1II Department of Infectious Diseases, L. Sacco Hospital, Milan, Italy
2Infectious Diseases Clinic, University of Milan, Milan, Italy.
Date of receipt: 3 June 1998; accepted: 10 June 1998.
Visceral leishmaniasis is the third most common protozoan infection in HIV-positive patients after toxoplasmosis and cryptosporidiosis in the Mediterranean basin. A T-helper (TH) 1 lymphocyte-mediated immune response is essential in controlling visceral leishmaniasis, and in severely immunodepressed HIV-positive patients the shift towards a TH2 response can result in uncontrolled replication of parasites . Experimental studies have shown persistence of Leishmania DNA in the blood of successfully treated immunocompetent patients, thus explaining the reactivation of the disease once an immune system dysfunction occurs and the high relapse rate observed in HIV-positive patients . Secondary prophylactic regimens are generally used for HIV-related opportunistic infections in which treatment cannot achieve radical cure (cytomegalovirus, toxoplasmosis), but attempts with several drugs in HIV-Leishmania coinfections have not proven effective [3,4] until now. Here we present a case of relapsing leishmaniasis in an HIV-positive patient in whom a secondary prophylactic regimen instituted after successful treatment obtained persistent negativization of PCR determination for blood Leishmania parasites.
MM, aged 40 years, was admitted on 30 September 1996 for fever, metabolic acidosis and severe anaemia. He had been HIV-positive since 1984 and had a diagnosis of AIDS, with Pneumocystis carinii pneumonia as the AIDS-defining condition, in 1987. On admission, hepatomegaly, splenomegaly and fever were present. Laboratory examination showed a CD4+ cell count of 4 × 106/1 despite antiretroviral treatment, anaemia (haemoglobin 7.5 g/dl), leukopenia (3540 × 106/1) and thrombocytopenia (59 × 109/1). Serology for Leishmania was negative. A whole blood DNA PCR assay targeted to the SSU rRNA gene of Leishmania  was positive. Bone-marrow examination showed massive colonization by Leishmania amastigotes and the patient was treated with liposomal amphotericin B (AMB) 3 mg/kg body weight per day up to a total of 1848 mg. A bone-marrow examination at 1 month of follow-up was negative for Leishmania parasites, whereas PCR was still positive. In September 1997, reactivation of leishmaniasis was diagnosed by the reappearance of fever, anaemia, leukopenia and thrombocytopenia, increase in gammaglobulin, presence of Leishmania amastigotes in bone-marrow examination and positive cultures. PCR was still positive and a semiquantitative analysis of parasite DNA was performed by serial dilution on blood and bone aspirate. A second course of liposomal AMB was administered (total drug dose 1100 mg). After treatment, parasite DNA was still detectable in blood samples, although it decreased by 3 log10 after 15 days and by 2 log10 after 30 days in the absence of clinical symptoms, biochemical evidence of active Leishmania infection, and absence of Leishmania amastigotes on bone-marrow examination (Fig. 1). Secondary prophylaxis with liposomal AMB 3 mg/kg monthly was instituted and Leishmania burden by serial determination of PCR on peripheral blood showed progressive reduction. Undetectable Leishmania DNA was observed on the fourth and fifth prophylactic treatment. On subsequent controls, positive DNA signal was observed in one out of five replicates of the same sample, indicating the presence, at very low concentration, of active parasites.
Although clinical improvements have been reported with several anti-Leishmania drugs, the optimal treatment for visceral leishmaniasis in HIV-infected patients is still undefined despite the high mortality rates during the first visceral leishmaniasis episode and the high relapse rate . Assessment of treatment effectiveness was formerly obtained by invasive procedures whose sensitivity was frequently insufficient to detect the residual parasites responsible for recurrences. Close PCR monitoring after clinically effective treatment in our patient showed persistence of parasite DNA, suggesting that secondary prophylaxis with anti-Leishmania drugs could be beneficial to prevent relapses. Clearance of detectable Leishmania DNA obtained in our patient after the fourth prophylactic dose with liposomal AMB is encouraging. The presence of parasite DNA, even at very low concentrations, at 6-month follow-up indicates the need for chronic suppressive treatment in those patients in whom impairment of immune system prevents the control of parasite growth.
1. Davidson RN, Konecny P: Immunology and treatment of leishmaniases
. Curr Opin Infect Dis
2. Alvar J, Canavate C, Gutierrez-Solar B, et al.
: Leishmania and human immunodeficiency virus coinfection: the first 10 years
. Clin Microbiol Rev
3. Perez Molina JA, Lopez Velez R, Montilla P, Guerrero A: Pentamidine isethionate as secondary prophylaxis against visceral leishmaniasis in HIV-positive patients [letter]
4. Lopez M, Gil A, Lavilla P, Pintado V, Valencia E, Martinez P, Garcia-Puig J: Efficacy of liposomal amphotericin B in the treatment and secondary prophylaxis of visceral leishmaniasis in HIV infected patients: report of two cases
. J Antimicrob Chemother
5. van Eys GJJM, Schoone GJ, Kroon NCM, Ebeling SB: Sequence analysis of small subunit ribosomal RNA genes and its use for detection and identification of Leishmania parasites
. Mol Biochem Parasitol
© 1998 Lippincott Williams & Wilkins, Inc.