Thesis (MSc (School of health systems and public health))--University of Pretoria, 2009. / Summary in English. Includes bibliographical references.

In this treatise a SEIR model for the transmission of tuberculosis was proposed. It assumes that the latent infected individuals progress to active tuberculosis through endogenous reactivation and exogenous re-infection and that the individuals who have recovered from the disease through treatment are not immune to tuberculosis re-infection. While most features of the original model were kept, the model was modified to incorporate two control measures in the form of post-exposure tuberculosis prophylaxis for the treatment of latent individuals and tuberculosis therapeutics for the treatmentof individuals with active tuberculosis. Mathematical analysis of the modelwas done under the assumption that the two control measures are positiveconstants. The disease-free equilibrium point was locally asymptotically stable when the basic reproduction number was less than unity and unstable when this epidemic threshold exceeds unity. An optimal control problem was formulated and the necessary conditions for optimality were derived.The numerical results based on data from Port Elizabeth suggest that using both forms of control measures simultaneously is more effective in reducing the total number of infected individuals than applying single controls separately.

En 10-plex GeneXpert analysmetod för diagnos av M. Tuberculosis infektion samt med kapacitet att särskilja aktiv och latent tuberkulos har utvecklats på Cepheid. Analysmetoden sker ex-vivo och kvantifierar uttryck av tuberkulos associerade mRNA biomarkörer i antigenstimulerat helblod. Ett original set av mRNA biomarkörer har nedselekterats till 9 biomarkörer som utgör mRNA signaturen i 10-plex analysmetoden. Urvalet av biomarkörer baserades på probescreening och optimeringstudier utfört med Cepheids ”in cartridge” qPCR teknologi. Den diagnostiska prestandan av mRNA signaturen utvärderades genom att analysera 380 antigenstimulerade kliniska prover klassificerade som M. Tuberculosis infekterad, aktiv tuberkulos, latent tuberkulos och icke infekterad. mRNA signaturens förmåga korrekt klassificera samt diskriminera aktiv och latent tuberkulos bestämdes genom att implementera ROC-kurvor vilket resulterade i ett optimalt AUC-värde på 0.784 vilket visar på diagnostisk kapacitet att separera aktiv och latent tuberkulos. / A 10-color prototype GeneXpert assay based on distinct mRNA expression profiles in ex-vivo antigen stimulated whole blood has been developed at Cepheid for diagnosis of M. Tuberculosis infection and separation of active and latent tuberculosis. An original larger set of mRNA biomarkers has been downselected to a set of 9 biomarkers constituting the mRNA signature in the 10-color assay. The downselection of biomarkers was based on probe screening and optimization studies performed with Cepheid’s “in cartridge” qPCR technology. The 10-color assay was evaluated for diagnostic performance by analyzing 380 banked antigen stimulated clinical samples classified as M. Tuberculosis infected, active tuberculosis, latent tuberculosis and not infected. The ability of the mRNA signature to correctly classify and separate active and latent tuberculosis was determined by implementing ROC curves using delta Ctvalues as test variables and resulted in an optimal AUC value of 0.784 indicating ability to separate active and latent tuberculosis.