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.
By World War I, the rate of typhoid in American soldiers was 37 per 100,000.During the second world war, the United States army authorized the use of a trivalent vaccine – containing heat-inactivated Typhoid, Paratyphi A and Paratyphi B pathogens.In 1934, discovery of the Vi capsular antigen by Arthur Felix and Miss S. R. Margaret Pitt enabled development of the safer Vi Antigen vaccine – which is widely in use today. Arthur Felix and Margaret Pitt also isolated the strain Ty2, which became the parent strain of Ty21a, the strain used as a live-attenuated vaccine for typhoid fever today. Antibiotics and resistance
Chloramphenicol was isolated from Streptomyces by Dr. David Gotlieb during the 1940s. In 1948 American army doctors tested its efficacy in treating typhoid patients in Kuala Lumpur, Malaysia. Individuals who received a full course of treatment cleared the infection, whereas patients given a lower dose had a relapse. Asymptomatic carriers continued to shed bacilli despite chloramphenicol treatment - only ill patients were improved with chloramphenicol. Resistance to chloramphenicol became frequent in Southeast Asia by the 1950s, and today chloramphenicol is only used as a last resort due to the high prevalence of resistance. Terminology
The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, pythogenic fever, drain fever and low fever. Notable people
Emperor Augustus of Rome (suspected based on historical record but not confirmed), survived.