Infection-associated Immune Perturbations Resolve 1 Year Following Treatment for Loa loa

Abstract

Background: We have previously demonstrated that eosinophil-associated processes underlie some of the differences in clinical presentation among patients with Loa loa infection prior to therapy and that some posttreatment adverse events appear to be dependent on eosinophil activation.

Methods: We first conducted a retrospective review of 204 patients (70 microfilaria [MF] positive/134 negative) with Loa loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pretreatment corticosteroids and/or apheresis in altering the efficacy of treatment.

Results: Patients without circulating microfilariae (MF negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels but also had significantly increased concentrations of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 5, and IL-4 compared with MF-positive patients. However, these differences had all resolved by 1 year after treatment, when all parameters approached the levels seen in uninfected individuals. Neither pretreatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects.

Conclusions: Our results highlight that, by 1 year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pretreatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of diethylcarbamazine as a curative agent in loiasis.

Clinical trials registration: NCT00001230.

Keywords: Loa loa; eosinophil; immunology; posttreatment.

Published by Oxford University Press for the Infectious Diseases Society of America 2020.

Figures

Figure 1.

Eosinophil counts and eosinophil granule protein levels, pretreatment and at 1 year after treatment. A, The AECs in the MF-negative (left, denoted by circles) and MF-positive (right, triangles) groups prior to treatment and at the 1-year follow-up time point. B, The concentration of each of the 4 eosinophil granule proteins prior to treatment and at the 1-year posttreatment time point for the MF-negative (left, circles) and MF-positive (right, triangles) groups. P values for the difference in concentrations at 1 year compared with baseline values, as determined by the Wilcoxon matched-pairs signed rank test, are shown above the horizontal bracket on each graph. P values listed as “ns” were not statistically significant (>.05). Abbreviations: AEC, absolute eosinophil count; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; EPO, eosinophil peroxidase; MBP, major basic protein; MF, microfilaria; Rx, treatment; Yr, year.

Figure 2.

Cytokine levels, pretreatment and 1 year following treatment. The concentration of each cytokine measured in the MF-negative (left, circles) and MF-positive (right, triangles) groups prior to and 1 year following treatment. P values for the difference in concentrations at 1 year compared with baseline values, as determined by the Wilcoxon matched-pairs signed rank test, are shown above the horizontal bracket on each graph. P values listed as “ns” were not statistically significant (>.05). Abbreviations: GM-CSF, granulocyte-macrophage colony–stimulating factor; IL, interleukin; MF, microfilaria; Rx, treatment; Yr, year.

Figure 3.

Response to treatment. A, The Loa loa–specific antibody responses specific for the Ll-SXP-1 (accession number AF174420) gene product at baseline and 1 year following treatment. B, The percentage of subjects in the MF-negative (blue line) and MF-positive (red line) groups who were cured following each round of treatment. Abbreviations: IgG, immunoglobulin G; MF, microfilaria; Rx, treatment.