Cell-mediated immunity: dealing a direct blow to pathogens.
Cytotoxic T lymphocytes are essential for defence against viral infections. Recent data demonstrating direct killing of intracellular bacteria by granulysin, a protein released from the granules of cytotoxic T lymphocytes, emphasize the contribution of these lymphocytes to the control of tuberculosis. (+info)
Tuberculosis outbreaks in prison housing units for HIV-infected inmates--California, 1995-1996.
During 1995-1996, staff from the California departments of corrections and health services and local health departments investigated two outbreaks of drug-susceptible tuberculosis (TB). The outbreaks occurred in two state correctional institutions with dedicated HIV housing units. In each outbreak, all cases were linked by IS6110-based DNA fingerprinting of Mycobacterium tuberculosis isolates. This report describes the investigations of both outbreaks; the findings indicated that M. tuberculosis can spread rapidly among HIV-infected inmates and be transmitted to their visitors and prison employees, with secondary spread to the community. (+info)
Issues in the treatment of active tuberculosis in human immunodeficiency virus-infected patients.
Most HIV-infected patients with tuberculosis can be treated satisfactorily with standard regimens with expectations of good results. Treatment of tuberculosis in these patients has been complicated by the introduction of HAART, which relies on drugs that interfere with the most potent class of antituberculous medications. Rifampin-free regimens or regimens that employ rifabutin may be acceptable strategies for patients who are receiving protease inhibitors, although these regimens have not been rigorously evaluated in patients with AIDS. At present, there is good reason to believe that a 6-month course of a rifabutin-containing regimen or a 9-12-month course of a regimen of streptomycin, isoniazid, and pyrazinamide should be adequate therapy for most patients with drug-susceptible disease. As the treatment of HIV infection with antiretroviral agents evolves, the treatment of tuberculosis in patients with AIDS is likely to evolve as well. This will require careful coordination of antituberculosis and antiretroviral therapies. (+info)
Norepinephrine, released from sympathetic neurons, and epinephrine, released from the adrenal medulla, participate in a number of physiological processes including those that facilitate adaptation to stressful conditions. The thymus, spleen, and lymph nodes are richly innervated by the sympathetic nervous system, and catecholamines are thought to modulate the immune response. However, the importance of this modulatory role in vivo remains uncertain. We addressed this question genetically by using mice that lack dopamine beta-hydroxylase (dbh-/- mice). dbh-/- mice cannot produce norepinephrine or epinephrine, but produce dopamine instead. When housed in specific pathogen-free conditions, dbh-/- mice had normal numbers of blood leukocytes, and normal T and B cell development and in vitro function. However, when challenged in vivo by infection with the intracellular pathogens Listeria monocytogenes or Mycobacterium tuberculosis, dbh-/- mice were more susceptible to infection, exhibited extreme thymic involution, and had impaired T cell function, including Th1 cytokine production. When immunized with trinitrophenyl-keyhole limpet hemocyanin, dbh-/- mice produced less Th1 cytokine-dependent-IgG2a antitrinitrophenyl antibody. These results indicate that physiological catecholamine production is not required for normal development of the immune system, but plays an important role in the modulation of T cell-mediated immunity to infection and immunization. (+info)
Susceptibilities of Mycobacterium tuberculosis and Mycobacterium avium complex to lipophilic deazapteridine derivatives, inhibitors of dihydrofolate reductase.
Twelve lipophilic 2,4-diamino-5-methyl-5-deazapteridine derivatives and trimethoprim were evaluated for activity against Mycobacterium tuberculosis and Mycobacterium avium in vitro. Six of the compounds had MICs of < or =12.8 mg/L and < or =1.28 mg/L against M. tuberculosis and M. avium, respectively; trimethoprim MICs were >128 mg/L and >12.8 but < or =128 mg/L, respectively. Two compounds, with either a 2-methyl-5-methoxy phenyl or 2-methoxy-5-trifluoromethyl phenyl linked at the 6-position of the deazapteridine moiety by a CH2NH bridge, had MICs of < or =0.13 mg/L against M. avium; the two compounds also had apparent I50 values for dihydrofolate reductase of 2 and 8 nM, respectively, compared with an I50 of 400 nM with trimethoprim. Four of the compounds were selectively toxic to mycobacteria as compared with Vero cells. These results demonstrated that lipophilic antifolates can be synthesized which are more active against mycobacteria than trimethoprim and which possess selective toxicity. (+info)
The future role of international agencies in control of acute respiratory tract infections.
Achievements in the control of acute respiratory infection (ARI) owe much to international collaboration in research, education, and delivery of services. This article highlights some of the current activities of the many international agencies involved and summarizes thoughts on their future roles. Key recent scientific advances include better surveillance, new and improved vaccines, refinement of standard clinical management plans and behavioral change techniques, and demonstration of the effectiveness of their application. Agencies involved include the World Health Organization, the International Union Against Tuberculosis and Lung Disease, national government agencies for overseas aid, many academic departments, and professional lung health associations. However, much remains to be done, especially in collaborative research, in the devising, implementing, and evaluating of health care delivery systems in low-income countries, and in mobilizing political will and resources. These are tasks beyond the capacity of any lone agency. Success will depend on how effectively we collaborate. (+info)
Observations on animal and human health during the outbreak of Mycobacterium bovis in game farm wapiti in Alberta.
This report describes and discusses the history, clinical, pathologic, epidemiologic, and human health aspects of an outbreak of Mycobacterium bovis infection in domestic wapiti in Alberta between 1990 and 1993, shortly after legislative changes allowing game farming. The extent and seriousness of the outbreak of M. bovis in wapiti in Alberta was not fully known at its onset. The clinical findings in the first recognized infected wapiti are presented and the postmortem records for the herd in which the animal resided are summarized. Epidemiologic findings from the subsequent field investigation are reviewed, the results of recognition and investigation of human exposure are updated, and recommendations for reduction of human exposure are presented. (+info)
Differential protective efficacy of DNA vaccines expressing secreted proteins of Mycobacterium tuberculosis.
The development of more-effective antituberculosis vaccines would assist in the control of the global problem of infection with Mycobacterium tuberculosis. One recently devised vaccination strategy is immunization with DNA plasmids encoding individual microbial genes. Using the genes for the M. tuberculosis secreted proteins MPT64 (23 kDa), Ag85B (30 kDa), and ESAT-6 (6 kDa) as candidate antigens, DNA vaccines were prepared and tested for immunogenicity and protective efficacy in a murine model of aerosolized tuberculosis (TB). Intramuscular immunization with DNA-64 or DNA-85B resulted in the activation of CD4(+) T cells, which produce gamma interferon (IFN-gamma), and high titers of specific immunoglobulin G antibodies. Further, DNA-64 induced major histocompatibility complex class I-restricted CD8(+) cytotoxic T cells. The addition of a eukaryotic leader sequence to mpt64 did not significantly increase the T-cell or antibody response. Each of the three DNA vectors stimulated a significant reduction in the level of M. tuberculosis infection in the lungs of mice challenged 4 weeks after immunization, but not to the levels resulting after immunization with Mycobacterium bovis BCG. The vaccines showed a consistent hierarchy of protection, with the most effective being Ag85B, followed by ESAT-6 and then MPT64. Coimmunization with the three vectors resulted in a greater degree of protection than that induced by any single vector. This protective efficacy was associated with the emergence of IFN-gamma-secreting T cells earlier than in infected animals immunized with a control vector. The efficacy of these DNA vaccines suggests that multisubunit vaccination may contribute to future vaccine strategies against TB. (+info)