Association of MICA and HLA-B alleles with leprosy in two endemic populations in Brazil.

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case-control and a family-based study in two endemic populations in Brazil. MICA and HLA-B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR-SSOP-Luminex-based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi-square or Fisher's exact test together with a multivariate analysis. Family-based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002-HLA-B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA-A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA-B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA-B markers rs2596498 and rs2507992, and high LD (R2  = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA-B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele.

Emergence and Transmission of Drug-/Multidrug-resistant Mycobacterium leprae in a Former Leprosy Colony in the Brazilian Amazon.

BACKGROUND: Leprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods. METHODS: A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR). RESULTS: Mycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae. CONCLUSIONS: A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.

Perceptions and experiences regarding the impact of race on the quality of healthcare in Southeast Brazil: a qualitative study.

Objective: To explore the impact of race on the quality of healthcare received by patients attending a primary care centre in Brazil.Design: This was a qualitative study consisting of 19 semi-structured interviews conducted on patients from six racial groups (as defined in Brazil as white, yellow, brown, black and indigenous and one self-identified 'other' group). The interviews were analysed using thematic analysis.Results: Four main themes were identified during analysis; factors affecting the access to healthcare, experiences regarding quality of healthcare, discrimination in healthcare and deep-rooted societal discrimination, which were categorised into a number of sub-themes. Within these themes, interviewees reported (1) experiences of racism in society towards the black racial group, (2) one personal perception and two observations of racial discrimination in healthcare, (3) perceived racial discrimination due to healthcare professional behaviour and (4) other factors, such as delays in appointments and long waiting times in health facilities were felt to impact access to care.Conclusion: The findings suggest that racial discrimination exists in Brazilian society but its direct impact on healthcare access was felt to be less obvious. Instead, organisational level factors were felt to contribute to difficulty accessing care. Interviewees perceived that racial discrimination may affect the quality of care, particularly for those designated as 'black'. Socio-economic factors were felt to influence discrimination in healthcare. The findings can help inform further studies and educational initiatives to help address discrimination and access to healthcare in Brazil.

Early detection of M. leprae by qPCR in untreated patients and their contacts: results for nasal swab and palate mucosa scraping.

To verify if the hard palate mucosa can be a site of relevance in the early molecular detection of Mycobacterium leprae in leprosy cases and their household contacts and if there is a correlation of results in nasal swab with those of the scraping of the palate mucosa. The quantitative polymerase chain reaction technique was used. Sample included 78 patients with untreated leprosy (G1), their 54 household contacts (G2), and 80 healthy individuals for the negative control (G3). The presence of M. leprae in both G1 and G2 was observed with the nasal swab and the palate mucosa scrapings methods, and it was shown that the sensitivity between the qPCR exams for RLEP and 85B genes is equivalent, with no statistically significant differences (G1 positivity of 35% in the hard palate mucosa and 44% for the nasal one, p = 0.3731 and for G2 of 31 and 38%, respectively, p = 0.6774). Results support the fact that the buccal mucosa and nasal mucosa may be important sites of primary infection of leprosy with repercussion in the transmission chain and that asymptomatic household contacts are heavily harbored by the causative agent of leprosy, which has a critical significance in the prevention and control action of this disease, since the evaluation of these sites arises as of importance in the early detection of M. leprae. Close monitoring and chemoprophylaxis of household contacts appear to be critical to attain interruption of the transmission of leprosy in endemic countries.

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

The patient perspective of the diagnostic process for leprosy in Brazil. An exploratory study.

OBJECTIVES: To explore the patient experience of being diagnosed with leprosy and the support provided during this process in selected populations in Brazil. To understand the information needs of patients during diagnosis. To identify characteristics of patients with different diagnostic experiences. To add to the evidence base used for improving the diagnostic process for leprosy patients. DESIGN: A self-constructed questionnaire delivered to 116 participants, at three leprosy health centres, across three states in Brazil. RESULTS: Most participants felt under-informed during diagnosis; 68.1% wanted more information about leprosy. Nearly one-quarter of patients reported feeling unable to ask questions at diagnosis. Almost half of patients reported being worried about treatment, yet 43.3% reported not having the chance to talk about their concerns. Younger participants were significantly more likely to report feeling unable to ask questions and talk about their worries. The majority of participants (59.5%) reported not being given any written information to take away with them. 36.5% reported not being given advice about how to reduce the chance of other family members becoming ill with leprosy. Older males were most likely to be given this advice despite females being in most contact with family members in most cultures. CONCLUSIONS: It is recommended that patients are encouraged to ask questions and invited to talk about their concerns, particularly younger patients. It is recommended that a simple information leaflet be provided to all patients. These suggestions may require some financial input, more staff and longer consultations but should significantly improve the diagnostic process.

NOD2 and CCDC122-LACC1 genes are associated with leprosy susceptibility in Brazilians.

Leprosy is a complex disease with phenotypes strongly influenced by genetic variation. A Chinese genome-wide association study (GWAS) depicted novel genes and pathways associated with leprosy susceptibility, only partially replicated by independent studies in different ethnicities. Here, we describe the results of a validation and replication study of the Chinese GWAS in Brazilians, using a stepwise strategy that involved two family-based and three independent case-control samples, resulting in 3,614 individuals enrolled. First, we genotyped a family-based sample for 36 tag single-nucleotide polymorphisms (SNPs) of five genes located in four different candidate loci: CCDC122-LACC1, NOD2, TNFSF15 and RIPK2. Association between leprosy and tag SNPs at NOD2 (rs8057431) and CCDC122-LACC1 (rs4942254) was then replicated in three additional, independent samples (combined OR(AA) = 0.49, P = 1.39e-06; OR(CC) = 0.72, P = 0.003, respectively). These results clearly implicate the NOD2 pathway in the regulation of leprosy susceptibility across diverse populations.

Influence of KIR genes and their HLA ligands in the pathogenesis of leprosy in a hyperendemic population of Rondonópolis, Southern Brazil.

BACKGROUND: The objective of this study was to investigate the association between KIR genes and the immunopathogenesis of leprosy. METHODS: The types of KIR and HLA genes were evaluated by PCR-SSOP-Luminex in 408 patients with leprosy and 413 healthy individuals. Statistical analysis was performed using the Chi-square or Fisher's exact test and stepwise multivariate analysis. RESULTS: There was a higher frequency of activating KIR genes (KIR2DS1, 2DS2 and 3DS1) together with their HLA ligands in the tuberculoid (TT) group as compared to the lepromatous leprosy (LL) group. KIR2DL2/2DL2-C1 was more frequent in the patient, TT and LL groups than in the control group. Borderline patients presented a higher frequency of inhibitory pairs when compared to the control group, and a higher frequency of activating pairs as compared to the LL group. Multivariate analysis confirmed the associations and demonstrated that being a female is a protective factor against the development of the disease per se and the more severe clinical form. CONCLUSIONS: This study showed that activating and inhibitory KIR genes may influence the development of leprosy - in particular, activating genes may protect against the more aggressive form of the disease - thereby demonstrating the role of NK cells in the immunopathology of the disease.

Toll-like receptor 1 N248S single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection.

Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio [OR], 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM3cysK4. The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR1 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function.

OFLOXACIN multicentre trial in MB leprosy FUAM-Manaus and ILSL-Bauru, Brazil.

UNLABELLED: Recently antimicrobials of the fluoroquinolone class (pefloxacin and ofloxacin) were found far more effective against Mycobacterium leprae in studies with both mice and patients than dapsone and clofazimine. As multicentre trial participants, we evaluated the therapeutic efficacy, in terms of rate of relapse, of two new multidrug regimens containing ofloxacin, comparing them to 1 year and 2 years of standard WHO-MDT regimen in multibacillary (MB) leprosy patients. A total of 198MB patients were recruited to participate in a randomized, double-blind trial. Among those, 53 patients were treated with 1 year of WHO-MDT (a regimen including dapsone, clofazimine, and rifampin), 55 patients received 1 year of WHO-MDT plus an initial 1 month of daily ofloxacin, 63 patients were treated with 1 month of daily rifampin and daily ofloxacin, whereas 27 were treated with 2 years of WHO-MDT. Patients were regularly monitored for signs of relapse, in at least 7 years follow-up after being released from treatment. RESULTS: Relapse occurred in those treated with 1-month regimen alone at a significant higher rate (P < 0.001): 388%, whereas in the other three regimens that included WHO-MDT it ranged from 0 to 5%. This study found that a short-course treatment for MB patients with rifampicin-ofloxacin combination had a higher failure rate. The addition of one month of daily ofloxacin to 12 months MB WHO-MDT did not increase its efficacy.

Molecular drug susceptibility testing and genotyping of Mycobacterium leprae strains from South America.

Possible drug resistance in Mycobacterium leprae strains from Venezuela and three other South American countries was surveyed by molecular methods. None of the 230 strains from new leprosy cases exhibited drug resistance-associated mutations. However, two of the three strains from relapsed cases contained dapsone resistance mutations, and one strain also harbored a rifampin resistance mutation. Single nucleotide polymorphism analysis of these strains revealed five subtypes: 3I (73.8%), 4P (11.6%), 1D (6.9%), 4N (6%), and 4O (1.7%).

Increased serum levels of interleukin-6 in erythema nodosum leprosum suggest its use as a biomarker.

BACKGROUND: Erythema nodosum leprosum (ENL) is a frequent complication of multibacillary leprosy that can result in significant morbidity, including peripheral nerve damage and physical disability. The identification of possible serum markers could be a valuable tool for the early detection of ENL. AIMS: The purpose of this study was to evaluate selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for ENL. METHODS: The levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17, interferon-γ, tumor necrosis factor, nitric oxide and anti-phenolic glycolipid-I antibodies were measured in the sera of leprosy patients with ENL [at the beginning of reaction (M0) and 1 month later (M1)], and then compared with the levels of the same markers in patients with untreated multibacillary leprosy without ENL (controls with leprosy: CTRL) and healthy individuals (healthy controls: CTRH). RESULTS: Significantly higher levels of serum interleukin-6 were observed in M0 than in CTRL. In addition, pairwise comparisons showed higher levels of interleukin-6 in M0 compared to M1. Levels of tumor necrosis factor were higher in M0 than in CTRL, with no significant difference between M0 and M1. There were no differences in the levels of interleukin-2, interleukin-4, interleukin-10, interleukin-17 or interferon-γ between groups. The CTRL group had higher levels of nitric oxide compared to M0 and M1. High levels of anti-phenolic glycolipid-I were observed in M0, M1 and CTRL than in CTRH. LIMITATIONS: Three patients were not assessed at M1, decreasing the number of evaluated patients from 14 to 11. CONCLUSION: High-serum levels of interleukin-6 were observed during ENL, primarily in patients with more severe reactions; levels decreased after specific therapy, suggesting a role for this cytokine in pathogenesis and its utility as an ENL biomarker. Further studies should explore whether interleukin-6 could also be used as a predictive marker for ENL or as a specific target for its treatment.

The long-term impact of the Leprosy Post-Exposure Prophylaxis (LPEP) program on leprosy incidence: A modelling study.

BACKGROUND: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence. METHODOLOGY: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040. PRINCIPAL FINDINGS: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme. CONCLUSIONS: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes.

Leprosy post-exposure prophylaxis with single-dose rifampicin (LPEP): an international feasibility programme.

BACKGROUND: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. METHODS: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. FINDINGS: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. INTERPRETATION: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. FUNDING: Novartis Foundation.

Views and Experiences of Adults who are Overweight and Obese on the Barriers and Facilitators to Weight Loss in Southeast Brazil: A Qualitative Study.

Background: Obesity in Brazil is increasing with 54% of the Brazilian population being overweight, of which 20% is obese. Obesity is a risk factor for non-communicable diseases such as cardiovascular disease: the leading cause of mortality in Brazil. This study aims to identify the barriers and facilitators to weight loss as perceived by patients with a view to reducing the burden of obesity-related diseases on patients and healthcare services. Methods: Fifteen qualitative, semi-structured, in-depth interviews were conducted in the preventive medicine department in a private health clinic in Bauru, Southeast Brazil. Inductive thematic analysis was conducted. Results: The barriers and facilitators were classified into three themes: lifestyle, motivation and education. Barriers include cost of a healthy lifestyle, time management, personal safety, mobility, junk food advertising, sustaining weight loss, mental health, lack of support and health education. Facilitators include change in eating habits, sleep quality, cooperative food networks, access to the multidisciplinary team and expert patients as health educators. Conclusion: Expert patients should be utilized as an education method, as they increase motivation, promote the facilitators and provide realistic expectations of the weight loss process. Barriers such as junk food advertising and accessibility to treatment need to be addressed. Abbreviations: BMI: Body Mass Index; NCD: Non-Communicable Disease; SUS: Sistema Único de Saúde; WHO: World Health Organization.

[Acceptability of chemoprophylaxis in an endemic area for leprosy: the PEP-Hans Brazil Project]. / Aceitabilidade da quimioprofilaxia em área endêmica para a hanseníase: projeto PEP-Hans Brasil.

The aim was to analyze the acceptability of chemoprophylaxis with single-dose rifampicin (PEP) in contacts, index leprosy cases, and health professionals and related factors that can influence adherence. A qualitative content analysis study was performed after application of semi-structured interviews according to the protocol proposed in the LPEP program (2016) drafted at Alta Floresta, Mato Grosso State, Brazil, in July 2016. Study participants included individuals with leprosy, contacts, and health professionals. The QRS NVivo software version 10 was used. A total of 80 individuals were contacted, including 54 (67%) contacts, 11 (14%) index cases, and 15 (19%) health professionals. 94% of the contacts (51/54) took PEP. Three PEP categories were identified: understanding, acceptance, and expectation towards the intervention. Understanding proved to be related to care by the health team. Acceptance (or lack thereof) of the medication was related to fear, trust, and protection, the strategy's operability, self-esteem, and insecurity regarding the intervention. Expectation towards the intervention was related to wellbeing, prevention of the disease, sequelae, decrease in public expenditures, and expanded access. Participants acknowledged the relevance of the PEP strategy based on the possibility of interrupting the transmission chain, reduction in new cases, and improved quality of life. Insecurity in taking the medication and the possibility of the disease manifesting itself had a negative influence on acceptance of PEP, while prior information on the PEP strategy helped strengthen trust in the health professionals and the medication's acceptance.

O objetivo deste artigo foi analisar a aceitabilidade da quimioprofilaxia com rifampicina em dose única (PEP) entre os contatos, casos índices de hanseníase e profissionais da saúde e fatores relacionados que possam influenciar na adesão. Realizou-se um estudo qualitativo de análise de conteúdo após aplicação de entrevistas semiestruturadas segundo protocolo proposto no programa LPEP (2016), realizado em Alta Floresta, Mato Grosso, Brasil, em julho de 2016. Participaram do estudo indivíduos notificados com hanseníase, contatos e profissionais da saúde. Utilizou-se o software QRS NVivo versão 10. Foram contatados 80 indivíduos, sendo 54 (67%) contatos, 11 (14%) casos índices e 15 (19%) profissionais de saúde. Dentre os contatos, 94% (51/54) tomaram PEP. Foram identificadas 3 categorias quanto à PEP: compreensão, aceitação e expectativa da intervenção. A compreensão se mostrou relacionada ao cuidado da equipe de saúde. Aceitar ou não a medicação revelou-se relacionada ao medo, confiança e proteção, operacionalidade da estratégia, autoestima e insegurança quanto à intervenção. A expectativa da intervenção relacionou-se ao bem-estar, prevenção da doença e de sequelas, diminuição de gastos públicos e ampliação do acesso. Houve reconhecimento da relevância da estratégia PEP pela possibilidade de interrupção da cadeia de transmissão, diminuição de casos novos e melhora na qualidade de vida. A insegurança em tomar a medicação e de a doença se manifestar influenciaram negativamente à aceitação da PEP; por outro lado, as informações prévias sobre a estratégia PEP contribuíram para o fortalecimento da confiança nos profissionais de saúde e para a aceitabilidade da medicação.

El objetivo fue analizar la aceptabilidad de la quimioprofilaxis con rifampicina en dosis única (PEP) entre los contactos, casos índices de hanseniasis y profesionales de salud, así como los factores relacionados que puedan influenciar en la adhesión al tratamiento. Se realizó un estudio cualitativo de análisis de contenido, tras la realización de entrevistas semiestructuradas, según el protocolo propuesto en el programa LPEP (2016), realizado en Alta Floresta, Mato Grosso, Brasil, en julio de 2016. Participaron en el estudio individuos diagnosticados con hanseniasis, contactos y profesionales de la salud. Se utilizó el software QRS NVivo versión 10. Se contactó con 80 individuos, siendo 54 (67%) contactos, 11 (14%) casos índices y 15 (19%) profesionales de salud. Entre los contactos 94% (51/54) tomaron PEP. Se identificaron 3 categorías respecto a la PEP: comprensión, aceptación y expectativa de intervención. La comprensión estuvo relacionada con el cuidado del equipo de salud. El aceptar o no la medicación estuvo relacionado con el miedo, confianza y protección, operatividad de la estrategia, autoestima e inseguridad de la intervención. La expectativa de la intervención estuvo relacionada con el bienestar, prevención de la enfermedad, así como secuelas, disminución de gasto público y ampliación del acceso. Existió un reconocimiento de la relevancia de la estrategia PEP por la posibilidad de interrupción de la cadena de transmisión, disminución de casos nuevos y mejora en la calidad de vida. La inseguridad en tomar la medicación y de que la enfermedad se manifestara influenciaron negativamente en la aceptación de la PEP, por otro lado, la información previa sobre la estrategia PEP contribuyó al fortalecimiento de la confianza en los profesionales de salud y a la aceptabilidad de la medicación.

Human Genetic Susceptibility of Leprosy Recurrence.

Host genetic susceptibility to leprosy has been intensively investigated over the last decades; however, there are no studies on the role of genetic variants in disease recurrence. A previous initiative identified three recurrent cases of leprosy for which none of the M. leprae strains, as obtained in the first and the second diagnosis, had any known genomic variants associated to resistance to Multidrug therapy; in addition, whole genome sequencing indicated that the same M. leprae was causing two out of the three recurrences. Thus, these individuals were suspected of being particularly susceptible to M. leprae infection, either as relapse or reinfection. To verify this hypothesis, 19 genetic markers distributed across 11 loci (14 genes) classically associated with leprosy were genotyped in the recurrent and in three matching non-recurrent leprosy cases. An enrichment of risk alleles was observed in the recurrent cases, suggesting the existence of a particularly high susceptibility genetic profile among leprosy patients predisposing to disease recurrence.

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.