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| Mycobacteria Mycobacterial diseases are serious menace to human and animal populations since mycobacteria persist chronically for a long period inside the host cells. Most of the mycobacterial species have developed a number of sophisticated strategies to circumvent their fate within the host cells and to defy the host immune responses. Relatively little is known about the host-pathogen interactions that regulate the pathogenesis of mycobacterial disease. Most common and pathogenic mycobacteria survive and replicate inside macrophages, hallmark of mycobacterial virulence, by altering fusion of phagolysosomes and subsequent lysis of bacteria. Failure to induce host cell apoptosis enables mycobacteria to survive within the host cells and subsequently induction of immune responses. On the other hand, most mycobacteria resist or evade host immune responses (Cravel et al., 2002; Clark-Curtiss and Haydel, 2003). While all these processes have been partially characterized, the mycobacterial genes that play role in these processes are yet to be identified (Barrow,1997). The study focused on interaction of live mycobacteria with their host cells would reveal the strategies that mycobacteria developed to circumvent the macrophage killing mechanisms in order to increase their chances of survival within the host. Tuberculosis Tuberculosis is a bacterial disease of human and animal species. The disease, contagious and chronic in nature, is caused by Mycobacterium tuberculosis. The bacterium is transmitted through droplets from the throat and lungs of infected people, who spread the germs into the air when they cough, sneeze, talk or spit. Tuberculosis bacilli can cause pathology in almost all the organ systems in the body, while lungs are the most commonly affected organs (Pulmonary Tuberculosis). The most complex and challenging form of tuberculosis occurs in an isolated organ (Extrapulmonary Tuberculosis) other than the lungs, where fewer bacilli can cause much greater damage. The lesions at these sites are mostly inaccessible for diagnosis by clinicians. The clinical manifestation of the disease with M. tuberculosis is quite varied and largely depends on a number of bacterial virulent determinants and tissue factors. Tuberculosis occurring at any site may cause symptoms and findings that are not related specifically to the organ or tissues involved but, rather, are systemic in nature or are remote from the site of the disease (Hopewell and Jasmer, 2005). Systemic manifestations of the disease, including fever, malaise and weight loss are probably mediated by host factors such as cytokines (eg. TNF-a), while the pathology and altered immune responses are mediated by bacterial virulent factors (eg. cell wall components). Certain manifestations that are not a result of anatomic site of the involvement include hematologic abnormalities, hyponatremia and psychological disorders have been reported in tuberculosis patient. The most common hematological changes are high numbers of blood leukocytes (mostly monocyte) and anemia, each of which occurs in approximately 10% of the patient with apparently localized tuberculosis. The increase in leukocyte counts is usually slight, but leukemoid reactions may occur. Leukopenia has also been reported often with disseminated tuberculosis. Anemia is common when the infection is disseminated. Other than weight loss, hyponatremia is most frequent metabolic effects of tuberculosis, which is caused by production of anti-diuretic hormone like substance found within affected lung tissue. The psychological effects of tuberculosis are very poorly defined but were commonly recognized prior to the advent of effective therapy. These effects include depression and, on occasion, hypomania. In many patients, tuberculosis is associated with other serious disorders including HIV infection, alcoholism, chronic renal failure etc (Hopewell and Jasmer, 2005). Pulmonary tuberculosis: Cough is the most common symptom of pulmonary tuberculosis. Early in the course of the illness, the cough may be nonproductive, but subsequently, as inflammation and tissue necrosis ensue, sputum is usually produced. Inflammation of the lung parenchyma adjacent to a pleural surface may cause pleuretic pain. Spontaneous pneumothorax may also occur, often causing chest pain and perhaps dyspnea. Tuberculosis may also cause severe respirtatory failure. Hemoptysis (blood in the sputum) may also be there in tuberculosis. Pulmonary tuberculosis results abnormalities on the chest radiograph, although an endobronchial lesion may not be associated with a radiographic finding (Hopewell and Jasmer, 2005). Extrapulmonary tuberculosis: The most common organs involved in extrapulmonary form of tuberculosis are lymph nodes, pleura, genitourinary organs, skeletal and central nervous systems. Prior to the epidemic of HIV infection, approximately 15% of newly reported cases of tuberculosis involved only extrapulmonary sites. For reasons that are not understood, as rates of pulmonary tuberculosis decreased, rates of extrapulmonary disease remained constant, resulting in an increasing proportion of cases of being extrapulmonary. With the onset of HIV epidemic, however, both absolute and relative number of extrapulmonary involvement have increased (Hopwell and Jasmer, 2005) Johne's Disease (Paratuberculosis) Paratuberculosis is a chronic progressive bacterial disease of the domestic and wild ruminants including cattle, buffalo, sheep, goat, bison, deer, bighorn sheep, Rocky mountain goats, moufflon sheep, tule elk and species of cervides and camelids (Clarke, 1997; Sivakumar et al., 2005; Sivakumar et al., 2006). It is the most serious devastating health problems among the herd animals. The disease is caused by a slow growing acid-fast bacterium called Mycobacterium paratuberculosis which preferably infects the young animals and manifests the clinical disease in adult animals after prolonged incubation within the host. The course of disease has been reported to be in two main forms, viz. early or subclinical and clinical disease. In subclinical form, the infected animals appear normal and do not exhibit obvious clinical signs but there will be gradual reduction in milk production or body weight gain, and occasionally diarrhoeic. The clinical disease is characterized by chronic intermittent and incurable diarrhoea, drastic reduction in milk production, emaciation and ultimately death of the animals. However, animal maintains normal appetite in both form of the disease till it dies. The bacterium affects mostly the intestinal tract and its associated mesenteric lymph nodes, and occasionally liver. Pathological lesions of paratuberculosis are characterized by enterocolitis with mucosal corrugations (Fig.1), and regional lymphadenitis and lymphangitis. The affected tissues show granulomatous inflammatory changes composed of lymphocytes, macrophages, epithelioid and plasma cells and infrequently Langhan's giant cells (Fig.2-5). Presence of acid-fast bacilli consistent with morphological features of M.paratuberculosis (Fig.6) in tissue lesions is considered to be the most specific and confirmatory methods of diagnosis. Wide spectrum of immunological responses including early cell-mediated and later humoral (antibody) response are produced, while these two phases of immune responses overlap in most cases. Isolation of bacteria as well diagnosis of infected animals is difficult in subclinical stages, but it is possible in clinical cases. However, none of the diagnostic methods based on bacterial culture, serologic and latest molecular techniques has shown better test sensitivity as well as specificity. Treating infected animals is mostly unsuccessful since M. paratuberculosis shows greater resistance to most chemotherapeutic agents. Control of paratuberculosis infection in a herd is difficult due to the long incubation period, lack of accurate tests for definite diagnosis, and insufficiency of available vaccines to produce protective immunity. The very characteristic feature of this disease is that it remains undetectable for several years until the onset of the debilitating diarrhoea in the adult life, when it is impossible to treat or control the infection. Although, partial protection could be achieved with current vaccines, potentially satisfactory vaccines need to be developed for paratuberculosis. | |
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