Primary hepatic Mycobacterium tuberculosis complex infection with terminal dissemination in a pig-tailed macaque (Macaca nemestrina)

Abstract

An adult, female, pig-tailed macaque (Macaca nemestrina) of Indonesian origin presented with profound weight loss, anemia (PCV, 29%; normal, 36% to 45%), hypoalbuminemia (1.0 g/dL; normal, 3.5 to 5.2 g/dL), elevated alkaline phosphatase (1990 U/L; normal, 26 to 98 U/L), and an elevated erythrocyte sedimentation rate (75 mm/h; normal, less than 20 mm/h). Abdominal ultrasonography demonstrated an enlarged liver with hyperechoic areas. Euthanasia was performed. Grossly, the liver had multifocal, effacing, white masses throughout and was enlarged with rounded edges. There were 2, small nodules in the right lung lobes. Histologically, the hepatic masses were densely fibrous-encapsulated granulomas with vast central necrosis. The lung nodules also were maturing granulomas, and one kidney and one atrium had small, early granulomas. Fite acid-fast stains of liver and lung revealed very few acid-fast bacilli. PCR analysis of paraffin-embedded liver identified Mycobacterium tuberculosis complex. Culture of the liver was negative twice. This macaque had 16 negative intradermal tuberculin skin tests over the course of 6 y. We hypothesize that the animal arrived with a latent hepatic or enteric infection that later recrudesced and disseminated. Primary hepatic mycobacteriosis is not a typical presentation of tuberculosis in macaques. Negative tuberculin skin tests can be seen with latent infections and extrapulmonary tuberculosis such as Pott disease. This case underscores the problems associated with current surveillance procedures and the risks associated with latent mycobacterial infections in macaques.

Figure 1.

Gross photographs of liver. (A) Unsectioned liver observed from the diaphragmatic side with overlying, adhered diaphragm. (B) Cut section. Notice the multifocal, coalescing granulomas effacing large regions of parenchyma.

Figure 2.

Histologic findings. (A) This low-power photomicrograph of liver reveals extensive effacement of normal parenchyma by coalescing granulomas. (B) At higher magnification, the hepatic granulomas have central, massive necrosis, surrounded by intense granulomatous infiltrates including scattered giant cells, and with peripheral fibrosis. In the lower right portion of the image, biliary hyperplasia can be seen. (C) A mesenteric lymph node shows effacement of normal structure by a large granuloma. (D) One of the grossly identified nodules in the lung consists of coalescing granulomas. Note the lack of a thick, fibrous capsule in the lung granulomas, indicating more recent development. Hematoxylin and eosin stain; bar, 0.5 mm (A), 100 µm (B), 200 µm (C, D).

Figure 3.

Fite acid-fast staining. (A) In the liver, a giant cell contains a solitary Fite acid-fast organism. (B) This section of lung has a small cluster of Fite acid-fast organisms. Notably, organisms were present in very low numbers. Fite acid fast stain; bar, 20 µm.