Tuberculosis in Imported Macaques: A Mycobacterium orygis Outbreak, 2023

Nonhuman primates (NHPs) such as monkeys can be infected with the same Mycobacterium species that cause tuberculosis in people. CDC therefore regulates their importation under the Public Health Service Act. Every imported NHP must come in through a CDC-registered importer and go through quarantine with at least three negative tuberculin skin tests (TSTs), given in the eyelid at least two weeks apart, before release. Any animal that dies or is euthanized with suspected tuberculosis must be tested. From 2013 to 2020, just 19 imported NHPs (0.009%) had a positive skin test, and none had tuberculosis confirmed by culture during quarantine.

Where research monkeys come from changed during the COVID-19 pandemic. In 2019, 60% of imported NHPs came from China; by 2021, imports from China had stopped and 65% came from Southeast Asia.

The shipment

In January 2023, 540 captive-bred cynomolgus macaques (Macaca fascicularis) were flown into the United States from Southeast Asia for research. They were quarantined at a CDC-approved facility in several rooms, each with its own air handling system keeping it at verified negative pressure. Transport and quarantine used a tuberculosis-killing disinfectant registered with the Environmental Protection Agency. Anyone coming within 5 feet of the animals had to wear protective equipment, including a fit-tested N95 or better respirator, and importers must run occupational health programs with medical clearance, respirator fit testing and training, and at least yearly tuberculosis screening.

Finding M. orygis

On February 7, 2023, the importer reported a macaque with a positive skin test. It was euthanized and examined. Tissue findings pointed to mycobacterial infection, and PCR testing of its lung and lymph nodes by the U.S. Department of Agriculture's National Veterinary Services Laboratories (NVSL) was positive for the Mycobacterium tuberculosis complex, though that test is not validated for NHPs. Culture and whole-genome sequencing then identified Mycobacterium orygis, a member of the tuberculosis complex believed to be found most often in people and animals in South Asia.

More infected animals

The remaining macaques had to stay in extended quarantine until they had at least five more negative skin tests, two weeks apart.

• On February 21, eight more had positive skin tests; seven were suspected of tuberculosis after postmortem examination, and all seven were confirmed to have M. orygis.
• Positive skin tests kept appearing until May 30, for a total of 32. Each of those animals was euthanized and tested.
• In all, 26 macaques (4.8% of the shipment) had M. orygis confirmed by culture: 24 of the 32 with positive skin tests and 2 of the 508 with negative ones.
• The importer also had blood from skin-test-positive animals tested experimentally with an interferon-gamma release assay (IGRA). In early April every remaining macaque was tested this way, giving one positive and four indeterminate results; two of those animals (one positive, one indeterminate) proved to be infected.
• Infected macaques were found in 67% of the quarantine rooms.
• All isolates shared a common ancestor.

The rest of the group was released on August 8, 2023, after five negative skin tests following removal of the last positive animal.

Because infected animals came from several rooms and their isolates were closely related, the macaques are thought to have been infected from a common human or animal source before they left Southeast Asia, consistent with a species found mainly in South Asia.

Protecting people

CDC informed the state health department and assessed the risk to workers. With the engineering controls, administrative rules and protective gear required in transport and quarantine, the risk was considered low, but everyone who worked in affected rooms was screened for tuberculosis more often. As of February 2024, eight months after the last infected macaque was found, none had a positive skin test or IGRA.

CDC also told the airline, airport staff and transporters that animals in the shipment had tuberculosis and advised them to see a health care provider about whether follow-up was needed. It recommended that the importer warn institutions receiving the released monkeys, since tuberculosis can take a long time to appear and skin tests can miss it. In July 2023 CDC sent a veterinary health alert, with a fact sheet on tuberculosis in NHPs, to primate veterinarians, animal health and public health veterinary associations, and every registered NHP importer. No human infection linked to the outbreak has been reported in the United States; nothing is known about the tuberculosis status of workers at the supplier in Southeast Asia.

Lessons

M. orygis was recognized as a separate species only in 2012, and much about it is unknown. It has infected people and animals, mostly ungulates, and in one report two wild-caught monkeys in a zoo; most cases have a link to South Asia, where it may be more common than recognized because standard tests may not tell it apart from other tuberculosis species.

Screening monkeys for tuberculosis is difficult. Infection ranges from no symptoms to sudden, severe or chronic disease, and the skin test can give both false positives and false negatives. Combining several tests might work better, but no such approach has been validated. U.S. research facilities usually screen their own workers, but it may be impossible to confirm that foreign suppliers do the same. The authors conclude that strict occupational safety programs, following the hierarchy of controls from elimination through protective equipment, remain essential for people who work closely with imported monkeys, and that the importer's careful compliance and close partnership with CDC may have prevented human cases. The risk to the general public remains low.

Sources

• Swisher SD, Taetzsch SJ, Laughlin ME, et al. Outbreak of Mycobacterium orygis in a Shipment of Cynomolgus Macaques Imported from Southeast Asia — United States, February–May 2023. MMWR Morb Mortal Wkly Rep 73(7). https://www.cdc.gov/mmwr/volumes/73/wr/mm7307a2.htm
• CDC, bringing monkeys into the United States: https://www.cdc.gov/importation/bringing-an-animal-into-the-united-states/monkeys.html