Whole blood transcriptomics reveals the enrichment of neutrophil activation pathways during erythema nodosum leprosum reaction.

Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Cytokines profile in pure neural leprosy.

Introduction: Pure Neural Leprosy (PNL) is a form of this long time known disease that affects only the peripheral nervous system. Since it is a rare form of the disease, its pathophisiology is still poorly understood. Objective: Describe the cytokines profile in patients with PNL. Methods: 30 Patients diagnosed with PNL in the Souza Araujo Outpatient Clinic and with cytokines evaluated were selected. They were evaluated by neurologists and diagnosed after a nerve biopsy. Serum levels of IL-1 ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-ϒ, CXCL-10/IP-10 and TGF-ß were evaluates at the moment of the diagnosis. Results: Neural thickening was a common clinical finding in this groups of patients. Small and medium sensitive fibers signs and symptoms were present in 92% of the patients and motor involvement in 53%. 43% of patients presented neuropathic pain and no one had neuritis TGF-beta, IL-17, CCl-2 and IP-10. CCL-2 levels were associated with demyelinating patters and IP-10 and IL-1o were associated with axonal patterns at NCS. Discussion: PNL patients' cytokine profile appears to be different of other clinical forms of leprosy, with the presence of cytokines described in both tuberculoid and lepromatous leprosy. High levels of CCl-2 may be related to the presence of silent neuritis as well as the presence of IL-10. PNL is unique a form of leprosy, therefore, understanding its immunological profiles essential to better understand the disease itself.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy.

BACKGROUND: The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES: To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS: We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS: Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS: Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

Housing characteristics of crack cocaine users in Northeast Brazil, 2011-2013. / Características de usuários de crack quanto à situação de moradia no Nordeste brasileiro, 2011-2013.

We compared sociodemographic characteristics, substance use patterns, sexual behavior, use of health services, and criminal records of homeless vs. domiciled users. Data are from the Brazilian National Survey on Crack Use. A discriminant model and correspondence analysis cross-compared characteristics of users according to their housing status. The logistic model revealed associations between "living in the streets" and female gender and intermittent work. "Homelessness" was also associated with the use of tobacco and "oxi" in the previous 30 days, reliance on soup kitchens, low access to public mental health services, and arrests in the previous year. Correspondence analysis highlighted the spatial proximity of the variables as follows: "having traded sex for drugs", "informal work", "age 31 years or older", "access to public mental health services", "problems with law enforcement", and female gender with homeless crack users. People who smoke crack cocaine in Northeast Brazil are seldom studied. Their profiles, stratified according to their housing conditions, show subgroups with specific characteristics. While domiciled users have access to specialized clinics, homeless users basically reported access to free food and harm reduction services.

Objetivou-se comparar características sociodemográficas, padrões de consumo de substâncias, comportamento sexual, utilização de serviços de saúde e envolvimento criminal de usuários, domiciliados e em situação de rua. Dados secundários do Inquérito Nacional sobre Uso do Crack, utilizando análise discriminante e de correspondência para comparar características dos usuários segundo condição de moradia. O modelo final de regressão logística evidenciou associações entre "situação de rua" e ser do sexo feminino, trabalho descontínuo, consumo de tabaco e "oxi" nos últimos 30 dias, uso de serviços de alimentação gratuita, baixo acesso a tratamento e frequentes detenções no último ano. Na análise de correspondência observou-se proximidade no espaço analítico de "troca de sexo por drogas", "trabalho informal", "idade" >31 anos, "baixo acesso a CAPS-ad", "problemas com a justiça criminal" e "sexo feminino" com os usuários de crack desabrigados. Pouco se sabe sobre usuários de crack em contexto na região Nordeste do Brasil. Os resultados evidenciam dois subgrupos com características específicas. Enquanto os domiciliados têm acesso aos serviços de CAPS-ad e outras clínicas especializadas, os usuários em situação de rua relataram, basicamente, acesso a serviços de alimentação gratuita e redução de danos.

Características de usuários de crack quanto à situação de moradia no Nordeste brasileiro, 2011-2013 / Housing characteristics of crack cocaine users in Northeast Brazil, 2011-2013

Resumo Objetivou-se comparar características sociodemográficas, padrões de consumo de substâncias, comportamento sexual, utilização de serviços de saúde e envolvimento criminal de usuários, domiciliados e em situação de rua. Dados secundários do Inquérito Nacional sobre Uso do Crack, utilizando análise discriminante e de correspondência para comparar características dos usuários segundo condição de moradia. O modelo final de regressão logística evidenciou associações entre "situação de rua" e ser do sexo feminino, trabalho descontínuo, consumo de tabaco e "oxi" nos últimos 30 dias, uso de serviços de alimentação gratuita, baixo acesso a tratamento e frequentes detenções no último ano. Na análise de correspondência observou-se proximidade no espaço analítico de "troca de sexo por drogas", "trabalho informal", "idade" >31 anos, "baixo acesso a CAPS-ad", "problemas com a justiça criminal" e "sexo feminino" com os usuários de crack desabrigados. Pouco se sabe sobre usuários de crack em contexto na região Nordeste do Brasil. Os resultados evidenciam dois subgrupos com características específicas. Enquanto os domiciliados têm acesso aos serviços de CAPS-ad e outras clínicas especializadas, os usuários em situação de rua relataram, basicamente, acesso a serviços de alimentação gratuita e redução de danos.

Abstract We compared sociodemographic characteristics, substance use patterns, sexual behavior, use of health services, and criminal records of homeless vs. domiciled users. Data are from the Brazilian National Survey on Crack Use. A discriminant model and correspondence analysis cross-compared characteristics of users according to their housing status. The logistic model revealed associations between "living in the streets" and female gender and intermittent work. "Homelessness" was also associated with the use of tobacco and "oxi" in the previous 30 days, reliance on soup kitchens, low access to public mental health services, and arrests in the previous year. Correspondence analysis highlighted the spatial proximity of the variables as follows: "having traded sex for drugs", "informal work", "age 31 years or older", "access to public mental health services", "problems with law enforcement", and female gender with homeless crack users. People who smoke crack cocaine in Northeast Brazil are seldom studied. Their profiles, stratified according to their housing conditions, show subgroups with specific characteristics. While domiciled users have access to specialized clinics, homeless users basically reported access to free food and harm reduction services.

Ultrasonography as a diagnostic tool for Neural Pain in Leprosy.

Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the disease. Acute neuropathy usually occurs during reaction episodes and is called neuritis. Twenty-two leprosy patients were included in this study. These patients had neural pain associated with ulnar sensory neuropathy, with or without adjunct motor involvement. The neurological picture began within thirty days of the clinical evaluation. The patients underwent a nerve conduction study and the demyelinating findings confirmed the diagnosis of neuritis. Ultrasonographic study (US) of the ulnar nerve was performed in all patients by a radiologist who was blinded to the clinical or neurophysiological results. Morphological characteristics of the ulnar nerve were analyzed, such as echogenicity, fascicular pattern, transverse cross-sectional area (CSA), aspect of the epineurium, as well as their anatomical relationships. The volume of selected muscles referring to the ulnar nerve, as well as their echogenicity, was also examined. Based on this analysis, patients with increased ulnar nerve CSA associated with loss of fascicular pattern, epineurium hyperechogenicity and presence of power Doppler flow were classified as neuritis. Therefore, patients initially classified by the clinical-electrophysiological criteria were reclassified by the imaging criteria pre-established in this study as with and without neuritis. Loss of fascicular pattern and flow detection on power Doppler showed to be significant morphological features in the detection of neuritis. In 38.5% of patients without clinical or neurophysiological findings of neuritis, US identified power Doppler flow and loss of fascicular pattern. The US is a method of high resolution and portability, and its low cost means that it could be used as an auxiliary tool in the diagnosis of neuritis and its treatment, especially in basic health units.

Leprosy Reactions and Neuropathic Pain in Pure Neural Leprosy in a Reference Center in Rio de Janeiro - Brazil.

Introduction: Leprosy reactions are complications that can occur before, during, or after multidrug therapy (MDT) and are considered a major cause of nerve damage. Neuritis is an inflammatory process that causes nerve function impairment associated with pain and tenderness along the nerve. Neuritis can be found in both type 1 and type 2 reactions and may also be the sole manifestation of a leprosy reaction. The objective of this study is to describe the incidence of leprosy reactions and its association with neuropathic pain in pure neural leprosy (PNL) patients. Methods: We selected 52 patients diagnosed with PNL and 67 patients with other clinical forms of leprosy. During the MDT the patients visited the clinic monthly to take their supervised dose. The patients were instructed to return immediately if any new neurological deficit or skin lesions occurred during or after the MDT. Results: Of the PNL patients, 23.1% had a leprosy reaction during or after the MDT, while this was 59.7% for patients with the other clinical forms of leprosy. There was an association between having PNL and not having any reaction during and after the MDT, as well as having PNL and having neuritis after the MDT.There was also an association between having previous neuritis and having neuropathic pain in the other clinical forms of leprosy group, although this association was not present in the PNL group. Discussion: Our data suggest that PNL is a different form of the disease, which is immunologically more stable. In addition, PNL patients have more neuritis than the classical leprosy skin reactions. In PNL there was no association between acute neuritis and neuropathic pain, suggesting that these patients may have had silent neuritis. Understanding and identifying neuritis is essential to reduce disability and the impact on public health.

Follow-up assessment of patients with Pure Neural Leprosy in a reference center in Rio de Janeiro-Brazil.

INTRODUCTION: Pure Neural Leprosy (PNL) is a rare clinical form of leprosy in which patients do not present with the classical skin lesions but have a high burden of the disability associated with the disease. Clinical characteristics and follow up of patients in PNL are still poorly described in the literature. OBJECTIVE: This paper aims to describe the clinical, electrophysiological and histopathological characteristics of PNL patients, as well as their evolution after multidrug therapy (MDT). METHODS: Fifty-two PNL patients were selected. Clinical, nerve conduction studies (NCS), histopathological and anti-PGL-1serology were evaluated. Patients were also assessed monthly during the MDT. At the end of the MDT, all of the patients had a new neurological examination and 44 were submitted to another NCS. RESULTS: Paresthesia was the complaint most frequently reported by patients, and in the neurological examination the most common pattern observed was impairment in sensory and motor examination and a mononeuropathy multiplex. Painful nerve enlargement, a classical symptom of leprosy neuropathy, was observed in a minority of patients and in the motor NCS axonal injuries, alone or in combination with demyelinating features, were the most commonly observed. 88% of the patients did not present any leprosy reaction during MDT. There was no statistically significant difference between the neurological examinations, nor the NCS pattern, performed before and after the MDT. DISCUSSION: The classical hallmarks of leprosy neuropathy are not always present in PNL making the diagnosis even more challenging. Nerve biopsy is an important tool for PNL diagnosis as it may guide therapeutic decisions. This paper highlights unique characteristics of PNL in the spectrum of leprosy in an attempt to facilitate the diagnosis and management of these patients.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy

BACKGROUND The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

The red flags of ulnar neuropathy in leprosy.

The diagnosis of pure neural leprosy is more challenging because patients share characteristics with other common pathologies, such as ulnar compression, which should be taken into consideration for differential diagnosis. In this study, we identify ulnar nerve conduction characteristics to aid in the differential diagnosis of ulnar neuropathy (UN) in leprosy and that of non-leprosy etiology. In addition, we include putative markers to better understand the inflammatory process that may occur in the nerve. Data were extracted from a database of people affected by leprosy (leprosy group) diagnosed with UN at leprosy diagnosis. A non-leprosy group of patients diagnosed with mechanical neuropathy (compressive, traumatic) was also included. Both groups were submitted to clinical, neurological, neurophysiological and immunological studies. Nerve enlargement and sensory impairment were significantly higher in leprosy patients than in patients with compressive UN. Bilateral impairment was significantly higher in the leprosy group than in the non-leprosy group. Leprosy reactions were associated to focal demyelinating lesions at the elbow and to temporal dispersion (TD). Clinical signs such as sensory impairment, nerve enlargement and bilateral ulnar nerve injury associated with eletrodiagnostic criteria such as demyelinating finds, specifically temporal dispersion, could be tools to help us decided on the best conduct in patients with elbow ulnar neuropathy and specifically decide if we should perform a nerve biopsy for diagnosis of pure neural leprosy.

Low rate of relapse after twelve-dose multidrug therapy for hansen's disease: A 20-year cohort study in a brazilian reference center.

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.

Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load.

BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients.

Reduction in incidence has been associated with the introduction of novel approaches, like chemo/immune-prophylaxis. Incidence determined through follow-up cohort studies can evaluate the implementation of these innovative policies towards control and prevention. We have assessed the incidence in our contacts cohort over past 33 years, considering the effect of demographic and clinical variables. Survival analysis was used to estimate the risk of leprosy. A total of 9024 contacts were evaluated, of which 192 developed leprosy, resulting in an overall incidence of 1.4/1000 person-years. The multivariate analysis showed that the major risk factors were (i) contact from MB index cases and (ii) consanguinity (iii) intra household contact. Lower risk was detected for contacts with BCG scar who were revaccinated. There was a significant decrease in accumulated risk between the 2011-2019 period compared with 1987, probably linked to the improvement in laboratory tools to monitor contacts, thereby providing early diagnosis of contacts at intake and reduction of transmission. Our findings suggest that a combination of contact surveillance and tracing, adequate neurodermatological examination, and availability of molecular tools is highly effective in supporting early diagnosis, while a second dose of the BCG vaccination can exert extra protection.

Morphometric analysis of nerve fibers in neural leprosy.

BACKGROUND: The present study assesses the contributions of axonal degeneration and demyelination in leprosy nerve damage. New clinical strategies can emerge from an in-depth understanding of the pathogenesis of neural leprosy (NL). METHODS: Morphometric analysis of myelinated nerve fibers was performed on 44 nerve biopsy samples collected from leprosy patients. Measures of density, diameter distribution, g-ratios, and the counting of axonal ovoids on the myelinated fibers were taken and compared to those in the control group. RESULTS: The proportion of small myelinated fibers increased in the leprosy group while large fiber frequency decreased. Indicative of axonal atrophy, the g-ratio was lower in the leprosy group. The frequency of axonal ovoids was identical to that found in the non-leprosy neuropathies. CONCLUSIONS: Axonal atrophy, Wallerian degeneration, and demyelination coexist in NL. Axonal degeneration predominates over demyelination in the chronic course of the disease; however, this may change during leprosy reactive episodes. This study regards demyelination and axon degeneration as concurrent mechanisms of damage to nerve fibers in leprosy. It also calls into question the view that demyelination is the primary and predominant mechanism in the complex pathogeny of NL.

Características de usuários de crack quanto à situação de moradia no Nordeste brasileiro, 2011-2013 / Housing Characteristics of Crack Cocaine Users in Northeast Brazil, 2011-2013

O questionário utilizado na Pesquisa Nacional Sobre o Uso de Crack, inquérito realizado entre 2011 e 2012 compreendia 7 (sete) blocos, a saber: (a) informações sociodemográficas, (b) uso de drogas, (c) mobilidade (vizinhança/municípios onde o usuário usou crack), (d) risco de doença infecciosa associada ao uso de crack e compartilhamento de objetos usados no consumo, (e) comportamento sexual; (f) estado de saúde auto referido, (f) utilização de serviços sociais e de saúde e (g) envolvimento com a justiça criminal.

Cytokine Levels in Neural Pain in Leprosy.

Pain is a frequent symptom in leprosy patients. It may be predominantly nociceptive, as in neuritis, or neuropathic, due to injury or nerve dysfunction. The differential diagnosis of these two forms of pain is a challenge in clinical practice, especially because it is quite common for a patient to suffer from both types of pain. A better understanding of cytokine profile may serve as a tool in assessing patients and also help to comprehend pathophysiology of leprosy pain. Patients with leprosy and neural pain (n = 22), neuropathic pain (n = 18), neuritis (nociceptive pain) (n = 4), or no pain (n = 17), further to those with diabetic neuropathy and neuropathic pain (n = 17) were recruited at Souza Araujo Out-Patient Unit (Fiocruz, Rio de Janeiro, RJ, Brazil). Serum levels of IL1ß, IL-6, IL-10, IL-17, TNF, CCL-2/MCP-1, IFN-γ, CXCL-10/IP-10, and TGF-ß were evaluated in the different Groups. Impairment in thermal or pain sensitivity was the most frequent clinical finding (95.5%) in leprosy neuropathy patients with and without pain, but less frequent in Diabetic Group (88.2%). Previous reactional episodes have occurred in patients in the leprosy and Pain Group (p = 0.027) more often. Analysis of cytokine levels have demonstrated that the concentrations of IL-1ß, TNF, TGF-ß, and IL-17 in serum samples of patients having leprosy neuropathy in combination with neuropathic or nociceptive pain were higher when compared to the samples of leprosy neuropathy patients without pain. In addition, these cytokine levels were significantly augmented in leprosy patients with neuropathic pain in relation to those with neuropathic pain due to diabetes. IL-1ß levels are an independent variable associated with both types of pain in patients with leprosy neuropathy. IL-6 concentration was increased in both groups with pain. Moreover, CCL-2/MCP-1 and CXCL-10/IP-10 levels were higher in patients with diabetic neuropathy over those with leprosy neuropathy. In brief, IL-1ß is an independent variable related to neuropathic and nociceptive pain in patients with leprosy, and could be an important biomarker for patient follow-up. IL-6 was higher in both groups with pain (leprosy and diabetic patients), and could be a therapeutic target in pain control.

Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011-2018.

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6-290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.