The interruption of leprosy transmission is one of the main challenges for leprosy control programs since no consistent evidence exists that transmission has been reduced after the introduction of multidrug therapy. Leprosy, a disease caused by Mycobacterium leprae, particularly affects the less privileged parts of the population in countries where the disease is endemic. This intracellular bacillus is assumed not to be very pathogenic, most infections do not result in chronic disease but in skin lesions that heal spontaneously (13).

Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) is time-consuming and operator dependent and lacks sensitivity. A new method is urgently needed. We investigated the potential of an electronic nose (EN) (gas sensor array) comprising 14 conducting polymers to detect different Mycobacterium spp. and Pseudomonas aeruginosa in the headspaces of cultures, spiked sputa, and sputum samples from 330 cultureproven and human immunodeficiency virus-tested TB and non-TB patients. The data were analyzed using principal-component analysis, discriminant function analysis, and artificial neural networks. The EN differentiated between different Mycobacterium spp. and between mycobacteria and other lung pathogens both in culture and in spiked sputum samples. The detection limit in culture and spiked sputa was found to be 1 ؋ 10 4 mycobacteria ml ؊1 . After training of the neural network with 196 sputum samples, 134 samples (55 M. tuberculosis culture-positive samples and 79 culture-negative samples) were used to challenge the model. The EN correctly predicted 89% of culture-positive patients; the six false negatives were the four ZN-negative and two ZN-positive patients. The specificity and sensitivity of the described method were 91% and 89%, respectively, compared to culture. At present, the reasons for the false negatives and false positives are unknown, but they could well be due to the nonoptimized system used here. This study has shown the ability of an electronic nose to detect M. tuberculosis in clinical specimens and opens the way to making this method a rapid and automated system for the early diagnosis of respiratory infections.

Although the prevalence of leprosy has declined over the years, there is no evidence that incidence rates are falling. A method of early detection of those people prone to develop the most infectious form of leprosy would contribute to breaking the chain of transmission. Prophylactic treatment of serologically identified high-risk contacts of incident patients should be an operationally feasible approach for routine control programs. In addition, classification of high-risk household contacts will allow control program resources to be more focused. In this prospective study, we examined the ability of serology used for the detection of antibodies to phenolic glycolipid I of Mycobacterium leprae to identify those household contacts of multibacillary leprosy patients who had the highest risk of developing leprosy. After the start of multidrug therapy for the index case, a new case of leprosy developed in one in seven of the 178 households studied. In households where new cases appeared, the seropositivity rates were significantly higher (P < 0.001) than those in households without new cases. Seropositive household contacts had a significantly higher risk of developing leprosy (relative hazard adjusted for age and sex [aRH], 7.2), notably multibacillary leprosy (aRH ‫؍‬ 24), than seronegative contacts.

The population structure of Mycobacterium tuberculosis is typically clonal therefore genotypic lineages can be unequivocally identified by characteristic markers such as mutations or genomic deletions. In addition, drug resistance is mainly mediated by mutations. These issues make multiplexed detection of selected mutations potentially a very powerful tool to characterise Mycobacterium tuberculosis. We used Multiplex Ligation-dependent Probe Amplification (MLPA) to screen for dispersed mutations, which can be successfully applied to Mycobacterium tuberculosis as was previously shown. Here we selected 47 discriminative and informative markers and designed MLPA probes accordingly to allow analysis with a liquid bead array and robust reader (Luminex MAGPIX technology). To validate the bead-based MLPA, we screened a panel of 88 selected strains, previously characterised by other methods with the developed multiplex assay using automated positive and negative calling. In total 3059 characteristics were screened and 3034 (99.2%) were consistent with previous molecular characterizations, of which 2056 (67.2%) were directly supported by other molecular methods, and 978 (32.0%) were consistent with but not directly supported by previous molecular characterizations. Results directly conflicting or inconsistent with previous methods, were obtained for 25 (0.8%) of the characteristics tested. Here we report the validation of the bead-based MLPA and demonstrate its potential to simultaneously identify a range of drug resistance markers, discriminate the species within the Mycobacterium tuberculosis complex, determine the genetic lineage and detect and identify the clinically most relevant non-tuberculous mycobacterial species. The detection of multiple genetic markers in clinically derived Mycobacterium tuberculosis strains with a multiplex assay could reduce the number of TB-dedicated screening methods needed for full characterization. Additionally, as a proportion of the markers screened are specific to certain Mycobacterium tuberculosis lineages each profile can be checked for internal consistency. Strain characterization can allow selection of appropriate treatment and thereby improve treatment outcome and patient management.