Natural outbreak of Mycobacterium caprae infection in imported laboratory cynomolgus macaques (Macaca fascicularis): diagnostic pitfalls and management of safety precautions

Tuberculosis (TB) is a major health threat for humans and for non-human primates used for toxicology or research purposes. Emerging mycobacterial species represent a major challenge for diagnosis and surveillance programs. Here, we report a natural outbreak of Mycobacterium caprae in imported cynomolgus macaques (Macaca fascicularis) that occurred at AnaPath Research S.A.U. (APR). The macaques underwent repeated negative intradermal tuberculin tests (IDT) before importation and at the European quarantine station. Exhaustive TB screening was started at APR after confirmation of one positive case at another facility. The animal in question belonged to the same colony received at APR. Diagnostic approaches included clinical examination, PCR, culture, spoligotyping, IDT testing, interferon-γ release assay (IGRA), and thoracoabdominal ultrasound (US). Three regulatory toxicity studies and stock animals were affected. The macaques lacked clinical signs, except for one showing a fistulizing nodule in the right inguinal area, which tested positive for the Mycobacterium tuberculosis complex by PCR. All animals were necropsied and 10 macaques (n=114) showed gross and histologic findings compatible with TB confirmed by PCR and culture. M. caprae was identified as the etiological agent by Direct Variable Repeat spacer oligonucleotide typing (DVR spoligotyping). The infection was traced to Asia via the SB1622 spoligotype involved, confirming that the animals were infected prior to their import into Europe. Tuberculin skin test (TST), IGRA, and US were only sensitive in detecting advanced cases of M. caprae infection. One staff member showed a positive TST reaction, which was handled in accordance with the Spanish government’s health regulations. All the sanitary measures implemented were effective in eradicating the disease.