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RIRDC Completed Projects in 1999-2000 & Research in Progress as at June 2000
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2.7 TEA TREE OIL  -  RESEARCH IN PROGRESS

PROJECT No
PROJECT TITLE
RESEARCHER
PHONE
ORGANISATION
DAN-151A The improvement of Australian tea tree through selection and breeding (contrinuation of project DAN-87A) Dr Ian Southwell 02 6626 1224 NSW Department of Agriculture, Wollongbar Agricultural Institute
UF-5A The anti-inflammatory activity of tea tree oil – second stage Prof John Finlay Jones 08 8201 3909 Flinders University of South Australia
UNC-7A Tea tree oil as a topical decolonisation solution for adult inpatients with Methicillin-Resistant Staphylococcus aureas Ms Meredith Caelli University of Newcastle
UWA-40A The antiviral activity of tea tree oil in vitro A/Professor Tom Riley 08 9346 3690 University of Western Australia
UWA-50A The antifungal activity of tea tree oil in vitro A/Professor Tom Riley 08 9346 3690 University of Western Australia
 
Project Title The improvement of Australian tea tree through selection and breeding (continuation of project DAN-87A)
RIRDC Project No.: DAN-151A
Start Date: 1/07/96
Finish Date: 30/06/01
Researcher:  Dr. Ian Southwell
Organisation: NSW Department of Agriculture
Wollongbar Agricultural Institute
Bruxner Highway
WOLLONGBAR NSW 2477
Phone: (02) 6626 1224
Fax: (02) 6628 3264
Objectives
· To systematically improve the yield and quality of oil from tea tree (Melaleuca spp) by
1. Continuing current, and establishing new selection trials.

2. Production of improved seed lines with yields up to 17% higher than current industry selections by 1997, 30% higher by 1999, and 60% higher by 2003.

Current Progress The tea tree breeding project has successfully released seed to the industry for the third consecutive year. Like the 1997 release of 1.5kg and the 1998 release of 2.7kg, the 1999 release of 2.8kg was again oversubscribed. The breeding project has now released 7kg of seed, enough to plant over 1000ha of tea tree plantation.

The success of all three sales augers well for the fourth release in 2000, however the current downward pressure on oil prices may restrict future plantings and hence the demand for seed in 2000. Seed available for sale will again be from best provenance and seedlots bulked. In addition to this and for the first time, improved seed from the seedling seed orchard (SSO1) will be available for sale.

Seedlots collected from the SSO1 in 1999 are currently being progeny tested. An early assessment in 2001 will determine their expected gains. Based on work with other species, a 30% increase in yield should be achievable. Further culling of the orchard this year is expected to give improvements of 60% by 2003.

A second generation orchard is to be established this year, yield and quality improvements greater than that achieved from the SSO1 seed is expected from the highly improved seed from this new orchard.


 
 
Project Title The anti-inflammatory activity of tea tree oil – second stage
RIRDC Project No.: UF-5A
Start Date: 1/08/99
Finish Date: 1/08/00
Researcher:  Prof. John Finlay-Jones, Dr Prue Hart, Ms C. Carson, Assoc. Prof. T. Riley
Organisation: Flinders University of South Australia
GPO Box 2100
ADELAIDE SA 5001
Phone: (08) 8201 3909
Fax: (08) 8201 3905
Email: John.Finlay-Jones@flinders.edu.au
Objectives To continue the assessment of the anti-inflammatory activity of tea tree oil, and its components. Their effects will be investigated on 
(a) the inflammatory profile of human monocytes, keratinocytes, neutrophils and mast cells activated in vitro

(b) the recall skin hypersensitivity response in an experimental animal model, and

(c) skin cell phenotype and activation status in situ, thus demonstrating the potential of tea tree oil as a safe, topical anti-inflammatory therapeutic agent.

Current Progress Previously we showed that the water soluble components of tea tree oil have potential anti-inflammatory effects. These components, in particular terpinen-4-ol (>40% of tea tree oil), suppressed lipopolysaccharide-induced IL-1, TNF, IL-10 and prostaglandin E2 production by human monocytes activated in vitro. They also suppressed the respiratory burst (superoxide production) by human monocytes activated in vitro by lipopolysaccharide. Both terpinen-4-ol and a-terpineol were responsible for this suppression, by a mechanism that did not involve changes to expression of CD14 (the receptor for lipopolysaccharide). In contrast, neither tea tree oil nor its water soluble components regulated a respiratory burst by human neutrophils activated in vitro by lipopolysaccharide. Neutrophils are a first line of defence against invading organisms, with the respiratory burst part of their microbicidal processes. We know that tea tree oil has potent and direct anti-microbial effects, so its use as an antiseptic on skin is further supported by this lack of an effect on neutrophil respiratory burst. In contrast uncontrolled superoxide production by activated monocytes may cause oxidative tissue damage. These observations enhance the scientific foundations of the potential use of tea tree oil for regulation of inflammatory conditions for which monocyte but not neutrophil activity requires regulation. We are currently determining the in vivo applications of these in vitro findings.
Project Title Tea tree oil as a topical decolonisation solution for adult inpatients with Methicillin-Resistant Staphylococcus aureas
RIRDC Project No.: UNC-7A
Start Date: 1/03/98
Finish Date: 30/12/00
Researcher:  Ms Meredith Caelli
Objectives Develop efficacy and safety data packages to support the registration of Tea Tree Oil for use as a medical product by providing sound epidemiological data to support its acceptance as an effective and safe antimicrobial by national and international registration authorities.
Current Progress Ethics Approval was granted from the Western Sydney Area Health Service Ethic Committee in August 1999. Recruitment of research assistants was completed by September 1999. Product delivery was completed by November 1999 and patient recruitment commenced in November 1999. Professor Lynn Gilbert is site supervisor for the program and monthly progress meetings are held to monitor progress and resolve any clinical issues.

At this stage, the participant recruitment is 47% completed with 84 participants recruited onto the research program over the 6-month period. Analysis of outcomes has yet to be undertaken. The initial review of the data and outcomes will be undertaken when the results of 90 participants are available. 

Adverse events:

To date 1 patient (2.5%) has complained of an unpleasant aftertaste in relation to the use of the Tea Tree Oil nasal ointment. It has been rated as mildly unpleasant, or 1 on the 5-point scale. Similarly 1 (2.5%) participant complained of headache after use of Mupirocin nasal ointment, and this rated a 4 on the 5-point scale. Two participants (2.5%) complained of dry, scaly skin whilst using the body wash gel – one in each treatment group, after 15 days of consecutive use. No participants have withdrawn from the research program due to adverse events from either treatment group. 

In March 2000, the results of the pilot study were presented at the 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections in Atlanta.


 
Project Title The antiviral activity of tea tree oil in vitro
RIRDC Project No.: UWA-40A
Start Date: 1/10/97
Finish Date: 30/09/00
Researcher:  A/Prof. Thomas V Riley
Organisation: University of Western Australia
Dept of Microbiology
Queen Elizabeth II Medical Centre
NEDLANDS WA 6009
Phone: (08) 9346 3690
Fax: (08) 9346 2912
Email: triley@cyllene.uwa.edu.au
Objectives The aim of this project is to develop and validate methods suitable for testing the antiviral activity of tea tree oil in vitro and to use these methods to assess its potential as a topical antiviral therapeutic agent. The outcomes will be the development of methods, the validation of these methods and an assessment of the suitability of tea tree as a topical antiviral agent.
Current Progress Further characterisation of the activity of TTO and components against herpes simplex virus 1 has been conducted. This has helped to identify the concentrations of TTO that may be useful in vivo. Concentrations of TTO in the range of 1-2% have been shown to inactivate herpes simplex viruses rendering them incapable of infecting host cells.

Meanwhile, a pilot study examining the in vivo efficacy of tea tree oil (TTO) as a treatment for cold sores, caused by the herpes simplex virus, has been completed. Twenty volunteers with cold sores were randomised to receive TTO gel (6%) or placebo gel applied up to five times daily. They were seen daily (except Sundays) for clinical assessment and swabbing for tissue culture and DNA detection by PCR. This continued until re-epithelialisation had occurred and two consecutive PCR results were negative. One of the TTO group who was subsequently negative for herpes simplex virus and did not develop a cold sore was withdrawn due to a possible adverse reaction. The treatment (n = 9) and placebo (n = 10) groups did not differ significantly in terms of mean age, gender or days to presentation. Outcomes for the TTO and placebo groups measured were: days to crust 3.7 ± 0.7 versus 4.6 ± 3.3, days to re-epithelialisation 9.9 ± 3.6 versus 12.0 ± 2.6, days PCR positive 6.5 ± 2.0 versus 7.9 ± 4.9. All of these outcomes favoured the TTO group, but did not reach statistical significance using the student's t-test due to the small sample size. Analysis of viral titres is underway to determine the effect on viable virus. A larger study is now planned to verify these results.


 
 
Project Title The antifungal activity of tea tree oil in vitro
RIRDC Project No.: UWA-50A
Start Date: 1/08/99
Finish Date: 1/08/00
Researcher:  A/Prof. Thomas V Riley
Organisation: University of Western Australia
Dept of Microbiology
Queen Elizabeth II Medical Centre
NEDLANDS WA 6009
Phone: (08) 9346 3690
Fax: (08) 9346 2912
Email: triley@cyllene.uwa.edu.au
Objectives To develop and assess methods for testing the susceptibility of fungi to tea tree oil and then use these methods to test recent clinical isolates. The outcome will be validated susceptibility data for fungi.
Current Progress Appropriate in vitro susceptibility testing methods have been developed, based on internationally standardised protocols. This includes the broth microdilution and agar dilution methods. The second major objective, which was to obtain reference strains of fungi and determine their susceptibility to tea tree oil, has also been achieved. Minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were determined for these isolates. 

Results of the broth microdilution method showed that the yeast isolates (n=115) (including members of the genera Candida, Cryptococcus, Rhodotorula, Saccharomyces and Trichosporon) were inhibited by tea tree oil in the range of 0.016% to 0.5% tea tree oil, and were killed by tea tree oil in the range 0.06% to 1.0% tea tree oil. Similarly, results for the dermatophytes, which includes the genera Epidermophyton, Microsporum and Trichophyton (n=106) obtained by the broth microdilution method showed that they were inhibited in the range of 0.004% to 0.06% tea tree oil and were killed in the range of <0.03% to 1.0% tea tree oil.

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