Salmonella Infections

John C. Christenson
Pediatrics in Review 2013;34;375
DOI: 10.1542/pir.34-9-375

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/34/9/375

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2013 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601.

Downloaded from http://pedsinreview.aappublications.org/ at Chulalongkorn University on September 30, 2013

Salmonella Infections
John C. Christenson
Pediatrics in Review 2013;34;375
DOI: 10.1542/pir.34-9-375

Updated Information &

Services

including high resolution figures, can be found at:

http://pedsinreview.aappublications.org/content/34/9/375

References

This article cites 24 articles, 9 of which you can access for free at:
http://pedsinreview.aappublications.org/content/34/9/375#BIBL

Permissions & Licensing

Information about reproducing this article in parts (figures, tables) or

in its entirety can be found online at:
http://pedsinreview.aappublications.org/site/misc/Permissions.xhtml

Reprints

Information about ordering reprints can be found online:

http://pedsinreview.aappublications.org/site/misc/reprints.xhtml

Downloaded from http://pedsinreview.aappublications.org/ at Chulalongkorn University on September 30, 2013

Article

infectious diseases

Salmonella Infections
John C. Christenson, MD*

Author Disclosure
Dr Christenson has
disclosed no financial
relationships relevant
to this article. This
commentary does not

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.

contain discussion of
unapproved/
investigative use of
a commercial product/
device.

Objectives
1.
2.
3.
4.
5.

After completing this article, readers should be able to:

Describe the epidemiology of nontyphoidal salmonellosis.

Recognize the clinical features of enteric fevers.
Appropriately treat the young child with Salmonella infection.
Understand ways to prevent Salmonella infections.
Use typhoid vaccines when indicated.

Introduction
Salmonella infection is a common cause of gastroenteritis and bacteremia worldwide. The
consumption of contaminated water and food and the close contact with colonized animals are frequent risk factors for acquisition. Young infants, persons with hemoglobin
disorders, and individuals who have immunocompromising conditions, such as human
immunodeciency virus (HIV) and cancer, are at risk for severe disease, such as bacteremia, meningitis, and osteomyelitis. Salmonella Typhi and Salmonella Paratyphi are responsible for signicant morbidity and mortality in developing countries. Clinicians must
learn 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 of
pathogens.

Microbiology
The genus Salmonella is composed of motile gram-negative bacteria within the family Enterobacteriaceae. They are oxidase-negative, indole-negative, and nonlactose fermenters.
The nomenclature of the genus Salmonella can be challenging. The Centers for Disease
Control and Prevention and the World Health Organization have been responsible for
maintaining the format for formula designation. There are 2 Salmonella species, Salmonella
enterica and Salmonella bongori, which are classied further into subspecies according to
their biochemical and genomic relatedness. Most human infections are caused by a serotype
of Salmonella enterica subsp enterica (subspecies I), which infect warm-blooded animals.
Five other subspecies (plus S bongori [subspecies V]) are known to colonize cold-blooded
animals and the environment: enterica subsp salamae (subspecies II), arizonae (subspecies
IIIa), diarizonae (subspecies IIIb), houtenae (subspecies IV), and indica (subspecies VI).
Although more than 2,600 serotypes of Salmonella have been identied, most disease
is caused by subspecies/serotypes Typhimurium and Enteritidis. Historically, serotypes
are 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.

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

infectious diseases

salmonella

subspecies/serotype (eg, Salmonella Typhi or Salmonella

Typhimurium). Nonsubspecies I are rarely reported as
human pathogens.
Certain serotypes frequently correlate with a disease
syndrome or food source. As examples, Salmonella choleraesuis and Salmonella dublin are both frequently associated with bacteremia and extraintestinal infections.
(1)(2)

Epidemiology
Nontyphoidal Salmonella Infections
Salmonella gastroenteritis is a serious public health problem in the United States. An estimated 1 million foodborne illnesses occur each year, resulting in 350 deaths.
(3) The world burden is estimated at 93.8 million illnesses, with 155,000 deaths each year. Salmonella Enteritidis is the most common isolated subspecies because it is
responsible for 65% of these infections, followed by S Typhimurium at 12%. In the United States, exposures to
chicken and eggs are most likely sources for infection.
Many risk factors are associated with infection and dissemination. Achlorhydria, the use of antacids or proton
pump inhibitors, and rapid gastric emptying favor bacterial
survival. Conditions that impair cell-mediated lymphocyte
function, such as HIV/AIDS, malnutrition, corticosteroid
therapy, and posttransplantation immunosuppressive therapy, are major risk factors. An overloaded reticuloendothelial system with iron or hemoglobin, such as in patients
with sickle cell anemia, hemolytic anemia, thalassemia,
and malaria, may increase the likelihood of severe disease.
Infarcts in the gastrointestinal tract and bone and defective
phagocytic and opsonic function also appear to contribute
to the severity of disease observed in patients who have
sickle cell anemia. Diseases such as leukemia and lymphoma also impair the reticuloendothelial system function.
The morbidity and mortality associated with Salmonella
infections are also inuenced by the serotype that causes
the infection. Salmonella choleraesuis is more likely to
cause invasive disease. In one study, 85% of isolates were
recovered from extraintestinal sites, especially blood.
(1) Seventy-two percent of patients were younger than
3 years. Pediatric patients were more likely to have diarrhea than adults. Most of the children with diarrhea were
also bacteremic. Mycotic aneurysms, a complication observed in adults, was not detected in any of the pediatric
cases. Of importance, only 21% of children had leukocytosis. Occult bacteremia, where the child presents only
with fever, was a common presentation.
In a population-based, case-control study of salmonellosis in infants younger than 1 year, infected infants were
376 Pediatrics in Review Vol.34 No.9 September 2013

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 infected infant. (4)
Most Salmonella infections are foodborne. In Mexico,
pork, meat, and poultry were frequently found to be
contaminated with Salmonella. Consumption of contaminated orange juice led to an outbreak in a theme
park. An intentional contamination of restaurant salad
bars was responsible for a large outbreak of Salmonella
gastroenteritis in Oregon in 1984. Contaminated peanut butter, ice cream, salami products, and mozzarella
cheese has been responsible for multistate outbreaks
in the United States. Outbreaks have also been associated with exposure to contaminated dry dog food and
pet treats.
Animals such as chickens, pigs, turtles, lizards, iguanas,
hedgehogs, and amphibians have been identied as reservoirs of Salmonella. Many of these colonizations have
resulted in human outbreaks. An outbreak of S Typhimurium was associated with exposures to pet rodents.
Feeder rodents used for the feeding of reptiles and amphibians were found to be colonized with Salmonella,
resulting in human infections. Patients with Salmonella
arizonae acquired from iguanas and snakes have a predisposition for musculoskeletal infections. In a rare event, 2
patients developed S Enteritidis sepsis (in one case fatal)
after a platelet transfusion. The donor most likely had
asymptomatic bacteremia from handling his pet boa
constrictor.
Nosocomial outbreaks are uncommon. However, inadequate infection control practices, understafng, and
overcrowding may lead to environmental contamination.
In some developing countries, asymptomatic carriage of
Salmonella can be high among children attending day
care centers. Outbreaks of salmonellosis in day care centers have been reported, but these are considered rare
events.
Although the incidence of salmonellosis related to
international travel appears to be decreasing in the
United States, many travel-acquired cases are still reported. Salmonella stanley, a common serotype in
Southeast Asia (second most common in Thailand),
has been frequently isolated in Europe. (5) In Southeast Asia, the serotype is frequently associated with
the pork industry.
Nontyphoidal Salmonella infections remain a frequent
cause of invasive disease in many regions of the world, especially in sub-Saharan Africa. Children younger than
3 years and those infected with HIV have the greatest
burden. Mortality remains high, especially in children with

infectious diseases

bacteremia and meningitis. Seasonal peaks of disease

coincide with the rainy season, which leads to fecal contamination of drinking water. In many countries, an association between malaria and Salmonella is well known.
This situation often delays treatment, causing greater
morbidity and mortality. Frequently, febrile persons are
treated only for malaria without considering the likelihood of a coinfection. Clinical features, such as fevers,
anemia, and splenomegaly, are frequent ndings in both
conditions.

Enteric Fever (Typhoid and Paratyphoid Fever)

Enteric fever, an infection caused by S Typhi (typhoid
fever) or S Paratyphi A, B, or C (paratyphoid fever), is
a common cause of death and disease in many parts of
the world. Approximately 22 million cases are thought to
occur worldwide 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 at
a lower frequency. In Asia, it is estimated that the incidence approximates 100 cases per 100,000 population.
Travelers to endemic regions are at risk. Most cases in
the United States have been associated with international
travel. Travelers visiting friends and relatives are at the
highest risk of infection.
In countries such as India, children and adolescents in
the 5- to 19-year age group are affected most. On rare
occasions, neonatal infections have been reported. These
infections are frequently acquired from the mother. In
South and Southeast Asia, S Typhi is the most common
cause of community-acquired bacteremia.
Between 1960 and 1999, 60 outbreaks of typhoid
fever had been reported in the United States. (7)
Ninety percent were domestically acquired. Recently,
cases were found to be related to the consumption of
a fruit shake made from frozen mamey fruit from
Guatemala. (7) In recent years, an outbreak of S Paratyphi B was found to be related to exposure to pet
turtles.
The major factor responsible for the magnitude of this
problem is poor sanitary infrastructure, resulting in substandard drinking water and contaminated food. Person-toperson transmission from chronic asymptomatic carriage
also contributes to the infection of susceptible individuals
(eg, typhoid Mary).

Pathogenesis
The pathogenesis of salmonellosis is complex. Several virulence genes are responsible for the severity of disease observed with certain species.

salmonella

Nontyphoidal isolates are rarely invasive because most

do not extend past the lamina propria or the intestinal
lymphatic system. However, interactions with host cells
in the intestines may lead to a release of proinammatory
cytokines that result in the recruitment of neutrophils to
the area, resulting in gastroenteritis. Some genes appear
to play a role in the survival of bacteria within the liver
and spleen and promote the replication within macrophages. (8)
Salmonella Typhi is known to adhere to epithelial cells
over the lymphatic Peyer patches, allowing for penetration through the intestinal mucosa. Engulfment by
macrophages and translocation into draining lymph
nodes results in bacteremia and subsequent dissemination. The organism survives within the host cells in a Salmonella-containing vacuole, assuring its ability to replicate,
survive, and invade and resulting in the multiplication
and survival of bacteria within the liver, spleen, and
bone marrow. After an incubation period of 7 to 14 days,
bacteremia occurs and symptoms emerge. Salmonella
Typhi can be found in the gallstones of individuals
who live in endemic regions. Its presence correlates with
fecal shedding, and these people are known to infect
others.

Clinical Aspects
Nontyphoidal Salmonella Infections
Gastroenteritis is the most frequent presentation. Most
affected children are younger than 1 year. The usual incubation period for Salmonella gastroenteritis is 6 to 12
hours. Nausea, vomiting, and diarrhea are common
symptoms. Diarrhea is usually nonbloody. Myalgias, arthralgias, and headaches are also reported. Although observed in children with Salmonella gastroenteritis, fever,
chills, and abdominal pain are more commonly observed
with shigellosis. The presence of rectal tenesmus accompanied by stools with mucus and/or blood is more distinctive of Shigella infections. Symptoms are generally
self-limited. Hepatomegaly and splenomegaly are infrequently noted.
Bacteremia is commonly observed in infants with gastroenteritis. Most children require hospitalization. Persistent bacteremia can be detected in approximately 40% of
patients. Salmonella Enteritidis was a frequently isolated
pathogen in bacteremic patients. In children, bacteremia
is rarely fatal. In contrast, one-third of adults presenting
with primary bacteremia have extraintestinal organ involvement and will die.
Clinical features or laboratory parameters were unable
to detect children more likely to have persistent bacteremia.
Pediatrics in Review Vol.34 No.9 September 2013 377

infectious diseases

salmonella

Although focal infections were observed in 2.5% of previously healthy children, one-third of children with underlying medical conditions had focal disease, consisting
of meningitis, osteomyelitis, septic arthritis, pneumonia,
or cholangitis. In parts of Africa, the fatality rate for bacteremia is close to 25%. Lower respiratory tract coinfections with tuberculosis and Streptococcus pneumoniae were
common.
Meningitis and musculoskeletal infections are common complications in infants younger than 3 months.
It is estimated that 50% to 75% of Salmonella meningitis
occurs in the rst year of life. Asymptomatic disease is also
common in young infants. A well-appearing infant with
Salmonella gastroenteritis may be bacteremic.
Malaria has been found to be a risk factor for invasive
nontyphoidal Salmonella infections in children. A reduction in cases of salmonellosis was associated with a decrease in the number of malaria cases.
Compared with children with gastroenteritis
alone, bacteremic children appear to have a longer duration of symptoms, a less severe clinical appearance,
and fewer signs of dehydration. This gradual presentation with less dehydration and fewer toxic effects
may lead to premature discharges from emergency
departments.

Typhoid and Paratyphoid Fever

Fever, gastrointestinal symptoms (eg, vomiting, severe
diarrhea, abdominal distension, and pain), cough, relative bradycardia, rose spots (pink macules frequently
observed on the abdomen and chest), and splenomegaly are frequently regarded as features of typhoid and
paratyphoid fever. However, many patients lack these
ndings, making diagnosis difcult if solely based on
clinical features. In a reported foodborne epidemic,
most patients had nonspecic symptoms, consisting
of fever, headache, diarrhea, and anorexia. Hepatomegaly was seen in 7% of patients, splenomegaly in
13% of patients, and rose spots in 5% of patients. Relative bradycardia and rose spots are seldom observed in
children. Jaundice is frequently observed among children. Febrile convulsions have been reported in children with enteric fever and may be the presenting
symptom in some children. The incubation period
for enteric fevers is generally 7 to 14 days, with a range
of 3 to 60 days.
In Pakistan, children younger than 5 years were
found to have more severe disease. More than 95% of
children had fever, 20% to 41% had hepatomegaly, 5%
to 20% had splenomegaly, 19% to 28% had abdominal
pain, and 8% to 35% had diarrhea. (9) Cough was
378 Pediatrics in Review Vol.34 No.9 September 2013

observed in approximately 15% of patients. Severe disease resulted in more hospitalizations. Intestinal perforation was a rare complication observed in less than 1%
of children.
Thrombocytopenia and disseminated intravascular coagulation are markers of severe disease. Splenic abscess,
brain abscess, and subdural empyema are rare complications of typhoid fever.
An analysis of travel-related cases in the United Kingdom found that S Typhi and S Paratyphi infections were
indistinguishable clinically. (10) Infections caused by S
Paratyphi 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 aminotransferase level. Among travelers, more cases of enteric fever
were caused by S Paratyphi A than by S Typhi. GuillainBarr syndrome has been described in association with S
Paratyphi A infection.
Mixed infections with multiple pathogens occur in
endemic tropical countries. Treatment against enteric
fever should be considered for children with unremitting fevers after completing adequate antimalarial
therapy.

Diagnosis
There are no features of Salmonella gastroenteritis that
would allow its diagnosis based on clinical ndings alone.
The routine microscopic stool examination for polymorphonuclear cells is of limited clinical utility because a large
number of children with gastroenteritis will have a negative test result (<5 polymorphonuclear cells per highpower eld). All young infants with diarrhea, especially
those younger than 3 months with a positive stool culture
result, should have a blood culture performed, even if the
infant is well-appearing. Infants younger than 3 months
with a positive blood culture result should undergo a lumbar puncture and careful examination assessing for the
presence of musculoskeletal involvement (Table 1).
(11) Any ill-appearing infant with a positive stool culture
result should undergo a blood culture and lumbar puncture, be hospitalized, and be treated with parenteral
antibiotics.
The Widal test, a classic test that measures antibodies
against O and H antigens of S Typhi, was used for the
diagnosis of typhoid fever. However, its lack of sensitivity
and specicity has limited its utility. A false-positive test
result may lead to overtreatment and a delay in considering other conditions. This outcome is especially likely in
parts of the world where typhoid fever is rare among children and signicantly less frequent than other bacterial
pathogens.

infectious diseases

Table 1.

salmonella

Management of Pediatric Salmonella Gastroenteritis

Signs and Symptoms

Age <3 months
Diarrhea (dysentery-like, bloody):
Diarrhea <5 days, not dysentery-like or bloody
Febrile

History of exposure to Salmonella

Diagnosis

Management

Obtain stool culture

Obtain blood culture
No stool culture
Stool culture positive
Blood culture negative
Stool culture positive
Blood culture positive

Hydration
No antibiotics
Treat with parenteral antibiotics, 5-7 days
Lumbar puncture
Treat with parenteral antibiotics:
Bacteremia only: 14 days
Meningitis: 4-6 weeks
Osteomyelitis: 4-6 weeks

Obtain stool culture

Obtain blood culture

Age >3 months

Diarrhea 5 days:
Afebrile

Obtain stool culture

Stool culture positive

Febrile, but nontoxic-appearing

Stool culture positive

Toxic, ill-appearing, or
immunocompromised host

Stool culture positive

Stool culture positive
Blood culture positive

Observation
No antibiotics
Blood culture
Observe off antibiotics
Blood culture
Lumbar puncture
Treat with parenteral antibiotics
Lumbar puncture
Treat with parenteral antibiotics:
Bacteremia only: 14 days
Meningitis: 4-6 weeks
Osteomyelitis: 4-6 weeks

Adapted from: St. Geme J, Hodes H, Marcy SM, et al. Consensus: Management of Salmonella infection in the rst year of life. Pediatric Infectious Disease
Journal. 1988; 7(9):615621. Copyright 1988 (c) by Wolters Kluwer Health/Williams & Wilkens.

In patients with typhoid fever, blood culture results

are frequently positive, but stool cultures are less so. Although liver enzyme levels are frequently elevated, leukocytosis is not always observed. Leukopenia and
anemia are frequently associated with enteric fevers. A
normal white blood cell count does not rule out invasive disease. Many suggest that bone marrow cultures
have a higher sensitivity. Obtaining this type of specimen is much more invasive and impractical in many circumstances. Approximately 20% of patients may have
pneumonia as documented by abnormal radiography
results.
Although pathogen-specic serologic and polymerase
chain reaction assays are the preferred methods for diagnosing enteric fever, diagnosis is still made using clinical
criteria in most lower-income countries. Unfortunately,
early features of enteric fever mimic other conditions,
such as pneumonia, malaria, sepsis, dengue, acute hepatitis, and rickettsial infections.

Treatment
Previously healthy children and adults with uncomplicated gastroenteritis do not require antimicrobial
therapy because the disease is self-limited. Infants
younger than 3 months with Salmonella gastroenteritis should be treated because they have a high
incidence of extraintestinal complications, such as bacteremia, meningitis, and osteomyelitis (Table 1). Antimicrobial therapy may prolong the carrier state. Therapy
should be considered for those individuals with high-risk
medical conditions, such as HIV, sickle cell anemia, and
cancer.
Antimicrobial treatment must take into account
the local epidemiology and therapeutic practice in
the country where the infection was acquired. Chloramphenicol, amoxicillin, and the combination of
trimethoprim and sulfamethoxazole are no longer recommended as rst-line agents for the treatment of enteric fevers. The high frequency of treatment failures,
Pediatrics in Review Vol.34 No.9 September 2013 379

infectious diseases

salmonella

resistance, and relapse rates has diminished their usefulness. Antimicrobial resistance observed in many
countries has inuenced the choice of agent for treating typhoid and paratyphoid fever. Ceftriaxone remains the recommended agent in the most severe
cases in which parenteral therapy is indicated. Cefotaxime is an acceptable alternative. Although uoroquinolones, such as ciprooxacin, are generally
associated with high cure rates, defervescence within
a week, and lower relapse and fecal carriage rates, isolates from many Asian countries demonstrate resistance,
rendering them ineffective. Azithromycin appears favorable in the treatment of these infections. (12) Until
recently, uoroquinolone resistance was uncommon in
most regions of Africa. In a recent study from the
Democratic Republic of the Congo, decreased ciprooxacin susceptibility was detected in 15.4% of tested
isolates. (13) Proper hydration, perfusion, and fever
control still remain integral components of treating
enteric fever.
More than 10 years ago, multidrug resistance was uncommon in Latin America. Susceptibility to ampicillin
was common, and susceptibility to ceftriaxone was almost
universal. At the same time, in some Mediterranean
countries, close to one-third of isolates were resistant
to ampicillin.
In infections by S choleraesuis, resistance to ciprooxacin was observed in 28% of pediatric cases in
Taiwan, whereas more than 60% of cases in adults
had a resistant strain. (1) Irrespective of age, resistance to trimethoprim-sulfamethoxazole remained
high.
Eighty-four percent of samples of ground meats
(beef, turkey, and pork) purchased at several supermarkets in the Washington, DC, area were found to be contaminated with Salmonella isolates that were resistant to
at least one antibiotic; 53% were resistant to 3 antibiotics. (14) Of greater concern, 16% of the isolates were
resistant to ceftriaxone, the drug of choice for the treatment of serious infections in children. In a recent
study of invasive salmonellosis among Thai children,
ceftriaxone resistance was detected in 17.4% of isolates. (15)
Patients with typhoid fever complicated by delirium,
obtundation, shock, and coma may benet from dexamethasone therapy. This adjunctive therapy appears to
lower mortality. (16)
Relapse rates in children are only 2% to 4% after therapy but have been reported after most regimens. Prolonged carrier rates occur in less than 2% of infected
children.
380 Pediatrics in Review Vol.34 No.9 September 2013

Prevention
Improving the quality of drinking water and food will
lead to a decrease in Salmonella cases, as will decreasing
exposure to high-risk animals (Table 2).
Routine vaccination of school-age children can be an
important component of a typhoid fever control program in an endemic region. (17) Vaccinating children
younger than 2 years living in slums in India with the
Vi capsular polysaccharide typhoid vaccine demonstrated a 61% protective effectiveness compared with
a placebo. In children age 2 to 5 years, the protective
effect was 80%. Of interest, the level of protection was
44% among unvaccinated members of Vi vaccinee clusters. (18) Similar favorable results have been observed in
other countries.

Preventing Salmonella
Infections
Table 2.

High-risk animals
1. Parents and children should be counseled about the
potential risk of acquiring Salmonella when owning
an iguana, lizard, snake, or turtle.
2. Owners need to wash their hands after handling
animals, their cages, or their tanks.
3. Individuals at high risk of severe disease, such as
children age <5 years and those who are
immunocompromised, should avoid contact with
high-risk animals.
4. High-risk animals should be kept out of child-care
centers.
5. High-risk animals should not be allowed to roam free
within the home. They should not be kept in kitchens
or where food is prepared. Cages and tanks should not
be washed in kitchen sinks.
Food handling
6. Hand hygiene should be practiced when handling raw
meat. Cutting boards must be cleaned thoroughly
after preparing raw meat and food items that contain
raw egg.
7. People should not consume raw eggs and undercooked
meats.
8. Mothers are encouraged to breastfeed young infants.
This practice has shown to reduce infections.
Infection control
9. Young children with enteric fever (Salmonella Typhi
and Salmonella Paratyphi) should be kept out of child
daycare centers until they have at least 3 consecutive
negative stool culture results.
10. Infants and children with nontyphoidal Salmonella
gastroenteritis can return to child daycare center
once diarrhea has subsided.

infectious diseases

Vaccination against typhoid fever is recommended

for all travelers to developing countries in Asia,
Latin America, and Africa, especially for those planning to visit friends and relatives with 2 vaccines
available (Table 3). Travel to India, Pakistan,
Mexico, and Bangladesh account for most travelrelated cases in the United States. Generally, typhoid
vaccines are 50% to 80% effective in preventing
disease.
In many highly endemic countries, S Paratyphi
causes close to 50% of all cases of enteric fever. In
the United States, most cases of paratyphoid fever
are related to international travel. No effective licensed
vaccine against S Paratyphi is available. However, crossprotective efcacy of Ty21a oral typhoid vaccine

against paratyphoid fever B has been demonstrated.

(19)(20)
Parents and their children need to be counseled about
the potential risk of acquiring Salmonella if they own
a high-risk pet, such as an iguana, lizard, snake, or turtle
(Table 2). Owners need to wash their hands after handling the animals. The Centers for Disease Control and
Prevention has advised that reptiles and amphibians
should be kept out of households with children younger
than 5 years. Individuals at high risk of severe disease
should have no contact with these animals. Reptiles
and amphibians should be kept out of child care centers
and households with children younger than 1 year.
All documented cases of Salmonella infection must be
reported to county and state health departments.

Vaccines Licensed for the Prevention of

Typhoid Fever

Table 3.

Oral typhoid
vaccine Ty21a
Live-attenuated

For persons age 6 years

Series: 4 doses; 1 capsule every other day
(days 0, 2, 4, and 6)
Take with cool water, 1 hour before meal
Must complete series at least 1 week before
exposure
Capsules must be refrigerated
Capsules should not be broken and contents
mixed with food/water because this
inactivates the vaccine; should not be taken
with antibiotics
Repeat 4-dose series every 5 years if exposure
continues
Contraindicated in individuals with
immunocompromising conditions
Potential adverse effects: Nausea,
abdominal pain, cramps, vomiting,
fever, headaches, and rash

Injectable Vi typhoid vaccine

Capsular polysaccharide

salmonella

For persons 2 years

Single injection, 0.5 mL, intramuscular,
deltoid
Vaccine must be administered at least
2 weeks before exposure.
Thimerosal-free
Booster: Every 2 years if exposure
continues
Potential adverse effects: Injection
site pain, erythema, and induration;
occasional fever and flulike symptoms.

Complications and Prognosis

Ileal perforations in the tropics
are frequently considered to be
associated with enteric fever.
Between 4% and 6% of ileal perforations were associated with S
Typhi and S Paratyphi A. In
parts of Africa, 50% of all admissions for typhoid-related ileal
perforation were in children,
with close to two-thirds occurring between ages 5 and 6 years.
Underdiagnosing milder cases
of enteric fever that resulted
in delayed or inadequate antimicrobial treatment may have
resulted in a higher rate of perforations.
Fever, vomiting, and abdominal
tenderness and distension are suggestive of ileal perforation. Postoperative complications are common,
such as surgical wound infection,
intra-abdominal abscesses, ileus,
and reperforation. Mortality is
high in children: close to 40% in
children younger than 5 years
and 20% in children older than 5
years. (21)
Rhabdomyolysis with acute renal
failure has been reported as a complication of typhoid fever.
Pediatrics in Review Vol.34 No.9 September 2013 381

infectious diseases

salmonella

Summary
On the basis of strong research evidence, exposures to
contaminated food, water, and colonized animals are
major risk factors for Salmonella infections. (3)(4)(7)(14)
On the basis of research evidence and consensus,
infants younger than 3 months with Salmonella
gastroenteritis are at an increased risk of
extraintestinal complications, such as bacteremia,
meningitis, and osteomyelitis, and must be treated
regardless of severity of illness. (4)(11)
On the basis of strong research and epidemiologic
evidence, antimicrobial resistance is a serious problem
in the treatment of typhoid fever. (12)(13)(14)
On the basis of strong research evidence, vaccines can
effectively prevent typhoid fever. (17)(18)(19)(20)
On the basis of published guidelines and current
standards of care, children younger than 5 years and
those with immunocompromising conditions, such as
human immunodeficiency virus and cancer, should
avoid contact with turtles, iguanas, and snakes. (3)

References
1. Chiu CH, Chuang CH, Chiu S, Su LH, Lin TY. Salmonella
enterica serotype Choleraesuis infections in pediatric patients.
Pediatrics. 2006;117(6):e1193e1196
2. Cohen JI, Bartlett JA, Corey GR. Extra-intestinal manifestations
of salmonella infections. Medicine (Baltimore). 1987;66(5):349388
3. Chai SJ, White PL, Lathrop SL, et al. Salmonella enterica
serotype Enteritidis: increasing incidence of domestically acquired
infections. Clin Infect Dis. 2012;54(suppl 5):S488S497
4. Jones TF, Ingram LA, Fullerton KE, et al. A case-control study
of the epidemiology of sporadic Salmonella infection in infants.
Pediatrics. 2006;118(6):23802387
5. Hendriksen RS, Le Hello S, Bortolaia V, et al. Characterization
of isolates of Salmonella enterica serovar Stanley, a serovar endemic
to Asia and associated with travel. J Clin Microbiol. 2012;50(3):
709720
6. Bhutta ZA. Current concepts in the diagnosis and treatment of
typhoid fever. BMJ. 2006;333(7558):7882
7. Loharikar A, Newton A, Rowley P, et al. Typhoid fever outbreak
associated with frozen mamey pulp imported from Guatemala to the
western United States, 2010. Clin Infect Dis. 2012;55(1):6166
8. Lahiri A, Lahiri A, Iyer N, Das P, Chakravortty D Visiting the
cell biology of Salmonella infection. Microbes Infect. 2010;12(11):
809-818.
9. Siddiqui FJ, Rabbani F, Hasan R, Nizami SQ, Bhutta ZA.
Typhoid fever in children: some epidemiological considerations
from Karachi, Pakistan. Int J Infect Dis. 2006;10(3):215222

10. Patel TA, Armstrong M, Morris-Jones SD, Wright SG,

Doherty T. Imported enteric fever: case series from the hospital
for tropical diseases, London, United Kingdom. Am J Trop Med
Hyg. 2010;82(6):11211126
11. Geme JW III, Hodes HL, Marcy SM, et al. Consensus:
management of Salmonella infection in the rst year of life. Pediatr
Infect Dis J. 1988;7(9):615621
12. Chinh NT, Parry CM, Ly NT, et al. A randomized controlled
comparison of azithromycin and ooxacin for treatment of multidrugresistant or nalidixic acid-resistant enteric fever. Antimicrob Agents
Chemother. 2000;44(7):18551859
13. Lunguya O, Lejon V, Phoba MF, et al. Salmonella Typhi in
the Democratic Republic of the Congo: uoroquinolone decreased susceptibility on the rise. PLoS Negl Trop Dis. 2012;6(11):
e1921
14. White DG, Zhao S, Sudler R, et al. The isolation of antibioticresistant salmonella from retail ground meats. N Engl J Med. 2001;
345(16):11471154
15. Punpanich W, Netsawang S, Thippated C. Invasive salmonellosis in urban Thai children: a ten-year review. Pediatr Infect Dis J.
2012;31(8):e105e110
16. Chisti MJ, Bardhan PK, Huq S, et al. High-dose intravenous
dexamethasone in the management of diarrheal patients with
enteric fever and encephalopathy. Southeast Asian J Trop Med
Public Health. 2009;40(5):10651073
17. Bhan MK, Bahl R, Bhatnagar S. Typhoid and paratyphoid
fever. Lancet. 2005;366(9487):749762
18. Sur D, Ochiai RL, Bhattacharya SK, et al. A cluster-randomized
effectiveness trial of Vi typhoid vaccine in India. N Engl J Med. 2009;
361(4):335344
19. Pakkanen SH, Kantele JM, Kantele A. Cross-reactive gutdirected immune response against Salmonella enterica serovar
Paratyphi A and B in typhoid fever and after oral Ty21a typhoid
vaccination. Vaccine. 2012;30(42):60476053
20. Wahid R, Simon R, Zafar SJ, Levine MM, Sztein MB. Live oral
typhoid vaccine Ty21a induces cross-reactive humoral immune
responses against Salmonella enterica serovar Paratyphi A and S.
Paratyphi B in humans. Clin Vaccine Immunol. 2012;19(6):
825834
21. Ekenze SO, Ikefuna AN. Typhoid intestinal perforation under
5 years of age. Ann Trop Paediatr. 2008;28(1):5358

Suggested Reading
Gordon MA. Invasive nontyphoidal Salmonella disease: epidemiology, pathogenesis and diagnosis. Curr Opin Infect Dis. 2011;24
(5):484489
Tsai MH, Huang YC, Chiu CH, et al. Nontyphoidal Salmonella
bacteremia in previously healthy children: analysis of 199
episodes. Pediatr Infect Dis J. 2007;26(10):909913
Whitaker JA, Franco-Paredes C, del Rio C, Edupuganti S. Rethinking typhoid fever vaccines: implications for travelers and
people living in highly endemic areas. J Travel Med. 2009;16
(1):4652

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

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

infectious diseases

salmonella

PIR Quiz
This quiz is available online at http://www.pedsinreview.aappublications.org. NOTE: Learners can take Pediatrics in Review quizzes and claim credit
online only. No paper answer form will be printed in the journal.

New Minimum Performance Level Requirements

Per the 2010 revision of the American Medical Association (AMA) Physicians Recognition Award (PRA) and credit system, a minimum performance
level must be established on enduring material and journal-based CME activities that are certified for AMA PRA Category 1 CreditTM. In order to
successfully complete 2013 Pediatrics in Review articles for AMA PRA Category 1 CreditTM, learners must demonstrate a minimum performance level
of 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 less
than 60% on the assessment, you will be given additional opportunities to answer questions until an overall 60% or greater score is achieved.

1. A 6yearold girl who presents with fever and diarrhea after a trip to India is suspected of having typhoid
fever. 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 9monthold with vomiting and nonbloody diarrhea has a stool culture result positive for
Salmonella. Which of the following is appropriate treatment of this infant?
A. Azithromycin.
B. Ceftriaxone.
C. Chloramphenicol.
D. No antibiotics.
E. Trimethoprim-sulfamethoxazole.
3. A 7monthold girl is traveling with her parents to Pakistan. Which of the following preventive measures is
most appropriate for this child?
A.
B.
C.
D.
E.

Avoid fresh fruits and vegetables.

Bathe only in fresh water ponds.
Injectable Vi typhoid vaccine.
Oral typhoid vaccine Ty21a.
Prophylaxis with azithromycin.

4. A 6monthold female has a stool culture result positive for Salmonella. Her parents inquire as to what they
could do to prevent this from happening again. Which of the following features is an established risk factor for
this infection?
A.
B.
C.
D.
E.

Breastfeeding.
Nanny at home.
Oatmeal cereal.
Pet turtle at home.
Travel to New Mexico.

5. Mixed infections with multiple pathogens occur in endemic tropical countries. Which of the following
disorders in children treated for enteric fever who present with unremitting fevers is therapy most appropriate?
A.
B.
C.
D.
E.

Dengue.
Malaria.
Rickettsia.
Shigella.
Tuberculosis.

Pediatrics in Review Vol.34 No.9 September 2013 383