Vetnews | Maart 2026 28 « BACK TO CONTENTS Antigen Detection Tests Lipoarabinomannan (LAM), a glycolipid component of the mycobacterial cell wall, can be detected in urine using rapid antigen-detection assays such as AlereLAM® (Abbott Diagnostics, Chicago, IL, USA) and FujiLAM® (Fujifilm Corporation, Tokyo, Japan). These tests are primarily used in human populations, especially among HIV-positive or immunocompromised patients with advanced tuberculosis, where non-sputum-based diagnostics are critical. However, the relevance of LAM-based assays to zTB remains unclear. These tests have not been validated specifically for detecting M. bovis, M. orygis, or M. caprae, and their performance in extrapulmonary or zoonotic cases has not been well established (10). Further studies are therefore needed to clarify their diagnostic utility in such contexts. DIAGNOSIS IN HUMANS VS. ANIMALS The diagnostic approach to TB differs substantially between the human and animal health sectors, reflecting differences in sample types, clinical presentations, surveillance priorities, and available laboratory infrastructure. These differences become especially relevant in the context of zTB, where effective control depends on harmonised detection strategies across species within a One Health framework. Diagnosis in Humans In humans, the diagnostic workup for pulmonary tuberculosis typically begins with smear microscopy of respiratory specimens, which allows rapid identification of AFB. Culture remains the gold standard for confirming infection and performing drug susceptibility testing, although it requires longer processing times. Nucleic acid amplification tests, such as the GeneXpert® and TrueNat® platforms, enable rapid detection of MTBC along with rifampicin resistance and are widely used in national TB control programs. In extrapulmonary TB, particularly cases involving lymph nodes or tissue biopsies, histopathological examination provides valuable diagnostic insights (5). Additionally, advanced molecular methods— including conventional PCR, line probe assays, and WGS—are increasingly employed in research or reference laboratory settings, particularly when species identification or drug resistance profiling is required. Although these tools are effective for identifying M. tuberculosis, they do not routinely distinguish zoonotic MTBC species. As a result, cases of zTB, especially those presenting with extrapulmonary disease, may remain unrecognised. This diagnostic gap is particularly problematic in settings where close contact with livestock or consumption of unpasteurized dairy products is common (14). Diagnosis in Animals In animals, particularly livestock, tuberculosis diagnosis focuses on identifying infected individuals or herds to control disease transmission and mitigate economic losses (15). The most widely used methods are skin tests, with the single intradermal test (SIT) and the SICCT test remaining the standard approaches in cattle. These tests assess delayed-type hypersensitivity reactions to PPD tuberculin and are central to herd-level surveillance programs Interferon-gamma release assays are used in some countries as adjuncts or alternatives to skin testing, particularly when the sensitivity of the SICCT test is suboptimal (4). Serological assays, including ELISAs, are also used for herd-level screening and in wildlife species such as deer and elephants, where they are most effective in chronic or advanced stages of infection. Post-mortem examination plays an important diagnostic role within abattoir surveillance systems (12), where lymph nodes and organs are inspected for TB-compatible lesions and subjected to culture or molecular confirmation when indicated. Culture-positive animal isolates may undergo molecular typing using PCR-based assays, spoligotyping, or whole genome sequencing. However, species-level identification is not routinely performed in many veterinary laboratories, especially in resourceconstrained settings, underscoring the need to strengthen diagnostic capacity for zTB surveillance. Bridging the Gap: Consequences of Diagnostic Fragmentation The stark differences between human and animal diagnostic strategies represent a fundamental barrier to effective zTB control. In human health systems, reliance on sputum-based NAATs and culture confirms MTBC infection but rarely identifies the infecting species, leaving the zoonotic origin unrecognised. Conversely, veterinary surveillance relies heavily on herd-level screening through skin tests and IGRAs, with limited routine use of culture or species-level molecular confirmation. As a result, cross-species transmission—such as transmission from cattle to humans via unpasteurized milk or occupational exposure— is frequently suspected but rarely confirmed microbiologically (13). Human and animal cases are managed within separate silos, using different tools, protocols, and reporting systems. This fragmentation prevents the establishment of integrated surveillance systems and makes it impossible to connect a human case of M. bovis or M. orygis back to its animal source. Overcoming this challenge requires coordinated One Healthoriented strategies. Key steps include establishing referral networks for confirmatory speciation, training veterinary staff in molecular techniques, the use of cartridge-based NAATs or TrueNat® platforms in the veterinary sector, and integrating species-level identification into routine clinical TB workflows. Such integration is essential for the accurate detection of zTB and for timely, species-specific public health responses. Advanced Diagnostic Approaches and Emerging Technologies Advancements in molecular diagnostics have expanded the capacity for species-level identification within the MTBC. These developments are particularly promising for detecting zTB, where conventional methods fall short. Despite their potential, accessibility, cost, and operational complexity continue to limit widespread implementation, especially in low-resource and rural settings. Whole Genome Sequencing Whole genome sequencing is the most definitive and comprehensive method for MTBC species identification, lineage classification, drug resistance prediction, and transmission Article Zoonotic Tuberculosis.... <<< 27
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