The Genus Brucella

Chapter 25 The Genus Brucella


Brucellosis was first described by British physician David Bruce, who in 1886 isolated a bacterium from the spleens of patients with a fatal disease known as Malta or Mediterranean fever. He named the agent Micrococcus melitensis. L.F. Benhard Bang, a Danish veterinarian, recovered what we now know as Brucella abortus from a bovine fetus in 1895. Recognition of brucellosis as a zoonosis in the early twentieth century contributed to establishment of requirements for pasteurization of milk.


Brucella spp. are gram-negative, strictly aerobic, nonmotile, coccobacilli or small rods. They are facultative intracellular parasites that are taxonomically categorized in the class α-Proteobacteria, order Rhizobiales, family Brucellaceae. They produce oxidase, catalase, nitrate reductase, and urease (except Brucella ovis); fail to produce indole; are nonhemolytic; do not liquefy gelatin; and have negative methyl red and Voges-Proskauer tests. Most (again except B. ovis); utilize glucose as an energy source. Brucella spp. have been classified as potential agents of bioterrorism because they may be spread by aerosol and there are no human vaccines.


According to the strict phylogenetic definition of a species, taxonomists have proposed that the genus comprise a single species, Brucella melitensis. However, historical precedent has led to retention of the six classical “species,” B. abortus, B. melitensis, Brucella suis, B. ovis, Brucella canis, and Brucella neotomae. Each “species” has a preferred host that serves as a main reservoir for infection (Table 25-1). These have been further divided into biovars based on agglutination by monospecific antisera prepared against A and M lipopolysaccharide antigens, and other phenotypic properties.




DISEASES AND EPIDEMIOLOGY


Members of the genus Brucella are the agents of brucellosis, a worldwide zoonotic illness. The disease is highly endemic in Mediterranean countries, Africa, the Middle East, India, central Asia, and Central and South America. It has virtually been eliminated from the United States and Canada as a result of extensive eradication programs. The host range includes humans, ruminants, swine, cervids, lagomorphs, rodents, canids, and marine mammals. Cats appear to be resistant to infection because there have been no reports of naturally occurring disease. Brucellosis remains a reportable disease in both the United States and Canada. Infection occurs through inhalation or ingestion of organisms.


Since brucellae are intracellular pathogens of animal hosts, they are not known to pursue an independent lifestyle. Animals are the reservoirs and can be the source of infection. Organisms reside inside cells of the reticuloendothelial system and reproductive tract and cause lifelong, chronic infections. They are the leading cause of abortion and sterility in domestic animals. High numbers of bacteria are shed in urine, milk, vaginal discharges, semen, and the products of birth.


Under appropriate conditions, Brucella can survive outside the host in the environment for extended periods. They may remain viable in carcasses and tissues for up to 6 months at approximately 0° C. They survive up to 125 days in dust or soil, and for as long as 1 year in feces. Brucellae are susceptible to many disinfectants, including 1% sodium hypochlorite, phenolics, 70% ethanol, iodophors, glutaraldehyde, and formaldehyde. The presence of organic matter or use in low temperatures may greatly reduce the efficacy of the disinfectant. The organisms are physically inactivated by moist heat (121° C, ≥15 minutes) and by dry heat (160°-170° C, ≥1 hour).


Brucella abortus is the etiologic agent of bovine brucellosis (Bang’s disease), and is found in most cattle-producing areas of the world. The organism preferentially infects bovidae, but is sometimes transmitted to other animals, including cervids, camels, dogs, horses, sheep, goats, and pigs. American bison and elk in the Yellowstone area are one remaining reservoir of B. abortus in the United States.


In cattle, brucellosis is primarily a disease of the cow. Bulls can be infected but they do not readily transmit the organism venereally. Brucella abortus localizes in the testicles, resulting in unilateral orchitis, epididymitis, and inflammation of the accessory reproductive organs, with decreased libido and impaired fertility. In the cow there is a predilection for udder, endometrium, and associated lymph nodes. Clinical signs in infected cows include abortion during or after the fifth month of gestation, birth of weak calves, or retained placenta. Although infected cows typically abort only once, the placenta becomes colonized by brucellae during each pregnancy. These subsequent offspring may be born weak or apparently healthy. Because of in utero infection or ingestion of contaminated milk in the neonatal period, apparently healthy heifer calves may become carriers and pose a significant risk to herd and human health. Brucella abortus is shed in large numbers in the afterbirth, placental fluids, aborted fetus, and vaginal discharge. Cattle become infected when they ingest contaminated forage or lick calves or aborted fetuses.


Horses may be naturally infected with B. abortus, and the organism has a tendency to localize in joints, bursae, or tendon sheaths. It has been recovered from lesions of fistulous withers, poll evil, and hygroma. The current opinion is that horses are relatively refractory to infection with Brucella and present a minimal hazard to other animals. Sporadic infections with B. abortus have been reported in dogs ingesting reproductive material from infected cows. Abortion, epididymitis, and joint lesions occur in affected animals. There is also circumstantial evidence that dog-to-cattle transmission occurs under field conditions.


Brucella melitensis most commonly infects sheep and goats. The organism is regarded as the most virulent of the Brucella species and accounts for most cases of human brucellosis. It has occasionally been isolated from camels and alpacas. Disease is endemic in the Middle East, the Iberian Peninsula, China, the former Soviet Union, parts of Africa, and Latin America. The epidemiology and pathogenesis are similar to that of B. abortus. The main risk factors are contact with contaminated genital discharges and ingestion of raw milk. Sexual transmission is more frequent than in bovine brucellosis. Breed susceptibility is variable in sheep, but goat breeds are highly susceptible. Some animals may spontaneously recover from infection, but the majority remain chronic carriers. Clinical signs include abortion, mastitis, lameness, and orchitis.


Brucella ovis has long been recognized as a pathogen of sheep and displays a high degree of host specificity. Ovine brucellosis is of great economic significance in most sheep-rearing countries. Although it occasionally is associated with abortion, it primarily affects rams. Infectious epididymitis, orchitis, and infertility are common disease manifestations. Persistent nephritis can develop in rams and is the most serious complication of infection. Ewes are often transiently infected, with vaginitis, stillbirths, or birth of weak lambs. Ovine brucellosis is most commonly spread directly from ram to ram by sexual contact, or indirectly, from sexual contact with ewes that have been inseminated by infected rams.


The host range of B. suis is variable. Swine are primary hosts for biovars 1, 2, and 3, and hares are important natural reservoirs of biovar 2. Disease in reindeer and caribou is associated with biovar 4, whereas biovar 5 is maintained by certain species of rodents in the Caucasus region of Eurasia. All biovars of B. suis can cause serious infections in man.


Swine brucellosis affects pigs of all ages and breeds. Males and females are equally susceptible to infection. In piglets, B. suis may produce a self-limiting infection that remains confined to the lymph nodes. However, most animals develop bacteremia that results in localization of the agent in the bones, joints, reproductive tract, and the organs of the reticuloendothelial system. The formation of abscesses or miliary lesions is a characteristic of infection. Swine brucellosis may cause no overt clinical signs, but in most instances, abortion, infertility, orchitis, lameness, or posterior paralysis is observed. Abortions occur between the fourth and twelfth weeks of gestation. Aborted placentae are usually edematous, hemorrhagic, and covered with yellowish brown exudates. Pregnancies proceeding to term may result in birth of weak, stillborn, or mummified piglets, or piglets may be completely normal.


Brucella canis is isolated from dogs in kennels, although natural disease has also been described in foxes and coyotes. Infection usually results from ingestion or inhalation of organisms aerosolized from aborted fetuses, vaginal discharges, milk, semen, or urine. Dogs become infected after 4 to 6 months of cohabitation with an infected individual. Only the uterine epithelial cells of the gravid bitch are colonized. This may result in early embryonic death or abortion. If pups are carried until term, both live and stillborns may be whelped in the same litter. Rarely do live infected pups survive. Nonpregnant bitches show no overt clinical signs of illness, but may shed organisms in salivary, nasal, or vaginal secretions. In the male, brucellosis manifests as infertility, with epididymitis, rather than orchitis, as the prominent feature. Spermatogenesis is severely reduced. The prostate remains persistently infected, explaining the presence of high numbers of brucellae shed in urine, but clinical signs of prostatitis are not evident. Brucella canis also infects other sites, causing anterior uveitis, osteomyelitis, discospondylitis, meningitis, pyogranulomatous dermatitis, and glomerulonephritis.


The desert wood rat (Neotoma lepida), which is native to the American West, is the natural host for B. neotomae. This organism has been isolated from rodents on few occasions, and apparently not in association with pathogenic processes. No verified cases of natural infection have been in other species, including humans.


Isolation of brucellae from marine mammals, in particular dolphins, porpoises, seals, and European otters, was first reported in 1994. Presumptive diagnosis in these cases was by demonstration of serum anti-Brucella antibodies, and additional hosts identified by this method include whales and walruses. Most isolations have been from animals without lesions, but a wide range of associated pathology has also been found, including placentitis and possible abortion, epididymitis, meningitis, subcutaneous abscessation, and discospondylitis. Proposed new species are B. cetaceae, for dolphin and porpoise isolates, and B. pinnipediae, for seal strains.


Brucellosis in humans is known as undulant fever because of fluctuations in body temperature that are characteristic of the disease. It is an occupational disease of veterinarians, abattoir workers, laboratorians, and farmers. All brucellae are potentially pathogenic for humans, but B. abortus, B. melitensis, B. canis, and B. suis are responsible for most clinical disease. Ruminants are the primary reservoirs for human infection and the most common mode of transmission is consumption of unpasteurized dairy products. Other routes of infection are contamination of abraded or unbroken skin, inhalation of infectious aerosols, and contamination of conjunctiva or other mucous membranes. The infectious dose by the inhalation route has been estimated at 10 to 100 organisms. The incubation period is variable, ranging from 5 days to 2 months. Human brucellosis is a systemic illness with an acute or insidious onset. Symptoms include intermittent fever, chills, sweating, headache, arthralgia, and weakness. Subclinical infections are frequent. Localized suppurative infections may also develop. The case fatality rate in untreated cases is less than 5%, and the relapse rate is high. Person-to-person transmission is very rare because humans tend to be dead-end hosts.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on The Genus Brucella

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