Vol. 16 No. 18

THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER

Monday, May 12, 1997

A. Provided by Carmela Groves, R.N., M.S., Chief, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene

No report at this time.

B. The Johns Hopkins Hospital (Information provided by Dr. Nancy S. Miller, Pathology Resident).

Clinical history: This patient was a 3 year-old boy with a 2 day history of fever, diarrhea and a diffuse macular rash that developed into purpura. He presented to the emergency department at The Johns Hopkins Hospital with fever, a purpuric rash, irritability, abdominal pain, and diarrhea with heme-positive stools that were not grossly bloody. His white blood cell count on admission was 8100 (31% polys with 25% bands, 28% lymphocytes, 15% monocytes). Empiric antibiotic coverage was begun. An initial concern of meningitis was ruled out by a negative evaluation of cerebral spinal fluid. A diagnosis of Henoch-Schnlein purpura (HSP) was considered; there were no renal manifestations and no specific therapy was given. An abdominal X-ray showed an abnormal bowel gas pattern suggestive of submucosal edema or hemorrhage consistent with either enteritis or HSP. A stool culture done on the day of admission was positive at 3 days for Campylobacter jejuni. Blood cultures remained negative for bacteria and viruses. The antibiotic regimen was changed to appropriate coverage for C. jejuni. The child's symptoms improved significantly over several days and he was discharged to home with follow-up care by his pediatrician.

General Information: Campylobacters are motile, 0.3-0.6 um diameter, gram-negative, comma-shaped bacterial rods that are responsible for both diarrheal and systemic illness. In otherwise healthy people, these illnesses tend to resolve spontaneously or after antimicrobial therapy. C. jejuni subsp. jejuni and C. coli are species most associated with diarrheal illness. C. fetus subsp. fetus is best known in the context of extraintestinal illness.

Epidemiology: Campylobacters are found as a commensal in the gastrointestinal (GI) tract of cattle, sheep, swine, goats, dogs, cats, rodents and fowl. Human infection is largely due to consumption of contaminated beef, poultry, shellfish, milk and water. Other reported modes of transmission include: direct contact with household pets, fecal-oral person-person contact, blood transfusions, and perinatal (in utero, via birth canal). HIV-infected individuals are at increased risk of infection in general and, in particular, from infection by "atypical" Campylobacters. There are at least an estimated 2 x 106 Campylobacter infections per year in the United States (peak incidence at <1 year and between 15-29 years of age). Compared to developed countries, developing countries show a declining infection-to-illness ratio with age, due to greater exposure-related immunity.

Pathogenesis: Factors important to producing illness include the dose of organism reaching the small intestine and the host immune status. The incubation period averages 1 to 7 days. C. jejuni grows well in bile-rich environments (e.g., small bowel). Other sites of infection and tissue injury are the colon and rectum. Primate models suggest tissue invasion is a pathogenic mechanism for C. jejuni. Other possible virulence factors include superficial adhesin proteins, outer membrane endotoxins (lipopolysaccharide), and flagellar motility. Fecal excretion of the organism (106 to 109 C. jejuni colony-forming-units per gram of stool) averages 2 to 3 weeks; convalescent excretion after 3 months is rare. With or without systemic symptoms, Campylobacteremia can be detected sometimes, but less so for C. jejuni because of its susceptibility to bactericidal activity in human serum. Patients develop specific IgG, IgM and IgA in serum, and IgA in intestinal secretions. Humoral immunology appears important to host defense, supported by observations that patients with hypogammaglobulinemic patients suffer severe, recurrent infections. C. jejuni shows great serotypic diversity, including serotypes based on somatic (O) antigens or heat-labile (capsular and flagellar) antigens. No group antigen has been identified, but several superficial proteins with broader serotypic specificity may prove useful in the development of a vaccine.

Microbiology and Diagnosis: Campylobacters require microaerophilic, selective isolation techniques at 37C. (C. jejuni prefers 42C.) These techniques include blood-based antibiotic media (cephalothin best isolates C. jejuni), enrichment broths, and filtration methods. Visible colonies often appear within 24-48 hours. Oxidase-positive colonies grown by such selective techniques, showing characteristic morphology can be read preliminarily as Campylobacter spp. Most strains of C. jejuni are distinguished from other species by positive hippurate hydrolysis. Diagnosis of enteric disease is made by direct microscopic examination of feces and by isolation of organisms in culture. Characteristic darting motility of Campylobacter spp. can be seen by darkfield or phase contrast microscopy within 2 hours of stool passage. Gram stain of stools is very specific but only 50-75% sensitive. Seventy-five percent of patients with Campylobacter enteritis also have red blood cells and neutrophils in their feces. The frequency of bacteremia in typical enteric Campylobacteriosis is unknown because most patients do not get concurrent blood cultures.

Clinical Manifestations of C. jejuni Infection: C. jejuni enteritis is often preceded by a 12-24 hour prodrome of fever, headache and myalgia. Acute enteritis can include diarrhea (loose to watery stools or grossly bloody ones), malaise, fever, and cramping abdominal pain relieved by defecation. The illness is usually self-limited, of 1 day to 1 week duration. Patients may present with acute colitis (fever, abdominal cramps, tenesmus, bloody diarrhea). The clinical picture may be confused with inflammatory bowel disease. When C. jejuni infection presents with limited symptoms, diagnosis may be confounded by its mimicry of other disease processes: abdominal pain (appendicitis), GI hemorrhage (bleeding peptic ulcer), bloody stools (intussusception in neonates), high fevers (typhoid fever or febrile convulsions in children). Rare manifestations of C. jejuni infection include meningitis and endocarditis. Extraintestinal disease in a compromised host can occur as sustained bacteremia with deep infection, skin lesions or osteomyelitis. C. jejuni has also been associated with septic abortions, acute cholecystitis, pancreatitis and cystitis. Complications of C. jejuni infection include: reactive arthritis in HLA B-27 individuals, hepatitis, interstitial nephritis, hemolytic uremic syndrome and IgA nephropathy. Guillain-Barr syndrome has been strongly associated with a single O-serotype of C. jejuni as a sequelum 2 to 3 weeks after diarrheal illness.

Therapy: Fluid and electrolyte replacement are the basis for treatment of diarrheal illnesses. Less than 1/2 of patients ill enough to seek medical attention require antibiotic therapy. These patients include those with high fevers, bloody diarrhea, >8 stools per day, worsening or persistent symptoms of >1 week duration. The agent of choice is erythromycin, which eliminates carriage of C. jejuni within 72 hours. (Resistance rates for C. jejuni average <5%.) Alternative agents include ciprofloxacin, tetracyclines (except in children <9 years old), clindamycin, amoxicillin or ticarcillin plus clavulanic acid. Resistance of Campylobacters to quinolones is increasing worldwide and may limit its empiric use in diarrheal illness. Very toxic patients or those with extraintestinal illness may benefit from gentamycin, imipenem, cefotaxime or chloramphenicol. Hypogammaglobulinemic patients with recurrent C. jejuni infection benefit from fresh frozen plasma plus antibiotics. Of note, susceptibility tests for Campylobacter spp. are not standardized.

C. jejuni and Henoch-Schnlein Purpura: HSP is a common, usually self-limited, IgA-mediated systemic vasculitis most often affecting children and young adults. The classic presentation includes a characteristic erythematous maculopapular rash and/or purpura. The clinical course may include varying degrees of colicky abdominal pain, arthritis/arthralgias, GI bleeding, and grossly or occult bloody stools. Fifty-percent of patients have renal involvement (from transient microscopic hematuria to progressive glomerulonephritides). Pathogenesis is thought to involve deposition of IgA-antigen complexes in vasculture, with activation of complement pathways. HSP can mimic many other disease processes, including acute enteritis. The etiology is elusive, although association between HSP and numerous infectious and non-infectious agents has been reported: enteric and streptococcal bacterial infections, viruses, insect bites, drugs and food allergies. A recent report (Lind, et.al., 1994) noted that HSP has not been previously associated with C. jejuni. They cite previous observations of C. jejuni in association with two different types of glomerulonephritis (GN). The authors report a case of C. jejuni enteritis in a 15 year-old boy in association with HSP, with subsequent focal proliferative GN, with IgA as the dominant immunoglobulin.

References:

Blaser M. Campylobacter and related species. In: Principle and Practice of Infectious Disease (Mandell GL, Bennett JE, Dolin R) Fourth Edition (1995), Churchill Livingstone Inc, New York, pp. 1948 -1956.

Causey AL, Woodall BN, Wahl NG, et.al. Henoch-Schnlein purpura: Four cases and a review. The Journal of Emergency Medicine 1994; 12(3): 331-341.

Lind KM, Gaub J, Pedersen, RS. Henoch-Schnlein purpura associated with Campylobacter jejuni enteritis. Case report. Scand J Urol Nephrol 1994; 28: 179-181.

Nachamkin I. Campylobacter and Arcobacter. In: Manual of Clinical Microbiology (Murray PR et.al., eds.) Sixth Edition (1995), ASM Press, Washington DC, pp. 483 - 491.

Announcements: Joint ID and MMI Seminar Series held at noon on Thursdays - 2030 Hygiene

05/15/97 - "The role of CR3 in the regulation of IL-12" Brian Kelsall, MD, National Institutes of Allergy & Infectious Diseases.