Jesica A Herrick1, Fanny Legrand1, Raceline Gounoue2, Godwin Nchinda3, Céline Montavon4, Jean Bopda5, Steve Mbickmen Tchana5, Bienvenu Etogo Ondigui6, Konrad Nguluwe7, Michael P Fay8, Michelle Makiya1, Simon Metenou1, Thomas B Nutman1, Joseph Kamgno5,9, Amy D Klion1. 1. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 2. Faculty of Sciences, University of Yaoundé I, Yaoundé, Cameroon. 3. Laboratory of Immunology, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS, Yaoundé, Cameroon. 4. Institut de recherche pour le développement, Montpellier, France. 5. Center for Research on Filariasis and Other Tropical Diseases, Yaoundé, Cameroon. 6. Central Hospital of Yaoundé, Yaoundé, Cameroon. 7. District Hospital of Akonolinga, Cameroon. 8. Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. 9. Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon.
Abstract
Background: Severe adverse reactions have been observed in individuals with Loa loa infection treated with eitherdiethylcarbamazine (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.
RCT Entities:
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.
Entities:
Keywords:
Loa loa; diethylcarbamazine; eosinophil; filariasis; ivermectin
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