Definition and evidence of transmission
The French doctors Pierre-Fidele Bretonneau and Pierre-Charles-Alexandre Louis are credited with describing typhoid fever as a specific disease, unique from typhus. Both doctors performed autopsies on individuals who died in Paris due to fever – and indicated that many had lesions on the Peyers patches which correlated with distinct symptoms before death. British medics were skeptical of the differentiation between typhoid and typhus because both were endemic to Britain at that time. However, in France only typhoid was present circulating in the population. Pierre-Charlles-Alexandre Louis also performed case studies and statistical analysis to demonstrate that typhoid was contagious - and that persons who already had the disease seemed to be protected. Afterward, several American doctors confirmed these findings, and then Sir William Jenner convinced any remaining skeptics that typhoid is a specific disease recognizable by lesions in the Peyers patches by examining sixty six autopsies from fever patients and concluding that the symptoms of headaches, diarrhea, rash spots, and abdominal pain were only present in patients which then had intestinal lesions after death; which solidified the association of the disease with the intestinal tract and gave the first clue to the route of transmission.In 1847 William Budd learned of an epidemic of typhoid fever in Clifton, and identified that all 13 of 34 residents who had contracted the disease drew their drinking water from the same well. Notably, this observation was two years prior to John Snow discovering the route of contaminated water as the cause for a cholera outbreak.
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 Peyers 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. Causes
Bacteria
The Gram-negative bacterium that causes typhoid fever is Salmonella enterica subsp. enterica serovar Typhi. Based on MLST subtyping scheme, the two main sequence types of the S. Typhi are ST1 and ST2, which are widespread globally. Global phylogeographical analysis showed dominance of a haplotype 58 (H58), which probably originated in India during the late 1980s and is now spreading through the world with multi-drug resistance. A more detailed genotyping scheme was reported in 2016 and is now being used widely.