Thypoid fever
Typhoid fever, also known as enteric fever, is a potentially fatal
multisystemic illness caused primarily by Salmonella typhi.
The protean manifestations of typhoid fever make this disease
a true diagnostic challenge. The classic presentation includes
fever, malaise, diffuse abdominal pain, and constipation.
Untreated, typhoid fever is a grueling illness that may progress
to delirium, obtundation, intestinal hemorrhage, bowel
perforation, and death within one month of onset.
Survivors may be left with long-term or permanent
neuropsychiatric complications.
Transmission
S typhi has no nonhuman vectors. The following are modes of transmission:
* Oral transmission via food or beverages handled by an individual who
chronically sheds the bacteria through stool or, less commonly, urine
* Hand-to-mouth transmission after using a contaminated toilet and
neglecting hand hygiene
* Oral transmission via sewage-contaminated water or shellfish (especially in
the developing world)3
An inoculum as small as 100,000 organisms causes infection in more than
50% of healthy volunteers.4
Typhoid fever begins 7-14 days after ingestion of S typhi. The fever pattern is
stepwise, characterized by a rising temperature over the course of each day
that drops by the subsequent morning. The peaks and troughs rise
progressively over time.
Over the course of the first week of illness, the notorious gastrointestinal
manifestations of the disease develop. These include diffuse abdominal pain
and tenderness and, in some cases, fierce colicky right upper quadrant pain.
Monocytic infiltration inflames Peyer patches and narrows the bowel lumen,
causing constipation that lasts the duration of the illness. The individual then
develops a dry cough, dull frontal headache, delirium, and an increasingly
stuporous malaise.2
At approximately the end of the first week of illness, the fever plateaus at
103-104°F (39-40°C). The patient develops rose spots, which are salmon-
colored, blanching, truncal, maculopapules usually 1-4 cm wide and fewer
than 5 in number; these generally resolve within 2-5 days.2 These are
bacterial emboli to the dermis and occasionally develop in persons with
shigellosis or nontyphoidal salmonellosis.22
During the second week of illness, the signs and symptoms listed above
progress. The abdomen becomes distended, and soft splenomegaly is
common. Relative bradycardia and dicrotic pulse (double beat, the second
beat weaker than the first) may develop.
In the third week, the still febrile individual grows more toxic and anorexic
with significant weight loss. The conjunctivae are infected, and the patient is
tachypneic with a thready pulse and crackles over the lung bases. Abdominal
distension is severe. Some patients experience foul, green-yellow, liquid
diarrhea (pea soup diarrhea). The individual may descend into the typhoid
state, which is characterized by apathy, confusion, and even psychosis.
Necrotic Peyer patches may cause bowel perforation and peritonitis. This
complication is often unheralded and may be masked by corticosteroids. At
this point, overwhelming toxemia, myocarditis, or intestinal hemorrhage may
cause death.
If the individual survives to the fourth week, the fever, mental state, and
abdominal distension slowly improve over a few days. Intestinal and
neurologic complications may still occur in surviving untreated individuals.
Weight loss and debilitating weakness last months. Some survivors become
asymptomatic S typhi carriers and have the potential to transmit the bacteria
indefinitely.
Differential Diagnoses
Abdominal Abscess
Tuberculosis
Malaria
Dengue Fever
Amebic Hepatic Abscesses Tularemia
Rickettsial diseases
Influenza
Appendicitis Typhus
Toxoplasmosis Leishmaniasis
Brucellosis
Other Problems to Be Considered
Endocarditis
Connective-tissue disease
Lymphoproliferative disorders
complication
Neuropsychiatric manifestations (In the past 2 decades, reports from
disease-endemic areas have documented a wide spectrum of
neuropsychiatric manifestations of typhoid fever.)
A toxic confusional state, characterized by disorientation, delirium, and
restlessness, is characteristic of late-stage typhoid fever. In some cases,
these and other neuropsychiatric features dominate the clinical picture at
an early stage.
Facial twitching or convulsions may be the presenting feature.
Meningismus is not uncommon, but frank meningitis is rare.
Encephalomyelitis may develop, and the underlying pathology may be
that of demyelinating leukoencephalopathy. In rare cases, transverse
myelitis, polyneuropathy, or cranial mononeuropathy develops.
Stupor, obtundation, or coma indicates severe disease.
Focal intracranial infections are uncommon, but multiple brain abscesses
have been reported.57
Other less-common neuropsychiatric manifestations events have
included spastic paraplegia, peripheral or cranial neuritis, Guillain-Barré
syndrome, schizophrenialike illness, mania, and depression.
Respiratory
Cough
Ulceration of posterior pharynx
Occasional presentation as acute lobar pneumonia (pneumotyphoid)
Cardiovascular
Nonspecific electrocardiographic changes occur in 10%-15% of patients
with typhoid fever.
Toxic myocarditis occurs in 1%-5% of persons with typhoid fever and is a
significant cause of death in endemic countries. Toxic myocarditis occurs in
patients who are severely ill and toxemic and is characterized by
tachycardia, weak pulse and heart sounds, hypotension, and
electrocardiographic abnormalities.
Pericarditis is rare, but peripheral vascular collapse without other cardiac
findings is increasingly described. Pulmonary manifestations have also been
reported in patients with typhoid fever.58
Hepatobiliary
Mild elevation of transaminases without symptoms is common in persons
with typhoid fever.
Jaundice may occur in persons with typhoid fever and may be due to
hepatitis, cholangitis, cholecystitis, or hemolysis.
Pancreatitis and accompanying acute renal failure and hepatitis with
hepatomegaly have been reported.
Intestinal manifestations
The 2 most common complications of typhoid fever include intestinal
hemorrhage (12% in one British series) and perforation (3%-4.6% of
hospitalized patients).
From 1884-1909 (ie, preantibiotic era), the mortality rate in patients with
intestinal perforation due to typhoid fever was 66%-90% but is now
significantly lower. Approximately 75% of patients have guarding,
rebound tenderness, and rigidity, particularly in the right lower quadrant.
Diagnosis is particularly difficult in the approximately 25% of patients with
perforation and peritonitis who do not have the classic physical findings.
In many cases, the discovery of free intra-abdominal fluid is the only sign
of perforation.
Genitourinary manifestation
Approximately 25% of patients with typhoid fever excrete S typhi in their
urine at some point during their illness.
Immune complex glomerulitis60 and proteinuria have been reported, and
IgM, C3 antigen, and S typhi antigen can be demonstrated in the
glomerular capillary wall.
Nephritic syndrome may complicate chronic S typhi bacteremia
associated with urinary schistosomiasis.
Nephrotic syndrome may occur transiently in patients with glucose-6-
phosphate dehydrogenase deficiency.
Cystitis: Typhoid cystitis is very rare. Retention of urine in the typhoid
state may facilitate infection with coliforms or other contaminants.
Hematologic manifestations
Subclinical disseminated intravascular coagulation is common in persons
with typhoid fever.
Hemolytic-uremic syndrome is rare.61
Hemolysis may also be associated with glucose-6-phosphate
dehydrogenase deficiency.
Musculoskeletal and joint manifestations
Skeletal muscle characteristically shows Zenker degeneration,
particularly affecting the abdominal wall and thigh muscles.
Clinically evident polymyositis may occur.62
Arthritis is very rare and most often affects the hip, knee, or ankle.
Late sequelae (rare in untreated patients and exceedingly rare in treated
patients)
Neurologic - Polyneuritis, paranoid psychosis, or catatonia63
Cardiovascular - Thrombophlebitis of lower-extremity veins
Genitourinary -Orchitis
Musculoskeletal
Periostitis, often abscesses of the tibia and ribs
Spinal abscess (typhoid spine; very rare)
Prognosis
The prognosis among persons with typhoid fever depends
primarily on the speed of diagnosis and initiation of correct
treatment. Generally, untreated typhoid fever carries a mortality
rate of 10%-20%. In properly treated disease, the mortality rate
is less than 1%.
An unspecified number of patients experience long-term or
permanent complications, including neuropsychiatric symptoms
and high rates of gastrointestinal cancers.
Patient Education
Because vigilant hand hygiene, vaccination, and the avoidance of risky
foods and beverages are mainstays of prevention, educating travelers
before they enter a disease-endemic region is important.
Because the protection offered by vaccination is at best partial, close
attention to personal, food, and water hygiene should be maintained. The
US Centers for Disease Control and Prevention dictum to "boil it, cook it,
peel it, or forget it" is a good rule in any circumstance. If disease occurs
while abroad despite these precautions, one can usually call the US
consulate for a list of recommended doctors.
For excellent patient education resources, visit eMedicine's Public Health
Center. Also, see eMedicine's patient education article Foreign Travel.
