Leprosy has turned out to be a minor health problem in Korea due to implementation of multidrug therapy, intensive case detection and mobile works for the villages for last 20 years. Even we have 20 new cases a year and national registry of 18,000, elimination of leprosy in Korea will require more decades in comparison with Japan, which seems to be an advanced country in leprosy work but still has new cases not more than 10 a year. As genome of M. leprae has unravelled to public in 2001, molecular biologic and genetic research work in leprosy area will progress rapidly near future. Range of leprosy research depends on the state of personal and grant resources in the nation. As Korea has only limited scientist, clinicians and financial support for research work to solve problems in leprosy. To maintain research capabilities and man powers in leprosy, it is reasonable to adjust our research works for priorities of the problems in leprosy work in Korea. Diagnosis, follow up and detection of drug resistance in new cases using molecular epidemiologic and genetic tools are one of high priorities in Korea. Management of neuritis and prevention of deformities on eyes, hands and foot of post-period of multidrug therapy appear to be an important area to improve the quality of life of the treated patients. Collaboration with researchers in tuberculosis, adoption of methods from them can expand research capacity and keep leprosy research alive in Korea.
Congenital Abnormalities ; Cooperative Behavior ; Diagnosis ; Drug Resistance ; Financial Support ; Financing, Organized ; Foot ; Genetic Research ; Genome ; Hand ; Humans ; Japan ; Korea ; Leprosy* ; Neuritis ; Quality of Life ; Tuberculosis

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.

There are several methods for diagnosis of leprosy, including AFB stain, the measurement of PGL-1 (phenolic glycolipid - 1) antigen titer, and DNA-PCR. In this study, we have used the DNA-PCR amplifying the RLEP repetitive sequence. Our result showed that the RLEP primer offered the more sensitive detection and identification of M. leprae DNA in clinical specimens, compared with the other primer, for example, 18-kDa antigen gene. To screen the resistant M. leprae strain of MDT (Multi-Drug Therapy), we have used the TD (Touch-Down) PCR. We arranged and amplified sequences of the genes, folP, rpoB, gyr, 23S rRNA, in M. leprae involved in MDT-resistance, and could obtain the PCR product each gene, simultaneously. This method, based on annealing temperature, was useful to the detection for diagnosis and the screen of MDT-resistant strain of M. leprae, rapidly. Thus, we suggest that the RLEP primer and TD-PCR method are effective in assessing the diagnosis of leprosy and the identification of drug-resistant M. leprae.
Diagnosis* ; DNA ; Leprosy* ; Polymerase Chain Reaction* ; Repetitive Sequences, Nucleic Acid

To prepare the postelimination phase of Hansen's disease in Korea, it is mandatory to review antileprosy strategies that we have pursued in the past, present and future in medical aspects of the plans. The status of Hansen's disease in Korea has reached beyond the elimination period defined as less than one case per 10000 population. The successful control of Hansen's disease up to postelimination stage totally due to the careful support from governmental level, endless efforts of medical staffs who have been engaging in leprosy works, and cooperations of patients. We can suppose that eradication of Hansen's disease will become a true dream within next 25-50 years. With one hundred percent coverage of MDT(multidrug therapy), gradual decrease of new cases and effective health care systems, no re-emergence of Hansen's disease as seen in 1960's and 1970's is conclusive. However we are in the period of elimination of the disease, new cases will continue to occur in small numbers not more than twenty. Special strategies will have to be developed for postelimination phase in Korea. The strategies for Hansen's disease surveillance system need to be different from the past Hansen's disease control system. It should contain regional core groups which includes surgical and medical rehabilitation experts, and a few research group and one referral center. The budget for the groups will come from contraction between government and scientists in medical schools, and NGOs. For national and regional plan of COT(completion of the treatment), it could be more reasonable to separate MB(multibacillary)cases into two groups depend on their possible reactions and relapse after cessation of MDT. First group contains those patients with high BI(bacterial index) more than 4+ need MDT for 24 months. The second group means those patients with low BI less than 4+ need for 12 months MDT as seen in recommendation of WHO short term regimen. In case of PB(paucibacillary) there is few report of relapse following 6 month MDT. In the past period implementation of MDT was so imperative that the other important things for patients cares like prevention of deformities and rehabilitation surgery are neglected and many of them lost golden opportunities to correct deformities in the field. When it is possible to find changes of nerve functions within 12 months, corresponding deformities could be preventable. The mission of mobile team in the past is focused on detection of new cases, but time changes to find no new cases with mobile works. The mobile teams from KLCA(Korean Leprosy Control Association) and NGOs should reshape their aims for care of foot ulcer and prevention of neurological deformities. Outpatient clinics for Hansen's disease will be integrated gradually to horizontal medical care system as like university affiliated hospitals which was done in Japan during from 1973 to 1983. It will give the patients more better quality of medical service. Though the elimination of leprosy does not mean elimination of leprosy research work, there happened brain drain from leprosy to tuberculosis or other research areas. There has been a sympathetic agreement to get gradual decline for support for leprosy research. This will hamper the development of new technologies which are needed for leprosy elimination and beyond. The priorities for research in leprosy have changed as a result of the success of the MDT. Possible recommended leprosy research priorities in Korea should include development of methods to improve the early detection of reactions and nerve damage, development of more effective methods of treatment for reactions and nerve damage, development of more effective and efficient prevention of disability(POD), development of more effective self-care and footwear for patients with impairment and other research works in leprosy.
Ambulatory Care Facilities ; Brain ; Budgets ; Congenital Abnormalities ; Delivery of Health Care ; Foot Ulcer ; Humans ; Japan ; Korea* ; Leprosy* ; Medical Staff ; Missions and Missionaries ; Recurrence ; Referral and Consultation ; Rehabilitation ; Schools, Medical ; Self Care ; Tuberculosis

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

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 method of cell lysate preparation of M. leprae is an important technique in the study of leprosy. This report describes the optimization of method for cell lysate preparation of M. leprae obtained from infected nude mouse. After M. leprae isolated from nude mouse foot-pad was disrupted by sonication, it was centrifuged and then whole lysate was prepared. With this method it was possible to isolate 0.3 mg whole cell lysate using 20 mg of M. leprae. By SDS-PAGE and Coomassie blue staining, the number of protein in M. leprae is less than that of other bacteria, for example, E. coli and M. smegmatis. It is likely that this is due to the small genome size. This work will contribute to the analysis of new protein antigen of M. leprae and the basic study for the development of vaccine in leprosy.
Animals ; Bacteria ; Electrophoresis, Polyacrylamide Gel ; Genome Size ; Leprosy ; Mice ; Mice, Nude* ; Sonication

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

Recently, many reports suggest that the activation of Toll-like receptor 2 (TLR2) by microbial lipoproteins may initiate innate defense mechanism against infectious pathogens. Especially, TLR2 is critical in the immune response to mycobacterial infections and the mutations in the TLR2 have been shown to confer the susceptibility to severe infection with mycobacteria. A previous study reported that there is a mutation of TLR2 (TLR2-R677W) in lepromatous leprosy. In this study, thus, we performed the functional study on TLR2 by measurement of IL-12 production in serum and monocytes from leprosy patients with TLR2 mutation (R677W) to verify the relation between TLR2 and the susceptibility to leprosy. Tuberculoid leprosy patients showed higher serum levels of IL-12p70 compared with those of lepromatous leprosy. In contrast with the lepromatous leprosy patient with TLR2 mutation, especially, the group with wild-type TLR2 showed 2-fold increase levels of IL-12p70. Functional studies demonstrated that monocytes from patient with the TLR2 mutation, in comparison to the wild-type TLR2, is significantly less responsive to Mycobacterium leprae lysate. Our results reveal that TLR2 has a important role in the IL-12 production from monocytes and the susceptibility of lepromatous leprosy.
Humans ; Interleukin-12* ; Leprosy* ; Leprosy, Lepromatous ; Leprosy, Tuberculoid ; Lipoproteins ; Monocytes ; Mycobacterium leprae ; Toll-Like Receptor 2