Campylobacter jejuni and Campylobacter coli

Description of the Pathogen

The genus Campylobacter (from the Greek and Latin meaning “curved rod”) comprises gram-negative, mostly microaerophilic bacteria. These curved, spiral, or S-shaped bacteria are 0.2–0.5 μm wide and 1–5 μm long and possess rapid and darting motility in corkscrew fashion by means of a single, unsheathed flagellum on one or both ends. Campylobacters are commensal organisms living in the gastrointestinal tract of birds and mammals. Campylobacter genomes are relatively small (approximately 1600−1900 genes). The complete genomes of several Campylobacter spp. have been sequenced and include a variety of genes involved in biosynthesis and modification of carbohydrate surface structures that may be involved in antigenic variation and molecular mimicry.

As of 2020, the genus Campylobacter included 26 species, two provisional species, and nine subspecies. ^, About one half of these are known human pathogens, although human illness is mostly due to C. jejuni and C. coli , and less frequently to C. upsaliensis, C. lari, and C. fetus ( Table 163.1 ). C. jejuni is reported in about 90% of diarrheal illnesses caused by Campylobacter . C. coli is not common in the US but may cause up to 25% of Campylobacter- related illness in certain regions. C. jejuni and C. coli have similar epidemiology and clinical features and belong to the same cluster phylogenetically.

Epidemiology

Enteric Campylobacter infections are common worldwide. C. jejuni is the most common species of Campylobacter isolated from patients with diarrhea in both resource-rich and resource-limited countries. ^{, ,} In resource-rich countries, illness occurs across all age groups but predominates in infants, children, and young adults. ^, Campylobacter can cause outbreaks. ^{, ,} The C. jejuni rate doubles in the summertime, which might be explained by poultry contamination during the hotter months of the year and increased consumption of more barbecued and undercooked poultry. In the US, Campylobacter is estimated to cause about 845,000 illnesses, 8,500 hospitalizations, and 76 deaths annually. Outbreaks of Campylobacter occur typically in the setting of contaminated poultry products, unpasteurized or ineffectively pasteurized dairy, or water exposure. ^{, ,} Data from the Foodborne Diseases Active Surveillance Network (FoodNet) showed that Campylobacter infection rates increased by 12% in 2018 (19.5 per 100,000) compared with 2015 to 2017. This increase was attributed, in part, to increased use of culture independent testing (CIDT). In 2015 Campylobacter accounted for 38% (686/1803) of cases reported to FoodNet, while Salmonella accounted for 38% (694) and Shigella accounted for 7% (131) of cases. Campylobacter also is a leading cause of international travel-associated diarrhea in the US.

In resource-limited settings, Campylobacter is detected year-round and is the most common bacteria isolated from infants with diarrhea due to continuous exposure to contaminated water and food. Seasonality is usually less pronounced or absent, asymptomatic infections are common, and diarrhea typically occurs in children but not adults. However, epidemiologic data are lacking in these settings owing to poor surveillance and insensitive methods of detection. A multinational population-based surveillance study of more than 9,000 children aged <60 months with moderate to severe diarrhea (and controls) in resource-limited settings detected C. jejuni as a significant pathogen in children aged <1 year in Bangladesh and Pakistan and in children aged 2–5 years in Pakistan and India. Campylobacter was not associated with significant burden of diarrhea in the African countries in this study (Mali, Kenya, The Gambia, and Mozambique). Additional data are needed to better understand the burden of Campylobacter in resource-limited settings.

Enteric Campylobacter infection has several well-defined modes of transmission. The most important is the ingestion of contaminated food such as undercooked poultry and meat and unpasteurized milk. ^, Ingestion of contaminated water and direct contact with animals, including pets and animals on farms and in slaughterhouses, also has been documented. Person-to-person transmission is rare but does occur in childcare centers and in families, as does perinatal transmission through contact with a contaminated birth canal and through sexual contact among men who have sex with men. ^,

Pathogenesis and Immunity

In susceptible individuals, as few as 360 colony-forming units are required to induce diarrhea. Although C. jejuni is killed by hydrochloric acid at pH 2.3, it can survive in milk or water for several weeks. The mechanisms by which C. jejuni induces disease are not well understood, but the process involves bacterial virulence and colonization factors involved in surviving passage through the stomach and small intestine and subsequent colonization and growth in the distal ileum and colon ( Table 163.2 ).

Three general stages during Campylobacter infection have been postulated to lead to different clinical syndromes: (1) colonization and adherence to the epithelium of the distal ileum and colon may result in noninflammatory diarrhea through unknown mechanisms; (2) invasion and proliferation within the intestinal epithelium causes cell damage and an inflammatory response clinically manifest as dysentery with fecal leukocytes; and (3) translocation across the intestinal epithelium with spread to mesenteric lymph nodes causes mesenteric adenitis and also causes spread to extraintestinal sites (e.g., bacteremia, meningitis). ^{, ,}

Immunity to C. jejuni develops after one or more infections. Children living in endemic areas have a progressive decrease in the illness-to-infection ratio with increasing age. Cohort studies also demonstrate that Campylobacter diarrhea occurring in young children protects against subsequent reinfections; however, no protection occurs after asymptomatic infection. Serum antibodies to specific antigens of Campylobacter increase after natural infection. ^, Experimental challenge studies in volunteers show that rechallenge with the same strain of C. jejuni is associated with protection at 1–2 months after the initial challenge and partial protection at 1 year after the initial challenge, resulting in milder illness. ^, Immunocompromised patients can develop prolonged, severe, and recurrent C. jejuni infections and fail to respond to therapy or mount a humoral response.

A rapid and intense serum response involving both monomeric and polymeric immunoglobulin A (IgA) occurs in the first week, reaches a peak after the second week, and declines to low levels within 30 days after the onset of symptoms. A local secretory IgA response also occurs after Campylobacter enteritis. Patients infected with C. jejuni O:19, the serotype most frequently associated with GBS, had a significantly higher IgA antibody response than did patients infected with other serotypes. Isotype-specific IgG and IgM antibodies peak on days 15–21 and decrease to low levels within 3 months after onset of symptoms. ^, In persons who are chronically exposed in hyperendemic areas, serum-specific IgA antibodies increase progressively through life. Campylobacter antibody levels in populations in resource-rich countries compared with resource-limited countries are significantly lower. Studies in breastfed Mexican children have demonstrated protection against Campylobacter diarrhea conferred by specific secretory IgA antibodies present in human milk. ^, Human and mouse experimental infections also suggest that cell-mediated immune responses are important and correlate with protection against Campylobacter enteric infections.

Clinical Manifestations

Campylobacter infections produce clinical manifestations that are particular to the species involved as well as the characteristics of the host, such as age, immunosuppression, and underlying chronic and debilitating illnesses (see Table 163.1 ). The most common clinical finding is enteritis, of which >90% of cases are caused by C. jejuni. ^{, ,} Bloodstream infections (BSI), extraintestinal infections, and perinatal infections are rare and typically are caused by other Campylobacter spp.