Background Information
Mycobacterium ulcerans infection, widely known as Buruli
ulcer (BU), is an emerging health problem in parts of the developing
world and also in areas of Australia. BU was made a notifiable
disease in the state of Victoria in 2004 because of a significant
increase in the number of cases in several localised coastal regions.
BU cases continue to present occasionally in other coastal regions
of Victoria, Far North Queensland, the Northern Territory and
in Papua New Guinea. Small numbers of cases have also been reported
from Japan, China and Malaysia, indicating that the disease may
be more widespread in the Western Pacific region than is currently
recognised. In 2005, the first case of BU aquired in the state
of New South Wales (NSW) was diagnosed. In Victoria, cases of
BU have also been described in several marsupial species, including
koalas, potoroos and possums and in 2006, the first cases in horses
and a cat were documented. Progress has been made over recent
years in the areas of diagnosis and treatment of BU, however knowledge
on transmission and the changing epidemiology of this challenging
disease is very limited. Australia is the only developed country
in which there is documented active transmission of M. ulcerans.
The creation of a collaborating centre in Australia, to collect
and manage information on the incidence, epidemiology and control
of BU in the Western Pacific Region, and to perform and coordinate
appropriate research projects with the aim of determining the
ecology and mode(s) of transmission of M. ulcerans to
humans and animals will potentially contribute to worldwide management
of BU.
Australian researchers are internationally recognised for research
on BU. Notable achievements include:
• the initial culture and description of M. ulcerans
and the associated infection (Bairnsdale ulcer) (1948)
• detailed descriptions of the histology and epidemiology
of M. ulcerans in Australia (1990s)
• the discovery of the M. ulcerans -specific insertion
sequence IS2404 (1995)
• the development of various molecular typing methods capable
of distinguishing between M. ulcerans isolates from different
geographic locations (1995, 2000)
• the development of a diagnostic PCR based on IS2404 (1997)
• the first detection of M. ulcerans in the environment
using PCR (1997, 2000)
• the identification of the M. ulcerans plasmid
carrying the genes encoding the polyketide synthases responsible
for mycolactone synthesis (2004)
• the development of a suite of real-time PCR assays for
the detection of M. ulcerans in clinical and environmental
samples, including mosquitoes (2006).
• Sequencing and annotation of the M. ulcerans
genome.
The Victorian Mycobacterium Reference Laboratory (MRL), originally
known as the TB laboratory at the Fairfield Infectious Diseases
Hospital, has been a department within the Victorian Infectious
Diseases Reference Laboratory (VIDRL) since 1993. The MRL is responsible
to the Victorian Department of Human Services for the notification
of all new cases of laboratory diagnosed BU in the state of Victoria,
and is responsible for entering relevant information regarding
all Australian BU using a standardised epidemiological instrument
(BU02).
The proposal to form the Collaborating Centre for Mycobacterium
ulcerans arose from an initial invitation to A/Prof. Hayman
and A/Prof. Paul Johnson from Dr. Kingsley Asiedu (Global Buruli
Ulcer Initiative, WHO, Geneva). A/Prof Paul Johnson, A/Prof John
Hayman and Mr John Buntine have been active members of the WHO
Buruli ulcer task force since its creation in 1998.
The WHO Collaborating Centre, with the support of the MRL staff
and VIDRL infrastructure, is headed by A/Prof Paul Johnson, with
Dr Janet Fyfe as deputy Head. In addition, the BU Pathogenesis
Research Group at Monash University, headed by Dr Tim Stinear
forms an integral part of the Collaborating Centre. A/Prof John
Hayman and Mr John Buntine provide additional expertise to the
team.
Structure of the Collaborating Centre:
Terms of Reference:
1. To perform molecular (PCR) and culture diagnosis of Mycobacterium
ulcerans infection in humans and animals for the Western
Pacific Region.
2. To perform molecular typing on all new M. ulcerans
isolates as an aid to epidemiological studies.
3. To systematically record and report all cases of M. ulcerans
infection in Australia to the relevant state and national health
authorities, and cases occuring in other countries in the the
Western Pacific Region to the relevant local and national health
authorities. All cases identified in the region would be reported
to WHO using the BU02 standard format.
4. To gather and map the likely geographic source of infection
for all cases of Buruli ulcer in the Western Pacific Region in
conjunction with the Victorian Department of Human Services and
contacts in Papua New Guinea.
5. To continue expanding the Centre's existing archive of isolates,
histological specimens and clinical photographs for future reference
and research and to continue sharing this resource with the worldwide
network of M. ulcerans researchers.
6. To continue to promote, facilitate and conduct outstanding
M. ulcerans research in a range of areas between local,
regional and international collaborators.
7. To further develop expertise in environmental PCR in terms
of providing reference, quality control, ongoing development and
improvement of techniques and sharing of protocols with the M.
ulcerans research community.
8. To provide ongoing excellent clinical support for the management
and treatment of M. ulcerans infection in humans and
and animals, both within Australia and other countries within
the Western Pacific Region where cases of M. ulcerans infection
are diagnosed
9. To provide training for scientists from developing countries
in molecular, histological and culture diagnosis of M. ulcerans
infection in humans and animals.
10. To communicate developments in the diagnosis, treatment and
control of M. ulcerans infection in humans and animals
to the medical, veterinary and scientific communities and the
general public.
11. To provide public advocacy designed to increase awareness
both locally and internationally of this important neglected disease.
Relevant recent references:
Tafelmeyer P, Laurent C, Lenormand P, Rousselle JC, Marsollier
L, Reysset G, Zhang R, Sickmann A, Stinear TP, Namane A, Cole
ST. (2008) Comprehensive proteome analysis of Mycobacterium ulcerans
and quantitative comparison of mycolactone biosynthesis.
Proteomics. Jul 9. [Epub ahead of print]
Elsner L, Wayne J, O’Brien CR, McCowan C, Malik R, Hayman
JA, Globan M, Lavender CJ, Fyfe J (2008) Localised Mycobacterium
ulcerans infection in a cat in Australia. J Feline Med Surg May
19 [Epub ahead of print]
Hong H, Demangel C, Pidot SJ, Leadlay PF, Stinear T. (2008)
Mycolactones: immunosuppressive and cytotoxic polyketides produced
by aquatic mycobacteria. Nat Prod Rep. Jun;25(3):447-454. Epub
2008 Apr 17
Stinear T, Johnson P. (2008) First Isolation of Mycobacterium
ulcerans from an Aquatic Environment: The End of a 60-Year Search?
PLoS Negl Trop Dis. 2008 Mar 26;2(3):e216
Johnson PDR, Azuolas J, Lavender CJ, Wishart E, Stinear TP, Hayman
JA, Brown L, Jenkin GA, Fyfe JAM. (2007) Mycobacterium ulcerans
in mosquitoes captured during outbreak of Buruli ulcer, southeastern
Australia. Emerg Infect Dis 13: 1653-1660.
Fyfe JAM, Lavender CJ, Johnson PDR, Globan M, Sievers A, Azuolas
J, Stinear TP. (2007) Development and application of two multiplex
real-time PCR assays for the detection of Mycobacterium ulcerans
in clinical and environmental samples. Appl Environ Microbiol
73: 4733-4740
Johnson PDR, Hayman JA, Quek TY, Fyfe J, Jenkin GA, Buntine JA,
Athan E, Birrell M, Johnstone B, Graham J, Lavender CJ on behalf
of the Mycobacterium ulcerans Study Team. (2007) Consensus recommendations
for the diagnosis, treatment and control of Mycobacterium ulcerans
infection (Bairnsdale ulcer) in Victoria, Australia. Med J Aust.
2007; 186 (2):64-68.
O'Brien DP, Hughes AJ, Cheng AC, Henry MJ, Callan P, McDonald
A, Holten I, Birrell M, Sowerby JM, Johnson PD, Athan E.Outcomes
for Mycobacterium ulcerans infection with combined surgery and
antibiotic therapy: findings from a south-eastern Australian case
series. Med J Aust. 2007 Jan 15;186(2):58-61.
Lavender CJ, Senanayake SN, Fyfe JA, Buntine JA, Globan M, Stinear
T, Hayman JA, Johnson PD. (2007) First case of Mycobacterium ulcerans
disease (Bairnsdale or Buruli ulcer) in New South Wales. Med J
Aust.186 (2):62-63.
