Mechanistic dose–response modelling of animal challenge data shows that intact skin is a crucial barrier to leptospiral infection
Abstract
Leptospirosis is a widespread and potentially life-threatening zoonotic disease caused by spirochaetes of the genus Leptospira . Humans become infected primarily via contact with environmental reservoirs contaminated by the urine of shedding mammalian hosts. Populations in high transmission settings, such as urban slums and subsistence farming communities, are exposed to low doses of Leptospira on a daily basis. Under these conditions, numerous factors determine whether infection occurs, including the route of exposure and inoculum dose. Skin wounds and abrasions are risk factors for leptospirosis, but it is not known whether broken skin is necessary for spillover, or if low-dose exposures to intact skin and mucous membranes can also cause infection. To establish a quantitative relationship between dose, route and probability of infection, we performed challenge experiments in hamsters and rats, developed mechanistic dose–response models representing the spatial dynamics of within-host infection and persistence, and fitted models to experimental data. Results show intact skin is a strong barrier against infection, and that broken skin is the predominant route by which low-dose environmental exposures cause infection. These results identify skin integrity as a bottleneck to spillover of Leptospira and underscore the importance of barrier interventions in the prevention of leptospirosis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 12, 2019
- Source ID
- 10.1098/rstb.2019.0367
Entities
People
- Albert Ko
- Camila Hamond
- Elsio Wunder
- James O. Lloyd-Smith
- Katelyn Gostic
- Timothy R. Julian
- Vimla Bisht
Organizations
- Defense Advanced Research Projects Agency
- Eawag
- John E. Fogarty International Center
- National Council for Scientific and Technological Development
- National Institute of Allergy and Infectious Diseases
- National Institute of General Medical Sciences
- National Institutes of Health
- National Science Foundation
- Oswaldo Cruz Foundation
- Swiss Tropical and Public Health Institute
- United States Department of Defense
- University of Basel
- University of California
- Yale School of Public Health