Leishmaniasis visceral

Leishmaniasis is the general term for protozoal infections of the species Leishmania. The cutaneous and visceral forms (kala azar) of leishmaniasis are differentiated, and the manifestations depend on the species (L. donovani, L. infantum, L. cagasi). According to WHO data, there are 12 million people infected with this parasite - 350 million live in risk areas. Epidemics have been described in Bangla desh, Brazil, India and the Sudan; in Europe, it is mainly the Mediterranean regions that are affected (usually L. infantum).

HIV infected patients become infected more commonly with visceral leishmaniasis. In Spain, the majority of patients with visceral leishmaniasis are HIV-infected (Pintado 2001). Although there is much in favor of it, leishmaniasis is not an AIDS-defining illness.

An evaluation of 15 cases in Germany showed significant immunosuppression (usually less than 100 CD4 cells/^l) in all patients. A few patients had not been in endemic areas for several years (Albrecht 1998).

Bone marrow involvement is reflected by the almost obligatory pancytopenia, which may be particularly severe in HIV infected patients (Pintado 2001). Other symptoms include fever, hepatosplenomegaly and mucocutaneous lesions. The diagnosis is usually made from bone marrow aspirate.

Treatment of visceral leishmaniasis is difficult (review: Olliaro 2005). Pentavalent antimony preparations such as stibogluconate (Pentostam™) and megluminanti-monate (Glucantime™) have been used for about 60 years. These preparations (dosage 20 mg/kg i.m. or - less painful - i.v. daily for 28 days) are cheap but very toxic. Myalgias, arthralgias, gastrointestinal complaints, pancreatitis and cardio-toxicity often lead to discontinuation of the drug (Laguna 1999). The German Association for Tropical Medicine therefore recommends liposomal amphotericin B (Ambisome™) as the treatment of choice (2-5 mg/kg daily). A very promising alternative - due to its good tolerability and efficacy, and whilst it is the only orally bioavailable leishmaniasis drug - is miltefosine (Impavido™), an alkyl-phosphocholine analog that was licensed in Germany in December 2004. It is still unclear how miltefosine inhibits leishmania metabolism, but a Phase III study in India demonstrated it to be highly effective (Sundar 2002). However, a newer randomized study in Ethiopia showed a somewhat weaker effect in HIV infected patients than stibogluconate, although a better tolerability (Ritmeijer 2006). It is administered at a dose of 100 mg daily (monthly cost: almost 2,300 Euro!). We have successfully treated two patients with miltefosine to date.

Relapses occur in almost half of all cases. HAART seems to change this - another argument for inclusion of visceral leishmaniasis in the AIDS classification (de La Rosa 2002, Fernandez-Cotarelo 2003).

References

1. Albrecht H, Sobottka I, Emminger C, et al. Visceral leishmaniasis emerging as an important opportunistic infection in HIV-infected persons living in areas nonendemic for Leishmania donovani. Arch Pathol Lab Med 1996, 120:189-98. http://amedeo.com/lit.php?id=8712898

2. Albrecht H. Leishmaniosis - new perspectives on an underappreciated opportunistic infection. AIDS 1998, 12:2225-6.

3. de La Rosa R, Pineda JA, Delgado J, et al. Incidence of and risk factors for symptomatic visceral leishmaniasis among HIV type 1-infected patients from Spain in the era of HAART. J Clin Microbiol 2002, 40:762-7. http://amedeo.com/lit.php?id=11880390

4. Fernandez-Cotarelo MJ, Abellan Martinez J, Guerra Vales JM, et al. Effect of highly active antiretrovi-ral therapy on the incidence and clinical manifestations of visceral leishmaniasis in human immunodeficiency virus-infected patients. Clin Infect Dis 2003, 37: 973-7. http://amedeo.com/lit.php?id=13130410

5. Laguna F, Lopez-Velez R, Pulido F, et al. Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing meglumine antimoniate with amphotericin B. AIDS 1999, 13:1063-9. http://amedeo.com/lit.php?id=10397536

6. Olliaro PL, Guerin PJ, Gerstl S, Haaskjold AA, Rottingen JA, Sundar S. Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980-2004. Lancet Infect Dis 2005, 5:763-74. http://amedeo.com/lit.php?id=16310148

7. Pintado V, Martin-Rabadan P, Rivera ML, Moreno S, Bouza E. Visceral leishmaniasis in HIV-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore) 2001, 80:54-73. http://amedeo.com/lit.php?id=11204503

8. Ritmeijer K, Dejenie A, Assefa Y, et al. A comparison of miltefosine and sodium stibogluconate for treatment of visceral leishmaniasis in an Ethiopian population with high prevalence of HIV infection. Clin Infect Dis 2006, 43:357-64. http://amedeo.com/lit.php?id=16804852

9. Sundar S, Jha TK, Thakur CP, et al. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 2002, 347:1739-46. http://amedeo.com/lit.php?id= 12456849

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