Dominique Frommel

Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica

Treatment of diffuse cutaneous leishmaniasis (DCL) caused by Leishmania aethiopica remains unsatisfactory as the parasite is relatively insensitive to antimonial compounds. Reports of the clinical effectiveness of aminosidine sulphate, especially in combination with sodium stibogluconate, in visceral leishmaniasis and the finding that this antibiotic is potent against L. aethiopica in vitro, prompted us to evaluate its usefulness in DCL. Two patients with long-standing, active DCL were treated for 60 d with aminosidine sulphate, 14 mg/kg/d parenterally. The skin lesions resolved completely in both patients although they relapsed subsequently. Synergism between aminosidine and stibogluconate was demonstrated in vitro against parasites isolated from the patients. This led us to administer combined therapy, aminosidine sulphate 14 mg/kg/d and sodium stibogluconate 10 mg/kg/d, to the 2 patients in relapse and to another, third patient. Treatment was continued for 2 months beyond parasitological cure. Side effects were minimal. Following treatment, a return of specific cell-mediated immunity occurred, as expressed by a moderate infiltration of lymphocytes into the lesions and by lymphocyte proliferation in vitro in the presence of live Leishmania antigen, with synthesis of interleukin-2 and interferon gamma with one patient and interleukin 4 with the other. During follow-up periods of 2 to 21 months after treatment, no sign of relapse was seen.

Cutaneous leishmaniasis in south-western Ethiopia: Ocholo revisited.

The borough of Ocholo, on the western side of the Ethiopian Rift Valley, is an endemic focus for Leishmania aethiopica infection and has been surveyed thrice between 1987 and 1990. In 1989, 3022 inhabitants (> 95% of the population) were interviewed and examined. The overall prevalence of localized cutaneous leishmaniasis (LCL) was 3.6-4.0%, with a peak value of 8.5% in the 0-10 years old age group. In half of the patients the active disease was estimated to last for 9.6 +/- 6 months; in 10%, it exceeded 3 years. Scars of LCL were present in 34.3% of the residents. Leishmanin skin tests were positive in 54% of 120 school-children without signs of the disease. Therefore, in Ocholo a minimum of 71.6% of the population has been exposed to L. aethiopica infection. Two cases of the diffuse form of cutaneous leishmaniasis were observed. In this highland biotope, Phlebotomus pedifer was found to be the major, and possibly the only, vector for L. aethiopica.

The use of DNA hybridization for the detection of Leishmania aethiopica in naturally infected sandfly vectors

Hybridization with kinetoplast deoxyribonucleic acid (kDNA) probes was used to detect Leishmania aethiopica in naturally infected sandflies in south-west Ethiopia, an endemic area for cutaneous leishmaniasis. 396 sandflies were dissected; microscopy revealed flagellates in the midgut of 5 Phlebotomus pedifer. The infecting flagellates were confirmed as L. aethiopica by isoenzyme typing. Gut specimens for all dissected sandflies were hybridized with total L. aethiopica kDNA as well as with a cloned kDNA probe specific for L. aethiopica. Samples from sandflies which were found to be infected microscopically also hybridized with the L. aethiopica kDNA probes. One additional sandfly hybridized but was not shown to be infected by microscopical examination. Hybridization experiments with 65 whole squash-blotted sandflies gave results that correlated very well with results obtained using microscopy. Our results indicate that DNA probing is a useful method to detect Leishmania infection in sandfly midguts as well as in whole squash-blotted sandflies, and can be used to follow changes of infection rate. DNA probing is therefore an alternative to microscopy in large-scale epidemiological studies as well as monitoring control programmes aimed at human leishmaniasis.