In the JournalsPerspective

New skin test for bovine TB outperforms standard assay

A new skin test for detecting bovine tuberculosis has shown equal or better sensitivity in diagnosing TB in cattle than the widely used standard assay, according to a recent study.

“Bovine tuberculosis (bTB) is a major zoonotic disease of cattle that is endemic in much of the world, limiting livestock productivity and representing a global public health threat,” Sreenidhi Srinivasan, graduate student in the department of animal sciences at the Penn State University College of Agricultural Sciences, and colleagues wrote, noting that bTB causes an estimated 10% of global human TB cases.

“Because the standard tuberculin skin test precludes implementation of bacille Calmette-Guérin (BCG) vaccine-based control programs” — the test cannot differential between infected and vaccinated cows — “we here developed and evaluated a novel peptide-based defined antigen skin test (DST) to diagnose bTB and to differentiate infected from vaccinated animals (DIVA).”

According to the study, the researchers developed a test that targets proteins missing from or not secreted by the BCG vaccine strain.

Photo of cows with bovine TB 
A new skin test can provide equal or better sensitivity in diagnosing tuberculosis in cattle when compared with the widely used standard assay.
Source: Program for Accelerating Bovine TB Control (ABTBC).

"Our diagnostic reagent is a simple cocktail of synthetic peptides representing antigens that are present in the naturally occurring TB bacteria but not recognized by the immune system following BCG vaccination," Srinivasan said in a news release. "These antigens, when applied to the skin, cause an immune reaction in cows that have TB, whereas no reaction occurs in animals that have been vaccinated with BCG."

According to the study, Srinivasa and colleagues used the new skin test on 25 naturally infected cattle in Ethiopia and confirmed that it was superior to the standard test, identifying more infected animals.

The researchers said the test may help scientists overcome regulatory restrictions in countries such as India, where the use of genetically modified proteins is prohibited or difficult to approve.

“The results, in laboratory assays and in experimentally or naturally infected animals, demonstrate that the peptide-based DST provides DIVA capability and equal or superior performance over the extant standard tuberculin surveillance test,” the authors concluded. “Together with the ease of chemical synthesis, quality control, and lower burden for regulatory approval compared with recombinant antigens, the results of our studies show that the DST considerably improves a century-old standard and enables the development and implementation of critically needed surveillance and vaccination programs to accelerate bTB control”. – by Caitlyn Stulpin

Disclosures: The authors report no relevant financial disclosures.

A new skin test for detecting bovine tuberculosis has shown equal or better sensitivity in diagnosing TB in cattle than the widely used standard assay, according to a recent study.

“Bovine tuberculosis (bTB) is a major zoonotic disease of cattle that is endemic in much of the world, limiting livestock productivity and representing a global public health threat,” Sreenidhi Srinivasan, graduate student in the department of animal sciences at the Penn State University College of Agricultural Sciences, and colleagues wrote, noting that bTB causes an estimated 10% of global human TB cases.

“Because the standard tuberculin skin test precludes implementation of bacille Calmette-Guérin (BCG) vaccine-based control programs” — the test cannot differential between infected and vaccinated cows — “we here developed and evaluated a novel peptide-based defined antigen skin test (DST) to diagnose bTB and to differentiate infected from vaccinated animals (DIVA).”

According to the study, the researchers developed a test that targets proteins missing from or not secreted by the BCG vaccine strain.

Photo of cows with bovine TB 
A new skin test can provide equal or better sensitivity in diagnosing tuberculosis in cattle when compared with the widely used standard assay.
Source: Program for Accelerating Bovine TB Control (ABTBC).

"Our diagnostic reagent is a simple cocktail of synthetic peptides representing antigens that are present in the naturally occurring TB bacteria but not recognized by the immune system following BCG vaccination," Srinivasan said in a news release. "These antigens, when applied to the skin, cause an immune reaction in cows that have TB, whereas no reaction occurs in animals that have been vaccinated with BCG."

According to the study, Srinivasa and colleagues used the new skin test on 25 naturally infected cattle in Ethiopia and confirmed that it was superior to the standard test, identifying more infected animals.

The researchers said the test may help scientists overcome regulatory restrictions in countries such as India, where the use of genetically modified proteins is prohibited or difficult to approve.

“The results, in laboratory assays and in experimentally or naturally infected animals, demonstrate that the peptide-based DST provides DIVA capability and equal or superior performance over the extant standard tuberculin surveillance test,” the authors concluded. “Together with the ease of chemical synthesis, quality control, and lower burden for regulatory approval compared with recombinant antigens, the results of our studies show that the DST considerably improves a century-old standard and enables the development and implementation of critically needed surveillance and vaccination programs to accelerate bTB control”. – by Caitlyn Stulpin

Disclosures: The authors report no relevant financial disclosures.

    Perspective
    Arnon Shimshony

    Arnon Shimshony

    The tuberculin in-vivo cattle test was initially introduced by the Danish veterinarian Bernhard Bang in 1891. The application of the “test and slaughter” policy in cattle herds has led to a significant reduction of bTB prevalence. According to data provided by the World Organisation of Animal Health (OIE) as of Dec. 31, 2018, 20 countries worldwide in which infections have been found declared “no cases” for at least the last 10 years; 19 island countries declared to have “never” recorded bTB. Although in other developed countries, the prevalence is low, the economic impact is still significant and wildlife is threatened; the worst situation prevails in poorer countries.

    Because bTB  seriously affects the health of livestock, humans and ecosystems, the OIE, WHO, Food and Agriculture Organization of the United Nations and the International Union Against Tuberculosis and Lung Disease have jointly announced its eradication as a One Health issue, indicating the urgent need to replace the old international standard with ”second-generation” tests. Such tests should be quicker, less laborious and more specific. The present study advances these goals.

    An upsurge of infections in cattle by Mycobacterium caprae, with potential public health implications, has recently been recorded in several countries. This deserves being considered when second-generation tests are developed. 

    Those interested in background information on the global bTB situation and in the “Roadmap for zoonotic tuberculosis,” are encouraged to access the recent publication “Eradication of bovine tuberculosis: a One Health issue.”

    • Arnon Shimshony, DVM
    • Infectious Disease News Editorial Board member

    Disclosures: Shimshony reports no relevant financial disclosures.