Kliniken & Institute … Institute Zentrum für… Sektion Klinische… Forschung Buruli Ulkus und…

Treat early and braod: thermotherapy of Buruli ulcer integrated into WHO-recommended wound management in West Africa

Finanzierung:  Else Kröner-Fresenius-Stiftung
Laufzeit:  2018 - 2020
Wissenschaftler (Sektion Klinische Tropenmedizin):  Thomas Junghanss, Marija Stojkovic

  • B. Bonfoh, Centre Suisse de Recherche Scientifique en Côte d'Ivoire (CSRS), Abidjan, Elfenbeinküste
  • G. Pluschke, Swiss Tropical and Public Health Institute, Basel, Schweiz

The project rolls out combined innovative low-tech thermotherapy with heat packs and WHO recommended wound management in a Buruli ulcer (BU)-endemic district of West Africa. It addresses three key areas of considerable clinical and public health importance in the region:

-  to better help people managing the disabling disease BU that primarily affects children in West Africa

-  to implement WHO recommended general wound management for all types of wounds with tools available at the peripheral level of the health care system

-  to prevent systemic life threatening sequelae (e.g. sepsis and rheumatic fever) and permanent local damage (e.g. motor and sensory disability) by early recognition and treatment of wounds at the community level.

The project translates available research findings already validated on the secondary health care level into clinical practice at the periphery (primary health care level). The string of our previous work from the development of the BU thermotherapy-wound management–package to the proof of its efficacy provides all necessary skills, tools and documents to immediately proceed into practical community application. Operational endpoints are

-  coverage and quality of WHO recommended wound management training of health care personnel at the primary health care level (health posts);
-  coverage, success rate and quality of care for patients with BU and other wounds; denominator controlled at health post level and high-quality Health and Demographic Surveillance Systems (HDSS) data.

The project is embedded into a stable multidisciplinary working environment at Côte d’Ivoire, including an HDSS with a longstanding record of partnership and successful community-based operational research.

The project builds on the principles laid out by the Sustainable Development Goals (SDGs) and Universal Health Coverage (UHC) and

·  targets all patients with a broken down skin barrier independent of the cause (patient centred health care)
·  brings diagnosis and treatment close to the community
·  educates and trains both community members and health care workers
·  measures the health intervention outcome

The project is fully in line with the new integrated strategy for the skin NTDs of WHO’s Department of Control of NTDs (WHO/NTD).

From Buruli anti-mycobacterial treatment to Ulcer would healing– A prospective evaluation of clinical and laboratory parameters to distinguish mycobacterial disease, paradoxical reaction and secondary bacterial infection for targeted treatment (extension)

Finanzierung: VolkswagenStiftung
Laufzeit: 2005-2008; 2008-2013
Wissenschaftler (Sektion Klinische Tropenmedizin): T. Junghanss, M. Vogel

· A. UmBoock, Fairmed, Yaoundé, Kamerun
· D. Yeboah-Manu, University of Ghana, Legon, Ghana
· E. Mensah-Quainoo, Ghana Health Service, Tema, Ghana
· G. Pluschke, Swiss Tropical and Public Health Institut, Basel, Schweiz

In the first phase we have successfully explored the use of an innovative heat application system to treat Mycobacterium ulcerans disease in a proof-of-principle study, confirmed the efficacy of heat treatment at the primary endpoint (six months after heat treatment) in a large GCP-conform trial, and studied the treatment-induced microbiological, histopathological and immunological evolution of BU lesions of relevance for the understanding of wound healing processes and clinical BU treatment management. We found strikingly heterogeneous treatment responses of BU lesions. Based on our standardized clinical observation and documentation and extensive laboratory work-up of the patients enrolled in the heat treatment trial we can now understand the determinants of heterogeneous treatment responses of BU lesions better.  Disturbance of wound healing may be related to: (1) M. ulcerans activity, (2) M. ulcerans-host interactions (so called paradoxical reaction) and (3) secondary bacterial infection.  The investigation of these often co-existing processes contributes to the clarification of unresolved principle questions such as the nature of immune protection against M. ulcerans disease after successful treatment and the resolution of the mycolactone-induced local immunosuppression during therapy.  The project now aims to improve our ability to define clinical, microbiological, cell biological and immunological features that influence progression of BU lesions to wound healing and tissue repair.  To achieve this, we will analyze in-depth the large clinical and laboratory dataset of our clinical trial and prospectively study markers of wound healing and their ability to predict clinical outcome in a cohort of BU patients in Ghana.  In addition, we will complete the heat treatment trial with the assessment of the relapse rate at month 24 after completion of heat treatment as well as the secondary endpoints and establish a modular reference database for BU patients.

Modification of host–pathogen interaction in Mycobacterium ulcerans disease (BU) through heat treatment: basic mechanisms and clinical applications

Finanzierung: VolkswagenStiftug
Laufzeit: 2005-2008; 2008-2013
Wissenschaftler (Sektion Klinische Tropenmedizin): T. Junghanss, M. Vogel

·  A. UmBoock, Fairmed, Yaoundé, Kamerun
·  D. Yeboah-Manu, University of Ghana, Legon, Ghana
·  E. Mensah-Quainoo, Ghana Health Service, Tema, Ghana
·  G. Pluschke, Swiss Tropical and Public Health Institut, Basel, Schweiz

The significance of Buruli Ulcer Disease

Buruli Ulcer (BU) is the third largest human mycobacterial disease after Tuberculosis and Leprosy. It has been classified a Neglected Tropical Disease by the WHO, because children living in impoverished areas of West Africa are by far the most affected. Cases have been reported from over 30 mainly tropical and sub-tropical countries around the world.
Characteristics of the causative organism include a toxin which causes local immunosuppression and destruction of the subcutaneous tissue, sensitivity to temperatures above 37°C and the tendency to develop satellite lesions distant from the primary infection. Standard therapy for decades was surgical removal.
In 1974 Meyers et al. were able to show that local application of 40°C for several weeks cured seven African patients from Buruli ulcer, a strategy that was not pursued for technical reasons. In 2004 the WHO recommended Streptomycin and Rifampicin as primary treatment. Without timely adequate treatment complications of the disease include devastating skin defects and permanent disabilities from contractures.


Our current work

In 2007/08 Junghanss et al. re-established heat treatment of Buruli ulcer using a Phase Change Material as heat source. This proof-of-principle trial was conducted in Ayos, Cameroon, with funding from the Volkswagen Foundation within the framework of the “Knowledge for Tomorrow- Cooperative Research in Sub-Saharan Africa” programme. Following its successful pilot phase the scientific cooperation was awarded funding by the Volkswagen Foundation for a larger, registered trial under Good Clinical Practice standards, which started to enrol patients in 2009. A particular focus lies on clinical and microbiological parameters of disease staging and the host-pathogen interaction in heat treatment. African scientific capacities are strengthened by educating a doctorial student and providing clinical, microbiological and administrative assistance.

Die vergessene Krankheit