Typhoid fever, caused by Salmonella enterica serovar Typhi, remains a significant clinical concern, particularly in regions with limited access to clean water and proper sanitation.
While often overshadowed by other febrile illnesses, typhoid continues to challenge medical professionals due to evolving resistance patterns and diagnostic ambiguities.
Etiologic Agent and Pathogenesis
Salmonella Typhi is a gram-negative, facultative intracellular bacterium. Its virulence lies in its ability to evade host immune responses, aided by its Vi capsular antigen and a sophisticated type III secretion system. Upon ingestion, the bacterium translocates through intestinal epithelium and disseminates via the bloodstream, initiating a systemic inflammatory response that underpins its clinical manifestations.
Global Burden and Epidemiological Trends
In 2024, typhoid affects over 11 million people each year, with the highest incidence in South Asia and sub-Saharan Africa. Dr. Priya Ramaswamy, an infectious disease expert, highlights that many cases go unreported because the symptoms often resemble those of dengue, malaria, and leptospirosis.
Clinical Presentation: A Diagnostic Puzzle
Typhoid fever's early symptoms prolonged high-grade fever, fatigue, and abdominal discomfort—are nonspecific and mimic other tropical infections. In atypical presentations, neuropsychiatric symptoms such as confusion or behavioral changes may arise, adding to the diagnostic complexity.
A stepwise fever pattern is traditionally associated with typhoid, but current observations suggest this classical description may not apply to all patients, particularly in those pre-treated with antibiotics. The Widal test, while still used in some regions, has largely been replaced by blood cultures and polymerase chain reaction (PCR)-based diagnostics in urban clinical settings.
Antibiotic Resistance and Therapeutic Challenges
Therapeutic success hinges on accurate antibiotic selection. Ceftriaxone and azithromycin have become mainstays in treating uncomplicated cases, yet resistance trends threaten their longevity. According to Dr. John D. Clemens, empirical therapy must be guided by local antibiograms and culture sensitivity whenever possible.
Prolonged fevers despite appropriate therapy may suggest complications or co-infections, requiring further investigation and possibly a multidisciplinary approach.
Vaccination and Prevention: The Current Landscape
Two vaccines are currently available: the Ty21a live vaccine and the Vi polysaccharide conjugate vaccine. The conjugate vaccine has demonstrated stronger immune responses in children and has been incorporated into the immunization programs of several countries where typhoid is common. Preventive strategies should also focus on improving sanitation, public health education, and access to clean drinking water.
Ongoing randomized trials are evaluating the effectiveness of booster doses and the herd immunity thresholds, especially in densely populated urban slums.
Typhoid fever represents more than a bacterial infection; it reflects systemic gaps in healthcare equity, antibiotic stewardship, and global preparedness. Clinicians must remain vigilant not only in diagnosis and treatment but also in advocating for broader interventions that address the socio-environmental roots of the disease.
