Phase change material for thermotherapy of Buruli ulcer: a prospective observational single centre proof-of-principle trial

Abstract

Background: Buruli ulcer (BU) is an infection of the subcutaneous tissue leading to chronic necrotizing skin ulcers. The causative pathogen, Mycobacterium ulcerans, grows best at 30 degrees C-33 degrees C and not above 37 degrees C. We explored the safety, tolerability and efficacy of phase change material (PCM), a novel heat application system for thermotherapy of BU.

Methodology/principal findings: In a prospective observational single centre proof-of-principle trial in Ayos/Cameroon, six laboratory reconfirmed patients with ulcerative Buruli lesions received 28-31 (ulcers < or = 2 cm) or 50-55 (ulcers > 2 cm) days of thermotherapy with the PCM sodium acetate trihydrate as heat application system. This PCM is widely used in commercial pocket heat pads, it is easy to apply, rechargeable in hot water, non-toxic and non-hazardous to the environment. All patients enrolled in the trial completed treatment. Being completely mobile during the well-tolerated heat application, acceptability of the PCM bandages was very high. In patients with smaller ulcers, wounds healed completely without further intervention. Patients with large defects had skin grafting after successful heat treatment. Heat treatment was not associated with marked increases in local inflammation or the development of ectopic lymphoid tissue. One and a half years after completion of treatment, all patients are relapse-free.

Conclusions/significance: Our reusable PCM-based heat application device appears perfectly suited to treat BU in endemic countries with limited resources and infrastructure.

Trial registration: Controlled-Trials.com ISRCTN88392614.

Figure 1. Mounting of the PCM-based heat application system and temperature monitoring device.

(A) PCM pack and bandage mounted for treating an ulcer on the lower limb (patient 2) and temperature monitoring system, (B) PCM pack with sodium acetate trihydrate in the fluid phase before initiating the crystallisation process with the starter (red), sodium acetate trihydrate in the solid phase after the stored heat has been discharged, (C) temperature monitoring system with the sensor connected to the data logger to record the temperature at the skin surface as part of the clinical trial documentation. This will not be needed when the device is put into routine use.

Figure 2. Baseline data, heat treatment schedules and results.

Figure 3. Healing of Buruli ulcers under PCM-based heat treatment and long term results.

(A) Patient 2, (B) patient 5: Progress of healing during heat treatment. Note in particular early onset of epithelialisation. Far right follow-up 12 months after completion of heat treatment. Patient 5 (B) after skin grafting.