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- Thorpe, H. A., et al.
(author)
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Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.
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- Borisov, S, et al.
(author)
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Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report
- 2019
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 54:6
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Journal article (peer-reviewed)abstract
- The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.
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- Parker, W. A. E., et al.
(author)
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Prevalence of microspirometry-defined chronic obstructive pulmonary disease in two European cohorts of patients with significant smoking history hospitalised for acute myocardial infarction
- 2023
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In: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 78:Suppl. 4, s. A66-A66
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Journal article (other academic/artistic)abstract
- Introduction: Smoking is a major risk factor for both chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI). Systemic inflammation also contributes to both diseases and has been suggested as a potential target for intervention. Prevalence of COPD in those with a significant smoking history hospitalised for MI has not been well-characterised. We sought to obtain an accurate estimate of COPD burden in this group and characterise the population.Methods: Two consecutive cohorts of patients hospitalised for MI with a smoking history of ≥10 pack-years were recruited in Sweden and the United Kingdom (UK). Baseline characteristics were recorded, including treatment with inhaled corticosteroids (ICS) and eosinophil count in blood. Microspirometry was performed using the Vitalograph COPD-6 device and symptom burden assessed using the COPD Assessment Test (CAT). The primary outcome was the prevalence of a preliminary diagnosis of clinically-significant COPD, here defined as a ratio of forced expiratory volume in 1 and 6 seconds (FEV1/FEV6) <0.7 and with FEV1 <80% of predicted value.Results: In the UK cohort, 216 participants with MI (26% female, median age 60 (IQR 53–67) years, smoking history 32 (23–45) pack-years) were recruited. The proportion with any COPD was 36%. Clinically-significant COPD was found in 30 participants (13.9%, 95% CI 9.5–19.2). Of these, 43% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 14.4 ± 9.3), 80% had high symptom burden (CAT score >10) and 23% were receiving ICS. The Swedish cohort included 302 participants with MI (24% female, median age 68 (IQR 61–76) years, 26 (15–38) pack years), and clinically-significant COPD was found in 52 (17.2%; 12.9–21.5). In these 52 participants, 17% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 12.9 ± 7.2, 63% had CAT score ≥10 and 15% had treatment with ICS.Conclusions: The prevalence of preliminary diagnosis of clinically-significant COPD in patients with a ≥10 pack-year smoking history hospitalised for MI is similar between two European cohorts and under-recognised. Further work is warranted to determine whether identification and treatment of COPD improves clinical outcomes following MI.
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- Weinberg, S.E., et al.
(author)
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Control and management of multidrug resistant Acinetobacter baumannii : A review of the evidence and proposal of novel approaches
- 2020
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In: Infection Prevention in Practice. - : Elsevier. - 2590-0889. ; 2:3
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Research review (peer-reviewed)abstract
- Hospital-acquired infections are on the rise and are a substantial cause of clinical and financial burden for healthcare systems. While infection control plays a major role in curtailing the spread of outbreak organisms, it is not always successful. One organism of particular concern is Acinetobacter baumannii, due to both its persistence in the hospital setting and its ability to acquire antibiotic resistance. A. baumannii has emerged as a nosocomial pathogen that exhibits high levels of resistance to antibiotics, and remains resilient against traditional cleaning measures with resistance to Colistin increasingly reported. Given the magnitude and costs associated with hospital acquired infections, and the increase in multidrug-resistant organisms, it is worth re-evaluating our current approaches and looking for alternatives or adjuncts to traditional antibiotics therapies. The aims of this review are to look at how this organism is spread within the hospital setting, discuss current treatment modalities, and propose alternative methods of outbreak management.
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