Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen

Author:

Endy Timothy P12,Keiser Paul B3,Cibula Don4,Abbott Mark1,Ware Lisa1,Thomas Stephen J1,Polhemus Mark E1

Affiliation:

1. Institute for Global Health and Translational Sciences, State University of New York Upstate Medical University, Syracuse, New York, USA

2. Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA

3. Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

4. Department of Public Health, State University of New York Upstate Medical University, Syracuse, New York, USA

Abstract

Abstract Background Chloroquine can impair the immune responses to intradermal rabies vaccination. Current guidelines recommend an extra intramuscular dose be given for postexposure prophylaxis in previously unvaccinated persons taking any antimalarial drug. Methods We conducted a randomized, open-label, single-site study in 103 previously unvaccinated healthy adults age ≥18 to ≤60 years old to evaluate the effects of chloroquine, atovaquone/proguanil (Malarone), and doxycycline on the antibody response to a purified chick embryo cell vaccine, given on a postexposure prophylaxis schedule. All treatment groups received antimalarials 14 days prior to and during vaccination. Results All subjects achieved accepted neutralizing antibody titers of ≥0.5 IU/mL following the second rabies vaccination dose and maintained this protection through the duration of the study. We observed a reduction in rabies antibody geometric mean titer in the chloroquine versus control groups 28 days after vaccination: 2.3 versus 6.87 IU/mL, respectively (P < .001, t test). A significant difference was not observed for those taking Malarone or doxycycline. Conclusions We conclude that there is no reduction of rabies antibody response in subjects taking Malarone or doxycycline, but a significant reduction in those taking chloroquine; however, accepted antibody levels were achieved for all 3 antimalarials. Clinical Trials Registration NCT02564471.

Funder

US Army Medical Research and Material Command

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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