Winahju, W. S.; Mukarromah, A.; Putri, S.
Leprosy is a chronic infectious disease caused by bacteria of leprosy (Mycobacterium leprae). Leprosy has become an important thing in Indonesia because its morbidity is quite high. Based on WHO data in 2014, in 2012 Indonesia has the highest number of new leprosy patients after India and Brazil with a contribution of 18.994 people (8.7% of the world). This number makes Indonesia automatically placed as the country with the highest number of leprosy morbidity of ASEAN countries. The province that most contributes to the number of leprosy patients in Indonesia is East Java. There are two kind of leprosy. They consist of pausibacillary and multibacillary. The morbidity of multibacillary leprosy is higher than pausibacillary leprosy. This paper will discuss modeling both of the number of multibacillary and pausibacillary leprosy patients as responses variables. These responses are count variables, so modeling will be conducted by using bivariate poisson regression method. Unit experiment used is in East Java, and predictors involved are: environment, demography, and poverty. The model uses data in 2012, and the result indicates that all predictors influence significantly.
Raut, Shweta; Kanade, Swapna; Nataraj, Gita; Mehta, Preeti
Despite India achieving the goal of elimination of leprosy as a public health problem, leprosy is still being transmitted in India. However, due to decreased clinical suspicion of leprosy and atypical case presentations, such cases may be not be diagnosed. We present a case report of an unusual presentation of multibacillary leprosy which presented as nodular lesions. This case report indicates that atypical presentations of leprosy may be missed out by primary care physicians. PMID:28042219
Morgado de Abreu, M A M; Roselino, A M; Enokihara, M; Nonogaki, S; Prestes-Carneiro, L E; Weckx, L L M; Alchorne, M M A
In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.
Nations, Marilyn K; Lira, Geison Vasconcelos; Catrib, Ana Maria Fontenelle
In response to the call for a new Science of Stigma, this anthropological study investigates the moral experience of patients diagnosed with severe multibacillary leprosy. From 2003 to 2006, fieldwork was conducted in the so-called 'United-States-of-Sobral', in Ceará State, Northeast Brazil. Sobral is highly endemic for leprosy, despite intensified eradication efforts and a 30% increase in primary care coverage since 1999. Of 329 active leprosy cases at two public clinics, 279 multibacillary patients were identified and six information-rich cases selected for in-depth ethnographic analysis, utilizing illness narratives, key-informant interviews, home visits, participant-observation of clinical consultations and semi-structured interviews with physicians. A 'contextualized semantic interpretation' revealed four leprosy metaphors: a repulsive rat's disease, a racist skin rash, a biblical curse and lethal leukemia. Far from value-free pathology, the disease is imbued with moral significance. Patients' multivocalic illness constructions contest physicians' disease discourse. 'Skin Spot Day' discriminates more than educates. Patients' 'non-compliance' with effective multi-drug therapy is due to demoralizing stigma more than a rejection of care. 'Social leprosy' in Northeast Brazil deforms patients' moral reputations and personal dignity.
Gaschignard, Jean; Grant, Audrey Virginia; Thuc, Nguyen Van; Orlova, Marianna; Cobat, Aurélie; Huong, Nguyen Thu; Ba, Nguyen Ngoc; Thai, Vu Hong; Abel, Laurent; Schurr, Erwin; Alcaïs, Alexandre
After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes. Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy. PMID:27219008
Mizoguti, Danielle de Freitas; Hungria, Emerith Mayra; Freitas, Aline Araújo; Oliveira, Regiane Morillas; Cardoso, Ludimila Paula Vaz; Costa, Mauricio Barcelos; Sousa, Ana Lúcia Maroclo; Duthie, Malcolm S; Stefani, Mariane Martins Araújo
Leprosy inflammatory episodes [type 1 (T1R) and type 2 (T2R) reactions] represent the major cause of irreversible nerve damage. Leprosy serology is known to be influenced by the patient's bacterial index (BI) with higher positivity in multibacillary patients (MB) and specific multidrug therapy (MDT) reduces antibody production. This study evaluated by ELISA antibody responses to leprosy Infectious Disease Research Institute diagnostic-1 (LID-1) fusion protein and phenolic glycolipid I (PGL-I) in 100 paired serum samples of 50 MB patients collected in the presence/absence of reactions and in nonreactional patients before/after MDT. Patients who presented T2R had a median BI of 3+, while MB patients with T1R and nonreactional patients had median BI of 2.5+ (p > 0.05). Anti-LID-1 and anti-PGL-I antibodies declined in patients diagnosed during T1R (p < 0.05). Anti-LID-1 levels waned in MB with T2R at diagnosis and nonreactional MB patients (p < 0.05). Higher anti-LID-1 levels were seen in patients with T2R at diagnosis (vs. patients with T1R at diagnosis, p = 0.008; vs. nonreactional patients, p = 0.020) and in patients with T2R during MDT (vs. nonreactional MB, p = 0.020). In MB patients, high and persistent anti-LID-1 antibody levels might be a useful tool for clinicians to predict which patients are more susceptible to develop leprosy T2R. PMID:26560982
Mizoguti, Danielle de Freitas; Hungria, Emerith Mayra; Freitas, Aline Araújo; Oliveira, Regiane Morillas; Cardoso, Ludimila Paula Vaz; Costa, Mauricio Barcelos; Sousa, Ana Lúcia Maroclo; Duthie, Malcolm S; Stefani, Mariane Martins Araújo
Leprosy inflammatory episodes [type 1 (T1R) and type 2 (T2R) reactions] represent the major cause of irreversible nerve damage. Leprosy serology is known to be influenced by the patient's bacterial index (BI) with higher positivity in multibacillary patients (MB) and specific multidrug therapy (MDT) reduces antibody production. This study evaluated by ELISA antibody responses to leprosy Infectious Disease Research Institute diagnostic-1 (LID-1) fusion protein and phenolic glycolipid I (PGL-I) in 100 paired serum samples of 50 MB patients collected in the presence/absence of reactions and in nonreactional patients before/after MDT. Patients who presented T2R had a median BI of 3+, while MB patients with T1R and nonreactional patients had median BI of 2.5+ (p > 0.05). Anti-LID-1 and anti-PGL-I antibodies declined in patients diagnosed during T1R (p < 0.05). Anti-LID-1 levels waned in MB with T2R at diagnosis and nonreactional MB patients (p < 0.05). Higher anti-LID-1 levels were seen in patients with T2R at diagnosis (vs. patients with T1R at diagnosis, p = 0.008; vs. nonreactional patients, p = 0.020) and in patients with T2R during MDT (vs. nonreactional MB, p = 0.020). In MB patients, high and persistent anti-LID-1 antibody levels might be a useful tool for clinicians to predict which patients are more susceptible to develop leprosy T2R.
Introduction Leprosy exhibits a wide spectrum of presentation, varying from the tuberculoid to the lepromatous pole, with immunologically unstable borderline forms in-between, depending upon the immune status of the individual. The clinical system of classification for the purpose of treatment includes the number of skin lesions and nerves involved as the basis for classifying the patients into multibacillary and paucibacillary. Case presentation A 20-year-old man belonging to a moderately endemic leprosy area in the Terai region of Nepal reported a large single, hypopigmented, well defined anaesthetic lesion on his left thigh extending to his knee which had been present for 2 years. There was no other nerve involvement. Clinical diagnosis was tuberculoid leprosy and immunological lateral flow test for anti-Phenolic glycolipid-I antibody was positive. Six months of paucibacillary multidrug treatment was advised immediately. However, the patient was reclassified as multibacillary on the basis of a positive skin smear and appropriate treatment of 24 months multibacillary multidrug regimen was commenced after only 1 week. Slit skin smear examination for Mycobacterium leprae from the lesion revealed a bacterial index of 4+ while it was negative from the routine sites. Histopathological examination from skin biopsy of the lesion further supported the bacterial index of the lesion granuloma which was 2+ and the patient was diagnosed as borderline tuberculoid. Bacteriological, histological, and immunological findings of this patient were borderline tuberculoid leprosy and he should have been treated with multibacillary regimen from the beginning. Five months after commencement of treatment, the patient developed a leprae reaction of Type 1 or reversal reaction with some nerve function impairment and enlargement of the lateral popliteal nerve of the left leg. This reversal reaction was managed by standard oral prednisolone whilst continuing the multibacillary multidrug
Jaiswal, Ashok Kumar; Subbarao, Nagesh Tumkur
Leprosy is one of the causes of gynaecothelia (enlargement of nipples), however little has been published about this common but usually ignored sign. Herein, we report nine male patients with multibacillary leprosy who had gynaecothelia although only two of them had associated gynaecomastia. None of these patients was aware of gynaecothelia until it was detected by the treating doctor during examination. This study is presented to highlight this common but ignored sign, which may occur specifically in multibacillary leprosy.
Horta-Baas, G; Hernández-Cabrera, M F; Barile-Fabris, L A; Romero-Figueroa, M del S; Arenas-Guzmán, R
Leprosy is an infectious chronic disease with a wide range of clinical and serological manifestations. We report a case of a woman presenting with a malar rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear antibodies test and leuko-lymphopenia. Our case illustrates an unusual presentation of leprosy initially diagnosed as systemic lupus erythematosus (SLE). After the confirmation of multibacillary leprosy and multidrug therapy recommended by the World Health Organization, a good clinical response was observed. Recognition of rheumatic manifestations in leprosy is important as they may be confused with SLE. A literature review is presented to encourage clinicians to consider leprosy as a differential diagnosis. Specifically in patients with unusual rheumatic manifestations and persistent skin lesions, and when neurological symptoms are present. Leprosy has not been eradicated, so misdiagnosis can be frequent. It is necessary to increase medical practitioner awareness in order start proper treatment.
Sampoonachot, P; Bundit, C; Kuhacharoen, N; Peerapakorn, S; Kampirapap, K; Poomlek, A; Bampenyu, S; Tiasiri, S; Rungruang, S; Surasondhi, S; Supanwanit, S; Wiriyawipart, S
The results of ofloxacin containing combined drug regimens in the treatment of 60 multibacillary leprosy cases from January 1989 to June 1995 are reported. The objective of the trial is to compare the antileprotic property of ofloxacin and rifampicin in multibacillary leprosy patients and to study the killing rate of M. leprae by ofloxacin and rifampicin before mass treatment can be recommended. The complications and side-effects of ofloxacin and rifampicin were of a mild nature and both drugs were well tolerated. Moderate to marked clinical improvement was noticed in a short period with ofloxacin containing regimens in multibacillary leprosy patients. No persisters were detected in any of the 33 specimens (of mouse footpads) that had been obtained after treatment for 6 months. Ofloxacin if added to the currently used WHO recommended MB-MDT regimen may shorten the duration of treatment. Ofloxacin, therefore, may be considered as a suitable alternative in suspected/proven rifampicin resistant cases and where rifampicin is contraindicated. The results were evaluated on the basis of the clinical conditions, mycobactericidal effectiveness, signs of drug toxicity and side effects.
Illarramendi, Ximena; Dupnik, Kathryn Margaret; Hacker, Mariana de Andrea; Nery, José Augusto da Costa; Jerônimo, Selma Maria Bezerra; Sarno, Euzenir Nunes
Background Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control. Methods A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads. Results A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country. Conclusion Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission. PMID:28192426
Escamilla-Tilch, Mónica; Estrada-García, Iris; Granados, Julio; Arenas-Guzmán, Roberto; Ramos-Payan, Rosalio; Pérez-Suárez, Thalía Gabriela; Salazar, Ma Isabel; Pérez-Lucas, Riky Luis; Estrada-Parra, Sergio; Torres-Carrillo, Nora Magdalena
Background. Leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli Mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. Thus, in this case-control study, we evaluated the possible association between the IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs and susceptibility to leprosy disease in Mexican population. Methods. Seventy-five leprosy patients and sixty-nine control subjects were included. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique. Results. We found nonsignificant differences in genotype and allele frequencies related to IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs in MB as well as subclinical forms of leprosy disease versus healthy individuals. Conclusions. Since the sample size is not large enough, it is difficult to sustain an association of susceptibility to leprosy with genotypes or allele frequencies of IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780), suggesting that IL-17 polymorphisms have no significant role in the genetic susceptibility to development of this disease in the Mexican Mestizo population.
Escamilla-Tilch, Mónica; Estrada-García, Iris; Granados, Julio; Arenas-Guzmán, Roberto; Ramos-Payan, Rosalio; Pérez-Suárez, Thalía Gabriela; Salazar, Ma. Isabel; Pérez-Lucas, Riky Luis; Estrada-Parra, Sergio; Torres-Carrillo, Nora Magdalena
Background. Leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli Mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. Thus, in this case-control study, we evaluated the possible association between the IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs and susceptibility to leprosy disease in Mexican population. Methods. Seventy-five leprosy patients and sixty-nine control subjects were included. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique. Results. We found nonsignificant differences in genotype and allele frequencies related to IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs in MB as well as subclinical forms of leprosy disease versus healthy individuals. Conclusions. Since the sample size is not large enough, it is difficult to sustain an association of susceptibility to leprosy with genotypes or allele frequencies of IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780), suggesting that IL-17 polymorphisms have no significant role in the genetic susceptibility to development of this disease in the Mexican Mestizo population. PMID:25431761
de la Barrera, S; Finiasz, D M; Fink, S; Valdez, R; Bottasso, O; Balina, L M; Sasiain, M C
In the present study we evaluated the contribution of CD4 and CD8 T cells on the antigen-specific cytotoxic activity induced by whole Mycobacterium leprae in leprosy patients and normal controls (N) as well as the modulation of this activity by some cytokines. Peripheral blood mononuclear cells (PBMC) from N or from leprosy patients were stimulated with antigen in the presence or absence of cytokines for 7 days. M. leprae-stimulated PBMC were depleted of CD4 or CD8 antigen-bearing cells and employed as effector cells in a 4-hr [31Cr]-release assay against autologous M. leprae-pulsed macrophages. Our results demonstrate that both CD4 and CD8 T cells contribute to M. leprae-induced cytotoxic activity, with differences observed in paucibacillary (PB) and multibacillary (MB) patients. CD8-mediated cytotoxic activity is higher than that of CD4 cells in PB patients, while in MB patients CD4 cytotoxicity is predominant. Our data also demonstrate that the generation of CD4 and CD8 cytotoxic T lymphocytes (CTL) can be modulated differentially by interleukin-4 (IL-4), IL-6, gamma interferon (IFN-gamma), or IL-2. Although MB patients developed the lowest CTL response, cytokines such as IL-6 plus IL-2 or IFN-gamma were able to generate both CD4 and CD8 cytotoxic T cells from MB patients. In PB patients, IL-6 plus IFN-gamma displayed the highest stimulation on CD8 effector cells. Thus, an important role may be assigned to IL-6, together with IL-2 or IFN-gamma, in the differentiation of M. leprae-specific CTL effector cells.
Thilakavathi, S; Manickam, P; Mehendale, S M
Stigma, isoIation and discrimination are typically associated with diagnosis of leprosy and its disclosure. Health care providers (HCPs) find it challenging to disclose the diagnosis of leprosy to patients and their family members. A qualitative study was done in a rural community near Chennai in Tamil Nadu, from August 2011 to March 2012, covering 155 out of 648 (23.9%) purposively selected leprosy patients from 53 out of 148 panchayats, representing 264 villages in the study area; Out of these 155 patients, 59% were males; 30% were illiterates; 70% were married; 56% were living in nuclear families; half the leprosy patients were either agricultural labourers or skilled workers (50%).Thirty two percent were multibacillary (MB) cases and 68% were pauci bacillary (PB) cases; 77% were old patients and 23% were new patients; 22% had leprosy deformity 12% had disfiguration; 23% had anaesthesia and 3% were with lagophthalmous. Of the 155 patients, 31 (20%) reported that they were not informed about diagnosis of their disease by the concerned HCPs. They were informed to be having a skin disease or a skin patch. Of these 31 patients, 22 (71%) were women; all except one with PB leprosy. Seven patients (23%) had not yet started on treatment 3 patients (10%) were given treatment when they were young and neither, them nor their parents were informed about this disease. Seven (33%) of the married patients who had the disease during their child had or when they were young, were not informed of the diagnosis by the HCPs. Ten respondents (32%) were neither bothered nor concerned about non disclosure of the disease by HCPs. Now, after knowing the diagnosis of the disease 4 females (13%) mentioned that they were having some fear, worry or stigma. As non-disclosure of leprosy by HCPs may adversely affect acceptance and adherence, to treatment by the patients, appropriate communication strategies should be developed and implemented.
Lavania, Mallika; Jadhav, Rupendra S; Chaitanya, Vedithi Sundeep; Turankar, Ravindra; Selvasekhar, Abraham; Das, Loretta; Darlong, Famkima; Hambroom, Ujjwal K; Kumar, Sandip; Sengupta, Utpal
Implementation of multidrug therapy (MDT) in leprosy control programmes has significantly reduced the global prevalence of the disease in the last two decades. After many years of use of MDT, it is expected that drug resistance in Mycobacterium leprae may emerge. This is a major concern, especially during the stage of elimination. In the present study, slit-skin smears were collected from 140 leprosy relapse cases from different Leprosy Mission hospitals across India. DNA extracted from 111 (79%) of these samples was analysed for the genes associated with drug resistance in M. leprae. More than 90% of the patients relapsed as multibacillary (MB) cases. In our study, four (3.6%) of the DNA samples analysed showed mutations associated with rifampicin resistance. We also observed that mutations associated with resistance to dapsone and ofloxacin were observed in 9 (8.1%) of the DNA samples each; two samples had both dapsone and ofloxacin resistance. Further surveillance and appropriate interventions are needed to ensure the continued success of chemotherapy for leprosy.
Moura, Rodrigo Scaliante; Penna, Gerson Oliveira; Cardoso, Ludimila Paula Vaz; de Andrade Pontes, Maria Araci; Cruz, Rossilene; de Sá Gonçalves, Heitor; Fernandes Penna, Maria Lúcia; de Araújo Stefani, Mariane Martins; Bührer-Sékula, Samira
The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was used to describe and report the performance of available tools to classify 830 leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a modified Ridley and Jopling (R&J) classification, considering clinical features, histopathological results of skin biopsies and the slit-skin smear bacterial load results were used as the gold standard method for classification. Anti-phenolic glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial load, and the number of skin lesions were evaluated. Considering the R&J classification system as gold standard, ML Flow tests correctly allocated 70% patients in the PB group and 87% in the MB group. The classification based on counting the number of skin lesions correctly allocated 46% PB patients and 99% MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy patients for treatment purposes is unnecessary because it does not impact clinical and laboratories outcomes. In this context, the identification of new biomarkers to detect patients at a higher risk to develop leprosy reactions or relapse remains an important research challenge.
Manickam, Ponnaiah; Mehendale, Sanjay M.; Nagaraju, Bathyala; Katoch, Kiran; Jamesh, Abdul; Kutaiyan, Ramalingam; Jianping, Shen; Mugudalabetta, Shivakumar; Jadhav, Vitthal; Rajkumar, Prabu; Padma, Jayasree; Kaliaperumal, Kanagasabai; Pannikar, Vijayakumar; Krishnamurthy, Padabettu; Gupte, Mohan D.
Background & objectives: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Methods: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. Results: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. Interpretation & conclusions: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696] PMID:28256460
Qasemi-Barqi, R; Bijani, B; Pahlevan, A A
Multi-drug therapy (MDT) and Leprosy Elimination Campaigns (LEC) are the major strategies for eliminating leprosy. We report the results of a LEC conducted in 2006 in Qazvin. A total of 1987 individuals (1379 household contacts of 319 registered leprosy patients and 608 people from 3 endemic villages with a high prevalence of leprosy) were examined for detection of new cases of leprosy. All new cases were given MDT and were reviewed after a year. There were 256 suspected cases of leprosy, 13 of whom were confirmed as new cases (7 were classified as multibacillary leprosy). None had visible deformity nor was < 20 years old. All patients completed the recommended MDT course. The few cases detected suggest that in low prevalence areas, a long-term approach of integrated leprosy services and disability management may be more appropriate than LEC as a leprosy elimination strategy.
Wang, Hongsheng; Liu, Weijing; Jin, Yali; Yu, Meiwen; Jiang, Haiqin; Tamura, Toshiki; Maeda, Yumi; Makino, Masahiko
Antibodies to phenolic glycolipid (PGL)-I and major membrane protein (MMP)-II were evaluated for serodiagnosis of leprosy in Southwest China, and the role in predicting the occurrence of the disease in household contacts (HHCs) of leprosy was examined. Using PGL-I (natural disaccharide-octyl-bovine serum albumin) antigen-based diagnosis (IgM antibodies), we could detect 94.9% of multibacillary (MB) leprosy and 38.9% paucibacillary (PB) leprosy patients, whereas using MMP-II (IgG antibody), 88.1% of MB and 61.1% of PB patients were positive. By combining the 2 tests and considering either test positive as positive, 100% of MB patients and 72.2% of PB patients were found to test positive. Of the HHCs of leprosy, 28.3% and 30% had positive levels of PGL-I and MMP-II Abs, respectively. Seven out of 21 HHCs, who had high Ab titer to either antigen, developed leprosy during the follow-up period of 3 years. These data suggest that the measurement of both anti-PGL-I as well as anti-MMP-II antibodies could facilitate early detection of leprosy.
Cakiner, T; Yüksel, A; Soydan, M; Saylan, T; Bahçeci, E
Women in Turkey have many social, cultural and economical problems. Women with leprosy have problems in common with other women as well as those related to physical and social consequences of leprosy. There are 2,414 patients with leprosy in Turkey, registered to Istanbul Leprosy Hospital and 829 of them are females. The mean age and duration of disease of our female leprosy patients are high. Most women with leprosy were born in eastern part of Turkey where prevalence of leprosy is higher and most have moved to western regions. The proportion of women who have some kind of social security is very low. Their economic status is also not good and 79% of patients had stigma about their disease. Three fourths of these cases have been hospitalized some time, for different reasons. Most of them (97.2%) have inactive disease at present. Disability degrees of patients are high. Patients with disability degrees over one constitute 54% of total for eyes, 55% for hands and 51% for feet. High percentage of multibacillary form and long duration of disease, delayed diagnosis, insufficient self-care of patients due to low socio-economic and cultural status and failure of health personnel to control patients periodically may be among the reasons for such high ratios of moderate and severe disabilities. In the light of the data obtained in our study, some measures to alleviate the problems of patients resulting from their socio-economic, cultural and social status have been suggested.
Duthie, Malcolm S.; Ireton, Greg C.; Kanaujia, Ganga V.; Goto, Wakako; Liang, Hong; Bhatia, Ajay; Busceti, Jean Marie; Macdonald, Murdo; Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Balagon, Marivic; Esfandiari, Javan; Carter, Darrick; Reed, Steven G.
Leprosy can be a devastating chronic infection that causes nerve function impairment and associated disfigurement. Despite the recent reduction in the number of registered worldwide leprosy cases as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains relatively stable. The diagnosis of leprosy is currently based on the appearance of clinical signs and requires expert clinical, as well as labor-intensive and time-consuming laboratory or histological, evaluation. For the purpose of developing an effective, simple, rapid, and low-cost diagnostic alternative, we have analyzed the serologic antibody response to identify Mycobacterium leprae proteins that are recognized by leprosy patients. More than 100 recombinant antigens were analyzed in a protein array format to select those with discriminatory properties for leprosy diagnosis. As expected, multibacillary leprosy patients recognized more antigens with stronger antibody responses than paucibacillary leprosy patients. Our data indicate, however, that multibacillary patients can be distinguished from paucibacillary patients, and both of these groups can be segregated from endemic control groups. We went on to confirm the diagnostic properties of antigens ML0405 and ML2331 and the LID-1 fusion construct of these two proteins by enzyme-linked immunosorbent assay. We then demonstrated the performance of these antigens in rapid test formats with a goal of developing a point-of-care diagnostic test. A serological diagnostic test capable of identifying and allowing treatment of leprosy could reduce transmission, prevent functional disabilities and stigmatizing deformities, and facilitate leprosy eradication. PMID:18716007
Cakiner, T; Karaçorlu, M A
The objective of this study was to detect ocular lesions of newly diagnosed leprosy cases admitted to Istanbul Leprosy Hospital. The patients were categorized according to sex, age, type of leprosy and duration of the disease. Their eyes were categorized as with or without ocular findings due to leprosy. The total number of patients was 21. The mean age was 22+/-4.6 years, the duration of the disease was 36.3+/-19.6 months. Madarosis was the most common finding in this group. It was found in 15 patients (71.4%, 95% confidence interval (CI) 47.8-88.7%). As a second common finding related to corneal alterations, 13 patients had nerve thickening (61.9%, 95% CI 38.4-81.8%). None of our patients had trichiasis, episcleritis, scleritis, cataract, iris atrophy, iris pearl, abnormal vitreous or retinal findings.
Hogeweg, M; Keunen, J E E
Leprosy control programmes are highly successful. As a result, leprosy control will be more and more integrated into the general health services. The existing vertical, specialized control programmes will be dismantled. Eye complications in leprosy have decreased. This is a result of earlier diagnosis and highly effective multidrug treatment (MDT) of leprosy, combined with timely treatment of secondary nerve damage by steroids. Most ocular morbidity is now found among elderly and disabled leprosy patients who were diagnosed before effective MDT treatment became available. Many of these patients live in leprosy settlements. Age-related cataract has become the leading cause of blindness in leprosy. The second cause of blindness is corneal opacification, mainly as a result of neglected exposure keratitis and corneal anaesthesia. The miotic pupils in late multibacillary leprosy, in combination with small central lens opacities, may also lead to blindness. The Vision 2020 Initiative prioritises cataract surgery. Leprosy patients should be actively included. Disabled leprosy patients can also benefit from screening programmes for refractive errors and the provision of spectacles and low vision aids. Determining the most feasible surgical methods for lagophthalmos surgery remains a challenge. For all health and eye care staff, training in leprosy and its eye complications is needed, as well as a change in attitude towards leprosy patients. Staff must be prepared to welcome them in the general health services.
de Andrade, Pedro Jose Secchin; Messias, Sulamita dos Santos Nascimento Dutra; Ferreira, Paola Cristina Brandão Oliveira; Sales, Anna Maria; Machado, Alice de Miranda; Nery, José Augusto da Costa
Leprosy is a neglected disease. We point up the need of recognizing the unusual clinical presentations of the disease in order to make early diagnosis and proper treatment possible, and break the transmission chain. The authors report a rare type of multibacillary leprosy: histoid leprosy and present images of numerous well-circumscribed indurated papules and nodules distributed throughout the entire body. PMID:26560226
Weshler, Z; Leviatan, A; Gordon, R; Kopolovic, J
We present a patient with leprosy who developed Hodgkin's disease of the nodular sclerosing type. There are two previous reports describing the combination of leprosy and Hodgkin's disease in a single patient [3, 9]. Hodgkin's disease was diagnosed 14 months after the complete disappearance of mycobacterium leprae from the skin lesions, under treatment with DDS (diamino-diphenyl-sulfone). Hodgkin's disease was treated by irradiation and chemotherapy. Obstructive jaundice developed which resolved under treatment by irradiation of the hilar area of the liver, chemotherapy and hormones. During two years of immuno-suppressive therapy, without DDS, no exacerbation of the leprosy occurred.
Hastings, R C; Gillis, T P; Krahenbuhl, J L; Franzblau, S G
Leprosy affects over 10 million people in the world. The disease is a model of graded cell-mediated immunity, in this case to the causative organism, Mycobacterium leprae. The clinical manifestations are due to (i) bacterial progression, (ii) immunologic responses of the host, (iii) peripheral nerve damage due to either or both bacterial progression and immunologic responses of the host, and (iv) preventable secondary deformities following nerve damage, which account for most of the stigma of the disease. Treatment modalities are now available to control or minimize the effects of bacterial progression, harmful immunologic responses of the host, peripheral nerve damage, and secondary deformities. Unique biochemical characteristics of M. leprae reside in the cell wall and associated macromolecules. Some of these molecules are potent immunogens in humans, while others constitute the structural integrity of the bacillus. Proteins of M. leprae are currently under intensive investigation as a result of deoxyribonucleic acid cloning of M. leprae genes. Structure-function and antigenic relationships of M. leprae proteins should become available by using recombinant deoxyribonucleic acid procedures coupled with T- and B-cell cloning to advance our understanding of the immunologic reactions encountered in Hansen's disease. Until recently, the study of the immunology of leprosy has been stymied by the lack of immunologically specific M. leprae antigens. The definition of specific antigens and production of recombinant and synthetic immunologic reagents have fostered state-of-the-art research efforts into new immunodiagnostic procedures and development of a leprosy vaccine. Also discussed is progress in understanding of the mechanism(s) underlying the M. leprae-specific immunodeficiency associated with lepromatous leprosy, including the role of suppressor T cells and defective macrophage function. Metabolic studies of M. leprae suggest intact catabolic pathways and energy
Chugh, K. S.; Damle, P. B.; Kaur, S.; Sharma, B. K.; Kumar, B.; Sakhuja, V.; Nath, I. V.; Datta, B. N.
Sixty consecutive patients with leprosy were investigated for renal involvement. Clinically overt renal disease was present in 4 patients; 3 presented with a nephrotic state and one patient with progressive renal failure. Urinalysis showed daily protein loss ranging from 0.4 to 8.9 g in 8 patients and microscopic haematuria in 4 cases. Elevated levels of blood urea and creatinine were seen only in one patient with diffuse proliferative glomerulonephritis. Of the 36 patients in whom distal tubular functions were evaluated, concentration and/or acidification defects were detected in 9 patients (25%). Renal histology revealed no abnormality in any of these patients. Serum C3 levels were decreased in 5 patients with lepromatous leprosy and 3 patients with borderline leprosy. Histological evidence of renal involvement was detected in 9 patients (15%). Amyloid deposits were seen in 3 (5%) patients of whom 2 had lepromatous leprosy and one had tuberculoid leprosy with chronic trophic ulcers. Mesangial proliferative lesions were seen in 5 (8.3%) and diffuse proliferative lesions (with crescents in more than 70% of glomeruli) in one patient. All of them had lepromatous leprosy. Three of the 5 patients with mesangial proliferative glomerulonephritis had erythema nodosum leprosum at the time of biopsy. Immunofluorescence studies revealed granular deposits of IgA, IgM and C3 in one patient with mesangial proliferation and IgA/IgM with or without C3 in 3 more patients in whom renal histology was normal. Glomerulonephritis associated with leprosy appears to be immune mediated but confirmation requires identification of lepra antigen in the glomerular immune complex deposits. Images Fig. 1 Fig. 2 Fig. 3 PMID:6647188
Queirós, Maria Iranilda; Ramos Júnior, Alberto Novaes; Alencar, Carlos Henrique Morais; Monteiro, Lorena Dias; Sena, Amanda Lima; Barbosa, Jaqueline Caracas
Background Leprosy is an infectious chronic condition associated with potentially serious physical, social and psychological impacts. Objectives To characterize the clinical and epidemiological profile of leprosy patients treated from 2007 to 2011 in the University Hospital of Ceará, Northeastern Brazil. Methods This is a retrospective and descriptive study. The study population consisted of residents in the state of Ceará treated in a dermatology clinic between 2007-2011. Clinical and epidemiological data analyzed were obtained from medical records and from the database of national Information System for Notifiable Diseases. Results 475 cases were analyzed, mostly women (51.8%), aged 45-59 years (35.0%) - mean of 45.2 years at diagnosis - with 6.3% of children under 15 , with low education (73.7%), white color (68.8%), residency in the city of Fortaleza (82.3%), and no defined work occupation (59.6%). At diagnosis, most patients were multibacillary (MB) (65.5%), had borderline clinical form (48.0%), and 22.7% had physical disability (8.0% with grade 2), predominantly in MB cases (p <0.001). We observe worsening of disability in 5.1% of cases post-MDT. The proportion of cases with reactional episodes was 42.7%, mainly during MDT (51.2%). Conclusion This is the first study conducted in this hospital context, revealing late diagnosis, high burden of disease, hidden endemicity, and high social vulnerability in the state of Ceará. This study reinforces the need to strengthen health care network for timely diagnosis and treatment, aiming at longitudinality of assistance. PMID:27438198
Lopes, V A P; Lourenço, D M R; Guariento, A; Trindade, M A; Avancini, J; Silva, C A
Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions.
Rocha, Adalgiza da Silva; Cunha, Maria das Graças; Diniz, Lucia Martins; Salgado, Claudio; Aires, Maria Araci P.; Nery, José Augusto; Gallo, Eugênia Novisck; Miranda, Alice; Magnanini, Monica M. F.; Matsuoka, Masanori; Sarno, Euzenir Nunes; Suffys, Philip Noel
Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary. PMID:22495562
Reibel, F; Cambau, E; Aubry, A
Leprosy is an infectious disease that has now been reported for more than 2000 years. The leprosy elimination goal set by the World Health Organization (WHO), i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in the year 2000, but more than 200,000 new case patients are still reported each year, particularly in India, Brazil, and Indonesia. Leprosy is a specific infection: (i) it is a chronic infection primarily affecting the skin and peripheral nerves, (ii) Mycobacterium leprae is one of the last bacterial species of medical interest that cannot be cultured in vitro (mainly because of its reductive genome evolution), and (iii) transmission and pathophysiological data is still limited. The various presentations of the disease (Ridley-Jopling and WHO classifications) are correlated with the patient's immune response, bacillary load, and by the delay before diagnosis. Multidrug therapy (dapsone, rifampicin, with or without clofazimine) has been recommended since 1982 as the standard treatment of leprosy; 6 months for patients presenting with paucibacillary leprosy and 12 months for patients presenting with multibacillary leprosy. The worldwide use of leprosy drugs started in the 1980s and their free access since 1995 contributed to the drastic decline in the number of new case patients. Resistant strains are however emerging despite the use of multidrug therapy; identifying and monitoring resistance is still necessary.
Wang, Dong; Zhang, Deng-Feng; Feng, Jia-Qi; Li, Guo-Dong; Li, Xiao-An; Yu, Xiu-Feng; Long, Heng; Li, Yu-Ye; Yao, Yong-Gang
Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy. PMID:27876828
Donoghue, Helen D.; Marcsik, Antónia; Matheson, Carney; Vernon, Kim; Nuorala, Emilia; Molto, Joseph E.; Greenblatt, Charles L.; Spigelman, Mark
Both leprosy and tuberculosis were prevalent in Europe during the first millennium but thereafter leprosy declined. It is not known why this occurred, but one suggestion is that cross-immunity protected tuberculosis patients from leprosy. To investigate any relationship between the two diseases, selected archaeological samples, dating from the Roman period to the thirteenth century, were examined for both Mycobacterium leprae and Mycobacterium tuberculosis DNA, using PCR. The work was carried out and verified in geographically separate and independent laboratories. Several specimens with palaeopathological signs of leprosy were found to contain DNA from both pathogens, indicating that these diseases coexisted in the past. We suggest that the immunological changes found in multi-bacillary leprosy, in association with the socio-economic impact on those suffering from the disease, led to increased mortality from tuberculosis and therefore to the historical decline in leprosy. PMID:15734693
Eichelmann, K; González González, S E; Salas-Alanis, J C; Ocampo-Candiani, J
Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium leprae. It primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. Clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. Leprosy is associated with disability and marginalization. Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the World Health Organization: hypopigmented or erythematous macules with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens are used depending on whether the patient has paucibacillary or multibacillary disease.
Bakker, Mirjam I; May, Linda; Hatta, Mochammad; Kwenang, Agnes; Klatser, Paul R; Oskam, Linda; Houwing-Duistermaat, Jeanine J
Background It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity. Methods The three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA. Results For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity. Conclusion Genetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance. PMID:16307680
Ozaki, Motoaki; Tomoda, Masakazu
The authors reported a conjugal leprosy infection observed in Japan. The husband, index case, first noticed sensory disturbance at the lower right leg in his forties. He developed edematous swelling with redness of the right hand and forearm at the age of 72 (1989), and then developed multiple erythema and hypesthesia at the extremities. He was diagnosed as BL type leprosy (reactional stage) and treated with multi-drug therapy. His 71-year-old wife developed a few erythema at the right forearm in 1993. She was classified as BT type. The duration of their marriage life was over forty years. The couple did not have consanguinity. No other leprosy patients were found in their lineage. From their clinical courses the authors concluded that the husband infected his wife. According to Japanese literatures, the frequency of conjugal leprosy among new patients in Japan was approximately 1%. There were worldwide observations that the husband often infected the wife, and mostly the index case was multibacillary and the secondary case paucibacillary. The authors reviewed definition and frequency of conjugal leprosy, factors in conjugal infection and leprosy infection among the adults.
Anjum, Vaseem; Vijayakumaran, P
The global leprosy burden in terms of new case detection does not seem to show a declining trend. India continues to be one of the major contributors to the leprosy burden. It is well known that the presence of an index case is a risk factor for leprosy among household contacts. The Blue Peter Health and Research centre (BPHRC), a leprosy referral centre in South India, observed the presence of an index case in 27.6% of leprosy patients newly diagnosed during 2009-2013. A majority of the index cases were either parents or siblings. Early case detection is recommended in global and national strategies, but active contact screening is not in the purview of integrated leprosy services in India. Active contact screening may be considered as one of the major activities to further reduce the leprosy burden.
Vega-Lopez, F; Stoker, N G; Locniskar, M F; Dockrell, H M; Grant, K A; McAdam, K P
Mycobacterium leprae sonic extracts prepared from armadillo-derived bacteria were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting (immunoblotting) procedures and probed with serum or plasma samples from 20 patients with lepromatous leprosy and 14 healthy endemic controls. Five proteins of 33, 25, 18, 15, and 12 kilodaltons (kDa) were frequently recognized; the 33- and 15-kDa proteins were, respectively, recognized with high intensity by 16 and 13 of the 20 samples from patients with leprosy, whereas only one healthy donor had antibodies that recognized the 15-kDa protein. By the use of M. leprae-specific murine monoclonal antibodies it was demonstrated that the 33-, 25-, and 15-kDa antigens were different from those bound by the available murine monoclonal antibodies. The 18- and 12-kDa proteins detected had molecular masses similar to those detected by the corresponding murine monoclonal antibodies. The serum and plasma samples from patients with leprosy were also used to probe Western blots of a soluble extract of M. tuberculosis. They recognized, among others, antigens with molecular weights similar to those detected in the M. leprae antigenic preparations, although with less intensity and at a lower frequency. Images PMID:3068245
Cartel, J L; Boutin, J P; Spiegel, A; Glaziou, P; Plichart, R; Cardines, R; Grosset, J H
The analysis of computerized data (OMSLEP system) on patients from French Polynesia followed since 1940 has shown a decrease in the mean annual detection rates for leprosy, all forms combined, from 24.73 per 100,000 inhabitants in 1946 to 8.1 per 100,000 in 1987 (y = -0.49 x + 45.83; p < 0.05). In fact, the decrease was significant (y = -1.18 x + 83.54; p < 0.05) during the first half of the study period (1946-66), but not during the second half (1967-87). Similarly, a significant decrease in all of the specific mean annual detection rates (according to the form of leprosy and to the sex and age of patients), in the proportion of multibacillary patients among the total of newly detected cases, and in the proportion of all patients with disabilities at the onset of leprosy was observed only during the first half of the study period (1946-66). Nevertheless, when comparing age-specific cumulative detection rates, calculated by 10-year age groups over the period 1946-66, to those of the period 1967-87, an ageing of the leprosy population was noted. Finally, the decrease of mean annual detection rates was greater in the smaller populations of remote islands than in the population of Tahiti, the main island, where 70% of the total population were living during the study period. This decline was shown to correspond to an effective improvement of the leprosy situation which could be attributed, among other factors (such as economic development and systematic BCG vaccination), to the implementation of a control programme for leprosy in 1950. The introduction in 1982 of multidrug therapy for all patients suffering active leprosy has raised the hope of a subsequent decline of leprosy in French Polynesia in the near future.
Cartel, J L; Naudin, J C
When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.
Kronvall, G; Husby, G; Samuel, D; Bjune, G; Wheate, H
The presence of amyloid-related serum component, protein ASC, in serum samples from 63 leprosy patients was investigated. Protein ASC was detected in 38% of the patients. A correlation to the disease spectrum of leprosy was apparent: polar lepromatous cases, 64% positive; borderline lepromatous, 50%; borderline tuberculoid, 36%; subpolar tuberculoid, 17%; and polar tuberculoid, negative. Antibody activity against the a antigen of Mycobacterium leprae was also determined, showing a similar correlation to the disease spectrum. Serum samples from 23 apparently healthy Ethiopians serving as controls showed a protein ASC incidence of 22%. This figure is significantly higher than the frequency found by others among healthy Norwegian blood donors. Immunoglobulin M levels among patients were elevated in the borderline lepromatous and poplar lepromatous groups. The three tuberculoid groups did not differ in this respect from the control group but were all elevated as compared to a normal Caucasian serum pool. Although raised immunoglobulin M levels seemed to parallel increased frequencies of protein ASC in the patient groups as well as in controls, this correlation might be only secondary to a primary derangement in T-cell function. PMID:804451
Lastória, Joel Carlos; de Abreu, Marilda Aparecida Milanez Morgado
Leprosy is caused by Mycobacterium leprae and has been known since biblical times. It is still endemic in many regions of the world and a public health problem in Brazil. The prevalence rate in 2011 reached 1.54 cases per 10,000 inhabitants in Brazil. The mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. Transmission occurs through inhalation of bacilli present in upper airway secretion. The nasal mucosa is the main entry or exit route of M. leprae. The deeper understanding of the structural and biological characteristics of M. leprae, the sequencing of its genome, along with the advances in understanding the mechanisms of host immune response against the bacilli, dependent on genetic susceptibility, have contributed to the understanding of the pathogenesis, variations in the clinical characteristics, and progression of the disease. This article aims to update dermatologist on epidemiological, clinical, and etiopathogenic leprosy aspects. PMID:24770495
Ozturk, Z; Tatliparmak, A
Leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to Mycobacterium leprae. It is now infrequent in Europe and is rarely reported during pregnancy. Leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. Therefore, it is important to treat leprosy during pregnancy. This article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug therapy during pregnancy and breastfeeding. The patient delivered a healthy baby girl without perinatal complications, and the infant's growth and development were normal during the 1-year follow-up period. Multidrug therapy consisting of dapsone, rifampicine, and clofazimine is highly effective for people with leprosy and considered safe, both for the mother and the child. Antileprosy drugs are excreted into human milk but there is no report of adverse effects except for skin discoloration of the infant due to clofazimine. Multidrug therapy for leprosy patients should be continued unchanged during pregnancy and breastfeeding.
Alves-Junior, Eduardo R.; Arruda, Talita A.; Lopes, Jose C.; Fontes, Cor J.F.
Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18–69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with
Prestes-Carneiro, Luiz Euribel; Nai, Gisele Alborghetti; Silva, Márcia G; Cristofano, Carlos; Crivelin, Luciana Leite; Calabreta, Carmela Beatriz Ramos; Moliterno, Ricardo Alberto; Morgado de Abreu, Marilda Aparecida Milanez
Epidermodysplasia verruciformis (EV) is triggered by a variety of mechanisms that at least partly include genetic background. We present a Brazilian man with a 30-year history of flat, wart-like lesions with clinical, histopathological, and evolutive aspects consistent with papillomavirus (HPV)-associated EV. Histological analysis of the wart lesions showed epidermis with hyperkeratosis, regular acanthosis, hypergranulosis, and cells with abundant basophilic cytoplasm. Moreover, a perivascular lymphocytic infiltrate was found in the superficial dermis, consistent with a viral wart. Type-2-HPV DNA was detected in various fragments of skin-wart lesions using the polymerase chain reaction (PCR). Two years after the EV diagnosis, the patient presented with an anesthetic well-demarcated, erythematous and mildly scaly plaque on his right forearm. A histopathological analysis of this lesion demonstrated the presence of a compact tuberculoid granuloma. Ziehl-Neelsen staining demonstrated the presence of rare acid-fast bacilli and confirmed the tuberculoid leprosy diagnosis. The patient's Mitsuda Intradermal Reaction was positive. To elucidate the possible mechanism involved in this case of EV, we genotyped the HLA genes of this patient. DQB genotyping showed the polymorphic HLA alleles DQB1*0301 and 0501. The patient was treated with a paucibacillary multi-drug therapy scheme, and the disease was cured in six months. This report describes an EV patient with an M. leprae infection, confirming that tuberculoid leprosy patients possess a relatively specific and efficient cell-mediated immunity against the bacillus and, therefore, localized forms of the disease. Moreover, we show the possible involvement of the polymorphic HLA alleles DQB1*0301 and 0501 in EV induction mechanisms.
Watson, S; Bullock, W; Nelson, K; Schauf, V; Gelber, R; Jacobson, R
Quantitation of interleukin 1 production by adherent mononuclear cells from peripheral blood was performed in patients with tuberculoid and lepromatous forms of leprosy. Cells from patients with tuberculoid leprosy either secreted interleukin 1 spontaneously or produced amounts within the normal range in response to lipopolysaccharide stimulation. Conversely, stimulated cells from lepromatous patients failed to produce interleukin 1 in 5 of 13 (38.5%) cases. PMID:6332077
Cavalheiro, Aretusa Lopes; da Costa, Debora Tacon; de Menezes, Ana Luiza Ferro; Pereira, Janser Moura; de Carvalho, Eliane Maria
Background Low temperatures and slow blood flow may result from peripheral neuropathy caused by leprosy, and the simple detection of cold fingers could already be a preliminary classification for these patients. Objective To investigate whether infrared thermography would be able to measure this change in temperature in the hands of people with leprosy. Method The study assessed 17 leprosy patients who were under treatment at the National Reference Center for Sanitary Dermatology and Leprosy, Uberlândia/MG, and 15 people without leprosy for the control group. The infrared camera FLIR A325 and Therma CAM Researcher Professional 2.9 software were used to measure the temperature. The room was air-conditioned, maintaining the temperature at 25°C; the distance between the camera and the limb was 70 cm. The vasomotor reflex of patients was tested by a cold stress on the palm. Results The study showed a significant interaction between the clinical form of leprosy and temperature, where the control group and the borderline-borderline form revealed a higher initial temperature, while borderline-lepromatous and lepromatous leprosy showed a lower temperature. Regarding vasomotor reflex, lepromatous leprosy patients were unable to recover the initial temperature after cold stress, while those with the borderline-tuberculoid form not only recovered but exceeded the initial temperature. Conclusion Thermography proved a potential tool to assist in the early detection of neuropathies, helping in the prevention of major nerve damage and the installation of deformities and disabilities that are characteristic of leprosy. PMID:27438192
Saha, G; Mandal, N K; Dutta, R N
A cross sectional observational study was conducted to assess knowledge, attitude and practices about leprosy among leprosy patients in six districts of West Bengal. Total patients selected for the study were 300; of them 185 patients were from three high prevalent districts and 115 from three low prevalent districts of West Bengal. 56.33% patients were male and 43.67% were female. Most of the patients (85.67%) belonged to Hindu community and 60% from socially backward group. 64.33% patients lived below poverty line. Thirty five percentage of patients had correct knowledge that leprosy is caused by a bacteria. Patients from high prevalent districts (41.62%) have better knowledge than those from low prevalent areas (26.09%). Difference was found to be statistically significant (p = 0.006). Correct knowledge about spread of leprosy through cough & sneezing, of the patients from high prevalent districts (30.81%) was more than those from low prevalent districts (14.78%) (p = 0.001). 74.05% patients from high prevalent districts could tell one or other forms of clinical presentation of a leprosy patients, while 56.52% from low prevalent areas could mention it correctly (p = 0.01). About infectiousness, duration of treatment, complications, patients from high prevalent districts showed better knowledge that those from low prevalent districts. Similarly, Attitude of the patients towards leprosy was found to be more adverse in low prevalent areas. 90% patients have idea that leprosy was curable, but only 51.67% patients heard about MDT. Place of residence (high prevalent districts) & level of education (secondary & above) attributed to better knowledge score of the patients, whereas Place of residence (high prevalent districts) & age (younger age group) attributed to better attitude score of the patients.
Duthie, Malcolm S; Balagon, Marivic F; Maghanoy, Armi; Orcullo, Florenda M; Cang, Marjorie; Dias, Ronaldo Ferreira; Collovati, Marco; Reed, Steven G
Leprosy remains an important health problem in a number of regions. Early detection of infection, followed by effective treatment, is critical to reduce disease progression. New sensitive and specific tools for early detection of infection will be a critical component of an effective leprosy elimination campaign. Diagnosis is made by recognizing clinical signs and symptoms, but few clinicians are able to confidently identify these. Simple tests to facilitate referral to leprosy experts are not widely available, and the correct diagnosis of leprosy is often delayed. In this report, we evaluate the performance of a new leprosy serological test (NDO-LID). As expected, the test readily detected clinically confirmed samples from patients with multibacillary (MB) leprosy, and the rate of positive results declined with bacterial burden. NDO-LID detected larger proportions of MB and paucibacillary (PB) leprosy than the alternative, the Standard Diagnostics leprosy test (87.0% versus 81.7% and 32.3% versus 6.5%, respectively), while also demonstrating improved specificity (97.4% versus 90.4%). Coupled with a new cell phone-based test reader platform (Smart Reader), the NDO-LID test provided consistent, objective test interpretation that could facilitate wider use in nonspecialized settings. In addition, results obtained from sera at the time of diagnosis, versus at the end of treatment, indicated that the quantifiable nature of this system can also be used to monitor treatment efficacy. Taken together, these data indicate that the NDO-LID/Smart Reader system can assist in the diagnosis and monitoring of MB leprosy and can detect a significant number of earlier-stage infections.
Bakker, Mirjam I; Hatta, Mochammad; Kwenang, Agnes; Klatser, Paul R; Oskam, Linda
We conducted a population-based survey on five small islands in South Sulawesi Province (Indonesia) to collect baseline data previous to a chemoprophylactic intervention study aiming at interrupting the transmission of Mycobacterium leprae. Here we describe the present leprosy epidemiology on these geographically isolated islands. Of the 4774 inhabitants living in the study area 4140 were screened for leprosy (coverage: 87%). We identified 96 leprosy patients (85 new and 11 old patients), representing a new case detection rate (CDR) of 205/10 000 and a prevalence rate of 195/10 000. CDRs were similar for males and females. Male patients were more often classified as multibacillary (MB) than women. Of the new patients, 33 (39%) were classified as MB, 16 (19%) as paucibacillary (PB) 2-5 lesions and 36 (42%) as PB single lesion. In this area of high leprosy endemicity leprosy patients were extensively clustered, i.e. not equally distributed among the islands and within the islands among the houses.
Rojas-Espinosa, O; Arenas, R; Arce-Parades, P; Miranda-Contreras, G
In this study we looked for the presence of antibodies to cardiolipin, cerebrosides, and whole lipids extracted from M. leprae, M. tuberculosis and M. habana, in the serum of patients with clinically cured lepromatous leprosy (sixteen) or tuberculosis (sixteen), 8 to 12 months after arresting the corresponding multi-drug therapy (MDT). Compared to healthy controls (sixteen), both leprosy and tuberculosis ex-patients had still significant levels of antibodies to the three mycobacterial lipids but no detectable levels of antibodies to cardiolipin or cerebroside lipids. Although leprosy and tuberculosis sera recognized the homologous mycobacterial lipids in a preferential fashion, all of them, on the average, reacted more strongly with the lipids of M. habana. This observation backs up, in a certain way, the proposition of using M. habana as a prospective vaccine for leprosy and tuberculosis.
Moreira, Shirlei Cristina; Batos, Claudilson José de Carvalho; Tawil, Lara
Mycobacterium leprae was first described as the bacillus that causes leprosy, a chronic granulomatous infectious disease, in 1873 by Amauer Hansen. Leprosy is part of a group of 10 neglected diseases and Bahia has endemic levels of this illness, varying between high and very high. The detection of 52 new cases of leprosy in children under 15 years old in Salvador in 2006 is alarming, and suggests an early contact with the disease. The aim of this review is to analyze the epidemiological situation, the detection rate and evaluate the clinical and epidemiological profile of leprosy in Salvador, in the period 2001-2009. A retrospective cross-sectional study was performed using secondary data collected at Notifiable Diseases Information System Database (SINAN) through the notification of patients with leprosy. Over these nine years 3,226 patients were reported, with a predominance of: females (51.5%), and clinical multibacillary forms in the general population (51.7%), but when we analyze those under 15 years old, paucibacillary forms (tuberculoid + indeterminate) prevailed. The tuberculoid form was the most diagnosed type of presentation. The annual detection rate in Salvador remained at a very high level of endemicity during the studied period and for those under 15 years old it ranged between high and very high. Grade 2 disabilities both at the time of diagnosis and at discharge after cure, varied between low and medium. Based on these data we conclude that the high levels of leprosy detection rates in the general population, plus the variation between high and very high levels in those under 15 years old, associated with the medium level of grade 2 disabilities at the time of diagnosis and discharge, demonstrate the need for improvement on the existing services, investment in active case finding and training of the healthcare professionals in Salvador.
Beaman, Blain L.; Kim, Kwang-Shin; Lanéelle, Marie A.; Barksdale, Lane
Chemical analyses of the cell walls of organisms isolated in various parts of the world from cases of lepromatous and tuberculoid leprosy make possible their assignment to one of the three genera: Corynebacterium, Mycobacterium, or Propionibacterium. One, bacterium 22M, remains unassigned. The combined chemical and enzymatic properties attributed to leprosy bacilli freshly harvested from lepromata are found collectively, but not individually, in these three genera. Images PMID:4813897
[Prevalence of disability among leprosy patients and effectiveness of leprosy reaction services with standard prednisolone treatment at field level in an endemic country--some data from joint leprosy research collaboration in Myanmar].
Prevalence of disability among leprosy patients and effectiveness of standard predonisolone treatment for leprosy reaction at field level in some place of Myanmar are shown in this paper as results of joint leprosy research collaboration. WHO disability grading was measured for all newly registered leprosy patients through 2007 in 5 selected townships of Ayeyarwaddy Division, with the results of G0 = 66.3%, GI = 18.9%, GII = 14.7% (N = 95). The cross-sectional disability survey at selected 9 townships in Mandalay, Sagaing and Magway Division for all registered patients who had completed WHO/MDT done by JICA project in 2003/4 showed G0 = 62.5%, GI = 2.4%, GII = 35.1% (N = 10,528). From these two data, it is supposed that considerable number of patients with G1 at registered time developed worsening of disability from G1 to G2. Proportion of G0 also reduced a little bit in patients who completed WHO/MDT. Early detection and proper treatment of leprosy reaction are one of the main issues of prevention of disability. Effectiveness of leprosy reaction services were evaluated at Mandalay Special Skin Clinic, where WHO fixed regimen of prednisolone were given as routine service. 100 cases were evaluated who developed leprosy reactions from 1st December 2007 to 31st December 2008 and identified severe reaction who needed oral prednisolone treatment. Evaluation criteria of "effective" was defined as "no more signs and symptoms of reactions were present after treatment. And "less effective" was defined as "more than one of signs and symptoms were still remained after treatment". Over all "effective" was 36 (36%) and "less effective" was 64 (64%). It was also found that rates of improvement of nerve functions, either in sensory or in motor, were little after the standard treatment.
Grauwin, M Y; Gentile, B; Chevallard, A; Cartel, J L
Between 1988 and 1992, 21 biopsies for pathological examination were taken from 20 Senegalese leprosy patients suffering from chronic plantar ulcers (CPU) suspected of malignant transformation. The diagnosis of squamous cell carcinoma was effectively made in 13 cases and that of pseudoepitheliomatous hyperplasia in the remaining 8 cases. The mean period of time between the onset of CPU and that of malignant transformation was 10 years (range: 1 to 15 years); the mean annual frequency of the malignant transformation was 2 per 1,000 CPU. In countries where pathological examination is not available, below knee amputation could be considered whenever main clinical signs of malignant transformation are present. In countries where pathological examination is available, the therapeutic decision may differ according to the diagnosis: below knee amputation supplemented with block dissection of inguinal lymph nodes whenever possible in cases of carcinoma; below knee amputation depending on the function status of the foot and on the volume of tumor in case of pseudo-epitheliomatous hyperplasia.
Karaçorlu, M A; Cakiner, T; Saylan, T
The intraocular pressures of a total of 286 eyes of patients with lepromatous and borderline lepromatous leprosy who never had regular ophthalmological care or local eye treatment were measured. The patients were categorised according to the type of leprosy they had, and the eyes were categorised as without or with chronic plastic iridocyclitis. In patients with lepromatous and borderline lepromatous types of leprosy the intraocular pressure was significantly lower in eyes with chronic plastic iridocylitis 10.1 (3.6) mmHg than in both unaffected eyes 11.0 (3.2) mmHg and control eyes 13.5 (2.5) mmHg. It has been shown that chronic plastic iridocyclitis which remains untreated for years results in a lower intraocular pressure than normal.
Karaçorlu, M A; Cakiner, T; Saylan, T
The intraocular pressures of a total of 286 eyes of patients with lepromatous and borderline lepromatous leprosy who never had regular ophthalmological care or local eye treatment were measured. The patients were categorised according to the type of leprosy they had, and the eyes were categorised as without or with chronic plastic iridocyclitis. In patients with lepromatous and borderline lepromatous types of leprosy the intraocular pressure was significantly lower in eyes with chronic plastic iridocylitis 10.1 (3.6) mmHg than in both unaffected eyes 11.0 (3.2) mmHg and control eyes 13.5 (2.5) mmHg. It has been shown that chronic plastic iridocyclitis which remains untreated for years results in a lower intraocular pressure than normal. PMID:1995040
Brown, D H
Leprosy in Hawaii dates back to about 1840. The first recorded ocular leprosy is from the 1880s. Robert Louis Stevenson and Jack London both wrote descriptions of the ocular signs of leprosy. Pinkerton in 1927 and Van Poole in 1934 reported large series of patients with ocular leprosy. In 1973 there were about 2,168 cases of leprosy in the 50 states. Most ophthalmologists practice in areas where there are leprosy patients.
Schalcher, Taysa Ribeiro; Borges, Rosivaldo S.; Coleman, Michael D.; Batista Júnior, João; Salgado, Claudio G.; Vieira, Jose Luiz F.; Romão, Pedro R. T.; Oliveira, Fabio R.; Monteiro, Marta Chagas
This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software. PMID:24465659
Kumar, Shishir; Ghosh, Manab Kumar; Sarkar, Somenath; Mallik, Sudeshna; Biswas, Pradyot Narayan; Saha, Bibhuti
Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported.
Rojas-Espinosa, O.; Mendez-Navarrete, I.; Estrada-Parra, S.
Presence of soluble immune complexes was investigated in sera from persons with a well documented clinical diagnosis of leprosy. The complexes were detected by their reactivity with the C1q component of complement. More than 70% of the studied patients with lepromatous-leprosy had immune complexes demonstrable by this method (39/51), while only a small proportion of the healthy control group (1/35 or about 3%) had precipitable complexes. Two out of nine sera from patients with tuberculoid leprosy reacted when tested with C1q component. The presence of free-antibody to mycobacterial antigens was determined as well. The possible relationship between the presence of such immune complexes and the pathology of some reactional states of the disease is discussed. ImagesFig. 1 PMID:4630778
Jacob Raja, S. A.; Raja, J. Johnson; Vijayashree, R.; Priya, B. Meena; Anusuya, G. Sai; Ravishankar, P.
Aim: After the introduction of the multidrug therapy, the incidence of leprosy is decreasing every year. However, periodontal complaints are commonly seen in these patients due to compromised immunity and impaired oral hygiene. The aim of the present study is to assess the oral and periodontal status of the leprosy patients in Dindigul district. Materials and Methods: The study was conducted on 62 patients treated in a leprosy center at Dindigul district. Among these, 22 (35.5%) were female patients and 40 were male patients (64.5%). Age ranges between 40 and 70 with the mean age being 52. Facial changes, periodontal status, dental caries, attrition, tooth loss, plaque index (Silness and Loe), and calculus component of oral hygiene index-simplified were assessed. Results: Majority of the patients presented with loss of eyebrows and eyelashes, saddle nose, ocular involvement, and leonine facies. Gingival recession (54.8%) was a predominant finding followed by tooth loss (69.5%), mobility (60.86%), attrition (56%), chronic pulpitis (34.7%), and dental caries (26%). Most of the patients had severe periodontitis. Conclusions: Compromised immunity and altered autonomy pave way for many dental complaints such as periodontitis and deposits in tooth with poor oral hygiene. Awareness about the oral health problems and reinforcement of oral hygiene should be insisted to the leprosy patients to prevent further morbidity. PMID:27829761
Silva, G A V; Ramasawmy, R; Boechat, A L; Morais, A C; Carvalho, B K S; Sousa, K B A; Souza, V C; Cunha, M G S; Barletta-Naveca, R H; Santos, M P; Naveca, F G
Polymorphisms present in the TNF promoter region has shown to influence the gene transcription. Leprosy displays different clinical manifestations according to the immune responses of the individual infected with Mycobacterium leprae. In this study, we evaluated the single nucleotide polymorphisms (SNPs) -238 G/A (rs361525), -308 G/A (rs1800629), -857 C/T (rs1799724), -863 A/C (rs1800630) and -1031 T/C (rs1799964) in the promoter region of the TNF to see whether these SNPs influence host-susceptibility to leprosy and the different clinical manifestation. Nucleotide sequencing was performed with DNA samples from 108 leprosy patients and 253 control subjects. An association between -1031 C/C genotype and protection from leprosy was observed when leprosy patients were compared to controls (OR 0.11; 95% CI=0.01-0.82; p=0.012). The -857 C/T genotype may be associated with susceptibility to leprosy (OR=1.81; 95% CI=1.09-3.00; p=0.028). Similar genotype and allele frequencies for the SNPs -308 G/A and -238 G/A were observed between leprosy patients and control subjects. Altogether, TNF polymorphisms in the promoter region may be predictive of leprosy outcome.
Rai, Keshav; Bhattarai, Narayan Raj; Agarwal, Sudha; Khanal, Basudha
Background Detection of Mycobacterium leprae in slit skin smear (SSS) is a gold standard technique for the leprosy diagnosis. Over recent years, molecular diagnosis by using PCR has been increasingly used as an alternative for its diagnosis due to its higher sensitivity. This study was carried out for comparative evaluation of PCR and SSS microscopy in a cohort of new leprosy cases diagnosed in B. P. Koirala Institute of health Sciences, Dharan, Nepal. Methodology/Principal Findings In this prospective crossectional study, 50 new clinically diagnosed cases of leprosy were included. DNA was extracted from SSS and PCR was carried out to amplify 129 bp sequence of M. leprae repetitive element. Sensitivity of SSS and PCR was 18% and 72% respectively. Improvement of 54% case detection by PCR clearly showed its advantage over SSS. Furthermore, PCR could confirm the leprosy diagnosis in 66% of AFB negative cases indicating its superiority over SSS. In the paucibacillary (PB) patients, whose BI was zero; sensitivity of PCR was 44%, whereas it was 78% in the multibacillary patients. Conclusions/Significance Our study showed PCR to be more sensitive than SSS microscopy in diagnosing leprosy. Moreover, it explored the characteristic feature of PCR which detected higher level of early stage(PB) cases tested negative by SSS. Being an expensive technique, PCR may not be feasible in all the cases, however, it would be useful in diagnosis of early cases of leprosy as opposed to SSS. PMID:28027305
Do Prado, Glauber Dias; Prado, Renata Bilion Ruiz; Marciano, Lúcia Helena Soares Camargo; Nardi, Susilene Maria Tonelli; Cordeiro, José Antonio; Monteiro, Henrique Luiz
Disability caused by leprosy may be associated with stigma. The aim of this work is to describe the degree of disability, quality of life and level of physical activity of individuals with leprosy and to identify possible correlations between these factors. Ninety-seven patients from two referral centres were studied. A complete medical history was taken and the World Health Organization degree of physical disability classification (WHO-DG), the International Physical Activity Questionnaire (IPAQ) and the Medical Outcome Study 36-item Short-form health Survey (SF36) were applied. The mean age of patients was 51 +/- 14.9 years old; participants were predominantly men, married, unemployed, had concluded treatment and had had lepromatous leprosy. The WHO-DG and the level of physical activity (P-value = 0.36) were not correlated. The WHO-DG showed that 72.2% of patients had disabilities, 37.1% of whom performed vigorous physical activities. No significant association was observed between the WHO-DG and the domains of the QoL SF-36 except for functional capacity (P-value = 0.02); the physical capacity is generally 'very good' when individuals have no disabilities and 'bad' with severe disabilities. In conclusion, the WHO-DG of leprosy patients does not affect the level of physica activities or quality of life except functional capacity. There is no significan association between physical activities and quality of life in these individuals.
van Hooij, Anouk; Tjon Kon Fat, Elisa M.; Richardus, Renate; van den Eeden, Susan J. F.; Wilson, Louis; de Dood, Claudia J.; Faber, Roel; Alam, Korshed; Richardus, Jan Hendrik; Corstjens, Paul L. A. M.; Geluk, Annemieke
Leprosy is a debilitating, infectious disease caused by Mycobacterium leprae. Despite the availability of multidrug therapy, transmission is unremitting. Thus, early identification of M. leprae infection is essential to reduce transmission. The immune response to M. leprae is determined by host genetics, resulting in paucibacillary (PB) and multibacillary (MB) leprosy associated with dominant cellular or humoral immunity, respectively. This spectral pathology of leprosy compels detection of immunity to M. leprae to be based on multiple, diverse biomarkers. In this study we have applied quantitative user friendly lateral flow assays (LFAs) for four immune markers (anti-PGL-I antibodies, IL-10, CCL4 and IP-10) for whole blood samples from a longitudinal BCG vaccination field-trial in Bangladesh. Different biomarker profiles, in contrast to single markers, distinguished M. leprae infected from non-infected test groups, patients from household contacts (HHC) and endemic controls (EC), or MB from PB patients. The test protocol presented in this study merging detection of innate, adaptive cellular as well as humoral immunity, thus provides a convenient tool to measure specific biomarker profiles for M. leprae infection and leprosy utilizing a field-friendly technology. PMID:27682181
Orlova, Marianna; Cobat, Aurélie; Huong, Nguyen Thu; Ba, Nguyen Ngoc; Van Thuc, Nguyen; Spencer, John; Nédélec, Yohann; Barreiro, Luis; Thai, Vu Hong; Abel, Laurent; Alcaïs, Alexandre; Schurr, Erwin
Leprosy reversal reactions type 1 (T1R) are acute immune episodes that affect a subset of leprosy patients and remain a major cause of nerve damage. Little is known about the relative importance of innate versus environmental factors in the pathogenesis of T1R. In a retrospective design, we evaluated innate differences in response to Mycobacterium leprae between healthy individuals and former leprosy patients affected or free of T1R by analyzing the transcriptome response of whole blood to M. leprae sonicate. Validation of results was conducted in a subsequent prospective study. We observed the differential expression of 581 genes upon exposure of whole blood to M. leprae sonicate in the retrospective study. We defined a 44 T1R gene set signature of differentially regulated genes. The majority of the T1R set genes were represented by three functional groups: i) pro-inflammatory regulators; ii) arachidonic acid metabolism mediators; and iii) regulators of anti-inflammation. The validity of the T1R gene set signature was replicated in the prospective arm of the study. The T1R genetic signature encompasses genes encoding pro- and anti-inflammatory mediators of innate immunity. This suggests an innate defect in the regulation of the inflammatory response to M. leprae antigens. The identified T1R gene set represents a critical first step towards a genetic profile of leprosy patients who are at increased risk of T1R and concomitant nerve damage. PMID:23874223
Lasry-Levy, Estrella; Hietaharju, Aki; Pai, Vivek; Ganapati, Ramaswamy; Rice, Andrew S. C.; Haanpää, Maija; Lockwood, Diana N. J.
Background Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated. Methodology/Principal Findings Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity. Conclusions/Significance One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity. PMID:21408111
Pieri, Flávia Meneguetti; Touso, Michelle Mosna; Rodrigues, Ludmila Barbosa Bandeira; Yamamura, Mellina; Pinto, Ione Carvalho; Dessunti, Elma Mathias; Crispim, Juliane de Almeida; Ramos, Antônio Carlos Vieira; Arroyo, Luiz Henrique; Neto, Marcelino Santos; Garcia, Maria Concebida da Cunha; Popolin, Marcela Paschoal; Silveira, Tatiane Ramos dos Santos; Arcêncio, Ricardo Alexandre
Background In Brazil, leprosy has been listed among the health priorities since 2006, in a plan known as the “Pact for life” (Pacto pela Vida). It is the sole country on the American continent that has not reached the global goal of disease elimination. Local health systems face many challenges to achieve this global goal. The study aimed to investigate how patients perceive the local health system's performance to eliminate leprosy and whether these perceptions differ in terms of the patients' income. Methodology/Principal Findings A cross-sectional study was conducted in Londrina, State of Paraná, Brazil. Interviews were performed with the leprosy patients. The local health system was assessed through a structured and adapted tool, considering the domains judged as good quality of health care. The authors used univariate, bivariate and multivariate analyses. One hundred and nineteen patients were recruited for the study, 50.4% (60) of them were male, 54.0% (64) were between 42 and 65 years old and 66.3% (79) had finished elementary school. The results showed that patients used the Primary Health Care service near their place of residence but did not receive the leprosy diagnosis there. Important advances of this health system were verified for the elimination of leprosy, verifying protocols for good care delivery to the leprosy patients, but these services did not develop collective health actions and did not engage the patients' family members and community. Conclusions/Significance The patients' difficulty was observed to have access to the diagnosis and treatment at health services near their homes. Leprosy care is provided at the specialized level, where the patients strongly bond with the teams. The care process is individual, with limited perspectives of integration among the health services for the purpose of case management and social mobilization of the community to the leprosy problem. PMID:25412349
Saini, Chaman; Ramesh, Venkatesh; Nath, Indira
Background Lepromatous leprosy caused by Mycobacterium leprae is associated with antigen specific T cell unresponsiveness/anergy whose underlying mechanisms are not fully defined. We investigated the role of CD25+FOXP3+ regulatory T cells in both skin lesions and M.leprae stimulated PBMC cultures of 28 each of freshly diagnosed patients with borderline tuberculoid (BT) and lepromatous leprosy (LL) as well as 7 healthy household contacts of leprosy patients and 4 normal skin samples. Methodology/Principle Findings Quantitative reverse transcribed PCR (qPCR), immuno-histochemistry/flowcytometry and ELISA were used respectively for gene expression, phenotype characterization and cytokine levels in PBMC culture supernatants. Both skin lesions as well as in vitro antigen stimulated PBMC showed increased percentage/mean fluorescence intensity of cells and higher gene expression for FOXP3+, TGF-β in lepromatous (p<0.01) as compared to tuberculoid leprosy patients. CD4+CD25+FOXP3+ T cells (Tregs) were increased in unstimulated basal cultures (p<0.0003) and showed further increase in in vitro antigen but not mitogen (phytohemaglutinin) stimulated PBMC (iTreg) in lepromatous as compared to tuberculoid leprosy patients (p<0.002). iTregs of lepromatous patients showed intracellular TGF-β which was further confirmed by increase in TGF-β in culture supernatants (p<0.003). Furthermore, TGF-β in iTreg cells was associated with phosphorylation of STAT5A. TGF-β was seen in CD25+ cells of the CD4+ but not that of CD8+ T cell lineage in leprosy patients. iTregs did not show intracellular IFN-γ or IL-17 in lepromatous leprosy patients. Conclusions/Significance Our results indicate that FOXP3+ iTregs with TGF-β may down regulate T cell responses leading to the antigen specific anergy associated with lepromatous leprosy. PMID:24454972
Turankar, R P; Lavania, M; Chaitanya, V S; Sengupta, U; Darlong, J; Darlong, F; Siva Sai, K S R; Jadhav, R S
The exact mode of transmission of leprosy is not clearly understood; however, many studies have demonstrated active transmission of leprosy around a source case. Families of five active leprosy cases and their household contacts were chosen from a high endemic area in Purulia. Fifty-two soil samples were also collected from different areas of their houses. DNA was extracted from slit-skin smears (SSS) and soil samples and the Mycobacterium leprae-specific RLEP (129 bp) region was amplified using PCR. Molecular typing of M. leprae was performed for all RLEP PCR-positive samples by single nucleotide polymorphism (SNP) typing and confirmation by DNA sequencing. SSS of these five patients and six out of the total 28 contacts were PCR positive for RLEP whereas 17 soil samples out of 52 showed the presence of M. leprae DNA. SNP typing of M. leprae from all RLEP PCR-positive subjects (patients and smear-positive contacts) and 10 soil samples showed the SNP type 1 genotype. M. leprae DNA from the five leprosy patients and the six contacts was further subtyped and the D subtype was noted in all patients and contacts, except for one contact where the C subtype was identified. Typing followed by subtyping of M. leprae clearly revealed that either the contacts were infected by the patients or both patients and contacts had the same source of infection. It also revealed that the type of M. leprae in the soil in the inhabited areas where patients resided was also of the same type as that found in patients.
Jessamine, Peter G; Desjardins, Marc; Gillis, Tom; Scollard, David; Jamieson, Frances; Broukhanski, George; Chedore, Pam; McCarthy, Anne
Here we present the first case of a patient from Ottawa Canada, presenting with leprosy-like illness associated with Mycobacterium lepromatosis. The patient had no history of travel to leprosy-endemic areas or any obvious risk factors. Clinically, the patient presented with an anesthetic maculopapular rash on the trunk, back, and extremities. A skin biopsy of a lesion revealed a dermal lymphohistiocytic infiltration involving the vessels with an inflammatory process extending to the nerves. A neurological exam also identified a severe sensorimotor polyneuropathy. Concurrently, the patient was diagnosed with non-resectable, non small cell carcinoma of the lung, further complicating his clinical presentation. A Kinyoun stain of nasal blows and a Fite stain of the skin biopsy revealed few to moderate acid fast bacilli respectively. Cultures of the skin biopsy and multiple nasal blows were negative. Molecular studies of a skin biopsy sample including sequence analysis of a 765 bp region of the 16s rRNA gene eventually identified the organism with 100% homology to M. lepromatosis. The patient was treated for leprosy and appeared to improve slightly on therapy but died as a result of his malignancy approximately five months after the initiation of therapy. This represents the first case of a patient with M. lepromatosis like illness outside of Mexico and Singapore.
Raicher, Irina; Stump, Patrick Raymond Nicolas Andre Ghislain; Baccarelli, Rosemari; Marciano, Lucia H S C; Ura, Somei; Virmond, Marcos C L; Teixeira, Manoel Jacobsen; Ciampi de Andrade, Daniel
Nerve impairment is a key clinical aspect of leprosy and may present the distribution of mononeuropathy or multiple nerve trunks, small cutaneous nerve fibers, and free nerve endings. The clinical range of leprosy is determined by individual cell-mediated immune response to infection that also may play a role in different types of pain syndromes in leprosy. Previous studies reported a high prevalence of neuropathic pain in leprosy. In an Ethiopian study with 48 patients, pure nociceptive pain was experienced by 43% of patients and pure neuropathic pain (NeP) by 11% of patients. In an Indian study, 21.8% of leprosy patients had pain with neuropathic characteristics. These rates underlie the need to develop tools for the early diagnosis and detection of infection and its complications, such as nerve damage and pain. In a larger sample with leprosy-associated NeP (n = 90), we have applied the Douleur Neuropathique en 4 questions (DN4) and found sensitivity = 97.1% and specificity = 57.9%. The high sensitivity of this tool in leprosy patients suggests that it could be a valuable tool to screen for neuropathic pain in this population and could be used as part of health care programs aimed at detecting, treating, and rehabilitating leprosy in endemic areas.
Amorim, Francianne M.; Nobre, Maurício L.; Ferreira, Leonardo C.; Nascimento, Larissa S.; Miranda, Alesson M.; Monteiro, Glória R. G.; Dupnik, Kathryn M.; Duthie, Malcolm S.; Reed, Steven G.; Jeronimo, Selma M. B.
Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. Challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. Although phenolic glycolipid (PGL)-I has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. The aim of this study was to evaluate the effectiveness of two related reagents, LID-1 and LID-NDO, for the detection of M. leprae infection. Sera from 98 leprosy patients, 365 household contacts (HHC) and 98 endemic controls from Rio Grande do Norte, Brazil, were evaluated. A subgroup of the HHC living in a hyperendemic area was followed for 7–10 years. Antigen-specific antibody responses were highest in multibacillary (MB) at the lepromatous pole (LL/BL) and lowest in paucibacillary (PB) at the tuberculoid pole (TT/BT). A positive correlation for both anti-LID-1 and anti-LID-NDO antibodies was found with bacterial burden (LID-1, r = 0.84, p<0.001; LID-NDO, r = 0.82, p<0.001), with higher sensitivity than bacilloscopy. According to Receiver Operating Curve, LID-1 and LID-NDO performed similarly. The sensitivity for MB cases was 89% for LID-1 and 95% for LID-NDO; the specificity was 96% for LID-1 and 88% for LID-NDO. Of the 332 HHC that were followed, 12 (3.6%) were diagnosed with leprosy in a median time of 31 (3–79) months after recruitment. A linear generalized model using LID-1 or LID-NDO as a predictor estimated that 8.3% and 10.4% of the HHC would become a leprosy case, respectively. Together, our findings support a role for the LID-1 and LID-NDO antigens in diagnosing MB leprosy and identifying people at greater risk of developing clinical disease. These assays have the potential to improve the diagnostic capacity at local health centers and aid development of strategies for the eventual control and elimination of leprosy from endemic areas. PMID:27658042
Amorim, Francianne M; Nobre, Maurício L; Ferreira, Leonardo C; Nascimento, Larissa S; Miranda, Alesson M; Monteiro, Glória R G; Dupnik, Kathryn M; Duthie, Malcolm S; Reed, Steven G; Jeronimo, Selma M B
Leprosy is caused by Mycobacterium leprae infection and remains a major public health problem in many areas of the world. Challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. Although phenolic glycolipid (PGL)-I has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. The aim of this study was to evaluate the effectiveness of two related reagents, LID-1 and LID-NDO, for the detection of M. leprae infection. Sera from 98 leprosy patients, 365 household contacts (HHC) and 98 endemic controls from Rio Grande do Norte, Brazil, were evaluated. A subgroup of the HHC living in a hyperendemic area was followed for 7-10 years. Antigen-specific antibody responses were highest in multibacillary (MB) at the lepromatous pole (LL/BL) and lowest in paucibacillary (PB) at the tuberculoid pole (TT/BT). A positive correlation for both anti-LID-1 and anti-LID-NDO antibodies was found with bacterial burden (LID-1, r = 0.84, p<0.001; LID-NDO, r = 0.82, p<0.001), with higher sensitivity than bacilloscopy. According to Receiver Operating Curve, LID-1 and LID-NDO performed similarly. The sensitivity for MB cases was 89% for LID-1 and 95% for LID-NDO; the specificity was 96% for LID-1 and 88% for LID-NDO. Of the 332 HHC that were followed, 12 (3.6%) were diagnosed with leprosy in a median time of 31 (3-79) months after recruitment. A linear generalized model using LID-1 or LID-NDO as a predictor estimated that 8.3% and 10.4% of the HHC would become a leprosy case, respectively. Together, our findings support a role for the LID-1 and LID-NDO antigens in diagnosing MB leprosy and identifying people at greater risk of developing clinical disease. These assays have the potential to improve the diagnostic capacity at local health centers and aid development of strategies for the eventual control and elimination of leprosy from endemic areas.
Martins, Marcia V S B; Guimarães, Marjorie M da S; Spencer, John S; Hacker, Mariana A V B; Costa, Luciana S; Carvalho, Fernanda M; Geluk, Annemieke; van der Ploeg-van Schip, Jolien J; Pontes, Maria A A; Gonçalves, Heitor S; de Morais, Janvier P; Bandeira, Tereza J P G; Pessolani, Maria C V; Brennan, Patrick J; Pereira, Geraldo M B
During recent years, comparative genomic analysis has allowed the identification of Mycobacterium leprae-specific genes with potential application for the diagnosis of leprosy. In a previous study, 58 synthetic peptides derived from these sequences were tested for their ability to induce production of IFN-γ in PBMC from endemic controls (EC) with unknown exposure to M. leprae, household contacts of leprosy patients and patients, indicating the potential of these synthetic peptides for the diagnosis of sub- or preclinical forms of leprosy. In the present study, the patterns of IFN-γ release of the individuals exposed or non-exposed to M. leprae were compared using an Artificial Neural Network algorithm, and the most promising M. leprae peptides for the identification of exposed people were selected. This subset of M. leprae-specific peptides allowed the differentiation of groups of individuals from sites hyperendemic for leprosy versus those from areas with lower level detection rates. A progressive reduction in the IFN-γ levels in response to the peptides was seen when contacts of multibacillary (MB) patients were compared to other less exposed groups, suggesting a down modulation of IFN-γ production with an increase in bacillary load or exposure to M. leprae. The data generated indicate that an IFN-γ assay based on these peptides applied individually or as a pool can be used as a new tool for predicting the magnitude of M. leprae transmission in a given population.
de Lima, Adma Silva; Pinto, Karin Cristine; Bona, Míryan Priscilla Santos; de Mattos, Suelen Mayara Lopes; Hoffmann, Marina Portiolli; Mulinari-Brenner, Fabiane Andrade; Ottoboni, Vanessa Cristhine Dallolmo
BACKGROUND Leprosy is an infectious disease that may lead to irreversible nerve damage, compromising patient's quality of life and leading to loss of working years. OBJECTIVES To evaluate the epidemiological profile of patients followed at a University Hospital. MATERIALS AND METHODS This is a retrospective observational study, based on a review of medical records. We studied the clinical and epidemiological features of patients with leprosy monitored at the Hospital de Clínicas of the Federal University of Paraná between January 2005 and January 2010. RESULTS The mean age was 47.51, while 35.94% of patients were aged 41-60. The male:female rate was 1.8:1. The most prevalent occupations were: retired, students or rural workers. Patients came mainly from Curitiba or nearby areas, but there were also patients from the countryside. The mean diagnostic delay was 24.57 months. Multibacillary forms prevailed, with the lepromatous variety being the most common, closely followed by the borderline type. Neural enlargement was found in more than 50% of the patients and 48.44% of them developed reactional states. Hemolysis was the most commonly detected drug side effect. Initial functional evaluation was possible in 70% of patients, 55% of whom had disabilities upon diagnosis. The most prevalent associated disease was hypertension. CONCLUSIONS This study showed an important diagnostic delay and a high rate of sequelae in this specific population. Brazil is one of the few remaining countries that has not yet eradicated leprosy and it is important to improve health policies in order to prevent sequelae and achieve eradication. PMID:26560210
Montenegro, Rosa Maria Natalli; Zandonade, Eliana; Molina, Maria Del Carmen Bisi; Diniz, Lúcia Martins
Leprosy may present acute/subacute inflammatory processes (leprosy reactions). The study characterized the reactional states of patients at health clinics in Vitória, Espírito Santo State, Brazil, and associated them with sociodemographic factors and clinical/nutritional variables. between January and December 2009, longitudinal follow-up of patients with leprosy continued until leprosy reactions occurred or patients completed 6 months of multidrug therapy. Of the 151 patients participating, 78 (51.7%) were females, 48 (31.8%) had 5 to 8 years schooling, 93 (61.6%) worked and earned from 1 to 3 minimum wages, and 55 (36.4 %) had leprosy reactions, but with no statistical association to socioeconomic characteristics or nutritional status. However, absence of reaction was more common in the low-weight group, suggesting a trend in this group to protection from the reaction (p = 0.0906). The study found no association between nutritional status and leprosy reaction.
Lockwood, D N
There are interesting challenges in leprosy right now. The last fifteen years have seen the world-wide implementation of multidrug therapy with tangible benefits for patients and doctors. Paradoxically this success has revealed how much we still need to understand about leprosy nerve damage. For patients it is imperative that nerve damage is detected at an early stage when damage is still reversible. They need effective education to prevent the development of disability and to minimise the social and economic effects of nerve damage. For doctors and paramedical workers nerve damage needs effective treatment. We need to use current treatments effectively and also develop new treatments. This lecture looks critically at the pathology, detection and treatment of nerve damage, reviewing our present knowledge and looking to future developments.
Montoya-Buelna, Margarita; Tovar-Cuevas, Alvaro J.; Alvarado-Navarro, Anabell; Valle, Yeminia; Padilla-Gutierrez, Jorge R.; Muñoz-Valle, Jose F.; Figuera-Villanueva, Luis E.
Background. Leprosy is a debilitating infectious disease of human skin and nerves. Genetics factors of the host play an important role in the disease susceptibility. Toll-interacting protein (TOLLIP) is an inhibitory adaptor protein within the toll-like receptor (TLR) pathway, which recognizes structurally conserved molecular patterns of microbial pathogens, initiating immune responses. The objective of this study was to investigate the association of variants in the TOLLIP gene with susceptibility to leprosy in Mexican patients. Methods. TOLLIP polymorphisms were studied using a case-control design of Mexican patients with lepromatous leprosy (LL). The polymorphisms of TOLLIP at loci −526 C>G (rs5743854), 1309956C>T (rs3750920), 1298430C>A (rs5744015), and 1292831 G>A (rs3750919) were analyzed by PCR, with sequence-specific primers in LL patients and healthy subjects (HS) as controls. Results. Genotype distributions were in Hardy Weinberg equilibrium for all sites except for rs3750920. Neither genotype nor allele frequencies were statistically different between LL patients and controls (P > 0.05). The maximum pairwise D' coefficient reached was 0.44 of linkage (P = 0.01) for all the polymorphisms except for rs5743854. The three loci haplotype comparison yielded no significant differences between groups. Conclusions. Just the individuals with genotype C/C of rs3750920 have a trend of protective effect to developing LL. PMID:24294608
Dewapura, D R
Even though health workers have treated all registered cases of leprosy in Sri Lanka with multiple drug therapy since 1982, it continues to be transmitted. The government has launched a social marketing and social mobilization campaign to reduce the incidence of leprosy. It has expanded the network of leprosy services. A national advertising program included mass media ads, posters, stickers on buses, and radio and television serials to create awareness of the early signs of leprosy and to reduce fear to leprosy. Health workers distributed leaflets and booklets to the general public and to new patients. The Anti-Leprosy Campaign of Sri Lanka organized 1-week health education programs for administrative officer, village leaders, religious leaders, teachers, and voluntary workers. Skin camps were set up to detect leprosy cases and to treat minor skin disorders. Teachers received flip charts on leprosy to help them teach colleagues and children about leprosy. All primary level staff, medical officers in hospital staff, and estate medical and paramedical staff have undergone special training on diagnosing leprosy and on reducing their fear of it. Almost every district has at least 1 leprosy control specialist. 2 leprosy control specialists work in those districts where leprosy is endemic Each district has a trained medical laboratory technician, who stains and interprets leprosy smears. In 1992, school, contact, and mass surveys have found 31, 149, and 225 new cases, respectively. Active case findings methods found 16.5% of new cases. 50% of new cases are self- reported, compared to less than 10% in 1989, suggesting increased awareness of early signs of leprosy and a reduced fear of it. 25 more clinics opened in 1991 to meet the demand for leprosy services.
da Rosa, Fernanda Borowsky; de Souza, Victor Costa; de Almeida, Tatiana Amaral Pires; do Nascimento, Valdinete Alves; Vásquez, Felicien Gonçalves; Cunha, Maria da Graça Souza; Naveca, Felipe Gomes
The aim of this study was to investigate sensitivity disorders in the oral cavity related to the presence of Mycobacterium leprae in the saliva of treatment-naïve patients with leprosy in the state of Amazonas, Brazil. A cross-sectional study was conducted involving 45 subjects with leprosy. The subjects were interviewed to evaluate the sensitivity of the oral cavity. For the detection of M. leprae, saliva and slit-skin smear samples were collected. The samples were analysed using a bacteriological index (BI) protocol and the real-time quantitative polymerase chain reaction (qPCR). The results indicated that 15 of the 45 (33.3%) subjects with leprosy showed decreased oral sensitivity, which confirmed the importance of the oral cavity sensitivity evaluation. There was not a direct relationship between the presence of M. leprae in saliva and changes in oral sensitivity. Positive saliva qPCR results from six (31.6%) of 19 paucibacillary (PB) patients suggested the possibility of a new site for sample collection. Positive results using these diagnostic techniques (BI, slit-skin smear and saliva qPCR) increased to 55.5%, thus opening the possibility of combining these different techniques to increase the rate of positive diagnoses, especially in PB patients. PMID:23903971
Rosa, Fernanda Borowsky da; Souza, Victor Costa de; Almeida, Tatiana Amaral Pires de; Nascimento, Valdinete Alves do; Vásquez, Felicien Gonçalves; Cunha, Maria da Graça Souza; Naveca, Felipe Gomes
The aim of this study was to investigate sensitivity disorders in the oral cavity related to the presence of Mycobacterium leprae in the saliva of treatment-naïve patients with leprosy in the state of Amazonas, Brazil. A cross-sectional study was conducted involving 45 subjects with leprosy. The subjects were interviewed to evaluate the sensitivity of the oral cavity. For the detection of M. leprae, saliva and slit-skin smear samples were collected. The samples were analysed using a bacteriological index (BI) protocol and the real-time quantitative polymerase chain reaction (qPCR). The results indicated that 15 of the 45 (33.3%) subjects with leprosy showed decreased oral sensitivity, which confirmed the importance of the oral cavity sensitivity evaluation. There was not a direct relationship between the presence of M. leprae in saliva and changes in oral sensitivity. Positive saliva qPCR results from six (31.6%) of 19 paucibacillary (PB) patients suggested the possibility of a new site for sample collection. Positive results using these diagnostic techniques (BI, slit-skin smear and saliva qPCR) increased to 55.5%, thus opening the possibility of combining these different techniques to increase the rate of positive diagnoses, especially in PB patients.
Li, Jinlan; Yang, Lili; Wang, Ying; Liu, Hang; Liu, Jie; Cross, Hugh
Although leprosy in China is controlled at a low endemic level, the number of new cases in Guizhou province has shown no significant decrease over the past 20 years. Guizhou remains the province with the second highest prevalence in China. The authors conducted a study in which the characteristics of newly detected leprosy cases, found between 2008 and 2012 in Guizhou, were analysed. These cases represented people from pocket areas of leprosy in a generally low endemic environment. The purpose of the study was to understand characters of newly detected cases, strong points and weakness of routine detection approaches for improving the effectiveness of early case detection in the future. The analysis considered data that was collected from a 'Leprosy Management Information' report system and also from annual statistical reports of leprosy that reflect the situation throughout the province. 1274 new patients were detected in Guizhou from 2008 to 2012. That number included 58 (4.6%) children (0-14 years old). The average age of patients at diagnosis was 42.6 ± 16.5 years. The proportion of people with WHO Grade 2 disability (WHO DG2) among new patients was 35.7% and the proportion of people with Grade 1 disability (DG1) constituted 10.1%. The average delay before diagnosis after the onset of symptoms of leprosy was 41.7 ± 49.8 months. Suspect survey was a major method by which most cases were detected. Trough this method 790 (62.0%) new patients were detected. It was also in this group that the highest proportion of people with WHO DG2 359 of 790 (45.4%) was reported. Self- reporting, diagnosis at a general skin clinic, household contact examination, and spot surveys accounted for 13.0%, 11.8%, 11.5% and 1.7% of other cases detected respectively. It was generally found that cases detected through household contact examinations were earlier cases (delay to diagnosis < 24 months = 70.7%). It was also recorded that fewer of these had WHO DG2 (12.9%). The proportion of
Wood, A M; Wood, C M; Bakker-Dyos, J
We present the case of a 26 year old Indian base worker who attended the Role 2 enhanced hospital in Iraq with a case of leprosy. The patient presented four times over a 12 month period with non-specific pain in the right hand and forearm combined with a large lesion of dry skin and reduced sensation in the forearm. A clinical diagnosis of leprosy was made, which was subsequently confirmed as paucibacillary leprosy by skin smears sent to the UK. It was not possible to treat the patient locally and a recommendation made to the patient's employer that the patient return to India to commence treatment.
Reis, E M; Araujo, S; Lobato, J; Neves, A F; Costa, A V; Gonçalves, M A; Goulart, L R; Goulart, I M B
Leprosy epidemiological studies have been restricted to Mycobacterium leprae DNA detection in nasal and oral mucosa samples with scarce literature on peripheral blood. We present the largest study applying quantitative real-time PCR (qPCR) for the detection of M. leprae DNA in peripheral blood samples of 200 untreated leprosy patients and 826 household contacts, with results associated with clinical and laboratory parameters. To detect M. leprae DNA a TaqMan qPCR assay targeting the M. leprae ML0024 genomic region was performed. The ML0024 qPCR in blood samples detected the presence of bacillus DNA in 22.0% (44/200) of the leprosy patients: 23.2% (16/69) in paucibacillary (PB), and 21.4% (28/131) in multibacillary (MB) patients. Overall positivity among contacts was 1.2% (10/826), with similar percentages regardless of whether the index case was PB or MB. After a follow-up period of 7 years, 26 contacts have developed leprosy. Comparing the results of healthy contacts with those that become ill, ML0024 qPCR positivity at the time of diagnosis of their index case represented an impressive 14.78-fold greater risk for leprosy onset (95% CI 3.6-60.8; p <0.0001). In brief, contacts with positive PCR in blood at diagnosis of index cases are at higher risk of later leprosy onset and this marker might be combined with other prognostic markers for management of contacts, which requires further studies.
Sales, Anna Maria; Campos, Dayse Pereira; Hacker, Mariana Andrea; da Costa Nery, José Augusto; Düppre, Nádia Cristina; Rangel, Emanuel; Sarno, Euzenir Nunes; Penna, Maria Lucia Fernandes
Objective To evaluate the risk factors related to worsening of physical disabilities after treatment discharge among patients with leprosy administered 12 consecutive monthly doses of multidrug therapy (MDT/WHO). Methods Cohort study was carried out at the Leprosy Laboratory in Rio de Janeiro, Brazil. We evaluated patients with multibacillary leprosy treated (MDT/WHO) between 1997 and 2007. The Cox proportional hazards model was used to estimate the relationship between the onset of physical disabilities after release from treatment and epidemiological and clinical characteristics. Results The total observation time period for the 368 patients was 1 570 person-years (PY), averaging 4.3 years per patient. The overall incidence rate of worsening of disability was 6.5/100 PY. Among those who began treatment with no disability, the incidence rate of physical disability was 4.5/100 PY. Among those who started treatment with Grade 1 or 2 disabilities, the incidence rate of deterioration was 10.5/100 PY. The survival analysis evidenced that when disability grade was 1, the risk was 1.61 (95% CI: 1.02–2.56), when disability was 2, the risk was 2.37 (95% CI 1.35–4.16), and when the number of skin lesions was 15 or more, an HR = 1.97 (95% CI: 1.07–3.63). Patients with neuritis showed a 65% increased risk of worsening of disability (HR = 1.65 [95% CI: 1.08–2.52]). Conclusion Impairment at diagnosis was the main risk factor for neurological worsening after treatment/MDT. Early diagnosis and prompt treatment of reactional episodes remain the main means of preventing physical disabilities. PMID:23937704
Frade, Marco Andrey Cipriani; Marques-Jr, Wilson; Foss, Norma Tiraboschi
Background Previous studies have shown that leprosy multi-drug therapy (MDT) does not stop the progression of nerve function impairment. There are no prospective studies investigating the evolution of nerve anatomic abnormalities after treatment. We examined leprosy patients aiming to investigate the evolution of nerve ultrasonography (US) abnormalities and the risk factors for poor outcomes after MDT. Methodology/Principal findings We performed bilateral US of the ulnar (U), median (M) and common fibular (CF) nerves in 9 paucibacillary (PB) and 64 multibacillary (MB) patients before and after MDT. Forty-two patients had leprosy reactions (type 1, type 2, acute neuritis) during the study. We analyzed nerve maximum cross-sectional areas (CSA), echogenicity and Doppler signal. Poor outcomes included a post-treatment CSA above normal limits with a reduction of less than 30% (U, M) or 40% (CF) from the baseline, echogenicity abnormalities or intraneural Doppler in the post-treatment study. We found that PB and patients without reactions showed significant increases in CSA at CF, whereas MB and patients with reactions had CSA reduction in some nerves after treatment (p<0.05). Despite this reduction, we observed a greater frequency of poor CSA outcomes in the MB compared to the PB (77.8% and 40.6%; p>0.05) and in the patients with reactions compared to those without (66.7% and 38.7%; p<0.05). There was significantly higher odds ratio (7.75; 95%CI: 1.56–38.45) for poor CSA outcomes only for M nerve in patients with reactions. Poor echogenicity outcomes were more frequent in MB (59.4%) compared to PB (22.2%) (p<0.05). There was significant association between poor Doppler outcomes and neuritis. Gender, disease duration, and leprosy classification were not significant risk factors for poor outcomes in CSA, echogenicity or Doppler. Conclusions/Significance US nerve abnormalities can worsen after treatment despite the leprosy classification or the presence of reactions
Hungria, Emerith Mayra; de Oliveira, Regiane Morillas; Aderaldo, Lúcio Cartaxo; Pontes, Araci de Andrade; Cruz, Rossilene; Gonçalves, Heitor de Sá; Penna, Maria Lúcia Fernandes; Penna, Gerson Oliveira; Stefani, Mariane Martins de Araújo
Background Leprosy reactions, reversal reactions/RR and erythema nodosum leprosum/ENL, can cause irreversible nerve damage, handicaps and deformities. The study of Mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil/U-MDT/CT-BR is suitable to evaluate its prognostic value for the development of reactions. Methodology IgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time. Principal findings Among these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p<0.0001). Seroreactivity in reactional and reaction-free patients was stratified by bacilloscopic index/BI categories. Among BI negative patients, higher anti-PGL-I levels were seen in RR compared to reaction-free patients (p = 0.014). In patients with 0
Rangel, Maria Luíza Sales; Sanchez, Tiago Arruda; Moreira, Filipe Azaline; Hoefle, Sebastian; Souto, Inaiacy Bittencourt; da Cunha, Antônio José Ledo Alves
Background Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS). Methods In a cross-sectional study design, we mapped bilaterally in the primary motor cortex (M1) the representations of the hand flexor digitorum superficialis (FDS), as well as of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent clinical assessment, handgrip dynamometry and motor and sensory nerve conduction exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were performed with an alpha-value of p<0.05. Findings Dynamometry performance of the patients’ most affected hand (MAH), was worse than that of the less affected hand (LAH) and of healthy controls participants (p = 0.031), confirming handgrip impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres in patients as compared to controls, and lower in the hemisphere contralateral to the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP) amplitudes collected in the FDS of the MAH were higher in comparison to those of controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes in the hemisphere contralateral to MAH as compared to those of the LAH and the control group. Taken together, these results are suggestive of a more robust representation of an extrinsic hand flexor and impaired intrinsic hand muscle function in the hemisphere contralateral to the MAH due to leprosy. Conclusion Decreased
Ismail, Hossam El-din Ali; El Fahar, Mohamed Hassan
Introduction: The sensory loss and alteration of the shape of the foot make the foot liable to trauma and pressure, and subsequently cause more callus formation, blisters, and ulcers. Foot ulcers usually are liable to secondary infection as cellulitis or osteomyelitis, and may result in amputations. Foot ulcers are a major problem and a major cause of handicaps in leprosy patients. The current study is to present our clinical experience and evaluate the use of sural flap with posterior tibial neurovascular decompression (PTND) in recurrent foot ulcers in leprosy patients. Patient and methods: A total number of 9 patients were suffering from chronic sequelae of leprosy as recurrent foot ulcers. All the patients were reconstructed with the reverse sural artery fasciocutaneous flap with posterior tibial neurovascular decompression from September 2012 to August 2015. Six patients were male and three were female with a mean age of 39.8 years (range, 30–50 years). All the soft tissue defects were in the weight-bearing area of the inside of the foot. The flap sizes ranged from 15/4 to 18/6 cm. Mean follow-up period was 21.2 months (range, 35–2 months). Results: All the flaps healed uneventfully. There was no major complication as total flap necrosis. Only minor complications occurred which were treated without surgical intervention except in two patients who developed superficial necrosis of the skin paddle. Surgical debridement was done one week later. The flap was completely viable after surgery, and the contour of the foot was restored. We found that an improvement of sensation occurred in those patients in whom the anesthesia started one year ago or less and no sensory recovery in patient in whom the anesthesia had lasted for more than two years. Conclusion: The reverse sural artery flap with posterior tibial neurovascular decompression provides a reliable method for recurrent foot soft tissue reconstruction in leprosy patients with encouraging function and
Grauwin, M Y; Dieye, M; Mane, I; Cartel, J L
Biopsies of the superficial sensory branch of the radial nerve are contested. Some authors mention it to be simple and without harm, but others are formally against this procedure. At ILAD, 274 biopsies were made between 1986 to 1992. We present a review of 112 leprosy patients for whom biopsy was done. On 112 reexamined patients, we observed 2 benign neuroma, hence 2%. The comparison of nerve function before biopsy and after, of 63 of the 112 patients, reexamination shows no significant modification of the functional score. Given even the occurrence of benign neuroma in only 2% of the cases, the authors do not recommend the biopsy of the superficial sensory branch of the radial nerve. For research purposes on neuritis in leprosy, as well as to assure diagnosis in primary neuritic leprosy, we propose the biopsy of the sensory branch of the musculo cutaneous nerve at elbow level.
Bernardes Filho, Fred; de Abreu, Marilda M. M.; Botini, Patrícia; Duthie, Malcolm S.; Spencer, John S.; Soares, Rosa Castália F. R.
Background Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. Methods A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. Results Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36–1.22). Conclusions The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring. PMID:28231244
da Silva, Geraldo Bezerra; Daher, Elizabeth De Francesco; Pires, Roberto da Justa; Pereira, Eanes Delgado Barros; Meneses, Gdayllon Cavalcante; Araújo, Sônia Maria Holanda Almeida; Barros, Elvino José Guardão
Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes. PMID:25651321
Kopparty, S N
Though the impact of social inequality on health conditions is widely known, its impact on the chronic and stigmatized disease, leprosy, has received little attention. Deformity sometimes leads to disabilities and to handicaps causing problems to the patient and his family. In this paper an attempt has been made to understand the impact of social inequality, prevalent in the form of the caste system in India on the deformed leprosy patients and on their families. This impact was examined in terms of the problems faced by the patients. A sample of 150 deformed patients and their families, drawn from two districts in Tamil Nadu, was selected for the study. About 57% of the deformed patients experienced their deformity as a handicap which caused social and economic problems while the rest did not. Of the three caste groups, the Lower Caste group experienced more severe economic problems while the Upper Caste group faced more social problems. The extent of acceptance of deformed patients in their family varied significantly among those facing and not facing problems due to their deformity. The deformed patients without any handicap were accepted in a large majority of their families (82%) regardless of their caste status. In contrast the deformed but handicapped patients were accepted differentially among the three caste groups with the Upper group accepting them in most of their families (80%) while in the Lower group much less number of families (54%) did. All the families of the deformed but not handicapped patients desired to keep their patients till their death irrespective of their caste status. On the contrary, while all the families in the Upper Caste group expressed their willingness to keep their handicapped patients in the family till their death, 10% in the Middle and 22% in the Lower Caste groups did not want to do so. This suggests the gradual marginalization, rejection and dehabilitation of the affected. Thus, one's caste status can be a broad indicator
Overbeek, S T; Tham, L M
In this investigation the effectiveness was studied of adhesive zinc oxide tape, as additional therapy to the usual application of povidone iodine (10%), for leprosy patients with plantar ulcers in Sulawesi Tengah, Indonesia. The effectiveness (degree of wound healing measured as surface reduction) of this experimental therapy was compared with that of the usual therapy alone. At the same time the influence of the physical activity level on the effectiveness of both therapies was studied. During six weeks 38 leprosy patients with simple ulcers were treated with either one of the therapies. The average wound healing of the experimental group and the control group was 388 mm2 (SD 498) and 260 mm2 (SD 260) respectively. Using the t-test, there was no statistically significant difference in wound healing between the two therapies (p = 1.7). The average wound healing of the experimental group with a high and a low activity level was 342 mm2 (SD 226) and 405 mm2 (SD 571) respectively. The average wound healing of the control group with a high and low activity level was 246 mm2 (SD 289) and 275 mm2 (SD 232) respectively. Using analyses of variance, there was no statistically significant influence on the effectiveness of the therapies (p greater than 0.1). Methodological problems possibly influenced on the results. Different problems which may be encountered during research in third world countries are mentioned.
Lockwood, Diana N. J.; Suneetha, Lavanya; Sagili, Karuna Devi; Chaduvula, Meher Vani; Mohammed, Ismail; van Brakel, Wim; Smith, W. C.; Nicholls, Peter; Suneetha, Sujai
Background Previous studies investigating the role of cytokines in the pathogenesis of leprosy have either been on only small numbers of patients or have not combined clinical and histological data. The INFIR Cohort study is a prospective study of 303 new multibacillary leprosy patients to identify risk factors for reaction and nerve damage. This study characterised the cellular infiltrate in skin and nerve biopsies using light microscopic and immunohistochemical techniques to identify any association of cytokine markers, nerve and cell markers with leprosy reactions. Methodology/Principal Findings TNF-α, TGF-β and iNOS protein in skin and nerve biopsies were detected using monoclonal antibody detection immunohistochemistry techniques in 299 skin biopsies and 68 nerve biopsies taken from patients at recruitment. The tissues were stained with hematoxylin and eosin, modified Fite Faraco, CD68 macrophage cell marker and S100. Conclusions/Significance Histological analysis of the biopsies showed that 43% had borderline tuberculoid (BT) leprosy, 27% borderline lepromatous leprosy, 9% lepromatous leprosy, 13% indeterminate leprosy types and 7% had no inflammation. Forty-six percent had histological evidence of a Type 1 Reaction (T1R) and 10% of Erythema Nodosum Leprosum. TNF-α was detected in 78% of skin biopsies (181/232), iNOS in 78% and TGF-β in 94%. All three molecules were detected at higher levels in patients with BT leprosy. TNF-α was localised within macrophages and epithelioid cells in the granuloma, in the epidermis and in dermal nerves in a few cases. TNF-α, iNOS and TGF-β were all significantly associated with T1R (p<0.001). Sixty-eight nerve biopsies were analysed. CD68, TNF-α and iNOS staining were detectable in 88%, 38% and 28% of the biopsies respectively. The three cytokines TNF-α, iNOS and TGF-β detected by immunohistochemistry showed a significant association with the presence of skin reaction. This study is the first to demonstrate an
Grauwin, M Y; Mane, I; Cartel, J L
Between 1984 and 1993, pseudoepitheliomatous hyperplasia developing in chronic ulcers were observed in 28 former Senegalese leprosy patients, which amounts to an annual frequency of 1.9 per 1000 ulcers. Correct diagnosis could only be made by histopathological examination of specimens taken from the depth of the lesion. Amputation was carried out on 17 patients and local excision on the other 10. Recurrence of growth was observed in 8 of the 10 patients treated by excision; in all of these 8 cases below knee amputation had to be subsequently performed. From our experience, it may be assumed that local excision should be carried out only in the case of small tumours. Since the aim of surgical procedure is to allow the patient to have physical autonomy, below knee amputation, followed by adaptation of prosthesis, should be the procedure chosen in the other cases.
Pinto, Pablo; Salgado, Claudio; Santos, Ney Pereira Carneiro; Santos, Sidney; Ribeiro-dos-Santos, Ândrea
Background Leprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry. Methodology/Principal Findings We investigated the possible effects of CYP19A1 [rs11575899], NFKβ1 [rs28362491], IL1α [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKβ1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKβ1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy. Conclusions/Significance NFKβ1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKβ1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy. PMID:26367014
Robins, R; Martin, D; Raj, K Durai; Raju, M S
To assess the level of awareness about the different provisions of the Persons with Disability Act (PWD Act) among leprosy patients and other disabled, 233 disabled persons from the self-help groups formed by Vadathorasalur Leprosy Control Unit have been interviewed using a structured interview checklist. The results show that 74.7% of the respondents were aware that identity cards are available for the disabled, 56.2% were aware of the free education benefit to the disabled, as low as 35.6% were aware of the scholarships, 33% knew about the employment reservations, 24.9% heard about the housing scheme of the government for the disabled, but 24.5% only knew about law against discrimination, 31.8% came in contact with institutions for the severely disabled and only 16% were aware of the unemployment allowance to the disabled. The level of awareness is low among women with regard to all components of the Act. It was found that students studying up to secondary level were not aware of the availability of scholarships and free education, which needs to be seriously looked into, especially by educational institutions. The level of formal education played a significant role in increasing awareness about the Act among literates. The knowledge is low among persons of all occupations. The study showed that there is a great need for an educational intervention programme to publicize the provisions of the Act among the disabled and their families.
Serafín-López, J.; Talavera-Paulin, M.; Amador-Molina, J. C.; Alvarado-Riverón, M.; Vilchis-Landeros, M. M.; Méndez-Ortega, P.; Fafutis-Morris, M.; Paredes-Cervantes, V.; López-Santiago, R.; León, C. I.; Guerrero, M. I.; Ribas-Aparicio, R. M.; Mendoza-Hernández, G.; Carreño-Martínez, C.; Estrada-Parra, S.; Estrada-García, I.
Leprosy is an infectious disease caused by Mycobacterium leprae, which is a noncultivable bacterium. One of the principal goals of leprosy research is to develop serological tests that will allow identification and early treatment of leprosy patients. M. habana is a cultivable nonpathogenic mycobacterium and candidate vaccine for leprosy, and several antigens that cross-react between M. leprae and M. habana have been discovered. The aim of the present study was to extend the identification of cross-reactive antigens by identifying M. habana proteins that reacted by immunoblotting with antibodies in serum samples from leprosy patients but not with antibodies in sera from tuberculosis (TB) patients or healthy donors (HDs). A 28-kDa antigen that specifically reacted with sera from leprosy patients was identified. To further characterize this antigen, protein spots were aligned in two-dimensional polyacrylamide gels and Western blots. Spots cut out from the gels were then analyzed by mass spectrometry. Two proteins were identified: enoyl-coenzyme A hydratase (lipid metabolism; ML2498) and antigen 85B (Ag85B; mycolyltransferase; ML2028). These proteins represent promising candidates for the design of a reliable tool for the serodiagnosis of lepromatous leprosy, which is the most frequent form in Mexico. PMID:21613461
Marques Jr., Wilson; Foss, Norma Tiraboschi
Background Neurological involvement occurs throughout the leprosy clinical spectrum and is responsible for the most feared consequences of the disease. Ultrasonography (US) provides objective measurements of nerve thickening and asymmetry. We examined leprosy patients before beginning multi-drug therapy aiming to describe differences in US measurements between classification groups and between patients with and without reactions. Methodology/Principal Findings Eleven paucibacillary (PB) and 85 multibacillary (MB) patients underwent nerve US. Twenty-seven patients had leprosy reactions (type 1, type 2 and/or acute neuritis) prior to US. The ulnar (at the cubital tunnel–Ut–and proximal to the tunnel–Upt), median (M) and common fibular (CF) nerves were scanned to measure cross-sectional areas (CSAs) in mm2 and to calculate the asymmetry indexes ΔCSA (absolute difference between right and left CSAs) and ΔUtpt (absolute difference between Upt and Ut CSAs). MB patients showed greater (p<0.05) CSAs than PB at Ut (13.88±11.4/9.53±6.14) and M (10.41±5.4/6.36±0.84). ΔCSAs and ΔUtpt were similar between PB and MB. The CSAs, ΔCSAs and ΔUtpt were similar between PB patients with reactions compared to PB patients without reactions. MB patients with reactions showed significantly greater CSAs (Upt, Ut and M), ΔCSAs (Upt and Ut) and ΔUtpt compared to MB patients without reactions. PB and MB showed similar frequencies of abnormal US measurements. Patients with reactions had higher frequency of nerve thickening and similar frequency of asymmetry to those without reactions. Conclusions/Significance This is the first study to investigate differences in nerve involvement among leprosy classification groups using US before treatment. The magnitude of thickening was greater in MB and in patients with reactions. Asymmetry indexes were greater in patients with reactions and did not significantly differ between PB and MB, demonstrating that asymmetry is a characteristic of
Brochado, Maria José Franco; Gatti, Maria Fernanda Chociay; Zago, Marco Antônio; Roselino, Ana Maria
Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.
Brochado, Maria José Franco; Gatti, Maria Fernanda Chociay; Zago, Marco Antônio; Roselino, Ana Maria
Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively. PMID:26814595
Medeiros, Priscila; da Silva, Weber Laurentino; de Oliveira Gimenez, Bruna Beatriz; Vallezi, Keren Bastos; Moraes, Milton Ozório; de Souza, Vânia Niéto Brito; Latini, Ana Carla Pereira
Leprosy outcome is a complex trait and the host-pathogen-environment interaction defines the emergence of the disease. Host genetic risk factors have been successfully associated to leprosy. The 10p13 chromosomal region was linked to leprosy in familial studies and GATA3 gene is a strong candidate to be part of this association. Here, we tested tag single nucleotide polymorphisms at GATA3 in two case-control samples from Brazil comprising a total of 1633 individuals using stepwise strategy. The A allele of rs10905284 marker was associated with leprosy resistance. Then, a functional analysis was conducted and showed that individuals carrying AA genotype express higher levels of GATA-3 protein in lymphocytes. So, we confirmed that the rs10905284 is a locus associated to leprosy and influences the levels of this transcription factor in the Brazilian population.
Reis, Felipe J J; Correia, Helia; Nagen, Roberto; Gomes, Maria Kátia
Leprosy leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. Autonomic dysfunctions may result in dryness and cracking of the skin. In this study, we present the use of ozone provided by a high-frequency device to treat hand ulcers (wounds) in an 80-year-old man who was diagnosed as multibacillary in 2007. In the first visit, the patient was evaluated and received verbal and written instructions about self-care. Treatment consisted of five sessions, once per week. The ozone provided by a high-frequency device seemed to be useful in the treatment of ulcers, thus, contributing to the healing process. Research that investigates the use of high frequencies in the treatment of ulcers associated or not with other interventions (self-care strategies, protective clothing, adapted tools and footwear adaptation) is strongly recommended.
Reis, Felipe J.J.; Correia, Helia; Nagen, Roberto; Gomes, Maria Kátia
Leprosy leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. Autonomic dysfunctions may result in dryness and cracking of the skin. In this study, we present the use of ozone provided by a high-frequency device to treat hand ulcers (wounds) in an 80-year-old man who was diagnosed as multibacillary in 2007. In the first visit, the patient was evaluated and received verbal and written instructions about self-care. Treatment consisted of five sessions, once per week. The ozone provided by a high-frequency device seemed to be useful in the treatment of ulcers, thus, contributing to the healing process. Research that investigates the use of high frequencies in the treatment of ulcers associated or not with other interventions (self-care strategies, protective clothing, adapted tools and footwear adaptation) is strongly recommended. PMID:26543396
Rachmani, Enny; Kurniadi, Arif; Hsu, Chien Yeh
After India and Brazil, Indonesia has the third highest incidence/prevalence of leprosy in the world. Every year thousands of new cases and case with grade-2 disability are reported and, while the recovery rate lingers only 80-90 %. Therefore, more than 10 % of leprosy patients drop out of treatment and can be a source of new infections in the community. Our research was aimed at determining apparent difficulties in the leprosy control program as well as how a health information system (HIS) could assist the Indonesian leprosy control program. We used qualitative method with deep interview and observation of document. One of the difficulties which the Indonesian leprosy control program faces is discontinuity of patient's data due to rotating staff as well as the treatment monitoring and queries patients which should be monitored after treatment has ceased. Technology implementation is feasible through short message service (sms) reminders and web base applications. The leprosy control program urgently needs to implement continuous monitoring and recording of patients because of the particular characteristics of this contagious disease.
Putinatti, Maria Stella de Mello Ayres; Lastória, Joel Carlos; Padovani, Carlos Roberto
BACKGROUND Leprosy can have its course interrupted by type 1 and 2 reactional episodes, the last named of erythema nodosum leprosum (ENL). Thalidomide has been the medication of choice for the control of ENL episodes since 1965. OBJECTIVES These episodes can repeat and cause damages to the patient. In order to prevent these episodes, an extra dose of 100 mg/day thalidomide was used during six months, followed by a follow-up period of six more months after thalidomide discontinuation. METHODS We included 42 patients with multibacillary (MB) leprosy who had episodes of ENL. They were male and female patients aged between 18 and 84 years. RESULTS Of the 42 patients, 39 (92.85%) had the lepromatous form and three (7.15%) had the borderline form. We found that 100% of patients had no reactional episode during the use of the drug. During the follow-up period after thalidomide discontinuation, 33 (78.57%) patients had no reactional episode and nine (21.43%), all of them with the lepromatous form, had mild episodes, which were controlled using non-steroidal anti-inflammatory. There were no thalidomide-related side effects. CONCLUSION A maintenance dose of 100 mg/day of thalidomide showed to be effective to prevent repeated type 2 reactional episodes of ENL. PMID:24770503
Background This study is about the contribution of occupational therapy inside a rehabilitation group, and we focus on the autonomy of patients with disabilities due to leprosy. There are few studies on the use of assistive technology by leprosy patients; to our knowledge, none of them aim to have a subjective approach of care. Our purpose was to analyze the repercussions of assistive technology on autonomy of care of the self in patients with sequels of leprosy. Methods A qualitative, descriptive exploratory study with a semi-structured interview and a field observation as a research method was conducted between November 2014 and February 2015 at a University Hospital in Rio de Janeiro. Findings Eight patients from the service of Occupational Therapy were interviewed, and 44 hours of observation were performed. Interviews followed a semi-structured script and a field journal was used to take notes. Analysis was conducted by the hermeneutic approach. Costs were obtained after a global cost analysis of the fixed and variable expenses and direct and indirect costs to the manufactured products with an amount of 100 dollars. Results were grouped according to the following categories: contribution of the adapted devices for the care of the self and feelings and sensations provoked by the use of self-help devices. The reports revealed feelings, perceptions and meaningful contents about the social, familiar and individual dimensions, also the stigma coupled with leprosy. However, forms of re-signification were elaborated. Conclusions Assistive technology empowers the subject to perform care of the self and promotes social inclusion. PMID:27124408
Legendre, Davey P; Muzny, Christina A; Swiatlo, Edwin
Hansen's disease, also known as leprosy, remains an important public health problem throughout the world, including North America. The causative microbe in Hansen's disease is Mycobacterium leprae, an acid-fast organism that is difficult to grow in vitro. The nine-banded armadillo is the major animal reservoir in the United States. Manifestations of disease vary based on host immune response and can range from tuberculoid to lepromatous leprosy (paucibacillary to multibacillary disease). Hansen's disease typically affects the skin, nerves, and eyes, and patients may present with skin lesions, weakness, numbness, eye pain, or loss of vision. Definitive diagnosis is based on a combination of physical examination findings and skin biopsy and/or smear. Modern antibacterial therapy typically consists of combinations of dapsone and rifampin with or without clofazimine. Clofazimine is available only as an investigational drug through the National Hansen's Disease Program. Other options include moxifloxacin, ofloxacin, minocycline, and clarithromycin. Hansen's disease is associated with type 1 (reversal) and type 2 (erythema nodosum leprosum) immunologic reactions, during which the disease process appears to worsen dramatically. These reactions may occur at any time before, during, or after treatment. Antibacterial therapy should usually be continued during these reactions. Treatment options for these reactions differ based on clinical manifestations and include corticosteroids, thalidomide, pentoxiphylline, tumor necrosis factor inhibitors, and T cell inhibitors. Prompt diagnosis, antimicrobial therapy, and treatment of reactions dramatically reduce complications of the disease.
Nogueira, Maria Renata Sales; Latini, Ana Carla Pereira; Nogueira, Maria Esther Salles
Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.
Nogueira, Maria Renata Sales; Latini, Ana Carla Pereira; Nogueira, Maria Esther Salles
Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions. PMID:27706378
Abide, John M; Webb, Risa M; Jones, Harriet L; Young, LaFarra
Three native-born patients from the Mississippi Delta presented with leprosy over a 13-month period. None had a history of foreign travel, contact with each other, or known leprosy patients. Two patients' lesions lacked anesthesia, and all had a history of armadillo exposure. These cases add to the association of armadillo exposure and the subsequent development of leprosy.
This article is a compilation of our findings recorded in the recent past where we have investigated the serological performance of Mycobacterium leprae antigens like-serine-rich 45 kDa protein (45 kD), early secretary antigenic target-6 (ESAT-6), culture filtrate protein-10 (CFP-10) and phenolic glycolipid-I (PGL-I) for detection (employing antibody detecting ELISA) of leprosy patients, particularly those belonging to the paucibacillary (PB) group. All of these antigens were capable of detecting, by themselves the majority (82-100%) of multibacillary (MB) patients. However, with respect to PB patients, only 18-47% (i.e. less than half) of the cases could be detected. Based on the results of serological assays for each of the four antigens separately a combinatorial approach was performed for these antigens, which increased the sensitivity for detection of PB patients to 73%, giving 36% improvement over conventional PGL-I based ELISA. Thus, the multi-antigenic serological approach is worthwhile for its establishment for detection of leprosy patients. Since ESAT-6 and CFP-10 are secreted proteins by nature, antibodies against them are worth exploring for detection of early infections and for monitoring of treatment efficiency. Nevertheless, efforts towards identification of more new antigens with serological potential are still desirable in order to further improve the detection rate of leprosy.
Mandal, B C; Bandyopadhyay, G
Leprosy and tuberculosis (TB) both are still rampant in India. Leprosy predominantly presents through skin manifestations whereas cutaneous manifestations of TB though not so frequent but are not rare. Lupus vulgaris (LV), the commonest of all cutaneous manifestations of TB, mimics leprosy very closely and may prompt the examiner to misdiagnose leprosy, especially, by health workers (HW), in a field situation, where leprosy is diagnosed and treated on clinical basis alone as per NLEP guidelines. Because of existing stigmata, such wrong diagnosis can put the patient and the party under psychological stress and creates unnecessary complications.
Sarker, U K; Uddin, M J; Chowdhury, R; Roy, N; Bhattacharjee, M; Roy, J
The objectives of the study were to see the association of peripheral neuropathy in leprosy and to find out the clinical profile of peripheral neuropathy and disability status in leprosy. It was descriptive type of cross sectional study was conducted among the cases of leprosy attended in the out-patient departments of neurology, Mymensingh Medical College Hospital (MMCH) and Mymensingh tuberculosis and leprosy hospital that fulfilled the inclusion criteria were included in this study, during the study period of January 2010 to December 2011.In this study of 62 cases revealed that leprosy is more common in male (71%) people and 21% leprosy patient had contact with known case of leprosy. Leprosy causes peripheral neuropathy (61.3%). Duration of occurrence of peripheral neuropathy was prolonged (>6 month) in most of the patients (47.4%) and the disease progression was also slow (63.2%). Numbness was complained by 89.4% patients and 65.8% subjects complained of weakness of limbs. Deformities and ulcers were present in 26.3% and 50% of patients respectively. Ulnar nerve (43.6%), Lateral popliteal nerve (41.9%), Posterior tibial nerve (41.9%) and Great auricular nerve (17.7%) were the most commonly involved thickened peripheral nerves. The rate of visible physical impairment (WHO Grade 2 disability) among people affected by leprosy in feet was 27.4% and in hands was 16.1%. The position and vibration sense was found to normal all patients of peripheral neuropathy.
Govindarajulu, Srinivas; Isaakidis, Petros; Shewade, Hemant Deepak; Rokade, Vasudev; Singh, Rajbir; Kamble, Sanjeev
Background Worldwide, leprosy is one of the major causes of preventable disability. India contributes to 60% of global leprosy burden. With increasing numbers of leprosy with grade 2 disability (visible disability) at diagnosis, we aimed to determine risk factors associated with grade 2 disability among new cases and explore patients and providers’ perspectives into reasons for late presentation. Methodology/Principal Findings This was an explanatory mixed-methods study where the quantitative component, a matched case-control design, was followed by a qualitative component. A total of 70 cases (grade 2 disability) and 140 controls (grade 0) matched for age and sex were randomly sampled from new patients registered between January 2013-January 2015 in three districts of Maharashtra (Mumbai, Thane and Amaravati) and interviewed using a structured close ended questionnaire. Eight public health care providers involved in leprosy care and 7 leprosy patients were purposively selected (maximum variation sampling) and interviewed using a structured open-ended interview schedule. Among cases, overall median (IQR) diagnosis delay in months was 17.9(7–30); patient and health system delay was 7(4–16.5) and 5.5(0.9–12.5) respectively; this was significantly higher than the delay in controls. Reasons for delayed presentation identified by the quantitative and qualitative data were: poor awareness of leprosy symptoms, first health care provider visited being private practitioners who were not aware about provision of free leprosy treatment at public health care facilities, reduced engagement and capacity of the general health care system in leprosy control. Conclusions Raising awareness in communities and health care providers regarding early leprosy symptoms, engagement of private health care provider in early leprosy diagnosis and increasing capacity of general health system staff, especially targeting high endemic areas that are hotspots for leprosy transmission may
Fernandes, Tania Rita Moreno de Oliveira; dos Santos, Talita Suzany Siqueira; Lopes, Ramon Rodrigues de Macedo
In Brazil, leprosy is a widespread infectious and contagious disease. Clinicians and specialists view leprosy broadly as a systemic infection, since, in its manifestations, it mimics many conditions, such as rheumatic, vascular, ENT, neurological and dermatological diseases. There are few studies that characterize the factors associated with ulcers in leprosy. These injuries should be prevented and treated promptly to avoid serious problems like secondary infections, sepsis, carcinomatous degeneration and amputations. We describe a patient with ulcers on his legs, involving late diagnosis of lepromatous leprosy. PMID:27828650
Garcia, Patricia; Alencar, Dayse; Pinto, Pablo; Santos, Ney; Salgado, Claudio; Sortica, Vinicius A.; Hutz, Mara H.; Santos, Sidney
Leprosy is an infectious disease caused by Mycobacterium leprae characterized by dermatoneurological signs and symptoms that has a large number of new cases worldwide. Several studies have associated interleukin 10 with susceptibility/resistance to several diseases. We investigated haplotypes formed by three single nucleotide polymorphisms (SNPs) located in the IL10 gene (A-1082G, C-819T, and C-592A) in order to better understand the susceptibility to and severity of leprosy in an admixed northern Brazil population, taking into account estimates of interethnic admixture. We observed the genotypes ACC/ACC (P = 0.021, odds ratio [OR] [95% confidence interval (CI)] = 0.290 [0.085 to 0823]) and ACC/GCC (P = 0.003, OR [95% CI] = 0.220 [0.504 to 0.040]) presenting significant results for protection against leprosy development, framed in the profiles of low and medium interleukin production, respectively. Therefore, we suggest that genotypes A-1082G, C-819T, and C-592A formed by interleukin-10 polymorphisms are closely related to protection of the leprosy development in an admixed northern Brazil population, in particular ACC/ACC and ACC/GCC genotypes. PMID:23966553
Fotedar, A; Mustafa, A S; Narang, B S; Talwar, G P
Two acetoacetylated derivatives of Mycobacterium leprae with variable hapten groups and a conjugate with tetanus toxoid were prepared. These were tested as antigens along with unmodified M. leprae in the leucocyte migration inhibition response of leucocytes from clinically, bacteriologically and histopathologically confirmed cases of lepromatous leprosy. LMI response was poor with M. leprae, but was significantly enhanced with acetoacetylated M. leprae. PMID:6751637
Circulating complexes in leprosy studied by the platelet aggregation test. The platelet aggregation test and its relation to the rubino test and other sero-immunological parameters in 135 patients with leprosy
Wager, O.; Penttinen, K.; Almeida, J. D.; Opromolla, D. V. A.; Godal, T.; Kronvall, G.
Sera from 135 patients with leprosy were tested by the platelet aggregation test (PAT), by the Rubino test and by other sero-immunological assays. PAT positivity (titre≥10) was 53% in the lepromatous subgroups and 5% in the tuberculoid subgroups (P<0·005). The higher PAT titres and Rubino titres clustered significantly (P<0·0005) toward the lepromatous end of the disease spectrum. A statistically significant correlation was found between the PAT and the Rubino titres (0·05>P>0·025). Removal of the effect of the disease spectrum, however, resulted in a partial correlation between the PAT and the Rubino titres that was not significant (P>0·1), suggesting different basic mechanisms for the platelet aggregation (PA) and the Rubino activity of the lepromatous sera. The correlation between the PAT titres and twenty-nine other sero-immunological parameters was calculated, and a highly significant correlation was found between the PAT and the IgG level (P<0·005) and between the PAT and the antistaphylolysin-α titre (P<0·005). The PA activity in most lepromatous sera studied sedimented in the heavy (>19S) fractions and was inhibitable by IgM rheumatoid factor. It thus fulfilled the criteria for IgG complexes as defined in previous studies with known model Ag/Ab complexes and with sera from patients with immune complex states. The addition of an excess of soluble mycobacterial antigens affected the PA activity of some lepromatous sera, which suggests that the putative complexes were composed of mycobacterial antigens complexed with corresponding IgG antibody. It was concluded that the PAT is a sensitive detector of IgG complexes peculiar to the lepromatous leprosy. In leprosy the discriminatory power of the PAT seems to be superior to that of other immune complex tests recently applied for the analysis of leprosy series. ImagesFIG. 1 PMID:369750
Reis, Felipe J J; Cunha, Antonio José Ledo A; Gosling, Artur Padão; Fontana, Ana Paula; Gomes, Maria Katia
Surgical nerve decompression in leprosy is indicated to prevent or treat nerve damage, and to improve sensory motor function and quality of life (QoL). The purpose of this study was to describe QoL of leprosy patients after surgical nerve decompression. Participants who underwent neurolysis in the last 5 years were recruited. The assessment consisted of collecting demographic and clinical information, QoL and its domain scores. Descriptive statistical analysis of demographic and clinical data was presented. Included 33 patients (43 +/- 11.0 years) who had neurolysis with a total of 61 nerves operated. The results of WHOQOL-bref showed that overall QoL mean was 11.2 (+/- 3.63) and domains scored as follow: physical (11.0 +/- 3.56), environment (11.47 +/- 2.11), psychological (13.29 +/- 2.79) and social relations (15.03 +/- 3.66). Measures of QoL should become part of the standard battery of tools used to assess health and well-being and it may contribute to identifying patients' needs in rehabilitation.
Cardona-Castro, Nora; Beltrán-Alzate, Juan Camilo; Romero-Montoya, Marcela
Follow-up of the household contacts (HHC) of leprosy patients is still the best strategy for early detection of leprosy. HHC from a post-elimination region of Colombia studied in 2001-2002 were re-contacted in 2007. They were tested at both times by clinical examination, bacillary index (BI), PCR from a slit skin smear (SSS) and anti PGL-1 IgM titres. Thirty-two of 61 HHC (52%) were re-contacted. Nine HHC (28%) showed sero-conversion and one had a skin lesion (BI negative, nested PCR positive). Periodic evaluation of HHC can contribute to the detection of infected HHC as well as new and early leprosy cases.
Blok, David J; de Vlas, Sake J; Fischer, Egil A J; Richardus, Jan Hendrik
Leprosy or Hansen's disease is an infectious disease caused by the bacterium Mycobacterium leprae. The annual number of new leprosy cases registered worldwide has remained stable over the past years at over 200,000. Early case finding and multidrug therapy have not been able interrupt transmission completely. Elimination requires innovation in control and sustained commitment. Mathematical models can be used to predict the course of leprosy incidence and the effect of intervention strategies. Two compartmental models and one individual-based model have been described in the literature. Both compartmental models investigate the course of leprosy in populations and the long-term impact of control strategies. The individual-based model focusses on transmission within households and the impact of case finding among contacts of new leprosy patients. Major improvement of these models should result from a better understanding of individual differences in exposure to infection and developing leprosy after exposure. Most relevant are contact heterogeneity, heterogeneity in susceptibility and spatial heterogeneity. Furthermore, the existing models have only been applied to a limited number of countries. Parameterization of the models for other areas, in particular those with high incidence, is essential to support current initiatives for the global elimination of leprosy. Many challenges remain in understanding and dealing with leprosy. The support of mathematical models for understanding leprosy epidemiology and supporting policy decision making remains vital.
Grauwin, M Y; Saboye, J; Cartel, J L
This paper deals with the results observed in 21 ancient leprosy patients suffering from lagophthalmos (13 of whom suffered from bilateral lagophthalmos) and treated by the Edgerton-Montandon surgical procedure which associates lateral canthopexy and tarsorraphy. Eighteen of the 21 treated patients were reviewed at one month after the procedure and, overall, results could be evaluated for 30 eyes. Improvement was noted in all of the 30 eyes and, globally, the residual palpebral fissure (during voluntary closing of the eyes by the patient) decreased from 6.7 mm before the procedure to 1.8 after the procedure. The following recommendations may be proposed. For young patients with intact corneal sensation, the Gillies procedure remains the procedure of choice to correct lagophthalmos. For older patients with corneal anesthesia, at high risk of blindness, the Edgerton-Montandon procedure should be recommended.
Santana, Nadja de Lima; Rêgo, Jamile Leão; Oliveira, Joyce Moura; de Almeida, Lucas Frederico; Braz, Marcos; Machado, Lídia Maria Medeiros; Machado, Paulo Roberto Lima; Castellucci, Léa Cristina
BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes. MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease. PMID:28327786
Antunes, Sérgio Luiz Gomes; Chimelli, Leila; Jardim, Márcia Rodrigues; Vital, Robson Teixeira; Nery, José Augusto da Costa; Corte-Real, Suzana; Hacker, Mariana Andréa Vilas Boas; Sarno, Euzenir Nunes
Nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (PNL). When acid-fast bacilli (AFB) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of Mycobacterium leprae DNA with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable PNL diagnosis. Three hundred forty nerve samples [144 from PNL patients and 196 from patients with non-leprosy peripheral neuropathies (NLN)] were examined. Both AFB-negative and AFB-positive PNL samples had more frequent histopathological alterations (epithelioid granulomas, mononuclear infiltrates, fibrosis, perineurial and subperineurial oedema and decreased numbers of myelinated fibres) than the NLN group. Multivariate analysis revealed that independently, mononuclear infiltrate and perineurial fibrosis were more common in the PNL group and were able to correctly classify AFB-negative PNL samples. These results indicate that even in the absence of AFB, these histopathological nerve alterations may justify a PNL diagnosis when observed in conjunction with pertinent clinical, epidemiological and laboratory data.
Avelleira, João Carlos Regazzi; Bernardes, Fred; Quaresma, Maria Victória; Vianna, Francisco Reis
The record of the first cases of leprosy in Rio de Janeiro dates from the seventeenth century. The first local host of leprosy patients was created from 1741, and the first colonies hospitals were built in the early twentieth century, in order to avoid contagion of the population. The first structures dedicated to research also date from this time: the Leprosy International Institute, the Leprology Institute, and the Leprosy Laboratory of the Oswaldo Cruz Foundation, where the most prestigious leprologists of Rio de Janeiro worked. Currently, investigations are focused on the Oswaldo Cruz Foundation; additionally, leprosy patients are treated at municipal health centers and state hospitals, and former colony hospitals only accept patients with severe disabilities. PMID:24937834
Beltrán-Alzate, Camilo; López Díaz, Fernando; Romero-Montoya, Marcela; Sakamuri, Rama; Li, Wei; Kimura, Miyako; Brennan, Patrick
An active search for Mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program. This program was a World Health Organization initiative for drug resistance surveillance in leprosy, where Colombia is a sentinel country. M. leprae DNA from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (DRDR) in rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone and ofloxacin drug-resistance, respectively. Three isolates exhibited mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu), suggesting multidrug resistance. One isolate had a double mutation in folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR that required in vivo evaluation of their association or not with drug resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to drug resistance and were isolated from relapsed patients; the likelihood of relapse was significantly associated with the presence of confirmed resistance mutations (OR range 20.1–88.7, p < 0.05). Five of these relapsed patients received dapsone monotherapy as a primary treatment. In summary, the current study calls attention to M. leprae resistance in Colombia, especially the significant association between confirmed resistance mutations and relapse in leprosy patients. A high frequency of DRDR mutations for rifampicin was seen in a region where dapsone monotherapy was used extensively. PMID:27706165
Hohmann, N; Voss-Böhme, A
While in antiquity both leprosy and tuberculosis were prevalent in Europe, leprosy declined thereafter and, simultaneously, tuberculosis prevalence increased. Since both diseases are caused by mycobacterial infections, it has been suggested that there might be a causal relationship between both epidemics. Chaussinand observed the inverse prevalence of leprosy and tuberculosis and suggested that individuals with a latent tuberculosis infection are protected from acquiring leprosy. His cross-immunity hypothesis has been countered more recently by a co-infection hypothesis. The latter suggestion, proposed by Donoghue, states that people being infected with multi-bacillary leprosy are more susceptible to tuberculosis, which leads to increased mortality from the disease. This study utilizes mathematical modeling to explore the epidemiological consequences of the co-infection hypothesis for realistically confined parameter values. While the co-infection hypothesis appears plausible at first glance, a second thought reveals that it comprises also substantial consequences for tuberculosis epidemics: if co-infection raises the mortality rate above that of purely tuberculosis infected persons, then tuberculosis might as well be eradicated by leprosy. It is the specific interplay of both increased susceptibility towards tuberculosis and increased death rate when co-infected that determines the epidemiological fate. As a result of this analysis, it is shown that there is a large parameter region where the eventual disappearance of leprosy could indeed be explained by co-infection. This parameter region is considerably larger than that predicted by the cross-immunity hypothesis. This shows that the co-infection hypothesis should be considered a significant alternative to the cross-immunity hypothesis. The time scales at which the effects of co-infection are observed depend critically on the spatial distribution of the individuals but reach epidemiologically realistic values for
Belone, Andrea de Faria F.; Rosa, Patrícia S.; Trombone, Ana P. F.; Fachin, Luciana R. V.; Guidella, Cássio C.; Ura, Somei; Barreto, Jaison A.; Pinilla, Mabel G.; de Carvalho, Alex F.; Carraro, Dirce M.; Soares, Fernando A.; Soares, Cleverson T.
Leprosy, an infectious disease caused by Mycobacterium leprae, affects millions of people worldwide. However, little is known regarding its molecular pathophysiological mechanisms. In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions by using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female). The evaluation identified 1580 differentially expressed mRNAs [Fold Change (FC) ≥ 2.0, p ≤ 0.05] in diseased lesions vs. healthy controls. Some of these genes were observed in all forms of the disease (CD2, CD27, chit1, FA2H, FAM26F, GZMB, MMP9, SLAMF7, UBD) and others were exclusive to reactional forms (Type “1” reaction: GPNMB, IL1B, MICAL2, FOXQ1; Type “2” reaction: AKR1B10, FAM180B, FOXQ1, NNMT, NR1D1, PTX3, TNFRSF25). In literature, these mRNAs have been associated with numerous pathophysiological processes and signaling pathways and are present in a large number of diseases. The role of these mRNAs maybe studied in the context of developing new diagnostic markers and therapeutic targets for leprosy. PMID:26635870
Pasipanodya, Jotam G.; Mubanga, Mwenya; Ntsekhe, Mpiko; Pandie, Shaheen; Magazi, Beki T.; Gumedze, Freedom; Myer, Landon; Gumbo, Tawanda; Mayosi, Bongani M.
Background Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis. Methods Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log10 colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients. Findings Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20–71) years. The median, follow up was for 11.97 (range: 0·03–74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4–58) days or 3.91(range: 0·5–8·96) log10CFU/mL, which overlapped with the range of 3.24–7.42 log10CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5·23 months on directly observed therapy, a CD4 + count of ≤ 199.5/mL, and TTP ≤ 14 days (bacillary load ≥ 5.53 log10 CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion. Interpretation Patients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drives mortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal
Andrade, Priscila Ribeiro; Ferreira, Helen; Nery, José Augusto da Costa; Côrte-Real, Suzana; da Silva, Gilberto Marcelo Sperandio; Rosa, Patricia Sammarco; Fabri, Mario; Sarno, Euzenir Nunes
Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages. PMID:28056107
Grzybowski, Andrzej; Sak, Jarosław; Pawlikowski, Jakub; Nita, Małgorzata
One of the most important dermatologic diseases from the sociologic viewpoint has been leprosy. Those with leprosy were isolated, excluded from society, and stigmatized. Such a stigma indicates the strong feeling that a leprosy patient is shameful and should not be accepted by society. During the first millennium, leprosy was rapidly inscribed in the system of religious prohibitions-the disease was a punishment by God for wrongdoing, and the disease was associated with the lower spheres of the society. Social perception of leprosy gradually changed during the time of Crusades. The care for lepers became a Christian obligation, and celebrating Holy Masses as for the dead was forsaken. The sick were forced to stay at leprosaria, particularly from the 14th through the 19th centuries when fear of leprosy was at a high point. Admission to a leprosarium was mandatory not only for patients with leprosy but also even those suspected of having the disease.
de Lima, Adma Silva; Pizzol, Vanessa Irusta dal; Fritsch, Scheila; Fonseca, Gabriela Poglia; Mulinari-Brenner, Fabiane Andrade; Muller, Carolina de Souza; Ottoboni, Vanessa Cristhine Dalombo
Due to mounting evidences of interaction between Hansen's bacilli with endothelial cells and the paucity of studies addressing the presence of nailfold capillaroscopic alterations in patients with Hansen's disease, a study was carried out in order to verify the presence of capillaroscopic alterations in patients with leprosy in its various forms and its correlation with clinical parameters. Ten patients were evaluated at a specialized university service. Sixty percent of those had some capillaroscopic change, such as micro-hemorrhages, ectatic, bushy and corkscrew capillaries. Such changes were unspecific, which suggests there is not a specific pattern for this disease. PMID:27828654
Rao, P Narasimha; Suneetha, Sujai
Pure neuritic leprosy has always been an enigma due to its clinical and management ambiguities. Although only the Indian Association of Leprologist's classification recognizes 'pure neuritic leprosy' as a distinct sub group of leprosy, cases nonetheless are reported from various countries of Asia, Africa, South America and Europe, indicating its global relevance. It is important to maintain pure neuritic leprosy as a subgroup as it constitutes a good percentage of leprosy cases reported from India, which contributes to more than half of global leprosy numbers. Unfortunately, a high proportion of these patients present with Grade 2 disability at the time of initial reporting itself due to the early nerve involvement. Although skin lesions are absent by definition, when skin biopsies were performed from the skin along the distribution of the affected nerve, a proportion of patients demonstrated leprosy pathology, revealing sub-clinical skin involvement. In addition on follow-up, skin lesions are noted to develop in up to 20% of pure neuritic leprosy cases, indicating its progression to manifest cutaneous disease. Over the decades, the confirmation of diagnosis of pure neuritic leprosy has been subjective, however, with the arrival and use of high-resolution ultrasonography (HRUS) for nerve imaging, we have a tool not only to objectively measure and record the nerve thickening but also to assess the morphological alterations in the nerve including echo texture, fascicular pattern and vascularity. Management of pure neuritic leprosy requires multidrug therapy along with appropriate dose of systemic corticosteroids, for both acute and silent neuritis. Measures for pain relief, self-care of limbs and physiotherapy are important to prevent as well as manage disabilities in this group of patients.
Spencer, John S; Kim, Hee Jin; Wheat, William H; Chatterjee, Delphi; Balagon, Marivic V; Cellona, Roland V; Tan, Esterlina V; Gelber, Robert; Saunderson, Paul; Duthie, Malcolm S; Reece, Stephen T; Burman, William; Belknap, Robert; Mac Kenzie, William R; Geluk, Annemieke; Oskam, Linda; Dockrell, Hazel M; Brennan, Patrick J
A simple serodiagnostic test based on the Mycobacterium leprae-specific phenolic glycolipid I(PGL-I), for individuals with leprosy is nearly universally positive in leprosy patients with high bacillary loads but cannot be used as a stand-alone diagnostic test for the entire spectrum of the disease process. For patients with early infection with no detectable acid-fast bacilli in lesions or with low or no antibody titer to PGL-I, as in those at the tuberculoid end of the disease spectrum, this diagnostic approach has limited usefulness. To identify additional M. leprae antigens that might enhance the serological detection of these individuals, we have examined the reactivity patterns of patient sera to PGL-I, lipoarabinomannan (LAM), and six recombinant M. leprae proteins (ML1877, ML0841, ML2028, ML2038, ML0380, and ML0050) by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Overall, the responses to ML2028 (Ag85B) and ML2038 (bacterioferritin) were consistently high in both multibacillary and paucibacillary groups and weak or absent in endemic controls, while responses to other antigens showed considerable variability, from strongly positive to completely negative. This analysis has given a clearer understanding of some of the differences in the antibody responses between individuals at opposite ends of the disease spectrum, as well as illustrating the heterogeneity of antibody responses toward protein, carbohydrate, and glycolipid antigens within a clinical group. Correlating these response patterns with a particular disease state could allow for a more critical assessment of the form of disease within the leprosy spectrum and could lead to better patient management.
Arora, M; Katoch, K; Natrajan, M; Kamal, R; Yadav, V S
A hospital based retrospective study was carried out to determine change in the profile of disease in leprosy patients taking 1995 as baseline and compared with the profile seen in year 2000. A total of 2149 and 1703 cases were studied respectively of year 1995 and 2000. Male to female ratio slightly increased from 2.95:1 in year 1995 to 3.4:1 in year 2000. Majority of patients were of borderline type in both years. Proportion of cases with MB leprosy was nearly same in females (60.8%) and males (63.1%) in year 1995 and in year 2000 (64.8% females and 67.6% males). Proportion of highly bacillary cases has decreased over the years in females (from 20.95% in 1995 to 11.7% in year 2000, p=0.03) as well as in males (from 25% in 1995 to 15.5% in year 2000, p=0.001). Incidence of total reactions increased from 27.6% to 35.4% over the years which is significant (p<0.01). Proportion of type 1 reactions were more in reproductive age group in females in both years (p<0.05) and of type 2 reactions were significantly (p > or = 0.05) more in males in both years. Incidence of disability (both grade 1 and grade 2) was significantly more in males than in females in both years (p > or = 0.04). Grade 1 disability has significantly increased over years in females from 10.11% to 14.8%(p<0.03) as well as in males from 13.27% to 21.3%(p<0.001). Onset of reactions was associated with pregnancy/lactation in 62% of cases and with menopause in 21% of cases in 2000, which suggests strong correlation with hormonal imbalance. To conclude while leprosy incidence has declined after MDT, recognition and management of reactions in women around changes in their hormonal levels should be properly monitored for early and effective management.
Leon, Kristoffer E; Jacob, Jesse T; Franco-Paredes, Carlos; Kozarsky, Phyllis E; Wu, Henry M; Fairley, Jessica K
Background. Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe the characteristics of patients with HD in a US clinic, including an assessment of delays in diagnosis and HD reactions, which have both been associated with nerve damage. Methods. A retrospective chart review was conducted on patients seen at an HD clinic in the southern United States between January 1, 2002 and January 31, 2014. Demographic and clinical characteristics were summarized, including delays in diagnosis, frequency of reactions, and other complications including peripheral neuropathy. Results. Thirty patients were seen during the study time period. The majority of patients were male (73%) and had multibacillary disease (70%). Brazil, Mexico, and the United States were the most frequent of the 14 countries of origin. Hansen's disease "reactions", severe inflammatory complications, were identified among 75% of patients, and nerve damage was present at diagnosis in 36% of patients. The median length of time between symptom onset and diagnosis was long at 12 months (range, 1-96), but no single factor was associated with a delay in diagnosis. Conclusions. The diagnosis of HD was frequently delayed among patients referred to our US clinic. The high frequency of reactions and neuropathy at diagnosis suggests that further efforts at timely diagnosis and management of this often unrecognized disease is needed to prevent the long-term sequelae associated with irreversible nerve damage.
Leon, Kristoffer E.; Jacob, Jesse T.; Franco-Paredes, Carlos; Kozarsky, Phyllis E.; Wu, Henry M.; Fairley, Jessica K.
Background. Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe the characteristics of patients with HD in a US clinic, including an assessment of delays in diagnosis and HD reactions, which have both been associated with nerve damage. Methods. A retrospective chart review was conducted on patients seen at an HD clinic in the southern United States between January 1, 2002 and January 31, 2014. Demographic and clinical characteristics were summarized, including delays in diagnosis, frequency of reactions, and other complications including peripheral neuropathy. Results. Thirty patients were seen during the study time period. The majority of patients were male (73%) and had multibacillary disease (70%). Brazil, Mexico, and the United States were the most frequent of the 14 countries of origin. Hansen's disease “reactions”, severe inflammatory complications, were identified among 75% of patients, and nerve damage was present at diagnosis in 36% of patients. The median length of time between symptom onset and diagnosis was long at 12 months (range, 1–96), but no single factor was associated with a delay in diagnosis. Conclusions. The diagnosis of HD was frequently delayed among patients referred to our US clinic. The high frequency of reactions and neuropathy at diagnosis suggests that further efforts at timely diagnosis and management of this often unrecognized disease is needed to prevent the long-term sequelae associated with irreversible nerve damage. PMID:27186586
Alves, Cynthia Rossetti Portela; Ribeiro, Maria Mônica Freitas; Melo, Elza Machado; Araújo, Marcelo Grossi
In the context of declining leprosy endemicity worldwide, keeping the interest in knowledge and expertise in leprosy alive has been a matter of concern. Approaching the problem only in primary care, without the proper integration with other levels of care in the health system fails to account for the complexity of the disease. Training professionals to work at different levels of health care is a current challenge. The objective of this review was to look for experiences related to the teaching of leprosy both in undergraduate courses in the field of health sciences and in training programs for professionals who work in patient care. We highlight the role of the dermatologist in the management of control programs, diagnosis and treatment of the disease, as well as in the continuous education of other health professionals. PMID:24937820
Chaduvula, Mehervani; Murtaza, A.; Misra, Namita; Narayan, N. P. Shankar; Ramesh, V.; Prasad, H. K.; Rani, Rajni; Chinnadurai, R. K.
Lsr2 protein of Mycobacterium leprae was shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphoproliferation to M. leprae and Lsr2 antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on the M. leprae nonresponders in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A to F and overlapping peptides p1 to p16) in in vitro T cell responses. A total of 125 leprosy and 13 tuberculosis patients and 19 healthy controls from the area of endemicity (here, healthy controls, or HC) were investigated. The highest responses were observed (67 to 100%) in HC for all peptides except p1 to p3, and the lowest was observed in tuberculosis patients. Significant differences in lymphoproliferation were observed in T, L, and HC groups (analysis of variance [ANOVA], P = 0.000 to 0.015) for all end-to-end peptides except B and for p5 and p7 to p10. Hierarchical recognition between lepromatous and tuberculoid leprosy was noted for p8 (P < 0.05) and between the HC and L groups for p7 to p10, p15, and p16 (P < 0.005 to P < 0.02). Significant lymphoproliferation was observed to peptides A to F and p1 to p9, p11, p12, p15, p16 (P = 0.000 to 0.001) with 40% responding to peptides C and p16 in L patients. Lepromatous patients also showed significantly higher levels of a gamma interferon (IFN-γ) response to peptide C than to other peptides (P < 0.05). Major histocompatibility complex (MHC) class II bias for peptide recognition was not observed. These studies indicate that Lsr2 has multiple T cell epitopes that induce in vitro T cell responses in the highly infective lepromatous leprosy patients. PMID:22144494
... of areas where drug resistance is occurring, and molecular epidemiology. To learn about risk factors for Leprosy ... research in leprosy today include genetic probes for molecular epidemiology, and new immunologic tests for early detection ...
Karaçorlu, M A; Sürel, Z; Cakiner, T; Hanyaloğlu, E; Saylan, T; Mat, C
Ocular complications of leprosy patients often develop insidiously and with few if any symptoms. This study involves measurement of the pupil cycle time (PCT) to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement. The study included 19 lepromatous (LL), 19 borderline lepromatous (BL), and five borderline tuberculoid (BT) leprosy patients and involved 25 healthy volunteers, 10 patients with pulmonary tuberculosis and eight with Duhring disease. The PCT was measured in these groups. In all leprosy groups included in the study the PCT was higher than in the control groups. Moreover, the PCT of the leprosy patients without any intraocular involvement was higher than in the controls. These results show that in the ophthalmic examination of leprosy patients without any symptoms the fact that autonomic nerve system of the eye is affected by the leprosy can often be determined by measuring the PCT. PMID:1991087
Karaçorlu, M A; Sürel, Z; Cakiner, T; Hanyaloğlu, E; Saylan, T; Mat, C
Ocular complications of leprosy patients often develop insidiously and with few if any symptoms. This study involves measurement of the pupil cycle time (PCT) to evaluate the autonomic nerve system of the iris to determine the presence of subclinical intraocular involvement. The study included 19 lepromatous (LL), 19 borderline lepromatous (BL), and five borderline tuberculoid (BT) leprosy patients and involved 25 healthy volunteers, 10 patients with pulmonary tuberculosis and eight with Duhring disease. The PCT was measured in these groups. In all leprosy groups included in the study the PCT was higher than in the control groups. Moreover, the PCT of the leprosy patients without any intraocular involvement was higher than in the controls. These results show that in the ophthalmic examination of leprosy patients without any symptoms the fact that autonomic nerve system of the eye is affected by the leprosy can often be determined by measuring the PCT.
Saylan, T; Sutlas, M; Yuksel, A; Cakiner, T; Aytekin, H
Between 1983-1987, the Istanbul Leprosy Centre (ILC) organized in Van a leprosy education program for medical personnel and the local population, subsequently whole population surveys and case contact surveys were carried out independently in different regions. 66 new cases were detected during those years 56 (85%) patients were diagnosed by ILC teams at the field and at the hospital. In 49 (74%) of the 66 there was one or more close contact within the family, in 17 (26%) there was none, but old patients in the village or nearby. It is concluded that the education of the local medical authorities and the population is of utmost importance for the early diagnosis and patient-close contact surveys are the best for our country.
Alotaibi, Mohammad H; Bahammam, Salman A; Ur Rahman, Saeed; Bahnassy, Ahmed A; Hassan, Imad S; Alothman, Adel F; Alkayal, Abdulkareem M
Leprosy is a chronic disease caused by Mycobacterium leprae. Although the occurrence of leprosy has declined in Saudi Arabia, it has not yet been eradicated. To our knowledge, this descriptive retrospective study is the first to assess the clinical presentation of leprosy at the time of diagnosis in Saudi Arabia. All study subjects were leprosy patients admitted to Ibn Sina hospital, the only referral hospital for leprosy in Saudi Arabia, between January 2000 and May 2012. A total of 164 subjects, the majority of whom (65%) were between 21 and 50 years of age, were included, and the male-to-female ratio was 2.8:1. Of these 164 patients, 63% were Saudis, and 77% of all admitted patients were from the western region. Lepromatous leprosy was observed most frequently (33%), and 31% of cases had a positive history of close contact with leprosy. At the time of diagnosis, 84% of all subjects presented with skin manifestation. The prevalence of neurological deficit at the time of diagnosis was 87%. Erythema nodosum leprosum (E.N.L.) developed in only 10% of all subjects. Further studies are needed to determine the clinical characteristics pertaining to each type of leprosy in the region, and training courses in caring for and diagnosing patients with leprosy should be organized for health workers.
Antia, N H
The anaesthetic foot in leprosy poses the most major problem in the rehabilitation of its patients. Various attempts have been made to produce protective footwear such as the microcellular rubber-car-tyre sandals. Unfortunately these attempts have had little success on a large scale because of the inability to produce them in large numbers and the stigma attached to such unusual footwear. While such footwear may be superior to the 'tennis' shoe in protecting the foot from injury by the penetration of sharp objects, it fails to distribute the weight-bearing forces which is the major cause of plantar damage and ulceration in the anaesthetic foot. This can be achieved by providing rigidity to the sole, as demonstrated by the healing of ulcers in plaster of paris casts or the rigid wooden clog. A new type of moulded plastic footwear has been evolved in conjunction with the plastic footwear industry which provides footwear that can be mass produced at a low price and which overcomes the stigma of leprosy. Controlled rigidity is provided by the incorporation of a spring steel shank between the sponge insole and the hard wearing plastic sole. Trials have demonstrated both the acceptability of the footwear and its protective effects as well as its hard wearing properties.
Chiaratti, Francielle Chiavelli; Daxbacher, Egon Luiz Rodrigues; Neumann, Antonielle Borges Faria; Jeunon, Thiago
Leprosy is a chronic disease characterized by manifestations in the peripheral nerves and skin. The course of the disease may be interrupted by acute phenomena called reactions. This article reports a peculiar case of type 2 leprosy reaction with Sweet's syndrome-like features as the first clinical manifestation of leprosy, resulting in a delay in the diagnosis due to unusual clinical presentation. The patient had clinical and histopathological features reminiscent of Sweet's syndrome associated with clusters of vacuolated histiocytes containing acid-fast bacilli isolated or forming globi. Herein, it is discussed how to recognize type 2 leprosy reaction with Sweet's syndrome features, the differential diagnosis with type 1 leprosy reaction and the treatment options. When this kind of reaction is the first clinical presentation of leprosy, the correct diagnosis might be not suspected clinically, and established only with histopathologic evaluation. PMID:27438203
Raju, M S; Reddy, J V
Divorcing a leprosy afflicted spouse is one of the manifestations of social stigma attached to leprosy. It mostly depends on the community's decision resulting from the physical and social threat perceived. In order to find out who were prone to divorce their leprosy afflicted spouses, 1199 community members drawn from two States, Orissa and Andhra Pradesh, were asked what their advice would be if a spouse of leprosy patient approached them for advice. The responses were cross tabulated against their demographic characteristics. While, only a small proportion of respondents advised divorce in Andhra Pradesh, they were mainly females, above SSC educated, those who did cultivation, labourers and were from poor economic group. On the other hand, in Orissa, a high proportion of the respondents suggested divorce.
Fernandes, Tania Rita Moreno de Oliveira; Korinfskin, Juliana Pedrosa; Espíndola, Mariana Mercês Mesquita; Corrêa, Lis Moreno de Oliveira
Leprosy is clinically characterized by involvement of peripheral nerves and skin. The immunological profile of the individual defines the diversity of clinical manifestations, from skin disorders to systemic manifestations, especially the articulation ones, common in multibacillary forms, which may mimic collagen diseases and often posing diagnostic difficulties in endemic areas. This is a case report of asymmetric polyarthritis of small and large articulations associated with skin lesions which had been treated by a rheumatologist for 2 years with initial clinical diagnosis of rheumatoid arthritis, and later, with the appearance of skin lesions, of systemic lupus erythematosus. PMID:24770512
Lambert, Saba M.; Alembo, Digafe T.; Nigusse, Shimelis D.; Yamuah, Lawrence K.; Walker, Stephen L.; Lockwood, Diana N. J.
Background Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. Results Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. Conclusions This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed. PMID:27046330
Grzybowski, Andrzej; Nita, Małgorzata
For many years, the biblical term tzaraat has referred to leprosy. In fact, the disease or diseases described under this name have no relationship to leprosy, as it was known in the Middle Ages or today; moreover, the term referred not only to skin disease, but also to the state of the ritual impurity and punishment for the sins. Although the real nature of tzaraat remains unknown, the differential diagnosis might include the following: Psoriasis, seborrheic dermatitis, favus, dermatophyte infections, nummular dermatitis, atopic dermatitis, pityriasis rosea, crusted scabies, syphilis, impetigo, sycosis barbae, alopecia areata, furuncles, scabies, neurodermatitis, scarlet fever, lupus erythematosus, lichen sclerosus et atrophicus, folliculitis decalvans, morphea, sarcoidosis, and lichen planopilaris. Leprosy became interchangeable with the biblical leprosy due to two inaccurate translations: The Hebrew tzaraat was first translated into Greek as leprosy in the sixth century, and later, the word leprosy was translated into Arabic as lepra in the ninth century.
Silva, Maria Eduarda Gomes da Cruz; de Souza, Carlos Dornels Freire; Silva, Susanne Pinheiro Costa e; da Costa, Flávia Monteiro; do Carmo, Rodrigo Feliciano
BACKGROUND Leprosy is an infectious disease caused by Mycobacterium leprae, able to infect large numbers of people. This work is relevant to Juazeiro-BA, a hyper-endemic area for leprosy, since unravel the behavior of the disease in the area, may suggest the decision making for sectors of surveillance, establishing strategies, organizing and evaluating programs and services. OBJECTIVES To analyze the epidemiology of leprosy in Juazeiro-BA, from 2002 to 2012. METHODS A descriptive, cross-sectional study was conducted based in data of the Diseases Notification System, assigned by the service of Epidemiology from Juazeiro-BA, between 2002 and 2012. RESULTS 1,916 new cases of leprosy were detected between 2002 and 2012, of which 921 (48.07%) represented male sex, 995 (51.93%) female, and there was a reduction in the incidence rate of leprosy per 100,000 inhabitants. Most carriers were brown individuals, with low levels of education, living in the urban area, being more prevalent in the economically active age group. Through statistical analysis we found that there are more chances of developing sequelae among men, and multibacillary individuals older than 45 years. CONCLUSIONS The work serves to direct efforts to control this disease, and highlights the importance of active search for new cases to achieve an early diagnosis, reducing the number of sequels and allowing breaking the chain of disease transmission. PMID:26734859
Stearns, A T
It is now the year 2001, and in many endemic regions leprosy remains a public health problem by any definition. It is clear that defining leprosy purely by prevalence side-steps some of the real issues. There is still much to do to solve the problem of leprosy. Control programmes require better tests for early diagnosis if leprosy is to be reduced much further. Treatment of the infection and of reactions is still far from ideal, whilst an effective vaccine would be valuable in high-risk regions. Research into the true incidence in each endemic area is essential, and control programs of the future will need a more detailed understanding of the transmission of M. leprae to permit new logical interventions. Leprosy remains a devastating disease. Much of the damage that it inflicts is irreversible, and leads to disability and stigmatization. This is perhaps the greatest problem posed. It is easy to dwell on the successes of the elimination campaign, so diverting attention from those populations of 'cured' patients who still suffer from the consequences of infection. Leprosy should be regarded as a problem unsolved so long as patients continue to present with disabilities. WHO has carried out a highly successful campaign in reducing the prevalence of leprosy, and this needs to be acknowledged, but what is happening to the incidence in core endemic areas? Maintaining this success, however, may be an even greater struggle if funding is withdrawn and vertical programmes are absorbed into national health structures. We must take heed of the historian George Santayana, 'those who cannot remember the past are condemned to repeat it'. We should take the example of tuberculosis as a warning of the dangers of ignoring a disease before it has been fully controlled, and strive to continue the leprosy elimination programmes until there are no new cases presenting with disability. The World Health Organisation has shown that leprosy is an eminently treatable disease, and has
Thompson, K; Job, C K
Iridectomy specimens from 59 leprosy patients who had adequate medical records of whom 33 belong to the lepromatous (LL) leprosy variety and 16 normal controls were studied histopathologically. All patients were bacteriologically negative and had received dapsone followed by multidrug therapy (MDT), or MDT only, or only dapsone for varying periods. It was found that leprosy, particularly lepromatous disease, did not significantly decrease the age of formation of cataract. Of the 33 LL patients studied 60.6% had silent iritis. The duration of treatment had no obvious influence on the persistence of iritis. Treatment with only 2 years of MDT for LL patients did not significantly increase the prevalence of persistent silent iritis compared to those who received other types of antileprosy therapy for long periods. It is pointed out that chronic iritis is a serious complication that continues even after the patient is declared clinically and bacteriologically cured, especially in patients who had a history of chronic iritis clinically.
Brito, Aline Lima; Monteiro, Lorena Dias; Ramos Junior, Alberto Novaes; Heukelbach, Jorg; Alencar, Carlos Henrique
The objective of this study was to characterize epidemiological and temporal trends of leprosy in the city of Fortaleza, Ceará, Brazil, from 2001 to 2012. A total of 9,658 new cases were reported. Their temporal trend was analyzed by the jointpoint regression model. The overall detection rate showed a declining trend, with annual percent change (APC) of -4.0 and 95% confidence interval (95%CI) -5.6 - -2.3. The detection rate in children under 15 years of age (APC = -1.4; 95%CI -5.4 - 2.8) and the detection rate of disability grade 2 (APC = -0.8; 95%CI -4.5 - 3.1) were stable. The proportion of female patients was descending (APC = -1,5; 95%CI -2.3 - -0.8). The proportion of multibacillary cases from 2005 to 2012 (APC = 1.4; 95%CI 0.6 - 2.3) and among them, lepromatous cases from 2004 to 2012 (APC = 6.0; 95%CI 3.4 - 8.6) were increasing. There was stability in the proportion of cases with grade 1 (APC = 1.4; 95%CI -0.9 - 3.7) and grade 2 disability (APC = 3.7; 95%CI -0.1 - 7.8). Despite the trend towards a reduction in detection, the disease transmission persists in the city. The data also suggest late diagnosis.
Citrus leprosis is one of the oldest citrus diseases, but is also one of the most important emerging citrus diseases in South and Central America, and it is apparently spreading northward towards the U.S. Research in our labs and by others has shown that citrus leprosis disease is caused by a compl...
Macedo, Raila de Brito; Santos, Tárcio; Ramos, Paulyane Bezerra Sampaio; Takano, Daniela Mayumi; Leal, Virgínia Sampaio Madeiro
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. This bacillus has a high predilection for skin and peripheral nerves. The scalp’s anatomical properties do not favor the development of such mycobacterium. We report a case of leprosy with scalp involvement, a rare occurrence in our literature. PMID:28300899
Pinho, J D; Rivas, P M S; Mendes, M B P; Soares, R E P; Costa, G C; Nascimento, F R F; Paiva, M F L; Aquino, D M C; Figueireido, I A; Santos, A M; Pereira, S R F
Leprosy is a highly infectious disease endemic to underdeveloped countries. In Maranhão State, Northeastern Brazil, the hyperendemic rate of 56.11 cases/100,000 inhabitants increased the necessity of better understanding the epidemiological profile of this population, particularly regarding efficient methods for evaluating individuals residing with diagnosed patients to understand disease transmission and the risk of infection. In this study, we examined the percentage of contacts with positive indices for Mycobacterium leprae DNA and phenol-glycolipid-1 antigen (PGL-1). PGL-1 was analyzed by an enzyme-linked immunosorbent assay, the ML-Flow test, and polymerase chain reaction of oral and nasal secretions of 808 leprosy contacts from Maranhão. PGL-1 was detected in 14.0% of patients and differed by operational classification of the index case (P < 0.05). Seropositive results of ML-Flow were 15.0% and identified individuals with and without Bacillus Calmette-Guérin vaccine scars. Molecular diagnosis detected M. leprae DNA in 5.6% of oral samples and 4.6% of nasal tissues, and 87% of subjects resided with high bacillary load patients. This study reinforces the efficacy of combining molecular and serological techniques to identify potential bacillus carriers in the asymptomatic stage of infection, such as in household contacts, highlighting the importance of these meth-ods for monitoring hyperendemic populations.
Martinez-Guzman, M A; Alvarado-Navarro, A; Pereira-Suarez, A L; Muñoz-Valle, J F; Fafutis-Morris, M
Lepromatous Leprosy (LL) is the most common presentation of leprosy in Mexico. LL patients are unable to activate an effective inflammatory response against Mycobacterium leprae probably due to the genetics of the host. Macrophage Migration Inhibitory Factor (MIF) is important to trigger inflammation processes. Two polymorphisms have been reported for human MIF: STR -794 CATT5-8 and SNP -173 G/C. 7-8 CATT repeats at -794 and the C allele at -173 increase the expression of MIF. We aim to determine the association between the polymorphisms in MIF gene and LL. We carried a case and controls study with 100 Mexican LL patients and 100 healthy subjects (HS). PCR was used for genotyping of STR -794 CATT5-8 polymorphism and PCR-RFLP for -173 G/C. We found that LL patients possess high -794 CATT repeats (47.1%) more often than HS (32.7%). In conclusion, a MIF polymorphism is associated with susceptibility to LL in Western Mexican population.
Wong, Mee Lian
The implementation of multidrug therapy (MDT) has been highly effective in curing patients and reducing leprosy prevalence. In some countries, however, a significant number of cases remain undetected or are detected late. Although compliance with drug therapy is generally good, a significant proportion still defaults treatment in countries where the leprosy burden is still high. This paper proposes that leprosy control or elimination efforts might be enhanced by the application of social marketing principles. It first outlines the principles of social marketing and then reviews a successful social marketing campaign in Sri Lanka to increase case detection and treatment. The paper concludes with a discussion of the opportunities for using social marketing principles to enhance the success of current leprosy community heath education programmes and leprosy treatment services.
Hansen’s disease (HD), or leprosy, is still considered a public health risk in much of Brazil. Understanding the dynamics of the infection at a regional level can aid in identification of targets to improve control. A compartmental continuous-time model for leprosy dynamics was designed based on understanding of the biology of the infection. The transmission coefficients for the model and the rate of detection were fit for each region using Approximate Bayesian Computation applied to paucibacillary and multibacillary incidence data over the period of 2000 to 2010, and model fit was validated on incidence data from 2011 to 2012. Regional variation was noted in detection rate, with cases in the Midwest estimated to be infectious for 10 years prior to detection compared to 5 years for most other regions. Posterior predictions for the model estimated that elimination of leprosy as a public health risk would require, on average, 44–45 years in the three regions with the highest prevalence. The model is easily adaptable to other settings, and can be studied to determine the efficacy of improved case finding on leprosy control. PMID:27532862
Saini, Chaman; Prasad, H. K.; Rani, Rajni; Murtaza, A.; Misra, Namita; Shanker Narayan, N. P.
The Lsr2 protein of Mycobacterium leprae and its synthetic peptides have been shown to elicit lymphoproliferation and gamma interferon (IFN-γ) release by peripheral blood mononuclear cells (PBMCs) of patients with lepromatous leprosy (M. Chaduvula, A. Murtaza, N. Misra, N. P. Narayan, V. Ramesh, H. K. Prasad, R. Rani, R. K. Chinnadurai, I. Nath, Infect. Immun. 80:742–752, 2012). PBMCs from 16 patients with lepromatous leprosy who were undergoing erythema nodosum leprosum (ENL) (type 2) and 5 patients with reversal reactions (RR) (type 1) were stimulated with M. leprae, recombinant Lsr2, and six end-to-end synthetic peptides (A through F) spanning the Lsr2 sequence. During the reaction all patients with ENL showed lymphoproliferation (stimulation index, >2) in response to peptides A and F, with other peptides eliciting responses in 75 to 88% of the subjects. In PBMC cultures, both lymphoproliferation and IFN-γ release for peptide E were significantly higher than for peptides B and C and recombinant Lsr2 (P < 0.05, Wilcoxon signed-rank test). Five patients with RR also showed enhanced lymphoproliferative responses and IFN-γ release in response to Lsr2, M. leprae, and peptide E. Six months postreaction, 14 patients with ENL continued to exhibit responses to Lsr2 and its peptides, with the highest responses being elicited by peptide E. However, 5 subjects showed no lymphoproliferation and had reduced IFN-γ release in response to Lsr2 peptides (P < 0.001, Kruskal-Wallis test) but responded to recombinant Lsr2. Six patients with ENL had HLA-A*68.01, which the STFPEITHI program showed to have high peptide-binding scores of 20 to 21 for peptides E, B, and C. Eleven patients had HLA-DRB1*1501 and HLA-DRB1*1502, which had high binding scores for peptides C and E. Thus, Lsr2 and its peptides are recognized in leprosy reactions during and well after the subsidence of clinical signs. PMID:23446220
Borenstein, Miriam Süssking; Padilha, Maria Itayra; Costa, Eliani; Gregório, Vitória Regina Petters; Koerich, Ana Maria Espíndola; Ribas, Dorotéa Löes
This study is a qualitative research with a socio-historic approach whose objective was to know the prejudice and stigma lived by the institutionalized patients/residents with hanseniase. To achieve this goal, three patients were intervewed who lived in a colony hospital during the research period, utilizing the oral history method. Data were collected and were further analysed, utilizing the stigma referencial. The results indicated that after the entry in the institution, these patients got their family bonds broken, lost their rights as citizens, regarding the situation, they took upon a new life, in a new environment. Concluding that, the nosocomial isolation for a long period of time (years of confinement and dismissal), caused the symbolic death of many patients that lived with the hope to cohabit with family and/or society.
Freitas, Aline Araújo; Hungria, Emerith Mayra; Costa, Maurício Barcelos; Sousa, Ana Lúcia Osório Maroccolo; Castilho, Mirian Lane Oliveira; Gonçalves, Heitor Sá; Pontes, Maria Araci Andrade; Duthie, Malcolm S; Stefani, Mariane Martins Araújo
Mycobacterium leprae-specific serological and cell-mediated-immunity/CMI test were evaluated for the differential diagnosis of multibacillary/MB, and paucibacillary/PB leprosy from other dermatoses. Whole-blood assay/WBA/IFNγ stimulated with LID-1 antigen and ELISA tests for IgG to LID-1 and IgM to PGL-I were performed. WBA/LID-1/IFNγ production was observed in 72% PB, 11% MB leprosy, 38% dermatoses, 40% healthy endemic controls/EC. The receiver operating curve/ROC for WBA/LID-1 in PB versus other dermatoses showed 72.5% sensitivity, 61.5% specificity and an area-under-the-curve/AUC=0.75; 74% positive predictive value/PPV, 59% negative predictive value/NPV. Anti PGL-I serology was positive in 67% MB, 8% PB leprosy, 6% of other dermatoses; its sensitivity for MB=66%, specificity=93%, AUC=0.89; PPV=91%, NPV=72%. Anti-LID-1 serology was positive in 87% MB, 7% PB leprosy, all other participants were seronegative; 87.5% sensitivity for MB, 100% specificity, AUC=0.97; PPV=100%, NPV=88%. In highly endemic areas anti-LID-1/PGL-I serology and WBA/LID-1-represent useful tools for the differential diagnosis of leprosy from other confounding dermatoses.
Wang, Zhu; Liu, Da-Yue; Lei, Yang-Yang; Yang, Zheng; Wang, Wei
A 23-year-old woman presented with a half-year history of right forearm sensory and motor dysfunction. Ultrasound imaging revealed definite thickening of the right ulnar nerve trunk and inner epineurium, along with heterogeneous hypoechogenicity and unclear nerve fiber bundle. Color Doppler exhibited a rich blood supply, which was clearly different from the normal ulnar nerve presentation with a scarce blood supply. The patient subsequently underwent needle aspiration of the right ulnar nerve, and histopathological examination confirmed that granulomatous nodules had formed with a large number of infiltrating lymphocytes and a plurality of epithelioid cells in the fibrous connective tissues, with visible atypical foam cells and proliferous vascularization, consistent with leprosy. Our report will familiarize readers with the characteristic sonographic features of the ulnar nerve in leprosy, particularly because of the decreasing incidence of leprosy in recent years.
Delgado, José Saulo Torres; Cavalcanti, Marília Lopes; Kac, Bernard Kawa; Pires, Claudia Lopes
Clinically and histopathologically paucibacillary leprosy shows similar features with initial morphea. In this case we report a 24 yr-old male patient who presented to our dermatology department with diagnosed paucibacillary leprosy by his local dermatologist, and confirmed by perineurovascular lymphocytic infiltrate in the histopathological exam. On physical examination we found new plaque lesions that were suggestive of morphea with alteration of sensitivity. A new biopsy was performed showing sclerotic superficial dermis with thickening of the collagen bundles in deep dermis and linear arrays lymphocytic infiltrate between the collagen bundles that confirm the diagnosis of morphea. PMID:23372229
This essay explores how the concept of social marketing can be employed to change attitudes towards leprosy. Firstly, the concept of social marketing is discussed, then the attitudes that people have about leprosy, the stigma that people with leprosy and their families may face, and the detrimental effects that this can have on their lives. The effect of knowledge and education on attitudes towards leprosy is discussed, as this can be a key component of social marketing campaigns. Various methods of social marketing used to change attitudes and reduce stigma are examined, such as mass media campaigns, school based education, methods which involve community leaders, and the integration and improvement of leprosy services. Principles of social marketing which can lead to the success of campaigns such as incorporating local beliefs are emphasized. The success of the social marketing campaign in Sri Lanka is described, which aimed to remove the fear of leprosy, and to encourage patients to seek and comply with treatment. Finally, it is argued that social marketing, used correctly, can be highly effective at changing community attitudes towards leprosy, reducing stigma and improving the lives of patients, who become able to seek treatment sooner as they lose their fear of stigmatization.
Bobosha, Kidist; Wilson, Louis; van Meijgaarden, Krista E.; Bekele, Yonas; Zewdie, Martha; van der Ploeg- van Schip, Jolien J.; Abebe, Markos; Hussein, Jemal; Khadge, Saraswoti; Neupane, Kapil D.; Hagge, Deanna A.; Jordanova, Ekaterina S.; Aseffa, Abraham; Ottenhoff, Tom H. M.; Geluk, Annemieke
Regulatory T (Treg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. However, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (TB). Despite high humoral responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL) patients have the characteristic inability to generate T helper 1 (Th1) responses against the bacterium. In this study, we investigated the unresponsiveness to M. leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of IFN-γ responses to M. leprae before and after depletion of CD25+ cells, by cell subsets analysis of PBMC and by immunohistochemistry of patients' skin lesions. Depletion of CD25+ cells from total PBMC identified two groups of LL patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after depletion of CD25+ cells, which was reversed to M. leprae-specific T-cell unresponsiveness by addition of autologous CD25+ cells. In contrast, 11/18 (61.1%) remained anergic in the absence of CD25+ T-cells. For both groups mitogen-induced IFN-γ was, however, not affected by depletion of CD25+ cells. In M. leprae responding healthy controls, treated lepromatous leprosy (LL) and borderline tuberculoid leprosy (BT) patients, depletion of CD25+ cells only slightly increased the IFN-γ response. Furthermore, cell subset analysis showed significantly higher (p = 0.02) numbers of FoxP3+ CD8+CD25+ T-cells in LL compared to BT patients, whereas confocal microscopy of skin biopsies revealed increased numbers of CD68+CD163+ as well as FoxP3+ cells in lesions of LL compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus, these data show that CD25+ Treg cells play a role in M. leprae-Th1 unresponsiveness in LL. PMID:24722473
Han, Xiang Y.; Sizer, Kurt Clement; Velarde-Félix, Jesús S.; Frias-Castro, Luis O.; Vargas-Ocampo, Francisco
Summary Background Mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named Mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in Mexico. Methods We sought to differentiate the leprosy agents among 120 Mexican patients with various clinical forms of leprosy and to compare their relative prevalence and disease features. Archived skin biopsy specimens from these patients were tested for both M. leprae and M. lepromatosis using polymerase chain reaction-based species-specific assays. Results Eighty-seven (72.5%) patients were confirmed for etiologic species, including 55 with M. lepromatosis, 18 with M. leprae, and 14 with both organisms. The endemic regions of each agent differed but overlapped. Patients with M. lepromatosis were younger and from more states, and their clinical diagnoses included 13 DLL, 34 lepromatous leprosy (LL), and eight other forms of leprosy. By contrast, the diagnoses of patients with M. leprae included none DLL, 15 LL and three other forms. Thus, M. lepromatosis caused DLL specifically (p=0.023). Patients with M. lepromatosis also showed more variable skin lesions and the extremities were the commonest biopsy sites. Finally, patients with dual infections manifested all clinical forms and accounted for 16.1% of all species-confirmed cases. Conclusions M. lepromatosis is another cause of leprosy and is probably more prevalent than M. leprae in Mexico. It mainly causes LL and also specifically DLL. Dual infections caused by both species may occur in endemic area. PMID:22788812
Schreuder, Pieter A M; Noto, Salvatore; Richardus, Jan Hendrik
Major gaps still exist in the knowledge about leprosy, particularly with regard to how it spreads. Leprosy epidemiology remains complicated due to the specific characteristics of Mycobacterium leprae. To describe epidemiologic trends for the 21st century, the first part of this paper gives an overview of the epidemiology of leprosy, followed by past trends and the present situation of new-case detection as a proxy of the incidence. The third part, regarding predicted epidemiologic trends for the 21st century, elaborates on the main topic of this paper. With limited diagnostic tools to detect infection with M leprae, other methods are necessary to estimate trends in incidence and transmission. A computer program has been developed for modeling the transmission and control of leprosy (SIMLEP). The effect of failure to sustain early case detection beyond 2005 on leprosy incidence and case detection is shown. Important unanswered questions are whether the incubation period is contagious and how rapid close contacts of leprosy patients are infected. As long as such key questions remain unanswered, it will be difficult to estimate the impact of control strategies on the transmission of M leprae on resulting disease incidence. In the meantime we can expect that the global new-case detection trends will stay more or less stable or only decrease slightly for many years to come. There is a need of new preventive interventions to change this situation and reduce the incidence of leprosy in the 21st century.
Munganda, Hariharan; Bangia, Amit; Rani, Uma; Budhiraja, Rajesh; Brajpuriya, Swapnil
Leprosy can present with a variety of clinical manifestations depending on the immune status of the individual. After dermatological and neurological involvement, rheumatic features specially various forms of arthritis are the third most common manifestation of the disease. We describe a unique case of a 22-year-old patient presenting with external ear involvement mimicking relapsing polychondritis along with inflammatory joint symptoms and skin lesions. Ear involvement in relapsing polychondritis characteristically is painful and spares the noncartilaginous ear lobules, in contrast to painless ear involvement in leprosy affecting the lobules as well. Histopathology confirmed the diagnosis, although the ear and skin lesions were not classical of leprosy. Such a presentation of leprosy closely mimicking relapsing polychondritis has not been described previously. Tissue diagnosis should always be attempted whenever possible in patients presenting with autoimmune features, so that inappropriate therapy with immunosuppressants is avoided. PMID:28116186
Muthuvel, Thirumugam; Isaakidis, Petros; Shewade, Hemant Deepak; Kattuppara, Lucy; Singh, Rajbir; Govindarajulu, Srinivas
Background Leprosy remains an important cause of preventable disabilities. After the advent of multidrug therapy, new leprosy cases have come down dramatically. Despite this achievement, India, which contributes 60% of the global leprosy burden, faces some challenges to eliminate the disease, including active transmission in the community and delayed diagnosis of leprosy patients. Objectives The objectives of the study were 1) to determine sociodemographic and clinical characteristics of newly diagnosed adults and children (less than 15 years) with leprosy and their trends over time (2008–2015) and 2) to describe the profile of surgical procedures among leprosy patients registered for reconstructive surgeries during 2006–2015. Design Retrospective descriptive study was conducted involving a record review of new patients with leprosy registered in Vimala Dermatological Centre, Mumbai. Results A total of 578 new leprosy cases were registered in the hospital during 2008–2015. There has been a steady increase in the trend of child cases (less than 15 years) registered in the facility (from 3% in 2008 to 18% in 2015), x2=12.11, p<0.01. The majority of the patients (68%) were migrants of Uttar Pradesh and Bihar. Conclusions Targeting children and migrants and ensuring early diagnosis and treatment initiation are essential components for leprosy elimination in an urban metropolis in India. PMID:27885973
Fwoloshi, Sombo; Machona, Sharon Musonda; Mudenda, Victor; Ngalamika, Owen
Leprosy is a granulomatous disease that mainly affects the skin and peripheral nerves. It is caused by infection with mycobacterium leprae or mycobacterium lepromatosus. In most instances, diagnosis of leprosy can easily be made based on the clinical signs and symptoms. However, when patients present with atypical features, clinical diagnosis can be a challenge. We report a case of a nursing mother with lepromatous leprosy who presented with dysphonia and skin lesions initially thought to be a deep cutaneous mycosis. PMID:26327983
In the light of successive therapeutical difficulties for leprosy control, the application of drug therapy combination over the last decades has brought about an expectation of cure for leprosy patients and also for the elimination of this illness as a Public Health problem. However, there has been a progressive reduction in the prevalence of leprosy, but without any apparent impact on transmission, which has led to recognized need for solid assessment of respective epidemiological evidence as grounds for interventions to solve the problem. In this regard, here we present a retroanalytical qualitative and quantitative study, combined with a prospective diachronic approach, based on the association of documental review techniques and analysis of content, involving the following phases in succession: assembly of an operational scheme, execution of search strategy, application of criteria, selection of studies, data extraction and processing, implementation of analysis plan and preparation of final text. The appropriate execution of the procedures, as applied, allows us to obtain and discuss the identification of three main scenarios: the elimination of the illness as a public health problem (Neglected Illness); therapeutic aspects (Resistance; Relapse; Non-Adherence; Persistence) and complexity (complications and physical incapacities). The conclusions that have been reached indicate,mainly, that the reality of leprosy control with the use of combination drug therapy, still needs to be handled with care, even more so as this is just a fragment of the set of people once under medical attention, which also correspond to a parcel of the set of people affected by the ailment.
Appelboom, Thierry; Cogan, Elie; Klastersky, Jean
Proposing a medical diagnosis a posteriori of a person who died a long time ago is not as impossible as it sounds if sufficient medical history is available.A whole book of the Bible is devoted to Job and his trials. The diagnosis of leprosy has been generally accepted by medieval commentators because the verses of the Book speak of ulcers disseminated over the skin, and also because leprosy is an exemplary sanction imposed by way of example by God to punish those who have committed a sin. In this paper, we have taken the different verses with a medical content from the Book of Job, and reconstructed the clinical picture as if the patient had turned up in the 21st century in order to see if the diagnosis of leprosy may be called into question, and to discuss the limits of the medico-historic approach. The clinical picture of the disease consists of deterioration in the general condition, with widespread pain, confusion, skin eruptions, bilious vomiting, and so on. Under these conditions, if Job did exist, and if the retrospective medical history is reliable, the most likely diagnosis is that of scabies rather than leprosy.
Sapkota, Bishwa R.; Macdonald, Murdo; Berrington, William R.; Misch, E. Ann; Ranjit, Chaman; Siddiqui, M. Ruby; Kaplan, Gilla; Hawn, Thomas R.
Background Although genetic variants in tumor necrosis factor (TNF), mannose binding lectin (MBL), and the vitamin D receptor (VDR) have been associated with leprosy clinical outcomes these findings have not been extensively validated. Methods We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I reversal reaction (RR), and 124 patients with erythema nodosum leprosum (ENL) reactions. We compared genotype frequencies in 933 cases and 101 controls of 7 polymorphisms, including a promoter region variant in TNF (G−308A), three polymorphisms in MBL (C154T, G161A and G170A), and three variants in VDR (FokI, BsmI, and TaqI). Results We observed an association between TNF −308A and protection from leprosy with an odds ratio (OR) of 0.52 (95% confidence interval (CI) of 0.29 to 0.95, P = 0.016). MBL polymorphism G161A was associated with protection from lepromatous leprosy (OR (95% CI) = 0.33 (0.12–0.85), P = 0.010). VDR polymorphisms were not associated with leprosy phenotypes. Conclusion These results confirm previous findings of an association of TNF −308A with protection from leprosy and MBL polymorphisms with protection from lepromatous leprosy. The statistical significance was modest and will require further study for conclusive validation. PMID:20650301
Maritati, Martina; Contini, Carlo
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, characterized by a very long incubation period, confounding signs and symptoms and difficulty to establish the onset time. Considering the stigma associated with the diagnosis and the difficulties in detecting asymptomatic leprosy, the incidence and prevalence of this disease are underestimated. In Italy, leprosy is currently included among the rare diseases and can occur as an imported pathology in native individuals or extra-EU immigrants. Currently, given its exceptional appearance in Italy, leprosy is extremely difficult to recognize. In fact, the incomplete knowledge by the medical class of geographical epidemiology and aetiology of tropical diseases including leprosy, often delays the definitive diagnosis. Due to the increasing rate of the migration flows, in Italy and in Europe, leprosy should be considered among the differential diagnosis in patients with cutaneous and neurological signs, especially when originating from endemic countries.
Kamath, Sonia; Vaccaro, Seth A; Rea, Thomas H; Ochoa, Maria T
Immunologic reactions are an important aspect of leprosy that significantly impacts the course of the disease and the associated disability. Reversal reaction (type 1), erythema nodosum leprosum (type 2), and Lucio phenomenon are the 3 leprosy reactions, and they are most commonly seen in patients with the lepromatous and borderline categories of the disease. Because these forms of leprosy are the most common types seen in the United States, it is particularly important for physicians to be able to recognize and treat them. The reactions may occur before, during, or after treatment with multidrug therapy. Reversal reactions are the most common cause of nerve damage in leprosy, and erythema nodosum leprosum may also lead to neuritis. Although there have not been enough studies to confirm the most effective management regimens, treatment of reversal reaction and Lucio phenomenon with prednisone and of erythema nodosum leprosum with thalidomide and/or prednisone may help improve symptoms and prevent further disability.
SUMMARY Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as “leprosy reactions,” which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research. PMID:25567223
Cakiner, T; Yüksel, A; Eğït, A S; Cağri, G; Karaçorlu, M; Kültür, A
This study was carried out between January and December 1992 at the Istanbul Leprosy Hospital. Seven hundred and eleven leprosy patients were evaluated according to their age, gender and type of disease and disability according to the WHO disability grading system (1980). There were 527 males (74.2%) and 184 females (25.8%) in the group. The average age was 50.0 +/- 13.5 years and the average duration of disease was 25.9 +/- 13.2 years. Six hundred and seventy-eight patients (95.4%) were in borderline (BL) and lepromatous (LL) leprosy. The extent of disabilities was very high in 711 leprosy patients. It was found that 539 of the patients (75.8%) had eye disabilities, 511 of them (71.8%) had hand disabilities, 521 of them (73.3%) had foot disabilities. The most frequent eye, hand and foot disabilities were a decrease of vision (52.7), acute or chronic iridocyclitis (48.8%), slightly-marked corneal sensory loss (43.2%), mobile claw hand (33.3%), palmar insensitivity (16.3%), plantar ulcer (37.2%) and plantar insensitivity (19.8%). Eye deformities were the most common of the three affected areas in this study.
Martelli, C. M.; Moraes Neto, O. L.; Andrade, A. L.; Silva, S. A.; Silva, I. M.; Zicker, F.
Reported is the spatial variation of leprosy in an urban area of Brazil and its correlation with socioeconomic indicators. From November 1991 to October 1992 a total of 752 newly diagnosed leprosy patients who were attending all outpatient clinics in Goiânia city, central Brazil, were identified. A database o leprosy cases was set up linking patients' addresses to 64 urban districts. Leprosy cases were detected in 86% of the districts and three risk strata were identified. The highest-risk area for leprosy was in the outskirts of the city and detection rates increased on moving from more developed to poorer areas. The risk of detecting leprosy cases was 5.3-fold greater (95% CI: 3.8-7.4) in the outskirts of the town than in the central zone. Discussed are the methodological issues related to leprosy case ascertainment, completeness and reliability of information, and the interpretation of the spatial distribution of leprosy per unit area. Highlighted also are the lack of leprosy control activities in primary health care units and the usefulness of geographical analysis in planning health services. PMID:7614663
Rao, P Narasimha; Jain, Suman
Newer management options are needed for leprosy control even at present, as it is predicted that new cases of leprosy will continue to appear for many more years in future. This article detail newer methods of clinical grading of peripheral nerve involvement (thickening, tenderness and nerve pain which are subjective in nature) and the advances made in the use of Ultrasonography and Colour Doppler as an objective imaging tool for nerves in leprosy. It also briefly discusses the newer drugs and alternative regimens as therapeutic management options which hold promise for leprosy in future. PMID:23372204
Juarez-Ortega, Mario; Hernandez, Víctor G; Arce-Paredes, Patricia; Villanueva, Enrique B; Aguilar-Santelises, Miguel; Rojas-Espinosa, Oscar
Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 106 splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy. PMID:25529580
Chen, X. S.; Li, W. Z.; Jiang, C.; Ye, G. Y.
OBJECTIVE: To report the epidemiological trends of leprosy in China from 1949 to 1998. METHOD: Data for the study were obtained from the computerized database of the National System of Leprosy Surveillance. FINDINGS: A total of 474,774 leprosy patients were detected during this 50-year period. Case detection rates per 100,000 population were highest in the 1950s and 1960s, with peaks appearing in 1957-58, 1963-66, 1969-70, and 1983-84, corresponding to mass surveys or screening surveys carried out in most areas or selected areas of the country. While the duration of the disease at the time of detection fell over the period, the disability rates, which were > 50% in the early 1950s, have decreased gradually to 20.8% by 1997-98 but are still too high. More than 50% of cases were found through active methods in the periods 1955-58, 1965-66, and 1969-76, but in recent years cases are mostly detected through dermatological clinics or by voluntary reporting. The peak prevalences of the 1960s (i.e. > 2 per 10,000 population) decreased annually from the 1970s onwards. By the end of 1998 the prevalence was 0.05 per 10,000 population. CONCLUSIONS: This study shows that leprosy was well controlled in China and that the WHO goal of elimination of leprosy as a public health problem has been achieved at the national and subnational levels. However, leprosy is still unevenly distributed in the country. According to the criterion for leprosy elimination in China--defined as a prevalence of < 1 per 100,000 in county or city--there are still more than 10% of counties or cities where this target has not yet been reached. Special attention must therefore be given to achieve elimination and final eradication of leprosy in China. PMID:11357209
Tiwary, P K; Kar, H K; Sharma, P K; Gautam, R K; Arora, T C; Naik, H; Dhir, V
This study was done by collecting the retrospective data from 1994 to 2009 of patients attending the urban leprosy centre attached to the department of dermatology, STD & leprosy of PGIMER & Dr. R M L Hospital, New Delhi. The data was analysed according to age, sex, type of leprosy, leprosy reactions, deformities and relapse and compared with the national figures by comparison of proportions after taking the national data per 10,000 population. A total of 3659 patients attended our ULC (Urban Leprosy Centre) among which 2741 were male and 945 females (M:F-3:1). 669 patients (18.2%) were children. The data analysed show a gradual decline in new case detection rate with a marginal rise in 2005 and 2008. Percentage of MB cases was falling consistently till 2005 after which it showed an abrupt rise. The incidence of type 1 reaction varied from 21% in 1994 to 10% in 2009 in PB patients and from 6% in 1994 to 8% in 2009 in MB patients. The trend of type 2 reactions in MB patients showed a slow declining trend. MDT completion rate showed an impressive improvement from 56% in 1994 to 90% in 2009. The number of patients revisiting the ULC with features of relapse also showed a decrease in number. The pattern of visible deformities showed an almost constant trend similar to national figures. Improved MDT completion rate helps in reducing the disease transmission, severity, reactions and disabilities.
Lee, Kyung-Hwa; Moon, Kyung-Sub; Yun, Sook Jung; Won, Young Ho; Lee, Jae-Hyuk; Lee, Min-Cheol; Jung, Shin
Leprosy has a predilection for peripheral nerves and is not considered to involve the CNS. The idea that the CNS is exempt from Mycobacterium leprae bacilli has been suspected from a clinical perspective or CSF study in leprosy patients. However, there has been no direct evidence for CNS involvement by leprosy in a living patient. To the best of the authors' knowledge, the present case is the first report providing histopathological and molecular evidence for CNS involvement by leprosy in a living patient. Brain MRI revealed a 2-cm cystic lesion in the right frontal lobe of the patient. The medical history revealed that the patient had been receiving multidrug therapy for borderline lepromatous leprosy. Neuronavigation-guided craniotomy and lesion removal were performed due to a presumptive diagnosis of low-grade glioma. The brain specimen demonstrated variably thickened blood vessels and densely scattered foamy macrophages in the perivascular spaces and parenchymal stroma. Fite acid-fast stain displayed red granular inclusions that were suggestive for fragmented M. leprae. M. leprae-specific nested polymerase chain reaction amplification showed positive bands, and DNA sequencing also demonstrated homology with the M. leprae genome. This case supports the notion that M. leprae can involve the cerebral cortex regardless of cranial nerve engagement.
Guerra Núñez, M; Mora Castillo, N; Abijana Damien, G
A study on the prevalence of leprosy is performed in "Emilio Daudinot" polyclinics, Guantanamo. The behaviour of leprosy according to clinical manifestations and results showing that lepromatous leprosy is the most frequent form, as well as the number of positive patients and the ones who present reactional status, are reported. The clinical course according to skin and general manifestations is analyzed, and it was determined that the greatest number of cases improved with treatment. Likewise, it was found that the greatest number of positive patients require a 1-4 year period for becoming negative. The immunologic status of cases studied according to the different clinical forms is reported and it was observed that the greatest number of cases are immunologically depressed which agrees with the fact that most of patients have the lepromatous form. Nurses play a very important role for the control and treatment of these patients.
Mori, Shuichi; Ishii, Norihisa
The leprosy policy of Japan began from when the government enacted "law No. 11 (The leprosy prevention act)" in 1907 (Meiji 40) and several leprosy sanatoriums were built and the patient who wanders about was received. Then, in rise of totalitarianism, the isolation policy of Japan gained national support under a slogan "Patient Relief", and it would become the big factor to which enactment of "Leprosy Prevention Law" in 1931 (Showa 6) and leprosy policy changed to segregation which aimed at internment of all leprosy patients. From today's research on the leprosy policy of Japan, it is internment of all leprosy patients, whole life isolation, social defense and neglect of patients' human-rights and led to many tragedy of patient. However, there is little research which can reply clearly to the question of whether the leprosy policy of Japan was really original and what the factors of led to the formation of the segregation policy. This paper focuses on the relation between leprosy policy and medicine, and from this, I make clear the similarity, or peculiarity of the isolation policy between Japan and the vest of the world, and clarify the factors of progress of the absolute isolation policy. The processes are historical and medical historical the verification of the relation between the formation of the national medicine and the progress of the isolation policy of Meiji Era, the proposal of the isolation policy by Dr. Keizo Dohi, Dr. Shibasaburo Kitasato, and Dr. Masatsugu Yamane, and the application by Dr. Kensuke Mitsuda, the decision to enact this policy and its support by the Health and Medical Bureau and the Department of the Interior, as well as many factors.
Fontes, Amanda Nogueira Brum; Gomes, Harrison Magdinier; Araujo, Marcelo Ivens de; Albuquerque, Edson Cláudio Araripe de; Baptista, Ida Maria Foschiani Dias; Moura, Maria Manuela da Fonseca; Rezende, Denise Silva; Pessolani, Maria Cristina Vidal; Lara, Flávio Alves; Pontes, Maria Araci de Andrade; Gonçalves, Heitor de Sá; Lucena-Silva, Norma; Sarno, Euzenir Nunes; Vissa, Varalakshmi D; Brennan, Patrick J; Suffys, Philip Noel
We analysed 16 variable number tandem repeats (VNTR) and three single-nucleotide polymorphisms (SNP) in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N)-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23), Pernambuco (n = 41), Rio de Janeiro (n = 22) and Rondônia (RO) (n = 78). All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1%) yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.
Parente, José Napoleão Tavares; Talhari, Carolina; Schettini, Antônio Pedro Mendes; Massone, Cesare
BACKGROUND Leprosy is characterized histologically by a spectrum of different granulomatous skin lesions, reflecting patients' immune responses to Mycobacterium leprae. Although CD4+CD25+ FoxP3+ T regulatory cells are pivotal in the immuneregulation, presence, frequency, and distribution of Tregs in leprosy, its reactional states have been investigated in few studies. OBJECTIVES This study aimed to verify the frequency and distribution of regulatory T cells in different clinical forms and reactional states of leprosy. METHODS We performed an immunohistochemical study on 96 leprosy cases [Indeterminate (I): 9 patients; tuberculoid tuberculoid: 13 patients; borderline tuberculoid: 26 patients; borderline borderline: 3 patients; borderline lepromatous: 8 patients; lepromatous lepromatous: 27 patients; reversal reaction: 8 patients; and erythema nodosum leprosum: 2 patients]. RESULTS FoxP3-positive cells were present in 100% of the cases with an average density of 2.82% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was a statistically significant increment of FoxP3 expression in patients with leprosy reversal reactions when compared with patients presenting with type I leprosy (P= 0.0228); borderline tuberculoid leprosy (P = 0.0351) and lepromatous leprosy (P = 0.0344). CONCLUSIONS These findings suggest that Tregs play a relevant role in the etiopathogenesis of leprosy, mainly in type I leprosy reaction. PMID:25672298
Sharma, Rahul; Singh, Pushpendra; Loughry, W.J.; Lockhart, J. Mitchell; Inman, W. Barry; Duthie, Malcolm S.; Pena, Maria T.; Marcos, Luis A.; Scollard, David M.; Cole, Stewart T.
Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and have been implicated in zoonotic transmission of leprosy. Early studies found this disease mainly in Texas and Louisiana, but armadillos in the southeastern United States appeared to be free of infection. We screened 645 armadillos from 8 locations in the southeastern United States not known to harbor enzootic leprosy for M. leprae DNA and antibodies. We found M. leprae–infected armadillos at each location, and 106 (16.4%) animals had serologic/PCR evidence of infection. Using single-nucleotide polymorphism variable number tandem repeat genotyping/genome sequencing, we detected M. leprae genotype 3I-2-v1 among 35 armadillos. Seven armadillos harbored a newly identified genotype (3I-2-v15). In comparison, 52 human patients from the same region were infected with 31 M. leprae types. However, 42.3% (22/52) of patients were infected with 1 of the 2 M. leprae genotype strains associated with armadillos. The geographic range and complexity of zoonotic leprosy is expanding. PMID:26583204
Marcos, Luis A; Dobbs, Thomas; Walker, Sue; Waller, William; Stryjewska, Barbara M
Hansen's disease or leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. In the U.S., leprosy is mainly reported in immigrants, but indigenous leprosy cases have been also reported in this country, especially in semitropical southern states (i.e., Texas, Louisiana). The objective of this series of cases is to describe indigenous leprosy cases reported in southern Mississippi (MS) during the period 2012-2014. Information was collected from medical records at Hattiesburg Clinic and the MS Department of Health. Four cases were reported during the period of study (3 Caucasian males, 1 African-American woman). Non of visited endemic leprosy country. The age ranged from 60 to 83 years (median: 75.5 years). Of the four cases, three presented with a slowly progressive erythematous rash disseminated mainly on the thorax and abdomen, with a lesser degree on the extremities. The time between onset of rash until the diagnosis ranged from 5 to 16 months (median: 7 months). Only one case had direct contact with armadillos (blood exposure). Non of these patients had a history of immunosuppression. The most common symptoms were neuropathic pain (n=2), generalized pruritus (n=2) and loss of sensation in extremities (n=2). One case had severe peripheral neuropathy with muscle weakness, atrophy in left arm, and wasting on left hand. Skin biopsies showed diffuse granulomatous infiltrate with foamy histiocytes along with acid fast bacilli by Fite stain. By Ridley-Jopling classification system, three cases were diagnosis as lepromatous leprosy, and one, borderline lepromatous. Treatment included clofazimine, dapsone and rifampin that was offered free of charge by the National Hansen's Diseases Program, Baton Rouge, L.A. One patient did not tolerate therapy. In conclusion, a slowly progressive disseminated erythematous skin rash on the trunk should raise suspicion for leprosy in the elderly population in south MS.
Pulido-Pérez, A; Mendoza-Cembranos, M D; Avilés-Izquierdo, J A; Suárez-Fernández, R
Leprosy reactions, which are abrupt changes in the clinical condition of patients with immunologically unstable forms of the disease, can mask the cardinal signs of leprosy, delaying both diagnosis and treatment. The main complications that arise from delayed diagnosis reflect the characteristic features of the disease, involving impaired nerve function and both local (ulcers, pyogenic infection, osteomyelitis) and systemic compromise. Through clinical examination, sensory testing, and, where necessary, histopathology and microbiology, are essential when leprosy is suspected. Rapid initiation of anti-inflammatory treatment reduces the risk of functional impairment, the main concern in leprosy. We describe type 1 and type 2 leprosy reactions in 2 patients who had not yet been diagnosed with the disease.
Mori, Shuichi; Ishii, Norihisa
The leprosy policy of Japan began from when the government enacted "law No. 11 (The leprosy prevention act)" in 1907 (Meiji 40) and several leprosy sanatoriums were built to receive previously homeless patients. Then, with the rise of totalitarianism, the isolation policy of Japan gained national support under the slogan "Patient Relief", which would become a major factor behind the enactment of "Leprosy Prevention Law" in 1931 (Showa 6) by which the leprosy policy was changed to one of absolute isolation aimed at the internment of all leprosy patients. From recent research on the leprosy policy of Japan, the internment of all leprosy patients, isolation for life, social defense, and neglect of patients' human-rights had tragic results in many cases. However, there is little research which can reply clearly to the question of whether the leprosy policy of Japan was really original and what factors led to the formation of the absolute isolation policy. This paper focuses on the relation between leprosy policy and treatment, and from this, I make clear the similarities, or peculiarities, of the isolation policy between Japan and the rest of the world, while clarifying the factors associated with the progress of the absolute isolation policy. The processes involved were historical and medical historical in that the relation between the formation of a national health system and the progress of the isolation policy of Meiji Era, the proposal of the isolation policy by Dr. Keizo Dohi, Dr. Shibasaburo Kitasato, and Dr. Masatsugu Yamane; the practical application of this policy by Dr. Kensuke Mitsuda, and the decision to enact this policy and its support by the Health and Medical Bureau and the Department of the Interior, as well as many other factors, all contributed to the final implementation of the absolute isolation policy.
Cunha, Carolina; Pedrosa, Valderiza Lourenço; Dias, Luiz Carlos; Braga, Andréa; Chrusciak-Talhari, Anette; Santos, Mônica; Penna, Gerson Oliveira; Talhari, Sinésio; Talhari, Carolina
Leprosy is an ancient infectious disease caused by Mycobacterium leprae. According to comparative genomics studies, this disease originated in Eastern Africa or the Near East and spread with successive human migrations. The Europeans and North Africans introduced leprosy into West Africa and the Americas within the past 500 years. In Brazil, this disease arrived with the colonizers who disembarked at the first colonies, Rio de Janeiro, Salvador and Recife, at the end of the sixteenth century, after which it was spread to the other states. In 1854, the first leprosy cases were identified in State of Amazonas in the north of Brazil. The increasing number of leprosy cases and the need for treatment and disease control led to the creation of places to isolate patients, known as leprosaria. One of them, Colonia Antônio Aleixo was built in Amazonas in 1956 according to the most advanced recommendations for isolation at that time and was deactivated in 1979. The history of the Alfredo da Matta Center (AMC), which was the first leprosy dispensary created in 1955, parallels the history of leprosy in the state. Over the years, the AMC has become one of the best training centers for leprosy, general dermatology and sexually transmitted diseases in Brazil. In addition to being responsible for leprosy control programs in the state, the AMC has carried out training programs on leprosy diagnosis and treatment for health professionals in Manaus and other municipalities of the state, aiming to increase the coverage of leprosy control activities. This paper provides a historical overview of leprosy in State of Amazonas, which is an endemic state in Brazil.
Antônio, João Roberto; Soubhia, Rosa Maria Cordeiro; Paschoal, Vania Del Arco; Amarante, Carolina Forte; Travolo, Ana Regina Franchi
Biological agents are widely used for various immune-mediated diseases, with remarkable effectiveness in the treatment of rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. However, attention needs to be drawn to the adverse effects of these therapies and the risk of reactivating underlying granulomatous infectious diseases such as tuberculosis, leprosy, syphilis, leishmaniasis, among others. The objective of this paper is to describe a case of leprosy in a patient with RA using anti-TNF alfa, demonstrating the need for systematic investigation of skin lesions suggestive of leprosy in patients who require rheumatoid arthritis therapeutic treatment, especially in endemic regions like Brazil. PMID:24346871
Karaçorlu, M A; Cakiner, T; Saylan, T
Leprosy is one of the leading causes of corneal hyposensitivity. In this article the corneal sensitivity of 143 leprosy patients was examined, and correlations between corneal hyposensitivity and anterior segment pathology were detected. Twenty four healthy volunteers were examined as controls. Various degrees of corneal loss of sensitivity were found in 46.2% of leprosy patients. Lagophthalmos, chronic lepromatous granulomatous uveitis, iris atrophy, and social blindness were found 4.5-16.6 times more frequently in eyes which developed severe corneal hyposensitivity.
Karaçorlu, M A; Cakiner, T; Saylan, T
Leprosy is one of the leading causes of corneal hyposensitivity. In this article the corneal sensitivity of 143 leprosy patients was examined, and correlations between corneal hyposensitivity and anterior segment pathology were detected. Twenty four healthy volunteers were examined as controls. Various degrees of corneal loss of sensitivity were found in 46.2% of leprosy patients. Lagophthalmos, chronic lepromatous granulomatous uveitis, iris atrophy, and social blindness were found 4.5-16.6 times more frequently in eyes which developed severe corneal hyposensitivity. PMID:1995039
Berrington, William Richard; Macdonald, Murdo; Khadge, Saraswoti; Sapkota, Bishwa Raj; Janer, Marta; Hagge, Deanna Alisa; Kaplan, Gilla; Hawn, Thomas Richard
Background Because of the wide spectrum of clinical manifestations and well-defined immunologic complications, leprosy is a useful disease for studying genetic regulation of the host response to infection. We hypothesized that polymorphisms in NOD2, a cytosolic receptor known to detect mycobacteria, are associated with susceptibility to leprosy and its clinical outcomes. Methods We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I (reversal) reaction (RR), and 124 patients with type 2 (erythema nodosum leprosum (ENL)) reactions. We compared 32 common NOD2 gene region polymorphism frequencies between the different clinical types of leprosy as well as 101 controls without leprosy. Results Four polymorphisms were associated with leprosy susceptibility when comparing allele frequencies and eight were associated when comparing genotype frequencies with a dominant model. Five polymorphisms were associated with protection from RR in an allelic analysis, and seven were associated with RR with a dominant model. Four polymorphisms were associated with increased susceptibility to ENL in an allelic analysis, while seven of 32 polymorphisms were associated with a dominant model. Conclusion These data suggest that NOD2 genetic variants are associated with leprosy susceptibility and the development of leprosy reactive states. PMID:20350193
Beltrame, Marcia Holsbach; Bini, Valéria Bumiller; Gonçalves, Letícia Boslooper; Boldt, Angelica Beate Winter; de Messias-Reason, Iara Jose
Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/FCN3 gene impact on leprosy is currently unknown. The aim of the present study was to investigate if FCN3 polymorphisms (rs532781899: g.1637delC, rs28362807: g.3524_3532insTATTTGGCC and rs4494157: g.4473C>A) and ficolin-3 serum levels play a role in the susceptibility to leprosy. We genotyped up to 190 leprosy patients (being 114 (60%) lepromatous), and up to 245 controls with sequence-specific PCR. We also measured protein levels using ELISA in 61 leprosy and 73 controls. FCN3 polymorphisms were not associated with disease, but ficolin-3 levels were higher in patients with FCN3 *2B1 (CinsA) haplotype (p = 0.032). Median concentration of ficolin-3 was higher in leprosy per se (26034 ng/mL, p = 0.005) and lepromatous patients (28295 ng/mL, p = 0.016) than controls (18231 ng/mL). In addition, high ficolin-3 levels (>33362 ng/mL) were more common in leprosy per se (34.4%) and in lepromatous patients (35.5%) than controls (19.2%; p = 0.045 and p = 0.047, respectively). Our results lead us to suggest that polymorphisms in the FCN3 gene cooperate to increase ficolin-3 concentration and that it might contribute to leprosy susceptibility by favoring M. leprae infection. PMID:28241035
Wagenaar, Inge; van Muiden, Lisanne; Alam, Khorshed; Bowers, Robert; Hossain, Md. Anwar; Kispotta, Kolpona; Richardus, Jan Hendrik
Background Food shortage was associated with leprosy in two recent studies investigating the relation between socioeconomic factors and leprosy. Inadequate intake of nutrients due to food shortage may affect the immune system and influence the progression of infection to clinical leprosy. We aimed to identify possible differences in dietary intake between recently diagnosed leprosy patients and control subjects. Methods In a leprosy endemic area of Bangladesh, newly diagnosed leprosy patients and control subjects were interviewed about their socioeconomic situation, health and diet. Dietary intakes were recorded with a 24-hour recall, from which a Dietary Diversity Score (DDS) was calculated. Body Mass Index (BMI) was calculated and Household Food Insecurity Access Scale (HFIAS) was filled out for every participant. Using logistic regression, a univariate, block wise multivariate, and an integrated analysis were carried out. Results 52 leprosy cases and 100 control subjects were included. Food shortage was more common, dietary diversity was lower and household food insecurity was higher in the patient group. Patients consumed significantly less items from the DDS food groups ‘Meat and fish’ and ‘Other fruits and vegetables.’ Lower food expenditure per capita, lower BMI, lower DDS and absence of household food stocks are the main factors associated with an increased risk of having leprosy. Conclusion Low income families have only little money to spend on food and consequently have a low intake of highly nutritious non-rice foods such as meat, fish, milk, eggs, fruits and vegetables. Development of clinical leprosy could be explained by deficiencies of the nutrients that these foods normally provide. PMID:25965879
Itoh, Masayoshi; Eason, Alice L.
The purpose of this manual is to introduce the general concepts and techniques in leprosy rehabilitation to physical therapy aides. Because of the lack of well-trained, qualified, physical therapists, the committee on leprosy rehabilitation considers it necessary to publish a teaching manual outlining leprosy rehabilitation for those who work with…
Comparative assessment of the leprosy antibody absorption test, Mycobacterium leprae extract enzyme-linked immunosorbent assay, and gelatin particle agglutination test for serodiagnosis of lepromatous leprosy.
Escobar-Gutiérrez, A; Amezcua, M E; Pastén, S; Pallares, F; Cázares, J V; Pulido, R M; Flores, O; Castro, E; Rodríguez, O
A comparative assessment of three serological methods for leprosy diagnosis (the fluorescent leprosy antibody absorption [FLA-ABS] test, the Mycobacterium leprae soluble-extract enzyme-linked immunosorbent assay [ELISA], and the M. leprae particle agglutination [MLPA] test) was carried out. The objective was to identify their performance in clinical and epidemiological diagnosis of leprosy. The study group included 45 lepromatous leprosy patients under treatment. Specificity was > 95% for all three assays, and sensitivity was 95, 58, and 74% for the FLA-ABS test, the MLPA test, and the ELISA, respectively. The only cross-reactivity for M. tuberculosis-infected patients was with the soluble-extract ELISA. Although the FLA-ABS test displayed the highest specificity and sensitivity values, it can only be used in well-developed laboratories, and the patient's clinical and epidemiological background must be considered when results are interpreted because the test remains positive after therapeutic success and could be positive for some household contacts. The MLPA test is easier to perform and interpret, and it is adequate for small laboratories and epidemiological studies intended to detect active untreated or irregularly treated leprosy cases. Therefore, the FLA-ABS and MLPA tests are complementary, and both should be used for serodiagnosis of leprosy. PMID:8501238
John, Heather Varughese
This article examines three campaigns through which patient activist Stanley Stein sought to combat the stigmatized connotations of the word "leprosy." In 1931, soon after starting the first patient newspaper at the U.S. national leprosy hospital at Carville, Stein became convinced of the necessity of finding an alternative to "leprosy." His ensuing campaign to promote the use of the words "Hansen's Disease" to describe the condition from which he and fellow Carville patients suffered became his most passionate and life-long project. In the 1950s, Stein became involved in efforts to change the translation of "leprosy" in the Bible. Finally, in 1960, he waged a campaign to de-stigmatize encyclopedia entries on leprosy. These campaigns illustrate how even elevation of the medical expert and a seeming disdain for the public can function as a protest of medical authority and reveal a presumption that a significant degree of authority actually resides with the public.
Stafford, S J; Wilson, R R
Leprosy was first recorded in 600 bc in India. Europe saw its first cases in the fourteenth century. The worldwide incidence is falling, but the disease can still present in the most unexpected places: this is a report of the first case of leprosy presenting to an emergency department in Northern Ireland. It is important for physicians in both community and hospital medicine to have a high index of suspicion for leprosy in patients with chronic skin conditions who were born outside the UK or other developed countries.
Scollard, D. M.; Adams, L. B.; Gillis, T. P.; Krahenbuhl, J. L.; Truman, R. W.; Williams, D. L.
Leprosy is best understood as two conjoined diseases. The first is a chronic mycobacterial infection that elicits an extraordinary range of cellular immune responses in humans. The second is a peripheral neuropathy that is initiated by the infection and the accompanying immunological events. The infection is curable but not preventable, and leprosy remains a major global health problem, especially in the developing world, publicity to the contrary notwithstanding. Mycobacterium leprae remains noncultivable, and for over a century leprosy has presented major challenges in the fields of microbiology, pathology, immunology, and genetics; it continues to do so today. This review focuses on recent advances in our understanding of M. leprae and the host response to it, especially concerning molecular identification of M. leprae, knowledge of its genome, transcriptome, and proteome, its mechanisms of microbial resistance, and recognition of strains by variable-number tandem repeat analysis. Advances in experimental models include studies in gene knockout mice and the development of molecular techniques to explore the armadillo model. In clinical studies, notable progress has been made concerning the immunology and immunopathology of leprosy, the genetics of human resistance, mechanisms of nerve injury, and chemotherapy. In nearly all of these areas, however, leprosy remains poorly understood compared to other major bacterial diseases. PMID:16614253
Mieras, Liesbeth; Anthony, Richard; van Brakel, Wim; Bratschi, Martin W; van den Broek, Jacques; Cambau, Emmanuelle; Cavaliero, Arielle; Kasang, Christa; Perera, Geethal; Reichman, Lee; Richardus, Jan Hendrik; Saunderson, Paul; Steinmann, Peter; Yew, Wing Wai
Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.
ESCAMILLA-TILCH, MONICA; TORRES-CARRILLO, NORA MAGDALENA; PAYAN, ROSALIO RAMOS; AGUILAR-MEDINA, MARIBEL; SALAZAR, MA ISABEL; FAFUTIS-MORRIS, MARY; ARENAS-GUZMAN, ROBERTO; ESTRADA-PARRA, SERGIO; ESTRADA-GARCIA, IRIS; GRANADOS, JULIO
Despite the introduction of multidrug therapy and the overall reduction of leprosy prevalence in Mexico, the disease remains endemic in certain regions of the country. A genetic basis for the immune susceptibility to Mycobacterium leprae has already been established in different populations worldwide. In this study, we investigated the possible association of the HLA-DRB1 alleles with leprosy in a Mexican Mestizo population. The results demonstrated that the HLA-DRB1*01 allele is associated with lepromatous and dimorphic leprosy [P<0.001, odds ratio (OR)=4.6, 95% confidence interval (95% CI): 1.8–11.4; and P=0.03, OR=6.2, 95% CI: 1.1–31.6, respectively] and the frequency of the HLA-DRB1*08 allele was found to be significantly lower among leprosy patients compared to controls (P=0.046, OR=2.4, 95% CI: 1–5.8). In conclusion, although the association of the HLA-DR locus with leprosy has been established in different populations and several studies have demonstrated significant differences in the DR alleles, this study demonstrated an association of the HLA-DRB1*01 allele with susceptibility to lepromatous and dimorphic leprosy, as well as an association of the HLA-DRB1*08 allele with protection against leprosy in a Mexican Mestizo population. PMID:24649058
Kwobah, Charles M.; Wools-Kaloustian, Kara K.; Gitau, Jane N.; Siika, Abraham M.
Mycobacteria leprae(leprosy) and HIV coinfection are rare in Kenya. This is likely related to the low prevalence (1 per 10,000 of population) of leprosy. Because leprosy is no longer a public health challenge there is generally a low index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1-leprosy-coinfected individual in a resource-constrained setting is challenging. Some of these challenges include difficulties in establishing a diagnosis of leprosy; the high pill burden of cotreatment with both antileprosy and antiretroviral drugs (ARVs); medications' side effects; drug interactions; scarcity of drug choices for both diseases. This challenge is more profound when managing a patient who requires second-line antiretroviral therapy (ART). We present an adult male patient coinfected with HIV and leprosy, who failed first-line antiretroviral therapy (ART) and required second-line treatment. Due to limited choices in antileprosy drugs available, the patient received monthly rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens, respectively. Six months into his cotreatment, he seemed to have adequate virological control. This case report highlights the challenges of managing such a patient. PMID:22649458
Gupta, Sunil Kumar
Leprosy is a chronic granulomatous inflammation primarily of the peripheral nervous system, skin, and reticuloendothelial system caused by Mycobacterium leprae. It presents clinically as an erythematous or hypopigmented anesthetic patch and a thickened and/or tender cutaneous nerve trunk. Leprosy is also called Hansen disease. Leprosy is a great imitator of other skin diseases, and it can present with different morphological lesions, which is why an expert eye is needed to diagnose it. One of the important clinical presentations of leprosy is histoid leprosy, which is very difficult to diagnose due to different clinical and histopathological findings that mimic, e.g., a fibromatous disorder. Histoid leprosy is a very rare clinicopathological variant of leprosy. It is clinically characterized by skin-colored, soft, succulent nodules, and plaques on apparently normal skin and histologically by a dense bundle of histiocytes arranged in storiform. Though histoid leprosy is a very rare type of leprosy, the higher load of lepra bacilli in these cases makes it a concern as a reservoir for leprosy.
Malathi, Munisamy; Thappa, Devinder Mohan
Leprosy has been considered a curable disease after the implementation of multidrug therapy (MDT), which has been proven to be safe and effective, by bringing about a significant change in the global and national scenario of leprosy by upgrading the control of leprosy to the next stage of eradication. Since its introduction, the MDT regimens for the treatment of leprosy have undergone several changes especially with regard to the duration of treatment. The advantages of shortened duration of treatment need to be balanced against the risk of relapse and a lot of controversies exist pertaining to this aspect. The fixed-duration (FD) therapy is not popular among academicians and private practitioners who prefer precise diagnosis and treatment with superior MDT regimens and for a longer duration. On the contrary, from a public health-care point of view, precise diagnosis and a longer treatment schedule are not cost effective and not feasible to be implemented in elimination programs. Hence, a fine balance needs to be maintained between achieving a cure for the patient and protecting the society at risk, and this review discusses the various limitations and opportunities of FD therapy with a note on the newer MDT regimens. PMID:23716796
Philip, Mariam; Samson, Joan Felicita; Simi, Puthenveedu Salahudeen
A 45-year-old man was treated with WHO multibacillary multidrug therapy for borderline leprosy and high dose daily Clofazimine for lepra reaction. Along with the expected side effect of skin pigmentation, the patient also noticed darkening of previously grey hair. This colour persisted eight months after completing multibacillary multidrug therapy.
Barth-Jaeggi, Tanja; Steinmann, Peter; Mieras, Liesbeth; van Brakel, Wim; Richardus, Jan Hendrik; Tiwari, Anuj; Bratschi, Martin; Cavaliero, Arielle; Vander Plaetse, Bart; Mirza, Fareed; Aerts, Ann
Introduction The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50–60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. Methods and analysis The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. Ethics and dissemination Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for
Scollard, D M; Skinsnes, O K
Advanced lesions of the face, nasopharynx, and oropharynx have played an important role in the medical and social history of Hansen's disease. Renaissance artists included detailed portrayals of these lesions in some of their paintings, a testimony not only to their artistic skill and powers of observation but also to the common presence of these patients in European cities and towns of the period. The disease is now understood as a broad immunologic spectrum of host responses to Mycobacterium leprae, with a variety of clinical and pathologic manifestations in nerve, soft tissues, and bone. This review incorporates the findings of 2 extraordinary studies (one from Europe and the other from Japan) of pharyngeal and facial lesions. In the 1950s, studies of skeletal remains from the churchyard of a Danish leprosarium revealed a triad of maxillofacial lesions unique to leprosy and designated facies leprosa. In pre-World War II Japan, before effective treatment had been discovered, a prominent otorhinolaryngologist studying oropharyngeal and nasopharyngeal lesions prepared watercolor illustrations of the natural progression of untreated Hansen's disease. As a result of effective antimicrobial therapy, such advanced lesions are now rarely seen, but the presenting signs and symptoms of leprosy still occasionally arise in the nasal and oral mucosa. The nasopharynx and oropharynx may be important early sites of inoculation and infection by M leprae, and they require additional emphasis in worldwide efforts toward early diagnosis and treatment of Hansen's disease.
Nardi, S M T; Ikehara, E; Pedro, H S P; Paschoal, V D A
People who had leprosy stay away from work and have difficulty of employability and to perform their functions or retire early. This study aimed at determining whether there is a relationship between profession/occupation and limitations in activities. This was a cross-sectional study that used the SALSA scale (Screening of Activity Limitation and Safety Awareness) to assess limitations and to classify professions/occupations as low, medium or high risk. Of the 277 people surveyed, 50.2% were men, the mean age was 53.8 years (SD = 16.3), 62.7% had multibacillary, 59.7% had family incomes of 3 minimum wages or less, 58.5% had up to 6 years schooling and 57% did not have paid jobs. As for occupations, 45.8% were considered low, 39.7% medium and 12.3% high risk. Of thetotal, 49.1% had mild/moderate, 8.7% severe/very severe and 42.2% did not have any limitations. The relationship between limitations in activities and occupational risk indicated that people with severe limitations tend to have low risk occupations (p value < 0.05). The limitations associated with employability showed that most active individuals have no limitations (p value < 0.05). Hence, most people who had leprosy have low risk professions/occupations; the limitations favor a shift from high-risk activities and interfere with employability.
In the course of a venereal disease survey in Egypt, 820 cases of leprosy and 720 cases of tuberculosis were serologically examined with the Wassermann, Meinicke (MKR II), and VDRL tests; the results are reported in this paper. On serological and anamnestic evidence, 31 cases of syphilis were discovered among the leprosy cases and 37 among the tuberculosis cases. Apparently false positive reactions were seen in 203 cases of leprosy (25%) and in 38 cases of tuberculosis (5%). The author discusses the probability that a fairly high proportion of these reactions were in fact caused by otherwise undetected syphilis or were non-specific. The Meinicke test proved the most specific of the three, followed, in that order, by the Wassermann and the VDRL tests. It was found that syphilis was more frequent among males with tuberculosis than among those with leprosy; this is attributed to the fact that leprosy patients are kept in greater isolation. Less easily explicable is the fact that more females than males with leprosy were found to have syphilis, whereas in tuberculous persons the difference in syphilis incidence between male and female patients was not very great. PMID:13284561
Martins, Ronald Jefferson; Carloni, Maria Emília Oliveira Gomes; Moimaz, Suzely Adas Saliba; Garbin, Cléa Adas Saliba; Garbin, Artênio José Ísper
This study aims to analyze the dental surgeons' knowledge about leprosy and its ways of transmission, clinical characteristics and treatment, besides analyzing their experience with respect to diagnostic suspicion and case referrals. The study population comprised 242 dental surgeons working in the public dental service of the city of Cuiabá, Mato Grosso, Brazil. A self-applicable questionnaire containing questions about the dental surgeon's profile was used, including his/her knowledge on leprosy, as well as his/her practices concerning the disease. The results showed a predominance of female dental surgeons (65.7%), with ages ranging between 30 and 39 years old (43%) and professionals having six to 10 years of experience since graduation. Concerning their time working in the Unified Health System (SUS), the highest percentage of dental surgeons referred more than 10 years. Regarding the knowledge about the disease, 30.6% did not know the efficacy of the treatment of leprosy, 47% did not know the disease had to be notified compulsorily and only 8.3% had received information about leprosy at work. Besides that, most of them mentioned feeling little security when treating patients with leprosy (61.6%). Thus, dental surgeons' deficient knowledge on issues related to leprosy may be highlighted.
MARTINS, Ronald Jefferson; CARLONI, Maria Emília Oliveira Gomes; MOIMAZ, Suzely Adas Saliba; GARBIN, Cléa Adas Saliba; GARBIN, Artênio José Ísper
SUMMARY This study aims to analyze the dental surgeons' knowledge about leprosy and its ways of transmission, clinical characteristics and treatment, besides analyzing their experience with respect to diagnostic suspicion and case referrals. The study population comprised 242 dental surgeons working in the public dental service of the city of Cuiabá, Mato Grosso, Brazil. A self-applicable questionnaire containing questions about the dental surgeon's profile was used, including his/her knowledge on leprosy, as well as his/her practices concerning the disease. The results showed a predominance of female dental surgeons (65.7%), with ages ranging between 30 and 39 years old (43%) and professionals having six to 10 years of experience since graduation. Concerning their time working in the Unified Health System (SUS), the highest percentage of dental surgeons referred more than 10 years. Regarding the knowledge about the disease, 30.6% did not know the efficacy of the treatment of leprosy, 47% did not know the disease had to be notified compulsorily and only 8.3% had received information about leprosy at work. Besides that, most of them mentioned feeling little security when treating patients with leprosy (61.6%). Thus, dental surgeons' deficient knowledge on issues related to leprosy may be highlighted. PMID:27828617
Chandler, David J.; Hansen, Kristian S.; Mahato, Bhabananda; Darlong, Joydeepa; John, Annamma; Lockwood, Diana N. J.
Background Erythema nodosum leprosum (ENL) is a common immune-mediated complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most patients experience chronic or multiple acute ENL over many years during an economically active period of their lives. Understanding the economic burden of ENL is essential to provide effective patient support, yet this area has not been investigated. Methods Ninety-one patients with LL or BL leprosy attending a leprosy hospital in Purulia district of West Bengal, India, were interviewed using a structured questionnaire. Cases (n = 53) were identified as those who had one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or BL leprosy but no history of ENL. Data were collected on household income, direct and indirect costs, and coping strategies. Findings The total household cost was Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases, and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for controls. Indirect costs accounted for 65% of total household costs for cases. Direct costs accounted for the remaining 35% of household costs, and resulted almost entirely from treatment-seeking in the private sector. Total household costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of controls (n = 1) [1 USD = 59 INR]. Interpretation Households affected by ENL face significant economic burden and are at risk of being pushed further into poverty. Health policy should acknowledge the importance of private sector provision and the significant contribution to total household costs of lost productivity (indirect cost). Further work is needed to explore this area and identify solutions. PMID:25590638
Ramos, José M.; Romero, David; Belinchón, Isabel
Background Although incidence of leprosy in Spain has declined steadily over the years, the fivefold increase in immigration since the turn of the century—much of it from countries where leprosy is still prevalent—has been linked to an uptick in registered cases. Objective To describe the epidemiologic trends of incident leprosy cases detected in Spain among Spanish- and foreign-born population groups. Methods Observational, retrospective study of suspected leprosy cases in Spain, as reported through the System of Compulsory Notification of Diseases from 2003 to 2013, with results disaggregated by country of birth. We collected statistical data on leprosy burden for other countries from WHO to estimate the expected number of imported cases. Results Of the 168 leprosy cases registered during the study period, 40 (24.6%) were in Spanish patients, while 128 (76.2%) were detected in legally resident immigrants. We identified a significantly higher number of imported leprosy cases during the 2008–2010 and 2011–2013 trienniums compared to the reference biennium 2003–2004 (OR 5.38, 95% CI 1.83–14.88 and OR 4.80, 95% CI 1.41–16.33, respectively). Most imported cases were diagnosed in Latin American immigrants (71.9%), especially Brazilians, but also Paraguayans, Bolivians and other nationalities from South and Central America. However, registered incidence was lower than expected for each year. For example, in 2003, the expected new cases in immigrants was 47.12, compared to only four cases that were actually detected (a 91% difference). Likewise, we expected to find 49.6 incident cases among immigrants in 2009, but only 15 new cases were reported (60% fewer than expected). Conclusion Imported cases of leprosy are responsible for most leprosy incidence in Spain, and we cannot rule out some under-diagnosis. Clinicians should be made more aware of the potential for leprosy incidence among patients from countries where the disease is endemic. PMID:26939132
Jorge, Karina T O S; Souza, Renan P; Assis, Marieta T A; Araújo, Marcelo G; Locati, Massimo; Jesus, Amélia M R; Baptista, Ida M F D; Lima, Cristiano X; Teixeira, Antônio L; Teixeira, Mauro M; Soriani, Frederico M
Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow cure and interrupt transmission of this infection. MiRNAs are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan Low Density Array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients, as well as skin specimens from healthy controls. In a second step, sixteen microRNAs were selected for validation experiments with qRT-PCR in skin samples from new individuals. Principal component analysis followed by logistic regression model and ROC curve analysis were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in TLDA experiment suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, miR-29c) was revealed as able to discriminate healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate lepromatous and tuberculoid patients with sensitivity of 83% and 80% of specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.
Fernandes, Tania Rita Moreno de Oliveira; Brandão, Graziele Áquila de Souza; Souza, Bruno de Castro e
Leprosy is aneasily recognizable disease due to its dermato-neurological manifestations. It must be present in the physician’s diagnostic repertoire, especially for those working in endemic areas. However, leprosy reaction is not always easily recognized by non-dermatologists, becoming one of the major problems in the management of patients with leprosy, as it presents clinical complications characterized by inflammatory process, accompanied by pain, malaise and sometimes the establishment or worsening of the patient’s disabilities. We report the case of a patient with type-1 periorbital reaction admitted to the hospital, diagnosed and treated as facial cellulitis, whose late diagnosis may have contributed to the appearance or worsening of facial neuritis. PMID:26312679
Weng, Xiaoman; Xing, Yan; Liu, Jian; Wang, Yonghong; Ning, Yong; Li, Ming; Wu, Wenbin; Zhang, Lianhua; Li, Wei; Heiden, Jason Vander; Vissa, Varalakshmi
Leprosy continues to be detected at near stable rates in China even with established control programs, necessitating new knowledge and alternative methods to interrupt transmission. A molecular epidemiology investigation of 190 patients was undertaken to define M. leprae strain types and discern genetic relationships and clusters in endemic and non-endemic regions spanning seventeen provinces and two autonomous regions. The findings support multiple locus variable number of tandem repeat (VNTR) analysis as a useful tool in uncovering characteristic patterns across the multiethnic and divergent geographic landscape of China. Several scenarios of clustering of leprosy from township to provincial to regional levels were recognized, while recent occupational or remote migration showed geographical separation of certain strains. First, prior studies indicated that of the four major M. leprae subtypes defined by single nucleotide polymorphisms (SNPs), only type 3 was present in China, purportedly entering from Europe/West/Central Asia via the Silk Road. However, this study revealed VNTR linked strains that are of type 1 in Guangdong, Fujian and Guangxi in southern China. Second, a subset of VNTR distinguishable strains of type 3, co-exist in these provinces. Third, type 3 strains with rpoT VNTR allele of 4, detected in Japan and Korea were discovered in Jiangsu and Anhui in the east and in western Sichuan bordering Tibet. Fourth, considering the overall genetic diversity, strains of endemic counties of Qiubei, Yunnan; Xing Yi, Guizhou; and across Sichuan in southwest were related. However, closer inspection showed distinct local strains and clusters. Altogether, these insights, primarily derived from VNTR typing, reveal multiple and overlooked paths for spread of leprosy into, within and out of China and invoke attention to historic maritime routes in the South and East China Sea. More importantly, new concepts and approaches for prospective case finding and tracking of
Arco, Rogerio Del; Nardi, Susilene Maria Tonelli; Bassi, Thiago Gasperini; Paschoal, Vania Del Arco
ABSTRACT Objective: to identify the difficulties in diagnosing and treating neuropathic pain caused by leprosy and to understand the main characteristics of this situation. Methods: 85 patients were treated in outpatient units with reference to leprosy and the accompanying pain. We used a questionnaire known as the Douleur Neuropathic 4 test and we conducted detailed neurological exams. As a result, 42 patients were excluded from the study for not having proved their pain. Results: Out of the 37 patients that experienced pain, 22 (59.5%) had neuropathic pain (or a mixture of this pain and their existing pain) and of these 90.8% considered this pain to be moderate or severe. 81.8% of the sample suffered with this pain for more than 6 months. Only 12 (54.5%) of the patients had been diagnosed with neuropathic pain and in almost half of these cases, this pain had not been diagnosed. With reference to medical treatment (n=12) for neuropathic pain, 5 (41.6%) responded that they became better. For the other 7 (58.4%) there were no changes in relation to the pain or in some cases the pain worsened in comparison to their previous state. Statistical analysis comparing improvements in relation to the pain amongst the patients that were treated (n=12) and those that were not, showed significant differences (value p=0.020). Conclusion: we noted difficulties in diagnosing neuropathic pain for leprosy in that almost half of the patients that were studied had not had their pain diagnosed. We attributed this to some factors such as the non-adoption of the appropriate protocols which led to inadequate diagnosis and treatment that overlooked the true picture. PMID:27508904
Barbieri, Raquel Rodrigues; Sales, Anna Maria; Hacker, Mariana Andrea; Nery, José Augusto da Costa; Duppre, Nádia Cristina; Machado, Alice de Miranda; Moraes, Milton Ozório; Sarno, Euzenir Nunes
Reorientation of the public health policies in Brazil over the last 20 years in association with a stable rate of new-case detection prompted the establishment of a decentralized leprosy control strategy. The aim was to move from a vertical model associated with general dermatological services to one in which the diagnosis and treatment of the disease would be integrated into the primary care level of the national health care facilities. Once patients demand for leprosy reference centers began to be affected by the process of integrating leprosy diagnosis into the basic health care services, it was necessary to determine the profile of all our referrals in light of the new decentralization policy. Objective We evaluated the profile of patients referred to the Fiocruz Outpatient Clinic, a reference center for the diagnosis and treatment of leprosy in Rio de Janeiro, RJ, and analyzed the origins and outcomes of these referrals. Methods This is an observational retrospective study based on information collected from the Leprosy Laboratory database at Fiocruz, Rio de Janeiro, RJ, Brazil. A total of 1,845 suspected leprosy cases examined at the reference center between 2010 and 2014 were included. The originating health service referrals and diagnostic outcomes were analyzed as well as the clinical and epidemiological data of patients diagnosed with leprosy. Result Our data show that the profile of the patients treated at the Clinic has changed in recent years. There was an increase in both the proportion of patients with other skin diseases and those who had visited only one health service prior to our Clinic. Among the total 1,845 cases analyzed, the outcomes of 1,380 were linked to other diseases and, in 74% of these cases, a biopsy was not necessary to reach a diagnostic conclusion. A decrease in new leprosy case detection among our patients was also observed. Yet, among the leprosy patients, 40% had some degree of disability at diagnosis. Conclusion The results of
Amaral, Julio J.; Antunes, Luis Caetano M.; de Macedo, Cristiana S.; Mattos, Katherine A.; Han, Jun; Pan, Jingxi; Candéa, André L. P.; Henriques, Maria das Graças M. O.; Ribeiro-Alves, Marcelo; Borchers, Christoph H.; Sarno, Euzenir N.; Bozza, Patrícia T.; Finlay, B. Brett; Pessolani, Maria Cristina V.
Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT) were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA) metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases. PMID:23967366
Chakrabarty, A N; Dastidar, S G
Leprosy is believed to be transmitted only through human contacts. However, many anomalous observations had gradually accumulated which had weakened such beliefs. These are: only 1/3 rd cases of leprosy give a definite history of being transmitted from other known cases; life-long spouses, in whom only one has leprosy, seldom lead to leprosy to others; while MDT applied intensively in most leprosy endemic countries, could successfully reduce incidence of leprosy, however, simultaneously new cases arise unabated. Besides, a close look at animal leprosies also suggested a mode of transmission other than human-type contact. Thus, a search for alternative hypothesis led to the findings that leprosy bacillus (LB) could be a soil chemoautotroph and could facultatively live both in the human body and the soil which could serve as an alternative source of infection. Evaluation of accumulated evidences points to this possibility.
de Oliveira, Marcela Bahia Barretto; Diniz, Lucia Martins
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, representing a public health issue in some countries. Though more prevalent in adults, the detection of new cases in children under 15 years of age reveals an active circulation of bacillus, continued transmission and lack of disease control by the health system, as well as aiding in the monitoring of the endemic. Among patients under 15 years of age, the most affected age group is children between 10 and 14 years of age, although cases of patients of younger than 1 year of age have also been reported. Household contacts are the primary source of infection, given that caretakers, such as babysitters and others, must be considered in this scenario. Paucibacillary forms of the disease prevailed, especially borderline-tuberculoid leprosy, with a single lesion in exposed areas of the body representing the main clinical manifestation. Reactional states: Lepra reactions are rare, although some authors have reported high frequencies of this phenomenon, the most frequent of which is Type 1 Lepra Reaction. Peripheral nerve involvement has been described at alarming rates in some studies, which increases the chance of deformities, a serious problem, especially if one considers the age of these patients. The protective effect of BCG vaccination was found in some studies, but no consensus has been reached among different authors. Children must receive the same multidrug therapy regimen and the doses should, ideally, be calculated based on the child´s weight. Adverse reactions to this therapy are rare within this age group. This article aims to review epidemiological, clinical, and therapeutic aspects of leprosy in patients under 15 years of age. PMID:27192519
Guerreiro, Luana Tatiana Albuquerque; Robottom-Ferreira, Anna Beatriz; Ribeiro-Alves, Marcelo; Toledo-Pinto, Thiago Gomes; Rosa Brito, Tiana; Rosa, Patrícia Sammarco; Sandoval, Felipe Galvan; Jardim, Márcia Rodrigues; Antunes, Sérgio Gomes; Shannon, Edward J.; Sarno, Euzenir Nunes; Pessolani, Maria Cristina Vidal; Williams, Diana Lynn; Moraes, Milton Ozório
Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy. PMID:23798993
Karaçorlu, M A; Cakiner, T; Sürel, Z; Ersoy, N; Saylan, T; Sütlas, M
Lagophthalmos and corneal hypaesthesia are amongst the most frequently encountered lesions in leprosy and they can easily give rise to blindness. Many measures (such as eye drops, protective conoid shields, muscle exercises, surgical treatment etc.) have been used to protect the eyes under such circumstances and this paper examines the protective role of methyl cellulose and conoid shields in 41 patients. All of them had lagophthalmos (5 mm or more) and corneal hypaesthesia. They were divided into three groups. Group one had 15 leprosy control patients (27 eyes) who did not use methyl cellulose or eye shields. Group two had 16 leprosy patients (28 eyes) and they used methyl cellulose and eye shields when they felt discomfort in their eyes. Group three had 10 leprosy patients (17 eyes) and they used methyl cellulose and eye shields regularly. Statistically significant improvement was seen in group three. Further studies on larger groups of patients including the effects of different concentrations of methyl cellulose, on Schirmer test and tear break up time, may be of value.
Lima, Estela de Oliveira; de Macedo, Cristiana Santos; Esteves, Cibele Zanardi; de Oliveira, Diogo Noin; Pessolani, Maria Cristina Vidal; Nery, José Augusto da Costa; Sarno, Euzenir Nunes; Catharino, Rodrigo Ramos
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which primarily infects macrophages and Schwann cells, affecting skin and peripheral nerves. Clinically, the most common form of identification is through the observation of anesthetic lesions on skin; however, up to 30% of infected patients may not present this clinical manifestation. Currently, the gold standard diagnostic test for leprosy is based on skin lesion biopsy, which is invasive and presents low sensibility for suspect cases. Therefore, the development of a fast, sensible and noninvasive method that identifies infected patients would be helpful for assertive diagnosis. The aim of this work was to identify lipid markers in leprosy patients directly from skin imprints, using a mass spectrometric analytical strategy. For skin imprint samples, a 1 cm(2) silica plate was gently pressed against the skin of patients or healthy volunteers. Imprinted silica lipids were extracted and submitted to direct-infusion electrospray ionization high-resolution mass spectrometry (ESI-HRMS). All samples were differentiated using a lipidomics-based data workup employing multivariate data analysis, which helped electing different lipid markers, for example, mycobacterial mycolic acids, inflammatory and apoptotic molecules were identified as leprosy patients' markers. Otherwise, phospholipids and gangliosides were pointed as healthy volunteers' skin lipid markers, according to normal skin composition. Results indicate that silica plate skin imprinting associated with ESI-HRMS is a promising fast and sensible leprosy diagnostic method. With a prompt leprosy diagnosis, an early and effective treatment could be feasible and thus the chain of leprosy transmission could be abbreviated.
Rivoire, Becky L.; Groathouse, Nathan A.; TerLouw, Stephen; Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Khadge, Saraswoti; Kunwar, Chatra B.; Macdonald, Murdo; Hawksworth, Rachel; Thapa, Min B.; Hagge, Deanna A.; Tibbals, Melinda; Smith, Carol; Dube, Tina; She, Dewei; Wolff, Mark; Zhou, Eric; Makhene, Mamodikoe; Mason, Robin; Sizemore, Christine; Brennan, Patrick J.
Background New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. Methods A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 µg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 µg (high dose) and 0.1 µg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. Findings In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens
Camuset, Guillaume; Lafarge, Sophie; Borgherini, Gianandrea; Gerber, Anne; Pouderoux, Nicolas; Foucher, Aurélie; Poubeau, Patrice; Manaquin, Rodolphe; Larrieu, Sophie; Vilain, Pascal; Huiart, Laetitita
Background Reunion Island is a French overseas territory located in the south-western of Indian Ocean, 700 km east of Madagascar. Leprosy first arrived on Reunion Island in the early 1700s with the African slaves and immigration from Madagascar. The disease was endemic until 1980 but improvement of health care and life conditions of inhabitants in the island have allowed a strong decrease in new cases of leprosy. However, the reintroduction of the disease by migrants from endemic neighbouring countries like Comoros and Madagascar is a real and continuing risk. This observational study was then conducted to measure the number of new cases detected annually on Reunion Island between 2005 and 2013, and to describe the clinical features of these patients. Methodology/Principal Findings Data were collected over two distinct periods. Incident cases between 2005 and 2010 come from a retrospective study conducted in 2010 by the regional Office of French Institute for Public Health Surveillance (CIRE of Indian Ocean), when no surveillance system exist. Cases between 2011 and 2013 come from a prospective collection of all new cases, following the implementation of systematic notification of all new cases. All patient data were anonymized. Among the 25 new cases, 12 are Reunion Island residents who never lived outside Reunion Island, and hence are considered to be confirmed autochthonous patients. Registered prevalence in 2014 was 0.05 /10 000 habitants, less than the WHO’s eradication goal (1/10 000). Conclusions/Significance Leprosy is no longer a major public health problem on Reunion Island, as its low prevalence rate indicates. However, the risk of recrudescence of the disease and of renewed autochthonous transmission remains real. In this context, active case detection must be pursued through the active declaration and rapid treatment of all new cases. PMID:27082879
Anandan, V.; Jameela, W. Afthab; Saraswathy, P.
Introduction Trophic ulcers secondary to leprosy pose a great stigma to the patients and remain a challenge to the treating dermatologists. The discovery of Platelet Rich Plasma (PRP) with its favourable role in wound healing is a boon for the patients. PRP introduces the growth factors directly into the wound and aids in rapid healing. Aim To study the efficacy and safety of PRP in the healing of trophic ulcers secondary to Hansen’s disease in a tertiary care centre in Southern India. Materials and Methods Based on inclusion and exclusion criteria, 50 patients were enrolled in the study. PRP was prepared by manual double spin method. After wound bed preparation, activated PRP was sprayed over the ulcer and occlusive dressings were applied. Same procedure was repeated every week until complete re-epithelisation or up to six sittings whichever occurred earlier. Results In our study, 46 patients (92%) showed complete healing. In 4 patients (8%), there was marked reduction in wound size with partial re-epithelization. In 88%, complete healing was seen after the fourth sitting. Mean time for ulcer healing was around 4.38 weeks. Conclusion PRP therapy leads to faster rate of induction of granulation tissue with rapid healing. Healing had no direct statistical correlation with the size, site and duration of ulcer, the leprosy spectrum and associated motor deformities. It is a simple, safe and cost effective in-office procedure, albeit requiring an optimal set-up and expertise. PMID:27891436
Yamamura, Mellina; Arroyo, Luiz Henrique; Popolin, Marcela Paschoal; Chiaravalloti Neto, Francisco; Palha, Pedro Fredemir; Uchoa, Severina Alice da Costa; Pieri, Flávia Meneguetti; Pinto, Ione Carvalho; Fiorati, Regina Célia; de Queiroz, Ana Angélica Rêgo; Belchior, Aylana de Souza; dos Santos, Danielle Talita; Garcia, Maria Concebida da Cunha; Crispim, Juliane de Almeida; Alves, Luana Seles; Berra, Thaís Zamboni; Arcêncio, Ricardo Alexandre
Background Although the detection rate is decreasing, the proportion of new cases with WHO grade 2 disability (G2D) is increasing, creating concern among policy makers and the Brazilian government. This study aimed to identify spatial clustering of leprosy and classify high-risk areas in a major leprosy cluster using the SatScan method. Methods Data were obtained including all leprosy cases diagnosed between January 2006 and December 2013. In addition to the clinical variable, information was also gathered regarding the G2D of the patient at diagnosis and after treatment. The Scan Spatial statistic test, developed by Kulldorff e Nagarwalla, was used to identify spatial clustering and to measure the local risk (Relative Risk—RR) of leprosy. Maps considering these risks and their confidence intervals were constructed. Results A total of 434 cases were identified, including 188 (43.31%) borderline leprosy and 101 (23.28%) lepromatous leprosy cases. There was a predominance of males, with ages ranging from 15 to 59 years, and 51 patients (11.75%) presented G2D. Two significant spatial clusters and three significant spatial-temporal clusters were also observed. The main spatial cluster (p = 0.000) contained 90 census tracts, a population of approximately 58,438 inhabitants, detection rate of 22.6 cases per 100,000 people and RR of approximately 3.41 (95%CI = 2.721–4.267). Regarding the spatial-temporal clusters, two clusters were observed, with RR ranging between 24.35 (95%CI = 11.133–52.984) and 15.24 (95%CI = 10.114–22.919). Conclusion These findings could contribute to improvements in policies and programming, aiming for the eradication of leprosy in Brazil. The Spatial Scan statistic test was found to be an interesting resource for health managers and healthcare professionals to map the vulnerability of areas in terms of leprosy transmission risk and areas of underreporting. PMID:28241038
Lavania, Mallika; Jadhav, Rupendra; Turankar, Ravindra P; Singh, Itu; Nigam, Astha; Sengupta, U
Leprosy is still a major health problem in India which has the highest number of cases. Multiple locus variable number of tandem repeat analysis (MLVA) and single nucleotide polymorphism (SNP) have been proposed as tools of strain typing for tracking the transmission of leprosy. However, empirical data for a defined population from scale and duration were lacking for studying the transmission chain of leprosy. Seventy slit skin scrapings were collected from Purulia (West Bengal), Miraj (Maharashtra), Shahdara (Delhi), and Naini (UP) hospitals of The Leprosy Mission (TLM). SNP subtyping and MLVA on 10 VNTR loci were applied for the strain typing of Mycobacterium leprae. Along with the strain typing conventional epidemiological investigation was also performed to trace the transmission chain. In addition, phylogenetic analysis was done on variable number of tandem repeat (VNTR) data sets using sequence type analysis and recombinational tests (START) software. START software performs analyses to aid in the investigation of bacterial population structure using multilocus sequence data. These analyses include data summary, lineage assignment, and tests for recombination and selection. Diversity was observed in the cross-sectional survey of isolates obtained from 70 patients. Similarity in fingerprinting profiles observed in specimens of cases from the same family or neighborhood locations indicated a possible common source of infection. The data suggest that these VNTRs including subtyping of SNPs can be used to study the sources and transmission chain in leprosy, which could be very important in monitoring of the disease dynamics in high endemic foci. The present study strongly indicates that multi-case families might constitute epidemic foci and the main source of M. leprae in villages, causing the predominant strain or cluster infection leading to the spread of leprosy in the community.
Braga, André Flores; Moretto, Daniela Ferraz; Gigliotti, Patrícia; Peruchi, Mariela; Vilani-Moreno, Fátima Regina; Campanelli, Ana Paula; Latini, Ana Carla Pereira; Iyer, Anand; Das, Pranab Kumar; Souza, Vânia Nieto Brito de
Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy.
Braga, André Flores; Moretto, Daniela Ferraz; Gigliotti, Patrícia; Peruchi, Mariela; Vilani-Moreno, Fátima Regina; Campanelli, Ana Paula; Latini, Ana Carla Pereira; Iyer, Anand; Das, Pranab Kumar; de Souza, Vânia Nieto Brito
Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy. PMID:26222022
... Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury ... Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury ...
... Kang G, Lalloo D, White NJ, eds. Manson's Tropical Diseases . 23rd ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 41. ... by: Jatin M. Vyas, MD, PhD, Assistant Professor in Medicine, Harvard Medical School; Assistant in Medicine, Division of ...
Azevedo, Michelle de Campos Soriani; Ramuno, Natália Mortari; Fachin, Luciana Raquel Vincenzi; Tassa, Mônica; Rosa, Patrícia Sammarco; Belone, Andrea de Faria Fernandes; Diório, Suzana Madeira; Soares, Cleverson Teixeira; Garlet, Gustavo Pompermaier; Trombone, Ana Paula Favaro
Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.
Bernink, E H; Voskens, J E
This paper presents a retrospective study on the detection of the treatment of leprosy reactions in a field situation, and the effect of prednisone on the various affected nerves. Two patient cohorts were analysed. The leprosy control programme in the testing area is not backed up by a specialized referral leprosy hospital, but patients are treated on an ambulatory basis at peripheral health centres by trained multipurpose health workers supervised by the health centre doctors. For operational purposes the guidelines and procedures for reaction management in the field were adjusted and partially simplified. In both studies it appeared that the time of the occurrence of severe reactions was the same: 80% or more of the severe reactions occurred in the first year of treatment, the majority in the first few months after the start of the multidrug (MDT) treatment. One third of all reaction patients suffered from a silent neuritis. Well-instructed fieldworkers proved to be competent in detecting and treating leprosy reactions. Treatment of severe reactions with prednisone in the field situation can preserve or considerably improve the functions of the affected nerves. It is interesting that often the motor function of a nerve was found to be impaired without any loss in sensibility, which was tested using the ballpoint pen method.
Boldsen, Jesper L; Rasmussen, Kaare Lund; Riis, Thomas; Dittmar, Manuela; Weise, Svenja
Leprosy was a well-recognized and dreaded disease in medieval Europe. The disease is reported to have reached Germany with the Roman invasion and it was present in Scandinavia in the first centuries AD. This paper estimates and analyzes the frequency of leprosy among adult people buried in one of five medieval cemeteries in the city of Schleswig. Seven different dichotomous osteological lesions indicative of leprosy were analyzed, and it was possible to score at least one of these conditions on 350 adult skeletons (aged 15 or older). The scores were transformed to a statistic indicating the likelihood that the person to whom the skeleton belonged suffered from leprosy. It was found that the frequency of leprosy in the five cemeteries varied between 9 and 44%. Four of the five cemeteries showed frequencies ranging from 35 and 44% and with no statistically significant differences among them. The fifth cemetery showed a significantly lower frequency of leprosy (9%). The distribution of female age at death does not appear to be affected by leprosy status. This means that females experienced a considerably elevated risk of dying once they had contracted leprosy as the disease usually has a mid-adulthood age of onset. In four of the five cemeteries males with leprosy died in higher ages than men without leprosy--in two of the cemeteries the difference was statistically significant. This indicates that leprosy usually added less to the risk of dying among men than among women in medieval Schleswig.
Cartel, J L; Spiegel, A; Nguyen Ngoc, L; Moulia-Pelat, J P; Martin, P M; Grosset, J H
In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease.
Dogra, Sunil; Narang, Tarun; Kumar, Bhushan
Leprosy is among the world's oldest and most dreaded diseases and it has been synonymous with stigma and discrimination due to the hideous deformities it produced, mystery around its aetiology and transmission and lack of any effective remedy till recently. Leprosy control started with the use of chaulmoogra oil and for the last three decades, multi drug therapy (MDT) has been our main tool against leprosy. In the last two decades, the reported global prevalence of active leprosy infection has dropped by almost 90 per cent by the combined efforts of the World Health Organization (WHO), local governments, health professionals, and non-governmental organizations (NGOs), however, a parallel drop in the incidence or new case detection rate (NCDR) has not occurred. From 1994 through 2011, more than 100,000 new cases are being detected annually, of whom maximum case load is from India. There is need for research on tools for early diagnosis, short and effective treatment, and prevention of deformities and disabilities. Evaluating the role of immunotherapy and immunoprophylaxis will also lead us to better understanding of their mode of action. Further molecular analysis of Mycobacterium leprae genome may provide the requisite basis for all this. The current reality is that there is a need to sustain and provide quality leprosy services to all persons through general health services, including good referral system. All these provisions in the integrated health care approach will go a long way in further reducing the stigma. Efforts need to be made to reduce deformity through early detection, self care, physiotherapy and reconstructive surgery and developing sound surveillance systems. With all the remarkable achievements in the fight against leprosy, the stage is now set for the final assault. It is hoped that with the efforts of all the stake holders and strong political will, the disease will be eradicated in the near future. PMID:23481049
Geluk, Annemieke; Spencer, John S.; Bobosha, Kidist; Pessolani, Maria C. V.; Pereira, Geraldo M. B.; Banu, Sayera; Honoré, Nadine; Reece, Stephen T.; MacDonald, Murdo; Sapkota, Bishwa Raj; Ranjit, Chaman; Franken, Kees L. M. C.; Zewdie, Martha; Aseffa, Abraham; Hussain, Rabia; Stefani, Mariane M.; Cho, Sang-Nae; Oskam, Linda; Brennan, Patrick J.; Dockrell, Hazel M.
The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking. The recent identification of M. leprae-unique genes has allowed the analysis of human T-cell responses to novel M. leprae antigens. Antigens with the most-promising diagnostic potential were tested for their ability to induce cytokine secretion by using peripheral blood mononuclear cells from leprosy patients and controls in five different areas where leprosy is endemic; 246 individuals from Brazil, Nepal, Bangladesh, Pakistan, and Ethiopia were analyzed for gamma interferon responses to five recombinant proteins (ML1989, ML1990, ML2283, ML2346, and ML2567) and 22 synthetic peptides. Of these, the M. leprae-unique protein ML1989 was the most frequently recognized and ML2283 the most specific for M. leprae infection/exposure, as only a limited number of tuberculosis patients responded to this antigen. However, all proteins were recognized by a significant number of controls in areas of endemicity. T-cell responses correlated with in vitro response to M. leprae, suggesting that healthy controls in areas where leprosy is endemic are exposed to M. leprae. Importantly, 50% of the healthy household contacts and 59% of the controls in areas of endemicity had no detectable immunoglobulin M antibodies to M. leprae-specific PGL-I but responded in T-cell assays to ≥1 M. leprae protein. T-cell responses specific for leprosy patients and healthy household contacts were observed for ML2283- and ML0126-derived peptides, indicating that M. leprae peptides hold potential as diagnostic tools. Future work should concentrate on the development of a sensitive and field-friendly assay and identification of additional peptides and proteins that can induce M. leprae-specific T-cell responses
Geluk, Annemieke; Spencer, John S; Bobosha, Kidist; Pessolani, Maria C V; Pereira, Geraldo M B; Banu, Sayera; Honoré, Nadine; Reece, Stephen T; MacDonald, Murdo; Sapkota, Bishwa Raj; Ranjit, Chaman; Franken, Kees L M C; Zewdie, Martha; Aseffa, Abraham; Hussain, Rabia; Stefani, Mariane M; Cho, Sang-Nae; Oskam, Linda; Brennan, Patrick J; Dockrell, Hazel M
The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking. The recent identification of M. leprae-unique genes has allowed the analysis of human T-cell responses to novel M. leprae antigens. Antigens with the most-promising diagnostic potential were tested for their ability to induce cytokine secretion by using peripheral blood mononuclear cells from leprosy patients and controls in five different areas where leprosy is endemic; 246 individuals from Brazil, Nepal, Bangladesh, Pakistan, and Ethiopia were analyzed for gamma interferon responses to five recombinant proteins (ML1989, ML1990, ML2283, ML2346, and ML2567) and 22 synthetic peptides. Of these, the M. leprae-unique protein ML1989 was the most frequently recognized and ML2283 the most specific for M. leprae infection/exposure, as only a limited number of tuberculosis patients responded to this antigen. However, all proteins were recognized by a significant number of controls in areas of endemicity. T-cell responses correlated with in vitro response to M. leprae, suggesting that healthy controls in areas where leprosy is endemic are exposed to M. leprae. Importantly, 50% of the healthy household contacts and 59% of the controls in areas of endemicity had no detectable immunoglobulin M antibodies to M. leprae-specific PGL-I but responded in T-cell assays to >or=1 M. leprae protein. T-cell responses specific for leprosy patients and healthy household contacts were observed for ML2283- and ML0126-derived peptides, indicating that M. leprae peptides hold potential as diagnostic tools. Future work should concentrate on the development of a sensitive and field-friendly assay and identification of additional peptides and proteins that can induce M. leprae-specific T
Kiran, C M; Menon, Roshni
Background: Pure neuritic leprosy (PNL) usually presents with neurological symptoms without skin involvement. Fine needle aspiration can play an important role in the management of PNL cases presenting as nerve abscesses. Aim: To assess the role of fine needle aspiration cytology (FNAC) in diagnosing and categorizing PNL cases presenting as nerve abscesses in the absence of neurological symptoms. Materials and Methods: Five patients with subcutaneous nerve related swellings without clinically evident neurological deficits were subjected to FNAC. As the cytological features were suggestive of nerve abscesses due to leprosy, Fite stain was performed in all cases. As none of the patients had any leprosy skin lesions, they were diagnosed as cases of PNL. Features like cellularity, caseous necrosis, presence or absence of lymphocytes, macrophages, epithelioid cells, granulomas, Langhans giant cells and nerve elements were analyzed with the bacteriological index, to categorize PNL according to the Ridley-Jopling classification. Results: Based on the cytological features and bacteriological indices, 3 cases were cytologically categorized into tuberculoid (TT)/borderline tuberculoid (BT) leprosy and the other two, as BT/borderline lepromatous (BL) and BL leprosy respectively in spite of having similar clinical presentation. Based on the cytological diagnoses, category-specific treatment could be instituted with clinical improvement. Conclusions: The simple and minimally invasive FNAC procedure allows diagnosis and a reasonably accurate categorization of PNL presenting as nerve abscess and therefore, highly useful in its clinical management. PMID:24648666
de Castro, Shamyr Sulyvan; Santos, Juliana Pereira Pontes; Abreu, Graziela Basílio; Oliveira, Vanessa Rossato; Fernandes, Luciane Fernanda Rodrigues Martinho
BACKGROUND: Leprosy is millenary disease and still persists in several countries. OBJECTIVES: To estimate the incidence of leprosy in the Brazilian states and for the country in the year 2010; to describe the cases reported according to the studied variables; to verify the correlation between the overall incidence and the studied variables. METHODS: Ecological descriptive study, with population data from the 27 states, 2010. Information about reported cases were collected: gender, race, percentage of patients younger than 15 years old and living conditions. The analysis was performed using percentages, means, incidence rates and the Spearman correlation test. RESULTS: The states of Mato Grosso and Tocantins recorded the highest incidence rates; Rio Grande do Sul and Santa Catarina, the lowest; there was a higher incidence of leprosy among men; the incidence of leprosy increases proportionally with the nonwhites among the inhabitants; patients younger than 15 years; the average number of residents per household; and a decrease in coverage of water supply and presence of bathrooms. CONCLUSION: The incidence of leprosy is related to factors as gender, race and house conditions (p<0,05 for all). PMID:26982775
Lockwood, Diana N. J.; Suneetha, Sujai
Can leprosy be eliminated? This paper considers the question against the background of the WHO programme to eliminate leprosy. In 1991 the World Health Assembly set a target of eliminating leprosy as a public health problem by 2000. Elimination was defined as reaching a prevalence of < 1 case per 10 000 people. The elimination programme has been successful in delivering highly effective antibiotic therapy worldwide. However, despite this advance, new-case detection rates remain stable in countries with the highest rates of endemic leprosy, such as Brazil and India. This suggests that infection has not been adequately controlled by antibiotics alone. Leprosy is perhaps more appropriately classed as a chronic stable disease than as an acute infectious disease responsive to elimination strategies. In many countries activities to control and treat leprosy are being integrated into the general health-care system. This reduces the stigma associated with leprosy. However, leprosy causes long-term immunological complications, disability and deformity. The health-care activities of treating and preventing disabilities need to be provided in an integrated setting. Detecting new cases and monitoring disability caused by leprosy will be a challenge. One solution is to implement long-term surveillance in selected countries with the highest rates of endemic disease so that an accurate estimate of the burden of leprosy can be determined. It is also critical that broad-based research into this challenging disease continues until the problems are truly solved. PMID:15798849
Cardona-Castro, Nora; Cortés, Edwin; Beltrán, Camilo; Romero, Marcela; Badel-Mogollón, Jaime E; Bedoya, Gabriel
Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations.
Cardona-Castro, Nora; Cortés, Edwin; Beltrán, Camilo; Romero, Marcela; Badel-Mogollón, Jaime E.; Bedoya, Gabriel
Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations. PMID:26360617
Previous experiments have shown that a mixture of cardiolipin and cholesterol in absolute ethanol (named “cardchol”) might be used as an antigen in complement-fixation tests. The reactivity in the complement-fixation test of CWRM (an “ordinary” cardiolipin antigen) was compared with that of cardchol in several experiments, and it could be demonstrated that the reactivity of cardchol was especially pronounced in sera from false-positive reactors. In about 50% of such cases, quantitative determination of the antibody content showed that cardchol was more reactive than CWRM, whereas in syphilitic cases the reactivity of cardchol was inferior to that of CWRM. An exception was primary syphilis, which showed a reactivity level with cardchol equal to or even superior to that of CWRM. Examinations of a certain number of sera from leprosy patients had shown them to be highly reactive with cardchol and non-reactive or weakly reactive with CWRM; this observation is fully confirmed by examination of a larger number of leprosy sera, on which this paper reports. These sera were examined with a battery of tests using lipoidal antigens and with the TPI test. Testing with cardchol proved to give the highest reactivity with these sera, which were mostly non-treponemal. Subdivision of the material according to the clinical stage of leprosy showed that the highest reactivity of cardchol occurred in patients with lepromatous leprosy, particularly in those with leprosy of relatively short duration. Electrophoretic fractionation of these sera demonstrated that the substances reacting with cardchol were situated in the gamma-globulin or gamma- and beta-globulin serum fractions. PMID:14443042
Facer, P; Mathur, R; Pandya, S S; Ladiwala, U; Singhal, B S; Anand, P
Loss of nociception and hypohidrosis in skin are hallmarks of leprosy, attributed to early invasion by Mycobacterium leprae of Schwann cells related to unmyelinated nerve fibres. We have studied skin lesions and contralateral clinically unaffected skin in 28 patients across the leprosy spectrum with a range of selective quantitative sensory and autonomic tests, prior to biopsy of both sites. Unaffected sites showed normal skin innervation, when antibodies to the pan-neuronal marker PGP (protein gene product) 9.5 were used, with the exception of intraepidermal fibres which were not detected in the majority of cases. Elevation of thermal thresholds and reduced sensory axon-reflex flare responses in affected skin correlated with decreased nerve fibres in the subepidermis, e.g. axon-reflex flux units (means+/-SEM) for no detectable innervation; decreased innervation; and clinically unaffected skin, were 23+/-3.1; 41.2+/-7.3; and 84.5+/-4.0, respectively. Reduced nicotine-induced axon-reflex sweating was correlated with decreased innervation of sweat glands. Where methacholine-induced direct activation of sweat glands was affected, there was inflammatory infiltrate and loss of sweat gland structure. This study demonstrates a correlation between selective nerve dysfunction on clinical tests and morphological changes in skin, irrespective of the type of leprosy, and is the first to show that loss of sweating in leprosy may result either from decreased innervation and/or involvement of the sweat glands. The findings have implications for the selection and monitoring of patients with leprosy in clinical trials which aim to restore cutaneous function.
Teles, Rosane M. B.; Wang, Zhiming; Hong, Patrick; Montoya, Dennis; Krutzik, Stephan; Lee, Seung; Kwon, Ohyun; Modlin, Robert L.; Cruz, Daniel
As circulating monocytes enter the site of disease, the local microenvironment instructs their differentiation into tissue macrophages (MΦ). To identify mechanisms that regulate MΦ differentiation, we studied human leprosy as a model, since M1-type antimicrobial MΦ predominate in lesions in the self-limited form, whereas M2-type phagocytic MΦ are characteristic of the lesions in the progressive form. Using a heterotypic co-culture model, we found that unstimulated endothelial cells (EC) trigger monocytes to become M2 MΦ. However, biochemical screens identified that IFN-γ and two families of small molecules activated EC to induce monocytes to differentiate into M1 MΦ. The gene expression profiles induced in these activated EC, when overlapped with the transcriptomes of human leprosy lesions, identified Jagged1 (JAG1) as a potential regulator of MΦ differentiation. JAG1 protein was preferentially expressed in the lesions from the self-limited form of leprosy, and localized to the vascular endothelium. The ability of activated EC to induce M1 MΦ was JAG1-dependent and the addition of JAG1 to quiescent EC facilitated monocyte differentiation into M1 MΦ with antimicrobial activity against M. leprae. Our findings indicate a potential role for the IFN-γ-JAG1 axis in instructing MΦ differentiation as part of the host defense response at the site of disease in human leprosy. PMID:27532668
In a retrospective study, data from the Guéra Leprosy and Disability Control Project in Chad, covering the years from 1992 to 1996, were analysed in order to determine whether there was any indication that the quality of care provided to female leprosy sufferers is inferior to the care provided for male patients. Data from a total of 741 patient registered for MDT, of whom 351 were newly diagnosed cases, are presented and discussed. The data indicate that women have access to diagnosis and treatment and health education. They do not present for treatment later than men, disability rates are lower and they have slightly higher treatment completion rates. Both women and men benefit from footwear and loan programs. More women than men are involved in patient self-help groups. The study shows that in this part of central Chad, there is no evidence of disadvantage for women with leprosy in either diagnosis, treatment or follow-up, but more qualitative data is needed to confirm these findings.
Donoghue, Helen D; Michael Taylor, G; Marcsik, Antónia; Molnár, Erika; Pálfi, Gyorgy; Pap, Ildikó; Teschler-Nicola, Maria; Pinhasi, Ron; Erdal, Yilmaz S; Velemínsky, Petr; Likovsky, Jakub; Belcastro, Maria Giovanna; Mariotti, Valentina; Riga, Alessandro; Rubini, Mauro; Zaio, Paola; Besra, Gurdyal S; Lee, Oona Y-C; Wu, Houdini H T; Minnikin, David E; Bull, Ian D; O'Grady, Justin; Spigelman, Mark
Leprosy was rare in Europe during the Roman period, yet its prevalence increased dramatically in medieval times. We examined human remains, with paleopathological lesions indicative of leprosy, dated to the 6th-11th century AD, from Central and Eastern Europe and Byzantine Anatolia. Analysis of ancient DNA and bacterial cell wall lipid biomarkers revealed Mycobacterium leprae in skeletal remains from 6th-8th century Northern Italy, 7th-11th century Hungary, 8th-9th century Austria, the Slavic Greater Moravian Empire of the 9th-10th century and 8th-10th century Byzantine samples from Northern Anatolia. These data were analyzed alongside findings published by others. M. leprae is an obligate human pathogen that has undergone an evolutionary bottleneck followed by clonal expansion. Therefore M. leprae genotypes and sub-genotypes give information about the human populations they have infected and their migration. Although data are limited, genotyping demonstrates that historical M. leprae from Byzantine Anatolia, Eastern and Central Europe resembles modern strains in Asia Minor rather than the recently characterized historical strains from North West Europe. The westward migration of peoples from Central Asia in the first millennium may have introduced different M. leprae strains into medieval Europe and certainly would have facilitated the spread of any existing leprosy. The subsequent decline of M. leprae in Europe may be due to increased host resistance. However, molecular evidence of historical leprosy and tuberculosis co-infections suggests that death from tuberculosis in leprosy patients was also a factor.
Wang, Zhenzhen; Sun, Yonghu; Fu, Xi'an; Yu, Gongqi; Wang, Chuan; Bao, Fangfang; Yue, Zhenhua; Li, Jianke; Sun, Lele; Irwanto, Astrid; Yu, Yongxiang; Chen, Mingfei; Mi, Zihao; Wang, Honglei; Huai, Pengcheng; Li, Yi; Du, Tiantian; Yu, Wenjun; Xia, Yang; Xiao, Hailu; You, Jiabao; Li, Jinghui; Yang, Qing; Wang, Na; Shang, Panpan; Niu, Guiye; Chi, Xiaojun; Wang, Xiuhuan; Cao, Jing; Cheng, Xiujun; Liu, Hong; Liu, Jianjun; Zhang, Furen
Leprosy, a chronic infectious disease, results from the uncultivable pathogen Mycobacterium leprae (M. leprae), and usually progresses to peripheral neuropathy and permanent progressive deformity if not treated. Previously published genetic studies have identified 18 gene/loci significantly associated with leprosy at the genome-wide significant level. However as a complex disease, only a small proportion of leprosy risk could be explained by those gene/loci. To further identify more susceptibility gene/loci, we hereby performed a three-stage GWAS comprising 8,156 leprosy patients and 15,610 controls of Chinese ancestry. Four novel loci were identified including rs6807915 on 3p25.2 (P=1.94 × 10−8, OR=0.89), rs4720118 on 7p14.3 (P=3.85 × 10−10, OR=1.16), rs55894533 on 8p23.1 (P=5.07 × 10−11, OR=1.15) and rs10100465 on 8q24.11 (P=2.85 × 10−11, OR=0.85). Altogether, these findings have provided new insight and significantly expanded our understanding of the genetic basis of leprosy. PMID:27976721
Nsagha, Dickson S; Bissek, Anne-Cécile Z K; Nsagha, Sarah M; Njunda, Anna L; Assob, Jules C N; Tabah, Earnest N; Bamgboye, Elijah A; Oyediran, Alain Bankole O O; Nde, Peter F; Njamnshi, Alfred K
Leprosy has been eliminated as a public health problem in most countries of the world according to the WHO, but the social stigma to the disease is still very high. The present study was performed to investigate the role of social stigma as a determinant for leprosy elimination in a leprosy endemic region of Cameroon. Focus group discussions, in-depth interviews and structured questionnaires were used to investigate leprosy social stigma among lepers, their contacts and a control group consisting of patients attending a health facility for reasons other than leprosy. Informed consent was sought and gained prior to starting the study. Focus group discussions and in-depth interviews identified three types of stigma: lack of self-esteem, tribal stigma and complete rejection by society. From the 480 structured questionnaires administered, there were overall positive attitudes to lepers among the study population and within the divisions (P=0.0). The proportion of participants that felt sympathetic with deformed lepers was 78.1% [95% confidence interval (CI): 74.4-81.8%] from a total of 480. Three hundred and ninety nine (83.1%) respondents indicated that they could share a meal or drink at the same table with a deformed leper (95% CI: 79.7-86.5%). Four hundred and three (83.9%) participants indicated that they could have a handshake and embrace a deformed leper (95% CI: 80.7-87.3%). A total of 85.2% (95.0% CI: 81.9-88.4%) participants affirmed that they could move with a deformed leper to the market or church. A high proportion of 71.5% (95.0% CI: 67.5%-75.5%) participants stated that they could offer a job to a deformed leper. The results indicate that Menchum division had the lowest mean score of 3.3 on positive attitudes to leprosy compared with Mezam (4.1) and Boyo (4.8) divisions. The high proportion of positive attitudes among the participants and in different divisions is a positive indicator that the elimination of leprosy social stigma is progressing in the
Nsagha, Dickson S.; Bissek, Anne-Cécile Z.K.; Nsagha, Sarah M.; Njunda, Anna L.; Assob, Jules C.N.; Tabah, Earnest N.; Bamgboye, Elijah A.; Oyediran, Alain Bankole O.O.; Nde, Peter F.; Njamnshi, Alfred K.
Leprosy has been eliminated as a public health problem in most countries of the world according to the WHO, but the social stigma to the disease is still very high. The present study was performed to investigate the role of social stigma as a determinant for leprosy elimination in a leprosy endemic region of Cameroon. Focus group discussions, in-depth interviews and structured questionnaires were used to investigate leprosy social stigma among lepers, their contacts and a control group consisting of patients attending a health facility for reasons other than leprosy. Informed consent was sought and gained prior to starting the study. Focus group discussions and in-depth interviews identified three types of stigma: lack of self-esteem, tribal stigma and complete rejection by society. From the 480 structured questionnaires administered, there were overall positive attitudes to lepers among the study population and within the divisions (P=0.0). The proportion of participants that felt sympathetic with deformed lepers was 78.1% [95% confidence interval (CI): 74.4–81.8%] from a total of 480. Three hundred and ninety nine (83.1%) respondents indicated that they could share a meal or drink at the same table with a deformed leper (95% CI: 79.7–86.5%). Four hundred and three (83.9%) participants indicated that they could have a handshake and embrace a deformed leper (95% CI: 80.7–87.3%). A total of 85.2% (95.0% CI: 81.9–88.4%) participants affirmed that they could move with a deformed leper to the market or church. A high proportion of 71.5% (95.0% CI: 67.5%–75.5%) participants stated that they could offer a job to a deformed leper. The results indicate that Menchum division had the lowest mean score of 3.3 on positive attitudes to leprosy compared with Mezam (4.1) and Boyo (4.8) divisions. The high proportion of positive attitudes among the participants and in different divisions is a positive indicator that the elimination of leprosy social stigma is progressing
In a previous study the reactivities of some lipoidal antigens in sera from patients with different types of leprosy were investigated. The present paper is a continuation of this earlier study and relates to an investigation of some 300 sera from leprosy patients in India. In particular, the reactivity of cardchol (a complement-fixing, lecithin-free, cardiolipin antigen) is compared with that of CWRM (an ”ordinary” cardiolipin antigen used in routine complement-fixation tests for the serodiagnosis of treponematoses). Cardchol, which is inferior to CWRM in reactivity with treponemal sera, has proved to be more reactive than CWRM in leprosy sera. The use of a lecithin-free cardiolipin antigen in serological investigations has revealed that the antilipoidal antibodies occurring in leprosy are most probably different from those demonstrated in treponematoses. Among the sera of non-syphilitic lepers, the percentage reactivity was significantly higher with cardchol than with CWRM. Thus, by changing the relative proportions of the three components of cardiolipin antigen, it has been possible to produce antigens with reactivities quite different from those of the antigens ordinarily used for the serological demonstration of syphilis. Cardchol is by no means a specific antigen for the demonstration of leprosy, but it has the ability to fix antibodies in certain leprosy sera that are not fixed by the ordinary CWRM antigen. PMID:14498723
Misch, Elizabeth A.; Macdonald, Murdo; Ranjit, Chaman; Sapkota, Bishwa R.; Wells, Richard D.; Siddiqui, M. Ruby; Kaplan, Gilla; Hawn, Thomas R.
Toll-like receptors (TLRs) are important regulators of the innate immune response to pathogens, including Mycobacterium leprae, which is recognized by TLR1/2 heterodimers. We previously identified a transmembrane domain polymorphism, TLR1_T1805G, that encodes an isoleucine to serine substitution and is associated with impaired signaling. We hypothesized that this TLR1 SNP regulates the innate immune response and susceptibility to leprosy. In HEK293 cells transfected with the 1805T or 1805G variant and stimulated with extracts of M. leprae, NF-κB activity was impaired in cells with the 1805G polymorphism. We next stimulated PBMCs from individuals with different genotypes for this SNP and found that 1805GG individuals had significantly reduced cytokine responses to both whole irradiated M. leprae and cell wall extracts. To investigate whether TLR1 variation is associated with clinical presentations of leprosy or leprosy immune reactions, we examined 933 Nepalese leprosy patients, including 238 with reversal reaction (RR), an immune reaction characterized by a Th1 T cell cytokine response. We found that the 1805G allele was associated with protection from RR with an odds ratio (OR) of 0.51 (95% CI 0.29–0.87, p = 0.01). Individuals with 1805 genotypes GG or TG also had a reduced risk of RR in comparison to genotype TT with an OR of 0.55 (95% CI 0.31–0.97, p = 0.04). To our knowledge, this is the first association of TLR1 with a Th1-mediated immune response. Our findings suggest that TLR1 deficiency influences adaptive immunity during leprosy infection to affect clinical manifestations such as nerve damage and disability. PMID:18461142
Neumann, Arthur da Silva; Dias, Felipe de Almeida; Ferreira, Jéssica da Silva; Fontes, Amanda Nogueira Brum; Rosa, Patricia Sammarco; Macedo, Rafael Enrique; Oliveira, José Henrique; Teixeira, Raquel Lima de Figueiredo; Pessolani, Maria Cristina Vidal; Moraes, Milton Ozório; Suffys, Philip Noel; Oliveira, Pedro L.; Sorgine, Marcos Henrique Ferreira; Lara, Flavio Alves
Leprosy is a chronic dermato-neurological disease caused by infection with Mycobacterium leprae. In 2013 almost 200,000 new cases of leprosy were detected around the world. Since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. Although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. In the present work, we experimentally investigated the hypothesis that the mosquitoes Aedes aegypti and Culex quinquefasciatus and the hemiptera Rhodnius prolixus act as leprosy vectors. By means of real-time PCR quantification of M. leprae 16SrRNA, we found that M. leprae remained viable inside the digestive tract of Rhodnius prolixus for 20 days after oral infection. In contrast, in the gut of both mosquito species tested, we were not able to detect M. leprae RNA after a similar period of time. Inside the kissing bug Rhodnius prolixus digestive tract, M. leprae was initially restricted to the anterior midgut, but gradually moved towards the hindgut, in a time course reminiscent of the life cycle of Trypanosoma cruzi, a well-known pathogen transmitted by this insect. The maintenance of M. leprae infectivity inside the digestive tract of this kissing bug is further supported by successful mice footpad inoculation with feces collected 20 days after infection. We conclude that Rhodnius prolixus defecate infective M. leprae, justifying the evaluation of the presence of M. leprae among sylvatic and domestic kissing bugs in countries endemic for leprosy. PMID:27203082
Neumann, Arthur da Silva; Dias, Felipe de Almeida; Ferreira, Jéssica da Silva; Fontes, Amanda Nogueira Brum; Rosa, Patricia Sammarco; Macedo, Rafael Enrique; Oliveira, José Henrique; Teixeira, Raquel Lima de Figueiredo; Pessolani, Maria Cristina Vidal; Moraes, Milton Ozório; Suffys, Philip Noel; Oliveira, Pedro L; Sorgine, Marcos Henrique Ferreira; Lara, Flavio Alves
Leprosy is a chronic dermato-neurological disease caused by infection with Mycobacterium leprae. In 2013 almost 200,000 new cases of leprosy were detected around the world. Since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. Although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. In the present work, we experimentally investigated the hypothesis that the mosquitoes Aedes aegypti and Culex quinquefasciatus and the hemiptera Rhodnius prolixus act as leprosy vectors. By means of real-time PCR quantification of M. leprae 16SrRNA, we found that M. leprae remained viable inside the digestive tract of Rhodnius prolixus for 20 days after oral infection. In contrast, in the gut of both mosquito species tested, we were not able to detect M. leprae RNA after a similar period of time. Inside the kissing bug Rhodnius prolixus digestive tract, M. leprae was initially restricted to the anterior midgut, but gradually moved towards the hindgut, in a time course reminiscent of the life cycle of Trypanosoma cruzi, a well-known pathogen transmitted by this insect. The maintenance of M. leprae infectivity inside the digestive tract of this kissing bug is further supported by successful mice footpad inoculation with feces collected 20 days after infection. We conclude that Rhodnius prolixus defecate infective M. leprae, justifying the evaluation of the presence of M. leprae among sylvatic and domestic kissing bugs in countries endemic for leprosy.
Kitajima, Shinichi; En, Junichiro; Kitajima, Shiori; Barua, Sumana; Goto, Masamichi
In 2012 the WHO Expert Committee on Leprosy published its 8th report, 14 years after the publication of its 7th report in 1998. This report, the first since the leprosy reduction goal was met in 2000, highlights key points such as improvements in the quality of various services available to patients and the efforts of individuals and societies, in addition to medical progress in diagnosis and treatment. This review will mainly describe the changes made since the 7th report. Some of the main modifications are the deletion of single lesion paucibacillary type, elongated treatment of patients with high bacterial indices, the introduction of promising new drugs, and a shift from reducing the statistical number of patients to a new target for disability prevention.
Nery, José Augusto da Costa; Filho, Fred Bernardes; Quintanilha, Juliana; Machado, Alice Miranda; Oliveira, Soraya de Souza Chantre; Sales, Anna Maria
A type 1 reaction or reversal reaction is expressed clinically by inflammatory exacerbation of the skin lesions and nerve trunks, consequently leading to sensory and motor alterations. It occurs in non-polar forms of leprosy, although it can occur in a small percentage of sub-polar LL treated patients. Disabilities, deformities and morbidity, still present in leprosy, are mainly caused by these acute episodes. The recognition of reactional states is imperative for an early approach and efficient management, to avoid the emergence of disabilities that stigmatize the disease. This review aims to describe the clinical aspects, immunopathogenesis, epidemiology, histopathological features and therapeutics of type 1 reactions. PMID:24173185
Saini, Chaman; Siddiqui, Anisuddin; Ramesh, Venkatesh; Nath, Indira
Background 50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions. Methodology and Principle Findings Quantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients. Conclusions Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation. PMID:27035913
Conde-Montero, Elena; Horcajada-Reales, Celia; Clavo, Petunia; Delgado-Sillero, Irene; Suárez-Fernández, Ricardo
Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy. Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet-rich plasma (PRP) may restore the healing process, leading to a reparative phase. We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. PRP therapy has been growing as a viable treatment alternative for chronic ulcers. However, stronger scientific evidence is required to support its potential benefit for use in chronic wounds.
Alvim, Iris Maria Peixoto; Nery, José Augusto da Costa; Lara, Flávio Alves; Sarno, Euzenir Nunes; Esquenazi, Danuza
In spite of hyporesponsivity to Mycobacterium leprae, borderline lepromatous (BL) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (T1R), which may cause nerve damages. This work focused on the participation of T cell subsets from blood and skin at T1R onset. We observed a significantly increased ex vivo frequency of both effector and memory CD4+ and CD8+ T cells in T1R group. Besides, ex vivo frequency of T cell homing receptor, the Cutaneous Leukocyte-associated Antigen (CLA) was significantly increased in T cells from T1R patients. M. leprae induced a higher frequency of CD4+ TEM and CD8+ TEF cells, as well as of CD8+/TEMRA (terminally differentiated effector T cells) subset, which expressed high CD69+. The presence of IFN-γ‒producing-CD4+ TEF and naïve and effector CD8+ T lymphocytes was significant in T1R. TBX21 expression was significantly higher in T1R, while BL showed increased GATA3 and FOXP3 expression. In T1R, TBX21 expression was strongly correlated with CD8+/IFN-γ‒ T cells frequency. The number of double positive CD8+/CLA+ and CD45RA+/CLA+ cells was significantly higher in skin lesions from T1R, in comparison with non-reactional BL group. The observed increase of ex vivo T cells at T1R onset suggests intravascular activation at the beginning of reactional episodes. The antigen-specific response in T1R group confirmed the higher number of CD8+/CLA+ and CD45RA+/CLA+ cells in T1R lesions suggests possible migration of these cells activated by M. leprae components inside the vascular compartment to skin and participation in T1R physiopathology. PMID:27764137
Bechelli, L. M.; Garbajosa, Gallego; Uemura, K.; Engler, V.; Domínguez, V. Martínez; Paredes, L.; Sundaresan, T.; Koch, G.; Matejka, M.
The use of BCG vaccine in the prevention of leprosy has been one of the most important subjects of investigation in the field of leprology in the last 25 years. The action of the vaccine was for many years investigated by determining its effect on the lepromin reaction. Field studies were later considered essential to determine whether BCG vaccination would be useful to leprosy contacts, to the child population probably exposed to infection, or to persons persistently lepromin-negative. The interest of the World Health Organization in this matter began in 1952 and, following the recommendations of certain advisory committees, it was decided to institute a field trial in Singu township in Burma. The main purpose of the investigation was to observe, in a highly endemic area, the protective effect, if any, of BCG vaccine against leprosy in the child population not exposed to Mycobacterium leprae at home but possibly exposed to the infection elsewhere. Field operations began at the end of August 1964 and the preliminary findings obtained up to the end of June 1968 relate to 3 annual re-examinations. So far, from the material studied, it appears that, under the conditions prevailing in Singu township, no significant effect of BCG vaccine can be seen within a period of 3 years. When children in both trial groups are followed-up for much longer periods, mainly children aged 0-4 years at intake, it is possible that a significant difference may emerge. However, to be operationally desirable, a merely significant difference is not enough; the protective effect of BCG should be substantial to warrant its large-scale use as an immunization procedure against leprosy. PMID:4246110
The study has been conducted in the Potka Block of East Singhbhum district of the state of Jharkhand. The district is mainly dominated by indigenous tribes, such as, Santhal, Munda, Ho, Bhumiz, Kharia, and Sabar. The unit of analysis of the study was an individual. The objectives were to: a) Understand the socio-economic and health status of LAP, b) Know the health seeking behavior and problems faced by the LAP, c) Assess the utilization of the programs related to Leprosy eradication in the study area and d), Suggest various measures for improving the socio-economic and health status of LAP. Fifty Leprosy affected persons (LAP) from the Potka block; comprising of 20% of LAP of that area have been selected as the study sample by using the method of Multi-Stage Random Sampling, with equal representation of men and women. The LAPs included leprosy patients, leprosy treated people and their family members. 39/50 (78%) of the respondents are illiterates and only 3/11 (6%) among the literate population have crossed matriculation and above. This seems to have resulted in the respondent's low level of awareness about the disease, resulting in delayed treatment. 14/25 (56%) percent of female and 13/25 (52%) of male respondents are considered untouchable by their natal families, thus forced to stay in congested leprosy colonies resulting in other social and health related issues. It was observed that leprosy cured children,and also children of LAP are being denied admission iany school, due to the social stigma attached to it. 27/50 (54%)of leprosy patients and leprosy cured people (mostly with visible deformities) were found to practice begging as their sole means of livelihood. Many LAPs are also engaged in cultivation and small scale business particularly among the rural population. An amount of gender disparity was also observed in the employment pattern among the LAPs. Among the, respondents 15/25 (60%) of the females are beggars as compared to 12/25 (48%) of the male
Saini, Chaman; Ramesh, V.; Nath, Indira
Background Patients with localized tuberculoid and generalized lepromatous leprosy show respectively Th1 and Th2 cytokine profile. Additionally, other patients in both types of leprosy also show a non discriminating Th0 cytokine profile with both interferon-γ and IL-4. The present study investigated the role of Th17 cells which appear to be a distinct subtype of Th subtypes in 19 tuberculoid and 18 lepromatous leprosy patients. Five healthy subjects with long term exposure to infection and 4 skin biopsies from healthy subjects undergoing cosmetic surgery were used as controls. Methodology/Principle Findings An array of Th17 related primers for cytokines, chemokines and transcription factors was used in real time reverse transcribed PCR to evaluate gene expression, ELISA for cytokine secretion in the supernatants of antigen stimulated PBMC cultures and flow cytometry for establishing the phenotype of the IL-17, IL-21 producing cells. Conclusions/Significance IL-17 isoforms showed significantly higher expression and release in supernatants of antigen stimulated PBMC cultures and dermal lesions of healthy contacts and tuberculoid leprosy as compared to lepromatous leprosy (p<0.003). This was further confirmed by Th17 associated transcription factor RORC, cytokines IL-21, IL-22, and IL-23, chemokines MMP13, CCL20, CCL22. Of interest was the association of IL-23R and not IL-6R with IL-17+ cells. The Th17 cells were CD4+ CCR6+ confirming their effector cell lineage. Polarized Th1 cytokines were seen in 3/7 tuberculoid and Th2 cytokines in 5/10 lepromatous leprosy patients. Of importance was the higher association of Th17 pathway factors with the non-polarized Th0 types as compared to the polarized Th1 and Th2 (p<0.01). Our study draws attention to a third type of effector Th cell that may play a role in leprosy. PMID:23936569
Debi, B P; Mohanty, H C; Tripathy, N; Tompe, D B; Sarangi, B K
Sixty arteriograms were done in twenty cases of lepromatous leprosy with thirty five plantar ulcers of six months to two years duration. Tortuosity, narrowing and obliteration of vascular lumen was mostly observed. Obliteration of vascular lumen was seen in twenty five percent of cases. Arteriographic findings were directly proportional with age of patient and duration of ulcer. Hyperemia and neovascularisation were seen in active and infected ulcers. Advanced vascular changes were associated with osteolytic changes of the bone along with neurological deficit.
Payne, Russell; Baccon, Jennifer; Dossett, John; Scollard, David; Byler, Debra; Patel, Akshal; Harbaugh, Kimberly
Hansen's disease, or leprosy, is a chronic infectious disease with many manifestations. Though still a major health concern and leading cause of peripheral neuropathy in the developing world, it is rare in the United States, with only about 150 cases reported each year. Nevertheless, it is imperative that neurosurgeons consider it in the differential diagnosis of neuropathy. The causative organism is Mycobacterium leprae, which infects and damages Schwann cells in the peripheral nervous system, leading first to sensory and then to motor deficits. A rare presentation of Hansen's disease is pure neuritic leprosy. It is characterized by nerve involvement without the characteristic cutaneous stigmata. The authors of this report describe a case of pure neuritic leprosy presenting as ulnar nerve neuropathy with corresponding radiographic, electrodiagnostic, and histopathological data. This 11-year-old, otherwise healthy male presented with progressive right-hand weakness and numbness with no cutaneous abnormalities. Physical examination and electrodiagnostic testing revealed findings consistent with a severe ulnar neuropathy at the elbow. Magnetic resonance imaging revealed diffuse thickening and enhancement of the ulnar nerve and narrowing at the cubital tunnel. The patient underwent ulnar nerve decompression with biopsy. Pathology revealed acid-fast organisms within the nerve, which was pathognomonic for Hansen's disease. He was started on antibiotic therapy, and on follow-up he had improved strength and sensation in the ulnar nerve distribution. Pure neuritic leprosy, though rare in the United States, should be considered in the differential diagnosis of those presenting with peripheral neuropathy and a history of travel to leprosy-endemic areas. The long incubation period of M. leprae, the ability of leprosy to mimic other conditions, and the low sensitivity of serological tests make clinical, electrodiagnostic, and radiographic evaluation necessary for diagnosis
Rivoire, Becky L.; TerLouw, Stephen; Groathouse, Nathan A.; Brennan, Patrick J.
True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3–10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial. PMID:24874086
Green Pastures Hospital is a specialist leprosy hospital in Pokhara, Nepal. As part of its service it offers a range of appliances aimed to assist in the rehabilitation of patients. This paper outlines the different orthoses and prostheses made at the Orthopaedic Appliances Centre in the hospital, their various indications and some of the benefits and problems associated with their use. Specific reference is made to the requirements related to local conditions and customs. The terrain, communications, facilities and materials available in Nepal make the work of the few rehabilitation engineers in the country somewhat different from that of those in the West. Some of these differences are described, drawing out contrasts in technical requirements of appliances and in organizational structures in the field of rehabilitation in the UK and Nepal.
Gutte, Rameshwar; Kharkar, Vidya; Mahajan, Sunanda; Chikhalkar, Siddhi; Khopkar, Uday
Granulomatous mycosis fungoides (GMF) is a rare type of cutaneous T cell lymphoma. A 38-year-old married male presented with decreased sweating all over the body for last 8 years, progressive redness and scaling over body for 2 years and multiple noduloulcerative lesions over the body for 1 year. Cutaneous examination revealed generalized erythema and scaling with poikilodermatous changes over chest and upper back along with multiple noduloulcerative lesions. Skin biopsy from a nodular lesion revealed dense granulomatous infiltrate of atypical lymphocytes with epidermotropism and sparing of appendages. Diagnosis of GMF was made. Computed tomographic scan of thorax, abdomen and pelvis revealed axillary and inguinal lymphadenopathy. Immunohistochemistry revealed leukocyte common antigen and CD3 positivity suggestive of T cell origin. Patient was started on CHOP (Cyclophosphamide, Hydroxydaunorubicin, Oncovin and Prednisolone) regimen of chemotherapy with marked improvement after three cycles of chemotherapy. This case had some clinical resemblance to lepromatous leprosy.
Citrus leprosis is a difficult viral disease causing significant damage to citrus fruit in South America and Central America. The disease is marked by dramatic lesions on fruit, leaves and stems resulting in unmarketable product. Citrus leprosis virus cytoplasmic types (CiLV-C and CiLV-C2) wer edete...
Karat, A. B. A.; Jeevaratnam, Anbu; Karat, S.; Rao, P. S. S.
A comparison of clofazimine and dapsone in the management of untreated lepromatous leprosy showed no significant differences between the two drugs in terms of morphological and bacterial indices. The incidence of erythema nodosum leprosum was similar in the two groups. Since dapsone is cheaper than clofazimine it remains the drug of choice for the routine management of untreated lepromatous leprosy. PMID:4942741
Presents information about the history, biology, and medical aspects of leprosy, including its description in historical documents, its cause and effects, statistics on its prevalence, and various attempts at treatment. Notes that leprosy is one of the few infectious diseases that, although treatable with medication, remains incurable. Contains 30…
Hungria, Emerith Mayra; Freitas, Aline Araújo; Pontes, Maria Araci Andrade; Gonçalves, Heitor Sá; Sousa, Ana Lúcia Osório Maroccolo; Costa, Maurício Barcelos; Castilho, Mirian Lane Oliveira Rodrigues; Duthie, Malcolm S; Stefani, Mariane Martins Araújo
To advance toward a whole blood assay (WBA)-based test capable of facilitating the diagnosis of paucibacillary (PB) leprosy, we evaluated a prototype in-tube WBA using combinations of Mycobacterium leprae antigens. Blood was collected from newly diagnosed untreated PB (n=38), multibacillary (MB) (n=30), healthy household contacts (HHC) of MB (n=27), and endemic controls (n=61) residing in Goiânia and Fortaleza, Brazil. Blood was incubated with M. leprae cell sonicate, recombinant proteins (46f+LID-1; ML0276+LID-1), or controls (phosphate-buffered saline, phytohemagglutinin, M. tuberculosis purified protein derivative). Antigen-specific IFNγ production was observed in 71-84% and 55% of PB and HHC, respectively. Antigen-specific CXCL10 levels were similarly assessed to determine if, unlike IFNγ, CXCL10 could differentiate PB from HHC with repeated exposure/asymptomatic M. leprae infection. The CXCL10 levels induced in response to M. leprae antigens could not, however, differentiate PB from HHC. Despite these limitations, the WBAs reported here still represent important tools for assessing M. leprae infection rates and evaluating the impact of control measures.
Sadhu, Soumi; Khaitan, Binod Kumar; Joshi, Beenu; Sengupta, Utpal; Nautiyal, Arvind Kumar; Mitra, Dipendra Kumar
T cell defect is a common feature in lepromatous or borderline lepromatous leprosy (LL/BL) patients in contrast to tuberculoid or borderline tuberculoid type (TT/BT) patients. Tuberculoid leprosy is characterized by strong Th1-type cell response with localized lesions whereas lepromatous leprosy is hallmarked by its selective Mycobacterium leprae specific T cell anergy leading to disseminated and progressive disease. FoxP3+ Regulatory T cells (Treg) which are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases also dampen proinflammatory T cells that include T helper 17 (Th17) cells. This study is aimed at evaluating the role of Treg cells in influencing other effector T cells and its relationship with the cytokine polarized state in leprosy patients. Peripheral blood mononuclear cells from of BT/TT (n = 15) and BL/LL (n = 15) patients were stimulated with M. leprae antigen (WCL) in presence of golgi transport inhibitor monensin for FACS based intracellular cytokine estimation. The frequency of Treg cells showed >5-fold increase in BL/LL in comparison to BT/TT and healthy contacts. These cells produced suppressive cytokine, IL-10 in BL/LL as opposed to BT/TT (p = 0.0200) indicating their suppressive function. The frequency of Th17 cells (CD4, CD45RO, IL-17) was, however, higher in BT/TT. Significant negative correlation (r = -0.68, P = 0.03) was also found between IL-10 of Treg cells and IL-17+ T cells in BL/LL. Blocking IL-10/TGF-β restored the IL-17+ T cells in BL/LL patients. Simultaneously, presence of Th17 related cytokines (TGF-β, IL-6, IL-17 and IL-23) decreased the number of FoxP3+ Treg cells concomitantly increasing IL-17 producing CD4+ cells in lepromatous leprosy. Higher frequency of Programmed Death-1/PD-1+ Treg cells and its ligand, PDL-1 in antigen presenting cells (APCs) was found in BL/LL patients. Inhibition of this pathway led to rescue of IFN-γ and IL-17 producing T cells
Karat, A B; Rao, P S
321 adult male lepromatous leprosy patients were studied for relationship between haematological findings, severity of disease and duration of treatment. Significant changes were noticed in relation in haemoglobin concentration, serum vitamin B12 and serum folate levels, serum albumin and globulin. No significant changes were observed in serum iron levels in relation to disease and treatment status. With rising bacterial load, there was a trend towards lower haemoglobin concentration, higher vitamin B12 level and lowered serum folate levels. Serum albumin showed a significant decline, while serum globulin showed a significant rise. The findings are discussed in relation to replacement of bone marrow by lepromatous tissue as well as possible interference in the metabolism of haematinics by M. leprae. The exact mechanism of neurlogical deficit in leprosy in relation to deficiency of vitamin B12 and folic acid need to be further elucidated.
Ramarozatovo, Lala S.; Ranaivo, Irina M.; Andrianarison, Malalaniaina; Cambau, Emmanuelle
We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. PMID:27579195
Westphal, Danielle Cristine; Pennini, Silmara Navarro; de Souza, Petra Pereira; Maquiné, Gustavo Ávila; Schettini, Antônio Pedro Mendes; Santos, Mônica
Primary follicular mucinosis is a rare dermatosis characterized by the accumulation of mucin in the follicular epithelium and sebaceous glands. Clinically, it is characterized by the presence of papules or well-circumscribed and infiltrated plaques. In this paper, we report the case of a female patient, seven years old, evolving for three months with an asymptomatic, erythematous and infiltrated plaque located in the chin region. The research of thermal, pain and tactile sensitivity was inconclusive. Histological findings confirmed the diagnosis of follicular mucinosis. There was regression of the lesion with the use of medium potency topical corticosteroids for 20 days. The pathogenesis of follicular mucinosis remains unknown, being in some cases associated with lymphoproliferative disorders. In endemic areas of leprosy, isolated and infiltrated follicular mucinosis lesions should be further differentiated from leprosy. PMID:26312699
Tallarida, Giuseppe; d'Alcontres, Francesco Stagno; Noto, Salvatore; Parodi, Aurora; Tagliafico, Alberto
Five years after both right ulnar and median nerve decompression for paraesthesias and palsy, a patient, coming from Nigeria but living in Italy, came to our unit claiming to have persistent pain and combined median and ulnar palsy. Under suspicion of leprosy, skin and left sural nerve biopsy were performed. Skin tests were negative, but Schwann cells resulted as positive for acid-fast bacilli (AFB), leading to the diagnosis of Pure Neuritic Leprosy (PNL). The patient was given PB multidrug therapy and recovered from pain in two months. After nine months both High Resolution Ultrasonography (HRUS) and Magnetic Resonance Imaging (MRI) were performed, revealing thickening of the nerves. Since demyelination is common in PNL, the Authors started to use Diffusion Tensor Imaging Tractography (DTIT) to get better morphological and functional data about myelination than does the traditional imaging. DTIT proved successful in showing myelin discontinuity, reorganization, and myelination, and the Authors suggest that it can give more information about the evolution of the disease, as well as further indications for surgery (nerve decompression, nerve transfers, and babysitting for distal effector protection), and should be added to traditional imaging tools in leprosy. PMID:27738537
Bloom, B. R.; Salgame, P.; Mehra, V.; Kato, H.; Modlin, R.; Rea, T.; Brennan, P.; Convit, J.; Lugozi, L.; Snapper, S.; Jacobs, W.
Leprosy is of interest to immunologists because the varied clinical manifestations of the disease correlate closely with the immunological spectrum. Resistance to infection is dependent on appropriate cell-mediated immunity, but patients with the lepromatous form fail to respond to antigens of M. leprae. In vitro studies have revealed the existence of T-suppressor cells of the phenotype CD8+, CD3+, HLA-DR+, FcR+, 9.3-, which are restricted by major histocompatibility complex (MHC) class II antigens. Several new candidate vaccines against leprosy have been effective in breaking immunological unresponsiveness and engendering cell-mediated immunity in lepromatous leprosy patients, including the combination of BCG + killed M. leprae. Because BCG has unique adjuvant properties, we have begun to use molecular genetic approaches to develop BCG into a multivaccine vehicle capable of immunizing simultaneously against several pathogens. Both phage-based and plasmid-based strategies have been successfully developed for introducing selectable markers into BCG for the first time. ImagesFigure 1
Tarique, Mohd; Naqvi, Raza Ali; Santosh, K V; Kamal, Vineet Kumar; Khanna, Neena; Rao, D N
Leprosy is an infectious disease caused by M. leprae. We analyzed 48 cytokine polymorphisms in 13 (pro as well as anti-inflammatory) cytokine genes using PCR-SSP assay in 102 leprosy patients and 120 healthy controls with intent to find out a link between cytokine polymorphisms and disease susceptibility. TNF-α (-308) GG, IL-10 (-819) TT, IL-10 (-1082) GG and IL1R (+1970) CC genotypes are found to be predominant (p=0.01, p=0.02, p=0.0001 and p=0.001, respectively) in both tuberculoid as well as lepromatous leprosy patients. This observation suggests these genotypes as play the central role(s) in the progression of disease. CBA assay demonstrates the varied serum concentration of these cytokines with respect to their genotypes. The above genotypes appeared as high producer genotypes in our study. Even in presence of high produce genotypes, TNF-α level are found to be affected/masked by the presence of IL-10 in leprosy patients. Expressional masking of TNF-α is associated with the expression of IL-10 in these patients. This is one the negative impact of SNP-SNP interaction in leprosy patients. Therefore, we can conclude that cytokine gene polymorphisms determine the predisposition to the leprosy progression.
This article sets out to expand the way stigma, and those affected by it, are understood within leprosy discourse and to apply these insights to the analysis of the experiences of leprosy workers. The term stigma is often used simply as shorthand for 'negative social experience'. However, to reduce the negative aspects of complex everyday life experiences to a single word is often overly simplistic and can serve to objectify, rather than illuminate, the experiences of those affected. This article argues that in order to understand the lived experience of stigma we must come to understand stigma as an ongoing, dialectical social process and develop an approach to stigma that analytically separates stigma from its negative social consequences. The article applies these insights to data collected during 14 months of fieldwork with front-line leprosy workers in India, which suggests that falling leprosy prevalence rates and a rapidly changing policy landscape have led to leprosy workers feeling marginalised and stigmatised within their own organisation. The article argues that, rather than seeing stigma merely as a negative process in which leprosy workers are passive victims, we must recognise that stigma also plays a key role in the creation and maintenance of leprosy workers' identity and is utilised as a strategic tool in the struggle for influence between different groups within the organisation. Finally, the article argues for the benefit of expanding our understanding of stigma across public health and of applying these insights to designing future interventions.
Singh, Pushpendra; Benjak, Andrej; Schuenemann, Verena J.; Herbig, Alexander; Avanzi, Charlotte; Busso, Philippe; Nieselt, Kay; Krause, Johannes; Vera-Cabrera, Lucio; Cole, Stewart T.
Mycobacterium lepromatosis is an uncultured human pathogen associated with diffuse lepromatous leprosy and a reactional state known as Lucio's phenomenon. By using deep sequencing with and without DNA enrichment, we obtained the near-complete genome sequence of M. lepromatosis present in a skin biopsy from a Mexican patient, and compared it with that of Mycobacterium leprae, which has undergone extensive reductive evolution. The genomes display extensive synteny and are similar in size (∼3.27 Mb). Protein-coding genes share 93% nucleotide sequence identity, whereas pseudogenes are only 82% identical. The events that led to pseudogenization of 50% of the genome likely occurred before divergence from their most recent common ancestor (MRCA), and both M. lepromatosis and M. leprae have since accumulated new pseudogenes or acquired specific deletions. Functional comparisons suggest that M. lepromatosis has lost several enzymes required for amino acid synthesis whereas M. leprae has a defective heme pathway. M. lepromatosis has retained all functions required to infect the Schwann cells of the peripheral nervous system and therefore may also be neuropathogenic. A phylogeographic survey of 227 leprosy biopsies by differential PCR revealed that 221 contained M. leprae whereas only six, all from Mexico, harbored M. lepromatosis. Phylogenetic comparisons indicate that M. lepromatosis is closer than M. leprae to the MRCA, and a Bayesian dating analysis suggests that they diverged from their MRCA approximately 13.9 Mya. Thus, despite their ancient separation, the two leprosy bacilli are remarkably conserved and still cause similar pathologic conditions. PMID:25831531
Kumar, Sudhir; Naqvi, Raza Ali; Bhat, Ajaz A; Rani, Richa; Ali, Riyasat; Agnihotri, Abhishek; Khanna, Neena; Rao, D N
The defective antigen presenting ability of antigen presenting cells (APCs) modulates host cytokines and co-stimulatory signals that may lead to severity of leprosy. In the present study, we sought to evaluate the phenotypic features of APCs along with whether DC SIGN (DC-specific intercellular adhesion molecule-grabbing nonintegrin) influences IL-10 production while moving from tuberculoid (BT/TT) to lepromatous (BL/LL) pole in leprosy pathogenesis. The study revealed an increased expression of DC SIGN on CD11c⁺ cells from BL/LL patients and an impaired form of CD83 (∼50 kDa). However, the cells after treatment with GM-CSF+IL-4+ManLAM showed an increased expression of similar form of CD83 on DCs. Upon treatment with ManLAM, DCs were found to show increased nuclear presence of NF-κB, thus leading to higher IL-10 production. High IL-10 production from ManLAM treated PBMCs further suggested the role of DC SIGN in subverting the DCs function towards BL/LL pole of leprosy. Anti-DC SIGN treatment resulting in restricted nuclear ingression of NF-κB as well as its acetylation along with enhanced T cell proliferation validated our findings. In conclusion, Mycobacterium leprae component triggers DC SIGN on DCs to induce production of IL-10 by modulating intracellular signalling pathway at the level of transcription factor NF-κB towards BL/LL pole of disease.
Benbow, C; Tamiru, T
This paper describes the development of self-care groups in Ethiopia by ALERT, and the successes and failures experienced in the process. The groups were started in 1995 in response to two main problems, the increasing number of people dependent on ALERT to heal their wounds despite years of health education, and the limited financial resources of ALERT for wound healing supplies. By December 1999, there were a total of 72 established groups. Group membership was voluntary. There have been a number of positive outcomes. Group members have taken up responsibility for managing and monitoring their own wounds and supplying their own wound healing materials. More attention is paid to their personal hygiene and personal appearance. They also report increased confidence to participate in society, restored dignity and self-respect, and a sense of belonging within the community. In addition, some members have started to pay more attention to their local environmental hygiene by building pit latrines and waste disposal sites. The ALERT staff involved in this initiative had to change their role from that of a leprosy service provider to a self-care group facilitator, but not all were successful in making this transition. The remaining challenge for the programme is sustainability and further development through the National Tuberculosis and Leprosy Control Programme, The Ethiopian National Association for Ex-Leprosy Patients and possibly other organizations too.
Rubini, Mauro; Zaio, Paola; Roberts, Charlotte
Tuberculosis (TB) and leprosy are infections caused by Mycobacteria. This paper documents new skeletal evidence in Italy from the Iron Age site of Corvaro (Central Italy; 5th century BCE) and the Roman site of Palombara (Central Italy; 4th-5th century CE), and briefly reviews the extant evidence for these infections in Italy. The skeletal evidence for TB in Italy is more ancient than for leprosy, and is more common. The oldest evidence for both mycobacterial diseases is in the North of Italy, but this could be by chance, even if biomolecular models suggest a land route from the East to central Europe, especially for leprosy.
Cartel, J L; Chanteau, S; Moulia-Pelat, J P; Plichart, R; Glaziou, P; Boutin, J P; Roux, J F; Grosset, J H
In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.
Henry, Mary; GalAn, Noêmi; Teasdale, Katherine; Prado, Renata; Amar, Harpreet; Rays, Marina S.; Roberts, Lesley; Siqueira, Pedro; de Wildt, Gilles; Virmond, Marcos; Das, Pranab K.
Background Leprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil. Methodology/ Principal Findings This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010). Conclusions/ Significance This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical
Lastória, Joel Carlos; de Abreu, Marilda Aparecida Milanez Morgado
Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis. PMID:24937811
Mazini, Priscila Saamara; Alves, Hugo Vicentin; Reis, Pâmela Guimarães; Lopes, Ana Paula; Sell, Ana Maria; Santos-Rosa, Manuel; Visentainer, Jeane Eliete Laguila; Rodrigues-Santos, Paulo
Leprosy is a chronic infectious disease caused by an obligate intracellular bacterium known as Mycobacterium leprae. Exposure to the bacillus is necessary, but this alone does not mean an individual will develop clinical symptoms of the disease. In recent years, several genes have been associated with leprosy and the innate immune response pathways converge on the main hypothesis that genes are involved in the susceptibility for the disease in two distinct steps: for leprosy per se and in the development of the different clinical forms. These genes participate in the sensing, main metabolic pathway of immune response activation and, subsequently, on the evolution of the disease into its clinical forms. The aim of this review is to highlight the role of innate immune response in the context of leprosy, stressing their participation in the signaling and targeting processes in response to bacillus infection and on the evolution to the clinical forms of the disease. PMID:26793196
Romero-Salazar, A; Parra, M C; Moya-Hernández, C; Rujano, R; Salas, J
Social representation of leprosy in active patients under medical control is made up elements that come from the medical discourse and also from the discourse that about this disease circulates in society. This syncretism is expressed in each context a specific way on the components of the representation notion, beliefs, attitudes and behaviors - making of it a complex reality. On account of beliefs importance, whose depth and roots are linked to the thousand of years this disease has been known and to the seclusion practices in force till recent times, it would be comprehensible the predominance of elements related to common sense or popular knowledge. Nevertheless, as the representation is a collective construction, its fundamental features would be defined according to the specific characteristics of the group. To this respect, the main finding of this research referred to: first, the limited knowledge around this disease and the existence of beliefs and inadequated attitudes for controlling programs of active patients registered in the Maracaibo Service of Sanitary Dermatology located in Venezuela (Servicio de Dermatologia Sanitaria de Maracaibo (SDSMJ, Venezuela); second, a predominance of a congnitive dimension of representation, notions and beliefs relate to the role of fortune and fate, sexual promiscuity or heritage in the contagion; third, a patient's tendency to reproduce a disqualified stereotype and hide the disease due to an exaggerated rejection fear.
Darlong, Joydeepa; Govindharaj, Pitchaimani; Kurian, Royce; Sundarrao, Pamidipani; John, Annamma S.
Background Leprosy Type 1 reactions are difficult to treat and only 70% of patients respond to steroid treatment. Azathioprine has been used as an immune-suppressant and we tested its efficacy in treating leprosy T1R. Methodology Randomised controlled trial adding azathioprine to steroid treatment for leprosy reactions. This trial was conducted in four leprosy hospitals in India. Patients with a new leprosy Type 1 reaction affecting either skin or nerve were recruited. They were given a 20 week course of oral prednisolone either with placebo or azathioprine 50mg for 24, 36 or 48 weeks. Outcomes were measured using a verified combined clinical reaction severity score (CCS) and the score difference between baseline and end of study calculated. An intention to treat analysis was done on the 279 patients who had an outcome. Principal findings 345 patients were recruited, 145 were lost due to adverse events, loss to follow up or death. 36% needed extra steroids due to a recurrence of their skin and/or nerve reaction. 76% of patients had improvements in their CCS the end of the study, 22% had no change and 1.1% deteriorated. Adding azathioprine to steroid treatment did not improve CCS. So the improvements were attributable to treatment with steroids. We analysed the skin, sensory and motor scores separately and found that skin improvement contributed most with 78.9% of patients having skin improvement, azathioprine treatment for 48 weeks improved sensory scores it also improved motor scores but so did treatment with prednisolone alone. We identified significant adverse effects attributable to steroid treatment. When azathioprine and Dapsone were given together significant numbers of patients developed significant anaemia. Conclusions Azathioprine is not recommended for the treatment of leprosy reactions and does not improve steroid treatment. Recurrent reactions are a major challenge. We have also identified that 65% of patients with sensory and 50% with motor nerve
Pinho, Adriano Bastos; Borghesan, Flaviano Henrique Pelloso; Lotufo, Marcelo Neves; Allet, Maurício de Araújo
Objective to compare the SALSA and risk awareness scales with the DASH scale in assessments on leprosy surgery. Method before the operation and 90 days afterwards, we applied the tests to 14 patients (11 females and three males) of ages from 28 to 67 years, who were operated between November 2011 and May 2012. Results the patients were evaluated after the operation using the SALSA and DASH scales, to measure their relationships and results. Conclusion despite the small sample, this study showed that there were similar relationships of results between the SALSA/risk awareness and DASH scales. PMID:26229815
González-Amaro, R; Salazar-González, J F; Baranda, L; Abud-Mendoza, C; Moncada, B; García, R; Alcocer-Varela, J
Some lepromatous leprosy (LL) patients are characterized by the presence of activated suppressor T cells that specifically inhibit the immune response to Mycobacterium leprae antigens. Immune contrasuppressor (CS) cell activity antagonize suppressor function. Whereas the former function has been extensively studied in leprosy, the latter has not been explored. We studied the peripheral blood mononuclear cells (PBMNC) of 20 patients with leprosy (10 lepromatous and 10 tuberculoid) and six healthy contacts. We found CS-like activity in the PBMNC from some LL patients when assayed in vitro using lepromin as antigen. This CS-like function was found in CD8+, vicia villosa adherent (VV+) T cells. CS-like activity was not detected in PBMNC from either tuberculoid patients or healthy contacts. Pre-treatment of CD8+, VV+ cells with either recombinant IL-2 (5 u/ml) or recombinant interferon-gamma (1,000 u/ml) did not modify significantly their putative CS function. However, in 50% of lepromatous patients the pre-incubation of CD8+, VV+ cells with both lymphokines together increased significantly the CS-like activity. These data suggest that the in vitro immune response to M. leprae in some LL patients can be augmented by either modifying numerically the contrasuppressor T cells or activating them with lymphokines. PMID:3133142
If it can be argued that no single attribute or condition (leprosy included) is inherently or universally considered to be 'deeply discrediting,' to quote Goffman, then we must consider how external factors shape stigma associated with that condition in different cultural and socioeconomic contexts. Often, an analysis of what is perceived to be stigma towards people affected by leprosy uncovers other prejudices or stigmatising attitudes associated with class, gender, and/or ethnic inequalities in that society. The movement of people across international borders adds new dimensions to the experience of leprosy, as affected individuals confront different sets of understandings of the disease among healthcare professionals, friends, family, and employers in host and sending countries. Preconceptions of the immigrant 'other' in host countries may be bound up with notions of disease and danger, further complicating the experience of leprosy treatment for immigrants. Drawing on the work of others and on early stage qualitative research on leprosy among Brazilian immigrants to the United States, this paper will consider the ways in which immigration and transnational processes could affect the experience of stigma among immigrants affected by leprosy.
Early historiography on medicine in British colonial Africa suggests that colonial government and missionary medicine occupied two relatively distinct spheres, and that government officials viewed medical missionaries with suspicion and distrust. Contrary to this paradigm, this article suggests that missionaries and colonial government officials collaborated extensively and amicably in the treatment of leprosy in Uganda. Mission, medical, and government correspondence and reports are drawn upon in order to demonstrate that the suspicion and tension that characterised so many other interactions between British colonial government officials and missionaries was largely absent in the treatment of leprosy in Uganda. The mutual social and cultural priorities of missionaries and government administrators led to a system of isolated, in-patient leprosy care that was limited in scope and reflective not of a goal for the public health of Uganda, but rather a vision for the future of Uganda as a “civilised” and Christian country. PMID:24949084
Gasink, Leanne B; Seymour, Christopher; Blumberg, Emily A; Goldberg, Lee R; Fishman, Neil O
The effect of solid-organ transplantation on the acquisition, presentation and course of leprosy is unknown. We present a case of leprosy in a heart transplant recipient with multiple unique features possibly attributed to altered immune function.
Bach, M A; Chatenoud, L; Wallach, D; Phan Dinh Tuy, F; Cottenot, F
T cell subsets and T cell functions were explored in 31 leprosy patients with the following methods: determination of the percentages of the different T cell subpopulations defined by monoclonal antibodies directed at total T cells, helper T cells and suppressor/cytotoxic T cells; measurement of the in vitro proliferative responses to mitogens; study of the concanavalin A-induced suppressive activity, assessed on MLC; measurement of delayed-type hypersensitivity by skin testing. The confrontation between immunological lepromatous patients without type-2 reaction (erythema nodosum leprosum), (2) lepromatous patients without ENL (erythema nodosum leprosum), (2) lepromatous patients was recent ENL and (3) tuberculoid patients. Unexpectedly, groups 1 and 3, although differing strongly in their clinical status and their sensitivity to lepromin (absent in group 1 and strong in group 3), showed a similar immunological profile with a normal percentage of T cells and a normal distribution of T cells among the major T cell subset contrasting with a moderate decrease of proliferative responses to mitogens and impaired delayed-type hypersensitivity reactions. Concanavalin A-induced suppressive activity was type-2 reaction) strongly differed from both other groups, showing striking abnormalities other groups, showing striking abnormalities of the repartition of the T cell subsets, with increased percentages of helper T cells and decreased percentages of suppressor T cells, and elevated proliferative responses to mitogens. Concanavalin A-induced suppressive activity was reduced in most patients of this group. It is suggested that this imbalance between T cell subsets contributes to the occurrence of ENL reactions in lepromatous patients. PMID:6459897
Wan, Eric L.; Rivadeneira, Andres F.; Jouvin, Renato Martinez
Summary: Plastic surgery has a tradition of caring for patients with facial deformity and hand deformity related to leprosy. The approach, however, to the progressive deformity and disability related to chronic nerve compression is underappreciated in the world today. A cohort of patients with leprous neuropathy from an indigenous area of leprosy in Ecuador was evaluated for the presence of chronic peripheral nerve compression, and 12 patients were chosen for simultaneous upper and lower extremity, unilateral, nerve decompression at multiple levels along the course of each nerve. The results at 1 year of follow-up show that 6 patients improved into the excellent category and 4 patients improved into the good category for improved function. Based on the early results in this small cohort of patients with leprous neuropathy, an approach to peripheral nerve decompression, encompassing the concept of multiple crush at multiple levels of each nerve, seems to offer optimism to improve upper and lower extremity limb function. Long-term studies with quality-of-life outcomes would be welcome. PMID:27257567
Bobosha, Kidist; Van Der Ploeg-Van Schip, Jolien J; Zewdie, Martha; Sapkota, Bishwa Raj; Hagge, Deanna A; Franken, Kees L M C; Inbiale, Wondmagegn; Aseffa, Abraham; Ottenhoff, Tom H M; Geluk, Annemieke
Ongoing transmission of leprosy is evident from the stable disease incidence in high burden areas. Tools for early detection of Mycobacterium leprae (M. leprae) infection, particularly in sub-clinically infected individuals, are urgently required to reduce transmission. Following the sequencing of the M. leprae genome, many M. leprae-unique candidate proteins have been identified, several of which have been tested for induction of M. leprae specific T cell responses in different leprosy endemic areas. In this study, 21 M. leprae-unique proteins and 10 peptide pools covering the complete sequence of five M. leprae-unique proteins (ML0576, ML1989, ML1990, ML2283, and ML2567) were evaluated in 160 individuals in Nepal and Ethiopia. These included: tuberculoid and borderline tuberculoid (TT/BT), borderline borderline and borderline lepromatous (BB/BL) leprosy patients; healthy household contacts (HHC); tuberculosis (TB) patients and endemic controls (EC). Immunogenicity of the proteins was determined by IFN-gamma secretion via stimulation of PBMC in 6 days lymphocyte stimulation tests (LST) or in whole blood assays (WBA). In LST, BB/BL patients (40%) responded to ML0573 and ML1601 whereas ML1604 was most immunogenic in TT/BT (35%) and HHC (36%). Additionally, significant numbers of EC displayed IFN-gamma production in response to ML0573 (54%), ML1601 (50%) and ML1604 (54%). TB patients on the other hand, hardly responded to any of the proteins except for ML1989. Comparison of IFN-gamma responses to ML0121, ML0141 and ML0188 for TT/BT patients showed specific increase in diluted 6 days WBA compared to the undiluted 24 hours WBA, whereas EC showed a reduced response in the diluted WBA, which may indicate detection of disease-specific responses in the 6 days WBA. In summary, identification of multiple M. leprae proteins inducing M. leprae-specific T cell responses in groups at high risk of developing leprosy may contribute to improve early detection for M. leprae
Tabah, Earnest Njih; Nsagha, Dickson Shey; Bissek, Anne-Cecile Zoung-Kanyi; Bratschi, Martin W.; Njamnshi, Theophilus Ngeh; Plushke, Gerd; Njamnshi, Alfred Kongnyu
Background Cameroon achieved the elimination target of leprosy in 2000, and has maintained this status ever since. However, a number of health districts in the country continue to report significant numbers of leprosy cases. The aim of this study was to assess the burden of leprosy in Cameroon from 2000 to 2014. Methods We obtained and analysed using the new leprosy burden concept of analysis, leprosy surveillance data collected between 2000 and 2014 from the National Leprosy Control Programme. Principal findings Cameroon achieved leprosy elimination in 2000, registering a prevalence rate of 0.94/10,000 population. The prevalence rate dropped further to reach 0.20/10,000 population (78% reduction) in 2014. Similarly, the new case detection rate dropped from 4.88/100,000 population in 2000 to 1.46/100,000 population (85.3% reduction) in 2014. All 10 regions of the country achieved leprosy elimination between 2000 and 2014; however, 10 health districts were still to do so by 2014. The number of high-leprosy-burden regions decreased from 8 in 2000 to 1 in 2014. Seven and two regions were respectively medium and low-burdened at the end of 2014. At the health districts level, 18 remained at the high-leprosy-burdened level in 2014. Conclusion The leprosy prevalence and detection rates as well as the overall leprosy burden in Cameroon have dropped significantly between 2000 and 2014. However, a good number of health districts remain high-leprosy-burdened. The National Leprosy Control Programme should focus efforts on these health districts in the next coming years in order to further reduce the burden of leprosy in the country. PMID:27732603
Song, S.P.; Elias, P.M.; Lv, C.Z.; Shi, Y.J.; Guang, P.; Zhang, X.J.; Feingold, K.R.; Man, M.Q.
Background/Objectives Leprosy prominently involves both the skin and peripheral neural tissues and some symptoms persist after microbial cure. Because alterations in the dermis also occur in leprosy, we assessed here whether there were changes in cutaneous resonance running time (CRRT), a parameter that is influenced by collagen properties, in cured leprosy subjects. Methods A reviscometer was used to measure the CRRT at various directions on the dorsal hand and the flexural forearms of 76 cured leprosy subjects aged 50–85 years and 68 age-matched normal subjects. Results In comparison to normal subjects, CRRTs on the hands and the forearms were significantly reduced in all directions in cured leprosy, except at the 1–7, 2–8 and 3–9 o'clock directions on the forearms. CRRTs were reduced significantly at both the 4–10 and 5–11 o'clock directions on the forearm in lepromatous (73.33 ± 4.19 at 4–10 o'clock and 67.44 ± 2.71 at 5–11 o'clock direction) and borderline lepromatous types (77.58 ± 5.84 at 4–10 o'clock and 79.85 ± 6.81 at 5–11 o'clock direction) as compared with normal (143.10 ± 7.75 at 4–10 o'clock and 125.18 ± 8.14 at 5–11 o'clock direction). On the hand, CRRTs at all directions, except that at 4–10 o'clock direction, were also significantly reduced in lepromatous and borderline lepromatous types in comparison with normal. Significant differences in CRRT at some directions were found among the various subtypes of leprosy. Conclusion CRRTs were abnormal in the cured leprosy subjects as a whole, but varied with leprosy subtypes, which suggested that the extent of reduction of CRRTs correlates with the severity of immune alteration. These results suggest that CRRT measurements could be a useful approach to quantify the extent of some residual abnormalities in cured leprosy and perhaps could also be used to evaluate the efficacy of treatment. PMID:19648783
Truman, Richard W.; Ebenezer, Gigi J.; Pena, Maria T.; Sharma, Rahul; Balamayooran, Gayathriy; Gillingwater, Thomas H.; Scollard, David M.; McArthur, Justin C.; Rambukkana, Anura
Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text. PMID:24615444
Synoptic life history accounts and case studies of people with leprosy have tended to follow conventionalised narrative forms, with the onset of leprosy causing a violent rupture in otherwise positively construed life courses. Many of those I worked with in India, well-versed in relating their stories to donor agencies, were also aware of the power of such narratives to access funding. While case studies can be informative about the politics of representation, then, they often obscure as much as they reveal about the lives of those described within them, emphasising leprosy-related stigma at the expense of other forms or drivers of social exclusion. Drawing upon a series of interviews with a leprosy affected man I have known and worked with for 25 years, this paper demonstrates how more nuanced--and, from a policy perspective, more useful--accounts might be achieved through intensive biographical interviews carried out over time. In particular, analysis of such biographies, set against the wider backdrop of ethnographic research, allows for a more subtle reading of leprosy-related stigma, contextualised in relation to a range of intersecting socio-political, cultural and economic concerns.
Fava, Vinicius M.; Sales-Marques, Carolinne; Alcaïs, Alexandre; Moraes, Milton O.; Schurr, Erwin
A current major challenge in leprosy control is the prevention of permanent disabilities. Host pathological inflammatory responses termed type 1 reaction (T1R) are a leading cause of nerve damage for leprosy patients. The environmental or inherited factors that predispose leprosy cases to undergo T1R are not known. However, studies have shown an important contribution of host genetics for susceptibility to T1R. We have previously identified variants encompassing the TNFSF15/TNFSF8 genes as T1R risk factors in a Vietnamese sample and replicated this association in a Brazilian sample. However, we failed to validate in Brazilian patients the strong association of TNFSF15/TNFSF8 markers rs6478108 and rs7863183 with T1R that we had observed in Vietnamese patients. Here, we investigated if the lack of validation of these variants was due to age-dependent effects on association using four independent population samples, two from Brazil and two from Vietnam. In the combined analysis across the four samples, we observed a strong association of the TNFSF15/TNFSF8 variants rs6478108, rs7863183, and rs3181348 with T1R (pcombined = 1.5E−05, pcombined = 1.8E−05, and pcombined = 6.5E−06, respectively). However, the association of rs6478108 with T1R was more pronounced in leprosy cases under 30 years of age compared to the global sample [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.54–2.46, pcombined = 2.5E−08 versus OR = 1.46, 95% CI = 1.23–1.73, pcombined = 1.5E−05]. A multivariable analysis indicated that the association of rs6478108 with T1R was independent of either rs7863183 or rs3181348. These three variants are known regulators of the TNFSF8 gene transcription level in multiple tissues. The age dependency of association of rs6478108 and T1R suggests that the genetic control of gene expression varies across the human life span. PMID:28261213
Lavania, M; Jadhav, R S; Turankar, R P; Chaitanya, V S; Singh, M; Sengupta, U
Earlier studies indicate that genotyping of Mycobaterium leprae based on single-nucleotide polymorphisms (SNPs) is useful for analysis of the global spread of leprosy. In the present study, we investigated the diversity of M. leprae at eight SNP loci using 180 clinical isolates obtained from patients with leprosy residing mainly in Delhi and Purulia (West Bengal) regions. It was observed that the frequency of SNP type 1 and subtype D was most predominant in the Indian population. Further, the SNP type 2 subtype E was noted only from East Delhi region and SNP type 2 subtype G was noted only from the nearby areas of Hoogly district of West Bengal. These results indicate the occurrence of focal transmission of M. leprae infection and demonstrate that analysis by SNP typing has great potential to help researchers in understanding the transmission of M. leprae infection in the community.
Hastings, R C; Jacobson, R R; Trautman, J R
Fifty-one leprosy patients receiving long-term clofazimine have undergone systematic clinical laboratory testing in a search for any toxicity secondary to the drug. In approximately 220 patient-years of observation and in analyzing approximately 40,000 test results, no statistically significant changes in the direction of abnormality have been observed in SGOT, thymol turbidity, serum globulins, uric acid, alkaline phosphatase, white blood cell count or differential, hematocrit, hemoglobin, BUN, serum creatinine, serum cholesterol, serum albumin, serum potassium, serum calcium, stool for occult blood, routine urinalysis, or reticulocyte count. Statistically significant changes toward abnormality were found in fasting blood sugar and total serum bilirubin. These statistically significant changes in the direction of abnormality were of a small magnitude, were not associated with related clinical signs or symptoms, and do not seem to be of major clinical significance. Despite the accumulation of relatively massive amounts of the drug in various tissues, clofazimine appears remarkably free of serious or life-threatening toxicity clinically. Although the skin and gastrointestinal side effects of clofazimine limit its usefulness, on the evidence to date, its advantages outweigh its disadvantages in those leprosy patients for whom it is indicated.
Biologics are relatively new drugs developed through modern monoclonal antibody techniques and became more familiar to some disease treatments such as Rheumatoid arthritis, psoriasis, ankylosing spondylitis, ulcerative colitis, malignant lymphoma, SLE and lupus nephritis. Some case reports shows development of leprosy during/after biolo- gics treatment and success treatment of ENL with biologics. Collection of reports was done through web search by using document retrieval engine such as Pub-med and ProQuest. 7 cases of development of leprosy with biologics and 2 cases of ENL treatment with biologics and they were reported in the mini-symposium of Annual academic meeting of Japan Leprosy association. The widespread use of biologics reminds us of development of some infectious diseases as a side-effect and leprosy might be one of them. Because number of the reports was still very limited, we cannot go to further discussion at this moment. Accu- mulation of reported cases will lead the detailed information about correlation between biologics and leprosy, either on effectiveness or on adverse ones.
Penna, Maria Lucia F.; Penna, Gerson O.; Iglesias, Paula C.; Natal, Sonia; Rodrigues, Laura C.
Background There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection. Methods A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta-analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value. Results Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%. Conclusions Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis. PMID:27192199
Louhenapessy, A A; Zuiderhoek, B
Random sample surveys in the past have revealed high estimated against low registered prevalences for leprosy in several parts of Indonesia. A pilot project showed that the problem of cases that had not yet been detected could not be solved without the active participation of the local authorities, who proved able to overcome the stigma and to convince potential patients to go for examination and treatment. The pilot project was based on the principle of what are called exploration surveys, which were introduced by Sitanala in Indonesia in 1931. The Indonesian government decided to reintroduce these surveys in 1977 under the name of chase or trace surveys. They are carried out within the framework of the leprosy workers' routine duties and no additional expenses are incurred. Since then, thousands of patients of all types and with long case histories have been detected and brought under treatment. Without this "push" it is fair to assume that many would never have sought treatment voluntarily. In view of the experience in Indonesia, one wonders whether leprosy can be eliminated without emphasizing the importance of active case finding, especially in areas in which the disease is still highly endemic. Chase surveys also provide rough information about the local leprosy situation. Although of great value, they are not, in high-endemic regions, an alternative to random sample surveys which reveal, besides a wealth of additional information, the possible unknown sources of infection.
Nsagha, Dickson Shey; Bamgboye, Elijah Afolabi; Assob, Jules Clement Nguedia; Njunda, Anna Longdoh; Kamga, Henri Lucien Foumou; Zoung-Kanyi Bissek, Anne-Cécile; Tabah, Earnest Nji; Oyediran, Alain Bankole OO; Njamnshi, Alfred Kongnyu
Introduction Leprosy is caused by Mycobacterium leprae and manifests as damage to the skin and peripheral nerves. The disease is dreaded because it causes deformities, blindness and disfigurement. Worldwide, 2 million people are estimated to be disabled by leprosy. Multidrug therapy is highly effective in curing leprosy, but treating the nerve damage is much more difficult. The World Health Assembly targeted to eliminate leprosy as a public health problem from the world by 2000. The objective of the review was to assess the successes of the leprosy elimination strategy, elimination hurdles and the way forward for leprosy eradication. Methods A structured search was used to identify publications on the elimination strategy. The keywords used were leprosy, elimination and 2000. To identify potential publications, we included papers on leprosy elimination monitoring, special action projects for the elimination of leprosy, modified leprosy elimination campaigns, and the Global Alliance to eliminate leprosy from the following principal data bases: Cochrane data base of systematic reviews, PubMed, Medline, EMBASE, and the Leprosy data base. We also scanned reference lists for important citations. Key leprosy journals including WHO publications were also reviewed. Results The search identified 63 journal publications on leprosy-related terms that included a form of elimination of which 19 comprehensively tackled the keywords including a book on leprosy elimination. In 1991, the 44th World Health Assembly called for the elimination of leprosy as a public health problem in the world by 2000. Elimination was defined as less than one case of leprosy per 10000-population. Elimination has been made possible by a confluence of several orders of opportunities: the scientific (the natural history of leprosy at the present state of knowledge), technological (multi-drug therapy and the blister pack); political (commitment of governments) and financial (support from NGOs for example
Noriega, Leandro Fonseca; Chiacchio, Nilton Di; Noriega, Angélica Fonseca; Pereira, Gilmayara Alves Abreu Maciel; Vieira, Marina Lino
Despite being an ancient disease, leprosy remains a public health problem in several countries - particularly in India, Brazil and Indonesia. The current operational guidelines emphasize the evaluation of disability from the time of diagnosis and stipulate as fundamental principles for disease control: early detection and proper treatment. Continued efforts are needed to establish and improve quality leprosy services. A qualified primary care network that is integrated into specialized service and the development of educational activities are part of the arsenal in the fight against the disease, considered neglected and stigmatizing. PMID:27579761
Noriega, Leandro Fonseca; Chiacchio, Nilton Di; Noriega, Angélica Fonseca; Pereira, Gilmayara Alves Abreu Maciel; Vieira, Marina Lino
Despite being an ancient disease, leprosy remains a public health problem in several countries -particularly in India, Brazil and Indonesia. The current operational guidelines emphasize the evaluation of disability from the time of diagnosis and stipulate as fundamental principles for disease control: early detection and proper treatment. Continued efforts are needed to establish and improve quality leprosy services. A qualified primary care network that is integrated into specialized service and the development of educational activities are part of the arsenal in the fight against the disease, considered neglected and stigmatizing.
Drawing on documents produced between the early nineteenth and mid-twentieth centuries, mainly medical reports, this paper indicates the prevailing conceptions in the colonial medical community and local populations about leprosy, its manifestations, and how to deal with it. It focuses on the tensions concerning the practice of segregating lepers and its social and sanitation implications. To comprehend the roots of the discourses and strategies in the Portuguese and colonial medical environment, the trajectory of the definitions of isolation, segregation, and leprosy are traced, as are their use in or absence from the writings of missionaries, chroniclers, and doctors in Angola and Mozambique as of the second half of the seventeenth century.
Stenström, S; Hallmans, G; De Jongh, A; De Wael, T
The use of adhesive tape as wound treatment in leprosy cases is described and found to be superior to the classical dressing as regards security and facility of application, and for the rapidity and quality of healing. Its use as a "preventive" treatment is stressed. The results of this study seem to justify the following conclusions: The adhesive tape is easy to handle, it heals the leprosy wounds in about half the time necessary for the classical dressing and it costs about 50 times less.
Boulton, Andrew J M
Leprosy and diabetes, though two very different conditions, may both result in severe loss of sensation in the feet, which are then a great risk of painless injury and ulceration. Seminal observations made by the late Dr Paul W. Brand, a surgeon working with leprosy patients in South India in the mid-20th century, resulted in the subsequent development of treatments to manage insensitive foot ulcers that are today entirely applicable to patients with diabetes. As a consequence of his research, the recognition of the relationship between insensitivity, repetitive pressures and skin breakdown has helped our understanding of the aetiopathogenesis of neuropathic foot lesions in diabetes: the development of the total contact cast and other casting devices to treat such lesions forms the basis of management of diabetic foot lesions with off-loading devices that are widely used in the 21st century in diabetic foot clinics around the world. Moreover, observations by Brand that the foot 'heats up before it breaks down' resulted in more recent research showing that self-skin temperature monitoring might help reduce the incidence of recurrent neuropathic foot ulcers in diabetes. In summary, Brand's understanding of 'the gift of pain' that, when lost, results in the late complications of diabetic neuropathy has guided the prevention, diagnosis and management of diabetic foot problems in the 21st century.
Orlova, Marianna; Van Thuc, Nguyen; Moraes, Milton O.; Sales-Marques, Carolinne; Latini, Ana Carla P.; Belone, Andrea F.; Thai, Vu Hong; Abel, Laurent; Alcaïs, Alexandre; Schurr, Erwin
Leprosy Type-1 Reactions (T1Rs) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage. Here, we employed a family-based GWAS in 221 families with 229 T1R-affect offspring with stepwise replication to identify risk factors for T1R. We discovered, replicated and validated T1R-specific associations with SNPs located in chromosome region 10p21.2. Combined analysis across the three independent samples resulted in strong evidence of association of rs1875147 with T1R (p = 4.5x10-8; OR = 1.54, 95% CI = 1.32–1.80). The T1R-risk locus was restricted to a lncRNA-encoding genomic interval with rs1875147 being an eQTL for the lncRNA. Since a genetic overlap between leprosy and inflammatory bowel disease (IBD) has been detected, we evaluated if the shared genetic control could be traced to the T1R endophenotype. Employing the results of a recent IBD GWAS meta-analysis we found that 10.6% of IBD SNPs available in our dataset shared a common risk-allele with T1R (p = 2.4x10-4). This finding points to a substantial overlap in the genetic control of clinically diverse inflammatory disorders. PMID:28222097
Chanteau, S; Glaziou, P; Plichart, C; Luquiaud, P; Plichart, R; Faucher, J F; Cartel, J L
In 1983, a cohort study to follow up the family contacts of leprosy cases was implemented in French Polynesia to assess the usefulness and applicability of phenolic glycolipid-I (PGL-I) serology in a leprosy control program. A total of 1201 contacts (666 females, 535 males) have been included in the study. The IgM anti-PGL-I seroprevalence determined on the initial sera was 17%. It was significantly higher among females than males (20% vs 15%, p = 0.02). From 1983 to 1992, 4 out of 204 (2%) anti-PGL-I seropositive contacts developed the disease (1 indeterminate, 1 BT, 1 BL, 1 LL) compared with 10 out of 997 (1%) seronegative contacts (4 indeterminate, 3 BT, 1 BB, 2 TT). Of these 10 patients, only 3 (2 indeterminate, 1 BT) converted to seropositivity when leprosy was diagnosed. The risk of developing leprosy was not significantly higher among seropositive than among seronegative groups (2% vs 1%, p = 0.2). A PGL-I circulating antigen test performed on 216 selected sera at entry into the trial showed a higher antigen prevalence when the antibody level was higher. PGL-I antigen was detectable in 5 of 12 patients tested prior to diagnosis (1 LL, 1 BL, 3 indeterminate). The median time to externalize the disease was not significantly different among antibody-positive and -negative contacts (17 vs 25 months, p = 0.3). The relative risk of developing leprosy for contact individuals was 30.8 times that of noncontacts, and 15% of the total new cases detected between 1983 and 1992 emerged from the study population.(ABSTRACT TRUNCATED AT 250 WORDS)
Koelewijn, L F; Meima, A; Broekhuis, S M; Richardus, J H; Mitchell, P D; Benbow, C; Saunderson, P R
The 10 g monofilament has been replaced by the ballpoint pen in routine sensory testing of nerves in leprosy control in Ethiopia. Results of sensory testing between the ballpoint pen and different monofilaments on hands and feet were compared. Ballpoint pen underdiagnosis of loss of sensation was defined to occur when the pen was felt and the monofilament was not. Differences were evaluated both for individual test points (test point level) and for the test points of extremities collectively (extremity level). An extremity (either a hand or a foot) was defined as having sensory nerve function impairment (SNFI) if a supplying nerve had SNFI, which was the case when sensation was absent in two or more test points in the area supplied by that nerve. At test point level, the percentages with ballpoint pen underdiagnosis relative to the 2, 10, 20 and 50 g monofilaments were 40, 21, 9 and 7%, respectively, in the hands, and 47, 30, 15 and 7% in the feet. Ballpoint pen underdiagnosis percentages of SNFI at extremity level were 32, 18, 8 and 9% in the hands, and 37, 26, 14 and 6% in the feet. The risk of ballpoint pen underdiagnosis appears to be higher in extremities without visible damage. In conclusion, substantial levels of underdiagnosis of sensory loss with the ballpoint pen were observed. However, the consequences for the prognosis of treatment with corticosteroids in patients with the more subtle sensation loss noted here need to be established. Development and testing of guidelines is a prerequisite for the use of the ballpoint pen.
Chaptini, Casandra; Marshman, Gillian
Leprosy, one of the oldest diseases known to man, is a stigmatising, potentially disabling disease. Throughout history, leprosy has been associated with fear, prejudice and immense social stigma. It remains one of the leading causes of deformity and physical disability from an infectious disease. Tremendous advances in leprosy control were made by the World Health Organization, and the 'elimination of leprosy', defined as a decrease of disease prevalence to less than 1 case per 10,000 population, was achieved by 2000. However, the reality is that true 'elimination' is yet to be achieved. Despite almost 30 years of effective multidrug treatment, the prevalence and incidence of leprosy have plateaued since 2005. Moreover, new cases with Grade 2 disability and new cases occurring in children remain unchanged since 2010, reflecting a failure in early leprosy detection, and indicating that transmission is clearly continuing. This review examines the challenges of elimination, and proposes further measures to reduce the disease burden, including future research possibilities.
Dey, Biswajit; Gochhait, Debasis; Prabhakaran, Nagendran; Chandrashekar, Laxmisha; Behera, Biswanath
Occurrence of pulmonary tuberculosis with leprosy is known but association of cutaneous tuberculosis with leprosy is rare. We report a case of borderline lepromatous leprosy coexistent with tuberculosis verrucosa cutis in a 29-year-old male, who presented with multiple skin coloured nodules and hyperkeratotic scaly lesions of 3-month duration. Dual infections are associated with high mortality and morbidity. Therefore early diagnosis and management helps to reduce mortality and to mitigate the effects of morbidity.
Prabhakaran, Nagendran; Chandrashekar, Laxmisha; Behera, Biswanath
Occurrence of pulmonary tuberculosis with leprosy is known but association of cutaneous tuberculosis with leprosy is rare. We report a case of borderline lepromatous leprosy coexistent with tuberculosis verrucosa cutis in a 29-year-old male, who presented with multiple skin coloured nodules and hyperkeratotic scaly lesions of 3-month duration. Dual infections are associated with high mortality and morbidity. Therefore early diagnosis and management helps to reduce mortality and to mitigate the effects of morbidity. PMID:28003920
De Souza Dias, Márcia Célia Freitas; Dias, Gutemberg Henrique; Nobre, Maurício Lisboa
There is a high incidence of leprosy in the municipality of Mossor6, Rio Grande do Norte state, where the detection coefficient has risen from 2.78/10,000 population in 1998 to 5.14 in 2004. While cases have been registered throughout the urban area, the disease is concentrated in select neighbourhoods. This study was undertaken using Geographical Information System (GIS) with the objective of defining low-cost, effective strategies to control leprosy. The land registry map of the city, Ikonos satellite images and the SINAN (National Morbidity Notification Information System) database were used as the cartographical basis for the study. The sample for the leprosy mapping was drawn from the 358 new cases of the disease diagnosed in the municipality between 1998 and 2002. The houses of 281 patients were located (78.5% of the total) and their addresses geo-referenced using a GPS handheld device. Subsequently, geographical analysis was carried out using ArcView 9.0 software showing predominant concentration of cases in the neighbourhoods of Barrocas, Santo Antônio, Bom Jardim and Paredões. This mapping served as the basis for four active case finding campaigns conducted in the most highly concentrated areas between March and September of 2005. Campaigns guided by spatial analysis led to the diagnosis of 104 new cases of the disease (50% of the total number of new cases detected in the municipality in 2005). The use of GIS in leprosy diagnosis has shown to be extremely effective, providing a clear visual understanding of the distribution of the disease in the municipality, which results in targeted interventions and important cost reductions in leprosy control activities.
Scollard, David M; Dacso, Mara M; Abad-Venida, Ma Luisa
Leprosy and tuberculosis are chronic mycobacterial infections that elicit granulomatous inflammation. Both infections are curable, but granulomatous injury to cutaneous structures, including cutaneous nerves in leprosy, may cause permanent damage. Both diseases are major global concerns: tuberculosis for its high prevalence and mortality, and leprosy for its persistent global presence and high rate of neuropathic disability. Cutaneous manifestations of both leprosy and tuberculosis are frequently subtle and challenging in dermatologic practice and often require a careful travel and social history and a high index of suspicion.
Murto, Christine; Chammartin, Frédérique; Schwarz, Karolin; da Costa, Lea Marcia Melo; Kaplan, Charles; Heukelbach, Jorg
Leprosy remains a public health problem in Brazil with new case incidence exceeding World Health Organization (WHO) goals in endemic clusters throughout the country. Migration can facilitate movement of disease between endemic and non-endemic areas, and has been considered a possible factor in continued leprosy incidence in Brazil. A study was conducted to investigate migration as a risk factor for leprosy. The study had three aims: (1) examine past five year migration as a risk factor for leprosy, (2) describe and compare geographic and temporal patterns of migration among past 5-year migrants with leprosy and a control group, and (3) examine social determinants of health associated with leprosy among past 5-year migrants. The study implemented a matched case-control design and analysis comparing individuals newly diagnosed with leprosy (n = 340) and a clinically unapparent control group (n = 340) without clinical signs of leprosy, matched for age, sex and location in four endemic municipalities in the state of Maranhão, northeastern Brazil. Fishers exact test was used to conduct bivariate analyses. A multivariate logistic regression analysis was employed to control for possible confounding variables. Eighty cases (23.5%) migrated 5-years prior to diagnosis, and 55 controls (16.2%) migrated 5-years prior to the corresponding case diagnosis. Past 5 year migration was found to be associated with leprosy (OR: 1.59; 95% CI 1.07–2.38; p = 0.02), and remained significantly associated with leprosy after controlling for leprosy contact in the family, household, and family/household contact. Poverty, as well as leprosy contact in the family, household and other leprosy contact, was associated with leprosy among past 5-year migrants in the bivariate analysis. Alcohol consumption was also associated with leprosy, a relevant risk factor in susceptibility to infection that should be explored in future research. Our findings provide insight into patterns of
Kumar, Bipin; Pradhan, Anju
Leprosy is a chronic infection affecting mainly the skin and peripheral nerve. Pure neuritic form of this disease manifests by involvement of the nerve in the absence of skin lesions. Therefore, it can sometimes create a diagnostic problem. It often requires a nerve biopsy for diagnosis, which is an invasive procedure and may lead to neural deficit. Fine needle aspiration cytology (FNAC) of an affected nerve can be a valuable and less invasive procedure for the diagnosis of such cases. We report five suspected cases of pure neuritic Hansen's disease involving the common and superficial peroneal, ulnar, and median nerve, who underwent FNAC. Smears revealed nerve fibers infiltrated by chronic inflammatory cells in all cases, presence of epithelioid cells granulomas, and Langhans giant cells in three cases, and acid fast bacilli in two cases. In conclusion, FNAC is a safe, less invasive, and time saving procedure for the diagnosis of pure neuritic leprosy. PMID:21660285
Rees, R. J. W.
Although Mycobacterium leprae was identified earlier than Myco. tuberculosis, it has still not been cultured in vitro and only in 1960 was an infection obtained in laboratory animals. However, important advances have been made in the field of experimental leprosy in the last decade due to the development of new techniques and models for studying Myco. leprae in vivo, thus overcoming the limitations imposed by a non-cultivable mycobacterium. Quantitative techniques using Myco. lepraemurium provided the first model for developing an indirect method for distinguishing dead (non-infectious) from living (infectious) bacilli, based on morphological differences in organisms stained by the Ziehl—Neelsen method. However, the most important advances resulted from the limited and localized growth of Myco. leprae when inoculated into the foot pads of mice and, later, the more substantial and generalized multiplication of Myco. leprae in immunologically deficient mice (thymectomized and irradiated with a dose of 900 r). Moreover, in the immunologically deficient animals, the infection eventually resulted in a disease replicating that of lepromatous type leprosy in man, including the involvement of peripheral nerves. The results from these studies and the future prospects for the study of leprosy in the laboratory are reviewed in this article. ImagesFIG. 5FIG. 6FIG. 4FIG. 7 PMID:4898388
Teo, T C; Richard, B M
In leprosy a functionally useless hand can be the sequelae of resorption of the sensation-impaired thumb and fingers resulting from repeated trauma and infection. When this process shortens the thumb to the level of the proximal phalanx or metacarpal, the effect is to produce a relatively shallow first web space which together with the shortening, can prevent the most basic hand manoeuvre of a pincer or pinch grip. The reconstructive procedure commonly used in this situation is to widen and deepen the web space with a z-plasty combined with excision of the second metacarpal but the result can be inadequate. We have used the posterior interosseous fasciocutaneous island flap, both as a simple and a compound flap, to solve this challenging problem and we report here our experience with four patients.
Stone, Andrew; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Shao, Jonathan; Levy, Laurene; Nakhla, Mark K.; Hollingsworth, Charla R.; Hartung, John S.; Schneider, William L.
The complete genome of citrus leprosis virus nuclear type (CiLV-N) was identified by small RNA sequencing utilizing leprosis-affected citrus samples collected from the state of Querétaro, Mexico. The nucleotide identity and phylogenetic analysis indicate that CiLV-N is very closely related to orchid fleck virus, which typically infects Cymbidium species. PMID:23887919
Peters, Ruth M. H.; Dadun; Lusli, Mimi; Miranda-Galarza, Beatriz; van Brakel, Wim H.; Zweekhorst, Marjolein B. M.; Damayanti, Rita; Seda, Francisia S. S. E.; Bunders, Joske F. G.; Irwanto
It is imperative to consider the meaning of leprosy and everyday experiences of people affected by leprosy and key persons in the community if one aims to make leprosy services more effective, which appears necessary in Indonesia given the large numbers of new cases detected annually. However, little is written in the international literature about the experiences of people currently being treated for leprosy, those cured, or other key informants. This paper analyses the narratives of the people by drawing upon in-depth interviews with 53 participants and 20 focus groups discussions. The participants were purposively selected. We provide insights into the experiences of people and the meaning they give to leprosy and highlight aspect of aetiology, spirituality, religion, darkening of the skin, and sorcery. We also examine experiences of seeking care and focused on the impact of the disease in particular on the elderly and children. In conclusion, the continued need for implementation of leprosy services in Indonesia is very evident. The diversities in people's experiences with leprosy indicate a demand for responsive leprosy services to serve the diverse needs, including services for those formally declared to be “cured.” PMID:23577037
Roy, Avijit; Stone, Andrew; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Shao, Jonathan; Levy, Laurene; Nakhla, Mark K; Hollingsworth, Charla R; Hartung, John S; Schneider, William L; Brlansky, Ronald H
The complete genome of citrus leprosis virus nuclear type (CiLV-N) was identified by small RNA sequencing utilizing leprosis-affected citrus samples collected from the state of Querétaro, Mexico. The nucleotide identity and phylogenetic analysis indicate that CiLV-N is very closely related to orchid fleck virus, which typically infects Cymbidium species.
Peters, Ruth M H; Dadun; Lusli, Mimi; Miranda-Galarza, Beatriz; van Brakel, Wim H; Zweekhorst, Marjolein B M; Damayanti, Rita; Seda, Francisia S S E; Bunders, Joske F G; Irwanto
It is imperative to consider the meaning of leprosy and everyday experiences of people affected by leprosy and key persons in the community if one aims to make leprosy services more effective, which appears necessary in Indonesia given the large numbers of new cases detected annually. However, little is written in the international literature about the experiences of people currently being treated for leprosy, those cured, or other key informants. This paper analyses the narratives of the people by drawing upon in-depth interviews with 53 participants and 20 focus groups discussions. The participants were purposively selected. We provide insights into the experiences of people and the meaning they give to leprosy and highlight aspect of aetiology, spirituality, religion, darkening of the skin, and sorcery. We also examine experiences of seeking care and focused on the impact of the disease in particular on the elderly and children. In conclusion, the continued need for implementation of leprosy services in Indonesia is very evident. The diversities in people's experiences with leprosy indicate a demand for responsive leprosy services to serve the diverse needs, including services for those formally declared to be "cured."
Citrus leprosis is a difficult viral disease causing significant damage to citrus fruit in South America and Central America. The disease is marked by dramatic lesions on fruit, leaves and stems resulting in unmarketable product. Citrus leprosis virus cytoplasmic type (CiLV-C) was detected in states...
Boudghene-Stambouli, O; Merad-Boudia, A
Leprosy is not a problem for public health in Algeria. For one century (from 1888 to 1987), a maximum of 250 cases were reported, only 75 of them were Algerians and 61 caught the disease in Algeria. Hence leprosy was mainly an imported disease. Will multiple exchanges with other countries increase the magnitude of the problem?
Chopra, Rupali; Kalaiarasan, Ponnusamy; Ali, Shafat; Srivastava, Amit K; Aggarwal, Shweta; Garg, Vijay K; Bhattacharya, Sambit N; Bamezai, Rameshwar N K
Objectives Cytokines and related molecules in immune-response pathways seem important in deciding the outcome of the host–pathogen interactions towards different polar forms in leprosy. We studied the role of significant and functionally important single-nucleotide polymorphisms (SNPs) in these genes, published independently from our research group, through combined interaction with an additional analysis of the in silico network outcome, to understand how these impact the susceptibility towards the disease, leprosy. Design The study was designed to assess an overall combined contribution of significantly associated individual SNPs to reflect on epistatic interactions and their outcome in the form of the disease, leprosy. Furthermore, in silico approach was adopted to carry out protein–protein interaction study between PARK2 and proinflammatory/anti-inflammatory cytokines. Setting Population-based case–control study involved the data of North India. Protein–protein interaction networks were constructed using cytoscape. Participants Study included the data available from 2305 Northern Indians samples (829 patients with leprosy; 1476 healthy controls), generated by our research group. Primary and secondary outcome measures For genotype interaction analysis, all possible genotype combinations between selected SNPs were used as an independent variable, using binary logistic regression with the forward likelihood ratio method, keeping the gender as a covariate. Results Interaction analysis between PARK2 and significant SNPs of anti-inflammatory/proinflammatory cytokine genes, including BAT1 to BTNL2-DR spanning the HLA (6p21.3) region in a case–control comparison, showed that the combined analysis of: (1) PARK2, tumour necrosis factor (TNF), BTNL2-DR, interleukin (IL)-10, IL-6 and TGFBR2 increased the risk towards leprosy (OR=2.54); (2) PARK2, BAT1, NFKBIL1, LTA, TNF-LTB, IL12B and IL10RB provided increased protection (OR=0.26) in comparison with their
Simoes Quaresma, Juarez Antonio; de Almeida, Fabrício Anderson Carvalho; de Souza Aarao, Tinara Leila; de Miranda Araujo Soares, Luis Paulo; Nunes Magno, Ismaelino Mauro; Fuzii, Hellen Thais; Feio Libonati, Rosana Maria; Xavier, Marilia Brasil; Pagliari, Carla; Seixas Duarte, Maria Irma
The course of leprosy depends of the host immune response which ranges from the lepromatous pole (LL) to the tuberculoid pole (TT). A comparative study was conducted in 60 patients with the LL and TT. The results showed a mean expression of TGF-β of 339 ± 99.4 cells/field for TT and of 519.2 ± 68.2 cells/field for LL. Frequency of apoptosis was 6.3 ± 1.8 in TT and 14.0 ± 6.1 in LL. A correlation (p = 0.0251) between TGF-β and caspase-3 in the LL was found. This finding indicates a role of TGF-β and apoptosis in the immune response in leprosy.
Izumi, S; Budiawan, T; Saeki, K; Matsuoka, M; Kawatsu, K
One of the most important unsolved questions in epidemiology of leprosy is the highly uneven geographic distribution of the disease. There are many hyperendemic "pockets" in endemic countries. Little is known about the reasons why leprosy is hyperendemic in these areas. We conducted, therefore, a series of epidemiological studies on Mycobacterium leprae infection and prevalence of leprosy in North Maluku district, Maluku Province, Indonesia where leprosy is highly endemic. It was found that considerable number of general inhabitants are seropositive to various mycobacterial antigens and 27% of the villagers were carrying leprosy bacilli on their surface of nasal cavity. These results suggested the importance of M. leprae in the residential environment in infection of the leprosy bacillus and the resulting transmission of the disease. Based on these observations, we conclude that new preventive measures are essential for global elimination of leprosy in addition to early diagnosis and multidrug therapy (MDT).
Santos, Karen da Silva; Fortuna, Cinira Magali; Santana, Fabiana Ribeiro; Gonçalves, Marlene Fagundes Carvalho; Marciano, Franciele Maia; Matumoto, Silvia
Abstract Objective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods. Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy. Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy. Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous. PMID:26444163
Azizi, Mohammad Hossein; Bahadori, Moslem
From ancient time leprosy has been regarded as a terrifying, stigmatized disease; nevertheless, its cause remained unidentified up to the late 19th century. For centuries numerous leprosy victims worldwide suffered from its morbidity and were socially isolated. The afflicted individuals were segregated because they were considered 'unclean' and had to live in leper colonies, generally under very poor conditions. Physicians believed that leprosy was an incurable, highly contagious, and hereditary disease. In 1873 the Norwegian physician, Gerhard Armauer Hansen (1841-1912), ended the myth of leprosy and discovered its causative agent, known as Mycobacterium leprae. Hansen's discovery was a great triumph in the fight against leprosy. In the 1930's, the first effective antileprosy drug, dapsone, was introduced and in the early 1980's multi-drug therapy was popularized because of high efficacy in resistant cases. Here, we have presented a brief look at the history of leprosy in the world with special focus on the historical account of leprosy in Iran, particularly during the 19th and 20th centuries.
Joseph, G. A.; Rao, P. S.
Leprosy is considered by many as not merely a medical condition, but as a condition encompassing psychological, socioeconomic and spiritual dimensions that dehabilitate an individual progressively, unless properly cared for. The present study was undertaken to document the nature and extent of decreases in the quality of life (QOL) of an affected person. The World Health Organization questionnaire on quality of life was given to a representative random sample of 50 leprosy-affected persons and 50 unaffected individuals in the Bommasamudram Taluk of Chittoor District, Andhra Pradesh, India. This questionnaire explores the following six domains; physical; psychological; level of independence; social relationships; spiritual; and environmental. The mean QOL score of the cases was significantly lower than that of the controls with the exception of the spiritual domain. The mean total score for women was higher than that of males in each domain and age group. Males with deformities had a significantly lower score than those with no visible deformities. Although the scores for females with deformities were also lower than those without deformities, the differences were not statistically significant. Analyses of economic status versus the QOL scores clearly showed that they were positively correlated. The study revealed that quality of life decreased progressively in leprosy-affected persons. Women had a better QOL score than men in almost every domain. Given the secondary role of women in Indian rural society, this may simply imply an acceptance of their situation. The findings are discussed in comparison with other diseases and in the context of a poor socioeconomic environment. With modern amenities, better education and higher expectations, the perception of an individual regarding his or her own quality of life is bound to change. The need for frequent assessments and further studies along these lines is emphasized. PMID:10427937
Sharma, Ankur; Jain, Vishal; Virjee, Karim; Singh, Shilpi
Introduction Role of dentists in prevention and sustainable care of leprosy is known. Changing leprosy scenario has led to requirement of change in leprosy education. However, knowledge and attitude of dental students on leprosy remains unknown. Aim Hence a study was conducted to assess knowledge and attitude of dental students about Leprosy. Materials and Methods A questionnaire based, cross-sectional survey was conducted among 350 undergraduate and the postgraduate dental students of two dental colleges in Faridabad, India. The score for knowledge ranged from 0 to 16 and scores for attitude ranged from 0 to 26. These scores were further coded as poor, fair and good. Results Mean knowledge score for the sample was 7.64±3.23. A total of 32.29% participants were under poor knowledge category; 57.42% had fair knowledge about Leprosy while 10.29% had good knowledge. Mean attitude score was 15.5 ± 5.98. A total of 30.57% had poor attitude scores, 42.57% had fair scores while 26.86% had good attitude scores. Univariate analysis showed year of training to be a significant predictor for knowledge level (t=7.12; p<0.001). Conclusion The results indicate need for three important changes towards Leprosy in Dentistry. These changes are need for incorporation of leprosy education in Dentistry, need for incorporation of problem based as well as evidence based learning in Dentistry integrated with general health and need for reestablishing public health programs for Leprosy utilizing dental workforce. PMID:27135001
Corruble, V.; Ganascia, J.G.
The role played by the inductive inference has been studied extensively in the field of Scientific Discovery. The work presented here tackles the problem of induction in medical research. The discovery of the causes of leprosy is analyzed and simulated using computational means. An inductive algorithm is proposed, which is successful in simulating some essential steps in the progress of the understanding of the disease. It also allows us to simulate the false reasoning of previous centuries through the introduction of some medical a priori inherited form archaic medicine. Corroborating previous research, this problem illustrates the importance of the social and cultural environment on the way the inductive inference is performed in medicine.
Kaplan, D L
Although there is a growing consensus that biblical leprosy was indeed not Hansen's disease, there has been no agreement as to the disease or diseases described in the Bible. Biblical scholars have recently provided valuable insights regarding the interpretation of the original text on the cutaneous diseases described in Leviticus, chapter 13. It is suggested by the author that no particular cutaneous disease was meant to be implicated. Rather the passages were written to exonerate persons whose only "sin" was to have an obvious cutaneous disorder.
Santos, Vicente Saul Moreira Dos
The 1920s creation of Sociedades de Assistência aos Lázaros e Defesa Contra a Lepra under Brazil's First Republic (1889-1930) represented a milestone in relations between assistance organizations and the government. Although these organizations were at first autonomous decision-makers, their guidelines changed after they established closer relations with the government, which enacted reforms in policies to fight leprosy following the 1930 creation of the Ministry of Education and Public Health, especially during the long tenure of Minister Gustavo Capanema (1934-1945).
Franco-Paredes, Carlos; Rodriguez-Morales, Alfonso J
Leprosy, a chronic mycobacterial infection caused by Mycobacterium leprae, is an infectious disease that has ravaged human societies throughout millennia. This ancestral pathogen causes disfiguring cutaneous lesions, peripheral nerve injury, ostearticular deformity, limb loss and dysfunction, blindness and stigma. Despite ongoing efforts in interrupting leprosy transmission, large numbers of new cases are persistently identified in many endemic areas. Moreover, at the time of diagnosis, most newly identified cases have considerable neurologic disability. Many challenges remain in our understanding of the epidemiology of leprosy including: (a) the precise mode and route of transmission; (b) the socioeconomic, environmental, and behavioral factors that promote its transmission; and
Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Mishra, Bishal; Bisht, Deepa; Gupta, U D; Sengupta, Utpal
Autoantibodies against various components of host are known to occur in leprosy. Nerve damage is the primary cause of disability associated with leprosy. The aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (MBP) in leprosy patients (LPs) and their correlation with clinical phenotypes of LPs. Further, probable role of molecular mimicry in nerve damage of LPs was investigated. We observed significantly high level of anti-MBP antibodies in LPs across the spectrum and a positive significant correlation between the level of anti-MBP antibodies and the number of nerves involved in LPs. We report here that 4 B cell epitopes of myelin A1 and Mycobacterium leprae proteins, 50S ribosomal L2 and lysyl tRNA synthetase are cross-reactive. Further, M. leprae sonicated antigen hyperimmunization was responsible for induction of autoantibody response in mice which could be adoptively transferred to naive mice. For the first time our findings suggest the role of molecular mimicry in nerve damage in leprosy.
Duthie, Malcolm S; Balagon, Marivic F
Leprosy is a complex infectious disease caused by Mycobacterium leprae that is a leading cause of nontraumatic peripheral neuropathy. Current control strategies, with a goal of early diagnosis and treatment in the form of multidrug therapy, have maintained new case reports at ~225,000 per year. Diagnostic capabilities are limited and even with revisions to multidrug therapy regimen, treatment can still require up to a year of daily drug intake. Although alternate chemotherapies or adjunct immune therapies that could provide shorter or simpler treatment regimen appear possible, only a limited number of trials have been conducted. More proactive strategies appear necessary in the drive to elimination. As a prevention strategy, most chemoprophylaxis campaigns to date have provided about a 2-year protective window. Vaccination, in the form of a single bacillus Calmette–Guérin (BCG) immunization, generally provides ~50% reduction in leprosy cases. Adapting control strategies to provide both chemoprophylaxis and immunoprophylaxis has distinct appeal, with chemoprophylaxis theoretically buttressed by vaccination to generate immediate protection that can be sustained in the long term. We also discuss simple assays measuring biomarkers as surrogates for disease development or replacements for invasive, but not particularly sensitive, direct measures of M. leprae infection. Such assays could facilitate the clinical trials required to develop these new chemoprophylaxis, immunoprophylaxis strategies, and transition into wider use. PMID:27175099
Rani, Poonam; Aggarwal, Radhika; Kaushal, Seema
Histoplasmosis is a genus of dimorphic fungi having various varieties of which the commonest one causing infection is Histoplasma capsulatum known to cause histoplasmosis. It has a varied disease spectrum ranging from an acute infection to chronic disease especially in lungs, disseminated disease and cutaneous disorder. Histoplasma capsulatum usually causes subclinical infection and serious infections only manifest in immunocompromised patients. Frank cases of infection are seen in pulmonary histoplasmosis. The spores of these organisms are seen to be strongly associated with droppings of birds and bats. A combination of these droppings and some soil types provide for an excellent environment for the proliferation of spores. Pulmonary histoplasmosis and disseminated disease are very common in AIDS patients and are a great cause of morbidity and mortality in these patients. Primary cutaneous histoplasmosis is very rare and occurs due to penetrating injuries. Once diagnosis is made, the lesions respond very well to oral itraconazole, fluconazole or amphotericicn B. We report a rare case of Cutaneous Histoplasmosis (CHP) in a 70-year-old male with complaints of multiple nodules all over his body in a HIV seronegative and otherwise immunocompetent patient. PMID:28273974
Schmitt, Karin M
Luke Demaitre's Leprosy in Premodern Medicine: A Malady of the Whole Body is a highly interesting study of the medical history of leprosy and the medical and social perceptions on leprosy that have been around for centuries. Remarkably, it is likely that leprosy will disappear from the face of the Earth in our generation, thanks to the development of a curative treatment and its increasing availability (although the battle has not yet been won completely). Demaitre's book is a very good read not only for its information about leprosy but also for all interested in or affected by the social phenomenon of stigma. In illnesses such as leprosy, HIV/AIDS, epilepsy, and mental disorders such as schizophrenia, the stigma attached to the condition may be worse than the condition itself.
Leprosy, or Hansen's disease, continues to be feared and poorly understood in the United States, where knowledge of the disease is limited and prevalence is low. The presence of leprosy among immigrants, however, provides fuel for those with an anti-immigration agenda. In recent years, there have been several examples of popular media distortions of statistics and of information on leprosy's properties and contagiousness. As in previous eras of U.S. history, public fears about leprosy seem to be related to anti-immigration or nativist sentiment, which often mask underlying concerns about the potential economic threat of immigrant populations. In this article, I analyse the role of the U.S. media and other stakeholders who may have an interest in generating public fear associated with leprosy, in presenting and at times manipulating data about the disease to create an association between leprosy and undocumented immigration.
Forty-four files of cats diagnosed as having feline leprosy were reviewed. All except one were from along the Pacific coast in the Province of British Columbia. The majority of cats were between one and three years of age and there was an increase in the number of diagnosis during the winter months. Two types of granulomatous responses similar to the tuberculoid and lepromatous phases of human leprosy were recognized. In spite of the overall similarities in the cellular response to human leprosy there were, however, significant differences such as areas of caseous necrosis and constant lack of nerve involvement. Still as there is presently no way to prove that Mycobacterium leprae is not the cause of feline leprosy the public health significance remains uncertain The treatment of choice would appear to be surgical removal. ImagesFigure 3.Figure 4.Figure 5. PMID:17422188
Rodrigues, J C V; Kitajima, E W; Childers, C C; Chagas, C M
Citrus leprosis is caused by Citrus leprosis virus (CiLV) that is transmitted by mites in the genus Brevipalpus (Acari: Tenuipalpidae). This disease directly reduces production and the life span of the citrus plant. The main symptoms of the disease include lesions on fruits, leaves, and twigs or small branches, causing premature fruit drop, defoliation, and death of the twigs or branches leading to serious tree decline. Leprosis is a highly destructive disease of citrus, wherever it occurs. The Brazilian citrus industry spends over 100 million US dollars annually on acaricides to control the vector, Brevipalpus phoenicis (Geijskes). This review contains information about the history of the etiology of citrus leprosis, its geographical distribution, host range, the role of the mite vectors, viral morphology and relationships with the infected cell, and transmissibility of the virus by the mite. In addition, data on the mite-virus-plant relationship, disease damage, and strategies for controlling disease spread are presented.
Malheiro, Luís; Pinto, Sofia Correia; Sarmento, Antonio; Santos, Lurdes
As we approach the third decade since the WHO started addressing the eradication of poliomyelitis and leprosy, a reflection of the previous campaigns efficacy and an evaluation of further elimination feasibility is important to adapt and intensify the next steps. We performed a critical review of the poliomyelitis and leprosy eradication campaigns to evaluate their technical and operational feasibilities. Vaccination and active case search are highly effective tools against poliomyelitis. If political stability and good vaccination coverage is achieved, poliomyelitis will be an easy target for eradication. Leprosy, on the other hand, faces many barriers towards elimination. The lack of a high efficacy vaccine, the long asymptomatic but infective period, the lack of screening tests and a poorly established elimination target, prevents this disease from being eliminated. In a world where resources and funding are limited, it is apparent that poliomyelitis is a more feasible target for elimination than leprosy.
Walsh, Gerald P; Dela Cruz, Eduardo C; Abalos, Rodolfo M; Tan, Esterlina V; Fajardo, Tranquilino T; Villahermosa, Laarni G; Cellona, Roland V; Balagon, Maria V; White, Valerie A; Saunderson, Paul R; Walsh, Douglas S
Cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to M. leprae is unknown. A cynomolgus model of leprosy could increase understanding of pathogenesis-importantly, neuritis and nerve-damaging reactions. We administered viable Mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1-19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (PGL-1) antibody serology, and lepromin skin testing. Most developed evanescent papules at intradermal M. leprae inoculation sites that, on biopsy, showed a robust cellular immune response akin to a lepromin skin test reaction; many produced PGL-1 antibodies. At necropsy, four monkeys, without cutaneous or gross neurological signs of leprosy but with elevated PGL-1 antibodies, including three with nasal smears (+) for acid fast bacilli (AFB), showed histological features, including AFB, suggestive of leprosy at several sites. Overall, however, cynomolgus monkeys seem minimally susceptible to leprosy after experimental M. leprae administration.
Sinha, A K; Banerjee, B G; Singh, S
Leprosy is one of the oldest ailments known to the mankind. Many of the ancient texts and scriptures reveal that leprosy was not categorised as a specified disease but was grouped along with other skin diseases. However, in certain texts categorical mention of this disease does exist. The prime objective of this article is to highlight the age old traditional line of perception about this disease. A literature review was done to up-date the socio-cultural perception of leprosy in Indian religions and ancient texts. References were obtained through examining relevant bibliographies and the views/suggestions of eminent scholars engaged in this field were also included. An analysis of the secondary sources of data, particularly the ancient texts reveals that in good old days, leprosy had been considered to be an infliction of wrong-doings and sins. This viewpoint has been significantly reflected in these texts.
Barreto, Josafá Gonçalves; Bisanzio, Donal; Guimarães, Layana de Souza; Spencer, John Stewart; Vazquez-Prokopec, Gonzalo M.; Kitron, Uriel; Salgado, Claudio Guedes
Background More than 200,000 new cases of leprosy were reported by 105 countries in 2011. The disease is a public health problem in Brazil, particularly within high-burden pockets in the Amazon region where leprosy is hyperendemic among children. Methodology We applied geographic information systems and spatial analysis to determine the spatio-temporal pattern of leprosy cases in a hyperendemic municipality of the Brazilian Amazon region (Castanhal). Moreover, we performed active surveillance to collect clinical, epidemiological and serological data of the household contacts of people affected by leprosy and school children in the general population. The occurrence of subclinical infection and overt disease among the evaluated individuals was correlated with the spatio-temporal pattern of leprosy. Principal Findings The pattern of leprosy cases showed significant spatio-temporal heterogeneity (p<0.01). Considering 499 mapped cases, we found spatial clusters of high and low detection rates and spatial autocorrelation of individual cases at fine spatio-temporal scales. The relative risk of contracting leprosy in one specific cluster with a high detection rate is almost four times the risk in the areas of low detection rate (RR = 3.86; 95% CI = 2.26–6.59; p<0.0001). Eight new cases were detected among 302 evaluated household contacts: two living in areas of clusters of high detection rate and six in hyperendemic census tracts. Of 188 examined students, 134 (71.3%) lived in hyperendemic areas, 120 (63.8%) were dwelling less than 100 meters of at least one reported leprosy case, 125 (66.5%) showed immunological evidence (positive anti-PGL-I IgM titer) of subclinical infection, and 9 (4.8%) were diagnosed with leprosy (8 within 200 meters of a case living in the same area). Conclusions/Significance Spatial analysis provided a better understanding of the high rate of early childhood leprosy transmission in this region. These findings can be applied to guide
Rodríguez-Acosta, Elva Dalia; Esquivel-Pedraza, Lilly; Saeb-Lima, Marcela; Arenas-Guzmán, Roberto; Granados-Arriola, Julio; Domínguez-Cherit, Judith
A 65-year-old unemployed man, originally from Michoacán and currently living in Toluca, state of Mexico, presented for medical consultation for disseminated dermatosis in all body segments. The condition was limited to the head and neck, was bilateral and symmetrical, and was characterized by infiltrated and confluent erythematous-edematous plates of diverse diameter covering 90% of the upper and lower extremities (Figure 1). The ailment had 2 years' evolution and a progressive course. The patient was diagnosed in private practice as having atopic dermatitis. After exacerbation of symptoms, he was treated with deflazacort and hydroxychloroquine with no improvement. Results from lesion biopsies revealed sarcoidal granulomas and the patient was therefore referred to the dermatology department at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán for further study and treatment with the presumptive diagnosis of mycosis fungoides vs sarcoidosis.
Robbins, Gwen; Tripathy, V. Mushrif; Misra, V. N.; Mohanty, R. K.; Shinde, V. S.; Gray, Kelsey M.; Schug, Malcolm D.
Background Leprosy is a chronic infectious disease caused by Mycobacterium leprae that affects almost 250,000 people worldwide. The timing of first infection, geographic origin, and pattern of transmission of the disease are still under investigation. Comparative genomics research has suggested M. leprae evolved either in East Africa or South Asia during the Late Pleistocene before spreading to Europe and the rest of the World. The earliest widely accepted evidence for leprosy is in Asian texts dated to 600 B.C. Methodology/Principal Findings We report an analysis of pathological conditions in skeletal remains from the second millennium B.C. in India. A middle aged adult male skeleton demonstrates pathological changes in the rhinomaxillary region, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton. The presence and patterning of lesions was subject to a process of differential diagnosis for leprosy including treponemal disease, leishmaniasis, tuberculosis, osteomyelitis, and non-specific infection. Conclusions/Significance Results indicate that lepromatous leprosy was present in India by 2000 B.C. This evidence represents the oldest documented skeletal evidence for the disease. Our results indicate that Vedic burial traditions in cases of leprosy were present in northwest India prior to the first millennium B.C. Our results also support translations of early Vedic scriptures as the first textual reference to leprosy. The presence of leprosy in skeletal material dated to the post-urban phase of the Indus Age suggests that if M. leprae evolved in Africa, the disease migrated to India before the Late Holocene, possibly during the third millennium B.C. at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of
Cortela, D. C. B.; de Souza Junior, A. L.; Virmond, M. C. L.; Ignotti, E.
Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental infections. To determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. A three-stage literature search was performed (Stage I, “leprosy reactions” and “inflammatory mediators”; Stage II, “dental infections” and “inflammatory mediators”; and Stage III, “leprosy reactions,” “dental infections,” and “inflammatory mediators”). Of the 911 eligible publications, 10 were selected in Stage I, 68 in Stage II, and 1 in Stage III. Of the 27 studied inflammatory mediators, the main proinflammatory mediators were IL-6, IFN-γ, TNF-α, IL-1β, and IL-17; the main anti-inflammatory mediators were IL-10 and IL-4. Serum IL-6 and TNF-α concentrations were significant during periodontal and reactional lesion evolution; IFN-γ and IL-1β were associated with types 1 and 2 reactions and chronic periodontal disease. The proinflammatory mediators in dental infections and leprosy reactions, especially IL-6 and TNF-α, were similar across studies, regardless of the laboratory technique and sample type. IFN-γ and IL-1β were significant for leprosy reactions and periodontal diseases. This pattern was maintained in serum. PMID:26339136
Aarão, Tinara Leila de Sousa; de Sousa, Jorge Rodrigues; Botelho, Beatriz Santos; Fuzii, Hellen Thais; Quaresma, Juarez Antonio Simões
Leprosy is a serious public health problem in peripheral and developing countries. Leprosy is a chronic infectious-contagious disease caused by the intracellular, bacillus Mycobacterium leprae, which causes tissue damage and demyelination of peripheral nerves. Recent studies have demonstrated the participation of new subtype's cytokines profile in the inflammatory response of leprosy. Since nerve functions are affected by inflammatory response during the course of leprosy, changes in the production of NGF and its receptor (NGF R) may be directly associated with disability and sensory loss. Skin biopsies were collected and submitted to immunohistochemistry using specific antibodies to IL-17, NGF and NGF R. Quantitative analysis of NGF, NGFR and IL-17 immunostaining showed a significant difference between the clinical forms, with higher expression of NGF and NGFR in lepromatous leprosy and IL-17 in tuberculoid leprosy. The present study showed that IL-17, in addition to stimulating an inflammatory response, negatively regulates the action of NGF and NGF R in the polar forms of the disease.
Sauer, Monica E D; Salomão, Heloisa; Ramos, Geovana B; D'Espindula, Helena R S; Rodrigues, Rafael S A; Macedo, Wilian C; Sindeaux, Renata H M; Mira, Marcelo T
A solid body of evidence produced over decades of intense research supports the hypothesis that leprosy phenotypes are largely dependent on the genetic characteristics of the host. The early evidence of a major gene effect controlling susceptibility to leprosy came from studies of familial aggregation, twins, and complex segregation analysis. Later, linkage and association analysis, first applied to the investigation of candidate genes and chromosomal regions and more recently, to genome-wide scans, have revealed several HLA and non-HLA gene variants as risk factors for leprosy phenotypes such as disease per se, its clinical forms, and leprosy reactions. In addition, powerful, hypothesis-free strategies such as genome-wide association studies have led to an exciting, unexpected development: Leprosy susceptibility genes seem to be shared with Crohn's and Parkinson's disease. Today, a major challenge is to find the exact variants causing the biological effect underlying the genetic associations. New technologies, such as Next Generation Sequencing-that allows, for the first time, the cost- and time-effective sequencing of a complete human genome-hold the promise to reveal such variants; thus, strategies can be developed to study the functional impact of these variants in the context of infection, hopefully leading to the development of new targets for leprosy treatment and prevention.
Fonseca, Adriana Barbosa de Lima; Simon, Marise do Vale; Cazzaniga, Rodrigo Anselmo; de Moura, Tatiana Rodrigues; de Almeida, Roque Pacheco; Duthie, Malcolm S; Reed, Steven G; de Jesus, Amelia Ribeiro
Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.
Fabri, Angélica da Conceição Oliveira Coelho; Carvalho, Ana Paula Mendes; Vieira, Nayara Figueiredo; Bueno, Isabela de Caux; Rodrigues, Rayssa Nogueira; Monteiro, Thayenne Barrozo Mota; Correa-Oliveira, Rodrigo; Duthie, Malcolm S; Lana, Francisco Carlos Félix
An integrative literature review was conducted to synthesize available publications regarding the potential use of serological tests in leprosy programs. We searched the databases Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol em Ciências da Saúde, Acervo da Biblioteca da Organização Pan-Americana da Saúde, Medical Literature Analysis and Retrieval System Online, Hanseníase, National Library of Medicine, Scopus, Ovid, Cinahl, and Web of Science for articles investigating the use of serological tests for antibodies against phenolic glycolipid-I (PGL-I), ML0405, ML2331, leprosy IDRI diagnostic-1 (LID-1), and natural disaccharide octyl-leprosy IDRI diagnostic-1 (NDO-LID). From an initial pool of 3.514 articles, 40 full-length articles fulfilled our inclusion criteria. Based on these papers, we concluded that these antibodies can be used to assist in diagnosing leprosy, detecting neuritis, monitoring therapeutic efficacy, and monitoring household contacts or at-risk populations in leprosy-endemic areas. Thus, available data suggest that serological tests could contribute substantially to leprosy management.
Chaitra, P.; Bhat, Ramesh Marne
Introduction. Leprosy, a statistically “eliminated” disease from the globe, continues to linger around in its endemic countries including India. Objective. This study describes the epidemiological and clinicopathological pattern of the disease seen in children over a period of 8 years following its elimination in India. Materials and Methods. Medical records of all leprosy cases up to 14 years of age registered between April 2005 and March 2013 were retrospectively analyzed. Data were retrieved using a predesigned proforma and entered into the database system for analysis. Results. Child proportion of newly registered leprosy cases did not show a significant decline in the years following its elimination. The disease seemed to manifest frequently in older children with an insignificant gender predilection. More than half of child cases had a history of household contact. Paucibacillary leprosy dominated in them with a solitary skin lesion as the most frequent presentation. Although nerve thickening was seen in nearly half of these children, neuritis and lepra reactions were less common. Deformity at the time of diagnosis was noted in 13.89% of cases. Although smear positivity was not a common feature in children affected with leprosy, a good clinicohistopathological correlation was observed in those who underwent biopsy. Conclusion. Our study and reports from different parts of the country depict the unturned curves in the epidemiology of childhood leprosy which mirrors active transmission in the community, lacunae in diagnosis, and the need to strengthen contact screening activities in the pediatric population to sustain elimination. PMID:24089672
van 't Noordende, Anna T.; Banstola, Nandlal; Dhakal, Krishna P.
Background. Leprosy is one of the most stigmatized diseases known today. The stigma surrounding leprosy can be a major burden and affects many dimensions of a person's life, including intimate relationships. We aimed to investigate the experiences of women affected by leprosy regarding marital life and sexuality, comparing these to the experiences of women with other physical disabilities and to those of able-bodied women in South-East Nepal. Methods. This study used a qualitative approach and a cross-sectional, nonrandom survey design. Thirty women underwent in-depth interviews about their marital and sexual relationship by means of a semi-structured interview guide. These thirty women included ten women affected by leprosy, ten women with other physical disabilities, and ten able-bodied women living in South-East Nepal. Results. We found that many women faced violence and abuse in their marriages. However, women affected by leprosy appeared to face more problems with regard to their marital and sexual relationships than women with physical disabilities and able-bodied women. Some of these related to the fear of leprosy. Conclusions. Further research is recommended to investigate the extent of this problem and ways to ameliorate the situation of the affected women. Education and counselling at diagnosis may help prevent many of the problems reported. PMID:27047548
Roy, Avijit; Hartung, John S; Schneider, William L; Shao, Jonathan; Leon, Guillermo; Melzer, Michael J; Beard, Jennifer J; Otero-Colina, Gabriel; Bauchan, Gary R; Ochoa, Ronald; Brlansky, Ronald H
Citrus leprosis complex is an emerging disease in the Americas, associated with two unrelated taxa of viruses distributed in South, Central, and North America. The cytoplasmic viruses are Citrus leprosis virus C (CiLV-C), Citrus leprosis virus C2 (CiLV-C2), and Hibiscus green spot virus 2, and the nuclear viruses are Citrus leprosis virus N (CiLV-N) and Citrus necrotic spot virus. These viruses cause local lesion infections in all known hosts, with no natural systemic host identified to date. All leprosis viruses were believed to be transmitted by one species of mite, Brevipalpus phoenicis. However, mites collected from CiLV-C and CiLV-N infected citrus groves in Mexico were identified as B. yothersi and B. californicus sensu lato, respectively, and only B. yothersi was detected from CiLV-C2 and CiLV-N mixed infections in the Orinoco regions of Colombia. Phylogenetic analysis of the helicase, RNA-dependent RNA polymerase 2 domains and p24 gene amino acid sequences of cytoplasmic leprosis viruses showed a close relationship with recently deposited mosquito-borne negevirus sequences. Here, we present evidence that both cytoplasmic and nuclear viruses seem to replicate in viruliferous Brevipalpus species. The possible replication in the mite vector and the close relationship with mosquito borne negeviruses are consistent with the concept that members of the genus Cilevirus and Higrevirus originated in mites and citrus may play the role of mite virus vector.
Nobre, Mauricio Lisboa; Dupnik, Kathryn Margaret; Nobre, Paulo José Lisboa; De Souza, Márcia Célia Freitas; Dűppre, Nádia Cristina; Sarno, Euzenir Nunes; Jerŏnimo, Selma Maria Bezerra
Summary Introduction Leprosy is a public health problem in Brazil where 31,044 new cases were detected in 2013. Rio Grande do Norte is a small Brazilian state with a rate of leprosy lower than other areas in the same region, for unknown reasons. Objectives We present here a review based on the analysis of a database of registered leprosy cases in Rio Grande do Norte state, comparing leprosy's geographic distribution among municipalities with local socio-economic and public health indicators and with historical documents about human migration in this Brazilian region. Results The current distribution of leprosy in Rio Grande do Norte did not show correlation with socio-economic or public health indicators at the municipal level, but it appears related to economically emerging municipalities 100 years ago, with spread facilitated by railroads and train stations. Drought-related migratory movements which occurred from this state to leprosy endemic areas within the same period may be involved in the introduction of leprosy and with its present distribution within Rio Grande do Norte. Conclusions Leprosy may disseminate slowly, over many decades in certain circumstances, such as in small cities with few cases. This is a very unusual situation currently and a unique opportunity for epidemiologic studies of leprosy as an emerging disease. PMID:26964429
A critical analysis of health control measures that historically took place in Peru to the present which has led Peru to officially consider leprosy as an "eliminated" public health problem. We will also discuss the validity of the status given the neglect of health surveillance, disbanded specialized control entities, health medical staff forgetting to account for leprosy in early stages, the presence of undiagnosed smear-positive leprosy in Lima and the undeniable hidden prevalence, suggest that there is a danger to the country and the region that a re-emergence of leprosy will occur, if relevant and appropriate sanitary measures are not taken.
Tiendrebeogo, A; Coulibaly, I; Sarr, A M; Sow, S O
To determine potential usefulness of antimicrobial agents and to guide their prescription in the treatment of leprosy plantar ulcers, we conducted an in vitro study about germs' nature and sensitivity to antibiotics. We took samples of plantar ulcers secretion from 107 patients at Marchoux Institute. 92.5% of those ulcers were infected. These samples revealed 145 strains of micro-organisms among those, Staphylococcus aureus (70 strains) and genus Pseudomonas (41 strains) were the most frequent. These bacteria were resistant to several antibiotics currently used at Marchoux Institute (tetracycline, penicillin, cotrimoxazol and erythromicin). Antibiotics, efficient at 80% on tested strains, were expensive for patients. They cannot be recommended for the treatment of local infections. These results outline that the main treatment in plantar ulcers is based upon antiseptic solutions and keeping feet at rest. Antibiotherapy in case of extension of local infection would be based on the results of a previous study of sensitivity.
Murto, C.; Kaplan, C.; Ariza, L.; Schwarz, K.; Alencar, C. H.; da Costa, L. M. M.; Heukelbach, J.
In Brazil, leprosy is endemic and concentrated in high-risk clusters. Internal migration is common in the country and may influence leprosy transmission and hamper control efforts. We performed a cross-sectional study with two separate analyses evaluating factors associated with migration in Brazil's Northeast: one among individuals newly diagnosed with leprosy and the other among a clinically unapparent population with no symptoms of leprosy for comparison. We included 394 individuals newly diagnosed with leprosy and 391 from the clinically unapparent population. Of those with leprosy, 258 (65.5%) were birth migrants, 105 (26.6%) were past five-year migrants, and 43 (10.9%) were circular migrants. In multivariate logistic regression, three independent factors were found to be significantly associated with migration among those with leprosy: (1) alcohol consumption, (2) separation from family/friends, and (3) difficulty reaching the healthcare facility. Separation from family/friends was also associated with migration in the clinically unapparent population. The health sector may consider adapting services to meet the needs of migrating populations. Future research is needed to explore risks associated with leprosy susceptibility from life stressors, such as separation from family and friends, access to healthcare facilities, and alcohol consumption to establish causal relationships. PMID:24194769
Hartung, John S; Roy, Avijit; Fu, Shimin; Shao, Jonathan; Schneider, William L; Brlansky, Ronald H
Leprosis refers to two diseases of citrus that present similar necrotic local lesions, often surrounded by chlorotic haloes on citrus. Two distinct viruses are associated with this disease, one that produces particles primarily in the nucleus of infected plant cells (Citrus leprosis virus nuclear type [CiLV-N]; Dichorhavirus) and another type that produces particles in the cytoplasm of infected plant cells (Citrus leprosis virus cytoplasmic type [CiLV-C]; Cilevirus). Both forms are transmitted by Brevipalpid mites and have bipartite, single-stranded, RNA genomes. CiLV-C and CiLV-N are present in South and Central America and as far north as parts of Mexico. Although leprosis disease was originally described from Florida, it disappeared from there in the 1960s. The United States Department of Agriculture-Agricultural Research Service maintains preserved citrus specimens identified at inspection stations 50 or more years ago with symptoms of citrus leprosis. We isolated RNA from these samples and performed degradome sequencing. We obtained nearly full-length genome sequences of both a typical CiLV-C isolate intercepted from Argentina in 1967 and a distinct CiLV-N isolate obtained in Florida in 1948. The latter is a novel form of CiLV-N, not known to exist anywhere in the world today. We have also documented the previously unreported presence of CiLV-N in Mexico in the mid-20th century.
Mahato, Margaret E
The stigma and discrimination due to disabilities in leprosy has a profound effect on a leprosy individual and the disability hampers his/her earning capacity and therefore socio-economic status. The Government of India has recently come out with an approved plan for disability prevention and medical rehabilitation. There are some objectives to provide appropriate services to the disabled or to prevent the disability. In order to prevent disability early treatment is necessary but there are a lot of studies on delayed presentation. It is in fact suggested that not only early correct treatment of leprosy with MDT but also early correct treatment of reactions and nuritis can prevent disability. Some cases as specified in the text require referral to prevent the menace. Many deformities can be corrected by reconstructive surgery. The management protocol to prevent primary impairment is depicted in Figs within the article.
Raju, M S; Rao, P S S
As part of a community-based action research to reduce leprosy stigma, village committees were formed in 3 hyper endemic states of India. From a total of 10 village committees with nearly 200 members from Uttar Pradesh, a systematic random sample of 69 men and 23 women were interviewed in-depth regarding their views on sustainability of integrated leprosy services, as currently adopted. Their recommendations were also sought for further enhancement. Percentages were computed and compared for statistical significance using the z-normal test. The findings show that less than 50% of the respondents were confident that the present trend in voluntary early reporting for MDT and management of complications was adequate to sustain the integrated leprosy services. There were no differences by men or women members and they felt that lack of proper facilities, training and orientation of staff are most influencing factors. Many suggestions were given for improving the sustainability.
Cardenas, Victor Manuel; Orloff, Mohammed S; Kaminaga, Joseph; Cardenas, Irma Carrillo; Brown, Joeline; Hainline-Williams, Sandra; Duthie, Malcolm S; Gonzalez-Puche, Angela C; Mukasa, Leonard; Patil, Naveen; Mcelfish, Pearl Ann; Bates, Joseph H
The cross-immunity between tuberculosis and leprosy is unknown. The aim of this pilot study was to evaluate the occurrence of Mycobacterium tuberculosis and M. leprae infection in Marshallese adult volunteers in Springdale, Arkansas, U.S.A., a population that experiences high rates of leprosy and tuberculosis. We used immunodiagnostic testing for tuberculosis and leprosy infection and found significant prevalence of latent tuberculosis infection (19.0%), and asymptomatic Mycobacterium leprae infection (22.2%). We found a negative association between presence of antibodies to Mycobacterium leprae and a positive interferon-γ release assay for Mycobacterium tuberculosis infection, prevalence odds ratio = 0.1 (95% CI = 0.0, 0.9). Although these findings require confirmation on a larger scale, they are supportive of the existence of cross-immunity.
Win, Le Le; Shwe, San; Maw, Win; Ishida, Yutaka; Myint, Kyaw; Mar, Kyi Kyi; Min, Thandar; Oo, Phyo Min; Khine, Aye Win
A cross-sectional study was carried out to identify methods of caring plantar ulcers in leprosy patients and the underlying causes of poor plantar ulcer care during January and February 2008. This was conducted in Pakokku zone as it was one of the "9 selected townships of the Disabilities survey, i.e., Basic Health Staff project 2003/4", which was funded by Japan International Cooperation Agency. After getting consent, all available leprosy cases, i.e., 101 cases with foot disability grade 2 were interviewed with the pre-tested questionnaire. Among 101 cases, 13 cases who took care of their ulcer poorly and 20 who did none of the recommended measures were recruited for in-depth interview (IDI). The subjects were largely old people, males and people with no marriage partner. The majority had earned money by doing sedentary job. Prolongation of ulcers was observed in 78 cases. Most had been suffering from ulcers for years. When asking face-to-face interview, all the recommended care measures were not reported. Among these recommended measures, a large number of respondents reported about soaking measure. However, these reported measures were contradicted to the preventive methods which they disclosed in IDI. Plantar ulcer care seemed to be an individualised practice. The individual ways of performing were related to their view of ulcer, the environment, and occupation, and custom, communication with family and health staff. The findings identified the actual practice of plantar ulcer care in study areas. It is suggested that the current performance of planar ulcer care is inadequate and more attention should be given to achieve the target set by the programme as a recommendation.
Leandro, José Augusto
Patronato de Leprosos, in Argentina, and Federação das Sociedades de Assistência aos Lázaros e Defesa Contra a Lepra, in Brazil, were created as institutions designed to help people with leprosy and their families. Headed by women from the ruling classes, these entities took very similar actions, despite the different national contexts in which they operated, both supplementing leprosy healthcare policies in their respective countries. This article aims to demonstrate the similarities in the strategies adopted by both philanthropic institutions, which, in the 1930s and 1940s, acted in harmony with the physicians who supported compulsory isolation.
Gaüzere, B A; Aubry, P
This article traces the history of leprosy in Reunion from the early eighteenth century, which long paralleled the slave trace. Lepers were confined to a lazaretto and treated with herbs. Father Raimbault, "doctor" and chaplain of the lepers in the middle of the twentieth century, is still honored today. The improvement in living standards and the use of sulfones finally resulted in the control of leprosy. Nonetheless, from 2005 to 2011, an average of three new cases per year were detected among a population of 800,000 inhabitants.
Leon, Kristoffer E; Salinas, Jorge L; McDonald, Robert W; Sheth, Anandi N; Fairley, Jessica K
In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is often underrecognized. Consequently, the literature is currently lacking in clinical descriptions of leprosy complications in the United States. Immune-mediated inflammatory states known as reactions are common complications of HD. Type 1 reactions are typical of borderline cases and occur in 30% of patients and present as swelling and inflammation of existing skin lesions, neuritis, and nerve dysfunction. Type 2 reactions are systemic events that occur at the lepromatous end of the disease spectrum, and typical symptoms include fever, arthralgias, neuritis, and classic painful erythematous skin nodules known as erythema nodosum leprosum. We report three patients with lepromatous leprosy seen at a U.S. HD clinic with complicated type 2 reactions. The differences in presentations and clinical courses highlight the complexity of the disease and the need for increased awareness of unique manifestations of lepromatous leprosy in non-endemic areas.
Leon, Kristoffer E.; Salinas, Jorge L.; McDonald, Robert W.; Sheth, Anandi N.; Fairley, Jessica K.
In non-endemic countries, leprosy, or Hansen's disease (HD), remains rare and is often underrecognized. Consequently, the literature is currently lacking in clinical descriptions of leprosy complications in the United States. Immune-mediated inflammatory states known as reactions are common complications of HD. Type 1 reactions are typical of borderline cases and occur in 30% of patients and present as swelling and inflammation of existing skin lesions, neuritis, and nerve dysfunction. Type 2 reactions are systemic events that occur at the lepromatous end of the disease spectrum, and typical symptoms include fever, arthralgias, neuritis, and classic painful erythematous skin nodules known as erythema nodosum leprosum. We report three patients with lepromatous leprosy seen at a U.S. HD clinic with complicated type 2 reactions. The differences in presentations and clinical courses highlight the complexity of the disease and the need for increased awareness of unique manifestations of lepromatous leprosy in non-endemic areas. PMID:26304919
Paixão, Maurício Pedreira; Miot, Hélio Amante; de Souza, Pedro Elias; Haddad, Ana Estela; Wen, Chao Lung
There is a high prevalence of leprosy in the Amazon region of Brazil. We have developed a distance education course in leprosy for training staff of the Family Health Teams (FHTs). The course was made available through a web portal. Tele-educational resources were mediated by professors and coordinators, and included the use of theoretical content available through the web, discussion lists, Internet chat, activity diaries, 3-D video animations (Virtual Human on Leprosy), classes in video streaming and case simulation. Sixty-five FHT staff members were enrolled. All of them completed the course and 47 participants received a certificate at the end of the course. At the end of the course, 48 course-evaluation questionnaires were answered. A total of 47 participants (98%) considered the course as excellent. The results demonstrate the feasibility of an interactive, tele-education model as an educational resource for staff in isolated regions. Improvements in diagnostic skills should increase diagnostic suspicion of leprosy and may contribute to early detection.
Lusli, Mimi; Zweekhorst, Marjolein B M; Miranda-Galarza, Beatriz; Peters, Ruth M H; Cummings, Sarah; Seda, Francisia S S E; Bunders, Joske F G; Irwanto
Persons affected by leprosy or by disabilities face forms of stigma that have an impact on their lives. This study seeks to establish whether their experiences of stigma are similar, with a view to enabling the two groups of people to learn from each other. Accounts of experiences of the impact of stigma were obtained using in-depth interviews and focus group discussion with people affected by leprosy and by disabilities not related to leprosy. The analysis shows that there are a lot of similarities in impact of stigma in terms of emotions, thoughts, behaviour, and relationships between the two groups. The main difference is that those affected by leprosy tended to frame their situation in medical terms, while those living with disabilities described their situation from a more social perspective. In conclusion, the similarities offer opportunities for interventions and the positive attitudes and behaviours can be modelled in the sense that both groups can learn and benefit. Research that tackles different aspects of stigmatization faced by both groups could lead to inclusive initiatives that help individuals to come to terms with the stigma and to advocate against exclusion and discrimination.
Citrus leprosis disease is at the same time an emerging, a current and a historical problem. Two distinct viruses are associated with this disease, one that produces particles primarily in the nucleus of infected plant cells (CiLV-N; Dichorhavirus) and another, much more widespread type that produc...
Citrus leprosis is a difficult viral disease causing significant damage to citrus fruit in South America and Central America. The disease is marked by dramatic lesions on fruit, leaves and stems, resulting in an unmarketable product. The disease is caused by a set of unrelated cytoplasmic cileviruse...
Goulart, Isabela Maria Bernardes; Araujo, Sergio; Filho, Adilson Botelho; de Paiva, Paulo Henrique Ribeiro; Goulart, Luiz Ricardo
Blood donor samples (1,007) were assessed for anti-phenolic glycolipid 1 (PGL-1) IgM antibodies and Mycobacterium leprae DNA presence, which had 3.8% and 0.3% positivity, respectively. After a 5-year follow-up period, six individuals with positive markers developed leprosy, raising the hypothesis that asymptomatic infection among blood donors may be an undisclosed mode of leprosy transmission via transfusion.
Shetty, V P; Pandya, S S; Arora, S; Capadia, G D
The special selective drive (SSD) was conducted on a request from the Joint Director of Health Services (Leprosy and TB) Government of Maharashtra. The study team comprised the Foundation for Medical Research (FMR), assisted by a member of the Acworth Leprosy Hospital Society for Research, Rehabilitation and Education in Leprosy and two from Kushtrog Nivaran Samiti (KNS). The drive was conducted in select villages covered by 6 primary health centers (PHCs) in Karjat taluka of Raigad district and 45 PHCs in Gadchiroli district from March to May 2009 and had the cooperation of the district and PHC level staff. The aim was to train and deploy community level workers (CWs) for early leprosy case detection and through them, to create leprosy awareness in the community. A total of 1053 CWs (126 in Karjat taluka, 927 in Gadchiroli district) were given intensive training by the team. The CWs then carried out a one-day house-to-house leprosy awareness drive in their areas and listed persons such 'suspects' in both Karjat taluka (no. = 514) and Gadchiroli district (no. = 1325). Around 40% of 'suspects' presented themselves at the PHCs for examination by the medical team; of these 38 (29%) and 281 (45%) respectively turned out to be previously undetected definite cases of leprosy. The PHC-wise NCDR ranged from 5 - 27/10,000 in Karjat (14/10,000) and 2 - 35/10,000 in Gadchiroli (average 13/10,000), both rates being much higher than the reported State average of 1.1/10,000. There was a high proportion of child cases (14 and 24% respectively) and grade 2 disability (18% and 12% respectively) which indicate continued transmission of leprosy and delayed diagnosis of cases. The study also notes poor diagnostic skills among the PHC staff. Significant shortage and irregular disbursement of MDT from district store PHCs, combined with transport problem which probably contributed to delay in treatment in over 50% of the cases confirmed by the team.
Al Samie, Abdul Rahim; Al Qubati, Yasin
Although the prevalence rate of leprosy in the Republic of Yemen has dropped below the WHO elimination level of less than one case per 10,000 of the population, it is still regarded as a serious public health problem calling for continued vigilance, notably in the detection and treatment of hidden and undiagnosed cases. In the past, religious misinterpretation has generated adverse behaviour patterns towards people affected by leprosy, characterized by aggression, negligence and isolation. Until about 1982, following a visit of a leprologist (Dr S. K. Noordeen) from the World Health Organization, there was no leprosy control programme and attempts to establish one remained ineffective until in 1989, when an agreement was signed between the Ministry of Public Health and Population and the German Leprosy Relief Association. This led to the development of a leprosy control programme in four governorates, later extended to the rest of the country. This paper describes the progress made in the control of leprosy in the Yemen, 1989-2003, by the Ministry of Health and Population and the GLRA, in association with two local societies.
This paper questions the relation between human health and society from the case study of leprosy. To discuss the cultural and social mediator factors of both the experience of leprosy and outcomes of medical practices, it examines the biomedical twist in the dialectic between citizenship and public good that aimed to turn leprosy into a disease like any other, with the advent of multidrug therapy during the 1980s. Such analysis is based on a multisited ethnography, developed between 2008 and 2013 in two divergent contexts from the global South and North: Brazil, which remains the country in the world with the highest relative cases of leprosy, and Portugal, in which leprosy has become an imported disease. The main results of this research point to the limits of a pharmaceuticalized governmentality of leprosy and to heterogeneous medicalization's processes, which evince the determinacy of historical intersections between the State and civil society, as well as the corollaries of the former in medical care. This paper concludes with an analysis of the partition between biomedical cure and the healing of leprosy, which unveils the intermediation of institutional and extrainstitutional factors in access to health and in the cure of leprosy. It is finally argued that such intermediation requires a public health approach that might resocialize leprosy through a paradigmatic shift toward intersectoral and participatory operational strategies.
Alvarado-Arnez, Lucia Elena; Amaral, Evaldo P; Sales-Marques, Carolinne; Durães, Sandra M B; Cardoso, Cynthia C; Nunes Sarno, Euzenir; Pacheco, Antonio G; Lana, Francisco C F; Moraes, Milton Ozório
Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the -819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the -819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal IL10 polymorphisms: -3575 T>A (rs1800890), -2849 G>A (rs6703630), -2763 C>A (rs6693899), -1082 G>A (rs1800896) and -592 C>A (rs1800872). Results from meta-analysis supported a significant susceptibility association for the -819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11-1.34) and P-value = 3x10(-5) confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10-1.31, P-value = 2x10(-5)). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03-1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r(2) = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other IL10 polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the -819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.
Richardus, Jan H; Withington, Stephen G; Anderson, Alison M; Croft, Richard P; Nicholls, Peter G; Van Brakel, Wim H; Smith, W Cairns S
Reactions in leprosy causing nerve function impairment (NFI) are increasingly treated with standardized regimens of corticosteroids, often under field conditions. Safety concerns led to an assessment of adverse events of corticosteroids, based on data of three trials studying prevention of NFI (the TRIPOD study). A multicentre, randomized, double-blind placebo-controlled trial was conducted in leprosy control programmes in Nepal and Bangladesh. Treatment was with prednisolone according to fixed schedules for 16 weeks, starting in one trial with 20 mg/day (prophylactic regimen: total dosage 1.96 g) and in the other two trials with 40 mg/day (therapeutic regimen: total dosage 2.52 g). Minor adverse events were defined as moon face, fungal infections, acne, and gastric pain requiring antacid. Major adverse events were defined as psychosis, peptic ulcer, glaucoma, cataract, diabetes and hypertension. Also, the occurrence of infected plantar, palmar, and corneal ulceration was monitored, together with occurrence of TB. Considering all three trials together, minor adverse events were observed in 130/815 patients (16%). Of these, 51/414 (12%) were in the placebo group and 79/401 (20%) in the prednisolone group. The relative risk for minor adverse events in the prednisolone group was 1.6 (P = 0.004). Adverse events with a significantly increased risk were acne, fungal infections and gastric pain. Major adverse events were observed in 15/815 patients (2%); 7/414 (2%) in the placebo group and 8/401 (2%) in the prednisolone group. No major adverse events had a significantly increased risk in the prednisolone arm of the trials. No cases of TB were observed in 300 patients who could be followed-up for 24 months. Standardized regimens of corticosteroids for both prophylaxis and treatment of reactions and NFI in leprosy under field conditions in developing countries are safe when a standard pre-treatment examination is performed, treatment for minor conditions can be carried out
Nery, Joilda Silva; Pereira, Susan Martins; Rasella, Davide; Penna, Maria Lúcia Fernandes; Aquino, Rosana; Rodrigues, Laura Cunha; Barreto, Mauricio Lima; Penna, Gerson Oliveira
Background Social determinants can affect the transmission of leprosy and its progression to disease. Not much is known about the effectiveness of welfare and primary health care policies on the reduction of leprosy occurrence. The aim of this study is to evaluate the impact of the Brazilian cash transfer (Bolsa Família Program-BFP) and primary health care (Family Health Program-FHP) programs on new case detection rate of leprosy. Methodology/Principal Findings We conducted the study with a mixed ecological design, a combination of an ecological multiple-group and time-trend design in the period 2004–2011 with the Brazilian municipalities as unit of analysis. The main independent variables were the BFP and FHP coverage at the municipal level and the outcome was new case detection rate of leprosy. Leprosy new cases, BFP and FHP coverage, population and other relevant socio-demographic covariates were obtained from national databases. We used fixed-effects negative binomial models for panel data adjusted for relevant socio-demographic covariates. A total of 1,358 municipalities were included in the analysis. In the studied period, while the municipal coverage of BFP and FHP increased, the new case detection rate of leprosy decreased. Leprosy new case detection rate was significantly reduced in municipalities with consolidated BFP coverage (Risk Ratio 0.79; 95% CI = 0.74–0.83) and significantly increased in municipalities with FHP coverage in the medium (72–95%) (Risk Ratio 1.05; 95% CI = 1.02–1.09) and higher coverage tertiles (>95%) (Risk Ratio 1.12; 95% CI = 1.08–1.17). Conclusions At the same time the Family Health Program had been effective in increasing the new case detection rate of leprosy in Brazil, the Bolsa Família Program was associated with a reduction of the new case detection rate of leprosy that we propose reflects a reduction in leprosy incidence. PMID:25412418
Sane, S B; Mehta, J M
Twelve cases of carcinomata arising in Trophic ulcers of Leprosy are presented. Out of these, 10 were on the plantar surface more commonly on the proximal part of foot, one on lower leg and dorsum of foot, and one in an ulcer over the lateral malleolus. Almost all presented with infected growths and regional lymphadenopathy. Three cases presented with advanced disease with fungating inguinal nodes and were fatal. Nine cases underwent below knee amputation under antibiotic cover as a definitive treatment and the lymph nodes were kept under observation. Histologically, all were low grade squamous cell carcinomas. In most cases lymph nodes regressed after removal of primary and in one case lymph nodes were positive for malignancy. This study was conducted at Dr. Bandorawalla Leprosy Hospital, Kondhawa, Pune 22 from the year 1981 to 1987.
Menke, Henk; Snelders, Stephen; Pieters, Toine
Leprosy was highly prevalent among African slaves in the Dutch West Indian colony of Suriname. Largely based on observations in Suriname, Dutch physicians described the aetiology of leprosy in terms of'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed ('seed and soil'). This explanatory model with multiple options for prevention and treatment left room for different developmental trajectories to control the spread of the disease in the various tropical colonies of the Dutch empire. In Suriname there was a growing worry in the 19th century regarding the spread of leprosy, threatening the health of slaves, settlers and colonial administrators. And this could be harmful to an already weakening plantation economy. This concern prompted the local administration to develop a rigorous policy of strict isolation of leprosy sufferers. This, in turn, intersected with a changing insight in Europe - including the Netherlands - that leprosy was non-contagious. However,'in splendid isolation' in the economically and politically marginal colony Suriname, Dutch physicians like Charles Landre and his son, Charles Louis Drognat Landré, could afford to ignore the European non-contagious approach and continue to support the strict isolation policies. Moreover, they developed a dissident radical explanation of leprosy as a disease caused only by contagion. In the absence of a receptive Dutch audience Drognat Landré published his contagion theory in French and so succeeded in inspiring the Norwegian Hansen, who subsequently discovered the culpable micro-organism. At the same time colonial administrators and physicians in the economically and politically important Dutch colonies in the East Indies adhered to the prevailing European concept and changed policies: the system of isolation was abolished. Given the rather different trajectories of leprosy health policies in the Dutch East and West Indies we point out the importance of a comparative
Hansen discovered the bacteria in 1873 in unstained material and is therefore recognized as the discoverer of the leprosy pathogen. Hansen is a very common surname but in contrast Armauer is a very rare surname. Gerhard Henrik Hansen added the maiden name of his grandmother on his mother's side to his name early on. This happened not only out of family attachments but also as a physician and aspiring scientist to set himself apart from other Hansens.
Wong, Sunny H.; Gochhait, Sailesh; Malhotra, Dheeraj; Pettersson, Fredrik H.; Teo, Yik Y.; Khor, Chiea C.; Rautanen, Anna; Chapman, Stephen J.; Mills, Tara C.; Srivastava, Amit; Rudko, Aleksey; Freidin, Maxim B.; Puzyrev, Valery P.; Ali, Shafat; Aggarwal, Shweta; Chopra, Rupali; Reddy, Belum S. N.; Garg, Vijay K.; Roy, Suchismita; Meisner, Sarah; Hazra, Sunil K.; Saha, Bibhuti; Floyd, Sian; Keating, Brendan J.; Kim, Cecilia; Fairfax, Benjamin P.; Knight, Julian C.; Hill, Philip C.; Adegbola, Richard A.; Hakonarson, Hakon; Fine, Paul E. M.; Pitchappan, Ramasamy M.; Bamezai, Rameshwar N. K.; Hill, Adrian V. S.; Vannberg, Fredrik O.
Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7×10−8, OR = 0.31, 95% CI = 0.20–0.48, and HLA-DQA1 rs1071630, case-control P = 4.9×10−14, OR = 0.43, 95% CI = 0.35–0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases. PMID:20617178
Santos, Selton Diniz; Penna, Gerson Oliveira; Costa, Maria da Conceição Nascimento; Natividade, Marcio Santos; Teixeira, Maria Glória
This original study describes the intra-urban distribution of cases of leprosy in residents under 15 years old in Salvador, Bahia, Brazil; the study also identifies the environment in which Mycobacterium leprae is being transmitted. The cases were distributed by operational classification, clinical forms, type of contact and the addresses were geo-referenced by neighborhood. Between 2007 and 2011, were reported 145 cases of leprosy in target population living in Salvador, corresponding to detection rates of 6.21, 6.14, 5.58, 5.41 and 6.88/100,000 inhabitants, respectively. The spatial distribution of the disease was focal. Of the 157 neighborhoods of Salvador, 44 (28.6%) notified cases of leprosy and in 22 (50%) of these were detected more than 10 cases per 100,000 inhabitants. The infectious forms were found in 40% of cases. Over 90% of cases had been living in Salvador for more than five years. Overall, 52.6% reported having had contact with another infected individual inside the household and 25% in their social circle. In Salvador, M. leprae transmission is established. The situation is a major concern, since transmission is intense at an early age, indicating that this endemic disease is expanding and contacts extend beyond individual households. PMID:27223655
Marques, João P R; Kitajima, Elliot W; Freitas-Astúa, Juliana; Appezzato-da-Glória, Beatriz
The leprosis disease shows a viral etiology and the citrus leprosis virus is considered its etiologic agent. The disease may show two types of cytopatologic symptom caused by two virus: nuclear (CiLV-N) and cytoplasmic (CiLV-C) types. The aim of this study was to compare the morpho-anatomical differences in the lesions caused by leprosis virus-cytoplasmic and nuclear types in Citrus sinensis (L.) Osbeck 'Pêra'. Leaf and fruit lesions were collected in Piracicaba/São Paulo (cytoplasmic type) and Monte Alegre do Sul/São Paulo and Amparo/São Paulo (nuclear type). The lesions were photographed and then fixed in Karnovsky solution, dehydrated in a graded ethylic series, embedded in hydroxy-ethyl methacrylate resin (Leica Historesin), sectioned (5 microm thick), stained and mounted in synthetic resin. The digital images were acquired in a microscope with digital video camera. Leaf and fruit lesions caused by the two viruses were morphologically distinct. Only the lesion caused by CiLV-N virus presented three well-defined regions. In both lesions there was the accumulation of lipidic substances in necrotic areas that were surrounded by cells with amorphous or droplets protein. Only leaf and fruit lesions caused by CiLV-N virus exhibited traumatic gum ducts in the vascular bundles.
Donoghue, Helen D; Spigelman, Mark; O'Grady, Justin; Szikossy, Ildikó; Pap, Ildikó; Lee, Oona Y-C; Wu, Houdini H T; Besra, Gurdyal S; Minnikin, David E
Many tuberculosis and leprosy infections are latent or paucibacillary, suggesting a long time-scale for host and pathogen co-existence. Palaeopathology enables recognition of archaeological cases and PCR detects pathogen ancient DNA (aDNA). Mycobacterium tuberculosis and Mycobacterium leprae cell wall lipids are more stable than aDNA and restrict permeability, thereby possibly aiding long-term persistence of pathogen aDNA. Amplification of aDNA, using specific PCR primers designed for short fragments and linked to fluorescent probes, gives good results, especially when designed to target multi-copy loci. Such studies have confirmed tuberculosis and leprosy, including co-infections. Many tuberculosis cases have non-specific or no visible skeletal pathology, consistent with the natural history of this disease. M. tuberculosis and M. leprae are obligate parasites, closely associated with their human host following recent clonal distribution. Therefore genotyping based on single nucleotide polymorphisms (SNPs) can indicate their origins, spread and phylogeny. Knowledge of extant genetic lineages at particular times in past human populations can be obtained from well-preserved specimens where molecular typing is possible, using deletion analysis, microsatellite analysis and whole genome sequencing. Such studies have identified non-bovine tuberculosis from a Pleistocene bison from 17,500 years BP, human tuberculosis from 9000 years ago and leprosy from over 2000 years ago.
Romero-Montoya, Marcela; Beltran-Alzate, Juan Camilo
Leprosy in Colombia is in a stage of post elimination—since 1997, prevalence of the disease is less than 1/10000. However, the incidence of leprosy has remained stable, with 400–500 new cases reported annually, with MB leprosy representing 70% of these case and 10% having grade 2 disability. Thus, leprosy transmission is still occurring, and household contacts (HHCs) of leprosy patients are a population at high risk of contracting and suffering from the effects of the disease during their lifetime. We performed a cross-sectional study with the aim of evaluating leprosy transmission within Family Groups (FGs) from four Colombian departments: Antioquia, Bolívar, Córdoba and Sucre. This study included 159 FGs formed by 543 HHCs; 45 FGs were monitored twice, first in 2003 and again in 2012. Migration, forced displacement by violence, loss of contact with the health center and the lack of an agreement to participate in the second monitoring were the primary reasons not all FGs were tested a second time. In each HHC, a clinical examination was performed, epidemiological data recorded, the bacillary index determined, DNA was isolated for M. leprae detection by nested PCR and IgM anti-phenolic glycolipid-I (PGL-I) titers were inspected. Further, DNA from M. leprae isolates were typed and compared among FGs. Twenty-two (4.1%) of the 543 HHCs had IgM anti-PGL-I positive antibody titers, indicating infection. Nasal swabs (NS) taken from 113 HHCs were tested by RLEP PCR; 18 (16%) were positive for M. leprae DNA and two new leprosy cases were detected among the HHCs. Of the confirmed HHCs with leprosy, it was possible to genotype the bacterial strains from both the index case and their HHCs. We found that the genotype of these two strains agreed at 9 markers, showing the individuals to be infected by the same strain, indicating familiar transmission. HHCs of leprosy patients not only are a high-risk population for M. leprae infection, they can act as M. leprae carriers
Citrus leprosis disease (CiLD) in Colombia was previously shown to be caused by cytoplasmic Citrus leprosis virus (CiLV-C). In 2011, ELISA and RT-PCR based diagnostic methods failed to identify CiLV-C from CiLD samples, but virions similar to CiLV-C were observed in cytoplasm of the symptomatic leav...
Roy, Avijit; Choudhary, Nandlal; Guillermo, Leon M; Shao, Jonathan; Govindarajulu, Ananthakrishnan; Achor, Diann; Wei, G; Picton, D D; Levy, L; Nakhla, M K; Hartung, John S; Brlansky, R H
Citrus leprosis in Colombia was previously shown to be caused by cytoplasmic Citrus leprosis virus (CiLV-C). In 2011, enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction (RT-PCR)-based diagnostic methods failed to identify CiLV-C from citrus samples with symptoms similar to citrus leprosis; however, virions similar to CiLV-C were observed in the cytoplasm of the symptomatic leaves by transmission electron microscopy. Furthermore, the causal organism was transmitted by the false spider mite, Brevipalpus phoenicis, to healthy citrus seedlings. A library of small RNAs was constructed from symptomatic leaves and used as the template for Illumina high-throughput parallel sequencing. The complete genome sequence and structure of a new bipartite RNA virus was determined. RNA1 (8,717 nucleotides [nt]) contained two open reading frames (ORFs). ORF1 encoded the replication module, consisting of five domains: namely, methyltransferase (MTR), cysteine protease-like, FtsJ-MTR, helicase (Hel), and RNA-dependent RNA polymerase (RdRp); whereas ORF2 encoded the putative coat protein. RNA2 (4,989 nt) contained five ORFs that encode the movement protein (MP) and four hypothetical proteins (p7, p15, p24, and p61). The structure of this virus genome resembled that of CiLV-C except that it contained a long 3' untranslated terminal region and an extra ORF (p7) in RNA2. Both the RNA1 and RNA2 of the new virus had only 58 and 50% nucleotide identities, respectively, with known CiLV-C sequences and, thus, it appears to be a novel virus infecting citrus. Phylogenetic analyses of the MTR, Hel, RdRp, and MP domains also indicated that the new virus was closely related to CiLV-C. We suggest that the virus be called Citrus leprosis virus cytoplasmic type 2 (CiLV-C2) and it should be unambiguously classified as a definitive member of the genus Cilevirus. A pair of CiLV-C2 genome-specific RT-PCR primers was designed and validated to detect its presence in citrus
When British attention was drawn to the issue of leprosy in the Empire, humanitarian organisations rose to take on responsibility for the ‘fight against leprosy’. In an effort to fundraise for a distant cause at a time when hundreds of charities competed for the financial support of British citizens, fundraisers developed propaganda to set leprosy apart from all other humanitarian causes. They drew on leprosy’s relationship with Christianity, its debilitating symptoms, and the supposed vulnerability of leprosy sufferers in order to mobilise Britain’s sense of humanitarian, Christian, and patriotic duty. This article traces the emergence of leprosy as a popular imperial humanitarian cause in modern Britain and analyses the narratives of religion, suffering, and disease that they created and employed in order to fuel their growth and sell leprosy as a British humanitarian cause. PMID:24932060
Cruz-Jaramillo, José Luis; Ruiz-Medrano, Roberto; Rojas-Morales, Lourdes; López-Buenfil, José Abel; Morales-Galván, Oscar; Chavarín-Palacio, Claudio; Ramírez-Pool, José Abrahán; Xoconostle-Cázares, Beatriz
The causal agents of Citrus leprosis are viruses; however, extant diagnostic methods to identify them have failed to detect known viruses in orange, mandarin, lime and bitter orange trees with severe leprosis symptoms in Mexico, an important citrus producer. Using high throughput sequencing, a virus associated with citrus leprosis was identified, belonging to the proposed Dichorhavirus genus. The virus was termed Citrus Necrotic Spot Virus (CNSV) and contains two negative-strand RNA components; virions accumulate in the cytoplasm and are associated with plasmodesmata-channels interconnecting neighboring cells-suggesting a mode of spread within the plant. The present study provides insights into the nature of this pathogen and the corresponding plant response, which is likely similar to other pathogens that do not spread systemically in plants.
Cruz-Jaramillo, José Luis; Ruiz-Medrano, Roberto; Rojas-Morales, Lourdes; López-Buenfil, José Abel; Morales-Galván, Oscar; Chavarín-Palacio, Claudio; Ramírez-Pool, José Abrahán; Xoconostle-Cázares, Beatriz
The causal agents of Citrus leprosis are viruses; however, extant diagnostic methods to identify them have failed to detect known viruses in orange, mandarin, lime and bitter orange trees with severe leprosis symptoms in Mexico, an important citrus producer. Using high throughput sequencing, a virus associated with citrus leprosis was identified, belonging to the proposed Dichorhavirus genus. The virus was termed Citrus Necrotic Spot Virus (CNSV) and contains two negative-strand RNA components; virions accumulate in the cytoplasm and are associated with plasmodesmata—channels interconnecting neighboring cells—suggesting a mode of spread within the plant. The present study provides insights into the nature of this pathogen and the corresponding plant response, which is likely similar to other pathogens that do not spread systemically in plants. PMID:25004279
Sato, Hajime; Frantz, Janet E
Background In both the US and Japan, the patient isolation policy for leprosy /Hansen's disease (HD) was preserved along with the isolation facilities, long after it had been proven to be scientifically unnecessary. This delayed policy termination caused a deprivation of civil liberties of the involuntarily confined patients, the fostering of social stigmas attached to the disease, and an inefficient use of health resources. This article seeks to elucidate the political process which hindered timely policy changes congruent with scientific advances. Methods Examination of historical materials, supplemented by personal interviews. The role that science played in the process of policy making was scrutinized with particular reference to the Garbage Can model. Results From the vantage of history, science remained instrumental in all period in the sense that it was not the primary objective for which policy change was discussed or intended, nor was it the principal driving force for policy change. When the argument arose, scientific arguments were employed to justify the patient isolation policy. However, in the early post-WWII period, issues were foregrounded and agendas were set as the inadvertent result of administrative reforms. Subsequently, scientific developments were more or less ignored due to concern about adverse policy outcomes. Finally, in the 1980s and 1990s, scientific arguments were used instrumentally to argue against isolation and for the termination of residential care. Conclusion Contrary to public expectations, health policy is not always rational and scientifically justified. In the process of policy making, the role of science can be limited and instrumental. Policy change may require the opening of policy windows, as a result of convergence of the problem, policy, and political streams, by effective exercise of leadership. Scientists and policymakers should be attentive enough to the political context of policies. PMID:15771781
Silva, Luciana Mota; Hirai, Kelly Emi; de Sousa, Jorge Rodrigues; de Souza, Juarez; Fuzii, Hellen Thais; Dias, Leonidas Braga; Carneiro, Francisca Regina Oliveira; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões
Leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. The main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. Skin samples were obtained from 16 patients with the tuberculoid (TT) form and 14 with the lepromatous (LL) form. The histologic sections were immunostained with anti-c-Fos and anti-c-Jun monoclonal antibodies for investigation of AP-1, anti-NFκB p65 for the study of NFκB, and anti-JAK2, STAT1, STAT3, and STAT4 for investigation of the JAK/STAT pathway. Cells expressing STAT1 were more frequent in the TT form than in LL lesions (P = .0096), in agreement with the protective immunity provided by IFN-γ. STAT4 was also more highly expressed in the TT form than in the LL form (P = .0098). This transcription factor is essential for the development of a Th1 response because it is associated with interleukin-12. NFκB (p65) and STAT4 expression in the TT form showed a strong and significant correlation (r = 0.7556 and P = .0007). A moderate and significant correlation was observed between JAK2 and STAT4 in the TT form (r = 0.6637 and P = .0051), with these factors responding to interleukin-12 in Th1 profiles. The results suggest that STAT1, JAK2, and NFκB, together with STAT4, contribute to the development of cell-mediated immunity, which is able to contain the proliferation of Mycobacterium leprae.
Monteiro, Lorena Dias; Martins-Melo, Francisco Rogerlândio; Brito, Aline Lima; Alencar, Carlos Henrique; Heukelbach, Jorg
ABSTRACT OBJECTIVE To describe the spatial patterns of leprosy in the Brazilian state of Tocantins. METHODS This study was based on morbidity data obtained from the Sistema de Informações de Agravos de Notificação (SINAN – Brazilian Notifiable Diseases Information System), of the Ministry of Health. All new leprosy cases in individuals residing in the state of Tocantins, between 2001 and 2012, were included. In addition to the description of general disease indicators, a descriptive spatial analysis, empirical Bayesian analysis and spatial dependence analysis were performed by means of global and local Moran’s indexes. RESULTS A total of 14,542 new cases were recorded during the period under study. Based on the annual case detection rate, 77.0% of the municipalities were classified as hyperendemic (> 40 cases/100,000 inhabitants). Regarding the annual case detection rate in < 15 years-olds, 65.4% of the municipalities were hyperendemic (10.0 to 19.9 cases/100,000 inhabitants); 26.6% had a detection rate of grade 2 disability cases between 5.0 and 9.9 cases/100,000 inhabitants. There was a geographical overlap of clusters of municipalities with high detection rates in hyperendemic areas. Clusters with high disease risk (global Moran’s index: 0.51; p < 0.001), ongoing transmission (0.47; p < 0.001) and late diagnosis (0.44; p < 0.001) were identified mainly in the central-north and southwestern regions of Tocantins. CONCLUSIONS We identified high-risk clusters for transmission and late diagnosis of leprosy in the Brazilian state of Tocantins. Surveillance and control measures should be prioritized in these high-risk municipalities. PMID:26603352
Job, C K; Harris, E B; Allen, J L; Hastings, R C
Both ears from 494 wild nine-banded armadillos (Dasypus novemcinctus) and nose specimens from 224 animals were collected and histopathologically studied. Lepromatous granulomas were present in the ear specimens of ten of 494 animals. There were thorns in the ears of 22.5% of animals, and in 36.6% of the nose specimens. In one armadillo, there was evidence to suggest that Mycobacterium leprae entered the tissue through the thorn pricks. In the normal habitat of the armadillo in Louisiana there are thorny bushes consisting mostly of the green briar and the southern dewberry. Thorn pricks as a means of transmission of leprosy in the wild armadillos is suggested.
Shah, Javeed A; Berrington, William R; Vary, James C; Wells, Richard D; Peterson, Glenna J; Kunwar, Chhatra B; Khadge, Saraswoti; Hagge, Deanna A; Hawn, Thomas R
Leprosy is a chronic disease characterized by skin and peripheral nerve pathology and immune responses that fail to control Mycobacterium leprae. Toll-interacting protein (TOLLIP) regulates Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) signaling against mycobacteria. We analyzed messenger RNA (mRNA) expression of candidate immune genes in skin biopsy specimens from 85 individuals with leprosy. TOLLIP mRNA was highly and specifically correlated with IL-1R antagonist (IL-1Ra). In a case-control gene-association study with 477 cases and 1021 controls in Nepal, TOLLIP single-nucleotide polymorphism rs3793964 TT genotype was associated with increased susceptibility to leprosy (recessive, P = 1.4 × 10(-3)) and with increased skin expression of TOLLIP and IL-1Ra. Stimulation of TOLLIP-deficient monocytes with M. leprae produced significantly less IL-1Ra (P < .001), compared with control. These data suggest that M. leprae upregulates IL-1Ra by a TOLLIP-dependent mechanism. Inhibition of TOLLIP may decrease an individual's susceptibility to leprosy and offer a novel therapeutic target for IL-1-dependent diseases.
The equivalent of US$ 75 million is spent each year in Brazil to control Brevipalpus phoenicis, a mite vector of Citrus leprosis virus C (CiLV-C). In this study we investigated the possibility that hedgerows, windbreaks, and weeds normally found in citrus orchards could host CiLV-C. Mites reared on ...
Duthie, Malcolm S; Coler, Rhea N; Laurance, John D; Sampaio, Lucas H; Oliveira, Regiane M; Sousa, Ana Lucia M; Stefani, Mariane M A; Maeda, Yumi; Matsuoka, Masanori; Makino, Masahiko; Reed, Steven G
Despite the dramatic reduction in the number of leprosy cases worldwide in the 1990s, transmission of the causative agent, Mycobacterium leprae, is still occurring, and new cases continue to appear. New strategies are required in the pursuit of leprosy elimination. The cross-application of vaccines in development for tuberculosis may lead to tools applicable to elimination of leprosy. In this report, we demonstrate that the chimeric fusion proteins ID83 and ID93, developed as antigens for tuberculosis (TB) vaccine candidates, elicited gamma interferon (IFN-γ) responses from both TB and paucibacillary (PB) leprosy patients and from healthy household contacts of multibacillary (MB) patients (HHC) but not from nonexposed healthy controls. Immunization of mice with either protein formulated with a Toll-like receptor 4 ligand (TLR4L)-containing adjuvant (glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) stimulated antigen-specific IFN-γ secretion from pluripotent Th1 cells. When immunized mice were experimentally infected with M. leprae, both cellular infiltration into the local lymph node and bacterial growth at the site were reduced relative to those of unimmunized mice. Thus, the use of the Mycobacterium tuberculosis candidate vaccines ID83/GLA-SE and ID93/GLA-SE may confer cross-protection against M. leprae infection. Our data suggest these vaccines could potentially be used as an additional control measure for leprosy.
Sharma, Rahul; Lahiri, Ramanuj; Scollard, David M; Pena, Maria; Williams, Diana L; Adams, Linda B; Figarola, John; Truman, Richard W
Leprosy (also known as Hansen's disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M. leprae, and they develop a systemically disseminated disease with extensive neurological involvement. M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. Because of the heavy burdens of bacilli they harbor, nine-banded armadillos have become the organism of choice for propagating large quantities of M. leprae, and they are now advancing as models of leprosy pathogenesis and nerve damage. Although armadillos are exotic laboratory animals, the recently completed whole genome sequence for this animal is enabling researchers to undertake more sophisticated molecular studies and to develop armadillo-specific reagents. These advances will facilitate the use of armadillos in piloting new therapies and diagnostic regimens, and will provide new insights into the oldest known infectious neurodegenerative disorder.
Sharma, Rahul; Lahiri, Ramanuj; Scollard, David M.; Pena, Maria; Williams, Diana L.; Adams, Linda B.; Figarola, John; Truman, Richard W.
Leprosy (also known as Hansen’s disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M. leprae, and they develop a systemically disseminated disease with extensive neurological involvement. M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. Because of the heavy burdens of bacilli they harbor, nine-banded armadillos have become the organism of choice for propagating large quantities of M. leprae, and they are now advancing as models of leprosy pathogenesis and nerve damage. Although armadillos are exotic laboratory animals, the recently completed whole genome sequence for this animal is enabling researchers to undertake more sophisticated molecular studies and to develop armadillo-specific reagents. These advances will facilitate the use of armadillos in piloting new therapies and diagnostic regimens, and will provide new insights into the oldest known infectious neurodegenerative disorder. PMID:23223615
Inskip, Sarah A.; Taylor, G. Michael; Zakrzewski, Sonia R.; Mays, Simon A.; Pike, Alistair W. G.; Llewellyn, Gareth; Williams, Christopher M.; Lee, Oona Y-C; Wu, Houdini H. T.; Minnikin, David E.; Besra, Gurdyal S.; Stewart, Graham R.
We have examined a 5th to 6th century inhumation from Great Chesterford, Essex, UK. The incomplete remains are those of a young male, aged around 21–35 years at death. The remains show osteological evidence of lepromatous leprosy (LL) and this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis, which provided evidence for both multi-copy and single copy loci from the Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains found in later medieval cases in southern Britain and also continental Europe. While a number of contemporaneous cases exist, at present, this case of leprosy is the earliest radiocarbon dated case in Britain confirmed by both aDNA and lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that the individual is likely to have originated from outside Britain. This potentially sheds light on the origins of the strain in Britain and its subsequent spread to other parts of the world, including the Americas where the 3I lineage of M. leprae is still found in some southern states of America. PMID:25970602
Choudhary, Nandlal; Roy, Avijit; Guillermo, Leon M; Picton, D D; Wei, G; Nakhla, M K; Levy, L; Brlansky, R H
Citrus leprosis virus C (CiLV-C), a causal agent for citrus leprosis disease, is present in South and Central America and is a threat for introduction into the U.S. citrus industry. A specific, inexpensive and reliable antibody based detection system is needed for the rapid identification of CiLV-C. The CiLV-C is very labile and has not been purified in sufficient amount for antibody production. The p29 gene of CiLV-C genome that codes for the putative coat protein (PCP) was codon optimized for expression in Escherichia coli and synthesized in vitro. The optimized gene was sub-cloned into the bacterial expression vector pDEST17 and transferred into E. coli BL21AI competent cells. The expression of PCP containing N-terminal His-tag was optimized by induction with l-arabinose. Induced cells were disrupted by sonication and expressed PCP was purified by affinity chromatography using Ni-NTA agarose. The purified expressed PCP was then used as an immunogen for injections into rabbits to produce polyclonal antibody (PAb). The PAb specific to the expressed PCP was identified using Western blotting. The antibody was successfully used to detect CiLV-C in the symptomatic CiLV-C infected tissues using double antibody sandwich-enzyme-linked-immunosorbent (DAS-ELISA), indirect ELISA and dot-blot immunoassay (DBIA) formats.
Phillips, David Alexander; Ferreira, José Antonio; Ansah, Deidra; Teixeira, Herica SA; Kitron, Uriel; de Filippis, Thelma; de Alcântara, Marcelo H; Fairley, Jessica K
BACKGROUND Despite public health efforts to reduce the global burden of leprosy, gaps remain in the knowledge surrounding transmission of infection. Helminth co-infections have been associated with a shift towards the lepromatous end of the disease spectrum, potentially increasing transmission in co-endemic areas. OBJECTIVES Using this biologically plausible association, we conducted a geographic information systems (GIS) study to investigate the spatial associations of schistosomiasis and leprosy in an endemic area of Minas Gerais (MG), Brazil. METHODS Data on new cases of Mycobacterium leprae and Schistosoma mansoni infections from 2007-2014 were retrieved from the Brazilian national notifiable diseases information system for seven municipalities in and surrounding Vespasiano, MG. A total of 139 cases of leprosy and 200 cases of schistosomiasis were mapped to a municipality level. For one municipality, cases were mapped to a neighborhood level and a stratified analysis was conducted to identify spatial associations. FINDINGS A relative risk of 6.80 [95% confidence interval (CI) 1.46 - 31.64] of leprosy was found in neighborhoods with schistosomiasis. Incidence rates of leprosy increased with corresponding incidence rates of schistosomiasis, and the temporal trends of both infections were similar. CONCLUSIONS The associations found in this project support the hypothesis that helminth infections may influence the transmission of leprosy in co-endemic areas. PMID:28327791
Phetsuksiri, Benjawan; Srisungngam, Sopa; Rudeeaneksin, Janisara; Bunchoo, Supranee; Lukebua, Atchariya; Wongtrungkapun, Ruch; Paitoon, Soontara; Sakamuri, Rama Murthy; Brennan, Patrick J; Vissa, Varalakshmi
Based on the discovery of three single nucleotide polymorphisms (SNPs) in Mycobacterium leprae, it has been previously reported that there are four major SNP types associated with different geographic regions around the world. Another typing system for global differentiation of M. leprae is the analysis of the variable number of short tandem repeats within the rpoT gene. To expand the analysis of geographic distribution of M. leprae, classified by SNP and rpoT gene polymorphisms, we studied 85 clinical isolates from Thai patients and compared the findings with those reported from Asian isolates. SNP genotyping by PCR amplification and sequencing revealed that all strains like those in Myanmar were SNP type 1 and 3, with the former being predominant, while in Japan, Korea, and Indonesia, the SNP type 3 was found to be more frequent. The pattern of M. leprae distribution in Thailand and Myanmar is quite similar, except that SNP type 2 was not found in Thailand. In addition, the 3-copy hexamer genotype in the rpoT gene is shared among the isolates from these two neighboring countries. On the basis of these two markers, we postulate that M. leprae in leprosy patients from Myanmar and Thailand has a common historical origin. Further differentiation among Thai isolates was possible by assessing copy numbers of the TTC sequence, a more polymorphic microsatellite locus.
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a microorganism that usually affects skin and nerves. Although it is usually well-controlled by multidrug therapy (MDT), the disease may be aggravated by acute inflammatory reaction episodes that cause permanent tissue damage particularly to peripheral nerves. Tuberculosis is predominantly a disease of the lungs; however, it may spread to other organs and cause an extrapulmonary infection. Both mycobacterial infections are endemic in developing countries including Brazil, and cases of coinfection have been reported in the last decade. Nevertheless, simultaneous occurrence of perianal cutaneous tuberculosis and erythema nodosum leprosum is very rare, even in countries where both mycobacterial infections are endemic. PMID:25180030
Melzer, Michael J; Sether, Diane M; Borth, Wayne B; Hu, John S
A Citrus volkameriana tree displaying symptoms similar to citrus leprosis on its leaves and bark was found in Hawaii. Citrus leprosis virus C (CiLV-C)-specific detection assays, however, were negative for all tissues tested. Short, bacilliform virus-like particles were observed by transmission electron microscopy in the cytoplasm of symptomatic leaves but not in healthy controls. Double-stranded (ds) RNAs ≈8 and 3 kbp in size were present in symptomatic leaf tissue but not in healthy controls. Excluding poly(A) tails, the largest molecule, RNA1, was 8,354 bp in length. The ≈3 kbp dsRNA band was found to be composed of two distinct molecules, RNA2 and RNA3, which were 3,169 and 3,113 bp, respectively. Phylogenetic analyses indicated that the RNA-dependent RNA polymerase (RdRp) domain located in RNA1 was most closely related to the RdRp domain of CiLV-C. A reverse-transcription polymerase chain reaction assay developed for the detection of this virus was used to screen nearby citrus trees as well as Hibiscus arnottianus plants with symptoms of hibiscus green spot, a disease associated with infection by Hibiscus green spot virus (HGSV). All nearby citrus trees tested negative with the assay; however, symptomatic H. arnottianus plants were positive. All three RNAs were present in symptomatic H. arnottianus and were >98% identical to the RNAs isolated from C. volkameriana. We contend that the virus described in this study is HGSV, and propose that it be the type member of a new virus genus, Higrevirus.
Han, Xiang Y; Sizer, Kurt C; Thompson, Erika J; Kabanja, Juma; Li, Jun; Hu, Peter; Gómez-Valero, Laura; Silva, Francisco J
Mycobacterium lepromatosis is a newly discovered leprosy-causing organism. Preliminary phylogenetic analysis of its 16S rRNA gene and a few other gene segments revealed significant divergence from Mycobacterium leprae, a well-known cause of leprosy, that justifies the status of M. lepromatosis as a new species. In this study we analyzed the sequences of 20 genes and pseudogenes (22,814 nucleotides). Overall, the level of matching of these sequences with M. leprae sequences was 90.9%, which substantiated the species-level difference; the levels of matching for the 16S rRNA genes and 14 protein-encoding genes were 98.0% and 93.1%, respectively, but the level of matching for five pseudogenes was only 79.1%. Five conserved protein-encoding genes were selected to construct phylogenetic trees and to calculate the numbers of synonymous substitutions (dS values) and nonsynonymous substitutions (dN values) in the two species. Robust phylogenetic trees constructed using concatenated alignment of these genes placed M. lepromatosis and M. leprae in a tight cluster with long terminal branches, implying that the divergence occurred long ago. The dS and dN values were also much higher than those for other closest pairs of mycobacteria. The dS values were 14 to 28% of the dS values for M. leprae and Mycobacterium tuberculosis, a more divergent pair of species. These results thus indicate that M. lepromatosis and M. leprae diverged approximately 10 million years ago. The M. lepromatosis pseudogenes analyzed that were also pseudogenes in M. leprae showed nearly neutral evolution, and their relative ages were similar to those of M. leprae pseudogenes, suggesting that they were pseudogenes before divergence. Taken together, the results described above indicate that M. lepromatosis and M. leprae diverged from a common ancestor after the massive gene inactivation event described previously for M. leprae.
Entezarmahdi, Rasool; Majdzadeh, Reza; Foroushani, Abbas Rahimi; Nasehi, Mahshid; Lameei, Abolfath; Naieni, Kourosh Holakouie
Background: Despite significant reduction in global disease prevalence, leprosy still has a high rate of disability while its determinants are unfair and many of them are amendable. The objective of this study was to measure inequality of disability in leprosy in Iran. Methods: This was a cross-sectional study (2006-2007) on all living people affected by leprosy registered in W. Azerbaijan province health center, Western North of Iran. The outcome of the study was the socio-economic inequality considering presence or absence of grade 2 disability (G2D) based on the WHO classifications. An extended concentration index decomposition approach was used for analysis. Results: Among 452 cases, 65.3% were male and 67% were affected by the multi bacillary type. Overall G2D was 65.3%. The estimated Concentration Index was −0.0782, showing presence of pro-poor socio-economic inequality of G2D, while extended CI estimation (ѵ = 5) was −0.163. Achievement index with coefficient (ѵ = 5) revealed that G2D mean was 16% more than classic mean in the poorest group. The result of decomposition of the existing inequality revealed that, some of the determinants such as receiving mono-therapy, education, urbanization, and bacillus calmette guerin (BCG) vaccination had shared contribution (67.4%, 61.8%, 59.2%, and 57.5% respectively). Conclusions: This study provided new perspective for the health system to leprosy control considering the significant gap between rich and poor (inequality) regarding G2D disability, and its effective elements in socio-economic strata. Some effective actions can be considered to reduce the scale of existing inequality. PMID:24829728
Bechelli, L. M.; Garbajosa, P. Gallego; Gyi, Mg Mg; Uemura, K.; Sundaresan, T.; Domínguez, V. Martínez; Matejka, M.; Tamondong, C.; Quagliato, R.; Engler, V.; Altmann, M.
A controlled study of the efficacy of BCG vaccination for the prevention of leprosy began in Burma at the end of August 1964. This paper presents the findings after 7 years—i.e., the results of 6 annual follow-up examinations up to the end of June 1971. The incidence rate in BCG-vaccinated children 0-4 years of age at intake was lower than that in children in the control group. The protection conferred by BCG was relatively low (44%) and applied only to early cases of leprosy, the great majority tuberculoid cases. BCG vaccination did not protect household contacts or children 5-14 years of age who were not exposed in the household. This reduction must be interpreted in the light of several factors: form of leprosy, bacterial status, lepromin reactivity, evolution of cases, and level of endemicity. Consequently it does not seem probable that the reduction in incidence would substantially affect the pattern or trend of the disease in an area similar to that where the study is being carried out; the probability would be much lower if not nil in regions of relatively low endemicity (1-2 per 1 000 or less). PMID:4270384
Porter, J D H; Ogden, J A; Rao, P V Ranganadha; Rao, V Prabhakar; Rajesh, D; Buskade, R A; Soutar, D
This paper reports on a partnership between LEPRA, a non-governmental organization (NGO), and the London School of Hygiene and Tropical Medicine (LSHTM) to explore the feasibility and appropriateness of incorporating operations research into the management and decision-making of a leprosy NGO. A pilot study in Orissa was used to determine the advantages and disadvantages of introducing operations research to assist in decision-making and programme implementation within the organization. The results highlight the difficulty and complexity of the process, but point to several important themes: partnership, changing perspectives, use of time and priority-setting, identification of gaps in systems, and building institutional and personal capabilities. The results of the study provide support to encourage NGOs to become actively involved in research. Because of their work and service to local communities, NGOs have the opportunity to collect information about the perceptions, resources and constraints of individuals, families and the communities themselves in accessing appropriate care. Their proximity to communities gives them a feeling of responsibility for ensuring that this information is translated to the district, national and ultimately international level. This will help to ensure the creation of appropriate infectious disease control policies that support the needs of patients. 'Outside' academic institutions can help NGOs to facilitate this up-stream flow of information from the local to the national and international level, to help to ensure that international disease control policies are appropriately serving local communities.
This paper presents a record of three interviews with groups of Ministry of Health personnel and consultants that took place in Jakarta, Indonesia in May 2012. Those contributing to the first interview were provincial and district supervisors with responsibility for leprosy. Those contributing to the second interview were consultants, three of whom were seconded to the Ministry of Health and one was a WHO consultant. A third interview was conducted with the Head and a technical staff member of the Sub Directorate of Leprosy and Yaws Control Programme, Ministry of Health, Indonesia. Leprosy control in Indonesia had been targeted for further enquiry after it became apparent, through an earlier survey of national programme managers and consultants, that the programme had been relatively successful in integrating POD into the government health delivery programme. The perspectives of significant representatives and actors in the national programme were recorded through the interviews undertaken in Jakarta. Limitations This report does not purport to be a study of integration of leprosy services in Indonesia. The perspectives of representatives and significant actors are offered here to enhance understanding of factors that contributed to POD becoming a routine component of general health care in Indonesia. It is also declared here that no independent verification of statements was undertaken and that the effectiveness of measures taken to integrate leprosy related POD has not been independently evaluated.
Peters, Ruth M. H.; Dadun; Van Brakel, Wim H.; Zweekhorst, Marjolein B. M.; Damayanti, Rita; Bunders, Joske F. G.; Irwanto
Background Stigma plays in an important role in the lives of persons affected by neglected tropical diseases, and assessment of stigma is important to document this. The aim of this study is to test the cross-cultural validity of the Community Stigma Scale (EMIC-CSS) and the Social Distance Scale (SDS) in the field of leprosy in Cirebon District, Indonesia. Methodology/principle findings Cultural equivalence was tested by assessing the conceptual, item, semantic, operational and measurement equivalence of these instruments. A qualitative exploratory study was conducted to increase our understanding of the concept of stigma in Cirebon District. A process of translation, discussions, trainings and a pilot study followed. A sample of 259 community members was selected through convenience sampling and 67 repeated measures were obtained to assess the psychometric measurement properties. The aspects and items in the SDS and EMIC-CSS seem equally relevant and important in the target culture. The response scales were adapted to ensure that meaning is transferred accurately and no changes to the scale format (e.g. lay out, statements or questions) of both scales were made. A positive correlation was found between the EMIC-CSS and the SDS total scores (r = 0.41). Cronbach's alphas of 0.83 and 0.87 were found for the EMIC-CSS and SDS. The exploratory factor analysis indicated for both scales an adequate fit as unidimensional scale. A standard error of measurement of 2.38 was found in the EMIC-CSS and of 1.78 in the SDS. The test-retest reliability coefficient was respectively, 0.84 and 0.75. No floor or ceiling effects were found. Conclusions/significance According to current international standards, our findings indicate that the EMIC-CSS and the SDS have adequate cultural validity to assess social stigma in leprosy in the Bahasa Indonesia-speaking population of Cirebon District. We believe the scales can be further improved, for instance, by adding, changing and
Silva, Leicy Francisca da
This article analyzes the root causes of the shortage of social support for the relatives of people with leprosy, especially their children, in the state of Goiás, Central West region of Brazil, between 1920 and 1962. It focuses on the constitution of discourses that defined the medical and philanthropic care for the children of people isolated in leper colonies as a problem, and how this process resulted in the organization of the Society for the Welfare of Lepers and Defense Against Leprosy, and the construction of Afrânio de Azevedo children's home in Goiânia, the state capital. These elements are directly associated with the construction of a new approach in the regional history and social and medical policies for leprosy.
Hussain, R; Dockrell, H M; Chiang, T J
Mycobacterium leprae-specific immunoglobulin G1 (IgG1) antibodies in patients with leprosy show a direct correlation with bacterial load (ρ=0·748; P < 0002) suggesting that IgG1 B-cell responses may be surrogate markers of disease progression. To investigate if this upregulation was a general feature of IgG1 responses to all M. leprae (ML) antigens, we analysed responses to several recombinant purified ML heat-shock proteins (HSP). Three recombinant HSPs (ML10 K, ML 18 K and ML 65 K) were tested for their ability to induce various IgG subclasses in patients with either the lepromatous (LL/BL, n = 26) or tuberculoid form (BT/TT, n = 39) of the disease as well as in healthy households (HC, n = 14) and endemic controls (EC = 19). Our major findings were: (1) selective augmentation of IgG1 antibody responses to ML10 K; (2) recognition of a restricted number of epitopes across the disease spectrum and healthy controls by IgG1 antibodies; (3) dominant recognition of cross-reactive epitopes which were common to both ML and MT 10 K. This response was not related to contamination with endotoxin. Epitope mapping using 15-mer overlapping peptides spanning the ML 10 000 MW revealed an immunodominant IgG1 binding peptide (aa41–55) in patients as well as healthy controls. This peptide is a shared epitope with M. tuberculosis 10 K suggesting that postswitched IgG1 B cells recognizing this epitope rather than naive B cells are being expanded. PMID:10233750
Taylor, G. Michael; Tucker, Katie; Butler, Rachel; Pike, Alistair W. G.; Lewis, Jamie; Roffey, Simon; Marter, Philip; Lee, Oona Y-C; Wu, Houdini H. T.; Minnikin, David E.; Besra, Gurdyal S.; Singh, Pushpendra; Cole, Stewart T.; Stewart, Graham R.
Nine burials excavated from the Magdalen Hill Archaeological Research Project (MHARP) in Winchester, UK, showing skeletal signs of lepromatous leprosy (LL) have been studied using a multidisciplinary approach including osteological, geochemical and biomolecular techniques. DNA from Mycobacterium leprae was amplified from all nine skeletons but not from control skeletons devoid of indicative pathology. In several specimens we corroborated the identification of M. leprae with detection of mycolic acids specific to the cell wall of M. leprae and persistent in the skeletal samples. In five cases, the preservation of the material allowed detailed genotyping using single-nucleotide polymorphism (SNP) and multiple locus variable number tandem repeat analysis (MLVA). Three of the five cases proved to be infected with SNP type 3I-1, ancestral to contemporary M. leprae isolates found in southern states of America and likely carried by European migrants. From the remaining two burials we identified, for the first time in the British Isles, the occurrence of SNP type 2F. Stable isotope analysis conducted on tooth enamel taken from two of the type 3I-1 and one of the type 2F remains revealed that all three individuals had probably spent their formative years in the Winchester area. Previously, type 2F has been implicated as the precursor strain that migrated from the Middle East to India and South-East Asia, subsequently evolving to type 1 strains. Thus we show that type 2F had also spread westwards to Britain by the early medieval period. PMID:23638071
Ramos-González, Pedro Luis; Chabi-Jesus, Camila; Guerra-Peraza, Orlene; Breton, Michèle Claire; Arena, Gabriella Dias; Nunes, Maria Andreia; Kitajima, Elliot Watanabe; Machado, Marcos Antonio; Freitas-Astúa, Juliana
Citrus leprosis virus C (CiLV-C) causes a severe disease affecting citrus orchards in the Western hemisphere. This study reveals the molecular variability of the virus by analyzing four genomic regions (p29, p15, MP and RNA2-intergenic region) distributed over its two RNAs. Nucleotide diversity (π) values were relatively low but statistically different over the analyzed genes and subpopulations, indicating their distinct evolutionary history. Values of πp29 and πMP were higher than those of πp15 and πRNA2–IR, whereas πMP was increased due to novel discovered isolates phylogenetically clustered in a divergent clade that we called SJP. Isolate BR_SP_SJP_01 RNA1 and RNA2 sequences, clade SJP, showed an identity of 85.6% and 88.4%, respectively, with those corresponding to CiLV-C, the type member of the genus Cilevirus, and its RNA2 5′-proximal region was revealed as a minor donor in a putative inter-clade recombination event. In addition to citrus, BR_SP_SJP_01 naturally infects the weed Commelina benghalensis and is efficiently transmitted by Brevipalpus yothersi mites. Our data demonstrated that negative selection was the major force operating in the evaluated viral coding regions and defined amino acids putatively relevant for the biological function of cilevirus proteins. This work provides molecular tools and sets up a framework for further epidemiological studies. PMID:27275832
Taylor, G Michael; Tucker, Katie; Butler, Rachel; Pike, Alistair W G; Lewis, Jamie; Roffey, Simon; Marter, Philip; Lee, Oona Y-C; Wu, Houdini H T; Minnikin, David E; Besra, Gurdyal S; Singh, Pushpendra; Cole, Stewart T; Stewart, Graham R
Nine burials excavated from the Magdalen Hill Archaeological Research Project (MHARP) in Winchester, UK, showing skeletal signs of lepromatous leprosy (LL) have been studied using a multidisciplinary approach including osteological, geochemical and biomolecular techniques. DNA from Mycobacterium leprae was amplified from all nine skeletons but not from control skeletons devoid of indicative pathology. In several specimens we corroborated the identification of M. leprae with detection of mycolic acids specific to the cell wall of M. leprae and persistent in the skeletal samples. In five cases, the preservation of the material allowed detailed genotyping using single-nucleotide polymorphism (SNP) and multiple locus variable number tandem repeat analysis (MLVA). Three of the five cases proved to be infected with SNP type 3I-1, ancestral to contemporary M. leprae isolates found in southern states of America and likely carried by European migrants. From the remaining two burials we identified, for the first time in the British Isles, the occurrence of SNP type 2F. Stable isotope analysis conducted on tooth enamel taken from two of the type 3I-1 and one of the type 2F remains revealed that all three individuals had probably spent their formative years in the Winchester area. Previously, type 2F has been implicated as the precursor strain that migrated from the Middle East to India and South-East Asia, subsequently evolving to type 1 strains. Thus we show that type 2F had also spread westwards to Britain by the early medieval period.
Lavania, M; Katoch, K; Parashar, D; Sharma, P; Das, R; Chauhan, D S; Sharma, V D; Katoch, V M
Non-tuberculous mycobacteria (NTM) are commonly found in the environment. As exposure to environmental mycobacteria has been reported to immunomodulatory in this study, the presence of environmental mycobacteria was investigated in soil, drinking water and drainage sample in Ghatampur, India, which is known for high endemicity for leprosy. Soil, drinking water from the hand pumps/wells and also drainage water collected in pools was collected in clean containers and cultured for environmental mycobacteria. Samples were processed according to the protocol established earlier. 69 soil, 62 drinking water and 31 drainage water samples were analysed from soil and water collected from 48 villages of this field area. After decontamination, cultures were set upon Lowenstein Jensen (LJ) medium. Mycobacteria were identified using biochemical tests and molecular techniques such as PCR-RFLP targeting hsp65 kD and rpoB region as well as 16S ribosomal sequencing in case of isolates showing variable biochemical features. NTM (non-tubercular mycobacteria) were isolated from 47.82% of soil samples, 20.69% of drinking water samples and 19.35% of the drainage water samples, overall mycobacteria could be isolated 52/162 of samples (32.09%). Among these mycobacteria, M. fortuitum-chelonae complex was predominant in this area; other species isolated were M. phlei, M. vaccae, M. terrae and M. flavescens. Relevance of exposure to these mycobacteria on endemicity needs to be studied by immunological and epidemiological parameters.
Rao, P S S
While the experienced or enacted stigma may be the same for all health related stigma, in terms of isolation, discrimination and social participation restrictions of the affected persons; the concept and origin of stigma varies from one disease to another. An understanding of the cause of stigma is, therefore, essential to formulate effective strategies for its reduction/elimination. This is especially imperative in the case of leprosy where the basis of stigma is significantly different from other health related stigma. In this paper, a comparison is made between the concept and origin of leprosy stigma with that of other stigmatised diseases.
Lusli, Mimi; Peters, Ruth; van Brakel, Wim; Zweekhorst, Marjolein; Iancu, Sorana; Bunders, Joske; Irwanto; Regeer, Barbara
Background This paper assesses the impact of a counselling intervention on reducing leprosy-related stigma in Cirebon District, Indonesia. The unique features of this intervention are its rights-based approach, the underlying Cognitive Behavioural Therapy (CBT) model, the three types of counselling and the lay and peer counsellors who were involved. Methodology/principal findings Mixed methods (e.g. three scales, interviews, focus group discussions and reflection notes) were used to assess the impact of the intervention, which ran over a two-year period. There was a control area with no interventions. The study participants were people affected by leprosy and other key persons (e.g. family members). The sample size differs per method, for example, data regarding 67 counselling clients and 57 controls from a cohort, and notes from 207 counselling clients were examined. The notes showed that most clients faced stigma on a daily basis, whether internalized, anticipated and/or enacted. A significant reduction was found between the before and after total scores of the SARI Stigma Scale (p-value < 0.001), Participation Scale Short (p-value < 0.001) and WHO Quality of Life score (p-value < 0.001) among the counselling clients. While there is also an effect in the control group, it is much larger in the intervention group. Qualitative data indicates that knowledge and rights trigger change. Clients took steps to improve their life such as re-connecting with neighbours, helping in household activities and applying for jobs. Challenges include the wish to conceal their condition. Conclusion/significance The findings show that the counselling intervention was effective in reducing stigma, promoting the rights of people with leprosy and facilitating their social participation. More research is needed on how to create a more sustainable intervention, preferably structurally embedded in the health or social services. PMID:27959932
Maslov, A K; Khivrina, S A
A model of leprosy was used to study the therapeutic effect of horse-radish root (HRR) containing peroxidase in combination with rifampicin (RFP) and potassium iodide (PI) as compared to routine combined therapy with RFP and diaminodiphenylsulfonum. Therapy with HRR and iodide showed the best antimicrobial effect than the routine combined therapy. A combination of RFP, HRR, and PI increased the activity of neutrophilic myeliperoxidase produced an anti-inflammatory activity and caused no persistent anemia or toxic effect on the murine liver.
Silva Miranda, Mayra; Rodríguez, Kendy Wek; Martínez Cordero, Erasmo; Rojas-Espinosa, Oscar
Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression.
Crespo, Fabian A; Klaes, Christopher K; Switala, Andrew E; DeWitte, Sharon N
It is possible that during long lasting chronic infections such as tuberculosis (TB) and leprosy individuals who generate a stronger immune response will produce a chronic shift in the systemic levels of inflammatory proteins. Consequently, the systemic immunological shift could affect inflammatory responses against other persistent pathogens such as Porphyromonas gingivalis associated with periodontal disease (PD).
Silva Miranda, Mayra; Rodríguez, Kendy Wek; Martínez Cordero, Erasmo; Rojas-Espinosa, Oscar
Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression. PMID:17222216
Sergio, Navarro-Fierros; Cecilia, Guillen-Vargas; Sonia, Luquin; la Mora Pedro, Garzon-De; Joaquin, Garcia-Estrada; Mary, Fafutis-Morris
While formaldehyde fixation preserves tissue morphology, it often hinders immunodetection of antigens in paraffin-embedded tissue because the antigens are masked. Antigen unmasking can be achieved with treatments such as microwave irradiation but they often lead to excessive tissue damage. Therefore, an electrochemical antigen-retrieval method (EAR) was devised in which an alternating electric current is passed through the tissue in a chamber containing an electrolyte buffer. The results obtained with this method were compared to those after microwave irradiation using archived samples of formaldehyde-fixed and paraffin-embedded lepromatous leprosy skin. The efficacy of the two unmasking procedures was assessed by the immunodetectability of several marker antigens using 24 antibodies. Fifteen antibodies that were directed against transmembrane proteins (CD), and the remaining 9 against cytokeratins 18.6 and 19, laminin, vimentin, S100a, BCG, Ulex europaeus lectin, PCNA, and P21ras. Simple and double immunohistochemistry was performed using the universal ENVISION and LSAB + AP detection systems. After unmasking with the EAR method, immunoreactivity was clearly detected with 22 of the 24 antibodies in single labeling reactions. They include the critical antigens CD3 and CD4 for identifying the T lymphocyte lineages. In contrast, only 20 of the antibodies reacted after microwave irradiation. After double immunolabeling, immunoreactivity was quantitatively similar with both methods. However, the EAR unmasking produced a stronger labeling reaction. Thus, with double labeling immunohistochemistry, EAR made it possible to use higher antibody dilutions and shorter incubation times. Heat damage was also prevented. In conclusion, EAR treatment produces better staining results than microwave irradiation treatment.
Rojas-Espinosa, Oscar; Wek-Rodríguez, Kendy; Arce-Paredes, Patricia
Mycobacterium lepraemurium (MLM) is a successful parasite of murine macrophages; in vitro, this microorganism infects macrophages without triggering these cells' ability to produce either the reactive oxygen intermediaries (ROI) or the reactive nitrogen intermediaries (RNI), and ends up lodging within these cells, that, in addition, do not contain myeloperoxidase (MPO). In this study, we analyzed the effect of exogenous peroxidase on the evolution of murine leprosy. Bacilli were intraperitoneally injected, either alone (MLM) or precoated with horseradish peroxidase (MLM-PO), into two different groups of mice. At two-week intervals, the groups were blood-sampled to measure the levels of antibodies to protein- or lipid-MLM antigens. The extent of the disease was also assessed by looking at the histopathologic changes that occurred both in the liver and the spleen of the infected animals. We found that the animals injected with MLM-PO developed a disease that evolved at a slower pace than the disease that occurred in the animals injected with intact MLM. The difference between groups, both in terms of antibody levels and histological changes, was clearly evident at the intermediate stages of the disease (2 to 2.5 months), but was not so obvious at the more advanced stage of 3 months. Several possibilities to explain how the PO-coated bacilli might have regained their infectiousness are discussed. Lowering the infective dose of MLM and MLM-PO from 5 x 10(7) bacilli to 5 x 10(6) bacilli would, probably, have resulted in a different outcome of the disease: more extended in the MLM-group than in the MLM-PO group.
Penchaszadeh, Victor B.; Schuler-Faccini, Lavinia
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976–1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program “Reencontro”, which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind. PMID:24764764
Penchaszadeh, Victor B; Schuler-Faccini, Lavinia
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.
Roy, Avijit; Stone, Andrew L; Shao, Jonathan; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Levy, Laurene; Nakhla, Mark K; Hartung, John S; Schneider, William L; Brlansky, Ronald H
Citrus leprosis is one of the most destructive diseases of Citrus spp. and is associated with two unrelated virus groups that produce particles primarily in either the cytoplasm or nucleus of infected plant cells. Symptoms of leprosis, including chlorotic spots surrounded by yellow haloes on leaves and necrotic spots on twigs and fruit, were observed on leprosis-affected mandarin and navel sweet orange trees in the state of Querétaro, Mexico. Serological and molecular assays showed that the cytoplasmic types of Citrus leprosis virus (CiLV-C) often associated with leprosis symptomatic tissues were absent. However, using transmission electron microscopy, bullet-shaped rhabdovirus-like virions were observed in the nuclei and cytoplasm of the citrus leprosis-infected leaf tissues. An analysis of small RNA populations from symptomatic tissue was carried out to determine the genome sequence of the rhabdovirus-like particles observed in the citrus leprosis samples. The complete genome sequence showed that the nuclear type of CiLV (CiLV-N) present in the samples consisted of two negative-sense RNAs: 6,268-nucleotide (nt)-long RNA1 and 5,847-nt-long RNA2, excluding the poly(A) tails. CiLV-N had a genome organization identical to that of Orchid fleck virus (OFV), with the exception of shorter 5' untranslated regions in RNA1 (53 versus 205 nt) and RNA2 (34 versus 182 nt). Phylogenetic trees constructed with the amino acid sequences of the nucleocapsid (N) and glycoproteins (G) and the RNA polymerase (L protein) showed that CiLV-N clusters with OFV. Furthermore, phylogenetic analyses of N protein established CiLV-N as a member of the proposed genus Dichorhavirus. Reverse-transcription polymerase chain reaction primers for the detection of CiLV-N were designed based on the sequence of the N gene and the assay was optimized and tested to detect the presence of CiLV-N in both diseased and symptom-free plants.
Naqvi, Ahmad Abu Turab; Ahmad, Faizan; Hassan, Md Imtaiyaz
Mycobacterium leprae is an intracellular obligate parasite that causes leprosy in humans, and it leads to the destruction of peripheral nerves and skin deformation. Here, we report an extensive analysis of the hypothetical proteins (HPs) from M. leprae strain Br4923, assigning their functions to better understand the mechanism of pathogenesis and to search for potential therapeutic interventions. The genome of M. leprae encodes 1604 proteins, of which the functions of 632 are not known (HPs). In this paper, we predicted the probable functions of 312 HPs. First, we classified all HPs into families and subfamilies on the basis of sequence similarity, followed by domain assignment, which provides many clues for their possible function. However, the functions of 320 proteins were not predicted because of low sequence similarity with proteins of known function. Annotated HPs were categorized into enzymes, binding proteins, transporters, and proteins involved in cellular processes. We found several novel proteins whose functions were unknown for M. leprae. These proteins have a requisite association with bacterial virulence and pathogenicity. Finally, our sequence-based analysis will be helpful for further validation and the search for potential drug targets while developing effective drugs to cure leprosy.
van Brakel, Wim H.; Nicholls, Peter G.; Wilder-Smith, Einar P.; Das, Loretta; Barkataki, Pramila; Lockwood, Diana N. J.
Background Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest. Methods and Findings One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%–50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more. Conclusions A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as
Choudhary, Nandlal; Wei, G; Govindarajulu, A; Roy, Avijit; Li, Wenbin; Picton, Deric D; Nakhla, M K; Levy, L; Brlansky, R H
Citrus leprosis virus C (CiLV-C), a causal agent of the leprosis disease in citrus, is mostly present in the South and Central America and spreading toward the North America. To enable better diagnosis and inhibit the further spread of this re-emerging virus a quantitative (q) real-time reverse transcription polymerase chain reaction (qRT-PCR) assay is needed for early detection of CiLV-C when the virus is present in low titer in citrus leprosis samples. Using the genomic sequence of CiLV-C, specific primers and probe were designed and synthesized to amplify a 73 nt amplicon from the movement protein (MP) gene. A standard curve of the 73 nt amplicon MP gene was developed using known 10(10)-10(1) copies of in vitro synthesized RNA transcript to estimate the copy number of RNA transcript in the citrus leprosis samples. The one-step qRT-PCR detection assays for CiLV-C were determined to be 1000 times more sensitive when compared to the one-step conventional reverse transcription polymerase chain reaction (RT-PCR) CiLV-C detection method. To evaluate the quality of the total RNA extracts, NADH dehydrogenase gene specific primers (nad5) and probe were included in reactions as an internal control. The one-step qRT-PCR specificity was successfully validated by testing for the presence of CiLV-C in the total RNA extracts of the citrus leprosis samples collected from Belize, Costa Rica, Mexico and Panama. Implementation of the one-step qRT-PCR assays for CiLV-C diagnosis should assist regulatory agencies in surveillance activities to monitor the distribution pattern of CiLV-C in countries where it is present and to prevent further dissemination into citrus growing countries where there is no report of CiLV-C presence.
de Matos, Haroldo José; Blok, David J.; de Vlas, Sake J.; Richardus, Jan Hendrik
Background Leprosy remains a public health problem in Brazil. Although the overall number of new cases is declining, there are still areas with a high disease burden, such as Pará State in the north of the country. We aim to predict future trends in new case detection rate (NCDR) and explore the potential impact of contact tracing and chemoprophylaxis on NCDR in Pará State. Methods We used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae, in a population structured by households. The model was quantified to simulate the population and observed NCDR of leprosy in Pará State for the period 1990 to 2014. The baseline scenario was the current control program, consisting of multidrug therapy, passive case detection, and active case detection from 2003 onwards. Future projections of the NCDR were made until 2050 given the continuation of the current control program (i.e. baseline). We further investigated the potential impact of two scenarios for future control of leprosy: 1) discontinuation of contact tracing; and 2) continuation of current control in combination with chemoprophylaxis. Both scenarios started in 2015 and were projected until 2050. Results The modelled NCDR in Pará State after 2014 shows a continuous downward trend, reaching the official elimination target of 10 cases per 100,000 population by 2030. The cessation of systematic contact tracing would not result in a higher NCDR in the long run. Systematic contact tracing in combination with chemoprophylaxis for contacts would reduce the NCDR by 40% and bring attainment of the elimination target two years forward to 2028. Conclusion The NCDR of leprosy continues to decrease in Pará State. Elimination of leprosy as a public health problem could possibly be achieved around 2030, if the current control program is maintained. Providing chemoprophylaxis would decrease the NCDR further and would bring elimination forward by two years. PMID:26938738
Peters, Ruth M. H.; Dadun; Zweekhorst, Marjolein B. M.; Bunders, Joske F. G.; Irwanto; van Brakel, Wim H.
Background Can deliberate interaction between the public and persons affected by leprosy reduce stigmatization? The study described in this paper hypothesises that it can and assesses the effectiveness of a ‘contact intervention’. Methods/Principal Findings This cluster-randomized controlled intervention study is part of the Stigma Assessment and Reduction of Impact (SARI) project conducted in Cirebon District, Indonesia. Testimonies, participatory videos and comics given or made by people affected by leprosy were used as methods to facilitate a dialogue during so-called ‘contact events’. A mix of seven quantitative and qualitative methods, including two scales to assess aspects of stigma named the SDS and EMIC-CSS, were used to establish a baseline regarding stigma and knowledge of leprosy, monitor the implementation and assess the impact of the contact events. The study sample were community members selected using different sampling methods. The baseline shows a lack of knowledge about leprosy, a high level of stigma and contrasting examples of support. In total, 91 contact events were organised in 62 villages, directly reaching 4,443 community members (mean 49 per event). The interview data showed that knowledge about leprosy increased and that negative attitudes reduced. The adjusted mean total score of the EMIC-CSS reduced by 4.95 points among respondents who had attended a contact event (n = 58; p <0.001, effect size = 0.75) compared to the score at baseline (n = 213); for the SDS this was 3.56 (p <0.001, effect size = 0.81). About 75% of those attending a contact event said they shared the information with others (median 10 persons). Conclusions/Significance The contact intervention was effective in increasing knowledge and improving public attitudes regarding leprosy. It is relatively easy to replicate elsewhere and does not require expensive technology. More research is needed to improve scalability. The effectiveness of a contact intervention to
Gill, H. K.; Mustafa, A. S.; Godal, T.
A killed armadillo-derived Mycobacterium leprae vaccine was examined for its ability to induce a delayed-type hypersensitivity (DTH) response in purified protein derivative (PPD)-positive human volunteers living in a leprosy non-endemic country. Four groups of individuals aged between 23 and 28 years were given 1.5 × 107, 5 × 107, 1.5 × 108 and 5 × 108 M. leprae intradermally. A marked increase in reactivity to the M. leprae-derived skin test antigen (MLSA) was observed in the vaccinated groups receiving the three highest doses of vaccine while there was very little change observed in their PPD reactivity. No unacceptable side-effects attributable to the vaccine were observed. The killed armadillo-derived M. leprae vaccine thus appears to be able to induce a DTH response in man at doses which do not cause unacceptable side-effects. PMID:3524883
van Schie, Carine H M; Slim, Frederik J; Keukenkamp, Renske; Faber, William R; Nollet, Frans
Not only plantar pressure but also weight-bearing activity affects accumulated mechanical stress to the foot and may be related to foot ulceration. To date, activity has not been accounted for in leprosy. The purpose was to compare barefoot pressure, in-shoe pressure and daily cumulative stress between persons affected by leprosy with and without previous or current foot ulceration. Nine persons with current plantar ulceration were compared to 15 with previous and 15 without previous ulceration. Barefoot peak pressure (EMED-X), in-shoe peak pressure (Pedar-X) and daily cumulative stress (in-shoe forefoot pressure time integral×mean daily strides (Stepwatch™ Activity Monitor)) were measured. Barefoot peak pressure was increased in persons with current and previous compared to no previous foot ulceration (mean±SD=888±222 and 763±335 vs 465±262kPa, p<0.05). In-shoe peak pressure was only increased in persons with current compared to without previous ulceration (mean±SD=412±145 vs 269±70kPa, p<0.05). Daily cumulative stress was not different between groups, although persons with current and previous foot ulceration were less active. Although barefoot peak pressure was increased in people with current and previous plantar ulceration, it did not discriminate between these groups. While in-shoe peak pressure was increased in persons with current ulceration, they were less active, resulting in no difference in daily cumulative stress. Increased in-shoe peak pressure suggests insufficient pressure reducing footwear in persons with current ulceration, highlighting the importance of pressure reducing qualities of footwear.
Chaitanya V, Sundeep; Das, Madhusmita; Bhat, Pritesh; Ebenezer, Mannam
The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy.
Stevelink, S A M; van Brakel, W H; Augustine, V
Stigma is a common phenomenon worldwide and infectious diseases like HIV/AIDS and leprosy are often associated with high levels of stigma. Several studies have been conducted concerning the effects of stigma and the impact on social participation, but comparative studies are rare. The objective of this study was to identify differences and similarities between HIV/AIDS and leprosy-related stigma. From April till July 2009, 190 questionnaire-based interviews were conducted to assess the levels of internalized stigma (Internalized Stigma of Mental Illness scale), perceived stigma (Explanatory Model Interview Catalogue stigma scale) and social participation (Participation scale) in a cross-sectional sample of people affected by leprosy (PL) and people living with HIV/AIDS (PLHA). Respondents were selected from several hospitals, charity projects and during home visits in Vellore district, Tamil Nadu. Our results showed that both PLHA (n = 95) and leprosy-affected respondents (n = 95) faced a substantial burden of internalized and perceived stigma, with the former reporting a significantly higher level of stigma. As a result, PLHA faced more frequent and also more severe participation restrictions than PL. Especially, restrictions in work-related areas were reported by the majority of the respondents. In conclusion, PLHA faced a significantly higher level of stigma and participation restriction than PL. However, the latter also reported a substantial burden of stigma and participation restrictions. The study suggests that it may be possible to develop joint interventions based on the commonalities found. More research is needed to define these more precisely and to test the effectiveness of such joint interventions in reducing stigma and improving social participation.
Chopra, Rupali; Ali, Shafat; Srivastava, Amit K; Aggarwal, Shweta; Kumar, Bhupender; Manvati, Siddharth; Kalaiarasan, Ponnusamy; Jena, Mamta; Garg, Vijay K; Bhattacharya, Sambit N; Bamezai, Rameshwar N K
Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.
Chopra, Rupali; Aggarwal, Shweta; Kumar, Bhupender; Manvati, Siddharth; Kalaiarasan, Ponnusamy; Jena, Mamta; Garg, Vijay K.; Bhattacharya, Sambit N.; Bamezai, Rameshwar N. K.
Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations. PMID:23861666