Over 850 Leishmania-human immunodeficiency virus (HIV) coinfection cases have been recorded, the majority in Europe, where 7 to 17% of HIV-positive individuals with fever have amastigotes, suggesting that Leishmania-infected individuals without symptoms will express symptoms of leishmaniasis if they become immunosuppressed. However, there are indirect reasons and statistical data demonstrating that intravenous drug addiction plays a specific role in Leishmania infantum transmission: an anthroponotic cycle complementary to the zoonotic one has been suggested. Due to anergy in patients with coinfection, L. infantum dermotropic zymodemes are isolated from patient viscera and a higher L. infantum phenotypic variability is seen. Moreover, insect trypanosomatids that are currently considered nonpathogenic have been isolated from coinfected patients. HIV infection and Leishmania infection each induce important analogous immunological changes whose effects are multiplied if they occur concomitantly, such as a Th1-to-Th2 response switch; however, the consequences of the viral infection predominate. In fact, a large proportion of coinfected patients have no detectable anti-Leishmania antibodies. The microorganisms share target cells, and it has been demonstrated in vitro how L. infantum induces the expression of latent HIV-1. Bone marrow culture is the most useful diagnostic technique, but it is invasive. Blood smears and culture are good alternatives. PCR, xenodiagnosis, and circulating-antigen detection are available only in specialized laboratories. The relationship with low levels of CD4+ cells conditions the clinical presentation and evolution of disease. Most patients have visceral leishmaniasis, but asymptomatic, cutaneous, mucocutaneous, diffuse cutaneous, and post-kala-azar dermal leishmaniasis can be produced by L. infantum. The digestive and respiratory tracts are frequently parasitized. The course of coinfection is marked by a high relapse rate. There is a lack of randomized prospective treatment trials; therefore, coinfected patients are treated by conventional regimens. Prophylactic therapy is suggested to be helpful in preventing relapses.

Leishmania and human immunodeficiency virus coinfection: the first 10 years.

Leishmaniasis and AIDS co-infection: the Spanish example.

Although, in southern Europe, there has been considerable experience in the treatment of visceral leishmaniasis (VL) in HIV-positive patients, the optimal therapy has yet to be established. Pentavalent antimony salts, free amphotericin B deoxycholate (ABD) and lipidic formulations of amphotericin B are the drugs most commonly used. Treatment with pentavalent antimonials requires daily injections for 28 days, is not well tolerated and leads to initial clinical cure in only 66% of the co-infected cases. Free ABD has to be given, intravenously, for just as long, has significant toxicity and leads to initial clinical cure in even fewer cases (62%). In a prospective, comparative trial, treatment of co-infected cases with a pentavalent antimonial was found to have similar efficacy and toxicity to treatment with free ABD. The duration of treatment and the associated toxicity may both be reduced by the use of lipidic formulations of amphotericin B. Anecdotal evidence and the results of non-randomized trials indicate that treatment with liposomal amphotericin B is highly effective. In a comparative trial, amphotericin B lipid complex was found to be not only as effective as a pentavalent antimonial but also better tolerated. At the moment, however, such lipidic formulations have only been tested against VL/HIV cases in Europe, not elsewhere in the world, and they remain very expensive. However successful the treatment in terms of initial clinical cure, almost all VL/HIV cases develop VL relapses. Although the data available on secondary prophylaxis are limited and often inconclusive, it appears that regular treatment with a pentavalent antimonial drug, liposomal amphothericin B or amphotericin B lipid complex can reduce the incidence of leishmanial relapses in HIV-positive patients with VL. The development of new regimens, use of new oral drugs (such as miltefosine) and the development of new antileishmanial drugs could all improve the treatment of HIV-related VL in the future.

https://www.who.int/leishmaniasis/burden/hiv_coinfection/en/ATMP12.pdf

Treatment of leishmaniasis in HIV-positive patients

The intracellular protozoan parasites of the genus Leishmania have been recognized as opportunistic pathogens in immunosuppressed individuals, including those infected with human immunodeficiency virus type-1 (HIV-1). Leishmaniasis and AIDS overlap in several sub-tropical and tropical regions around the world, including the Mediterranean area. In 1994, 3%-7% of HIV-1-infected individuals in southern Europe developed visceral leishmaniasis. In humans, interestingly, both HIV-1 and Leishmania interact with, invade, and multiply within cells of myeloid or lymphoid origin. The combined modulation of Leishmania - and HIV-1-related pathogenesis in the co-infected cases is therefore probably a realistic goal. In the light of the recent demonstration that L. donovani can up-regulate HIV-1 replication, both in monocytoid and lymphoid cells in vitro and in co-infected individuals, it is clear from the epidemiological data available that Leishmania can probably act as a powerful co-factor in the pathogenesis...

The pathogenesis of Leishmania/HIV co-infection: cellular and immunological mechanisms.

In this study, we demonstrated that the protozoan parasite Leishmania donovani and one of its major surface molecules, the lipophosphoglycan (LPG), can induce human immunodeficiency virus type 1 (HIV-1) expression in U1 and OM-10.1, two cell lines of monocytoid origin latently infected with HIV-1. Treatment of U1 cells with various concentrations of LPG (1, 5, and 10 microM) resulted in a dose-dependent secretion of tumor necrosis factor alpha (TNF-alpha). Suppression of LPG-induced HIV-1 expression by polyclonal anti-TNF-alpha antibodies further confirmed the involvement of this cytokine. Results from these studies indicate that the protozoan parasite L. donovani can induce the secretion of TNF-alpha that will function in an autocrine or paracrine manner to upregulate HIV-1 expression. Our data suggest for the first time that this protozoan parasite can be viewed as a potential cofactor in the pathogenesis of AIDS.

J. Verdejo

Papers

Visceral leishmaniasis in a patient seropositive for HIV.