Natural Infection of Burkholderia pseudomallei in an Imported Pigtail Macaque (Macaca nemestrina) and Management of the Exposed Colony

Identification of the select agent Burkholderia pseudomallei in macaques imported into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca nemestrina) imported from Southeast Asia was received from a commercial vendor at our facility in March 2012. After the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. The wound was treated and resolved over 3 mo. In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited neurologic clinical signs. Postmortem microbiologic analysis revealed that the macaque was infected with B. pseudomallei. This case report describes the clinical evaluation of a B. pseudomallei-infected macaque, management and care of the potentially exposed colony of animals, and protocols established for the animal care staff that worked with the infected macaque and potentially exposed colony. This article also provides relevant information on addressing matters related to regulatory issues and risk management of potentially exposed animals and animal care staff.Abbreviations: CDC, Centers for Disease Control and Prevention; IHA, indirect hemagglutination assay; PEP, postexposure prophylacticBurkholderia pseudomallei, formerly known as Pseudomonas pseudomallei, is a gram-negative, aerobic, bipolar, motile, rod-shaped bacterium. B. pseudomallei infections (melioidosis) can be severe and even fatal in both humans and animals. This environmental saprophyte is endemic to Southeast Asia and northern Australia, but it has also been found in other tropical and subtropical areas of the world.^7,22,32,42 The bacterium is usually found in soil and water in endemic areas and is transmitted to humans and animals primarily through percutaneous inoculation, ingestion, or inhalation of a contaminated source.^{8, 22,28,32,42} Human-to-human, animal-to-animal, and animal-to-human spread are rare.^8,32 In December 2012, the National Select Agent Registry designated B. pseudomallei as a Tier 1 overlap select agent.³⁹ Organisms classified as Tier 1 agents present the highest risk of deliberate misuse, with the most significant potential for mass casualties or devastating effects to the economy, critical infrastructure, or public confidence. Select agents with this status have the potential to pose a severe threat to human and animal health or safety or the ability to be used as a biologic weapon.³⁹Melioidosis in humans can be challenging to diagnose and treat because the organism can remain latent for years and is resistant to many antibiotics.^12,37,41 B. pseudomallei can survive in phagocytic cells, a phenomenon that may be associated with latent infections.^19,38 The incubation period in naturally infected animals ranges from 1 d to many years, but symptoms typically appear 2 to 4 wk after exposure.^13,17,35,38 Disease generally presents in 1 of 2 forms: localized infection or septicemia.²² Multiple methods are used to diagnose melioidosis, including immunofluorescence, serology, and PCR analysis, but isolation of the bacteria from blood, urine, sputum, throat swabs, abscesses, skin, or tissue lesions remains the ‘gold standard.’^9,22,40,42 The prognosis varies based on presentation, time to diagnosis, initiation of appropriate antimicrobial treatment, and underlying comorbidities.^7,28,42 Currently, there is no licensed vaccine to prevent melioidosis.There are several published reports of naturally occurring melioidosis in a variety of nonhuman primates (NHP; 2,10,13,17,25,30,31,35 The first reported case of melioidosis in monkeys was recorded in 1932, and the first published case in a macaque species was in 1966.³⁰ In the United States, there have only been 7 documented cases of NHP with B. pseudomallei infection.^2,13,17 All of these cases occurred prior to the classification of B. pseudomallei as a select agent. Clinical signs in NHP range from subclinical or subacute illness to acute septicemia, localized infection, and chronic infection. NHP with melioidosis can be asymptomatic or exhibit clinical signs such as anorexia, wasting, purulent drainage, subcutaneous abscesses, and other soft tissue lesions. Lymphadenitis, lameness, osteomyelitis, paralysis and other CNS signs have also been reported.^{2,7,10,22,28,32} In comparison, human''s clinical signs range from abscesses, skin ulceration, fever, headache, joint pain, and muscle tenderness to abdominal pain, anorexia, respiratory distress, seizures, and septicemia.^7,9,21,22

Table 1.

Summary of reported cases of naturally occurring Burkholderia pseudomalleiinfections in nonhuman primates

Countrya	Imported from	Date reported	Species	Reference
Australia	Borneo	1963	Pongo sp.	36
Brunei	Unknown	1982	Orangutan (Pongo pygmaeus)	33
France		1976	Hamlyn monkey (Cercopithecus hamlyni) Patas monkey (Erythrocebus patas)	11
Great Britain	Philippines and Indonesia	1992	Cynomolgus monkey (Macaca fascicularis)	10
				38
Malaysia	Unknown	1966	Macaca spp.	30
	Unknown	1968	Spider monkey (Brachytelis arachnoides) Lar gibbon (Hylobates lar)	20
	Unknown	1969	Pig-tailed macaque (Macaca nemestrina)	35
	Unknown	1984	Banded leaf monkey (Presbytis melalophos)	25
Singapore	Unknown	1995	Gorillas, gibbon, mandrill, chimpanzee	43
Thailand	Unknown	2012	Monkey	19
United States	Thailand	1970	Stump-tailed macaque (Macaca arctoides)	17
	India		Pig-tailed macaque (Macaca nemestrina)
	Africa		Rhesus macaque (Macaca mulatta) Chimpanzee (Pan troglodytes)
	Unknown	1971	Chimpanzee (Pan troglodytes)	3
	Malaysia	1981	Pig-tailed macaque (Macaca nemestrina)	2
	Wild-caught, unknown	1986	Rhesus macaque (Macaca mulatta)	13
	Indonesia	2013	Pig-tailed macaque (Macaca nemestrina)	Current article

Open in a separate window^aCountry reflects the location where the animal was housed at the time of diagosis.Here we describe a case of melioidosis diagnosed in a pigtail macaque (Macaca nemestrina) imported into the United States from Indonesia and the implications of the detection of a select agent identified in a laboratory research colony. We also discuss the management and care of the exposed colony, zoonotic concerns regarding the animal care staff that worked with the shipment of macaques, effects on research studies, and the procedures involved in reporting a select agent incident.