Potential of rapid diagnosis for controlling drug-susceptible and drug-resistant tuberculosis in communities where Mycobacterium tuberculosis infections are highly prevalent

Abstract

The long-term persistence of Mycobacterium tuberculosis in communities with high tuberculosis prevalence is a serious problem aggravated by the presence of drug-resistant tuberculosis strains. Drug resistance in an individual patient is often discovered only after a long delay, particularly if the diagnosis is based on current culture-based drug sensitivity testing methods. During such delays, the patient may transmit tuberculosis to his or her contacts. Rapid diagnosis of drug resistance would be expected to reduce this transmission and hence to decrease the prevalence of drug-resistant strains. To investigate this quantitatively, a mathematical model was constructed, assuming a homogeneous population structure typical of communities in South Africa where tuberculosis incidence is high. Computer simulations performed with this model showed that current control strategies will not halt the spread of multidrug-resistant tuberculosis in such communities. The simulations showed that the rapid diagnosis of drug resistance can be expected to reduce the incidence of drug-resistant cases provided the additional measure of screening within the community is implemented.

FIG. 1.

Schematic flow diagram depicting the various disease states and transitions among them. The boxes represent cohorts of persons in a particular state. Single arrows indicate flows of people from one state to the next according to some probability. Double arrows indicate flows, involving time lags, of people from one state to the next. Broken arrows indicate removal of persons from the indicated state due to death. The subscripts S and R refer to susceptible and resistant strains, respectively, of TB. Endogenous refers to reactivation of an earlier infection to produce an actual episode of disease. Double borders signify a state involving resistant TB. The large block arrows indicate a flow of persons at a rate dependent on the time since infection.

FIG. 2.

Annual costs of treating susceptible cases and MDR cases shown as a multiple of the present-day annual cost of treating susceptible cases. Although the actual case load for MDR TB is considerably less than that for susceptible TB, the costs are far greater, since the cost of treating a patient with MDR TB is 2 orders of magnitude greater than that for susceptible TB.

FIG. 3.

Conceptual chart showing relative numbers (represented approximately by the areas of the shapes and not to accurate scale) of people in different categories and relative durations (represented by the lengths of the boxes) of the illness and treatment phases. Note that patients with MDR TB may incorrectly receive treatment for susceptible TB for a period (dark shaded box). The situation of resistant disease compared to susceptible disease is asymmetrical by virtue of the one-way flow depicted by the double arrow from the box representing patients undergoing therapy for susceptible TB who develop resistance. The time a TB patient is ill before diagnosis and the start of treatment is indicated by the lengths of the hatched boxes. All actively diseased people contribute to further infection events until their treatment starts. All flows are directly proportional not only to the numbers in the source categories, but also to the length of time before commencement of treatment or the detection of conversion to resistant disease.

FIG. 4.

Incidence of susceptible disease for various diagnostic sensitivities as a multiple of the base year incidence with 2- and 28-week diagnostic delays.

FIG. 5.

Incidence of resistant disease for various diagnostic sensitivities as a multiple of the base year incidence with 2- and 28-week diagnostic delays.