From the Guidelines
Typhoid fever is a life-threatening infection caused by the bacterium Salmonella Typhi, which invades the intestinal mucosa, multiplies within macrophages, and spreads to various organs, leading to a range of systemic and intestinal complications. The pathophysiology of typhoid fever involves several key steps, including ingestion of contaminated food or water, survival of the bacteria in the stomach, invasion of the small intestinal mucosa, and uptake by macrophages [ 1 ]. Within these cells, the bacteria multiply and spread via the lymphatic system to the liver, spleen, and bone marrow, where they replicate during the 1-2 week incubation period [ 1 ].
Key Pathophysiological Steps
- Ingestion of contaminated food or water
- Survival of the bacteria in the stomach
- Invasion of the small intestinal mucosa
- Uptake by macrophages and replication within the reticuloendothelial system
- Reentry into the bloodstream, causing bacteremia and the classic fever pattern
- Colonization of various organs, particularly the gallbladder, which serves as a reservoir for continued shedding into the intestines
Clinical Presentation and Complications
The clinical presentation of typhoid fever is characterized by fever, headache, constipation or diarrhea, and dry cough, with potential complications including gastrointestinal bleeding, intestinal perforation, and typhoid encephalopathy [ 1 ]. The bacteria produce an endotoxin that contributes to the systemic inflammatory response, while the Vi antigen helps it evade host immune detection.
Treatment and Management
Treatment of typhoid fever requires appropriate antibiotics, such as azithromycin (500mg daily for 7 days), ceftriaxone (2g IV daily for 10-14 days), or ciprofloxacin (500mg twice daily for 7-10 days), depending on resistance patterns, along with supportive care for fever and dehydration [ 1 ]. It is essential to note that vaccination provides incomplete protection against typhoid fever and does not protect from paratyphoid, highlighting the importance of prompt and effective treatment [ 1 ].
From the Research
Pathophysiology of Typhoid Fever
- Typhoid fever is a common cause of non-specific febrile infection in adults and children, particularly in low-resource settings such as South Asia 2
- The disease is caused by Salmonella typhi, which can develop resistance to antimicrobial agents, making treatment challenging 2, 3, 4
- The pathophysiology of typhoid fever involves the invasion of Salmonella typhi into the bloodstream, leading to fever, headache, and abdominal pain 3
Treatment Options
- Various antimicrobial agents have been used to treat typhoid fever, including ciprofloxacin, ceftriaxone, and azithromycin 2, 5, 3, 4, 6
- Ceftriaxone has been shown to be effective in treating typhoid fever, particularly in cases where other antimicrobial agents have failed 5, 4, 6
- Azithromycin has also been used to treat typhoid fever, although its effectiveness compared to other antimicrobial agents is still being studied 2, 3
Resistance Patterns
- Resistance to antimicrobial agents is a significant concern in the treatment of typhoid fever, with some strains of Salmonella typhi developing resistance to multiple agents 2, 3, 4
- Ciprofloxacin resistance is common in some regions, such as South Asia, making it less effective as a treatment option 2, 3
- Ceftriaxone and azithromycin may be effective alternatives in areas where resistance to other antimicrobial agents is high 2, 5, 3, 4, 6
Clinical Outcomes
- Clinical outcomes in typhoid fever treatment can vary depending on the antimicrobial agent used and the presence of resistance 2, 5, 3, 4, 6
- Ceftriaxone has been shown to result in faster defervescence and lower rates of clinical failure compared to other antimicrobial agents in some studies 5, 4, 6
- Azithromycin may also be effective in treating typhoid fever, although more research is needed to determine its comparative effectiveness 2, 3