Clinical Manifestations Of Leprosy Research Articles

LEPVAX AS A PROMISING SPECIFIC VACCINE FOR LEPROSY: A NARRATIVE REVIEW

Leprosy is a disease with a high rate of transmission around the world. Leprosy is hard to eradicate because treatment is difficult and there is no vaccine to prevent it. The response of the immune system plays a role in determining the form of the clinical manifestation of leprosy. LepVax is a vaccine made from the Mycobacterium leprae antigens ML2531, ML2380, ML2055 and ML2028 formulated with the Toll-like receptor 4 agonist Glucopyranosyl Lipid Adjuvant in Stable Emulsion. LepVax can prevent infection with M. leprae through stimulation of the immune system and resulting regulation of pathogenic bacteria. LepVax can prevent nerve cell damage which is a target of the M. leprae bacterium. Further research is needed on the safety of LepVax as a vaccine to eradicate leprosy in the future.

A clinical case of borderline leprosy

Background. Described a rare case of leprosy, borderline form in the active stage.
 Aim. To present a clinical case of the development of leprosy with atypical manifestations in a patient outside a region endemic for leprosy.
 Case report. A 67-year-old patient from 2018 to 2020 received treatment for allergic dermatitis, pyoderma, no effect was observed; in 2020 he was examined for sarcoidosis, the diagnosis was not confirmed. In the Leprosy Research Institute, an examination was carried out, including a bacterioscopic examination of skin scarificates, a pathomorphological examination of skin biopsies, and molecular genetic methods.
 Results. Based on complaints, anamnesis, examination data and physical examination, the results of clinical and laboratory examination, the diagnosis was made: leprosy, borderline form (ICD-10 A30.3), active stage.
 Conclusion. The presented observation indicates that the variety of clinical manifestations of leprosy and the lack of alertness in relation to this disease, about the difficulty in establishing the correct clinical diagnosis in the patient, given the lack of history of data on contact with patients with leprosy.

Clinical and microbiological profile of Hansen’s diseases in a tertiary care centre of southwest Bihar

Leprosy or Hansen’s disease is a slowly progressive infection caused by mycobacterium Lepra. It has been reported from Bihar that false positive diagnosis is a major issue and decline in false positive diagnosis is not statistically significant. Present study has been designed primarily to study the clinical presentation and microbiological profile of patients presenting with symptoms of Hansen disease and secondarily to know the smear positivity of patients with clinical manifestation of leprosy. After enrolment of patients a detail clinical examination was done and demographic information of patient was recorded on predesigned Performa. After taking consent from enrolled patients slit skin smear was obtained as pre standard protocol. All patients below 20 years of age were slit smear staining smear negative for AFB. In our study 55(38.19%) patients with clinical manifestation were from 31 to 50 years of age among them 18(30 % of total AFB positive) was AFB positive. Among 30 patients with 16 (53.34%) patients have bacteriological index 6+ and 8 patients have bacteriological index 1+. From present study we can conclude that there was male predominance and in most of the patients who were smear staining positive have bacteriological index more than 6+. Most common age group presented with clinical symptom and AFB positive were in 3 and 4 decade of life. Hypopigmented macules were common presentation and AFB positive was most frequent in them.

Association of MBL2 Exon 1 Polymorphisms With Multibacillary Leprosy.

Mannose-binding lectin (MBL) is a serum protein of innate immunity, with a central role in the activation of the complement system through the lectin pathway. This protein is encoded by MBL2 gene, and single-nucleotide polymorphisms located at exon 1, such as rs5030737 C>T (D variant), rs1800450 G>A (B variant), and rs1800451 G>A (C variant), may change the MBL structure and the serum concentration. MBL2 polymorphisms have been associated with several infectious diseases, including leprosy. Host immune response has a major impact on the clinical manifestation of leprosy since only a few individuals infected with Mycobacterium leprae will develop the disease. Therefore, the aim of this study was to evaluate the influence of MBL2 exon 1 polymorphisms (rs5030737, rs1800450, and rs1800451) on the MBL levels and leprosy immunopathogenesis. This case–control study included 350 leprosy patients from Southern Brazil, with 279 classified as multibacillary (MB) and 71 as paucibacillary (PB). The control group consisted of 350 non-consanguineous individuals, who were not diagnosed with leprosy or other infectious and autoimmune diseases. Genotyping was performed by PCR–sequence specific primers, and the MBL serum concentrations were evaluated by ELISA. MBL2 exon 1 polymorphisms were analyzed individually and grouped as genotypes, considering “A” as the wild allele and “O” as the presence of at least one polymorphism (D, B, or C variants). Differences were not observed in the distribution of genotypic and allelic frequencies between leprosy per se patients and controls. However, in a haplotypic analysis, the TGG haplotype presented a risk for development of leprosy per se in women when compared to the wild haplotype (CGG) (OR = 2.69). Comparing patients with MB and PB, in a multivariate analysis, the B variant was associated with the susceptibility of developing the MB form of leprosy (OR = 2.55). Besides that, the CAG haplotype showed an increased susceptibility to develop MB leprosy in women compared to men. It was observed that the A/O genotype in women was associated with a susceptibility to leprosy development per se (OR = 1.66) and progression to MB leprosy (OR = 3.13). In addition, the MBL serum concentrations were in accordance with the genotyping analysis. In summary, our data suggest that MBL2 exon 1 polymorphisms are associated with an increased risk to leprosy development and progression.

A Clinicohistopathological Correlation of Hansen's Disease in a Rural Tertiary Care Hospital of Central India.

Background:Leprosy is an ancient, chronic granulomatous infectious disease caused by Mycobacterium leprae, principally affecting the skin and peripheral nerves. The clinical manifestations of leprosy are variable and can mimic a variety of other skin diseases. Thus, histopathological examination plays an important role in early diagnosis and management.Aim:The aim was to study the clinicohistopathological correlation of all suspected cases of Hansen's disease.Materials and Methods:A retrospective study was conducted on 207 skin biopsies obtained from patients clinically diagnosed as new lesion of leprosy in the department of pathology from 2016 to 2019. Demographic, clinical details of the patients were retrieved from hospital information system. Hematoxylin–eosin- and Fite–Faraco-stained sections were evaluated for features confirming leprosy and further categorized as per Ridley–Jopling system. Sensitivity, specificity, and concordance rates were studied.Results:The male-to-female ratio was 1.5:1. The agreement between histopathological and clinical diagnoses was more than 90% in all the subclasses except for borderline tuberculoid leprosy (BT) and tuberculoid leprosy (TT) which showed an agreement of 86.5% and 88.4%, respectively. The sensitivity of clinical diagnosis ranged from 69.70% for indeterminate to 100% for histoid and neuritic types. The specificity ranged from 90% for BT and TT to 100% for neuritic leprosy.Conclusion:Clinical diagnosis of early leprosy lesions offers difficulties even to experienced dermatologists as a patient presents in different clinicopathological forms, depending on host immune status. Thus, the correlation between clinical, histopathological, and bacteriological features is required for diagnosis and classification of leprosy. Nerve damage is irreversible; therefore, early detection and treatment is important to prevent Grade 2 disabilities.

The AFIP history of ocular leprosy

PurposeTo investigate the Armed Forces Institute of Pathology (AFIP) experience with Ocular Leprosy. MethodsThe AFIP data banks were screened for cases with diagnosis of ocular leprosy. Files and slides stained with Hematoxylin-eosin and acid-fast staining were reviewed by the Division of Ocular Pathology and by the Infectious Diseases Pathology Branch. ResultsTwenty-five cases were found from 1951 to 1985 and there were 15 males and 7 females and in 3 cases the sex was not given. The disease process ran from 4 months to 50 years in this series. Three patients also had systemic mycobacterium tuberculosis infections. The clinical manifestations of leprosy did not correlate with the histopathological findings. Clinically, corneal manifestations were the most common clinical presentation in 15 cases with only one perforation, iridocyclitis following in 9 patients and eyelid abnormalities ranging from ectropion to trichiasis in 7 patients. Two patients at autopsy had lepromatous cells in the ciliary body as the only ocular manifestation. ConclusionsIn summary, this paper represents a series of ocular leprosy cases from the AFIP which shows the severity of ocular involvement, the predilection of anterior segment involvement and a large number of histopathologic indeterminate cases. The current immigrant and refugee crisis warrants revisting this ancient disease in the differential diagnosis.

Lepromatous leprosy mimicking systemic lupus erithematosus: a case report

The clinical manifestations of leprosy are highly variable, and the disease is notorious for being “a great imitator” of several other conditions. Leprosy may manifest with a variety of phenomena resembling those of autoimmune diseases. Herein, we report a 33-year-old male presenting with wounds on his left leg and hyperpigmented skin lesions all over his body. Six years earlier, the patient was diagnosed with systemic lupus erythematosus (SLE). However, therapy for SLE did not control his symptoms; instead, the patient developed features of leprosy, such as anesthetic skin lesions, nerve enlargement, and tenderness. Tests for antinuclear antibodies and anti-double stranded DNA antibodies were negative. Slit-skin smear showed a bacterial index of 6+ and morphological index of 10 %. Lupus band test results were negative. Histological findings were compatible with lepromatous leprosy. The clinical and serological similarities between leprosy and SLE may lead to erroneous diagnosis. Thus, clinicians should be aware of this characteristic for correct diagnosis.

Transcription factors STAT-4, STAT-6 and CREB regulate Th1/Th2 response in leprosy patients: effect of M. leprae antigens

BackgroundLeprosy is an ideal human disease to study T cell regulation as patients show correlation between cytokine skewed Th1-Th2 responses and clinical forms of the disease. The Role of transcription factors on the modulation of Th1 and Th2 responses by M. leprae antigens has not been adequately studied. In the present study, we studied the effect of M. leprae antigens on transcription factors STAT-4, STAT-6 and CREB and their correlation with Th1/Th2 cell mediated immune responses in leprosy.MethodsLeprosy patients of both categories of tuberculoid leprosy (BT/TT) and lepromatous leprosy (BL/LL) were selected from the OPD of NJ1L & OMD, (ICMR), Agra and healthy individuals (H) were chosen from the staff and students working in the institute. Peripheral blood mononuclear cells (PBMCs) of the study subjects were stimulated with M. leprae antigens (WCL, MLSA, and PGL-1). Sandwich ELISA was done in the culture supernatants of healthy and leprosy patients to detect IL-4, IL-10 and IFN-γ. Further, expression of IFN-γ and IL-4 and activation of STAT4, STAT6 and CREB transcription factors in CD4+ T cell with or without stimulation of M. leprae antigens was investigated by flow cytometry.ResultsLepromatous leprosy patients showed significantly lower IFN-γ and higher IL-4 levels in culture supernatant and significantly low expression of IFN-γ and higher expression of IL-4 by CD4+ T cells than healthy individuals with or without antigenic stimulation. Antigenic stimulation significantly increased IL-10 in BL/LL patients but not in BT/TT patients or healthy individuals. PGL-1 stimulation led to significantly higher activation of STAT-6 in BT/TT and BL/LL patients in comparison to healthy individuals. All the three antigens led to activation of CREB in healthy and BT/TT patients but not in BL/LL patients.ConclusionOur findings show that M. leprae antigens differentially modulate activation of T cell transcription factors STAT-4/STAT-6 and CREB. These transcription factors are well known to regulate Th1 and Th2 mediated immune response which in turn could play vital role in the clinical manifestations of leprosy. These observations may help to determine how these T cell transcription factors affect the development of immune dysfunction and whether these new pathways have a role in immunomodulation in intracellular diseases like leprosy and TB.

Host Lipid Mediators in Leprosy: The Hypothesized Contributions to Pathogenesis.

The spectrum of clinical forms observed in leprosy and its pathogenesis are dictated by the host’s immune response against Mycobacterium leprae, the etiological agent of leprosy. Previous results, based on metabolomics studies, demonstrated a strong relationship between clinical manifestations of leprosy and alterations in the metabolism of ω3 and ω6 polyunsaturated fatty acids (PUFAs), and the diverse set of lipid mediators derived from PUFAs. PUFA-derived lipid mediators provide multiple functions during acute inflammation, and some lipid mediators are able to induce both pro- and anti-inflammatory responses as determined by the cell surface receptors being expressed, as well as the cell type expressing the receptors. However, little is known about how these compounds influence cellular immune activities during chronic granulomatous infectious diseases, such as leprosy. Current evidence suggests that specialized pro-resolving lipid mediators (SPMs) are involved in the down-modulation of the innate and adaptive immune response against M. leprae and that alteration in the homeostasis of pro-inflammatory lipid mediators versus SPMs is associated with dramatic shifts in the pathogenesis of leprosy. In this review, we discuss the possible consequences and present new hypotheses for the involvement of ω3 and ω6 PUFA metabolism in the pathogenesis of leprosy. A specific emphasis is placed on developing models of lipid mediator interactions with the innate and adaptive immune responses and the influence of these interactions on the outcome of leprosy.

Two Cases of Delayed Diagnosis of Leprosy in Mauritania

Leprosy is a chronic infectious disease that mainly affects the skin, mucous membranes, and peripheral nervous system. The clinical manifestations of leprosy are numerous and polymorphic with the most frequent signs involving skin and neurological damage. Some of its manifestations, such as joint pain, are unusual. Its elimination as a public health problem in many countries seems to lead to a lack of practical knowledge among health care personnel and as a consequence a risk of late diagnosis. As in other countries, leprosy has become rare in Mauritania. We report two cases of misdiagnosed leprosy in two male patients aged 17 and 65 years. Clinical manifestations included polyarthritis, bilateral plantar perforation, and severely deformed hands and feet in the first case and lichenoid lesions, hypopigmented papules, and unilateral bronchial rales in the second case. The duration of development and persistence of clinical signs before establishment of correct diagnosis was seven to ten years despite the presence of anesthetic, hypochromic maculopapular skin lesions and neurologic signs suggestive of leprosy in both cases. A multilevel chemotherapeutic regimen recommended by the World Health Organization (WHO) was effective, and the patients' condition evolved satisfactorily. The scarcity of leprosy in our health care facilities often leads to a wrong diagnosis. It is imperative to inform physicians to increase their vigilance for appropriate screening and reporting of these cases. The prognosis depends largely on early diagnosis and appropriate treatment.

Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia.

BackgroundThe clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R).MethodsHistory or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants.ResultsThere are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018).ConclusionsOur results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions.

Clinical manifestations of leprosy after BCG vaccination: An observational study in Bangladesh

BackgroundAlthough BCG is used as a vaccine against tuberculosis, it also protects against leprosy. Previous evaluation over 18 years of an intervention of two doses BCG for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy, developed symptoms 2–10 months after vaccination. This study describes contacts of leprosy patients in Bangladesh who developed leprosy within 12 weeks after receiving a single BCG dose. MethodsA cluster RCT in Bangladesh aims to study the effectiveness of the BCG vaccine versus BCG in combination with single dose rifampicin (SDR) given 2 to 3 months after BCG, in the prevention of leprosy among contacts of newly diagnosed leprosy patients. During the first 1,5 years of this ongoing trial we identified contacts who developed leprosy within the first 12 weeks after receiving BCG vaccination, the timeframe before SDR is given. ResultsWe identified 21 contacts who developed leprosy within 12 weeks after BCG vaccination among 5196 vaccinated contacts (0.40%). All 21 cases presented with paucibacillary (PB) leprosy, including children and adults. About half of these cases had previously received BCG vaccination as indicated by the presence of a BCG scar; 43% presented with signs of nerve function impairment and/or Type 1 (reversal) reaction, and 56% of the index patients had multibacillary (MB) leprosy. ConclusionAn unexpectedly high proportion of healthy contacts of leprosy patients presented with PB leprosy within 12 weeks after receiving BCG vaccination, possibly as a result of boosted cell-mediated immunity by homologues of Mycobacterium leprae antigens in BCG. Various immunological mechanisms could underlie this phenomenon, including an immune reconstitution inflammatory syndrome (IRIS). Further studies are required to determine whether BCG vaccination merely altered the incubation period or actually changed the course of the infection from self-limiting, subclinical infection to manifest disease.

Apresentação atípica de Hanseníase ao diagnóstico: Eritema Multiforme (reação tipo 2)

This study describes a case of erythema multiforme (EM) as the first clinical manifestation of leprosy in a 35-year-old woman. She presented at the hospital with fever, arthralgia and erythematous plaques on both elbows and knees, some of them with bullous or necrotic center areas. The diagnosis was confirmed by skin biopsy, which revealed a well-known EM pattern, and also showed the presence of Virchow cells and acid-fast bacilli. Physicians should be aware that leprosy must be considered in the differential diagnosis of EM, especially in endemic regions.

Variations in Leprosy Manifestations among HIV-Positive Patients, Manaus, Brazil

Variations in Leprosy Manifestations among HIV-Positive Patients, Manaus, Brazil

Specificity of IgG subclass antibodies in different clinical manifestations of leprosy.

We analysed specific IgG subclasses levels to Mycobacterium leprae sonicate extract (MSE), lipoarabinomannan B (LAM) and phenolic glycolipid I (PGL-I) in the sera of leprosy patients with different clinical manifestations. IgG2 was found to be the predominant antibody to MSE regardless of clinical manifestations, and IgG1 response was mostly seen in lepromatous patients. IgG3 reacted only rarely but IgG4 reacted relatively more in certain clinical groups such as borderline lepromatous and lepromatous with erythema nodosum leprosum (ENL) reaction. Most of the IgG subclass responses to MSE could be accounted for reactivity with LAM, suggesting that LAM is the major immunogen involved in the pathogenesis of leprosy. In contrast to LAM, PGL-I antigen showed considerably lower reactivities for IgG subclasses. An association between IgG subclass responses and clinical manifestations of leprosy was also seen. Whereas borderline lepromatous patients were found to have significantly higher levels of IgG2 and IgG4 to MSE, lepromatous patients had elevated levels of IgG1 and lower levels of IgG2. An interesting observation, however, was the significantly higher levels of IgG2 to LAM in the pure neuritic leprosy patients.

Association of C4B deficiency (C4B*Q0) with erythema nodosum in leprosy.

A considerable number of studies have postulated significant associations between susceptibility to the different clinical manifestations of leprosy and the MHC. In this investigation, the association between the MHC class III complement proteins C2, BF, C4A and C4B and leprosy in a patient population of Southern Brazil was studied. A total of 109 non-related leprosy patients was investigated; 73 presented with lepromatous leprosy (LL), 46 of them had the immunopathological reaction of erythema nodosum (ENL), the remaining 36 were tuberculoid, borderline and indeterminate leprosy (TIBL) patients. The control group included 172 healthy individuals matched with the patients according to their ethnic and geographical origin. C2, BF, C4A and C4B allotypes were determined by standard technologies including Western blots for C2 and C4 variant alleles with monoclonal and polyclonal antibodies. Non-expressed ('silent') C4 alleles in hemizygously deficient individuals were estimated semiquantitatively on the basis of the C4A and C4B isotype ratio and by the MASC ('minimal chi-square') method. The results showed a significantly elevated presence of the non-expressed C4B allele (C4B*Q0) in the LL and ENL patient groups in comparison with the controls. The most significant difference was observed in the ENL group when compared with the controls. In addition, all patients who were homozygously C4B-deficient had ENL, and most of them had the BF*F1 allele. The comparison between LL patients with and without ENL also showed a statistically significant difference in the presence of C4B*Q0, indicating that C4B deficiency itself is associated with ENL. The relative risk of LL patients with the C4B*Q0 allele suffering from ENL was 5.3 compared with LL patients without C4B*Q0. Since immune complexes (IC) are considered to be the pathogenic cause of ENL, our findings indicate that C4B deficiency may play an important role in the abnormal immune response against Mycobacterium leprae and in the lack of IC clearance, leading to ENL reactions. Individuals with this allele seem to be at a higher risk of developing pathological immune reactivity in lepromatous leprosy.

Hanseníase: uma doença genética?

A hanseníase é doença infecciosa milenar que, apesar da existência de terapêutica eficaz, ainda persiste como problema de saúde pública em seis países, entre eles o Brasil, líder mundial em prevalência da doença. Ao longo das últimas décadas, a hanseníase vem sendo estudada por perspectiva talvez inesperada para uma doença infecciosa: modernos métodos de análise experimental têm sido empregados para evidenciar a importância do componente genético no controle da susceptibilidade do hospedeiro à hanseníase e seus fenótipos. Esses estudos indicam que constituição genética favorável do hospedeiro, somada a fatores propícios, ambientais e relativos ao agente patogênico, tem alto impacto na definição da susceptibilidade tanto à infecção propriamente dita quanto à evolução clínica da doença. Hoje, diversos genes e regiões genômicas já foram relacionados ao controle da susceptibilidade à hanseníase. Outros estudos estão em andamento, visando ao avanço no entendimento das bases moleculares de controle da susceptibilidade do hospedeiro à doença. O conjunto de resultados desses estudos pode levar a formas mais eficazes de diagnóstico, tratamento e prevenção da hanseníase e outras doenças infecciosas.

Six cases of leprosy associated with allogeneic hematopoietic SCT

We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.

Serological reactivity to a synthetic analog of phenolic glycolipid I and early detection of leprosy in an area of low endemicity.

A total of 23,863 individuals living in an area of low endemicity for leprosy were tested by enzyme-linked immunosorbent assay with a semisynthetic analogue of the phenolic glycolipid I antigen of Mycobacterium leprae. The proportion found positive was 3.86% which was significantly higher than that in a sample of a population known to be free of leprosy. Clinical examinations as well as Mitsuda and skin smear tests were organized for those defined as seropositive. The proportion of individuals with lepromin reactions of less than 3 mm increased 18.9% per serological interval as antibodies rose though it was not statistically significant. As a result of the clinical and bacteriological examinations, 2 cases with clinical signs and heavy bacillary load were found, whereas acid-fast bacilli were demonstrated in 2 other individuals without clinical manifestations of leprosy. The usefulness of the system for control purposes is discussed.

Hsp70 synthesis in Schwann cells in response to heat shock and infection with Mycobacterium leprae.

Induction of heat shock protein synthesis was monitored in murine and monkey Schwann cells exposed to elevated temperatures. Synthesis of the stress-inducible 70-kDa heat shock protein (hsp70) was detected in both murine and primate Schwann cells by metabolic labelling and by immunoblotting with a specific monoclonal antibody. hsp70 synthesis was also induced in Schwann cells after infection with Mycobacterium leprae and was detected from 24 h to 1 week postinfection. These results are discussed with respect to the possible role of heat shock proteins in immunopathological events associated with the clinical manifestations of leprosy.