Tuberculosis
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Randomized Controlled Trial
Safety and immunogenicity of the M72/AS01 candidate tuberculosis vaccine when given as a booster to BCG in Gambian infants: an open-label randomized controlled trial.
We evaluated the candidate tuberculosis vaccine M72/AS01 in Bacille-Calmette-Guérin (BCG)-vaccinated infants after or concomitantly with Expanded-Programme-on-Immunization (EPI) vaccines. ⋯ M72/AS01 given to infants after or concomitantly with EPI vaccines had an acceptable safety profile. Our results suggest no interference of immunogenicity profiles occurred following co-administration of M72/AS01 and EPI vaccines. Two M72/AS01 doses elicited higher immune responses than one dose.
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Treatment of multidrug-resistant tuberculosis (MDR-TB) is hindered by limited efficacy and significant toxicity of second-line drugs. The need for new therapeutic options is critical to combat the global MDR-TB epidemic. Bedaquiline is a novel oral diarylquinoline approved by Food and Drug administration (FDA) for the treatment of adults with pulmonary MDR-TB on the basis of Phase IIb trial data under the provisions of the accelerated approval regulations for serious or life-threatening conditions. ⋯ While bedaquiline approval is a story of many firsts and certainly a welcome addition to the existing arsenal of anti-TB agents, a cautiously optimistic approach is required to assess the risk benefit profile of the drug. Acceleration of further Phase III trials and clinical studies is imperative, as is timely analysis of emerging data on the real world use of the drug. This mini review outlines the clinical pharmacology of bedaquiline highlighting the potential promises and challenges that implicate the risk benefit profile of drug.
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Piperine a trans-trans isomer of 1-piperoyl-piperidine was evaluated for its immunomodulatory activity to enhance the efficacy of rifampicin in a murine model of Mycobacterium tuberculosis infection. In-vitro immunomodulation of piperine was tested on mouse splenocytes for lymphocyte proliferation, cytokine production and macrophage activation. Protective efficacy of piperine was tested in a mice infection model of M. tuberculosis for the activation of Th-1 response and synergistic combination efficacy with rifampicin. ⋯ The qRT-PCR studies revealed corresponding increases in the mRNA transcripts of IFN-γ and IL-2 in the infected lung tissues. Combination of piperine and rifampicin (1 mg/kg) exhibited better efficacy of and resulted in additional 1.4 to 0.8 log reduction in lung cfu as compared to rifampicin alone. The up-regulation of Th1 immunity by piperine can be synergistically combined with rifampicin to improve its therapeutic efficacy in immune-compromised TB patients.
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There are many funded efforts going on focused on tuberculosis research and drug or vaccine development. There is little if any global coordination or collaboration and subsequently there are likely to be huge data silos and duplication of efforts. We now propose steps to remedy this by fostering more open science in TB research.
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Options for the treatment of children with drug-resistant tuberculosis (DR-TB) are limited. Emerging evidence in adults from systematic reviews and a randomized trial has shown good efficacy of linezolid in difficult cases of DR-TB but with frequent serious adverse effects. Published data in children are limited and we are unaware of formal guidelines for linezolid in treatment of paediatric DR-TB, though it will likely be an important component of DR-TB treatment for a growing number of children. ⋯ Adverse events were reported in 9 of 18; a linezolid dose reduction was required in 5 of 18, and 2 of 18 permanently discontinued linezolid because of adverse events. We make specific recommendations for the use of linezolid in children with DR-TB, and identify priority questions for future research. For children with multidrug-resistant (MDR)-TB with additional resistance or with extensively drug-resistant (XDR)-TB, linezolid may make the difference between a successful or poor outcome, and until newer antituberculosis agents with better efficacy and safety become available in children, linezolid will be an important component of treatment for children with the worst forms of DR-TB.