The family Campylobacteraceae includes three closely related genera: Campylobacter, Arcobacter, and Sulfurospirillum. Campylobacter (from the Greek word meaning curved rod) are slender, S-shaped or spirally curved, mostly microaerobic, motile, gram-negative bacilli with a flagellum at one or both ends. More than 16 species have been identified in the Campylobacter genus, but not all of them are considered pathogenic in humans (Table 157.1). The diagnosis of Campylobacter infection relies on pathogen isolation, mainly from stools and occasionally from blood. C. jejuni is the species most commonly isolated from children. C. fetus is a rare cause of bloodstream and systemic infections, occurring primarily in immunocompromised and debilitated hosts. C. fetus also is associated with perinatal infections and abortion. With respect to disease manifestations associated with Campylobacter genus, C. jejuni is the prototype for enteric infections, and C. fetus is the prototype for extraintestinal infections. Other Campylobacter species are associated with symptoms and signs including diarrhea, abdominal pain, fever, and vomiting, and with lung, perianal, groin, and axillary abscesses.

Campylobacter species are mainly zoonotic, with a variety of animals and birds implicated as reservoirs for infection. Both C. jejuni and C. coli have been isolated from the gastrointestinal tracts of cattle, sheep, pigs, and numerous wild and commercially raised birds. Contamination of meat during slaughter may be the route by which bacteria enter the human food chain. The main source of C. jejuni and C. coli infections in humans is poultry, although pet dogs, cats, and hamsters are potential sources. Transmission of Campylobacter species occurs via the fecal-oral route through contaminated food and
water or by direct contact with fecal material from infected animals or people. Reservoirs for Campylobacter species are shown in Table 157.1. Humans appear to be the only reservoir for the periodontal pathogens.

Outbreaks of diarrhea caused by C. jejuni and C. coli have been associated with consumption of improperly handled or undercooked poultry and, less frequently, red meat, unpasteurized milk, and contaminated water. Person-to-person transmission of Campylobacter has been reported, specifically when the index cases were young children who were incontinent of stool, such as children in child-care facilities and neonates of infected mothers. Intrafamilial spread is an uncommon finding.

According to a FoodNet surveillance report, the incidence of infection with C. jejuni in 2003 decreased to 12.6 per 100,000 persons. This incidence rate is close to the 2010 national health objective of 12.3 cases per 100,000 persons and appears to be due in part to programs directed at providers and health care consumers and improvements in food safety programs. The incidence of C. jejuni infection follows a bimodal age distribution, with the highest isolation rates occurring in infants and young children, followed by a second peak in people 15 to 30 years of age. The rate of asymptomatic carriage is low in economically developed countries, but may be as high as 40% in economically developing nations, particularly in areas with poor hygiene, limited access to water, free-roaming poultry in houses, and areas that lack adequate excreta disposal. In developing countries, isolation rates of Campylobacter are 20% to 40% among young children with diarrhea, with an annual incidence of two infections per child. Asymptomatic infections are common occurrences, especially in older children. Male and female subjects have equal rates of infection. In temperate climates, infections occur more frequently in summer and early fall, but in tropical climates, the incidence appears to be greater during the rainy season.

C. fetus subspecies venerealis causes abortion in sheep and cattle and has been isolated from bile, blood, intestine, and placenta of these animals. C. fetus subspecies fetus is associated primarily with bacteremia and extraintestinal infections in humans, with isolation rates peaking in children younger than 1 year of age. In adults, infection occurs predominantly in patients with other comorbidities, including underlying illnesses that may be associated with immunoincompetence. Perinatal infections caused by C. fetus have been associated with maternal infections during pregnancy or at the time of delivery. Infection with C. fetus comprises less than 0.5% of all Campylobacter species reported. C. fetus is not a recognized cause of gastroenteritis, but because the organism does not grow well at 42°C, at which stool cultures for Campylobacter are held, and because of the uncommon occurrence of disease, the incidence of C. fetus infection is unknown.

After ingestion, C. jejuni are killed rapidly by gastric acid, which is an effective barrier against infection. Controlled studies have shown a wide variation in the number of C. jejuni organisms needed to produce an infection. Although some people have symptoms after ingesting 500 organisms, others ingest more than 10⁶ organisms without effect. Thus, the critical inoculum size is not characterized completely. If organisms survive the gastric milieu, they must attach to the intestinal epithelial cells for infection to persist. This attachment apparently occurs because of the ability of C. jejuni to penetrate the mucous layer and to adhere to apical surfaces of host intestinal cells. In vitro adherence occurs through both specific and nonspecific adhesion-receptor interactions that involve numerous bacterial surface-associated proteins and glycolipids, namely, flagella, lipopolysaccharides, and surface structures of the outer membrane of bacteria. The attachment and subsequent uptake of C. jejuni into enterocytes is regulated at least by nonfimbriated bacterial surface proteins that bind to specific fucosylated oligosaccharide cell receptors.

After C. jejuni adhere to epithelial cells, the organisms are capable of causing illness by three postulated mechanisms. The first involves cell attachment and production of an enterotoxin, similar to cholera toxin, with subsequent development of secretory diarrhea. Second, like Shigella, bacteria can penetrate and proliferate within the intestinal epithelium and produce at least two cytotoxins, causing cell damage and death, that can be manifested as bloody diarrhea. The third mechanism, referred to as translocation, manifests by bacteria penetrating the epithelial lining without causing cellular damage and then proliferating in the lamina propria and mesenteric lymph nodes. These organisms then can reach the bloodstream to cause extraintestinal infection such as mesenteric adenitis, arthritis, meningitis, and cholecystitis. C. jejuni infection also has resulted in a variety of immune-mediate conditions.

Clinical manifestations of infection caused by Campylobacter depend on the species involved and characteristics of the host, such as age, immunosuppression, or underlying chronic and debilitating diseases. Acute diarrhea is the most common clinical presentation, and more than 90% of diarrheal cases caused by Campylobacter species are due to C. jejuni and C. coli. However, overall estimates may be inaccurate because culture techniques used in many laboratories may not detect other species or differentiate between these two species, which are clinically indistinguishable. Approximately 5% to 10% of cases of diarrhea caused by C. jejuni in the United States are caused by C. coli. After an incubation period of 1 to 7 days, patients typically experience prodromal symptoms of fever, headache, and myalgia. Diarrhea, accompanied by nausea, vomiting, and abdominal cramps, usually occurs within 24 hours, with stools that vary from loose and watery to grossly bloody. Substantial differences in the clinical presentation of diarrhea occur in children from economically developed compared with children residing in developing countries. The incidence of bloody diarrhea is greater than 50% in most studies conducted in developed countries, but in developing nations, watery diarrhea is the most frequent presentation; bloody diarrhea occurs in fewer than 20% of cases. In economically developing countries, however, C. jejuni is the pathogen most commonly isolated from children with dysentery, followed by Shigella, Escherichia coli, and Entamoeba histolytica. The frequency of stools varies, but many patients have at least 1 day with more than ten stools. Acute resolution is the rule, but diarrhea lasts longer than 2 weeks in 20% of cases, and chronic diarrhea accompanied by failure to thrive may occur in some children.

Abdominal pain affects more than 90% of patients older than 2 years of age and can be severe enough to mimic appendicitis. The complex of acute colitis with bloody stools, tenesmus, and low-grade fever has been reported and needs to be distinguished from inflammatory conditions such as ulcerative colitis or Crohn colitis. Thus, when this symptom complex occurs in an older child or adolescent, the illness can be confused easily with ulcerative colitis. Exclusion of C. jejuni infection is important if a diagnosis of inflammatory bowel disease is suspected. Immunoreactive complications as a result of Campylobacter infection have been described and include Guillain-Barré syndrome, a leading cause of acute flaccid paralysis; the Miller-Fisher syndrome, a variant characterized by ophthalmoplegia, areflexia, and ataxia; or a more dramatic presentation of an acute motor axonal neuropathy, a rapidly progressive tetraplegia associated with respiratory failure; reactive
arthritis; Reiter syndrome (asymmetric arthritis, urethritis, and ophthalmitis in HLA B27-positive patients); erythema nodosum; and immunoproliferative states.

Bloodstream and extraintestinal infections are uncommon events, occurring more frequently in malnourished children or patients with chronic debilitating illnesses or immunosuppression. Bacteremia has been estimated to occur in one in 3,000 children with enteritis and in one in 170 in the elderly. Bacteremia almost always is transient and asymptomatic, although secondary bacteremia with a focal infection, such as meningitis, pneumonia, endocarditis, or thrombophlebitis, can occur. Additionally, infection can be severe or chronic with relapses that can persist for weeks, mostly in immunosuppressed patients. C. jejuni is the Campylobacter species most commonly isolated from immunosuppressed patients, followed by C. fetus. In developing countries, however, other species, including C. jejuni subspecies doylei, C. upsaliensis, and C. hyointestinalis have been isolated. C. fetus infections in children occur mainly during the perinatal period. This predilection may be caused by the ability of C. fetus to colonize the genital tract and colon and by tropism for fetal tissue. Perinatal C. fetus infections can induce abortion, stillbirth, premature labor, or neonatal sepsis and meningitis, with considerable morbidity and mortality rates that can be as high as 80%. Extraintestinal infections caused by C. jejuni are rare occurrences. Septicemia, meningitis, cholecystitis, hepatitis, pancreatitis, peritonitis, urinary tract infection, and septic arthritis have been reported. Other species of Campylobacter infect humans less commonly (Table 157.1).

Clinical diagnosis of Campylobacter diarrhea is difficult to establish because of variations in the clinical presentation, from watery to grossly bloody diarrhea, and a similarity in presentation to other causes of diarrhea. However, when inflammatory diarrhea with bloody stools, fever, and abdominal pain occurs, Campylobacter always should be considered in the differential diagnosis. A microbiologic diagnosis is needed to differentiate C. jejuni from other causes of colitis such as Salmonella, Shigella, Shigatoxin-producing E. coli, or E. histolytica. Direct examination of stool with Wright stain often shows the presence of fecal leukocytes. Rectal swabs can be cultured for C. jejuni, but rectal swabs are less effective than are stool samples for growing the organism. A stool transport media should be used, especially for rectal swabs. Campylobacter species have fastidious culture requirements, and these organisms can be slow growing. In addition, species other than C. jejuni and C. coli may be significantly underdiagnosed as causes of gastrointestinal tract disease because of (a) use of selective media and growth conditions that lack hydrogen that may inhibit their growth, (b) procedures used in many microbiology laboratories that do not identify Campylobacter isolates to the species level, and (c) lack of use of stool filtration techniques.

Ideally, for isolating Campylobacter from feces, two systems are used: selective enrichment media containing antimicrobial agents to specifically suppress the colonic microflora and a filtration method using cellulose membranes. The use of the filtration method allows for isolation of species such as C. jejuni subspecies doylei, C. upsaliensis, C. fetus, and C. hyointestinalis that are inhibited by antimicrobial agents contained in the selective enrichment medium. Studies using both the selective medium and the filtration method demonstrate that Campylobacter species other than C. jejuni may account for 30% to 60% of all Campylobacter isolates from patients with diarrhea. When both isolation methods were used, 73% of all Campylobacter isolates were C. jejuni, 13% were C. upsaliensis, and 12% were C. coli in one study.

Campylobacter are microaerophilic, requiring 5% oxygen, 10% carbon dioxide, and 85% nitrogen for optimal growth. Gas-generating envelopes that reproducibly provide the correct environment are available commercially. Although all Campylobacter species grow at 37°C, the optimal temperature for growth of a thermophilic group of Campylobacter composed of C. jejuni, Campylobacter coli, and Campylobacter lari is 42°C. The slow growth of Campylobacter requires selective media that allow isolation from more rapidly growing enteric flora. Because C. jejuni is the species that usually causes intestinal illness, many laboratories place stool specimens on one of the selective media and incubate stool cultures at 42°C to help optimally isolate this organism. With this method, several other species will be missed, especially those not thermotolerant and susceptible to cephalothin.