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

Conclusion & Future Perspective

A total of four leprosy cases have been reported in chimpanzees imported from Africa for the purpose of medical experiments. With the most recent case in Japan, the existence of M. leprae was proven with DNA analysis. Furthermore, by identification of M. leprae SNPs, it was shown that the chimpanzee was infected by the age of 2 years in West Africa, and that the symptoms appeared after an incubation period of at least 30 years. In this case, anti-PGL-I antibody levels were negative before the onset of the disease, turned positive after the onset, and returned again to negative along with the improvement of the symptoms.

These cases also suggest that isolated clinical leprosy in the wild may exist,[17,36,37] yet have escaped detection due to reduced fitness and shorter lifespans in the wild. Since the habitat of chimpanzees and other apes is becoming increasingly restricted, contact with humans may become more frequent, increasing the risks of many zoonoses.[20,23,36] Although humans appear to be the major reservoir of M. leprae infection, naturally occurring infection has been reported in wild animals, including the nine-banded armadillo and several species of primates.[17,19,20,28,29,31–33,35–37] A recent study found that the same genotypic strain of M. leprae was detected at high incidence in wild armadillos and leprosy patients in the southern USA, suggesting that leprosy may be a zoonotic in regions in which armadillos serve as a reservoir.[38] Thus, leprosy is clearly a common disease among humans and other animals. Even after worldwide efforts to reduce the disease burden of leprosy were successfully completed, isolated leprosy cases in wild animals may still exist, which may serve as potential sources of human infection. It will be imperative, therefore, to reconsider the relationship between humans and nonhuman primates in the wild. Careful attention needs to be paid, as both have the possibility to transmit infectious diseases to each other.

Since infection of the four chimpanzees is unlikely to have taken place in the USA or in Japan, they seem to be infected in Africa and disease manifested 5–30 years after infection. However, risk of infection and the clinical manifestations of leprosy depend on multiple factors, but are not restricted to infection during infancy via the nasopharynx. Large numbers of prospective cohort studies of human leprosy patients and their contacts suggest that the risk of leprosy is associated with consanguinity, BCG vaccination and the clinical form of the transmitting cases.[39–41] It was long thought that leprosy might have a strong host genetic component. Genome-wide association studies and searches for susceptibility loci have provided a list of genes associated with host immune response in human leprosylesions.[42–45] Since emergence from dormancy, as well as leprae reaction, appear to be related to stress and changes of immunological status in humans,[46] this is possibly also the case with chimpanzees. Research on the role of various stressors in the onset of leprosy and leprae reactions is needed.

Chimpanzees are the closest genetic relatives to humans that have been used for medical research, including infectious diseases research.[21–26] Although chimpanzees and humans have very similar immune systems, fewer genes on the chimpanzee Y chromosome are responsible for immune function.[47] The innate immune systems could also differ, as the living environments of chimpanzees and humans are quite different. Whether these immune system differences affect the occurrence of mycobacterial diseases in chimpanzees is not clear.

The parents of these four chimpanzees must have been killed in order to capture them during their infancy before they were brought to the USA or Japan. Since 1980, approximately 150 chimpanzees have been imported to Japan. They have been used to test the safety of HBV vaccines. During this time, the development of vaccines from human virus carrier plasma was innovative and untested, and the vaccines were tested on chimpanzees in order to eliminate the possibility of the vaccines containing the active virus. The chimpanzees introduced in this article have contributed not only to the medical experiments for which they were originally intended, but have also unexpectedly contributed to leprosy research. The fourth case discussed in this report, Haruna, fortunately does not have any notable peripheral neuropathy or leprae reactions. She is living her life in the sanctuary peacefully. We truly wish her peace for the rest of her life there.

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