GeneHealth - Your precision medicine

Typhoid Fever

Disease Details

Family Health Simplified

Buy Membership

Description: Typhoid fever is a bacterial infection caused by Salmonella typhi, characterized by prolonged fever, abdominal pain, and systemic symptoms.
Type: Typhoid fever is an infectious disease caused by the bacterium *Salmonella enterica* serotype Typhi. It is not genetically transmitted but rather spread through the ingestion of contaminated food or water.
Signs And Symptoms: Classically, the progression of untreated typhoid fever has three distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated.
In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for S. enterica subsp. enterica serovar Typhi. The Widal test is usually negative.
In the second week, the person is often too tired to get up, with high fever in plateau around 40 °C (104 °F) and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium can occur, where the patient is often calm, but sometimes becomes agitated. This delirium has given typhoid the nickname "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi (rattling breathing sounds) are heard in the base of the lungs. The abdomen is distended and painful in the right lower quadrant, where a rumbling sound can be heard. Diarrhea can occur in this stage, but constipation is also common. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive.
In the third week of typhoid fever, a number of complications can occur:
The fever is still very high and oscillates very little over 24 hours. Dehydration ensues along with malnutrition, and the patient is delirious. A third of affected people develop a macular rash on the trunk.
Intestinal haemorrhage due to bleeding in congested Peyer's patches occurs; this can be very serious, but is usually not fatal.
Intestinal perforation in the distal ileum is a very serious complication and often fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
Respiratory diseases such as pneumonia and acute bronchitis
Encephalitis
Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.
Metastatic abscesses, cholecystitis, endocarditis, and osteitis.
Low platelet count (thrombocytopenia) is sometimes seen.
Prognosis: The prognosis for typhoid fever varies depending on the timeliness and effectiveness of treatment. With prompt and appropriate antibiotic therapy, most patients recover fully within a few weeks. However, if left untreated, typhoid fever can lead to severe complications and has a higher risk of becoming fatal. The mortality rate of untreated cases can be as high as 20%, while with treatment, it drops significantly to around 1-2%.
Onset: The onset of typhoid fever typically occurs 6 to 30 days after exposure to the bacteria Salmonella Typhi.
Prevalence: Prevalence data for typhoid fever vary widely by region. Approximately 11-20 million cases occur globally each year, with higher rates in South Asia, Southeast Asia, and parts of sub-Saharan Africa. It is less common in developed countries due to better sanitation and vaccination programs.
Epidemiology: In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths. It occurs most often in children and young adults between 5 and 19 years old. In 2013, it resulted in about 161,000 deaths – down from 181,000 in 1990. Infants, children, and adolescents in south-central and Southeast Asia have the highest rates of typhoid. Outbreaks are also often reported in sub-Saharan Africa and Southeast Asia. In 2000, more than 90% of morbidity and mortality due to typhoid fever occurred in Asia. In the U.S., about 400 cases occur each year, 75% of which are acquired while traveling internationally.Before the antibiotic era, the case fatality rate of typhoid fever was 10%–20%. Today, with prompt treatment, it is less than 1%, but 3%–5% of people who are infected develop a chronic infection in the gall bladder. Since S. enterica subsp. enterica serovar Typhi is human-restricted, these chronic carriers become the crucial reservoir, which can persist for decades for further spread of the disease, further complicating its identification and treatment. Lately, the study of S. enterica subsp. enterica serovar Typhi associated with a large outbreak and a carrier at the genome level provides new insight into the pathogenesis of the pathogen.In industrialized nations, water sanitation and food handling improvements have reduced the number of typhoid cases. Third world nations have the highest rates. These areas lack access to clean water, proper sanitation systems, and proper health-care facilities. In these areas, such access to basic public-health needs is not expected in the near future.In 2004–2005 an outbreak in the Democratic Republic of Congo resulted in more than 42,000 cases and 214 deaths. Since November 2016, Pakistan has had an outbreak of extensively drug-resistant (XDR) typhoid fever.In Europe, a report based on data for 2017 retrieved from The European Surveillance System (TESSy) on the distribution of confirmed typhoid and paratyphoid fever cases found that 22 EU/EEA countries reported a total of 1,098 cases, 90.9% of which were travel-related, mainly acquired during travel to South Asia.
Intractability: Typhoid fever is not generally considered intractable. It is typically treatable with appropriate antibiotic therapy. Early diagnosis and prompt treatment are crucial for a favorable outcome. However, some strains of Salmonella Typhi, the bacterium responsible for typhoid fever, have developed resistance to common antibiotics, which can complicate treatment.
Disease Severity: Typhoid fever is considered a serious and potentially life-threatening illness if not treated promptly.
Healthcare Professionals: Disease Ontology ID - DOID:13258
Pathophysiology: Pathophysiology:
Typhoid fever is caused by the bacterium Salmonella enterica serotype Typhi. The infection occurs through ingestion of contaminated food or water. Once ingested, the bacteria invade the small intestine's mucosal lining, enter the bloodstream (bacteremia), and disseminate to various organs, including the liver, spleen, and bone marrow. The bacteria multiply within macrophages and get released into the bloodstream, leading to systemic infection. The resultant inflammation and immune response cause the clinical manifestations of typhoid fever, such as fever, abdominal pain, and hepatosplenomegaly.
Carrier Status: Carrier status for typhoid fever refers to individuals who continue to harbor and excrete the bacteria *Salmonella typhi* in their stool or urine, often for years, even after symptoms have resolved. These carriers can spread the infection to others without showing symptoms themselves.
Mechanism: Typhoid fever is caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi). The mechanism involves the bacterium's entry, survival, and proliferation within the host.

**Mechanism:**
1. **Entry:** S. Typhi is typically ingested through contaminated food or water. It survives the acidic environment of the stomach and enters the small intestine.
2. **Penetration and Colonization:** The bacteria adhere to and invade the epithelial cells of the intestinal lining, often using specialized structures like pili.
3. **Intracellular Survival:** S. Typhi can survive and replicate within the phagocytes of the host by evading the host's immune response. It uses type III secretion systems to inject effector proteins into host cells, manipulating host cellular functions to favor bacterial survival.
4. **Systemic Spread:** Once inside the phagocytes, S. Typhi can translocate to other tissues and organs, such as the liver, spleen, and bone marrow, via the lymphatic system and bloodstream.
5. **Persistent Infection:** The bacteria can establish a systemic infection, leading to prolonged fever, gastrointestinal disturbances, and sometimes severe complications.

**Molecular Mechanisms:**
1. **Type III Secretion System (T3SS):** S. Typhi utilizes two distinct T3SSs (encoded by Salmonella pathogenicity islands, SPI-1, and SPI-2) to inject effector proteins into host cells. SPI-1 is primarily involved in the invasion of intestinal epithelial cells, while SPI-2 is critical for intracellular survival and replication.
2. **Vi Antigen:** The Vi capsule polysaccharide helps S. Typhi avoid detection by the host immune system. It inhibits phagocytosis and reduces the inflammatory response, aiding in immune evasion.
3. **Effector Proteins:** Various effector proteins such as SopE, SopB, and SptP modify host cell pathways to promote bacterial entry, prevent apoptosis, and facilitate intracellular survival by modifying the endocytic vesicle trafficking and preventing lysosomal fusion.
4. **PhoPQ and PmrAB Regulatory Systems:** These two-component regulatory systems are activated in response to hostile conditions within the host's phagosomes. They regulate genes that enhance bacterial resistance to antimicrobial peptides and oxidative stress.
5. **Quorum Sensing:** S. Typhi employs quorum sensing mechanisms to regulate the expression of virulence genes in response to its population density, optimizing infection and survival strategies based on the environment.

Understanding these mechanisms can help in the development of targeted therapies and vaccines for typhoid fever.
Treatment: Typhoid fever is typically treated with antibiotics. Commonly used antibiotics include ciprofloxacin for non-pregnant adults and azithromycin. In areas where antibiotic resistance is prevalent, ceftriaxone or other effective antibiotics might be used. It is important for patients to complete the full course of antibiotics even if symptoms improve to ensure complete eradication of the bacteria. Hydration and supportive care are also important during treatment. Nano-therapeutic approaches are still experimental and not widely used in clinical practice for typhoid fever as of now.
Compassionate Use Treatment: Compassionate use treatments for typhoid fever are typically considered in severe cases where standard treatments are not effective or available. This may include the use of novel antibiotics or investigational drugs that are still undergoing clinical trials.

Off-label or experimental treatments might include the use of advanced-generation antibiotics such as azithromycin and carbapenems, especially in areas with high levels of antimicrobial resistance. Additionally, the re-evaluation of older antibiotics, possibly in combination therapies, might also be considered under experimental contexts to address resistant strains.

It is advisable to conduct these treatments under strict medical supervision and often within clinical trial settings to ensure patient safety and accurate data collection.
Lifestyle Recommendations: Lifestyle recommendations for typhoid fever:

1. **Hydration**: Drink plenty of fluids to stay hydrated, as typhoid fever often causes diarrhea and sweating, leading to fluid loss.

2. **Rest**: Ensure ample bed rest to help your body fight the infection and recover more quickly.

3. **Diet**:
- Eat easily digestible foods such as soups, broths, and steamed vegetables.
- Avoid spicy, fatty, and high-fiber foods that may irritate the digestive system.
- Consume small, frequent meals rather than large ones.

4. **Hygiene**: Practice good hygiene to prevent the spread of infection.
- Wash hands thoroughly with soap and water, especially before eating and after using the bathroom.
- Avoid preparing food for others until fully recovered.

5. **Avoid Potentially Contaminated Water and Food**:
- Drink only boiled or bottled water.
- Avoid raw fruits and vegetables that can’t be peeled.
- Steer clear of street food and undercooked meats.

6. **Medical Follow-up**: Complete the full course of antibiotics as prescribed by your doctor, even if you start feeling better.

7. **Vaccination**: If you live in or are traveling to an area where typhoid fever is common, consider getting vaccinated and discuss preventive measures with your doctor.
Medication: Medication commonly used to treat typhoid fever includes antibiotics such as ciprofloxacin, azithromycin, and ceftriaxone. Dosage and treatment duration depend on the severity of the infection and the patient's overall health.
Repurposable Drugs: Repurposable drugs for typhoid fever include fluoroquinolones (such as ciprofloxacin), third-generation cephalosporins (such as ceftriaxone), and azithromycin. These antibiotics, originally developed to treat other bacterial infections, are effective against Salmonella Typhi, the bacterium responsible for typhoid fever.
Metabolites: Typhoid fever is caused by the bacterium Salmonella enterica serotype Typhi. During infection, several metabolites fluctuate, including intermediates in energy metabolism such as glucose, lactate, and amino acids like tyrosine and tryptophan. Pathogenic bacteria also produce unique metabolites like endotoxins (lipopolysaccharides) that can be detected in infected individuals. Nanotechnology is being explored for rapid detection and treatment, utilizing nanosensors for early diagnosis or nanoparticle-based drug delivery systems for more effective therapy.
Nutraceuticals: For typhoid fever, there is currently no specific evidence supporting the use of nutraceuticals for its treatment or prevention. The primary approach to managing typhoid fever includes the use of appropriate antibiotics and supportive care measures. It is essential for patients to consult healthcare providers for accurate diagnosis and effective treatment.
Peptides: Typhoid fever is caused by the bacterium Salmonella Typhi. Although the bacterium itself is not a peptide, the immune response to infection involves peptides known as antigens, which can be targeted by the body's immune system or used in diagnostic tests and vaccines. Research into peptide-based vaccines and treatments is ongoing, considering the specific antigens of Salmonella Typhi to potentially enhance immunity and improve disease management.

**Peptides:** In the context of typhoid fever, these often refer to antigenic peptides derived from Salmonella Typhi used in diagnostic methods or vaccine development.

**Nan:** It appears there might be a typo. If "nan" refers to "nanotechnology," current research is exploring nanotechnology-based delivery systems for vaccines and antibiotics, aimed at improving the treatment and prevention of typhoid fever.