Epidemiología y clínica de los pacientes con lepra en un centro de referencia de Paraguay / Epidemiology and clinical features of patients with leprosy in a reference center in Paraguay

RESUMEN Introducción: lepra (enfermedad de Hansen) es una patología infecciosa desatendida que afecta piel y nervios periféricos, desencadenando neuropatías y complicaciones como deformidades y discapacidades. Objetivos: determinar características epidemiológicas y clínicas de pacientes con lepra en el Centro de Especialidades Dermatológicas del Ministerio de Salud Pública y Bienestar Social de Paraguay, de enero 2021 a diciembre 2022. Metodología: estudio descriptivo, observacional, retrospectivo, de corte transversal. La gestión y análisis de datos se realizó en planilla electrónica (Excel del programa Microsoft Office 365 versión 2405), luego se realizó estadística descriptiva. Resultados: se diagnosticaron 123 casos de lepra, 45 (36,58 %) eran mujeres y 78 (63,42 %) varones; las edades estaban entre 17 y 86 años, el rango más afectado fue de 41 a 50 años. Eran lepra multibacilar 112 casos (91,06%). El signo más frecuente fue la placa infiltrada, presentada en 88 casos (71,54%). 58 pacientes (47,15%) presentaron reacciones lepromatosas, siendo, 31 casos de tipo 1 (53,45 %). 34 casos (27,64%) presentaron discapacidad grado 1 y 10 casos (8,13%) discapacidad grado 2. Conclusión: el perfil del paciente con lepra fue del sexo masculino entre 41 a 50 años, siendo la mayoría casos multibacilares. Es fundamentales el diagnóstico precoz y el tratamiento adecuado para reducir la carga de la enfermedad y las discapacidades.

ABSTRACT Introduction: Leprosy (Hansen's disease) is a neglected infectious disease that affects skin and peripheral nerves, triggering neuropathies and complications such as deformities and disabilities. Objective: determine epidemiological and clinical characteristics of patients with Leprosy in the Dermatological Specialties Center of the Ministry of Public Health and Social Welfare of Paraguay, from January 2021 to December 2022. Methodology: descriptive, observational, retrospective, cross-sectional study. Data management and analysis was carried out in an electronic spreadsheet (Excel from Microsoft Office 365 version 2405), then descriptive statistics were performed. Results: 123 cases of leprosy were diagnosed, 45 (36.58 %) were women and 78 (63.42 %) were men; the ages were between 17 and 86 years, the most affected range was 41 to 50 years. 112 cases (91.06 %) were multibacillary leprosy. The most frequent sign was infiltrated plaque, present in 88 cases (71.54 %). 58 patients (47.15 %) presented lepromatous reactions, 31 cases of type 1 (53.45 %). 34 cases (27.64 %) presented grade 1 disability and 10 cases (8.13 %) grade 2 disability. Conclusion: The profile of the patient with leprosy was male between 41 and 50 years, the majority being multibacillary cases. Early diagnosis and adequate treatment are essential to reduce the burden of the disease and disabilities.

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.

Analysis of leprosy cases in the state of Pará between 2001 and 2020 / Análise dos casos de hanseníase no estado do Pará entre 2001 e 2020 / Análisis de los casos de lepra en el estado de Pará entre 2001 y 2020

Background and Objectives: leprosy is a mycobacteriosis known for centuries and prevalent to this day and, despite the reduction in the number of cases, it still affects many Brazilians. To this end, this study aimed to assess the clinical forms of leprosy in the state of Pará between 2001 and 2020. Methods: an ecological study was carried out using data from the Notifiable Diseases Information System (SINAN) of patients with leprosy according to three classifications, such as notified clinical form, notified operational classification and notified degree of disability, collected between 2001 and 2020. Results: the milder forms of leprosy showed a greater decrease than the more severe form, combined with a greater drop in cases in the paucibacillary class compared to the multibacillary classification. Furthermore, grade zero disability showed a large reduction in cases, in contrast to grades one and two, which remained stationary. Conclusion: despite the evident decrease in leprosy in the state, the most serious forms of the disease, which are related to higher levels of disability and transmission, showed little reduction.(AU)

Justificativa e Objetivos: a hanseníase é uma micobacteriose conhecida há séculos e prevalente até os dias atuais e, apesar da diminuição dos números de casos, ainda atinge diversos brasileiros. Para tanto, este estudo tem como objetivo avaliar as formas clínicas da hanseníase no estado do Pará entre 2001 e 2020. Métodos: foi realizado estudo ecológico a partir de dados do Sistema de Informação de Agravos de Notificação (SINAN) de pacientes com hanseníase de acordo com três classificações, como forma clínica notificada, classificação operacional notificada, e grau de incapacidade notificado, coletados entre os anos de 2001 e 2020. Resultados: as formas mais brandas da hanseníase tiveram um decrescimento maior do que a forma mais grave, aliado a uma maior queda dos casos da classe paucibacilar em comparação com a classificação multibacilar. Além disso, o grau zero de incapacidade apresentou grande redução dos casos, em contraste aos graus um e dois, que se mantiveram estacionários. Conclusão: apesar do decréscimo evidente da hanseníase no estado, as formas mais graves da doença, que estão relacionadas a maiores níveis de incapacidade e transmissão, apresentaram pouca redução. (AU)

Justificación y Objetivos: la lepra es una micobacteriosis conocida desde hace siglos y prevalente hasta el día de hoy y, a pesar de la reducción del número de casos, todavía afecta a muchos brasileños. Para ello, este estudio tiene como objetivo evaluar las formas clínicas de lepra en el estado de Pará entre 2001 y 2020. Métodos: se realizó un estudio ecológico utilizando datos del Sistema de Información de Enfermedades de Declaración Obligatoria (SINAN) de pacientes con lepra según tres clasificaciones, tales como forma clínica notificada, clasificación operativa notificada y grado de invalidez notificado, recopiladas entre 2001 y 2020. Resultados: las formas más leves de lepra tuvieron una disminución mayor que la forma más grave, combinado con una mayor caída de casos en la clase paucibacilar, en comparación con la clasificación multibacilar. Además, la discapacidad de grado cero mostró una gran reducción de casos, en contraste con los grados uno y dos, que se mantuvieron estacionarios. Conclusiones: a pesar de la evidente disminución de la lepra en el estado, las formas más graves de la enfermedad, que se relacionan con mayores niveles de discapacidad y transmisión, mostraron poca reducción.(AU)

Transcription Factor HES-1: How Is the Expression of This Transcriptional Factor in Paucibacillary Leprosy Patients?

INTRODUCTION: Leprosy is an ancient and chronic infectious disease caused by 2 mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). Recently, our research group observed that HES-1, an innate cellular component of the Notch signaling pathway, is related to the pathogenesis of leprosy. Therefore, it could be helpful in its detection. OBJECTIVE: To determine the expression of HES-1 in the skin of patients with paucibacillary (PB) leprosy. METHODS: A cross-sectional, descriptive, observational study was conducted. Forty-five skin samples from patients with leprosy were evaluated (30 samples from MB leprosy and 15 from PB leprosy) using immunohistochemistry of HES-1 and S-100. RESULTS: PB leprosy biopsies revealed a reduction of HES-1 in 66.7% of the epidermis, 80% of the eccrine glands, and 62.5% of the hair follicles of these patients, with statistical differences in the control group (P < 0.0001). Besides, HES-1 showed similar utility to S-100 immunostaining in detecting the MB and PB leprosy. CONCLUSIONS: HES-1 is a transcriptional factor also reduced in PB patients' epidermis and skin appendages. Finally, our data show that HES-1 could be a biomarker in diagnosing PB and MB leprosy.

Boletim epidemiológico: frequência de contatos não examinados de casos novos de hanseníase virchowiana e dimorfa com baciloscopia positiva - Goiás, 2017 a 2021 / Epidemiological bulletin: frequency of unexamined contacts of new cases of Virchowian and borderline leprosy with positive bacilloscopy - Goiás, 2017 to 2021

A hanseníase é uma doença infecciosa crônica, causada pelo Mycobacterium leprae, um bacilo com tropismo pela pele e pelos nervos periféricos, com potencial de provocar deformidades físicas e incapacidades. O período de incubação da doença é longo, de 2 a 7 anos, podendo chegar a 20 anos ou mais. Este estudo consiste em uma análise retrospectiva, quantitativa, descritiva, das fichas de notificação do Sistema de Informação de Agravos de Notificação - SINAN dos pacientes com diagnóstico de hanseníase (CID A30), nos anos de 2017 a 2021 e os Boletins de acompanhamento das referidas fichas

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, a bacillus with tropism for the skin and peripheral nerves, with the potential to cause physical deformities and disabilities. The incubation period of the disease is long, from 2 to 7 years, and can reach 20 years or more. This study consists of a retrospective, quantitative, descriptive analysis of the notification of the Notifiable Diseases Information System - SINAN of patients diagnosed with leprosy (ICD A30), in the years 2017 to 2021 and the follow-up Bulletins of the referred forms

Association between SNPs in microRNAs and microRNAs-Machinery Genes with Susceptibility of Leprosy in the Amazon Population.

Leprosy is a chronic neurodermatological disease caused by the bacillus Mycobacterium leprae. Recent studies show that SNPs in genes related to miRNAs have been associated with several diseases in different populations. This study aimed to evaluate the association of twenty-five SNPs in genes encoding miRNAs related to biological processes and immune response with susceptibility to leprosy and its polar forms paucibacillary and multibacillary in the Brazilian Amazon. A total of 114 leprosy patients and 71 household contacts were included in this study. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate individual proportions of case and control groups. The SNP rs2505901 (pre-miR938) was associated with protection against the development of paucibacillary leprosy, while the SNPs rs639174 (DROSHA), rs636832 (AGO1), and rs4143815 (miR570) were associated with protection against the development of multibacillary leprosy. In contrast, the SNPs rs10739971 (pri-let-7a1), rs12904 (miR200C), and rs2168518 (miR4513) are associated with the development of the paucibacillary leprosy. The rs10739971 (pri-let-7a1) polymorphism was associated with the development of leprosy, while rs2910164 (miR146A) and rs10035440 (DROSHA) was significantly associated with an increased risk of developing multibacillary leprosy.

Association of CD209 (DC-SIGN) rs735240 SNV with paucibacillary leprosy in the Brazilian population and its functional effects.

BACKGROUND: Leprosy, caused by Mycobacterium leprae, is a public health problem in Brazil that affects peripheral nerves, resulting in physical disabilities. During host-pathogen interactions, the immune response determines leprosy outcomes from a localised (paucibacillary) form to a disseminated (multibacillary) form. The recognition of M. leprae involves the DC-SIGN receptor, which is present on the dendritic cells (DCs) and participates in immune activation. OBJECTIVES: To evaluate the association of polymorphisms in the promoter region of the gene encoding DC-SIGN (CD209) and the clinical form of leprosy, and to investigate its functional effects. METHODS: The study population included 406 leprosy patients from an endemic area in Brazil [310 multibacillary (MB); 96 paucibacillary (PB)]. A functional evaluation based on the effects of the single nucleotide variant (SNV) associated with PB leprosy on the specific immune response was also performed. RESULTS: The GA genotype and the presence of the A allele of rs735240 (-939G>A) were associated with PB leprosy [OR: 2.09 (1.18-3.69) and 1.84 (1.07-3.14), respectively]. Carriers of the A allele showed reduced expression of CD209 and TGF-ß1 in leprosy lesions in comparison with individuals with GG genotype, in addition to a higher response to the Mitsuda test. CONCLUSION: These data suggest that rs735240 influences the immune response against M. leprae and clinical presentation of leprosy.

Sensitivity and specificity of multibacillary and paucibacillary leprosy laboratory tests: A systematic review and meta-analysis.

This systematic review (number register: CRD42018112736) was performed to compare the sensitivity and specificity of leprosy diagnostic methods. The search was conducted in 3 electronic databases in January 2021. Studies evaluating leprosy diagnostic tests were included according the eligibility criteria. Meta-analysis was performed to calculate the sensibility and specificity of the groups. We included 36 studies. The test sensitivity for paucibacillary patients was 0.31 (95%CI: 0.29-0.33) and the specificity was 0.92 (95%CI: 0.92-0.93). In multibacillary patients, the sensitivity was 0.78 (95%CI: 0.77-0.80) and specificity was 0.92 (95%CI: 0.92-0.93). Comparing the sensitivity and specificity of the different techniques included, it should be noted that polymerase chain reaction (PCR) test presented the highest sensitivity for paucibacillary patients, while the western blot technique showed the highest sensitivity for multibacillary patients. However, further studies are needed to optimise the diagnosis of leprosy, requiring research with a larger number of samples and more uniform protocols.

Indeterminate leprosy

Leprosy in its determinate from (I) is a clinical presentation of the disease preceding the forms described in the Ridley and Jopling (R & J) classification and any other special forms of leprosy or the reactions. In this chapter, the histopathological and bacilloscopic characteristics of the I form of leprosy are described, and the main differential diagnoses are discussed. The histopathological criteria that distinguish the I form from the other forms of leprosy and the reaction processes that may occur during the disease course are also discussed. The identification of the histopathological characteristics of I leprosy is of great importance with respect to the selection of the treatment. I leprosy should not be confused with other forms of leprosy, especially the multibacillary forms, wich require more prolonged treatment and wich can develop reaction phenomena, causing permanent sequelae.

Intermediate or Borderline forms (BT, BB, and BL)

Leprosy is a long-term spectrum disease and can present various clinical and histopathological aspects. Between the two poles of leprosy, there is a wide range of types, consisting of intermediate or borderline forms. In this chapter, the clinical, histopathological, and bacilloscopic characteristics of the intermediate forms (borderlibe-tuberculoid [BT], borderline-borderline [BB], and borderline lepromatous [BL]) are presented and discussed. The main clinical and pathological characteristics that allow the diagnosis and classification of leprosy among the different borderline forms are described and illustrated in panel form, as well as their most significant clinical and histopathological differential diagnoses are also discussed. The clinical-pathological classification of this disease has important implications in the choice of the correct treatment, the understanding of the pathophysiology, and the development of the reaction phenomena typical of leprosy,.

World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.

Comparison of quality of life evaluated by SF-36 and DLQI in multibacillary and paucibacillary leprosy patients from Sao Paulo, Brazil.

BACKGROUND: Dermatological diseases have a negative impact on quality of life (QoL), affecting mental and physical health. Leprosy patients usually present with a worse QoL compared with those affected by other conditions. Reactions, neural damage, and pain are some of the consequences that contribute to the lower QoL. However, due to the wide spectrum of the disease, symptoms vary according to leprosy's subtype. This study aimed to compare the QoL between paucibacillary and multibacillary leprosy patients. Individuals were also compared considering the presence of reactions and a correlation between questionnaires was performed. METHODS: A total of 104 patients with leprosy aged 18 years old and over were selected. QoL was assessed by the Brazilian-Portuguese validated versions of the Medical Outcomes Study 36-item short-form health survey (SF-36) and the Dermatology Life Quality Life Index (DLQI). RESULTS: Multibacillary patients showed a more impaired physical function, worse bodily pain, lower score of SF-36, and higher interference of skin on the performance of daily activities when compared to the paucibacillary group. Individuals without reactions presented lower bodily pain and less effect of the skin on clothing choices compared to those with reactions. The SF-36 domains exhibited weak correlations with most DLQI questions, and the linear regression model showed that 32% of changes in QoL were related to the skin aspect. CONCLUSIONS: Multibacillary leprosy patients have a worse QoL when compared to paucibacillary patients. Reactions played a small role in the QoL of our cohort of patients.

Quantitative polymerase chain reaction in paucibacillary leprosy diagnosis: A follow-up study.

OBJECTIVE: The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. METHODS: One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established. RESULTS: In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity. CONCLUSION: The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses.

Leprosy survey among rural communities and wild armadillos from Amazonas state, Northern Brazil.

There is evidence that in southern US, leprosy is a zoonosis infecting wild Dasypus novemcinctus armadillos but the extent of this finding is unknown. This ecological study investigated leprosy in rural communities and in wild armadillos from the Brazilian Amazon. The study area was the Mamiá Lake of Coari municipality, Amazonas State, Northern region, a hyper endemic leprosy area where residents live on subsistence farming, fishing and armadillo hunting and its meat intake are frequent. The leprosy survey was conducted in sixteen communities by a visiting team of specialists. Local partakers provided wild armadillos to investigate M. leprae infection. Volunteers had complete dermato-neurological examination by a dermatologist with expertise in leprosy diagnosis, suspect skin lesions were biopsied for histopathology (Hematoxylin-eosin/HE, Fite-Faraco/FF staining); slit skin smears were collected. Armadillos' tissue fragments (skins, spleens, livers, lymph nodes, adrenal glands, others) were prepared for histopathology (HE/FF) and for M. leprae repetitive element-RLEP-qPCR. Among 176 volunteers, six new indeterminate leprosy cases were identified (incidence = 3.4%). Suspect skin sections and slit skin smears were negative for bacilli. Twelve wild D. novemcinctus were investigated (48 specimens/96 slides) and histopathological features of M. leprae infection were not found, except for one skin presenting unspecific inflammatory infiltrate suggestive of indeterminate leprosy. Possible traumatic neuroma, granuloma with epithelioid and Langhans cells, foreign-body granuloma were also identified. Granulomatous/non-granulomatous dermatitides were periodic-acid-Schiff/PAS negative for fungus. M. leprae-RLEP-qPCR was negative in all armadillos' tissues; no bacillus was found in histopathology. Our survey in rural communities confirmed the high endemicity for leprosy while one armadillo was compatible with paucibacillary M. leprae infection. At least in the highly endemic rural area of Coari, in the Brazilian Amazon region where infectious sources from untreated multibacillary leprosy are abundant, M. leprae infected armadillos may not represent a major source of infection nor a significant public health concern.

Performance of serological tests PGL1 and NDO-LID in the diagnosis of leprosy in a reference Center in Brazil.

BACKGROUND: Early detection of leprosy and multidrug therapy are crucial to achieve zero transmission and zero grade II incapacities goals of World Health Organization. Leprosy is difficult to diagnose because clinical forms vary and there are no gold standard methods to guide clinicians. The serological rapid tests aid the clinical diagnosis and are available for field use. They are easy to perform, do not require special equipment or refrigeration and are cheaper than the molecular tests. METHODS: We evaluated the performance of two rapid serological tests (PGL1 and NDO-LID) in the discrimination of leprosy cases from healthy individuals at the Alfredo da Matta Foundation, a reference center for the disease in Manaus, Amazonas, Brazil. PGL1 and NDO-LID rapid tests are capable of detecting specific antibodies of M. leprae, IgM and IgM/IgG, respectively. A total of 530 healthy subjects and 171 patients (50 with paucibacillary and 121 multibacillary leprosy) were included in the study. RESULTS: Among the paucibacillary leprosy patients, the sensitivity was 34.0 and 32.0% for the NDO-LID and PGL1, respectively. In multibacillary leprosy patients, the NDO-LID sensitivity was 73.6% and the PGL1 was 81.0%. Serological tests demonstrated specificities of 75.9% for PGL-1 and 81.7% for NDO-LID. The positive predictive value (PPV), negative predictive value (NPV) and accuracy in multibacillary patients were 47.9, 93.1, and 80.2% respectively for the NDO-LID, and 43.4, 94.6 76.8% for PGL1. CONCLUSIONS: The tests showed limited capacity in the diagnosis of the disease, however, the high negative predictive value of the tests indicates a greater chance of true negatives in this group favoring exclusion of leprosy. This characteristic of the ML flow test is important in aiding clinical Diagnosis, especially in a region endemic to the disease and with other confounding skin conditions.

Leprosy survey among rural communities and wild armadillos from Amazonas state, Northern Brazil

There is evidence that in southern US, leprosy is a zoonosis infecting wild Dasypus novemcinctus armadillos but the extent of this finding is unknown. This ecological study investigated leprosy in rural communities and in wild armadillos from the Brazilian Amazon. The study area was the Mamia´ Lake of Coari municipality, Amazonas State, Northern region, a hyper endemic leprosy area where residents live on subsistence farming, fishing and armadillo hunting and its meat intake are frequent. The leprosy survey was conducted in sixteen communities by a visiting team of specialists. Local partakers provided wild armadillos to investigate M. leprae infection. Volunteers had complete dermato-neurological examination by a dermatologist with expertise in leprosy diagnosis, suspect skin lesions were biopsied for histopathology (Hematoxylin-eosin/HE, Fite-Faraco/FF staining); slit skin smears were collected. Armadillos' tissue fragments (skins, spleens, livers, lymph nodes, adrenal glands, others) were prepared for histopathology (HE/FF) and for M. leprae repetitive elementRLEP-qPCR. Among 176 volunteers, six new indeterminate leprosy cases were identified (incidence = 3.4%). Suspect skin sections and slit skin smears were negative for bacilli. Twelve wild D. novemcinctus were investigated (48 specimens/96 slides) and histopathological features of M. leprae infection were not found, except for one skin presenting unspecific inflammatory infiltrate suggestive of indeterminate leprosy. Possible traumatic neuroma, granuloma with epithelioid and Langhans cells, foreign-body granuloma were also identified. Granulomatous/non-granulomatous dermatitides were periodic-acid-Schiff/ PAS negative for fungus. M. leprae-RLEP-qPCR was negative in all armadillos' tissues; no bacillus was found in histopathology. Our survey in rural communities confirmed the high endemicity for leprosy while one armadillo was compatible with paucibacillary M. leprae infection. At least in the highly endemic rural area of Coari, in the Brazilian Amazon region where infectious sources from untreated multibacillary leprosy are abundant, M. leprae infected armadillos may not represent a major source of infection nor a significant public health concern.

Factors associated with leprosy in a municipality of the Pre-Amazon region, state of Maranhão, Brazil.

INTRODUCTION: The Integrated Program of Leprosy Control was initiated in the municipality of Buriticupu, Maranhão, Brazil, an area considered hyperendemic for leprosy in 2003. It aims at assessing the clinical and epidemiological characteristics of the disease to reduce the detection rate of new cases until 2015. Here, we present the evolution of the indicators of leprosy within the period from 2003 to 2015. METHODS: We conducted a descriptive analytical study based on the active search for and voluntary referral of cases of leprosy. The detection rate of new cases was analyzed over time. We included individuals diagnosed with leprosy between January 2003 and December 2015. The association between categorical variables was assessed using the chi-square test of independence, considering a level of significance of 5%. When the association was significant, the detection rate (with a confidence interval of 95%) was calculated. RESULTS: Overall, 879 new leprosy cases were detected; the majority of the affected individuals were men (65.9%). Multibacillary leprosy was the most common type of the disease, according to the operational classification (55.5%); it showed the strongest association with an age ≥60 years. We also detected an association between the male sex and both, lepromatous and multibacillary leprosy. The detection rate reduced from 211.09/100,000 population in 2003 to 50.26/100,000 population in 2015. CONCLUSIONS: We found an improvement in leprosy control, with a reduction in the detection rate and the absolute number of cases. Strengthening of disease control measures should be prioritized to eliminate leprosy as a public health concern in this municipality.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population.

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Factors associated with leprosy in a municipality of the Pre-Amazon region, state of Maranhão, Brazil

Abstract INTRODUCTION: The Integrated Program of Leprosy Control was initiated in the municipality of Buriticupu, Maranhão, Brazil, an area considered hyperendemic for leprosy in 2003. It aims at assessing the clinical and epidemiological characteristics of the disease to reduce the detection rate of new cases until 2015. Here, we present the evolution of the indicators of leprosy within the period from 2003 to 2015. METHODS: We conducted a descriptive analytical study based on the active search for and voluntary referral of cases of leprosy. The detection rate of new cases was analyzed over time. We included individuals diagnosed with leprosy between January 2003 and December 2015. The association between categorical variables was assessed using the chi-square test of independence, considering a level of significance of 5%. When the association was significant, the detection rate (with a confidence interval of 95%) was calculated. RESULTS: Overall, 879 new leprosy cases were detected; the majority of the affected individuals were men (65.9%). Multibacillary leprosy was the most common type of the disease, according to the operational classification (55.5%); it showed the strongest association with an age ≥60 years. We also detected an association between the male sex and both, lepromatous and multibacillary leprosy. The detection rate reduced from 211.09/100,000 population in 2003 to 50.26/100,000 population in 2015. CONCLUSIONS: We found an improvement in leprosy control, with a reduction in the detection rate and the absolute number of cases. Strengthening of disease control measures should be prioritized to eliminate leprosy as a public health concern in this municipality.