Pesquisa Nacional de Saúde revela alto percentual de sinais e sintomas de hanseníase no Brasil / National Health Survey reveals high percentage of signs and symptoms of leprosy in Brazil

Resumo A hanseníase é uma doença dermato-neurológica, infecciosa, sistêmica ou localizada, debilitante, causada por Mycobacterium leprae. No Brasil, a magnitude e o alto poder incapacitante mantêm a doença como um problema de saúde pública. Mancha na pele e dormência são sinais e sintomas patognomônicos na hanseníase. A Pesquisa Nacional de Saúde de 2019 (PNS-2019), do Instituto Brasileiro de Geografia e Estatística (IBGE), considerou a seguinte pergunta como proxy para estimar sua magnitude no país. "O(a) sr(a). tem mancha com dormência ou parte da pele com dormência?". No Brasil, 1.921.289 adultos referiram ter mancha ou parte da pele com dormência, sem diferenças regionais. Com relação ao grupo etário, quanto mais velho, maior a prevalência. Por exemplo, entre os de 18 a 29 anos (235.445) e de 30 a 39 anos (236.485), 0,7% possuía a condição, entre 40 e 59 anos (827.887), 1,5%, e entre os idosos, 1,8% (621.472). Poder estimar, em pesquisas de base populacional, com representatividade estatística, uma morbidade referida tal como a hanseníase é fundamental para apoiar a formulação de políticas públicas, notadamente as relativas às ações da atenção primária à saúde. Dessa forma, o IBGE cumpre seu papel constitucional de retratar a realidade da população brasileira e hoje é o principal avaliador externo do Sistema Único de Saúde (SUS) e das políticas públicas instituídas no âmbito federal.

Abstract Leprosy is a debilitating, infectious, systemic or localized dermato-neurological disease caused by Mycobacterium lepra. In Brazil, the magnitude and high disabling power keep the disease as a public health problem. Skin spotting and numbness are pathognomonic signs and symptoms in leprosy. The Instituto Brasileiro de Geografia e Estatística (IBGE) 2019 National Health Survey (PNS-2019) considered the following question as a proxy to estimate its magnitude in the country. "Do you have a spot with numbness or part of the skin with numbness?". In Brazil, 1,921,289 adults reported having a patch or part of the skin with numbness, with no regional differences. As for the age group, the older, the higher the prevalence, for example, between 18 to 29 years old (235,445) and 30 to 39 years old (236,485), 0.7% had the condition, between 40 to 59 years old (827,887), 1.5% and among the elderly, 1.8% (621,472). Being able to estimate, in population-based surveys, with statistical representativeness, a reported morbidity such as leprosy is essential to support the formulation of public policies, notably those related to primary health care actions. In this way, the IBGE fulfills its constitutional role of portraying the reality of the Brazilian population and today it is the main external evaluator of the Unified Health System (SUS) and of public policies developed by the federal level.

Lucius phenomenon: the importance of a primary dermatological care

Abstract Leprosy presents a varied clinical spectrum. Lucius phenomenon is a rare leprosy reaction characterized by erythematous, painful, slightly infiltrated macules and hemorrhagic bullae that progress to ulceration. This case report describes a patient whose diagnosis of leprosy occurred in the presence of Lucius phenomenon. Late diagnosis and delay in the implementation of specific therapy contributed to an unfavorable outcome, highlighting the importance of early identification and treatment of this disease, as well as its complications.

Clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): adverse effects approach

Abstract: BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Presence of Mycobacterium leprae genotype 4 in environmental waters in Northeast Brazil

Abstract INTRODUCTION: This study quantified Mycobacterium leprae bacilli in environmental water samples from five municipalities in the State of Ceará by quantitative polymerase chain reaction (qPCR) and compared the identified genotypes with those obtained from leprosy patient biopsies. METHODS: We collected five replicas from each of the 30 selected reservoirs and skin lesion biopsies from 25 new leprosy cases treated at a reference center in Fortaleza, Ceará from 2010 to 2013. The 16S rRNA gene region of M. leprae was amplified by qPCR and a standard curve was created with the pIDTBlue 16SrRNAMlep plasmid. The Juazeiro do Norte water samples and the biopsies were genotyped (single nucleotide polymorphism [SNP] 1 to 4) and the SNP 4 genotypes were subtyped. RESULTS: Of the 149 water samples analyzed, 54.4% were positive for the M. leprae DNA. The M. leprae bacilli copy number ranged from 1.42 × 10 -1 to 1.44 × 10 + 2 . Most biopsies showed SNP type 4 (64%), while all samples from Juazeiro do Norte were SNP type 4, with subtype 4-N appearing at the highest frequency. CONCLUSIONS: We suggest that environmental waters containing M. leprae bacilli play an important role in disease transmission, justifying PGL-1 seropositivity in individuals living in areas where there is no reported case, and in leprosy cases individuals who report no previous contact with other case. Therefore, further investigation is needed to clarify disease transmission in this region and to explore the role of the environment. We also suggest that in this area surveillance for leprosy cases should be intensified.

Carcinoma basocelular desenvolvido sobre nevo sebáceo: tratamento com terapia fotodinâmica abordando campo de cancerização / Basal cell carcinoma growth over a nevus sebaceous: treatment of the field cancerization with photodynamic therapy

Nevo sebáceo de Jadassohn é hamartoma congênito que pode apresentar evolução para neoplasia cutânea maligna. A terapia fotodinâmica é utilizada para tratamento de ceratoses actínicas e carcinomas basocelulares superficiais ou nodulares, podendo-se observar o campo de cancerização cutâneo através da lâmpada de Wood, durante a realização da técnica. Relata-se um caso do uso da terapia fotodinâmica para o tratamento de um carcinoma basocelular, que se desenvolveu sobre nevo sebáceo, demonstrando-se o campo cancerizável através do uso da lâmpada de Wood. O procedimento consistiu em alternativa de tratamento não cirúrgico para o carcinoma basocelular, com excelente resultado estético. A paciente encontra-se em seguimento clínico, não apresentando recidiva da neoplasia 18 meses após o tratamento.

The sebaceous nevus of Jadassohn is a congenital hamartoma that may develop into a malignant cutaneous neoplasia. Photodynamic therapy is used to treat actinic keratoses and superficial or nodular basal cell carcinomas, and the cutaneous field cancerization can be observed using the Wood's lamp during the performance of the technique. This article describes a case of photodynamic therapy used in the treatment of a basal cell carcinoma, which developed on a sebaceous nevus, where the field cancerization was demonstrated through the use of Wood's lamp. The procedure is a non-surgical alternative for the treatment of the basal cell carcinoma, with excellent aesthetic outcome. The patient is on clinical follow-up, with absence of recurrence of the neoplasia 18 months after the treatment.

Widespread nasal carriage of Mycobacterium lepraeamong a healthy population in a hyperendemic region of northeastern Brazil

A case-control study was conducted to determine the presence ofMycobacterium lepraeDNA in nasal secretions of leprosy cases and nonleprosy individuals in Fortaleza, Brazil. It included 185 cases identified by physicians at the Dona Libânia National Reference Centre for Sanitary Dermatology (CDERM). A control group (Co) (n = 136) was identified among individuals from CDERM not diagnosed as leprosy cases. To augment the spatial analysis of M. leprae specific repetitive element (RLEP) positive prevalence, an external group (EG) (n = 121), a convenience sample of healthy students, were included. Polymerase chain reaction for the RLEP sequence was conducted for all participants. Prevalence of RLEP positivity for cases and Co were 69.2% and 66.9%, respectively, significantly higher than for EG (28.1%), and reported elsewhere. Male sex, belonging to a lower socioeconomic status (D/E), history of a previous contact with a case and being older, were associated with being a leprosy case. Our geographical analysis demonstrated that the bacillus is widespread among the healthy population, with clusters of RLEP positive multibacillary cases concentrated in distinct areas of the city. Our results suggest that in endemic areas, as in Fortaleza, surveillance for both nonhousehold leprosy contacts and members of the general population living in cluster areas should be implemented.

Genotyping of Mycobacterium leprae present on Ziehl-Neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of Brazil

We analysed 16 variable number tandem repeats (VNTR) and three single-nucleotide polymorphisms (SNP) in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N)-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23), Pernambuco (n = 41), Rio de Janeiro (n = 22) and Rondônia (RO) (n = 78). All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1%) yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.

A clinical trial for uniform multidrug therapy for leprosy patients in Brazil: rationale and design

Leprosy will continue to be a public health problem for several decades. The World Health Organization (WHO) recommends that, for treatment purposes, leprosy cases be classified as either paucibacillary or multibacillary (MB). A uniform leprosy treatment regimen would simplify treatment and halve the treatment duration for MB patients. The clinical trial for uniform multidrug therapy (U-MDT) for leprosy patients (LPs) in Brazil is a randomised, open-label clinical trial to evaluate if the effectiveness of U-MDT for leprosy equals the regular regimen, to determine the acceptability of the U-MDT regimen and to identify the prognostic factors. This paper details the clinical trial methodology and patient enrolment data. The study enrolled 858 patients at two centres and 78.4% of participants were classified as MB according to the WHO criteria. The main difficulty in evaluating a new leprosy treatment regimen is that no reliable data are available for the current treatment regimen. Relapse, reaction and impaired nerve function rates have never been systematically determined, although reaction and impaired nerve function are the two major causes of nerve damage that lead to impairments and disabilities in LPs. Our study was designed to overcome the need for reliable data about the current treatment and to compare its efficacy with that of a uniform regimen.

Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

Mycobacterium leprae virulence-associated peptides are indicators of exposure to M: leprae in Brazil, Ethiopia and Nepal

Silent transmission of Mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. Therefore, the development of tools for the early diagnosis of M. leprae infection should be emphasised in leprosy research. As part of the continuing effort to identify antigens that have diagnostic potential, unique M. leprae peptides derived from predicted virulence-associated proteins (group IV.A) were identified using advanced genome pattern programs and bioinformatics. Based on human leukocyte antigen (HLA)-binding motifs, we selected 21 peptides that were predicted to be promiscuous HLA-class I T-cell epitopes and eight peptides that were predicted to be HLA-class II restricted T-cell epitopes for field-testing in Brazil, Ethiopia and Nepal. High levels of interferon (IFN)-γ were induced when peripheral blood mononuclear cells (PBMCs) from tuberculoid/borderline tuberculoid leprosy patients located in Brazil and Ethiopia were stimulated with the ML2055 p35 peptide. PBMCs that were isolated from healthy endemic controls living in areas with high leprosy prevalence (EChigh) in Ethiopia also responded to the ML2055 p35 peptide. The Brazilian EChigh group recognised the ML1358 p20 and ML1358 p24 peptides. None of the peptides were recognised by PBMCs from healthy controls living in non-endemic region. In Nepal, mixtures of these peptides induced the production of IFN-γ by the PBMCs of leprosy patients and EChigh. Therefore, the M. leprae virulence-associated peptides identified in this study may be useful for identifying exposure to M. leprae in population with differing HLA polymorphisms.

A demanda de um centro de referência nacional para hanseníase no nordeste brasileiro: por que o excesso de pacientes? / The need for a national reference center in Brazil's northeastern region: why the excess of patients?

Até 2000, o controle da hanseníase no Brasil foi verticalizado. Depois desta data, o processo de descentralização desta doença deu início a ações que priorizaram o nível primário de atenção à saúde. Entretanto, a assistência ainda permane centralizada em algumas unidades, como o Centro Nacional de Referência em Dermatologia Sanitária D. Libânia (CDERM), em Fortaleza, Ceará. Este centro responde por 84 por cento da detecção do município. O objetivo deste estudo foi investigar os fatores associados à demanda excessiva de casos em nível secundário de atenção representado por este centro de referência. Um estudo transversal foi realizado com 600 usuários selecionados aleatoriamente nos ambulatórios do CDERM. Foram coletados dados: sócio econômico e demográficos, sobre conhecimento da doença e percepção dos serviços. Oitenta e dois por cento dos participantes tinham baixa situação sócio econômica, 90 por cento vieram encaminhados por outras unidades de saúde e 87 por cento tinham a forma multibacilar. Sessenta e nove por cento receberam atendimento prévio em outras Unidades de Saúde, 49 por cento jamais ouviram falar de hanseníase, 24 por cento referiram sentir medo da doença ou terem sofrido discriminação, 39 por cento dos usuários referiram que o atendimento ininterrupto no horário do almoço favorece a permanência no CDERM, 57 por cento e 27 por cento, respectivamente, referiram que a medicação complementar nunca faltou no CDERM e nas Unidades Básicas de Saúde (UBS). Sessenta e um por cento considerou que o compromisso dos profissionais no CDERM foi ótimo contra 14 por cento nas UBS. Os fatores relatados pelos usuários, especialmente logísticos e de qualidade de atendimento e dos profissionais, poderiam explicar a concentração de usuários neste centro de referência.

A demenda de um Centro de Referência Nacional para Hanseníase no Nordeste Brasileiro: por que o excesso de pacientes? / The need for a national reference center in Brazil's northeastern region: why the excess of patients?

Até 2000, o controle de hanseníase no Brasil foi verticalizado. Depois desta data, o processo de descentralização desta doença deu ínicio a ações que priorizaram o nível primário de atenção à saúde. Entretanto, a assistência ainda permanece centralizada em algumas unidades, como o Centro Nacional de Referência em Dermatologia Sanitária D. Libânia (CDERM), em Fortaleza, Ceará. Este centro responde por 84% da detecção do município. O objetivo deste estudo foi investigar os fatores associados à demanda excessiva de casos em nível secundário de atenção representado por este centro de referência. Um estudo transversal foi realizado com 600 usuários selecionados aleatoriamente nos ambulatórios do CDERM. Foram coletados dados: sócio-econômico e demográficos, sobre conhecimento da doença e percepção dos serviços. Oitenta e dois por cento dos participantes tinham baixa situação socio-econômica, 90% vieram encaminhados por outras unidades de saúde e 87% tinham a forma multibacilar. Sessenta e nove por cento receberam atendimento prévio em outras Unidades de Saúde, 49% jamais ouviram falar de hanseníase, 24% referiram sentir medo da doença ou terem sofrido discriminação, 39% dos usuários referiram que o atendimento ininterrupto no horário do almoço favorece a permanência no CDERM, 57% e 27%, respectivamente, referiram que a medicação complementar nunca faltou no CDERM e nas Unidades Básicas de Saúde (UBS). Sessenta e um por cento considerou que o compromisso dos profissionais no CDERM foi ótimo contra 14% nas UBS. Os fatores relatados pelos usuários, especialmente logísticos e de qualidade de atendimento e dos profissionais, poderiam explicar a concentração de usuários neste centro de referência.

Perfil clínico-epidemiológico dos pacientes diagnosticados com hanseníase em um centro de referência na região nordeste do Brasil / Clinical and epidemiological profile of patients diagnosed with leprosy in a reference center in the notheast of Brazil

FUNDAMENTOS: A hanseníase permanece sério problema de saúde pública mundial. O conhecimento das características epidemiológicas da doença é importante ferramenta para o controle da endemia. OBJETIVO: Descrever as características clínicas e epidemiológicas dos pacientes diagnosticados com hanseníase no ano de 2004 em um centro de referência da Região Nordeste do Brasil. MÉTODO: Foram avaliados prontuários de pacientes que deram entrada no registro ativo do Centro de Dermatologia Dona Libânia, em Fortaleza, Ceará, no período de janeiro a dezembro de 2004. RESULTADOS: dos 967 casos que deram entrada nesse Centro naquele ano, 909 foram casos novos. Cerca de 7,7 por cento eram pacientes entre zero e 14 anos de idade, e a distribuição por gênero foi de 483 (49,95 por cento) homens e 484 (50,05 por cento) mulheres. A maioria apresentava a forma clínica dimorfa (54,6 por cento), sendo 82,2 por cento dos pacientes provenientes de Fortaleza, CE. Foi realizada a avaliação do grau de incapacidades no diagnóstico em 94,2 por cento dos pacientes, com 21,7 por cento apresentando grau diferente de zero no diagnóstico. CONCLUSÃO: Com base nos resultados obtidos, constatou-se a presença de elevado percentual (7,7 por cento) de casos detectados em menores de 15 anos, associado a baixo percentual (5,8 por cento) de pacientes diagnosticados na forma indeterminada e elevado percentual (21,7 por cento) de casos com incapacidade ao diagnóstico.

BACKGROUND: Leprosy continues to represent a serious public health problem worldwide. Knowledge of epidemiological characteristics of the disease is an important tool for the endemy control. OBJECTIVES: To describe the clinical and epidemiological characteristics of patients diagnosed with leprosy during 2004, in a Reference Center in the Northeast of Brazil. METHODS: We analyzed the records referring to patients who entered de active register of the Center of Dermatology Dona Libânia, in Fortaleza, Ceará, from January to december 2004. RESULTS: Out of 967 cases that entered this Center in this year, 909 were new detected cases. About 7,7 percent were between zero e 14 years old, and distribution per gender was of 483(49,95 percent) men and 484(50,05 percent) women. Most of them presented the borderline clinical form (54,6 percent), and 82,2 percent resided in the city of Fortaleza/CE. Measurement of disabilities degree in diagnosis was made in 94,2 percent of the patients, and 21,7 percent of total showed a degree different from zero. CONCLUSION: Based in the results, we noted a high percentual (7,7 percent) of patients under fifteen years old, associated with low percentual of indeterminate forms and a high percentual of cases with disabilities at diagnosis. These factors are expressive enough to make the authorities consider the difficulties to reach the goal of eliminating leprosy by the end of 2005, and the necessity of new approaches and strategies to control leprosy endemy.