The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis.

The in-vitro activity of a group of antifungal compounds known to inhibit ergosterol synthesis was investigated against Leishmania donovani grown as intracellular amastigotes in the human leukaemia monocyte cell line, THP-1. Toxicity on the host cells was assessed using the colorimetric MTT assay. Compounds inhibiting 2,3 oxidosqualene lanosterol cyclase; RO 43-3815, RO 43-5955, RO 43-8208, RO 42-6589 and RO 43-0688 displayed high activity with a median effective dose (ED50) of 0.6, 0.9, 3.5, 2.2 and 0.7 mg/L respectively. Of the azole compounds, oxiconazole had an ED50 value of 3.3 mg/L while ketoconazole showed the least activity. The delta-14-reductase and delta-8-delta-7 isomerase inhibitor, amorolfine, gave the highest therapeutic index with an ED50 value of 1.6 mg/L. Most compounds tested had a lower ED50 value than the standard antileishmanial drugs, sodium stibogluconate (5.5 mg Sbv/L) and meglumine antimoniate (3.0 mg Sbv/L) indicating the clean potential of these antifungal compounds in treating leishmaniasis.

The in vitro activity of Vernonia amygdalina on Leishmania aethiopica.

Anti-leishmanial activity of chloroform and methanol extracts of Vernonia amygdalina, a plant widely used in Ethiopia for the treatment of parasitic infections, has been assessed in vitro on Leishmania aethiopica. Amastigotes were more sensitive to V. amygdalina than promastigotes. The chloroform extract had a stronger parasiticidal activity, with median effective doses (ED50) of 18.5 micrograms/ml and 13.3 micrograms/ml for promastigotes and amastigotes, than the methanol extract with ED50 of 74.4 micrograms/ml and 45.8 micrograms/ml respectively. Cytotoxicity caused by V. amygdalina to host cells, the human leukaemia monocyte THP-1 cell line, as determined by the methyl tetrazolium assay, resulted in a median lethal dose (LD50) of 19.6 micrograms/ml for the chloroform extract and 243.4 micrograms/ml for the methanol extract. In comparison, the ED50 and LD50 of pentamidine, a standard anti-leishmanial drug, were 0.5 micrograms/ml and 1.4 micrograms/ml respectively. These results indicate that V. amygdalina displays potent anti-leishmanial activities and warrants further investigation.

Sero-epidemiological survey of Toxoplasma gondii infection in Ethiopia.

In Ethiopia the prevalence of IgG antibodies to Toxoplasma gondii has been determined by an enzyme-linked immunosorbent assay (ELISA). One thousand and sixteen sera collected in six different geographical regions were analyzed. Antibody titres > 15 IU/ml were detected in 74.4% of the specimens, titres exceeding 200 IU/ml in one third of the ELISA-positive sera. The highest antibody titres were found in children and 75% of young adults had sero-converted. As infection with the human immunodeficiency virus 1 (HIV-1) frequently leads to a resurgence of toxoplasmosis, the diagnosis of T. gondii encephalitis should be considered in the clinical management of the HIV-immunocompromised Ethiopian patients.

An in vitro model for screening antileishmanial drugs: the human leukaemia monocyte cell line, THP-1.

Standard anti-leishmanial drugs were tested for their ability to inhibit the growth of intracellular amastigotes of Leishmania aethiopica, L. donovani and L. infantum in the human leukemia monocyte THP-1 cell line. Sodium stibogluconate and meglumine antimoniate were active against L. donovani with ED50 values of 8.9 micrograms SbV/ml and 2.9 micrograms SbV/ml, respectively. L. aethiopica was less sensitive to sodium stibogluconate with an ED50 value of 25.3 micrograms SbV/ml while pentamidine had an ED50 value of 0.6 microM. Both L. donovani (ED50, 9.3 microM), and L. aethiopica (ED50, 6.4 microM), were sensitive to aminosidine sulphate. An L. infantum isolate, clinically resistant to meglumine antimoniate treatment, had an ED50 of 22.2 micrograms SbV/ml. The toxic level of drugs on host cells was determined by colorimetric Methyl Tetrazolium (MTT) assay prior to activity tests. The results obtained with the THP-1 in vitro drug screening model were similar to those obtained in the mouse peritoneal macrophage model.