Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy

Objective To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. Design Single centre, double blind, cluster randomised, placebo controlled trial. SettingLeprosy control programme in two districts of northwest Bangladesh with a population of more than four million. Participants28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements. Interventions A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient’s treatment, with follow-up for four years. Main outcome measure Development of clinical leprosy. Results 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. ConclusionA single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. Trial registration Current Controlled Trials ISRCTN61223447

Multi-Omics Analysis Reveals MicroRNAs Associated With Cardiometabolic Traits

MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. Extensive research has explored the role of miRNAs in the risk for type 2 diabetes (T2D) and

Feasibility of magnetic bead technology for concentration of mycobacteria in sputum prior to fluorescence microscopy

<p>Abstract</p> <p>Background</p> <p>Direct sputum smear microscopy is the mainstay of TB diagnosis in most low and middle income countries, and is highly specific for <it>Mycobacterium tuberculosis </it>in such settings. However it is limited by low sensitivity, particularly in HIV co-infected patients. Concentration by centrifugation has been reported to be more sensitive than direct smear preparation, but is only suitable for referral laboratories. Simpler concentration methods that could be applied in peripheral laboratories are urgently needed.</p> <p>Methods</p> <p>We evaluated the feasibility of an early prototype ligand-coated magnetic bead technology to concentrate <it>M. tuberculosis </it>prior to detection by LED-based fluorescence microscopy compared with direct Ziehl-Neelsen microscopy and direct and concentrated fluorescence microscopy in a reference laboratory in Kampala, Uganda. Results were compared with MGIT 960 liquid culture and Lowenstein-Jensen culture.</p> <p>Results</p> <p>Compared to culture, concentrated FM had significantly higher sensitivity than direct ZN (74.8% and 51.4%), magnetic bead-FM (65.4%) and direct FM (58.9%). The sensitivity of magnetic bead FM was significantly higher than direct ZN (p < 0.001) but not significantly higher than direct FM (p = 0.210). The specificity of magnetic bead FM and concentrated FM was significantly lower than direct ZN (88.6%, 94.3% and 98.9% respectively) and direct FM (99.4%). There was no significant difference in specificity between magnetic bead FM and concentrated FM. Allowing for blinded resolution of discrepant results, the specificity of magnetic bead FM increased to 93.1%. Direct microscopy was simpler than concentrated FM and Magnetic bead FM which both had a similar number of steps.</p> <p>Conclusion</p> <p>The sensitivity of the early prototype magnetic bead FM was lower than concentrated FM, similar to direct FM, and significantly higher than direct ZN. Both magnetic bead and concentration by centrifugation led to reduced specificity compared with the direct smear methods. Some magnetic bead FM false positive results were not easily explained and should be further investigated. The prototype version of the magnetic bead procedure tested here was of similar complexity to concentration by centrifugation. As such, if the sensitivity of the magnetic bead FM could be improved in future versions of the technology, this may offer a viable alternative to centrifugation.</p

Pre-Existing Isoniazid Resistance, but Not the Genotype of Mycobacterium Tuberculosis Drives Rifampicin Resistance Codon Preference in Vitro

Both the probability of a mutation occurring and the ability of the mutant to persist will influence the distribution of mutants that arise in a population. We studied the interaction of these factors for the in vitro selection of rifampicin (RIF)-resistant mutants of Mycobacterium tuberculosis. We characterised two series of spontaneous RIF-resistant in vitro mutants from isoniazid (INH)-sensitive and -resistant laboratory strains and clinical isolates, representing various M. tuberculosis genotypes. The first series were selected from multiple parallel 1 ml cultures and the second from single 10 ml cultures. RIF-resistant mutants were screened by Multiplex Ligation-dependent Probe Amplification (MLPA) or by sequencing the rpoB gene. For all strains the mutation rate for RIF resistance was determined with a fluctuation assay. The most striking observation was a shift towards rpoB-S531L (TCG→TTG) mutations in a panel of laboratory-generated INH-resistant mutants selected from the 10-ml cultures (p<0.001). All tested strains showed similar mutation rates (1.33×10−8 to 2.49×10−7) except one of the laboratory-generated INH mutants with a mutation rate measured at 5.71×10−7, more than 10 times higher than that of the INH susceptible parental strain (5.46–7.44×10−8). No significant, systematic difference in the spectrum of rpoB-mutations between strains of different genotypes was observed. The dramatic shift towards rpoB-S531L in our INH-resistant laboratory mutants suggests that the relative fitness of resistant mutants can dramatically impact the distribution of (subsequent) mutations that accumulate in a M. tuberculosis population, at least in vitro. We conclude that, against specific genetic backgrounds, certain resistance mutations are particularly likely to spread. Molecular screening for these (combinations of) mutations in clinical isolates could rapidly identify these particular pathogenic strains. We therefore recommend that isolates are screened for the distribution of resistance mutations, especially in regions that are highly endemic for (multi)drug resistant tuberculosis

Public policy, health system, and community actions against illness as platforms for response to NCDs in Tanzania: a narrative review

This review was supported by grants from the Netherlands Organization for International Co-operation in Higher Education and the Ifakara Health Institute, Tanzania