History

Classic typhoid fever syndrome

S typhi and paratyphi are clinically indistinguishable from each other. Symptoms of disease develop 7-14 days after ingestion of the organism. The peaks and troughs of fever rise progressively in stepwise fashion.

Over the course of the first week of illness, a wide variety gastrointestinal symptoms of the disease develop. These include diffuse abdominal pain and tenderness and, in some cases, fierce colicky right upper quadrant pain.Inflamed Peyer patches narrow the bowel lumen to the point of causing significant constipation that may persist for the duration of the illness. If untreated the individual may develop a dry cough, dull frontal headache, delirium, and severe malaise associated with marked stupor.^[2]

Seven to 10 days into the illness, the fever plateaus at 103-104°F (39-40°C). The patient develop Rose Spots, salmon-colored, blanching, truncal, maculopapules that are 1-4 cm wide and fewer than 5 in number. These generally resolve within 2-5 days.^[2] They are caused by bacterial emboli to the dermis Occsasionally , they may be seen in cases of Shigellosis or nontyphoidal Salmonellosis.^[29]

During the second week, 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 lead to 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.^{[2, 4, 22, 30, 31]}

Various presentations of typhoid fever

The clinical course of an untreated patient with typhoid fever may deviate from that describe above . The timing of the symptoms and host response may vary based on geographic region, race factors, and the infecting bacterial strain. The stepladder fever pattern that was once the hallmark of typhoid fever now occurs in as few as 12% of cases. In most contemporary presentations of typhoid fever, the fever has a steady insidious onset.

Young children, individuals with AIDS, and at least one third of immunocompetent adults who develop typhoid fever develop diarrhea rather than constipation.

Atypical manifestations of typhoid fever include isolated severe headaches that may mimic meningitis, acute lobar pneumonia, isolated arthralgias, urinary symptoms, severe jaundice, or fever alone. Some patients, especially in India and Africa, present primarily with neurologic manifestations such as delirium or, in extremely rare cases, parkinsonian symptoms or Guillain-Barré syndrome. Other unusual complications include pancreatitis,^[32]meningitis, orchitis, osteomyelitis, and abscesses anywhere on the body.^[2]

Table 1. Incidence and Timing of Various Manifestations of Untreated Typhoid Fever^{[2, 33, 34, 35, 36, 37]} (Open Table in a new window)

	Incubation	Week 1	Week 2	Week 3	Week 4	Post
Systemic					Recovery phase or death (15% of untreated cases)	10%-20% relapse; 3%-4% chronic carriers; long-term neurologic sequelae (extremely rare); gallbladder cancer (RR=167; carriers)
Stepladder fever pattern or insidious onset fever		Very common^a	Very common
Acute high fever		Very rare^b
Chills		Almost all^c
Rigors		Uncommon
Anorexia		Almost all
Diaphoresis		Very common
Neurologic
Malaise		Almost all	Almost all	Typhoid state (common)
Insomnia			Very common
Confusion/delirium		Common^d	Very common
Psychosis		Very rare	Common
Catatonia		Very rare
Frontal headache (usually mild)		Very common
Meningeal signs		Rare^e	Rare
Parkinsonism		Very rare
Ear, nose, and throat
Coated tongue		Very common
Sore throat^f
Pulmonary
Mild cough		Common
Bronchitic cough		Common
Rales		Common
Pneumonia		Rare (lobar)	Rare	Common (basal)
Cardiovascular
Dicrotic pulse		Rare	Common
Myocarditis		Rare
Pericarditis		Extremely rare^g
Thrombophlebitis				Very rare
Gastrointestinal
Constipation		Very common	Common
Diarrhea		Rare	Common (pea soup)
Bloating with tympany		Very common (84%)^[37]
Diffuse mild abdominal pain		Very common
Sharp right lower quadrant pain		Rare
Gastrointestinal hemorrhage		Very rare; usually trace	Very common
intestinal perforation				Rare
Hepatosplenomegaly		Common
Jaundice		Common
Gallbladder pain		Very rare
Urogenital
Urinary retention		Common
Hematuria		Rare
Renal pain		Rare
Musculoskeletal
Myalgias	Very rare
Arthralgias	Very rare
Rheumatologic
Arthritis (large joint)	Extremely rare
Dermatologic
Rose spots		Rare
Miscellaneous
Abscess (anywhere)		Extremely rare	Extremely rare	Extremely rare
^a Very common: Symptoms occur in well over half of cases (approximately 65%-95%). ^b Very rare: Symptoms occur in less than 5% of cases. ^c Almost all: Symptoms occur in almost all cases. ^d Common: Symptoms occur in 35%-65% of cases. ^e Rare: Symptoms occur in 5%-35% of cases. ^f Blank cells: No mention of the symptom at that phase was found in the literature. ^g Extremely rare: Symptoms have been described in occasional case reports.

Treated typhoid fever

If appropriate treatment is initiated within the first few days of full-blown illness, the disease begins to remit after about 2 days, and the patient's condition markedly improves within 4-5 days. Any delay in treatment increases the likelihood of complications and recovery time.

Physical

See History.

Causes

S typhi and Salmonella paratyphi cause typhoid/enteric fever.

Physical Examination

See History.

Complications

See History.

Differential Diagnoses

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Life cycle of Salmonella typhi.

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Table 1. Incidence and Timing of Various Manifestations of Untreated Typhoid Fever ^{[2, 33, 34, 35, 36, 37]}

	Incubation	Week 1	Week 2	Week 3	Week 4	Post
Systemic					Recovery phase or death (15% of untreated cases)	10%-20% relapse; 3%-4% chronic carriers; long-term neurologic sequelae (extremely rare); gallbladder cancer (RR=167; carriers)
Stepladder fever pattern or insidious onset fever		Very common^a	Very common
Acute high fever		Very rare^b
Chills		Almost all^c
Rigors		Uncommon
Anorexia		Almost all
Diaphoresis		Very common
Neurologic
Malaise		Almost all	Almost all	Typhoid state (common)
Insomnia			Very common
Confusion/delirium		Common^d	Very common
Psychosis		Very rare	Common
Catatonia		Very rare
Frontal headache (usually mild)		Very common
Meningeal signs		Rare^e	Rare
Parkinsonism		Very rare
Ear, nose, and throat
Coated tongue		Very common
Sore throat^f
Pulmonary
Mild cough		Common
Bronchitic cough		Common
Rales		Common
Pneumonia		Rare (lobar)	Rare	Common (basal)
Cardiovascular
Dicrotic pulse		Rare	Common
Myocarditis		Rare
Pericarditis		Extremely rare^g
Thrombophlebitis				Very rare
Gastrointestinal
Constipation		Very common	Common
Diarrhea		Rare	Common (pea soup)
Bloating with tympany		Very common (84%)^[37]
Diffuse mild abdominal pain		Very common
Sharp right lower quadrant pain		Rare
Gastrointestinal hemorrhage		Very rare; usually trace	Very common
intestinal perforation				Rare
Hepatosplenomegaly		Common
Jaundice		Common
Gallbladder pain		Very rare
Urogenital
Urinary retention		Common
Hematuria		Rare
Renal pain		Rare
Musculoskeletal
Myalgias	Very rare
Arthralgias	Very rare
Rheumatologic
Arthritis (large joint)	Extremely rare
Dermatologic
Rose spots		Rare
Miscellaneous
Abscess (anywhere)		Extremely rare	Extremely rare	Extremely rare
^a Very common: Symptoms occur in well over half of cases (approximately 65%-95%). ^b Very rare: Symptoms occur in less than 5% of cases. ^c Almost all: Symptoms occur in almost all cases. ^d Common: Symptoms occur in 35%-65% of cases. ^e Rare: Symptoms occur in 5%-35% of cases. ^f Blank cells: No mention of the symptom at that phase was found in the literature. ^g Extremely rare: Symptoms have been described in occasional case reports.

Table 2. Sensitivities of Cultures ^{[2, 39, 40, 41]}

	Incubation	Week 1	Week 2	Week 3	Week 4
Bone marrow aspirate (0.5-1 mL)		90% (may decrease after 5 d of antibiotics)
Blood (10-30 mL), stool, or duodenal aspirate culture	40%-80%		~20%	Variable (20%-60%)
Urine		25%-30%, timing unpredictable

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Author

John L Brusch, MD, FACP Corresponding Faculty Member, Harvard Medical School

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Roberto Corales, DO, AAHIVS Senior Director, HIV Medicine and Clinical Research, Trillium Health

Roberto Corales, DO, AAHIVS is a member of the following medical societies: American Medical Association, International AIDS Society, American Osteopathic Association

Disclosure: Nothing to disclose.

Steven K Schmitt, MD Staff Physician, Department of Infectious Disease, Cleveland Clinic

Steven K Schmitt, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Thomas Garvey, MD, JD † Primary Care Physician, Burlington Medical Associates; Co-Chair, Medical Advisory Committee For the Elimination of Tuberculosis

Thomas Garvey, MD, JD is a member of the following medical societies: American College of Legal Medicine, American College of Physicians, American Society of Law, Medicine & Ethics

Disclosure: Nothing to disclose.