Treatment Of African Trypanosomiasis Research Articles

720. Efficacy of Nifurtimox + Eflornithine in the Treatment of African Trypanosomiasis. Systematic Review

BackgroundSleeping sickness is an infectious disease transmitted mainly by the Trypanosoma Brucei, with the tsetse fly as a vector. The condition has two stages: The hemolymphatic and the meningo-encephalitic stage. The second stage is caused mainly by the Trypanosoma Brucei Gambiense. The treatment of the second stage has changed from melarsoprol, eflornithine, to now nifurtimox-eflornithine (NECT). This systematic review will focus on the efficacy and the toxicity of the medication.MethodsWe use PRISMA and MOOSE protocol for this review. On figure 1, we detail the methodology used for the extraction of information from the systematic review. To assess the study's bias, we used Cochrane Collaboration’s tool for risk assessment of the clinical trials and the Robins I tool for the observational studies.ResultsWe collected four clinical trials and two observational studies after an extensive search. Three clinical trials showed that NECT was non-inferior to eflornithine with the following cure rates (NECT VS eflornithine): 1) 96.3% vs. 94.1% ; 2) 90.9% vs. 88.9%; 3) 91.6% vs. 96.5%. An additional clinical trial revealed that the proportion of patient discharge from the hospital was 98.4% (619/629); 95% CI [97.1%; 99.1%]). The two observational studies discussed the pharmacovigilance of the drug and toxicity related to NECT. In one study, patients treated with NECT, 589 (86%) experienced at least one adverse effect (AE) during treatment, and 70 (10.2%) experience serious AE. On average, children experienced fewer AEs than adults. In the other study at least one AE was described in 1043 patients (60.1%), and Serious AE was reported in 19 patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%). The major limitations of the studies were the lack of blinding because most of them were open-label. Also, there was heterogenicity in the definition of the outcomes in the observational studies.PRISMA Flow Chart ConclusionNECT is not inferior to eflornithine, and the proportion of patients discharged from the hospital alive showed favorable results. The observational studies revealed a high frequency of AE. However, NECT is more convenient and safe than Eflornithine and Melarsoprol.Disclosures All Authors: No reported disclosures

Efficacy and Toxicity of Fexinidazole and Nifurtimox Plus Eflornithine in the Treatment of African Trypanosomiasis: A Systematic Review.

Human African trypanosomiasis (HAT), or sleeping sickness disease, is an infection caused mainly by Trypanosoma brucei gambiense-human African trypanosomiasis (g-HAT) and is transmitted by tsetse flies. The disease goes through two stages: hemolymphatic and meningo-encephalic phases. The treatment for the second stage has changed from melarsoprol or eflornithine to nifurtimox-eflornithine combination therapy (NECT) and fexinidazole. We aimed to systematically review the literature on the efficacy and toxicity of fexinidazole and NECT. We used PubMed advanced strategy and Google Scholar databases, including clinical trials and observational studies on humans in the last 20 years in the English literature. Applying the inclusion/exclusion criteria, we reviewed eight studies. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol. For assessing bias, we used the Cochrane Collaboration’s tool for risk assessment of the clinical trials and the Robins-I tool for the observational studies. Overall, the clinical trials showed that NECT was non-inferior to eflornithine. The proportion of patients discharged alive is higher in patients treated with NECT vs. patients treated with eflornithine. Gastrointestinal complaints are a common side effect of NECT therapy, while fearful but relatively rare convulsions can also occur. The main limitation among the studies of NECT was the lack of blinding because most of them were open-label. Fexinidazole, the new oral medication showed is effective and safe for the treatment of g-HAT infection. Because of their convenience, fexinidazole is preferred over NECT therapy, oral vs. IV infusion in the first and second stages of the disease. Compared to older therapies, fexinidazole and NECT are more effective and safer than eflornithine and melarsoprol monotherapy.

Validating 3-Phosphoinositide Dependent Protein Kinase-1 as a Drug Target in African Trypanosoma

Introduction: Human African trypanosomiasis is a parasitic disease that is transmitted to the mammalian host through the bite of an infected tsetse fly of the genus Glossina species. The disease is caused by two species, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, disease outcome is dependent on the infective species. Currently, treatment of African trypanosomiasis is dependent on drugs that are highly toxic and drug resistance has been observed. Therefore, there is a need for development of new drugs and vaccines. The genome of T. brucei has been completely sequenced and analysis of the kinome has revealed 156 eukaryotic protein kinases. One such kinase is a homolog of the mammalian 3-phosphoinositide dependent protein kinase-1 (PDK-1), a member of the AGC family of protein kinases which shares 35% similarity with the human PDK-1.
 Methods: In this study, RNA interference of 3-phosphoinositide dependent protein kinase-1 was carried out to investigate the effect of gene knock down on Trypanosoma brucei brucei.
 Results: Trypanosoma brucei 3-phosphoinositide-dependent protein kinase-1 is important in T. brucei brucei cell proliferation. Further investigations using DAPI and fluorescence microscopy showed that gene knockdown had an impact on cell phenotype.
 Conclusion: RNA interference was effective in knocking down genes corresponding to Trypanosoma brucei 3-phosphoinositide-dependent protein kinase-1. Findings of the study demonstrate that TbPDK-1 is important in cell proliferation in blood stream form Trypanosoma brucei brucei. These results validate TbPDK-1 as a potential drug target for African trypanosomes.

Anti-trypanosomal evaluation of Ximenia americana root bark and chromatographic-mass spectrometric profile

Medicinal plants are the richest bio-resource of drugs for traditional systems of medicine, modern medicines, food supplements, pharmaceutical intermediates and chemical entities for synthetic drugs. Human African Trypanosomiasis (HAT) is a challenging and deadly disease due to its complex epidemiology and clinical presentations. This study was conducted to investigate anti-trypanosomal action of Ximenia americana root bark on Trypanosoma brucei brucei using various solvent extracts and to develop thin layer (TLC-MS) and liquid chromatography-mass spectrometric (LC-MS) profiles of the plant. Soxhlet extraction was used to obtain acetone, 70% ethanol total extracts in addition to n-hexane, dichloromethane, ethyl acetate and methanol fractions by sequential extraction. The inhibitory activity of the various extracts was compared by testing against T. b. brucei using isometamidium chloride as standard drug. The most active extract was separated by solid-phase extraction (C18 stationary phase) to obtain fractions which were profiled by TLC-MS (+ESI) and LC-MS. It was observed that anti-trypanosomal activity of acetone (16.83% yield) and 70% ethanol (18.23% yield) were comparable. However, methanol extract exhibited the highest activity with 99.18%, 97.5% and 87.50% inhibition at 3 h incubation (room temperature) using 1000 µg, 500 µg and 250 µg concentrations respectively. The activities at 1000 µg for methanol extract and isometamidium chloride were comparable with 95% CI [-1.10, 1.77]. TLC-MS and LC-MS analyses suggested gallic acid, 2,3,4,5-tetrahydroxybenzoic acid, 2ʹ,5-dimethoxyflavone, quercetin, dihydroquercetin and sesquiterpene when compared with literature database. This study presents data that could be useful in standardisation and preparation of alternative medicine in the treatment of African trypanosomiasis.

In vitro anti-trypanosomal effects of selected phenolic acids on Trypanosoma brucei.

African trypanosomiasis remains a lethal disease to both humans and livestock. The disease persists due to limited drug availability, toxicity and drug resistance, hence the need for a better understanding of the parasite’s biology and provision of alternative forms of therapy. In this study, the in vitro effects of phenolic acids were assessed for their trypanocidal activities against Trypanosoma brucei brucei. The effect of the phenolic acids on Trypanosoma brucei brucei was determined by the alamarBlue assay. The cell cycle effects were determined by flow cytometry and parasite morphological analysis was done by microscopy. Effect on cell proliferation was determined by growth kinetic analysis. Reverse Transcriptase quantitative Polymerase Chain Reaction was used to determine expression of iron dependent enzymes and iron distribution determined by atomic absorption spectroscopy. Gallic acid gave an IC50 of 14.2±1.5 μM. Deferoxamine, gallic acid and diminazene aceturate showed a dose dependent effect on the cell viability and the mitochondrion membrane integrity. Gallic acid, deferoxamine and diminazene aceturate caused loss of kinetoplast in 22%, 26% and 82% of trypanosomes respectively and less than 10% increase in the number of trypanosomes in S phase was observed. Gallic acid caused a 0.6 fold decrease, 50 fold increase and 7 fold increase in the expression levels of the transferrin receptor, ribonucleotide reductase and cyclin 2 genes respectively while treatment with deferoxamine and diminazene aceturate also showed differential expressions of the transferrin receptor, ribonucleotide reductase and cyclin 2 genes.The data suggests that gallic acid possibly exerts its effect on T. brucei via iron chelation leading to structural and morphological changes and arrest of the cell cycle. These together provide information on the cell biology of the parasite under iron starved conditions and provide leads into alternative therapeutic approaches in the treatment of African trypanosomiasis.

Gene mutations in parasitic diseases Part II: Parasite gene mutations

Gene mutation may occur either in the parasite or in the host, which may be beneficial or harmful for each. As we previously discussed, part I covered causes and types of gene mutations as well as their relation(s) to or effect(s) on parasitic diseases; part II deals with parasite gene mutations. The most apparent manifestation is drug resistance especially with anti-malarial drugs for falciparum malaria. The majority of P. falciparum isolates are able to undergo gene mutations in genes encoding enzymes that control drug uptake. Parasite gene mutations are suggested to influence parasite virulence in toxoplasmosis and malignant malaria, and to have impact on the occurrence of malignancy in schistosomiasis and clonorchiasis. It is intended in the present review to present mechanism(s) of drug resistance due to parasite gene mutations, with special emphasis on anti-malarial drugs, albendazole, metronidazole, and other drugs used in treatment of African trypanosomiasis and toxoplasmosis. The review also presents other effects of parasite gene mutations on disease outcome and progress as well as occurrence of false diagnosis in falciparum malaria using ICTs utelizing histidine rich protein.

Impact of Ganogerma applanatum extraction on haematological profiles of laboratory rats: a preliminary study in Nigeria

ObjectiveExtracts of Ganoderma species have been widely used as herbal medicines in the treatment of several infections. This study was carried out to ascertain the haematological properties of aqueous Ganoderma applanatum (G. applanatum). MethodsSixty albino rats grouped into six equal groups (10 each) of A to F consisting of tests and controls. Laboratory albino rats in groups A, B and C were infected with Trypanosoma brucei brucei (T. brucei brucei) while groups A and B (test) were treated with aqueous G. applanatum extract; other groups served as control. Microscopy and haematological profiles from the albino rats were monitored on daily basis for blood parasites, packed cell volume (PCV), haemoglobin concentration (HC), total red blood cell count (RBC), mean cell haemoglobin (MCH), mean cell volume (MCV), mean cell haemoglobin concentration (MCHC), and total white blood cell count (WBC). ResultsAlbino rats in groups A, B and C infected with T. brucei brucei and treated with various concentrations of aqueous G. applanatum showed a progressive reduction in PCV, HC, RBC, MCH and MCHC compared to the controls (P<0.05). All the infected rats died by day 14 of the experiment from parasitaemia. ConclusionsG. applanatum lacks ability to boost haematological profiles of anaemic laboratory rats and also of no use in the treatment of African trypanosomiasis. Higher doses of the fungal extract may be required to test on laboratory rats with less lethal biological stimulants of anaemia before proving or otherwise its true haematological properties.

Impact of G. applanatum, a multifunctional herbal extract on haematological profiles of laboratory rats: a preliminary study in Nigeria

ObjectiveTo ascertain the haematological properties of aqueous extract of G. applanatum(G. applanatum). MethodsSixty albino rats were grouped into six equal groups (10 each) from A to F, consisting of tests and controls. Laboratory albino rats in groups A, B and C were infected with Trypanosoma brucei (T. brucei) while groups A and B (Test) were treated with aqueous G. applanatum extract; other groups served as control. Microscopy and haematological profiles from the albino rats were monitored on daily basis for blood parasites, Packed Cell Volume (PCV), Haemoglobin Concentration (HC), Total Red Blood Cell Count (RBC), Mean Cell Haemoglobin (MCH), Mean Cell Volume (MCV), Mean Cell Haemoglobin Concentration (MCHC), and Total White Blood Cell Count (WBC). ResultsAlbino rats in groups A, B and C infected with T. brucei and treated with various concentrations of aqueous G. applanatum showed a progressive reduction in PCV, HC, RBC, MCH and MCHC compared to the controls (P < 0.05). All the infected rats died by day 14 of the experiment from parasitaemia. ConclusionsG. applanatum lacks ability to boost haematological profiles of anaemic laboratory rats and also of no use in the treatment of African Trypanosomiasis. Higher doses of the fungal extract may be required to test on laboratory rats with less lethal biological stimulants of anaemia before proving or otherwise its true haematological properties.

New Prodrugs of the Antiprotozoal Drug Pentamidine

Pentamidine is an effective antimicrobial agent that is approved for the treatment of African trypanosomiasis but suffers from poor oral bioavailability and central nervous system (CNS) penetration. This work deals with the development and systematic characterisation of new prodrugs of pentamidine. For this reason, numerous prodrugs that use different prodrug principles were synthesised and examined in vitro and in vivo. Another objective of the study was the determination of permeability of the different pentamidine prodrugs. While some of the prodrug principles applied in this study are known, such as the conversion of the amidine functions into amidoximes or the O-alkylation of amidoximes with a carboxymethyl residue, others were developed more recently and are described here for the first time. These newly developed methods aim to increase the affinity of the prodrug for the transporters and mediate an active uptake via carrier systems by conjugation of amidoximes with compounds that improve the overall solubility of the prodrug. The different principles chosen resulted in several pentamidine prodrugs with various advantages. The objective of this investigation was the systematic characterisation and evaluation of eight pentamidine prodrugs in order to identify the most appropriate strategy to improve the properties of the parent drug. For this reason, all prodrugs were examined with respect to their solubility, stability, enzymatic activation, distribution, CNS delivery, and oral bioavailability. The results of this work have allowed reliable conclusions to be drawn regarding the best prodrug principle for the antiprotozoal drug pentamidine.

Treatment of African Trypanosomiasis with Cordycepin and Adenosine Deaminase Inhibitors in a Mouse Model

There is an urgent need to discontinue the use of highly toxic compounds still in use for treatment of the encephalitic stage of human African trypanosomiasis (HAT). We show here that intraperitoneal injection of the adenosine analogue cordycepin (3'-deoxyadenosine), together with an adenosine deaminase (ADA) inhibitor (coformycin or deoxycoformycin), cures Trypanosoma brucei brucei infection in mice. Treatment was also effective at a stage when the trypanosomes had penetrated into the brain parenchyma, as determined by double immunolabeling of parasites and cerebral vessel endothelial cells in brain sections. At this stage, the parasites were eliminated not only from the blood but also from the brain parenchyma. In parallel with the elimination of parasites, in treated mice, the number of CD45+ inflammatory cells in the brain parenchyma was reduced. Treatment was not immunosuppressive. In vitro incubation with cordycepin reduced the growth of T. brucei brucei and T. cruzi, as well as Leishmania major and L. amazonensis. Administration of cordycepin plus deoxycofomycin to T. cruzi-infected mice also significantly reduced parasitemia. Accordingly, we propose nucleoside analogues resistant to ADA as candidates for treatment of late-stage HAT.

Activity of D-carnitine and its derivatives on Trypanosoma infections in rats and mice.

Little progress has been made in the treatment of African trypanosomiasis over the past decades. L-carnitine has a major role in glycolysis-based energy supply of blood trypanosomes for it stimulates constant ATP production. To investigate whether administration of the isomer D-carnitine could exert a competitive inhibition on the metabolic pathway of the L-form, possibly resulting in parasite replication inhibition, several formulations of this compound were tested on Trypanosoma lewisi and T. brucei rhodesiense in rodent models. High oral dosages of D-cornitine inner salt and proprionyl-D-carnitine were not toxic to animals and induced about 50% parasite growth inhibition in reversible, i.e. competitive, fashion. A putative mechanism could be an interference in pyruvate kinase activity and hence ATP production. Considering both, lack of toxicity and inhibitory activity, D-carnitine may have a role in the treatment of African trypanosomiasis, in association with available trypanocidal drugs.

Effects of anti-protozoal drugs and histopathological studies on trypanosome species

The trypanosomostatic and trypanosomicidal effects of four anti-protozoal drugs, namely halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine, on species of trypanosomes, viz. Trypanosoma brucei brucei (MBOS/NG/94/NITR) Bassa strain, T. congolense (MBOS/NG/93/NVRI) Zaria strain and T. brucei gambiense (MHOM/NG/92/NITR) Abraka strain, were investigated. In vitro and in vivo studies on these drugs vis-a-vis the parasites were carried out. The histopathological changes in organs and tissues of experimentally infected rats were also studied. Results from the in vitro studies indicated that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine appeared to be effective trypanosomicidal agents against T. brucei brucei (Bassa strain), T. congolense (Zaria strain) and T. brucei gambiense (Abraka strain). The in vivo studies showed that these drugs were sub-curative by prolonging the survival period of the trypanosome-infected rats, but not necessarily curing the infection. Histopathological findings indicated inflammatory reactions characterised by infiltration to variable degrees in the majority of tissues, mostly in the lungs and liver. The most consistent lesions were interstitial pneumonia, multifocal necrosis and oedema. Pathological findings showed the T. brucei brucei and T. brucei gambiense strains studied to be both intravascular and extravascular parasites. These results suggest that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine could be used as supportive, suppressive and/or synergistic/additive drugs in the treatment of African trypanosomiasis. Their effects on species of trypanosomes have been studied and are reported for the first time.

Effects of anti-protozoal drugs and histopathological studies on trypanosome species.

The trypanosomostatic and trypanosomicidal effects of four anti-protozoal drugs, namely halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine, on species of trypanosomes, viz. Trypanosoma brucei brucei (MBOS/NG/94/NITR) Bassa strain, T. congolense (MBOS/NG/93/NVRI) Zaria strain and T. brucei gambiense (MHOM/NG/92/NITR) Abraka strain, were investigated. In vitro and in vivo studies on these drugs vis-a-vis the parasites were carried out. The histopathological changes in organs and tissues of experimentally infected rats were also studied. Results from the in vitro studies indicated that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine appeared to be effective trypanosomicidal agents against T. brucei brucei (Bassa strain), T. congolense (Zaria strain) and T. brucei gambiense (Abraka strain). The in vivo studies showed that these drugs were sub-curative by prolonging the survival period of the trypanosome-infected rats, but not necessarily curing the infection. Histopathological findings indicated inflammatory reactions characterised by infiltration to variable degrees in the majority of tissues, mostly in the lungs and liver. The most consistent lesions were interstitial pneumonia, multifocal necrosis and oedema. Pathological findings showed the T. brucei brucei and T. brucei gambiense strains studied to be both intravascular and extravascular parasites. These results suggest that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine could be used as supportive, suppressive and/or synergistic/additive drugs in the treatment of African trypanosomiasis. Their effects on species of trypanosomes have been studied and are reported for the first time.

Molecular Mechanisms and Therapeutic Approaches to the Treatment of African Trypanosomiasis

Molecular Mechanisms and Therapeutic Approaches to the Treatment of African Trypanosomiasis

Suramin Affects Human Peripheral Blood Mononuclear Cells in vitro: Inhibition of T Cell Growth and Modulation of Cytokine Secretion

Suramin, a polyanionic compound, which has been in clinical use for the treatment of African trypanosomiasis for several decades, has recently been introduced in clinical oncology. Its effects on the immune system seemed therefore of interest. In the present study we tried to elucidate in vitro how suramin affected different functions of human peripheral blood mononuclear cells (PBMC). Suramin suppressed the proliferation of PBMC in response to various stimuli, including OKT3, phytohemagglutinin (PHA), phorbolmyristate-acetate (PMA) and ionomycin, purified protein derivate of Mycobacterium tuberculosis (PPD) and antibodies against CD2. It also inhibited the binding of monoclonal antibodies to T cell surface antigens. This effect was not dependent on the isotype of the antibody, but seemed to be highly epitope-specific. Among a panel of antibodies against one antigen, only a few were affected by the compound. Whereas the binding of Leu3a and OKT3 was for instance fully suppressed by suramin, OKT4 and Leu4 binding was only slightly affected. Suramin also decreased the expression of T cell surface molecules such as CD2, CD25 and CD4 in preactivated PBMC and had pronounced effects on cytokine production. Interestingly the compound had adverse regulatory effects on different cytokines. Whereas the secretion of interferon-gamma was completely suppressed by suramin, interleukin-2 (IL-2) and IL-4 production was stimulated. These results demonstrate that suramin affects T cell function in multiple different ways. This will have to be considered, when suramin is used in the treatment of cancer patients.

Interactions between immunity and chemotherapy in the treatment of the trypanosomiases and leishmaniases.

The immune status of a host infected with Trypanosoma spp. or Leishmania spp. can play an important role in successful chemotherapy. In animal models, treatment of African trypanosomiasis with difluoromethylornithine or melarsoprol requires an appropriate antibody-mediated immune response. An intact immune system is also necessary for rapid clearance of trypanosomes from the bloodstream following treatment with suramin or quinapyramine. Similarly, an efficient cell-mediated immune responses is required for maximal efficacy of pentavalent antimonials in the treatment of leishmaniasis. However, the potential relationship between parasite-induced or acquired immunosuppression and effective chemotherapy has been poorly studied. Macrophages which have been activated by bacterial cell wall components or gamma-interferon are known to display increased activity against Leishmania donovani or Trypanosoma cruzi. In experimental and clinical visceral leishmaniasis, use of macrophage activators together with pentavalent antimonials has lowered the dose of antimony required to cure the infection.

Necessity of antibody response in the treatment of African trypanosomiasis with α-difluoromethylornithine

The role of the immune system in the clearance of Trypanosoma brucei brucei from the bloodstream during α-difluoromethylornithine (DFMO) treatment was studied by determining the effects of dexamethasone on immune and therapeutic responses in rats infected with T.b. brucei. Normal DFMO-treated animals exhibited strong antibody responses to trypanosomes and were cured of T. b. brucei infection by a 7-day regimen of 2% DFMO in drinking water. Animals pretreated with dexamethasone were not cured by the same level of DFMO treatment. Nonetheless, in rats pretreated with dexamethasone, trypanosomes were cleared from blood during treatment with DFMO, but all immunocompromised animals eventually succumbed to relapses of the infection. Athymic (nude) mice were cured of T. b. brucei infection by a 72-hr course of treatment with 2% DFMO in their drinking water. These findings suggest that relatively low levels of T-cell-independent, antitrypanosomal antibodies are adequate to clear the bloodstream of parasites during DFMO therapy but that an intact immune response is necessary for cures of the disease to be obtained.

Selective inhibition of the in vitro murine B lymphocyte response by pentamidine.

A study was undertaken on the immunomodulating properties of pentamidine, a diamidine used in the treatment of African trypanosomiasis, pneumocystosis and leishmaniasis. Pentamidine inhibited the ability of mouse splenic lymphocytes to respond to mitogens. In particular inhibition of the B lymphocyte response was observed. At concentrations of 1 microgram/ml (1.7 x 10(-6) M), pentamidine markedly inhibited the response to the B cell mitogen, lipopolysaccharide (LPS), while concentrations of 10 micrograms/ml had to be attained to produce a similar effect on the response to the T cell mitogens phytohaemagglutinin (PHA) and concanavalin A (ConA). Further studies showed that pentamidine was not toxic to either resting or proliferating cells and probably acts by interacting directly with B cells rather than modifying the regulatory cell populations.

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.

The results of treatment of African trypanosomiasis in Europeans with tryparsamide and bayer 205

The results of treatment of African trypanosomiasis in Europeans with tryparsamide and bayer 205