|
A systemic disease caused by S.
typhi and characterized by fever, prostration, abdominal pain and a
rose-colored rash.
Epidemiology
and Pathology
About 400 to 500 cases of typhoid
fever are reported annually in the USA. Typhoid bacilli are shed in the
feces of asymptomatic carriers or in the stool or urine of those with
active disease. Inadequate hygiene after defecation may spread S. typhi to
communal food or water supplies. In endemic areas where sanitary measures
are generally inadequate, S. typhi is transmitted more frequently by water
than by food. In developed countries, transmission is chiefly by food that
has been contaminated by healthy carriers during preparation. Flies may
spread the organism from feces to food. Occasional transmission by direct
contact (anal-oral route) may occur in children during play and in adults
during sexual practices. Rarely, hospital personnel who have not taken
adequate enteric precautions have acquired the disease when changing
soiled bedclothes.
The organism enters the body via the
GI tract and gains access to the bloodstream via the lymphatic channels.
Monocytic inflammation occurs in the ileum and colon, within the lamina
propria and Peyer's patches, where local tissue necrosis is common.
Ulceration, hemorrhage, and intestinal perforation may result in severe
cases.
About 3% of untreated patients shed
organisms in their stool for > 1 yr and are referred to as chronic
enteric carriers. Some carriers have no history of clinical illness and
apparently were asymptomatically infected. Obstructive uropathy related to
schistosomiasis may predispose certain typhoid patients to developing a
urinary carrier state. Most of the estimated 2000 carriers in the USA are
elderly women with chronic biliary disease. Epidemiologic data indicate
that typhoid carriers are more likely than the general population to
acquire hepatobiliary cancer.
Symptoms
and Signs
The incubation period (usually 8 to
14 days) is inversely related to the number of organisms ingested. Onset
is usually gradual, with fever, headache, arthralgias, pharyngitis,
constipation, anorexia, and abdominal pain and tenderness. Less common
symptoms include dysuria, nonproductive cough, and epistaxis.
If no therapy is begun, the
temperature rises in steps over 2 to 3 days, remains elevated (usually to
39.4 to 40° C [103 to 104° F]) for another 10 to 14 days, begins to fall
gradually at the end of the 3rd wk, and reaches normal levels during the
4th wk. Prolonged fever is often accompanied by relative bradycardia and
prostration, and CNS symptoms such as delirium, stupor, or coma occur in
severe cases. In about 10% of patients, discrete pink, blanching lesions
(rose spots) appear in crops on the chest and abdomen during the 2nd wk
and resolve in 2 to 5 days. Intestinal perforation, usually involving the
distal ileum, occurs in 1 to 2% of patients. An acute abdomen and
leukocytosis during the 3rd wk of illness may suggest perforation.
Splenomegaly, leukopenia, anemia, liver function abnormalities,
proteinuria, and a mild consumption coagulopathy are common. Acute
cholecystitis and hepatitis may occur. Late in the disease, when
intestinal lesions are most prominent, florid diarrhea may occur, and the
stool may contain blood (20% occult, 10% gross). In about 2% of patients,
severe bleeding occurs during the 3rd wk, with a mortality rate of about
25%. Pneumonia may develop during the 2nd or 3rd wk and is usually due to
pneumococcal infection, although S. typhi can also cause infiltrates.
Atypical presentations such as pneumonitis, fever only, or symptoms
consistent with UTI may delay diagnosis. Convalescence may last several
months. In addition, bacteremia occasionally leads to focal infections
such as osteomyelitis, endocarditis, meningitis, soft tissue abscesses,
glomerulitis, or GU tract involvement.
In 8 to 10% of untreated patients,
symptoms and signs similar to the initial clinical syndrome may recur
about 2 wk after defervescence. For unclear reasons, antibiotic therapy
during the initial illness increases the incidence of febrile relapse to
15 to 20%. If antibiotic therapy is reinstituted at the time of relapse,
the fever abates rapidly, unlike the slow defervescence seen during the
primary illness. Occasionally, a second relapse occurs.
Diagnosis
Diagnosis is ultimately based on
isolation of typhoid bacilli in cultures, although the clinical setting
and hematologic abnormalities may suggest typhoid fever. Typhoid bacilli
are usually isolated from cultures of blood or bone marrow only during the
first 2 wk of illness, while stool cultures are usually positive during
the 3rd to 5th wk. Urine cultures are often positive. Cultures of liver
biopsies or rose spots may also yield the organism.
Typhoid bacilli contain antigens (O
and H) that stimulate the host to form corresponding antibodies. A
fourfold rise in O and H antibody titers in paired specimens acquired 2 wk
apart suggests S. typhi infection. However, this test (Widal's
agglutination reaction) is only moderately sensitive (30% of
culture-proven cases have negative tests) and lacks specificity (many
nontyphoidal Salmonella strains have cross-reacting O and H antigens;
cirrhosis is associated with nonspecific antibody production, causing a
falsely positive Widal's reaction). Tests such as an enzyme immunoassay
for detection of S. typhi antigens in the serum or urine early in the
course of the illness are under study.
Differential diagnosis includes
other Salmonella infections causing enteric fever, the major rickettsioses,
leptospirosis, disseminated TB, malaria, brucellosis, tularemia,
infectious hepatitis, psittacosis, Yersinia enterocolitica infection, and
lymphoma. Early in its clinical course, typhoid fever may resemble viral
URI or UTI.
Prognosis
Without antibiotics, the mortality
rate is about 12%; with prompt therapy the mortality rate is < 1%.
Most deaths occur in malnourished persons, infants, and the elderly.
Stupor, coma, or shock reflects severe disease and a poor prognosis.
Complications occur mainly in patients who are untreated or in whom
treatment is delayed.
Prophylaxis
For prevention, drinking water
should be purified, sewage should be effectively disposed of, milk should
be pasteurized, chronic carriers should avoid food handling, and adequate
patient isolation precautions should be implemented. Special attention to
enteric precautions is important. Travelers in endemic areas should avoid
eating raw leafy vegetables, other foods stored or served at room
temperature, and unbottled water. Unless water is known to be safe, it
should be boiled or chlorinated before drinking.
A live, attenuated oral typhoid
vaccine is available (Ty21a strain) and is about 70% effective. It is
administered every other day for a total of 4 doses. Because the vaccine
contains living S. typhi organisms, it is contraindicated in patients who
are immunosuppressed. In the USA, the Ty21a vaccine is not approved for
children < 6 yr. An alternative is the single dose, parenteral Vi
polysaccharide vaccine, which is 64 to 72% effective and is well
tolerated. This vaccine is given as a single IM injection.
Treatment
Antibiotics markedly decrease the
severity and duration of illness and also reduce complications and
mortality. Ceftriaxone and cefoperazone are first-choice drugs.
Ceftriaxone is given 30 mg/kg/day IM or IV in 2 divided doses for 2 wk (eg,
1 g IV q 12 h for adults), and cefoperazone is given 60 mg/kg/day IV in 2
divided doses for 2 wk. Chloramphenicol is still widely used throughout
the world, but resistance is increasing. Quinolones may be helpful. They
might be used as follow-up oral therapy (eg, ciprofloxacin 500 mg po q 12
h) after initial parenteral therapy with a 3rd-generation cephalosporin.
Quinolones are not recommended in prepubertal children. An alternative
therapy, depending on in vitro sensitivity, is ampicillin 100 mg/kg/day IV
or IM in 4 divided doses for 14 days.
Glucocorticoids may be used to treat
severe toxicity in addition to antibiotics. Defervescence and clinical
improvement usually follow. Prednisone 20 to 40 mg/day po (or equivalent)
for the first 3 days of treatment usually suffices. Higher doses of
glucocorticoids (dexamethasone 3 mg/kg IV initially, followed by 1 mg/kg q
6 h for 48 h total) are used in patients with marked delirium, coma, or
shock.
As supportive measures, nutrition
should be maintained with frequent feedings. Patients are generally kept
on bed rest while febrile. Salicylates (which may cause hypothermia and
hypotension), as well as laxatives and enemas, should be avoided. Diarrhea
may be minimized with a clear liquid diet and, if necessary, parenteral
nutrition. Fluid and electrolyte therapy and blood replacement may be
needed.
Intestinal perforation and
associated peritonitis call for broader gram-negative and anaerobic
antibiotic coverage. Surgical intervention plus antibiotics is preferred
in treating perforation, although medical therapy alone has been
moderately successful.
Relapses are treated the same as the
initial illness, although duration of antibiotic therapy seldom needs to
be > 5 days.
Carriers must be reported to the
local health department and prohibited from handling food. Typhoid bacilli
may be isolated for as long as 3 to 6 mo after the acute illness in
persons who do not become carriers; thereafter, three negative stool
cultures at weekly intervals must be acquired to exclude a carrier state.
In carriers with normal biliary tracts, the cure rate is about 60% with
antibiotics such as ampicillin 1.5 g po or IV qid for 6 wk or amoxicillin
2 g po tid for 4 wk. Probenecid 0.5 g po qid may be given with ampicillin.
In some carriers with gallbladder disease, eradication has been achieved
with TMP-SMX and rifampin. In other cases, cholecystectomy with 1 to 2
days of preoperative and 2 to 3 wk of postoperative antibiotics (ampicillin
6 g/day IV in 4 divided doses) usually cures the carrier state.
|
|
The epidemiology of the other
salmonelloses is similar to but more complicated than that of typhoid
fever, since disease may also occur in humans by direct and indirect
contact with numerous species of infected animals, the foodstuffs derived
from them, and their excreta. Infected meat-producing animals, poultry,
raw milk, eggs, and egg products are common sources of Salmonella. Other
reported sources include infected pet turtles, carmine red dye, and
contaminated marijuana.
Subtotal gastrectomy, achlorhydria
(or ingestion of antacids), sickle cell anemia, splenectomy, louse-borne
relapsing fever, malaria, bartonellosis, cirrhosis, leukemia, lymphoma,
and HIV infection predispose to Salmonella infection. Except for typhoid
fever, Salmonella enteritidis infections remain a significant public
health problem in the USA. Many serotypes of S. enteritidis have been
given names and are referred to informally as if they were separate
species, even though they are not. The most common Salmonella serotypes in
the USA include S. typhimurium, S. heidelberg, S. newport, S. infantis, S.
agona, S. montevideo, and S. saint-paul.
Symptoms
and Signs
Salmonella infection may present
clinically as gastroenteritis, enteric fever, a bacteremic syndrome, or
focal disease. Each Salmonella serotype can produce any or all of the
clinical syndromes described below, although a given serotype is often
associated with a specific syndrome. An asymptomatic carrier state may
also occur.
Gastroenteritis usually starts 12 to
48 h after ingestion of organisms with nausea and crampy abdominal pain,
followed by diarrhea, fever, and sometimes vomiting. Usually the stool is
watery but may be paste-like semisolid. Rarely, mucus or blood is present.
The disease is usually mild, lasting 1 to 4 days. Occasionally, a more
severe, protracted illness occurs. In stool specimens stained with
methylene blue, WBCs are often seen, indicating inflammatory colitis.
Diagnosis is confirmed by culturing Salmonella from stool specimens or
rectal swabs.
Enteric fever is a systemic syndrome
characterized by fever, prostration, and septicemia. The prototype,
typhoid fever, is described above. An identical presentation, although
often less severe, is caused by S. paratyphi A, B, and C.
Focal manifestations of Salmonella
infection may occur with or without sustained bacteremia. In patients with
bacteremia, localized infection may occur, involving the GI tract (liver,
gallbladder and appendix), endothelial surfaces (atherosclerotic plaques,
ileofemoral or aortic aneurysms, heart valves), pericardium, meninges,
lungs, joints, bones, GU tract, or soft tissues. Preexisting solid tumors
will occasionally be seeded and develop abscesses that may, in turn,
become a source of Salmonella bacteremia. S. choleraesuis and S.
typhimurium are the most common causes of focal infection.
Bacteremia is relatively uncommon in
patients with gastroenteritis. However, S. choleraesuis, S. typhimurium,
and S. heidelberg, among others, can cause a sustained bacteremic syndrome
lasting >= 1 wk. Although blood cultures are positive, stool cultures
are generally negative. Patients with AIDS or HIV infection may have
recurrent episodes of bacteremia or other invasive infections (eg, septic
arthritis) due to Salmonella. Multiple Salmonella infections in a patient
without other risk factors should prompt HIV testing.
Carriers do not appear to play a
major role in large outbreaks of nontyphoidal gastroenteritis. Persistent
shedding of organisms in the stool for >= 1 yr occurs in only 0.2 to
0.6% of patients with nontyphoidal Salmonella infections.
Diagnosis is made by isolating the
organism from stool or another infected site. The prognosis is usually
good, unless severe underlying disease is present.
Prophylaxis
and Treatment
Preventing contamination of
foodstuffs by infected animals and humans is paramount. Poultry, meat,
eggs, and other foods must be properly cooked, handled, stored, and
refrigerated. Infected animals (eg, pet reptiles) and potentially
contaminated substances (eg, carmine red dye) must be identified and
controlled. The preventive measures for travelers discussed under Typhoid
Fever, above, also apply to most other enteric infections. Case
reporting is essential.
Gastroenteritis is treated
symptomatically with fluids and bland diet (see Shigellosis,
below, and General Principles of Treatment).
Antibiotics prolong excretion of the organism and are unwarranted in
uncomplicated cases. Because of increased mortality, elderly nursing home
residents, infants, and patients with HIV infection or AIDS should be
treated with antibiotics. Antibiotic resistance is even more common with
nontyphoidal Salmonella than with S. typhi. TMP-SMX, 5 mg/kg of TMP
component po every 12 h for children, or ciprofloxacin 500 mg po q 12 h
for adults, is an acceptable regimen. Nonimmunocompromised patients should
be treated for 3 to 5 days, but those with AIDS may require prolonged
suppression to prevent relapses. Systemic or focal disease should be
treated with antibiotic doses as outlined above for typhoid fever.
Sustained bacteremia is generally treated for 4 to 6 wk. Abscesses should
be drained surgically; at least 4 wk of antibiotic therapy should follow
surgery. Infected aneurysms, heart valves, and bone or joint infections
usually require surgical intervention and prolonged courses of
antibiotics.
Asymptomatic carriage is usually
self-limited, and antibiotic treatment is rarely required. Antibiotics can
prolong the shedding of organisms in the stool after the drug has been
discontinued. In unusual cases (eg, in food handlers or health care
workers), eradication may be attempted with ciprofloxacin 500 mg po q 12 h
for 1 mo, but follow-up stool cultures should be obtained in the weeks
after drug administration to document elimination of Salmonella.
|