Modern history of Hansen's Disease (HD) in Korea begins with nationwide use of the chemotherapeutic agent Diamino Diphenyl Sulphone for the patients in 1955. Definition of the case was different from time to time. Based on World Health Organization (WHO) criteria, Ministry of Health and Welfare (MOHW) reported 4,393 registered patients and same number 4,393 as new cases in 1977. This is the turning point they accepted patient reporting system of WHO, but total number of registered and managed as leprosy patients was 28,029 in 1977, which means the people who needs HD service from government at that time. The number of new cases decreased from 4,393 in 1977, 39 in 1996 to 4 in 2017. Regarding to new cases, it takes 40 years to accomplish from thousands level to below 10. Now we have 166 active cases (registered patients) and reported them as patients to the WHO. Korea Civil Assistance Command invited Dr. RG Cochrane who visited Korea for six weeks to make blue print for eradication of HD in Korea. With his advice and MOHW set HD project and plan for manpower to solve HD problems in 1955. Dr. Joon Lew and his colleagues founded Korean Leprosy Prevention Association in 1947 to combat leprosy, enlighten the public, and solve social problems caused by HD. The Korean Leprosy Prevention Association led by him changed its name to the Korean Leprosy Association in 1956, and grew into the current Korean Hansen Welfare Association. This organization is now playing a leading role in the eradication and management of HD in Korea.

Modern history of Hansen's Disease (HD) in Korea begins with nationwide use of the chemotherapeutic agent Diamino Diphenyl Sulphone for the patients in 1955. Definition of the case was different from time to time. Based on World Health Organization (WHO) criteria, Ministry of Health and Welfare (MOHW) reported 4,393 registered patients and same number 4,393 as new cases in 1977. This is the turning point they accepted patient reporting system of WHO, but total number of registered and managed as leprosy patients was 28,029 in 1977, which means the people who needs HD service from government at that time. The number of new cases decreased from 4,393 in 1977, 39 in 1996 to 4 in 2017. Regarding to new cases, it takes 40 years to accomplish from thousands level to below 10. Now we have 166 active cases (registered patients) and reported them as patients to the WHO. Korea Civil Assistance Command invited Dr. RG Cochrane who visited Korea for six weeks to make blue print for eradication of HD in Korea. With his advice and MOHW set HD project and plan for manpower to solve HD problems in 1955. Dr. Joon Lew and his colleagues founded Korean Leprosy Prevention Association in 1947 to combat leprosy, enlighten the public, and solve social problems caused by HD. The Korean Leprosy Prevention Association led by him changed its name to the Korean Leprosy Association in 1956, and grew into the current Korean Hansen Welfare Association. This organization is now playing a leading role in the eradication and management of HD in Korea.

The nucleotide-oligomerization domain (NOD) is an important molecule involved in host defense against bacterial infection. To study the role of NODs in the host response to Mycobacterium leprae, we measured the mRNA levels of NODs and related genes in infected mouse tissues. The mRNA expression of NOD1, NOD2, caspase-1 and ASC was increased in mouse footpads. Whereas NOD2 expression in macrophages was increased at 2 and 24 h post-infection with M. leprae, there was no expression of NOD1 at these time points. An increase in caspase-1 expression was observed at 2 h and continued at 24 h. However, the expression of ASC was increased only at the early time point. The expression of caspase-1 is regulated by NOD2-dependent pathway in established HEK 293. Our results suggest NOD2, rather than NOD1, may be associated with the host response to M. leprae and that caspase-1 activation is essential for the host response.
Animals ; Bacterial Infections ; Macrophages ; Mice* ; Mycobacterium leprae* ; Mycobacterium* ; RNA, Messenger

The nucleotide-oligomerization domain (NOD) proteins are members of the NOD-like receptor (NLR) family, which are intracellular and cytoplasmic receptors. We analyzed the role of NODs for cytokine production by macrophages infected with intracellular pathogen M. leprae, the causative agent of leprosy. Production of pro-inflammatory cytokines such as IL-1beta and TNF-alpha was inhibited in the presence of cytochalasin D, an agent blocking phagocytosis, suggesting that intracellular signaling was, partially, required for macrophage activation to M. leprae infection. Next, we investigated the role of NOD1 and NOD2 proteins on NF-kappaB activation and cytokine expression. Treatment with M. leprae significantly increased NF-kappaB activation and expression of TNF-alpha and IL-1beta in NOD1- and NOD2-transfected cells. Interestingly, their activation and expression were inhibited by cytochalasin D, suggesting that stimulation of NOD proteins may be associated with the enhancement of cytokine production in host to M. leprae.
Cytochalasin D ; Cytokines ; Humans ; Leprosy ; Macrophage Activation ; Macrophages ; Mycobacterium ; Mycobacterium leprae ; NF-kappa B ; Phagocytosis ; Proteins ; Receptors, Cytoplasmic and Nuclear ; Tumor Necrosis Factor-alpha

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.
DNA Restriction Enzymes ; Genotype ; Humans ; Macrophages ; Prevalence ; Receptors, Calcitriol ; Tuberculosis ; Vitamin D ; Vitamins

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.
DNA Restriction Enzymes ; Genotype ; Humans ; Macrophages ; Prevalence ; Receptors, Calcitriol ; Tuberculosis ; Vitamin D ; Vitamins

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-alpha. Since NF-kappaB is a major transcription factor that regulates genes for TLR2 and TNF-alpha, we examined the effect of rifampicin on the LPS-induced NF-kappaB activation. Rifampicin inhibited NF-kappaB DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKKalpha/beta activity. However, rifampicin slightly inhibited the nuclear translocation of NF-kappaB p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-kappaB p65, suggesting pregnane X receptor interferes with NF-kappaB binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-kappaB DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-kappaB DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.
DNA ; Down-Regulation ; Mycobacterium tuberculosis ; NF-kappa B ; Receptors, Steroid ; Rifampin ; RNA, Messenger ; Toll-Like Receptor 2 ; Toll-Like Receptors ; Transcription Factors ; Tumor Necrosis Factor-alpha

The variance of tandem repeats in the rpoT gene of Mycobacterium leprae was recently demonstrated. The objects of this study was to examine the proportion and distributions of the genotypes of M. leprae in Korea and to compared it with genotypes of M. leprae form foreign leprosy patients using difference of the tandem repeats. Among 101 cases, 72 isolated from Korea and 4 cases from Japan (except Okinawa) demonstrated four copies of the 6 bp tandem repeats in the rpoT gene, and three copies were found in isolates from two korean, 2 cases of Okinawa in Japan, and those from Southeast Asian countries, Peru and Paraguay. These results reveal the genetic diversity of M. leprae and the related genotype-specific distribution in the world. In this study, a more detailed explanation can be also possible regarding the transmission route of M. leprae.
Asian Continental Ancestry Group ; Genetic Variation ; Genotype ; Humans ; Japan ; Korea ; Leprosy* ; Mycobacterium leprae ; Paraguay ; Peru ; Tandem Repeat Sequences

Receptor-interacting serine/threonine kinase 2(RIPK2) is an adaptor molecule involved in the signal pathway of TLRs. However, there is no report on association between RIPK2 expression and infectious disease including mycobacterial disease in which TLRs play main role on interaction of infection. We evaluated relationship between Mycobacterium leprae and RIPK 2 by real-time RT-PCR. This study revealed that RIPK2 expression was down-regulated in the footpads and skin but was up-regulated in the liver, lymph node, and spleen of Mycobacterium leprae-infected nu/nu mice compared with those of non-infected nu/nu mice. It was observed that the IL-12p40, IFN-gamma, and IL-18 involved in the susceptibility of Mycobacterium leprae were down-regulated in the skin and footpad but up-regulated in the liver. These results suggest that regulation of RIPK2 expression is tissue-specific and is associated with M. leprae infection.
Animals ; Communicable Diseases ; Interleukin-12 ; Interleukin-12 Subunit p40 ; Interleukin-18 ; Liver ; Lymph Nodes ; Mice ; Mycobacterium leprae* ; Mycobacterium* ; Phosphotransferases ; Signal Transduction ; Skin ; Spleen

The emergence of multiple drug resistant Mycobacterium leprae has emphasized the need for early decision of effective antileprosy drug in the treatment for leprosy patients. Mutations in the genes associated with multiple drug resistance in Mycobacterium leprae isolates from 17 South Korean patients, who were already confirmed to have mutations in folP1 gene, were investigated using a PCR - single strand conformation polymorphism (SSCP) - DNA sequencing assay. Two strains, which has double mutations, were found in the two unrelated patients : one missense mutation in folP1 (Arg 55 for Pro) and in rpoB (Gly 522 for Ser), and in folP1 (Ala 53 for Thr) and in gyrB (Asn 426 for Asp), respectively. The patients were treated with the long monotheraphy of dapsone or with the inappropriate regimen of antileprosy drugs. These results emphasize the importance of multi-drug theraphy in order to prevent mult-idrug resistance and assist in the choice of the appropriate regimens for treating leprosy.
Dapsone ; Drug Resistance, Multiple* ; Humans ; Korea* ; Leprosy ; Mutation, Missense ; Mycobacterium leprae* ; Mycobacterium* ; Polymerase Chain Reaction ; Sequence Analysis, DNA