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The Top End region of the Northern Territory, Australia, is noted for its relatively unmodified natural state. To gain some insight into the potential for maintaining ecosystem health in this region we undertook a study that assessed the distribution of weeds across very extensive transects. This weed survey was distinct from other studies in that many of the sample sites were distant from tracks or other infrastructure. Twenty-one weed species were recorded along 2000 km of transects. Weeds were reported from 18.7% of the 718 sample points. The incidence of weeds was found to be significantly associated with land tenure, being highest on pastoral lands and peri-urban areas, and very low on Aboriginal lands. The incidence of weeds increased significantly with increasing levels of infrastructure and with increasing proximity to watercourses. There are three main conclusions from this study. First, much of the Top End, particularly remote Aboriginal lands, has exceptionally low levels of weed infestation. Secondly, in such areas, given the relatively small extent of vegetation change through weed invasion, maintenance or re-imposition of traditional fire regimes should be achievable. Thirdly, there is substantial potential for spread of weeds to remote areas, with such spread most likely to occur through increased penetration by infrastructure. Importantly this study indicates that there is still opportunity to prevent widespread weed invasion across the Top End, which is timely given the current Government consideration of the potential for the region to support future agricultural expansion and the fast-paced development of mining, oil and gas resources.