Typhoid fever
The bacterium Salmonella enterica subsp. enterica serovar Typhi grows inside the intestines of infected humans. It replicates within Peyer's patches, mesenteric lymph nodes, spleen, liver, gallbladder, bone marrow and blood. This specific strain infects only people. No known animal reservoir exists for this pathogen. Humans are the sole source of infection. The disease spreads through the fecal-oral route from infected individuals or asymptomatic carriers. Contaminated water or food carries the bacteria into a new host. Risk factors include limited access to clean drinking water and poor sanitation. Those who have not yet been exposed to it and ingest contaminated drinking water or food are most at risk for developing symptoms. Asymptomatic human carriers excrete typhoid bacteria in stool even after the acute stage of infection ends. An asymptomatic carrier can remain infectious for years.
Classically, untreated typhoid fever progresses through three distinct stages, each lasting about one week. During these weeks, patients become exhausted and emaciated. In the first week, body temperature rises slowly with relative bradycardia known as Faget sign. Malaise, headache, and cough accompany the rising fever. A bloody nose appears in a quarter of cases. Abdominal pain is also possible. White blood cell counts decrease while eosinopenia and relative lymphocytosis occur. Blood cultures test positive for Salmonella enterica subsp. enterica serovar Typhi. The Widal test usually remains negative during this initial phase. By the second week, high fever plateaus around 40 degrees Celsius. Patients often cannot get out of bed due to exhaustion. Delirium occurs where the patient may be calm or agitated. This mental state gave typhoid the nickname nervous fever. Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi, or rattling breathing sounds, are heard at the base of lungs. The spleen and liver enlarge and become tender. Diarrhea can occur but constipation is common. In the third week, complications include intestinal hemorrhage from bleeding in congested Peyer's patches. Intestinal perforation in the distal ileum becomes critical and often fatal. Dehydration ensues along with malnutrition. Respiratory diseases such as pneumonia develop alongside neuropsychiatric symptoms like muttering delirium.
Diagnosis relies on culturing Salmonella Typhi from patient samples or detecting an immune response via blood tests. The Widal test identifies specific antibodies by mixing serum with dead bacterial suspension. If clumping occurs, the result indicates infection. This method takes time and produces significant false positives. It may also yield falsely negative results in recently infected people. Rapid diagnostic tests like Tubex, Typhidot, and Test-It show moderate accuracy. Typhidot detects IgM and IgG antibodies against a 50Kd OMP antigen. Two colored bands indicate a positive result while a single control band means negative. These rapid tests lack quantitative data. Diagnostic tools in regions where typhoid is most prevalent remain limited in accuracy and specificity. The time required for proper diagnosis creates hardships for under-resourced healthcare systems. Increasing spread of antibiotic resistance complicates treatment decisions. Cost of testing remains a barrier for many communities. In epidemics, doctors sometimes conduct therapeutic trials with chloramphenicol while awaiting culture results. New advances in large-scale data collection allow researchers to detect changing abundances of small molecules in blood that may specifically indicate typhoid fever.
Sanitation and hygiene form the foundation of prevention efforts worldwide. Careful food preparation and handwashing are crucial to stop transmission. Industrialization eliminated public health hazards associated with horse manure on streets which led to fly populations carrying pathogens. Chlorination of drinking water caused dramatic decreases in typhoid transmission according to U.S. Centers for Disease Control statistics. Vaccines prevent about 40, 90% of cases during the first two years. Protection may last up to seven years depending on the formulation. The World Health Organization endorsed vaccination programs starting in 1999 to decrease rates in developing nations. Prices normally stay below one US dollar per dose making them accessible to poverty-stricken communities. Two licensed vaccines exist today: live oral Ty21a sold as Vivotif and injectable polysaccharide vaccine sold as Typhim Vi. Boosters are recommended every five years for the oral version and every two years for injections. An older killed whole-cell vaccine remains available but is no longer recommended due to side effects like pain and inflammation at injection sites. A phase 3 trial of typhoid conjugate vaccine reported 81% fewer cases among children in December 2019. Combining vaccines with public health efforts remains the only proven way to control this disease.
Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin has become common globally. These agents are no longer used as first-line treatment for typhoid fever. Ciprofloxacin resistance presents an increasing problem especially in the Indian subcontinent and Southeast Asia. Many centers now shift from ciprofloxacin to ceftriaxone as the primary choice for suspected cases originating in South America, India, Pakistan, Bangladesh, Thailand or Vietnam. Azithromycin appears better at treating resistant strains than fluoroquinolone drugs or ceftriaxone. This drug can be taken orally and costs less than injectable alternatives. Laboratory testing for reduced susceptibility to ciprofloxacin faces challenges. Current recommendations require isolates to be tested simultaneously against ciprofloxacin and nalidixic acid. An analysis of 271 isolates found that around 18% of those with reduced susceptibility would not be detected by standard methods. Multidrug-resistant typhoid strains have evolved rapidly since the 1950s when resistance to chloramphenicol became frequent in Southeast Asia. Today chloramphenicol serves only as a last resort due to high prevalence of resistance.
The Plague of Athens during the Peloponnesian War likely represented an outbreak of typhoid fever. Mass burial sites examined in 2006 revealed DNA fragments similar to modern Salmonella Typhi dating back to approximately 430 B.C. In 1897 Maidstone England became the first town to chlorinate its entire water supply following an outbreak. That same year recorded 1,847 patients with typhoid fever. Almoth Edward Wright's vaccine deployment marked the first time a typhoid vaccine was used during a civilian outbreak. The American army suffered over 21,000 cases resulting in 2,200 deaths during the Spanish-American war. Guests at mayoral banquets in Southampton and Winchester fell ill in 1902 after consuming oysters from Emsworth contaminated with raw sewage. Jamaica Plain neighborhood in Boston experienced a major outbreak linked to milk delivery in 1908. Mary Mallon known as Typhoid Mary caused 51 cases and three deaths between 1907 and 1915 while working as a cook for upper-class families. She became the first known asymptomatic carrier of an infectious disease. Portland Oregon faced an outbreak in 1924 consisting of 26 cases and five deaths all due to intestinal hemorrhage. A single milk farm worker shed large amounts of the pathogen in his urine. Dushanbe Tajikistan reported 10,677 cases and 108 deaths during 1996, 1997. Kinshasa Democratic Republic of Congo saw more than 43,000 cases and over 200 deaths in 2004.
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Common questions
What causes typhoid fever and who can be infected?
Typhoid fever is caused by the bacterium Salmonella enterica subsp. enterica serovar Typhi which grows inside human intestines. This specific strain infects only people with no known animal reservoir existing for this pathogen.
How does untreated typhoid fever progress through its stages?
Untreated typhoid fever progresses through three distinct stages each lasting about one week where patients become exhausted and emaciated. The first week features rising body temperature and relative bradycardia while the second week shows high fever plateaus around 40 degrees Celsius and delirium. Complications in the third week include intestinal hemorrhage from bleeding in congested Peyer's patches and intestinal perforation in the distal ileum.
When did Maidstone England become the first town to chlorinate its water supply?
Maidstone England became the first town to chlorinate its entire water supply following an outbreak in 1897. That same year recorded 1,847 patients with typhoid fever before the intervention took effect.
Which vaccines are currently licensed for typhoid fever prevention?
Two licensed vaccines exist today including live oral Ty21a sold as Vivotif and injectable polysaccharide vaccine sold as Typhim Vi. Protection may last up to seven years depending on the formulation with boosters recommended every five years for the oral version and every two years for injections.
Why has resistance to common antibiotics become a problem for treating typhoid fever?
Resistance to ampicillin chloramphenicol trimethoprim-sulfamethoxazole and streptomycin has become common globally so these agents are no longer used as first-line treatment. Multidrug-resistant typhoid strains have evolved rapidly since the 1950s when resistance to chloramphenicol became frequent in Southeast Asia.