Risk of development of clinical tuberculosis among infected individuals identified by a single blood PCR test

Date of Award


Document Type


Degree Name

Master of Science in Epidemiology & Biostatistics (MSc Epidemiology & Biostats)


Community Health Sciences


Tuberculosis is still a major health problem of most developing countries including Pakistan. It is also re-emerging as a significant cause of morbidity and mortality in the developed countries. Literature review indicates that despite availability of good anti-tuberculosis medicines, it is difficult to eradicate or control tuberculosis. One reason for this, among others, is the limitations of current laboratory tests widely used for its diagnosis. In recent past, polymerase chain reaction (PCR), for detection of Mycobacterium tuberculosis DNA has been gaining popularity, particularly because of its rapidity and its ability to detect TB infection much earlier then it becomes detectable by any other method. While PCR can be considered good at identifying TB infection, it can be considered a useful adjunct or replacement test for the current diagnostic methods only after its meaning in terms of the disease is better understood. If early identification of TB infection by PCR means, that a large proportion of such individuals will go on to develop clinical disease if left untreated, then PCR has good utility in terms of disease prevention and is a useful tool from public health aspect. We therefore performed a community based study to estimate the risk of development of clinical tuberculosis among PCR for MTB DNA positive individuals, with no or minimal symptoms, during July - September 1998. A total of sixty-five individuals who were diagnosed infected by a positive blood PCR for MTB DNA and were AFB sputum smear and culture negative, were identified from a study that started in June of 1996. We successfully retraced 42 of these individuals and interviewed them to determine the proportion of those among them who, in the course of two years developed tuberculosis and also to identify the factors associated with increased risk of development of tuberculosis disease. Results show that 38% of these individuals were diagnosed as tuberculosis patients by general practitioners at some time during the two years period. For various sub groups based on demographic characteristics, presence or absence of symptoms like fever, blood in sputum and weight loss and the Presence or absence of chronic illness; statistical analysis was done to determine the proportion of PCR positive individuals who developed clinical tuberculosis over the two years' period. Risk in the sub groups with a characteristic, relative to those without the characteristic (relative risk) was also determined. We found that presence of blood in sputum, at the time of identification of infection was associated with a risk of 70% for the development of disease. Infected individuals with blood in their sputum were more likely to develop the disease than those infected individuals who did not have blood in their sputum at the time infection was identified (RR 3.69, 95% CI 1.65 - 6.13). Also, it was learnt that the risk increased with the increase in the duration for which a person have had cough. Each month's increase in the duration of cough was associated with an increase of 1.3% in the risk of TB (RR 1.013, 95% CI 1.002 - 1.026). Our results show that identification of tuberculosis infection by blood PCR, even early in the disease process is associated with a fairly high probability of the development of disease in just two years time.

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