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

A Case of Leprosy in a Chimpanzee in Japan

Haruna is a female chimpanzee who was imported to Japan from West Africa for use in medical research in March 1980 when she was approximately 2 years old,[35] and was used for HBV and HCV research. In March 2002, at 21 years she was healthy and was retired to live in a primate sanctuary. In January 2009 at 30 years, her caretaker noticed swelling and nodes on her face. In April, swelling of her eyelids and lips were observed, but no decrease in appetite or other symptoms were observed. Lesions on her face were notable and leontiasis developed. Whole body examination, blood tests, skim smears and biopsies were conducted under anesthesia. The tuberculin reaction was negative, but staining of a nasal swab and a skin smear from a nodule on the left forearm demonstrated acid-fast bacilli. Numerous foamy histiocytes were found in tissue sections of skin biopsies, and diagnosis of lepromatous leprosy was made. PCR analysis for M. leprae Hsp-70 DNA using skin tissue was positive, but M. tuberculosis DNA was not detected. 16S RNA sequencing revealed a 100% match with M. leprae genetics. Therefore, it was concluded that the pathogenic bacteria was the same M. leprae that causes human leprosy.

On June 1 2009, the MDT for MB regimen was administered as suggested by the WHO by mixing the drug with fruit or juice. After 2 months of MDT, her skin hives disappeared, and after 5 months nasal swab staining for acid-fast bacillus became negative. The treatment was continued for 1 year, as recommended by the WHO.[34] Anti-PGL-I antibody in the preserved sera was negative between 2001 and 2004. In 2008 a false positive was recorded, and the sera turned positive after the onset of symptoms in 2009. After the treatment, the sera again turned negative and it has remained negative for anti-PGL-I antibodies since then. In general, the specificity of anti-PGL-I antibody was uncertain, since the antibody has been detected in some household contacts and even in some healthy individuals in addition to MB patients.[15] However, in Haruna's case, the antibody response against M. leprae correlated with acid-fast bacteria detected in her body. Since skin lesions were first noticed in January 2009, the false-positive result of anti-PGL-I in 2008 suggests that M. leprae started to grow well before clinical manifestations were evident.

In order to determine the possible origin of the M. leprae found in Haruna, SNPs for three reported loci in the M. leprae genome were studied.[9,10] PCR amplification followed by direct sequencing identified the SNP type 4 M. leprae genotype. This genotype was identified to have originated in West Africa and been introduced to parts of the Caribbean islands and South America (most probably by the slave trade), but has not been found in any other areas. Therefore, infection of Haruna is highly unlikely to have taken place in Japan, particularly given the strict biosafety standards of primate housing facilities in experimental laboratories and the very low prevalence of leprosy in Japan. Evidence strongly suggests that Haruna was infected with M. leprae when she was in West Africa by the age of 2 years, and she developed leprosy after an incubation period of at least 30 years.[35]

All of the other 13 chimpanzees imported into Japan at the same time lived together in the same cage as Haruna. They have all tested negative for anti-PGL-I antibody. Also, nasal swab staining for acid-fast bacilli and PCR detection of M. leprae DNA for 32 other chimpanzees in Japan have all been negative. A survey was conducted at zoos and other facilities which have chimpanzees in Japan, but no other chimpanzees were reported to have had skin symptoms like Haruna. At the sanctuary, no human caretakers have reported skin hives with decreased consciousness.[35]

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