•In 2020, COVID-19 dislodged TB as the top infectious disease cause of mortality globally.•Globally, an estimated 10.0 million people developed active TB disease in 2019, with 1.4 million TB ...deaths.•The WHO regions of South-East Asia, Africa, and the Western Pacific had the most cases of TB.•Progress in achieving the United Nations (UN) General Assembly End TB targets remains slow.•TB services need to be ramped up, and underlying drivers of TB need be addressed.
The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.
Treatment options for highly drug-resistant tuberculosis are limited. In this study in South Africa, a new agent, pretomanid, was combined with bedaquiline and linezolid for a 26-week course to treat ...extensively drug-resistant and complicated multidrug-resistant pulmonary TB. Although there were toxic effects, 90% of patients had favorable outcomes.
Tuberculosis remains the leading cause of death from an infectious disease worldwide. Early and accurate diagnosis and detection of drug-sensitive and drug-resistant tuberculosis is essential for ...achieving global tuberculosis control. Despite the introduction of the Xpert MTB/RIF assay as the first-line rapid tuberculosis diagnostic test, the gap between global estimates of incidence and new case notifications is 4·1 million people. More accurate, rapid, and cost-effective screening tests are needed to improve case detection. Diagnosis of extrapulmonary tuberculosis and tuberculosis in children, people living with HIV, and pregnant women remains particularly problematic. The diagnostic molecular technology landscape has continued to expand, including the development of tests for resistance to several antituberculosis drugs. Biomarkers are urgently needed to indicate progression from latent infection to clinical disease, to predict risk of reactivation after cure, and to provide accurate endpoints for drug and vaccine trials. Sophisticated bioinformatic computational tools and systems biology approaches are being applied to the discovery and validation of biomarkers, with substantial progress taking place. New data have been generated from the study of T-cell responses and T-cell function, serological studies, flow cytometric-based assays, and protein and gene expression studies. Alternative diagnostic strategies under investigation as potential screening and triaging tools include non-sputum-based detection with breath-based tests and automated digital radiography. We review developments and key achievements in the search for new tuberculosis diagnostics and biomarkers. We highlight gaps and challenges in evaluation and rollout of new diagnostics and biomarkers, and prioritise areas needing further investment, including impact assessment and cost–benefit studies.
One approach to improving tuberculosis therapy is to shorten the duration from 6 months to 4 months. In this trial in over 1900 patients with smear-positive tuberculosis, two 4-month ...moxifloxacin-based regimens did not perform as well as the standard 6-month regimen.
A short-term tuberculosis treatment regimen could improve rates of adherence, reduce rates of adverse events, and lower costs. Fluoroquinolones have shown promising activity against mycobacteria
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and are established as a critical component of the treatment of multidrug-resistant tuberculosis,
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,
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with later fluoroquinolones recognized as having a more potent effect. It has been proposed that these drugs may have a role in reducing the duration of tuberculosis treatment.
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Moxifloxacin has been approved for a range of indications globally.
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It has favorable pharmacokinetics, a large volume of distribution, and penetration into epithelial-lining fluid and macrophages.
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–
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The activity of moxifloxacin in vitro . . .
Summary About 1·3 million people died of tuberculosis in 2012, despite availability of effective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in ...poor patient adherence and loss of patients to follow-up), complex regimens that involve expensive and toxic drugs, toxic effects when given with antiretroviral therapy, and multidrug resistance. After 50 years of no antituberculosis drug development, a promising pipeline is emerging through the repurposing of old drugs, re-engineering of existing antibacterial compounds, and discovery of new compounds. A range of novel antituberculosis drugs are in preclinical development, several phase 2 and 3 trials are underway, and use of adjunct therapies is being explored for drug-sensitive and drug-resistant tuberculosis. Historical advances include approval of two new drugs, delamanid and bedaquiline. Combinations of new and existing drugs are being assessed to shorten the duration of therapy and to treat multidrug-resistant tuberculosis. There has also been progress in development of new antituberculosis drugs that are active against dormant or persister populations of Mycobacterium tuberculosis . In this Review, we discuss recent advances in antituberculosis drug discovery and development, clinical trial designs, laboratory methods, and adjunct host-directed therapies, and we provide an update of phase 3 trials of various fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB, and REMoxTB). We also emphasise the need to engage the community in design, implementation, and uptake of research, to increase international cooperation between drug developers and health-care providers adopting new regimens.
•Three patients were diagnosed with monkeypox in the United Kingdom in September 2018 the index case being from Nigeria.•Nigeria is currently experiencing a large outbreak of monkeypox with a total ...of 116 cases as per September 2018.•The median age of the cases are 31 years.•The cases belong to an age group not immunized against smallpox.•After the eradication of smallpox and the end of the immunization program a nice for a new poxvirus may have been created.
The identification of monkeypox in 3 separate patients in the United Kingdom in September raised media and political attention on an emerging public health threat. Nigeria, whose last confirmed case of monkeypox was in 1978, is currently experiencing an unusually large and outbreak of human monkeypox cases, a ‘One Human-Environmental-Animal Health’ approach is being effectively used to define and tackle the outbreak. As of 13th October 2018, there have been one hundred and sixteen confirmed cases the majority of whom are under 40 years. Over the past 20 years ten Central and West African countries have reported monkeypox cases which have risen exponentially. We review the history and evolution of monkeypox outbreaks in Africa and USA, the changing clinical presentations, and discuss possible factors underlying the increasing numbers being detected including the cessation of smallpox vaccination programs. Major knowledge gaps remain on the epidemiology, host reservoir, and emergence, transmission, pathogenesis and prevention of monkeypoz.
The current methods available to diagnose antimicrobial-resistant
infections require a positive culture or only test a limited number of resistance-associated mutations. A rapid accurate ...identification of antimicrobial resistance enables the prompt initiation of effective treatment. Here, we determine the utility of whole-genome sequencing (WGS) of
directly from routinely obtained diagnostic sputum samples to provide a comprehensive resistance profile compared to that from mycobacterial growth indicator tube (MGIT) WGS. We sequenced
from 43 sputum samples by targeted DNA enrichment using the Agilent SureSelectXT kit, and 43 MGIT positive samples from each participant. Thirty two (74%) sputum samples and 43 (100%) MGIT samples generated whole genomes. The times to antimicrobial resistance profiles and concordance were compared with Xpert MTB/RIF and phenotypic resistance testing from cultures of the same samples. Antibiotic susceptibility could be predicted from WGS of sputum within 5 days of sample receipt and up to 24 days earlier than WGS from MGIT culture and up to 31 days earlier than phenotypic testing. Direct sputum results could be reduced to 3 days with faster hybridization and if only regions encoding drug resistance are sequenced. We show that direct sputum sequencing has the potential to provide comprehensive resistance detection significantly faster than MGIT whole-genome sequencing or phenotypic testing of resistance from cultures in a clinical setting. This improved turnaround time enables prompt appropriate treatment with associated patient and health service benefits. Improvements in sample preparation are necessary to ensure comparable sensitivities and complete resistance profile predictions in all cases.
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