospital-Libreville, Gabon. They were 5 boys and 2 girls, aged 4-17 years, five of them under 15 years. The main reasons of hospitalization were somnolence (4 cases), psychical disorders (5 cases), neurological disorders (4 cases), asthenia (3 cases), loss of weight (3 cases) and fever (3 cases). Increased sedimentation rate (5 cases) and hypergammaglobulinemia (6 cases) were the most important biological disturbances. Serodiagnosis (CATT, indirect immunofluorescence test) was positive in all cases. The parasite was detected in blood seven times, and four times in cerebrospinal fluid (CSF). According to CSF status, six children have been classified in second stage of the disease. Six patients were treated by melarsoprol, and one by eflornithine. Tolerance and response to treatment were good in six cases. Three children presented sequels when leaving hospital. No patient was seen again after the study.

The stage of human African trypanosomiasis (HAT) is important to define precisely as far as it is directly related to the type of treatment used. The beginning of the neurological involvement is difficult to find out because there is no known specific clinical or biological sign. This study is trying to look for a precise marker and has been realized in Congo. 70 subjects with parasitologically confirmed HAT and 70 controls are included. The stage of HAT is determined according to the classical definition on the field using the cerebrospinal fluid (CSF) cell count: less than 5 cells/microliters for the first stage (P1), more than 5 cells/microliters for the second stage (P2). The blood analysis has included: glucose, urea, creatinine, sodium, potassium, calcium, chloride, phosphorus, uric acid, total bilirubin, unconjugated bilirubin, total cholesterol, triglycerides, total proteins, aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, alkaline phosphatase, gamma-glutamyltransferase, immunoglobulins M and G, C3c fraction of complement, transferrin, seromucoid alpha 1, haptoglobin and albumin. In CSF we have analyzed IgM, IgG, protein levels and the bloodbrain barrier (BBB) impairment. The comparison between the subjects and their controls, the subjects in P1 and in P2, the CSF cell count and the other CSF alterations show the interest of the IgM level in CSF and the BBB impairment to identify subjects in P2. However there is a low gradation in the biological disturbances and not a precise threshold point. Nevertheless it seems reasonable to raise the CSF cell count level to 20 cells/microliters to define the beginning of the nervous involvement.

The toxicity of gossypol, a compound occurring naturally in the cotton plant, was investigated in Trypanosoma brucei-infected, gossypol-treated rats, with and without protein malnutrition. The liver, heart, lungs, spleen and adrenal glands were enlarged in all gossypol-treated rats. Gossypol treatment or trypanosome infection, either alone or together, invariably caused significant reductions in the serum activity of creatine phosphokinase and amylase and in the serum concentration of cortisol. The serum biochemical changes, together with histopathological findings in various organs, indicated that the toxicity of gossypol and pathology of trypanosome infection, either alone or in concert, could be exacerbated by protein malnutrition. This finding suggests that the previously reported antiparasitic properties of gossypol may be of little ultimate benefit due to these serious side effects. The spleen in the protein-malnourished, trypanosome-infected and gossypol-treated animals exhibited only a slight decrease in the number of lymphatic nodules, but a marked cellular depletion, especially of cortical tissue, was observed in the thymus. These observations would seem to justify further study of the immune status of trypanosome-infected, gossypol-treated animals.

Reproductive parameters were investigated in gossypol-treated male rats that had been infected experimentally with Trypanosoma brucei and then place on one of two diets of differing (low and normal) protein content. The endpoints assessed were reproductive organ weights, semen epididymal sperm counts, serum testosterone and histological, stereological and histomorphometric evaluation of the testis and accessory reproductive organs. Most of the parameters studied were lowest in the protein-malnourished, gossypol-treated, trypanosome-infected animals, when compared to those obtained from the corresponding animals that were only gossypol-treated or trypanosome-infected. Mean testicular size and the diameter and the total length of seminiferous tubules were especially reduced, indicating that the overall volume of the seminiferous epithelium in these animals was smaller. These findings suggest that reproductive capacity could be impaired in protein-malnourished, trypanosome-infected animals fed on gossypol-containing products, even when there are no obvious clinical signs of disease. This could translate into increased production costs in a farm enterprise. Screening for haemoparasitism would also seem to be worthwhile prior to evaluation and/or use of gossypol (or perhaps other potential contraceptives) in human subjects, especially in communities that are confronted with severe food shortages.

Human African trypanosomiasis (HAT) is characterized by a major deregulation of the immune system. Hypergammaglobulinemia, auto-antibodies, and immunodepression are cardinal features. Parasitemia occurs in waves due to the successive appearance of parasites with different variable glycoprotein surface antigens (VGSA). Antigenic variation enables parasites to elude the host's immune defenses. Although high levels of immune complexes have been detected during HAT, it seems unlikely that they play a significant pathophysiological role. Numerous auto-antibodies have been detected. B lymphocyte activation is uncommon. In vitro T lymphocytes do not proliferate normally, but synthesize cytokines, such as interferon-g which enhance parasite development. Macrophages bind and destroy parasites in the presence of antibodies. They also synthesize large quantities of TNF-alpha which promote parasite destruction but also increase the severity of clinical symptoms. Nitric acid synthesized by activated macrophages has an antiparasitic effect but induces immunosuppression. In the meningoencephalitic stage of HAT, a severe inflammatory reaction is observed. This event is preceded by astroglia which could be induced by astrocytes secreting TNF-a and IL-1. Auto-antibodies against the central nervous system (e.g. anti-galactocerebrosides, anti-tryptophan-like auto-antibodies) may also be involved in the development of encephalitis. VGSA play a key role in the immunopathology of HAT (antigenic variation, induction of cytokine and autoantibody production). Successive relapses occur with the appearance of new antigenic variants and production of antibodies. The resulting continuous stimulation of the immune system leads to deregulation of immunoglobulin production and cytokine network.

To assess the association between human immunodeficiency virus (HIV) infection and human African trypanosomiasis (HAT) in Côte d'Ivoire, West Africa, a cross-sectional case-control study was conducted on 301 HAT patients recruited in the main foci of the country. For each HAT patient, 3 controls, matched for sex, age and residence, were selected. Data relating to socio-demographic factors and potential risk factors for Trypanosoma brucei gambiense and HIV infections were obtained, and serum samples were collected for HIV-1 and HIV-2 tests. A positive test consisted of enzyme immunoassay reactive to HIV-1, HIV-2 or both and confirmed by a synthetic peptide test or Western blot. Data were analyzed using conditional logistic regression with EGRET software. No statistically significant difference was found between the prevalence of HIV infection in HAT patients and controls (4.3% and 3.5% respectively; crude odds ratio (OR) 1.28, 95% confidence interval (CI) 0.65-2.50). In multivariate analysis, allowance for 5 covariates did not change the association between the 2 infections (adjusted OR 1.27, 95% CI 0.64-2.52). Although this study had limited statistical power, no significant association was found between HIV infection and T.b. gambiense infection in rural Côte d'Ivoire. Studies are needed to determine whether HIV infection influences the clinical course of HAT, a question not addressed in the present study.

Background: Dermatologists may evaluate patients with African trypanosomiasis. The currently available dermatologic literature does not review the cutaneous manifestations of African trypanosomiasis., Observation: We describe an American man who acquired African trypanosomiasis while hunting in Tanzania, and we review and classify the cutaneous findings of this disease. This article reports the results of the first biopsy of a trypanid and depicts trypanosomes on the first touch preparation done from a trypanid biopsy specimen. Rare color photographs of trypanids are shown., Conclusions: Recognition of the unique cutaneous manifestations of African trypanosomiasis may allow dermatologists to make a rapid diagnosis that is essential for timely treatment and survival. Classifying the disease with primary chancriform, secondary hemolymphatic, and tertiary central nervous system stages should improve the understanding of the complex natural history of African trypanosomiasis.

The development of anaemia is a major pathological manifestation in chronic trypanosomosis. The anaemia in African trypanosomosis coincides with a marked decrease in plasma concentration of both thyroxine (T4) and 3,5,3' triiodothyronine (T3). To evaluate the effect of trypanosome-induced hypothyroidism on the development of anaemia, sexually mature white New Zealand rabbits were used. Three groups were set up, each of ten rabbits: one group was infected with Trypanosoma congolense; the second group was infected but given replacement doses of thyroxine (treated); the third group was not infected. Small volumes of blood were collected for the determination of parasitaemia and packed cell volume (PCV). The concentrations of T3 and T4 were measured in plasma by radioimmunoassay. The decrease in PCV correlated closely (y = -0.38x + 15.2; r = 0.82, P = 0.001) with the intensity and duration of parasitaemia. The critical PCV value was 0.15 11-1 with a peak parasitaemia of approximately 5 x 10(6) trypanosomes ml-1 of blood. There was a significant correlation between the plasma T3 and PCV (y = 0.049x + 0.57; r = 0.66, P = 0.020). There was also a good positive correlation between T4 and PCV (y = 14.5 + 3.03; r = 0.95, P < 0.001) in the infected untreated group. The PCV levels were significantly different among the three groups of animals (P < 0.05). The infected-treated animals sustained longer periods of infection than the infected and untreated ones. The sustained physiological level of bioactive thyroid hormones T3 and T4 significantly arrested the decline in PCV as the disease progressed.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to evaluate the interaction between protein malnutrition, gossypol treatment and blood parasitosis (Trypanosoma brucei) in the Wistar rat. Haematological and serum biochemical changes were evaluated in the rats, which were placed on two planes of nutrition--low protein (LP) and normal protein (NP)--and either treated with gossypol or infected with Trypanosoma brucei, or both. Higher parasitaemia occurred in gossypol-treated NP rats than in the corresponding LP group. Gossypol treatment and trypanosomal infection, either alone or in concert, caused an anaemia that was both macrocytic and hypochromic. Both treatments together also caused increases in serum alkaline phosphatase and alanine aminotransferase activities, which were accompanied by depressed serum albumin concentrations, suggestive of hepatic dysfunction in affected rats. These results suggest that, with adequate protein intake, the growth and infectivity of trypanosomes is not inhibited by gossypol but that protein malnutrition has a beneficial effect of reduced parasitaemia. Unfortunately, this beneficial effect is counteracted by gossypol enhancement of hepatic dysfunction caused by trypanosomes.

Using in vitro clonogenic assays, the changes in haemopoietic progenitor cell levels were compared in the bone marrow of three adult trypanotolerant N'Dama cattle and three age-matched trypanosusceptible Boran cattle over 17 weeks (119 days) of a primary Trypanosoma congolense (clone IL 1180) infection. As the infection progressed, a clear tendency of the parasitaemia to decrease was seen in the N'Damas, while it remained high throughout the infection in the Borans. The decline in the colony-forming units-granulocyte macrophage (CFU-GM) between 7 and 42 days postinfection (dpi) corresponded with the decreased numbers of neutrophils and monocytes in the blood observed in both breeds. Thereafter, a further significant drop in the CFU-GM levels was observed in the Borans which may partially explain the continued decrease in the numbers of neutrophils and monocytes in blood. In contrast, a significant peak of CFU-GM above preinfection levels was observed in the N'Damas on 49 dpi, which could partially explain the subsequent recovery of the numbers of neutrophils and monocytes in blood. When compared to the N'Damas, the Borans had a more dramatic drop in the packed cell volume (PCV) from 25 dpi onwards, resulting in significantly lower PCV. From 46-49 dpi onwards, the mean PCV stabilised at significantly lower levels in the Borans than in the N'Damas. The mean corpuscular volume (MCV) levels increased in both breeds, but at a much faster rate in the Borans. The clonogenic assays demonstrated an erythropoietic response, characterised by peaks above pre-infection levels of both the early and late erythroid progenitor cells (respectively, burst-forming units-erythroid, BFU-E, and colony-forming units-erythroid, CFU-E), occurring between 35 and 70 dpi in both breeds of cattle. However, despite a more severe anaemia in the Borans, the magnitude of their erythroid response was similar to that of the N'Damas, suggesting that the response of the Borans was insufficient to compensate for the greater degree of anaemia. Moreover, the mean PCV did not improve in the Borans, indicating the ineffectiveness of their erythropoietic response. An increased rate of erythrocyte destruction and/or a defective differentiation and maturation of erythroid precursors have also been shown to be partially responsible for this persistent anaemia. From 98 dpi onwards, despite the persistent low PCV, the MCV decreased to preinfection levels and low CFU-E numbers were observed in the Borans. Over the same period, in the N'Damas the mean PCV progressively increased to reach 25%, which fell within the low normal range for cattle.(ABSTRACT TRUNCATED AT 400 WORDS)

Mice infected with Trypanosoma brucei rapidly develop anemia, with the number of circulating erythrocytes reduced by 50% within a week after infection. The present study investigated the relationship between anemia and bone marrow nitric oxide (NO) production. Bone marrow cell populations from T. brucei-infected mice exhibited elevated levels of NO synthase activity which was inhibitable by NG-nitro-L-arginine methyl ester. NO production was found to coincide with suppressed bone marrow T-cell proliferation in response to stimulation with the mitogen concanavalin A both in vitro and in vivo. As this indicated that NO may inhibit proliferation in other cell types, particularly hemopoietic precursors, we examined the role of NO in anemia during trypanosome infection. NO production correlated directly with the development of anemia, and treatment of infected mice with NG-nitro-L-arginine methyl ester in vivo to systemically inhibit NO synthesis led to a significant reduction in the anemia. Thus, elevated NO production in the bone marrow of T. brucei-infected mice is likely to play a significant role in the anemia resulting from T. brucei infection.

Trypanosomiasis, caused by Trypanosoma congolense, was diagnosed for the first time in Israel in two boxer dogs imported from Kenya. The dogs developed clinical signs two days after arrival and succumbed to the disease within four days. The major clinical and clinicopathological findings included anaemia, haemorrhages, lymphadenomegaly, hepatosplenomegaly and neurological signs. Histopathology showed lymphocytic-plasmacytic infiltration in the skin, brain, meninges, kidney and liver.

Damage to the nervous system occurs in both African and American trypanosomiases, but it differs considerably in form and extent in each disease, and with different strains and disease stages. With Trypanosoma brucei infections there is a progressive central nervous system (CNS) pathology which involves the meninges, choroid, blood-brain barrier, and immunopathological changes including perivascular infiltrations, astrocyte activation and alterations in the cytokine/mediator network. These changes underly the altered behaviour in the late or secondary disease stages, prevalent in the chronic gambian form, characterized by hypersomnia leading, if untreated or if treatment is followed by reactive changes, to coma and death. T. cruzi infections can be divided into 3 stages; acute, intermediate and chronic. Each stage has a different neurological involvement. In the acute stage the parasite produces direct destructive and inflammatory changes in the CNS which can be life-threatening, but which normally resolve, giving way to an intermediate period with effective parasite suppression and little or no perpetuation in the nervous system. The chronic stage is characterized by alteration to a progressive peripheral neuroimmunopathology, with autoimmune destruction of many nerve components, especially the autonomic innervation of the heart and gut.

During a four-week trip to Nigeria a 54-year-old German developed a fever of 39 degrees C. Later on he had lymphadenopathy, pretibial oedema, dyspnoea and weight loss. After 16 weeks a wreath-like pale pink skin rash, increased pulse rate with pulse deficit and hepatosplenomegaly were noted. Abnormal laboratory findings were an increased blood sedimentation rate (95 mm), raised immunoglobulin M (483 mg/dl), haemoglobin of 12.0 g/dl, mean corpuscular volume of 76 fl and Borrelia IgM antibody titre of 1:512. The electrocardiogram was suggestive of myocarditis: the cardiac symptoms were controlled with digoxin and verapamil. The patient's general condition deteriorated while he was receiving antibiotic treatment with tetracycline and penicillin. Cerebrospinal fluid (CSF) showed an increased cell count (39/microliters) and albumin (0.98 g/dl). There was a mild, predominantly proximal, tetraplegia which--on the basis of electromyographic and biopsy findings--was thought to be due to polyneuritis and myositis. At this stage blood smear and CSF examination revealed Trypanosoma. He thereupon received suramin (1.0 g) and prednisolone (120 mg down to 40 mg) daily, to which melarsoprol was added after 6 days (0.5 ml up to 5.0 ml daily for 36 days). Almost all symptoms then regressed within 6 weeks.

Chronic African trypanosomiasis is associated with progressive behavioural deficits, for which there is a complex underlying central nervous system (CNS) pathology. This has been extensively studied in man and a range of experimental animals. An initial meningitis, which can occur quite early in the infection, is followed by a breakdown of the choroid plexus, movement of the parasite into certain localized brain areas, and subsequent encephalitis. The encephalitis consists of a chronic, widespread inflammation with perivascular infiltrations of B-cells, plasma cells, inactivated T-cells and macrophages. The blood-brain barrier is damaged and a vasogenic oedema ensues. Astrocytes and microglia become reactive and the cytokine/mediator network is perturbed. The alterations in some of these signalling substances, e.g. the prostaglandins, may induce some of the behavioural changes, e.g. the hypersomnia. The immunopathology in the CNS may be brought about by elevated levels of active substances in the cerebrospinal fluid, caused by parasite infection.

The effects of experimental Trypanosoma congolense infection in Gambian N'dama and Gobra zebu cattle on number of naturally-occurring adult ticks attaching were studied. An indirect fluorescent antibody test was performed to detect serological prevalence of Cowdria ruminantium antibody. The intravenously imposed trypanosome infection did not result in significant (P > 0.05) differences in Amblyomma variegatum and Hyalomma spp. infestations between control and infected N'dama cattle. Control N'damas carried significantly (P < 0.001) lower numbers of A. variegatum and Hyalomma spp. than the control zebus. Serological frequency of C. ruminantium antibody was similar in both control or infected N'dama and in control or infected zebu cattle. No deaths occurred among N'dama cattle, while all six trypanosome infected zebus progressively died within nine weeks post-infection but trypanosomosis was excluded as the primary cause of death. Examined Giemsa-stained blood smears were negative for the presence of tick-borne micro-organisms. Four positive cases of cowdriosis were identified during post-mortem examination. It was concluded that N'damas, even when submitted to trypanosome infection, react consistently better than Gobra zebus to tick attachment. These results emphasize the benefits of rearing disease resistant cattle breeds, such as N'dama, in areas where risks of trypanosomosis and cowdriosis coexist.

Glomerulonephritis in BALB/c mice following infection with Trypanosoma brucei is characterized by albuminuria and glomerular deposition of immunoglobulins. Electron-dense deposits are present in the mesangium, as well as subendothelially and subepithelially along the glomerular capillary wall. In this study the nature of intracytoplasmic, electron-dense, round structures observed in glomerular endothelial cells was investigated by immunoelectron-microscopy and enzyme histochemistry. The presence of these structures was related in time with the development of proteinuria. Mice from the C57BL10 strain, which upon infection develop glomerular immune complexes without proteinuria, were examined as well. The results demonstrated that the first endothelial changes, occurring 3-4 weeks after infection, were swelling of endothelial cells containing intracytoplasmic, electron-dense, round structures. These changes were seen prior to the onset of proteinuria, and were not present in glomeruli of mice that did not develop proteinuria. The endothelial granules were shown to contain immunoglobulins and typical lysosomal enzymes, providing evidence for phagocytosis by the glomerular endothelial cells. Liver endothelial cells did not show comparable changes. Thus, local phagocytosis by glomerular endothelial cells is shown to be a specific event in the development of glomerular disease.

A murine model using Heligmosomoides polygyrus and Trypanosoma congolense has been developed for studying the effects of concurrent chronic gastrointestinal nematode and trypanosome infections. Female outbred mice were infected either with 500 infective larvae (L3) of H. polygyrus or with 10(4) bloodstream forms of T. congolense or both. In concurrent infections, animals were dosed with both parasites simultaneously or the trypanosomes were injected 5 or 10 days after the mice were infected with the nematode. The course of infection was monitored by routine parasitological and immunological techniques for 30 days after the H. polygyrus infection. Concurrently infected mice were severely compromised, except when T. congolense was superimposed on a 10-day-old (adult) H. polygyrus infection. In H. polygyrus-infected mice, simultaneous or subsequent infection with trypanosomes did not markedly influence worm establishment or fecundity, but the female worms were slightly stunted. Surviving mice displayed a markedly reduced antibody response to H. polygyrus antigens and a slightly reduced antibody response to T. congolense antigens.

The prevalence of concurrent nematode-trypanosome infections in traditionally reared West African Dwarf sheep and goats in eastern Nigeria was monitored over a 12-month period during 1987-1988. The most prevalent nematodes were Haemonchus contortus and Trichostrongylus colubriformis, which usually occurred together in all nematode infected animals. Their combined prevalence rates ranged from 90 to 100% throughout the year and they accounted for 66 to 98% of the total monthly worm burdens. Of the 107 animals examined 13.6% were infected with trypanosome species comprising Trypanosoma brucei (50%), Trypanosoma congolense (43%) and Trypanosoma vivax (36%). No clear seasonal pattern was observed in the prevalence of concurrent nematode-trypanosome infection but owing to the widespread prevalence of gastrointestinal nematode infections, all trypanosome infected animals were invariably infected with H. contortus and Trichostrongylus colubriformis.

The involvement of endotoxins in Trypanosoma brucei brucei infection in CD-1 mice was investigated by the Limulus amoebocyte lysate (LAL) test. At 7 days post-infection mean serum endotoxin level was elevated by 2.5 times (36.4 pg/ml cf. control 14.25 pg/ml, P < 0.001) and a similar increase was maintained throughout the infection (survival 28-35 days). Purified disrupted parasites contained significant endotoxin activity (mean value 280 pg/mg protein). The mouse infections were also associated with progressive Gram-negative bacteraemia (present in 4 out of 5 infected animals by day 28 p.i.). The increased endotoxin levels may be due to parasite products, the products of intercurrent bacterial infections, other unidentified sources (e.g. from the gut), or a combination of these. It is concluded that the raised endotoxins may be important contributive factors in the pathogenesis of experimental murine trypanosomiasis.

The intensity of parasitaemia, degree of anaemia, blood biochemical changes and live weight gains were measured in two groups of Scottish Blackface sheep infected experimentally with bloodstream forms of Trypanosoma congolense and given either a high or a low protein diet. It was observed that infected animals on a high protein diet tended to develop a higher intensity of parasitaemia than those on a low protein diet. Both groups of infected sheep exhibited similar degrees of anaemia, but the erythropoietic activity, as judged by the increase in mean corpuscular volume and appearance of normoblasts in the circulation, was significantly greater in animals on a high protein diet. The infected animals on a high protein diet gained weight at a similar rate to their uninfected controls, while those on a low protein diet gained significantly less than their controls between 0 and 70 days after infection. Following treatment with the trypanocidal drug isometamidium chloride, both infected groups recovered from the anaemia. However, the rate of recovery was faster in animals on a high protein diet than in those on a low protein diet. It was concluded that high protein intake ameliorates the adverse effects arising from infection, as assessed by the severity of anaemia and weight changes, and also enhances the rate of recovery following chemotherapy.

1. The clinical syndromes of the African trypanosomiasis (also called sleeping sickness in humans) are defined. The basic knowledge on the hypothalamo-anterior pituitary-gonad axis functions is briefly recalled. 2. Hypogonadism caused by the trypanosomes both in men and in women as well as in male and female animals are extensively reviewed in publications over the last two decades as well as on our own very recent works which provided new insights on the physiopathology of the gonadal disorders.

Five trypanotolerant N'Dama (Bos taurus) and five susceptible Boran (Bos indicus) cattle were challenged by tsetse flies infected with Trypanosoma congolense IL 13-E3. These animals had experienced five previous infections with T. congolense, each terminated by drug therapy. Immunoblotting and ELISA were used to determine isotype and specificity of antibody responses to trypanosome invariant antigens. Both IgM and IgG1 were elicited, but the IgG1 responses were directed against a greater diversity of antigens. A 69 kD antigen was the major invariant antigen which elicited IgM antibodies in both breeds, but the N'Damas also responded with high levels of specific IgG1. Analysis of isotypic responses to whole trypanosome extract also revealed lower levels of IgG1 and higher levels of IgM in the Borans than in the N'Damas, suggesting that a dysfunction in the switch from IgM to IgG might occur in infected Boran cattle. A 33 kD antigen appeared to elicit only IgG1. Sera from all five N'Damas and the two Borans which were most resistant to the disease reacted with this antigen prior to and following re-infection. Furthermore, during the primary T. congolense infection in the same animals, anti-33 kD antibodies were detectable in all five trypanotolerant N'Damas, but in none of the five susceptible Borans. Thus, the presence of antibodies to the 33 kD antigen of T. congolense appeared to be associated with a capacity to control the disease.

Strongyle faecal egg output was estimated in N'Dama, Zebu and N'Dama x Zebu crossbred (F1) cattle. N'Dama cattle showed a significantly lower prevalence of strongyle infection, as measured by faecal egg output, than F1 (P < 0.01) and Zebu (P < 0.001) cattle. In strongyle-infected animals, mean egg output was also significantly lower in N'Damas (P < 0.03) than in Zebus. A previous trypanosomiasis infection did not affect the results. The presence of a natural resistance trait to strongyle infection in N'Dama cattle is postulated.

To determine if there is an association between human immunodeficiency virus type 1 (HIV-1) infection and Trypanosoma brucei gambiense sleeping sickness, all incident cases of trypanosomiasis and a control group of blood donors presenting to the same rural hospital in Zaire were tested for anti-human immunodeficiency virus type 1 (anti-HIV-1) antibodies. There was no significant difference in the prevalence of HIV-1 infection between the two groups (7 of 220, [3.2%] for the incident cases and 8 of 388 [2.1%] for the blood donors; P = 0.56). Among the three HIV-1 seropositive incident cases of trypanosomiasis treated with difluoromethylornithine, two (67%) relapsed after treatment compared with four of 39 (10%) HIV-1 seronegative incident cases treated with the same drug (P = 0.05). These findings suggest that at the present time, HIV-1 infection is not having a significant impact on the incidence of T. brucei gambiense sleeping sickness in rural Zaire, but the possibility that incident cases of trypanosomiasis concurrently infected with HIV-1 may be at higher risk of treatment failure warrants further investigation.

The effects of Trypanosoma brucei brucei infection during the first, second or third trimesters of pregnancy in 13 ewes were studied. All infected ewes were anaemic with the anaemia being most severe, moderate and least in ewes infected in the second, third and first trimesters, respectively. Weight loss occurred in all infected ewes but was most severe in ewes infected in the third trimester. Three of the four ewes infected in the first trimester died without aborting while one aborted and later died. Of the four ewes infected in the second trimester, three died without aborting while one lambed and later died. In the third trimester ewes, one aborted, two lambed and all three later died while one died without aborting. None of the lambs was viable. The control ewe lambed normally. The infection resulted in 16.7% abortion, 100% death and 33.3% neonatal deaths. This study demonstrates that T. brucei brucei has a devastating effect on pregnancy irrespective of the trimester of infection.

The interactions between Trypanosoma congolense and Haemonchus contortus infections were studied in N'Dama calves. A total of 38 N'Dama bulls was divided into four groups and each group infected either with H. contortus 1 week after infection with T. congolense or with T. congolense 4 weeks after infection with H. contortus, or with either infection singly. Parasitological (faecal egg counts, parasitaemia), haematological (packed cell volume, white blood cell counts, albumin) and clinical parameters (body weight change, mortality rate) were compared among the various groups. The results showed a reduced prepatent period and a markedly increased pathogenicity of H. contortus infections in animals with a concurrent T. congolense infection. The most harmful combination was a H. contortus infection 1 week after the T. congolense infection which resulted in a progressive and severe anaemia, accompanied by hypoalbuminaemia, increased weight loss and high mortality. The anaemia induced by dual infections showed a low responsiveness to chemotherapy and in several cases supportive treatment did not help recovery. The results also showed that animals with a concurrent T. congolense and H. contortus infection ran a higher risk of succumbing during the infection, and also during 10 weeks following treatment. Although infections with T. congolense alone produced no clinical signs, they were found to significantly reduce the ability of infected animals to mount a normal response to a subsequent H. contortus infection. It was concluded that the increased H. contortus egg excretion observed in animals infected with both parasites might significantly increase the risk of nematode infections and that the reduced prepatent period might necessitate more frequent anthelmintic treatments. These interactions should, therefore, be considered wherever attempts are made to control these two diseases.

Three Boran (Bos indicus) cattle infected with T. congolense IL 1180, and two uninfected control Boran cattle were used to study the effect of trypanosomiasis on the function of the thyroid gland. On a weekly basis, plasma thyroxine (T4) was measured by 125I-radioimmunoassay. Results indicated that T. congolense caused a significant decline in plasma T4 concentration in infected animals.

We investigated the pathogenesis of glomerulonephritis in mice that had been infected with Trypanosoma brucei. Polyclonal B cell activation was evaluated, with special attention to the presence of autoantibodies, which are known to be involved in other models for glomerulonephritis. The BALB/c mice studied developed severe albuminuria. Light-microscopy of the kidneys showed increase of mesangial matrix and thickening of the glomerular capillary walls. Immunofluorescence studies showed immunoglobulins in a mixed linear-granular pattern along the glomerular capillary wall and in the mesangium. Trypanosomal antigens were not found in these aggregates. Electron-microscopy revealed mesangial, subendothelial, and subepithelial electron-dense deposits. During the course of this infection, significant levels of antibodies directed against known nephritogenic renal autoantigens, i.e. GBM, laminin, RTE, and gp330, were measured in serum and glomerular eluates. These findings led us to conclude that mice infected with T. brucei and treated with diminazene aceturate develop an autoimmune-mediated glomerulonephritis, characterized by mesangial, subendothelial, and subepithelial immune aggregates. This murine model seems to offer a useful tool for the study of immunological aspects of polyclonal B cell activation in infection-related glomerular disease.

The purpose of the study was to assess the long-term effects of melarsoprol on awakening electroencephalogram (EEG) in 18 patients at the meningo-encephalic stage of human African gambiense trypanosomiasis. Electroencephalographic data were taken prior to then 1 and 3 months after therapy. Before treatment EEG tracings showed important abnormalities (delta bursts organized in a more or less periodic fashion); 1 and 3 months after treatment a clear improvement was observed in 10 patients; however, it was unusual that the EEG completely returned to the normal pattern and a case of relapse was noted 3 months after the end of therapy. As indicated by persistence of the EEG abnormalities, several patients were unresponsive and one of them reacted negatively to melarsoprol. The use of regular EEG investigations as a means of long-term supervision of patients with trypanosomiasis is discussed.

148 one-year-old N'Dama cattle, progeny of 29 sires, were exposed for 92 days to a medium natural tsetse-trypanosome challenge in Gabon, Central Africa. Matching health and performance data were recorded on 11 occasions. Average packed red cell volume percent (PCV) and lowest PCV reached during the period were evaluated as measures of ability to control the development of anaemia. Attempts were made to systematically control other possible causes of anaemia. In animals detected as parasitaemic, those with above average average PCV values or above average lowest PCV reached had 34% and 35% respectively higher daily weight gains than those with below average. Even when not detected as parasitaemic, those with above average average PCV values or above average lowest PCV reached had 14% and 12% respectively higher gain indicating that a proportion of these animals actually were parasitaemic. When all environmental and parasitaemia information was taken into account, the heritability of growth, average PCV and lowest PCV reached was 0.39 +/- 0.31, 0.64 +/- 0.33 and 0.50 +/- 0.32 respectively. The genetic correlation between average PCV and growth was 0.70 +/- 0.42 and between lowest PCV reached and growth was 0.28 +/- 0.55. While the standard errors are large, the higher heritabilities of PCV measures compared to animal growth and the positive genetic correlations between PCV and growth do indicate an opportunity for selection on PCV when animals can be detected as parasitaemic. All heritabilities and genetic correlations increased in size when parasitaemia information was utilized in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sprague-Dawley rats were infected by intraperitoneal injections of a strain of Trypanosoma brucei brucei. This parasite spreads early to areas in the nervous system which lack a so-called blood-brain or blood-nerve barrier including spinal ganglia. Signs of sensory disturbance in the form of hyperalgesia were observed already seven days post infection, using a hot plate analgesimeter. The sensory disturbances progressed and the rats started to lose weight about 3 weeks post infection, and died about one week later. Immunohistochemistry showed no reduction in density of calcitonin gene-related peptide or substance P immunoreactive fibres in the skin or spinal cord. It is suggested that the sensory disturbances are mediated via release of kinin or interleukin-1 which are known as potent hyperalgesic agents. The hot plate analgesimeter is a simple and reliable method and may be useful in experimental trypanosomiasis to test drugs developed to combat this disease.

Authors are reporting results from 3 control-case surveys carried out in sleeping sickness foci in Cameroon, Central African Republic and Congo. HIV seroprevalence rates are comparable among sleeping sickness patients and trypanonegative control persons. These results lead towards the absence of inter-relationships between sleeping sickness and retroviral infection.

A case is reported of a 32-year-old traveller with loiasis, schistosomiasis and African trypanosomiasis. The patient had been working in oil exploration in Nigeria and Gabon and presented with Calabar swellings and carpal tunnel syndrome. Serology for all 3 diseases was positive but microfilariae of Loa loa and ova of schistosomiasis were not found. Treatment with diethylcarbamazine and praziquantel was given for loiasis and schistosomiasis respectively. Trypanosomes were isolated from a lymph node aspirate only after repetition of the procedure 2 months later and the patient was treated with suramin. He developed a drug induced nephritis and was then treated successfully with alpha-difluoromethylornithine. There is a discussion of the difficulties encountered making these diagnoses in Europeans particularly where there are atypical clinical features. The risks of rural work in West Africa are noted and the importance of considering all parasitic diseases relevant to the travel/occupational history is emphasised.

The effects on the fertility of small East African male goats of intravenous infection with Trypanosoma (t) (b) evansi were studied. Six infected bucks developed erratic, low but persistent parasitaemia, the packed cell volume dropped gradually but significantly (p less than 0.001) and they became emanciated. Half of these bucks developed clinical orchitis. Two bucks died of the disease during the experiment. Semen from all the infected bucks deteriorated in quality and quantity and those with clinical orchitis became totally aspermic. Spermatozoal abnormalities and the number of dead spermatozoa rose significantly. Later in the disease, the testicles of the infected bucks atrophied. Histologically, the testicles from the infected animals became devoid of spermatozoa, the testicular blood vessels contained microthrombi and there was infiltration of inflammatory cells. Subsequently, diffuse calcification set in, with calcium deposits obliterating most of the seminiferous vesicles and ducts and also the epididymal ducts.

One hundred and forty six calving interval records were built up from 64 N'Dama cows maintained for 3.5 years under a high natural tsetse challenge in Zaire. Matching health and performance data were recorded monthly to allow simultaneous evaluation of the effects of different criteria of trypanotolerance represented by time detected parasitaemic, parasitaemia score and packed red cell volume percent (PCV) on reproductive performance, calf weaning weight and cow productivity. Control of development of anaemia, measured by PCV value during trypanosome infection, had the major effect on all three performance traits. The repeatability of this criterion (0.33) was almost equal to that of calf weaning weight, indicating PCV measurement might be suitable for identification of more trypanotolerant animals. Simultaneous evaluation of the relative effects of control of development of anaemia in both the pre-weaner calf and its dam, on calf performance, suggested that its measurement in an animal might be feasible at an early post-weaner stage. Guidelines for work to develop practical field tests for trypanotolerance involving post-weaners maintained for varying lengths of time in high natural challenge situations are suggested.

In three separate tests in 1987, 1988 and 1989, a total of 436 one-year-old N'Dama cattle were maintained for 12, 18 and 24 weeks under a medium natural tsetse-trypanosome challenge in Gabon, Central Africa. Matching health and performance data were recorded on 4, 10 and 13 occasions respectively, to allow simultaneous evaluation of the effect of different criteria of trypanotolerance on animal performance. Under trypanosome prevalences of 25, 31 and 9%, respectively, ability to control the development of anaemia had a very major effect on daily weight gain, four times that of the ability to control parasitaemia, while previous exposure to trypanosome infection from birth to one year had no effect. Anaemia control, measured by average packed red cell volume percent (PCV) over the test period or by lowest PCV reached, was more closely associated with animal performance than when measured by average PCV when detected as parasitaemic. Above average PCV values in the first two measures resulted in a 44% to 48% superior daily weight gain over below average PCV values. PCV post-test recovery was shown to be rapid following a single trypanocidal drug treatment. In practice, it appeared that a suitable field test would be where natural infection could be effected as early in the test as possible and anaemia control measurements carried out over 6 weeks of detected parasitaemia. A field test would become even more feasible if satisfactory correlation could be obtained between the results of natural infection and those of an experimental alternative.

Two recently isolated stocks of Trypanosoma brucei gambiense of human origin gave rise to a moderate to severe proliferative or membranoproliferative glomerulonephritis in 40 or 44 NMRI and C57BL/6J mice infected for 7-22 weeks. Extensive granular deposits of C3, IgG1 and IgG3 were found in the mesangium, together with smaller quantities of IgG2a, IgG2b, and IgM. No trypanosomal antigen could be detected in the deposits though specific anti-trypanosoma antibodies were found in kidney eluates. By electron microscopy, a conspicuous proliferation of mesangial and endothelial cells was observed and electron-dense deposits were seen in a mesangial and subepithelial localization. With one of these trypanosome stocks, four of seven Wistar rats infected for 9-15 weeks developed morphologically similar glomerular lesions. Four other trypanosome stocks did not evoke renal alterations in 17 other rats infected for 13-56 weeks. Experimental infection in mice or rats appears to be a suitable model for the study of renal disease in chronic African sleeping sickness.

In all of four patients with African trypanosomiasis, thrombocytopenia was present on admission to hospital or developed during the course of the illness. One patient with severe thrombocytopenia died following gastrointestinal haemorrhage shortly after admission to hospital. Kinetic studies in the other three patients showed marked pooling of platelets in the spleen in all, but severe shortening of platelet life-span in only one. Evidence of disseminated intravascular coagulation (DIC) was found in 3 patients, 2 of whom received heparin therapy. These findings provide evidence that thrombocytopenia is a feature of African trypanosomiasis and is due mainly to hypertrophy of the reticuloendothelial system which accompanies the infection. In some patients immune damage to platelets or platelet consumption as part of DIC may be an additional factor contributing to the thrombocytopenia.

Experimental infection in rabbits with a human isolate of Trypanosoma rhodesiense led to the formation of circulating immune complexes and glomerulonephritis. Granular deposits of C3 and lesser amounts of IgM and IgG were seen deposited in the glomeruli in a primarily mesangial pattern. The glomeruli became hypercellular beginning on day 7. This was associated with diffuse swelling and vacuolation of endothelial cells with focal loss of fenestrae, as well as vacuolation of mesangial cells processes protruding into the capillary lumina. The hypercellularity became maximal on day 21 and was accompanied by proteinuria and increased tubular hyaline droplets. The hypercellularity was in large part due to the accumulation of monocytes as demonstrated by nonspecific cytoplasmic esterase stains. Counts of the number of monocytic cellular profiles per glomerulus showed that maximal numbers were reached on the 21st day of the infection. Ultrastructural examination confirmed the presence of monocytes within capillary lumina and macrophages within mesangial regions. Electron-dense deposits were rarely seen by transmission electron microscopy, and the heavy granular deposits of IgM and C3 observed by immunofluorescence were attributed to ingested proteins within macrophages. This study implies an active role for monocytes and macrophages in immune complex-mediated glomerulonephritis.

Rats infected with Trypanosoma brucei rhodesiense developed anemia, thrombocytopenia, and hypocomplementemia. Anemia, thrombocytopenia, and sharp reductions in parasitemia were associated with elevated titers of cold-active hemagglutinin, antibody to fibrinogen/fibrin-related products, and immunoconglutinin. Depletion of lytic complement, prolonged partial thromboplastin times, and presence of fibrin monomers in the blood occurred at the time anemia and significant elevations in precipitable immune complexes were observed. Terminally, consumption of immunologic factors coincided with accelerated partial thromboplastin times. At death, convulsions and hemoptysis with labored breathing suggested that the animals died of respiratory failure and that disseminated intravascular coagulation may have occurred. It is suggested that microthrombiosis might have resulted from the immunologic interaction of complex-coated blood cells with immunoconglutinin and contributed to the terminal disease signs.