Chapter 55
Infectious Agents: Campylobacter
Misty A. Edmondson
Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA
Introduction
Bovine venereal campylobacteriosis is caused by Campylobacter fetus subsp. venerealis and is an important cause of infertility, death of the late embryo or early fetus, and sporadic abortion in cattle. This organism was first recognized in the early 1900s as a cause of abortion in cattle and was initially called Vibrio fetus.1 Based on differences in clinical presentation the agent was further classified as Vibrio fetus subsp. intestinalis and Vibrio fetus subsp. venerealis. Vibrio fetus subsp. intestinalis was associated with sporadic abortions due to bacteremia from the intestinal tract of the pregnant cow. Vibrio fetus subsp. venerealis was also associated with occasional abortions, but the primary importance of infection was a significant decrease in herd fertility. However in the 1960s there was evidence that many of the Vibrio species were sufficiently different to warrant classification under a separate genus, Campylobacter.2 Consequently Vibrio fetus subsp. intestinalis was renamed Campylobacter fetus subsp. fetus and Vibrio fetus subsp. venerealis was renamed Campylobacter fetus subsp. venerealis. The term “vibrio” is still commonly used to refer to the venereal disease caused by Campylobacter fetus subsp. venerealis.
Etiology
Campylobacter fetus subsp. venerealis, a slender, motile, Gram-negative, comma-shaped or S-shaped rod that appears as “seagull wings” in silhouette, requires a microaerophilic environment for growth.2,3 Campylobacter spp. require an atmosphere of 10–20% CO2 with reduced oxygen concentration at 5% or less and optimal growth occurring at 37°C.2 There are two biotypes within the subspecies, biotype venerealis and biotype intermedius. These biotypes are differentiated by the production of hydrogen sulfide with lead acetate strips when organisms are grown in media containing cysteine. Biotype intermedius produces hydrogen sulfide, whereas biotype venerealis does not. Both biotypes are capable of causing disease; however, biotype intermedius appears to be less pathogenic than biotype venerealis.4
Pathogenesis
Campylobacter fetus subsp. venerealis is primarily transmitted by the venereal route. Bulls serve as carriers and are the major mode of transmitting the organism to naive cows. The rate of transmission from infected bulls to naive cows is quite high, approaching 100%. The bacterium may be spread to cows and heifers at the time of artificial insemination (AI) with infected semen. Direct transmission from cow to cow is unlikely, although contaminated insemination equipment may allow for transmission of the organism.5 Campylobacteriosis may be spread from bull to bull if contaminated semen collection equipment is not sufficiently cleaned between bulls.4 In addition, transmission has been reported to occur from bull to bull due to contaminated bedding.6
Bull
It is uncertain if the age of the bull has a role in the course and duration of infection. One study demonstrated no difference in duration of infection between bulls 5.5–6 years of age and 3.5–4 years of age.7 However, another study revealed a higher incidence of infection in bulls greater than 6 years of age.8 It has been speculated that younger bulls may be more resistant to infection, more likely to clear infection, and clear infections within a few weeks. In addition, it has also been speculated that older bulls are more likely to become persistent carriers due to an increase in the number and depth of crypts in the preputial epithelium.4 However, more recent work evaluating the surface architectural anatomy of bulls revealed no differences in penile and preputial epithelial anatomy between young and old bulls.9
The prepuce of bulls is the natural reservoir of infection of naive cows through natural mating.10 The addition of carrier bulls poses a significant risk to a naive herd, although the disease is most commonly seen in newly introduced cows and heifers in herds where bovine campylobacteriosis is endemic.11
Cow/fetus
Venereal campylobacteriosis causes low reproductive efficiency with severe economic losses.12 This is associated with temporary infertility with mild endometritis, death of the early embryo or early fetus (30–70 days of gestation), and sporadic abortions.13,14 After exposure the bacteria colonize in the mucosa of the anterior vagina and cervix of cows.10 The infection then spreads to the uterus and oviducts under the influence of progesterone. Fertilization and development of the embryo are not directly affected by C. fetus subsp. venerealis. The resulting inflammatory response in the uterus and/or oviducts results in early embryonic death. The majority of pregnancy loss occurs between 30 and 70 days of gestation.13,15 Reactions associated with heat-stabile endotoxins produced by C. fetus subsp. venerealis are thought to be responsible for the occasional mid-term abortion.4 In addition, C. fetus subsp. venerealis can reach the placenta and the amniotic fluid and cause severe placentitis and fetal hypoxia.16 Cows and heifers are normally capable of mounting an immune response, clearing the infection, and returning to normal fertility 4–8 months after the initial infection.13
Immune response
Infection with C. fetus subsp. venerealis in cows and bulls does not produce significant systemic antibodies during or after infections.17 Unlike bulls, cows and heifers infected with C. fetus subsp. venerealis produce a local antibody response in the vagina and uterus. Heifers challenged with C. fetus subsp. venerealis had transient agglutinating and immobilizing IgM antibodies followed by persistent IgA and IgG antibodies in vaginal secretions and predominantly IgG antibodies in uterine secretions.17,18 Both IgA and IgG antibodies to C. fetus subsp. venerealis surface antigens immobilize and mediate neutrophil and mononuclear cell killing of the bacteria.19 The production of IgG in the uterus directs clearance through opsonization and phagocytosis. In the lower reproductive tract, IgA is also produced and helps immobilize the bacteria and block adherence. Conversely, IgA may also be responsible for blocking opsonization and promoting persistent colonization of the lower genital tract. Because of the stronger antibody response in cows and heifers, prolonged infections in females are not as persistent as they are in bulls.18,20 However, in the case of the chronic carrier cow, the bacterium may be able to elude the immune response and be maintained in the cervix through a full gestation, although this is quite unusual (<1%).6 Persistence of infection in the cervix and vagina in the presence of an immune response may be partly due to antigenic changes in the organism that allow for avoidance of the host immune response. Antigenic changes in the S-layer, a regular array of high-molecular-mass surface proteins that compose the outermost part of the cell envelope, result in the expression of different immunodominant epitopes and persistence of the organism.4
Clinical signs
Herd
A herd history of poor conception rates, infertility, or second trimester abortions may be one of the first signs that bovine venereal campylobacteriosis could be a problem. Trichomoniasis, poor detection of estrus, and bull subfertility or infertility should also be considered as possible differential diagnoses. A confirmatory diagnosis of bovine venereal campylobacteriosis should be attempted through laboratory evaluation of samples obtained from the herd. Samples for diagnosis include tissues from aborted fetuses, vaginal mucus samples, vaginal washings, or preputial scrapings.
When beginning a diagnostic evaluation of a herd, it seems advantageous to begin with the breeding males in the herd due to the fewer number of males and the self-limiting type of infection associated with females. Thus preputial scrapings should be obtained from herd bulls. If bulls are not available, then vaginal mucus samples should be obtained from a representative sample of cows and heifers and submitted to the diagnostic laboratory.
Cow
In females the main clinical signs are related to infertility. Venereal campylobacteriosis is characterized by repeat breeding, irregular estrous cycles, prolonged calving seasons, and reduced calf crops.13,21 The average number of services per conception is extended to 2.5–3.5. When infection is introduced into a naive herd, the initial pregnancy rates are quite low. Over time the conception rate of the herd improves as animals clear the infection. However, the resulting calving season is extended as more cows conceived later in the season. Infected cows show few signs of infection. Most infected cows do not have any vaginal discharge. However, a mucopurulent secretion may be detected in the occasional cow.4 As previously stated, the majority of pregnancy loss occurs between 30 and 70 days of gestation.13,15 Although uncommon, abortion due to C. fetus subsp. venerealis has been reported between 4 and 8 months of gestation.13 Abortions appear to be more commonly associated with biotype intermedius than with biotype venerealis. When mid-term abortions due to C. fetus subsp. venerealis are reported, there is typically a recent history of infertility in the herd.4
Bull
Infection with C. fetus subsp. venerealis in bulls is not apparent as bulls show no clinical signs of infection. Although genital infections in mature bulls may persist for months or years, there are no alterations in semen quality.22–24
Pathology
The pathology associated with infection of C. fetus subsp. venerealis is limited to the reproductive tract. Endometritis, mild cervicitis, and salpingitis are usually the only lesions seen in cows and heifers.25 Grossly the cervix may appear reddened and the uterus may have a small amount of mucopurulent exudate that can extend through the cervix into the vagina. Histologically, the lesions have mild infiltration of inflammatory cells (plasma cells and foci of lymphocytes in the stroma) with slight desquamation of the superficial epithelium with no significant vascular changes.25 Involvement of the endometrial glands is minimal, although cystic glands with slight periglandular fibrosis have been noted on clearance of infection.25
No gross abnormalities are seen on the penis and prepuce of infected bulls. Histologically, there is only a diffuse infiltration of mononuclear cells within the lamina propria.22 Plasma cells are located in clusters at the apex of the dermal papillae.7 However, the infiltration of subepithelial lymphocytes and plasma cells has been found in both infected and uninfected bulls.22,24,26
The most common fetal lesions associated with C. fetus subsp. venerealis are neutrophilic bronchopneumonia and interstitial pneumonia.16 Other commonly observed lesions include nonsuppurative interstitial enteritis, hepatitis, pericarditis, myositis, myocarditis, serositis, occasional abomasitis, and meningitis.16,27,28
Diagnosis
It is important to be able to differentiate C. fetus subsp. venerealis from C. fetus subsp. fetus. The natural habitat for C. fetus subsp. fetus is the intestinal tract of cattle, but it can also cause sporadic abortions.29 Differences in the epidemiology and clinical relevance of these bacteria make accurate detection imperative. The traditional means for differentiating between both species, and the recommended international standard, is based on tolerance to 1% glycine;30 C. fetus subsp. venerealis is sensitive to glycine whereas C. fetus subsp. fetus is tolerant to glycine. However, the glycine tolerance characteristic may not be completely reliable for differentiation of the two subspecies as it has been demonstrated that glycine tolerance can be acquired by transduction or mutation.31 In addition, glycine-tolerant variants of C. fetus subsp. venerealis have also been described and designated as C. fetus subsp. venerealis biotype intermedius.30,32 Glycine-sensitive C. fetus subsp. fetus isolates have also been detected as well.33
