Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy.

BACKGROUND: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. METHODS: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. RESULTS: In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. CONCLUSION: Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.

Haemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis in a patient with leprosy.

Multidrug therapy has significantly reduced the global burden of Hansen's disease; however, complications from long-term treatment persist. A male resident of southern Kentucky, in his 30s and of Micronesian descent, presented with worsening abdominal pain associated with anorexia, fatigue, functional decline and occasional haemoptysis. He was compliant with multidrug therapy for leprosy. Laboratory investigations revealed pancytopenia. He was initially treated under a sepsis protocol and later switched to high-dose steroids due to a suspected immune reaction from missed corticosteroid doses. Despite aggressive treatment for refractory pancytopenia, the patient's condition deteriorated, and he passed away from cardiac arrest. Posthumous bone marrow biopsy revealed haemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis with bone marrow infiltration. This case highlights the importance of proactive fungal screening in immunocompromised leprosy patients, particularly in endemic regions, as early detection and timely intervention can prevent severe complications.

Hidden leprosy in a low-endemic area in southern Brazil: changes in endemicity following an active search.

BACKGROUND: Leprosy, a neglected tropical disease, is reported in over 120 countries, with upwards of 200,000 new cases annually. This Cross-Sectional Cohort Study aimed to delineate the epidemiological profile of leprosy in a low-endemic area in southern Brazil, both before and after implementing an active search strategy. METHODS: The study examined two surveillance periods in Caçador, Santa Catarina, Brazil. The active search strategy was carried out through the application of the LSQ by the community health workers as a screening and detection tool for new cases of leprosy and this was compared with passive case detection. The first spanned from 2014 to 2020, and the second from January 2021 to August 2023. FINDINGS: 48 leprosy cases were reported throughout the study, 83.3 % of which were diagnosed as multibacillary. The first period had an average detection rate of 0.38 cases per 10,000 inhabitants, increasing to 1.19 cases per 10,000 inhabitants in the second period. Notably, there was a substantial shift in the degree of physical disability (GD), with more Grade 0 and Grade 1 disabilities observed post-active search. MAIN CONCLUSIONS: The study underscores the efficacy of active search strategies in early diagnosis, highlighting a 300 % increase in the annual average of diagnosed cases. This large number of detected cases demonstrates the high sensitivity of the LSQ. This approach significantly aids in uncovering hidden cases of leprosy, enhancing disease management and control in low-endemic areas indicating that the Ministry of Health should intensify leprosy control activities in these regions.

Diagnostic Utility of Multiplex Polymerase Chain Reaction in Patients of Clinically Suspected Pure Neuritic Leprosy by Identifying Mycobacterium leprae in Skin Biopsy Samples and Nasal Swabs.

Pure neuritic leprosy (PNL) often remains underdiagnosed due to the lack of simple, reliable diagnostic tools to detect Mycobacterium leprae. This study aimed to investigate the utility of multiplex polymerase chain reaction (MPCR) in easily accessible and less invasive biopsy sites, including skin biopsy samples and nasal swabs (NSs), to detect M. leprae. A total of 30 (N = 30) clinically suspected and untreated patients with PNL were recruited. Nasal swabs and skin biopsy samples from the innervation territory of an "enlarged nerve" were collected. DNA was extracted and subjected to MPCR (targeting leprae-specific repetitive element [RLEP], 16S rRNA, and SodA genes) and RLEP-PCR (individual gene PCR). The PCR products were analyzed by 3% agarose gel electrophoresis. In 30 patients with clinically suspected PNL, 60% (N = 18) of skin biopsy samples and 53% (N = 16) of NSs were found positive for M. leprae DNA by MPCR, whereas only 23.3% (N = 7) of skin biopsy samples and 10% (N = 3) of NSs were found positive by RLEP-PCR. MPCR demonstrated a greater positivity rate than did RLEP-PCR for detection of M. leprae. Serologic positivity for anti-natural disaccharide-octyl conjugated with bovine serum albumin (ND-O-BSA) antibodies was 80% (16/20), including 35% (7/20) of PNL patients for which the skin MPCR was negative. Both serologic positivity and skin MPCR positivity were observed in 65% of patients (N = 20). Multiplex polymerase chain reaction is a useful tool for detection for M. leprae in skin biopsy samples and NSs in clinically suspected cases of PNL, with the added advantages of being less invasive and technically easier than nerve biopsy.

Systemic Lupus Erythematosus Complicated with Mycobacterium Leprae Infection: a Rare Case Report.

BACKGROUND: In December 2023, our hospital confirmed a case of systemic lupus erythematosus complicated with Mycobacterium leprae infection. The patient has extensive patchy erythema on the back and face, with obvious itching. There are multiple subcutaneous masses on both hands, some of which are accompanied by tenderness, wave sensation, and other symptoms. The patient's mother has a history of leprosy and close contact with the patient. The patient tested positive for syphilis antibodies 2 years ago and did not receive formal treatment. There is no other history of chronic illness. METHODS: Under local anesthesia, the left hand skin lesion was excised, followed by tissue pathological biopsy, acid-fast staining, mNGS, and serum Treponema pallidum antibody detection. RESULTS: Pathological biopsy results: A large number of foam-like histiocytes, lymphocytes, and plasma cells were mainly found in the superficial and deep layers of the dermis, as well as around the blood vessels and sweat glands in the subcutaneous fat. Cellulose-like degeneration is seen in some blood vessel walls. Tissue acid-fast staining: positive, tissue mNGS detection: Mycobacterium leprae. CLINICAL DIAGNOSIS: 1. Borderline leprosy, 2. Subacute cutaneous lupus erythematosus. Treat with methylprednisolone 32 mg qd po + aluminum magnesium suspension 15 mL tid po + calcium carbonate D3 tablets 0.6 g qd po + rifampicin 450 mg qd po + dapsone 100 mg qd. After 10 days of treatment, the patient improved and was discharged from the hospital. CONCLUSIONS: Mycobacterium leprae infection occurs during SLE treatment and is often difficult to distinguish from skin symptoms caused by SLE. In the clinical treatment of infectious diseases, the effect of conventional anti-bacterial drugs is not good. The auxiliary examination indicates severe infection and the routine culture is negative. The possibility of special pathogen infection should be considered in combination with the medical history. With the popularity of new detection methods such as mNGS, the importance of traditional smear detection methods cannot be ignored.

Community tuberculosis screening, testing and care, Uganda.

Objective: To assess the effectiveness of a community-based tuberculosis and leprosy intervention in which village health teams and health workers conduct door-to-door tuberculosis screening, targeted screenings and contact tracing. Methods: We conducted a before-and-after implementation study in Uganda to assess the effectiveness of the community tuberculosis intervention by looking at reach, outputs, adoption and effectiveness of the intervention. Campaign 1 was conducted in March 2022 and campaign 2 in September 2022. We calculated percentages of targets achieved and compared case notification rates during the intervention with corresponding quarters in the previous year. We also assessed the leprosy screening. Findings: Over 5 days, campaign 1 screened 1 289 213 people (2.9% of the general population), of whom 179 144 (13.9%) fulfilled the presumptive tuberculosis criteria, and 4043 (2.3%) were diagnosed with bacteriologically-confirmed tuberculosis; 3710 (91.8%) individuals were linked to care. In campaign 2, 5 134 056 people (11.6% of the general population) were screened, detecting 428 444 (8.3%) presumptive tuberculosis patients and 8121 (1.9%) bacteriologically-confirmed tuberculosis patients; 5942 individuals (87.1%) were linked to care. The case notification rate increased from 48.1 to 59.5 per 100 000 population in campaign 1, with a case notification rate ratio of 1.24 (95% confidence interval, CI: 1.22-1.26). In campaign 2, the case notification rate increased from 45.0 to 71.6 per 100 000 population, with a case notification rate ratio of 1.59 (95% CI: 1.56-1.62). Of the 176 patients identified with leprosy, 137 (77.8%) initiated treatment. Conclusion: This community tuberculosis screening initiative is effective. However, continuous monitoring and adaptations are needed to overcome context-specific implementation challenges.

Neurological features of Hansen disease: a retrospective, multicenter cohort study.

To elucidate the neurological features of Hansen disease. The medical records of patients with confirmed Hansen disease transferred from the neurology department were reviewed, and all medical and neurological manifestations of Hansen disease were assessed. Eleven patients with confirmed Hansen disease, 10 with newly detected Hansen disease and 1 with relapsed Hansen disease, who visited neurology departments were enrolled. The newly detected patients with Hansen disease were classified as having lepromatous leprosy (LL, n = 1), borderline lepromatous leprosy (BL, n = 2), borderline leprosy (BB, n = 2), borderline tuberculoid leprosy (BT, n = 1), tuberculoid leprosy (TT, n = 2), or pure neural leprosy (PNL, n = 2). All of the patients with confirmed Hansen were diagnosed with peripheral neuropathy (100.00%, 11/11). The symptoms and signs presented were mainly limb numbness (100.00%, 11/11), sensory and motor dysfunction (100.00%, 11/11), decreased muscle strength (90.90%, 10/11), and skin lesions (81.81%, 9/11). Nerve morphological features in nerve ultrasonography (US) included peripheral nerve asymmetry and segmental thickening (100.00%, 9/9). For neuro-electrophysiology feature, the frequency of no response of sensory nerves was significantly higher than those of motor nerves [(51.21% 42/82) vs (24.70%, 21/85)(P = 0.0183*)] by electrodiagnostic (EDX) studies. Nerve histological features in nerve biopsy analysis included demyelination (100.00%, 5/5) and axonal damage (60.00%, 3/5). In addition to confirmed diagnoses by acid-fast bacteria (AFB) staining (54.54%, 6/11) and skin pathology analysis (100.00%, 8/8), serology and molecular technology were positive in 36.36% (4/11) and 100.00% (11/11) of confirmed patients of Hansen disease, respectively. It is not uncommon for patients of Hansen disease to visit neurology departments due to peripheral neuropathy. The main pathological features of affected nerves are demyelination and axonal damage. The combination of nerve US, EDX studies, nerve biopsy, and serological and molecular tests can improve the diagnosis of Hansen disease.

Dermoscopic features of nails in Leprosy patients in a tertiary referral hospital in West Java, Indonesia.

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. PURPOSES: We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. METHOD: This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. RESULT: Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. CONCLUSION: Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.

Navigating diagnostic and therapeutic challenges in ocular manifestations of Hansen's disease and trachoma: A narrative review.

Neglected tropical diseases (NTDs) encompass a group of approximately 20 diseases prevalent in tropical and subtropical regions, closely associated with poverty, affecting over a billion people in low-income countries. This manuscript aims to explore the ocular manifestations and burden of two significant NTDs, namely Hansen's disease and trachoma while addressing gaps in understanding and management. Hansen's disease, caused by Mycobacterium leprae , has a long history and presents with diverse neurological and ocular manifestations. Despite the availability of treatment, ocular complications persist, leading to significant visual impairment in some cases. The manuscript emphasizes the importance of early diagnosis, regular ophthalmic examinations, and follow-ups to prevent and control ocular complications, reducing the burden of visual impairment and blindness. Trachoma, caused by Chlamydia trachomatis , remains the leading infectious cause of blindness in underdeveloped and remote areas. The manuscript highlights the clinical diagnosis and implementation of the World Health Organization's (WHO's) SAFE (surgery, antibiotics, facial hygiene, and environmental sanitation) strategy to prevent transmission and associated blindness. However, challenges in health surveillance tools and underreporting of trachoma cases are addressed, emphasizing the need for improved strategies to combat the disease effectively. Through a comprehensive review of the ocular manifestations and management of Hansen's disease and trachoma, this manuscript contributes to the existing knowledge base and enhances a deeper understanding of these NTDs. Addressing gaps in understanding and management emphasizes the importance of implementing WHO's strategies and collaborative efforts to achieve the global goal of reducing the burden of NTDs and improving community health and well-being. The manuscript underscores the significance of early intervention, preventive measures, and technological advancements, providing valuable insights for policymakers, healthcare professionals, and researchers working in the field of NTDs.

Half a Century in Hiding: A Unique Case of Tuberculoid Leprosy with an Unprecedented Incubation Period.

BACKGROUND Leprosy, also known as Hansen's disease, is a neglected tropical disease with low prevalence in the United States. The disease's long incubation period can cause delayed presentation, and most affected individuals have a history of travel or work in leprosy-endemic regions. The immune response to Mycobacterium leprae determines the clinical characteristics of leprosy, with tuberculoid leprosy being characterized by well-defined granulomas and involvement of peripheral nerves. The recommended treatment is a combination of dapsone and rifampin for 12 months. CASE REPORT A 78-year-old man with a history of extensive travel to Africa and Asia 50 years ago, presented with a non-tender, non-pruritic, and hypopigmented skin lesion on his left knee. Biopsy results confirmed granulomatous inflammation and the presence of Mycobacterium leprae, leading to a diagnosis of tuberculoid/paucibacillary leprosy. The patient received dapsone and rifampin treatment, which resulted in symptom improvement. CONCLUSIONS The patient's long incubation period of 50 years between exposure and symptom onset is remarkable and possibly one of the longest reported for tuberculoid leprosy. It emphasizes the importance of considering leprosy in cases with an extensive travel history and long incubation periods. Our patient's case presented contradictory staining results, suggesting potential sampling variation or a rare mixed leprosy form. Based on his clinical findings, he was diagnosed with tuberculoid leprosy. Early diagnosis and treatment are crucial to prevent irreversible nerve damage and improve patient outcomes. Healthcare providers should be vigilant in acquiring a detailed travel history to facilitate early diagnosis and appropriate management of leprosy cases.

Leprosy mimicking autoimmune diseases: a case series.

OBJECTIVES: Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Less frequently, there is involvement of the musculoskeletal system, and occurrence of systemic manifestation with non-specific symptoms such as fever, fatigue and myalgia. Therefore, leprosy can often mimic autoimmune diseases such as arthritis, vasculitis, or collagenosis and be mis-diagnosed. METHODS: This study describes a series of cases of leprosy mimicking autoimmune diseases in patients treated in the Rheumatology Department of our centre in the period 2019 to 2023. All patients were investigated regarding leprosy criteria and had clinical evaluation, serum markers, and histopathological analyses recorded. The diagnosis of leprosy was confirmed using skin biopsy followed by testing for acid-fast bacillus (AFB) or smear microscopy. RESULTS: Six patients who were initially investigated for autoimmune diseases were identified as diagnosed as leprosy cases, fulfilling both clinical and histopathologic criteria, two of whom presented with symptoms of polyarthritis with an inflammatory characteristic, two diffuse erythematous-violaceous lesions, three recurrent fever, three arthralgia, and one Raynaud's phenomenon, which are all characteristics present most frequently in rheumatologic diseases. CONCLUSIONS: We must consider the bacillary infection as a differential diagnosis of autoimmune diseases. Histopathological analysis is an important tool and the gold standard for diagnostic confirmation.

Perfil de conhecimento sobre hanseníase entre pacientes de um hospital universitário: um estudo transversal / Profile of Leprosy knowledge among patients at a university hospital: a cross-sectional study / Perfil de conocimientos sobre la lepra entre los pacientes de un hospital universitario: estudio transversal

Introdução: a hanseníase é uma doença causada pelo bacilo Mycobacterium leprae, que afeta a pele e o sistema nervoso periférico, apresentando alta endemicidade no Brasil. As representações sociais negativas sobre ela resultam da construção histórica baseada em crenças e medos. Uma das estratégias preconizadas pelo Ministério da Saúde para reduzir a carga de hanseníase é a educação em saúde, já que um dos obstáculos para a diminuição da incidência da doença é a falta de informação. Objetivo: este estudo tem como objetivo identificar o conhecimento dos pacientes de um ambulatório de dermatologia acerca da hanseníase. Metodologia: trata-se de um estudo observacional e transversal, que se desenvolveu por meio de um questionário com nove questões sobre hanseníase, elaborado pelos autores e aplicados em pacientes do ambulatório de dermatologia de um hospital público em Pernambuco. Resultados: quinhentas pessoas responderam ao questionário, sendo a maioria mulheres e pessoas com mais de 60 anos. Cerca de 92% já haviam ouvido falar sobre lepra/hanseníase, mas menos da metade sabia que se tratava da mesma doença. Além disso, apenas 50,4% tinham alguma informação sobre a doença, sendo a identificação da lesão cutânea a mais conhecida, enquanto a transmissão e o tratamento eram menos conhecidos. Conclusão: percebe-se, portanto, que medidas de educação em saúde visando melhorar o conhecimento acerca da transmissão e do tratamento são de grande importância, principalmente por parte de profissionais de saúde, educação e mídia. Além disso, mais estudos que evidenciem o conhecimento da população sobre a doença precisam ser realizados para que a falta de informação possa ser suprida pelos profissionais e, assim, o combate à hanseníase e ao preconceito associado a ela seja realizado de modo mais efetivo. (AU)

Introduction: Hansen's disease is caused by the bacillus Mycobacterium leprae, which affects the skin and peripheral nervous system. It is highly endemic in Brazil. Negative social representations about leprosy are the result of historical beliefs and fears. Health education is a recommended strategy by Brazil's Ministry of Health to reduce the burden of leprosy. Lack of health information is one of the obstacles to reducing the incidence of the disease. Objective: this study aims to identify the level of knowledge that the patients at a dermatology outpatient clinic have about leprosy. Methods: this is a cross-sectional observational study, that utilized a nine-question leprosy questionnaire and was administered to patients at a public hospital dermatology outpatient clinic in Pernambuco. Results: five hundred people answered the questionnaire. The majority of respondents were women over the age of 60. Approximately 92% of respondents were aware of leprosy/Hansen's disease, but less than half correctly identified it as the same disease. Furthermore, only 50.4% of respondents had any knowledge about the disease. The identification of skin lesions was the most well-known symptom, while transmission and treatment were less familiar. Conclusion: therefore, it is evident that health education measures aimed at improving knowledge about the transmission and treatment of leprosy are crucial, particularly among health, educators, and media professionals. Additionally, conducting more studies to assess the population's knowledge of the disease is necessary to address the lack of information and enable professionals to combat leprosy and prejudices more effectively. (AU)

Challenges and advances in serological and molecular tests to aid leprosy diagnosis.

Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, Mycobacterium leprae and Mycobacterium lepromatosis. Despite multidrug therapy (MDT) success, leprosy accounts for more than 200,000 new cases yearly. Leprosy diagnosis remains based on the dermato-neurologic examination, but histopathology of skin biopsy and bacilloscopy of intradermal scraping are subsidiary diagnostic tests that require expertise and laboratory infrastructure. This minireview summarizes the state of the art of serologic tests to aid leprosy diagnosis, highlighting enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (POCT) biotechnologies. Also, the impact of the postgenomic era on the description of new recombinantly expressed M. leprae-specific protein antigens, such as leprosy Infectious Disease Research Institute (IDRI) diagnostic (LID)-1 is summarized. Highly specific and sensitive molecular techniques to detect M. leprae DNA as the quantitative polymerase chain reaction (qPCR) and the loop-mediated isothermal amplification (LAMP) are briefly reviewed. Serology studies using phenolic glycolipid-I (PGL-I) semi-synthetic antigens, LID-1 fusion antigen, and the single fusion complex natural disaccharide-octyl (NDO)-LID show high sensitivity in multibacillary (MB) patients. However, serology is not applicable to paucibacillary patients, as they have weak humoral response and robust cell-mediated response, requiring tests for cellular biomarkers. Unlike ELISA-based tests, leprosy-specific POCT based on semi-synthetic PGL-I antigens and NDO-LID 1 antigen is easy to perform, cheaper, equipment-free, and can contribute to early diagnosis avoiding permanent incapacities and helping to interrupt M. leprae transmission. Besides its use to help diagnosis of household contacts or at-risk populations in endemic areas, potential applications of leprosy serology include monitoring MDT efficacy, identification of recent infection, especially in young children, as surrogate markers of disease progression to orient adult chemoprophylaxis and as a predictor of type 2 leprosy reactions. Advances in molecular biology techniques have reduced the complexity and execution time of qPCR confirming its utility to help diagnosis while leprosy-specific LAMP holds promise as an adjunct test to detect M. leprae DNA.

Leprosy with type 1 reaction in a patient from Ontario, Canada without recent travel misdiagnosed as vasculitic neuropathy: a case report.

BACKGROUND: Leprosy is rare within non-endemic countries such as Canada, where cases are almost exclusively imported from endemic regions, often presenting after an incubation period of as many as 20 years. Due to its rarity and prolonged incubation period, diagnosis is often delayed, which may result in neurologic impairment prior to the initiation of treatment. In this report we describe a case that is novel in its incubation period, which is the longest reported to-date and may have contributed to diagnostic delay. The case also uniquely demonstrates the challenges of distinguishing leprosy reactions from new rheumatologic manifestations in a patient with established autoimmune disease. CASE PRESENTATION: We describe an 84-year-old male patient with rheumatoid arthritis on methotrexate and hydroxychloroquine, with no travel history outside Canada for 56 years, who presented in 2019 with new-onset paresthesias and rash. His paresthesias persisted despite a short course of prednisone, and his rash recurred after initial improvement. He underwent skin biopsy in May 2021, which eventually led to the diagnosis of leprosy. He was diagnosed with type 1 reaction and was started on rifampin, dapsone, clofazimine and prednisone, with which his rash resolved but his neurologic impairment remained. CONCLUSION: This case report serves to highlight the potential for leprosy to present after markedly prolonged incubation periods. This is especially relevant in non-endemic countries that is home to an aging demographic of individuals who migrated decades ago from endemic countries. The importance of this concept is emphasized by the persistent neurologic impairment suffered by our case due to untreated type 1 reaction. We also demonstrate the necessity of skin biopsy in distinguishing this diagnosis from other autoimmune mimics in a patient with known autoimmune disease.

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.

Catastrophic ocular complications in leprosy: a case report.

Leprosy is a chronic, granulomatous infectious disease commonly affecting the skin, nerves, mucosa and eyes. The stigma associated with the disease frequently leads to delay in presentation to health professionals. Treated patients, though considered cured presumptively, many continue to live with physical disabilities and deformities. Intact visual acuity prevents humans from trauma and any reduction in visual acuity, especially in leprosy, increases the risk of getting injured by many folds. Here, we present a case of leprosy with complete loss of vision due to bilateral anterior staphyloma secondary to keratitis and his physical deformities preventing him to take care of his eyes. This paper aims to emphasize on the importance of a baseline ophthalmology consultation in all newly diagnosed leprosy patients and repeat examination at onset of any new symptoms of the eye.

Hi-plex deep amplicon sequencing for identification, high-resolution genotyping and multidrug resistance prediction of Mycobacterium leprae directly from patient biopsies by using Deeplex Myc-Lep.

BACKGROUND: Expansion of antimicrobial resistance monitoring and epidemiological surveillance are key components of the WHO strategy towards zero leprosy. The inability to grow Mycobacterium leprae in vitro precludes routine phenotypic drug susceptibility testing, and only limited molecular tests are available. We evaluated a culture-free targeted deep sequencing assay, for mycobacterial identification, genotyping based on 18 canonical SNPs and 11 core variable-number tandem-repeat (VNTR) markers, and detection of rifampicin, dapsone and fluoroquinolone resistance-associated mutations in rpoB/ctpC/ctpI, folP1, gyrA/gyrB, respectively, and hypermutation-associated mutations in nth. METHODS: The limit of detection (LOD) was determined using DNA of M. leprae reference strains and from 246 skin biopsies and 74 slit skin smears of leprosy patients, with genome copies quantified by RLEP qPCR. Sequencing results were evaluated versus whole genome sequencing (WGS) data of 14 strains, and versus VNTR-fragment length analysis (FLA) results of 89 clinical specimens. FINDINGS: The LOD for sequencing success ranged between 80 and 3000 genome copies, depending on the sample type. The LOD for minority variants was 10%. All SNPs detected in targets by WGS were identified except in a clinical sample where WGS revealed two dapsone resistance-conferring mutations instead of one by Deeplex Myc-Lep, due to partial duplication of the sulfamide-binding domain in folP1. SNPs detected uniquely by Deeplex Myc-Lep were missed by WGS due to insufficient coverage. Concordance with VNTR-FLA results was 99.4% (926/932 alleles). INTERPRETATION: Deeplex Myc-Lep may help improve the diagnosis and surveillance of leprosy. Gene domain duplication is an original putative drug resistance-related genetic adaptation in M. leprae. FUNDING: EDCTP2 programme supported by the European Union (grant number RIA2017NIM-1847 -PEOPLE). EDCTP, R2Stop: Effect:Hope, The Mission To End Leprosy, the Flemish Fonds Wetenschappelijk Onderzoek.

Percepção dos pacientes sobre a busca pelo diagnóstico da hanseníase e o atendimento nas Redes de Atenção à Saúde / Patients' perception of the search for a leprosy diagnosis and care in health care networks

O objetivo do estudo foi avaliar a percepção dos pacientes quanto ao atendimento nas Redes de Atenção à Saúde, desde o surgimento dos sintomas até o diagnóstico de hanseníase. Trata-se de um estudo qualitativo com 15 pacientes com hanseníase atendidos em um centro de referência no estado do Piauí. A coleta de dados foi realizada entre agosto e setembro de 2022, com o uso de um roteiro de entrevista semiestruturado de três blocos: 1) perfil sociodemográfico e econômico; 2) dados clínicos; e 3) questões semidirigidas relacionadas ao itinerário terapêutico para o diagnóstico e tratamento. Foram incluídos pacientes com hanseníase em tratamento e idade superior a 18 anos. Excluiu-se aqueles que não responderam questionamentos essenciais para os objetivos do estudo ou tangenciaram o tema nesse sentido. Predominaram pacientes mulheres, casadas, com média de idade de 58 anos, ensino fundamental completo, que recebiam menos de um salário-mínimo, autodeclaradas como pardas, residentes em Teresina e com a forma multibacilar da doença. Após a análise de conteúdo, emergiram três categorias temáticas: 1) dificuldades no autorreconhecimento das manifestações clínicas da hanseníase; 2) itinerário terapêutico do usuário com hanseníase na rede de atenção à saúde; e 3) percepção dos pacientes com hanseníase sobre o aten-dimento dos profissionais de saúde. A percepção dos pacientes permite concluir que a busca pelo diagnóstico e o atendimento em saúde foi um processo longo e conflituoso até que estes chegassem a ser atendidos na Atenção Primária.(AU)

The aim of the study was to evaluate patients' perception regarding care in healthcare networks, from the emergence of symptoms to the diagnosis of leprosy. This is a qualitative study with 15 patients with leprosy managed in a referral center in the state of Piauí. Data collection occurred from August to September 2022, with the use of a 3-block semi-structured interview guide: 1) sociodemographic and economic profile; 2) clinical data; and 3) semi-structured questions about the therapeutic itinerary taken for diagnosis and treatment. Included were leprosy patients aged undergoing treatment aged 18 years or above. Excluded were patients who failed to answer questions that were essential to meet study objectives or who barely touched upon the subject. There was a predominance of female, married patients, self-declared as brown (parda), at a mean age of 58 years, with complete elementary school education that earned less than minimum wage and lived in Teresina, with the multibacillary form of disease. After content analysis, three thematic categories emerged: 1) difficulty in self-recognizing the clinical manifestations of leprosy; 2) therapeutic route of the leprosy user in the healthcare network; and 3) perception of leprosy patients about treatment provided by healthcare professionals. The patients' perception allows us to conclude that the search for diagnosis and health care was a long and conflicting process until they reached Primary Care.(AU)

Evolução do grau de incapacidade física e do escore olhos, mãos e pés em casos novos de hanseníase: do diagnóstico à alta medicamentosa / Evolution of the degree of physical disability and the eye, hand and foot score in new cases of leprosy: from diagnosis to medication discharge

Este estudo tem por objetivo avaliar a evolução do grau de incapacidade física e do escore olhos, mãos e pés, do diagnóstico à alta medicamentosa, segundo as variáveis sociodemográficas e clínicas, em pacientes diagnosticados com hanseníase. Trata-se de estudo transversal, baseado na análise de 71 pacientes com diagnóstico de hanseníase, acompanhados no Hospital Eduardo de Menezes, centro de referência em Belo Horizonte, Minas Gerais, Brasil, entre janeiro de 2017 a dezembro de 2020. Foi observado predomínio do sexo feminino (53,5%), média de idade de 46 anos, sendo a maioria procedente de outros municípios do interior de Minas Gerais (54,9%). A forma clínica mais frequente foi a dimorfa (64,8%), classificação operacional multibacilar (84,5%). O grau de incapacidade física 0 foi o mais prevalente no diagnóstico (56,5%) e na alta (53,1%), e em relação ao escore olhos, mãos e pés, houve variação entre 0 e 10 no diagnóstico e entre 0 e 8 na alta. Pelo teste de McNemar foi observado que dentre os pacientes que apresentavam algum grau de incapacidade física no momento do diagnóstico, 30,8% apresentaram ausência de incapacidade na alta. Ao comparar a evolução do grau de incapacidade física de paucibacilares e multibacilares no momento do diagnóstico e da alta, houve manutenção em 59,3% e melhora em 17,2% dos pacientes. Os dados apresentados indicam que muitos pacientes foram tratados tardiamente já apresentando as formas graves e com sequelas, já que o estudo foi desenvolvido em um centro de referência, que atende casos mais complexos e com complicações já instaladas. Os dados sugerem que pacientes assistidos que realizam o tratamento com poliquimioterapia podem ter melhora das incapacidades já instaladas. O mesmo ocorreu com o escore olhos, mãos e pés, que ao final do tratamento instituído houve melhora se comparado com a admissão.(AU)

This study aims to evaluate the evolution of the degree of physical disability and the eye, hand and foot score, from diagnosis to medication discharge, according to sociodemographic and clinical variables, in patients diagnosed with leprosy. This is a cross-sectional study, based on the analysis of 71 patients diagnosed with leprosy, followed by Hospital Eduardo de Menezes, a reference center in Belo Horizonte, Minas Gerais, Brazil, between January 2017 and December 2020. There was a predominance of females (53.5%), average age of 46 years old, the majority coming from other municipalities in the interior of Minas Gerais (54.9%). The most frequent clinical form was borderline (64.8%), multibacillary operational classification (84.5%). Degree of physical disability 0 was the most prevalent at diagnosis (56.5%) and at discharge (53.1%); in relation to the eye, hand and foot score, there was variation between 0 and 10 at diagnosis and between 0 and 8 at discharge. By the McNemar test, it was observed that of the patients who had degree of physical disability at the time of diagnosis, 30.8% had no disability at discharge. When comparing the evolution of the GIF in paucibacillary and multibacillary patients at the time of diagnosis and discharge, there was maintenance in 59.3% and improvement in 17.2% of the patients. The presented data indicates that many patients were treated late, already presenting severe forms and with sequelae, since the study was carried out in a reference center, which treats cases with complications already installed and more complex cases. The data suggest that assisted patients undergoing treatment with multidrug therapy may experience improvement in disabilities already established. The same occurred with eye, hand and foot score, at the end of the established treatment there was an improvement compared to admission.(AU)