What is Typhoid Fever?
Typhoid and paratyroid fever are both illnesses that cause fever and affect multiple systems in the body (multisystemic illnesses). They’re caused by bacteria called Salmonella serotypes Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C. All together, these diseases are known as enteric fever, which affects more than 9 million people and causes approximately 110,00 deaths around the world every year. Enteric fever is the major cause of bloodstream infections obtained within the community in South and Southeast Asia. In the United States and many other developed countries, it is a reportable disease and is a leading cause of severe and sometimes life-threatening infections in travelers, second only to malaria.
Enteric fever takes 6 to 30 days after exposure to show symptoms, which usually start gradually with fever, fatigue, loss of appetite, headache, general discomfort and abdominal symptoms. If not treated promptly or properly, severe complications like meningitis, sepsis, or a tear in the wall of the intestine can occur. The bacteria S Typhi and S Paratyphi have developed resistance to many types of antibiotics over time, making treatment more complex. Now, the emergence of extensively drug-resistant strains is causing concern.
It’s said that these bacteria spread by the “4 Fs”, which stands for flies, fingers, feces, and fomites (objects or materials which are likely to carry infection). They affect people living or traveling in low-income and middle-income countries that lack clean water, proper sanitation, and hygiene. These are all known collectively as WASH. Improving WASH infrastructure is key to reducing enteric fever and other diseases that are spread by the fecal-oral route, which is when infected feces come into contact with a person’s mouth.
Compared to diseases like HIV/AIDs, tuberculosis, and malaria, less time and resources have been dedicated to tackling enteric fever historically. However, with untreatable strains looming, efforts to control enteric fever have been renewed. New typhoid vaccines, better monitoring and understanding of antibiotic resistance, and WASH initiatives have helped lower the disease burden.
We will cover aspects of enteric fever like its prevalence, causes, treatment, management, complications, patient education, prevention measures, and the role of healthcare teams in improving patient care and reducing the impact of this disease. Despite many challenges, recent advancements give hope that we can limit or even eliminate the impact of enteric fevers in the future.
What Causes Typhoid Fever?
Salmonella, like other Enterobacteriaceae family members, is a bacterium that does not stain with Gram stain, is acid-resistant, and can survive with or without oxygen. It primarily includes two species: Salmonella enterica and Salmonella bongori. Salmonella enterica further breaks down into six subspecies, the most important of which is the most abundant in terms of serovars or serotypes, i.e., distinct variations within a species of bacteria. This group includes S Typhi and S Paratyphi, both of which only cause disease in humans.
Various other species within Salmonella, known as nontyphoidal salmonella (NTS), can cause diseases in humans or other animals. Usually, NTS infections in humans remain confined to gastroenteritis, an inflammation of the digestive tract, but some strains can invade and affect other parts of the body.
Since the early 1900s, the variations of S Typhi and S Paratyphi have been identified using a method called phage typing. However, with the progression of genetic techniques, identifying the exact type of Salmonella causing enteric fever (a group of diseases caused by the consumption of contaminated food or water) is becoming increasingly focused on genotypes. Studying these genetic variations can help track outbreaks and antimicrobial resistance, as well as anticipates the rise of new resistance mechanisms. When combined with up-to-date information on clinical antimicrobial susceptibility, this information can guide antibiotic treatment decisions.
For more information on Salmonella bacteria and related diseases, see the companion article “Salmonella” on StatPearls.
Risk Factors and Frequency for Typhoid Fever
Enteric fever, also known as typhoid or paratyphoid fever, spreads primarily through the consumption of food or water that has been contaminated by the feces of an infected person. Sexually transmitted enteric fever among men is rare. Notably, the bacteria that cause enteric fever can survive for a long time in the environment, even when it is not actively reproducing. This means that contaminated environments can lead to outbreaks, for example, through contaminated crops.
There are various risk factors for enteric fever, especially based on whether a person is in an endemic country (where the disease is common) or a non-endemic country. In non-endemic countries, risks include travel to endemic countries, contact with a traveler from an endemic country, or exposure to food prepared by an infected person. In endemic countries, things like individual health, environment, and climate and geography can influence the risk.
- The bacteria that cause enteric fever are typically destroyed by stomach acid, though they can cause illness if ingested in large amounts.
- People with a weakened immune system, taking certain medications, or suffering from other illnesses (like HIV, malaria, or sickle cell anemia) can have a more severe case of the disease.
- Some medications and conditions that trap bacteria from being destroyed in the stomach can increase susceptibility to the infection.
- Healthy gut microbiota can protect against the disease. Use of broad-spectrum antibiotics, which destroy these protective bacteria, can make people more susceptible.
- A poor diet can also harm these helpful bacteria and make people more prone to infection.
- Human genetics can influence susceptibility to enteric fever, with certain genetic markers potentially being associated with resistance.
On the environmental side, poor sanitation and use of contaminated water increase the chances of infection. The risk can be cut by half by using clean water sources and reduced further by treating household water. Keeping water containers clean and covered can lower the risk, while storing water in open, dirty containers can double it.
Lack of proper sanitation facilities also raises the risk of enteric fever. People who don’t have access to a toilet have 1.2 times the risk of getting the disease. Those without a facility to wash their hands with soap and water at home have 2.3 times the odds of getting the disease. Living in a house with adequate water, sanitation, and hygiene facilities significantly reduces the risk independent of vaccination.
Certain climates and geographical locations also influence the prevalence of the disease. The further from the Equator, the more the disease incidence varies with the season. The incidence also tends to be higher at higher temperatures. Climate change, such as increased flooding, drought, and fluctuating temperatures, threatens to increase the incidence of the disease by jeopardizing food and water safety.
Enteric fever affects countries differently according to their income levels. In high-income countries, it is mostly seen in travelers returning from endemic regions and is therefore less common. In contrast, the disease incidents remain high in low- and middle-income countries with poor sanitation standards. However, due to factors like diagnostic challenges, underdeveloped surveillance systems, and lack of universal healthcare, the true prevalence of the disease can only be estimated.
Outbreaks give a clue of the disease burden. Between 2017 and 2022, there were seven confirmed outbreaks reported globally, with the most significant outbreak occurring in Pakistan in 2018 and 2019, which affected 14,894 people.
Antimicrobial resistance (the ability of bacteria to resist the effects of medication) is also a problem, especially in low to middle-income countries, where resistance patterns often align with the pattern of antibiotic use and the spread of mutations.
The rising rates of antibiotic resistance among the bacteria that cause enteric fever are a cause for concern. There has especially been an upwards trend of resistance towards fluoroquinolone antibiotics, although the rates vary heavily across countries and regions. In extreme cases, some bacteria accumulate resistance towards many commonly used antibiotics, becoming extensively drug-resistant (XDR). There is an exceptionally high prevalence of XDR strains in Pakistan. XDR strains are not prevalent in other countries based on the current data but should be monitored closely.
The nature of the disease can change over time and in different spaces. Therefore, it’s important to remain up-to-date with the latest research and trends.

bacterium Salmonella Typhi. Symptoms of typhoid fever may include a sustained
fever as high as 103 to 104 °F (39 to 40 °F), weakness, stomach pains, headache,
and loss of appetite. In some cases, patients have a rash of flat, rose-colored
spots.
Signs and Symptoms of Typhoid Fever
Typhoid and paratyphoid are diseases that show up as feverish, non-specific illnesses. They can be hard to differentiate from each other, as well as from other diseases associated with fever. These illnesses can occur in people who travel or live in areas where they are common. When a person shows signs of these illnesses, it is important to perform a medical history and physical exam to either confirm or rule out the possibility of typhoid, paratyphoid, malaria, meningitis, dengue, and other feverish illnesses they could be at risk of.
Usually, after a period of 10 to 14 days from the point of infection, individuals start showing signs of enteric fever such as a gradual increase in fever and fatigue. The fever typically starts low in the morning and peaks in the afternoon or evening. Other widespread symptoms include loss of appetite, headache, uneasiness, and abdominal issues like pain, bloating, constipation, and diarrhea. Some with the illness may also experience dry cough, muscle pain, and sore throat.
The way children react to the infection is different from adults. They may have diarrhea, vomiting, fever-induced seizures, or other neurological symptoms more frequently. Individuals whose immune systems are weakened by HIV, especially those with lower CD4 counts, often show severe diarrhea and are more prone to contracting serious infections that spread to different parts of the body.
- Onset and progression of symptoms
- Complete review of symptoms
- Severe symptoms such as changes in consciousness, severe abdominal pain worsened by movement, or heavy bloody diarrhea
- Signs of complications like hepatitis (pale stools and darkened urine) or heart inflammation (chest pain)
- Severe upper abdominal pain radiating to the back might indicate pancreatitis
- Bone pain could indicate osteomyelitis
- Symptoms of abscess depend on their location in the body
Furthermore, a thorough travel history aids in confirming risk for acquiring the illness, excluding other infectious diseases, and guiding treatment. This includes:
- Recent travel history or permanent residence in endemic or outbreak areas
- Purpose of travel
- Any potential exposures to infectious diseases
Previous medical history can highlight risks for complications or severe illness. Other factors like the individual’s socio-economic status, vaccination history, previous or ongoing treatments (including prior antibiotics or malaria-preventive drugs, dosage, and medication frequency) are important details to explore. It is also important to ascertain if there are other ill individuals in the patient’s household or if they traveled with others who were unwell.
Physical exam findings in typhoid and paratyphoid can be non-specific. At the start of the illness, patients may appear pale, slow, and dehydrated. If left untreated, the disease can progress causing the patients to appear unwell and have significant weight loss. Other signs may include rose spots, jaundice, and signs of lung or heart inflammation. Abdominal examination may reveal liver and spleen enlargement, and severe abdominal tautness and tenderness might indicate internal bleeding or perforation.
Testing for Typhoid Fever
It’s crucial we quickly and accurately diagnose enteric fever, a condition resulting from certain types of bacteria, to minimize complications and potential death. However, confirming this diagnosis in the early stages, particularly in the first week, can be challenging due to limitations in current lab tests. Therefore, there is a pressing need for rapid, more effective tests for this condition.
If you have a persistent fever for three out of seven days, and no other obvious cause can be found, your doctor may suspect enteric fever. This is particularly true if you live in or have traveled within 28 days from an area known for infections or if you’ve been in close contact with a confirmed typhoid patient.
Confirmation of typhoid or related fever involves isolating specific bacteria or bacterial DNA from places in the body normally free of microbes. While this is not always necessary in resource-restricted settings, where lab diagnosis may not be essential for managing straightforward cases, it is still ideal to get laboratory confirmation whenever possible.
One of the most accurate methods of diagnosing enteric fever is by culturing or growing these bacteria isolated from your blood or bone marrow. However, cost and technical difficulties often limit the use of this method, particularly in countries with frequent occurrence of the disease. Sensitivity issues and the time it takes for culturing to yield results further limit its usefulness. Despite these challenges, when used and interpreted correctly, this type of testing can be invaluable for guiding effective treatment.
The Widal agglutination test is another method used to detect typhoid, often in endemic countries. Although it’s controversial due to its low sensitivity and specificity, it’s still widely used because it’s cost-effective and yields quick results. Some other serological tests (those based on reactions between antibodies and antigens) are becoming increasingly popular for the same reasons. However, their sensitivity and specificity are only moderate, meaning they aren’t entirely reliable for diagnosing typhoid.
Molecular tests, such as the multiplex polymerase chain reaction (PCR), can be more accurate. These tests identify specific genetic signatures of the bacteria, including any resistance to antibiotics, which can be critical for effective treatment. However, because they are more expensive, these tests are not often used in settings with limited resources.
Some additional tests are currently under investigation. These include examining different metabolites – small molecules involved in your body’s metabolic processes – that change during infection with these bacteria. The results may help to distinguish enteric fever from other conditions with similar symptoms, improving the accuracy of diagnosis.
Apart from tests for enteric fever, your doctor may order additional tests based on your symptoms. For example, they may order blood tests for malaria or extract some spinal fluid for testing, if you have a severe headache or neck stiffness. They may also order additional tests to rule out complications that could arise from enteric fever, such as inflammation of the heart muscle, abscesses, or bowel perforations.
Treatment Options for Typhoid Fever
Enteric fever, a type of bacterial infection, is primarily treated with antibiotics. It’s crucial to start treatment as soon as there’s suspicion of the illness, as any delay can extend the sickness and increase the risk of severe complications. While in certain countries like the United States patients are usually hospitalized, in regions where the disease is more common, uncomplicated cases can be managed with home treatment.
The AWaRe (access, watch, reserve) antibiotic guide offers recommendations for preliminary treatment choices, based on how sick the patient is when they arrive for care and how common resistance to a certain antibiotic (like ciprofloxacin) is in the region where the illness was likely contracted. It’s common to switch to an antibiotic more appropriate for the specific bacteria causing the illness, once test results come back. This might occur if the patient’s condition doesn’t improve after 48 hours of fever-free time.
In regions where resistance to ciprofloxacin is high, such as much of Asia and sub-Saharan Africa, the recommended antibiotic for adults with mild cases of enteric fever is azithromycin. For severe cases, ceftriaxone is typically used. In regions where resistance to fluoroquinolones like ciprofloxacin is low, ciprofloxacin itself is the first choice.
These antibiotics are similarly effective when it comes to treating enteric fever caused by susceptible bacteria. Azithromycin has slightly outperformed fluoroquinolones in some studies, and ceftriaxone might have a higher chance of relapse compared to azithromycin. These same antibiotics are recommended for children, with doses adjusted according to the child’s weight.
In places with high rates of extensively drug-resistant (XDR) enteric fever, like Pakistan or Iraq, azithromycin is recommended for uncomplicated illness and a type of antibiotic called carbapenem for more severe cases. If additional information is available, like local antimicrobial resistance patterns or national guidelines, these can help guide the choice of initial treatment.
If the starting antibiotic works, the fever tends to decrease within 3 to 5 days. If the fever lasts longer than 5 days, doctors might look further for persistent infection or consider switching antibiotics. Resistance to older first-line antibiotics like chloramphenicol, ampicillin, and co-trimoxazole has resurfaced in some areas, but these are no longer recommended due to the lingering threat of multidrug-resistance. They are only used as alternatives in areas with known susceptibility.
There’s current research into combining antibiotics to cover both the intracellular and extracellular spaces where the bacteria operate. Preliminary tests in Nepal showed promising results when azithromycin was added to either oral cefixime or intravenous ceftriaxone, drastically reducing the time it took to eliminate the fever. Results from a large-scale study on this approach are expected in late 2024.
Outside of antibiotic use, treatment also commonly includes antipyretics (to reduce fever), and fluids to replace those lost due to vomiting or diarrhea. Severe cases might require hospitalization and intensive care, including intravenous fluids, blood products, ventilation and oxygen if there are complications affecting the lungs, and steroids in the case of severe illness involving the central nervous system or shock.
What else can Typhoid Fever be?
Enteric fever, often confused with malaria, appears as a fever that’s difficult to differentiate from many other infectious diseases. Clues such as how long a person’s been back from traveling, whether their travel companions are ill, or any unique exposures might hint towards or weed out certain diagnoses. Unfortunately, though there are many symptoms associated with different conditions, most are not distinct enough at their onset to be very helpful in confirming or ruling out specific diseases.
The Centers for Disease Control and Prevention (CDC’s) Yellow Book offers a method for handling a feverish patient who’s returned from travel, together with a detailed list of possible illnesses and their related incubation periods.
The most severe form of malaria is caused by the Plasmodium falciparum parasite. This organism has an incubation period of 8 to 11 days, while other Plasmodium species generally have an incubation period of 9 to 17 days. An exception to this is P. malaria, the incubation period of which can be anywhere from 18 to 40 days, but very occasionally extending over several years. Chills and fever are more commonly associated with malaria than with enteric fever. The use of preventive medicine doesn’t necessarily eliminate the possibility of malaria. Amoebiasis, a less common parasitic infection, can also mimic enteric fever. Like enteric fever, amoebiasis is passed on via the fecal-oral pathway and can lead to fever, bloody diarrhea, and stomach pain.
Many bacterial illnesses also share symptoms with enteric fever. Some of these include leptospirosis, scrub and murine typhus, bacterial meningitis, brucellosis, and bacterial gastroenteritis. For instance, those with leptospirosis might have a history of contact with animals or adventurous sports that involve contact with mud. Typhus patients could have a bite mark that initially looks like a cigarette burn but soon turns into a black eschar. Those suffering from bacterial gastroenteritis are more likely to experience heavy diarrhea.
Various viral diseases can also appear as a fever that’s difficult to distinguish from others. These include the flu, COVID-19, dengue, hepatitis caused by a virus, Chikungunya, viral meningitis, yellow fever, Ebola and many others based on the patient’s location or travel history. A cough is generally more pronounced in flu and COVID-19, along with associated upper respiratory symptoms. People suffering from dengue or “breakbone” fever may experience severe joint pain. If the patient got home more than 6 days before symptoms began, yellow fever, dengue, and Chikungunya can likely be ruled out.
What to expect with Typhoid Fever
Enteric fever, also known as typhoid fever, can lead to serious health issues and even death, especially if the antibiotic treatment is delayed or not strong enough. However, thanks to advances in medicine, the overall death rate for people who get this infection has dropped significantly. Back in the time before antibiotics, about 10% to 30% of people who got sick from S Typhi, the bacteria that causes enteric fever, would pass away. Nowadays, less than 1% of patients die if they get their treatment early.
But there’s still a large variation in the death rate depending on the region of the world and whether or not the patients are treated in a hospital. For instance, when taking into account only non-surgical hospitals around the world, the estimated average death rate is about 4.2%. Breaking it down by region, it’s roughly 0.9% in Asia, 5.4% in Africa, 7.2% in Oceania, 6.7% in the Americas, and 1% in Europe. As for cases that happen outside of hospitals across the world, the estimated death rate is lower, at about 0.2%.
Possible Complications When Diagnosed with Typhoid Fever
Complications usually arise 2 to 3 weeks after a person gets ill from Typhoid fever. Research from 2020 indicates that 26% of lab-confirmed, predominantly hospitalized cases of typhoid experienced a complication.
- Gastrointestinal Complications: Kids younger than 5 often suffer from diarrhea and dehydration more frequently than adults and older children. Also, 36% of kids in this age group may get hepatitis. The end of the small intestine, also known as the terminal ileum, may get perforated in about 1.3% of hospitalized confirmed cases of typhoid due to an overgrowth and dying of certain gut tissues. Intestinal perforation is more likely to occur in men than women and mainly in people older than 15. This complication is more common in sub-Saharan Africa (7.6%), compared to Asia (0.7%). Surgery with intensive cleaning of the abdominal cavity is necessary for intestinal perforation. Patients may also need wide range antibiotics, medications to strengthen the heart’s work, and fluids in a high-care setting. Blood transfusion may be necessary in severe bleeding cases. The average hospital stay for surgically treated perforation is 18 days.
- Neuropsychiatric Complications: Confusion or delirium is a common complication of typhoid, occurring in a quarter of confirmed hospitalized cases. Meningitis, altered mental state, sleep irregularities, sudden psychological disorder, inflammation of spinal cord, loss of full control of bodily movements, muscle stiffness, and localized neurological deficiencies can occur, though rare in adults. Confusion, alterations in mental state and febrile seizures frequently happen in school-aged children. Such symptoms are believed to be due to irritation of the brain by typhoid toxin. Steroids have been suggested for severe cases of encephalopathy.
- Other Complications: Anemia is one of the most common complications of typhoid, affecting up to one-fifth of hospitalized cases and more common in South Asia than anywhere else in the world. Other complications include miscarriage in pregnant women, multiorgan failure, rare occurrences of focal abscesses, and lung complications primarily in children and patients with lung cancer, use of steroids, and other structural lung diseases.
- Relapse: Relapse is when symptoms of Typhoid fever return with lab confirmation, usually 1 to 3 weeks after clinical recovery. This requires further antibiotic treatment.
- Chronic Carriage: Sometimes, typhoid fever may continue for a few weeks to months even after treatment of the disease. This usually clears without further treatment. However, it persists in around 1% to 4% of patients who become chronic carriers, showing shedding for at least 12 months after finishing antibiotics. Chronic carriage is less likely with adequate antibiotic treatment and particular types of typhoid. It’s worth noting that chronic carriers pose a higher risk for developing biliary cancer.
- Treatment for Chronic Carriage: The evidence for treating chronic carriage is slim. A 2022 review and guidance from the World Health Organization (WHO) in 2003 are based on older evidence. Gallbladder removal can cure chronic carriage in 70% to 90% of cases but carries significant risks, so it’s only recommended if other indicators for surgery exist. Household members of chronic typhoid carriers may be suggested to get vaccinated.
Preventing Typhoid Fever
If you are an outpatient (treated without being admitted to a hospital) or have returned home after being treated for enteric fever in a hospital, it’s very important to understand how to stop the illness from spreading to others in your house. Enteric fever, caused by S Typhi and S Paratyphi bacteria, can stay in your system for weeks or even months after you start to feel better. Washing your hands regularly with soap and water is one of the best ways to prevent others from getting sick.
Anyone caring for a person going through enteric fever should also use gloves, always maintain strict hygiene, and safely dispose of any waste that may be contaminated, such as feces or urine. If you’ve had enteric fever before, it does not mean that you’re immune to it – the protection does not last for long. So, you need to get vaccinated if you’re at risk of getting the illness again.
To avoid enteric illnesses, wash your hands with soap and water and dry them thoroughly. Always do this before preparing meals, after using the restroom, or after caring for a sick person. When soap and water are not available, sanitizers with at least 60% alcohol can be used, but they are not as good as soap and water for some germs. Therefore, always wash your hands thoroughly after using sanitizers.
Be very careful with the food and water you consume. Avoid raw or undercooked meats, fish, shellfish, and vegetables, unpasteurized juice, salads, fruits, and dairy products. Whenever you eat out, avoid food items that may have been cooked much earlier and then reheated before serving, such as lasagna. Also, avoid food stalls on the streets and buffets. When the safety of drinking water is uncertain, you should either treat it to make it safe or drink only bottled water. This applies to all uses of water, including preparation of food and drinks, brushing teeth, making ice, and cooking. If you have a baby who is bottle-fed, you should either use a readily prepared liquid formula, or be very careful when making one. Any leftover formula after feeding should not be used again.
Getting a typhoid vaccination is important for those traveling to places where enteric fever is common. These vaccines don’t completely protect you against the illness and you still need to maintain hand hygiene and take care of food and water safety.
There are two common vaccines available in the United States. One is a shot given to people over the age of 2. This needs to be given at least 2 weeks before you travel and should be followed by a booster shot every 2 to 3 years. The other is a vaccine that is given orally (by mouth) to people over the age of 6. This consists of 4 doses, taken with a liquid no warmer than body temperature, at least one hour before a meal. The doses should be taken every other day and completed at least one week before possible exposure to the bacteria. A booster dose is given every 5-7 years.
It’s important to note that the oral vaccine shouldn’t be taken by people with weak immune systems, those with a severe intestinal illness, or breastfeeding women. It should only be given to pregnant women if the shot is unavailable after evaluating their risks. It may also provide some protection against Salmonella Paratyphi B bacteria.
There are two typhoid conjugate vaccines (TCVs) approved by the WHO, Typbar-TCV, and TYPHIBEV. These work by inducing a stronger and longer lasting immune response than earlier vaccines. These can be given to infants as young as 6 months. They are given as a single shot and have been found to provide 79% to 95% protection in the first 2 years. The protection can last for up to 7 years. These vaccines are being used in countries where the illness is usually found but aren’t licensed in Europe or North America which prevents their use for travel purposes.