Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus

Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide

Cystatin C and alpha-1-Microglobulin Predict Severe Acute Kidney Injury in Patients with Hemorrhagic Fever with Renal Syndrome

Puumala orthohantavirus causes hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury (AKI), an abrupt decrease in renal function. Creatinine is routinely used to detect and quantify AKI; however, early AKI may not be reflected in increased creatinine levels. Therefore, kidney injury markers that can predict AKI are needed. The potential of the kidney injury markers urea, cystatin C, α1-microglobulin (A1M) and neutrophil gelatinase-associated lipocalin (NGAL) to detect early AKI during HFRS was studied by quantifying the levels of these markers in consecutively obtained plasma (P) and urine samples (U) for 44 HFRS patients. P-cystatin C and U-A1M levels were significantly increased during early HFRS compared to follow-up. In a receiver operating characteristic (ROC) curve analysis, P-cystatin C, U-A1M and P-urea predicted severe AKI with area under the curve 0.72, 0.73 and 0.71, respectively, whereas the traditional kidney injury biomarkers creatinine and U-albumin did not predict AKI. Nearly half of the HFRS patients (41%) fulfilled the criteria for shrunken pore syndrome, which was associated with the level of inflammation as measured by P-CRP. P-cystatin C and U-A1M are more sensitive and earlier markers compared to creatinine in predicting kidney injury during HFRS

Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis

OBJECTIVES: To investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE). METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/CSF sampling and brain MRI the first 3 months along with cognitive assessment by Mattis Dementia Rating Scale (MDRS) during 24 months. CSF samples were analyzed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The pre-defined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months. RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-NMDAR (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006). CONCLUSIONS: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE

Particle number concentrations over Europe in 2030: the role of emissions and new particle formation

The aerosol particle number concentration is a key parameter when estimating impacts of aerosol particles on climate and human health. We use a three-dimensional chemical transport model with detailed microphysics, PMCAMx-UF, to simulate particle number concentrations over Europe in the year 2030, by applying emission scenarios for trace gases and primary aerosols. The scenarios are based on expected changes in anthropogenic emissions of sulfur dioxide, ammonia, nitrogen oxides, and primary aerosol particles with a diameter less than 2.5 μm (PM2.5) focusing on a photochemically active period, and the implications for other seasons are discussed. For the baseline scenario, which represents a best estimate of the evolution of anthropogenic emissions in Europe, PMCAMx-UF predicts that the total particle number concentration (Ntot) will decrease by 30–70% between 2008 and 2030. The number concentration of particles larger than 100 nm (N100), a proxy for cloud condensation nuclei (CCN) concentration, is predicted to decrease by 40–70% during the same period. The predicted decrease in Ntot is mainly a result of reduced new particle formation due to the expected reduction in SO2 emissions, whereas the predicted decrease in N100 is a result of both decreasing condensational growth and reduced primary aerosol emissions. For larger emission reductions, PMCAMx-UF predicts reductions of 60–80% in both Ntot and N100 over Europe. Sensitivity tests reveal that a reduction in SO2 emissions is far more efficient than any other emission reduction investigated, in reducing Ntot. For N100, emission reductions of both SO2 and PM2.5 contribute significantly to the reduced concentration, even though SO2 plays the dominant role once more. The impact of SO2 for both new particle formation and growth over Europe may be expected to be somewhat higher during the simulated period with high photochemical activity than during times of the year with less incoming solar radiation. The predicted reductions in both Ntot and N100 between 2008 and 2030 in this study will likely reduce both the aerosol direct and indirect effects, and limit the damaging effects of aerosol particles on human health in Europe

Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya

Background Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV) transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity. Methodology Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo),cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis. Findings Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia). The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290), was totally absent in all Isiolo sites. Fourteen virus isolates including Sindbis, Bunyamwera, and West Nile fever viruses were isolated mostly from Ae. mcintoshi sampled in Tana-River. RVFV was not detected in any of the mosquitoes. Conclusion This study presents the geographic distribution and abundance of arbovirus vectors in two Kenyan counties, which may assist with risk assessment for mosquito borne diseases

Eastern Pacific Emitted Aerosol Cloud Experiment

Aerosol–cloud–radiation interactions are widely held to be the largest single source of uncertainty in climate model projections of future radiative forcing due to increasing anthropogenic emissions. The underlying causes of this uncertainty among modeled predictions of climate are the gaps in our fundamental understanding of cloud processes. There has been significant progress with both observations and models in addressing these important questions but quantifying them correctly is nontrivial, thus limiting our ability to represent them in global climate models. The Eastern Pacific Emitted Aerosol Cloud Experiment (E-PEACE) 2011 was a targeted aircraft campaign with embedded modeling studies, using the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) Twin Otter aircraft and the research vessel Point Sur in July and August 2011 off the central coast of California, with a full payload of instruments to measure particle and cloud number, mass, composition, and water uptake distributions. EPEACE used three emitted particle sources to separate particle-induced feedbacks from dynamical variability, namely 1) shipboard smoke-generated particles with 0.05–1-μm diameters (which produced tracks measured by satellite and had drop composition characteristic of organic smoke), 2) combustion particles from container ships with 0.05–0.2-μm diameters (which were measured in a variety of conditions with droplets containing both organic and sulfate components), and 3) aircraft-based milled salt particles with 3–5-μm diameters (which showed enhanced drizzle rates in some clouds). The aircraft observations were consistent with past large-eddy simulations of deeper clouds in ship tracks and aerosol– cloud parcel modeling of cloud drop number and composition, providing quantitative constraints on aerosol effects on warm-cloud microphysics

Primary marine aerosol-cloud interactions off the coast of California

Primary marine aerosol (PMA)-cloud interactions off the coast of California were investigated using observations of marine aerosol, cloud condensation nuclei (CCN), and stratocumulus clouds during the Eastern Pacific Emitted Aerosol Cloud Experiment (E-PEACE) and the Stratocumulus Observations of Los-Angeles Emissions Derived Aerosol-Droplets (SOLEDAD) studies. Based on recently reported measurements of PMA size distributions, a constrained lognormal-mode-fitting procedure was devised to isolate PMA number size distributions from total aerosol size distributions and applied to E-PEACE measurements. During the 12 day E-PEACE cruise on the R/V Point Sur, PMA typically contributed less than 15% of total particle concentrations. PMA number concentrations averaged 12 cm^(−3) during a relatively calmer period (average wind speed 12 m/s^1) lasting 8 days, and 71 cm^(−3) during a period of higher wind speeds (average 16 m/s^1) lasting 5 days. On average, PMA contributed less than 10% of total CCN at supersaturations up to 0.9% during the calmer period; however, during the higher wind speed period, PMA comprised 5–63% of CCN (average 16–28%) at supersaturations less than 0.3%. Sea salt was measured directly in the dried residuals of cloud droplets during the SOLEDAD study. The mass fractions of sea salt in the residuals averaged 12 to 24% during three cloud events. Comparing the marine stratocumulus clouds sampled in the two campaigns, measured peak supersaturations were 0.2 ± 0.04% during E-PEACE and 0.05–0.1% during SOLEDAD. The available measurements show that cloud droplet number concentrations increased with >100 nm particles in E-PEACE but decreased in the three SOLEDAD cloud events

Nucleation and condensational growth to CCN sizes during a sustained pristine biogenic SOA event in a forested mountain valley

The Whistler Aerosol and Cloud Study (WACS 2010), included intensive measurements of trace gases and particles at two sites on Whistler Mountain. Between 6–11 July 2010 there was a sustained high-pressure system over the region with cloud-free conditions and the highest temperatures of the study. During this period, the organic aerosol concentrations rose from <1 μg m<sup>−3</sup> to ∼6 μg m<sup>−3</sup>. Precursor gas and aerosol composition measurements show that these organics were almost entirely of secondary biogenic nature. Throughout 6–11 July, the anthropogenic influence was minimal with sulfate concentrations <0.2 μg m<sup>−3</sup> and SO<sub>2</sub> mixing ratios ≈ 0.05–0.1 ppbv. Thus, this case provides excellent conditions to probe the role of biogenic secondary organic aerosol in aerosol microphysics. Although SO<sub>2</sub> mixing ratios were relatively low, box-model simulations show that nucleation and growth may be modeled accurately if <i>J</i><sub>nuc</sub> = 3 × 10<sup>−7</sup>[H<sub>2</sub>SO<sub>4</sub>] and the organics are treated as effectively non-volatile. Due to the low condensation sink and the fast condensation rate of organics, the nucleated particles grew rapidly (2–5 nm h<sup>−1</sup>) with a 10–25% probability of growing to CCN sizes (100 nm) in the first two days as opposed to being scavenged by coagulation with larger particles. The nucleated particles were observed to grow to ∼200 nm after three days. Comparisons of size-distribution with CCN data show that particle hygroscopicity (κ) was ∼0.1 for particles larger 150 nm, but for smaller particles near 100 nm the κ value decreased near midway through the period from 0.17 to less than 0.06. In this environment of little anthropogenic influence and low SO<sub>2</sub>, the rapid growth rates of the regionally nucleated particles – due to condensation of biogenic SOA – results in an unusually high efficiency of conversion of the nucleated particles to CCN. Consequently, despite the low SO<sub>2</sub>, nucleation/growth appear to be the dominant source of particle number

Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever virus

The spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. This is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. Hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. Climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infections. In northern Sweden, a form of haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala hantavirus (PUUV) is endemic and during 2006–2007 an unexpected, sudden and large outbreak of NE occurred in this region. The incidence was 313 cases/100,000 inhabitants in the most endemic areas, and from January through March 2007 the outbreak had a dramatic and sudden start with 474 cases in the endemic region alone. The PUUV rodent reservoir is bank voles and immediately before and during the peak of disease outbreak the affected regions experienced extreme climate conditions with a record-breaking warm winter, registering temperatures 6–9°C above normal. No protective snow cover was present before the outbreak and more bank voles than normal came in contact with humans inside or in close to human dwellings. These extreme climate conditions most probably affected the rodent reservoir and are important factors for the severity of the outbreak