Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.
Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design.
Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, UK; NIHR Oxford Biomedical Research Centre, The Joint Research Office, Block 60, The Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK. Electronic address: cwaddington@ichr.uwa.edu.au.
Claire S
CS
Waddington
Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, UK; NIHR Oxford Biomedical Research Centre, The Joint Research Office, Block 60, The Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
Thomas C
TC
Darton
Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
William E
WE
Woodward
Nuffield Department of Clinical Medicine, University of Oxford, Henry Wellcome Building for Molecular Physiology, Old Road Campus, Headington, Oxford OX3 7BN, UK.
Brian
B
Angus
Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Room 480, Baltimore, MD 21201-1509, USA.
Myron M
MM
Levine
Oxford Vaccine Group, Department of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, UK; NIHR Oxford Biomedical Research Centre, The Joint Research Office, Block 60, The Churchill Hospital, Old Road, Headington, Oxford OX3 7LE, UK.
Andrew J
AJ
Pollard
D049673:History, 20th Century; D006801:Humans; D012485:Salmonella typhi / Q000276:immunology / Q000302:isolation & purification*; D036302:Therapeutic Human Experimentation / Q000266:history*; D014435:Typhoid Fever / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification
D014436:Typhoid-Paratyphoid Vaccines
Controlled human infection; Enteric infection; Human challenge; Quailes strain; Salmonella Typhi; Typhoid fever