Molecular characterisation of selected gastrointestinal microbiota in South African HIV-positive patients during HAART

Includes bibliographical references.Progression of the HIV disease is characterised by a massive depletion of CD4+ T cells and it has been shown that patients living with a more advanced HIV infection have a higher risk of developing diarrhoea due to the disruption of the gastrointestinal microbiota caused by either the HIV-infection or the use of antibiotics and drugs such as highly active antiretroviral therapy (HAART). An imbalance in the microbial composition, attributable to a disturbed mucosal barrier, as well as increased permeability and inflammation caused by HIV, can influence the metabolic (carbohydrate fermentation) and protective functions provided by the microbiota. The effect of HIV on the intestinal microbiota has not been widely examined and those studies that have focused on HIV and the gastrointestinal tract, have investigated it mainly from a virological perspective. Consequently, the aim of the study was to ascertain whether the diversity and/or abundance of the endogenous intestinal microbiota of South African HIV-positive patients was disrupted on account of HIV within the gastrointestinal tract. An additional aim was to determine whether the administration of HAART affected the microbiota during a 6 month longitudinal study. The diversity of the intestinal microbial composition was characterised with respect to the total bacteria, Bifidobacterium and Lactobacillus species using PCR-DGGE. qPCR was used to determine the abundance of total bacteria, Bifidobacterium, Lactobacillus, Escherichia coli, the Bacteroides/Prevotella, Clostridium coccoides and Clostridium leptum groups. ... In addition, three potential intestinal pathogens (Clostridium difficile, Campylobacter jejuni and Salmonella enterica) were monitored by qPCR during this period, to determine their prevalence in the HIV-positive patients

Pneumocystis jiroveci and respiratorey bacterial pathogens in cases of pneumonia at hospitals in Port Elizabeth

Pneumocystis jiroveci, Mycoplasma pneumoniae and Mycobacterium tuberculosis are respiratory pathogens associated with pneumonia, with increasing prevalence of Pneumocystis pneumonia (PcP) and tuberculosis (TB) in AIDS patients. Increased resistance of M. tuberculosis has emphasized the need for rapid susceptibility testing, such as flow cytometry. Sputum specimens (102) were assessed by PCR employing primers directed at the following genes: P. jiroveci: mitochondrial large subunit ribosomal RNA (mtLSUrRNA), dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), and for M. pneumoniae: 16S rRNA and P1 adhesin. Positive P. jiroveci samples were genotyped by PCR-SSCP (single-strand conformation polymorphism) targeting the: internal transcribed spacer region (ITS), intron of the nuclear 26S rRNA gene (26S), variable region of the mitochondrial 26S rRNA gene (mt26S) and β-tubulin gene (β-tub). Multi-drug resistant (MDR-TB) cultures grown in the presence and absence of four antibiotics (rifampicin, isoniazid, ethambutol and ofloxacin) were heat killed, stained with SYTO16 and Propidium Iodide and analysed using flow cytometry. Rifampicin resistance gene mutations were screened by PCR and DNA sequencing. Details of patient’s gender, age, HIV and M. tuberculosis status were provided by the hospitals. Women were seen to be at high risk for community-acquired P. jiroveci colonisation. Overall, prevalence of P. jiroveci was 55.1 percent (54/102 patients). P. jiroveci was mainly associated with HIV (25/102 P. jiroveci positive patients for which clinical data was available) and co-colonisation with M. tuberculosis was observed in 11 cases. Sequence analysis of DHPS and DHFR products found no resistance associated mutations. M. pneumoniae was detected in one patient. Four simple SSCP patterns were identified and there were no co-infections with other P. jiroveci strains. Nine M. tuberculosis samples [8 MDR-TB isolates (NHLS) and M. tuberculosis ATCC® 27294TM] were tested. There was a 53 percent (19 out of 36 tests) agreement of flow cytometry with the BACTEC MGIT 960. Mutations (at two specific codons, namely 516 and 531) in the rifampicin resistance-determining region (RRDR) of the rpoB gene were observed in eight M. tuberculosis isolates. Evaluation of methods for genotyping and drug susceptibility testing of PcP and TB are imperative for epidemiology and drug resistance studies, and impact on treatment protocols

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A synthesis of three decades of socio-ecological change in False Bay, South Africa: setting the scene for multidisciplinary research and management

Over the past three decades, marine resource management has shifted conceptually from top-down sectoral approaches towards the more systems-oriented multi-stakeholder frameworks of integrated coastal management and ecosystem-based conservation. However, the successful implementation of such frameworks is commonly hindered by a lack of cross-disciplinary knowledge transfer, especially between natural and social sciences. This review represents a holistic synthesis of three decades of change in the oceanography, biology and human dimension of False Bay, South Africa. The productivity of marine life in this bay and its close vicinity to the steadily growing metropolis of Cape Town have led to its socio-economic significance throughout history. Considerable research has highlighted shifts driven by climate change, human population growth, serial overfishing, and coastal development. Upwelling-inducing winds have increased in the region, leading to cooling and likely to nutrient enrichment of the bay. Subsequently the distributions of key components of the marine ecosystem have shifted eastward, including kelp, rock lobsters, seabirds, pelagic fish, and several alien invasive species. Increasing sea level and exposure to storm surges contribute to coastal erosion of the sandy shorelines in the bay, causing losses in coastal infrastructure and posing risk to coastal developments. Since the 1980s, the human population of Cape Town has doubled, and with it pollution has amplified. Overfishing has led to drastic declines in the catches of numerous commercially and recreationally targeted fish, and illegal fishing is widespread. The tourism value of the bay contributes substantially to the country’s economy, and whale watching, shark-cage diving and water sports have become important sources of revenue. Compliance with fisheries and environmental regulations would benefit from a systems-oriented approach whereby coastal systems are managed holistically, embracing both social and ecological goals. In this context, we synthesize knowledge and provide recommendations for multidisciplinary research and monitoring to achieve a better balance between developmental and environmental agendas.https://www.elementascience.orgam2020Mammal Research Institut

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant