Search

Background: East Java has become one of the provinces that have higher prevalence of leprosy, especially in the coastal region. Environment has also influenced for leprosy transmission and early detection could reduce the incidence rate of new leprosy cases. Epidemiological studies of leprosy in children can give an illustration of the important aspects of the environment. Presence of Mycobacterium leprae (M. leprae) DNA in nasal swabs and seropositivity level among them can describe M. leprae exposure in that area. Objective: Analyzing PCR from nasal swab and seropositivity level among elementary school children between northern coast and southern coast of East Java province. Methods: Five hundred and thirty children in Pacitan and Lamongan were involved. Both areas are representation of northern and southern coastal region in East Java Province. After clinical examination, nasal swab and blood samples were obtained. ELISA test was performed to measure the titer of IgM anti Phenolic Glicolipid-1 (PGL-1) antibody then continued by PCR to detect M. leprae DNA. Results: From 301 students in Pacitan, 25 students (8.3%) are sero-positives and 9 students (2.9%) are PCR positives. from 229 students in Lamongan, 110 (48.3%) students are sero-positives and 49 students (21.4%) are PCR positives. Both are analyzed by Chi-Square, and from the PCR and ELISA, it concluded that there are statistically significant differences between the two regions. Conclusion: From study above shows that in the northern coast of East Java, incidence of subclinical leprosy is still high, it means that in this area still has a high risk of new cases of leprosy in the future and early detection tools need to performed as a preventative measure.

Leprosy remains a public health problem in Indonesia. Diagnostic tools have been developed in order to aid early diagnosis and prompt treatment. Phenolic glycolipid (PGL)-1 has been considered as a good candidate for leprosy diagnosis but has been found to have several limitations. More recently, the conjugation between natural disaccharide octyl (NDO) and leprosy IDRI diagnostic (LID)-1, known as NDO-LID, shows great promise because of its high specificity and sensitivity and its ability to detect leprosy before any clinical signs are present. The test incorporates the detection of IgM antibodies towards NDO and IgG antibodies towards LID-1. This study aimed to show the profile of IgM, IgG, and IgAMG antibody titers against NDO-LID to further discover its diagnostic potential. Sera from eight new leprosy patients from Surabaya, Indonesia were evaluated using ELISA detecting levels of IgG, IgM and IgAMG antibodies against NDO-LID antigen. Skin slit biopsy was also taken for smear and histopathology test. This study shows that the titer levels IgAMG anti NDO-LID were consistent with the results from smear and were consistently higher compared to IgM or IgG titer alone. IgAMG might have the potential to improve the sensitivity of NDO-LID serologic tests but further investigation is needed.

Multiple Locus Variable Number of Tandem Repeat (VNTR) analysis has been proposed as a means of genotyping for tracking leprosy transmission due to tandem repeats’ potential as genetic markers to differentiate M. leprae strains. However, characteristics of polymorphism can vary depending on the population. This study aimed to compare the copy number of repeats in four genetic markers: TTC, AC8a, AC9 and 6-7 in leprosy patients from Surabaya and Bandung. Twenty three patients from Dr. Soetomo General Hospital and 21 from Hasan Sadikin Hospital were recruited. Multiple locus VNTR analysis was applied using total DNA extracts from Slit Skin Smear (SSS). From Surabaya, 7 samples showed the same copy number of four genetic markers (TTC=15; AC8a=10; AC9=10 and 6-7=6) and 2 showed another (TTC=16; AC8a=10; AC9=11 and 6-7=6); as for samples from Bandung, 2 showed the same copy number (TTC=15; AC8a=8; AC9=10 and 6-7=8) and 2 showed another (TTC=16; AC8a=10; AC9=11 and 6-7=6). The multiple locus VNTR analysis showed two identical M. leprae VNTR profiles from Bandung and Surabaya which supports the use of VNTR loci for transmission studies.

Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. The Leprosy IDRI Diagnostic (LID)-1 antigen has demonstrated potential to improve the diagnostic capacity of local health centers and aid the development of strategies for the eventual control and elimination of leprosy from endemic areas. The diagnostic capacity of LID-1 has not yet, however, been studied in Indonesia. Objective: To determine the proportion of Indonesian leprosy patients that have circulating antibodies against LID-1. Sera from thirtyfive leprosy patients from Surabaya, Indonesia were evaluated using an Enzyme Linked Immunosorbent Assay (ELISA) detecting IgG antibodies against the LID-1 antigen. Anti-LID-1 antibody levels correlated with both the clinical form of leprosy and the bacterial index (BI). LID-1-specific IgG responses were higher in multibacillary (MB) than in paucibacillary (PB) leprosy patients. Our data indicate that the detection and measurement of serum IgG against LID-1 could be an effective tool for use in control programs in various states and municipalities in Indonesia.

The high prevalence among children shows continued transmission from adult and lack of disease control by the health system. Detection of anti-NDO-LID-1 has been known to be more effective to predict the development of leprosy in household contacts than just detecting PGL-1 or LID- 1 alone. However, serodiagnosis is not available in poorer-settings area and the procedure (venepuncture) is still inconvenient to some people. These problems can be solved by using finger-prick blood sample on filter paper. This study aims to prove the effectiveness of using capillary blood samples on filter paper to detect the positivity of Ig G antibody against NDO-LID-1 antigen in asymptomatic household contacts. Seventeen samples of capillary blood on filter paper and sera were tested for IgG anti-NDO-LID-1 using ELISA. There was no significant difference between IgG level from filter paper and serum (p=0.754) and there was also a strong positive correlation (R=0.906) between the two procedures. These findings show that the use of filter paper and NDO-LID-1 is worthy of further investigations, especially for those with lower bacillary load or contacts of leprosy patients.

Delays of leprosy detection and treatment can lead to disability and potential transmission. Serologic examination has the advantage in detecting Subclinical Leprosy. The procedure of serologic test, which is one of its main limitation, could be simplified by the use filter paper. This study aims to assess the effectiveness of the use of capillary blood dropped on filter paper as a substitute for venous blood in household contact of leprosy patients. Seventeen samples of capillary blood dried on filter paper and venous blood samples from the same individual were examined by ELISA method to determine the levels of IgM anti-Phenolic glycolipid-1 (PGL-1). The mean of anti- PGL-1 IgM levels of filter paper samples 163.31±126.16; whereas the mean of levels from venous samples was 473.16±411.26. There was significant difference and correlation between these two groups. Samples on filter paper in household contact can be used to determine the level of anti-PGL-1 IgM in serum by converting on the regression basis. Further study is required to evaluate the potency of filter paper methods to conduct large-scale serological screening.

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries. The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly. The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists. The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80–90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance. The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

Objective/Background: Phagolysosome process in macrophage of leprosy patients' is important in the early phase of eliminating Mycobacterium leprae invasion. This study was to clarify the involvement of Rab5, Rab7, and trytophan aspartate-containing coat protein (TACO) from host macrophage and leprae lipoarabinomannan (Lep-LAM) and phenolic glycolipid-1 (PGL-1) from M. leprae cell wall as the reflection of phagolysosome process in relation to 16 subunit ribosomal RNA (16S rRNA) M. leprae as a marker of viability of M. leprae. Methods: Using a cross sectional design study, skin biopsies were obtained from 47 newly diagnosed, untreated leprosy at Dr Soetomo Hospital, Surabaya, Indonesia. RNA isolation and complementary DNA synthesis were performed. Samples were divided into two groups: 16S rRNA M. leprae-positive and 16S rRNA M. leprae-negative. The expressions of Rab5, Rab7, TACO, Lep-LAM, and PGL-1 were assessed with an immunohistochemistry technique. Result: Using Mann–Whitney U analysis, a significant difference in the expression profile of Rab5, Rab7, Lep-LAM, and PGL-1 was found (p < .05), but there was no significant difference of TACO between the two groups (p > .05). Spearman analysis revealed that there was a significant correlation between the score of Rab5, Rab7, Lep-LAM, and PGL-1 and the score of 16S rRNA M. leprae (p < .05). Conclusion: In M. leprae infection, Rab5, Rab7, and Lep-LAM play important roles in the failure of phagolysosome process via a membrane trafficking pathway, while PGL-1 plays a role via blocking lysosomal activities. These inventions might be used for the development of an early diagnostic device in the future.

Multidrug therapy (MDT) regiment has been used for leprosy all over the world for more than 20 years. Drug resistances of Mycobacterium have been reported from many areas. The resistance mostly occurred due to mutation on the gene coding protein targeted by anti-leprosy drugs. Two hundreds and seventy M. leprae isolates from some area in Indonesia were examined for studying the profile of mutation among isolates collected during 2003-2011. Drug resistance determining region of the folP1 gene and the rpoB gene was sequenced. The results showed 5 isolates of M. leprae harboured mutation only in the folP1 gene and another isolate harbored mutation in both the folP1 and rpoB gene. The point mutation in the folP1 gene that was found in 2 isolates occurred in codon 53 (ACC→GCC; Thr→Ala). Double point mutations on codon 53 that was found in two isolates were ACC→AGA (Thr→Arg) and ACC→AGG (Thr→Arg). The point mutation in the folP1 geneoccurred in codon 55 were found in two isolates were CCC→CTC (Pro→Leu) and CCC→CGC (Pro→Arg). Whereas mutation in the rpoB gene in one isolate occurred in codon 410 was GAT→TAT (Asp→Tyr). These mutations that altered the amino acids of the protein revealed that isolates of M. leprae were resistant to drug with variable profiles

The “Iceberg phenomene” has been used to explain this situation which indicate that these new leprosy cases is originated from Subclinical Leprosy. Fifty eight healthy school children who live in Jeneponto Regency, a leprosy endemic area in South Sulawesi were recruited. The first examination was performed in 2007 and sera samples were kept in deep freeze refrigerator. In 2010 these children were re-examined for clinical leprosy and sera were collected again. ELISA study was performed simultaneously to these 58 pairs of sera (2007 & 2010) for measuring the titer of IgM anti PGL-1 antibody (ELISA) and the level 605u/ml was regarded as cut off value. After three years evaluation, none of these children showed any clinical signs of leprosy, but 20 of 22 ( 90.9%) children were remained sero-positive and only 2 (9.1%) became sero-negatives. In other sites, 5 children that previously sero-negatives became sero-positives after 3 years. Eight of 10 (80%) children who showed sero (+) with high titer (>1.000u/ml) in 2007, were also remained in high titer. The mean titer of 2007 was 627.8 u/ml, and after3 years became 723.9 u/ml (p

Finding of Mycobacterium leprae from water of leprosy endemic areas were reported. East Java Province is ranked number eight as the endemic area of leprosy in Indonesia and Lamongan district is the local area with the highest new cases reported. To study the transmission of Mycobacterium leprae infection in endemic areas, it is important to detect the distribution of Mycobacterium leprae in the environment and population, also to analyze the genetic variation pattern. Keywords: endemic; environment; genotyping; leprosy; Mycobacterium leprae.

Recent discovery of genetic diversity of Mycobacterium leprae such as variable number of tandem repeats opened a new era in molecular epidemiology of leprosy infection. It was revealed that the leprosy bacillus in residential environment of endemic villages is an important source of infection. The global elimination strategy will be revised taking new molecular epidemiological knowledge into account. Responsibility of leprosy specialist is to propose feasible control program to local administration based on the epidemiological analysis on transmission of the disease.

Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (TH2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a TH2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and TH2 commitment are poorly understood. IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells-, IL-4- and STAT6-dependent fashion. IL-18 and T cell receptor-mediated stimulation could induce naïve CD4+ T cells to develop into IL-4-producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.

One of the most important unsolved problems in epidemiology of leprosy is the heterogeneous geographic distribution of the disease. There are highly endemic area called "Pocket" in the endemic countries. Little is known why leprosy is so endemic in the area. We conducted, therefore, an epidemiological study on M. leprae infection and distribution of leprosy bacilli in the environment by using serological and molecular biological techniques. It was found that considerable number of general inhabitants in the pocket are infected with leprosy bacilli and more than 20% of the villagers are carrying M. leprae on the surface of the nasal cavity; suggesting that leprosy bacilli in the residential environment play an important role in high prevalence of leprosy in the endemic area. New preventive measures such as chemoprophylaxis, in addition to MDT, will be needed for global elimination of the disease.

長期治療にもかかわらず活動的ならい腫型らいの病像を呈した症例を報告する。患者は初回再発の後に光田反応が陰転, その後2回目の再発を来した。初診時の生検で未治療のらい腫らいに特徴的な桿状の菌を多数認め, それまで使用されていたDDSとrifampicinの効果に疑問が持たれた。Ofloxacine(OFLX)とclindamycine, 後にOFLXとminocyclineの併用に変更した。約1年半後に臨床症状, 菌形態指数の著明な改善がみられた。その時消退傾向にあるらい腫を生検し, 顆粒状に破壊された菌を認めた。治療経過中, 重度のらい反応はみられず, 主としてthalidomideの間欠的な投与のみにて対応できた。また経過を追って, らい菌特異的なphenolic glycolipid-I(PGL)と, 抗酸菌特異的なlipoarabinomannan-B(LAM)に対するIgG, IgM抗体をELISA法にて測定した。これらは臨床症状の改善とともにいずれも低下したが, とりわけPGL-IgMの低下が著明であった。これら抗体価の測定は, とくにらい腫型らいにおいては菌指数, 菌形態指数とともに有力な治療の指針となりうると考えられた。

We examined 24 dermatologically cured leprosy patients with ongoing uveitis (UV+) and 22 age and type matched controls (UV-) to study the late phase leprous UV. All patients have been skin smear negative for more than 10 years. The history of chemotherapy, 5 years before and after a accomplishing bacterial negativity, was evaluated and represented by "SCORE". It was found that anti-PGL-I and anti-LAM-B antibodies were significantly higher in UV+ group compared to the controls. The mean SCORE of chemotherapy in UV+ group was significantly lower than in the controls. Iris pearls were seen in 10 cases or 42% out of 24 UV+ patients. No iris pearls were seen in control group. These results suggest that insufficient chemotherapy and consequent incomplete elimination of bacilli are the risk factors for leprous UV in the quiescent stage of the disease.

Serological exarnination of leprosy in endemic areas of cutaneous leishmaniasis were carried out using the sera collected during a survey for cutaneous leishmaniasis and several parasitic diseases in Ecuador. There was no correlation between prevalence rates for leprosy and seropositive rates of the antibodies (anti-PGL-1 and LAM-B antibodies) in the subjects living in several provinces in Ecuador. Seropositive rates of anti-PGL-1 antibodies of the leprosy patients and their families in Los Ranchos, Department of Manabi, were relatively high (84.6%, 11/13) in comparison with the average seropositive rates (42.4%, 154/365) of the subjects from other areas of Ecuador. It was suggested that serological survey of families of leprosy patients might be useful for screening of household contacts in a low endemic areas

We developed an immunopathological staining of LAM-B antigen in formalin-fixed paraffin-embedded tissues, and compared it with, PGL-I immunostaining, Fite Faraco's stain and periodic acid carbol pararosaniline (PACPR) stain. Out of the total 28 leprosy cases, 27 were positive to LAM-B immunostaining while 23 were positive to PGL-I stain. Fite's stain was positive in 21 cases while PACPR stain was positive in 24 cases. In scrofuloderma, LAM-B antigen was observed only in the granuloma while no other positive findings were noted with other stains. Normal skin did not give any positive findings with any of the stains. Other dermatoses showed no positive findings to any of the stains tested. LAM-B staining was observed in the nerve even in the absence of bacilli in leprosy tissues. Presence of LAM-B in the cutaneous nerves is helpful in discriminating leprosy from other mycobacterioses. Considering the high sensitivity of LAM-B and the predilection of M. leprae for the nerves, we concluded that LAM-B staining can be a useful new tool in the prompt diagnosis of leprosy, especially in suspected or early cases.

East Java province still has some pocket of leprosy endemic areas. In order to solve the problem, molecular typing will make it feasible to study the transmission pattern of Mycobacterium leprae in leprosy endemic area. The present study is to analyze the presence of M.leprae DNA in the environment and to study variation number of TTC repeats and their distribution. Poteran Island is located in Madura, East Java and was chosen because this island has a high prevalence of leprosy and remains stable for the last five years. All samples were analyzed by PCR and the numbers of TTC repeats were confirmed by direct sequencing. Of all collected samples, 26.4% isolates of water resources (24); 61.9% nasal swabs (26); and 35.3% skin tissues (24) are positives. No statistically difference in the pattern distribution of TTC repeats between skin tissues of patients and nasal swab of households contact (p=0.594); also distribution of TTC repeats between skin tissues of leprosy patients and those of water resources (p=0.441); and distribution of TTC repeats between nasal swab of households contact with water resources (p=0.906). It means that the transmission of M.leprae in leprosy endemic area has closely related in 3 aspects: agent, host & environment.

The drug resistant problem of Mycobacterium leprae has been developing since the last decade and this has become a leprosy elimination problem in several countries, including Indonesia. Using biological on molecular methods, it is now possible to test for drug resistant cases in relatively simple and less time consuming ways. The purpose of the study is to analyze the prevalence of drug resistance M. leprae to dapsone and rifampicin in East Java based on the etection of mutations in the folP and rpoB genes. All samples were obtained from multibacillary leprosy patients in East Java, who have admitted to the Dr Sutomo Hospital Surabaya in 2003-2005. Isolates were analyzed by PCR, and the presence of nucleotide sequence of the folP and rpoB genes from M. leprae were confirmed by direct sequencing. Of 94 specimens which were collected, all were analyzed for their folP and rpoB genome. From 94 isolates, 70 showed a positive result by the folP1-folPR test and 77 out of 94 isolates showed positive by the rpoBF-rpoBR test. From 70 isolates for folP gene examination, there were 3 isolates which had mutation in the amino acid at codon 53; 2 cases Threonin (ACC) became Alanin (GCC) and 1 case Threonin (ACC) became Arginin (AGA). These mutations are responsible to dapsone resistance. For the rpoB gene, no mutation was found. The result suggested that 3 isolates (4.3%), 1 from a new case and 2 from relapse cases in this experiment, were resistant to dapsone and all isolates (100%) were susceptible to rifampicin.

An improved protocol for PCR analysis of Mycobacterium leprae-infected tissues, based on enzymatic lysis, has been developed and used to demonstrate the feasibility of using PCR for detecting M. leprae in routine skin biopsies taken from leprosy patients throughout the clinical spectrum. Of 92 multibacillary patients tested, 99% were PCR-positive using gel electrophoresis or DNA hybridization to detect the amplified product. Similar analysis of paucibacillary patients, in which only one of 27 biopsies had demonstrable AFB microscopically, gave a positivity rate of 74%. No PCR signals were demonstrated from skin biopsies from seven patients with non-leprosy dermatoses and one AIDS patient with a disseminated atypical mycobacteriosis. Evaluation of leprosy patients with antileprosy drug therapy prior to biopsy demonstrated that PCR signals were either greatly diminished or absent after 2 months of continuous antibiotic therapy. PCR was also able to detect the presence of M. leprae in tissues of patients receiving antibacterial therapy when patients were suspected of harbouring drug-resistant M. leprae.

Harada employed periodic acid-carbol pararosaniline and periodic acid-methenamine silver stain for demonstrating chromophobic bacilli which do not get stained with conventional carbol fuchsin or counter stain. This staining method takes considerable time for complete oxidation with periodic acid. We have succeeded in reducing the oxidation time by using hydrogen peroxide treatment prior to periodic acid and with the use of acidified sodium hydrogen sulfite treatment before carbol pararosaniline stain. We also found that in methenamine silver stain, combined use of semicarbazide and microwave treatment can shorten the whole staining time up to four hours without losing ito sensitivity.

The multi-sections, which were stained by Fite method, of skin biopsies taken from twelve active BT cases were examined under the guidance of special stains for demonstration of nerve components. All cases were AFB positive. Bacilli were found in infiltrated nerves in 11 cases, of which, in 7 cases, bacilli were detected in nerve fragments within epithelioid cell granuloma. And bacilli were seen in arrector pili muscles in 2 cases. No bacilli were detected in other sites. Since the survival of M. leprae in nerves is one of the reasons causing relapse, this paper suggests that it would be better to treat active BT cases with multibacillary regimen recommended by WHO even though smear-negative.

A comparative study on the usefulness of Kawatsu's silver impregnating staining method compared with S-100 protein ABC technique for the differential diagnosis of tuberculoid leprosy was carried out. The results of neurohistological examination obtained from both methods were almost the same. It can be said that Kawatsu's method is useful and cost-effective, and thus suitable for practical use in developing countries.

Glycolipids of Mycobacterium leprae obtained from armadillo tissue nodules infected with the bacteria were analyzed. Mass spectrometric analysis of the glycolipids indicated the presence of trehalose 6,6′-dimycolate (TDM) together with trehalose 6-monomycolate (TMM) and phenolic glycolipid-I (PGL-I). The analysis showed that M. leprae-derived TDM and TMM possessed both α- and keto-mycolates centering at C78 in the former and at C81 or 83 in the latter subclasses, respectively. For the first time, MALDI-TOF mass analyses showed the presence of TDM in M. leprae.

In our previous study, elderly leprosy patients showed a low prevalence of senile dementia of the Alzheimer type, but the frequency of apolipoprotein E (APO-E) epsilon 4 was elevated in non-demented elderly leprosy patients. Recent study has shown that Alzheimer's disease risk associated with APO-E epsilon 4 is significantly increased by the alpha 1-antichymotrypsin (ACT) genotype AA. Therefore we examined an association between ACT polymorphism and the APO-E epsilon 4 allele in 350 leprosy patients. None of our data showed an association of ACT genotype and APO-E epsilon 4 allele in leprosy patients. The allelic frequencies of the ACT gene did not differ even between demented patients with leprosy and age-matched controls. Our present data suggest that ACT polymorphism is not associated with the increased frequency of APO-E epsilon 4 in leprosy patients.

Apolipoprotein E (apo E) genotypes in 350 leprosy patients were examined and compared with those of 870 age-matched controls. The allelic frequencies of the apo E gene did not differ between demented patients with leprosy and controls. However, the frequency of apo E epsilon 4 allele was significantly higher in non-demented leprosy patients than in controls (P0.001). Of special interest is that the prevalence of E3/4 genotype in non-demented leprosy patients increased significantly with age, being 14.1%, 24.4%, and 28.3% in the 60s, 70s, and 80s, respectively (P0.05). These data suggest that apo E epsilon 4 is not a risk factor for senile dementia in elderly leprosy patients, and there exist factors to overcome the risk of apo E4 in leprosy patients.

The polymorphism of TTC repeats in Mycobacterium leprae was examined using the bacilli obtained from residents in villages at North Maluku where M. leprae infections are highly endemic (as well as from patients at North Sulawesi of Indonesia) to elucidate the possible mode of leprosy transmission. TTC genotypes are stable for several generations of passages in nude mice footpads and, hence, are feasible for the genotyping of isolates and epidemiological analysis of leprosy transmission. It was found that bacilli with different TTC genotypes were distributed among residents at the same dwelling in villages in which leprosy is endemic and that some household contacts harbored bacilli with a different genotype from that harbored by the patient. Investigations of a father-and-son pair of patients indicated that infections of bacilli with 10 and 18 copies, respectively, had occurred. Genotypes of TTC repeats were found to differ between a son under treatment and two brothers. These results reveal the possibility that in addition to exposure via the presence of a leprosy patient with a multibacillary infection who was living with family members, there might have been some infectious sources to which the residents had been commonly exposed outside the dwellings. A limited discriminative capacity of the TTC polymorphism in the epidemiological analysis implies the need of searching other useful polymorphic loci for detailed subdivision of clinical isolates.

PURPOSE: To report a patient with multiple sclerosis and associated with granulomatous uveitis, and how anti-lipoarabinomannan (LAM)-B antibody can play a key role in differential diagnosis. METHODS: Case report. RESULTS: A 35-year-old Japanese woman with multiple sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye. Ophthalmological examinations revealed granulomatous iridocyclitis in her left eye and retinal periphlebitis in both eyes. The diagnosis of tuberculosis was suspected because of a positive tuberculin skin test. However, a further examination by an anti-LAM-B antibody test excluded active tuberculosis. Her clinical findings were thought most likely to be caused by multiple sclerosis and treated with corticosteroids. CONCLUSION: We should consider the possibility of multiple sclerosis as the underlying origin in patients with granulomatous uveitis. A measurement of anti-LAM-B antibody titer may be useful in the differential diagnosis of granulomatous uveitis.

IgG and/or IgM antibodies against mycobacterial cord factor (trehalose 6,6'-dimycolate, TDM) in sera of 65 patients of Hansen's disease (21 cases with smear-positive and 44 cases with smear-negative) and 60 healthy individuals were tested by enzyme-linked immunosorbent assay (ELISA) with TDM purified from Mycobacterium tuberculosis H37Rv as an antigen. Of 65 patients with Hansen's disease, 58 cases (89.2%) had positive results (21 samples from 21 patients, 100% with acid-fast bacilli positive in the lesion, and 37 samples from 44 patients, 84.0% with acid-fast bacilli negative Hansen's disease diagnosed clinically). The sensitivity and specificity of anti-cord factor ELISA were higher than those of anti-phenolic glycolipid-I (PGL-I) agglutination test. Among the total, 34 patients were classified clinically into three types of the disease, lepromatous leprosy (LL), borderline lepromatous (BL) and borderline tuberculoid (BT). The antibody titer showed LL > BL > BT, indicating that the elevation of anti-cord factor antibody titers appeared to be parallel with the degree of humoral immune response against M. leprae. By using semisynthetic cord factor consisting of a single subclass of mycolic acid from M. tuberculosis, it was revealed that sera from patients with Hansen's disease were highly reactive against alpha-mycoloyl cord factor (alpha-TDM) and less reactive against methoxy mycoloyl TDM (methoxy TDM), differed from sera of tuberculosis patients, which were highly reactive against both methoxy and alpha-mycoloyl cord factor (alpha-TDM). Most of sera from patients with Hansen's disease were more reactive against TMM than TDM, differed from sera of tuberculosis patients which were highly reactive against TDM. ELISA using TDM as an antigen is simple, reproducible and useful for the rapid serodiagnosis of Hansen's disease, especially for smear-negative cases.