Buruli ulcer

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Classification according to ICD-10
A31.1 Infection of the skin by other mycobacteria
Infection by Mycobacterium ulcerans [Buruli ulcer]
ICD-10 online (WHO version 2019)

The Buruli ulcer ( ulcer tropicum ) is a common in the tropics, but the skin and soft tissues not (also comes in Japan and Australia before) to the tropical climate linked infectious disease with educational part of extensive ulcers . The pathogen is the atypical mycobacterium ( MOTT ) Mycobacterium ulcerans , which is related to the causative agents of tuberculosis and leprosy .

Epidemiology

The disease is widespread in many countries in West, Central and East Africa, but also occurs in South Asia, Latin America and Australia. The rural population near bodies of water or marshland is often affected. For example, the prevalence in several rural areas of the Democratic Republic of the Congo ranged from 0 to 27.5 per 1000.

The transmission mechanisms are not fully understood. Transmission through certain mosquito species seems possible.

clinic

In most cases the extremities are affected; in children, ulcerations can occur anywhere. The ulcer develops from a papule-like to nodular swelling of the skin, which can expand considerably. It is fatal that the lesion is painless and is therefore often presented to a doctor very late. After months to years, it occasionally heals on its own, but it can also lead to severe mutilation, scarred contractures or lymphedema .

diagnosis

Buruli ulcer on the hand of a Peruvian patient. A) at the time of diagnosis. B) The ulcer four weeks later. C) Surgical debridement , five and a half weeks after diagnosis. D) Healed wound five months after A and one month after autologous skin grafting

In endemic areas , the diagnosis is usually clinically supported by microscopy of wound swabs or fine needle aspirates for acid-fast rod bacteria according to Ziehl-Neelsen as a first-line test in the field. The histopathological examination of excised tissue or 3 mm punch biopsies is a highly sensitive and specific method. It is rarely available in endemic areas. The laboratory diagnostic detection method with the highest sensitivity and specificity is the PCR of the repetitive insertion sequence IS2404 of the M. ulcerans genome. It is only available as conventional PCR or real-time PCR in national reference laboratories. The culture of the bacterium is characterized by a low sensitivity (40–70%) and a long incubation period of at least 6 weeks. This method is therefore unsuitable for prompt diagnosis and initiation of therapy, but it is currently the only way to prove the viability of the pathogen, which is necessary for further therapy decisions in the event of therapy failures and relapses.

treatment

Cut out

Until 2004, the therapy was largely carried out by surgical excision. Here were recurrence rates up to 30% because the mycobacteria penetrate far into the macroscopically healthy appearing tissue. Cutting out is advisable primarily in pre-ulcerative forms of the disease.

Antibiotics

Since 2004 the WHO has recommended standardized antimycobacterial therapy with rifampicin p.o. and streptomycin i.m. over 8 weeks, which is associated with hearing loss in around 20% of those treated. The recurrence rate is below 2%. Antibiotic resistance has been reported with monotherapy with rifampicin from Ghana. They are not yet a limiting factor for therapy. Clinical studies on the use of a purely oral therapy regimen with rifampicin and clarithromycin have shown promising results, mainly in the early stages.

An imidazopyridinamide was confirmed to be highly effective - also against rifampicin - in vitro and in vivo in a phase I study. Since the bacterium M. ulcerans is adapted to life in a stable environment, many of its genes are inactivated, as many cell functions are only required by free-living organisms. The breathing of the more robust TB bacteria is based on two metabolic pathways. The imidazopyridinamide blocks one of them. M. ulcerans lost the imidazopyridinamide-resistant signaling pathway and therefore did not survive treatment for long.

Heat treatment

Consistent heating of the ulcers to 40 ° C inactivates the bacteria. In one study, six patients wore bandages with warm packs for a few weeks. Each ulcer healed, and there were no relapses even 18 months later. The method is now being tested on more patients.

Clay mineral treatment

A healing effect has also been observed with certain illites (clay minerals). This could make inexpensive preparations possible.

literature

  • N. Schoeffel, M. Braun, MHK Bendels, DA Groneberg: Buruli ulcer. In: Zentralblatt für Arbeitsmedizin, Arbeitsschutz und Ergonomie. Volume 69, Number 2, 2019, doi : 10.1007 / s40664-018-0271-z .

Web links

Individual evidence

  1. ↑ Delphin Mavinga Phanzu, Patrick Suykerbuyk u. a .: Burden of Mycobacterium ulcerans Disease (Buruli Ulcer) and the Underreporting Ratio in the Territory of Songololo, Democratic Republic of Congo. In: PLoS Neglected Tropical Diseases. 7, 2013, p. E2563, doi: 10.1371 / journal.pntd.0002563 .
  2. ↑ M. Beissner, KH Herbinger, G. Bretzel: Laboratory diagnosis of Buruli ulcer disease. In: Future microbiology. Volume 5, Number 3, March 2010, pp. 363-370, ISSN  1746-0921 . doi: 10.2217 / fmb.10.3 . PMID 20210548 . (Review).
  3. Jump up ↑ KH Herbinger, D. Brieske, J. Nitschke, V. Siegmund, W. Thompson, E. Klutse, NY Awua-Boateng, E. Bruhl, L. Kunaa, M. Schunk, O. Adjei, T. Löscher, G Bretzel: Excision of pre-ulcerative forms of Buruli ulcer disease: a curative treatment? In: Infection. Volume 37, Number 1, February 2009, pp. 20-25, ISSN  1439-0973 . doi: 10.1007 / s15010-008-8073-4 . PMID 19139811 .
  4. ↑ M. Beissner, NY Awua-Boateng, W. Thompson, WA Nienhuis, E. Klutse, P. Agbenorku, J. Nitschke, KH Herbinger, V. Siegmund, E. Fleischmann, O. Adjei, B. Fleischer, TS van der Werf, T. Loscher, G. Bretzel: A genotypic approach for detection, identification, and characterization of drug resistance in Mycobacterium ulcerans in clinical samples and isolates from Ghana. In: The American journal of tropical medicine and hygiene. Volume 83, Number 5, November 2010, pp. 1059-1065, ISSN  1476-1645 . doi: 10.4269 / ajtmh.2010.10-0263 . PMID 21036838 . PMC 2963970 (free full text).
  5. ↑ WA Nienhuis, Y. Stienstra, WA Thompson, PC Awuah, KM Abass, W. Tuah, NY Awua-Boateng, EO Ampadu, V. Siegmund, JP Schouten, O. Adjei, G. Bretzel, TS van der Werf: Antimicrobial treatment for early, limited Mycobacterium ulcerans infection: a randomized controlled trial. In: The Lancet , Volume 375, Number 9715, February 2010, pp. 664-672, doi: 10.1016 / S0140-6736 (09) 61962-0 . PMID 20137805 .
  6. ↑ WHO : Buruli ulcer. Information, Education and Communication (IEC) materials. ( online )
  7. ↑ N. Scherr et al .: Targeting the Mycobacterium ulcerans cytochrome bc1: aa3 for the treatment of Buruli ulcer. In: Nature Communications , 2018, doi: 10.1038 / s41467-018-07804-8
  8. ↑ Thomas Junghanss, Alphonse Um Boock, Moritz Vogel, Daniela Schuette, Helmut Weinlaeder, Gerd Pluschke, David J. Diemert: Phase Change Material for Thermotherapy of Buruli Ulcer: A Prospective Observational Single Center Proof-of-Principle Trial. In: PLoS Neglected Tropical Diseases. 3, 2009, p. E380, doi: 10.1371 / journal.pntd.0000380 .
  9. ↑ Lynda B. Williams, Shelley E. Haydel, Rossman F. Giese, Jr., Dennis D. Eberl: Chemical and Mineralogical Characteristics of French Green Clays Used for Healing. In: Clays and Clay Minerals. 56, 2008, pp. 437-452, doi: 10.1346 / CCMN.2008.0560405 .