Lepromatous Form Research Articles

NURSING CARE FOR PATIENTS WITH LEPROSY TREATED BY PRIMARY CARE: INTEGRATIVE REVIEW

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Its predilection for the skin and peripheral nerves gives this disease particular characteristics, making its diagnosis simple. Brazil continues to be the second country in the world in terms of the number of cases, after India. Approximately 94% of known cases in the Americas and 94% of newly diagnosed cases are reported in Brazil. The disease manifests itself in two stable and opposing poles (virchowian and tuberculoid) and two unstable groups (indeterminate and dimorphic). In another classification, the disease is divided into tuberculoid, borderline or dimorphic forms, which are divided into dimorphic-tuberculoid, dimorphic-dimorphic and dimorphic-lepromatous and lepromatous forms. Microscopic examination of smears is the most useful complementary test for diagnosis. Treatment of leprosy includes: specific chemotherapy, suppression of reactive eruptions, prevention of physical disability, physical and psychosocial rehabilitation. Polychemotherapy based on rifampicin, dapsone and clofazimine has proven to be very effective and the prospects for controlling the disease in Brazil are real in the short term.

Comparative host transcriptomics as a tool to identify candidate biomarkers for immune reactions in leprosy using meta-analysis.

Background Leprosy is no longer considered an imprecation, as an effective multidrug therapy regimen is available worldwide for its cure. However, its diverse clinical manifestations sometimes involve acute inflammatory reactions. These complications result in irreversible nerve damage, neuritis and anatomical deformities that emerge before, during the treatment or after the completion of treatment. Reversal reaction (Type-I) and erythema nodosum leprosum (Type-II) are the leprosy reactions generally seen in patients with lepromatous and borderline forms of leprosy. At present, there is no accurate diagnostic test available to detect these leprosy reactions. Objectives To identify potential biomarkers indicative of Type-I and Type-II leprosy reactions that could help in their early diagnosis. Methods and Results Host-transcriptomics investigations have been utilised in this study to decipher a correlation between host-gene expression-based biomarkers and exacerbation of leprosy reactions. We present a comparative analysis of publicly available host transcriptomics datasets (from Gene Expression Omnibus) related to leprosy reactions. Individual datasets were analysed and integration of results was carried out using meta-analysis. Common differentially expressed genes (DEGs) were identified using the frequentist and Bayesian ratio association test methods. We have identified several genes - ADAMTS5, ADAMTS9, IFITM2, IFITM3, KIRREL, ANK3, CD1E, CTSF, DOCK9 and KRT73 to name a few - which can serve as potential biomarkers for Type-II reaction. Similarly, ACP5, APOC1, CCL17, S100B, SLC11A1 among others may likely serve as biomarkers for Type-I reaction. Limitations The number of datasets related to leprosy reactions found after the systematic search is less (n = 4) and may limit the accuracy of identified biomarker genes. This could be resolved by including more studies in the data analysis. Conclusion We provide a comprehensive list of gene candidates which could be prioritised further in research focusing on immune reactions in leprosy, as they are likely important in understanding its complexities and could be useful in its early diagnosis.

Joint-related manifestations of leprosy: A case report

Leprosy is a chronic granulomatous disease in which the musculoskeletal system has been described as the third most commonly affected system. Leprosy infections may manifest with various autoimmune phenomena reminiscent of classic autoimmune diseases. Among the leprosy factors affecting the prognosis of the disease, early diagnosis was reported to be the most effective. A 46-year-old married woman was referred to the hospital with initial articular symptoms. The patient also had deep folds, increased thickness of the skin in the forehead area, and dryness of the skin with a progressive course. The finger deformities and swelling are certainly misleading, but they may constitute an unsuspected inaugural form of leprosy, especially in its lepromatous form. The skin smear and biopsy confirmed leprosy, and treatment consisting of multi-drug therapy, as suggested by the WHO, was prescribed for the patient. According to these findings, it seems that one of the major symptoms of leprosy is musculoskeletal involvement and rheumatological manifestations, which may obscure and mislead diagnostic and treatment plans.

Description of electroneuromiographic and laboratorial findings in leprosy neuropathy, according to its clinical forms: the confirmation of a spectral disease.

Leprosy is one of the most common infectious cause of peripheral neuropathy in the world and can lead to sequelae and physical disabilities. Electroneuromyography (ENMG) is the gold-standard test for evaluating neural impairment, detecting from subclinical abnormalities to advanced lesions. This study aims to describe the electroneuromyographic findings in patients with leprosy, according to their clinical forms. The study is a retrospective observational analysis of the medical records of patients with leprosy, of a National Reference Center of Sanitary Dermatology and Leprosy in Brazil between 2014 and 2022. 513 patients underwent ENMG at leprosy diagnosis and also underwent a clinical, serological and molecular evaluation of the disease. The electroneuromyographic findings showed 2,671 altered nerves, with an average of 6.9 (±5.1) altered nerves per patient. The most affected sensory nerves were the superficial peroneal (25.0%; 413/1649), sural (15.1%; 397/2627) and ulnar (13.8%; 363/2627), with average of 4.3 (±3.2) affected sensory nerves per patient. The most affected motor nerves were the ulnar (33.1%; 338/1022) and common peroneal (12.1%; 319/2627), with average of 2.6 (±2.5) motor nerves affected per patient. 126 patients presented normal ENMG and, among the 387 with abnormalities in the exam, 13.2% (51/387) had mononeuropathy and 86.8% (336/387) had multiple mononeuropathy. Axonal involvement was more frequent in primary neural leprosy, borderline-tuberculoid, borderline-lepromatous and lepromatous forms. Our findings support that leprosy is a spectral disease, characterized by a balance between host immunity and bacillary load. Therefore, the impairment and electroneuromyographic characteristics are distinct and may vary according to the clinical form.

Rhinophyma in a Patient with Multibacterial Indeterminate Leprosy

INTRODUCTION: According to the clinical recommendations, the primacy in diagnosis of leprosy still remains with the laboratory methods, but the disease can also be suspected by the external pathological alterations in the face and limbs. This article presents a case report of one of leprosy masks commonly observed in lepromatous form of multibacterial leprosy (facies leonine), and also shows a combination of leprosy and acne rosacea in the form of rhinophyma.
 CONCLUSION: Differential diagnosis did not permit the authors to rest only on the diagnosis of leprosy, because too many details indicated the simultaneous presence of vascular and fibrous alterations of the soft nose tissues uncharacteristic of leprosy, which were diagnosed as a concomitant rhinophyma. The case is indicative as an example of a possible combination of vivid clinical manifestations of two diseases of different nature, which can both hide and imitate each other.

Immunoexpression of TGF-β: An utility marker in hansen’s disease

TGF-β is a pleiotropic cytokine that deploys several functions on different types of cells. In the lepromatous (LL) form of Leprosy, there is predominance of M2 macrophages, which induce the production of growth factors, such as TGF-β which is important for the mechanisms that cause apoptosis and healing. To study the immunoexpression of TGF-β in Hansen’s disease and to assess the severity of infection with potential response to treatment. The present study was carried out in 45 patients of Hansen’s disease after a detailed history and thorough physical examination performed in every subject and punch biopsies were performed. The specimens were fixed, paraffin embedded and sections of 3-5 microns thickness were cut and stained with hematoxylin and eosin stains. Additional sections of 3-4 microns thickness were cut and immunohistochemical staining by TGF-β antibody was performed. Of the 45 cases of Hansen’s disease, most of the cases were of Borderline Tuberculoid and Borderline Lepromatous, constituting 14 (31.1%) cases each, followed by 9 (20.0%) cases of Lepromatous Leprosy. Maximum cases, 12 (26.7%) each with intense reaction were of Borderline Tuberculoid and Borderline Lepromatous, followed by 6 (13.3%) cases of Lepromatous Leprosy. Most of the cases, 9 (20.0%) were of Borderline Lepromatous category with highest proportion score, followed by 7 cases (15.6%) of Borderline Tuberculoid. Highest number of cases, 9 (20.0%) with high immunoreactivity score were in Borderline Lepromatous, whereas most of the cases, 7(15.6%) with low immunoreactivity score were in Borderline Tuberculoid. The immunoexpression of TGF-β was more intense in lepromatous side of the spectrum as compared to the tuberculoid, which indicates the severity of the disease with less cure potential.

Oral Lesions In Leprosy – A Study of 100 Patients

Abstract: Leprosy is a chronic infectious disease affecting primarily the skin, peripheral nerves, respiratory system and the eyes. The clinical spectrum of leprosy ranges from the tuberculoid form (TT) to the disseminative and progressive lepromatous form (LL). Oral lesions are rare but, when present, occur in the lepromatous form. Objective: The goal of this study was to evaluate the oral lesions in leprosy patients. Materials and Methods: 100 patients diagnosed with leprosy were clinically and histopathologically examined for oral mucosal changes. Results: Of 100 patients examined, 22 showed evident oral mucosal lesions, gingivitis and periodontitis being the commonest. Conclusion: Although, a reduced number or absence of patients exhibiting oral manifestations of leprosy is attributed to the efficacy of the multidrug therapy carried out in recent times, along with the early diagnosis of the disease. Still role of dental supervision cannot be overlooked while considering rehabilitation of these patients.

Downmodulation of Regulatory T Cells Producing TGF-β Participates in Pathogenesis of Leprosy Reactions.

Leprosy reactions are an acute and systemic manifestation, which occurs suddenly, can be severe and lead leprosy patients to disability. Reactional episodes are observed among half of the multibacillary patients, mainly in borderline lepromatous and lepromatous forms. They may begin at any time during multidrug therapy, and even before the treatment. Physical disabilities, which are the source of extreme suffering and pain for patients, occur in progression of the cellular immune response associated with a reaction and are still poorly understood. Thus, this work aimed to phenotypically and functionally characterize CD4+ and CD8+ Treg cells ex vivo and in response to Mycobacterium leprae (ML). We studied 52 individuals, including 18 newly diagnosed and untreated multibacillary leprosy patients, 19 reactional multibacillary patients (Type I or Type II episodes) and 15 healthy volunteers, included as controls, all residents of the city of Rio de Janeiro. The functional activity and frequencies of these cells were evaluated through multiparametric flow cytometry. In addition, the production of cytokines in supernatant from peripheral blood mononuclear cell cultures was also investigated against ML by enzyme-linked immunosorbent assay. Our results showed a decrease in CD4+TGF-β+ Treg and CD8+ TGF-β+ Treg in leprosy multibacillary patients during both types of reactional episodes. Alterations in the cytokine profile was also observed in Type II reactions, along with upregulation of IL-17 and IL-6 in supernatant. Thus, our study suggests that downregulation of Treg cells is related with both classes of reactional episodes, improving our understanding of immune hyporesponsiveness in multibacillary patients and hyperesponsiveness in both reactions.

The two extremes of Hansen's disease-Different manifestations of leprosy and their biological consequences in an Avar Age (late 7th century CE) osteoarchaeological series of the Duna-Tisza Interfluve (Kiskundorozsma-Daruhalom-dűlő II, Hungary).

To give an insight into the different manifestations of leprosy and their biological consequences in the Avar Age of the Hungarian Duna-Tisza Interfluve, two cases from the 7th-century-CE osteoarchaeological series of Kiskundorozsma-Daruhalom-dűlő II (Hungary; n = 94) were investigated. Based on the macromorphology of the bony changes indicative of Hansen's disease, KD271 (a middle-aged male) and KD520 (a middle-aged female) represent the two extremes of leprosy. KD271 appears to have an advanced-stage, long-standing near-lepromatous or lepromatous form of the disease, affecting not only the rhinomaxillary region but also both upper and lower limbs. This has led to severe deformation and disfigurement of the involved anatomical areas of the skeleton, resulting in his inability to perform the basic activities of daily living, such as eating, drinking, grasping, standing or walking. The skeleton of KD520 shows no rhinomaxillary lesions and indicates the other extreme of leprosy, a near-tuberculoid or tuberculoid form of the disease. As in KD271, Hansen's disease has resulted in disfigurement and disability of both of the lower limbs of KD520; and thus, the middle-aged female would have experienced difficulties in standing, walking, and conducting occupational physical activities. KD271 and KD520 are amongst the very few published cases with leprosy from the Avar Age of the Hungarian Duna-Tisza Interfluve, and the only examples with detailed macromorphological description and differential diagnoses of the observed leprous bony changes. The cases of these two severely disabled individuals, especially of KD271 -who would have required regular and substantial care from others to survive-imply that in the Avar Age community of Kiskundorozsma-Daruhalom-dűlő II there was a willingness to care for people in need.

Serum Levels of Ficolin-3 and Mannose-Binding Lectin in Patients with Leprosy and Their Family Contacts in a Hyperendemic Region in Northeastern Brazil.

The present study aimed at analyzing the serum levels of mannose-binding lectin (MBL) and ficolin-3 (FCN3) in leprosy patients and their healthy family contacts in a hyperendemic region in northeastern Brazil. A cross-sectional study was carried out with 90 patients who had been diagnosed with leprosy and 79 healthy family contacts. Serum levels of the MBL and FCN3 proteins were measured using the immunofluorometric assay (ELISA). Clinical information was determined from the patients’ charts. It was observed that the leprosy patients were more likely to be male (OR = 2.17; p = 0.01) and younger than fifteen years of age (OR = 2.01; p = 0.03) when compared to the family contacts. Those under 15 years of age had higher levels of MBL (4455 ng/mL) than those over 15 years of age (2342 ng/mL; p = 0.018). Higher FCN3 levels were identified in patients with indeterminate leprosy (41.9 µg/mL) compared to those with the lepromatous form (34.3 µg/mL; p = 0.033) and in those with no physical disabilities (38.1 µg/mL) compared to those with some disability (p = 0.031). Higher FCN3 levels were also observed in the group of patients without leprosy reactions (37.4 µg/mL) compared to those with type 1 (33.7 µg/mL) and type 2 (36.1 µg/mL) reactions. The MBL levels were higher in children under 15 years of age than they were in adults. It was evidenced that higher FCN3 serum levels were associated with early and transient clinical forms and lower expression in severe forms of leprosy.

Life and death of a leprosy sufferer from the 8th-century-CE cemetery of Kiskundorozsma-Kettőshatár I (Duna-Tisza Interfluve, Hungary)-Biological and social consequences of having Hansen's disease in a late Avar Age population from Hungary.

The aim of our paper is to demonstrate a middle-aged male (KK61) from the 8th-century-CE cemetery of Kiskundorozsma-Kettőshatár I (Duna-Tisza Interfluve, Hungary), who appears to represent the lepromatous form of Hansen's disease. Leprosy has affected not only the rhinomaxillary region of his face but also his lower limbs, with severe deformation and disfigurement of the involved anatomical areas (saddle-nose and flat-foot deformity, respectively). Consequently, he would have experienced disability in performing the basic activities of daily living, such as eating, drinking, standing or walking; and thus, he would have required regular and substantial care from others to survive. Despite his very visible disease and associated debility, it seems that KK61 was accepted as a member of the community in death, since he has been buried within the cemetery boundaries, among others from his community. In addition, his grave has conformed to the mortuary practices characteristic of the Kiskundorozsma-Kettőshatár I cemetery (e.g., burial orientation, position of the body in the grave, and type and quantity of accompanying grave goods). Although distinction or segregation in life do not preclude normative treatment in death, the long-lasting survival of KK61 with Hansen's disease implies that he would not have been abandoned but cared for by others. KK61 is one of the few published historic cases with leprosy from the Avar Age of the Hungarian Duna-Tisza Interfluve. His case gives us a unique insight into the biological consequences of living with Hansen's disease and illustrates the social attitude toward leprosy sufferers in early mediaeval Hungary.

Evaluation of clinical and demographic profile of leprosy with special reference to WHO-fixed duration multidrug therapy non-responders: a cross-sectional analysis at a tertiary care centre in Maharashtra

<p class="abstract"><strong>Background:</strong> India remains one of the highest contributors to the global burden of leprosy despite declaring elimination in 2005 under National Leprosy Elimination Program (NLEP). The objective of this study was to document the clinical and socio-demographic profile of leprosy patients, determine the proportion suspected with inadequate/non-response to standard World Health Organisation (WHO)-Fixed duration multi drug therapy (FD-MDT) and identify contributory factors.</p><p class="abstract"><strong>Methods:</strong> A cross-sectional study was conducted on 123 leprosy patients over 2 months. Screened patients were categorised into suspected MDT non-responders (Group A, 21) and those not satisfying criteria (Group B, 102) for non-responders. Medical records were abstracted and patients subjected to detailed history and clinical examination.</p><p class="abstract"><strong>Results:</strong> Burden of WHO-MDT non-responders was 17 % (mean age 37.64 years).Majority were male in both groups. Borderline lepromatous (33%) and borderline tuberculoid (58%) were the predominant types in group A and B respectively. Among non-responders, male gender and grade 1disabilitywere significant associations, 17 were on extended-MDT;1 patient was prescribed second-line drugs,3 received both MDT and second-line drugs. More-than-half had relapsed within 5 years.</p><p class="abstract"><strong>Conclusions: </strong>This study highlights the need for customised-treatment in selective situations to minimise relapses. Determinants in WHO-FD-MDT non- responders/relapse cases were male gender, young adults, lower socioeconomic status, lepromatous form, disability, high initial bacteriological index, non-compliance and early relapses. Leprosy eradication can be facilitated by individually focused management strategies including judicious use of bacteriological index, counseling and long- term follow-up depending on the patient profile. Active surveillance and early detection of relapse may prevent further complications and decrease drug resistance. </p>

Borderline lepromatous leprosy with primary clinical manifestation in a patient with a long-term dermatological history

Despite the low number, the cases of leprosy continue to be detected, more often on endemic territories. In Russian Federation one of the endemic territories is located in Astrakhan region. The long incubation period eventually leads to inability to identify the source of infection. The combination of the leprosy with other dermatoses complicates the diagnosing. The isolated and early skin manifestations of leprosy can be mistaken for the clinical features of other dermatoses. This article presents the description of a case study of border line lepromatosis leprosy in a patient with a long-term dermatological background. A 66-year-old male was followed up for 14 years under different dermatological diseases. In 2017, after a change in the nature of rashes, atypical for supervised nosological forms, and in connection with the resistance of clinical manifestations of diseases to the therapy, a clinical diagnosis of leprosy was established. To verify this diagnosis, the patient was sent to the Federal State Budgetary Institution "Research Institute for the Study of Leprosy". At admission, he complained of rashes on the skin of the face, trunk, extremities, accompanied by itching, swelling, weakness and numbness in the distal extremities. As a result of clinical, laboratory examination (bacterioscopic examination of scarification from the skin, serological examination, pathomorphological examination of skin biopsies), the diagnosis of the underlying disease was made: leprosy, borderline lepromatous form, active stage. Complications of the underlying disease: chronic specific polyneuropathy with sensitive disorders. The described clinical situation illustrates the problem of early diagnosis of leprosy due to the variety of manifestations and low alertness of clinicians.

Borderline lepromatous leprosy with primary clinical manifestation in a patient with a long-term dermatological history

Despite the low number, the cases of leprosy continue to be detected, more often on endemic territories. In Russian Federation one of the endemic territories is located in Astrakhan region. The long incubation period eventually leads to inability to identify the source of infection. The combination of the leprosy with other dermatoses complicates the diagnosing. The isolated and early skin manifestations of leprosy can be mistaken for the clinical features of other dermatoses. This article presents the description of a case study of border line lepromatosis leprosy in a patient with a long-term dermatological background. A 66-year-old male was followed up for 14 years under different dermatological diseases. In 2017, after a change in the nature of rashes, atypical for supervised nosological forms, and in connection with the resistance of clinical manifestations of diseases to the therapy, a clinical diagnosis of leprosy was established. To verify this diagnosis, the patient was sent to the Federal State Budgetary Institution "Research Institute for the Study of Leprosy". At admission, he complained of rashes on the skin of the face, trunk, extremities, accompanied by itching, swelling, weakness and numbness in the distal extremities. As a result of clinical, laboratory examination (bacterioscopic examination of scarification from the skin, serological examination, pathomorphological examination of skin biopsies), the diagnosis of the underlying disease was made: leprosy, borderline lepromatous form, active stage. Complications of the underlying disease: chronic specific polyneuropathy with sensitive disorders. The described clinical situation illustrates the problem of early diagnosis of leprosy due to the variety of manifestations and low alertness of clinicians.

Paratuberculosis in Captive Scimitar-Horned Oryxes (Oryx dammah).

Simple SummaryParatuberculosis is a bacterial infection occurring globally in ruminants, with an impact on animal health and welfare. The chronic nature of the disease, the variability in infection progression, and immune response can make diagnosis difficult. The disease can have severe consequences in zoological parks where threatened animal species are hosted. In the present study, we investigated paratuberculosis in a group of scimitar-horned oryx, an endangered ruminant species, hosted in a Northern Italy zoological park. The animals were derived from a flock imported from Slovakia. We report the results of different diagnostic techniques and underline the contribution of each to reach a complete diagnosis. Moreover, bacterial genomic investigation yielded an epidemiological contribution, suggesting an Italian origin of the infection, because the bacteria isolates were more similar to strains endemic in Italian cattle livestock than East European isolates. We emphasize the importance of molecular analyses to trace the origin of infections in terms of both geographical and cross-species tracing. We highlight that paratuberculosis has to be taken into account when dealing with endangered ruminant species, because even the death of a single animal can reduce genetic variability.Paratuberculosis, a chronic disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), in ten scimitar-horned oryxes (SHOs) hosted in an Italian zoological park and originating from a Slovakian flock, was documented by pathology, molecular, cultural, and serological testing. The infection origin in this threatened species was also investigated by genomic analyses. Following the death of six of the 10 SHOs, serial investigations of dead and alive animals were performed. Necropsy, carried out on five out of six animals, identified intestinal thickening and mesenteric lymphadenomegaly in one of the animals. Histopathology (5/6) revealed lepromatous (2/5) and tuberculoid (2/5) intestinal forms or lack of lesions (1/5). Ziehl-Neelsen and immunohistochemistry stains identified two multibacillary, two paucibacillary forms, and one negative case. MAP was identified by quantitative PCR (qPCR) in tissue samples in five out of five SHOs and was microbiologically isolated from two of the three animals whose fresh tissue samples were available. Fecal samples were collected in four of the six dead animals: all four resulted positive to qPCR and in MAP was isolated in three. ELISA identified MAP-specific antibodies in three of the five dead animals whose serum was available. qPCR identified MAP in the freshly deposited feces of two out of the four alive animals. From the feces of these two animals, MAP was microbiologically isolated in one case. All isolates were classified as MAP type C and profiled as INMV2 and MVS27 by molecular analysis. Genomic analysis of a field isolate revealed clusterization with a European clade but was more similar to Italian than East European isolates. Our findings underline that paratuberculosis should always be considered in zoological parks in which endangered species are hosted. Infection can be subclinical, and multiple combined testing techniques may be necessary.

Erythema nodosum as Leprosy reaction

Purpose.To present a clinical case of leprosy exacerbation on the background of ongoing therapy.
 Materials and methods.A 52-year-old patient with a diagnosis of "lepromatous (cutaneous) leprosy, leprosy LL" (multi-bacterial leprosy, lepromatous form, active stage), has an exacerbation in the form of nodular erythema at 3.5 years after the start of treatment. Due to the exacerbation of the leprosy process, dexamethasone therapy was performed intravenously in a dose of 4 mg/ml 3.0 ml + 0.9% NaCl 200.0 ml daily No. 10.
 Results. An exacerbation was diagnosed leprosy nodular erythema. The prescription of adequate therapy led to a complete regression of clinical manifestations.
 Conclusion.The described case is presented in connection with the rarity of this dermatosis.

Report of two cases of lepromatous leprosy at an early age

Leprosy is an infectious disease that has a broad spectrum of clinical manifestations. Lepromatous leprosy has a deficient cellular immune response and high bacillary multiplication. It has epidemiological importance, as it is the most contagious clinical form of the disease. Its manifestation in children and adolescents is unusual. In the present study, we report two cases of leprosy at an early age, manifesting the lepromatous clinical form, highlighting the auricular involvement in one case. Early diagnosis is an essential tool to avoid deformities and deficiencies.

CLINICAL AND IMMUNOHISTOPATHOLOGICAL STUDY OF ORAL LESIONS OF LEPROSY

Objective. To compare clinical and immunohistopathological features of oral lesions with clinically normal oral mucosa from patients with leprosy. Study design. This is a cross-sectional study of patients with leprosy showing specific oral lesions selected from January 2000 to June 2018. Patients with leprosy who did not have oral lesions and agreed to oral biopsy were included in the comparisons of analysis, which consisted of clinical and immunohistopathological (anti-PGL1 and MLSA expression) study. Results. A total of 416 patients with leprosy were evaluated and patients with leprosy-specific oral lesions (n = 14) were included. All were men, and the majority had the lepromatous form. The oral mucosa showed acanthosis, lymphocyte exocytosis, foamy macrophages, and nonfragmented bacilli. Patients without oral lesions (n = 14) mostly had the multibacillary (MB) form, and the oral mucosa showed minimal inflammatory infiltrates and no foamy macrophages in most of the samples. PGL1 and MLSA were detected in all oral lesions and in 6 specimens from clinically normal mucosa. Conclusions. The oral cavity may be affected by leprosy in advanced stages of the MB form. Histopathological findings of oral lesions seem similar to cutaneous lesions, and anti-PGL1 and MLSA are effective markers to determine Mycobacterium leprae presence either in oral lesions or clinically normal mucosa of patients with the MB form of leprosy.

Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.

To maintain homeostasis, macrophages must be capable of assuming either an inflammatory or an anti-inflammatory phenotype. To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis. Transcriptomic analysis of TLR stimulation in the presence of IC predicted the downstream activation of AKT and the inhibition of GSK3. Consequently, we pretreated LPS-stimulated human macrophages with small molecule inhibitors of GSK3 to partially phenocopy the regulatory effects of stimulation in the presence of IC. The upregulation of DC-STAMP and matrix metalloproteases was observed on these cells and may represent potential biomarkers for this regulatory activation state. To demonstrate the presence of these anti-inflammatory, growth-promoting macrophages in a human infectious disease, biopsies from patients with leprosy (Hanseniasis) were analyzed. The lepromatous form of this disease is characterized by hypergammaglobulinemia and defective cell-mediated immunity. Lesions in lepromatous leprosy contained macrophages with a regulatory phenotype expressing higher levels of DC-STAMP and lower levels of IL-12, relative to macrophages in tuberculoid leprosy lesions. Therefore, we propose that increased signaling by FcγR cross-linking on TLR-stimulated macrophages can paradoxically promote the resolution of inflammation and initiate processes critical to tissue growth and repair. It can also contribute to infectious disease progression.

Serological evidence of Toxoplasma gondii infection as potential risk for the development of lepromatous leprosy in an endemic area for both neglected tropical diseases in Brazil

BackgroundMycobacterium leprae and Toxoplasma gondii infections are both neglected tropical diseases highly prevalent in Brazil. Infection with certain parasite species can significantly alter susceptibility to other important pathogens, and/or influence the development of pathology. Here we investigated the possible influence of M. leprae/T. gondii co-parasitism on the manifestation of leprosy and its clinical forms.MethodsParticipants (n = 291) were recruited in Campos dos Goytacazes city, Rio de Janeiro state, southeast Brazil, from August 2015 to December 2019 and clinically diagnosed for leprosy. Participants were selected based on the presence (patients) or absence (healthy controls) of the leprosy disease. Contacts of patients were also recruited for this study. Serum samples from patients (n = 199) with leprosy, contacts (n = 40) and healthy controls (n = 52) were investigated for levels of IgM and IgG anti-phenolic glycolipid-1 (PGL-1) by ELISA. Additionally, IgG antibody against soluble Toxoplasma antigen (STAg) was measured in sera samples from leprosy patients, contacts and healthy controls for Toxoplasma gondii serology by ELISA. Anti-PGL-1 IgG and IgM levels were compared using one-way ANOVA Kruskal-Wallis or Mann-Whitney, while Spearman test was used to correlate levels of IgG anti-STAg and IgM/IgG anti-PGL-1 from seropositive and seronegative individuals for T. gondii infection. The risk of T. gondii infection for leprosy disease was assessed using Fisher’s test.ResultsLevels of IgM anti-PGL-1 antibodies were significantly higher in multibacillary (MB) patients compared to paucibacillary (PB) patients (P = 0.0068). Higher IgM and IgG levels anti-PGL-1 were detected in patients with the lepromatous forms. The serologic prevalence for T. gondii infection was 74.9%. We detected increased anti-STAg antibody levels in leprosy patients (79.4%), reaching 88.8% within those with lepromatous form of this disease. The leprosy risk increase in T. gondii seropositive individuals was two-fold (odds ratio [OR] = 2.055; 95% confidence intervals [95% CI]: 1.18–3.51) higher than those seronegative, and considering the lepromatous leprosy risk this increase was even dramatic (OR = 4.33; 95% CI: 1.76–9.69) in T. gondii seropositive individuals. Moreover the leprosy risk in T. gondii seropositive individuals was weakly correlated to the levels of IgG anti-STAg and IgM/IgG anti-PGL-1.ConclusionsAltogether, our results suggest that T. gondii infection may exert immunomodulatory properties that influence to the susceptibility of leprosy, mainly on its more severe clinical form. A better understanding of parasite immunomodulation can ultimately contribute to the development of medical applications.