Typhoid Fever Clinical Presentation

  • Author: John L Brusch, MD, FACP; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Sep 21, 2011
 

History

A severe nonspecific febrile illness in a patient who has been exposed to S typhi should always raise the diagnostic possibility of typhoid fever (enteric fever).

Classic typhoid fever syndrome

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.[16, 23, 24, 2, 6]

Various presentations of typhoid fever

The clinical course of a given individual with typhoid fever may deviate from the above description of classic disease. 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 one third of immunocompetent adults who develop typhoid fever develop diarrhea rather than constipation. In addition, in some localities, typhoid fever is generally more apt to cause diarrhea 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,[25] meningitis, orchitis, osteomyelitis, and abscesses anywhere on the body.[2]

Table 1. Incidence and Timing of Various Manifestations of Untreated Typhoid Fever[2, 26, 27, 28, 29, 30] (Open Table in a new window)

IncubationWeek 1Week 2Week 3Week 4Post
SystemicRecovery 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 feverVery commonaVery common
Acute high feverVery rareb
ChillsAlmost allc
RigorsUncommon
AnorexiaAlmost all
DiaphoresisVery common
Neurologic
MalaiseAlmost allAlmost allTyphoid state (common)
InsomniaVery common
Confusion/deliriumCommondVery common
PsychosisVery rareCommon
CatatoniaVery rare
Frontal headache



(usually mild)



Very common
Meningeal signsRareeRare
ParkinsonismVery rare
Ear, nose, and throat
Coated tongueVery common
Sore throatf
Pulmonary
Mild coughCommon
Bronchitic coughCommon
RalesCommon
PneumoniaRare (lobar)RareCommon



(basal)



Cardiovascular
Dicrotic pulseRareCommon
MyocarditisRare
PericarditisExtremely rareg
ThrombophlebitisVery rare
Gastrointestinal
ConstipationVery commonCommon
DiarrheaRareCommon (pea soup)
Bloating with tympanyVery common (84%)[30]
Diffuse mild abdominal painVery common
Sharp right lower quadrant painRare
Gastrointestinal hemorrhageVery rare; usually traceVery common
intestinal perforationRare
HepatosplenomegalyCommon
JaundiceCommon
Gallbladder painVery rare
Urogenital
Urinary retentionCommon
HematuriaRare
Renal painRare
Musculoskeletal
MyalgiasVery rare
ArthralgiasVery rare
Rheumatologic
Arthritis (large joint)Extremely rare
Dermatologic
Rose spotsRare
Miscellaneous
Abscess (anywhere)Extremely rareExtremely rareExtremely 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.

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Physical

See History.

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Causes

S typhi and Salmonella paratyphi cause typhoid fever.

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Contributor Information and Disclosures
Author

John L Brusch, MD, FACP  Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

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

Disclosure: Nothing to disclose.

Coauthor(s)

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, and American Society of Law, Medicine & Ethics

Disclosure: Nothing to disclose.

Roberto Corales, DO  Medical Director, Principal Investigator, AIDS Community Health Center

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

Disclosure: Nothing to disclose.

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Martin J Wood, MD †  Former Consulting Staff, Department of Infection and Tropical Medicine, Birmingham Heartlands Hospital, UK

Martin J Wood, MD † is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, American Society for Microbiology, Infectious Diseases Society of America, International Society for Infectious Diseases, and Royal College of Physicians

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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Life cycle of Salmonella typhi.
Table 1. Incidence and Timing of Various Manifestations of Untreated Typhoid Fever[2, 26, 27, 28, 29, 30]
IncubationWeek 1Week 2Week 3Week 4Post
SystemicRecovery 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 feverVery commonaVery common
Acute high feverVery rareb
ChillsAlmost allc
RigorsUncommon
AnorexiaAlmost all
DiaphoresisVery common
Neurologic
MalaiseAlmost allAlmost allTyphoid state (common)
InsomniaVery common
Confusion/deliriumCommondVery common
PsychosisVery rareCommon
CatatoniaVery rare
Frontal headache



(usually mild)



Very common
Meningeal signsRareeRare
ParkinsonismVery rare
Ear, nose, and throat
Coated tongueVery common
Sore throatf
Pulmonary
Mild coughCommon
Bronchitic coughCommon
RalesCommon
PneumoniaRare (lobar)RareCommon



(basal)



Cardiovascular
Dicrotic pulseRareCommon
MyocarditisRare
PericarditisExtremely rareg
ThrombophlebitisVery rare
Gastrointestinal
ConstipationVery commonCommon
DiarrheaRareCommon (pea soup)
Bloating with tympanyVery common (84%)[30]
Diffuse mild abdominal painVery common
Sharp right lower quadrant painRare
Gastrointestinal hemorrhageVery rare; usually traceVery common
intestinal perforationRare
HepatosplenomegalyCommon
JaundiceCommon
Gallbladder painVery rare
Urogenital
Urinary retentionCommon
HematuriaRare
Renal painRare
Musculoskeletal
MyalgiasVery rare
ArthralgiasVery rare
Rheumatologic
Arthritis (large joint)Extremely rare
Dermatologic
Rose spotsRare
Miscellaneous
Abscess (anywhere)Extremely rareExtremely rareExtremely 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, 32, 33, 34]
IncubationWeek 1Week 2Week 3Week 4
Bone marrow aspirate (0.5-1 mL)90% (may decrease after 5 d of antibiotics)
Blood (10-30 mL), stool, or duodenal aspirate culture40%-80%~20%Variable (20%-60%)
Urine25%-30%, timing unpredictable
Table 3. Antibiotic Recommendations by Origin and Severity
LocationSeverityFirst-Line AntibioticsSecond-Line Antibiotics
South Asia, East Asia[45]



[48, 40]



UncomplicatedCefixime POAzithromycin PO
ComplicatedCeftriaxone IV or



Cefotaxime IV



Aztreonam IV or



Imipenem IV



Eastern Europe, Middle East, sub-Saharan Africa, South America[46, 49] UncomplicatedCiprofloxacin PO or



Ofloxacin PO



Cefixime PO or



Amoxicillin PO or



TMP-SMZ PO



or Azithromycin PO



ComplicatedCiprofloxacin IV or



Ofloxacin IV



Ceftriaxone IV or



Cefotaxime IV or



Ampicillin IV



or



TMP-SMZ IV



Unknown geographic origin or Southeast Asia[50, 45]



[48, 40, 46, 49]



UncomplicatedCefixime PO plus



Ciprofloxacin PO or



Ofloxacin PO



Azithromycin PO*
ComplicatedCeftriaxone IV or



Cefotaxime IV, plus



Ciprofloxacin IV or



Ofloxacin IV



Aztreonam IV or



Imipenem IV, plus



Ciprofloxacin IV



or



Ofloxacin IV



*Note that the combination of azithromycin and fluoroquinolones is not recommended because it may cause QT prolongation and is relatively contraindicated.
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