Chimpanzees Used for Medical Research Shed Light on the Pathoetiology of Leprosy

Koichi Suzuki; Kazunari Tanigawa; Akira Kawashima; Tatsuo Miyamura; Norihisa Ishii

Disclosures

Future Microbiol. 2011;6(10):1151-1157. 

In This Article

Cases of Naturally Acquired Leprosy in Chimpanzees

There have only been four reports of leprosy in chimpanzees in the literature (Table 1). All four chimpanzees were brought from Africa when they were infants for the purpose of being used for medical studies. The first three cases of leprosy were diagnosed solely by clinical and pathological evaluation, and M. leprae DNA was not identified.

The first reported case was a male chimpanzee who was captured in Sierra Leone, West Africa.[20,27–29] He was one of eight chimpanzees being used for experiments on bovine leukemia virus infections. After 2 months of virus infection in 1975, a leprosy-like skin lesion (macular rash) appeared and was followed by a progressive maculopapular rash with a crust that covered his abdomen and the medial aspect of his thighs. The other seven chimpanzees used for the same experiment did not develop gross or microscopic lesions. After that, his entire trunk and limbs were covered with a rash and nodular thickening of the ear margins appeared. Lepromatous leprosy was diagnosed due to acid-fast bacteria that were identified in biopsy specimens of the granulomas. The infection progressed with appearance of nodular lesions in the lower lip, nostrils, nasal septum, eyebrows, carpus and scrotum. No specific treatment for leprosy was administered. The chimpanzee died inadvertently following sedation with phencyclidine and ketamine 33 months after the first appearance of the lesions. A necropsy was performed 2 h after death.[29] Marked atrophy of skeletal muscles, alopecia and diffuse thickening of the skin of the hands, feet and digits were observed as gross lesions. Microscopically, there were diffuse and multifocal infiltrations of foamy histiocytes with acid-fast bacilli in the dermis, nasal mucosa, epiglottis, lung interstitium and parenchyma, liver, spleen, kidneys, lymphnodes, peripheral nerves, both eyes (especially the sclera, cornea, ciliary body and iris) and testicular tunics.

In 1989, the second and third chimpanzees were diagnosed with leprosy after they had both been held in research facilities in the USA for many years.[30–33] The second case was a male who was brought from Africa when he was approximately 2-years-old.[31] The chimpanzee began self-mutilating his digits at 7 years. At 9 years, he had a positive reaction to an intradermal tuberculin test and was treated with antibiotics. However, after several examinations, it was revealed that there was no evidence of tuberculosis. At 13 years, his tuberculin test results again showed positive, but no evidence of active tuberculosis was found. At 18 years, he developed nodular and papular eruptions of his eyelids, face, ear margins, lips, distal portion of the penis and scrotum. Histologic evaluation of the cutaneous lesions revealed granulomatous dermatitis consisting predominantly of foamy histiocytes containing acid-fast bacilli. A diagnosis of borderline leprosy was made on the bases of clinical and histopathological findings and bacterial indices. Retrospective evaluations of tissue sections of an amputated finger revealed leprosy with neural involvement. Serum PGL-I antibodies were above baseline. A multidrug treatment (MDT) regimen was started as recommended by the WHO study group for human patients, and was continued for 4 years.[34] A total of 6 months after the start of treatment, a severe leprae reaction developed with the subject manifesting pain and marked impairment of locomotion. Although treatment with prednisone and aspirin restored quadrupedal locomotion and some climbing activity, he sustained permanent neurologic and musculoskeletal dysfunction.

The third case was a male chimpanzee who was imported to the USA when he was approximately 3 years old.[31–33] He had three episodes of ulcerative gingivitis of unknown origin. When he was 26-years-old, he initially developed a persistent clear nasal discharge and chronic areas of epidermal erosions, which were followed by a development of coalescent nodules in the skin of the supraorbital area, lips, chin, ear and scrotum. He was diagnosed as having subpolar lepromatous to borderline leprosy by histological examination. Intracellular aggregates of acid-fast bacilli were found in the liver histiocytes. Antibodies against lipoarabinomannan (LAM) and PGL-I were markedly elevated. He was treated with MDT, but died suddenly 1.5 years later when recovering from anesthesia with ketamine. Necropsy revealed that the immediate cause of death was heart failure secondary to acute, severe myocardial necrosis and hemorrhage.

Gormus et al. measured serum anti-PGL-I and anti-LAM antibodies in 160 chimpanzees housed in two research facilities in the USA.[30] This includes the cases 2 and 3 as described earlier and other wild-born adults, captive-born adults and adolescents, and colony-born infants, juveniles and adolescents. Among the chimpanzee cases with anti-PGL-I positive serum, there were four with IgG and five with IgM antibodies. Samples from cases 2 and 3 were the only cases that were sera positive for both IgG and IgM anti-PGL-I. On the other hand, among the anti-LAM positive serum samples there were three with IgG and three with IgM antibodies, but only the serum from case 2 was positive for both IgG and IgM antibodies.

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