Household contacts of leprosy patients are the group with the highest risk of developing the disease, and although many risk or prevention factors have been identified, they have not been employed in leprosymonitoring programs. This investigation aimed to establish the relative risks or the preventive effects of the presence of BCG vaccination, the Mitsuda test, and the ML-Flow assay. Household contacts (1,396) were monitored for a 5-year period. Twenty-eight contacts (2%) developed leprosy and had their clinical and operational classifications established. All immunological tests were performed, and intradermal BCG vaccination was given after the BCG scar count. Of the affected contacts, 75% developed the disease in the first year, and 71.4% were classified as having paucibacillary forms. Contacts of lepromatous leprosy patients presented a 3.8-fold-higher risk of developing leprosy. BCG vaccination and the Mitsuda test showed a protective effect against leprosy of 0.27 (at least one scar) and 0.16 (>7 mm), respectively, and the positive ML-Flow test indicated a relative risk approximately sixfold higher for occurrence of the disease. All unfavorable combinations of two and three assays generated significant risk values that ranged from 5.76 to 24.47, with the highest risk given by the combination of no BCG scar, negative Mitsuda test, and positive ML-Flow test. We suggest that the BCG vaccination may be given to stimulate Mitsuda test positivity, reducing the patient's risk of developing multibacillary forms. The high significance of these tests may have a great impact on programs to monitor contacts and should be used to improve early detection and treatment.

Resumo A implementação da poliquimioterapia (PQT/OMS) -composta pelas drogas dapsona, clofazimina e rifampicina -possibilitou a cura da hanseníase, porém não foram priorizados o manejo dos efeitos adversos pelas equipes de saúde. Objetivando determinar a magnitude dos efeitos adversos da poliquimioterapia para hanseníase e relacioná-los como possível causa de não adesividade do paciente ao tratamento, revisou-se prontuários de 187 pacientes tratados com PQT, de 1995 a 2000, no Centro de Saúde Escola (CSE) -UFU, com registro de efeitos colaterais em 71 pacientes (37,9%). Dentre os 113 efeitos adversos, 80 (70,7%) relacionaramse à dapsona, 7 (6,2%) à rifampicina, 26 (20,5%) à clofazimina. Esses efeitos levaram à mudança de esquema terapêutico em 28 (14,9%) dos 187 pacientes ou 39,4% dos 71 com efeitos adversos. Discute-se a importância de considerar os efeitos adversos da PQT na capacitação das equipes de saúde para maior adesão do paciente ao tratamento, colaborando para eliminar a hanseníase como problema de saúde pública. Palavras-chaves: Hanseníase. Reações adversas. Poliquimioterapia. Adesividade ao tratamento.Abstract The introduction of multidrug therapy (WHO/MDT) -composed by the drugs dapsone, clofazimine and rifampicin has enabled the cure of Hansen's disease, however, the adverse effects of these drugs were not given priority by the health team. Aiming to determine MDT's adverse effects' magnitude and relate them to the nonadhesion of patients to the treatment, a study of 187 charts of patients treated with MDT from January of 1995 to May 2000, was carried out at a Health Center of the Federal University of Uberlândia. Side effects were recorded in 71 patients' charts. Among the 113 side effects found, 80 (70.7%) were related to dapsone, 7 (6.2%) were caused by rifampicin and 26 (20.5%) were attributed to clofazimine. These effects induced 28 (14.9%), patients to change the therapeutic scheme, representing 39.4% from the 71 patients with adverse effects. Throughout this study, the importance is discussed of considering MDT's adverse effects when training the health team to heighten the patient's adhesion to the treatment and thereby collaborating to eliminate Hansen's disease as a public health problem. Key-words: Hansen's disease. Adverse effects. Multidrug therapy. Adhesion to treatment. A hanseníase é uma doença infecciosa, de evolução crônica que acomete predominantemente os nervos periféricos e, secundariamente, pele e mucosas. Seu agente etiológico é o Mycobacterium leprae descoberto por G.A. Hansen, em 1873.A infecção ativa pelo M. leprae é caracterizada por uma grande variabilidade no curso clínico, variando de uma doença paucibacilar na qual poucos bacilos estão presentes, a uma doença multibacilar, na qual uma grande carga bacilar está presente nas lesões.A detecção e o tratamento dos casos são ainda, na atualidade, os principais métodos usados para combater a hanseníase visando a interrupção da cadeia de transmissão da doença 23 . A hanseníase já foi objeto dos mais diversos tipos de tratamen...

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an ‘RR signature’ of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria.

BackgroundThe establishment of therapeutic regimens for mycobacteriosis depends on the accurate identification of Mycobacterium species, and misdiagnosis can result in inappropriate treatment and increased mortality of patients. Differential diagnosis among Mycobacterium species has been made by conventional phenotypic and biochemical tests after a long culture period. Specialized molecular diagnostics of mycobacteria allows rapid detection and species identification; however, such tests are not available in public health programs. Our aim was to demonstrate the clinical implications of erroneous diagnosis by performing molecular genotyping of mycobacterial infections in patients that were diagnosed based on symptoms, culture and bacilloscopy.MethodsCulture samples of mycobacterial infections from 55 patients clinically diagnosed as tuberculosis in 2013 and 2014, based on conventional methods, were identified by PCR -RFLP and results are discussed.ResultsWe have confirmed 35 (63.6 %) positive samples as M. tuberculosis, but 18 (32.7 %) were identified as non-tuberculous mycobacteria (M. avium type 1, M. avium type 2, M. kansasii type 1 type 1, M. mucogenicum, M. chelonae, M. terrae type 3, and 1 unknown RFLP pattern) and two were negative. Regarding clinical diagnosis, 61.8 % (34/55) was classified as pulmonary tuberculosis. It is important to emphasize that 36.4 % (20/55) of samples were misdiagnosed by conventional methods, and 11 (61.1 %) of the HIV positive patients (18/55) were NTM-coinfected.ConclusionThe identification of species in mycobacterial infections is essential for correct diagnosis and choice of treatment regimen, and misdiagnosis by conventional tools can lead to chronic disease, increased resistance and death.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1474-6) contains supplementary material, which is available to authorized users.

A new bioelectrode for gene detection of Mycobacterium leprae, also known as Hansen's bacillus, was produced by immobilizing of single-stranded DNA (ssDNA) with 78 bases long (specific gene related to Mycobacterium leprae) on graphite electrode modified with poly(4-aminophenol). This biosensing platform was able to recognize complementary DNA molecules via hybridization process. Hybridization between probe and target was monitored by voltammetry, using ferrocenecarboxyaldehyde as electrochemical DNA hybridization indicator. The hybridization of nucleic acid probe with the DNA target resulted in significant decrease in the oxidation peak current of ferrocenecarboxyaldehyde, indicating greater affinity of this compound for ssDNA than for double-strand DNA (dsDNA). The linear range of detection for the DNA target was found to be 0.35 -35 ng/lL. ssDNA hybridization with the DNA target was also investigated by electrochemical impedance spectroscopy (EIS), showing significant modification in Nyquist plot, by modification in electrode surface after addition of the complementary target. The effective immobilization of specific gene of Mycobacterium leprae onto graphite electrode modified with poly(4-aminophenol) and the detection of the hybridization process with the DNA target, monitored by voltammetry and EIS indicate that this is a new and promising biosensing platform to gene detection of Hansen's bacillus.

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Here, we describe 4-dimethylaminoantipyrine (4-DMAA)-mediated interfacing as a broad biochemical indicator to stabilize and promote the higher response of electrodes for immunological detection. We hypothesized that the improved biological interactions of 4-DMAA with electrodes and biological samples may be due to the interaction properties of the benzene and pyrazole chemical groups with graphite and proteins, respectively. In order to demonstrate that 4-DMAA could be used as a general indicator in electrochemical immunoassays, we used peptides as probes for the diagnosis of four neglected tropical infectious diseases Tegumentary leishmaniasis, Visceral leishmaniasis, Strongyloidiasis, and Leprosy on commercial graphite screen-printed electrodes. 4-DMAA oxidation was used to indicate specific biological recognition between the epitope-based peptide and serum immunoglobulin G (IgG) from infected patients. We demonstrated that 4-DMAA should be incorporated into the electrodes prior to serum application, which avoids interference with its sensitivity and specificity. In addition, 4-DMAA oxidizes at a low anodic potential, and the oxidation peak is useful for detecting proteins in biological fluids. In summary, we have successfully demonstrated the broad application of 4-DMAA as a general indicator for the specific diagnosis of four infectious diseases in electrochemical immunosensors. Such a strategy is quite advantageous for indirect detection of proteins that lack electrochemical activities or are spatially inaccessible on the electrode surface. This new indicator opens a new avenue for monitoring biological recognition, especially for immunosensors.