Campylobacter

Etiology

Twenty-six species and 9 subspecies of Campylobacter are recognized (as of December 2014). Most of these have been isolated from humans, and many are considered pathogenic. The most significant of these are C. jejuni and C. coli, which are believed to cause the majority of human enteritis. More than 100 serotypes of C. jejuni have been identified. C. jejuni has been subspeciated into C. jejuni subsp. jejuni and C. jejuni subsp. doylei. Although C. jejuni subsp. doylei has been isolated from humans, it is much less common, less hardy, and more difficult to isolate. Other species, including Campylobacter fetus, Campylobacter lari, and Campylobacter upsaliensis, have been isolated from patients with diarrhea, although much less frequently ( Table 229.1 ). Emerging Campylobacter spp. have been implicated in acute gastroenteritis, inflammatory bowel disease, and peritonitis, including C. concisus , and C. ureolyticus . Additional Campylobacter spp. have been isolated from clinical specimens, but their roles as pathogens have not been established.

Campylobacter organisms are gram-negative, curved, thin (0.2-0.8 µm wide), non–spore-forming rods (0.5-5 µm long) that usually have tapered ends. They are smaller than most other enteric bacterial pathogens and have variable morphology, including short, comma-shaped or S -shaped organisms and long, multispiraled, filamentous, seagull-shaped organisms. Individual organisms are usually motile with a flagellum at one or both poles depending on the species. Such morphology enables these bacteria to colonize the mucosal surfaces of both the gastrointestinal (GI) and respiratory tracts and move through them in a spiraling motion. Most Campylobacter organisms are microaerophilic, occasionally partially anaerobic, and oxidase positive. Most can transform into coccoid forms under adverse conditions, especially oxidation.

Epidemiology

Worldwide, Campylobacter enteritis is a leading cause of acute diarrhea. Efforts to reduce Campylobacter contamination and use of safe handling practices have led to decreased incidence. Campylobacter infections can be both food-borne and water-borne and most frequently result from ingestion of contaminated poultry (chicken, turkey) or raw milk . Less often, the bacteria come from drinking water, household pets (cats, dogs, hamsters), and farm animals. Infections are more common in resource-limited settings, are prevalent year-round in tropical areas, and can exhibit seasonal peaks in temperate regions (late spring with a peak midsummer in most of the United States, with a smaller secondary peak in late fall). In industrialized countries, Campylobacter infections peak in early childhood and again in young adulthood (15-44 yr). This 2nd peak is not seen with Salmonella and Shigella infections. In developing countries, repeated infections are common in childhood, leading to increased immunity and rare disease in adulthood. Each year in the United States, there are an estimated 2.5 million cases of Campylobacter infection. Of these, death is rare, with 50-150 reports annually. In The Netherlands, medical record review shows that on average each resident acquires asymptomatic Campylobacter colonization every 2 yr, progressing to symptomatic infection in approximately 1% of colonized people.

Food-borne infection is most common and can be seen with the consumption of raw or undercooked meat, as well as by cross-contamination of other foods. Although chickens are the classic source of Campylobacter, many animal sources of human food can also harbor Campylobacter, including seafood. C. coli has been linked to swine. Poultry is more likely to be heavily contaminated, whereas red meats often have fewer organisms. Unpasteurized milk products are also a documented source. Additionally, many pets can carry Campylobacter, and flies inhabiting contaminated environments can acquire the organism. Shedding from animals can contaminate water sources. Humans can acquire infection from water, although much less frequently than from contaminated food. Airborne (droplet) transmission of Campylobacter has occurred in poultry workers. Use of antimicrobials in animal foods may increase the prevalence of antibiotic-resistant Campylobacter isolated from humans.

Human infection can result from exposure to as few as 500 bacteria, although a higher dose (>9,000 bacteria) is often needed to cause illness reproducibly. Inoculum effectiveness is dependent on host factors, including immune status and stomach acidification. C. jejuni and C. coli spread person to person, perinatally, and at childcare centers where diapered toddlers are present. People infected with C. jejuni usually shed the organism for weeks, but some can shed for months, with children tending toward longer shedding. Handwashing is critical to preventing spread in these environments.

Pathogenesis

Most Campylobacter isolates are acid sensitive and should, in theory, be eradicated in the stomach. Therefore, models for the pathogenesis of C. jejuni enteritis include mechanisms to transit the stomach, adhere to intestinal mucosal cells, and initiate intestinal lumen fluid accumulation. Host conditions associated with reduced gastric acidity, such as proton pump inhibitor use, and foods capable of shielding organisms in transit through the stomach may help allow Campylobacter to reach the intestine. Once there, Campylobacter is able to adhere to and invade intestinal mucosal cells through motility, including use of flagellae, as well as by the use of surface proteins (e.g., PEB1, CadF), large plasmids (e.g., pVir), surface adhesins (e.g., JIpA), and chemotactic factors. Lumen fluid accumulation is associated with direct damage to mucosal cells resulting from bacterial invasion and potentially from an enterotoxin and other cytotoxins. Additionally, C. jejuni has mechanisms that enable transit away from the mucosal surface. The factors used depend on the species involved.

Campylobacter spp. differ from other enteric bacterial pathogens in that they have both N - and O -linked glycosylation capacities. N -linked glycosylation is associated with molecules expressed on the bacterial surface, and O -linked glycosylation appears limited to flagellae. Slipped-strand mispairing in glycosylation loci results in modified, antigenically distinct surface structures. It is hypothesized that antigenic variation provides a mechanism for immune evasion.

C. fetus possesses a high-molecular-weight S-layer protein that mediates high-level resistance to serum-mediated killing and phagocytosis and is therefore thought to be responsible for the propensity to produce bacteremia . C. jejuni and C. coli are generally sensitive to serum-mediated killing, but serum-resistant variants exist. Some suggest these serum-resistant variants may be more capable of systemic dissemination.

Campylobacter infections can be followed by Guillain-Barré syndrome , reactive arthritis , and erythema nodosum . Such complications are thought to be from molecular mimicry between nerve, joint, and dermal tissue and Campylobacter surface antigens. Most Campylobacter infections are not followed by immunoreactive complications, indicating that host conditions as well as other factors, in addition to molecular mimicry, are required for these complications. It is proposed that low-grade inflammation caused by Campylobacter, below the threshold that can be detected by endoscopy, results in crosstalk with gut nerves, leading to symptoms.

Clinical Manifestations

There are a variety of clinical presentations of Campylobacter infections, depending on host factors such as age, immunocompetence, and underlying conditions. Infection presents most often as gastroenteritis, but also as bacteremia, neonatal infections, and, less often, extraintestinal infections.