Overview
Typhoid fever is a systemic bacterial infection caused by Salmonella enterica serotype Typhi, a bacterium that infects only humans. Unlike many other infectious diseases, there is no animal or environmental reservoir for Salmonella Typhi. The bacterium survives exclusively within the human body and is transmitted exclusively through human waste contaminating water or food. This means typhoid is not a disease of the environment in a general sense , it is a disease of human sanitation and hygiene.
The disease is transmitted through what is called the fecal-oral route. A person infected with Salmonella Typhi , either ill or a chronic carrier showing no symptoms , sheds the bacteria in their stool and occasionally their urine. When that waste contaminates water sources or food, and when another person consumes that water or food without adequate hygiene, the bacteria enter the digestive system and begin their invasion of the body.
Once ingested, Salmonella Typhi passes through the stomach into the small intestine, penetrates the intestinal lining, and is taken up by immune cells that are supposed to destroy it. Instead, the bacteria survive and multiply inside these cells, travel through the lymphatic system, and enter the bloodstream. From there, they seed multiple organs including the liver, spleen, gallbladder, and bone marrow, producing the widespread systemic illness that makes typhoid distinct from a simple gut infection.
Typhoid fever is estimated to cause 9 to 11 million cases and between 110,000 and 161,000 deaths annually worldwide, with the vast majority of this burden falling on low- and middle-income countries in sub-Saharan Africa and South Asia. In Ghana, typhoid ranks among the most common outpatient illnesses, with an estimated incidence of 389 cases per 100,000 person-years among children under 15.
The incubation period , the time between ingesting the bacteria and developing symptoms , ranges from six to thirty days, with most cases presenting within eight to fourteen days of exposure.
Key Fact
Important
AT A GLANCE
Disease Summary
Symptoms
Common Symptoms
Typhoid fever develops gradually over several days, unlike malaria which typically presents more abruptly. Most people with typhoid experience one or more of the following symptoms.
Gradually Rising Fever
Headache
Loss of Appetite
Abdominal Discomfort
Constipation
Fatigue and Malaise
Dry Cough
Danger Signs
Seek urgent medical attention immediately if any of the following symptoms develop. These may indicate serious complications.
Confusion or Altered Mental State
Sudden Severe Abdominal Pain
Blood in Stool
Fever Not Improving After Five Days of Treatment
Diagnosis
Clinical Assessment
Physical Examination
Laboratory Confirmation
Assessment for Complications
Laboratory Tests
Blood Culture
Blood culture is the reference standard for diagnosing typhoid fever. A blood sample is placed in a growth medium and incubated to allow Salmonella Typhi to multiply to detectable levels. A positive result confirms the diagnosis with 100 percent certainty , no other available test can make this claim. A single blood culture detects typhoid in approximately 40 to 80 percent of cases, with sensitivity highest in the first week of illness. Multiple draws improve sensitivity. Prior antibiotic use significantly reduces the chance of a positive result, which is particularly important in Ghana where self-medication before attending a health facility is common.
Widal Test
The Widal test measures antibodies against the O and H antigens of Salmonella Typhi. It is the most widely used diagnostic test for typhoid in Ghana due to its low cost and wide availability. However, its limitations are well-documented and must be understood. The mean sensitivity is approximately 63 percent and the mean specificity is approximately 73 percent. In Ghana and other endemic settings, false positive results are common because malaria (Plasmodium falciparum) cross-reacts with Widal antigens, prior typhoid infections or vaccinations elevate background antibody levels, and endemic populations often carry measurable Widal antibody titres without active infection. A single positive Widal result without a known baseline for that patient is of limited diagnostic value. The Infectious Diseases Society of America recommends against relying solely on the Widal test.
Complete Blood Count (FBC)
The full blood count does not diagnose typhoid but provides important supportive evidence. Characteristic findings in typhoid include a normal or low white blood cell count (leucopenia), a relatively high proportion of lymphocytes, and low neutrophil count. A normal or low white cell count during a febrile illness is unusual and should increase clinical suspicion for typhoid. Anaemia and low platelet count may also be present in more advanced disease.
Stool Culture
Stool culture detects Salmonella Typhi shed through the gut via the gallbladder. It is not useful in the first week of illness and has lower sensitivity than blood culture overall, detecting typhoid in approximately 30 to 40 percent of cases. It becomes more useful from the second week onward and is also used to confirm clearance of infection and to identify chronic carriers after recovery.
Rapid Diagnostic Tests (Typhidot, TUBEX)
Rapid diagnostic tests detect antibodies against specific Salmonella Typhi antigens and return results within an hour. They are available in some Ghanaian facilities. However, current evidence shows that these tests also have suboptimal sensitivity and specificity and are not reliably accurate enough to replace blood culture. They may provide useful supporting information when interpreted alongside the full clinical picture.
Laboratory Note
Blood culture is the only test that can confirm typhoid fever with certainty. The earlier a blood culture is taken , ideally in the first week of illness and before antibiotics are started , the higher the chance of a positive result. If you have already taken antibiotics before your blood was tested, tell your healthcare provider, as this is important information for interpreting the results.
Treatment
Azithromycin
Azithromycin is currently the preferred first-line treatment for uncomplicated typhoid fever. The WHO prioritizes it based on superior clinical outcomes and significantly lower relapse rates compared to other antibiotics. It achieves high concentrations inside cells , which matters because Salmonella Typhi lives and replicates inside the body’s own immune cells. Adults receive a loading dose of 1g on day one, followed by 500mg once daily for the remaining six days. Children receive weight-adjusted dosing. Completing the full seven-day course is essential.
Ceftriaxone
Ceftriaxone is the preferred treatment for severe typhoid fever requiring hospitalization, for patients who cannot take medication by mouth, and in cases where oral agents are not available. It is given by injection and cannot be taken orally. Once a patient improves clinically, transitioning to oral azithromycin is appropriate. Ceftriaxone has higher relapse rates than azithromycin when used as a standalone course.
Ciprofloxacin
Ciprofloxacin remains an option in Ghana where susceptibility is confirmed by laboratory testing. A 2025 systematic review from Ghana found ciprofloxacin retained relatively low resistance rates compared to other antibiotics in the Ghanaian context. However, it should not be used empirically , meaning without confirmed susceptibility , particularly given widespread resistance in parts of South Asia. Local drug susceptibility testing guides this decision.
Treatment Note
Patients treated with effective antibiotics may continue to have fever for three to five days after starting treatment, with the temperature gradually decreasing each day. This is expected and does not mean the treatment is failing. If fever does not begin to improve within five days of starting treatment, return to your healthcare provider. Completing the full prescribed course , even after feeling better , is essential to reduce the risk of relapse and drug resistance.
Prevention
Drink safe, treated water
Salmonella Typhi enters the body through contaminated water. Drinking water from a treated piped supply, boiling water before drinking, or using water purification methods reduces this risk. In communities where the water supply is inconsistent, safe water practices are one of the most important protective measures available.
Practice safe food hygiene
Food prepared without clean water, by handlers who do not wash their hands, or left uncovered in environments where it may be contaminated carries transmission risk. Eating food that is freshly cooked and hot, washing fruits and vegetables with clean water, and avoiding raw foods in high-risk settings reduces exposure to Salmonella Typhi.
Wash hands thoroughly with soap
Thorough handwashing with soap and water before eating, before preparing food, and after using the toilet interrupts the fecal-oral transmission route directly. This applies to everyone in a household, but is especially important for anyone who prepares food for others.
Typhoid Conjugate Vaccine (TCV)
The Typhoid Conjugate Vaccine is a single injectable dose approved from six months of age and provides protection against typhoid for several years. Large trials in Africa and Asia showed efficacy of 79 to 85 percent in children aged 9 months to 16 years. The WHO recommends TCV for routine immunization in typhoid-endemic countries. Vaccination reduces but does not eliminate risk , safe water, food hygiene, and handwashing remain essential alongside vaccination.
Prevention Note
No single preventive measure is sufficient on its own. Safe water, food hygiene, handwashing, and vaccination each address a different part of the transmission chain. Together, they provide the most effective protection against typhoid fever.
Risk Factors
Water and Sanitation Risk Factors
These environmental conditions directly increase the chance of exposure to Salmonella Typhi.
- Drinking water from rivers, wells, or unprotected sources that may be contaminated
- Living in communities without reliable treated water supply
- Limited or no access to adequate sanitation and toilet facilities
- Living in areas where open defecation occurs near water sources
Social and Household Risk Factors
These conditions increase the likelihood of transmission within households and communities.
- Living in crowded housing conditions with shared sanitation facilities
- Household contact with a known or unidentified typhoid carrier
- Consuming food prepared by someone who carries Salmonella Typhi without adequate hand hygiene
- Rural residence in Ghana, where incidence rates are documented to be approximately twice those of urban areas
Individual Risk Factors
These personal factors increase the risk of contracting typhoid or developing more severe disease.
- Children aged 5 to 15 years, who bear the highest disease burden in Ghana
- Immunocompromised individuals including those living with HIV
- Malnourished individuals with impaired immune response
- Travelers to typhoid-endemic areas without prior vaccination
- Taking antibiotics before diagnostic testing, which reduces the sensitivity of blood culture and the Widal test and can delay accurate diagnosis
Risk Note
In Ghana, the highest typhoid burden falls on children and communities with limited access to safe water and sanitation. Addressing these underlying conditions is the most important long-term strategy for reducing typhoid risk.
Complications
Intestinal Perforation
The most dangerous complication of typhoid fever. As Salmonella Typhi multiplies in the lymphoid tissue of the small intestinal wall, these tissues can ulcerate through the gut wall, creating a perforation. This spills intestinal contents into the abdominal cavity, causing severe and life-threatening peritonitis. Intestinal perforation is a surgical emergency. It occurs in approximately 1 to 3 percent of hospitalized typhoid patients globally, but the case fatality rate in African settings ranges from 14 to 28 percent , significantly higher than in other regions , largely due to limited access to emergency surgery and critical care.
Gastrointestinal Hemorrhage
Ulceration of the intestinal wall can cause bleeding without perforation. Hemorrhage ranges from mild to massive and typically occurs in the third week of untreated illness. It requires urgent medical management and may require blood transfusion.
Encephalopathy and Neurological Complications
Confusion, delirium, and altered consciousness occur in approximately one quarter of hospitalized typhoid cases. More severe neurological complications including encephalopathy, psychosis, and meningitis can develop in untreated or inadequately treated disease. Dexamethasone is used in severe neurological presentations and has been shown to reduce mortality.
Chronic Carrier State
Approximately 2 to 5 percent of people who recover from typhoid fever become chronic carriers, continuing to harbor Salmonella Typhi in the gallbladder for 12 months or more after apparent recovery, shedding the bacteria intermittently in their stool while appearing completely healthy. Chronic carriers are the most important reservoir for sustained typhoid transmission in endemic communities, because Salmonella Typhi has no animal or environmental reservoir. Approximately 90 percent of chronic carriers have gallstones, which provide the surface for bacterial biofilm formation.
Complication Note
Most complications of typhoid fever occur when the illness has been present for more than two weeks without appropriate treatment. Early diagnosis and timely antibiotic treatment are the most effective ways to prevent serious complications.
When to Seek Medical Care
Fever Lasting More Than Three Days
A fever that has persisted for three or more days , especially one that is gradually rising rather than spiking and resolving , warrants medical evaluation. The step-ladder fever pattern of typhoid is a reason to seek care rather than wait.
Fever Not Responding to Antimalarial Treatment
If you have been treated for malaria but your fever has not improved within two to three days of treatment, this is a recognized clinical signal to suspect an alternative or additional diagnosis including typhoid. Return to a health facility for further evaluation.
Negative Malaria Test With Ongoing Fever
A negative malaria rapid diagnostic test in someone with ongoing fever does not rule out typhoid. If your malaria test is negative but fever persists and you have had possible exposure to contaminated water or food, seek evaluation specifically for typhoid.
Confusion or Change in Mental State
Any confusion, extreme drowsiness, or change in mental state alongside fever requires urgent medical attention. These symptoms may indicate encephalopathy, one of the serious neurological complications of typhoid.
Sudden Severe Abdominal Pain
A sudden onset of severe abdominal pain during a typhoid illness , particularly if the abdomen becomes rigid , is a medical emergency that may indicate intestinal perforation. Go to a health facility immediately.
Emergency Advice
In Ghana, many patients take antibiotics, antimalarials, or analgesics before attending a health facility. Both practices can partially mask typhoid symptoms and significantly reduce the sensitivity of diagnostic tests, making accurate diagnosis harder. Seeking care earlier , particularly if fever has persisted for more than three days , improves the chance of an accurate diagnosis and a better outcome.
Prognosis
Excellent with Early Treatment
The case fatality rate for typhoid fever with appropriate antibiotic treatment falls to less than 1 percent in settings with good access to medical care. Most patients with uncomplicated typhoid who receive timely and effective treatment recover fully. Fever typically begins to resolve within three to five days of starting effective antibiotic therapy.
Significantly Worse With Complications or Delayed Treatment
The prognosis changes substantially when complications develop or when treatment is delayed. Typhoid intestinal perforation carries a case fatality rate of 14 to 28 percent in African settings. The median case mortality for typhoid intestinal perforation in Africa is significantly higher than in Asia, largely reflecting differences in access to quality surgical and critical care. The earlier treatment begins, the better the outcome.
Relapse in a Small Number of Patients
Fewer than 10 percent of patients experience relapse, typically one to three weeks after clinical recovery. A relapse is usually milder than the original illness and responds to antibiotic treatment. Completing the full prescribed antibiotic course reduces the risk of relapse.
Prognosis Note
The prognosis of typhoid fever in Ghana is more strongly shaped by how early treatment begins than by the disease itself. Early diagnosis, appropriate antibiotic treatment, and completion of the full prescribed course are the most important factors influencing recovery.
Differential Diagnosis
Malaria
The most important differential diagnosis for typhoid fever in Ghana. Both diseases are endemic in the same communities, both present with fever, headache, and fatigue, and both can be present simultaneously. Key distinguishing features: malaria typically presents more abruptly with pronounced chills and sweating episodes; typhoid fever develops gradually with a step-ladder rising fever without rigors. Prolonged fever not responding to antimalarial treatment is a recognized clinical signal to suspect typhoid. A negative malaria test does not diagnose typhoid, and a positive Widal test does not rule malaria out. Laboratory confirmation of both is the only reliable way to distinguish or confirm co-infection.
Brucellosis
A bacterial infection transmitted from animals through consumption of unpasteurized dairy products or direct animal contact. Causes prolonged fever, fatigue, sweating, and joint pain that overlaps clinically with typhoid. An important differential diagnosis in agricultural communities across Ghana. Requires specific blood culture methods and serological testing to distinguish from typhoid.
Viral Hepatitis (Hepatitis A and E)
Both Hepatitis A and Hepatitis E are transmitted through the fecal-oral route , the same mechanism as typhoid , and are endemic in settings with inadequate sanitation. They can present with fever, malaise, and abdominal discomfort. Jaundice (yellowing of the skin or eyes) and elevated liver enzymes on blood testing help distinguish hepatitis from typhoid.
Dengue Fever
Dengue fever is increasingly recognized in Ghana and is transmitted by Aedes mosquitoes. It presents with sudden onset high fever, severe headache, pain behind the eyes, and intense muscle and joint pain. A characteristic skin rash may appear. Dengue does not cause the gradual step-ladder fever of typhoid and typically resolves within seven to ten days. Blood tests showing low platelets and low white cell count with elevated haematocrit help identify dengue.
Clinical Note
The overlap between typhoid and malaria is the central diagnostic challenge in Ghana. Both a negative malaria test and a positive Widal test are insufficient to resolve the confusion , only blood culture confirms typhoid. When clinical suspicion is high and initial tests are inconclusive, this must be communicated clearly to the treating healthcare provider.
References
World Health Organization (WHO) , Typhoid Fact Sheet
World Health Organization guidance on typhoid fever epidemiology, transmission, diagnosis, treatment and prevention. Updated March 2023.
Centers for Disease Control and Prevention (CDC) , Clinical Overview of Typhoid Fever
CDC clinical guidance covering the diagnosis, treatment, and management of typhoid fever and paratyphoid fever. Updated May 2024.
CDC Yellow Book 2024 , Typhoid and Paratyphoid Fever
Comprehensive clinical reference for typhoid fever including diagnostic criteria, treatment regimens, and travel guidance. Updated April 2025.
StatPearls , Typhoid Fever (NBK557513)
Evidence-based clinical overview of typhoid fever covering pathophysiology, diagnosis, treatment, and complications. Updated April 2024.
Ghana Health Service , National Disease Control
National disease control guidelines and public health recommendations for Ghana, including guidance on typhoid fever management and prevention.
Frequently Asked Questions
I had a Widal test and it came back positive. Does that mean I definitely have typhoid?
A positive Widal test is not a confirmed diagnosis of typhoid fever. The Widal test measures antibodies against Salmonella Typhi, but those antibodies can be elevated for several reasons unrelated to an active typhoid infection. Malaria , which is common in Ghana , is documented to cause false positive Widal results. Prior typhoid infections or vaccinations can also leave behind elevated antibody levels. People living in areas where typhoid is common often carry a baseline level of antibodies that can produce a positive result without active infection.
A positive Widal test is one piece of clinical information. It raises the possibility of typhoid , not the certainty. A blood culture, which grows the actual bacteria from your blood, is the only test that can confirm a typhoid diagnosis. If you have had a positive Widal test, the right next step is a conversation with your healthcare provider about what further testing may be appropriate.
I was treated for malaria but my fever did not go away. Could it be typhoid?
Yes. This is a clinically recognized situation. Malaria and typhoid fever share many early symptoms , fever, headache, fatigue, and body aches , and in Ghana, both diseases are common. When a person is treated for malaria but the fever persists and does not improve within two to three days of treatment, this is a documented reason to suspect an alternative or additional diagnosis, including typhoid.
The CDC specifically notes that healthcare professionals should consider typhoid fever in a person who is not responding to antimalarial treatment. If you or someone you know has been treated for malaria and the fever is not resolving, returning to a health facility for further evaluation , and specifically asking about typhoid , is the right step. It is also possible, though less common, to have both infections at the same time.
How is typhoid different from malaria? They seem to have the same symptoms.
They share a number of early symptoms, which is exactly why they are so frequently confused in Ghana. But there are several documented differences worth understanding.
Typhoid fever develops gradually over several days, with the fever rising step by step rather than appearing suddenly. Malaria typically presents more abruptly, often with pronounced chills and heavy sweating. Typhoid does not usually cause the dramatic fever-sweat-chill cycle that malaria produces. Typhoid also tends to last longer , two to four weeks if untreated , while malaria treated appropriately typically resolves within a few days. Constipation is a common early symptom of typhoid in adults; it is not a feature of malaria.
None of these features is diagnostic on its own. They are clinical clues, not conclusions. The most reliable way to distinguish between the two diseases is laboratory testing , specifically blood culture for typhoid and a rapid diagnostic test or blood film for malaria.
My child recovered from typhoid but now has a fever again three weeks later. What does this mean?
A fever returning one to three weeks after recovery from typhoid is a recognized pattern called relapse. It occurs in fewer than 10 percent of patients who have been treated for typhoid. A relapse is usually less severe than the original illness and typically responds well to antibiotic treatment.
There are several reasons a relapse may occur. The antibiotic course may not have been completed. The antibiotic used may not have cleared all bacteria from the body’s deeper reservoirs, particularly the gallbladder. In some cases, the infecting strain may have reduced susceptibility to the antibiotic used.
If someone who has recently recovered from typhoid develops fever again, they should return to a health facility for evaluation. This is not an emergency in most cases, but it needs to be assessed and treated.
Is typhoid contagious? Can I catch it from being near someone who has it?
Typhoid is not spread through the air or by casual contact. You cannot catch typhoid fever by breathing the same air as someone who has it, by touching them, or by being in the same room.
Typhoid spreads through the fecal-oral route. The bacteria are present in the stool , and occasionally the urine , of an infected person. Transmission occurs when those bacteria contaminate water or food, typically through inadequate sanitation, poor hygiene, or food prepared by someone who carries the bacteria without washing their hands properly.
The risk is not from the person themselves, but from what comes from their body entering the water or food supply. This is why household members of a person with typhoid may be at elevated risk , not from direct contact, but from sharing water sources, food, or toilet facilities that may become contaminated if hygiene is not carefully maintained.