Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust ...Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance.
In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time.
Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016.
The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting.
Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Context
Cultural landscapes provide essential ecosystem services to local communities, especially in poor rural settings. However, potentially negative impacts of ecosystems—or disservices—remain ...inadequately understood. Similarly, how benefit–cost outcomes differ within communities is unclear, but potentially important for cultural landscape management.
Objectives
Here we investigated whether distinct forest ecosystem service–disservice outcomes emerge within local communities. We aimed to characterize groups of community members according to service–disservice outcomes, and assessed their attitudes towards the forest.
Methods
We interviewed 150 rural households in southwestern Ethiopia about locally relevant ecosystem services (provisioning services) and disservices (wildlife impacts). Households were grouped based on their ecosystem service–disservice profiles through hierarchical clustering. We used linear models to assess differences between groups in geographic and socioeconomic characteristics, as well as attitudes toward the forest.
Results
We identified three groups with distinct ecosystem service–disservice profiles. Half of the households fell into a “lose–lose” profile (low benefits, high costs), while fewer had “lose–escape” (low benefits, low costs) and “win–lose” (high benefits, high costs) profiles. Location relative to forest and altitude explained differences between the “lose–escape” profile and other households. Socioeconomic factors were also important. “Win–lose” households appeared to be wealthier and had better forest use rights compared to “lose–lose” households. Attitudes towards the forest did not differ between profiles.
Conclusions
Our study demonstrates the importance of disaggregating both ecosystem services and disservices, instead of assuming that communities receive benefits and costs homogenously. To manage cultural landscapes sustainably, such heterogeneity must be acknowledged and better understood.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Field-based sports require athletes to run sub-maximally over significant distances, often while contending with dynamic perturbations to preferred coordination patterns. The ability to adapt ...movement to maintain performance under such perturbations appears to be trainable through exposure to task variability, which encourages movement variability. The aim of the present study was to investigate the extent to which various wearable resistance loading magnitudes alter coordination and induce movement variability during running. To investigate this, 14 participants (three female and 11 male) performed 10 sub-maximal velocity shuttle runs with either no weight, 1%, 3%, or 5% of body weight attached to the lower limbs. Sagittal plane lower limb joint kinematics from one complete stride cycle in each run were assessed using functional data analysis techniques, both across the participant group and within-individuals. At the group-level, decreases in ankle plantarflexion following toe-off were evident in the 3% and 5% conditions, while increased knee flexion occurred during weight acceptance in the 5% condition compared with unloaded running. At the individual-level, between-run joint angle profiles varied, with six participants exhibiting increased joint angle variability in one or more loading conditions compared with unloaded running. Loading of 5% decreased between-run ankle joint variability among two individuals, likely in accordance with the need to manage increased system load or the novelty of the task. In terms of joint coordination, the most considerable alterations to coordination occurred in the 5% loading condition at the hip-knee joint pair, however, only a minority of participants exhibited this tendency. Coaches should prescribe wearable resistance individually to perturb preferred coordination patterns and encourage movement variability without loading to the extent that movement options become limited.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
New biomarkers of liver injury are required in the clinic and in preclinical pharmaceutical evaluation. Previous studies demonstrate that two liver‐enriched microRNAs (miR‐122 and miR‐192) are ...promising biomarkers of acetaminophen‐induced acute liver injury (APAP‐ALI) in mice. We have examined these molecules, for the first time, in humans with APAP poisoning. Serum miR‐122 and miR‐192 were substantially higher in APAP‐ALI patients, compared to healthy controls (median ΔΔCt 25th, 75th percentile) (miR‐122: 1,265 491, 4,270 versus 12.1 7.0, 26.9, P < 0.0001; miR‐192: 6.9 2.0, 29.2 versus 0.44 0.30, 0.69, P < 0.0001). A heart‐enriched miR‐1 showed no difference between APAP‐ALI patients and controls, whereas miR‐218 (brain‐enriched) was slightly higher in the APAP‐ALI cohort (0.17 0.07, 0.50 versus 0.07 0.04, 0.12; P = 0.01). In chronic kidney disease (CKD) patients, miR‐122 and ‐192 were modestly higher, compared to controls (miR‐122: 32.0 21.1, 40.9 versus 12.1 7.0, 26.9, P = 0.006; miR‐192: 1.2 0.74, 1.9 versus 0.44 0.30, 0.69, P = 0.005), but miR‐122 and ‐192 were substantially higher in APAP‐ALI patients than CKD patients (miR‐122: P < 0.0001; miR‐192: P < 0.0004). miR‐122 correlated with peak ALT levels in the APAP‐ALI cohort (Pearson R = 0.46, P = 0.0005), but not with prothrombin time. miR‐122 was also raised alongside peak ALT levels in a group of patients with non‐APAP ALI. Day 1 serum miR‐122 levels were almost 2‐fold higher in APAP‐ALI patients who satisfied King's College Criteria (KCC), compared to those who did not satisfy KCC, although this did not reach statistical significance (P = 0.15). Conclusion: This work provides the first evidence for the potential use of miRNAs as biomarkers of human drug‐induced liver injury. (HEPATOLOGY 2011;)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Short substitution of glucose with galactose in HepG2 media reveals mito-toxicity.•Parallel ATP/cytotoxicity measurement provides a mitochondrial functional endpoint.•A sensitive, cost-effective and ...fast first tier mitochondrial screen is proposed.•HepG2 cells are a better model than fresh human hepatocytes to define mito-toxicity.
Drug-induced mitochondrial dysfunction has been hypothesized to be an important determining factor in the onset of drug-induced liver injury. It is essential to develop robust screens with which to identify drug-induced mitochondrial toxicity and to dissect its role in hepatotoxicity. In this study we have characterised a mechanistically refined HepG2 model, using a panel of selected hepatotoxicants and non-hepatotoxicants. We have demonstrated that acute metabolic modification, via glucose-deprivation over a 4h period immediately prior to compound addition, is sufficient to allow the identification of drugs which induce mitochondrial dysfunction, in the absence of cell death over a short exposure (2–8h) using a plate-based screen to measure cellular ATP content and cytotoxicity. These effects were verified by measuring changes in cellular respiration, via oxygen consumption and extracellular acidification rates. Overall, these studies demonstrate the utility of HepG2 cells for the identification of mitochondrial toxins which act directly on the electron transport chain and that the dual assessment of ATP content alongside cytotoxicity provides an enhanced mechanistic understanding of the causes of toxicity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Unprecedented developments in stem cell research herald a new era of hope and expectation for novel therapies. However, they also present a major challenge for regulators since safety assessment ...criteria, designed for conventional agents, are largely inappropriate for cell-based therapies. This article aims to set out the safety issues pertaining to novel stem cell-derived treatments, to identify knowledge gaps that require further research, and to suggest a roadmap for developing safety assessment criteria. It is essential that regulators, pharmaceutical providers, and safety scientists work together to frame new safety guidelines, based on “acceptable risk,” so that patients are adequately protected but the safety “bar” is not set so high that exciting new treatments are lost.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reframing the Food–Biodiversity Challenge Fischer, Joern; Abson, David J.; Bergsten, Arvid ...
Trends in ecology & evolution (Amsterdam),
05/2017, Volume:
32, Issue:
5
Journal Article
Peer reviewed
Given the serious limitations of production-oriented frameworks, we offer here a new conceptual framework for how to analyze the nexus of food security and biodiversity conservation. We introduce ...four archetypes of social-ecological system states corresponding to win–win (e.g., agroecology), win–lose (e.g., intensive agriculture), lose–win (e.g., fortress conservation), and lose–lose (e.g., degraded landscapes) outcomes for food security and biodiversity conservation. Each archetype is shaped by characteristic external drivers, exhibits characteristic internal social-ecological features, and has characteristic feedbacks that maintain it. This framework shifts the emphasis from focusing on production only to considering social-ecological dynamics, and enables comparison among landscapes. Moreover, examining drivers and feedbacks facilitates the analysis of possible transitions between system states (e.g., from a lose–lose outcome to a more preferred outcome).
Food security and biodiversity conservation are interrelated challenges.
Their integration cannot be achieved by focusing only on food production.
We propose a social-ecological framework that integrates food security and biodiversity conservation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background A year following the onset of the COVID-19 pandemic, new infections and deaths continue to increase in Europe. Serological studies, through providing evidence of past infection, can aid ...understanding of the population dynamics of SARS-CoV-2 infection. Objectives This systematic review of SARS-CoV-2 seroprevalence studies in Europe was undertaken to inform public health strategies including vaccination, that aim to accelerate population immunity. Methods We searched the databases Web of Science, MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews and grey literature sources for studies reporting seroprevalence of SARS-CoV-2 antibodies in Europe published between 01/12/2019-30/09/20. We provide a narrative synthesis of included studies. Studies were categorized into subgroups including healthcare workers (HCWs), community, outbreaks, pregnancy and children/school. Due to heterogeneity in other subgroups, we only performed a random effects meta-analysis of the seroprevalence amongst HCWs stratified by their country. Results 115 studies were included spanning 17 European countries, that estimated the seroprevalence of SARS-CoV-2 from samples obtained between November 2019 -August 2020. A total of 54/115 studies included HCWs with a reported seroprevalence among HCWs ranging from 0.7% to 45.3%, which did not differ significantly by country. In community studies significant heterogeneity was reported in the seroprevalence between different age groups and the majority of studies reported there was no significant difference by gender. Conclusion This review demonstrates a wide heterogeneity in reported seroprevalence of SARS-CoV-2 antibodies between populations. Continued evaluation of seroprevalence is required to understand the impact of public health measures and inform interventions including vaccination programmes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess ...PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.
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