AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Salmonella are gram-negative facultative intracellular anaerobes causing a wide spectrum of disease. This spectrum can range from a gastroenteritis, enteric fever (caused by typhoid and paratyphoid serotypes), bacteremia, focal infections, to a convalescent lifetime carrier state. The type of infection depends on the serotype of Salmonella and host factors. It maintains a broad host range, and for unknown reasons, results in different diseases in different hosts.

Although the taxonomy of Salmonella can be confusing, all Salmonella serotypes are members of a single species, Salmonella enterica. More than 2500 serovars^{1, 2} have been described of which humans are almost exclusively infected by Salmonella enterica subsp enterica serotypes typhi, typhimurium, and choleraesuis worldwide.³ In the United States, Salmonella enteritidis (17%), Salmonella typhimurium (16%), Salmonella newport (10%), and Salmonella javiana (5%) account for nearly one half of the human isolates.⁴

Salmonellosis caused by Salmonella enteritidis is the most common bacterial infectious cause of food-borne disease in the United States.⁵ Ninety-five percent of cases of Salmonella infection are food-borne; however, the incidence of direct contact exposure with animal carriers is on the rise.⁵ Once infected, salmonellosis harbors a significant morbidity and mortality. One third of untreated patients experience complications and account for three fourths of deaths associated with salmonellosis.³ Campylobacter and Salmonella are the most common bacterial pathogens found in stool cultures recovered from patients who present with gastroenteritis or severe diarrhea.⁶

Salmonella has a widespread distribution in the environment, and certain host factors make humans particularly susceptible to infection. Its increasing antimicrobial resistance, prevalence, virulence and adaptability, are a challenge worldwide.

For a related CME/CE activity, see CME/CE - Companion Animals and Human Health: Part II -- Zoonotic Diseases.

Pathophysiology

Salmonella infection most commonly begins with ingestion of bacteria in contaminated food or water. However, direct contact with animal and human carriers has also been implicated. Reptile and amphibian carriers are the most commonly recognized sources of direct contact.⁵ Studies involving healthy human volunteers required a median dose of 1 million bacteria to produce disease. However, point outbreaks suggest as few as 200 bacteria may produce nontyphoid gastroenteritis.⁶

Once the bacteria survive the acidic stomach, it colonizes the intestine and translocates across the intestinal epithelium via 3 routes: (1) invasion of the enterocytes, (2) invasion of epithelial cells called M cells, and (3) through dendritic cells that intercalate epithelial cells.² Interaction with the epithelium and resident cells promote a proinflammatory response to include cytokines, chemokines, neutrophils, macrophages, dendritic cells, and T and B cells. This inflammatory host response can actually benefit the intestinal pathogens and contribute to the nature and severity of the infection by establishing a competitive advantage against the native flora.²

After crossing this epithelial layer, the bacteria replicate in macrophages in Peyer’s patches, mesenteric lymph nodes, and the spleen. Once colonized, the bacteria may then potentially disseminate to the lungs, gallbladder, kidneys, or central nervous system. The nontyphoid species of Salmonella tend to produce a more localized response because they are felt to lack the human-specific virulence factors. However, the typhi serotype can develop the more invasive disease resulting in bacteremia. The severity of disease is related to the serotype, number of organisms, and host factors.

Eggs and poultry are the most common sources of infection.^{7, 5} Ingestion of contaminated water, milk, milk products, beef, fruit, vegetables, and dairy products are also common sources. Potential sources of infection for infants with Salmonella are exposure to reptiles, riding in a shopping cart next to meat or poultry, or consuming liquid infant formula.⁸ Recent outbreaks have been associated with contaminated peanut butter, frozen potpies, puffed vegetable snacks, and exposure to turtles.⁴

Reservoirs of the bacteria include humans, poultry, swine, cattle, rodents, and pets such as iguanas, tortoises, turtles, terrapins, chicks, dogs, and cats. Up to 90% of reptiles and amphibians harbor Salmonella in their gastrointestinal tracts, and 6% of nontyphoid disease is related to direct contact with these animals.⁵

Fecal-oral transmission from person to person in areas with poor sanitation and contaminated or nonchlorinated water is the route for enteric or typhoid fever. Humans are the only known carriers of Salmonella typhi.⁵

Individual susceptibility to Salmonella infection increases with extremes of age, immunodeficiency states, prior antibiotic use, neoplastic disease, achlorhydria or antacid use, recent bowel surgery, and malnutrition.

Frequency

United States

Prevalence estimates vary secondary to inconsistent diagnosis and reporting techniques. However, an estimated 1.4 million people in the United States are infected with nontyphoid Salmonella annually. The incidence of nontyphoid disease in the United States has been stable since 2004 but has decreased approximately 8% from 1996-1998 levels.⁴ The true burden of nontyphoid Salmonella in the United States is calculated to be 520 cases per 100,000 compared with 13.4 cases per 100,000 of laboratory-confirmed cases annually, taking into account approximately 38.6 cases of nontyphoid Salmonella for each culture confirmed case.^{9, 10} The reported 2007 incidence is 14.9 cases per 100,000.⁴ 

Additionally, an estimated 500 people are infected with typhoid Salmonella annually.⁵ Most cases of documented typhoid disease are related to foreign travel to developing nations such as India (30%), Pakistan (13%), Mexico (12%), Bangladesh (8%), Philippines (8%), and Haiti (5%).⁵

International

Fully industrialized nations report frequencies of gastroenteritis similar to that of the United States. However, worldwide estimates of nontyphoid Salmonella range from 200 million to 1.3 billion, with an estimated death toll of 3 million each year.¹ 

The serovars responsible for typhoid or enteric fever, typhi and paratyphi, that cause systemic illness lead to 16-20 million cases and 200,000 deaths worldwide.^{11, 12} Compared with tourists, travelers visiting friends or relatives in developing nations exhibit a much higher incidence of typhoid or enteric fever.⁵

Mortality/Morbidity

Twenty percent of patients require hospitalization, with an estimated death rate of 0.6%.¹⁰ Infection with drug-resistant nontyphoid Salmonella and Salmonella typhi increase the likelihood of hospitalization and death.¹⁰

Invasive nontyphoid Salmonella infection occurs in about 5% of cases in Israel¹⁰ and is responsible for 400-600 deaths in the United States each year⁵. Mortality for nontyphoid Salmonella is reported to be as high as 60% in African patients with HIV.¹¹ Mycotic abdominal aortic aneurysms are more common in immunocompromised and HIV patients.

Treated typhoid cases have a 2% mortality rate with a 15% relapse rate.³ A significant number of typhoid patients become chronic asymptomatic carriers and can shed high numbers of bacteria in the stool for a lifetime without obvious symptoms.¹¹ Depending on the serotype, roughly 1% of adults and 5% of children excrete organisms for greater than a year.¹³

Age

Attack rates are highest in persons younger than 20 years or older than 70 years. The highest rate is found in infants (130 isolates per 100,000).

Neonates are at a greater risk to fecal-oral transmission secondary to relative decreased stomach acidity and buffering of ingested breast milk and formula.

Elderly persons are at a relative greater risk to infection secondary to chronic underlying illness and weakened immunity. Nursing home residents have a particularly higher risk.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

• Obtain a dietary history. Inquire about potential restaurant sources, food preparation techniques, and exposure to potentially contaminated or nonchlorinated water sources.
• Obtain a travel history. Typhoid fever is increasingly associated with international travel to developing nations.
• Determine if other patient contacts have similar illnesses, food ingestions, or animal contacts.
• Salmonella syndromes can be divided into gastroenteritis, enteric fever, bacteremia, localized infection, and a chronic carrier state.
• Gastroenteritis
• • Incidence is highest during May through October in temperate climates.⁶
  • The incubation period is from 8-48 hours after the ingestion of contaminated food or water.
  • Symptoms are acute onset of fever and chills, nausea and vomiting, abdominal cramping, and diarrhea.
  • If a fever is present, it generally abides in 72 hours.
  • Diarrhea is usually self-limited, lasting 3-7 days and may be grossly bloody. Diarrhea lasting more than 10 days suggests another diagnosis.⁶  
• Enteric (typhoid) fever
• • The incubation period of enteric (typhoid) fever is 5-21 days.
  • Transmission is generally from contaminated water or animal products or contact with an infected person or carrier.
  • The initial prodrome lasting 7-10 days includes headache, cough, diaphoresis, anorexia, weakness, sore throat, malaise, abdominal pain, and constipation or “pea soup” diarrhea.
  • • Abdominal pain is present in 20-40% of patients.⁶
    • Constipation is found in 10-38% of patients.⁶
  • These prodromal symptoms typically plateau as the fever increases in a stepwise fashion peaking in the second week of illness.
  • After the prodrome, splenomegaly, abdominal distention and pain, relative bradycardia, rash, meningismus, and mental confusion may occur. It may disseminate to lungs, gallbladder, kidneys, or CNS.
  • Untreated patients experience either complications or resolution by the fourth week.
  • • Intestinal perforation occurs in 3-10% of patients.⁶
    • Other complications include endocarditis, pericarditis, pneumonitis, orchitis, and focal abscess.
• Bacteremia
• • Bacteremia typically occurs in immunocompromised patients.
  • Prolonged or recurrent fevers may occur.
  • It may include focal infections.
  • Mycotic abdominal aortic aneurysm may occur.  
•  Localized infection
• • Localized infection occurs in 5-10% of persons with bacteremia.⁶
  • The endocardium, arteries, CNS (more commonly infants), lungs, bones, joints, muscles, soft tissues, reticuloendothelial system, kidneys, and genital regions have all been documented sites of extraintestinal infection. 
• Chronic carrier state
• • Chronic carrier state is defined as Salmonella in the stool or urine for greater than 1 year.
  • A chronic carrier state occurs in 0.2-0.6% of patients with nontyphoid Salmonella.⁶
  • A chronic carrier state occurs in 1-4% of patients with untreated typhoid Salmonella.

Physical

Physical findings can vary depending on the clinical syndrome, serotype, and patient’s immune status. However, the physical findings in gastroenteritis, enteric (typhoid) fever, and bacteremia frequently overlap.

• Gastroenteritis 
• • Fevers 38-39°C are common.
  • Physical signs of dehydration may be found.
  • Stool examination can be negative to grossly bloody.
  • Diffuse nonfocal abdominal tenderness is commonly present.
  • In rare cases, Salmonella infection mimics inflammatory bowel disease or pseudoappendicitis.⁶
• Enteric or typhoid fever
• • A stepwise increase in temperature that plateaus in the second week at 39-40°C may be noted.
  • Cervical adenopathy may occur.
  • Relative bradycardia occurs in fewer than 50% of cases.
  • Abdominal examination may reveal distention with pain on deep palpation.
  • Hepatosplenomegaly is found in 50% of patients.⁶
  • A rose spot rash that typically occurs in the second week of disease is seen in 30% of patients. This rash is described as a faint salmon-colored 2-3 mm papule lesion located primarily on the trunk that fades with pressure.
  • Findings of meningismus may appear after the early prodrome.
• Bacteremia
• • Bacteremia is usually associated with a prolonged or recurrent fever.
  • Generally, it is associated with a localized infection.
  • It may be a part of a mixed Salmonella infection.¹⁴
• Chronic carrier state is asymptomatic.

Causes

Currently, more than 2500 serotypes of Salmonella enterica have been identified.^{1, 2} Although clinical manifestations of each overlap, typhi and paratyphi tend to cause enteric or typhoid fever and the more invasive form of the disease, whereas most others cause a self-limited form of gastroenteritis.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

• Gastroenteritis
• • Shigellosis
  • Amebic dysentery
  • Viral gastroenteritis
  • Food poisoning
  • Acute ulcerative colitis
• Enteric or typhoid fever
• • Tuberculosis
  • Infective endocarditis
  • Brucellosis
  • Lymphoma
  • Q fever
  • Viral hepatitis
  • Malaria
  • Amebiasis

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Serologic testing lacks overall sensitivity and specificity and varies with the stage of infection.^{6, 15, 3}
• Complete blood cell count
• • Anemia is a result of blood loss and inflammation.
  • The white blood cell (WBC) count in enteric or typhoid fever is often low.
  • Leukocytosis is common in the first 10 days in children and may also result from bacteremia, localized infection, bowel perforation, or other extraintestinal complications.
  • Reversible thrombocytopenia may occur.
• Liver function tests may be mildly elevated. Elevated alanine aminotransferase level (>70 IU/L) can be seen in enteric fever.¹⁶
• A reversible form of a mild disseminated intravascular coagulopathy (DIC) may occur.
• Cultures
• • The diagnosis of Salmonella infection is based on isolation of the infecting organism.
  • Stool culture results can take 3-7 days. 
  • • Three to ten grams collected over several days are preferred.¹³
    • Due to the time involved with stool culture detection, treatment decisions should be based on the patient’s presentation. 
    • Rapid testing technologies, such as polymerase chain reaction (PCR), have not yet been proven feasible.¹⁷
  • Culture sensitivity decreases after the first week of illness and antibiotic therapy.^{15, 3}
  • Bone marrow evaluation has a sensitivity of 90% but is rarely performed.
  • Blood culture results in enteric fever are positive in 50-70% of cases.
  • PCR sensitivity on blood is 84.5% and is as high as 95% when performed in the first 5 days.¹⁵
  • PCR evaluations on urine and feces are 69% and 47% sensitive, respectively.¹⁵

Imaging Studies

• A focused ultrasonographic examination or CT scan should be performed if an extraintestinal manifestation is of concern. This should include muscle/soft tissue, hepatobiliary, spleen, urinary, genital, and bone.
• An acute abdominal series for free air under the diaphragm may be needed to rule out intestinal perforation.
• A CT scan of the brain should be performed if central nervous system complications arise (more commonly neonates).

Procedures

• A rectal examination is needed to assess for bleeding. A blood transfusion is rarely required.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Prehospital Care

• Perform a standard evaluation of airway, breathing, and circulation.
• Provide intravenous fluids if signs or symptoms of dehydration are present.

Emergency Department Care

• Perform a standard evaluation of airway, breathing, and circulation.
• Treat with rehydration and electrolyte replacement via oral or intravenous solutions for an uncomplicated gastroenteritis.
• Transfusions should be based on hemoglobin and hematocrit levels.
• Symptomatically manage pain, nausea, vomiting, and diarrhea.
• Antibiotics are indicated for infants up to 2 months of age, elderly patients, immunocompromised patients, those with a history of sickle-cell disease or prosthetic grafts, or patients who have extraintestinal findings.

Consultations

• Admission may be required if the patient exhibits unstable vitals signs, harbors significant risk factors, is younger than 2 months of age or elderly, is immunocompromised, or shows signs or symptoms of an extraintestinal manifestation.
• Appropriate specialty consultation for specific extraintestinal manifestations is indicated.
• Arrange for follow-up care on an outpatient basis with the patient’s primary care physician if discharged from the emergency department.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Antibiotics, antidiarrheals, and glucocorticoids are used to treat symptoms and/or documented Salmonella infection.

Drug Category: Antibiotics

Nontyphoid Salmonella gastroenteritis is generally self-limited. A Cochrane Database Systematic Review of 12 trials showed no significant change in the overall length of the illness or the related symptoms in otherwise healthy children and adults treated with a course of antibiotics for nontyphoid Salmonella disease. Antibiotics tend to increase adverse effects and prolong Salmonella detection in stools.¹⁸ However, antibiotic treatment should be considered on a case-by-case basis to include patients with severe symptoms.¹⁹

Antibiotics are currently indicated for infants up to 2 months of age, elderly persons, immunocompromised persons, those with a history of sickle-cell disease or prosthetic grafts, or patients who have extraintestinal findings. Treatment for those at-risk patients should last 2-5 days or until the patient is afebrile.^{6, 3} Nontyphoid Salmonella infections are commonly treated with fluoroquinolones and third-generation cephalosporins, such as ciprofloxacin and ceftriaxone. In 2004, the prevalence of resistance among nontyphoid Salmonella isolates was 2.6% for quinolones and 3.4% for third-generation cephalosporins.²⁰ 

Enteric or typhoid fever is best treated with antibiotics for 5-7 days for uncomplicated cases and up to 10-14 days for a severe infection.^{6, 3} Fluoroquinolone resistance is an important factor in S typhi and was reported by the CDC to be 41.8% in 2004. Trimethoprim-sulfamethoxazole and chloramphenicol has a 13.2% prevalence of resistance in S typhi, while ampicillin, streptomycin, and sulfisoxazole are 11.8%.²⁰

Some evidence exists that fluoroquinolones may be used in children with infections that are difficult to treat. When treating children and pregnant women, it should be noted that treatment with fluoroquinolones should be carefully weighed against the possibility of damaging developing cartilage.²¹

Bacteremia and focal infections may require antibiotics for up to 4-6 weeks depending on the site of infection and serotype of Salmonella. Specific surgical intervention is often necessary in conjunction with antibiotic management.

Chronic Salmonella carriers require 1-3 months of oral antibiotics depending on the serotype, susceptibility, and antibiotic used.⁶

Salmonella antibiotic resistance is a global concern that includes multi–drug-resistant strains.¹⁰ Recent outbreaks show that a connection may exist between antimicrobial drug treatment and the risk of disease from Salmonella.²² Subsequently, stool and blood cultures and sensitivities are important, as susceptibilities not only vary depending on region of the world but also locally.

Drug Category: Antidiarrheals

These agents may prolong the course of the disease. If used, they should be used sparingly.

Drug Category: Glucocorticoids

These agents may be indicated in patients with severe enteric or typhoid fever or significant complications such as CNS manifestations or DIC.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Outpatient Care

• Follow-up treatment with the patient's primary care physician is highly recommended.
• Worsening symptoms warrant a return visit to the ED.
• Antibiotic treatment for a chronic carrier in coordination with the patient’s primary care physician may be indicated. Asymptomatic carriage occurs on average for about 5 weeks, with prolonged duration existing in children younger than 5 years.²³

Deterrence/Prevention

Deterrence and prevention measures include the following:

• Proper hygiene and food storage
• Keeping raw meat and poultry away from unprepared foods
• Cleaning surfaces, utensils, and hands after contact with raw foods
• Avoiding eating raw or undercooked eggs
• Control of animal reservoir
• Vaccination for enteric or typhoid fever
• • Current multi-dose oral vaccine (5 years) or single-dose parental vaccine (3 years) with an efficacy of 50-80%⁵
  • Trials underway for a single-dose oral vaccine¹¹

Complications

• Hypovolemic shock
• Urinary retention
• Metastatic abscess formation
• Acute or chronic hydrocephalus
• Meningitis
• Psychosis
• Cholecystitis
• Toxic megacolon
• Intestinal perforation
• Septic thrombophlebitis
• Mycotic abdominal aortic aneurysm
• Myocarditis
• Nephritis
• Osteomyelitis
• An asymptomatic chronic carrier state
• DIC in infants with typhoid fever²⁴

Prognosis

• Nontyphoid Salmonella is generally self-limiting.
• • Most patients are treated on an outpatient basis.
  • Extremes of age and an immunocompromised state increases morbidity and mortality.
• Typhoid Salmonella generally requires treatment.
• • Mortality rate for treated cases is 2%, while complications occur in 30% of untreated cases.³
  • Morbidity and mortality increases with drug-resistant S typhi.¹⁰

Patient Education

• Emphasize good hand-washing, thorough cleaning of cooking utensils, appropriate food preparation techniques, and adequate cooking temperature for killing the bacteria.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Failure to aggressively manage patients who are immunocompromised, extremes of age, or have complicating factors such as sickle-cell disease or prosthetic grafts 
• Failure to recognize an extraintestinal manifestation
• Failure to query about recent travel to underdeveloped nations
• Failure to ask about previous gastric surgery, use of antacids and H2 antagonists, or any predisposition toward reduced stomach acid production
• Failure to consider alternative diagnoses - Perforated viscous and atypical presentation of appendicitis needs to be considered.
• Failure to recognize that a sudden outbreak of Salmonella may be secondary to an intentional contamination²⁵

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Robert A Barrali Jr, MD, to the development and writing of this article. We would like to acknowledge the assistance of Michelle Manfredi in researching this topic.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

1. Coburn B, Grassl GA, Finlay BB. Salmonella, the host and disease: a brief review. Immunol Cell Biol. Feb-Mar 2007;85(2):112-8. [Medline].
2. Grassl GA, Finlay BB. Pathogenesis of enteric Salmonella infections. Curr Opin Gastroenterol. Jan 2008;24(1):22-6. [Medline].
3. Chambers HF. McPhee SJ, Papadakis MA, Tierney LM, eds. Current Medical Diagnosis & Treatment. 47^th ed. McGraw-Hill Co; 2008:1250-1252.
4. Centers for Disease Control and Prevention. Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food--10 states, 2007. MMWR Morb Mortal Wkly Rep. Apr 11 2008;57(14):366-70. [Medline].
5. Linam WM, Gerber MA. Changing epidemiology and prevention of Salmonella infections. Pediatr Infect Dis J. Aug 2007;26(8):747-8. [Medline].
6. Peques DA, Ohl M, Miller S. Mandell, Douglas, and Bennett's: Principles and Practice of Infectious Diseases. 6^th ed. Elsevier; 2005:chap 220.
7. Braden CR. Salmonella enterica serotype Enteritidis and eggs: a national epidemic in the United States. Clin Infect Dis. Aug 15 2006;43(4):512-7. [Medline].
8. Jones TF, Ingram LA, Fullerton KE, et al. A case-control study of the epidemiology of sporadic Salmonella infection in infants. Pediatrics. Dec 2006;118(6):2380-7. [Medline].
9. Voetsch AC, Van Gilder TJ, Angulo FJ, et al. FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States. Clin Infect Dis. Apr 15 2004;38 Suppl 3:S127-34. [Medline].
10. Weinberger M, Keller N. Recent trends in the epidemiology of non-typhoid Salmonella and antimicrobial resistance: the Israeli experience and worldwide review. Curr Opin Infect Dis. Dec 2005;18(6):513-21. [Medline].
11. Boyle EC, Bishop JL, Grassl GA, et al. Salmonella: from pathogenesis to therapeutics. J Bacteriol. Mar 2007;189(5):1489-95. [Medline].
12. Sethuraman U, Kamat D. Management of child with fever after international travel. Clin Pediatr (Phila). Apr 2007;46(3):222-7. [Medline].
13. Heymann DL. Control of Communicable Diseases Manual. 18^th ed. American Public Health Association; 2004:469-473.
14. Perera N, Geary C, Wiselka M, et al. Mixed Salmonella infection: case report and review of the literature. J Travel Med. Mar-Apr 2007;14(2):134-5. [Medline].
15. Hatta M, Smits HL. Detection of Salmonella typhi by nested polymerase chain reaction in blood, urine, and stool samples. Am J Trop Med Hyg. Jan 2007;76(1):139-43. [Medline].
16. Bottieau E, Clerinx J, Van den Enden E, et al. Fever after a stay in the tropics: diagnostic predictors of the leading tropical conditions. Medicine (Baltimore). Jan 2007;86(1):18-25. [Medline].
17. Abubakar I, Irvine L, Aldus CF, et al. A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food. Health Technol Assess. Sep 2007;11(36):1-216. [Medline].
18. Sirinavin S, Garner P. Antibiotics for treating salmonella gut infections. Cochrane Database Syst Rev. 2000;CD001167. [Medline].
19. Wiström J, Jertborn M, Ekwall E, et al. Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Swedish Study Group. Ann Intern Med. Aug 1 1992;117(3):202-8. [Medline].
20. Centers for Disease Control and Prevention. National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS): Human Isolates Final Report, 2004. [Full Text].
21. Grady R. Safety profile of quinolone antibiotics in the pediatric population. Pediatr Infect Dis J. Dec 2003;22(12):1128-32. [Medline].
22. Mølbak K. Human health consequences of antimicrobial drug-resistant Salmonella and other foodborne pathogens. Clin Infect Dis. Dec 1 2005;41(11):1613-20. [Medline].
23. Buchwald DS, Blaser MJ. A review of human salmonellosis: II. Duration of excretion following infection with nontyphi Salmonella. Rev Infect Dis. May-Jun 1984;6(3):345-56. [Medline].
24. Bhutta ZA. Current concepts in the diagnosis and treatment of typhoid fever. BMJ. Jul 8 2006;333(7558):78-82. [Medline].
25. Torok TJ, Tauxe RV, Wise RP, et al. A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA. Aug 6 1997;278(5):389-95. [Medline].
26. Amieva MR. Important bacterial gastrointestinal pathogens in children: a pathogenesis perspective. Pediatr Clin North Am. Jun 2005;52(3):749-77, vi. [Medline].
27. Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis. Oct 2005;5(10):623-8. [Medline].
28. Hoffman SL, Punjabi NH, Kumala S, et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med. Jan 12 1984;310(2):82-8. [Medline].
29. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med. Nov 28 2002;347(22):1770-82. [Medline].
30. Punjabi NH, Hoffman SL, Edman DC, et al. Treatment of severe typhoid fever in children with high dose dexamethasone. Pediatr Infect Dis J. Aug 1988;7(8):598-600. [Medline].

Article Last Updated: Jul 17, 2008