Материал: Bovine Viral Diarrhea Virus Diagnosis, Management, and Control

tive consequences. Simulation modeling suggests that as herd immunity to BVDV wanes, and more and more animals become susceptible to infection, the number of PI animals will increase (Innocent et al. 1997).

SUMMARY

In summary, BVDV can be transmitted briefly by animals following an acute infection and continuously by animals with a persistent BVDV infection. Although presumably rare, it is not known the extent to which virus shedding can be reactivated in acutely infected animals some time after an initial infectious period has waned or by which shedding can be intermittent in PI animals. Animals in the infectious phase of a BVDV infection shed less virus than PI animals, and R0 values for transmission from acutely infected animals typically can be expected to be in the order of magnitude of <5, whereas those for transmission from PI animals generally would be >10–20. Consequently, vaccine efficacy and/or the proportion of animals immunized by vaccination must be higher to offer protection against infection acquired from PI animals than from acutely infected animals. Vaccine efficacy aimed at preventing infection is correlated with the degree of homology between the strain of virus used in the vaccine and the strain of virus being prevented. Vaccination may be ineffective in herds with field strains sufficiently heterologous to the vaccine strain to prevent development of adequate protecting cross-reacting SN antibodies. Vaccines employing only one genotype of the virus should not be expected to be efficacious in preventing infection with a strain of the other genotype.

As with other infectious diseases, the forces driving transmission of BVDV in a susceptible population are the infectiousness of the virus (coefficient of infectiousness = ß), the contact rate between infectious and susceptible animals, the duration of infectiousness (or proportion of the population that is infectious), and the proportion of the population that is susceptible to infection. Each of these forces should be addressed in programs to limit or control BVDV infection. Vaccination is aimed generally at slowing or stopping transmission by promoting herd immunity; specifically, this is accomplished by reducing the proportion of susceptible animals (increasing the proportion that are immune), and by shortening the shedding period (reducing the duration of infectiousness) and lowering the amount of virus shed (reducing ß) for animals that do become infected.

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INTRODUCTION

Understanding the clinical manifestations of bovine viral diarrhea virus (BVDV) has been a continual challenge for the veterinarian (Tremblay, 1996). Grooms et al. (2002) described five forms of clinical BVDV: acute BVDV infection, severe acute BVDV infection, hemorrhagic BVDV infection, acute BVDV infection–bovine respiratory disease (BRD), and acute BVDV infection–immunosuppression. A significant percentage (70–90%) of BVDV infections results in subclinical infections. However, whether the BVDV infection is one of the acute forms or is subclinical in nature, there is a certain period of virus shedding. These transiently infected (TI) cattle can be a source of virus to susceptible ruminants in the population (Cherry et al., 1998). If the susceptible animal is pregnant, there is a risk of fetal exposure resulting in early embryonic death, abortion, or congenital infections/defects (Mickelsen and Evermann, 1994; Muñoz-Zanzi et al., 2003). An important consequence of congenital infection results from infection of the fetus between 90 and 120 days of gestation. Infection of naive cows during this period results in the birth of calves, which are immunologically vulnerable to BVDVspecific induced tolerance (McClurkin et al., 1984). This tolerance results in a condition commonly referred to as persistent infection (PI). The hallmark of the BVDV PI is that while the animal may appear clinically normal, it has a prolonged viremia (in most cases lifelong) during which it sheds large quantities of virus (Figure 6.1; Bolin, 1995).

This chapter focuses primarily on the clinical outcome of BVD viral infection, and in the process, poses key questions on the ecology and epidemiology of BVDV. These questions will include the following:

•Is the clinical presentation of BVDV infection changing as new strains of virus emerge?

•Is the acute (transient) or chronic (persistent) phase of BVDV infection altered due to the use of BVDV vaccination?

•Is fetal infection with BVDV increasing or decreasing?

We also review the course of initial BVDV infection in naive immunocompetent cattle, recognition of clinical symptoms associated with acute and persistent BVDV infections, duration and severity of clinical symptoms, and recovery from subclinical and clinical symptoms.

An important aspect of BVDV infection is interspecies transmission and the possible spread of BVDV strains among small and large domestic ruminants, as well as wildlife species such as deer, elk, and moose (Loken, 1995; Nettleton and Entrican, 1995). This topic concludes with the feasibility of BVDV control in populations, and whether eradication is achievable at different levels of livestock production.

COURSE OF INITIAL INFECTION IN NAIVE IMMUNOCOMPETENT CATTLE POPULATION

Infection of cattle with BVDV can result in a wide spectrum of clinical manifestations, from imperceptible subclinical infections to fulminant signs ending in death (Baker, 1995). The clinical response to infection is complex and depends on several host and agent factors (Ames, 1986). Host factors that influence the outcome of clinical disease include immunocompetance, immunotolerance, pregnancy status, gestational age of the fetus, the immune status (passive or active immunity from previous infection or vaccination), and the level of environmental stress (Baker, 1995). Viral factors influencing clinical outcome include genomic and antigenic diversity among BVDV isolates (Archambault et al., 2000;

Bolin and Ridpath, 1996; Ridpath et al., 2000). Currently, two distinct genotypes (BVDV type 1 and BVDV type 2), as well as 11 subgenotypes (BVDV types 1a–1k) are recognized (Brownlie et al., 2000; Vilcek et al., 2001). Differences in virulence among isolates have been recognized for over a decade (Bolin and Ridpath, 1992). Interestingly, recent epidemiologic studies have revealed that the incidence of infection with specific genotypes, as well as the clinical outcome after infection, have changed over time (Evermann and Ridpath, 2002).

Bovine viral diarrhea virus is acquired primarily through aerosols that infect nasal mucosa. The aerosols may become suspended in ambient air and retain infectivity for distances as short as 1.5 m and as far as 10 m (Niskanen and Lindberg, 2003). Direct nose-to-nose contact between an infected animal and a susceptible animal is considered to be the most effective route for BVDV transmission. There are reports of indirect spread of BVDV by use of nose tongs and housing animals in recently (within 2 hrs) contaminated pens (Niskanen and Lindberg, 2003). The virus replicates in draining lymph nodes and from there spreads via circulating lymphoid cells to the blood (Figure 6.2). Viremia can be detected as early as 24 hours postinfection (Mills and Luginbuhl, 1968), and this viremic phase is closely paralleled by the presence of virus in urine 48 hours postinfection. The course of the viremia and the presence of virus in the urine are dependent upon

the presence or absence of colostral antibodies. Colostral BVDV antibody is believed to persist for up to 6 months of age, which accounts for the higher incidence of BVDV-associated disease after this time period (Baker, 1995; Bolin, 1995).

BVDV IN COLOSTRUM-DEPRIVED CALVES

In experimentally infected, colostrum-deprived calves there were diphasic pyrexia, leukopenia, anorexia, and various degrees of diarrhea (Mills and Luginbuhl, 1968). Infectious BVDV was isolated from the spleen and thymus for at least 25 days postinfection (dpi). Lymph nodes draining the forestomachs and intestines were positive for virus until 39 dpi, while those of the duodenum were positive up to 56 dpi. Virus was also isolated from the trachea, lungs, and bronchial lymph nodes at 56 dpi. On the basis of these studies, it was concluded that BVDV is carried in the respiratory tract and may constitute the single most important epizootiologic factor in the pathogenesis of the disease (Mills and Luginbuhl, 1968). These prophetic words were supported repeatedly in subsequent reports on the clinical descriptions of BVDV (Callan and Garry, 2002; Grooms, 1999; Potgieter et al., 1984a).

BVDV IN 6-MONTH-OLD SERONEGATIVE

CALVES

A later study using 6-month-old calves reported clinical symptoms limited to a mild bilateral serous nasal