High frequency of ofloxacin resistance patterns of Mycobacterium leprae from India: An indication to revisit second line anti-leprosy treatment regimen.

OBJECTIVES: Drug resistance in leprosy is an emerging concern, leading to treatment failures, recurrences, and potential spread of resistant Mycobacterium leprae in the community. In this study, we aimed to assess drug resistance prevalence and patterns amongst leprosy patients at a tertiary care referral hospital in India. METHODS: Mutations in drug resistance determining regions for dapsone, rifampicin, and ofloxacin of the M. leprae genome in DNA extracted from skin biopsies of 136 leprosy patients (treatment-naive = 67, with persistent skin lesions = 35, with recurrence = 34) were analysed by polymerase chain reaction followed by Sanger sequencing. Wild-type strain (Thai-53) was used as a reference strain. RESULTS: Resistance mutations were identified in a total of 23 patients, constituting 16.9% of the cohort. Within this subset of 23 cases, resistance to ofloxacin was observed in 17 individuals (12.5%), while resistance to both dapsone and rifampicin was detected in three patients each (2.2% for both). The occurrence of ofloxacin resistance showed minimal disparity between recurrent and treatment-naive cases, at 17.6% and 16.4%, respectively. Dapsone resistance emerged in two treatment-naive cases and one case with persistent skin lesions. Notably, none of the treatment-naive cases or those with recurrence/relapse exhibited rifampicin resistance. Subsequently, no statistically significant correlation was identified between other clinical variables and the presence of antimicrobial resistance. CONCLUSIONS: The occurrence of resistance to the current multidrug therapy regimen (specifically dapsone and rifampicin) and to ofloxacin, a secondary antileprosy medication in M. leprae, represents a concerning scenario. This calls for an expansion towards bactericidal drug options and the establishment of robust surveillance for drug resistance in countries burdened with high leprosy rates. Moreover, the introduction of stringent antimicrobial stewardship initiatives is imperative. As a single centre study, it represents a limited, cross-sectional view of the real situation in the field.

Leprosy in a Patient With Lymphoma: A Challenge in the Twenty-First Century.

Leprosy, or Hansen's disease, mistakenly considered a disease from the past by some, is still common nowadays, especially in tropical and subtropical regions. In the absence of appropriate medical treatment, it may progress and cause permanent damage to multiple organs. This case report illustrates the diagnostic challenge of a south-american adult man who had been living in Europe for over 14 years. He was referred to the Hematology department due to persistent lymphocytosis and a CD5+ B-cell lymphoproliferative disorder was identified. During clinical surveillance, the patient developed skin lesions in his limbs with associated hypoesthesia. A histological diagnosis of lepromatous leprosy was made, and he underwent a long-term three-drug therapeutic regimen (dapsone, rifampicin, and clofazimine). Adding to the complexity of the case, the patient progressed with splenomegaly and constitutional symptoms, more than 7 years after development of lymphocytosis. Through a comprehensive evaluation, a definitive diagnosis of mantle cell lymphoma was established and received 6-cycle R-CHOP induction, followed by maintenance rituximab. Importantly, prophylaxis for leprosy reactivation was not administered as there were no recommendations in available guidelines. Eventually, the patient experienced a leprosy relapse while on maintenance therapy, 58 months after completing the initial anti-leprous treatment. Clinical response was attained with a new treatment regimen consisting of rifampicin, clofazimine, and minocycline.  Although leprosy is primarily observed in tropical and subtropical regions, the long incubation period of this disease combined with the global flow of migrants, made us consider it. Despite being rare, leprosy relapses can occur even after a few decades. The contribution of rituximab or previously administered chemotherapeutic agents is still unknown. The question remains whether antibiotic prophylaxis should be performed in patients undergoing immunochemotherapy for malignant diseases.

An evidence and reasoning based differential diagnosis of a case of leprosy reinfection from reaction and relapse.

Leprosy is caused by Mycobacterium leprae (M. leprae) and is unique in terms of the chronicity of the disease and its prolonged treatment protocol. Even after the introduction of multidrug therapy (MDT) by World health organization (WHO), large numbers of new cases (nearly 200,000) of leprosy are reported yearly, indicating active transmission, especially in developing countries. Recurrent clinical manifestations after MDT can occur due to leprosy reactions, relapse or reinfection. It is very difficult to differentiate reaction, relapse and reinfection. Here we categorized a recent case of reoccurrence of leprosy as reinfection by differentiating it from reaction and relapse based on evidence and by analysing the clinical data of the patient.

Leprosy Relapse: A Retrospective Study on Epidemiologic, Clinical, and Therapeutic Aspects at a Brazilian Referral Center.

OBJECTIVES: We aimed to characterize the profile of patients diagnosed with leprosy relapse and understand the influence of different multidrug therapy (MDT) treatments and initial disease presentation. METHODS: This retrospective study included patients diagnosed with leprosy relapse at a referral center in Brazil from 2013 to 2018. We analyzed their clinico-epidemiologic characteristics, laboratory data, and bacilloscopic tests. Survival analysis was used to determine the time elapsed until relapse according to the previous treatment and clinical forms of the disease. RESULTS: A total of 126 cases of relapse were analyzed, which comprised 11.89% (126/1059) of the cases. The median time elapsed until a relapse was 10 years, and most patients had previously undergone 12 doses of MDT (40.48%; 51/126). Undergoing 24 doses of MDT was associated with a better prognosis regarding relapse over time compared with 6 or 12 doses of MDT therapy. Most cases of relapse were classified as multibacillary (96.03%; 121/126). CONCLUSION: The incidence of relapse was greater than observed in other studies. The high percentage of multibacillary patients who had negative bacillary indices demonstrated that the bacillary index cannot be considered to be an essential criterion for relapse, especially concerning making an early diagnosis.

Altered cytokine profiles in relapsed paucibacillary leprosy: a case report.

BACKGROUND: Individuals with relapses of leprosy should be monitored carefully, however, with respect to paucibacillary (PB) leprosy, it is sometimes difficult to make a definitive diagnosis of relapse, because the bacillary index is often negative. To evaluate the usefulness of cytokine profiling in a patient with relapsed PB leprosy who tested negative for anti-phenolic glycolipid-I antibodies, we analyzed the Mycobacterium leprae protein-induced cytokine expression in peripheral blood mononuclear cells of the patient. CASE PRESENTATION: An 89-year-old-male relapsed PB patient, first treated for leprosy over 50 years prior, was examined. In April 2012, he noticed three skin lesions consisting of annular erythema in the thighs. Slit skin smear tests were negative, and skin biopsies revealed a pathology of indeterminate-to-borderline tuberculoid leprosy. He received 600 mg of rifampicin once per month and 75 mg of dapsone daily for 12 months. The annular erythemas disappeared after starting treatment. Before treatment, and 6 and 12 months after starting treatment, the Th1/Th2 cytokine profiles in the supernatant of mononuclear cells from the patient before and after stimulation with Mycobacterium leprae soluble protein (MLS) were examined using a Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II. The CBA Enhanced Sensitivity Flex Set system was applied to detect small amounts of cytokines in the serum just before treatment and one year before relapse. In the culture supernatant, just before treatment, increases in IFN-γ level and the IFN-γ/IL-10 ratio and a decreased IL-6 level were observed without stimulation. Upon stimulation with MLS, just before treatment, both the IFN-γ and TNF levels increased markedly, and twelve months after starting treatment, the IFN-γ and TNF levels decreased greatly. In the serum, just before treatment, increases in IFN-γ and TNF levels and the IFN-γ/IL-10 ratio were evident compared with those measured one year before relapse. CONCLUSIONS: Cytokine profiling using culture supernatants and serum samples may be useful for the diagnosis of relapsed PB leprosy.

Health Burden of Hansen's Disease in Central India: A 4-Year Retrospective Study.

BACKGROUND: Despite the implementation of multidrug therapy by WHO to treat Hansen's disease (HD), new case detection rates are still high indicating active transmission. AIMS AND OBJECTIVES: To study the clinical profile of HD in central India along with its epidemiological characteristics. MATERIALS AND METHODS: Medical records of clinically diagnosed Hansen's patients were recruited retrospectively during January 2015 to December 2018. Case records were evaluated with respect to demographic, clinical, histopathological, and bacteriological investigations, development of reaction, and deformities. Patients were classified based on Ridley Jopling classification and treated accordingly. Statistical analysis was done using proportion, mean, and percentage. RESULTS: A total of 400 new patients were enrolled and males outnumbered females. Maximum cases, 115 (28.75%), were in the age group of 31-40 years. Sixteen (4%) cases belonged to the pediatric age (less than 18 years) group. Most common clinical spectrum was borderline lepromatous (n = 156, 39%) followed by lepromatous HD (n = 120, 30%). Eleven patients had pure neuritic HD and nine had histoid HD. Grade 2 deformity was found in 52 and grade 1 deformity was found in 16 patients. Most common lepra reaction was type 2 lepra reaction (n = 112, 28%). Thirteen (3.25%) patients were of relapse of HD among which maximum eight were BL HD followed by LL HD three (0.75%) and TT HD two (0.5%). CONCLUSION: Early diagnosis is very important for timely and proper implementation of treatment which will prevent sequelae and physical disabilities that can have an impact on the individual's social and working life, which are responsible for stigma and prejudice regarding the disease. Detection of this huge number of cases signifies a high burden of HD in this area even in the post elimination era.

Levantamento de dados para estudo dos fatores associados à falha terapêutica em hanseníase / Data collection to study the factors associated with failure leprosy therapy

A Hanseníase é uma doença infectocontagiosa de caráter crônico, evolução lenta, causada pelo Mycobacterium leprae (M. leprae). A transmissão ocorre por meio do trato respiratório, e para o desenvolvimento da doença existe a necessidade da susceptibilidade, além do contato íntimo e prolongado. Para fins terapêuticos a Organização Mundial da Saúde (OMS) traz uma classificação mais simples que é baseada no número de lesões cutâneas. Os casos com até cinco lesões são considerados paucibacilares e aqueles com mais de cinco lesões são multibacilares. Apesar da implantação da poliquimioterapia (PQT) pela OMS ter sido um importante avanço técnico na história do controle da doença, em 2019 ainda foram notificados 202.185 novos casos no mundo, sendo o Brasil o segundo em concentração de casos. Um indicador importante para o controle da hanseníase são as taxas de retratamento, definido como nova notificação de hanseníase em paciente que já tenha recebido tratamento anterior, suas causas incluem abandono, insuficiência terapêutica, falência terapêutica, alteração de esquema por erro diagnóstico e recidiva. Embora um grande número de casos de recidivas seja detectado no Brasil, apenas 8,4%, 13,3% e 1,9% dos casos podem ser explicados por mutações que sabidamente conferem resistência bacilar aos medicamentos utilizados na PQT: rifampicina (RFP), dapsona (DDS) e ofloxacina (OFLO), respectivamente. Além dos aspectos relacionados ao patógeno, a contribuição do hospedeiro para esse cenário, apesar de pouco estudada, deve ser de grande importância. No geral a resposta ao medicamento é variável entre indivíduos, ocasionando falta de eficácia farmacológica ou reação adversas, em partes esses eventos podem ser explicados pela farmacogenética. Conhecer fatores genéticos que interferem no metabolismo dos medicamentos pode contribuir para melhores resultados terapêuticos. Dentre os desafios para atingir a eliminação da hanseníase estão a ausência de novas ferramentas de diagnóstico e de entendimento das causas associadas a recidiva e à não adesão a PQT, uma vez que a resistência medicamentosa explica pouco da reativação da doença, deste modo, o presente estudo teve como finalidade constituir banco de dados em hanseníase para estudos de associação do tipo caso-controle sobre os fatores associados com a falha terapêutica da PQT convencional. Dos 240 prontuários avaliados, 119 foram classificados como casos de falência terapêutica ou recidiva e 121 como sucesso terapêutico, aqui denominados como controles, a maioria dos pacientes era do sexo masculino, branco e procedente do estado de São Paulo; Em relação à faixa etária de diagnóstico, 18% foram diagnosticados com idade entre 40 e 49 anos, enquanto nos controles 14% tiveram diagnóstico com idade inferior a 19 anos; quanto à forma clínica da doença, 59% dos casos e 47% dos controles foram classificados como virchoviano. Dentre os casos de falência terapêutica ou recidiva, a resistência molecular explicou apenas 5,8 % dos casos de retratamento. Esse dado reforça a urgência de estudos que esclareçam as causas da falha terapêutica em hanseníase, contribuindo assim para o estabelecimento de medidas que visem o alcance de melhores índices relacionados aos desfechos terapêuticos.(AU)

Leprosy is a chronic infectious disease with insidious evolution, caused by Mycobacterium leprae (M. leprae). Transmission occurs through the respiratory tract, and the onset of the disease depends on susceptibility, in addition to intimate and prolonged contact with untreated patients. For therapeutic purposes, the World Health Organization's (WHO) classification is based on the number of skin lesions. Cases with up to five lesions are considered paucibacillary and those with more than five lesion are multibacillary. Although the implementation of multidrugtherapy (MDT) by WHO was an important technical advance in the history of disease control. In 2019, 202,185 new cases were reported in the world, with Brazil the second in the highest number of cases. An important indicator for the control of leprosy is retreatment rate, defined as a new notification of leprosy in a patient who has already received previous treatment. Its causes include abandonment, therapeutic failure, , alteration of the regimen due to diagnostic error and relapse. Although a large number of cases of relapses are detected in Brazil, only 8.4%, 13.3% and 1.9% of cases can be explained by mutations that are known to confer bacillary resistance to drugs used in the MDT: rifampicin (RFP), dapsone (DDS) and ofloxacin (OFLO), respectively. In addition to aspects related to the pathogen, the host's contribution to this scenario, although little studied, is highly important. In general, the response to the drug treatment is variable between individuals, causing a lack of pharmacological efficacy or adverse reactions. , These events may be explained by pharmacogenetics. Knowing genetic factors that interfere with drug metabolism can contribute to better therapeutic results. Among the challenges to achieve leprosy elimination are the absence of new diagnostic tools and understanding of the causes associated with relapse and non-adherence to MDT, since drug resistance explains little about the reactivation of the disease. Thus, the present study aimed at constituting a leprosy database for case-control association studies on factors associated with conventional MDT therapeutic failure. Of the 240 medical records evaluated, 119 were classified as cases of therapeutic failure or relapse and 121 as therapeutic success, here referred to as controls. The majority of patients were male, white and from the state of São Paulo. Regarding the age of diagnosis, 18% were diagnosed between 40 and 49 years, while in controls, 14% were diagnosed under 19 years; as to the clinical form of the disease, 59% of the cases and 47% of the controls were classified as lepromatous. Among the cases of therapeutic failure or relapse, molecular resistance explained only 5.8% of retreatment cases. This data reinforces the urgency of studies that clarify the causes of therapeutic failure in leprosy, thus contributing to the establishment of measures aimed at achieving better therapeutic outcomes(AU).

Regression and relapse

Immediately after leprosy treatment initiation, changes in leprosy lesions also commence. The histopathological and bacilloscopic characeristics of the regressing lesions undergo continuous changes over years of decades. It is important to recognize these changes as they allow for the assessment od whether a particular lesion is in regression or if there are signs of disease reactivation. Interpretation of the findings will depend on a close correlation among histopathological patterns, bacilloscopic characteristics, and clinical data. This chapter discusses the main factors that allow the recognition of the histopathological characteristics of regressive phenomena from initial phases to late or residual phases, the changes typical in effectiveness, the reaction phenomena triggered after treatment initiation on regressing lesions, and the evaluation of leprosy recurrence. Further, this chapter includes a discussion on the main differential diagnoses of leprosy regression and relapse.

Relapse in leprosy and drug resistance assessment in a tertiary hospital of the state of Espírito Santo, Brazil

Abstract INTRODUCTION: Leprosy recurrence is the reappearance of the disease after treatment with current schemes and discharged for cure and may have variable incubation periods. METHODS: This is a descriptive observational study of leprosy recurrence in Espírito Santo diagnosed between January 2018 and January 2020. RESULTS: One hundred and ninety-two cases were available, of which 30 were diagnosed with leprosy recurrence. CONCLUSIONS: In 25 cases, the incubation period was 5-15 years after the first treatment, favoring bacillary persistence. In the remaining 5 cases, the disease had recurred after 15 years, pointing to reinfection as none of them exhibited drug resistance.

Peripheral nerve biopsy: a tool still needed in the early diagnosis of neural leprosy?

BACKGROUND: The early recognition of neural impairment in leprosy, especially in primary neural forms, represents a challenge in clinical practice and a peripheral nerve biopsy may be required for diagnostic confirmation. This study aims to characterize the epidemiological, clinical, electroneuromyographic, laboratory and histopathological aspects of patients undergoing peripheral nerve biopsy during investigation of primary neural cases in leprosy. METHODS: A total of 104 patients with peripheral neuropathy who were referred to a national reference centre for leprosy were biopsied from 2014 to 2018. All cases underwent clinical, laboratory, histopathological and electroneuromyographic evaluations. RESULTS: Of 104 biopsied patients, leprosy was confirmed in 89.4% (93/104). The biopsied nerves were the ulnar (67.8% [63/93]), superficial fibular (21.5% [20/93]), sural (8.6% [8/93]), radial (1.1% [1/93]) and deep fibular (1.1% [1/93]). Twenty-nine percent (27/93) presented histopathological abnormalities and 4.4% (4/93) presented acid-fast bacilli. Nerve and superjacent skin quantitative polymerase chain reaction were positive in 49.5% (46/93) and 24.8% (23/93) of cases, respectively. Patients with multiple mononeuropathy had a higher frequency of histopathological abnormalities (p=0.0077). CONCLUSIONS: This study reinforces peripheral nerve biopsy's role as an important tool in the investigation of primary neural cases, contributing to the early diagnosis and also reducing diagnostic errors and the need for empirical treatment.

Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment.

A case of Mycobacterium leprae rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.

Leprosy: Treatment and management of complications.

In the second article in this continuing medical education series, we review the treatment of leprosy, its immunologic reactions, and important concepts, including disease relapse and drug resistance. A fundamental understanding of the treatment options and management of neuropathic sequelae are essential to reduce disease burden and improve patients' quality of life.

Identification of clinical and immunological factors associated with clinical relapse of pemphigus vulgaris in remission.

BACKGROUND: Pemphigus vulgaris is a potentially fatal autoimmune epidermal blistering disease with a chronic and relapsing course. It is difficult to predict clinical relapse. Identification of clinical and immunological factors that are associated with early clinical relapse in a prospective study design may help in planning treatment for better maintenance of clinical remission. AIM: The aim of our study was to identify clinical and immunological factors associated with clinical relapse within 9 months of study inclusion in patients with pemphigus vulgaris in clinical remission. METHODS: Forty consecutive consenting patients who had been diagnosed to have pemphigus vulgaris and were in clinical remission on minimal therapy or off therapy were included. The patients were followed up every 3 months until 9 months. Clinical factors considered relevant were recorded at the beginning of the study. Immunological factors such as CD19+ B-cell count and CD19+CD27+ memory B cells/plasma cell count in peripheral blood were assessed at baseline [anti-desmoglein (Dsg) 1 and 3 titers were first assessed at 3 months, not at baseline] and repeated every 3 months, until 9 months or clinical relapse whichever was earlier. Direct immunofluorescence (DIF) of skin biopsy specimen was performed at study initiation and again at the time of clinical relapse or study completion, whichever occurred earlier. All patients completed the study. RESULTS: Of 40 patients, 11 (27.5%) experienced relapse as per definition, while 29 (72.5%) remained in complete remission. Clinical relapse during study duration was significantly more common in those who had onset of disease in oral mucosa [odds ratio (OR), 10.71; 95% confidence interval (CI) 1.21-94.86, P = 0.02], pruritus (OR 8.4; 95% CI 1.76-40.02, P = 0.01), and extensive cutaneous involvement during previous disease activity (OR 7.36; 95% CI 1.34-40.55, P = 0.03) and also pruritus during remission (P = 0.004). Immunological factors found to be significantly associated with early clinical relapse were raised CD19+ B-cell count at baseline (OR 7.84; 95% CI 1.39 - 53.41, P = 0.01), immunoglobulin G (OR 4.85; 95% CI 1.09-23.44, P = 0.04), and C3 (OR 20.33; 95% CI 3.02-199.5, P < 0.001) positivity in the intercellular space of the epidermis on DIF at study onset and rising anti-Dsg 3 antibody titers (OR 19.96; 95% CI 1.85- 310.9, P = 0.03). LIMITATIONS: Limited sample size, short follow-up duration, and inability to perform anti-Dsg enzyme linked immunosorbent assay for all the patients at all the time points of assessment are limitations of this study. CONCLUSION: Immunological relapse can be determined before clinical relapse, so that treatment can be restarted/modified and clinical remission can be maintained.

Effectiveness and safety analysis of rituximab in 146 Indian pemphigus patients: A retrospective single-center review of up to 68 months follow-up.

BACKGROUND: Rituximab is being increasingly used for the treatment of pemphigus. Data derived from single-center studies following a uniform treatment protocol are limited. Effect of demography and disease type on treatment response is poorly characterized. OBJECTIVE: Our aim was to assess the effectiveness of biosimilar rituximab in pemphigus patients who had received rituximab as per rheumatoid arthritis protocol (2 doses, 1g each, infused 14 days apart). METHODS: It was a retrospective review of 146 eligible patients to assess the proportion of patients achieving complete remission off treatment, time to achieve complete remission off treatment, proportion of patients who relapsed after achieving complete remission off treatment, time taken to relapse, duration and total cumulative dose of corticosteroids administered after rituximab. Additionally, we tried to find whether a correlation existed between age, gender, total duration of illness before rituximab and pemphigus disease type with the above-mentioned outcome measures. RESULTS: Of 146 patients, 107 (73.3%) attained complete remission off treatment. Mean interval between first dose rituximab administration and complete remission off treatment was 6.6 ± 3.4months. Complete remission off treatment was sustained for a mean duration of 9.1 ± 8.5 months before relapse. Over a mean follow-up duration of 24.9 ± 17.1 months (median 23, maximum 68 months), 75 of 107 patients (76.5%) who had achieved complete remission after first cycle of rituximab relapsed. A mean total cumulative dose of 3496 ± 2496 mg prednisolone was prescribed over a mean duration of 7.2 ± 4.7 months after first cycle of rituximab. Time taken to achieve remission was significantly longer in pemphigus foliaceus and these patients required significantly higher cumulative dose of prednisolone over a longer duration after rituximab. No deaths and long-term complications were recorded. LIMITATIONS: Only clinical parameters were assessed. Immunological parameters including B-cell counts and enzyme-linked immunosorbent assay for anti-desmoglein antibody titers were not carried out. CONCLUSION: This study reinforces the beneficial role of rituximab in pemphigus. Pemphigus foliaceus patients required a higher total cumulative dose of prednisolone over a longer time to achieve remission and the remission lasted longer than that in pemphigus vulgaris.

Report on an unusual case of leprosy from Germany: just an exception of the rule?

CASE PRESENTATION: We report on a German leprosy patient originating from Pakistan who had a relapse more than 5 years after completion of multi-drug therapy (MDT) of his first episode of multibacillary (MB) leprosy. State-of-the-art laboratory techniques (histopathology, PGL-I serology, microscopy and DNA/RNA qPCR) were applied for laboratory confirmation and monitoring of treatment outcome. Serology indicated the relapse long before the presence of unambiguous clinical signs. At the time of diagnosis of the relapse the patient had a remarkably high bacterial load suggesting increased risk for a second relapse. Furthermore, unexpectedly prolonged excretion of viable bacilli through the upper respiratory tract for more than 3 months after onset of MDT was shown. Therefore, MDT was administered for 2 years. DISCUSSION AND CONCLUSIONS: The clinical course of the patient, as well as the prolonged excretion of viable bacilli, underlines the usefulness of laboratory assessment. Laboratory tools including up-to-date molecular assays facilitate rapid diagnosis, timely MDT, identification of individuals excreting viable bacilli and patients at risk for relapses, monitoring of treatment outcome and respective adaptation of treatment where appropriate.

Genomic Reduction at TTC Repeats in the Bacterial Genome of Treated Cases of Hansen's Disease: A Possible Survival Mechanism of Mycobacterium leprae.

INTRODUCTION: Mycobacterium leprae has a small genome and a tendency of persisting as a very low-grade infection. The authors have shown earlier, that the changes in TTC repeats, in M. leprae genome may contribute to the restriction of the pathogenicity of the bacterium and its survival strategy in case of pure neural Hansen's disease. We suspect, that a similar genomic reduction if happens in treated cases of Hansen's disease, can be a determining factor for developing persisters and relapse. AIM: The present study aimed to find out if there was any evidence of genomic reduction in treated cases of Hansen's disease that showed microbiological nonresponse. METHODS: Skin biopsies were taken from treated cases of Hansen's disease at tertiary centers in Kolkata and at Raipur who had bacterial index (BI) unchanged or increased compared to their pretreatment BI. Analysis for the mutation in rpoB gene and folP1 gene were done to rule out rifampicin and dapsone resistance, respectively. The entire TTC repeat region of the bacteria was amplified by polymerase chain reaction and was subjected to sequencing. The obtained sequences were then analyzed by CLUSTALW. RESULTS: A total of 127 patients were included in the study of which in 52 the BI remained same and 75 had an increase in BI, even after 6 months of completion of multidrug therapy. Among the samples, 2 had positive rpoB gene mutation. No mutation was found in the folP1 gene. The TTC repeat of both the rpoB-resistant samples was found to have 17 copies, which matched their pretreatment copy number. In other 125 cases, 60 cases showed no change from their pretreatment TTC number. Of those 65 samples that showed evidence of genomic reduction, 11 samples showed one copy, 41 showed 2 copies, and 13 showed 3 copies deletion. We also observed a significant regional variation. CONCLUSION: We concluded that there was evidence of genomic reduction, which might lead to microbiological nonresponse in treated cases of Hansen's disease. This indicated a possibility of future persistence and relapse.

Effects of wages on smoking decisions of current and past smokers.

PURPOSE: We used longitudinal data and instrumental variables (IVs) in a prospective design to test for the causal effects of wages on smoking prevalence among current and past smokers. METHODS: Nationally representative U.S. data were drawn from the 1999-2009 waves of the Panel Study of Income Dynamics. Our overall sample was restricted to full time employed persons, aged 21-65 years. We excluded part time workers and youths because smoking and wage correlations would be complicated by labor supply decisions. We excluded adult never smokers because people rarely begin smoking after the age of 20 years. IVs were created with state-level minimum wages and unionization rates. We analyzed subsamples of men, women, the less educated, the more educated, quitters, and backsliders. Validity and strength of instruments within the IV analysis were conducted with the Sargan-Hansen J statistic and F tests. RESULTS: We found some evidence that low wages lead to more smoking in the overall sample and substantial evidence for men, persons with high school educations or less (<13 years of schooling), and quitters. Results indicated that 10% increases in wages lead to 5.5 and 4.6 percentage point decreases in smoking for men and the less educated; they also increased the average chance of quitting among base-year smokers from 17.0% to 20.4%. Statistical tests suggested that IVs were strong and valid in most samples. Subjects' other family income, including spouses' wages, was entered as a control variable. CONCLUSIONS: Increases in an individual's wages, independent of other income, decreased the prevalence of smoking among current and past smokers.

Recidiva de lepra y reacción tipo II en paciente tratado con poliquimioterapia (PQT) / Relapse in leprosy and type II reaction in a patient treated with multidrug therapy (MDT)

La lepra es una enfermedad infecciosa crónica propia de países de áfrica, Asia, Oceanía y América Latina. Es causada por el Mycobacterium leprae que se manifiesta de forma variada como zonas de hipo o anestesia, máculas hipocrómicas, con o sin engrosamiento neural. En algunas ocasiones, después de haber completado el ciclo terapéutico recomendado por la Organización Mundial de la Salud, puede presentar recidivas, apareciendo nuevas lesiones clínicas o aumentando el índice bacilar. Esta características pueden confundirse con el eritema nodoso leproso, caracterizado por ser una reacción antígenoanticuerpo que fija complemento mediante la cual el sistema inmune combate antígenos bacilares. En este texto se describe un caso de recidiva de lepra lepromatosa y lesiones compatibles con eritema nodoso leproso después de haber sido tratado con poliquimioterapia.

Leprosy is a chronic infectious disease endemic to African, Asian, Latin America and South Pacific countries. It is caused by Mycobacterium leprae that manifests itself as varied as areas of hypo or anesthesia, macules hypochromic, with or without neura thickening. On some occasions, after having completed the course of therapy recommended by the World Health Organization, it can recur, showing new clinical lesions or increasing the bacillary index. These features can be confused with erythema nodosum leprosum, characterized by an antigenantibody reaction that secures a complement through which the immune system combats antigen cells. This text describes a case of recurrence of lepromatous leprosy and lesions compatible with erythema nodosum leprosum after it has been treated with combination chemotherapy.

Características clínico-laboratoriais no retratamento por recidiva em hanseníase / Clinical and laboratory characteristics in the retreatment of leprosy relapse

OBJETIVO: Comparar as características clínico-laboratoriais dos doentes de hanseníase durante o tratamento inicial e no retratamento por recidiva diagnosticada em unidades de saúde de referência no Estado de Mato Grosso MÉTODO: Estudo transversal de casos diagnosticados de recidiva em hanseníase em unidades de referência de 2005 a 2007 em cinco municípios do Estado. O tratamento inicial foi considerado t1 e a recidiva t2. Fontes de dados: Sistema de Informação de Agravos de Notificação, prontuários, exames laboratoriais, ficha de notificação individual e de avaliação de incapacidade física. Utilizou-se para a comparação e cálculo de proporções o teste do Qui-quadrado (c²) ao nível de significância de 5%. RESULTADOS: Verificou-se predomínio da forma clínica dimorfa em t2 quando comparada a t1 (39,6% versus 11,3%; p = 0,003); 20,8%, dos casos em recidivas apresentaram índice baciloscópico ≥ 4+ se comparados aqueles em t1 (p = 0,034); aumento (17%) dos casos de recidiva com grau zero de incapacidade quando comparados aos pacientes avaliados no momento do diagnóstico (58,5% versus 41,5%); aumento (7,5%) de recidivas com incapacidades grau 2 quando comparadas a t1 (9,4% versus 1, 9%); predomínio de casos não avaliados quanto a incapacidade física entre t1 (45,3%) e t2 (22,6%); (p = 0,040). CONCLUSÃO: Os casos de recidiva caracterizam o agravamento da doença indicadas pelo aumento do índice baciloscópico e do grau de incapacidade física. Recomenda-se maior atenção à confirmação diagnóstica de recidiva por meio de exames baciloscópicos, em especial nos multibacilares, e da avaliação neurológica sistemática de todos os pacientes de hanseníase.

OBJECTIVE: To compare clinical and laboratory data of leprosy patients diagnosed in specialized services in the State of Mato Grosso, Brazil, during the initial treatment and the retreatment of relapse. METHODS: A cross-sectional study of patients with diagnosis of leprosy relapse was conducted in specialized health services of five cities, between 2005 and 2007. Initial treatment was described as t1 and relapse treatment as t2. DATA SOURCE: Sistema de Informação de Agravos de Notificação (Sinan - Reportable Diseases Information System), medical records, laboratory tests, and files of individual reports and of physical disability assessments. The chi-square test (c2) was applied at a significance level of 5%. RESULTS: The clinical dimorphic form prevailed in t2 when compared with t1 (39.6% versus 11.3%; p = 0.003); 20.8% of relapse cases showed a bacilloscopy index ≥ 4+ in relation to those in t1 (p = 0.034)]; an increase in the number of (17%) cases of relapse with physical disability at level 0 was found, compared to patients evaluated during the diagnosis (58.5% versus 41.5%); an increase (7.5%) in the recurrence of disabilities at level 2 was observed, when compared to t1 (9.4% versus a 9%); and there was a higher prevalence of cases not evaluated for disability between t1 (45.3%) and t2 (22.6%) (p = 0.040). CONCLUSION: Cases of relapse characterized the aggravation of the disease, indicated by the increase in the bacilloscopy index and level of physical disability. Attention should be paid to the diagnostic confirmation of relapse using bacilloscopy tests, especially in multibacillary cases, and systematic neurological assessment of all leprosy patients.