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.

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.

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.

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.

Clinical and Neurophysiological Features of Leprosy Patients with Neuropathic Pain.

Neural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive-neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was "burning." In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.

[Analysis of the geographical distribution of cases of leprosy. Rio de Janeiro, 2001-2012]. / Análise da distribuição geográfica dos casos de hanseníase. Rio de Janeiro, 2001 a 2012.

Studies have demonstrated that the geographical distribution of leprosy is related to different socioeconomic factors. This article aims to study the geographical distribution of leprosy in the state of Rio de Janeiro. The cases of leprosy reported in the 2001-2012 period were mapped according to municipality. Epidemiological and socioeconomic indicators were calculated. The ArcMap program was used for the construction of maps and Earth View to calculate the Bayesian rate. It was observed that leprosy is presented in hyper-endemic levels especially in the metropolitan area. However, there is also a reduction of the detection rate in the most recent study period. In municipalities in the metropolitan region and the north western region detection in children under 15 is high, indicating an active transmission situation. In municipalities in the south-central region and especially in the coastal region, there was a high proportion of cases diagnosed with level II disability, reflecting late diagnosis. There was no linear correlation between socioeconomic indicators and leprosy rate. These results contribute to the analysis of the geographical distribution of leprosy, important for the identification of areas for resource allocation, aiming to control and eliminate the disease.

Análise da distribuição geográfica dos casos de hanseníase. Rio de Janeiro, 2001 a 2012 / Analysis of the geographical distribution of cases of leprosy. Rio de Janeiro, 2001-2012

Resumo Trabalhos demonstraram que a distribuição geográfica da hanseníase está relacionada a diferentes fatores socioeconômicos. O objetivo deste artigo é estudar a distribuição geográfica da hanseníase no estado do Rio de Janeiro. Os casos de hanseníase notificados no período 2001-2012 foram mapeados segundo município. Foram calculados indicadores epidemiológicos e socioeconômicos. Utilizou-se o programa ArcMap para a construção dos mapas e o Terra View para o cálculo de taxa bayesiana. Observou-se que a hanseníase apresenta-se em níveis hiperendêmicos, especialmente na região metropolitana. No entanto, observa-se também uma redução do coeficiente de detecção no período mais recente do estudo. Em municípios da região metropolitana e da região noroeste a detecção em menores de 15 anos é elevada, indicando situação de transmissão ativa. Em municípios da região centro-sul e especialmente na baixada litorânea, observou-se elevada proporção de casos diagnosticados com grau II de incapacidade, refletindo alto índice de diagnóstico tardio. Não foi observada correlação linear entre os indicadores socioeconômicos e a detecção da hanseníase. Esses resultados contribuem para a análise da distribuição geográfica da hanseníase, importante para a identificação de áreas para alocação de recursos, visando controle e eliminação da doença.

Abstract Studies have demonstrated that the geographical distribution of leprosy is related to different socioeconomic factors. This article aims to study the geographical distribution of leprosy in the state of Rio de Janeiro. The cases of leprosy reported in the 2001-2012 period were mapped according to municipality. Epidemiological and socioeconomic indicators were calculated. The ArcMap program was used for the construction of maps and Earth View to calculate the Bayesian rate. It was observed that leprosy is presented in hyper-endemic levels especially in the metropolitan area. However, there is also a reduction of the detection rate in the most recent study period. In municipalities in the metropolitan region and the north western region detection in children under 15 is high, indicating an active transmission situation. In municipalities in the south-central region and especially in the coastal region, there was a high proportion of cases diagnosed with level II disability, reflecting late diagnosis. There was no linear correlation between socioeconomic indicators and leprosy rate. These results contribute to the analysis of the geographical distribution of leprosy, important for the identification of areas for resource allocation, aiming to control and eliminate the disease.

Terapia con corticosteroides en pacientes de lepra borderline tuberculoide coinfectados con VIH y con reacción de reversión: estudio clínico / No disponible

Antecedentes: El Mycobacterium leprae y el VIH causan enfermedades de tipo infecciosas muy preocupantes para la sanidad mundial. Son especial motivo de preocupación cuando los pacientes se coinfectan con ambos agentes patógenos. El objetivo de este estudio es evaluar los episodios de reacción de reversión (RR) y el efecto del uso de corticosteroides sobre el tratamiento de pacientes de lepra borderline tuberculoide co-infectados con el virus de inmunodeficiencia humana (VIH). Métodos: Este trabajo es un estudio retrospectivo de cohortes en el que se observan las respuestas a la terapia con corticoides y sus manifestaciones clínicas. Se analizan variables durante y después de la multiterapia farmacológica de la Organización Mundial de la Salud (OMS) entre el primer y último día de la toma de prednisona, con un máximo de hasta 6 meses posteriores a haber iniciado la terapia corticosteroidea. Resultados: Se incluye un total de 22 casos VIH-positivos y 28 VIH-negativos. La pérdida de sensibilidad y el engrosamiento neural eran estadísticamente significativos mientras que las lesiones ulceradas sólo se detectaron en el grupo coinfectado. La mayoría de pacientes fueron diagnosticados de lepra en fase de leprorreacción RR y seis pacientes manifestaron RR como un síndrome inflamatorio de restitución inmunológica. De promedio, ambos grupos recibieron dosis similares de corticosteroides (diferencia de 0·1 mg/kg/día). Conclusiones: Las manifestaciones clínicas de ambos grupos fueron similares y la mejoría general fue debida a la administración de corticoides. Registro del ensayo: Este trabajo fue presentado y aprobado por el Ethics Committee on Research of the Oswaldo Cruz Institute el 8 de agosto de 2011 (registro 616/11)

Background: Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods: This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results: A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).Conclusions: It is of special interest that the clinical manifestations in both groups were found to be similar and that overall improvement occurred as a result of corticosteroid therapy.Trial registration This work was submitted to and approved by the Ethics Committee on Research of the Oswaldo Cruz Institute on August 8, 2011 (registration 616/11)

[Patients from a reference center for leprosy: Rio de Janeiro and Duque de Caxias, 1986-2008]. / Pacientes em centro de referência para Hanseníase: Rio de Janeiro e Duque de Caxias, 1986-2008.

UNLABELLED: The scope of this study was to compare epidemiological data on leprosy patients living in two cities with different socioeconomic and endemic profiles that were monitored in a single center of reference. A descriptive study was made of data from patients in the Souza Araújo Outpatient facility treated in the period 1986-2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de Caxias (n = 336). RESULTS: Among patients from Duque de Caxias, in comparison with patients from Rio de Janeiro, there was a higher proportion of cases: below the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and cases detected through surveillance of contacts. Patients in Duque de Caxias had lower average incomes and education levels. There were no statistically significant differences regarding gender, disability level, reaction in the diagnosis, final BI, bandonment and regularity of treatment. The differences found between the patients monitored in a single center of reference, could be partly related to contextual differences between the municipalities. On the other hand, it was observed that the provision of treatment and monitoring can minimize the effect of different contextual factors on health outcomes.

Pacientes em centro de referência para Hanseníase: Rio de Janeiro e Duque de Caxias, 1986-2008 / Patients from a Reference Center for Leprosy: Rio de Janeiro and Duque de Caxias, 1986-2008

O objetivo deste trabalho foi comparar dados epidemiológicos de pacientes de hanseníase residentes em dois municípios com perfil socioeconômico e nível de endemicidade diferentes e que foram acompanhados em um mesmo centro de referência. Foi realizado um estudo descritivo dos dados de pacientes tratados no ambulatório Souza Araújo, 1986 a 2008, residentes nos municípios do Rio de Janeiro (n = 1353) e Duque de Caxias (n = 336). Entre os pacientes desta cidade, em comparação com os da outra, observou-se maior proporção de casos: com idade inferior a 15 anos, multibalicares, com maior índice baciloscópico (IB) inicial, e detectados através da vigilância de contatos. Os pacientes de Duque de Caxias apresentaram menor renda média e nível de escolaridade. Não foram observadas diferenças estatisticamente significativas quanto ao sexo, grau de incapacidade inicial, reação no diagnóstico, IB final, abandono e regularidade do tratamento. As diferenças encontradas entre os pacientes acompanhados em um mesmo centro de referência poderiam estar, em parte, relacionadas a diferenças contextuais existentes entre os municípios. Por outro lado, observou-se que a oferta de tratamento e acompanhamento podem minimizar o efeito que os fatores contextuais apresentam sobre os desfechos de saúde.

The scope of this study was to compare epidemiological data on leprosy patients living in two cities with different socioeconomic and endemic profiles that were monitored in a single center of reference. A descriptive study was made of data from patients in the Souza Araújo Outpatient facility treated in the period 1986-2008, who were resident in the cities of Rio de Janeiro = 1353) and Duque de Caxias (n = 336). Results: Among patients from Duque de Caxias, in comparison with patients from Rio de Janeiro, there was a higher proportion of cases: below the age of 15 years, multibacillary, higher initial bacilloscopic index (BI) and cases detected through surveillance of contacts. Patients in Duque de Caxias had lower average incomes and education levels. There were no statistically significant differences regarding gender, disability level, reaction in the diagnosis, final BI, bandonment and regularity of treatment. The differences found between the patients monitored in a single center of reference, could be partly related to contextual differences between the municipalities. On the other hand, it was observed that the provision of treatment and monitoring can minimize the effect of different contextual factors on health outcomes.