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Article infectious diseases

Salmonella Infections
John C. Christenson, MD*
Practice Gaps
1. Because Salmonella disease causes 93.8 million illnesses and 155,000 deaths
Author Disclosure worldwide and 1 million foodborne illnesses and 350 deaths in the United States,
Dr Christenson has clinicians must learn to recognize, treat, and prevent these infections.
disclosed no financial 2. Young infants, persons with hemoglobin disorders, and individuals who are immune
relationships relevant compromised, such as those with human immunodeficiency virus and cancer, are at
to this article. This risk for severe Salmonella disease, including bacteremia, meningitis, and
commentary does not osteomyelitis.
contain discussion of
unapproved/
Objectives After completing this article, readers should be able to:
investigative use of
a commercial product/ 1. Describe the epidemiology of nontyphoidal salmonellosis.
device. 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.

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 ani-
mals are frequent risk factors for acquisition. Young infants, persons with hemoglobin
disorders, and individuals who have immunocompromising conditions, such as human
immunodeficiency 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 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 En-
terobacteriaceae. 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 classified 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 identified, 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.

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subspecies/serotype (eg, Salmonella Typhi or Salmonella more likely to be bottle fed, have exposure to reptiles,
Typhimurium). Non–subspecies I are rarely reported as have ridden in a shopping cart next to meat or poultry,
human pathogens. traveled abroad, or attended a day care center with an in-
Certain serotypes frequently correlate with a disease fected infant. (4)
syndrome or food source. As examples, Salmonella chol- Most Salmonella infections are foodborne. In Mexico,
eraesuis and Salmonella dublin are both frequently asso- pork, meat, and poultry were frequently found to be
ciated with bacteremia and extraintestinal infections. contaminated with Salmonella. Consumption of con-
(1)(2) taminated 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
Epidemiology gastroenteritis in Oregon in 1984. Contaminated pea-
Nontyphoidal Salmonella Infections nut butter, ice cream, salami products, and mozzarella
Salmonella gastroenteritis is a serious public health prob- cheese has been responsible for multistate outbreaks
lem in the United States. An estimated 1 million food- in the United States. Outbreaks have also been associ-
borne illnesses occur each year, resulting in 350 deaths. ated with exposure to contaminated dry dog food and
(3) The world burden is estimated at 93.8 million ill- pet treats.
nesses, with 155,000 deaths each year. Salmonella Enter- Animals such as chickens, pigs, turtles, lizards, iguanas,
itidis is the most common isolated subspecies because it is hedgehogs, and amphibians have been identified as res-
responsible for 65% of these infections, followed by S Ty- ervoirs of Salmonella. Many of these colonizations have
phimurium at 12%. In the United States, exposures to resulted in human outbreaks. An outbreak of S Typhi-
chicken and eggs are most likely sources for infection. murium was associated with exposures to pet rodents.
Many risk factors are associated with infection and dis- Feeder rodents used for the feeding of reptiles and am-
semination. Achlorhydria, the use of antacids or proton phibians were found to be colonized with Salmonella,
pump inhibitors, and rapid gastric emptying favor bacterial resulting in human infections. Patients with Salmonella
survival. Conditions that impair cell-mediated lymphocyte arizonae acquired from iguanas and snakes have a predis-
function, such as HIV/AIDS, malnutrition, corticosteroid position for musculoskeletal infections. In a rare event, 2
therapy, and posttransplantation immunosuppressive ther- patients developed S Enteritidis sepsis (in one case fatal)
apy, are major risk factors. An overloaded reticuloendothe- after a platelet transfusion. The donor most likely had
lial system with iron or hemoglobin, such as in patients asymptomatic bacteremia from handling his pet boa
with sickle cell anemia, hemolytic anemia, thalassemia, constrictor.
and malaria, may increase the likelihood of severe disease. Nosocomial outbreaks are uncommon. However, in-
Infarcts in the gastrointestinal tract and bone and defective adequate infection control practices, understaffing, and
phagocytic and opsonic function also appear to contribute overcrowding may lead to environmental contamination.
to the severity of disease observed in patients who have In some developing countries, asymptomatic carriage of
sickle cell anemia. Diseases such as leukemia and lym- Salmonella can be high among children attending day
phoma also impair the reticuloendothelial system function. care centers. Outbreaks of salmonellosis in day care cen-
The morbidity and mortality associated with Salmonella ters have been reported, but these are considered rare
infections are also influenced by the serotype that causes events.
the infection. Salmonella choleraesuis is more likely to Although the incidence of salmonellosis related to
cause invasive disease. In one study, 85% of isolates were international travel appears to be decreasing in the
recovered from extraintestinal sites, especially blood. United States, many travel-acquired cases are still re-
(1) Seventy-two percent of patients were younger than ported. Salmonella stanley, a common serotype in
3 years. Pediatric patients were more likely to have diar- Southeast Asia (second most common in Thailand),
rhea than adults. Most of the children with diarrhea were has been frequently isolated in Europe. (5) In South-
also bacteremic. Mycotic aneurysms, a complication ob- east Asia, the serotype is frequently associated with
served in adults, was not detected in any of the pediatric the pork industry.
cases. Of importance, only 21% of children had leukocy- Nontyphoidal Salmonella infections remain a frequent
tosis. Occult bacteremia, where the child presents only cause of invasive disease in many regions of the world, es-
with fever, was a common presentation. pecially in sub-Saharan Africa. Children younger than
In a population-based, case-control study of salmonel- 3 years and those infected with HIV have the greatest
losis in infants younger than 1 year, infected infants were burden. Mortality remains high, especially in children with

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bacteremia and meningitis. Seasonal peaks of disease Nontyphoidal isolates are rarely invasive because most
coincide with the rainy season, which leads to fecal con- do not extend past the lamina propria or the intestinal
tamination of drinking water. In many countries, an as- lymphatic system. However, interactions with host cells
sociation between malaria and Salmonella is well known. in the intestines may lead to a release of proinflammatory
This situation often delays treatment, causing greater cytokines that result in the recruitment of neutrophils to
morbidity and mortality. Frequently, febrile persons are the area, resulting in gastroenteritis. Some genes appear
treated only for malaria without considering the likeli- to play a role in the survival of bacteria within the liver
hood of a coinfection. Clinical features, such as fevers, and spleen and promote the replication within macro-
anemia, and splenomegaly, are frequent findings in both phages. (8)
conditions. Salmonella Typhi is known to adhere to epithelial cells
over the lymphatic Peyer patches, allowing for penetra-
Enteric Fever (Typhoid and Paratyphoid Fever) tion through the intestinal mucosa. Engulfment by
Enteric fever, an infection caused by S Typhi (typhoid macrophages and translocation into draining lymph
fever) or S Paratyphi A, B, or C (paratyphoid fever), is nodes results in bacteremia and subsequent dissemina-
a common cause of death and disease in many parts of tion. The organism survives within the host cells in a Salmo-
the world. Approximately 22 million cases are thought to nella-containing vacuole, assuring its ability to replicate,
occur worldwide each year, with 200,000 deaths as a result. survive, and invade and resulting in the multiplication
(6) Most infections occur in Southern and Southeast Asia. and survival of bacteria within the liver, spleen, and
Parts of Africa and Latin America are also affected but at bone marrow. After an incubation period of 7 to 14 days,
a lower frequency. In Asia, it is estimated that the inci- bacteremia occurs and symptoms emerge. Salmonella
dence approximates 100 cases per 100,000 population. Typhi can be found in the gallstones of individuals
Travelers to endemic regions are at risk. Most cases in who live in endemic regions. Its presence correlates with
the United States have been associated with international fecal shedding, and these people are known to infect
travel. Travelers visiting friends and relatives are at the others.
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 Clinical Aspects
occasions, neonatal infections have been reported. These Nontyphoidal Salmonella Infections
infections are frequently acquired from the mother. In Gastroenteritis is the most frequent presentation. Most
South and Southeast Asia, S Typhi is the most common affected children are younger than 1 year. The usual in-
cause of community-acquired bacteremia. cubation period for Salmonella gastroenteritis is 6 to 12
Between 1960 and 1999, 60 outbreaks of typhoid hours. Nausea, vomiting, and diarrhea are common
fever had been reported in the United States. (7) symptoms. Diarrhea is usually nonbloody. Myalgias, ar-
Ninety percent were domestically acquired. Recently, thralgias, and headaches are also reported. Although ob-
cases were found to be related to the consumption of served in children with Salmonella gastroenteritis, fever,
a fruit shake made from frozen mamey fruit from chills, and abdominal pain are more commonly observed
Guatemala. (7) In recent years, an outbreak of S Para- with shigellosis. The presence of rectal tenesmus accom-
typhi B was found to be related to exposure to pet panied by stools with mucus and/or blood is more dis-
turtles. tinctive of Shigella infections. Symptoms are generally
The major factor responsible for the magnitude of this self-limited. Hepatomegaly and splenomegaly are infre-
problem is poor sanitary infrastructure, resulting in substan- quently noted.
dard drinking water and contaminated food. Person-to- Bacteremia is commonly observed in infants with gas-
person transmission from chronic asymptomatic carriage troenteritis. Most children require hospitalization. Persis-
also contributes to the infection of susceptible individuals tent bacteremia can be detected in approximately 40% of
(eg, typhoid Mary). patients. Salmonella Enteritidis was a frequently isolated
pathogen in bacteremic patients. In children, bacteremia
is rarely fatal. In contrast, one-third of adults presenting
Pathogenesis with primary bacteremia have extraintestinal organ in-
The pathogenesis of salmonellosis is complex. Several vir- volvement and will die.
ulence genes are responsible for the severity of disease ob- Clinical features or laboratory parameters were unable
served with certain species. to detect children more likely to have persistent bacteremia.

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Although focal infections were observed in 2.5% of pre- observed in approximately 15% of patients. Severe dis-
viously healthy children, one-third of children with un- ease resulted in more hospitalizations. Intestinal perfo-
derlying medical conditions had focal disease, consisting ration was a rare complication observed in less than 1%
of meningitis, osteomyelitis, septic arthritis, pneumonia, of children.
or cholangitis. In parts of Africa, the fatality rate for bac- Thrombocytopenia and disseminated intravascular co-
teremia is close to 25%. Lower respiratory tract coinfec- agulation are markers of severe disease. Splenic abscess,
tions with tuberculosis and Streptococcus pneumoniae were brain abscess, and subdural empyema are rare complica-
common. tions of typhoid fever.
Meningitis and musculoskeletal infections are com- An analysis of travel-related cases in the United King-
mon complications in infants younger than 3 months. dom found that S Typhi and S Paratyphi infections were
It is estimated that 50% to 75% of Salmonella meningitis indistinguishable clinically. (10) Infections caused by S
occurs in the first year of life. Asymptomatic disease is also Paratyphi can be just as severe as those caused by S Typhi.
common in young infants. A well-appearing infant with Most patients had normal white blood cell counts (91%),
Salmonella gastroenteritis may be bacteremic. and 82% of patients had an elevated alanine aminotrans-
Malaria has been found to be a risk factor for invasive ferase level. Among travelers, more cases of enteric fever
nontyphoidal Salmonella infections in children. A reduc- were caused by S Paratyphi A than by S Typhi. Guillain-
tion in cases of salmonellosis was associated with a de- Barré syndrome has been described in association with S
crease in the number of malaria cases. Paratyphi A infection.
Compared with children with gastroenteritis Mixed infections with multiple pathogens occur in
alone, bacteremic children appear to have a longer du- endemic tropical countries. Treatment against enteric
ration of symptoms, a less severe clinical appearance, fever should be considered for children with unremit-
and fewer signs of dehydration. This gradual presen- ting fevers after completing adequate antimalarial
tation with less dehydration and fewer toxic effects therapy.
may lead to premature discharges from emergency
departments. Diagnosis
There are no features of Salmonella gastroenteritis that
Typhoid and Paratyphoid Fever would allow its diagnosis based on clinical findings alone.
Fever, gastrointestinal symptoms (eg, vomiting, severe The routine microscopic stool examination for polymor-
diarrhea, abdominal distension, and pain), cough, rel- phonuclear cells is of limited clinical utility because a large
ative bradycardia, rose spots (pink macules frequently number of children with gastroenteritis will have a nega-
observed on the abdomen and chest), and splenomeg- tive test result (<5 polymorphonuclear cells per high-
aly are frequently regarded as features of typhoid and power field). All young infants with diarrhea, especially
paratyphoid fever. However, many patients lack these those younger than 3 months with a positive stool culture
findings, making diagnosis difficult if solely based on result, should have a blood culture performed, even if the
clinical features. In a reported foodborne epidemic, infant is well-appearing. Infants younger than 3 months
most patients had nonspecific symptoms, consisting with a positive blood culture result should undergo a lum-
of fever, headache, diarrhea, and anorexia. Hepato- bar puncture and careful examination assessing for the
megaly was seen in 7% of patients, splenomegaly in presence of musculoskeletal involvement (Table 1).
13% of patients, and rose spots in 5% of patients. Rel- (11) Any ill-appearing infant with a positive stool culture
ative bradycardia and rose spots are seldom observed in result should undergo a blood culture and lumbar punc-
children. Jaundice is frequently observed among chil- ture, be hospitalized, and be treated with parenteral
dren. Febrile convulsions have been reported in chil- antibiotics.
dren with enteric fever and may be the presenting The Widal test, a classic test that measures antibodies
symptom in some children. The incubation period against O and H antigens of S Typhi, was used for the
for enteric fevers is generally 7 to 14 days, with a range diagnosis of typhoid fever. However, its lack of sensitivity
of 3 to 60 days. and specificity has limited its utility. A false-positive test
In Pakistan, children younger than 5 years were result may lead to overtreatment and a delay in consider-
found to have more severe disease. More than 95% of ing other conditions. This outcome is especially likely in
children had fever, 20% to 41% had hepatomegaly, 5% parts of the world where typhoid fever is rare among chil-
to 20% had splenomegaly, 19% to 28% had abdominal dren and significantly less frequent than other bacterial
pain, and 8% to 35% had diarrhea. (9) Cough was pathogens.

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Table 1. Management of Pediatric Salmonella Gastroenteritis


Signs and Symptoms Diagnosis Management
Age <3 months
Diarrhea (dysentery-like, bloody): Obtain stool culture
Obtain blood culture
Diarrhea <5 days, not dysentery-like or bloody No stool culture Hydration
No antibiotics
Febrile Stool culture positive Treat with parenteral antibiotics, 5-7 days
Blood culture negative
Stool culture positive Lumbar puncture
Blood culture positive Treat with parenteral antibiotics:
Bacteremia only: 14 days
Meningitis: 4-6 weeks
Osteomyelitis: 4-6 weeks
History of exposure to Salmonella Obtain stool culture
Obtain blood culture
Age >3 months
Diarrhea ‡5 days: Obtain stool culture
Afebrile Stool culture positive Observation
No antibiotics
Febrile, but non–toxic-appearing Stool culture positive Blood culture
Observe off antibiotics
Toxic, ill-appearing, or Stool culture positive Blood culture
immunocompromised host Lumbar puncture
Treat with parenteral antibiotics
Stool culture positive Lumbar puncture
Blood culture positive 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 first year of life. Pediatric Infectious Disease
Journal. 1988; 7(9):615–621. Copyright 1988 (c) by Wolters Kluwer Health/Williams & Wilkens.

In patients with typhoid fever, blood culture results Treatment


are frequently positive, but stool cultures are less so. Al- Previously healthy children and adults with uncompli-
though liver enzyme levels are frequently elevated, leu- cated gastroenteritis do not require antimicrobial
kocytosis is not always observed. Leukopenia and therapy because the disease is self-limited. Infants
anemia are frequently associated with enteric fevers. A younger than 3 months with Salmonella gastroen-
normal white blood cell count does not rule out inva- teritis should be treated because they have a high
sive disease. Many suggest that bone marrow cultures incidence of extraintestinal complications, such as bac-
have a higher sensitivity. Obtaining this type of speci- teremia, meningitis, and osteomyelitis (Table 1). Antimi-
men is much more invasive and impractical in many cir- crobial therapy may prolong the carrier state. Therapy
cumstances. Approximately 20% of patients may have should be considered for those individuals with high-risk
pneumonia as documented by abnormal radiography medical conditions, such as HIV, sickle cell anemia, and
results. cancer.
Although pathogen-specific serologic and polymerase Antimicrobial treatment must take into account
chain reaction assays are the preferred methods for diag- the local epidemiology and therapeutic practice in
nosing enteric fever, diagnosis is still made using clinical the country where the infection was acquired. Chlor-
criteria in most lower-income countries. Unfortunately, amphenicol, amoxicillin, and the combination of
early features of enteric fever mimic other conditions, trimethoprim and sulfamethoxazole are no longer rec-
such as pneumonia, malaria, sepsis, dengue, acute hepa- ommended as first-line agents for the treatment of en-
titis, and rickettsial infections. teric fevers. The high frequency of treatment failures,

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resistance, and relapse rates has diminished their use- Prevention


fulness. Antimicrobial resistance observed in many Improving the quality of drinking water and food will
countries has influenced the choice of agent for treat- lead to a decrease in Salmonella cases, as will decreasing
ing typhoid and paratyphoid fever. Ceftriaxone re- exposure to high-risk animals (Table 2).
mains the recommended agent in the most severe Routine vaccination of school-age children can be an
cases in which parenteral therapy is indicated. Cefo- important component of a typhoid fever control pro-
taxime is an acceptable alternative. Although fluo- gram in an endemic region. (17) Vaccinating children
roquinolones, such as ciprofloxacin, are generally younger than 2 years living in slums in India with the
associated with high cure rates, defervescence within Vi capsular polysaccharide typhoid vaccine demon-
a week, and lower relapse and fecal carriage rates, iso- strated a 61% protective effectiveness compared with
lates from many Asian countries demonstrate resistance, a placebo. In children age 2 to 5 years, the protective
rendering them ineffective. Azithromycin appears fa- effect was 80%. Of interest, the level of protection was
vorable in the treatment of these infections. (12) Until 44% among unvaccinated members of Vi vaccinee clus-
recently, fluoroquinolone resistance was uncommon in ters. (18) Similar favorable results have been observed in
most regions of Africa. In a recent study from the other countries.
Democratic Republic of the Congo, decreased cipro-
floxacin susceptibility was detected in 15.4% of tested
isolates. (13) Proper hydration, perfusion, and fever
control still remain integral components of treating Preventing Salmonella
Table 2.
enteric fever.
More than 10 years ago, multidrug resistance was un- Infections
common in Latin America. Susceptibility to ampicillin
High-risk animals
was common, and susceptibility to ceftriaxone was almost 1. Parents and children should be counseled about the
universal. At the same time, in some Mediterranean potential risk of acquiring Salmonella when owning
countries, close to one-third of isolates were resistant an iguana, lizard, snake, or turtle.
to ampicillin. 2. Owners need to wash their hands after handling
animals, their cages, or their tanks.
In infections by S choleraesuis, resistance to cipro-
3. Individuals at high risk of severe disease, such as
floxacin was observed in 28% of pediatric cases in children age <5 years and those who are
Taiwan, whereas more than 60% of cases in adults immunocompromised, should avoid contact with
had a resistant strain. (1) Irrespective of age, resis- high-risk animals.
tance to trimethoprim-sulfamethoxazole remained 4. High-risk animals should be kept out of child-care
centers.
high.
5. High-risk animals should not be allowed to roam free
Eighty-four percent of samples of ground meats within the home. They should not be kept in kitchens
(beef, turkey, and pork) purchased at several supermar- or where food is prepared. Cages and tanks should not
kets in the Washington, DC, area were found to be con- be washed in kitchen sinks.
taminated with Salmonella isolates that were resistant to Food handling
at least one antibiotic; 53% were resistant to 3 antibiot- 6. Hand hygiene should be practiced when handling raw
ics. (14) Of greater concern, 16% of the isolates were meat. Cutting boards must be cleaned thoroughly
resistant to ceftriaxone, the drug of choice for the treat- after preparing raw meat and food items that contain
raw egg.
ment of serious infections in children. In a recent
7. People should not consume raw eggs and undercooked
study of invasive salmonellosis among Thai children, meats.
ceftriaxone resistance was detected in 17.4% of iso- 8. Mothers are encouraged to breastfeed young infants.
lates. (15) This practice has shown to reduce infections.
Patients with typhoid fever complicated by delirium, Infection control
obtundation, shock, and coma may benefit from dexa- 9. Young children with enteric fever (Salmonella Typhi
methasone therapy. This adjunctive therapy appears to and Salmonella Paratyphi) should be kept out of child
lower mortality. (16) daycare centers until they have at least 3 consecutive
negative stool culture results.
Relapse rates in children are only 2% to 4% after ther-
10. Infants and children with nontyphoidal Salmonella
apy but have been reported after most regimens. Pro- gastroenteritis can return to child daycare center
longed carrier rates occur in less than 2% of infected once diarrhea has subsided.
children.

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Vaccination against typhoid fever is recommended against paratyphoid fever B has been demonstrated.
for all travelers to developing countries in Asia, (19)(20)
Latin America, and Africa, especially for those plan- Parents and their children need to be counseled about
ning to visit friends and relatives with 2 vaccines the potential risk of acquiring Salmonella if they own
available (Table 3). Travel to India, Pakistan, a high-risk pet, such as an iguana, lizard, snake, or turtle
Mexico, and Bangladesh account for most travel- (Table 2). Owners need to wash their hands after han-
related cases in the United States. Generally, typhoid dling the animals. The Centers for Disease Control and
vaccines are 50% to 80% effective in preventing Prevention has advised that reptiles and amphibians
disease. should be kept out of households with children younger
In many highly endemic countries, S Paratyphi than 5 years. Individuals at high risk of severe disease
causes close to 50% of all cases of enteric fever. In should have no contact with these animals. Reptiles
the United States, most cases of paratyphoid fever and amphibians should be kept out of child care centers
are related to international travel. No effective licensed and households with children younger than 1 year.
vaccine against S Paratyphi is available. However, cross- All documented cases of Salmonella infection must be
protective efficacy of Ty21a oral typhoid vaccine reported to county and state health departments.

Complications and Prognosis


Vaccines Licensed for the Prevention of
Table 3. Ileal perforations in the tropics
Typhoid Fever are frequently considered to be
associated with enteric fever.
Oral typhoid Between 4% and 6% of ileal per-
vaccine Ty21a For persons age ‡6 years forations were associated with S
Live-attenuated
Typhi and S Paratyphi A. In
Series: 4 doses; 1 capsule every other day parts of Africa, 50% of all admis-
(days 0, 2, 4, and 6) sions for typhoid-related ileal
Take with cool water, 1 hour before meal
perforation were in children,
Must complete series at least 1 week before
exposure with close to two-thirds occur-
Capsules must be refrigerated ring between ages 5 and 6 years.
Capsules should not be broken and contents Underdiagnosing milder cases
mixed with food/water because this of enteric fever that resulted
inactivates the vaccine; should not be taken
in delayed or inadequate anti-
with antibiotics
Repeat 4-dose series every 5 years if exposure microbial treatment may have
continues resulted in a higher rate of per-
Contraindicated in individuals with forations.
immunocompromising conditions Fever, vomiting, and abdominal
Potential adverse effects: Nausea,
tenderness and distension are sug-
abdominal pain, cramps, vomiting,
fever, headaches, and rash gestive of ileal perforation. Postop-
Injectable Vi typhoid vaccine erative complications are common,
For persons ‡2 years
Capsular polysaccharide such as surgical wound infection,
Single injection, 0.5 mL, intramuscular, intra-abdominal abscesses, ileus,
deltoid
and reperforation. Mortality is
Vaccine must be administered at least
2 weeks before exposure. high in children: close to 40% in
Thimerosal-free children younger than 5 years
Booster: Every 2 years if exposure and 20% in children older than 5
continues years. (21)
Potential adverse effects: Injection
Rhabdomyolysis with acute renal
site pain, erythema, and induration;
occasional fever and flulike symptoms. failure has been reported as a com-
plication of typhoid fever.

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


Summary Doherty T. Imported enteric fever: case series from the hospital
for tropical diseases, London, United Kingdom. Am J Trop Med
Hyg. 2010;82(6):1121–1126
• On the basis of strong research evidence, exposures to 11. Geme JW III, Hodes HL, Marcy SM, et al. Consensus:
contaminated food, water, and colonized animals are management of Salmonella infection in the first year of life. Pediatr
major risk factors for Salmonella infections. (3)(4)(7)(14) Infect Dis J. 1988;7(9):615–621
• On the basis of research evidence and consensus, 12. Chinh NT, Parry CM, Ly NT, et al. A randomized controlled
infants younger than 3 months with Salmonella comparison of azithromycin and ofloxacin for treatment of multidrug-
gastroenteritis are at an increased risk of resistant or nalidixic acid-resistant enteric fever. Antimicrob Agents
extraintestinal complications, such as bacteremia, Chemother. 2000;44(7):1855–1859
meningitis, and osteomyelitis, and must be treated 13. Lunguya O, Lejon V, Phoba MF, et al. Salmonella Typhi in
regardless of severity of illness. (4)(11) the Democratic Republic of the Congo: fluoroquinolone de-
• On the basis of strong research and epidemiologic creased susceptibility on the rise. PLoS Negl Trop Dis. 2012;6(11):
evidence, antimicrobial resistance is a serious problem e1921
in the treatment of typhoid fever. (12)(13)(14) 14. White DG, Zhao S, Sudler R, et al. The isolation of antibiotic-
• On the basis of strong research evidence, vaccines can resistant salmonella from retail ground meats. N Engl J Med. 2001;
effectively prevent typhoid fever. (17)(18)(19)(20) 345(16):1147–1154
• On the basis of published guidelines and current 15. Punpanich W, Netsawang S, Thippated C. Invasive salmonel-
standards of care, children younger than 5 years and losis in urban Thai children: a ten-year review. Pediatr Infect Dis J.
those with immunocompromising conditions, such as 2012;31(8):e105–e110
human immunodeficiency virus and cancer, should 16. Chisti MJ, Bardhan PK, Huq S, et al. High-dose intravenous
avoid contact with turtles, iguanas, and snakes. (3) dexamethasone in the management of diarrheal patients with
enteric fever and encephalopathy. Southeast Asian J Trop Med
Public Health. 2009;40(5):1065–1073
17. Bhan MK, Bahl R, Bhatnagar S. Typhoid and paratyphoid
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enterica serotype Choleraesuis infections in pediatric patients. effectiveness trial of Vi typhoid vaccine in India. N Engl J Med. 2009;
Pediatrics. 2006;117(6):e1193–e1196 361(4):335–344
2. Cohen JI, Bartlett JA, Corey GR. Extra-intestinal manifestations 19. Pakkanen SH, Kantele JM, Kantele A. Cross-reactive gut-
of salmonella infections. Medicine (Baltimore). 1987;66(5):349–388 directed immune response against Salmonella enterica serovar
3. Chai SJ, White PL, Lathrop SL, et al. Salmonella enterica Paratyphi A and B in typhoid fever and after oral Ty21a typhoid
serotype Enteritidis: increasing incidence of domestically acquired vaccination. Vaccine. 2012;30(42):6047–6053
infections. Clin Infect Dis. 2012;54(suppl 5):S488–S497 20. Wahid R, Simon R, Zafar SJ, Levine MM, Sztein MB. Live oral
4. Jones TF, Ingram LA, Fullerton KE, et al. A case-control study typhoid vaccine Ty21a induces cross-reactive humoral immune
of the epidemiology of sporadic Salmonella infection in infants. responses against Salmonella enterica serovar Paratyphi A and S.
Pediatrics. 2006;118(6):2380–2387 Paratyphi B in humans. Clin Vaccine Immunol. 2012;19(6):
5. Hendriksen RS, Le Hello S, Bortolaia V, et al. Characterization 825–834
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associated with frozen mamey pulp imported from Guatemala to the (5):484–489
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8. Lahiri A, Lahiri A, Iyer N, Das P, Chakravortty D Visiting the bacteremia in previously healthy children: analysis of 199
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Typhoid fever in children: some epidemiological considerations people living in highly endemic areas. J Travel Med. 2009;16
from Karachi, Pakistan. Int J Infect Dis. 2006;10(3):215–222 (1):46–52

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


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infectious diseases salmonella

PIR Quiz
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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) Physician’s 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 6–year–old 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 9–month–old 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 7–month–old girl is traveling with her parents to Pakistan. Which of the following preventive measures is
most 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 they
could do to prevent this from happening again. Which of the following features is an established risk factor for
this 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 following
disorders 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.

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


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

Updated Information & including high resolution figures, can be found at:
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http://pedsinreview.aappublications.org/content/34/9/375#BIBL
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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.

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