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

Abstract and Introduction

Abstract

Leprosy is a chronic infectious disorder caused by Mycobacterium leprae, which mainly affects skin and peripheral nerves. It is classified as either paucibacillary or multibacillary based upon clinical manifestations and slit-skin smear results. It is speculated that leprosy develops after a long latency period following M. leprae infection. However, the actual time of infection and the duration of latency have never been proven in human patients. To date, four cases of spontaneous leprosy have been reported in chimpanzees who were caught in West Africa in infancy and used for medical research in the USA and Japan. One of these chimpanzees was extensively studied in Japan, and single-nucleotide polymorphism analysis for the M. leprae genome was conducted. This analysis revealed that the chimpanzee was infected with M. leprae during infancy in West Africa and the pathognomonic signs of leprosy appeared after at least 30 years of incubation. Analysis of leprosy in chimpanzees can contribute not only to medical research but also to the understanding of the pathoetiology of leprosy.

Introduction

Leprosy is caused by a chronic infection with Mycobacterium leprae and has afflicted humans for millennia. Leprosy is a systemic disease that primarily affects the skin, nerves and eyes. The diverse clinical manifestations of the disease are produced by variations in host immune responses.[1]M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. The inability to cultivate in vitro and the lack of animal models have been major disadvantages for leprosy research. The genome sequence of M. leprae has revealed that only half of the small genome contains protein-coding genes, while the remainder consists of pseudogenes and noncoding regions.[2,3] However, analyses have demonstrated that some of these pseudogenes and noncoding regions are highly expressed at the RNA level. In clinical samples, these RNAs show varying expression patterns among patients, which suggests they have yet unknown functions.[4–7] The analysis of single-nucleotide polymorphisms (SNPs) revealed four primitive subtypes of M. leprae, but the number is increasing as the analysis progresses.[8–10]

Multibacillary (MB) patients excrete bacilli from their nasal mucosa and skin,[11] making close and repeated contact with these patients, directly and/or indirectly, a potential source of transmission. It is believed that clinical manifestations are only apparent after many years of incubation.[12,13] Although serum antibodies against phenolic glycolipid (PGL)-I have been widely evaluated in diagnosis and community surveys, there have been some arguments for their specificity.[14–16] Therefore, there is no definitive method that can be used to prove the existence of subclinical infection in humans.

The M. leprae bacterium was first described in modern literature in 1873, prior to the first description of Mycobacterium tuberculosis in 1882. Nevertheless, despite the passing of more than 130 years since its discovery, methods for in vitro cultivation of M. leprae have still not been established, and there is no effective animal model for the human disease. Therefore, the processes of infection, dormancy and disease activation of M. leprae remain unclear.

Since primates are humans' closest relatives, studying human diseases in primates is sometimes helpful when trying to understand the nature of diseases. Naturally acquired leprosy cases have been reported in mangabey monkeys and cynomologus macaques.[17–20] Among primates, the chimpanzee is considered to be an anthropoid as it is genetically known to be very similar to humans. In fact, the genetic difference between humans and chimpanzees is only 1.23% of genomic DNA.[21] For this reason, many infectious diseases that humans acquire are infectious in chimpanzees as well. Many of those infectious diseases are contagious from humans to chimpanzees and vice versa. For example, HIV, HBV and HCV are infectious diseases that are common in both humans and chimpanzees.[22–26] With this genetic similarity in mind, and keeping ethical considerations of using chimpanzees as subjects for animal research in mind, it can be argued that it is unfortunate for chimpanzees to be used as experimental animal models because they are so very similar to humans.

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