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

Jesica A Herrick, Fanny Legrand, Raceline Gounoue, Godwin Nchinda, Céline Montavon, Jean Bopda, Steve Mbickmen Tchana, Bienvenu Etogo Ondigui, Konrad Nguluwe, Michael P Fay, Michelle Makiya, Simon Metenou, Thomas B Nutman, Joseph Kamgno, Amy D Klion

Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2017;64(8):1017-1025

PMID: 28329346

Abstract

BACKGROUND

Severe adverse reactions have been observed in individuals with Loa 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.

Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Address: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon.; Laboratory of Immunology, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS, Yaoundé, Cameroon.; Institut de recherche pour le développement, Montpellier, France.; Center for Research on Filariasis and Other Tropical Diseases, Yaoundé, Cameroon.; Central Hospital of Yaoundé, Yaoundé, Cameroon.; District Hospital of Akonolinga, Cameroon.; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon.
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