Effect of anti-ganglioside antibody in experimental Trypanosoma brucei infection in mice

The effect of antibody against ganglioside antigen on Trypanosoma brucei parasites was examined in vitro and in vivo using anti-ganglioside GM1 (AGM-1) monoclonal antibody. The antibody showed complement-dependent cytotoxicity against T. brucei with mouse complement. Furthermore, mice given AGM-1 were challenged intraperitoneally with T. brucei. Although all non-treated control mice died within six days after infection, all of AGM-1-injected mice had survived by six days post-infection. These data suggest that antibody against ganglioside antigen on T. brucei has potential in protection against T. brucei infection.     

Some plasma biochemical changes in experimental Trypanosoma brucei infection of Sokoto Red goats.

Plasma biochemical changes were studied for 8 consecutive weeks in Sokoto Red goats experimentally infected by intravenous route injection of 1.6 x 10(7) Trypanosoma brucei. The strain 8/18 was highly infective. The mean packed cell volume significantly decreased from 1 to 8 weeks post-infection (PI) at P < 0.05. During this period, the mean plasma total bilirubin concentrations significantly increased (P < 0.05). The mean plasma direct and indirect bilirubin concentrations significantly increased from 2 to 8 weeks PI (P < 0.05). The mean plasma albumin concentrations did not vary significantly (P > 0.05), but the mean total plasma proteins and mean plasma globulin concentrations significantly increased between 5 and 8 weeks post infection (P < 0.05). There were no significant changes in the mean plasma bicarbonate, creatinine and cholesterol concentration (P > 0.05).     

Haematology of experimental Trypanosoma brucei gambiense infection. II. Erythrocyte and leucocyte changes.

Chronic Trypanosoma b. gambiense infection of rabbits induced mild anaemia which was initially macrocytic normochromic, but became later microcytic hypochromic. Moderate anisocytosis and poikilocytosis were evident from 14 days post infection (p.i.). Nucleated red cells which were observed prior to the infection (normal feature of rabbits) declined in number as the infection progressed. Leucocytosis with neutrophilia, eosinophilia, monocytosis and terminal lymphopaenia were also observed. The main changes in the morphology of leucocytes were the presence of atypical lymphocytes as well as increased levels of band neutrophils in the peripheral circulation. It is concluded that the main erythrocytic and leucocytic changes in the T.b. gambiense infection were mild anaemia which was terminally microcytic hypochromic and transient leucocytosis due to neutrophilia and monocytosis.     

Epididymal and testicular lesions in rams following experimental infection with Actinobacillus seminis

AIM: To investigate and assess the epididymal and testicular lesions in rams up to 44 days after inoculation with Actinobacillus seminis via various routes. METHODS: Forty-four young (18-24 months old) rams were randomly divided into nine test and two control groups (n=4 per group). The test rams were infected by installation, drenching or injection of A. seminis organisms cultured for 24 h in a brain-heart infusion (BHI) broth containing 2.3 x 10(9) cells/ml, via the following nine routes: intra-epididymal (1 ml), intravenous (3 ml), intra-urethral (3 ml), intra-preputial (3 ml), vas deferens (1 ml), intramuscular (3 ml), oral (10 ml), intranasal (3 ml), and intra-conjunctival (3 drops). All test rams were necropsied 9-44 days post-inoculation (p.i.). Control rams were subdivided into in-contact and non-contact groups and necropsied at 45 and 46 days p.i., respectively. Thin tissue sections were examined for histopathology. RESULTS: Gross lesions were evident only in rams inoculated intra-epididymally. Epididymides on the inoculated side were two to three times larger than those on the un-inoculated side, and the testes attached to the inoculated epididymides were also enlarged. Fibrinopurulent periorchitis and tunica vaginalitis were seen in three rams and atrophy in one. Microscopically, epididymitis was present in 17 (47%) rams, the highest incidence being in the cauda, followed by the caput and the corpus epididymis. Seminiferous tubular degeneration with areas of lymphocytic infiltration were seen in four rams: three inoculated via the cauda epididymis and one via the urethra. No epididymal and/or testicular lesions were seen in rams inoculated via the nasal and conjunctival routes. CONCLUSIONS: Injection of A. seminis in young rams by all routes except intra-conjunctival and intranasal resulted in epididymitis, predominantly in the cauda epididymis. Development of lesions in the reproductive tract following non-genital routes of inoculation supports earlier suggestions that non-venereal transmission of genital actinobacillosis occurs. This study confirmed the predilection of A. seminis for the epididymis, especially the cauda.     

Effects of infection with Trypanosoma brucei brucei on different trimesters of pregnancy in ewes.

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.     

Relapse infection after chemotherapy in dogs experimentally infected with Trypanosoma brucei brucei

Studies on relapsing Trypanosoma brucei brucei infections in dogs after Berenil treatment revealed that the first relapse occurred 13 to 64 days after chemotherapy and 36 to 79 days after inoculation. A second relapse infection was observed in two dogs 43 and 60 days after a second Berenil treatment. During the aparasitaemic period following chemotherapy in four dogs, successful transmission (as evidenced by subsequent parasitaemia) following the intraperitoneal inoculation of homogenate of brain from two of the dogs into recipient rats was obtained. Transmission with blood collected just before the animals were sacrificed was, however, negative. Hornogenates of other organs (liver, spleen, eyes, testes, kidneys, heart and lymph node) were also non-infective. One dog inoculated with relapsed trypanosomes and treated with Berenil soon after showing parasitaemia was completely cured of the infection. It was considered that the brain is the source of relapse in T b brucei infection after Berenil therapy and that the relapse was not due to drug resistance.     

Effect of Trypanosoma vivax infection on semen characteristics of Yankasa rams.

Twelve Yankasa rams aged between 2 1/2 and 3 years with good semen characteristics were used in this 15-week study. Six rams were infected with Trypanosoma vivax, while six served as controls. The infected rams developed chronic trypanosomosis accompanied by fluctuating pyrexia, lethargy, anaemia, scrotal oedema and cachexia. There was a drastic and progressive deterioration in semen quality in all infected rams manifested by a decrease in volume or cessation of semen production, oligozoospermia, a sharp decrease in progressively motile sperm, elevated numbers of dead (eosinophilic) sperm and 100% morphological abnormalities of sperm in most animals. The rams were all deemed unfit for breeding by 3 weeks post-infection. Uninfected rams were healthy and had good semen characteristics throughout the investigation. The results show that rams infected with T. vivax may become infertile within a short interval due to rapid deterioration of semen characteristics and this trypanosome species may be an important causative agent of infertility in endemic areas.     

Pathogenicity of Trypanosoma brucei brucei in experimentally infected pigs.

An experimental infection of 4-to 5-month old pigs with a stock of Trypanosoma brucei brucei resulted in a high parasitaemia, anorexia, pyrexia and a decline in the packed cell volume by one third. Nervous sign of circling and wobbling of the hind legs occurred in one of the pigs which at necropsy revealed a very severe meningo-encephalitis and the presence of trypanosomes in the brain. These results confirm that T. b. brucei might cause a severe disease in pigs.     

Flurbiprofen and immunosuppression of Trypanosoma brucei infection in the goat

Goats infected with Trypanosoma brucei and treated with the non-steroidal anti-inflammatory agent flurbiprofen, showed a marked increase in parasitaemia, followed in one of the four goats by death. The in vitro response to mitogens of peripheral blood lymphocytes and separated T- and B-lymphocytes from healthy goats treated with flurbiprofen was normal when compared with non-treated animals. T. brucei-infected goats, not treated with flurbiprofen, showed a marked immunosuppression which was mainly localized in the B-enriched lymphocyte fraction. A combination of T. brucei infection and treatment with flurbiprofen led to even more suppression, because the T-lymphocyte function was also suppressed. It is concluded that flurbiprofen first causes a rise in the parasitaemia and that this high parasitaemia is responsible for the observed immunosuppression.     

DL-alpha-difluoromethylornithine (DFMO)-Berenil combination: therapeutic and prophylactic activity against Trypanosoma brucei brucei infection in mice.

The therapeutic and prophylactic activity of difluoromethylornithine (DFMO) (2% in drinking water for 4 days) and Berenil (7 mg/kg live weight intraperitoneally) combination was investigated in mice infected with Trypanosoma brucei brucei. Using a previously described mouse model of the African trypanosomosis of the central nervous system, it was demonstrated that the combination was curative and acted synergistically. However, if used prophylactically it had no advantage over Berenil alone.     

Comparative efficacy assessment of pentamidine isethionate and diminazene aceturate in the chemotherapy of Trypanosoma brucei brucei infection in dogs

The chemotherapeutic efficacy of diminazene aceturate (Berenil)--a standard veterinary trypanocide and pentamidine isethionate (PMI)--a human trypanocide was compared in dogs experimentally infected with Trypanosoma brucei brucei. Also, the activities of the drugs on some serum liver enzymes were evaluated before and after treatment to ascertain the relative safety of the drugs. Fifteen local dogs (mongrels) were used for the study. Three of the dogs were uninfected controls, and twelve were infected with a stock of T. brucei brucei. Three of the infected dogs were untreated controls, three were given diminazene aceturate (DA) at 7 mg/kg body weight intramuscularly (i/m), another three received pentamidine isethionate (PMI) at 4 mg/kg i/m on days 14, 17, 19, 27, 29, and 31 post infection (PI) and the remaining three dogs were also given same dose of PMI on days 14, 16, 18, 20, 22, 24 and 26 PI. Both trypanocides effectively cleared the parasites from the blood of the infected treated dogs. However, the infection subsequently relapsed at day 42 PI in one of the dogs in the DA treated group which later died at day 70 PI. Relapse infection was not recorded with the PMI treated groups although two dogs died in the PMI treated group II (treatment at days 14, 17, 19, 27, 29, and 31 PI) without showing relapsed parasitaemia. The packed cell volume (PCV), red blood cell (RBC) count, and haemoglobin (Hb) level which decreased significantly following infection, were reversed by the trypanocidal treatment. The reversal in the red cell values was faster in the PMI treated groups than in the DA treated group. The serum alkaline phosphate (SAP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels increased following infection and drug administration. The increase in the enzyme levels was greater in the DA treated groups than PMI treated groups. It was thus concluded that PMI given at 4 mg/kg i/m at days 14, 16, 18, 20, 22, 24, and 26 PI constituted a safe and efficient trypanocide and exhibited a superior trypanocidal action than DA in T. brucei brucei infected dogs.     

Adrenal and thyroid dysfunctions in experimental Trypanosoma congolense infection in cattle.

Severe pathological changes were observed in the adrenal and thyroid glands of Zebu (Bos indicus) heifers infected with Trypanosoma congolense. In the adrenal glands, severe inflammatory changes characterised by mononuclear cellular infiltration in the subcapsular areas, zona glomerulosa, zona fasciculata and zona reticularis were observed. In addition, there were hyperaemia, haemorrhage and hyperplasia resulting in increased adrenal weight in the two heifers slaughtered on Days 50 and 70 post-infection (p.i.). In the medullary areas of these two heifers, there was only mononuclear cellular infiltration. In the two heifers slaughtered on Day 113, localised mononuclear cellular infiltration was observed in addition to cortical cell depletion and fibrosis, resulting in reduced adrenal weight when compared with the controls. In the thyroid glands of the infected heifers, gross enlargement of the follicles filled with pale staining colloids were observed in association with squamous metaplasia of the follicular epithelium and fibroplasia. Serum cortisol concentrations showed an appreciable but non-significant increase (P less than 0.05) between Weeks 2 and 6 p.i. in the infected heifers (5.6 +/- 0.86 ng ml-1 vs. 4.4 +/- 0.34 ng ml-1) when compared with the uninfected controls or the pre-infection level. Thereafter, cortisol levels declined though non-significantly throughout the rest of the study. However, there was a steady increase towards normal levels from Week 12 p.i. until the end of the experiment. Changes in the basal serum concentrations of thyroxine (T4) were also measured weekly. There was a progressive decrease in the levels of T4 from the third until the 11th week p.i., when the decrease became significant (P less than 0.05) and remained so until the 16th week when the experiment ended.