Molecular epidemiology of a hepatitis C virus outbreak in a leprosy sanatorium in Japan.

The hepatitis C virus (HCV) outbreak that occurred between 1940 and 1999 in a closed leprosy sanatorium located on a small island in Japan was analyzed. The analysis of 318 nucleotides in the NS5B region of HCV allowed us to establish the existence of at least three different HCV strains in this sanatorium.

[Novel method for simple detection of mutations conferring drug resistance in Mycobacterium leprae, based on a DNA microarray, and its applicability in developing countries].

The simple method to detect mutations conferring resistant to dapsone, rifampicin, and quinolone was exploited in Mycobacterium. leprae on the basis of reverse DNA hybridization with capture probe fixed to the glass slide. Mutations were discriminated by a series of oligonucleotide probes corresponding to each mutation in the folP1, rpoB, and gyrA genes of M. leprae. The method was transferred to two laboratories in developing countries. The results obtained with the kit at those laboratories were highly concordant with results of sequencing. The method is feasible for the testing by local person in areas with high prevalence of leprosy.

[Learning from the history of leprosy--looking back at one hundred years of medicine at the leprosaria].

This year is the centennial anniversary of the five national leprosaria in Japan. It means that the official accommodation of leprosy patients who were wandering on the streets started in 1909. At that time, the existence of these leprosy patients on the streets was considered as a national shame and also an evidence of falling behind the Western cultured countries. Japanese people and the government were hypersensitive of such notoriety, especially from the Western countries. Some doctors, politicians and bureaucrats were really concerned about the situation and made great efforts to establish the leprosy separation law. It was implemented in 1907, but it took two more years for the preparation of the sanatoria for accommodation. The leprosy separation law has persisted until 1996. It has been revised to the leprosy segregation law in 1931, and to the leprosy isolation law in 1953. Although the law underwent two revisions, the main ideology of isolation has been abundant for almost ninety years. This law has been infamous for its misery and pointed out to be abolished by the WHO. This paper will focus attention on the doctors, politicians and bureaucrats who have worked for the institution of this cruel law, and also discuss the reason why this law had prevailed.

Hepatitis C virus infection in a Japanese leprosy sanatorium for the past 67 years.

Oku-Komyo-En is one of the national leprosy sanatoria, located on a small island in Setouchi city, Okayama prefecture of Japan since 1938. Since autopsies were carried out routinely on almost all patients who had died in the sanatorium up to 1980, approximately 1,000 formalin-fixed autopsy tissue samples were available for analysis. When these samples were reviewed, the pathological data indicated a sharp rise in the death rate caused by cirrhosis of the liver and hepatocellular carcinoma (HCC) since 1960 and 1970, respectively. Hepatitis C virus (HCV) infection is a common cause of HCC in Japan. The presence of HCV RNA was demonstrated in paraffin sections prepared from the autopsied liver tissue fixed in formalin for a prolonged period of time, by employing nested RT-PCR using type-specific primers. The data showed that HCV RNA was detectable in samples of the liver archived as early as 1940, representing the liver tissues kept in formalin for up to 67 years. HCV genotypes 1b and 2a were found by RT-PCR at 85.7% and 14.3%, respectively, in patients with leprosy.

A novel method for simple detection of mutations conferring drug resistance in Mycobacterium leprae, based on a DNA microarray, and its applicability in developing countries.

A simple method to detect mutations in the genome of Mycobacterium leprae that confer resistance to key drugs for leprosy was exploited on the basis of a reverse hybridization system. A series of oligonucleotide probes corresponding to each mutation in the folP1, rpoB and gyrA genes for dapsone, rifampicin and ofloxacin resistance, respectively, were selected and fixed on a glass slide as capture probes, to develop a DNA microarray termed the leprosy drug susceptibility-DNA microarray (LDS-DA). Mutations in clinical isolates of M. leprae were successfully identified by the LDS-DA. Feasibility studies were conducted to evaluate the performance of the LDS-DA in two developing countries, Myanmar and the Philippines. The high concordance of the results obtained by this method with the results of nucleotide sequencing strongly supports the applicability of the LDS-DA as a drug susceptibility test in place of sequencing, a time-consuming and costly procedure. This is a rapid and simple method for the simultaneous susceptibility testing of three front-line drugs for leprosy, and solves the problems of previously reported methods.

[Survey of newly diagnosed leprosy patients in Japan (1993-2000)].

We analyzed the medical and social problems of newly registered leprosy patients in the past 8 years from 1993 to 2000 in a low endemic country, Japan. There were 56 registered Japanese patients (males, 32; females, 24), and 76 registered foreign patients (males, 56; females, 20). The number of Japanese patients in each year was between 5 and 9, and 2/3 of them were from Okinawa Prefecture, located in subtropical zone. But the number of foreign patients in each year was between 5 and 18, and 2/5 of them were from Brazil. The number of foreign patients was greater than that of Japanese patients. Male/female ratio has decreased among the Japanese.