Mathematical models of wound formation, disease progression and treatment pathways of Buruli ulcer disease

Abstract

Buruli ulcer (BU) is a skin-related neglected tropical disease caused by infection with Mycobacterium ulcerans (M. ulcerans). Our research elucidates the evolution of BU skin lesions, early detection and treatment of the BU-infected population. First, we formulate a mathematical model that describes the formation of an ulcer, including the space-time dynamics of M. ulcerans bacteria, mycolactone toxin, endothelial and stromal skin cell densities. The skin cell death processes causing the large ulcers in BU are ischaemia and direct cytotoxicity. Our results show that cell death occurs when either direct cytotoxicity, ischaemia, or both are present, and we also illustrate the speed of wound enlargement. Second, we develop an epidemiological model for the incidence, progression and treatment of BU. Our model shows the trend that populations in dierent compartments can take after being infected with BU. In our model results, an increase in the transfer rates between categories of infection leads to a decrease in the proportion of the population infected. Additionally, increasing the rate of transitioning to treatment decreases the proportion of cases that progress to ulcerative categories. Third, we investigate the cost-eectiveness of introducing a rapid diagnostic test (RDT) for testing BU from a healthcare provider perspective in Ghana. We develop a decision tree model and compare the RDT with the polymerase chain reaction test (PCR). The main result was the incremental cost-eectiveness ratio (ICER) of −$272.73 per disability-adjusted life year (DALY) averted from using an RDT compared to a PCR. In the probabilistic sensitivity analysis, most ICER pairs spread out in the southeast quadrant, where the RDT was less costly and yielded fewer DALY. Finally, we develop an agent-based model to explore the eects of introducing community health volunteers (CHV) in referring BU patients for treatment. We compare the eect of either self-referral (SR) independently or both SR and CHV in the early diagnosis and treatment of BU. Our results show that using CHV in active case nding leads to an increase in the detection of BU in early categories, spearheading the early start of treatment and hence reducing disability. Keywords: Buruli ulcer; Mycobacterium ulcerans; mycolactone; ischaemia; direct cytotoxicity; endothelial cells; cost-eectiveness analysis, rapid diagnostic test, community health volunteers, agent-based model

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Identifiers

ORCID for Christine Currie: orcid.org/0000-0002-7016-3652

ORCID for Rebecca Hoyle: orcid.org/0000-0002-1645-1071

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