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1.
Front Med (Lausanne) ; 10: 1233220, 2023.
Article in English | MEDLINE | ID: mdl-37564037

ABSTRACT

Introduction: Leprosy reactions (LR) are severe episodes of intense activation of the host inflammatory response of uncertain etiology, today the leading cause of permanent nerve damage in leprosy patients. Several genetic and non-genetic risk factors for LR have been described; however, there are limited attempts to combine this information to estimate the risk of a leprosy patient developing LR. Here we present an artificial intelligence (AI)-based system that can assess LR risk using clinical, demographic, and genetic data. Methods: The study includes four datasets from different regions of Brazil, totalizing 1,450 leprosy patients followed prospectively for at least 2 years to assess the occurrence of LR. Data mining using WEKA software was performed following a two-step protocol to select the variables included in the AI system, based on Bayesian Networks, and developed using the NETICA software. Results: Analysis of the complete database resulted in a system able to estimate LR risk with 82.7% accuracy, 79.3% sensitivity, and 86.2% specificity. When using only databases for which host genetic information associated with LR was included, the performance increased to 87.7% accuracy, 85.7% sensitivity, and 89.4% specificity. Conclusion: We produced an easy-to-use, online, free-access system that identifies leprosy patients at risk of developing LR. Risk assessment of LR for individual patients may detect candidates for close monitoring, with a potentially positive impact on the prevention of permanent disabilities, the quality of life of the patients, and upon leprosy control programs.

2.
Sci Rep ; 10(1): 1284, 2020 Jan 28.
Article in English | MEDLINE | ID: mdl-31992776

ABSTRACT

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.


Subject(s)
Genetic Loci , Genetic Predisposition to Disease , Leprosy/genetics , Mycobacterium leprae , Polymorphism, Single Nucleotide , Whole Genome Sequencing , Female , Humans , Male , Recurrence
3.
Front Immunol ; 9: 915, 2018.
Article in English | MEDLINE | ID: mdl-29867930

ABSTRACT

Leprosy serology reflects the bacillary load of patients and multidrug therapy (MDT) reduces Mycobacterium leprae-specific antibody titers of multibacillary (MB) patients. The Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil (U-MDT/CT-BR) compared outcomes of regular 12 doses MDT/R-MDT and the uniform 6 doses MDT/U-MDT for MB leprosy, both of regimens including rifampicin, clofazimine, and dapsone. This study investigated the impact of R-MDT and U-MDT and the kinetic of antibody responses to M. leprae-specific antigens in MB patients from the U-MDT/CT-BR. We tested 3,400 serum samples from 263 MB patients (R-MDT:121; U-MDT:142) recruited at two Brazilian reference centers (Dona Libânia, Fortaleza, Ceará; Alfredo da Matta Foundation, Manaus, Amazonas). Enzyme-linked immunosorbent assays with three M. leprae antigens [NT-P-BSA: trisaccharide-phenyl of phenollic glycolipid-I antigen (PGL-I); LID-1: Leprosy Infectious Disease Research Institute Diagnostic 1 di-fusion recombinant protein; and ND-O-LID: fusion complex of disaccharide-octyl of PGL-I and LID-1] were performed using around 13 samples per patient. Samples were collected at baseline/M0, during MDT (R-MDT:M1-M12 months, U-MDT:M1-M6 months) and after MDT discontinuation (first, second year). Statistical significance was assessed by the Mann-Whitney U test for comparison between groups (p values < 0.05). Mixed effect multilevel regression analyses were used to investigate intraindividual serological changes overtime. In R-MDT and U-MDT groups, males predominated, median age was 41 and 40.5 years, most patients were borderline lepromatous and lepromatous leprosy (R-MDT:88%, U-MDT: 90%). The bacilloscopic index at diagnosis was similar (medians: 3.6 in the R-MDT and 3.8 in the U-MDT group). In R-MDT and U-MDT groups, a significant decline in anti-PGL-I positivity was observed from M0 to M5 (p = 0.035, p = 0.04, respectively), from M6 to M12 and at the first and second year posttreatment (p < 0.05). Anti-LID-1 antibodies declined from M0 to M6 (p = 0.024), M7 to M12 in the R-MDT; from M0 to M4 (p = 0.003), M5 to M12 in the U-MDT and posttreatment in both groups (p > 0.0001). Anti-ND-O-LID antibodies decreased during and after treatment in both groups, similarly to anti-PGL-I antibodies. Intraindividual serology results in R-MDT and U-MDT patients showed that the difference in serology decay to all three antigens was dependent upon time only. Our serology findings in MB leprosy show that regardless of the duration of the U-MDT and R-MDT, both of them reduce M. leprae-specific antibodies during and after treatment. In leprosy, antibody levels are considered a surrogate marker of the bacillary load; therefore, our serological results suggest that shorter U-MDT is also effective in reducing the patients' bacillary burden similarly to R-MDT. Clinical Trial Registration: ClinicalTrials.gov, NCT00669643.


Subject(s)
Antibodies, Bacterial/blood , Antitubercular Agents/therapeutic use , Leprosy, Multibacillary/drug therapy , Mycobacterium leprae/drug effects , Adolescent , Adult , Aged , Antigens, Bacterial/immunology , Brazil , Child , Clofazimine/administration & dosage , Dapsone/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin M/blood , Male , Middle Aged , Randomized Controlled Trials as Topic , Rifampin/administration & dosage , Treatment Outcome , Young Adult
4.
An Bras Dermatol ; 93(3): 377-384, 2018 06.
Article in English | MEDLINE | ID: mdl-29924240

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.


Subject(s)
Clofazimine/adverse effects , Dapsone/adverse effects , Leprostatic Agents/adverse effects , Leprosy/drug therapy , Rifampin/adverse effects , Adolescent , Adult , Anemia/blood , Anemia/chemically induced , Brazil , Child , Clofazimine/administration & dosage , Dapsone/administration & dosage , Drug Therapy, Combination/adverse effects , Female , Hemoglobins/analysis , Humans , Leprostatic Agents/administration & dosage , Leprosy/blood , Leprosy/complications , Male , Middle Aged , Rifampin/administration & dosage , Risk Factors , Treatment Outcome , Young Adult
5.
An. bras. dermatol ; 93(3): 377-384, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-949891

ABSTRACT

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.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Young Adult , Rifampin/adverse effects , Clofazimine/adverse effects , Dapsone/adverse effects , Leprostatic Agents/adverse effects , Rifampin/administration & dosage , Brazil , Hemoglobins/analysis , Risk Factors , Treatment Outcome , Clofazimine/administration & dosage , Dapsone/administration & dosage , Drug Therapy, Combination/adverse effects , Anemia/chemically induced , Anemia/blood , Leprostatic Agents/administration & dosage , Leprosy/complications , Leprosy/drug therapy , Leprosy/blood
6.
An. bras. dermatol ; 92(6): 761-773, Nov.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-887114

ABSTRACT

Abstract: In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.


Subject(s)
Humans , Leprostatic Agents/therapeutic use , Leprosy/pathology , Leprosy/drug therapy , Rifampin/therapeutic use , Treatment Outcome , Patient Satisfaction , Clofazimine/therapeutic use , Dapsone/therapeutic use , Drug Therapy, Combination
7.
PLoS Negl Trop Dis ; 11(7): e0005725, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28704363

ABSTRACT

BACKGROUND: Leprosy control is based on early diagnosis and multidrug therapy. For treatment purposes, leprosy patients can be classified as paucibacillary (PB) or multibacillary (MB), according to the number of skin lesions. Studies regarding a uniform treatment regimen (U-MDT) for all leprosy patients have been encouraged by the WHO, rendering disease classification unnecessary. METHODOLOGY AND FINDINGS: An independent, randomized, controlled clinical trial conducted from 2007 to 2015 in Brazil, compared main outcomes (frequency of reactions, bacilloscopic index trend, disability progression and relapse rates) among MB patients treated with a uniform regimen/U-MDT (dapsone+rifampicin+clofazimine for six months) versus WHO regular-MDT/R-MDT (dapsone+rifampicin+clofazimine for 12 months). A total of 613 newly diagnosed, untreated MB patients with high bacterial load were included. There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups, with more than 25% disability progression in both groups. The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group. During active follow up, four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up (95% CI [0·81, 6·2] per 1000). During passive follow up three patients relapsed in U-MDT and one in R-MTD. As this period corresponds to passive follow up, sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year. CONCLUSION: Our results on the first randomized and controlled study on U-MDT together with the results from three previous studies performed in China, India and Bangladesh, support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669643.


Subject(s)
Clofazimine/administration & dosage , Dapsone/administration & dosage , Leprostatic Agents/administration & dosage , Leprosy, Multibacillary/drug therapy , Rifampin/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Child , Child, Preschool , Drug Therapy, Combination/methods , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Recurrence , Time Factors , Treatment Outcome , Young Adult
8.
PLoS Negl Trop Dis ; 11(6): e0005598, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28617800

ABSTRACT

BACKGROUND: Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using next generation sequencing and bioinformatics analysis of Mycobacterium leprae DNA present in human skin. METHODOLOGY: DNA was isolated by means of optimized extraction and enrichment methods from samples from three recurrent cases in leprosy patients participating in an open-label, randomized, controlled clinical trial of uniform MDT in Brazil (U-MDT/CT-BR). Genome-wide sequencing of M. leprae was performed and the resultant sequence assemblies analyzed in silico. PRINCIPAL FINDINGS: In all three cases, no mutations responsible for resistance to rifampicin, dapsone and ofloxacin were found, thus eliminating drug resistance as a possible cause of disease recurrence. However, sequence differences were detected between the strains from the first and second disease episodes in all three patients. In one case, clear evidence was obtained for reinfection with an unrelated strain whereas in the other two cases, relapse appeared more probable. CONCLUSIONS/SIGNIFICANCE: This is the first report of using M. leprae whole genome sequencing to reveal that treated and cured leprosy patients who remain in endemic areas can be reinfected by another strain. Next generation sequencing can be applied reliably to M. leprae DNA extracted from biopsies to discriminate between cases of relapse and reinfection, thereby providing a powerful tool for evaluating different outcomes of therapeutic regimens and for following disease transmission.


Subject(s)
Genome, Bacterial , Leprosy/diagnosis , Molecular Typing/methods , Mycobacterium leprae/classification , Mycobacterium leprae/genetics , Sequence Analysis, DNA/methods , Adolescent , Adult , Brazil , Computational Biology/methods , DNA, Bacterial/isolation & purification , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Mycobacterium leprae/isolation & purification , Randomized Controlled Trials as Topic , Recurrence , Young Adult
9.
PLoS Negl Trop Dis ; 11(2): e0005396, 2017 02.
Article in English | MEDLINE | ID: mdl-28222139

ABSTRACT

BACKGROUND: Leprosy reactions, reversal reactions/RR and erythema nodosum leprosum/ENL, can cause irreversible nerve damage, handicaps and deformities. The study of Mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil/U-MDT/CT-BR is suitable to evaluate its prognostic value for the development of reactions. METHODOLOGY: IgM and IgG antibody responses to PGL-I, LID-1, ND-O-LID were evaluated by ELISA in 452 reaction-free leprosy patients at diagnosis, enrolled and monitored for the development of leprosy reactions during a total person-time of 780,930 person-days, i.e. 2139.5 person-years, with a maximum of 6.66 years follow-up time. PRINCIPAL FINDINGS: Among these patients, 36% (160/452) developed reactions during follow-up: 26% (119/452) RR and 10% (41/452) had ENL. At baseline higher anti-PGL-I, anti-LID-1 and anti-ND-O-LID seropositivity rates were seen in patients who developed ENL and RR compared to reaction-free patients (p<0.0001). Seroreactivity in reactional and reaction-free patients was stratified by bacilloscopic index/BI categories. Among BI negative patients, higher anti-PGL-I levels were seen in RR compared to reaction-free patients (p = 0.014). In patients with 0

Subject(s)
Antibodies, Bacterial/blood , Leprosy/diagnosis , Mycobacterium leprae/immunology , Serologic Tests/methods , Adult , Brazil , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Predictive Value of Tests , Prognosis , Sensitivity and Specificity
10.
An Bras Dermatol ; 92(6): 761-773, 2017.
Article in English | MEDLINE | ID: mdl-29364430

ABSTRACT

In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.


Subject(s)
Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Leprosy/pathology , Clofazimine/therapeutic use , Dapsone/therapeutic use , Drug Therapy, Combination , Humans , Patient Satisfaction , Rifampin/therapeutic use , Treatment Outcome
12.
Infect Dis Poverty ; 5(1): 110, 2016 Dec 06.
Article in English | MEDLINE | ID: mdl-27919284

ABSTRACT

BACKGROUND: The predictive value of the serology to detection of IgM against the Mycobacterium leprae-derived phenolic glycolipid-I/PGL-I to identify leprosy patients who are at higher risk of developing reactions remains controversial. Whether baseline results of the ML Flow test can predict leprosy reactions was investigated among a cohort of patients enrolled in The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR). METHODS: This was a descriptive study focusing on the main clinical manifestations of leprosy patients enrolled in the U-MDT/CT-BR from March 2007 to February 2012 at two Brazilian leprosy reference centers. For research purposes, 753 leprosy patients were categorized according to a modified Ridley-Jopling (R&J) classification and according to the development of leprosy reactions (reversal reaction/RR and erythema nodosum leprosum/ENL), and whether they had a positive or negative bacillary index/BI. RESULTS: More than half of the patients (55.5 %) reported leprosy reaction: 18.3 % (138/753) had a RR and 5.4 % (41/753) had ENL. Leprosy reactions were more frequent in the first year following diagnosis, as seen in 27 % (205/753) of patients, while 19 % (142/753) developed reactions during subsequent follow-up. Similar frequencies of leprosy reactions and other clinical manifestations were observed in paucibacillary (PB) and multibacillary (MB) leprosy patients treated with U-MDT and regular MDT (R-MDT) (P = 0.43 and P = 0.61, respectively). Compared with PB patients, leprosy reactions were significantly more frequent in MB patients with a high BI, and more patients developed RR than ENL. However, RR and neuritis were also reported in patients with a negative BI. At baseline, the highest rate of ML Flow positivity was observed in patients with a positive BI, especially those who developed ENL, followed by patients who had neuritis and RR. Among reaction-free patients, 81.9 % were ML Flow positive, however, the differences were not statistically significant compared to reactional patients (P = 0.45). CONCLUSIONS: MB and PB patients treated with R-MDT and U-MDT showed similar frequencies of RR and other clinical manifestations. Positive ML Flow tests were associated with MB leprosy and BI positivity. However, ML Flow test results at baseline showed limited sensitivity and specificity for predicting the development of leprosy reactions.


Subject(s)
Erythema Nodosum/drug therapy , Immunoglobulin M/immunology , Leprostatic Agents/therapeutic use , Leprosy, Lepromatous/drug therapy , Adolescent , Adult , Aged , Antigens, Bacterial/immunology , Brazil , Child , Cohort Studies , Erythema Nodosum/microbiology , Female , Follow-Up Studies , Glycolipids/immunology , Humans , Leprosy, Lepromatous/microbiology , Male , Middle Aged , Young Adult
13.
An Bras Dermatol ; 90(5): 741-3, 2015.
Article in English | MEDLINE | ID: mdl-26560222

ABSTRACT

Mycobacterium abscessus is a rapidly growing mycobacterium that has been affecting people undergoing invasive procedures, such as videosurgery and mesotherapy. This bacterium has global distribution, being found in numerous niches. The frequency of published reports of infection by rapidly growing mycobacteria associated with tattooing procedures has increased in recent years. However, in Brazil there were no case reports of M. abscessus after tattooing in the literature until now. In this paper, we describe the case of a patient with a nine-month history of lesion on a tattoo site. The diagnosis of infection with Mycobacterium abscessus was established by correlation between dermatological and histopathological aspects, culture and molecular biology techniques. The patient had significant improvement of symptoms with the use of clarithromycin monotherapy.


Subject(s)
Mycobacterium Infections, Nontuberculous/etiology , Skin Diseases, Bacterial/etiology , Tattooing/adverse effects , Adult , Brazil , Female , Humans , Mycobacterium Infections, Nontuberculous/pathology , Nontuberculous Mycobacteria , Skin Diseases, Bacterial/pathology
14.
An. bras. dermatol ; 90(5): 741-743, graf
Article in English | LILACS | ID: lil-764408

ABSTRACT

AbstractMycobacterium abscessus is a rapidly growing mycobacterium that has been affecting people undergoing invasive procedures, such as videosurgery and mesotherapy. This bacterium has global distribution, being found in numerous niches. The frequency of published reports of infection by rapidly growing mycobacteria associated with tattooing procedures has increased in recent years. However, in Brazil there were no case reports of M. abscessus after tattooing in the literature until now. In this paper, we describe the case of a patient with a nine-month history of lesion on a tattoo site. The diagnosis of infection with Mycobacterium abscessus was established by correlation between dermatological and histopathological aspects, culture and molecular biology techniques. The patient had significant improvement of symptoms with the use of clarithromycin monotherapy.


Subject(s)
Adult , Female , Humans , Mycobacterium Infections, Nontuberculous/etiology , Skin Diseases, Bacterial/etiology , Tattooing/adverse effects , Brazil , Mycobacterium Infections, Nontuberculous/pathology , Nontuberculous Mycobacteria , Skin Diseases, Bacterial/pathology
15.
Am J Trop Med Hyg ; 92(6): 1280-4, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25940192

ABSTRACT

The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was used to describe and report the performance of available tools to classify 830 leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a modified Ridley and Jopling (R&J) classification, considering clinical features, histopathological results of skin biopsies and the slit-skin smear bacterial load results were used as the gold standard method for classification. Anti-phenolic glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial load, and the number of skin lesions were evaluated. Considering the R&J classification system as gold standard, ML Flow tests correctly allocated 70% patients in the PB group and 87% in the MB group. The classification based on counting the number of skin lesions correctly allocated 46% PB patients and 99% MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy patients for treatment purposes is unnecessary because it does not impact clinical and laboratories outcomes. In this context, the identification of new biomarkers to detect patients at a higher risk to develop leprosy reactions or relapse remains an important research challenge.


Subject(s)
Leprostatic Agents/therapeutic use , Leprosy/classification , Adolescent , Adult , Aged , Biopsy , Brazil , Child , Cross-Sectional Studies , Female , Humans , Leprosy/diagnosis , Leprosy/drug therapy , Leprosy/pathology , Leprosy, Multibacillary/classification , Leprosy, Multibacillary/diagnosis , Leprosy, Multibacillary/drug therapy , Leprosy, Multibacillary/pathology , Leprosy, Paucibacillary/classification , Leprosy, Paucibacillary/diagnosis , Leprosy, Paucibacillary/drug therapy , Leprosy, Paucibacillary/pathology , Male , Middle Aged , Skin/microbiology , Skin/pathology , Young Adult
16.
J Immunol Methods ; 412: 35-41, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24983877

ABSTRACT

The presence of anti-BSA antibodies may interfere in serological tests, as ELISA or immunochromatographic assays. BSA is frequently used as a blocking agent or as "inert" carrier of antigens, such as the NT-P-BSA, the semi-synthetic trisaccharide analogue of the PGL-I (phenolic glycolipid-I) antigen from the cell wall of the Mycobacterium leprae. PGL-I was prepared and linked to human serum albumin based in the hypothesis that replacing BSA by a human protein carrier would enhance the performance of leprosy serological tests. A total of 1162 serum samples were tested by ELISA and by the ML Flow rapid test using NT-P-BSA or NT-P-HSA antigens. When grouping leprosy patients as paucibacillary (PB) or multibacillary (MB) according to the Ridley & Jopling classification, ML Flow BSA and ML Flow HSA tests correctly allocated 70.9% and 68.6% of patients in the PB group, and 87% and 81% of patients in the MB group, respectively. Concordant results were found in 82.0% (953/1162) (kappa value=0.637; sd=0.023) of samples between ML Flow tests and 85.7% (996/1162) (kappa value=0.703; sd=0.021) between ELISA tests. ML Flow results were statistically similar and the same was true for ELISA tests using HSA or BSA. However, we noticed a tendency to decreased capacity to detect MB patients and an increased positivity among PB patients, HHC, TB patients and healthy controls by the HSA carrier in both ML Flow and ELISA. The PGL-I serology performed by the ML Flow test with BSA or HSA as antigen carriers can be a useful, friendly auxiliary tool to identify patients with higher bacterial load.


Subject(s)
Antigens, Bacterial/metabolism , Glycolipids/metabolism , Leprosy/classification , Leprosy/diagnosis , Mycobacterium leprae/metabolism , Serologic Tests/methods , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Bacterial/blood , Bacterial Load , Cattle , Child , Chromatography, Affinity , Enzyme-Linked Immunosorbent Assay , False Positive Reactions , Female , Glycolipids/chemical synthesis , Humans , Immunoglobulin M/metabolism , Male , Middle Aged , Mycobacterium leprae/immunology , Serum Albumin/chemical synthesis , Serum Albumin/metabolism , Serum Albumin, Bovine/chemical synthesis , Serum Albumin, Bovine/metabolism , Young Adult
17.
Lepr Rev ; 85(4): 267-74, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25675651

ABSTRACT

OBJECTIVE: To describe the profile of patients who participated in the Randomised Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR) and determine the level of satisfaction with a uniform therapy regimen, especially among paucibacillary patients. DESIGN: This is a descriptive cross-sectional epidemiologic study nested in the wider U-MDT/CT-BR. The study was conducted using a convenience sample composed of patients from the Dona Libânia Dermatology Centre in Fortaleza, Ceará and from the Alfredo da Matta Foundation in Manaus, Amazonas in Brazil. The absolute and relative frequencies of categorical variables and the median age were calculated. Hypothesis testing was done using the Chi-squared and Mann-Whitney tests with a 0.05 level of significance. RESULTS: Of the 859 patients included in the clinical trial, 342 were interviewed. The majority of patients were male (58.2%) and multibacillary (78.3%) with a median age of 42 (7-65) years. Most of the interviewees had not completed primary education (48.0%), earned an income below three times the minimum wage (53.8%), were non-smokers (85.1%), did not regularly consume alcohol (88.3%), had not experienced any leprosy-related discrimination (69.2%) and showed a basic knowledge of the disease. With regards to paucibacillary patients, 87.8% and 90.9% of the PB U-MDT and PB R-MDT groups, respectively, indicated that they had not thought of defaulting treatment at any time. On a satisfaction scale of 1-5 (with five as the highest score), 92.7% of PB U-MDT and 100.0% of PB R-MDT patients gave a mark between three and five. CONCLUSIONS: The data suggest that the introduction of clofazimine into the therapeutic regimen did not diminish the level of treatment satisfaction among PB patients.


Subject(s)
Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Leprosy/psychology , Patient Satisfaction , Adolescent , Adult , Aged , Brazil/epidemiology , Child , Cross-Sectional Studies , Drug Therapy, Combination , Female , Humans , Leprosy/epidemiology , Male , Middle Aged , Socioeconomic Factors , Young Adult
18.
Lepr Rev ; 85(4): 262-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25675650

ABSTRACT

BACKGROUND: Many believe that the regular treatment for multibacillary (MB) leprosy cases could be shortened. A shorter treatment allowing uniformity in treatment for all cases renders case classification superfluous and therefore simplifies leprosy control. OBJECTIVE: To evaluate the association between treatment duration and the trend in bacteriological index (BI) decrease over time among patients given Uniform MDT (UMDT) compared to those given regular MDT (RMDT). METHODS: An open-label randomised clinical trial to compare the present routine treatment with one lasting six month. Patient intake was from March 2007 to February 2012. To evaluate the trend of BI as a function of time, a multilevel linear with mixed effects model was fixed to the two study groups and also four groups after stratification by BI, less than 3 and 3 or more. RESULTS: The BI fall was higher among those taking RMDT, this difference however was not statistically significant. CONCLUSION: The results presented here support the possibility of use of UMDT in the field, but further follow up is still needed for a final conclusion.


Subject(s)
Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Leprosy/microbiology , Bacterial Load/drug effects , Brazil , Drug Therapy, Combination , Follow-Up Studies , Humans , Mycobacterium leprae/drug effects , Regression Analysis
19.
Rev. Bras. Med. Fam. Comunidade (Online) ; 8(27): 127-131, abr./jun. 2013. ilus
Article in Portuguese | LILACS | ID: biblio-880906

ABSTRACT

A Teledermatologia estuda o uso das tecnologias de telecomunicação e informática na assistência dermatológica sem a atuação presencial do especialista. Neste trabalho, é relatado o processo diagnóstico de um caso de escabiose crostosa (sarna norueguesa) em paciente idoso da região do Alto Rio Solimões, por meio de recursos de Teledermatologia. Além disso, os autores discutem os avanços dessa tecnologia que possibilita a assistência a distância para comunidades ribeirinhas e indígenas, sobretudo em áreas isoladas da Amazônia Legal, nas quais inúmeras doenças são negligenciadas e subdiagnosticadas.


Teledermatology uses telecommunication technology and informatics on dermatologic practice without the presence of a specialist. This paper describes the diagnostic process of a Crusted Scabies (Norwegian Scabies) case in an elderly patient from the Alto Solimões River region using teledermatology resources. Moreover, the authors discuss the progress of these technologies, which allow healthcare assistance for those living in remote indigenous and riverine communities, particularly in isolated areas of the Legal Amazon where many diseases are neglected or underdiagnosed.


La Teledermatología usa las tecnologías de las telecomunicaciones y de la informática para dar asistencia dermatológica sin la presencia de un especialista. Este artículo describe el proceso de diagnóstico de un caso de escabiosis costrosa (sarna norueguesa) en un paciente anciano de la región del Alto Rio Solimões, a través de recursos de la Teledermatología. Además, los autores discuten los avances de estas tecnologías que permiten llevar asistencia médica a las comunidades costeras e indígenas remotas, especialmente a aquellas de zonas aisladas del Legal Amazon, en las cuales numerosas enfermedades son negligenciadas y subdiagnosticadas.


Subject(s)
Sarcoptes scabiei , Scabies , Rural Health , Telemedicine , Dermatology , Aged
20.
Mem. Inst. Oswaldo Cruz ; 107(supl.1): 22-27, Dec. 2012. graf, tab
Article in English | LILACS | ID: lil-659736

ABSTRACT

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.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Clinical Protocols , Leprostatic Agents/administration & dosage , Leprosy, Multibacillary/drug therapy , Leprosy, Paucibacillary/drug therapy , Brazil , Drug Therapy, Combination/methods , Treatment Outcome
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