Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis

Abstract

Background: Mild to moderate adverse events (AEs) are common after treatment of lymphatic filariasis (LF) and pose a major challenge for the global LF elimination program. We studied changes in cytokine levels and filarial worm components in plasma of subjects with and without AEs following treatment of LF.

Methods: Participants (n = 24) were hospitalized and monitored for AEs following treatment. Cytokines (27), filarial DNA, circulating filarial antigen (CFA), and immune complexes were measured in plasma samples collected before and after treatment.

Results: Levels for 16 cytokines increased after treatment in individuals with moderate AEs compared to individuals with no and/or mild AEs. These included 3 major proinflammatory cytokines (interleukin 6, tumor necrosis factor α, and interleukin 1β). Eotaxin-1 levels were elevated at baseline in individuals who developed moderate AEs after treatment; thus, eotaxin-1 is a potential biomarker for AE risk. CFA and filarial DNA levels increased more in individuals with moderate AEs after treatment than in people with no/mild AEs.

Conclusions: Increases in cytokine, filarial DNA, and CFA levels were associated with development of AEs following treatment of LF. Improved understanding of the pathogenesis of AEs may lead to improved methods for their prevention or management that could increase compliance in elimination programs.

Keywords: adverse events; circulating filarial antigenemia; cytokines; lymphatic filariasis; therapy.

Figure 1.

Mean cytokine levels (± standard error [SE]) in the 3 adverse event (AE) groups over time. Interleukin 6 (IL-6) (A), interleukin 10 (IL-10) (B), monocyte chemoattractant protein 1 (MCP-1) (C), and macrophage inflammatory protein 1β (MIP-1β) (D) increased posttreatment in the moderate AE group, whereas there were no significant changes in the no or mild AE groups. Significance (Kruskal–Wallis H test): * P < .05; **P < .01.

Figure 2.

Mean eotaxin-1 levels (± standard error) for all 3 adverse event (AE) groups over time. Eotaxin-1 levels were significantly higher at all time-points in the moderate AE group compared with the no and/or mild AE groups. Significance (Kruskal–Wallis H test): *P < .05; **P < .01.

Figure 3.

Mean W. bancrofti (Wb) circulating filarial antigen (CFA) levels (± standard error) for each adverse event (AE) group over time. CFA levels were significantly higher in the moderate AE group than in the no and mild AE groups. Significance (Kruskal–Wallis H test): *P < .05; **P < .01. CFA levels were significantly higher at 48 hours posttreatment compared with baseline in the moderate AE group (P = .048 by Wilcoxon signed-rank test).

Figure 4.

Filarial DNA levels in plasma (expressed as ∆ cycle threshold [Ct] ± standard error) after treatment by adverse event (AE) group. Ct values decreased after treatment in all 3 AE groups, signifying an increase in filarial DNA levels in plasma. Mean ∆Ct values were significantly greater in the moderate AE group compared with the mild AE group at 12 (P = .025) and 24 (P = .020) hours posttreatment (by analysis of variance). *P < .05.