The Dormant State of Tuberculosis - Literature review Example

Simone Pedrini The Dormant of Tuberculosis 27 January Literature of Research Studies L.G. Wayne. “Dormancy of Mycobacterium tuberculosis and latency of disease”. European Journal of Clinical Microbiology and Infectious Disease. (1994). Retrieved from http://link.springer.com/article/10.1007%2FBF02111491?LI=true.[Web]. The scholarly research journal, European Journal of Clinical Microbiology and Infectious Diseases, documents “circumstantial evidence, via observation, of the natural history of tuberculosis in humans and experimental animals. Mycobacterium tuberculosis is capable of adapting to prolonged periods of dormancy in tissues (in vivo). These dormant bacilli are responsible for the latency of the disease itself” (Wayne, 1994, p. 908). Experimental studies on “the dormancy of Mycobacterium tuberculosis” were conducted at the Tuberculosis Research Laboratory, Department of Veteran Affairs Medical Center (Long Beach, CA, USA). In the context of the clinical research laboratories, quantitative experiments were designed and conducted that observed analyzed latency (a stable, nonreplicative state – Chao & Rubin, 2010) of the dormant bacilli’s ability to become “resistant to killing by antimycobacterial agents” (Wayne, 1994, p. 908). The laboratory experiments demonstrated that “the development of active human (in vivo) tuberculosis is usually the consequence of one of the following combinations of events, according to Wayne experimental in vivo research: (1) Inhalation of droplet nuclei that contain Mycobacterium tuberculosis, followed by a decline in the body’s immune system. Replication of the bacterium can not be controlled; This causes progression of the infection to become the active tuberculosis disease (p. 908). (2) Inhalation of droplet nuclei that contain Mycobacterium tuberculosis followed by an immune response of the host that initially suppresses and/or kills the bacilli and prevents clinical manifestations of disease. After prolonged periods time, some of the bacilli may become dormant or latent. Later, the break down of the immune system may cause reactivation of the latent disease; (Wayne, 1994, p. 908). (3) Mycobacterium tuberculosis is also the result of prior active tuberculosis disease that has been controlled by chemotherapy and/or the host’s immune system; some of the bacilli become dormant and are subject to revival and reactivation of the disease” (Wayne, 1994). With further conducting of the Mycobacterium tuberculosis microbiology experiments, Wayne (1994) pointed out, “…only when a means is found to prevent dormancy of the tuberculosis bacillus or to kill the organism when it is in its dormant state, will the goal of eradication of tuberculosis become a realistic prospect” (p. 908). Current understanding of the latency of Mycobacterium tuberculosis is based on observation of infection of in vivo models – both human and experimental, laboratory animals. The emergence of in vivo used in analyzing and observing the dormant bacilli were sometimes used when collecting data and information on physiologic studies of dormancy in culture (p. 909). Wayne (1994) also points out that while interpreting information and calculating quantitative data for research tables, figures, and diagrams his findings determined “… individuals with positive tuberculin reactions, it is evident that decades may intervene between infections with Mycobacterium tuberculosis and development of detectable tuberculosis disease. In drawing conclusions from the in vivo models during experimental processes, Wayne (1994) indicated that there was a capacity for prolonged periods (even decades) of dormant or latency, inactivity of Mycobacterium tuberculosis and this accounted for increasing development of active tuberculosis in elderly individuals. This was concluded to be associated with age-related decline in the individual’s immune response system. (p. 909). Dick, T. & the British Society for Antimicrobial Chemotherapy. “Dormant tubercule bacilli: the key to more effective TB chemotherapy”. Oxford Journal of Antibacterial Chemotherapy. (2001). Retrieved from http://jac.oxfordjournals.org/content/47/1/117/ [Web]. In the research-based article, “Dormant tubercule bacilli: the key to more effective TB chemotherapy” by T. Dick (2001), the key research question explored states, “…the problem in tuberculosis control is the persistence of Mycobacterium tuberculosis despite prolonged chemotherapy” (p. 117). As demonstrated during in vivo specimen and culture analysis, “treatment for six to twelve months is required to cure acute disease or eliminate latent or dormant infection. The research question: Why does it take so long to eradicate the bacilli once they reside within the human host”? (Dick, 2001, p. 117). The answer, Dick proposed, could lie in the development of physiological (as opposed to genetic) drug resistance. According to research conducted within Dick’s Mycobacterium laboratory, supported by the Institute of Molecular and Cell Biology (IMCB), the link between the Mycobacterium being categorized as an obligate aerobe – a bacterium that can live only in the presence of oxygen (O2) -- drug resistance and latency was a focus of in vitro research studies. Via laboratory studies, it was established that “there was a link between starvation for oxygen and drug resistance (Wayne & Hayes, 1996). During in vitro analysis, it was demonstrated that depletion of oxygen experimental culture, Mycobacterium tuberculosis terminates growth and develops latency, a defined non-replicating dormant form. The dormant, latent form of the bacilli is anaerobic and can remain dormant for extended periods of time. Scientifically speaking, “…the bacilli is arrested at a uniform stage of the cell cycle and and play a significant role in in vivo cultures” (Dick& Wayne, 1996, p. 117). It was in observing and analyzing both the in vitro and in vivo laboratory findings together that the working model, often used to explain activities of genetically drug-sensitive bacilli during chemotherapy, can be proposed. From the laboratory findings, Dick (1996) and Wayne (1996) also demonstrated that in vivo studies help in “the development of drugs that specifically target dormant bacilli, thus having a profound effect and impact on tuberculosis therapy” (p. 117). As result, the outcome could mean effective treatment of sixteen-million patients suffering from acute tuberculosis and a method of more efficient treatment for two-billion latently infected people might become feasible (p. 117). The importance of “the development of a culture model for dormancy in Mycobacterium tuberculosis (The Wayne Model, 1996) has two significant implications: (1) the model can be utilized as a cell-based assay system for anti-dormancy drug screening; (2) it creates an experimentally accessible model of the molecular mechanism expressing dormant, latency response” (p. 117). The Wayne Model demonstrates the first culture system for mycobacterium dormancy. The significance furthers the research and experimentally-based data on ‘oxygen starvation-induced dormancy. The Wayne Model, conducted in in vitro experimental environments, is based on gradual, self-generated oxygen withdrawal due to growth of the bacilli in sealed, stirred test tubes (p. 117). Bhakta, Sanjib, Dr. “World TB Day 2011” (2011. Targeted News Service, Washington DC. Proquest Database: Retrieved from http://searchproquest.com.ezproxy.lapl.org/docview/ 85864038/13BE3F7844B74A371DA/ Thursday 24 March 2011 was announced to be ‘World TB Day’. Dr. Sanjib Bhakta, along with students and collaboratives of the ISMB Mycobacteria Research Laboratory addressed current issues of research that focused on new drug treatment for TB – a treatment and curable disease, yet still the cause of death for two-million people worldwide. Dr. Bhakta is the Senior Lecturer in Microbiology and Head of ISMB Mycobacteria Research Laboratory at Birbeck University, London… More articles of scientific research (inclusive of fact and data tables), case studies, conferences, and summit symposiums compose the remaining of the research assignment. In turn, inclusive information from the articles and literature may be included in the dissertation conclusion. Read More