Eosinophil-associated processes underlie differences in clinical presentation of loiasis between temporary residents and those indigenous to Loa-endemic areas

Abstract

Background: Loa loa has emerged as an important public health problem due to the occurrence of immune-mediated severe posttreatment reactions following ivermectin distribution. Also thought to be immune-mediated are the dramatic differences seen in clinical presentation between infected temporary residents (TR) and individuals native to endemic regions (END).

Methods: All patients diagnosed with loiasis at the National Institutes of Health between 1976 and 2012 were included. Patients enrolled in the study underwent a baseline clinical and laboratory evaluation and had serum collected and stored. Stored pretreatment serum was used to measure filaria-specific antibody responses, eosinophil-related cytokines, and eosinophil granule proteins.

Results: Loa loa infection in TR was characterized by the presence of Calabar swelling (in 82% of subjects), markedly elevated eosinophil counts, and increased filaria-specific immunoglobulin G (IgG) levels; these findings were thought to reflect an unmodulated immune response. In contrast, END showed strong evidence for immune tolerance to the parasite, with high levels of circulating microfilariae, few clinical symptoms, and diminished filaria-specific IgG. The striking elevation in eosinophil counts among the TR group was accompanied by increased eosinophil granule protein levels (associated with eosinophil activation and degranulation) as well as elevated levels of eosinophil-associated cytokines.

Conclusions: These data support the hypothesis that differing eosinophil-associated responses to the parasite may be responsible for the marked differences in clinical presentations between TR and END populations with loiasis.

Keywords: Loa loa; eosinophil; loiasis.

Figure 1.

A–C, Pretreatment serum levels of eosinophil granule proteins. Each symbol represents an individual patient at presentation. The horizontal lines are the geometric mean. The dashed horizontal lines represent the limits of detection of the assay; values below these lines were calculated based on the standard curves. D, Correlation of serum eosinophil-derived neurotoxin (EDN) levels with absolute eosinophil count in the total patient group. Each dot represents an individual patient. Abbreviations: END, individuals native to endemic regions; TR, temporary residents.

Figure 2.

Serum cytokine levels in individuals native to endemic regions and temporary residents with loiasis. Each symbol represents an individual patient. Horizontal bars represent the geometric mean in each group. Abbreviations: END, individuals native to endemic regions; GM-CSF, granulocyte macrophage colony-stimulating factor; IL-4, interleukin 4; IL-5, interleukin 5; TR, temporary residents.

Figure 3.

Cytokine levels in microfilaria-positive and -negative patients. Each symbol represents an individual patient. Horizontal bars represent the geometric mean in each group. Abbreviations: GM-CSF, granulocyte macrophage colony-stimulating factor; IFN-γ, interferon gamma; IL-4, interleukin 4; IL-5, interleukin 5; MF, microfilaria.