Low Plasma Lipids Are Associated with Relapsing and Lethal Visceral Leishmaniasis in HIV-Infected Patients.

Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.

The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS.

BACKGROUND: Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. METHODS: From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients' complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. RESULTS: CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = -0.71, P = 0.015). CONCLUSIONS: This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages.

Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort.

Some patients with visceral leishmaniasis (VL), or kala-azar, suffer relapses and low quality of life despite adequate drug therapy, especially those co-infected with HIV. Occasionally, physicians indicate splenectomy, but the benefit of the procedure needs to be analyzed systematically. Therefore, a retrospective open cohort study was conducted in Teresina, Brazil. Inpatients from a reference hospital with relapsing VL who had a rescue splenectomy between 2012 and 2019 after the nationally recommended drug therapy failed were studied. The procedure's risks and benefits were assessed in a limited-resource setting. The primary outcomes were surgical complications, complete blood count, CD4+ cell count, hospitalizations, survival time, and medical complications preceding death. Thirteen adult patients received medical and surgical indications of splenectomy (12 men and one woman). Eleven had HIV infection. Two had early and two had late complications. Four died, all of whom were infected with HIV. An additional HIV-coinfected patient, apart from the cohort, died just before surgery. The death rate after surgery was 13.3 overall and 22.1 per 100 person-years among HIV-infected patients (31% overall and 36%, respectively). The impressive rise of complete blood counts and reduction of blood transfusions and hospitalizations were observed among all patients. Also, a meaningful increase in CD4+ cells in HIV-infected patients was noted. Splenectomy may benefit patients with relapsing VL. However, before performing splenectomy, available combined drug therapy for VL should be tried.