Typhoid fever pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Pathophysiology

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Innoculation Orofecal transmission Infective dose 1000 to 1 million

Gastrointestinal Infection Stomach Enters stomach High tolerance for acid Survives PH as low as 1.5 Small intestine Adherence to mucosal cells Invade mucosal M cells overlying payers patches Internalisation in M cells Translocation to underlying lymphoid tissue and draining lymph nodes

Systemic spread Dissemination of S.typhi to reticuloendothelial system Spreads via lymph and blood Replication within reticuloendothelial system Evades immune system

Chronic carrier state Resides and multiplies in gall bladder Excretion in urine and stool

Genetics

Typhoid fever may be associtated with genes of the Class II and Class III Major Histocompatibility Complex. Two types of HLA associations can be found with typhoid fever:

• HLA-DRB1*0301/6/8, HLA-DQB1*0201-3, and TNFA*2(–308) associated with increased susceptibility to typhoid fever.
• HLA-DRB1*04, HLA-DQB1*0401/2, and TNFA*1(–308)associated with increased disease resistance.