infeksi salmonela

Salmonella InfectionsJohn C. Christenson, MD*

Author Disclosure

Dr Christenson has

disclosed no financial

relationships relevant

to this article. This

commentary does not

contain discussion of

unapproved/

investigative use of

a commercial product/

device.

Practice Gaps

1. Because Salmonella disease causes 93.8 million illnesses and 155,000 deaths

worldwide and 1 million foodborne illnesses and 350 deaths in the United States,

clinicians must learn to recognize, treat, and prevent these infections.

2. Young infants, persons with hemoglobin disorders, and individuals who are immune

compromised, such as those with human immunodeficiency virus and cancer, are at

risk for severe Salmonella disease, including bacteremia, meningitis, and

osteomyelitis.

Objectives After completing this article, readers should be able to:

1. Describe the epidemiology of nontyphoidal salmonellosis.

2. Recognize the clinical features of enteric fevers.

3. Appropriately treat the young child with Salmonella infection.

4. Understand ways to prevent Salmonella infections.

5. Use typhoid vaccines when indicated.

IntroductionSalmonella infection is a common cause of gastroenteritis and bacteremia worldwide. Theconsumption of contaminated water and food and the close contact with colonized ani-mals are frequent risk factors for acquisition. Young infants, persons with hemoglobindisorders, and individuals who have immunocompromising conditions, such as humanimmunodeficiency virus (HIV) and cancer, are at risk for severe disease, such as bacter-emia, meningitis, and osteomyelitis. Salmonella Typhi and Salmonella Paratyphi are re-sponsible for significant morbidity and mortality in developing countries. Clinicians mustlearn to recognize these infections and know how to effectively treat and prevent them.This review article provides the reader with enhanced knowledge of this diverse group ofpathogens.

MicrobiologyThe genus Salmonella is composed of motile gram-negative bacteria within the family En-terobacteriaceae. They are oxidase-negative, indole-negative, and nonlactose fermenters.The nomenclature of the genus Salmonella can be challenging. The Centers for DiseaseControl and Prevention and the World Health Organization have been responsible formaintaining the format for formula designation. There are 2 Salmonella species, Salmonellaenterica and Salmonella bongori, which are classified further into subspecies according totheir biochemical and genomic relatedness. Most human infections are caused by a serotypeof Salmonella enterica subsp enterica (subspecies I), which infect warm-blooded animals.Five other subspecies (plus S bongori [subspecies V]) are known to colonize cold-bloodedanimals and the environment: enterica subsp salamae (subspecies II), arizonae (subspeciesIIIa), diarizonae (subspecies IIIb), houtenae (subspecies IV), and indica (subspecies VI).Although more than 2,600 serotypes of Salmonella have been identified, most diseaseis caused by subspecies/serotypes Typhimurium and Enteritidis. Historically, serotypesare frequently reported as species. For simplicity, in this review we use genus and

*Ryan White Center for Pediatric Infectious Disease, Indiana University School of Medicine, Riley Hospital for Children,

Indianapolis, IN.

Article infectious diseases

Pediatrics in Review Vol.34 No.9 September 2013 375

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subspecies/serotype (eg, Salmonella Typhi or SalmonellaTyphimurium). Non–subspecies I are rarely reported ashuman pathogens.

Certain serotypes frequently correlate with a diseasesyndrome or food source. As examples, Salmonella chol-eraesuis and Salmonella dublin are both frequently asso-ciated with bacteremia and extraintestinal infections.(1)(2)

EpidemiologyNontyphoidal Salmonella Infections

Salmonella gastroenteritis is a serious public health prob-lem in the United States. An estimated 1 million food-borne illnesses occur each year, resulting in 350 deaths.(3) The world burden is estimated at 93.8 million ill-nesses, with 155,000 deaths each year. Salmonella Enter-itidis is the most common isolated subspecies because it isresponsible for 65% of these infections, followed by S Ty-phimurium at 12%. In the United States, exposures tochicken and eggs are most likely sources for infection.

Many risk factors are associated with infection and dis-semination. Achlorhydria, the use of antacids or protonpump inhibitors, and rapid gastric emptying favor bacterialsurvival. Conditions that impair cell-mediated lymphocytefunction, such as HIV/AIDS, malnutrition, corticosteroidtherapy, and posttransplantation immunosuppressive ther-apy, are major risk factors. An overloaded reticuloendothe-lial system with iron or hemoglobin, such as in patientswith sickle cell anemia, hemolytic anemia, thalassemia,and malaria, may increase the likelihood of severe disease.Infarcts in the gastrointestinal tract and bone and defectivephagocytic and opsonic function also appear to contributeto the severity of disease observed in patients who havesickle cell anemia. Diseases such as leukemia and lym-phoma also impair the reticuloendothelial system function.

The morbidity and mortality associated with Salmonellainfections are also influenced by the serotype that causesthe infection. Salmonella choleraesuis is more likely tocause invasive disease. In one study, 85% of isolates wererecovered from extraintestinal sites, especially blood.(1) Seventy-two percent of patients were younger than3 years. Pediatric patients were more likely to have diar-rhea than adults. Most of the children with diarrhea werealso bacteremic. Mycotic aneurysms, a complication ob-served in adults, was not detected in any of the pediatriccases. Of importance, only 21% of children had leukocy-tosis. Occult bacteremia, where the child presents onlywith fever, was a common presentation.

In a population-based, case-control study of salmonel-losis in infants younger than 1 year, infected infants were

more likely to be bottle fed, have exposure to reptiles,have ridden in a shopping cart next to meat or poultry,traveled abroad, or attended a day care center with an in-fected infant. (4)

Most Salmonella infections are foodborne. In Mexico,pork, meat, and poultry were frequently found to becontaminated with Salmonella. Consumption of con-taminated orange juice led to an outbreak in a themepark. An intentional contamination of restaurant saladbars was responsible for a large outbreak of Salmonellagastroenteritis in Oregon in 1984. Contaminated pea-nut butter, ice cream, salami products, and mozzarellacheese has been responsible for multistate outbreaksin the United States. Outbreaks have also been associ-ated with exposure to contaminated dry dog food andpet treats.

Animals such as chickens, pigs, turtles, lizards, iguanas,hedgehogs, and amphibians have been identified as res-ervoirs of Salmonella. Many of these colonizations haveresulted in human outbreaks. An outbreak of S Typhi-murium was associated with exposures to pet rodents.Feeder rodents used for the feeding of reptiles and am-phibians were found to be colonized with Salmonella,resulting in human infections. Patients with Salmonellaarizonae acquired from iguanas and snakes have a predis-position for musculoskeletal infections. In a rare event, 2patients developed S Enteritidis sepsis (in one case fatal)after a platelet transfusion. The donor most likely hadasymptomatic bacteremia from handling his pet boaconstrictor.

Nosocomial outbreaks are uncommon. However, in-adequate infection control practices, understaffing, andovercrowding may lead to environmental contamination.In some developing countries, asymptomatic carriage ofSalmonella can be high among children attending daycare centers. Outbreaks of salmonellosis in day care cen-ters have been reported, but these are considered rareevents.

Although the incidence of salmonellosis related tointernational travel appears to be decreasing in theUnited States, many travel-acquired cases are still re-ported. Salmonella stanley, a common serotype inSoutheast Asia (second most common in Thailand),has been frequently isolated in Europe. (5) In South-east Asia, the serotype is frequently associated withthe pork industry.

Nontyphoidal Salmonella infections remain a frequentcause of invasive disease in many regions of the world, es-pecially in sub-Saharan Africa. Children younger than3 years and those infected with HIV have the greatestburden. Mortality remains high, especially in children with

infectious diseases salmonella

376 Pediatrics in Review Vol.34 No.9 September 2013



bacteremia and meningitis. Seasonal peaks of diseasecoincide with the rainy season, which leads to fecal con-tamination of drinking water. In many countries, an as-sociation between malaria and Salmonella is well known.This situation often delays treatment, causing greatermorbidity and mortality. Frequently, febrile persons aretreated only for malaria without considering the likeli-hood of a coinfection. Clinical features, such as fevers,anemia, and splenomegaly, are frequent findings in bothconditions.

Enteric Fever (Typhoid and Paratyphoid Fever)Enteric fever, an infection caused by S Typhi (typhoidfever) or S Paratyphi A, B, or C (paratyphoid fever), isa common cause of death and disease in many parts ofthe world. Approximately 22 million cases are thought tooccurworldwide each year, with 200,000 deaths as a result.(6) Most infections occur in Southern and Southeast Asia.Parts of Africa and Latin America are also affected but ata lower frequency. In Asia, it is estimated that the inci-dence approximates 100 cases per 100,000 population.Travelers to endemic regions are at risk. Most cases inthe United States have been associated with internationaltravel. Travelers visiting friends and relatives are at thehighest risk of infection.

In countries such as India, children and adolescents inthe 5- to 19-year age group are affected most. On rareoccasions, neonatal infections have been reported. Theseinfections are frequently acquired from the mother. InSouth and Southeast Asia, S Typhi is the most commoncause of community-acquired bacteremia.

Between 1960 and 1999, 60 outbreaks of typhoidfever had been reported in the United States. (7)Ninety percent were domestically acquired. Recently,cases were found to be related to the consumption ofa fruit shake made from frozen mamey fruit fromGuatemala. (7) In recent years, an outbreak of S Para-typhi B was found to be related to exposure to petturtles.

The major factor responsible for the magnitude of thisproblem is poor sanitary infrastructure, resulting in substan-dard drinking water and contaminated food. Person-to-person transmission from chronic asymptomatic carriagealso contributes to the infection of susceptible individuals(eg, typhoid Mary).

PathogenesisThe pathogenesis of salmonellosis is complex. Several vir-ulence genes are responsible for the severity of disease ob-served with certain species.

Nontyphoidal isolates are rarely invasive because mostdo not extend past the lamina propria or the intestinallymphatic system. However, interactions with host cellsin the intestines may lead to a release of proinflammatorycytokines that result in the recruitment of neutrophils tothe area, resulting in gastroenteritis. Some genes appearto play a role in the survival of bacteria within the liverand spleen and promote the replication within macro-phages. (8)

Salmonella Typhi is known to adhere to epithelial cellsover the lymphatic Peyer patches, allowing for penetra-tion through the intestinal mucosa. Engulfment bymacrophages and translocation into draining lymphnodes results in bacteremia and subsequent dissemina-tion. The organism survives within the host cells in a Salmo-nella-containing vacuole, assuring its ability to replicate,survive, and invade and resulting in the multiplicationand survival of bacteria within the liver, spleen, andbone marrow. After an incubation period of 7 to 14 days,bacteremia occurs and symptoms emerge. SalmonellaTyphi can be found in the gallstones of individualswho live in endemic regions. Its presence correlates withfecal shedding, and these people are known to infectothers.

Clinical AspectsNontyphoidal Salmonella Infections

Gastroenteritis is the most frequent presentation. Mostaffected children are younger than 1 year. The usual in-cubation period for Salmonella gastroenteritis is 6 to 12hours. Nausea, vomiting, and diarrhea are commonsymptoms. Diarrhea is usually nonbloody. Myalgias, ar-thralgias, and headaches are also reported. Although ob-served in children with Salmonella gastroenteritis, fever,chills, and abdominal pain are more commonly observedwith shigellosis. The presence of rectal tenesmus accom-panied by stools with mucus and/or blood is more dis-tinctive of Shigella infections. Symptoms are generallyself-limited. Hepatomegaly and splenomegaly are infre-quently noted.

Bacteremia is commonly observed in infants with gas-troenteritis. Most children require hospitalization. Persis-tent bacteremia can be detected in approximately 40% ofpatients. Salmonella Enteritidis was a frequently isolatedpathogen in bacteremic patients. In children, bacteremiais rarely fatal. In contrast, one-third of adults presentingwith primary bacteremia have extraintestinal organ in-volvement and will die.

Clinical features or laboratory parameters were unableto detect childrenmore likely to have persistent bacteremia.





Although focal infections were observed in 2.5% of pre-viously healthy children, one-third of children with un-derlying medical conditions had focal disease, consistingof meningitis, osteomyelitis, septic arthritis, pneumonia,or cholangitis. In parts of Africa, the fatality rate for bac-teremia is close to 25%. Lower respiratory tract coinfec-tions with tuberculosis and Streptococcus pneumoniae werecommon.

Meningitis and musculoskeletal infections are com-mon complications in infants younger than 3 months.It is estimated that 50% to 75% of Salmonella meningitisoccurs in the first year of life. Asymptomatic disease is alsocommon in young infants. A well-appearing infant withSalmonella gastroenteritis may be bacteremic.

Malaria has been found to be a risk factor for invasivenontyphoidal Salmonella infections in children. A reduc-tion in cases of salmonellosis was associated with a de-crease in the number of malaria cases.

Compared with children with gastroenteritisalone, bacteremic children appear to have a longer du-ration of symptoms, a less severe clinical appearance,and fewer signs of dehydration. This gradual presen-tation with less dehydration and fewer toxic effectsmay lead to premature discharges from emergencydepartments.

Typhoid and Paratyphoid FeverFever, gastrointestinal symptoms (eg, vomiting, severediarrhea, abdominal distension, and pain), cough, rel-ative bradycardia, rose spots (pink macules frequentlyobserved on the abdomen and chest), and splenomeg-aly are frequently regarded as features of typhoid andparatyphoid fever. However, many patients lack thesefindings, making diagnosis difficult if solely based onclinical features. In a reported foodborne epidemic,most patients had nonspecific symptoms, consistingof fever, headache, diarrhea, and anorexia. Hepato-megaly was seen in 7% of patients, splenomegaly in13% of patients, and rose spots in 5% of patients. Rel-ative bradycardia and rose spots are seldom observed inchildren. Jaundice is frequently observed among chil-dren. Febrile convulsions have been reported in chil-dren with enteric fever and may be the presentingsymptom in some children. The incubation periodfor enteric fevers is generally 7 to 14 days, with a rangeof 3 to 60 days.

In Pakistan, children younger than 5 years werefound to have more severe disease. More than 95% ofchildren had fever, 20% to 41% had hepatomegaly, 5%to 20% had splenomegaly, 19% to 28% had abdominalpain, and 8% to 35% had diarrhea. (9) Cough was

observed in approximately 15% of patients. Severe dis-ease resulted in more hospitalizations. Intestinal perfo-ration was a rare complication observed in less than 1%of children.

Thrombocytopenia and disseminated intravascular co-agulation are markers of severe disease. Splenic abscess,brain abscess, and subdural empyema are rare complica-tions of typhoid fever.

An analysis of travel-related cases in the United King-dom found that S Typhi and S Paratyphi infections wereindistinguishable clinically. (10) Infections caused by SParatyphi can be just as severe as those caused by S Typhi.Most patients had normal white blood cell counts (91%),and 82% of patients had an elevated alanine aminotrans-ferase level. Among travelers, more cases of enteric feverwere caused by S Paratyphi A than by S Typhi. Guillain-Barré syndrome has been described in association with SParatyphi A infection.

Mixed infections with multiple pathogens occur inendemic tropical countries. Treatment against entericfever should be considered for children with unremit-ting fevers after completing adequate antimalarialtherapy.

DiagnosisThere are no features of Salmonella gastroenteritis thatwould allow its diagnosis based on clinical findings alone.The routine microscopic stool examination for polymor-phonuclear cells is of limited clinical utility because a largenumber of children with gastroenteritis will have a nega-tive test result (<5 polymorphonuclear cells per high-power field). All young infants with diarrhea, especiallythose younger than 3 months with a positive stool cultureresult, should have a blood culture performed, even if theinfant is well-appearing. Infants younger than 3 monthswith a positive blood culture result should undergo a lum-bar puncture and careful examination assessing for thepresence of musculoskeletal involvement (Table 1).(11) Any ill-appearing infant with a positive stool cultureresult should undergo a blood culture and lumbar punc-ture, be hospitalized, and be treated with parenteralantibiotics.

The Widal test, a classic test that measures antibodiesagainst O and H antigens of S Typhi, was used for thediagnosis of typhoid fever. However, its lack of sensitivityand specificity has limited its utility. A false-positive testresult may lead to overtreatment and a delay in consider-ing other conditions. This outcome is especially likely inparts of the world where typhoid fever is rare among chil-dren and significantly less frequent than other bacterialpathogens.





In patients with typhoid fever, blood culture resultsare frequently positive, but stool cultures are less so. Al-though liver enzyme levels are frequently elevated, leu-kocytosis is not always observed. Leukopenia andanemia are frequently associated with enteric fevers. Anormal white blood cell count does not rule out inva-sive disease. Many suggest that bone marrow cultureshave a higher sensitivity. Obtaining this type of speci-men is much more invasive and impractical in many cir-cumstances. Approximately 20% of patients may havepneumonia as documented by abnormal radiographyresults.

Although pathogen-specific serologic and polymerasechain reaction assays are the preferred methods for diag-nosing enteric fever, diagnosis is still made using clinicalcriteria in most lower-income countries. Unfortunately,early features of enteric fever mimic other conditions,such as pneumonia, malaria, sepsis, dengue, acute hepa-titis, and rickettsial infections.

TreatmentPreviously healthy children and adults with uncompli-cated gastroenteritis do not require antimicrobialtherapy because the disease is self-limited. Infantsyounger than 3 months with Salmonella gastroen-teritis should be treated because they have a highincidence of extraintestinal complications, such as bac-teremia, meningitis, and osteomyelitis (Table 1). Antimi-crobial therapy may prolong the carrier state. Therapyshould be considered for those individuals with high-riskmedical conditions, such as HIV, sickle cell anemia, andcancer.

Antimicrobial treatment must take into accountthe local epidemiology and therapeutic practice inthe country where the infection was acquired. Chlor-amphenicol, amoxicillin, and the combination oftrimethoprim and sulfamethoxazole are no longer rec-ommended as first-line agents for the treatment of en-teric fevers. The high frequency of treatment failures,

Table 1. Management of Pediatric Salmonella Gastroenteritis

Signs and Symptoms Diagnosis Management

Age <3 monthsDiarrhea (dysentery-like, bloody): Obtain stool culture

Obtain blood cultureDiarrhea <5 days, not dysentery-like or bloody No stool culture Hydration

No antibioticsFebrile Stool culture positive Treat with parenteral antibiotics, 5-7 days

Blood culture negativeStool culture positive Lumbar punctureBlood culture positive Treat with parenteral antibiotics:

Bacteremia only: 14 daysMeningitis: 4-6 weeksOsteomyelitis: 4-6 weeks

History of exposure to Salmonella Obtain stool cultureObtain blood culture

Age >3 monthsDiarrhea ‡5 days: Obtain stool cultureAfebrile Stool culture positive Observation

No antibioticsFebrile, but non–toxic-appearing Stool culture positive Blood culture

Observe off antibioticsToxic, ill-appearing, orimmunocompromised host

Stool culture positive Blood cultureLumbar punctureTreat with parenteral antibiotics

Stool culture positive Lumbar punctureBlood culture positive Treat with parenteral antibiotics:

Bacteremia only: 14 daysMeningitis: 4-6 weeksOsteomyelitis: 4-6 weeks

Adapted from: St. Geme J, Hodes H, Marcy SM, et al. Consensus: Management of Salmonella infection in the first year of life. Pediatric Infectious DiseaseJournal. 1988; 7(9):615–621. Copyright 1988 (c) by Wolters Kluwer Health/Williams & Wilkens.





resistance, and relapse rates has diminished their use-fulness. Antimicrobial resistance observed in manycountries has influenced the choice of agent for treat-ing typhoid and paratyphoid fever. Ceftriaxone re-mains the recommended agent in the most severecases in which parenteral therapy is indicated. Cefo-taxime is an acceptable alternative. Although fluo-roquinolones, such as ciprofloxacin, are generallyassociated with high cure rates, defervescence withina week, and lower relapse and fecal carriage rates, iso-lates from many Asian countries demonstrate resistance,rendering them ineffective. Azithromycin appears fa-vorable in the treatment of these infections. (12) Untilrecently, fluoroquinolone resistance was uncommon inmost regions of Africa. In a recent study from theDemocratic Republic of the Congo, decreased cipro-floxacin susceptibility was detected in 15.4% of testedisolates. (13) Proper hydration, perfusion, and fevercontrol still remain integral components of treatingenteric fever.

More than 10 years ago, multidrug resistance was un-common in Latin America. Susceptibility to ampicillinwas common, and susceptibility to ceftriaxone was almostuniversal. At the same time, in some Mediterraneancountries, close to one-third of isolates were resistantto ampicillin.

In infections by S choleraesuis, resistance to cipro-floxacin was observed in 28% of pediatric cases inTaiwan, whereas more than 60% of cases in adultshad a resistant strain. (1) Irrespective of age, resis-tance to trimethoprim-sulfamethoxazole remainedhigh.

Eighty-four percent of samples of ground meats(beef, turkey, and pork) purchased at several supermar-kets in the Washington, DC, area were found to be con-taminated with Salmonella isolates that were resistant toat least one antibiotic; 53% were resistant to 3 antibiot-ics. (14) Of greater concern, 16% of the isolates wereresistant to ceftriaxone, the drug of choice for the treat-ment of serious infections in children. In a recentstudy of invasive salmonellosis among Thai children,ceftriaxone resistance was detected in 17.4% of iso-lates. (15)

Patients with typhoid fever complicated by delirium,obtundation, shock, and coma may benefit from dexa-methasone therapy. This adjunctive therapy appears tolower mortality. (16)

Relapse rates in children are only 2% to 4% after ther-apy but have been reported after most regimens. Pro-longed carrier rates occur in less than 2% of infectedchildren.

PreventionImproving the quality of drinking water and food willlead to a decrease in Salmonella cases, as will decreasingexposure to high-risk animals (Table 2).

Routine vaccination of school-age children can be animportant component of a typhoid fever control pro-gram in an endemic region. (17) Vaccinating childrenyounger than 2 years living in slums in India with theVi capsular polysaccharide typhoid vaccine demon-strated a 61% protective effectiveness compared witha placebo. In children age 2 to 5 years, the protectiveeffect was 80%. Of interest, the level of protection was44% among unvaccinated members of Vi vaccinee clus-ters. (18) Similar favorable results have been observed inother countries.

Table 2. Preventing SalmonellaInfections

High-risk animals1. Parents and children should be counseled about the

potential risk of acquiring Salmonella when owningan iguana, lizard, snake, or turtle.

2. Owners need to wash their hands after handlinganimals, their cages, or their tanks.

3. Individuals at high risk of severe disease, such aschildren age <5 years and those who areimmunocompromised, should avoid contact withhigh-risk animals.

4. High-risk animals should be kept out of child-carecenters.

5. High-risk animals should not be allowed to roam freewithin the home. They should not be kept in kitchensor where food is prepared. Cages and tanks should notbe washed in kitchen sinks.

Food handling6. Hand hygiene should be practiced when handling raw

meat. Cutting boards must be cleaned thoroughlyafter preparing raw meat and food items that containraw egg.

7. People should not consume raw eggs and undercookedmeats.

8. Mothers are encouraged to breastfeed young infants.This practice has shown to reduce infections.

Infection control9. Young children with enteric fever (Salmonella Typhi

and Salmonella Paratyphi) should be kept out of childdaycare centers until they have at least 3 consecutivenegative stool culture results.

10. Infants and children with nontyphoidal Salmonellagastroenteritis can return to child daycare centeronce diarrhea has subsided.





Vaccination against typhoid fever is recommendedfor all travelers to developing countries in Asia,Latin America, and Africa, especially for those plan-ning to visit friends and relatives with 2 vaccinesavailable (Table 3). Travel to India, Pakistan,Mexico, and Bangladesh account for most travel-related cases in the United States. Generally, typhoidvaccines are 50% to 80% effective in preventingdisease.

In many highly endemic countries, S Paratyphicauses close to 50% of all cases of enteric fever. Inthe United States, most cases of paratyphoid feverare related to international travel. No effective licensedvaccine against S Paratyphi is available. However, cross-protective efficacy of Ty21a oral typhoid vaccine

against paratyphoid fever B has been demonstrated.(19)(20)

Parents and their children need to be counseled aboutthe potential risk of acquiring Salmonella if they owna high-risk pet, such as an iguana, lizard, snake, or turtle(Table 2). Owners need to wash their hands after han-dling the animals. The Centers for Disease Control andPrevention has advised that reptiles and amphibiansshould be kept out of households with children youngerthan 5 years. Individuals at high risk of severe diseaseshould have no contact with these animals. Reptilesand amphibians should be kept out of child care centersand households with children younger than 1 year.

All documented cases of Salmonella infection must bereported to county and state health departments.

Complications and PrognosisIleal perforations in the tropicsare frequently considered to beassociated with enteric fever.Between 4% and 6% of ileal per-forations were associated with STyphi and S Paratyphi A. Inparts of Africa, 50% of all admis-sions for typhoid-related ilealperforation were in children,with close to two-thirds occur-ring between ages 5 and 6 years.Underdiagnosing milder casesof enteric fever that resultedin delayed or inadequate anti-microbial treatment may haveresulted in a higher rate of per-forations.

Fever, vomiting, and abdominaltenderness and distension are sug-gestive of ileal perforation. Postop-erative complications are common,such as surgical wound infection,intra-abdominal abscesses, ileus,and reperforation. Mortality ishigh in children: close to 40% inchildren younger than 5 yearsand 20% in children older than 5years. (21)

Rhabdomyolysis with acute renalfailure has been reported as a com-plication of typhoid fever.

Table 3. Vaccines Licensed for the Prevention ofTyphoid Fever

Oral typhoidvaccine Ty21a For persons age ‡6 years

Live-attenuated

Series: 4 doses; 1 capsule every other day(days 0, 2, 4, and 6)

Take with cool water, 1 hour before mealMust complete series at least 1 week before

exposureCapsules must be refrigeratedCapsules should not be broken and contents

mixed with food/water because thisinactivates the vaccine; should not be takenwith antibiotics

Repeat 4-dose series every 5 years if exposurecontinues

Contraindicated in individuals withimmunocompromising conditions

Potential adverse effects: Nausea,abdominal pain, cramps, vomiting,fever, headaches, and rash

Injectable Vi typhoid vaccineFor persons ‡2 years

Capsular polysaccharideSingle injection, 0.5 mL, intramuscular,

deltoidVaccine must be administered at least

2 weeks before exposure.Thimerosal-freeBooster: Every 2 years if exposure

continuesPotential adverse effects: Injection

site pain, erythema, and induration;occasional fever and flulike symptoms.





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Suggested ReadingGordon MA. Invasive nontyphoidal Salmonella disease: epidemiol-

ogy, pathogenesis and diagnosis. Curr Opin Infect Dis. 2011;24(5):484–489

Tsai MH, Huang YC, Chiu CH, et al. Nontyphoidal Salmonellabacteremia in previously healthy children: analysis of 199episodes. Pediatr Infect Dis J. 2007;26(10):909–913

Whitaker JA, Franco-Paredes C, del Rio C, Edupuganti S. Re-thinking typhoid fever vaccines: implications for travelers andpeople living in highly endemic areas. J Travel Med. 2009;16(1):46–52

Summary

• On the basis of strong research evidence, exposures tocontaminated food, water, and colonized animals aremajor risk factors for Salmonella infections. (3)(4)(7)(14)

• On the basis of research evidence and consensus,infants younger than 3 months with Salmonellagastroenteritis are at an increased risk ofextraintestinal complications, such as bacteremia,meningitis, and osteomyelitis, and must be treatedregardless of severity of illness. (4)(11)

• On the basis of strong research and epidemiologicevidence, antimicrobial resistance is a serious problemin the treatment of typhoid fever. (12)(13)(14)

• On the basis of strong research evidence, vaccines caneffectively prevent typhoid fever. (17)(18)(19)(20)

• On the basis of published guidelines and currentstandards of care, children younger than 5 years andthose with immunocompromising conditions, such ashuman immunodeficiency virus and cancer, shouldavoid contact with turtles, iguanas, and snakes. (3)

Parent Resources From the AAP at HealthyChildren.org

The reader is likely to find material relevant to this article to share with parents by visiting these links:

• English: http://www.healthychildren.org/English/health-issues/conditions/infections/Pages/Salmonella-Infections.aspx• Spanish: http://www.healthychildren.org/spanish/health-issues/conditions/infections/paginas/salmonella-infections.aspx





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New Minimum Performance Level RequirementsPer the 2010 revision of the American Medical Association (AMA) Physician’s Recognition Award (PRA) and credit system, a minimum performancelevel must be established on enduring material and journal-based CME activities that are certified for AMA PRA Category 1 CreditTM. In order tosuccessfully complete 2013 Pediatrics in Review articles for AMA PRA Category 1 CreditTM, learners must demonstrate a minimum performance levelof 60% or higher on this assessment, which measures achievement of the educational purpose and/or objectives of this activity.

In Pediatrics in Review, AMA PRA Category 1 CreditTM may be claimed only if 60% or more of the questions are answered correctly. If you score lessthan 60% on the assessment, you will be given additional opportunities to answer questions until an overall 60% or greater score is achieved.

1. A 6–year–old girl who presents with fever and diarrhea after a trip to India is suspected of having typhoidfever. Which of the following findings is most frequently noted with this diagnosis?

A. Normal hemoglobin level.B. Normal liver enzyme level.C. Normal white blood cell count.D. Positive blood culture result.E. Positive stool culture result.

2. A previously healthy 9–month–old with vomiting and nonbloody diarrhea has a stool culture result positive forSalmonella. Which of the following is appropriate treatment of this infant?

A. Azithromycin.B. Ceftriaxone.C. Chloramphenicol.D. No antibiotics.E. Trimethoprim-sulfamethoxazole.

3. A 7–month–old girl is traveling with her parents to Pakistan. Which of the following preventive measures ismost appropriate for this child?

A. Avoid fresh fruits and vegetables.B. Bathe only in fresh water ponds.C. Injectable Vi typhoid vaccine.D. Oral typhoid vaccine Ty21a.E. Prophylaxis with azithromycin.

4. A 6–month–old female has a stool culture result positive for Salmonella. Her parents inquire as to what theycould do to prevent this from happening again. Which of the following features is an established risk factor forthis infection?

A. Breastfeeding.B. Nanny at home.C. Oatmeal cereal.D. Pet turtle at home.E. Travel to New Mexico.

5. Mixed infections with multiple pathogens occur in endemic tropical countries. Which of the followingdisorders in children treated for enteric fever who present with unremitting fevers is therapy most appropriate?

A. Dengue.B. Malaria.C. Rickettsia.D. Shigella.E. Tuberculosis.





DOI: 10.1542/pir.34-9-3752013;34;375Pediatrics in Review

John C. Christenson InfectionsSalmonella

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