Kenyan purple tea anthocyanins and coenzyme-Q10 ameliorate post treatment reactive encephalopathy associated with cerebral human African trypanosomiasis in murine model.

Human African trypanosomiasis (HAT) is a tropical disease caused by two subspecies of Trypanosoma brucei, the East African variant T. b. rhodesiense and the West African variant T. b. gambiense. Melarsoprol, an organic arsenical, is the only drug used to treat late stage T. b. rhodesiense infection. Unfortunately, this drug induces an extremely severe post treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. A highly reproducible mouse model was adapted to assess the use of Kenyan purple tea anthocyanins and/or coenzyme-Q10 in blocking the occurrence of PTRE. Female Swiss white mice were inoculated intraperitoneally with approximately 10(4) trypanosome isolate T. b. rhodesiense KETRI 2537 and treated sub-curatively 21days post infection with 5mg/kg diminazene aceturate (DA) daily for 3days to induce severe late CNS infection that closely mirrors PTRE in human subjects. Thereafter mice were monitored for relapse of parasitemia after which they were treated with melarsoprol at a dosage of 3.6mg/kg body weight for 4days and sacrificed 24h post the last dosage to obtain brain samples. Brain sections from mice with PTRE that did not receive any antioxidant treatment showed a more marked presence of inflammatory cells, microglial activation and disruption of the brain parenchyma when compared to PTRE mice supplemented with either coenzyme-Q10, purple tea anthocyanins or a combination of the two. The mice group that was treated with coenzyme-Q10 or purple tea anthocyanins had higher levels of GSH and aconitase-1 in the brain compared to untreated groups, implying a boost in brain antioxidant capacity. Overall, coenzyme-Q10 treatment produced more beneficial effects compared to anthocyanin treatment. These findings demonstrate that therapeutic intervention with coenzyme-Q10 and/or purple tea anthocyanins can be used in an experimental mouse model to ameliorate PTRE associated with cerebral HAT.

Erythrina abyssinica prevents meningoencephalitis in chronic Trypanosoma brucei brucei mouse model.

Human African trypanosomiasis is prevalent in Sub-sahara African countries that lie between 14° North and 29° south of the equator. Sixty million people are at risk of infection. Trypanosoma brucei gambesience occurs in West and Central Africa while Trypanosoma brucei rhodesience occurs in East and Southern Africa. The neurological stage of the disease is characterized by neuroinflammation. About 10% of patients treated with the recommended drug, melarsoprol develop post treatment reactive encephalopathy, which is fatal in 50% of these patients, thus melarsoprol is fatal in 5% of all treated patients. This study was aimed at establishing the potential activity of Erythrina abyssinica in reducing neuroinflammation following infection with Trypanosoma brucei brucei. Swiss white mice were divided into ten groups, two control groups and eight infected groups. Infected mice received either methanol or water extract of Erythrina abyssinica at 12.5, 25, 50 or 100 mg/kg body weight. Parasite counts were monitored in peripheral circulation from the third day post infection up to the end of the study. Brains were processed for histology, immunohistochemistry scanning and transmission electron microscopy. Following infection, trypanosomes were observed in circulation 3 days post-infection, with the parasitaemia occurring in waves. In the cerebrum, typical brain pathology of chronic trypanosomiasis was reproduced. This was exhibited as astrocytosis, perivascular cuffing and infiltration of inflammatory cells into the neuropil. However, mice treated with Erythrina abyssinica water extract exhibited significant reduction in perivascular cuffing, lymphocytic infiltration and astrocytosis in the cerebrum. The methanol extract did not have a significant difference compared to the non-treated group. This study provides evidence of anti-inflammatory properties of Erythrina abyssinica and may support its wide use as a medicinal plant by various communities in Kenya.

Lactone-rich fraction from Vernonia blumeoides: antitrypanosomal activity and alleviation of the parasite-induced anemia and organ damage.

The anti-Trypanosoma brucei brucei activity in vitro and in vivo of a lactone-rich fraction of Vernonia blumeoides leaves (VBLF) and its potential in alleviating trypanosome-induced anemia and organ damage were investigated. Gas chromatography-mass spectrometry (GC-MS) analysis of VBLF revealed the presence of a number of lactone-containing compounds. In an in vitro study, VBLF showed concentration-dependent activity and was further used to treat T. brucei brucei-infected rats. The VBLF treatments, especially at 300 mg/kg body weight (BW), significantly (P < 0.05) kept the parasites reduced during the entire experimental period compared with the infected untreated group. At the end of the experiment, the trypanosome-induced anemia and hepatic damage were significantly (P < 0.05) alleviated in all the VBLF treatment groups, but renal damage was only prevented in the 200 and 300 mg/kg BW treatment groups. Furthermore, the trypanosome-induced increase in the relative weights of liver, spleen and kidney were significantly (P < 0.05) alleviated by the 300 mg/kg BW VBLF treatment. It was concluded that orally administered VBLF, especially at 300 mg/kg BW, possessed antitrypanosomal activity and could alleviate parasite-induced anemia and organ damage.

New insights in staging and chemotherapy of African trypanosomiasis and possible contribution of medicinal plants.

Human African trypanosomiasis (HAT) is a fatal if untreated fly-borne neuroinflammatory disease caused by protozoa of the species Trypanosoma brucei (T.b.). The increasing trend of HAT cases has been reversed, but according to WHO experts, new epidemics of this disease could appear. In addition, HAT is still a considerable burden for life quality and economy in 36 sub-Saharan Africa countries with 15-20 million persons at risk. Following joined initiatives of WHO and private partners, the fight against HAT was re-engaged, resulting in considerable breakthrough. We present here what is known at this day about HAT etiology and pathogenesis and the new insights in the development of accurate tools and tests for disease staging and severity monitoring in the field. Also, we elaborate herein the promising progresses made in the development of less toxic and more efficient trypanocidal drugs including the potential of medicinal plants and related alternative drug therapies.

Co-administration of Na-EDTA and diminazene aceturate (DA) to mice infected with DA-resistant Trypanosoma brucei.

This study investigated the effects of co-administration of Na-EDTA and diminazene aceturate (DA) on the level of parasitaemia (LOP), parasite clearance, packed cell volume (PCV) and post-infection survival time (PIST) in mice infected with DA-resistant Trypanosoma brucei. Five groups of 10 mice were treated as follows: infected and treated with Na-EDTA+DA; infected and treated with DA alone; infected and treated with Na-EDTA alone; infected-untreated; and uninfected-untreated. The co-administration of Na-EDTA and DA led to reduced LOP and improvements in PCV (P<0.05), as compared with treatment with DA alone. Mice treated with Na-EDTA+DA had a marginally (P>0.05) higher PIST than did mice treated with DA alone. Comparison of the group given Na-EDTA alone with the infected-untreated group showed that the former group had a significantly lower (P<0.01) LOP, improved PCV (P<0.05) and higher (P<0.01) PIST. It was concluded that the co-administration of Na-EDTA and DA led to a slight potentiation of DA in the treatment of mice infected with DA-resistant T. brucei, and that the administration of Na-EDTA alone significantly enhanced the resistance of the infected mice.

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice.

Chemotherapy for human African trypanosomiasis (HAT), or sleeping sickness, is unreliable because of resistance, refraction and toxic and adverse side-effects. Using a long-term experimental model of HAT with involvement of the central nervous system (CNS), we tested the ability of a megazol and suramin combination treatment to eliminate CNS trypanosomes. This consisted of 20 mg suramin per kg body weight administered intraperitoneally (i.p.), followed 24 h later by 4 daily doses (80 mg/kg) of megazol given either i.p. or per os. One week post-treatment, neurological disorders had disappeared. One of 15 mice relapsed in each application group at 81 and 98 days after treatment, respectively. At six months, no signs of relapse were seen in remaining mice, indicating that this chemotherapy regimen was curative. Immunohistochemical (astrocytosis) and histological (inflammatory lesions) examinations of brain tissues showed that animals returned to normal from 2 months post-treatment. These results suggest that the megazol-suramin combination reversed the CNS pathology in this model.