Analysis of socioeconomic condition and bacillary index with respect to the development of Hansen's disease.

Background: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae or Mycobacterium lepromatosis and mainly affects the skin and peripheral nerves. Although treatable, its early intervention can significantly reduce the occurrence of disability. India accounts for more than half of new cases globally. This study was undertaken to better understand the clinical traits of newly diagnosed cases in a tertiary facility of Western Uttar Pradesh, and a few from Madhya Pradesh and Uttarakhand. Methods: The observational prospective study was carried out on all the newly diagnosed leprosy cases who visited the Outpatient Department of ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra, during October 2019-December 2022. After obtaining answers to a prestructured questionnaire with their consent, participants were enrolled in the study and underwent clinical examination and a slit-skin smear test. Results: A total of 56 cases were investigated, and among them, 20 (35.7%) and 36 (64.3%) women and men, respectively, had positive contact with persons affected by leprosy either within family, friends, or neighbors. It is observed that due to the delayed detection of leprosy cases, paucibacillary (PB) patients converted into multibacillary (MB) patients, and the number of MB cases is much higher compared to PB cases. Conclusion: Leprosy instances continue to spread frequently from sick to healthy people indicating continued transmission of leprosy in society. Multidrug therapy in the management of leprosy cases is effective; however, early diagnosis of PB cases is still a challenge and needs to be addressed on priority.

Negligência no diagnóstico precoce de hanseníase na atenção primária: um relato de caso / Negligence in the early diagnosis of leprosy in primary care: a case report

A hanseníase é uma doença infecciosa, transmissível, de caráter crônico, com potencial grau de incapacidade, que ainda persiste como problema de saúde pública no Brasil. A demora e a falta de conhecimento técnico para realizar o diagnóstico resulta em inúmeros prejuízos aos pacientes acometidos pela doença, sendo que, a prevenção das incapacidades está relacionada diretamente com o diagnóstico precoce da doença. Com a finalidade de evitar a negligência diagnóstica e o desenvolvimento de incapacidades físicas, ressaltamos a importância do conhecimento técnico sobre o diagnóstico e o manejo da hanseníase por profissionais da saúde em qualquer nível de atenção à saúde ou especialidade.

Hansen is an infectious disease, transmissible, of a chronic nature, with serious potential for disability, which still persists as a public health problem in Brazil. The delay and the lack of technical knowledge to carry out the diagnosis with numerous prejudices to the patients affected by the disease, since the prevention of disabilities is directly related to the early diagnosis of the disease. In order to avoid diagnostic negligence and the development of physical disabilities, we highlight the importance of technical knowledge about the diagnosis and management of training by health professionals at any level of health care or special care.

Efficacy of fixed duration multidrug therapy for the treatment of multibacillary leprosy: A prospective observational study from Northern India.

BACKGROUND: In endemic regions of several countries, the prevalence of leprosy has not come down to the level of elimination. On the contrary, new cases are being detected in large numbers. Clinically, it is frequently noted that despite completion of multibacillary multidrug therapy for 12 months, the lesions remain active, especially in cases with high bacteriological indices. AIM: The present study focused on finding out the viable number of Mycobacterium leprae during the 12-month regimen of multibacillary multidrug therapy, at six and 12 months intervals and, attempting to determine their role in disease transmission. METHODS: Seventy eight cases of multibacillary leprosy cases were recruited from leprosy patients registered at The Leprosy Mission hospitals at Shahdara (Delhi), Naini (Uttar Pradesh) and Champa (Chhattisgarh), respectively. Slit skin smears were collected from these patients which were transported to the laboratory for further processing. Ribonucleic acid was extracted by TRIzol method. Total Ribonucleic acid was used for real-time reverse transcription-polymerase chain reaction (two-step reactions). A standard sample with a known copy number was run along with unknown samples for a reverse transcription-polymerase chain reaction. Patients were further assessed for their clinical and molecular parameters during 6th month and 12th month of therapy. RESULTS: All 78 new cases showed the presence of a viable load of bacilli at the time of recruitment, but we were able to follow up only on 36 of these patients for one year. Among these, using three different genes, 20/36 for esxA, 22/36 for hsp18 and 24/36 for 16S rRNA cases showed viability of M. leprae at the time of completion of 12 months of multidrug therapy treatment. All these positive patients were histopathologically active and had bacillary indexes ranging between 3+ and 4+. Patients with a high copy number of the Mycobacterium leprae gene, even after completion of treatment as per WHO recommended fixed-dose multidrug therapy, indicated the presence of live bacilli. LIMITATIONS: Follow up for one year was difficult, especially in Delhi because of the migratory nature of the population. Patients who defaulted for scheduled sampling were not included in the study. CONCLUSION: The presence of a viable load of bacilli even after completion of therapy may be one of the reasons for relapse and continued transmission of leprosy in the community.

Clinico-Epidemiological Trends of Leprosy at a Tertiary Care Centre of South Rajasthan: A 10-Year Retrospective Study.

Background: Leprosy is a major public health problem in India, which affects many people every year and has significantly high new case detection rates in certain districts and blocks. According to the National Leprosy Elimination Program (NLEP) report of March 2019, there were a total of 1.14 lakhs new cases of leprosy in India with an Annual New Case Detection Rate (ANCDR) of 8.1 per 100,000 population. Aim: The present study aimed at determining the epidemiological and clinical profile of leprosy patients from a tertiary level teaching hospital in South Rajasthan. Materials and Methods: A retrospective, record-based study was carried out on patients registered in the leprosy clinic of a tertiary level teaching hospital of South Rajasthan during a period of ten years (2010-2019). Data regarding the demographic profile, clinical features, treatment given, and complications were analysed. Results: A total of 1372 patients registered in the leprosy clinic during a period of 10 years were evaluated. There were 1007 (73.4%) males and 365 (26.6%) females with a male-female ratio of 2.76:1. The majority of patients 671 (48.9%) belonged to the middle age group (21-40 years). Multibacillary leprosy was the most common clinical type seen in 1109 patients (80.8%). Borderline leprosy was the most common morphological type, determined in 625 (45.6%) patients, of which BL (21.0%) was the most common group. 16.7% patients presented with leprosy reaction at the time of initial diagnosis. Type 1 reaction was seen in 91(6.6%) and type 2 reaction in 138 (10.1%) patients. Grade I disability was observed in 347 (25.3%) patients whereas grade II disability was seen in 456 (33.2%) patients. 54 patients (3.9%) had a definite history of contact in the family. 28 patients defaulted during the study period. Yearly trend of epidemiological and operational parameters was observed, and the parameters were compared with the national data. Conclusion: Persistent high proportion of multibacillary cases and grade 2 disability indicates that leprosy continues to be a significant health care problem despite statistical elimination. There is a clear need to strengthen early detection, treatment and regular follow-up of these cases in both high and low endemic settings.

Epidemiological characteristics of leprosy in China from 2016 to 2020 / 中华皮肤科杂志

Objective:To analyze epidemiological characteristics of leprosy in China from 2016 to 2020, and to provide a scientific basis for further elimination of leprosy.Methods:Data collation and statistical analysis were conducted on annual reports on leprosy epidemic surveillance in China (excluding Hong Kong, Macao, and Taiwan regions) from 2016 to 2020.Results:From 2016 to 2020, a total of 2 697 new cases of leprosy were reported in China, including 46 (1.71%) children, 894 (33.15%) females, 374 (13.87%) floating people, 2 443 (90.58%) multibacillary cases, and 546 (20.24%) cases of grade 2 disabilities. A total of 203 relapsed cases were reported in the meantime. By the end of 2020, there had been 1 893 registered leprosy cases in China, and the number of cases was 68.62% fewer than that in 2010 (6 032 cases) ; there were 36 (1.2%) counties or cities with a prevalence rate above 1 per 100 000, and 72 (17.73%) new cases suffered from grade 2 disabilities.Conclusion:From 2016 to 2020, the reported incidence and prevalence of leprosy in China steadily decreased year by year, and overall, leprosy was still lowly prevalent.

Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

Necrotic erythema nodosum reaction associated with histological alterations of Lucio's phenomenon

Abstract Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.

Symmetrical Centrofacial Erythematous Plaques and Papules: A Clinicopathological Challenge.

Facial papular eruptions remain a diagnostic dilemma for the dermatologist with a wide range of inflammatory and infectious conditions manifesting in this manner. Here, we present a case of a 29-year-old, otherwise healthy man from North India with asymptomatic well-defined normoaesthetic symmetrical papules and plaques over the upper and mid-face of 3 months duration. Skin biopsy showed perivascular and periappendageal well-defined collections of foamy macrophages and epithelioid cells in superficial and deep dermis, characteristic of borderline lepromatous leprosy. Though acid-fast stain for lepra bacilli was negative both on lesional biopsy specimen and lesional and ear lobe slit skin smear, a 16s ribosomal ribonucleic acid (16s-r-RNA) polymerase chain reaction on skin biopsy specimen was found to be positive for lepra bacilli. A final diagnosis of borderline lepromatous leprosy in type I reaction was made and the patient received World Health Organization (WHO) multibacillary (MB) multidrug therapy along with oral steroids. This case highlights the unusual localized involvement in a case of MB leprosy lacking all the three cardinal features of leprosy, i.e. sensory loss, peripheral nerve involvement, and acid-fast bacilli positivity on biopsy or slit skin smear but diagnosed on the basis of characteristic histology and positive polymerase chain reaction results.

Necrotic erythema nodosum reaction associated with histological alterations of Lucio's phenomenon.

Patients with lepromatous or borderline leprosy may present two types of vasculonecrotic reactions: Lucio's phenomenon (LP) and necrotic erythema nodosum leprosum (nENL). These are serious conditions, which mostly lead to life-threatening infectious and thrombotic complications. The authors report the case of a patient with leprosy recurrence associated with an atypical type II reaction with LP characteristics on histopathology.

Histoid leprosy presenting as a large tumor

Abstract Histoid leprosy is a rare form of multibacillary leprosy, characterized by the presence of papules, plaques, or nodules whose appearance is keloid-like, skin colored, or erythematous. Fusiform cells are the main histopathological feature. Due to the fact that it can simulate other dermatological lesions, for example, dermatofibroma and neurofibroma, it constitutes a diagnostic challenge for clinicians and pathologists. It is a bacilliferous form of leprosy, and it plays an important role in disease transmission. A case of a patient with histoid leprosy living in the Northeast Region of Brazil is reported.

Renaissance of Hansen's Disease in Post-Elimination Era in North India: A Retrospective Clinico-Bacteriological Study.

Introduction Hansen's disease is a chronic infectious disease caused by Mycobacterium leprae. India declared the elimination of leprosy in December 2005, but a slow resurgence of the disease still continues in several parts of India. The diagnosis of leprosy is primarily clinical but slit-skin smear microscopy aids in an accurate diagnosis. There are very few studies on clinico-bacteriological patterns of leprosy at this post-elimination phase. Aim This study aimed to analyze the clinical and bacteriological findings of newly diagnosed cases of Hansen's disease in the post-elimination era. Materials and methods This is a descriptive, hospital-based, retrospective study of newly diagnosed cases of Hansen's disease, enrolled in the Hansen's disease clinic attached to the dermatology outpatient department (OPD) of a tertiary care hospital in North India. A retrospective chart review of newly diagnosed cases of leprosy for a period of one year was done. Information about demographics, clinical characteristics, spectrum of disease, and slit skin smear data of patients were collected. Statistical analysis was performed using SPSS Version 16.0 (Chicago, IL, SPSS Inc.). Result A total of 116 patients were included of which 68.1% (79) were males. The age of patients ranged from 7 to 72 years and children (<15 years) constituted 6% (7/116) of all cases. The most common clinical spectrum was borderline lepromatous leprosy 37.9% (44/116) followed by lepromatous leprosy 32.8% (38/116). Out of 116 cases, 39.6% of cases showed slit-skin smear positivity. Conclusion The study brings forth evidence on the slow re-emergence of leprosy in India. In this study, multibacillary cases outnumber the paucibacillary cases; also, childhood cases were encountered indicating active community spread of the disease in the "post-elimination era." There is an urgent need to step up the surveillance for Hansen's disease to curb the further spread of the bacilli in the community.

Histoid leprosy - A rare clinical presentation

Abstract Histoid leprosy is considered a rare form of lepromatous leprosy. Its peculiar clinical picture makes its diagnosis a challenging one, which can delay starting treatment and perpetuate the disease as endemic. In addition to representing a reservoir of bacilli, and being an important means of contamination, these patients have greater resistance to standard treatment. This is a report of a typical case of this rare presentation, aiming to share the knowledge and favor earlier diagnosis of the disease.

Histoid leprosy presenting as a large tumor.

Histoid leprosy is a rare form of multibacillary leprosy, characterized by the presence of papules, plaques, or nodules whose appearance is keloid-like, skin colored, or erythematous. Fusiform cells are the main histopathological feature. Due to the fact that it can simulate other dermatological lesions, for example, dermatofibroma and neurofibroma, it constitutes a diagnostic challenge for clinicians and pathologists. It is a bacilliferous form of leprosy, and it plays an important role in disease transmission. A case of a patient with histoid leprosy living in the Northeast Region of Brazil is reported.

A genetic variant in the TRAF1/C5 gene lead susceptibility to active pulmonary tuberculosis by decreased TNF-α levels.

Host genetics are important to consider in the role of resistance or susceptibility for developing active pulmonary tuberculosis (TB). Several association studies have reported the role of variants in STAT4 and TRAF1/C5 as risk factors to autoimmune diseases. Nevertheless, more data is needed to elucidate the role of these gene variants in infectious disease. Our data reports for the first time, variant rs10818488 in the TRAF1/C5 gene (found 47% of the population worldwide), is associated with susceptibility (OR = 1.51) to development TB. Multivariate analysis evidenced association between rs10818488 TRAF1/C5 and risk to multibacillary TB (OR = 4.18), confers increased bacteria load in the lung, indicates a decreased ability to control pathogen levels in the lung, and spread of the pathogen to new hosts. We showed that the "loss-of-function" variant in TRAF1/C5 led to susceptibility for TB by decreased production of TNF-α. Our results suggest the role of variant TRAF1/C5 in susceptibility to TB as well as in clinical presentation of multibacillary TB.

Patterns and determinants of treatment completion and default among newly diagnosed multibacillary leprosy patients: A retrospective cohort study.

BACKGROUND: Poor treatment adherence among leprosy patients contribute to relapse, development of antimicrobial resistance, and the eventual plateauing of the prevalence and incidence of leprosy not just in the Philippines, but also worldwide. For this reason, we aimed to identify the patterns and determinants affecting treatment completion and default among multibacillary leprosy patients. METHODS: We conducted a retrospective cohort study involving three large hospitals in Metro Manila, Philippines. Patients who started the World Health Organization - Multiple Drug Therapy for multibacillary leprosy between January 1, 2007 and December 31, 2013 were included in the study. Selected socio-demographic and clinical data were abstracted from the patient treatment records. Survival analysis and proportional hazards regression were used to analyze the data. RESULTS: Records of 1,034 patients with a total follow-up time of 12,287 person-months were included in the analysis. Most patients were male, younger than 45 years old, had an initial bacterial index between 1 and 4, and were residents of Metro Manila. Less than 20% had their treatment duration extended to more than 12 months. Treatment adherence of the patients was poor with less than 60% completing treatment. Most patients complete their treatment within 12 months, but treatment duration may be extended for up to three years. Patients who default from treatment usually do so a few months after initiating it. After adjusting for other variables, hospital, initial bacterial index, and non-extended treatment duration were associated with treatment completion. These factors, in addition to age, were also found to be associated with treatment default. CONCLUSION: This study provides quantitative evidence that there might be marked variations in how doctors in particular hospitals manage their patients, and these findings underscore the need to revisit and re-evaluate clinical practice guidelines to improve treatment outcomes and adherence.

Histoid leprosy - A rare clinical presentation.

Histoid leprosy is considered a rare form of lepromatous leprosy. Its peculiar clinical picture makes its diagnosis a challenging one, which can delay starting treatment and perpetuate the disease as endemic. In addition to representing a reservoir of bacilli, and being an important means of contamination, these patients have greater resistance to standard treatment. This is a report of a typical case of this rare presentation, aiming to share the knowledge and favor earlier diagnosis of the disease.

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.

Case for diagnosis. Infiltrated areas on the trunk

Abstract Leprosy is an infectious disease with chronic evolution, caused by Mycobacterium leprae, an acid-fast bacillus that mainly affects the skin and peripheral nervous tissue. Many of the clinical manifestations of leprosy can mimic connective tissue diseases. The authors present the case of a 49-year-old woman who had been treated for four years for systemic lupus erythematosus in a rheumatological service. Skin biopsy of a plaque on the inguinal region was compatible with borderline lepromatous leprosy associated with a type 1 lepra reaction. The patient is undergoing treatment with multibacillary multidrug therapy, showing clinical improvement.

Case for diagnosis. Infiltrated areas on the trunk.

Leprosy is an infectious disease with chronic evolution, caused by Mycobacterium leprae, an acid-fast bacillus that mainly affects the skin and peripheral nervous tissue. Many of the clinical manifestations of leprosy can mimic connective tissue diseases. The authors present the case of a 49-year-old woman who had been treated for four years for systemic lupus erythematosus in a rheumatological service. Skin biopsy of a plaque on the inguinal region was compatible with borderline lepromatous leprosy associated with a type 1 lepra reaction. The patient is undergoing treatment with multibacillary multidrug therapy, showing clinical improvement.

An unusual case of multibacillary leprosy mimicking prurigo nodularis.

Leprosy is a chronic infectious disease with a wide range of clinical manifestations. The early diagnosis of leprosy is a worldwide challenge. We present a case of leprosy with unusual severe pruritus and generalized excoriated papules and nodules.