Academic journal article Bulletin of the World Health Organization

Treatment of Mediterranean Visceral Leishmaniasis

Academic journal article Bulletin of the World Health Organization

Treatment of Mediterranean Visceral Leishmaniasis

Article excerpt

Up-to-date information is given on the epidemiological situation of zoonotic visceral leishmaniasis (ZVL) in nine Mediterranean countries, and on drug regimens adopted in the management of ZVL patients in each country. Results of experimental and clinical trials on the efficacy and tolerability of liposomal amphotericin B in laboratory animals and in patients with ZVL are presented, as well as conclusions and recommendations on drug regimens to be used in the treatment of ZVL.

Introduction

Zoonotic visceral leishmaniasis (ZVL), caused by Leishmania infantum, is endemic in all countries bordering the Mediterranean basin. Although its overall prevalence among the immunocompetent population is low, the focal transmission of the disease may result in case clusters that can be underestimated in the absence of appropriate surveillance, and can present a severe health problem in many rural and periurban areas (1). The number of ZVL cases among patients with human immunodeficiency virus (HIV) infection has increased rapidly in recent years, and represents about 50% of all ZVL cases in adults in some areas (2).

The first-line drugs against ZVL for more than 40 years have been pentavalent antimonials. They are available in the form of sodium stibogluconate (Pentostam[R]) and meglumine antimoniate (Glucantime[R]). The does recommended by WHO is 20 mg Sb(v)/kg daily for 28 days by intramuscular injections (3). However, no information is available on treatment regimens actually employed in different Mediterranean countries, or on drug efficacy and tolerability in different categories of patients (immunocompetent children and adults, HIV-positives, etc.)

Status, by country, and therapeutic approaches

Algeria. The disease affects only children, more than 80% of whom are under 5 years of age. Since 1985, some 150--200 cases were diagnosed each year parasitologically and/or serologically. Most of them originate from Kabylia in north-eastern Algeria, which is a sub-humid bioclimatic zone. No HIV--Leishmania co-infections have been reported. The causative agent has been identified isoenzymatically as L. infantum MON 1.

Paediatricians treat ZVL with meglumine antimoniate, usually in a dose of 60 mg (18 mg Sb (v)/kg/d for 15 days. After a 15-day rest, a second course is administered for 15 days. Assessment of parasitological cure is made on bone-marrow smears. Unresponsiveness to antimonial treatment occurs in a few cases. These are treated with pentamidine given in a dose of 4 mg/kg on alternate days for 3--5 weeks.

France. Alpes-Maritimes (Nice area). Until 1975, ZVL was mainly diagnosed in children. Thereafter, the number of adult cases has steadily increased, and from 1985 to 1992 only 18 out of 65 recorded cases (28%) were children. Almost half of the adult cases are now represented by HIV co-infections. About 50 strains have been isolated from ZVL cases and identified isoenzymatically as L. infantum MON 1.

Meglumine antimoniate in a daily dose of 60 mg (18 mg Sb(v)/kg, or sodium stibogluconate in a daily dose of 6 ml in adult patients (i.e., about 10 mg Sb(v)/kg) are the first-line drugs used in standard schedules. There is no consensus on the duration of treatment: two courses of 15--21 days with a 15--30-day interval (or a single course for 15--28 days) are commonly employed. No serious side-effects or parasitological or clinical relapses have been recorded. Intravenous amphotericin B (Fungizone[R]) in a dose of 1 mg/kg/d for 15 to 28 days has been used with success in some immunocompetent patients. In 21 HIV--Leishmania co-infection cases, none of the above regimens led to parasitological cure.

Marseilles area. From 1985 to 1992, 150 ZVL cases have been recorded (11 to 24 per year). HIV--Leishmania co-infection cases have steadily increased in recent years. From May 1992 to November 1993, ten out of 17 new cases were HIV-positive adults, one was an HIV-negative adult, and six were children. …

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