Posttreatment Reactions After Single-Dose Diethylcarbamazine or Ivermectin in Subjects With Loa loa Infection

Abstract

Background. Severe adverse reactions have been observed in individuals withLoa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology.Methods. Twelve patients with loiasis and microfilarial counts <2000 mf/mL were randomized to receive single-dose DEC (8 mg/kg) or IVM (200 µg/kg). Clinical and laboratory assessments were performed at 4, 8, 24, 48, and 72 hours and 5, 7, 9, and 14 days posttreatment.Results. Posttreatment adverse events were similar following DEC or IVM, but peaked earlier in subjects who received DEC, consistent with a trend toward more rapid and complete microfilarial clearance in the DEC group. After a transient rise (post-IVM) or fall (post-DEC) in the first 24 hours posttreatment, the eosinophil count rose significantly in both groups, peaking at day 5 in the DEC group and day 9 in the IVM group. Serum interleukin 5 levels and eosinophil activation, as assessed by surface expression of CD69 and serum levels of eosinophil granule proteins, were increased posttreatment in both groups.Conclusions. Despite differences in eosinophil and lymphocyte counts during the first 24 hours posttreatment, the overall pattern of hematologic and immunologic changes suggest that posttreatment reactions following DEC and IVM share a common pathophysiology.Clinical Trials Registration. NCT01593722.

Imported loiasis in France: a retrospective analysis of 167 cases with comparison between sub-Saharan and non sub-Saharan African patients

“…The higher is the parasite load the higher is the risk of developing marked or serious adverse events such as encephalopathy when microfilaremia is above 50,000/ml [9,12]. Recent data suggest that post-treatment reactions following DEC and ivermectin occur earlier with DEC but share a common pathophysiology [29].…”

Cervical Lymphatic Filariasis in a Pediatric Patient: Case Report and Database Analysis of Lymphatic Filariasis in the United States

“…26,27,29,30 It is often used in lieu of DEC in areas where onchocerciasis is endemic-to avoid the severe adverse events related to killing of microfilariae. 30,31 For a similar reason, albendazole is often used as a pretreatment before administration of DEC in patients with high circulating levels of L. loa microfilariae. 31,32 Surgical excision is not considered part of standard treatment of lymphatic filariasis in endemic areas.…”

“…30,31 For a similar reason, albendazole is often used as a pretreatment before administration of DEC in patients with high circulating levels of L. loa microfilariae. 31,32 Surgical excision is not considered part of standard treatment of lymphatic filariasis in endemic areas. Although numerous case reports have described excision biopsies of affected lymph nodes without any apparent complications, it is unknown whether intraoperative violation of the specimen would lead to an anaphylactic reaction similar to those reported in hydatid cyst excisions.…”

Reduction of Loa loa Microfilaremia with Imatinib — A Case Report

“…2 The current case suggests that it may be possible to lower L. loa microfilarial levels in the blood safely and slowly with a single oral dose of imatinib so that definitive diethylcarbamazine treatment or ivermectin treatment as part of a mass administration program can be given to persons with previously unsafe levels of L. loa microfilariae. A larger prospective trial is planned (ClinicalTrials.gov number, NCT02644525) so that more definitive conclusions can be drawn regarding the use of imatinib in the treatment of L. loa infection.…”

“…1 The pathogenesis of these serious adverse events after ivermectin treatment (or after diethylcarbamazine treatment) is believed to involve an inflammatory response to the massive release of parasite antigens that occurs with the rapid death of L. loa microfilariae. 2 Recently, elimination efforts have begun to focus on screening potential recipients of ivermectin and excluding from drug treatment those who have high levels of L. loa microfilariae to avoid these adverse effects — a strategy that is termed “test and not treat.” 3 We have previously reported in the L. loa genome the presence of a homologue of the human c-Abl tyrosine kinase. 4 The inhibition of this L. loa c-Abl–like tyrosine kinase with imatinib led to the slow death of microfilariae in vitro, 4 probably because imatinib targets the tyrosine kinase expression in the nuclei of the microfilariae.…”