Parasitaemic Wave Research Articles

Comparative pathogenicity of Trypanosoma brucei rhodesiense strains in Swiss white mice and Mastomys natalensis rats

We evaluated Mastomys natelensis rat as an animal model for Rhodesian sleeping sickness. Parasitaemia, clinical and pathological characteristics induced by T. b. rhodesiense isolates, KETRI 3439, 3622 and 3637 were compared in Mastomys rats and Swiss white mice. Each isolate was intra-peritonially injected in mice and rat groups (n=12) at 1×104 trypanosomes/0.2mL. Pre-patent period (PP) range for KETRI 3439 and KETRI 3622-groups was 3–6 days for mice and 4–5 days for rats while for KETRI 3637-infected mice and rats was 5–9 and 4–12 days, respectively. Pairwise comparison between PP of mice and rats separately infected with either isolate showed no significant difference (p>0.05). The PP’s of KETRI 3637-infected mice were significantly (p>0.01) longer than those infected with KETRI 3439 or KETRI 3622, a trend also observed in rats. The second parasitaemic wave was more prominent in mice. Clinical signs included body weakness, dyspnoea, peri-orbital oedema and extreme emaciation which were more common in rats. Survival time for KETRI 3439 and 3622-infected groups was significantly (p<0.05) longer in mice than rats but similar in KETRI 3637-infected groups. Inflammatory lesions were more severe in rats than mice. All mice and KETRI 3622-infected rats had splenomegaly, organ congestion with rats additionally showing prominent lymphadenopathy. KETRI 3439-infected rats showed hemorrhagic pneumonia, enteritis with moderate splenomegaly and lymphadenopathy. KETRI 3637-infected rats had the most severe lesions characterized by prominent splenomegaly, lymphadenopathy, hepatomegaly, enlarged adrenal glands, organ congestion, generalized oedemas, gastroenteritis, pneumonia and brain congestion. KETRI 3637-infected Mastomys is a suitable model for studying pathophysiology of HAT.

Studies on effects of lactose on experimental &lt;i&gt;Trypanosoma vivax&lt;/i&gt; infection in Zebu cattle. 2. Packed cell volume

The ability of intravenously administered lactose in normal saline to prevent a decline in packed cell volume (PCV) during experimental trypanosomosis was studied in Zebu cattle. During the lactose infusion period, the PCV was stable up to Day 5 post-infection (p.i.) in a lactose-infused group, compared to that in an uninfused group in which the PCV dropped significantly (P < 0.05) as shown by the values of cumulative percentage change. Furthermore the mean rate of change in PCV was significantly (P < 0.05) higher in the uninfused group relative to the lactose-infused group during the same period. While the PCV fell markedly in the lactose-infused group a day after lactose infusion was stopped (Day 13 p.i.), subsequent PCV values were significantly (P < 0.05) higher compared to those in the uninfused group, up to the end of experiment on Day 17 p.i. However the mean rates of change in PCV did not vary significantly (P > 0.05) between the groups during the period in which lactose infusion was stopped. The mean levels of parasitaemic waves and parasitaemia were higher, more prolonged and more frequent in the lactose-infused group. It was inferred that the lactose was able to prevent an early onset of anaemia in the Trypanosoma vivax-infected Zebu cattle.

Studies of infectivity and pathogenicity of an isolate of Trypanosoma evansi in Yankasa sheep

The course of experimental infection and pathogenicity of an isolate of Trypanosoma evansi were investigated using eight infected and six uninfected control Yankasa sheep. The sheep were each infected intravenously via the jugular vein with approximately 2.0 × 10 6 T. evansi parasites. The effects of the parasite on body temperature, packed cell volume (PCV), haemoglobin, erythrocytes, total protein, were monitored three times a week for approximately 9 weeks. Body weights were determined once every week for the duration of the experiment. The results showed that all the infected sheep were positive for the parasite. The prepatent period varied between 3 and 6 days. T. evansi produced parasitaemic waves at an average of 8.3 days interval. Two distinct forms of the disease were produced namely, acute (4–14 days postinfection), and chronic (43–59 days postinfection). Anaemia was a distinct feature of the disease. While the mean rectal temperatures were significantly elevated ( P < 0.05), the mean values of the haematological parameters of the infected sheep dropped significantly ( P < 0.05) compared to the preinfection levels. Observed clinical signs included pale mucous membrane, epiphora, loss of appetite, emaciation, dullness and rough hair coat together with fluctuating pyrexia which in most cases coincided with rise in parasitaemia. It is suggested that the isolate of T. evansi is pathogenic for Yankasa sheep.

Artificially induced Trypanosoma brucei brucei infection in Lagune and Borgou cattle in Benin

Lagune ( n = 10) and Borgou ( n = 10) cattle of Benin were inoculated subcutaneously with Trypanosoma brucei brucei AnTat, 1.1E. Clinical signs, packed cell volume (PCV), parasitaemia, specific trypanolytic antibodies and haemolytic complement were monitored to evaluate the between-and-within breed variations. All the animals showed only transitory symptoms with clinical recovery within 20 days post infection. Infected animals showed a moderate drop in PCV after 5–10 days of infection. The drop in PCV at day 20 was 2.9 ± 2.7% for Borgou and 1.2 ± 1.8% for Lagune. Except two animals of Borgou breed, all animals developed detectable parasitaemia. Two peaks of parasitaemia, the first on day 5–6 and the second on day 9–10 post infection, were observed. Parasitaemia persisted for 25 days in two Borgou and one Lagune cattle. There were large individual variations in PCV and parasitaemia. AnTat 1.1 specific trypanolytic antibodies were detected from day 6–7 in all animals, except one Borgou and they persisted until the end of observation on day 30. A drop in serum haemolytic complement occurred corresponding to the first parasitaemic waves. After day 15, complement level was restored rapidly largely exceeding the initial values of day 0. The results indicate that all the artificially infected individuals belonging to the Borgou breed as well as to the better known Lagune breed are tolerant to Trypanosoma brucei brucei infection.

Comparison of the effects of immune killing mechanisms on Trypanosoma brucei parasites of slender and stumpy morphology

Trypanosoma brucei slender forms predominate over stumpy forms as the parasite population grows but at the peak of a parasitaemic wave and during remission of infection stumpy forms predominate. To determine whether this change in predominance might be caused by selective killing of slender forms, the fates of slender and stumpy form trypanosomes in two in vitro assays of immune-mediated killing were compared. Parasite populations in which > 90% of cells were of slender morphology were observed to be killed by antibody-dependent complement-mediated lysis approximately five times faster than populations in which < 15% of cells were slender and most were of intermediate or stumpy morphology. Quantification of the relationship between the proportion of slender forms in the population and the rate of lysis indicated that slender forms were killed approximately 7.3 times faster than other forms. In an opsonization assay, no differences were observed between slender and stumpy forms in the extent to which they attached to macrophages in an antibody-dependent manner. These results suggest that the change in proportions of slender and stumpy forms at the peak of a parasitaemic wave results from slender forms being more susceptible to complement-mediated killing as the antibody response develops.

Peripheral blood leucocytes subpopulation dynamics during Trypanosoma congolense infection in Boran and N'Dama cattle: an analysis using monoclonal antibodies and flow cytometry.

A panel of monoclonal antibodies (MoAb) with specificities for bovine leucocyte subsets were used in conjunction with routine haematological procedures to analyse sequential changes in peripheral blood leucocyte populations during the course of tsetse fly-transmitted Trypanosoma congolense infection in trypanotolerant N'Dama and trypanosusceptible Boran cattle. Subsequent to the first parasitaemic wave, the N'Dama cattle maintained packed cell volumes (PCV) above 22 and lower levels of parasitaemia than Boran throughout the 160 days of the experiment. In contrast, the Borans developed severe anaemia and required curative drug therapy (i.e., PCV dropped to less than 15) by 55 days (range: 22-55 days) post infection. There were significant (P less than 0.05) decreases in total white blood cells and total lymphocytes from pre-infection levels to the first peak of parasitaemia (day 16 post-infection) in both groups. Flow cytometric analyses using MoABs revealed that this change was due to an absolute decrease in T cells expressing BoT2 and either BoT4 or BoT8, surface immunoglobulin M-positive (sIgM+) B cells, and null cells which did not express T cell, B cell or monocyte markers. During this period there was significant variation over time, but no overall increase or decrease, in the number of cells expressing class II major histocompatibility (MHC) molecules or monocyte markers, or in the number of circulating neutrophils or eosinophils. The BoT4/BoT8 ratios were significantly (P less than 0.01) increased in both groups of infected animals at the first peak of parasitaemia. After day 22 in the infected N'Damas and in the Borans which required drug therapy, there was a leucocytotic response characterized by an increase in the total number of B cells, T cells, and null cells. Prior to infection and throughout the course of the experiment N'Dama cattle had significantly (P less than 0.01) higher numbers of B cells and null cells than Boran.

Regulation of parasite-specific antibody responses in resistant (C57BL/6) and susceptible (C3H/HE) mice infected with Trypanosoma (trypanozoon) brucei brucei.

After infection with 10(3) T. brucei GUTat 3.1, C57BL/6 mice produced antibody responses and controlled the first parasitaemic wave whereas C3H/He mice did not. The inability of C3H/He mice to control parasitaemia resulted from an impaired ability of parasite-induced antibody-containing cells to secrete immunoglobulin. Antibody-containing cells in infected C3H/He mice regained the ability to secrete antibody within 24 h after trypanosome elimination by treatment with Berenil, suggesting that the block in antibody secretion was maintained by living parasites or short-lived components of degenerating parasites. Infected C3H/He mice also had an impaired ability to produce a rabbit erythrocyte-specific antibody response on challenge with rabbit erythrocytes and this response recovered when parasites were eliminated from the blood 24 h before analysis. It was not possible to inhibit secretion of antibody by rabbit erythrocyte-induced plasma cells either by incubating them with serum from infected C3H/He mice or by injecting large numbers of living trypanosomes into C3H/He mice already responding to rabbit erythrocytes. The process leading to failure of parasite and rabbit erythrocyte-induced antibody-containing cells to become high rate antibody-secreting cells was not identified but did not appear to correlate with any obvious change in the intra-cellular morphology of the antibody-containing cells.

Effect of trypanocides on jugular concentration of Trypanosoma congolense in the West African dwarf sheep

The effects of various trypanocides on parasitaemia was investigated in sheep experimentally-infected with Trypanosoma congolense strain 58/98. Intravenous injection of Berenil at the height of the first parasitaemic wave increased jugular parasite concentration by 12 and 16 times at the 9th and 20th minute post-treatment, respectively. With Pentamidine, maximum counts were 5.0–8.6 times zero-time concentration during the same periods. Peak effects of Samorin, Novidium and Ethidium were observed between the 60th and 90th minutes after drug administration and were 9.5, 6.3 and 3.5 times initial values, respectively. Injection of trypanocides resulted in double peaks of parasitaemia in which the second was usually higher than the first, except with Antrypol and Germani which had no significant effect on parasitaemia. The amplitude, but not the onset of the increase in parasitaemia in sheep, was found to be related to the therapeutic efficacy of the trypanocides in the treatment of Trypanosoma congolense infection in rats. Animals treated with the diamidines (Berenil and Pentamidine) exhibited apparent parasitologic cure of infection in sheep two to four days after treatment. However, administration of any of the drugs one week after the first treatment resulted in flushing of cryptic trypanosomes into the jugular vein and counts as high as 7.63 × 10 3 μl −1 were observed within ten minutes with Berenil. It is suggested that besides their therapeutic use, the diamidines may be of value in the parasitologic diagnosis of sub-patent trypanosomiasis due to Trypanosoma congolense.

Variation in erythrocyte surface and free serum sialic acid concentrations during experimental Trypanosoma vivax infection in cattle

Erythrocyte surface and free serum sialic acid concentrations were determined during experimental Trypanosoma vivax infection in cattle. All infected calves developed mild trypanosomiasis, with significant decreases in mean packed cell volume occurring 15, 16, 20, 22 and 24 days after infection. The anaemia was preceded by significant decreases in mean erythrocyte surface sialic acid concentrations on days 7, 13 and 14, with yet another significant decrease on day 31 after infection. These decreases in erythrocyte surface sialic acid concentrations coincided with the parasitaemic waves. Free serum sialic acid concentration, however, showed an increase, though non-significantly, on day 8, which coincided with both a decrease in erythrocyte surface sialic acid and the initial parasitaemic wave. It is postulated that the early anaemia observed in infected animals may be attributable to the activities of the circulating trypanosomes which produce neuraminidase which, in turn, cleaves off surface sialic acid, thus rendering the erythrocyte more prone to phagocytosis by the recticuloendothelial system.