Gondar University Leishmaniasis Research and Treatment Centre, University of Gondar, Gondar, Ethiopia.
PLoS Negl Trop Dis. 2013;7(1):e1977. doi: 10.1371/journal.pntd.0001977. Epub 2013 Jan 17.
Visceral leishmaniasis is a parasitic disease associated with high mortality. The most important foci of visceral leishmaniasis in Ethiopia are in the Northwest and are predominantly associated with high rates of HIV co-infection. Co-infection of visceral leishmaniasis patients with HIV results in higher mortality, treatment failure and relapse. We have previously shown that arginase, an enzyme associated with immunosuppression, was increased in patients with visceral leishmaniasis and in HIV seropositive patients; further our results showed that high arginase activity is a marker of disease severity. Here, we tested the hypothesis that increased arginase activities associated with visceral leishmaniasis and HIV infections synergize in patients co-infected with both pathogens.
METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with visceral leishmaniasis and a cohort of patients with visceral leishmaniasis and HIV infection from Gondar, Northwest Ethiopia, and recorded and compared their clinical data. Further, we measured the levels of arginase activity in the blood of these patients and identified the phenotype of arginase-expressing cells. Our results show that CD4(+) T cell counts were significantly lower and the parasite load in the spleen was significantly higher in co-infected patients. Moreover, our results demonstrate that arginase activity was significantly higher in peripheral blood mononuclear cells and plasma of co-infected patients. Finally, we identified the cells-expressing arginase in the PBMCs as low-density granulocytes.
Our results suggest that increased arginase might contribute to the poor disease outcome characteristic of patients with visceral leishmaniasis and HIV co-infection.
内脏利什曼病是一种寄生虫病，死亡率高。埃塞俄比亚内脏利什曼病的最重要焦点在西北部，主要与艾滋病毒合并感染率高有关。内脏利什曼病患者与艾滋病毒合并感染会导致更高的死亡率、治疗失败和复发。我们之前已经表明，与免疫抑制有关的酶精氨酸酶在内脏利什曼病患者和艾滋病毒血清阳性患者中增加；此外，我们的结果表明，高精氨酸酶活性是疾病严重程度的标志物。在这里，我们检验了这样一个假设，即与内脏利什曼病和艾滋病毒感染相关的精氨酸酶活性增加，在同时感染两种病原体的患者中具有协同作用。
方法/主要发现：我们从埃塞俄比亚西北部的贡德尔招募了一组内脏利什曼病患者和一组内脏利什曼病合并艾滋病毒感染的患者，并记录和比较了他们的临床数据。此外，我们测量了这些患者血液中的精氨酸酶活性，并确定了表达精氨酸酶的细胞表型。我们的结果表明，CD4+T 细胞计数在合并感染患者中显著降低，脾脏中的寄生虫负荷显著增加。此外，我们的结果表明，合并感染患者外周血单核细胞和血浆中的精氨酸酶活性显著升高。最后，我们确定了在 PBMCs 中表达精氨酸酶的细胞为低密度粒细胞。
我们的结果表明，精氨酸酶的增加可能导致同时感染内脏利什曼病和艾滋病毒的患者疾病预后不良。
