bovine herpesvirus 1 infections
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Top of pagePreferred Scientific Name
- bovine herpesvirus 1 infections
International Common Names
- English: encephalitic bovine herpesvirus type 5 or type 1 infection in cattle; ibr, infectious bovine rhinotracheitis-contaminated semen; infectious bovine rhinotracheitis; infectious bovine rhinotracheitis virus, ibr, in swine; infectious bovine rhinotracheitis/infectious pustular vulvovaginitis; infectious pustular vulvovaginitis; neonatal septicemic infectious bovine rhinotracheitis, ibr
English acronym
- BHV
- IBR
- IPB
- IPV
Overview
Top of pageInfectious bovine rhinotracheitis (IBR) is a contagious viral disease of cattle caused by bovine herpesvirus 1 (BHV-1) (Gibbs and Rweyemamu, 1977; Pastoret et al., 1982; Wyler et al., 1989; Tikoo et al., 1995). This virus is also responsible for infectious pustular vulvovaginitis (IPV), balanoposthitis and abortion.
IPV was the only known infection caused by BHV-1 prior to the 1950s, when the respiratory disease IBR, emerged in North America as a consequence of the intensification of cattle husbandry. The respiratory disease spread all over the world and arrived in Europe during the 1970s. The IBR form is the most frequently diagnosed BHV-1 disease.
Pathogenicity of BHV-1 can vary from mild to severe and the relative importance of each syndrome varies between countries. Although mortality is low, BHV-1 infection is economically important as it may cause a drop in production and affect trade restrictions. When animals survive, a life-long latent infection is established in sensory ganglia. Several reactivation stimuli can lead to viral re-excretion, which is responsible for the maintenance of BHV-1 within a cattle herd (Muylkens et al. 2007). The latency and reactivation cycle have a significant impact on the epidemiology and control of BHV-1. Europe has a long history of fighting against BHV-1 infections, but only a small number of countries have achieved IBR-eradication (Ackermann et al., 1990; Ackermann and Engels, 2006).
This disease is on the list of diseases notifiable to the World Organisation for Animal Health (OIE). The distribution section contains data from OIE's WAHID database on disease occurrence. Please see the AHPC library for further information on this disease from OIE, including the International Animal Health Code and the Manual of Standards for Diagnostic Tests and Vaccines. Also see the website: www.oie.int.
Host Animals
Top of pageHosts/Species Affected
Top of pageThe natural hosts are bovine species. The hosts table shows the ruminant species from which BHV-1 has been isolated or when serological data have given evidence of the infection. Despite this apparent broad range, BHV-1 has a narrow species specificity. The truly susceptible species can be defined as animals in which BHV-1 can establish a latent infection: cattle, sheep (Thiry et al., 2001), goats (Six et al., 2001) and other species belonging to the subfamily Bovidae, such as wildebeest (Karstad et al., 1974).
Systems Affected
Top of pagereproductive diseases of pigs
reproductive diseases of small ruminants
respiratory diseases of large ruminants
respiratory diseases of small ruminants
Distribution
Top of pageBHV-1 is distributed worldwide and has been diagnosed in all countries tested (Straub, 1990). A few European countries have successfully eradicated the infection by applying a strict culling policy, including Denmark, Sweden, Finland, Switzerland and Austria (OIE, 2005). Other countries have started similar control programmes.
For current information on disease incidence, see OIE's WAHID Interface.
Distribution Table
Top of pageThe distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.
Last updated: 04 Jan 2022Continent/Country/Region | Distribution | Last Reported | Origin | First Reported | Invasive | Reference | Notes |
---|---|---|---|---|---|---|---|
Africa |
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Algeria | Absent | Jul-Dec-2019 | |||||
Benin | Absent, No presence record(s) | ||||||
Botswana | Absent | Jul-Dec-2018 | |||||
Burundi | Absent | Jul-Dec-2018 | |||||
Cabo Verde | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Central African Republic | Absent, No presence record(s) | ||||||
Chad | Absent | Jul-Dec-2019 | |||||
Congo, Democratic Republic of the | Absent, No presence record(s) | ||||||
Djibouti | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Egypt | Absent | Jul-Dec-2019 | |||||
Eritrea | Absent | Jul-Dec-2019 | |||||
Ethiopia | Absent | Jul-Dec-2018 | |||||
Gabon | Absent, No presence record(s) | ||||||
Ghana | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Kenya | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Lesotho | Absent | Jan-Jun-2020 | |||||
Liberia | Absent | Jul-Dec-2018 | |||||
Libya | Absent, No presence record(s) | ||||||
Madagascar | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Malawi | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Mali | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Mauritius | Absent | Jul-Dec-2019 | |||||
Mayotte | Present | Jul-Dec-2019 | |||||
Morocco | Absent | Jul-Dec-2019 | |||||
Mozambique | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Namibia | Absent | Jul-Dec-2019 | |||||
Niger | Absent | Jul-Dec-2019 | |||||
Réunion | Present | Jul-Dec-2019 | |||||
Rwanda | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Saint Helena | Absent, No presence record(s) | Jan-Jun-2019 | |||||
São Tomé and Príncipe | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Seychelles | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Sierra Leone | Absent | Jan-Jun-2018 | |||||
Somalia | Absent | Jul-Dec-2020 | |||||
South Africa | Absent | Jul-Dec-2019 | |||||
Sudan | Absent | Jul-Dec-2019 | |||||
Tanzania | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Togo | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Tunisia | Absent | Jul-Dec-2019 | |||||
Uganda | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Zambia | Present | Jul-Dec-2018 | |||||
Zimbabwe | Absent | Jul-Dec-2019 | |||||
Asia |
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Armenia | Absent | Jul-Dec-2019 | |||||
Azerbaijan | Absent | Jul-Dec-2019 | |||||
Bahrain | Absent, No presence record(s) | Jul-Dec-2020 | |||||
Bangladesh | Absent | Jan-Jun-2020 | |||||
Bhutan | Absent | Jan-Jun-2020 | |||||
Brunei | Absent, No presence record(s) | Jul-Dec-2019 | |||||
China | Present, Localized | Jul-Dec-2018 | |||||
Georgia | Absent | Jul-Dec-2019 | |||||
India | Absent | Jan-Jun-2019 | |||||
Indonesia | Present, Localized | Jul-Dec-2019 | |||||
Iran | Present | Jan-Jun-2019 | |||||
Iraq | Absent | Jul-Dec-2019 | |||||
Israel | Absent | Jul-Dec-2020 | |||||
Japan | Present | Jan-Jun-2020 | |||||
Jordan | Present | Jul-Dec-2018 | |||||
Kazakhstan | Absent | Jul-Dec-2019 | |||||
Kuwait | Absent | Jan-Jun-2019 | |||||
Kyrgyzstan | Absent | Jan-Jun-2019 | |||||
Laos | Absent | Jan-Jun-2019 | |||||
Lebanon | Absent | Jul-Dec-2019 | |||||
Malaysia | Absent | Jan-Jun-2019 | |||||
-Peninsular Malaysia | Absent, No presence record(s) | ||||||
Maldives | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Mongolia | Absent | Jan-Jun-2019 | |||||
Myanmar | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Nepal | Absent | Jul-Dec-2019 | |||||
North Korea | Absent, No presence record(s) | ||||||
Oman | Absent | Jul-Dec-2019 | |||||
Palestine | Absent | Jul-Dec-2019 | |||||
Philippines | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Qatar | Absent | Jul-Dec-2019 | |||||
Saudi Arabia | Absent | Jan-Jun-2020 | |||||
Singapore | Absent, No presence record(s) | Jul-Dec-2019 | |||||
South Korea | Present | Jul-Dec-2019 | |||||
Sri Lanka | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Syria | Absent | Jul-Dec-2019 | |||||
Taiwan | Absent | Jul-Dec-2019 | |||||
Tajikistan | Absent | Jan-Jun-2019 | |||||
Thailand | Absent | Jan-Jun-2020 | |||||
Turkmenistan | Absent | Jan-Jun-2019 | |||||
United Arab Emirates | Absent | Jul-Dec-2020 | |||||
Uzbekistan | Absent | Jul-Dec-2019 | |||||
Vietnam | Absent | Jul-Dec-2019 | |||||
Europe |
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Andorra | Present | Jul-Dec-2019 | |||||
Austria | Absent | Jul-Dec-2019 | |||||
Belarus | Present, Localized | Jul-Dec-2019 | |||||
Belgium | Present, Localized | Jul-Dec-2019 | |||||
Bosnia and Herzegovina | Absent | Jul-Dec-2019 | |||||
Bulgaria | Absent | Jan-Jun-2019 | |||||
Croatia | Absent | Jul-Dec-2019 | |||||
Cyprus | Present | Jul-Dec-2019 | |||||
Czechia | Absent | Jul-Dec-2019 | |||||
Denmark | Absent | Jan-Jun-2019 | |||||
Estonia | Present | Jul-Dec-2019 | |||||
Faroe Islands | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Finland | Absent | Jul-Dec-2019 | |||||
France | Present | Jul-Dec-2019 | |||||
Germany | Absent | Jul-Dec-2019 | |||||
Greece | Present | Jan-Jun-2018 | |||||
Hungary | Present | Jul-Dec-2019 | |||||
Iceland | Absent | Jul-Dec-2019 | |||||
Ireland | Present | Jul-Dec-2019 | |||||
Isle of Man | Present | ||||||
Italy | Absent | Jul-Dec-2020 | |||||
Jersey | Absent, No presence record(s) | ||||||
Latvia | Present | Jul-Dec-2020 | |||||
Liechtenstein | Absent | Jul-Dec-2019 | |||||
Lithuania | Absent | Jul-Dec-2019 | |||||
Luxembourg | Present | ||||||
Malta | Present | Jan-Jun-2019 | |||||
Moldova | Absent | Jan-Jun-2020 | |||||
Montenegro | Present, Localized | Jul-Dec-2019 | |||||
Netherlands | Present | Jul-Dec-2019 | |||||
North Macedonia | Present | Jul-Dec-2018 | |||||
Norway | Absent | Jul-Dec-2019 | |||||
Poland | Present | Jan-Jun-2019 | |||||
Portugal | Present | Jul-Dec-2019 | |||||
Romania | Absent | Jul-Dec-2018 | |||||
Russia | Present, Localized | Jan-Jun-2020 | |||||
San Marino | Absent | Jan-Jun-2019 | |||||
Serbia | Absent | Jul-Dec-2019 | |||||
Serbia and Montenegro | Present | ||||||
Slovakia | Absent | Jul-Dec-2020 | |||||
Slovenia | Present, Localized | Jul-Dec-2018 | |||||
Spain | Present | Jul-Dec-2020 | |||||
Sweden | Absent | Jul-Dec-2020 | |||||
Switzerland | Present | Jul-Dec-2020 | |||||
Ukraine | Absent | Jul-Dec-2020 | |||||
United Kingdom | Present | Jul-Dec-2019 | |||||
-Northern Ireland | Present | ||||||
North America |
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Bahamas | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Barbados | Absent | Jul-Dec-2020 | |||||
Belize | Absent | Jul-Dec-2019 | |||||
Bermuda | Absent, No presence record(s) | ||||||
British Virgin Islands | Absent, No presence record(s) | ||||||
Canada | Present | Jul-Dec-2019 | |||||
Cayman Islands | Absent | Jan-Jun-2019 | |||||
Costa Rica | Present | Jul-Dec-2019 | |||||
Cuba | Absent | Jan-Jun-2019 | |||||
Curaçao | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Dominica | Absent, No presence record(s) | ||||||
Dominican Republic | Present | Jan-Jun-2019 | |||||
El Salvador | Present | Jul-Dec-2019 | |||||
Greenland | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Guatemala | Present | Jan-Jun-2019 | |||||
Haiti | Absent, No presence record(s) | Jul-Dec-2019 | |||||
Honduras | Present, Localized | Jul-Dec-2018 | |||||
Jamaica | Absent | Jul-Dec-2018 | |||||
Martinique | Present | Jul-Dec-2019 | |||||
Mexico | Present, Localized | Jul-Dec-2019 | |||||
Nicaragua | Present | Jul-Dec-2019 | |||||
Panama | Present | Jan-Jun-2019 | |||||
Saint Kitts and Nevis | Absent, No presence record(s) | ||||||
Saint Lucia | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Saint Vincent and the Grenadines | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Trinidad and Tobago | Absent, No presence record(s) | Jan-Jun-2018 | |||||
United States | Present | Jul-Dec-2019 | |||||
Oceania |
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Australia | Present | Jul-Dec-2019 | |||||
Cook Islands | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Federated States of Micronesia | Absent, No presence record(s) | Jan-Jun-2019 | |||||
Fiji | Absent | Jan-Jun-2019 | |||||
French Polynesia | Present | Jan-Jun-2019 | |||||
Kiribati | Absent, No presence record(s) | Jan-Jun-2018 | |||||
Marshall Islands | Absent, No presence record(s) | Jan-Jun-2019 | |||||
New Caledonia | Present | Jul-Dec-2019 | |||||
New Zealand | Present | Jul-Dec-2019 | |||||
Palau | Absent | Jul-Dec-2020 | |||||
Samoa | Absent | Jan-Jun-2019 | |||||
Timor-Leste | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Tonga | Absent | Jul-Dec-2019 | |||||
Vanuatu | Absent | Jan-Jun-2019 | |||||
South America |
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Argentina | Present | Jul-Dec-2019 | |||||
Bolivia | Present | Jan-Jun-2019 | |||||
Brazil | Present | Jul-Dec-2019 | |||||
Chile | Present | Jan-Jun-2019 | |||||
Colombia | Present | Jul-Dec-2019 | |||||
Ecuador | Present | Jul-Dec-2019 | |||||
Falkland Islands | Absent | Jul-Dec-2019 | |||||
French Guiana | Absent | Jul-Dec-2019 | |||||
Guyana | Absent, No presence record(s) | Jul-Dec-2018 | |||||
Paraguay | Present, Localized | Jul-Dec-2019 | |||||
Peru | Present, Localized | Jan-Jun-2019 | |||||
Suriname | Absent | Jan-Jun-2019 | |||||
Uruguay | Present | Jul-Dec-2019 | |||||
Venezuela | Present | Jan-Jun-2019 |
Pathology
Top of pageSubclinical infection
Infectious bovine rhinotracheitis (IBR) is a sporadic viral disease. Outbreaks are observed during winter, but the incidence of the disease is low, whatever the prevalence rate in a given region. High seroprevalence without a high incidence of disease is generally explained by the circulation of hypovirulent strains, as suggested by the results of experimental inoculation of calves with strains of varying virulence (Kaashoek et al., 1996). However, subclinical infection with a BHV-1 strain normally associated with clinically severe respiratory disease has been reported in a high health status dairy herd, which had previously been seronegative for 13 years. Although over 70% of the herd had seroconverted to BHV no clinical signs were observed apart from a slight bilateral serous ocular discharge in a few cows; performance and productivity were unaffected (Pritchard et al., 2003).
Infectious bovine rhinotracheitis (IBR)
The respiratory form is the most frequently observed disease provoked by BHV-1. It affects all categories of animals. Calves are usually protected by colostral antibodies until 3-4 months of age. The severity of clinical signs varies considerably. Because of its ability to induce immune suppression, BHV-1 is an important agent in the multifactorial disorder, bovine respiratory disease complex (Jones and Chowdhury, 2010). The virus is also responsible for a typical respiratory disease called infectious bovine rhinotracheitis (IBR).
The virus is excreted in the nasal secretions as early as 24 hours after infection. After an incubation period of 2 to 4 days, nasal secretions are more profuse and evolve from sero-mucous to mucopurulent discharge. Young animals show ptyalism. Around 4 days after the beginning of excretion, elevated temperatures are recorded, and animals are depressed and anorexic. In lactating cows, the milk production suddenly drops.
Ulcers and redness are visible on the nasal mucosa, in the pharynx and trachea (see pictures). Lesions are usually restricted in the upper respiratory tract. Bronchitis and pneumonia can also be observed, but usually as a consequence of secondary bacterial infections. Coughing and sneezing are observed. Conjunctivitis is associated with the respiratory form and is manifest by increased eye secretions.
Animals recover within 14 days, due to the rise of the specific immune response. Some highly virulent BHV-1 strains induce a high mortality rate.
Lesions are almost exclusively restricted to the upper respiratory tract: rhinitis, laryngitis and tracheitis. Respiratory mucosae are red and oedematous, foci of ulcers are observed and some lesions are haemorrhagic (Gibbs and Rweyemamu, 1977; Wyler et al., 1989; Straub, 1990).
Abortion
A review by Graham (2013) highlights the negative reproductive outcomes associated with BHV-1. Infection at the time of service may reduce fertility, with the potential to cause chronic necrotising endometritis and oophoritis, accompanied by a shortened oestrous cycle. Infection later in the oestrous cycle may result in a decreased conception rate, whereas infection later in pregnancy can lead to abortion.
Abortion is observed between 4 and 8 months of gestation. Early embryonic death can also occur. Abortion is a consequence of respiratory infection of pregnant cows. Viraemia allows the virus to enter the uterine artery and cross the placenta. Abortion is due to a lytic infection of the fetus. All internal organs of the fetus, especially the liver and renal cortex, show foci of necrosis. A generalized multifocal necrosis is diagnosed (Smith, 1997).
Infection of cows during the last trimester of gestation can lead to neonatal death, and death of weak calves can occur during the first 2 weeks of life (Thiry et al., 1984).
Infectious pustular vulvovaginitis (IPV) - infectious pustular balanoposthitis (IPB)
A pustular inflammation occurs in the male or female genital mucosa, together with a rise in body temperature: up to 41.5°C. The genital mucosa is red and oedematous, and vesicles and pustules evolve into ulcers. The lesions resolve within 1 to 2 weeks (Straub, 1990).
Metritis
Metroperitonitis has been observed in cows infected with BHV-1 around parturition, and especially after caesarean section (Lomba et al., 1976).
Encephalitis
Encephalitis cases have been mostly reported in calves but can also occur in older animals (Roels et al., 2000). In the case of bovine encephalitis, the distinction must be made between BHV-1 and BHV-5, the latter being the usual etiological agent of bovine encephalitis (Meyer et al., 2001).
Neonatal diseases
Neonatal calves often succumb after a generalized infection. They show coughing, nasal and ocular discharge, bronchopneumonia, diarrhoea, ulcers in the digestive tract and hyperthermia. The lesions can be concentrated in the mouth, with ulcers and profuse salivation. A pure respiratory form is rarely observed in neonates. Encephalitis has been observed in 3 to 8 day-old calves (Thiry et al., 1984).
Other clinical signs
Although BHV-1 has been associated with clinical mastitis, there is little concrete evidence for its involvement in the syndrome (Gourlay et al., 1974). Isolation of BHV-1 from milk can be simply a consequence of viraemia. BHV-1 has also been isolated from ulcerative lesions of the mouth and the interdigital space (Dhennin et al., 1979), thus potentially leading to confusion with other vesicular diseases such as foot and mouth disease, vesicular stomatitis and mucosal disease (Holliman, 2005).
Diagnosis
Top of pageClinical diagnosis
An outbreak of acute respiratory disease with profuse nasal discharge, fever and depression suggests IBR. In a naive herd, the epidemic progresses quickly and respiratory signs are associated with neonatal deaths and abortions at 4 to 8 months of pregnancy. Hypovirulent strains can circulate without obvious clinical signs. The IPV form is suspected if animals have vesicular and pustular lesions of the genital mucosa and there is evidence of venereal transmission.
Postmortem examination
Postmortem examination can be performed in cases of fatal IBR, abortion and neonatal deaths. The IBR form is suspected when there is intense inflammation of the mucosa of the anterior respiratory tract, from the nasal cavities to the trachea. Aborted fetuses show multifocal necrosis disseminated in various internal organs. The same lesions are observed in neonates.
Laboratory diagnosis
Virus isolation from nasal or vaginal swabs, or from triturated tissue, is performed in cell cultures, using either established cell lines like Madin-Darby Bovine Kidney cells (MDBK) or primary bovine cells of renal, lung or testicular origin. A cytopathic effect is visible, with cell rounding within 24 hours. Indirect immunofluorescence or immunoperoxidase assays confirm the presence of specific BHV-1 antigens using monoclonal antibodies against one of the major BHV-1 glycoproteins: gB, gC or gD. The restriction pattern of BHV-1 DNA is characteristic and can also discriminate between subtypes 1 and 2 (Engels et al., 1981). The use of endonucleases with a high number of cleavage sites, such as Pst1, allows strain-specific patterns to be obtained (Whetstone et al., 1993).
BHV-1 DNA can also be detected by polymerase chain reaction (PCR). Many PCR methods are reported in the literature (Vilcek et al., 1994). As viral isolation from bovine semen is difficult, PCR has also been developed for BHV-1 detection in semen (Smits et al., 2000). A specific PCR has been developed to diagnose gE negative BHV-1 strains (Schynts et al., 1999). A universal PCR combined with restriction enzyme analysis of the amplicons has been developed for detection and identification of ruminant alphaherpesviruses related to BHV-1, including BHV-5, CapHV-1, CerHV-1 and RanHV-1 (Ross and Belak, 1999). In addition, specific nested-PCR systems have also been developed, which allow the safe detection of each ruminant alphaherpesvirus without cross-reactions with heterologous viruses (Ross et al., 1999).Serological diagnosis can be performed using sero-neutralization and ELISA. Sero-neutralization requires the use of cell cultures and is rarely undertaken for diagnostic purposes. The most sensitive sero-neutralization test requires a 24-h incubation of serum with the virus at 37°C (Bitsch, 1978). Several ELISA kits are available. Blocking ELISAs have replaced most of the indirect ELISA tests. Blocking ELISAs are based on the recognition of glycoprotein gB. Glycoprotein gE blocking ELISAs are companion (DIVA – differentiation of infected from vaccinated animals) kits, used to distinguish between naturally infected animals and those immunized with a gE negative vaccine. The gB blocking ELISAs cannot distinguish between BHV-1 infection and infection with related alphaherpesviruses. A gE blocking ELISA has been shown to differentiate between BHV-1 and BHV-5 infection (Wellenberg et al., 2001).
The antigen source for most gE blocking ELISAs is a crude viral preparation in which gE is associated with other envelope glycoproteins, leading to a lack of specificity (Lehmann et al., 2002). The specificity of serological discrimination between BHV-infected animals and animals vaccinated with marker vaccines can be improved by preadsorption of serum samples with a preparation of antigen devoid of gE, prior to the blocking ELISA.
ELISAs have also been developed to detect BHV-1 antibodies in bulk milk, or in milk samples from individual cows. Milk ELISAs have been found to perform well when compared with standard serum ELISAs; there is no evidence that stage of lactation or transport or storage of the samples had a significant effect (Pritchard et al., 2002).A combination of ELISAs, for example the Danish combination test system, provides better sensitivity; (de Wit et al., 1998). It is made up of a combination of a blocking and an indirect ELISA.
In IBR control programmes, serological diagnosis aims to identify latently infected animals. However, a few animals are seronegative latent carriers (SNLC), i.e. they are latently infected with BHV-1 without detectable antibodies. Such animals can be produced experimentally by infection of neonatal calves protected with specific colostral antibodies (Lemaire et al., 2000a,b).
List of Symptoms/Signs
Top of pageSign | Life Stages | Type |
---|---|---|
Cardiovascular Signs / Tachycardia, rapid pulse, high heart rate | Sign | |
Digestive Signs / Anorexia, loss or decreased appetite, not nursing, off feed | Sign | |
Digestive Signs / Dysphagia, difficulty swallowing | Sign | |
Digestive Signs / Excessive salivation, frothing at the mouth, ptyalism | Sign | |
Digestive Signs / Grinding teeth, bruxism, odontoprisis | Sign | |
Digestive Signs / Tongue weakness, paresis, paralysis | Sign | |
General Signs / Abnormal proprioceptive positioning, knuckling | Sign | |
General Signs / Ataxia, incoordination, staggering, falling | Sign | |
General Signs / Dysmetria, hypermetria, hypometria | Sign | |
General Signs / Fever, pyrexia, hyperthermia | Sign | |
General Signs / Generalized weakness, paresis, paralysis | Sign | |
General Signs / Inability to stand, downer, prostration | Sign | |
General Signs / Opisthotonus | Sign | |
General Signs / Paraparesis, weakness, paralysis both hind limbs | Sign | |
General Signs / Sudden death, found dead | Sign | |
General Signs / Tetraparesis, weakness, paralysis all four limbs | Sign | |
General Signs / Trembling, shivering, fasciculations, chilling | Sign | |
Nervous Signs / Abnormal behavior, aggression, changing habits | Sign | |
Nervous Signs / Circling | Sign | |
Nervous Signs / Coma, stupor | Sign | |
Nervous Signs / Constant or increased vocalization | Sign | |
Nervous Signs / Dullness, depression, lethargy, depressed, lethargic, listless | Sign | |
Nervous Signs / Excitement, delirium, mania | Sign | |
Nervous Signs / Head pressing | Sign | |
Nervous Signs / Head tilt | Sign | |
Nervous Signs / Hyperesthesia, irritable, hyperactive | Sign | |
Nervous Signs / Propulsion, aimless wandering | Sign | |
Nervous Signs / Seizures or syncope, convulsions, fits, collapse | Sign | |
Nervous Signs / Tremor | Sign | |
Ophthalmology Signs / Blindness | Sign | |
Ophthalmology Signs / Chemosis, conjunctival, scleral edema, swelling | Sign | |
Ophthalmology Signs / Conjunctival, scleral, injection, abnormal vasculature | Sign | |
Ophthalmology Signs / Conjunctival, scleral, redness | Sign | |
Ophthalmology Signs / Lacrimation, tearing, serous ocular discharge, watery eyes | Sign | |
Ophthalmology Signs / Nystagmus | Sign | |
Pain / Discomfort Signs / Colic, abdominal pain | Sign | |
Pain / Discomfort Signs / Pain, penis | Sign | |
Pain / Discomfort Signs / Pain, vulva, vagina | Sign | |
Reproductive Signs / Abnormal length estrus cycle, long, short, irregular interestrus period | Sign | |
Reproductive Signs / Abortion or weak newborns, stillbirth | Sign | |
Reproductive Signs / Female infertility, repeat breeder | Sign | |
Reproductive Signs / Female infertility, repeat breeder | Sign | |
Reproductive Signs / Male infertility | Sign | |
Reproductive Signs / Mucous discharge, vulvar, vaginal | Sign | |
Reproductive Signs / Papule, pustule, vesicle, ulcer penis or prepuce | Sign | |
Reproductive Signs / Purulent discharge, penis or prepuce | Sign | |
Reproductive Signs / Purulent discharge, vulvar, vaginal | Sign | |
Reproductive Signs / Vaginal or cervical ulcers, vesicles, erosions, tears, papules, pustules | Sign | |
Respiratory Signs / Abnormal lung or pleural sounds, rales, crackles, wheezes, friction rubs | Sign | |
Respiratory Signs / Dyspnea, difficult, open mouth breathing, grunt, gasping | Sign | |
Respiratory Signs / Increased respiratory rate, polypnea, tachypnea, hyperpnea | Sign | |
Respiratory Signs / Mucoid nasal discharge, serous, watery | Sign | |
Skin / Integumentary Signs / Alopecia, thinning, shedding, easily epilated, loss of, hair | Sign | |
Skin / Integumentary Signs / Pruritus, itching skin | Sign |
Disease Course
Top of pageBHV-1 is excreted in the respiratory, ocular and genital secretions of infected cattle. Nasal secretions contain high concentrations of virus and constitute the main source of infection. The virus is transmitted by direct contact, by aerosol over short distances, or by material or clothes contaminated by infectious mucus. Sperm can be infected and the virus can be transmitted genitally. As the virus is well preserved in liquid nitrogen, artificial insemination must only be made with sperm from BHV-1 free bulls. Embryo transfer is also a potential risk for BHV-1 transmission. Embryo treatment with trypsin removes the virus, which may have been adsorbed onto the pellucid membrane.
After virus replication at the portal of entry (nasal or genital mucosa),BHV-1 disseminates in the blood, the nerves and by cell-to-cell transmission inside the infected tissue. Primary infection is followed by a transient viraemia, allowing the virus to infect secondary sites such as the digestive tract, udder, fetus and ovaries (Miller et al., 1985). Infection of the neonate provokes a generalized fatal infection in the absence of specific colostral antibodies. In other animals, the infection of peripheral nerves at the site of infection induces a retrograde axonal transport of the virus to the regional nervous ganglia, i.e. the trigeminal ganglion in the case of respiratory infection and the sacral ganglion after genital infection. Other sites of latency cannot be excluded, such as the tonsils (Winkler et al., 2000).
After respiratory infection, virus is excreted in the nasal secretions at very high titres - up to 1010 tissue culture infectious doses (TCID50) - over 10 to 16 days. Virus replication is controlled by non-specific, followed by specific, immune responses (Denis et al., 1994). The virus establishes a latent infection after primary infection, re-infection or vaccination with an attenuated virus. Latent infection is lifelong and may be interrupted by virus reactivation and re-excretion. BHV-1 reactivation is provoked by several stimuli. These are transport, parturition, glucocorticoid treatment, viral superinfection and infestation with Dictyocaulus viviparus (Thiry et al., 1986). Re-excretion is usually clinically silent, but the amount of re-excreted virus can be high and the process lasts for several days. The level of re-excretion is directly related to the level of the specific immune response at the time of reactivation (Engels and Ackermann, 1996; Pastoret et al., 1984; Lemaire et al., 1994; Thiry et al., 1986, 1999).
Recombination is an important source of genetic variation in BHV-1, like other herpesviruses, and may be significant when vaccines containing deletion mutants are used. Recombination of two BHV-1 mutants lacking either glycoprotein C (gC-) or E (-gE-) was found to be a frequent event in calves coinfected with these strains. After reactivation from latency, no viruses of the originally inoculated mutants were detected, although gC+/gE- mutants, when inoculated alone, were detected after reactivation treatment (Schynts et al., 2003).
Epidemiology
Top of pageTransmission
BHV-1 is transmitted by nasal or genital secretions. Transmission is mainly direct, from animal to animal, by the respiratory or the genital route. Indirect transmission via infected clothes or materials is also possible (Wentink et al., 1993). Aerosols can disseminate the virus over 4 meters in field conditions (Mars et al., 2000). Vertical transmission occurs in cows, when the virus crosses the placenta and infects the fetus.
Morbidity and mortality
The clinical consequences of BHV-1 circulation in a herd depend on the virulence of the prevalent strain. Where virulent strains circulate, morbidity rate is up to 100% in a naïve herd. Otherwise morbidity rate is approximately 20%. The mortality rate varies between 0 and 10%. Genital strains causing IPV are less virulent (Straub, 1990).
Temporal and spatial evolution
In a herd, BHV-1 circulation is initiated by virus reactivation and re-excretion in a latently infected animal already present, or more often by the introduction of an acutely or latently infected animal. In the absence of clinical signs, virus circulation is evidenced by seroconversion in young animals (van Nieuwstadt and Verhoeff, 1983). Two patterns of virus circulation are observed: rapid seroconversion of seronegative animals, most likely due to a virulent strain; or seroconversion of animals over a long period of time (several weeks to several months) usually due to hypovirulent strains (Van Nieuwstadt and Verhoeff, 1983). The basic reproduction ratio (R0) was calculated in a herd after experimental reactivation of virus in three seropositive cows. All seronegative animals seroconverted over a period of 4 weeks and an average of 7 new cases were generated by each infected animal (Hage et al., 1996). This result shows the rapid transmission of the virus in a susceptible herd.
A study of natural transmission of BHV-1 in the Netherlands involved 50 herds with 3300 head of cattle. Herds were divided into 3 groups: seronegative, vaccinated, and mixed. Three outbreaks of BHV1 occurred due to the introduction of infectious cattle, and another due to reactivation of latent BHV1 in seropositive cattle. The basic reproduction ratio within herds was estimated to be at least 4. Only one of the outbreaks led to secondary outbreaks in seronegative herds; the between herds basic reproduction ratio was estimated to be 0.6 (Hage et al., 2003).
Between herds transmission is a major risk of BHV-1 circulation. However, it can be better controlled than within herd spread. Sanitary measures can be taken to prevent the introduction of seropositive animals or animals originating from a seropositive herd. Airborne transmission of BHV-1 has been demonstrated over short distances and can provide an explanation of between herds transmission, without the introduction of any new animal (Mars et al., 1999).
Risk factors
The risk factors for BHV-1 infection in a herd have been studied on dairy farms. BHV-1 positive farms purchase cattle and participate in cattle shows more often than negative farms. Positive farms have also had more visitors who are less likely to use dedicated farm clothing. Positive farms are also situated closer to other cattle farms (van Schaik et al., 1998). As cattle are the main source of virus spread, risk factors for virus infection are associated with cattle movement (Wentink et al., 1993).
Impact: Economic
Top of pageThe economic importance of BHV-1 infection can be envisaged from two points of view:
- At the herd level: an IBR outbreak can cause a severe epidemic of respiratory disease with direct economic losses due to death, growth retardation, decreased milk production and abortion (Hage et al., 1998). The genital IPV form is usually much less severe.
- At a regional level: the status ‘BHV-1 free’ can confer commercial advantages to a country or a region. European member states such as Denmark, Finland, Sweden and Austria are officially free of BHV-1. Only cattle, sperm and embryos from BHV-1 free herds or countries may be imported into these countries.
The impact of the infection is directly linked to the prevalence of seropositive animals. This value can vary from 0% in countries free of the disease, like Denmark and Sweden, to 67% in Belgium (Boelaert et al., 2000) and 84 % in the Netherlands (van Wuyckhuise et al., 1998). However, exact figures that describe actual losses have not been calculated.
Disease Treatment
Top of pageNo antiviral drugs are used. Antimicrobial therapy is needed to overcome bacterial superinfection. The use of corticosteroids is contraindicated since these drugs provoke BHV-1 reactivation and are likely to aggravate the severity of the outbreak by increasing virus circulation. Therefore, only nonsteroidal anti-inflammatory compounds, such as carprofen, are recommended for use (Eltok and Eltok, 2004). Immunomodulators have been found to limit the spread of infection, decrease viral shedding and reduce the severity of clinical signs in experimental BHV-1 infection in calves (Castrucci et al., 2000).
Prevention and Control
Top of pageVaccination
Vaccination against BHV-1 is widely used. Both inactivated and live attenuated vaccines are available. The vaccination schedule consists of two vaccinations at a 3-week interval for inactivated vaccines, starting from the age of 3-4 months to avoid interference with colostral antibodies. Live attenuated vaccines are administered either once or twice depending on the type of vaccine. Duration of immunity usually lasts from six months to one year. Vaccination is recommended for young calves to prevent clinical signs. Vaccination of calves less than 3 months of age can be achieved by intranasal administration of attenuated vaccine. This route is better for overcoming interference due to maternal immunity. Vaccinations should protect cattle clinically in case of infection and significantly reduce the shedding of field virus. It is important that the vaccines themselves do not induce disease, abortion or any other adverse reaction, and they must be genetically stable (OIE, 2005). BHV-1 is incorporated in various multivalent vaccines for cattle (for example, Ellsworth et al., 2003).
It is thought that the rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or both modified-live and killed BHV-1 is associated with virus-specific interferon gamma production (Woolums et al., 2003). Studies have been carried out to evaluate the shedding of BHV- 1 and bovine viral diarrhoea viruses after vaccination of calves with a multivalent modified-live virus vaccine (Kleiboeker et al., 2003). Seventeen of 18 vaccinated calves seroconverted to BHV-1, but viral shedding was not detected. Pregnant in-contact cattle remained seronegative throughout the study. However, reactivation of some live attenuated vaccine viruses has been induced by administration of dexamethasone to calves three months after vaccination (Castrucci et al., 2002). The vaccine virus appears to have established latency in the host, but the calves remained clinically protected from challenge exposure.Vaccines can be effective against the genital form of BHV-1 infection, IPV. However, they must be tested specifically to protect against experimental genital infection. Most of the available BHV-1 vaccines have only been tested against respiratory infection.
Vaccination can be a tool in IBR control programmes. Repeated vaccination is needed to achieve epidemiological protection and reduce virus circulation. Indeed, in the context of control programmes, the efficacy of vaccination is not based on the reduction of clinical signs but on a decrease in the incidence of infection to reduce the prevalence of seropositive animals. Marker vaccines are recommended. The marker consists of a deletion of the glycoprotein gE gene in the vaccine strain (Kaashoek et al., 1994); such vaccines first became available in 1995 (OIE, 2005). Vaccinated animals develop an immune response against all the antigens of BHV-1, except glycoprotein gE. A DIVA (differentiation of infected from vaccinated animals) serological test (gE blocking ELISA) is used to differentiate vaccinated (gE negative) calves from those that have been naturally infected (gE positive) (Van Oirschot et al., 1996).
Experiments have been carried out to study the safety and efficacy of different immunisation protocols with marker vaccines (Kerkhofs et al., 2003). A comparison of 4 immunisation protocols based on inactivated and live attenuated marker vaccines for BHV-1 showed that cellular and humoral immune responses were highest in the groups which received at least one injection of inactivated vaccine. Virological protection was observed in all vaccinated calves after a challenge infection, but calves which received one dose of the inactivated vaccine as a booster, or two doses of the inactivated vaccine, excreted significantly less challenge virus than calves which were vaccinated only with attenuated vaccine.
Like other live attenuated strains used for vaccine production, gE-deleted mutants have been reported in field infections of cattle vaccinated with the strain several months previously (Dispas et al., 2003). BHV-1 gE-negative vaccine strains can establish latency in naive or passively immunized neonatal calves after a single intranasal inoculation. Moreover, a gE-negative vaccine, when used in passively immunized calves, has been shown to give rise to seronegative vaccine virus carriers (Lemaire et al., 2001).
Numerous recent reports describe other developments in BHV-1 vaccination technology, including DNA vaccines. Such experimental vaccines include gD alone (Castrucci et al., 2004) or fused with bovine CD154 (Manoj et al., 2004), vaccinia virus expressing gB (Huang et al., 2005), and plasmids encoding the membrane-anchored or secreted forms of gB and gD (Caselli et al., 2005). Although DNA vaccines have several advantages over conventional vaccines, particularly with regard to safety, antibody production and protection are often inadequate, particularly in single plasmid vaccine formulations, and none of the vaccines described are currently suitable for field use.
IBR control and eradication
Several European countries have initiated IBR control programmes aimed at eradicating BHV-1 infection. On other continents IBR control is not considered an important issue. Reasons for and against eradication are reviewed by Ackermann and Engels (2006). Where seroprevalence is low, the programme only consists of the identification and removal of seropositive animals. Regular serological testing of pooled serum samples or bulk tank milk can monitor the status of each farm (Hartman et al., 1997). Where seroprevalence is high, the culling of seropositive animals is too expensive. In this case the control programme starts with massive vaccination campaigns. Repeated vaccination every six months is able to reduce the circulation of the virus among animals. The use of marker gE negative vaccines helps to identify gE seropositive animals, which are latently infected with a wild-type strain. The progressive elimination of seropositive (gE positive) animals decreases the number of infected animals and reduces the seroprevalence. When it reaches a low threshold value, vaccination can be stopped and serosurveillance identifies seropositive farms from which seropositive animals are removed (Lemaire et al., 1994; Thiry et al., 1999).
A new monitoring programme for IBR, introduced in Denmark in 2004, aims to be more cost-effective and enables cases to be tracked down more rapidly. The risk-based programme tailors the monitoring programme based on factors such as type of herd, herd size, recording of separate cases or systematic sampling, time of year and proximity to known outbreaks (Chriel et al., 2005).
The effect of surveillance programmes on the spread of BHV-1 between certified cattle herds has been modelled (Graat et al., 2001). The goal of the control programmes used in many European countries is that infection in a certified herd is detected early enough to prevent spread of infection to other certified herds. The net reproduction ratio, R, (the average number of certified herds infected by one infected certified herd) should be kept below 1. The R between herds is mainly influenced by vaccination status, sampling frequency, and contacts between herds. The results showed that sampling individual cows once a year could prevent spread of infection between herds of up to 50 cattle. The frequency should be increased to twice yearly for larger herds and/or those with extensive contacts. When bulk milk is sampled, sampling should be done at least every 5 months for small herds or monthly for larger herds with more contacts.
For a country to qualify as free from IBR/IPV it must categorise the disease as notifiable, have undertaken no vaccination against BHV-1 for at least three years, and document that at least 99.8% of its herds are free from IBR/IPV (OIE, 2005). A serological survey must be carried out annually on a random sample of the cattle population of the country sufficient to provide a 99% level of confidence of detecting the infection if it is present at a prevalence higher than 0.2% of herds, and import restrictions apply (OIE, 2005). The OIE also gives requirements for certification of individual herds as IBR/IPV-free.
References
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OIE Handistatus, 2004. World Animal Health Publication and Handistatus II (data set for 2003). Paris, France: Office International des Epizooties
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Distribution References
OIE Handistatus, 2005. World Animal Health Publication and Handistatus II (dataset for 2004)., Paris, France: Office International des Epizooties.
OIE, 2009. World Animal Health Information Database - Version: 1.4., Paris, France: World Organisation for Animal Health. https://www.oie.int/
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