Typhoid fever is a serious illness caused by the bacterium Salmonella Typhi. It spreads mainly through eating food or drinking water contaminated with the feces or urine of an infected person. The disease is most common in places with poor sanitation, limited clean water, and inadequate hygiene.
Symptoms usually start with a lasting high fever, tiredness, stomach pain, headache, and loss of appetite. Some people may also have diarrhea or constipation, and a few develop small pink spots on the skin. If not treated, typhoid fever can cause dangerous complications such as holes in the intestine (intestinal perforation), internal bleeding, brain problems (encephalopathy), or widespread infection in the body (sepsis).
Treatment requires antibiotics, which are medicines that kill bacteria. The choice of antibiotic depends on local drug resistance, meaning how well the bacteria can survive standard medicines. Supportive care such as drinking enough fluids, using fever-reducing medicines, and maintaining good nutrition is also important. A growing problem is antibiotic resistance, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, which make treatment more difficult.
Typhoid fever remains a major health challenge in parts of Asia, Africa, and Latin America. Prevention includes improving access to clean water and sanitation, safe food handling, public health education, and vaccination. Available vaccines include the injectable Vi polysaccharide vaccine and the oral Ty21a vaccine, both recommended for people in high-risk areas.
Classification
Typhoid fever is caused by the bacterium Salmonella enterica subspecies enterica serotype Typhi, commonly referred to as Salmonella Typhi. It belongs to the family Enterobacteriaceae, a large group of Gram-negative bacteria that includes many intestinal pathogens.
The disease is classified as an enteric fever, a term that refers to systemic infections caused by invasive Salmonella serotypes, primarily S. Typhi and Salmonella Paratyphi (A, B, and C). Enteric fevers differ from non-typhoidal salmonellosis, which is typically caused by other serotypes of Salmonella enterica and usually results in acute, self-limiting gastroenteritis rather than invasive disease.
Unlike non-typhoidal Salmonella, which can infect a wide range of animals and serve as zoonotic pathogens, S. Typhi is strictly human-adapted and has no known animal reservoir. This human specificity is an important factor in its transmission cycle, as the bacteria spread only through fecal–oral contamination, primarily via unsafe food, water, or inadequate hygiene practices.
Within the broader classification, S. Typhi is further distinguished by its possession of the Vi capsular polysaccharide antigen, which plays a role in immune evasion and is also the basis for certain diagnostic tests and vaccines. The presence of this antigen differentiates it from some other Salmonella serotypes, particularly those responsible for paratyphoid fever.
History and Epidemiology
Typhoid fever has been recognized for centuries, with descriptions dating back to ancient texts. The disease became prominent in the 19th century in Europe and North America due to urbanization and poor sanitation.
The causative agent, Salmonella enterica serotype Typhi, was first identified in 1880 by Karl Joseph Eberth, with further characterization provided by Robert Koch. Widespread improvements in water treatment, sewage disposal, food safety, and hygiene during the late 19th and early 20th centuries led to a dramatic decline in incidence across industrialized nations. The introduction of antibiotics, beginning with chloramphenicol in the mid-20th century, further reduced both mortality and transmission.
Despite these advances, typhoid fever continues to be endemic in many low- and middle-income countries, particularly in South Asia, sub-Saharan Africa, and parts of Latin America. Epidemiological patterns in recent decades have been shaped by the emergence of antibiotic-resistant strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi, which complicate treatment and increase the risk of severe outbreaks. In many endemic areas, cases peak during the rainy season when flooding increases contamination of water sources.
According to the World Health Organization (WHO), typhoid fever affects an estimated 11 to 20 million people annually and causes between 128,000 and 161,000 deaths worldwide. The highest incidence occurs in children and young adults, who account for the majority of cases and deaths. Rural and peri-urban populations without access to safe drinking water, proper sanitation, or adequate healthcare services are most vulnerable.
The burden of typhoid fever is unevenly distributed, with South Asia reporting the largest number of cases, followed by sub-Saharan Africa. In high-income countries, cases are now relatively rare and usually associated with travel to endemic regions.
Control measures for typhoid fever include mass vaccination campaigns, improving access to clean water and sanitation, and public health programs that encourage good hygiene and safe food practices. Another important strategy is antibiotic stewardship, which means using antibiotics responsibly to prevent the bacteria from becoming resistant to treatment. Although these efforts have reduced the impact of the disease in some regions, typhoid fever continues to be a serious global health problem, especially in places where rapid population growth has outpaced the development of clean water systems, sanitation, and healthcare services.
| Region | Estimated Cases (Millions) | Mortality (Thousands) |
| South Asia | 7-10 | 80-100 |
| Sub-Saharan Africa | 2-4 | 30-40 |
| Southeast Asia | 1-3 | 10-15 |
Causes and Transmission
Typhoid fever results from infection by a specific bacterium. It spreads primarily through contaminated food and water, affecting certain groups more than others, depending on exposure and immunity.
Causative Agent: Salmonella Typhi
Unlike many other Salmonella species that can infect both humans and animals, S. Typhi is uniquely adapted to humans and does not naturally infect animals, making human carriers the only reservoir.
Once ingested, the bacteria survive passage through the stomach and invade the intestinal mucosa. From there, they penetrate the intestinal lining and enter the lymphatic system and bloodstream, leading to systemic infection affecting multiple organs, including the liver, spleen, bone marrow, and gallbladder. The bacterium is capable of persisting in contaminated food, water, and soil for prolonged periods, allowing sustained transmission in endemic regions.
A characteristic feature of S. Typhi is its ability to establish a carrier state in some individuals. In these cases, the bacteria remain in the gallbladder or intestinal tract without causing symptoms, yet carriers can shed the pathogen for months or even years, posing a continued risk to others. The most well-known example is “Typhoid Mary” (Mary Mallon), an asymptomatic carrier in early 20th-century New York who caused multiple outbreaks.
Modes of Transmission
The primary route of transmission is the fecal–oral pathway, where bacteria from human feces or urine contaminate food or water that is later consumed by others. Several key transmission pathways include:
- Contaminated water: Drinking water drawn from polluted rivers, wells, or municipal supplies is a major source of infection. Flooding during rainy seasons often increases contamination risks.
- Contaminated food: Raw vegetables washed in unsafe water, undercooked shellfish harvested from polluted waters, and street-vended foods can all harbor S. Typhi.
- Food handlers: Asymptomatic carriers working in food preparation can transmit the bacteria to large groups if strict hygiene practices are not followed.
- Person-to-person spread: Direct household contact with an infected individual or a chronic carrier increases the risk, especially in crowded or resource-limited settings.
High-Risk Populations
Certain groups are more vulnerable to typhoid fever due to environmental, occupational, or biological factors:
- Residents of endemic regions: Communities in parts of South Asia, sub-Saharan Africa, and Latin America face the highest burden because of limited access to clean water and sanitation infrastructure.
- Travelers to endemic areas: Visitors from non-endemic countries often lack immunity and are at increased risk when exposed to unsafe food and water.
- Children: Young children, particularly those under 5 years of age, are more likely to develop severe disease because their immune systems are still developing.
- Immunocompromised individuals: People with weakened immune defenses, such as those with HIV/AIDS or malnutrition, are more susceptible to severe infections.
- Food handlers and healthcare workers: In endemic regions, individuals in frequent contact with contaminated food, water, or patients face higher occupational exposure.
Symptoms and Clinical Manifestations
Typhoid fever presents with a range of symptoms that evolve over time, starting with mild signs and potentially advancing to severe complications. The clinical picture is varied and requires close attention to detect progression.
Early Signs and Symptoms
Initial symptoms usually appear 1 to 2 weeks after exposure to Salmonella Typhi. Patients often experience gradual onset of fever that rises daily and can reach as high as 39-40°C (102-104°F).
Headache, malaise, and loss of appetite are common. Some patients complain of abdominal discomfort or a dry cough. Constipation is more frequent than diarrhea in the early phase.
Physical examination may reveal bradycardia (lower heart rate despite high fever) and rose spots, which are faint pink rash-like spots primarily on the trunk. These signs occur in about 30-50% of cases.
Progression and Severe Manifestations
If untreated, symptoms worsen typically during the second or third week. The fever becomes continuous and severe. Patients often develop abdominal tenderness and distension.
Diarrhea or constipation may alternate. Intestinal bleeding and perforation risk increases in this phase. Neuropsychiatric symptoms such as confusion, delirium, or stupor can manifest, sometimes described as “typhoid encephalopathy.”
The liver and spleen enlarge slowly, and there may be noticeable weakness or fatigue. Persistent high fever and worsening abdominal signs are indicators of severe disease progression.
Complications of Typhoid Fever
Serious complications can occur, especially without timely treatment. The most critical is intestinal perforation, which leads to peritonitis, an emergency requiring immediate surgery.
Other complications include gastrointestinal bleeding, hepatitis, myocarditis, and pneumonia. Septic shock can develop in advanced cases, increasing mortality risk.
Relapses happen in about 5-10% of patients despite antibiotic treatment. Chronic carriage of Salmonella Typhi in the gallbladder causes ongoing infection and spread to others.
Diagnosis of Typhoid Fever
Diagnosis of typhoid fever involves a combination of symptom evaluation, laboratory tests, and ruling out other illnesses with similar presentations. Accurate identification depends on confirming the presence of the bacteria and distinguishing it from other febrile diseases.
Clinical Assessment
Patients typically present with a prolonged high fever, abdominal pain, headache, weakness, and loss of appetite.
In some cases, physical signs such as relative bradycardia—a slower than expected heart rate despite fever—may be observed. Other characteristic findings include rose-colored spots on the trunk and hepatosplenomegaly, which refers to the enlargement of both the liver and spleen.
A detailed medical history is also important; recent travel to regions where typhoid fever is common or consumption of potentially contaminated food or water strengthens the clinical suspicion. Physicians often take into account the patient’s age, immune status, and the pattern of symptom onset when forming an initial assessment.
However, clinical evaluation alone is insufficient for confirmation since the symptoms overlap significantly with other febrile illnesses.
Laboratory Testing Methods
Blood culture remains the gold standard for confirming S. Typhi infection and is most effective during the first week of illness, although its sensitivity decreases as the disease progresses or if antibiotics have already been taken. Bone marrow culture offers the highest sensitivity and can detect the bacterium even after antibiotic treatment, but the procedure is invasive and less commonly performed. Stool and urine cultures can help identify carriers or cases with prolonged bacterial shedding, though they are less reliable for early diagnosis.
Serological tests such as the Widal test are widely used in resource-limited settings, as they detect antibodies against S. Typhi. However, their accuracy is limited in endemic regions where prior exposure or cross-reactivity with other infections may cause false positives. Molecular methods, including polymerase chain reaction (PCR), allow rapid and highly specific detection of the bacterium, but these techniques are not yet widely accessible in low-resource healthcare systems due to cost and technical requirements.
Differential Diagnosis
Because typhoid fever shares many features with other infectious diseases, careful differential diagnosis is essential. Conditions such as malaria, dengue fever, leptospirosis, and bacterial sepsis often present with prolonged fever and systemic symptoms, making laboratory confirmation necessary to distinguish them.
Gastrointestinal illnesses, including shigellosis, cholera, and amebiasis, may also mimic typhoid’s digestive symptoms, requiring stool testing to clarify the diagnosis. In addition, physicians sometimes consider non-infectious causes of fever, such as autoimmune or inflammatory diseases, particularly if infectious agents are not identified.
Treatment and Management
Effective treatment of typhoid fever relies on targeted antibiotic use, supportive measures to maintain patient stability, and timely intervention for potential complications. Prompt medical care reduces the risk of prolonged illness and severe outcomes.
Antibiotic Therapy
Antibiotics remain the primary treatment for typhoid fever. Commonly used agents include ceftriaxone, azithromycin, and fluoroquinolones such as ciprofloxacin, depending on regional resistance patterns.
Treatment generally lasts between 7 and 14 days, and whenever possible, susceptibility testing is recommended to guide antibiotic selection. This is particularly important in regions where multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains have emerged.
In such cases, alternative agents or combination therapy may be required. Early initiation of antibiotics not only shortens the duration of fever and illness but also reduces bacterial shedding in the stool, lowering the risk of further transmission within the community.
Supportive Care
Supportive care focuses on hydration and symptom management. Fever, diarrhea, abdominal discomfort, and generalized weakness are common features, often leading to dehydration and fatigue. Ensuring adequate hydration is critical, and this may involve oral rehydration solutions in mild cases or intravenous fluids in patients who are severely dehydrated or unable to tolerate oral intake.
Nutritional support helps maintain strength during convalescence; bland, soft foods that are easy to digest are generally recommended once appetite returns. Medications such as acetaminophen may be given to relieve fever and associated discomfort.
Continuous monitoring of clinical status is vital because deterioration can occur quickly, especially in untreated or partially treated patients. Persistent vomiting, confusion, or abdominal swelling should prompt further evaluation and escalation of care.
Management of Complications
Complications represent the most serious aspect of typhoid fever and require urgent medical attention. Intestinal perforation is one of the most dangerous outcomes, typically presenting with sudden, severe abdominal pain and signs of peritonitis. In such cases, surgical intervention is usually necessary, alongside intensive antibiotic therapy and supportive measures.
Gastrointestinal hemorrhage, another serious complication, may require blood transfusions and endoscopic or surgical management if bleeding is extensive. Neurological complications such as encephalopathy, although less common, demand close observation and supportive treatment in a hospital setting. Patients who develop severe complications are generally managed in inpatient facilities, where vital signs can be closely monitored and intravenous medications administered.
Preventing these outcomes depends heavily on early diagnosis, adherence to appropriate antibiotic regimens, and careful follow-up throughout the course of illness.
Prevention and Control Strategies
Preventing typhoid fever requires multiple coordinated approaches to reduce infection risk and control outbreaks. It is essential to use specific protective measures in vaccination, water sanitation, and food handling to limit the spread of Salmonella Typhi.
Vaccination Options
Typhoid vaccines provide significant protection, especially for travelers to high-risk areas and residents of endemic regions. Two main vaccines are available: the inactivated injectable vaccine and the live oral vaccine. The injectable vaccine requires a single dose and is recommended for people over two years old. Its protection lasts about two years.
The oral vaccine is given in four doses over one week and is suitable for children over six years old. It provides protection for approximately five years. Neither vaccine is 100% effective, so vaccination should be combined with other preventive measures.
Boosters are recommended every few years for individuals continuously exposed to typhoid risk.
Although both vaccines significantly reduce the risk of infection, they do not guarantee complete protection. Breakthrough cases can still occur, especially in settings where sanitation is poor and exposure is frequent. For this reason, vaccination programs are most effective when combined with improvements in hygiene, clean water supply, and safe food handling practices.
In countries such as India, Nepal, and parts of sub-Saharan Africa, large-scale vaccination campaigns have been shown to lower disease incidence, especially in children who are disproportionately affected.
Global health agencies, including the World Health Organization (WHO), continue to recommend vaccination for travelers to endemic regions, healthcare workers in high-exposure environments, and populations living in areas with persistent outbreaks.
Safe Water and Sanitation
Access to safe drinking water and proper sanitation is fundamental to controlling typhoid fever. Because Salmonella Typhi spreads through fecal contamination, ensuring that human waste does not enter water supplies is a critical public health measure. Many outbreaks in developing countries are directly linked to untreated sewage mixing with drinking water sources.
- To reduce risk, communities and households are advised to follow key practices:
- Boil water before drinking or use reliable purification methods such as chlorination or filtration.
- Ensure sewage systems are properly managed to prevent leakage into water supplies.
- Separate wastewater drainage from sources of drinking water.
- Promote regular handwashing with soap, particularly after defecation and before eating or preparing food.
- Invest in sanitation infrastructure, including latrines and sewage treatment plants, to reduce environmental contamination.
Food Safety Practices
Typhoid fever also spreads through contaminated food. Recommended practices include:
- Wash hands thoroughly before handling or consuming food.
- Cook meat, poultry, and seafood thoroughly before eating.
- Consume food while it is still hot and freshly prepared.
- Avoid raw or undercooked foods, especially meat and seafood.
- Peel fruits and vegetables before eating, or wash them with safe, treated water.
- Avoid unpasteurized dairy products and untreated milk.
- Clean and disinfect kitchen utensils, cutting boards, and surfaces regularly.
- Purchase food only from hygienic and trusted vendors.
Typhoid Fever in Different Populations
Typhoid fever affects various groups differently, with variations in symptoms, severity, and treatment challenges. Certain populations require specialized attention due to their unique physiological or immunological conditions.
Children and Adolescents
In children and adolescents, typhoid fever often presents with more severe symptoms than in adults. High and persistent fever, abdominal pain, and diarrhea are frequently reported, and younger patients are more likely to experience dangerous complications such as intestinal perforation, which occurs when the lining of the intestine develops a hole, and encephalopathy, which involves brain dysfunction due to severe infection.
Malnutrition, which weakens the immune system, can worsen outcomes in children, leading to prolonged illness and delayed recovery. Early diagnosis and rapid initiation of antibiotic therapy are essential to prevent long-term complications. Preventive vaccination is strongly recommended for children living in or traveling to endemic regions, as it significantly reduces disease incidence in this vulnerable group.
Pregnant Women
Pregnant women infected with typhoid fever face additional risks, both for themselves and for their unborn child. The illness can lead to severe complications such as miscarriage, stillbirth, or premature delivery, and high fever may directly interfere with fetal development.
Treatment requires special caution because many antibiotics commonly used for typhoid fever, including fluoroquinolones, are unsafe during pregnancy. Safer alternatives, such as ceftriaxone or azithromycin, are often preferred, but the choice of therapy must balance maternal health with fetal safety. Close monitoring is crucial to reduce the risk of maternal and neonatal complications.
Immunocompromised Individuals
Immunocompromised individuals, including patients living with HIV/AIDS, cancer patients undergoing chemotherapy, and people on long-term immunosuppressive drugs after organ transplantation, are at increased risk of severe and prolonged typhoid fever.
Their weakened immune systems struggle to control the infection, making them more prone to persistent illness, relapse after treatment, and secondary complications such as bloodstream infections. These patients often require longer courses of antibiotics and closer clinical follow-up to ensure complete recovery. While vaccination is recommended, the immune response in this group may be weaker than in healthy individuals, reducing vaccine effectiveness but still offering some level of protection.
Prognosis and Long-Term Outcomes
Typhoid fever generally responds well to appropriate antibiotic treatment, though outcomes vary by patient and healthcare access. Some patients experience relapses, while a minority develop a chronic carrier state, necessitating ongoing medical attention.
Recovery and Relapse Rates
With proper antibiotic treatment, most people with typhoid fever recover within two to four weeks. Commonly used medications include ceftriaxone, azithromycin, or fluoroquinolones, depending on local patterns of antibiotic resistance. Early treatment not only speeds up recovery but also reduces the risk of life-threatening complications such as intestinal perforation or severe bleeding. In areas where resistant strains of Salmonella Typhi are widespread, longer treatment courses or alternative drugs may be required, which can influence how quickly patients recover.
Relapse, which is the return of symptoms after apparent recovery, occurs in about 5–10% of patients. This usually happens two to three weeks after completing treatment. Relapse symptoms are generally milder than the first episode but still include fever, abdominal pain, and weakness. Additional antibiotic therapy is required to fully eliminate the infection.
Relapse often results from the bacteria not being completely cleared during the initial treatment, which may happen if antibiotics were stopped too early, if the prescribed dose was insufficient, or if the infecting strain is resistant. Because relapse can easily be mistaken for other illnesses, careful monitoring of patients after treatment is important in preventing further complications.
Chronic Carrier State
A small proportion of patients, estimated at about 1–5%, develop what is known as a chronic carrier state. This means the bacteria remain in the body—most often in the gallbladder or intestines—for a year or longer after symptoms have disappeared. These individuals may feel healthy and show no signs of illness, yet they continue to shed bacteria in their stool or urine. Carriers play a significant role in maintaining the transmission of typhoid fever within communities, especially in areas where sanitation is poor.
Diagnosis of chronic carriers requires repeated stool or urine cultures, since bacteria are not always shed continuously. Treatment can be challenging. Prolonged courses of antibiotics such as ciprofloxacin may be attempted, but success rates vary. In some cases where the gallbladder is a persistent source of infection, surgical removal of the gallbladder (cholecystectomy) may be considered.
Women, older adults, and individuals with gallstones are at a higher risk of becoming chronic carriers. Historical examples, such as “Typhoid Mary” in the early 20th century United States