SUMMARYHuman T-cell leukemia virus type 1 (HTLV-1), the first human retrovirus to be discovered, is present in diverse regions of the world, where its infection is usually neglected in health care settings and by public health authorities. Since it is usually asymptomatic in the beginning of the infection and disease typically manifests later in life, silent transmission occurs, which is associated with sexual relations, breastfeeding, and blood transfusions. There are no prospects of vaccines, and screening of blood banks and in prenatal care settings is not universal. Therefore, its transmission is active in many areas such as parts of Africa, South and Central America, the Caribbean region, Asia, and Melanesia. It causes serious diseases in humans, including adult T-cell leukemia/lymphoma (ATL) and an incapacitating neurological disease (HTLV-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) besides other afflictions such as uveitis, rheumatic syndromes, and predisposition to helminthic and bacterial infections, among others. These diseases are not curable as yet, and current treatments as well as new perspectives are discussed in the present review.

Resumo A hanseníase é doença infecciosa crônica causada pelo Mycobacterium leprae. A predileção pela pele e nervos periféricos confere características peculiares a esta moléstia, tornando o seu diagnóstico simples. O Brasil continua sendo o segundo país em número de casos no mundo, após a Índia. Aproximadamente 94% dos casos conhecidos nas Américas e 94% dos novos diagnosticados são notificados pelo Brasil. A doença manifesta-se em dois pólos estáveis e opostos (virchowiano e tuberculóide) e dois grupos instáveis (indeterminado e dimorfo). Em outra classificação a doença é dividida em forma tuberculóide, borderline ou dimorfa que são subdivididos em dimorfa-tuberculóide, dimorfa-dimorfa e dimorfa-virchowiana, e virchowiana. A baciloscopia é o exame complementar mais útil no diagnóstico. O tratamento da hanseníase compreende: quimioterapia específica, supressão dos surtos reacionais, prevenção de incapacidades físicas, reabilitação física e psicossocial. A poliquimioterapia com rifampicina, dapsona e clofazimina revelou-se muito eficaz e a perspectiva de controle da doença no Brasil é real no curto prazo. Palavras-chaves: Hanseníase. Lepra. Micobacteriose. Mycobacterium leprae.Abstract Leprosy or Hansen's disease is a chronic infectious disease caused by the Mycobacterium leprae. The skin and nervous manifestations of the disease present a singular clinical picture that is easily recognized. After India, Brazil still is the second country with the greatest number of cases in the world. Around 94% of the known cases and 94% of the new cases reported in America, come from Brazil. The disease presents itself in two well-defined stable and opposite poles (lepromatous and tuberculoid) and two unstable groups (indeterminate and dimorphic). The spectrum of presentation of the disease may also be classified as: tuberculoid tuberculoid (TT), borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL) and lepromatous lepromatous (LL). The finding of acid fast bacillus in tissue is the most useful method of diagnosis. The effective treatment of leprosy includes the use of specific therapy, suppression of lepra reactions, prevention of physical incapacity, and physical and psychosocial rehabilitation. Chemotherapy with rifampin, dapsone and clofazimine have produced very good results and the control of the disease in Brazil in the foreseeable future is likely. Key-words:Leprosy. Hansen's disease. Mycobacterium leprae. Mycobacteriosis. A hanseníase é doença infecciosa crônica causada pelo M. leprae. A predileção pela pele e nervos periféricos confere características peculiares a esta moléstia, tornando o seu diagnóstico simples na maioria dos casos. Em contrapartida, o dano neurológico responsabiliza-se pelas seqüelas que podem surgir. Constitui importante problema de saúde pública no Brasil e em vários países do mundo (Tabela 1), e persiste como endemia em 15 países ao final de 2000 (prevalência acima de 1,0/10.000 habitantes). Apesar de todo o empenho em sua eliminação, o Brasil continua sendo o seg...

BackgroundLeprosy 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 findingsAn 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.ConclusionOur 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 registrationClinicalTrials.gov: NCT00669643

No abstract

Leprosy is an important cause of disability in the developing world. Early diagnosis is essential to allow for cure and to interrupt transmission of this infection. MicroRNAs (miRNAs) are important factors for host-pathogen interaction and they have been identified as biomarkers for various infectious diseases. The expression profile of 377 microRNAs were analyzed by TaqMan low-density array (TLDA) in skin lesions of tuberculoid and lepromatous leprosy patients as well as skin specimens from healthy controls. In a second step, 16 microRNAs were selected for validation experiments with reverse transcription-quantitative PCR (qRT-PCR) in skin samples from new individuals. Principal-component analysis followed by logistic regression model and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of selected miRNAs. Four patterns of differential expression were identified in the TLDA experiment, suggesting a diagnostic potential of miRNAs in leprosy. After validation experiments, a combination of four miRNAs (miR-101, miR-196b, miR-27b, and miR-29c) was revealed as able to discriminate between healthy control and leprosy patients with 80% sensitivity and 91% specificity. This set of miRNAs was also able to discriminate between lepromatous and tuberculoid patients with a sensitivity of 83% and 80% specificity. In this work, it was possible to identify a set of miRNAs with good diagnostic potential for leprosy.KEYWORDS biomarker, leprosy, miRNA L eprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The infection affects primarily the skin and can cause damage to peripheral nerves, mucosa, and other organs, including liver and eyes. Leprosy is classified as a neglected tropical disease and remains one of the main causes of disability in the world (1-3). According to a World Health Organization (WHO) report including data from 138 countries, 211,974 newly diagnosed patients were notified in the year 2015 and 96% of them were reported from 22 countries, including Brazil (4).Leprosy presents a spectrum of clinical manifestations depending on the host immune response against M. leprae. It can be classified according to histopathological (Ridley-Jopling) criteria into different forms across two opposing poles: a so-called resistance pole responsible for a localized form of the disease (tuberculoid tuberculoid [TT]) and a susceptibility pole that is a disseminated form, which leads to the development of more severe clinical manifestations (lepromatous leprosy [LL]). There are also three intermediate and unstable forms: borderline tuberculoid (BT), borderline

The incidence of human T cell lymphotropic virus type 1 (HLTV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is not well defined in the literature. Several studies have reported different incidence rates, and recent publications suggest a higher incidence and prevalence of HAM/TSP. The interdisciplinary HTLV Research Group (GIPH) is a prospective open cohort study of individuals infected with HTLV-1/2. This study describes the demographic data and HAM/TSP incidence rate observed in 181 HTLV-1-seropositive individuals and compares the results with previous reports in the literature. HAM/TSP was diagnosed on the basis of the World Health Organization diagnostic criteria and De Castro-Costa et al. [Proposal for diagnostic criteria of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). AIDS Res Hum Retroviruses 2006;22:931-935]. Seven HAM/TSP incident cases were observed during the follow-up. The HAM/TSP incidence density was 5.3 cases per 1,000 HTLV-1-seropositive cases per year (95% confidence interval: 2.6-10.9), with a mean follow-up of 7±4 years (range: 1 month to 15 years). HAM/TSP was more frequent in women in their 40s and 50s with probable infection via the sexual route. The HAM/TSP incidence density among HTLV-1-seropositive cases observed in the present study is higher than that in previous studies. HAM/TSP may be underdiagnosed in countries like Brazil where HTLV infection is prevalent. Orientation and prevent transmission of HTLV programs are needed. Currently, preventing HTLV-1 transmission is the most effective way to reduce the impact of HAM/TSP on society.

In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4+HLA-DR+, CD8+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

OBJECTIVE:To describe the evolution and outcome of children hospitalized with community‐acquired pneumonia receiving penicillin .METHODS:A search was carried out for all hospitalized community‐acquired pneumonia cases in a 37‐month period. Inclusion criteria comprised age ≥2 months, intravenous penicillin G use at 200,000 IU/kg/day for ≥48 h and chest x‐ray results. Confounders leading to exclusion included underlying debilitating or chronic pulmonary illnesses, nosocomial pneumonia or transference to another hospital. Pneumonia was confirmed if a pulmonary infiltrate or pleural effusion was described by an independent radiologist blind to the clinical information. Data on admission and evolution were entered on a standardized form.RESULTS:Of 154 studied cases, 123 (80%) and 40 (26%) had pulmonary infiltrate or pleural effusion, respectively. Penicilli was substituted by other antibiotics in 28 (18%) patients, in whom the sole significant decrease was in the frequency of tachypnea from the first to the second day of treatment (86% vs. 50%, p = 0.008). Among patients treated exclusively with penicillin G, fever (46% vs. 26%, p = 0.002), tachypnea (74% vs. 59%, p = 0.003), chest indrawing (29% vs. 13%, p<0.001) and nasal flaring (10% vs. 1.6%, p = 0.001) frequencies significantly decreased from admission to the first day of treatment. Patients treated with other antimicrobial agents stayed longer in the hospital than those treated solely with penicillin G (16±6 vs. 8±4 days, p<0.001, mean difference (95% confidence interval) 8 (6–10)). None of the studied patients died.CONCLUSION:Penicillin G successfully treated 82% (126/154) of the study group and improvement was marked on the first day of treatment.