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Campylobacter jejuni Infections: Updateon Emerging Issues and Trends Ban Mishu Allos
Departments of Preventive Medicine and Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee Infection with Campylobacter jejuni is one of the most common causes of gastroenteritis worldwide; it occurs more frequently
than do infections caused by Salmonella
species, Shigella species, or Escherichia coli O157:H7. In developed countries, the
incidence of Campylobacter jejuni
infections peaks during infancy and again during early adulthood. Most infections are
acquired by the consumption and handling of poultry. A typical case is characterized by diarrhea, fever, and abdominal
cramps. Obtaining cultures of the organism from stool samples remains the best way to diagnose this infection. An alarming
recent trend is the rapid emergence of antimicrobial agent–resistant Campylobacter
strains all over the world. Use of antibiotics
in animals used for food has accelerated this trend. It is fortunate that complications of C. jejuni
infections are rare, and
most patients do not require antibiotics. Guillain-Barre´ syndrome is now recognized as a post-infectious complication of C.
infection, but its incidence is !1 per 1000 infections. Careful food preparation and cooking practices may prevent
some Campylobacter
Campylobacter jejuni infection is one of the most commonly 1957 [4], and their impact in terms of sheer numbers of human identified bacterial causes of acute gastroenteritis worldwide. In infections emerged only in the past 20 years. The first recog- developing countries, Campylobacter species are an important nized Campylobacter infections were reported in the early part cause of childhood morbidity caused by diarrheal illness. They of the 20th century and occurred in farm animals. The infec- are among the most common causes of diarrhea in travelers tions were attributed to Vibrio fetus (now known to be Cam- from developed nations. Remarkably, in many studies in the pylobacter fetus) and were realized by veterinarians to be a cause United States and other industrialized countries, Campylobacter of septic abortions in sheep and cattle. In 1947, V. fetus was infections were found to cause diarrheal disease 12–7 times as reported to be the cause of septic abortion in a woman, and frequently as infections with Salmonella species, Shigella species, during the next 3 decades, the organism was believed to be a or Escherichia coli O157:H7 [1, 2]. Although 14 species of Cam- rare, opportunistic, invasive pathogen that occurred principally pylobacter have been identified, in the United States 199% of reported infections with Campylobacter are with C. jejuni [3].
In 1973, the new genus Campylobacter was proposed [5].
Therefore, this paper will be limited to a discussion of C. jejuni. Finally, the development and increasingly widespread use ofselective media for isolation of Campylobacter from stool sam-ples in the 1970s led to the recognition in the early 1980s of the importance of these infections as a cause of human gas- Despite their widespread occurrence, Campylobacter species trointestinal illness. By the mid-to-late 1980s, it had been de- were not understood as a cause of diarrhea in humans until termined that Campylobacter species are one of the most com-mon bacterial causes of diarrhea worldwide.
Received 4 August 2000; revised 4 December 2000; electronically published 28 March Reprints or correspondence: Dr. Ban Mishu Allos, A3310 Medical Center North, Division MICROBIOLOGY
of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN 37232(
Campylobacter species are gram-negative bacilli that have a Clinical Infectious Diseases
2001; 32:1201–6
curved or spiral shape (hence their initial classification as vib- 2001 by the Infectious Diseases Society of America. All rights reserved.
rios). Recently, the complete genome sequence of C. jejuni was • CID 2001:32 (15 April) • 1201
characterized. Of note was the finding of hypervariable regions not yet a standard practice. Species-specific assays, such as PCR- that might be important in the survival of the organism [6].
enzyme-linked immunosorbent assays to detect Campylobacter Campylobacter species are motile by means of unipolar or bi- antigens in stool samples, have been developed and also may polar flagellae. The organisms grow quite slowly; 72–96 h are become useful in the diagnosis of Campylobacter infections required for primary isolation from stool samples, and isolation from blood can take even longer. They grow best at 42ЊC.
Because most Campylobacter species are resistant to cephalothin(an agent to which most other stool flora are susceptible), the COMPLICATIONS OF CAMPYLOBACTER
usual method for isolation from stool samples is use of a me- INFECTIONS
dium that contains cephalothin. Because some Campylobacterspecies, especially non-jejuni Campylobacter species, are sus- Local complications of Campylobacter infections occur as a re- ceptible to cephalothin, the filter method and antibiotic-free sult of direct spread from the gastrointestinal tract and can media should be used if initial results of cultures are negative include cholecystitis, pancreatitis, peritonitis, and massive gas- and the suspicion of Campylobacter infection is high. This trointestinal hemorrhage. Extraintestinal manifestations of method involves first filtering the stool onto an antibiotic-free Campylobacter infection are quite rare and may include men- medium through 0.45–0.65-mm filters; the filters will block the ingitis, endocarditis, septic arthritis, osteomyelitis, and neonatal passage of most stool flora but will permit the passage of smaller sepsis. Bacteremia is detected in !1% of patients with Cam- bacteria such as Campylobacter species [7].
pylobacter enteritis and is most likely to occur in patients whoare immunocompromised or among the very young or veryold [12]. Transient bacteremia in immunocompetent hosts with CLINICAL CHARACTERISTICS
C. jejuni enteritis may be more common but not detected be- OF CAMPYLOBACTER GASTROENTERITIS
cause most strains are rapidly cleared by the killing action ofnormal human serum and because blood cultures are not rou- Most typically, infection with C. jejuni results in an acute, self- tinely performed for patients with acute gastrointestinal illness.
limited gastrointestinal illness characterized by diarrhea, fever, Serious systemic illness caused by Campylobacter infection and abdominal cramps. Clinically, Campylobacter infection is rarely occurs but can lead to sepsis and death. The case-fatality indistinguishable from acute gastrointestinal infections pro- rate for Campylobacter infection is 0.05 per 1000 infections.
duced by other bacterial pathogens, such as Salmonella, Shigella, The most important postinfectious complication of C. jejuni and Yersinia species. In most patients, the diarrhea is either infection is the Guillain-Barre´ syndrome (GBS). GBS is an acute loose and watery or grossly bloody; 8–10 bowel movements demyelinating disease of the peripheral nervous system that per day occur at the peak of illness [2]. In some patients, the affects 1–2 persons per 100,000 population in the United States diarrhea is minimal and abdominal cramps and pain are the each year. Although C. jejuni infections are a common trigger predominant features; this can lead to a mistaken diagnosis of of GBS (probably preceding 30% of GBS cases), the risk of acute abdomen and unnecessary laparotomy. Fever is reported developing GBS after C. jejuni infection is actually quite small by 190% of patients and can be low-grade or 140ЊC and persist (!1 case of GBS per 1000 C. jejuni infections) [13]. The risk for up to 1 week. By that time, the illness has usually resolved, of developing GBS is increased after infection with certain Cam- even in the absence of specific antibiotic treatment. Occasion- pylobacter serotypes. In the United States, Penner type O:19 is ally, however, patients can develop a longer, relapsing diarrheal most commonly associated with GBS [14]; in South Africa, illness that lasts several weeks [8]. Although Campylobacter is Penner type O:41 is the serotype most frequently associated rarely identified in the stools of healthy persons, depending upon the population studied, as many as 50% of persons who GBS that occurs after C. jejuni infection is usually a more are infected during outbreaks are asymptomatic [9].
severe disease, associated with extensive axonal injury, a greater Fecal leukocytes and RBCs are detected in the stools of 75% likelihood of the need for mechanical ventilation, and increased of infected persons [10]. The peripheral WBC count may be risk of irreversible neurological damage. In contrast, the severity mildly elevated. Other laboratory studies, including liver func- of C. jejuni infection is not associated with an increased risk tion, electrolytes, and hematocrit levels, are normal. Because of the development of GBS. Indeed, many GBS-associated C. diffuse colonic inflammation may be seen on sigmoidoscopic jejuni infections are asymptomatic [15]. Because the neurolog- examination, Campylobacter enteritis may be confused with ical symptoms of GBS that follow C. jejuni infection typically early inflammatory bowel disease. Diagnosis of Campylobacter occur 1–3 weeks after the onset of diarrheal illness, humoral enteritis is confirmed by obtaining cultures of the organism immunopathogenic mechanisms are likely involved. Molecular from stool samples. Some laboratories have begun performing mimicry between peripheral nerve glycolipids or myelin pro- PCR analysis on stool samples for Campylobacter, but this is teins and structures on the lipopolysaccharides of some Cam- 1202 • CID 2001:32 (15 April) • FOOD SAFETY
Rates of selected enteric bacterial infections
pylobacter strains likely plays a role in the pathogenesis of Cam- detected by the Foodborne Active Surveillance Network
of the Centers for Disease Control and Prevention (United
Persons with the HLA-B27 histocompatibility antigen are States, 1996–1999).
prone to the development of reactive arthritis several weeksafter infection with Campylobacter [17]. Other postinfectious complications of infection include uveitis, hemolytic anemia, hemolytic uremic syndrome, carditis, and encephalopathy.
In the United States, Campylobacter infections became reportable illnesses in many states in the early 1980s; Active surveillance was done in Maryland, Oregon, se- however, from the outset, the reporting systems routinely un- lected counties in California, Connecticut, and Georgia. Table is mod- derestimated the impact of these infections. In the early years of Campylobacter surveillance, many hospital microbiology lab-oratories did not seek Campylobacter when they performedstool cultures for other enteric pathogens. Later studies con- early 1980s, the infections have demonstrated a marked sea- firmed that when diarrheal stool samples were cultured for sonal distribution, with a surge that begins in May and peaks Campylobacter every time they cultured for Salmonella or Shi- gella, Campylobacter was identified 2–7 times more frequently Sources and transmission of infection.
than was Salmonella or Shigella. Even currently, estimates have important route of Campylobacter infections in the United shown that only 1 in 38 cases of detected Campylobacter in- States and other industrialized nations remains the consump- tion and handling of chicken. In studies in many parts of the Accurate estimates of the true incidence of Campylobacter United States, Europe, and Australia, 50%–70% of all Cam- infections in the United States and other industrialized nations pylobacter infections have been attributed to consumption of depend upon many data sources. In 1996, the Emerging In- chicken [20–22]. Perhaps this should not be surprising in light fections Program Foodborne Diseases Active Surveillance Net- of the frequency with which poultry products are consumed work (Foodnet) of the Centers for Disease Control and Pre- and the nearly universal contamination of chicken carcasses vention (CDC) began the collection of data on 9 foodborne with Campylobacter [23]. Indeed, it has been estimated that illnesses in selected United States cities. In the first year, Cam- just 1 drop of chicken juice may contain 500 infectious or- pylobacter was detected more frequently than was any other ganisms [24]. Even with strict attention to good handwashing pathogen—more frequently than Salmonella and Shigella com- and cleaning of cutting boards, it is easy to see how simple bined. However, from 1996 through 1999, the incidence of errors in the handling of food might result in cross-contami- Campylobacter infection decreased 26%, although the organism nation in the kitchen and, therefore, human illness. Because remained the most commonly identified enteric pathogen [19] heat kills viable Campylobacter species, thorough cooking of (table 1).The decreased rates were attributed to disease pre- chicken should be emphasized as an important food-safety vention efforts that had been implemented in food service es- tablishments, meat and poultry processing plants, and egg pro- Other foods and activities also have been implicated as duction farms [19]. Currently, the CDC estimates that 2.4 sources of Campylobacter infection. Although outbreaks of in- million cases of Campylobacter infection occur in the United fection account for a small fraction of Campylobacter infections States each year, involving almost 1% of the entire population in humans (most infections are sporadic), consumption of un- pasteurized milk is the most frequently reported cause of out- Demographic data.
The age and sex distributions of Cam- breaks of infection [3]. Other sources of sporadic infection pylobacter infections are unique among bacterial enteric path- include sausages or red meat (especially in Scandinavian coun- ogens. In industrialized nations, 2 age-peaks occur: the first is tries), contaminated water, contact with pets (especially birds at !1 year of age, and a second surge occurs during young and cats), and international travel [25–27].
adulthood, at 15–44 years of age. Furthermore, there is a pre- Because the infectious dose of Campylobacter is quite high ponderance of males among infected persons, which begins in comparison with that of Shigella or Giardia (800–106 ingested during early childhood and persists until old age [3]. The rea- organisms are needed to produce illness in 10%–50% of per- sons for these age and sex distributions remain unknown. Since sons) [28], person-to-person transmission is unusual. Out- the beginning of national reporting on Campylobacter in the breaks of Campylobacter infection in day care centers or mental FOOD SAFETY • CID 2001:32 (15 April) • 1203
institutions are almost unheard of. Although the reported in- cultures. Fluoroquinolones were especially apt to be used for cidence of Campylobacter infection among homosexual men is the treatment of traveler’s diarrhea.
almost 40 times greater than in the general population [29], However, in the past few years, a rapidly increasing pro- recent analysis shows the rate is not higher than among het- portion of Campylobacter strains all over the world have been found to be fluoroquinolone-resistant (table 2). Primary resis- Campylobacter in developing countries.
tance to quinolone therapy in humans was first noted in the ogy of Campylobacter infections is quite different in developing early 1990s in Asia and in European countries such as Sweden, countries than in the industrialized world. In tropical devel- The Netherlands, Finland, and Spain. Not surprisingly, this oping countries, Campylobacter infections are hyperendemic coincided with initiation of the administration of the fluoro- among young children, especially those aged !2 years. Asymp- quinolone, enrofloxacin, to food animals in those countries tomatic infections occur commonly in both children and adults, [31]. A similar increase in rates of resistance to fluoroquino- whereas, in developed countries, asymptomatic Campylobacter lones in Campylobacter isolates from humans was observed in infections are unusual. In addition, in developing countries, out- the United Kingdom after the approval of the use of fluoro- breaks of infection are uncommon and the illness lacks the quinolones in veterinary animals there as well [32].
marked seasonal nature observed in industrialized nations. Nev- In the United States, the licensure of sarafloxacin in 1995 ertheless, in both developed and developing countries, Campy- and enrofloxacin in 1996 for use in poultry flocks contributed lobacter remains one of the most common bacterial causes of to an increase in the number of domestically acquired fluor- oquinolone-resistant Campylobacter infections in Minnesota[33]. In that state, fluoroquinolone resistance among Campy-lobacter isolates from humans increased from 1.3% in 1992 to TREATMENT AND RESISTANCE
10.2% in 1998. The impact of the use of fluoroquinolones infood animals upon human health was the subject of a recent Maintenance of hydration and electrolyte balance, not anti- World Health Organization meeting [34]. In addition to more biotic treatment, is the cornerstone of treatment for Campy- prudent use of these agents in people, international controls lobacter enteritis. Indeed, most patients with Campylobacter in- on the use of antibiotics in food animals may become necessary fection have a self-limited illness and do not require antibiotics to curtail the development of additional resistance among food- at all. Nevertheless, there are specific clinical circumstances in which antibiotics should be used. These include high fevers, Erythromycin has once again come to be considered the bloody stools, prolonged illness (symptoms that last 11 week), optimal drug for treatment of Campylobacter infections. Despite pregnancy, infection with HIV, and other immunocompromised decades of use, the rate of resistance of Campylobacter to eryth- romycin remains quite low. Other advantages of erythromycin The decision to use antibiotics should be made judiciously.
include its low cost, safety, ease of administration, and narrow In the United States, the most common cause of bloody di- spectrum of activity. Unlike the fluoroquinolones and tetra- arrhea is not Campylobacter but E. coli O157:H7 infection [1].
cyclines, erythromycin may be administered safely to children Recent studies suggest that administration of antibiotics to chil- and pregnant women and is less likely than many agents to dren with E. coli O157:H7 infection actually increases the risk exert an inhibitory effect on other fecal flora. Erythromycin of the hemolytic uremic syndrome (HUS) [30], a recognized stearate is acid-resistant, stable, and incompletely absorbed.
sequela of this infection. Therefore, young children with bloody Therefore, in addition to its systemic effects, it may be capable diarrhea (and others who might be at risk of infection with E. of exerting a contact effect throughout the bowel [35]. The coli O157:H7 and HUS) should not be treated with antibioticsunless it is absolutely necessary or until this infection is ruled Percentage of Campylobacter isolates (from humans)
with primary resistance to fluoroquinolones.
Until a few years ago, if antimicrobial therapy was indicated for Campylobacter infection, fluoroquinolones were considered the drugs of choice. This approach was the simplest for phy- sicians and patients alike because the symptoms of Campylo- bacter enteritis (fever, abdominal cramps, and diarrhea) are clinically indistinguishable from those of bacterial gastroenter- itis caused by other organisms, such as Salmonella or Shigella species. Because these other pathogens were also generally sus- ceptible to fluoroquinolones, empirical treatment with these drugs could be used without waiting for the results of stool 1204 • CID 2001:32 (15 April) • FOOD SAFETY
recommended dosage for adults is 500 mg administered orally sumption of unpasteurized milk; this should be emphasized to 2 times per day for 5 days. For children, the recommended pregnant women, the elderly, immunocompromised persons, dosage is 40 mg per kg per day in 2 divided doses for 5 days.
or other persons in whom C. jejuni infection may have serious The newer macrolides, azithromycin and clarithromycin, are consequences. Persons who travel to developing countries and also effective against C. jejuni infections, but they are more campers should be cautioned against drinking untreated water.
expensive than erythromycin and provide no clinical advantage.
Routine use of antibiotic prophylaxis to prevent Campylobacter Campylobacter species also are generally susceptible to amino- glycosides, chloramphenicol, clindamycin, nitrofurans, and im-ipenem. High rates of resistance make tetracycline, amoxicillin, References
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