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.

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.

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.

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.

Any resurgence of leprosy cases in the Togo's post-elimination period? Trend analysis of reported leprosy cases from 2010 to 2022.

BACKGROUND: Leprosy, or Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. Togo achieved the target of eliminating leprosy as a public health problem in 2000 (less than 1 case/10 000 population). However, new cases of leprosy are still being reported. The aim of this study was to describe and map trends of leprosy cases notified in Togo from 2010 to 2022. METHODS: This was a descriptive cross-sectional study covering a thirteen-year period from January 1, 2010, to December 31, 2022. The data of the study were leprosy surveillance system's data collected monthly between 2010 and 2022. The estimated number of leprosy cases and the incidence rate of leprosy cases were reported for the whole population by region, by district, by calendar year (2010-2022) and by target sub-population (children under 15, women and people with disabilities). Observed case incidence rates were mapped by health district and by year. RESULTS: From January 1, 2010, to December 31, 2022, 1031 new cases of leprosy were diagnosed in Togo. The median age of subjects was 46 years (interquartile range: 33-60), with extremes from 4 to 96 years. Half the subjects were women (50.7%). Variations in the leprosy incidence rate by year show an increase between 2010 and 2022, from 0.7 cases /100,000 population to 1.1 /100,000 population respectively. From 2010 to 2022, the proportion of cases in children remained low, between 0 and 9%. The proportion of women fluctuated between 39.7% and 67.2% between 2010 and 2017, then stabilized at an average of 50% between 2018 and 2022. The proportion of multi-bacillary leprosy cases increased quasi-linearly between 2010 and 2022, from 70 to 96.6%. Mapping of leprosy cases showed that leprosy was notified in all Togo health districts during the study period, apart from the Lacs district, which reported no leprosy cases. CONCLUSION: Togo has achieved the elimination of leprosy as a public health problem. However, the increase in the number of new leprosy cases and the proportion of leprosy cases in children indicate that transmission of the disease is continuing and that supplementary measures are needed.

IgG seroprevalence of Toxoplasma gondii and Leishmania infantum in leprosy patients: Implications for screening and management of co-infections.

Parasitic co-infections are common in developing countries and can interfere with leprosy treatment, leading to an increased risk of inflammatory leprosy reactions. This study assessed serum immunoglobulin G (IgG) levels against Toxoplasma gondii and Visceral Leishmaniasis (VL) antigens in 270 leprosy patients from Brazilian states. Regarding the respective cut-offs, the prevalence of IgG seropositivity for T. gondii and VL were 21.05 % and 47.36 % in the leprosy-negative group, and 77.7 % and 52.6 % in the leprosy-positive group. Of the 270 leprosy patients, 158 (58.5 %) presented with inflammatory leprosy reactions. Of those, 72 (59.5 %) had neuritis, 35 (48.6 %) had reverse reactions, and 28 (38.9 %) had ENL in both Brazilian states. Leprosy patients with anti-Leishmania IgG seropositivity were 3.25 times more likely to develop neuritis (95 % C.I.: 1.187 - 9.154; p = 0.019). These findings are particularly relevant for clinical settings where both leprosy and parasitic diseases are prevalent and could provide essential guidance for detecting and addressing complications arising from parasitic co-infections in leprosy patients, thereby improving clinical management strategies.

MIP vaccine in leprosy: A scoping review and future horizons.

Mycobacterium Indicus Pranii (MIP) vaccine is a killed vaccine developed in India for leprosy with immunotherapeutic as well as immunoprophylactic effects. MIP, earlier known as Mycobacterium welchii, is a rapidly growing non-pathogenic mycobacterium. The novelty of this bacterium is due to its translational application as an immunotherapeutic agent. When administered intradermally, the vaccine induces cell-mediated immunity in the host towards Mycobacterium leprae. It leads to faster clinical and histopathological improvement, rapid bacillary clearance, and also lepromin conversion in anergic leprosy patients. The beneficial role of the MIP vaccine in augmenting the therapeutic efficacy of Multidrug Therapy (MDT), particularly in highly bacillated leprosy patients, is well documented in various studies from India. The role of the vaccine in reactional states is controversial, with varied results in different studies. Overall, it is found to decrease the frequency of type 2 lepra reactions and is useful in recalcitrant erythema nodosum leprosum. Even though there may be an increased likelihood of type 1 reactions, no additional nerve function impairment is attributed to the vaccine in various studies. In household contacts of leprosy who are administered MIP, it is noted to confer protection from disease lasting up to 10 years. It may prove to be a cost-effective strategy in national leprosy programmes. Apart from local injection site reactions, the vaccine is relatively safe, but it is not recommended in pregnancy and lactation. This article provides an overview of the MIP vaccine's clinical application in the context of leprosy spanning over 40 years. It also considers the vaccine's possible future applications in the management of disease-related complications and achieving the long-term goal of zero leprosy.

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.

Split Dose of Prednisolone in the Treatment for Erythema Nodosum Leprosum: A Case Series.

Background Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that clinically presents as tender erythematous evanescent nodules, mostly associated with systemic symptoms. Oral prednisolone is the drug of choice, with doses ranging from 0.5 to 1 mg/kg. Some cases may develop new lesions and systemic symptoms despite 1 mg/kg prednisolone, and in ideal practice, physicians escalate the prednisolone dose for immediate arrest of inflammation to prevent complications. However, a high dose of prednisolone has more side effects in the long term and causes more immunosuppression. Methods In cases of ENL, those not responding to a conventional once-daily regimen were given a split dose of oral prednisolone instead of increasing the dose. They were followed up for response, and serum cortisol was measured to see for hypothalamic-pituitary-adrenal (HPA) axis suppression. Results Eight cases of ENL (three nodular, three necrotic, one pustular, and one nodulcerative) had a dramatic response to split-dose therapy without any relapse and HPA axis suppression. Conclusion A split-dosing regimen can be a good treatment option in ENL with better control, less steroid dependency, and a lower relapse rate.

Association of polymorphisms in the TNFA, TNFRSF1A and TNFRSF1B genes with lepromatous leprosy in Western Mexican patients.

INTRODUCTION: Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). METHODOLOGY: The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. RESULTS: We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. CONCLUSIONS: The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.

Leprosy in Spain: A Descriptive Study of Admissions at Fontilles Sanatorium between 1909 and 2020.

BACKGROUND: The study aimed to characterize patients with leprosy admitted to Fontilles throughout the 20th and 21st centuries, focusing on differences across three periods (I, II, and III). It also explored variables linked to patient survival. METHODS: This was a retrospective descriptive study analyzing the medical records of Fontilles patients from 1909 to 2020. It assessed 26 clinical, sociodemographic, and temporal variables (n = 2652). RESULTS: Most patients were male, single, multibacillary (MB), and farmers, from Andalusia and the Valencian Community. The origin of patients shifted over time towards being mostly foreign-born in period III. More than a half were previously admitted and had family members with leprosy. While leprosy reactions decreased over time, neurological symptoms were increasingly diagnosed. The age at onset, admission, and death increased progressively over time. The survival of patients with leprosy at Fontilles depended on the age at admission and the period. CONCLUSIONS: Improved knowledge, services, and awareness regarding leprosy led to increased age at onset and more favorable outcomes. The prolonged time between symptom onset and diagnosis indicates that leprosy is still a neglected disease. Although MB forms are more severe, leprosy classification did not significantly impact the survival rates of patients at Fontilles.

Human Skin as an Ex Vivo Model for Maintaining Mycobacterium leprae and Leprosy Studies.

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium for 60 days. Explants were evaluated by RT-PCR-16SrRNA and cytokine gene expression. The viability and infectivity of bacilli recovered from explants (D28 and D60) were evaluated using the Shepard's model. All explants were RT-PCR-16SrRNA positive. The viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice, showed an average positivity of 31%, with the highest positivity in the D28 groups (80%). Furthermore, our work showed different patterns in cytokine gene expression (TGF-ß, IL-10, IL-8, and TNF-α) in the presence of alive or dead bacilli. Although changes can be made to improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

Erythema nodosum leprosum necroticans: a case report of an atypical severe type 2 leprosy reaction and literature review.

Until now, leprosy remains a problem and challenge in the world because it can cause disability and morbidity in affected individuals, including problems due to the emergence of type 2 lepra reaction or erythema nodosum leprosum (ENL). The clinical picture of ENL can appear in an atypical and severe form, called ENL necroticans (ENN), which becomes a problem in diagnosis and therapy. We report a 17-year-old female with lepromatous leprosy and ENN who received therapy in the form of a combination of steroids and methotrexate. Four months after consuming this therapy, the ulcers on the patient's body improved, leaving atrophic and hypertrophic scars. ENN's unusual clinical presentation poses diagnostic difficulties in that its appearance does not follow the typical patterns, making it challenging to identify correctly. Furthermore, managing cases of ENN may necessitate supplementary treatment beyond steroids alone.

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.

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.