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Title: The emergence, transmission, and control of drug resistant tuberculosis epidemics
Author: Bahcall, Orli Gilat
ISNI:       0000 0004 2737 4926
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2007
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With one third of the world's population infected with tuberculosis, and 8 million new cases of active disease estimated annually, tuberculosis has been declared a global health emergency. Of particular concern has been the finding that drug resistance has developed in every country surveyed, and has reached high levels in a number of settings. Treatment of resistant cases, which require costly and difficult specialized regimens, has added considerable strain to health programs. Crucial questions in the global control of tuberculosis are raised, including where and to what extent will resistance emerge? And, can current control programs adequately manage resistance or are modifications needed? This problem is addressed in this thesis at three levels: the emergence, transmission and control of resistance. Emergence and transmission Drug resistance is a man made problem which first emerges by the acquisition of drug resistance mutations during the treatment of a drug sensitive case. This acquired resistance can then be transmitted to new susceptible individuals in the population, who are said to develop primary resistance. A mathematical model for the transmission of tuberculosis was developed on the basis of current understanding of the epidemiology of TB. The structure of the model includes the emergence of acquired and the transmission of primary resistance, in the context of a drug sensitive epidemic. Drug resistance was shown to emerge in a series of linked sub-epidemics following the start of treatment of a sensitive epidemic. Poor control practices, including a low treatment cure rate and a high acquired resistance rate, allows for the development of a high prevalence of resistance. Control In order to consider the impact of different control strategies, the model was expanded to incorporate elements of first and second line control, including case detection, treatment cure rates, drug susceptibility testing, and specialized resistance regimens. In addition, the importance of waiting times to treatment and return of drug susceptibility tests was examined. Case detection and treatment was found to be the most important control measure for reducing disease levels. For controlling resistance, the cure and drug susceptibility testing rates were most important. In high burden countries, control priorities should focus on increasing the case detection and cure rates. In areas where poor treatment practices have already resulted in a high prevalence of resistance, control measures should be first improved before expanding the program. In regions of low incidence, control measures should be improved through detection and treatment of latent infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available