Heart failure associated with imported malaria:a nationwide Danish cohort study

Abstract Aims Despite adequate treatment, recent studies have hypothesized that malaria may affect long‐term cardiovascular function. We aimed to investigate the long‐term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark. Methods Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all‐cause death (1 January 1994 to 1 January 2017). The population was age‐ and sex‐matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion. Results We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow‐up was 9.8 years (interquartile range 3.9–16.4 years). Event rates per 1000 person‐years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all‐cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21–2.09], P = 0.001), but not MI (HR: 1.00 [0.72–1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74–1.35], P = 0.98) or all‐cause death (HR 1.11 [0.94–1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14–2.36], P = 0.008). Conclusion Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

The footprint of continental-scale ocean currents on the biogeography of seaweeds

Explaining spatial patterns of biological organisation remains a central challenge for biogeographic studies. In marine systems, large-scale ocean currents can modify broad-scale biological patterns by simultaneously connecting environmental (e.g. temperature, salinity and nutrients) and biological (e.g. amounts and types of dispersed propagules) properties of adjacent and distant regions. For example, steep environmental gradients and highly variable, disrupted flow should lead to heterogeneity in regional communities and high species turnover. In this study, we investigated the possible imprint of the Leeuwin (LC) and East Australia (EAC) Currents on seaweed communities across ~7,000 km of coastline in temperate Australia. These currents flow poleward along the west and east coasts of Australia, respectively, but have markedly different characteristics. We tested the hypothesis that, regional seaweed communities show serial change in the direction of current flow and that, because the LC is characterised by a weaker temperature gradient and more un-interrupted along-shore flow compared to the EAC, then coasts influenced by the LC have less variable seaweed communities and lower species turnover across regions than the EAC. This hypothesis was supported. We suggest that this pattern is likely caused by a combination of seaweed temperature tolerances and current-driven dispersal. In conclusion, our findings support the idea that the characteristics of continental-scale currents can influence regional community organisation, and that the coupling of ocean currents and marine biological structure is a general feature that transcends taxa and spatial scales.Thomas Wernberg, Mads S. Thomsen, Sean D. Connell, Bayden D. Russell, Jonathan M. Waters, Giuseppe C. Zuccarello, Gerald T. Kraft, Craig Sanderson, John A. West, Carlos F. D. Gurge