Antibody detection tests improve the sensitivity of tuberculosis diagnosis in cattle

Highlights

• Cellular and humoral-based diagnostic tests were used in parallel for diagnosis of tuberculosis.

• The sensitivity reported using serology was higher in cattle showing TB lesions which are more likely to spread M. bovis.

• A higher sensitivity of serology than that reported with the official diagnostic tests was described for the first time.

• Results obtained suggest that serology can be included as ancillary tool for diagnosis of bovine tuberculosis.

Abstract

We evaluated the sensitivity (Se) of the single cervical intradermal tuberculin (SIT) test, two interferon-gamma (IFN-γ) assays and three different antibody detection techniques for bovine tuberculosis (bTB) diagnosis in 131 mixed beef breed cattle. The results of the diagnostic techniques performed over the whole herd, and over the animals confirmed as infected based on the presence of lesions compatible with the disease and/or M. bovis isolation were compared to determine apparent prevalence (AP) and Se.

The Se of the SIT test (severe interpretation) was 63.7% (95% CI, 54.54–72.00), while the Se of the IFN-γ assays ranged between 60.2% and 92%. The proportion of infected cattle detected by the different antibody detection techniques ranged from 65.5% to 87.6%. Three of the antibody detection techniques yielded a significant higher (p < 0.05) Se than that achieved with the official diagnostic techniques. In addition, the interpretation in parallel of cellular and antibody detection techniques reached the highest Se: 98.2% (95% CI, 93.78–99.51) suggesting that the use of diagnostic techniques detecting both cellular and humoral responses could be considered as an alternative in the control of bTB outbreaks in high prevalence settings.

Introduction

Bovine tuberculosis (bTB) is one of the most relevant animal infections worldwide (Reviriego Gordejo and Vermeersch, 2006, Schiller et al., 2010, Schiller et al., 2011) and is included by the Office International des Epizooties in the list of notifiable diseases. Bovine TB is considered to be of socio-economic and public health importance with implications for the international trade of animals and animal products (OIE, 2011). The infection is caused by members included in the Mycobacterium tuberculosis complex (MTBC) being M. bovis and M. caprae the most common agents detected in domestic livestock (Rodriguez-Campos et al., 2014). After infection, the cell-mediated Th1 immune response (CMI), mainly mediated by macrophages and lymphocytes, is the first attempt to contain the pathogen (Brostoff et al., 1991). Once the animal is infected there is a high variability in the development of the immune response depending on the infective dose (Dean et al., 2005), co-infection with other disease that may affect the immune system (Jones, 2012), age and nutritional state of the animals (Humblet et al., 2009) and even the strain involved in the outbreak (de la Fuente et al., 2015).

As the disease progresses, a decrease in the CMI response occurs in parallel with an increase in the production of antibodies against the pathogen (McNair et al., 2007, Pollock and Neill, 2002, Welsh et al., 2005). Diagnostic techniques included in the eradication programs currently in use are based on the detection of the CMI response (Buddle et al., 2009): intradermal tuberculin tests (Monaghan et al., 1994) and the interferon-gamma (IFN-γ) assay (Rothel et al., 1992). Positive animals are culled (test and slaughter policy) with the aim of stopping the transmission within the herd at early stages.

In the last decade many countries have reported high bTB prevalence rates (Pavlik, 2006, Reviriego Gordejo and Vermeersch, 2006, Schiller et al., 2011). Moreover, in spite of the efforts spent in the eradication programs against bTB, several factors limit the sensitivity (Se) and specificity (Sp) of the diagnostic techniques (Álvarez et al., 2014, Allepuz et al., 2011, Humblet et al., 2009). As a consequence, infected animals may stay in the herd maintaining the disease (Barlow et al., 1997) producing significant economic losses and compromising the confidence of both veterinarians (Humblet et al., 2011a, Humblet et al., 2011b) and farmers (Locke and Fishwick, 2011). An alternative approach for bTB diagnosis may be the development of antibody detection techniques (Green et al., 2009, Lyashchenko et al., 2000, Waters et al., 2006). Other alternative strategies are based on improving the CMI diagnostic techniques by using different antigens (Vordermeier et al., 2001) obtaining higher rates of Se while maintaining the Sp.

We aimed to evaluate the results achieved using official techniques (single cervical intradermal tuberculin test and IFN-γ assay) and different antibody detection ELISAs, applying single and/or parallel interpretation under a high bTB prevalence situation. In the present study, we demonstrate that antibody detection tests could contribute to the management and control of bTB outbreaks accelerating the eradication process.