Abstract
Brucella abortus strain 19 (S19), Brucella melitensis Rev 1 (Rev1), and B. abortus strain RB51 (RB51) are the three licensed animal brucellosis vaccines, and they have been most commonly and successfully used in prevent brucellosis in animals. However, many adverse events (AEs) have been associated with these three vaccines after their administering to animals or being accidentally exposed to humans. In this study, 27 peer-reviewed publications containing animal and human AE reports associated with these three brucellosis vaccines were manually annotated from the PubMed database. Our meta-analysis identified 20 animal AEs and 46 human AEs associated with the three vaccines. Based on the Ontology of Adverse Events (OAE) hierarchical classification, these animal AEs were enriched in the immune and reproductive systems that might eventually result in the occurrence of abortion or infertility. The human AEs were concentrated in the behavioral and neurological conditions, and these AEs showed flu-like symptoms that are consistent with human brucellosis. Furthermore, an analysis of variance (ANOVA) statistics analysis with linear model fits was used to determine the major variables that might affect the occurrence of abortion AE in animals. The ANOVA results indicated that three variables (P-value < 0.05) are significantly associated with the occurrence of abortion AE: animal species, vaccination dose, and vaccination route. The other two variables (i.e., vaccine type and animal age at vaccination) did not significantly (P-value > 0.05) associated with the occurrence of abortion AE. Overall, this study represents the first ontology-based meta-analysis of adverse events associated with animal vaccines. The results of such a study led to the better understanding of brucellosis vaccine AEs, facilitating rational design of more secure and effective vaccines.
Highlights
Brucellosis, the most common bacterial zoonosis worldwide, is caused by Gram-negative intracellular coccobacillus Brucella (Corbel, 1997)
A total of 27 papers (Supplementary Presentation S2) were identified to have reported the adverse events (AEs) associated with at least one of these three vaccines. Six of these 27 papers (22.2%) reported AEs associated with strain 19 (S19) vaccination, 7/27 (25.9%) papers reported AEs associated with Rev 1 (Rev1) vaccination, and 16/27 (59.3%) papers reported AEs associated with RB51 vaccination
Our meta-analysis identified a total of 20 AEs associated with S19, Rev1, and/or RB51 in 15 different species of animals (Table 1)
Summary
Brucellosis, the most common bacterial zoonosis worldwide, is caused by Gram-negative intracellular coccobacillus Brucella (Corbel, 1997). Brucella spp. infects a variety of domestic and wild animals such as cattle, sheep, goats, pigs, and Brucellosis Vaccine Adverse Events dogs. Brucella infections of these animals may result in serious illnesses (e.g., arthropathy and abortion) and even death. As reported in 2006, an annual average of 110 human Brucella infection cases were reported to the National Notifiable Diseases Surveillance System (NNDSS) in the United States; more than half a million of new human brucellosis cases occurred each year worldwide (Pappas et al, 2006). Undulant fever is the most common symptom of brucellosis, followed by osteoarticular involvement (e.g., arthralgia and arthritis), sweating, and constitutional symptoms (e.g., malaise and weight loss) (Franco et al, 2007)
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