Early Stage

4. Immunologic Response to Ivermectin Treatment of Loiasis

Introduction: Loiasis related post-ivermectin (IVM) adverse events (AEs) hinder lymphatic filariasis (LF)/onchocerciasis elimination in co-endemic areas. Findings from LF suggest that post-IVM AEs might be the result of immune responses to filarial or Wolbachia antigens released by dying microfilariae (Mf). The aim of this study was to determine whether IVM treatment of loiasis, devoid of Wolbachia, generates similar immunologic responses and to assess if specific loa antigens are involved in this process.

Methods: Thirty-nine loiasis infected patients with daytime Mf counts between 3,720-16,020 (median: 8,600; IQR 5,580-11,980), were enrolled in Central Cameroon. After receiving 150µg/Kg IVM, they were followed-up daily for seven days. Blood was collected before treatment and 8, 16-, 32-, 40-, and 56-hours post-treatment for Mf count, circulating filarial antigen (CFA) quantification/identification and measurement of serum immune mediators. CFA levels were quantified using in-house direct sandwich ELISA and cytokines levels measured using the Bio-Plex Pro Human Cytokine 27-plex Assay.

Results: Daytime L. loa Mf counts decreased post-treatment by ~75% (median: 1,860, IQR: 1,155-2,910) by 56hrs. A subset of participants developed detectable CFA post-treatment, with the highest levels at 56hrs. Fifteen of 27 assayed cytokines significantly increased post-treatment (MIP-1b, MIP-1a, Eotaxin, FGF-b, MCP-1, TNF-a, INF-g, G-CSF, GM-CSF, IP-10, IL-1ra, IL-8, IL-10, IL-13, and IL-17), with a peak level at 32hrs. Conversely, RANTES, PDGF-BB, IL-2, IL-4 and IL-7 transiently increased post-treatment but then decreased lower than baseline levels by 56hrs. Unlike previous findings from LF, no significant association was found between cytokines levels and baseline Mf counts. No serious treatment-emergent AEs were observed; in fact, participants reported fewer AEs post-treatment that at baseline, despite baseline Mf counts much higher than those typically seen in LF. 

Impact: These data suggest that different mechanisms may be involved in the immune response to IVM treatment of loiasis vs. LF, and are consistent with a role for Wolbachia antigens in initiating treatment-emergent AEs in LF.

Organization – Washington University in St. Louis

Djune Yemeli L, Nana-Djeunga HC, Rush A, Kamgno J, Budge P