Cenário atual da tuberculose / Current scenario of tuberculosis

Mesmo após 133 anos desde a descoberta do Mycobacterium tuberculosis, a tuberculose continua ser uma das principais causas de morte por doenças infecciosas no mundo, principalmente em países em desenvolvimento.O objetivo deste estudo foi mostrar aspectos relevantes da doença visando uma atualização literária e a busca de um olhar mais atento à problemática da tuberculose no contexto atual. Foram utilizados 130 artigos advindos das bases LILACS, MEDLINE/PUBMED, SCielo, Paho, Biblioteca Cochrane, WHOLIS, IBECS e Scopus, com as principais palavras-chaves selecionadas em terminologia em saúde encontradas no DECS. As espécies pertencentes ao Complexo M. tuberculosis compartilham cerca de 99% de identidade do DNA,com sequências altamente conservadas, mas diferem na distribuição geográfica, patogenicidade e hospedeiros. O mecanismo de resistência clinicamente significativo para rifampicina é uma mutação do gene rpoB, que codifica o alvo desse antibiótico. Há grandes avanços no diagnóstico da TB, com novos instrumentos de biologia molecular e testes rápidos, mas ainda não substituem os métodos clássicos bacteriológicos, apesar de suas conhecidas limitações. Atualmente, a associação de métodos moleculares, principalmente aqueles baseados em reações da PCR tem proporcionado grande impulso nos estudos da epidemiologia molecular do MT. Embora haja uma diminuição do número de casos no mundo, dentre os desafios da doença estão a necessidade de pesquisas na área, envolvimento político para solucionar as questões sociais atribuídas à TB, treinamento permanente dos profissionais e monitoramento de vigilância dos casos para eliminar a doença no cenário mundial.

Even 133 years after the discovery of Mycobacterium tuberculosis, tuberculosis continues to be one of the main causes of death due to infectious diseases worldwide, especially in developing countries. The objective of this study was, after a survey of recent publications, to show issues relevant to the disease and to takea closer look at the tuberculosis problem in the current context. A total of 130 articles were found in the LILACS, MEDLINE/PubMed, SciELO, Paho, Cochrane Library, WHOLIS, IBECS and Scopus databases using the main keywords selected from health terminology of MeSH. Species belonging to the M. tuberculosis complex have highly conserved sequences and share about 99% DNA identity, but differ in their geographic distribution, pathogenicityand host. The clinically significant mechanismof rifampicin resistance is due to a mutation of the rpoB gene which encodes the target of the antibiotic. Great advances in the diagnosis of tuberculosis have occurred, with new molecular biology tools and rapid tests, but without replacing classical bacteriological methods, despite their known limitations. Recently, the association of molecular methods, especially based on PCR, has provided great impetus in molecular epidemiology studies of M. tuberculosis. Although the number of cases in the world has decreased, among the challenges are the need for further research, political involvement to solve social issues linked to tuberculosis, permanent training and the surveillance of cases in order to eliminate the disease on the world stage.

Association of pulmonary tuberculosis and dermatological conditions among patients of a rural medical college hospital.

INTRODUCTION: Pulmonary tuberculosis (PTB) affects a significant proportion of the population. There are many contributory aetiological factors common to tuberculosis (TB) and dermatological conditions. AIM: To study the spectrum of concurrent skin conditions in patients with PTB and to compare with patients having other diseases. METHODS: All patients with PTB admitted to our Institute during the period of the study were included in the study. A comparable number of patients admitted in other departments constituted the control group. All patients were screened for skin diseases. RESULTS: There were 498 patients in each group, matched for age and gender. There were 126 patients with skin conditions in the study group as against 60 patients in the control group. Pityriasis versicolor was the commonest skin condition in both the groups. Whereas acniform eruptions and pruritis were more common in the control group. Pityriasis versicolor, herpes zoster, erythema nodosum and leprosy were significantly more frequent among patients. CONCLUSION: There is a high frequency of concurrent skin diseases in patient with PTB that should be managed along with it.

Dermatomyositis in a human immunodeficiency virus infected person.

It is interesting to study an autoimmune condition like dermatomyositis (DM) in the setting of immunosuppression due to human immunodeficiency virus (HIV) infection. An HIV seropositive female aged 30 years, presented with a nonitchy rash over the face, breathlessness, diarrhoea and difficulty in raising her hands above her head. A heliotrope rash around the eyes, Gottron's papules and proximal muscle weakness were found to be present. C reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase levels were raised, but creatinine phosphokinase and anti-nuclear antibody profile were normal. Her HIV serostatus was confirmed by Western blotting, keeping in mind the potential for false positive HIV serology in an autoimmune disorder. Her CD4 count was 379 cells/mm3. An X-ray of the chest showed bilateral pleural effusion with raised pleural fluid adenosine deaminase levels. Clinical findings and laboratory investigations favored the diagnosis of DM and HIV infection with tuberculous effusion in an HIV seropositive patient. She was treated with antibiotics, four-drug anti-tubercular treatment, systemic steroids and later, antiretroviral treatment. Chances of a false positive antibody test for HIV should be considered in a patient having an autoimmune disease such as DM.

[Human mycobacterial infections: impact of host genetic factors]. / Infections mycobactériennes humaines: impact des facteurs génétiques de l'hôte.

Humans are exposed worldwide to a variety of environmental mycobacteria (EM) and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. Although rarely pathogenic, poorly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. M. tuberculosis and M. leprae are more virulent, causing tuberculosis, and leprosy, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. There is now accumulating evidence that the large interindividual variability of clinical outcome results in part from variability in the human genes that control host defense. We review here in current knowledge about genetic predisposition to common (leprosy and tuberculosis) and rare (BCG and EM infections) mycobacterial infections.

Infections mycobactériennes humaines: im´pact des facteurs génetiques de lhôte / Human mycobacterial infections: impact of host genetic factors

Humans are exposed worldwide to a variety of environmental mycobacteria (EM) and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. Although rarely pathogenic, poorly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. M. tuberculosis and M. leprae are more virulent, causing tuberculosis, and leprosy, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. There is now accumulating evidence that the large interindividual variability of clinical outcome results in part from variability in the human genes that control host defense. We review here in current knowledge about genetic predisposition to common (leprosy and tuberculosis) and rare (BCG and EM infections) mycobacterial infections.

Infectious complications of human T cell leukemia/lymphoma virus type I infection.

Infection with human T cell leukemia/lymphoma virus type I (HTLV-I) has been etiologically associated with two diseases: adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Increasing evidence suggests that HTLV-I infection may be associated with immunosuppression and, as a consequence, affect the risk and expression of several other infectious diseases, of which the best studied are strongyloidiasis, tuberculosis, and leprosy. In strongyloidiasis, coinfection with HTLV-I appears to result in a higher rate of chronic carriage, an increased parasite load, and a risk of more severe infection. In tuberculosis, a decrease in delayed-type hypersensitivity to Mycobacterium tuberculosis has been established, but whether this decrease is clinically significant has yet to be determined. In leprosy, an increased risk of disease is suggested, but the published studies are all too poorly controlled to draw definite conclusions.

Mycobacterial infections: are the observed enigmas and paradoxes explained by immunosuppression and immunodeficiency?

The enigmas and paradoxes observed in tuberculous patients, in Bacille Calmette-Guérin-vaccinated people and in Bacille Calmette-Guérin-treated cancer patients have been examined, in an attempt to explain them through the mechanisms of immunodeficiency and immunosuppression. A dual effect is postulated: an immunosuppression induced by the infecting mycobacteria that adds to a pre-existing or emerging state of immunodeficiency of the infected individual. The immunological cellular and humoral anergies observed at the beginning of a tuberculous therapy are usually lifted after the first two weeks of treatment. This restoration of immune responsiveness may be attributed to the destruction or to the growth inhibition of immunosuppressive mycobacteria. The observation that drugs cytocidal in vitro do not always sterilize the patients under treatment whereas bacteriostatic drugs do, may find an explanation in the dual immunosuppression induced by cytocidal drugs and mycobacteria. The fact that Bacille Calmette-Guérin applied as an immunotherapy to residual cancer has either a favorable or an unfavorable action may be due to the immunosuppressive activity attached to some Bacille Calmette-Guérin strains and to some cancers. The variable protective activity of Bacille Calmette-Guérin vaccines may be due to the immunological status of the vaccinated people and the compositional differences between strains. The protective activity of subunit vaccines in experimental models can be attributed to the elimination of immunosuppressive factors present in whole killed mycobacteria.

The pathology and pathophysiology of mycobacterial infections.

Classic tuberculosis is the result of infection with the human strain of Mycobacterium tuberculosis, and atypical tuberculosis is the result of infection with atypical mycobacteria. The pathology and course of the disease depend on the sensitivity of the host. Primary tuberculosis is the first infection in an unsensitized host, and secondary, postprimary, or chronic tuberculosis results from reactivation of previously acquired infection or, rarely, reinfection of a sensitized host. The pathology of infection with M avium-intracellulare in patients with acquired immunodeficiency syndrome (AIDS) is different from that of tuberculosis; formation of noncaseating lesions and a marked macrophage response resemble changes seen in lepromatous leprosy. These infections in patients with AIDS are predominantly extrapulmonary.

Undernutrition in lepromatous leprosy. V. Severe nutritional deficit in lepromatous patients co-infected with pulmonary tuberculosis.

We have compared the nutritional status of patients with lepromatous leprosy coinfected with pulmonary tuberculosis (18 cases) with that of lepromatous leprosy (239 cases) and of pulmonary tuberculosis (21 cases) and with that of healthy controls. There was a severe weight loss and reduction of skinfold thickness in the patients with pulmonary tuberculosis as well as in lepromatous patients with associated pulmonary tuberculosis, but not in patients with lepromatous leprosy. Levels in sera of diet-dependent proteins, such as albumin, prealbumin and retinol binding protein, were significantly decreased in all three groups of patients; on the other hand, levels of the diet-independent proteins, such as the immunoglobulins, were raised in all the groups, particularly in the pulmonary tuberculosis patients as compared with healthy controls. Serum transferrin levels were decreased only in the tuberculosis patients with or without lepromatous leprosy, but not in patients with leprosy alone. While haemoglobin levels decreased in all patient groups, serum iron concentrations were reduced most in lepromatous patients concomitantly infected with pulmonary tuberculosis. Serum ferritin levels increased in the sera of pulmonary tuberculosis and lepromatous leprosy patients, but was severely reduced in lepromatous patients with associated pulmonary tuberculosis. Mean serum zinc and calcium levels were decreased in all three groups of patients, while the serum copper concentration was increased in all of them compared with healthy controls. Also, inorganic phosphorus was elevated in tuberculosis and lepromatous patients coinfected with pulmonary tuberculosis, but not in lepromatous patients. Serum calcitonin levels were increased in all patient groups indicating an inverse correlation between serum calcium and calcitonin levels. This is the first comparative report describing the status of macro- and micronutrients in two most important mycobacterial diseases of the third world countries.

Immune responses and immunostimulation in tuberculosis therapy.

Despite a reasonably extensive literature on cellular and humoral immune responses in tuberculous disease, abnormalities tend to be secondary rather than predisposing to disease. No discrete immune deficiency or failure, which would explain the progression from non-infection to infection with Mycobacterium tuberculosis to tuberculous disease, has been identified. There is evidence that tuberculous disease occurs in a spectrum, analogous to leprosy, and it would seem that if immunostimulants, as adjuncts to standard therapy, are to be of any value in the treatment of tuberculosis, they should be used for non-reactive tuberculosis patients. The range of immunostimulants currently available tends to be indiscriminate in action and their targets in tuberculous disease largely uncertain; their role in therapy in discussed.