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. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

Leptospirosis caprina: los riesgos de una enfermedad descuidada

“…As condições favoráveis para a sobrevivência das leptospiras incluem solo alcalino ou neutro, solo de origem vulcânica (Schneider et al, 2013), umidade elevada, temperatura próxima aos 20°C e proteção contra radiação solar. Esses fatores, juntamente à ampla gama de sorovares e potenciais hospedeiros, garantem a perpetuação da doença (Higino & Azevedo, 2014) apesar da incapacidade da bactéria de perdurar em altas densidades no solo ou água (Gostic et al, 2019), água salgada (Grennan, 2019), pH ácido, sob radiação solar direta e em ambientes secos (Genovez, 2016).…”

“…Para o estabelecimento da infecção, entretanto, é necessário que o agente etiológico realize a travessia de barreiras físicas como pele e mucosas, as quais constituem a principal linha de defesa imunológica eficiente. Assim, a perda da integridade de barreiras físicas favorece a instalação da infecção e, quando comparada à pele ilesa, requer uma quantidade inferior de antígeno para infectar o animal (Gostic et al, 2019).…”

Severe leptospirosis after rat bite: A case report

“…The transmission during a rat bite could be due to short-term saliva contamination during urogenital area grooming [15]. Alternatively, broken skin, a predominant route to cause infection in environments of low exposure [16], could have been a portal entry for leptospires. However, the subject did not report contact with water or soil potentially contaminated with Leptospira during the 11 days before symptoms.…”

Dynamic and integrative approaches to understanding pathogen spillover

“…Gostic et al . [ 37 ] next provide an example of the epidemiological insights such an approach can yield. They present a modelling analysis of dose–response experiments for Leptospira interrogans , a globally important bacterial zoonosis for which environmental exposure to soil or water contaminated by urine of infected reservoir hosts is the primary transmission route [ 38 ].…”