Tecnologias em saúde da hanseníase no âmbito da Atenção Primária à Saúde: revisão de escopo / Leprosy health technologies in Primary Health Care: a scoping review / Tecnologías en salud de la lepra en el ámbito de la Atención Primaria a la Salud: revisión del alcance

Objetivo: mapear as tecnologias em saúde para manejo no cuidado à pessoa com hanseníase na Atenção Primária à Saúde. Método: revisão de escopo baseada na metodologia do JBI, em seis bases de dados, seguindo a checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Foram incluídos estudos publicados em qualquer idioma, com diferentes abordagens metodológicas. Resultados: os 14 estudos incluídos na revisão mostram que a aplicabilidade de tecnologias para o manejo do cuidado a pessoa com hanseníase na Atenção Primária à Saúde, possibilitam a confirmação de diagnóstico, acompanhamento, monitoramento e prevenção de incapacidades. Conclusão: nota-se que tecnologia em saúde se apresentam como ferramentas que auxiliam no processo de cuidado na assistência a pessoas com hanseníase, a fim de permitir aos profissionais de saúde conhecimento sobre a doença, proporcionando qualidade na sua prática de saúde.

Objective: to map health technologies for managing the care of people with leprosy in Primary Health Care. Method: scoping review based on the JBI methodology in six databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Studies published in any language were included, with different methodological approaches. Results: the 14 studies included in the review show that the applicability of technologies for the management of care for people with leprosy in Primary Health Care makes it possible to confirm diagnosis, follow-up, monitoring, and prevention of disabilities. Conclusion: it has been noted that health technologies are tools that help in the process of caring for people with leprosy, to provide health professionals with knowledge about the disease, improving quality of health practice.

Objetivo: mapear las tecnologías en salud para el manejo en el cuidado a la persona con lepra en la Atención Primaria a la Salud. Método: revisión del alcance basada en la metodología del JBI, en seis bases de datos, siguiendo la checklist Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Se han incluido estudios publicados en cualquier idioma, con diferentes enfoques metodológicos. Resultados: los 14 estudios incluidos en la revisión muestran que la aplicabilidad de tecnologías para el manejo del cuidado a la persona con lepra en la Atención Primaria a la Salud posibilita la confirmación de diagnóstico, seguimiento, monitoreo y prevención de incapacidades. Conclusión: se percibe que las tecnologías en salud se presentan como herramientas que ayudan en el proceso de cuidado en la asistencia a personas con lepra, con fines de permitir a los profesionales de salud el acceso al conocimiento sobre la enfermedad, proporcionando calidad en su práctica de salud.

Lepromatous Leprosy and Charcot Neuroarthropathy of Insensate Feet: A Case Report.

Leprosy is a chronic infection of the skin, eyes, and peripheral nerves due to the slow-growing, acid-fast bacillus Mycobacterium leprae. Devastating complications include Charcot neuroarthropathy and insensate hands and feet. We present the case of an 81-year-old female with rheumatoid arthritis and 50 years of polar lepromatous leprosy who suffered from bilateral collapsed arches, flat feet, and bone deformities of Charcot feet.

Adenosine A2A receptor as a potential regulator of Mycobacterium leprae survival mechanisms: new insights into leprosy neural damage.

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells-glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host-pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron-glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae-Schwann cell interaction. Methods: M. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay. Results: We demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB. Conclusion: These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.

Buruli ulcer, tuberculosis and leprosy: Exploring the One Health dimensions of three most prevalent mycobacterial diseases: A narrative review.

ΟBJECTIVES: Although Buruli ulcer, tuberculosis, and leprosy are the three most common mycobacterial diseases, One Health dimensions of these infections remain poorly understood. This narrative review aims at exploring the scientific literature with respect to the presence of animal reservoir(s) and other environmental sources for the pathogens of these infections, their role in transmission to humans and the research on/practical implementation of One Health relevant control efforts. METHODS: The literature review was conducted using the online databases PubMed, Scopus, ProQuest and Google Scholar, reviewing articles that were written in English in the last 15 years. Grey literature, published by intergovernmental agencies, was also reviewed. RESULTS: For the pathogen of Buruli ulcer, evidence suggests possums as a possible animal reservoir and thus having an active role in disease transmission to humans. Cattle and some wildlife species are deemed as established animal reservoirs for tuberculosis pathogens, with a non-negligible proportion of infections in humans being of zoonotic origin. Armadillos constitute an established animal reservoir for leprosy pathogens with the transmission of the disease from armadillos to humans being deemed possible. Lentic environments, soil and other aquatic sources may represent further abiotic reservoirs for viable Buruli ulcer and leprosy pathogens infecting humans. Ongoing investigation and implementation of public health measures, targeting (sapro)zoonotic transmission can be found in all three diseases. CONCLUSION: Buruli ulcer, tuberculosis and leprosy exhibit important yet still poorly understood One Health aspects. Despite the microbiological affinity of the respective causative mycobacteria, considerable differences in their animal reservoirs, potential environmental sources and modes of zoonotic transmission are being observed. Whether these differences reflect actual variations between these diseases or rather knowledge gaps remains unclear. For improved disease control, further investigation of zoonotic aspects of all three diseases and formulation of One Health relevant interventions is urgently needed.

A case report and literature review: Mycobacterium leprae infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) that is responsible for deformities and irreversible peripheral nerve damage and has a broad spectrum of clinical and serological manifestations. Leprosy primarily affects the peripheral nerves and rarely presents with central nervous system involvement. Diagnosing leprosy can still be difficult in some cases, especially when the infection involves uncommon clinical manifestations and extracutaneous sites. Delayed diagnosis and treatment of leprosy may lead to irreversible damage and death. CASE PRESENTATION: We report a case of a 30-year-old female presenting with "repeated high fever with symptoms of headache for 14 days". On the day of admission, physical signs of lost eyebrows and scattered red induration patches all over her body were observed. The patient's diagnosis was based on the clinical characteristics using a combination of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and slit-skin smear. After confirming Listeria meningitis and multibacillary leprosy with erythema nodosum leprosum (ENL), a type 2 reaction, she was treated with ampicillin sodium, dapsone, rifampicin, clofazimine, methylprednisolone, and thalidomide. At the 1-year follow-up, the frequency and severity of headaches have significantly decreased and a good clinical response with improved skin lesions was found. CONCLUSION: This case highlights the importance of considering leprosy, which is a rare and underrecognized disease, in the differential diagnosis of skin rashes with rheumatic manifestations, even in areas where the disease is not endemic, and physicians should be alerted about the possibility of central nervous system infections. In addition, mNGS can be used as a complementary diagnostic tool to traditional diagnostic methods to enhance the diagnostic accuracy of leprosy.

Leprosy knowledge among primary care physicians in Southern Brazil: are we underdiagnosing?

BACKGROUND: Leprosy is a chronic infection with high morbidity in Brazil. Primary care physicians' lack of knowledge about the disease may play a significant role in underdiagnosis. This study aimed to assess primary care physicians' ability to identify typical leprosy skin lesions and their knowledge of the subject. METHODS: This cross-sectional study relied on a questionnaire in which participating doctors chose one main diagnostic hypothesis and two differential diagnoses for each skin lesion presented. Five leprosy lesions were included. Questions regarding management, follow-up, and diagnostic workup for the disease were also included. The questionnaire was sent to primary care physicians working in Curitiba, in the Southern Brazilian state of Paraná, and dermatologists, who constituted the control group. RESULTS: Thirty-two primary care physicians and 26 dermatologists agreed to participate in the study. Primary care physicians accurately identified a mean of 1.8 ± 1.2 of the five leprosy skin lesions, while dermatologists accurately identified 2.5 ± 0.9 (P = 0.009). The main misdiagnosed leprosy forms were the lepromatous and histoid variants. Among primary care physicians, 56.2% claimed to have little knowledge of the subject and a large share of participants was unaware of recent updates in treating paucibacillary forms, even within the dermatologist subgroup. CONCLUSIONS: Primary care physicians in Curitiba have little information regarding the diagnosis, treatment, and follow-up of leprosy. Even dermatologists had difficulties with treatment and patient management, emphasizing the constant need for education on this subject.

Molecular and Serological Surveillance for Mycobacterium leprae and Mycobacterium lepromatosis in Wild Red Squirrels (Sciurus vulgaris) from Scotland and Northern England.

Leprosy is a poverty-associated infectious disease in humans caused by Mycobacterium leprae or M. lepromatosis, often resulting in skin and peripheral nerve damage, which remains a significant public health concern in isolated areas of low- and middle-income countries. Previous studies reported leprosy in red squirrels in the British Isles, despite the fact that autochthonous human cases have been absent for centuries in this region. To investigate the extent of M. leprae and M. lepromatosis presence in wild red squirrels in the northern UK, we analyzed 220 blood/body cavity fluid samples from opportunistically sampled red squirrels (2004-2023) for specific antibodies against phenolic glycolipid-I, a cell wall component specific for these leprosy bacilli. Additionally, we assessed bacillus-derived DNA by real-time PCR (qPCR) in 250 pinnae from the same cohort. M. lepromatosis and M. leprae DNA were detected by qPCR in 20.4% and 0.8% of the squirrels, respectively. No cases of co-detection were observed. Detectable levels of anti-PGL-I antibodies by UCP-LFA were observed in 52.9% of animals with the presence of M. lepromatosis determined by qPCR, and overall in 15.5% of all animals. In total, 22.6% (n = 296) of this UK cohort had at least some exposure to leprosy bacilli. Our study shows that leprosy bacilli persist in red squirrels in the northern UK, emphasizing the necessity for ongoing molecular and serological monitoring to study leprosy ecology in red squirrels, gain insight into potential zoonotic transmission, and to determine whether the disease has a conservation impact on this endangered species.

Childhood leprosy in Buenos Aires: four cases report. / Lepra infantil en Buenos Aires. Reporte de cuatro casos.

Childhood leprosy, which affects children up to 14 years old, is characterized by a delay in diagnosis since it is usually confused with other dermatoses. Its presence in a child is a relevant epidemiological indicator since it signals active disease transmission. We present 4 patients between 5 and 14 years old who attended a public hospital in Buenos Aires -two patients with borderline tuberculoid leprosy, one with lepromatous leprosy, and one with indeterminate leprosy.The World Health Organization provides therapy for people between 10 and 14 but does not consider children under 10. This difficulty implies adapting the dosage and pharmaceutical form to each patient under this age. Finally, it should be noted that the diagnosis of the patients led to the diagnosis and treatment of the disease in adult cohabitants.

La lepra infantil, aquella que afecta a niños de hasta 14 años, se caracteriza por la demora en su diagnóstico, ya que habitualmente es confundida con otras dermatosis. Su presencia en un niño es un indicador epidemiológico relevante, dado que señala la transmisión activa de la enfermedad. Presentamos 4 pacientes de entre 5 y 14 años asistidos en un hospital público de la Ciudad de Buenos Aires. Dos pacientes presentaron lepra borderline tuberculoide; uno, lepra lepromatosa; y otra, lepra indeterminada. La Organización Mundial de la Salud facilita la terapéutica para la población entre 10 y 14 años, pero no contempla a los menores de 10 años. Esta dificultad implica adecuar la dosis y la forma farmacéutica a cada paciente menor de la edad referida. Finalmente, es de destacar que el diagnóstico de los pacientes llevó al diagnóstico y tratamiento de la enfermedad en convivientes adultos.

Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

OBJECTIVE: This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. METHODS: A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. RESULTS: Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. CONCLUSIONS: Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

Neurologic Complications of Leprosy: A Case Series.

Leprosy, caused by the Mycobacterium leprae complex, manifests as a chronic infection. Its hallmark presentation involves the neurocutaneous syndrome, characterized by peripheral nerve involvement and dermatologic lesions. Neurological complications significantly contribute to disability in leprosy patients. Peripheral neuropathy may manifest acutely or chronically, in either axonal or demyelinating forms, and can present as mononeuropathy, mononeuropathy multiplex, or polyneuropathy. The diverse clinical presentations emphasize the importance of considering leprosy in the differential diagnosis of peripheral neuropathy, enabling appropriate investigative approaches. Skin and nerve biopsies, slit skin smears, and nerve conduction studies serve as crucial diagnostic tools for identifying peripheral nerve involvement in leprosy. In this paper, we present three cases of leprosy with peripheral nerve involvement, discussing their clinical spectrum, diagnostic approach, and management.

A Cross-Sectional Study to Evaluate the Role of the Nuclear Factor Kappa B (Nf-κB) Pathway in Regulating the Cytokine Cascade and as a Potential Therapeutic Target in Leprosy.

Pattern recognition receptors (PRRs), which are found in microorganisms but not in hosts, allow Leprae bacilli to be recognized as foreign. Several kinds of pattern recognition receptors, such as toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-1-like receptors (RLRs), are present in the innate immune system. Sen and Baltimore (1986) discovered the transcription factor nuclear factor kappa-B (NF-B), employed by eukaryotic cells to regulate immunity, cell differentiation and proliferation. This study aimed to evaluate the role of the nuclear factor kappa B (NF-B) pathway in controlling the cytokine cascade in leprosy due to a lack of understanding of the link between cytokines and the severity of leprosy. Clinically suspected Hansen's patients were analysed for 4 years. Newly diagnosed leprosy patients were considered to have leprosy disease control (LDC). The cases with active or new lesions and an increase in BI by at least 2+, 12 months after completion of MDT were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (HC). An ELISA was performed to measure the concentration of five human cytokines. By qRT-PCR, the quantitative expression of receptor genes (NOD1 and NOD2), cytokine genes and the expression of the transcription factor NFκß were evaluated. This was followed by a transcription factor NFκß assay to see its expression in the monocytes of study subjects. Nuclear factor NF-κß was found to have a pronounced response in monocytes of HC and LDC patients and LDR cases when treated with NOD1 and NOD2 ligands. Our study concludes that the NF-kB pathway is involved in the induction and regulation of the cytokine cascade that contributes to chronic inflammation in leprosy.

Morphological Index as a Sensitive Marker of Drug Resistance in Leprosy: A Case Series.

Resistance to antileprosy drugs is one of the main contributors for the persistence of leprosy in the present era. In the absence of universal antimicrobial resistance (AMR) surveillance through the national program, the indications for resistance testing remain a important dilemma to clinicians. WHO recommendations mainly focus on clinical relapse, which could be picked up late with continued transmission and repeated leprosy reactions in the patient. We report here a series of eighteen leprosy cases who were tested for AMR in view of the positive morphological index after completion of multidrug therapy, chronic Erythema nodosum leprosum, and clinical relapse.

An Observational Study to Correlate the Histopathological and Dermoscopic Features in Leprosy Patients in a Tertiary Care Hospital.

Introduction: Leprosy is a chronic granulomatous infection with varied clinical presentations. Dermoscopy is a noninvasive technique widely used in the diagnosis of various skin diseases. Objective: To see the correlation between the clinical and dermoscopic features with the histopathological findings in leprosy. Materials and Methods: A prospective observational study was conducted on clinically suspected leprosy patients attending the dermatology outpatient department (OPD) for 18 months. Representative lesions were observed by dermoscopy, and a biopsy was performed, followed by histopathology for final diagnosis. Patients were categorized by Ridley-Jopling classification. Results: A total of 70 clinically suspected leprosy patients were included in the study. Amongst 70 cases, 56 cases were diagnosed as leprosy by dermoscopy, and 53 cases were confirmed as leprosy by histopathology (hematoxylin and eosin [H and E] staining and Fite-Faraco staining). The other six cases were diagnosed as other nonspecific dermatitis by histopathological findings. Eleven cases that were dermoscopically negative were also confirmed by histopathology to be truly negative. There are three inconclusive cases of dermoscopic findings, which were diagnosed as mid-borderline leprosy by histopathology. Dermoscopic and histopathological correlation was found above 87% in all types of leprosy except mid-borderline leprosy, which showed only a 25% correlation. Conclusion: Dermoscopy is a useful noninvasive tool to assess lesions of leprosy, requires less time for diagnosis, skin features are magnified several times and may become evident before clinical presentation. It definitely helps to reduce the number of biopsies in case of diagnosis of leprosy. However, in doubtful cases, histopathology is required for definitive diagnosis as it is the gold standard to date.

Lepra Reactions: Mimickers and Mirror to Unmask Complex Cases of Leprosy.

Leprosy is a silent disease with protean manifestations, especially during lepra reactions (LRs). Cases with atypical leprosy or LR simulate a number of conditions misdiagnosed frequently. Here, three classical cases of leprosy are reported for their complex presentation. Leprosy was hidden in Case 1 due to co-existing diabetes. COVID vaccination induced LR unmasked all leprosy lesions, which were extensive, large, bizarre and spreading to various immune zones. Case 2 presented with high-grade fever, tachycardia, generalized erythema and body aches. A detailed workup unveiled his leprosy with a rare presentation of Type 1 lepra reaction (T1LR) with erythroderma and severe systemic symptoms. Case 3 mimicked sarcoidosis and lupus erythematosus (LE) on routine workup. She had facial lesions in the malar area, photosensitivity, joint pains, raised angiotensin-converting enzyme (ACE) levels and positive anti-nuclear antibodies. Peri-appendageal granulomas on histopathology and therapeutic response to multidrug therapy helped in the early diagnosis of leprosy.

Molecular and spatial evaluation of small rodents and Didelphimorphis infected with Mycobacterium leprae in the southern Amazon, Brazil.

BACKGROUND: The high levels of recent transmission of leprosy worldwide demonstrate the necessity of epidemiologic surveillance to understand and control its dissemination. Brazil remains the second in number of cases around the world, indicating active transmission of Mycobacterium leprae (M. leprae) in the population. At this moment, there is a consensus that the bacillus is transmitted by inter-human contact, however, different serologic, molecular, and histopathological approaches indicate the existence of non-human transmission sources. METHODS AND RESULTS: The qPCR assay was used to amplify the molecular targets 16S RNAr and RLEP, in samples of liver, spleen, and ear of wild animals belonging to Didelphimorphia and Rodentia orders, in highly endemic areas of Mato Grosso, Brazil. The RLEP repetitive sequence was positive in 202 (89.0%) samples, with 96 (42.3%) of these also being positive for the 16S gene. Regarding the collection sites, it was observed that the animals were found in areas profoundly deforested, close to urban areas. CONCLUSIONS: Our results suggest that wild animals can play an important role in the maintenance of M. leprae in endemic regions with major anthropic action in Brazil. Therefore, integrating human, animal, and environmental health care with the One Health initiative is highly efficient for the development of effective strategies to contain and control leprosy in Brazil.

Nerve function impairment and quality of life in patients with leprosy: a prospective, observational study.

BACKGROUND: There is a limited number of studies assessing the alterations in nerve function impairment (NFI) in leprosy over an extended period of time. To the best of our knowledge, no published study has evaluated neurological state longitudinally during treatment utilizing a combination of clinical, functional (activity limitation), electrophysiological, and patient-reported quality of life (QOL) outcomes. METHODS: This prospective, observational study included leprosy patients of all spectra. Over 1 year of treatment, cutaneous and neurological examinations were done in addition to a nerve conduction study (NCS) and sympathetic skin response (SSR) assessment. QOL and activity limitation assessments using the World Health Organization Quality of Life brief version (WHOQOL-BREF) and Screening of Activity Limitation and Safety Awareness scale (SALSA), respectively, were also performed. RESULTS: Out of 63 leprosy patients, loss of sensation was noted in 43 (68.2%) at baseline. At the completion of treatment, proportionate change revealed no change in 18 (28.5%), restored function in 9 (14.2%), improved status in 34 (53.9%), and deteriorated NFI in only 2 (3.1%) cases. The association between NCS-SSR abnormalities was significant for a longer duration of disease at presentation (P = 0.04), in multibacillary cases [OR 9.12 (95% CI, 1.22-67.93)], in those in reaction [OR 3.56 (95% CI, 0.62-20.36)] and in those aged over 40 [OR 1.93 (95% CI, 0.28-13.41)]. There was an improvement in WHOQOL-BREF and SALSA scores at release from treatment (P = 0.005 and P = 0.01, respectively). CONCLUSION: The majority of leprosy patients on treatment show improvement in NFI at the completion of therapy. However, change is influenced by critical factors such as bacillary load, disease duration, age, and the presence of reaction(s).