Image by Olwen Golden, UCD School of Veterinary Medicine. A longitudinal section of a liver fluke (Fasciola hepatica).
As many as a third of tuberculosis cases in dairy cattle could be missed, because if an animal is also infected with liver fluke, it can affect a commonly used diagnostic test for bovine TB. That’s according to a new study published in Nature Communications, which involved University College Dublin researchers. The findings could help to explain why bovine TB is continuing to spread in the United Kingdom despite an eradication programme.
The new study builds on previous work carried out by researchers at UCD School of Veterinary Medicine, where cattle were experimentally co-infected with Fasciola hepatica, which is the liver fluke parasite, and Mycobacterium bovis BCG, an attenuated version of the bacterium which causes TB in cattle.
“We have known for a long time from our work on the immunology of liver fluke that the parasite had the potential to suppress immune responses,” says researcher Prof Grace Mulcahy, Dean of the School of Veterinary Medicine and Professor of Veterinary Microbiology and Parasitology at UCD. “And in that previous study, we could experimentally show that the response to the TB test was diminished in cattle infected with liver fluke.”
For the new study, researchers from UCD and the Agri-Food and Biosciences Institute experimentally infected calves either with liver fluke and fully virulent M. bovis, or with M. bovis alone. In animals that were exposed to both, the response to the standard ‘single intradermal comparative cervical tuberculin’ (SICCT) test for TB was significantly lower at 10 and 21 weeks after infection.
Meanwhile, researchers at the University of Liverpool mapped areas of liver fluke and TB infection among 3,026 dairy herds in England and Wales, and what they saw was surprising. “It was really unexpected,” says Prof Mulcahy. “The original hypothesis we had was that the liver fluke-affected areas would have a higher incidence of TB, but it turned out to be the opposite.”
However the patterns they saw make sense if a liver fluke co-infection means that the ability to detect TB is impaired.
“It’s not that this diagnostic test doesn’t work at all in animals with liver fluke, you are just shifting the sensitivity a little bit,” explains Prof Mulcahy. “And there will be a subset of animals for which that may be enough to push them into the non-responder part of the curve.”
In practice, this means that some animals infected with TB could be missed.
Another surprise came when statistical analysis at the University of Lancaster worked out the possible scale of that problem. “The research was able to demonstrate that up to a third of animals, around 30 per cent, would be missed in some statistical models,” says Prof Mulcahy. “We had been aware of the issue, but this aspect of the work told us about the possible extent.”
Future research will look at whether treating animals for liver fluke before testing for TB could improve the detection rates, and UCD researchers are already working on Science Foundation Ireland and EU-supported projects to look at how liver fluke affects the progression of TB in co-infected cattle.
Papers
Claridge, J. et al. Fasciola hepatica is associated with the failure to detect bovine tuberculosis in dairy cattle. Nat. Commun. 3:853 doi: 10.1038/ncomms1840 (2012).
Flynn, RJ, Mannion, C,Golden, O, Hacariz, O, Mulcahy, G; (2007) 'Experimental Fasciola hepatica infection alters responses to tests used for diagnosis of bovine tuberculosis'. Infection and Immunity, 75 :1373-1381.
