Chapter 256. Campylobacter

Campylobacter species are among the most common pathogens in humans and are commensal in birds, swine, and cattle. It is the most common cause of culture-proven bacterial gastroenteritis in developed and developing countries, responsible for 400 to 500 million cases of diarrhea each year.1,2 Although diarrhea is the most frequent clinical manifestation, a broad clinical spectrum is associated with this infection, from asymptomatic carriage to systemic illness. Guillain-Barrè syndrome (GBS), occurs as an immunoreactive complication.

Campylobacter organisms are motile, comma-shaped, gram-negative bacilli that derive their name from the Greek words meaning “curved rod.” Campylobacter has been recognized as a pathogen of many animal species including humans. There are 21 species of the genus Campylobacter, but only 13 are responsible for illness in humans. The species most frequently associated with acute infectious diarrhea are C jejuni and C coli. Campylobacter jejuni is a leading cause of bacterial enteritis. Campylobacter upsaliensis, C lari, C hyointestinalis, and C jejuni subspecies doylei are associated with diarrhea, abdominal pain, fever, and vomiting. Campylobacter fetus is an infrequent cause of bacteremia and occasionally of meningitis in debilitated and immunocompromised individuals, including neonates.

Epidemiology

Campylobacter jejuni is found in the intestinal tract of turkeys, chickens, sheep, cattle, and other farm animals and birds, all of which serve as reservoirs of infection. Contamination of meat, especially chickens, during slaughter may be the way bacteria enter the human food chain. The main source of C jejuni and C coli infection in humans is poultry, although unpasteurized milk, water, dogs, cats, hamsters, and ferrets are potential sources. In the United States, an estimated 2 million cases of campylobacteriosis occur each year. It is the most common bacterial cause of food-borne illness.1 The overall incidence of laboratory-confirmed Campylobacter infection in 2007 in the United States was 12.7 cases per 100,000 population, representing a 31% decrease since 1996.3-5 However, the incidence of symptomatic Campylobacter species infection has been estimated at 760 to 1100 cases per 100,000 populations.2,3 Age-specific rates of Campylobacter jejuni isolation in patients with diarrhea differ among countries. In industrialized countries, C jejuni is isolated from 5% to 16% of children with diarrhea, with a prevalence of infection in healthy children of up to 1.5%.1 The disease occurs in all ages but is more common in children less than 5 years of age, with a second peak at 15 to 29 years of age. In children under 5 years of age, the incidence of laboratory-confirmed Campylobacter species infection is 43.4 cases per 100,000 person-years (up to 54.3 cases per 100,000 person-years in children < 1 year of age), and the associated male-to-female ratio is 1.34:1.6 It is the third most common cause of hospitalization for gastroenteritis after rotavirus and Salmonella species infection, with a hospitalization rate of 10.8% for all Campylobacter species infections.7-9 Studies of the disease burden of Campylobacter species infection in the Netherlands have estimated that intestinal infection in general accounts for 67,000 disability-adjusted life years per year, and that Campylobacter species infections represent at least one third of the disease burden of all intestinal infections.10 The cost per case of gastrointestinal infection in Europe has been estimated to be US$94 to US$132. In England, the total cost of gastrointestinal infections was estimated to be US$1.23 billion each year. Of this amount, US$116 million is spent on cases of Campylobacter species infection, the highest cost associated with a particular pathogen (including rotavirus and Salmonella).11Campylobacter species infection is generally associated with mild illness and only occasionally is fatal.12 The mortality rate associated with symptomatic Campylobacter species infection has been estimated at 24 deaths per 10,000 culture-confirmed cases or 200 deaths per year in the United States. In developing countries, the isolation rate in children with diarrhea is 8% to 45%, with a similar rate of isolation in asymptomatic children.13-16 Infections occur early in life, with the highest proportion of C jejuni isolates obtained from children under 5 years of age.13-15 The annual incidence of Campylobacter species infections can be as high as 2.1 episodes per child. Infections acquired early in life are more likely to be associated with diarrhea, whereas those occurring beyond the age of 4 years, although relatively common, are mostly asymptomatic.14

Rates of C jejuni infection in the United States peak in the summer and fall, but cases occur throughout the year. Modes of transmission of Campylobacter differ between economically developed and developing countries. In industrialized regions, most sporadic cases can be attributed to the handling, preparation, and consumption of contaminated raw or undercooked poultry.1,4,5,17,18 Common-source outbreaks have occurred in schoolchildren following ingestion of unpasteurized milk.19 The main factors involved in transmission in developing regions are free-roaming poultry in the household, toddlers in the family, a limited water supply, and lack of adequate disposal of excrement. Transmission can be reduced substantially by education regarding personal and domestic hygiene, penning of chickens outside the house, avoidance of contact with their feces, piped water, flush toilets, and hand washing.20C coli has been isolated more frequently in populations with intimate contact with swine. C jejuni subsp doylei is isolated more often in socially deprived communities and in people who have contact with cats and dogs. Perinatal human infections due to C fetus have been related to maternal infections during pregnancy or at the time of delivery. The incubation period is usually 1 to 7 days, but it can be longer.

Clinical Manifestations

Symptoms of Campylobacter infection range from none to fulminant sepsis and depending upon the species involved and characteristics of the host, including age and immune status.

The most common clinical manifestation of C jejuni and C coli infection is gastroenteritis. Predominant symptoms include diarrhea, abdominal cramps (which occasionally are severe and sometimes mistaken for appendicitis), fever, headache, malaise, and myalgia. Diarrhea may be initially watery and profuse. After the first few days, stools contain blood in approximately 20% of individuals in developed countries, with lower rates of bloody diarrhea occurring in developing countries. Most persons recover in 5 to 7 days, but in 20%, the disease may be severe and prolonged or may recur. Severe or persistent infection in older children and adolescents can mimic acute inflammatory bowel disease.

Immunoreactive complications including reactive arthritis, Guillain-Barré syndrome, Reiter syndrome, and erythema nodosum have been associated with C jejuni during the convalescent stage of infection. Serologic studies and culture results indicate that 20% to 40% of patients with Guillain-Barré syndrome are infected with C jejuni in the 1 to 3 weeks prior to onset of neurologic symptoms. Patients with C jejuni-associated GBS are more likely than other patients with GBS to have heightened neurophysiologic features of axonal neuropathy, antibodies to ganglioside GM1, pure motor GBS, a less elevated cerebrospinal fluid protein concentration, and a worse outcome.21-23

Campylobacter bacteremia is uncommon and occurs mostly in malnourished children or patients with chronic debilitating illnesses or immunodeficiency. Bacteremia has been estimated to occur in 1.5 per 1000 patients with enteritis and almost always is transient and asymptomatic but can be severe in immunosuppressed hosts.24,25 Extraintestinal infections caused by C jejuni include cholecystitis,26urinary tract infection,27spontaneous splenic rupture, pancreatitis,28 arthritis and osteomyelitis,29 meningitis,30 and endocarditis.31 These manifestations are uncommon and generally occur in patients who are immunosuppressed or at the extremes of age.

Bacteremia due to other species, including C upsaliensis, C hypointestinalis, C jejuni subspecies doylei, and C concisus, generally occurs in debilitated and immunocompromised individuals.

Perinatal infections are associated with C fetus but rarely with C jejuni. The association of C fetus and perinatal infection may be the consequence of colonization of the maternal genital tract and tropism for fetal tissue. Perinatal infections include abortion, stillbirth, premature labor, and neonatal sepsis and meningitis, each responsible for considerable morbidity and mortality.32,33

Diagnosis

The diagnosis of Campylobacter enteritis can be suggested clinically by the occurrence of watery diarrhea sometimes followed by blood-streaked stools and preceded or accompanied by abdominal pain, but a microbiologic diagnosis is needed to differentiate this condition from other causes of watery diarrhea or colitis. A rapid diagnosis of Campylobacter enteritis can be made tentatively by direct examination of stool with carbolfuchsin stain, the indirect fluorescent antibody test, or darkfield microscopy.34 Isolation of the organism from stool requires a selective enrichment medium containing antibiotics to suppress colonic microflora and a filtration method using cellulose membranes for isolation of species inhibited by antibiotics. Standard blood culture media are acceptable for the isolation of Campylobacter from blood and other sterile body sites, but slow growth requires that bottles be kept for at least 2 weeks. Polymerase chain reaction (PCR) techniques using oligonucleotide primers encoding for 16S ribosomal RNA have been designed for specific detection of C jejuni, C coli, and other species.35

Treatment and Prevention

Rehydration and correction of electrolyte abnormalities are the mainstays of treatment for patients with Campylobacter enteritis. Debate exists over the need to use antibiotics in uncomplicated infections. Antimicrobial therapy should be considered for C jejuni-infected patients who have bloody diarrhea, fever, worsening of symptoms, or a large number of stools, and in people who are immunosuppressed. Antimotility agents have been associated with prolongation of symptoms and fatalities and should not be used. Campylobacter species often are resistant to penicillin, ampicillin, and cephalosporins, with an alarming increase in fluoroquinolone resistance in the last decade in most countries.36 This rise in resistance coincides with the recent licensure of fluoroquinolones (sarafloxacin and enrofloxacin) for use in poultry and veterinary medicine in general, which has increased the reservoir of resistant Campylobacter.2 Most strains of C jejuni and C coli are susceptible to erythromycin, azithromycin, gentamicin, tetracycline, and chloramphenicol. When antimicrobial therapy is indicated, erythromycin is the drug of choice and is given at 40 mg/kg/day, maximum 2 g/day for 5 to 7 days.37 When given early in the course of infection, antimicrobial therapy serves to shorten the duration of clinical symptoms and the period of stool shedding of the organism. Therapy given later in the course of gastroenteritis does not affect clinical signs or symptoms but may decrease the period of shedding of the organism.2,38Human immunodefiency virus (HIV)-infected individuals and other immunocompromised persons also should receive antibiotics for treatment of Campylobacter gastroenteritis.

Bacteremia should be treated for 2 to 3 weeks with an antimicrobial agent to which the organism is susceptible, generally aminoglycosides, meropenem, or imipenem. The duration of therapy may need to be extended depending on clinical and microbiological response and the host’s underlying immune status.

Precautions against fecal–oral spread, especially hand washing, should be taken in homes and in childcare facilities. Appropriate handling, storage, and cooking of poultry should be stressed. Poultry and meat should be cooked until no longer pink in the middle [internal temperature greater than 73°C (165°F)]. Unpasteurized milk should not be consumed. HIV-infected persons should avoid animals less than 6 months of age, especially those with diarrhea. In the hospital, in addition to standard precautions, contact precautions are recommended for diapered and incontinent children for the duration of illness.