Introduction Tuberculosis (TB) transmission is determined by contact between infectious and susceptible individuals. A recent study reported a 4% annual risk of child TB infection (ARTI) in a Southern African township. A model was used to explore the interactions between prevalence of adult TB infection, adult-to-child contacts and household ventilation which could result in such a high ARTI. Methods Number of residents per household and TB incidence were derived from a household census and community TB registers. Using the “Wells-Riley” equation and probability analyses of contact between TB infectious adults and pre-school children, we estimated the ARTI within and outside of the home. Results There was a mean of 2.2 adults per child-household with a 1.35% annual adult smear-positive TB notification rate. The maximal household ARTI was 3% which was primarily determined by the number of resident adults. Transmission risk outside the home increased with numbers of households visited. Transmission probabilities were sensitive to exposure time, ventilation and period of adult infectivity. The benefits of increased ventilation were greatest when the period of infectivity was reduced. Similar reductions in household transmission could be achieved by increasing ventilation from 2 to 6 air changes/hour or separating child and adult sleeping areas. Conclusions The ARTI of pre-school children predominantly results from infectious residents in the home. However, even with limited social interactions, a substantial proportion of transmission may occur from non-resident adults. The benefits of increased ventilation are maximized when the period of infectivity is reduced by prompt treatment of source cases.

BackgroundNumerous patient and healthcare system-related delays contribute to the overall delay experienced by patients from onset of TB symptoms to diagnosis and treatment. Such delays are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic.Methodology/Principal FindingsWe present an analysis of the factors that contribute to the overall delay in TB diagnosis and treatment, in a resource-poor setting. Impact on the distribution of diagnostic delay times was assessed for various factors, the sensitivity of the diagnostic method being found to be the most significant. A linear relationship was found between the sensitivity of the test and the predicted mean delay time, with an increase in test sensitivity resulting in a reduced mean delay time and a reduction in the drop-out rate.Conclusions/SignificanceThe results show that in a developing country a number of delay factors, particularly the low sensitivity of the initial sputum smear microscopy test, potentially increase total diagnostic delay times experienced by TB patients significantly. The results reinforce the urgent need for novel diagnostic methods, both for smear positive and negative TB, that are highly sensitive, accessible and point of care, in order to reduce mean delay times.

BackgroundIn many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission.Methodology/Principal FindingsThis study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic.Conclusions/SignificanceThe analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed.

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.Multidrug resistance in Mycobacterium tuberculosis poses a threat to the success of tuberculosis (TB) control programs and creates an enormous financial burden in regions where TB prevalence is high. The current WHO DOTS (directly observed treatment, short course) TB control strategy recommends passive case detection and diagnosis by sputum smear microscopy. TB patients are first detected when they seek help for symptomatic disease, rather than being identified through active screening. Since there is often a long delay between the onset of infectiousness and the time when a patient presents, this means that patients are frequently diagnosed only after they may have transmitted infection to others (3, 16). Once identified, patients suspected of having TB then undergo sputum smear microscopy to detect acid-fast bacilli. Smear positivity correlates well with the bacterial burden in the lungs, as well as with levels of transmissibility, and thus, this approach ensures the identification of the most infectious cases of TB. Nonetheless, recent data demonstrate that smear-negative patients are also able to transmit TB (4), and since they are not rapidly detected, we propose that they may transmit for a longer period than the more infectious smear-positive cases. In settings where TB incidence is high, once a patient is diagnosed with TB by smear microscopy, due to resource limitations, no further microbiological tests are performed, and instead, diagnosis is primarily done by microscopy. In South Africa, culture and drug susceptibility testing on solid medium are routinely done only for retreatment cases. These test results are not available for a minimum of 3 weeks and may take as long as 10 weeks in high-throughput laboratories (average, 1,000 samples per week) (11). A full description of the setting in which this investigation was conducted, with an emphasis ...