Abstract
Transmission of M. ulcerans, the etiological agent of Buruli ulcer, from the environment to humans remains an enigma despite decades of research. Major transmission hypotheses propose 1) that M. ulcerans is acquired through an insect bite or 2) that bacteria enter an existing wound through exposure to a contaminated environment. In studies reported here, a guinea pig infection model was developed to determine whether Buruli ulcer could be produced through passive inoculation of M. ulcerans onto a superficial abrasion. The choice of an abrasion model was based on the fact that most bacterial pathogens infecting the skin are able to infect an open lesion, and that abrasions are extremely common in children. Our studies show that after a 90d infection period, an ulcer was present at intra-dermal injection sites of all seven animals infected, whereas topical application of M. ulcerans failed to establish an infection. Mycobacterium ulcerans was cultured from all injection sites whereas infected abrasion sites healed and were culture negative. A 14d experiment was conducted to determine how long organisms persisted after inoculation. Mycobacterium ulcerans was isolated from abrasions at one hour and 24 hours post infection, but cultures from later time points were negative. Abrasion sites were qPCR positive up to seven days post infection, but negative at later timepoints. In contrast, M. ulcerans DNA was detected at intra-dermal injection sites throughout the study. M. ulcerans was cultured from injection sites at each time point. These results suggest that injection of M. ulcerans into the skin greatly facilitates infection and lends support for the role of an invertebrate vector or other route of entry such as a puncture wound or deep laceration where bacteria would be contained within the lesion. Infection through passive inoculation into an existing abrasion appears a less likely route of entry.
Highlights
Buruli ulcer, a severe cutaneous infection caused by the environmental pathogen Mycobacterium ulcerans is a major cause of morbidity in West and Central Africa [1,2]
The causative bacterium, M. ulcerans has been detected in many aquatic sources, but how bacteria enter the skin is an enigma
Two major hypotheses for infection are 1) that bacteria are injected into the skin through the bite of an aquatic insect, or 2) that bacteria enter open wounds on a person’s body
Summary
A severe cutaneous infection caused by the environmental pathogen Mycobacterium ulcerans is a major cause of morbidity in West and Central Africa [1,2]. The disease begins with a painless nodule that can lead to severe ulceration. In 1998, the World Health Organization declared Buruli ulcer a neglected tropical disease and established the Global Buruli Ulcer Initiative focused on prevention, awareness, and improved treatment options for those suffering from this disease. The transmission of M. ulcerans from the environment to humans is a central enigma in M. ulcerans research [1]. Infection has been consistently linked with exposure to aquatic environments, but the exact mode of transmission is unknown [3]. Person-to-person transmission is extremely rare [4]
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