Tuberculosis Transmission in a Primary School and a Private Language School. An Estimation of Infectivity.

Introduction: Belgium is a country with low incidence of tuberculosis (TB) and a very low number of TB cases in children. Children in contact with an adult smear-positive TB case are at high risk of transmission. Early diagnosis is important as young children have a significant predisposition of developing TB disease. In this paper, we describe two outbreaks after exposure to, respectively, two teachers with smear-positive pulmonary TB: one in a primary school, a nursery teacher, and another in a private language school. Methods: An exposure investigation was carried out in both index cases household and school, according to the stone-in-the-pond principle. The tuberculin skin test (TST) was used a screening tool. The time elapsed between TB diagnosis in the index case and contact investigation was, respectively, 1 and 3 weeks. If this initial test was negative, it was repeated after a "window period" of ≥8 weeks. Results: Index cases showed a transmission rate of, respectively, 13 and 40% in their classes at school, defined as casual contacts. The proximity of contact increased the risk of infection. TB disease was observed in, respectively, 4 and 11% of all the casual contacts; all of them were children younger than 5 years old. TB-infected and children with active TB disease had good compliance with recommended treatment. Uptake of chemoprophylaxis during the "window period" was poor, respectively, only 32-42%, in children under 5 years with an initially negative TST. Discussion: The World Health Organization recommends to screen all young children (<5 years old) who have close contact with a person affected by pulmonary TB and to initiate Latent tuberculosis infection treatment even before infection can be demonstrated, after ruling out active TB disease. Despite this knowledge, a small percentage of the children younger than 5 years with no proof of infection was treated with the proposed chemoprophylactic treatment, in both cases. Conclusion: This exposure investigation of two teachers detects high transmission among family contacts and school casual contacts. Recommendations for chemoprophylactic treatment in children <5 years showed low compliance, reflecting the difficulty of communication to staff, parents, and children in a school outbreak. It is essential to develop a new approach for this vulnerable group of patients. This approach could be improved, applied, and evaluated by National TB Control Programs, involving public and private health services. Public health authorities play a role in raising public awareness about the risks of TB for young children.

Straightforward palladium-mediated synthesis and biological evaluation of benzo[j]phenanthridine-7,12-diones as anti-tuberculosis agents.

In 1991, WHO recognized the resurgence of tuberculosis as a global health problem. Although modern chemotherapy is effective against the causative pathogen Mycobacterium tuberculosis, the current drug regimens have failed to eradicate the disease. The success of the pathogen, partially attributed to drug resistance, necessitates the development of novel anti-tuberculosis drugs. Benzo[j]phenanthridine-7,12-diones, tetracyclic derivatives of the natural product benz[g]isoquinoline-5,10-dione, were conveniently synthesized via palladium-catalyzed intramolecular cyclization of N-methanesulfonyl-3-bromo-2-(arylamino)methyl-1,4-naphthoquinones. Here we report on the bioactivity of eight benzo[j]phenanthridine-7,12-dione derivatives as candidate drug molecules against M. tuberculosis and on their cytotoxicity on C3A human hepatocytes. The strongest antimicrobial activity (as detected by growth inhibition of bacteria, using luminometry and BACTEC 460-TB) and lowest cytotoxicity was found for 3-methylbenzo[j]phenanthridine-7,12-dione 5e, which was also effective in targeting intracellular M. tuberculosis (in murine J774 macrophages) and was not genotoxic for C3A hepatocytes.

Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis.

Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, high-throughput genotyping of Mycobacterium tuberculosis. However, even the combination of these two methods is still less discriminatory than IS6110 fingerprinting. Here, we define an optimized set of MIRU-VNTR loci with a significantly higher discriminatory power. The resolution and the stability/robustness of 29 loci were analyzed, using a total of 824 tubercle bacillus isolates, including representatives of the main lineages identified worldwide so far. Five loci were excluded for lack of robustness and/or stability in serial isolates or isolates from epidemiologically linked patients. The use of the 24 remaining loci increased the number of types by 40%--and by 23% in combination with spoligotyping--among isolates from cosmopolitan origins, compared to those obtained with the original set of 12 loci. Consequently, the clustering rate was decreased by fourfold--by threefold in combination with spoligotyping--under the same conditions. A discriminatory subset of 15 loci with the highest evolutionary rates was then defined that concentrated 96% of the total resolution obtained with the full 24-locus set. Its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing, as shown in a companion population-based study. This 15-locus system is therefore proposed as the new standard for routine epidemiological discrimination of M. tuberculosis isolates and the 24-locus system as a high-resolution tool for phylogenetic studies.