Last updated:
9/30/2025
Years published: 1989, 1990, 2000, 2009, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for the preparation of this report.
Summary
Typhoid fever is a potentially life-threatening infectious disease. The symptoms may include fever, fatigue, malaise and headache, as well as gastrointestinal problems such as diarrhea, abdominal pain, constipation, nausea and increased size of the liver and spleen (hepatosplenomegaly). Without prompt medical treatment with antibiotics, the illness can become severe, leading to serious complications or even death.1,2,3
Typhoid fever is caused by a bacteria known as Salmonella enterica serotype Typhi. It spreads primarily through ingestion of contaminated food or water and remains endemic in areas with poor sanitation. While typhoid is preventable through vaccination and treatable with antibiotics, antimicrobial resistance (AMR) is a growing threat.2,3
While it is rare in United States, as of 2019, typhoid fever affects approximately 9 million people annually and causes around 110,000 deaths worldwide.1,3
Like many other infectious diseases, signs and symptoms may be unspecific. The incubation period is about 10–14 days (range 6–30 days). Typical symptoms of typhoid fever include:
Children present with vomiting, febrile seizures and altered consciousness more frequently than adults.1,3
In severe cases, symptoms include:
Without prompt medical treatment with antibiotics, the illness can become severe, leading to serious complications or even death.
Typhoid fever is caused by Salmonella enterica subspecies enterica serovar Typhi (S. Typhi), a human-specific gram-negative bacillus. Paratyphoid fever, a clinically similar illness, is caused by S. Paratyphi A, B, or C. Transmission occurs via the fecal-oral route through contaminated water, food, or contact with carriers.3
Typhoid fever spreads primarily through the ingestion of food or water contaminated with the Salmonella Typhi bacteria. One of the most common ways this happens is through food or beverages prepared by someone who carries the bacteria without showing symptoms. These individuals, known as chronic carriers, continue to shed the bacteria in their stool, or less commonly, in their urine, over time. If proper hygiene isn’t followed during food preparation, the bacteria can easily be passed on to others. This is especially a concern in areas with limited access to clean water and sanitation, where people may not realize they are consuming contaminated items.3
Another major route of transmission is through poor hand hygiene, particularly after using a contaminated toilet. If someone neglects to wash their hands properly and then touches their mouth, eats, or handles food, they can ingest the bacteria and become infected. In many developing regions, typhoid is also contracted by drinking sewage-contaminated water or eating shellfish from polluted sources. These environmental risks make typhoid fever particularly challenging to control in communities lacking safe water systems and effective waste management.3,4
Typhoid fever is a rare condition in United States but in many countries is very common and remains a heavy burden, especially in some low-income countries. Although the global burden has decreased over the past three decades.
Typhoid incidence was high in Africa and Asia, and among young children, thus affirming an ongoing need to prioritize vaccine and non-vaccine prevention of typhoid fever in this age group and for these regions.4 It is most common in South Asia, Southeast Asia and sub-Saharan Africa.1,3,5,6,7
The highest incidence is among children aged 5–9, but infants and people with immune problems are also at risk. Risk factors for the disease include poor sanitation, unsafe water, use of surface water and lack of hand hygiene facilities.6
Some types of typhoid bacteria have become harder to treat because they no longer respond to the usual antibiotics. These are called drug-resistant strains. In some places, like Pakistan, about 7 out of 10 typhoid cases are caused by a type that resists almost all commonly used antibiotics.2,3
In high-income countries, including the United States, typhoid fever is mainly seen in travelers, especially those visiting friends and relatives in endemic regions.2,3,6,7
The diagnosis of typhoid fever can be confirmed by growing the germ from a blood sample or, in special cases, from the bone marrow (the soft tissue inside bones that makes blood cells). This is called a culture.3
Researchers are developing biomarkers (measurable signals in the blood that indicate infection) and multiplex assays (single tests that check for several germs or markers at once). These tests may improve speed and accuracy in the future.
When treatment can’t wait: In places where typhoid is common (endemic areas), doctors may start empirical treatment, begin antibiotics based on symptoms and risk, after about three days of fever, even if lab confirmation isn’t available yet. This helps prevent complications while testing continues.
The best method for diagnosis is with blood or bone marrow culture.
Treatment
Empiric (symptom-based) antibiotic treatment for typhoid fever should begin as soon as the diagnosis is suspected, especially if a person recently returned from an area where typhoid fever is common or ate food prepared by a known carrier. Starting treatment promptly lowers the risk of complications and death and should not wait for lab confirmation.2,3
When resistance to older antibiotics is common in the place the infection was likely acquired, typical first choices include azithromycin for milder illness, ceftriaxone (an intravenous antibiotic) for more severe illness and a carbapenem such as meropenem when the germ is extensively drug-resistant (XDR).1,2,3,4 XDR means the bacteria resist many standard drugs, so stronger medications are required. In contrast, fluoroquinolones like ciprofloxacin often no longer work in parts of South Asia because the bacteria there have developed resistance.1,2
Most treatment courses last 7–10 days. If the fever has not settled for at least 48 hours or if the person is still febrile after about 5 days, treatment continues, or medicines may be changed based on test results.3,4 Possible complications include a hole in the intestine (intestinal perforation), confusion or agitation (delirium), liver inflammation (hepatitis) and relapse, meaning symptoms return after improvement, occur in up to about 1 in 10 people.1,3 A small number of people (about 1–4%) continue to carry and shed the bacteria after recovery (chronic carriers) and need longer treatment and follow-up stool testing to make sure the infection is cleared.1,2
Antibiotics are the mainstay of care, but supportive measures are also important: fluids, medicines for fever, and, when illness is severe, hospital treatment with intravenous fluids, blood products if needed, and, in selected cases, steroids for serious complications.3,4
Prevention is equally important. Vaccination helps protect against typhoid fever. The World Health Organization recommends typhoid conjugate vaccines (TCVs) for routine childhood use in countries where typhoid is common, effective from 6 months of age, and older “unconjugated” vaccines (ViCPS injection and Ty21a oral capsules) are options for travelers aged ≥2 years and ≥6 years, respectively.1,2,3 Because no vaccine is 100% effective, it remains essential to use safe-water and safe-food practices, wash hands regularly (especially for food handlers and caregivers) and support community measures that improve water, sanitation, and hygiene (WASH) and regulate food safety.1,2
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/
All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
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Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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