Lesion resolution may contribute to TB persistence in the face of control
Recent trials to directly measure the rate at which infected possums transmit TB to uninfected possums in free-living populations have raised more questions than they have answered.
While TB transmission in possums was successfully experimentally induced and monitored, the rates at which it occurred were too low to account for TB persistence based on current understanding of the disease in possums.
Past fieldwork observations led Dan Tompkins and colleagues to wonder whether infected individuals surviving for long periods of time could be the missing link. While it is generally assumed that TB infected possums survive for only a few months, there are now several documented cases of individuals surviving years of TB lesion development and resolution (Fig.1).
Dan discovered the existence of such possums while he was conducting a field trial to assess the efficacy of oral vaccination against the disease in 2004–6. During that trial, the team encountered a naturally infected possum that survived with periodic relapses of TB lesions for more than 2 years – far longer than the few months generally assumed. Even then, the long-surviving infected individual was euthanased at the end of the trial, rather than succumbing to disease.
Searching through the literature has revealed the occurrence of such possums in at least two other studies. In addition, a Massey University student, Ian Lugton, argued strongly in his PhD thesis in 1997 that such long-lived, infected individuals, were likely to have a median survival time after infection of more than 3 years. Also of great interest was that 90% of these long-lived individuals were male.
These observations fit the general pattern observed for TB in mammals, which is of variation among individuals in their innate resistance to the disease. To explore how such variation could influence TB persistence in possum populations, Pen Holland led a small modelling study to assess the potential influence of lesion resolution on persistence, relative to other likely sources of variation.
Pen constructed a generic contact-network model for simulating disease, loosely based on TB in possums. With this, Pen and Dan considered the effects on disease persistence of lesion resolution, in addition to the effects of spatial clustering of individuals, with those individuals being the ‘most connected’ in the network also being the most infectious. The latter two effects were motivated by recent evidence that suggests greater levels of TB transmission when possums are more clustered, and that adult males may play a disproportionately high role in TB transmission due to both greater contact rates with other possums and longer survival when infected.
Upon simulating Pen’s model, she and Dan found that while there was no potential for the other factors to favour disease persistence, there was clear potential for the phenomenon of lesion resolution. This may thus help to explain how TB manages to persist in possum populations even though, in reality, disease transmission among possums is at a lower rate than is generally assumed. Also, long-lived infected individuals may be one of the reasons why TB can re-emerge in controlled areas, potentially driven more by male possums (the greater dispersing sex).
We now need to gain a better understanding of the likely size and impact of long-lived, infected individuals in the real world of intensive TB possum control.
This work was funded by the Royal Society of New Zealand Marsden Fund, TBFree New Zealand, and Landcare Research.