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PubMed1974

Thrombocytopenia in experimental trypanosomiasis.

The effect of experimental trypanosomiasis on coagulation was studied because a patient in this hospital with Rhodesian trypanosomiasis developed thrombocytopenia with disseminated intravascular coagulation. Rats injected intraperitoneally with this strain of Trypanosoma rhodesiense consistently developed trypanosomiasis and severe thrombocytopenia without changes in hematocrit or concentration of fibrinogen or fibrin split products. At the time of 50% mortality (4-5 days) mean platelet counts per cubic millimeter of infected rats were 18,000+/-9,000 (+/-2 SEM) compared to 1,091,000+/-128,000 in uninfected controls. In vitro, concentrated trypanosomes and trypanosomefree supernates of disrupted organisms added to normal rat, rabbit, or human blood produced platelet aggregation within 30 min. This platelet aggregation was not blocked by inhibitors of ADP, kinins, or early or late components of complement. In vivo thrombocytopenia also occurred in infected rabbits congenitally deficient in C6 and in infected, splenectomized rats. Although the aggregating substance obtained from disrupted trypanosomes is heat-labile, it is active in the presence of complement inhibitors, suggesting that this trypanosomal product may be a protein enzyme or toxin. Since the phenomenon is independent of immune complexes, complement, ADP, and kinins, it appears to represent a new mechanism of microbial injury of platelets and the induction of thrombocytopenia.

Adenosine↗

PubMed2004

Bovine trypanosomiasis in south-western Uganda: packed-cell volumes and prevalences of infection in the cattle.

Following confirmed cases of trypanosomiasis ('nagana') and reports of trypanosome-attributable deaths among local cattle, a cross-sectional study was undertaken to determine the prevalence of bovine infection with trypanosomes in south-western Uganda. Cattle from 10 different localities were checked by the microscopical examination of wet bloodsmears and thin, stained bloodsmears, and by blood centrifugation followed by the examination of the resultant buffy coats. Of the 1309 cattle investigated, 6.42% (5.56% and 7.26% of those from the Mbarara and Mubende districts, respectively) were found to be infected. Of the positive animals, 71 (84.5%), 11 (13.1%) and two (2.4%) appeared to be infected with Trypanosoma vivax only, T. congolense only and both T. vivax and T. congolense, respectively. The prevalence of infection with T. vivax was significantly higher than that with T. congolense (P<0.001). The mean packed-cell volumes (PCV) for the trypanosome-positive animals were lower than those for the trypanosome-negative, whether the cattle considered were all those investigated (22.3% v. 29.0%; P<0.001) or just those from the Mbarara (22.8% v. 28.2%) or Mubende (21.5% v. 29.7%) districts. South-western Uganda has been relatively free of both human and bovine trypanosomiasis for the past three decades. The factors leading to the current resurgence of bovine trypanosomiasis need further investigation.

Animals↗

PubMed2005

Effective measures for controlling trypanosomiasis.

African trypanosomiasis, otherwise known as sleeping sickness in humans and 'Nagana' in cattle, is a disease that is resurgent in Africa. Research on the disease suggests that the development of a vaccine is still far away; even existing drugs are becoming ineffective on account of the emergence of drug-resistant trypanosomes. All this contributes to heavy economic losses and a sociopolitical crisis in the continent, thus underscoring the pressure to intensify research for inexpensive, less toxic and affordable trypanocides. This review discusses the current treatment of trypanosomiasis and the progress made towards the effective control of trypanosomiasis.

Animals↗

PubMed2006

Immunology and immunopathology of African trypanosomiasis.

Major modifications of immune system have been observed in African trypanosomiasis. These immune reactions do not lead to protection and are also involved in immunopathology disorders. The major surface component (variable surface glycoprotein,VSG) is associated with escape to immune reactions, cytokine network dysfunctions and autoantibody production. Most of our knowledge result from experimental trypanosomiasis. Innate resistance elements have been characterised. In infected mice, VSG preferentially stimulates a Th 1-cell subset. A response of gamma delta and CD8 T cells to trypanosome antigens was observed in trypanotolerant cattle. An increase in CD5 B cells, responsible for most serum IgM and production of autoantibodies has been noted in infected cattle. Macrophages play important roles in trypanosomiasis, in synergy with antibodies (phagocytosis) and by secreting various molecules (radicals, cytokines, prostaglandins,...). Trypanosomes are highly sensitive to TNF-alpha, reactive oxygen and nitrogen intermediates. TNF-alpha is also involved in cachexia. IFN-gamma acts as a parasite growth factor. These various elements contribute to immunosuppression. Trypanosomes have learnt to use immune mechanisms to its own profit. Recent data show the importance of alternative macrophage activation, including arginase induction. L-ornithine produced by host arginase is essential to parasite growth. All these data reflect the deep insight into the immune system realised by trypanosomes and might suggest interference therapeutic approaches.

Animals↗

PubMed2006

Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis.

Millions of people in the developing world are affected by diseases caused by the kinetoplastid parasites: the leishmaniases, African trypanosomiasis, and Chagas disease. In many cases the drugs employed for treatment are toxic, marginally effective, given by injection, and/or compromised by the development of resistance. Since safe, effective, and affordable chemotherapeutic agents for leishmaniasis and trypanosomiasis are clearly needed, the identification of new antikinetoplastid drug candidates should be an urgent priority. Numerous plant-derived natural products from different structural classes have been investigated as antileishmanial and antitrypanosomal candidates, including various alkaloids, terpenoids, flavonoids, and quinonoids. This review outlines the antikinetoplastid activities of plant-derived natural products reported in the literature and also provides an overview of mechanistic studies that have been conducted with these compounds. Given the activities of these agents and their diverse range of effects on parasite biology, natural products are a potentially rich source of drug candidates and leads against leishmaniasis and trypanosomiasis.

Biological Products↗

PubMed2006

A rare case of human trypanosomiasis caused by Trypanosoma evansi.

Human trypanosoma infections like the ones seen in Africa and South America are unknown in India. The only exception in literature is of two documented cases of a self-limiting febrile illness, being attributed to Trypanosoma lewisi like parasites. We are reporting an unusual case of trypanosomiasis from the rural parts of Chandrapur district in Maharashtra. An adult male farmhand who used to practice veterinary medicine also, presented with history of febrile episodes on and off since five months and drowsiness before admission to this Institute. Though routine blood and other investigations were within normal limits, the peripheral smear showed a large number of trypanosomes which morphologically resembled the species Trypanosoma evansi, the aetiological agent of surra - a form of animal trypanosomiasis. A battery of assays covering the spectrum of parasitology, serology, and molecular biology confirmed the infecting parasite to be T. evansi. Failure to demonstrate the central nervous system (CNS) involvement, as evidenced by the absence of parasite in cerebrospinal fluid (CSF) advocated the use of suramin - the drug of choice in early stage African trypanosomiasis without any CNS involvement. Suramin achieved cure in our patient. The case is being reported because of its unique nature as the patient was not immunocompromised and showed infestation with a parasite which normally does not affect human beings.

Animals↗

PubMed1977

Application of the enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of human African trypanosomiasis (sleeping sickness).

An enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of human African trypanosomiasis (sleeping sickness) is described. A crude extract of a Trypanosoma brucei suspension which was purified from all blood components was used as antigen. In rabbits experimentally infected with T. brucei or T. rhodesiense both homologous (anti-T. brucei) and heterologous (anti-T. rhodesiense) Trypanosoma antibodies could be detected with ELISA using T. brucei as antigen. The sensitivity of ELISA was comparable with that of the immunofluorescence (IF) technique. Sera of patients with sleeping sickness were examined with ELISA and IF. It proved possible to discriminate between groups of individuals with and without trypanosomiasis. Cross reactions were only observed with serum from a patient in which antibodies to Leishmania were detected. No cross reactions were observed in sera from patients with malaria, toxoplasmosis, schistosomiasis, or echinococcosis. ELISA represents a good alternative to IF in the serology of African trypanosomiasis, and may be particularly suitable for mass screening purposes.

Animals↗

PubMed1984

New drug combination for experimental late-stage African trypanosomiasis: DL-alpha-difluoromethylornithine (DFMO) with suramin.

Using a previously described mouse model of late-stage African trypanosomiasis (i.e., involvement of the central nervous system), we demonstrate that a combination of DL-alpha-difluoromethylornithine (DFMO) and suramin is curative. In the curative protocol, DFMO is given as a 2% solution in the drinking water for 14 days and suramin is administered as a single dose (20 mg/kg intravenously) on day 1 of DFMO administration. Since: 1) DFMO has very low toxicity, 2) suramin is one of the least toxic of the presently used trypanocides, and 3) suramin and DFMO act synergistically in mouse models of both acute and late stage trypanosomiasis, we conclude that this combination offers special promise in the treatment of African trypanosomiasis in man.

Animals↗

PubMed1996

The efficacy of pentamidine in the treatment of early-late stage Trypanosoma brucei gambiense trypanosomiasis.

Fifty-eight patients in the early-late stage (early central nervous system involvement) of Trypanosoma brucei gambiense trypanosomiasis were treated with pentamidine and divided into four groups (G1, G2, G3, and G4) according to cerebrospinal fluid (CSF) indicators: white blood cell (WBC) count, protein level (CSF protein), and the presence or absence of trypanosomes. Group G1 consisted of eight patients with normal CSF WBC counts and CSF protein levels and trypanosomes in the CSF. Group G2 consisted of nine patients with elevated CSF WBC counts, normal level of CSF protein, and trypanosomes in the CSF. Group G3 consisted of 31 patients with high CSF WBC counts, normal CSF protein levels, but no trypanosomes in the CSF. Group G4 consisted of 10 patients with normal CSF WBC counts and CSF protein levels and trypanosomes demonstrated by CSF culture. Post-treatment follow-up of all patients for at least one year revealed three relapses. There were two deaths from diseases unrelated to trypanosomiasis or to the treatment protocol. Of these patients, 52 were followed for more than two years, the time necessary to confirm a complete cure, indicating a cure rate of 94%. Pentamidine is therefore effective in treating the early-late stage of T. b. gambiense trypanosomiasis, and is comparable with melarsoprol or eflornithine in terms of its tolerance and availability.

Adolescent↗

PubMed1999

Rhodesian trypanosomiasis in a splenectomized patient.

We report the first apparent case of a splenectomized individual who developed severe trypanosomiasis with central nervous system involvement. The patient was a 41-year-old man who participated in an east African safari. Upon his return to the United States, the patient presented with an infection with Trypanosoma brucei rhodesiense that was treated successfully with suramin and melarsoprol. The onset of symptoms, laboratory studies, and disease progression did not differ from previously reported cases in the literature. The role of the spleen in trypanosomiasis is not well understood and the few reports available describe only animal models. This report suggests that asplenia had no apparent effect on the onset of symptoms and overall severity of illness. Further studies are necessary to ultimately define the role of the spleen in trypanosomiasis.

Adult↗

PubMed2004

Anaemia in human African trypanosomiasis caused by Trypanosoma brucei rhodesiense.

OBJECTIVE: To find out if indeed anaemia is a major sign in human trypanosomiasis caused by Trypanosoma brucei rhodensiense. DESIGN: A one year cross-sectional study of all admitted and surveyed Trypanosoma brucei rhodensiense infected patients (June 2001-June 2002) SETTING: Nkhotakota District Hospital-Central Region of Malawi. RESULTS: After survey and investigations, 28 patients (16 males and 12 females) were admitted to Nkhotakota District Hospital with a parasite positive Trypanosoma brucei rhodensiense infection. Twenty four (85.7%) of them were anaemic. Their mean haemoglobin was 8.96 +/- 3.07 g/dl compared to controls that had a mean haemoglobin concentration of 12.17 +/- 1.35 g/dl (p < 0.000001, 95% CI -4.342 to -2.0785) (n = 45). None of the trypanosomiasis infected individuals had schistosomiasis or hookworms. Two patients had malaria. One of them was an 18-year-old pregnant woman with hepatosplenomegaly, who developed ante partum haemorrhage. She was jaundiced and had haemoglobin of 10 g/dl. She died after two weeks following the diagnosis and treatment. The other was a two-year-old girl who had haemoglobin of 8.4 g/dl. She also had hepatosplenomegaly. All the other patients looked well nourished with no other signs of chronic diseases. Hepatosplenomegaly was significantly related to the severity of illness (p = 0.011) but not to anaemia. CONCLUSION: Though basic, this study has shown that anaemia is indeed a complication of human Africa trypanosomiasis caused by Trypanosoma brucei rhodesiense. There is need for further investigation to investigate the type of anaemia that is caused by this disease.

Adolescent↗

PubMed1991

Evaluation of microbial metabolites for trypanocidal activity: significance of biochemical and biological parameters in the mouse model of trypanosomiasis.

Trypanosomiasis is a parasitic disease, prevailing in both humans and animals, caused by a single-cell parasite, Trypanosoma spp. Three microbial metabolites, namely antiamoebin, F-857 and 6-MFA, were evaluated for trypanocidal activity by using a mouse model of trypanosomiasis, which is caused by T. evansi. The significance of the biological and biochemical parameters with respect to physio-pathology of trypanosomiasis and their implications in the evaluation of new trypanocidal compounds were discussed.

Animals↗

PubMed1975

Bovine leukosis. IV. Trypanosomiasis, lymphocytosis and DNA synthesis.

The possible influence of natural trypanosome infection on lymphocytosis and DNA synthesizing lymphocyte counts in peripheral blood was determined on 220 cows from two leukosis herds and 25 cows from leukosis free control herd. Trypanosome incidences were determined during summers of 1969 and 1970 by inoculating whole blood onto blood agar slants and incubating at room temperature. Incidence of trypanosomiasis in cattle was found to be variable, possibly due to factors affecting the primary isolation of Trypanosoma theileri. A small trypanosome resembling Trypanosoma uniforme was found occasionally as a concomitant infection with T. theileri. Trypanosomiasis occurred with equal frequency in the animals of the leukosis and the control herds. No correlations were noted between trypanosomiasis, lymphocytosis and DNA synthesizing lymphocytes in peripheral circulation.

Animals↗

PubMed2001

[Human African trypanosomiasis from Trypanosoma brucei gambiense with inoculation chancre in a French expatriate].

This report describes a case of West African trypanosomiasis involving a Caucasian Frenchman living in Conackry, Guinea. The patient presented with fever and two skin chancres highly suggestive of very early lymphatic stage trypanosomiasis. Examination of peripheral blood smears confirmed diagnosis of west African trypanosomiasis. Further immunologic evaluation showed elevated serum levels of specific IgM and IgG. The patient was treated by intravenous perfusion Pentacarinat at dose 5 x 4 mg/kg/day over a period of ten days. Clinical signs improved and parisitemia decreased within two days. The remarkable feature of this case was the presence of two chancres in association with the Gambian form. Since this finding allowed early diagnosis, treatment was well-tolerated and effective. This case also demonstrates the important role of travellers or expatriate workers as sentinels for emerging/re-emerging infectious diseases.

Animals↗

PubMed2002

Evaluation of the micro-CATT, CATT/Trypanosoma brucei gambiense, and LATEX/T b gambiense methods for serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa.

OBJECTIVE: To evaluate the performance of serological tests using dried blood on filter-papers (micro-card agglutination test for trypanosomiasis (micro-CATT)) performed under field and laboratory conditions and using whole blood ((CATT/T.b. gambiense) (wb-CATT) and latex agglutination (LATEX/T.b. gambiense) (wb-LATEX)) for the serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa. METHODS: We evaluated the micro-CATT, wb-CATT and wb-LATEX methods in Côte d'Ivoire and the Central African Republic by screening 940 people. Sensitivity and specificity were calculated for each serological test; only patients with the confirmed presence of trypanosomes in the blood or lymph aspirate were considered true positives. Positive and negative predictive values were also calculated. FINDINGS: Each of the tests showed a lower sensitivity in the Central African Republic than in Côte d'Ivoire. CONCLUSION: The results confirmed the efficiency of the classic wb-CATT to detect sleeping sickness patients. The micro-CATT method can be used for human African trypanosomiasis surveillance if the test is performed on the same day as the blood collection, or if samples are stored at 4 degrees C. Otherwise, micro-CATT can be used when absolute sensitivity is not required. wb-LATEX should only be used for high-specificity screening.

Agglutination Tests↗

PubMed2003

[Human African trypanosomiasis in an urban area: an emerging problem?].

The human African trypanosomiasis is essentially a rural disease. The notification of cases in urban area has always been incidental; either a diagnosis made in town revealed a disease contracted in rural environment or it meant the preservation of a complete epidemiological cycle in a remaining urban micro-focus. In Kinshasa, in Democratic Republic of Congo, about forty cases have been notified each year. All of them came from the nearby foci of Bandundu, Lower Congo and Kasaï. In 1996 the number of cases reached suddenly 254 and today the average annual number comes up to 500 in spite of all the efforts undertaken to fight the disease. A study of cases in 1998 and 1999 shows that patients are essentially distributed in suburbs and that the most affected by the disease are the 15-49 year old ones whose job is related with agricultural or fishing activities. Two phenomena seem to explain this sudden increase: the massive inflow of refugees in outskirts of town coming from provinces where trypanosomiasis is endemic and a major economic crisis throwing out urban population in suburbs living on a subsistence micro-agriculture. These concomitant factors have contributed to the setting up of a trypanosomiasis belt around the capital. Today a strategy has to be reconsidered in order to fight against the disease in the capital itself and to make the medical staff aware of the diagnosis of a disease still unknown in their sanitary district.

Adolescent↗

PubMed1992

Chemotherapy of CNS-trypanosomiasis: the combined use of diminazene aceturate or pentamidine with DL-alpha-difluoromethylornithine (DFMO).

The chemotherapy of CNS-trypanosomiasis with DL-alpha-difluoromethylornithine (Eflornithine, DFMO) with the diamidine, pentamidine (Lomidine) or diminazene aceturate (Berenil) was examined using the mouse model for CNS-trypanosomiasis. Although combined DFMO/pentamidine therapy can give complete cures, one or more doses of 100 mg/kg pentamidine was required with continuous administration of DFMO for 14-16 days, and even this treatment failed to cure the mice in a repeat experiment. Diminazene aceturate was more efficient and provided a 40 mg-kg dose was utilised, it was possible to reduce the period of DFMO to approximately 12 days. Attempts to reduce the dose rate of diminazene to less than 40 mg-kg failed. Of the two compounds, diminazene aceturate was the more successful and could possibly be used in combination with DFMO in the treatment of CNS-trypanosomiasis.

Animals↗

PubMed1990

Prevalence of domestic animal trypanosomiasis in the Fontem sleeping sickness focus, Cameroon.

Three hundred-fourteen domestic animals: 114 goats, 93 sheep, 67 dogs and 30 pigs in the Fontem sleeping sickness focus (Cameroon) were screened for infection with trypanosomes using parasitological and serological tests. Nannomonas was the only sub-genus detected in the animals with a prevalence of 28.3%. The card agglutination test (Testryp CATT) for trypanosomiasis showed a positivity rate of 38.2%, indicating that it allowed a better estimation of animal trypanosomiasis. The absence of trypanosomes of the sub-genus Trypanozoon seems to indicate that human African trypanosomiasis is not a zoonosis in this sleeping sickness focus.

Animals↗