Siblings with typhoid fever: An investigation of intrafamilial transmission, clonality, and antibiotic susceptibility.

Abstract

Typhoid fever usually manifests as an acute disease. However, asymptomatic carriage with Salmonella Typhi may occur. This study investigated a family setting of severe typhoid fever in Switzerland months after return from Bangladesh. Standard microbiological procedures were performed. Testing for S. Typhi IgM antibodies was done using a novel immunochromographic lateral flow assay. Whole genome sequencing (WGS) followed by comparative core genome multilocus sequence typing (cgMLST) was performed on the S. Typhi isolates. Four months after returning from a visit to Bangladesh sibling 1 (9 months) was diagnosed with a S. Typhi meningitis and sibling 3 (8 years) was identified as asymptomatic S. Typhi carrier. Sibling 2 (2 years) was retrospectively diagnosed with typhoid fever by IgM serology at the time point of admission to the hospital. Parents were asymptomatic and culture-negative. WGS analysis of family S. Typhi isolates showed clonality and strongest homology with S. Typhi strains occurring in Bangladesh. The S. Typhi strain showed resistance against fluoroquinolones. A 4-week course of ceftriaxone resulted in full recovery of sibling 1. S. Typhi was eradicated from sibling 3 following azithromycin treatment for 14 days. S. Typhi, acquired from a visit to Bangladesh, was most likely transmitted within the family from one brother as asymptomatic shedder to his 9-month-old brother who manifested S. Typhi meningitis as a very rare and life-threatening presentation of typhoid fever. S. Typhi infection should be considered even in case of uncommon manifestations and irrespective of the interval between disease presentation and travel to an endemic area.