Typhoid Fever

What it is

Typhoid fever is a life-threatening bacterial infection caused by Salmonella enterica serotype Typhi, with an estimated 9 million cases and about 110,000 deaths worldwide each year. It is also called enteric fever or typhoid, and it spreads mainly through food or water contaminated with human feces. Humans are the only known reservoir for S. Typhi, which means the infection passes from person to person directly or indirectly through poor sanitation, unsafe water, or contaminated food handling.

Typhoid is still a major public health problem in parts of South Asia, including India, where crowded settings, inconsistent access to safe water, and sanitation gaps can increase transmission. Children and adolescents often carry a high burden, but adults can also become seriously ill. Without treatment, typhoid can cause intestinal bleeding, intestinal perforation, sepsis, and death.

Common symptoms include prolonged fever, headache, weakness, poor appetite, abdominal pain, constipation or diarrhea, and sometimes a faint rash called “rose spots.” The illness can begin gradually over several days. Typhoid and paratyphoid fever look very similar clinically, but typhoid is specifically caused by S. Typhi.

How it works

After a person swallows S. Typhi in contaminated food or water, the bacteria survive the stomach, enter the intestine, and cross into the bloodstream and lymphatic system. They can then spread to the liver, spleen, bone marrow, and gallbladder. This bloodstream spread is why typhoid is considered a systemic infection rather than just a stomach infection.

The incubation period is often about 6 to 30 days, depending on the infectious dose and host factors. Early disease may look nonspecific, with fever and malaise. As the infection progresses, sustained fever becomes more typical, and some people develop abdominal symptoms, cough, enlarged liver or spleen, or altered mental status in severe cases.

A key public health issue is chronic carriage. Some people continue to shed S. Typhi in stool after recovery, especially if the bacteria persist in the gallbladder. These carriers may have no symptoms but can still infect others, which is one reason outbreaks can continue even when obvious cases are treated.

Diagnosis / how it's measured

Typhoid cannot be diagnosed reliably from symptoms alone because malaria, dengue, leptospirosis, viral infections, and other bacterial infections can look similar. Laboratory confirmation is important.

The main diagnostic methods are:

Test	What it shows	Key point
Blood culture	Grows S. Typhi from blood	Best established test early in illness
Bone marrow culture	Detects bacteria in marrow	More sensitive than blood culture, but invasive
Stool culture	Detects intestinal shedding	Can help later in illness or in carriers
Serologic tests such as Widal	Measures antibodies	Limited accuracy; should not be used alone to confirm typhoid

Blood culture is the standard practical test in many settings, especially in the first week of illness, but sensitivity is imperfect and may fall if antibiotics were started before testing. CDC surveillance criteria note that isolation of S. Typhi from blood, stool, or another clinical specimen is required for laboratory confirmation; serology alone is not sufficient.

Routine blood tests may show nonspecific changes such as low or normal white blood cell count, abnormal liver enzymes, or inflammatory markers, but these findings do not confirm the diagnosis. In places where typhoid is common, clinicians may start treatment based on symptoms and local epidemiology while awaiting culture results.

Evidence and uses

The main treatment is antibiotics plus supportive care such as fluids, nutrition, and monitoring for complications. Choice of antibiotic depends on local resistance patterns, severity of illness, travel history, and culture results when available. This matters because antimicrobial resistance in typhoid has become a major problem, including multidrug-resistant and extensively drug-resistant strains in some regions.

Commonly used antibiotic approaches may include:

1. Azithromycin for some uncomplicated cases.
2. Ceftriaxone or another third-generation cephalosporin for more severe disease or when resistance is a concern.
3. Fluoroquinolones only when susceptibility is known, because resistance is now common in many endemic areas.

Treatment should be guided by a clinician. Self-treating with leftover antibiotics or stopping early can increase the risk of treatment failure, relapse, and ongoing transmission.

Prevention is strongly evidence-based and includes safe water, sanitation, hand hygiene, food safety, and vaccination. WHO recommends typhoid conjugate vaccines in endemic settings; these vaccines can be used from 6 months of age, depending on the product, and have been introduced in some national immunization programs. Vaccination is useful but does not replace safe water and sanitation.

For travelers to endemic areas, vaccination lowers risk but is not fully protective. People still need to avoid unsafe water, raw foods washed in unsafe water, and food from unhygienic sources.

When to see a clinician

Seek medical care promptly for fever lasting more than a few days, especially if it is accompanied by abdominal pain, severe weakness, vomiting, diarrhea, constipation, or recent travel to or residence in a typhoid-endemic area. Early treatment reduces the risk of complications.

Urgent evaluation is needed if there are warning signs such as confusion, severe abdominal pain, abdominal swelling, blood in stool, persistent vomiting, dehydration, fainting, or inability to drink fluids. These can suggest severe infection, intestinal bleeding, or perforation.

People diagnosed with typhoid should follow up after treatment if fever returns, symptoms do not improve, or stool testing is advised to check for continued carriage. Food handlers, healthcare workers, and caregivers may need extra public health guidance before returning to work, depending on local rules.

Limitations and open questions

Typhoid remains difficult to control because symptoms overlap with many other febrile illnesses, culture testing is not always available, and resistance patterns change over time. In many low-resource settings, delayed diagnosis and empiric antibiotic use can reduce culture yield and make surveillance less accurate.

Another challenge is antimicrobial resistance. Evidence supports antibiotic treatment, but the best regimen can differ by region and may change quickly as resistance evolves. This means older treatment advice may no longer be appropriate in some areas.

Vaccines are an important advance, but they do not prevent every case and do not solve the underlying drivers of transmission. Long-term control depends on sanitation, safe water systems, food safety, and detection of carriers.

There is also ongoing work to improve rapid diagnostics. Evidence for some commonly used serologic tests is limited, and they may give false-positive or false-negative results. Better point-of-care tests would help clinicians distinguish typhoid from other causes of fever more accurately and earlier in the illness.