Cargando…

Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs

To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by...

Descripción completa

Detalles Bibliográficos
Autores principales: Arega, Sintayehu, Conan, Anne, Sabeta, Claude T., Crafford, Jan E., Wentzel, Jeanette, Reininghaus, Bjorn, Biggs, Louise, Leisewitz, Andrew L., Quan, Melvyn, Toka, Felix, Knobel, Darryn L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157201/
https://www.ncbi.nlm.nih.gov/pubmed/32178448
http://dx.doi.org/10.3390/tropicalmed5010045
_version_ 1783522329672810496
author Arega, Sintayehu
Conan, Anne
Sabeta, Claude T.
Crafford, Jan E.
Wentzel, Jeanette
Reininghaus, Bjorn
Biggs, Louise
Leisewitz, Andrew L.
Quan, Melvyn
Toka, Felix
Knobel, Darryn L.
author_facet Arega, Sintayehu
Conan, Anne
Sabeta, Claude T.
Crafford, Jan E.
Wentzel, Jeanette
Reininghaus, Bjorn
Biggs, Louise
Leisewitz, Andrew L.
Quan, Melvyn
Toka, Felix
Knobel, Darryn L.
author_sort Arega, Sintayehu
collection PubMed
description To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.
format Online
Article
Text
id pubmed-7157201
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-71572012020-05-01 Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs Arega, Sintayehu Conan, Anne Sabeta, Claude T. Crafford, Jan E. Wentzel, Jeanette Reininghaus, Bjorn Biggs, Louise Leisewitz, Andrew L. Quan, Melvyn Toka, Felix Knobel, Darryn L. Trop Med Infect Dis Article To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms. MDPI 2020-03-12 /pmc/articles/PMC7157201/ /pubmed/32178448 http://dx.doi.org/10.3390/tropicalmed5010045 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arega, Sintayehu
Conan, Anne
Sabeta, Claude T.
Crafford, Jan E.
Wentzel, Jeanette
Reininghaus, Bjorn
Biggs, Louise
Leisewitz, Andrew L.
Quan, Melvyn
Toka, Felix
Knobel, Darryn L.
Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
title Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
title_full Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
title_fullStr Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
title_full_unstemmed Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
title_short Rabies Vaccination of 6-Week-Old Puppies Born to Immunized Mothers: A Randomized Controlled Trial in a High-Mortality Population of Owned, Free-Roaming Dogs
title_sort rabies vaccination of 6-week-old puppies born to immunized mothers: a randomized controlled trial in a high-mortality population of owned, free-roaming dogs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157201/
https://www.ncbi.nlm.nih.gov/pubmed/32178448
http://dx.doi.org/10.3390/tropicalmed5010045
work_keys_str_mv AT aregasintayehu rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT conananne rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT sabetaclaudet rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT craffordjane rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT wentzeljeanette rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT reininghausbjorn rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT biggslouise rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT leisewitzandrewl rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT quanmelvyn rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT tokafelix rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs
AT knobeldarrynl rabiesvaccinationof6weekoldpuppiesborntoimmunizedmothersarandomizedcontrolledtrialinahighmortalitypopulationofownedfreeroamingdogs