Download Volume 26 - No 15: Salmonella typhi

JOHNS HOPKINS
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Department of Pathology
600 N. Wolfe Street / Baltimore MD 21287-7093
(410) 955-5077 / FAX (410) 614-8087
Division of Medical Microbiology
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER Vol. 26, No. 15
Tuesday, August 28, 2007
A. Provided by Emily Luckman, Division of Outbreak Investigation, Maryland Department
of Health and Mental Hygiene.
There is no information available at this time
B. The Johns Hopkins Hospital, Department of Pathology, Information provided by,
Terina Chen, M.D.
Case presentation: A 34 year-old previously healthy South Asian male residing in Maryland presented to
a local Emergency Department complaining of persistent fevers and diarrhea. His symptoms began 2
weeks after he returned from a visit to Pakistan. A stool culture grew Salmonella typhi at four days. The
same organism was isolated from a subsequent blood culture. The isolates were susceptible to multiple
antibiotics, including ciprofloxacin, chloramphenicol, ceftriaxone and cefepime. The patient was admitted
to the outside hospital for intravenous antibiotic therapy and management of dehydration.
Epidemiology: In developed countries, Salmonella typhi is an uncommon cause of febrile illness with
accompanying abdominal complaints. S. typhi is the predominant cause of the clinical disease
“typhoid fever,” followed by a related organism S. paratyphi. Approximately 400 cases of typhoid
fever with disease onset in the US are reported to the CDC annually. A history of recent travel to
endemic areas such as South or Southeast Asia is elicited in the vast majority of cases. The worldwide
burden of disease attributable to S. typhi is substantial with an estimated 22 million cases of typhoid
fever and 200,000 related deaths per year. S. typhi has no known reservoir in nature and causes disease
only in humans. Organisms are transmitted by ingestion of contaminated food or water or via direct
contact with an infected person. Small foodborne outbreaks have occurred intermittently in recent US
history.
Microbiology: Salmonella is a genus within the family Enterobacteriaceae. The classification of
salmonellae has undergone multiple revisions over the years, but based upon DNA evidence, all are
now placed under one of two species: Salmonella enterica or Salmonella bongori. S. typhi is a
subspecies of S. enterica. Surface antigens O (somatic), Vi (capsular) and H (flagellar) play a central
role in the laboratory classification of salmonellae. Importantly, the Vi antigen is unique to S typhi and
S paratyphi.
Clinical features & related pathogenesis: Symptoms of typhoid fever typically begin 1 to 3 weeks after
exposure, owing to S. typhi’s replication cycle. Unlike nontyphoidal Salmonellae, S. typhi does not usually
cause fulminant enteritis. Organisms which survive the stomach’s acid environment enter small intestinal
epithelial cells and replicate, leading to reactive hyperplasia of the regional lymphoid elements. Engulfed
organisms survive and replicate within macrophages. During this incubation period, patients may
experience transient diarrhea or constipation. From the intestinal lymphoid tissue, S. typhi enters the
lymphatic system and bloodstream, usually within the 1st week of clinical illness. At this time, patients
exhibit high fevers and abdominal pain. Bacterial emboli in the skin cause a “rose spot” rash, while growth
in the liver and spleen results in hepatosplenomegaly. Shock, bradycardia (pulse-fever dissociation) and
varied other systemic symptoms may be present. Necrosis of the hyperplastic ileal lymphoid tissue
contributes to abdominal pain, intestinal bleeding and sometimes perforation. S. typhi ultimately infects the
gallbladder and returns to the GI tract to be excreted in stool. Without antibiotic therapy, the course is
protracted ( 4 weeks) with a mortality rate of ~15%. This is reduced to 1 to 2% with treatment, and marked
clinical improvement is seen within 4-5 days. About 10% of untreated individuals relapse, and 1 to 4%
become chronic carriers (defined as persistent positive stool cultures for > 1 year). Women and those with
biliary tract abnormalities are more likely to become carriers. Gallstones in particular are felt to act as a
nidus of infection.
Diagnosis: Cultures are definitive in the diagnosis of typhoid fever. Blood cultures are positive in 40 to
80% of patients, while stool cultures are positive 30 to 40% of the time, depending upon when the cultures
are taken. The highest yields are seen in the 1st week of symptoms. In later stages and if antibiotics have
been given, bone marrow aspirate cultures may be helpful if the blood and stool are negative. It should be
noted that transaminases are frequently elevated in typhoid fever. In this regard and on clinical grounds, the
disease may mimic acute viral hepatitis.
Treatment & Prevention: The emergence of multidrug resistant strains of S. typhi has complicated therapy
for typhoid fever in recent years. Plasmid-encoded resistance to chloramphenicol, ampicillin and
trimethoprim is well-described. In the absence of susceptibility data, therapy should be guided by the region
in which the disease was acquired. Fluoroquinolones are preferred as they are bactericidal and concentrate
within cells and bile. Unfortunately, fluoroquinolone-resistant strains are emerging, particularly in
Southeast Asia. Alternative therapy, such as a third-generation cephalosporin, is indicated in this setting.
Fluoroquinolone resistance may be predicated by resistance to nalidixic acid in the laboratory.
Cholecystectomy may be considered for organism eradiation in chronic carriers, particularly if gallstones
are present. The CDC recommends typhoid vaccination for travelers to endemic areas. Among available
vaccines, the oral live attenuated vaccine and the IM Vi capsular polysaccharide vaccine have comparable
protection rates (50-80%). Vaccination cannot substitute for hygienic food and water practices. CDC
guidelines are summarized by the statement: "boil it, cook it, peel it, or forget it."
References:
1. Ackers, M et al. “Laboratory-based surveillance of Salmonella serotype typhi infections in the United
States” JAMA 2000; 283:2668-73.
2. Centers for Disease Control and Prevention: Health Information for International Travel 2008
http://wwwn.cdc.gov/travel/yellowBookCh4-Typhoid.aspx.
3. Parry, CM et al. “Randomized controlled comparison of ofloxacin, azithromycin and an ofloxacinazithromycin combination for treatment of multidrug-resistant and nalidixic acid-resistant typhoid
fever” Antimicrob Agents Chemother 2007; 51:819-825.
4. Pegues, DA. “Salmonella species, including Salmonella typhi” in Mandell, Bennett & Dolan Principles
and Practice of Infectious Diseases, 6th edition. 2005.