Efficacy of bovine viral diarrhea virus vaccination to prevent reproductive disease: A meta-analysis

Abstract

Bovine viral diarrhea virus (BVDV) is an important reproductive pathogen of cattle worldwide. The reproductive outcome of BVDV infection is largely dependent on the immune status of the dam and the stage of gestation at the time of infection. Potential sequelae include failure of conception, abortion, a variety of congenital malformations, and fetal infection. Vaccination is a possible tool in the control of BVDV, and there has been a recently renewed focus on providing fetal protection through vaccination. Consequently, the aim of this study was to evaluate the efficacy of BVDV vaccination to prevent reproductive disease by performing a quantitative synthesis of previously published studies. Pertinent articles to be included in the analysis were identified by performing a search in four relevant scientific databases (PubMed, CAB abstracts, National Agricultural Library catalog, and Web of Science) and examining the reference lists of 10 germane review articles. Inclusion criteria for the meta-analysis mandated that the studies were controlled, primary studies that included necessary data for use in the meta-analysis (e.g., group size, number of abortions). Forty-six studies in 41 separate articles matched the inclusion criteria. Risk ratio effect sizes were used in random effects, weighted meta-analyses to assess the impact of BVDV vaccination on three outcomes: risk of fetal infection, abortion risk, and pregnancy risk. Within each outcome, subanalyses were performed to evaluate the effect of a variety of interventions, including modified live, inactivated, polyvalent and monovalent vaccination, homologous, heterologous, or field challenge, and studies with only bovine subjects. The analysis revealed a decrease in abortions of nearly 45% and a nearly 85% decrease in fetal infection rate in cattle vaccinated for BVDV compared with unvaccinated cohorts. Additionally, pregnancy risk was increased by approximately 5% in field trials of BVDV vaccinates. This meta-analysis provides quantitative support for the benefit of vaccination in the prevention of BVDV-associated reproductive disease.

Introduction

Bovine viral diarrhea virus (BVDV) is the prototype virus of the Pestivirus genus and a principal viral pathogen in both dairy and beef cattle populations. Viral infection leads to a wide array of clinical signs including diarrhea, thrombocytopenia and hemorrhagic diatheses, respiratory disease, and ulcerations of the gastrointestinal tract. However, the largest economic consequence of BVDV infection may be through reproductive losses [1]. Reproductive disease as a result of BVDV infection has been recognized from the time the virus was first reported [2] and remains a major concern on dairy farms, cow-calf ranches, and breeding stock operations. The consequence of BVDV infection on reproduction depends largely on the immune status of the dam and the stage of gestation at the time of infection. Exposure of naive cattle to the virus at or near the time of breeding can result in reduced pregnancy rates because of decreased conception rates and early embryonic death [3], [4]. Abortion is most common in the first trimester but may occur at any time during gestation, including the third trimester. Viral exposure of the fetus between 18 and 125 days of gestation may lead to immunotolerance and persistent infection. Persistently infected (PI) calves are often weak at birth but may be phenotypically normal and are important to the epidemiologic aspects of viral propagation as they consistently shed high levels of virus in the environment. Infection during crucial times of organogenesis may also result in congenital defects including cerebellar hypoplasia, microphthalmia, hydranencephaly, hypotrichosis, and brachygnathism.

Control of BVDV is currently exerted primarily through strict biosecurity, eradication efforts, vaccination, or a combination of these factors. One of the primary aims of BVDV vaccination is to prevent the creation of PI calves that act as reservoirs of the virus. Although this goal was recognized by the mid-1970s [5], [6], the efficacy of early vaccines to prevent fetal infection was often incomplete [7], [8]. Improper vaccine usage has also contributed to their limited efficacy [9], [10]. More recently, several BVDV vaccines have been licensed that carry fetal protection claims with at least 365 days duration of immunity. Despite this, accounts of fetal infection in calves born to vaccinated dams continue to be reported in the literature [11], [12], [13] leading some to question the efficacy of BVDV vaccination to prevent reproductive disease. Consequently, the objective of this study was to analyze the published data in regard to the efficacy of BVDV vaccination to decrease the risk of abortion, the probability of fetal infection, or to prevent a decrease in pregnancy risk.