Typhoid Fever: Symptoms, Causes & Treatment

What Is Typhoid Fever?

Typhoid fever is a serious bacterial infection caused by Salmonella enterica serotype Typhi (S. typhi). The bacteria spread through contaminated water and food, causing high fever, headache, muscle pain, and gastrointestinal symptoms. Without treatment, the infection can progress to sepsis and be fatal.

Typhoid fever, also known as enteric fever, is one of the most significant bacterial infections affecting travelers and populations in developing countries. The disease has plagued humanity for centuries, with historical outbreaks causing widespread mortality before the advent of modern sanitation and antibiotics. Today, typhoid fever remains a major public health concern, particularly in regions with inadequate water treatment and sanitation infrastructure.

The causative bacterium, Salmonella typhi, is uniquely adapted to human hosts. Unlike other Salmonella species that infect various animals, S. typhi only infects humans, which has important implications for disease transmission and control. When ingested through contaminated food or water, the bacteria penetrate the intestinal wall and enter the bloodstream, causing a systemic infection that can affect multiple organ systems.

The global burden of typhoid fever is substantial, with the World Health Organization estimating 11 to 21 million cases and 128,000 to 161,000 deaths annually. The highest incidence occurs in South Asia (particularly India, Pakistan, and Bangladesh), Southeast Asia, and sub-Saharan Africa. In developed countries, cases are almost exclusively travel-related, making it essential for travelers to endemic regions to understand prevention strategies.

Typhoid vs. Paratyphoid Fever

A related but distinct condition called paratyphoid fever is caused by Salmonella paratyphi A, B, or C. While the symptoms are similar, paratyphoid fever is generally milder than typhoid fever. Both conditions are collectively referred to as "enteric fever." The diagnostic tests and treatments are largely the same, though the epidemiology and geographic distribution may differ slightly.

What Causes Typhoid Fever?

Typhoid fever is caused by the bacterium Salmonella enterica serotype Typhi. Transmission occurs through the fecal-oral route, primarily via contaminated water or food prepared by infected individuals. The bacteria can survive in water for weeks and in contaminated food at room temperature.

Understanding the transmission mechanisms of typhoid fever is essential for effective prevention. The bacterium S. typhi is shed in the feces and, less commonly, the urine of infected individuals. When sanitation is inadequate, human waste can contaminate water supplies, crops irrigated with contaminated water, or food handled by infected individuals with poor hand hygiene.

Several factors contribute to the spread of typhoid fever. Water contamination occurs when sewage systems fail or are non-existent, allowing bacteria to enter drinking water sources. In many endemic areas, untreated sewage flows into rivers and streams used for drinking water, bathing, and irrigation. Additionally, the practice of using human waste as fertilizer (night soil) in some agricultural settings can introduce bacteria directly onto crops consumed raw.

Food-borne transmission represents another major pathway. Fruits and vegetables can become contaminated through irrigation with contaminated water or handling by infected food preparers. Shellfish harvested from waters contaminated with sewage may harbor the bacteria. Street food vendors in endemic areas may lack access to clean water for handwashing, increasing transmission risk. The bacteria can also survive in dairy products, particularly unpasteurized milk.

Chronic Carriers

An important aspect of typhoid epidemiology is the phenomenon of chronic carriage. Approximately 2-5% of people who recover from typhoid fever become long-term carriers, continuing to shed bacteria in their feces for months or even years without experiencing symptoms themselves. These carriers can unknowingly transmit the disease to others, particularly if they work in food preparation. The most famous historical example is "Typhoid Mary" (Mary Mallon), a cook in early 20th century New York who infected dozens of people while remaining asymptomatic herself.

The bacteria establish chronic infection by colonizing the gallbladder, where they can persist indefinitely. Gallstones provide a particularly favorable environment for bacterial attachment and persistence. Treatment of chronic carriage typically requires prolonged antibiotic therapy and sometimes surgical removal of the gallbladder (cholecystectomy) in cases that do not respond to antibiotics.

What Are the Symptoms of Typhoid Fever?

Typhoid fever symptoms develop gradually over 1-3 weeks and include sustained high fever (39-40°C/102-104°F), severe headache, muscle pain, constipation followed by diarrhea, abdominal pain, confusion, and characteristic rose-colored spots on the chest. Without treatment, symptoms can persist for weeks and progress to life-threatening complications.

The clinical presentation of typhoid fever follows a characteristic pattern, though individual cases may vary significantly. The incubation period typically ranges from 10 to 14 days but can be as short as 3 days or as long as 60 days, depending on the number of bacteria ingested. Higher infectious doses generally lead to shorter incubation periods and more severe disease.

The first week of illness is characterized by gradually increasing fever, which rises in a stepwise pattern over several days to reach 39-40°C (102-104°F). Unlike many other infections where fever fluctuates, typhoid fever typically causes sustained high fever that remains elevated throughout the day. Accompanying symptoms include severe frontal headache, malaise, muscle aches, and loss of appetite. Interestingly, constipation is more common than diarrhea in the early stages, particularly in adults.

During the second week, the fever reaches its peak and remains high. Patients may develop rose spots - small, flat, rose-colored spots appearing on the chest and abdomen in about 30% of cases. These spots blanch with pressure and are more easily visible on light-skinned individuals. Abdominal symptoms become more prominent, including distension, tenderness, and a characteristic "pea soup" diarrhea. Mental status changes can occur, ranging from confusion to what was historically called "typhoid state" - a condition of delirium and obtundation.

Complications of Untreated Typhoid Fever

Without appropriate treatment, typhoid fever can lead to serious and potentially fatal complications. The most dangerous is intestinal perforation, which occurs when the bacteria erode through the intestinal wall, spilling bowel contents into the abdominal cavity and causing peritonitis. This complication occurs in 1-3% of untreated cases and has a high mortality rate even with surgical intervention.

Other serious complications include intestinal hemorrhage from bleeding ulcers in the intestinal wall, septic shock from overwhelming infection, myocarditis (inflammation of the heart muscle), encephalitis (brain inflammation), and bone infections (osteomyelitis). The risk of complications increases significantly after the second week of illness in untreated patients.

How Is Typhoid Fever Diagnosed?

Typhoid fever is definitively diagnosed through blood culture, which is positive in 60-80% of cases during the first week. Other diagnostic methods include bone marrow culture (most sensitive at 90%), stool and urine cultures, and serological tests like the Widal test, though the latter has limited accuracy.

Accurate diagnosis of typhoid fever is crucial for appropriate treatment but can be challenging because the symptoms overlap with many other febrile illnesses. A thorough travel history is essential - any patient presenting with fever who has traveled to an endemic area within the past 60 days should be evaluated for typhoid fever. The diagnosis requires both clinical suspicion and laboratory confirmation.

Blood culture remains the gold standard for typhoid diagnosis and should be collected before antibiotic therapy begins. The sensitivity of blood culture is highest during the first week of illness (60-80%) and decreases as the disease progresses. Collecting multiple blood samples over consecutive days can improve diagnostic yield. Modern automated blood culture systems can detect bacterial growth within 2-5 days.

Bone marrow culture has the highest sensitivity (approximately 90%) and remains positive even after antibiotics have been started, making it valuable when initial blood cultures are negative but clinical suspicion remains high. However, bone marrow aspiration is more invasive and is typically reserved for cases where diagnosis is uncertain. Stool and urine cultures become increasingly positive in the second and third weeks of illness and can help confirm diagnosis and detect chronic carriers.

Serological and Molecular Tests

The Widal test, a serological assay that detects antibodies against S. typhi, has been used for over a century but has significant limitations. False positives can occur due to cross-reactions with other bacteria or previous vaccination, and false negatives are common early in the disease. The test is most useful in endemic areas where baseline antibody levels in the population are known, allowing interpretation of rising titers in paired samples.

Newer rapid diagnostic tests using polymerase chain reaction (PCR) technology can detect bacterial DNA in blood samples with high sensitivity and specificity. These molecular tests can provide results within hours rather than days, enabling faster treatment decisions. However, availability and cost remain barriers to widespread use, particularly in resource-limited settings where typhoid is most common.

How Is Typhoid Fever Treated?

Typhoid fever is treated with antibiotics for 7-14 days. First-line treatments include fluoroquinolones (ciprofloxacin), azithromycin, or third-generation cephalosporins (ceftriaxone). Drug-resistant strains are increasingly common, making culture and sensitivity testing important for treatment selection.

The introduction of antibiotics in the mid-20th century transformed typhoid fever from a frequently fatal disease to a curable infection. Before antibiotics, mortality rates ranged from 10-30%; today, with appropriate treatment, death is rare (less than 1%). However, the emergence of antibiotic-resistant strains presents an ongoing challenge to treatment efficacy.

For uncomplicated typhoid fever, fluoroquinolones such as ciprofloxacin have traditionally been the treatment of choice due to their excellent tissue penetration and oral bioavailability. A typical course is 500mg twice daily for 7-14 days. However, fluoroquinolone resistance has become widespread in South Asia, where most cases originate, necessitating alternative treatments.

Azithromycin has emerged as an effective alternative, particularly for fluoroquinolone-resistant strains. The typical dose is 1 gram on day one followed by 500mg daily for 5-7 days. Third-generation cephalosporins, particularly ceftriaxone, are used for hospitalized patients and severe cases. These are typically given intravenously at 2 grams daily for 10-14 days.

Drug Resistance Concerns

The emergence of extensively drug-resistant (XDR) typhoid presents a serious global health threat. First identified in Pakistan in 2016, XDR strains are resistant to all first-line antibiotics as well as fluoroquinolones and third-generation cephalosporins. Treatment options for XDR typhoid are limited to azithromycin and carbapenems (reserved for the most severe cases). This underscores the critical importance of vaccination and prevention strategies.

All patients diagnosed with typhoid fever should have culture and antibiotic susceptibility testing performed to guide treatment selection. Empiric therapy should be based on local resistance patterns and adjusted once laboratory results are available.

Supportive Care

In addition to antibiotics, supportive care is essential for recovery. This includes maintaining adequate hydration through oral or intravenous fluids, managing fever with acetaminophen (paracetamol), and ensuring adequate nutrition. Patients should rest and avoid strenuous activity until fever has resolved. Hospitalization is recommended for patients with severe disease, complications, or inability to tolerate oral intake.

How Can I Prevent Typhoid Fever?

Typhoid fever prevention combines vaccination with food and water safety practices. Two vaccines are available: injectable Vi polysaccharide (single dose, 2-3 years protection) and oral Ty21a (4 doses, 5-7 years protection). Both provide 50-80% protection. Safe food and water practices remain essential even for vaccinated individuals.

Prevention of typhoid fever relies on two complementary strategies: vaccination and behavioral measures to avoid exposure. Neither approach alone provides complete protection, so both should be employed by travelers to endemic areas. Understanding these prevention strategies is essential for anyone planning travel to regions where typhoid fever is common.

Vaccination is recommended for all travelers to endemic areas, particularly those visiting South Asia (India, Pakistan, Bangladesh), Southeast Asia, Africa, and parts of South America. Vaccination should be completed at least 1-2 weeks before departure to allow time for immunity to develop. The vaccines are also recommended for laboratory workers handling S. typhi and household contacts of chronic carriers.

Available Vaccines

Two types of typhoid vaccines are currently available. The Vi capsular polysaccharide vaccine (ViCPS) is given as a single intramuscular injection and provides protection for approximately 2-3 years. It can be given to individuals aged 2 years and older and is the more commonly used vaccine due to its convenience. Side effects are generally mild, including soreness at the injection site and low-grade fever.

The oral live attenuated Ty21a vaccine requires four doses taken on alternate days (days 1, 3, 5, and 7). Each dose is a capsule that must be swallowed whole with cool liquid at least one hour before meals. This vaccine provides protection for approximately 5-7 years and can be given to individuals aged 6 years and older. It should not be given to immunocompromised individuals or those taking antibiotics.

A newer typhoid conjugate vaccine (TCV) has been developed and is recommended by WHO for routine childhood immunization in endemic countries. TCV provides stronger, longer-lasting immunity and can be given to children as young as 6 months of age. It is increasingly being incorporated into national immunization programs in high-burden countries.

Food and Water Safety

Regardless of vaccination status, travelers should follow safe food and water practices, summarized by the phrase "boil it, cook it, peel it, or forget it." These practices significantly reduce exposure to typhoid and many other travel-related infections:

• Drink only safe water: Bottled water with intact seals, water boiled for at least 1 minute, or water purified with iodine or chlorine
• Avoid ice: Unless you are certain it was made from purified water
• Eat only cooked foods: Served steaming hot; avoid food that has been sitting at room temperature
• Peel fruits and vegetables yourself: Avoid pre-cut fruits and salads
• Avoid raw seafood: Particularly shellfish, which can concentrate bacteria from contaminated water
• Practice hand hygiene: Wash hands frequently with soap and water, or use alcohol-based sanitizer
• Avoid street food: Unless you can see it being cooked fresh at high temperature

When Should I Seek Medical Care?

Seek immediate medical attention if you develop high fever (above 38.5°C/101°F) within 60 days of travel to a typhoid-endemic area. Inform healthcare providers about your travel history. Emergency care is needed for severe abdominal pain, bloody stools, confusion, or signs of dehydration.

Early recognition and treatment of typhoid fever significantly improves outcomes. Anyone who develops fever within 60 days of travel to an endemic area should be evaluated for typhoid fever, even if they received vaccination (which is only 50-80% effective). The most important action is to provide healthcare providers with a complete travel history, including specific countries visited and dates of travel.

Primary care physicians or travel medicine specialists can evaluate suspected cases through blood culture and physical examination. However, certain warning signs require emergency department evaluation due to the risk of serious complications:

• Temperature above 40°C (104°F) that does not respond to fever reducers
• Severe or worsening abdominal pain, particularly with rigidity
• Black, tarry, or bloody stools indicating intestinal bleeding
• Persistent vomiting preventing oral fluid intake
• Signs of severe dehydration (decreased urination, dizziness, rapid heartbeat)
• Confusion, difficulty speaking, or altered level of consciousness

What Is the Prognosis for Typhoid Fever?

With appropriate antibiotic treatment, typhoid fever has an excellent prognosis with mortality below 1%. Most patients recover fully within 2-4 weeks. However, 10-15% experience relapse requiring additional treatment, and 2-5% become chronic carriers. Long-term complications are rare with proper treatment.

The prognosis for typhoid fever has improved dramatically since the introduction of antibiotics. In the pre-antibiotic era, mortality rates ranged from 10% to 30%, with death typically occurring from intestinal perforation, hemorrhage, or overwhelming sepsis. Today, with appropriate treatment, fewer than 1% of patients die from the disease, and full recovery is the expected outcome.

Most patients begin to feel better within 3-5 days of starting effective antibiotic therapy, though fever may take up to a week to fully resolve. Complete recovery typically occurs within 2-4 weeks. During recovery, patients should maintain good nutrition, adequate hydration, and gradual return to normal activities. Some patients experience prolonged fatigue even after the infection has resolved.

However, several factors can complicate recovery. Approximately 10-15% of patients experience relapse within 2-3 weeks of completing antibiotic treatment. Relapse episodes are usually milder than the initial illness and respond well to another course of antibiotics. Risk factors for relapse include inadequate antibiotic treatment duration and underlying immune compromise.

Long-term complications are rare when typhoid fever is properly treated. The most significant concern is chronic carriage, which develops in 2-5% of recovered patients. Chronic carriers can transmit the disease to others and may face occupational restrictions in food handling. Treatment of chronic carriage requires prolonged antibiotic therapy (4-6 weeks) and sometimes surgical removal of the gallbladder.