On 6 December 2013, two laboratory-confirmed cases of chikungunya without a travel history were reported on the French part of the Caribbean island of Saint Martin, indicating the start of the first ...documented outbreak of chikungunya in the Americas. Since this report, the virus spread to several Caribbean islands and French Guiana, and between 6 December 2013 and 27 March 2014 more than 17,000 suspected and confirmed cases have been reported. Further spread and establishment of the disease in the Americas is likely, given the high number of people travelling between the affected and non-affected areas and the widespread occurrence of efficient vectors. Also, the likelihood of the introduction of the virus into Europe from the Americas and subsequent transmission should be considered especially in the context of the next mosquito season in Europe. Clinicians should be aware that, besides dengue, chikungunya should be carefully considered among travellers currently returning from the Caribbean region.
Wastewater-based epidemiology is experiencing exponential development. Despite undeniable advantages compared to patient-centered approaches (cost, anonymity, survey of large populations without ...bias, detection of asymptomatic infected peoples…), major technical limitations persist. Among them is the low sensitivity of the current methods used for quantifying and sequencing viral genomes from wastewater. In situations of low viral circulation, during initial stages of viral emergences, or in areas experiencing heavy rains, the extremely low concentrations of viruses in wastewater may fall below the limit of detection of the current methods. The availability during crisis and the cost of the commercial kits, as well as the requirement of expensive materials such as high-speed centrifuge, can also present major blocks to the development of wastewater-based epidemiological survey, specifically in low-income countries. Thereby, highly sensitive, low cost and standardized methods are still needed, to increase the predictability of the viral emergences, to survey low-circulating viruses and to make the results from different labs comparable. Here, we outline and characterize new protocols for concentrating and quantifying SARS-CoV-2 from large volumes (500 mL-1 L) of untreated wastewater. In addition, we report that the methods are applicable for monitoring and sequencing. Our nucleic acid extraction technique (the routine C: 5 mL method) does not require sophisticated equipment such as automatons and is not reliant on commercial kits, making it readily available to a broader range of laboratories for routine epidemiological survey. Furthermore, we demonstrate the efficiency, the repeatability, and the high sensitivity of a new membrane-based concentration method (MBC: 500 mL method) for enveloped (SARS-CoV-2) and non-enveloped (F-specific RNA phages of genogroup II / FRNAPH GGII) viruses. We show that the MBC method allows the quantification and the monitoring of viruses in wastewater with a significantly improved sensitivity compared to the routine C method. In contexts of low viral circulation, we report quantifications of SARS-CoV-2 in wastewater at concentrations as low as 40 genome copies per liter. In highly diluted samples collected in wastewater treatment plants of French Guiana, we confirmed the accuracy of the MBC method compared to the estimations done with the routine C method. Finally, we demonstrate that both the routine C method processing 5 mL and the MBC method processing 500 mL of untreated wastewater are both compatible with SARS-CoV-2 sequencing. We show that the quality of the sequence is correlated with the concentration of the extracted viral genome. Of note, the quality of the sequences obtained with some MBC processed wastewater was improved by dilutions or enzyme substitutions suggesting the presence of specific enzyme inhibitors in some wastewater. To the best of our knowledge, our MBC method is one of the first efficient, sensitive, and repeatable method characterized for SARS-CoV-2 quantification and sequencing from large volumes of wastewater.
The emergence of SARS-CoV-2 was accompanied by great uncertainty regarding the main epidemiological characteristics of the transmission. In a context where epidemiological surveillance was mainly ...targeted on symptomatic patients, we assessed the extent of SARS-CoV-2 transmission in French Guiana conducting an intra-household transmission study and population-based seroprevalence surveys repeated over time.
Household monitoring included virological and clinical follow-up for all household members for the first 28 days after the date of confirmation of the index case and serological follow-up over a 12-month period. Three seroprevalence surveys were conducted in July and September 2020 and in September 2021.
A total of 57 dwellings including 245 individuals were included in the intra-household study. The average time between the date of onset of symptoms and the date of confirmation of diagnosis and inclusion in the study was 4.2 days and 7.2 days respectively. Secondary transmission was found in three quarters of households with a secondary infection rate of 35%. The highest transmission rate were observed in the most disadvantaged populations, within couples and from adults to children. Population-based seroprevalence studies have made it possible to monitor seroprevalence rates, which have varied from 15% at the time of the epidemic peak of the first epidemic wave to 65% of the population at the beginning of the fourth wave, despite the low impact of vaccination in French Guiana.
The results obtained highlighted a high transmission of the virus in French Guiana associated with a low severity rate linked to the structure of the particularly young population. The project has provided health authorities with useful data to support prevention and control strategies and has allowed to evaluate the impact of interventions implemented during the pandemic.
•HCQ pharmacokinetics in COVID-19 patients cannot be predicted using data from lupus or rheumatoid arthritis patients.•Bronchoalveolar lavage fluid may be a more instructive matrix than plasma on the ...degree of HCQ lung exposure.•Low plasma concentrations should not induce an increase in drug dosage because lung exposure could already be high.
Different dosage regimens of hydroxychloroquine (HCQ) have been used to manage COVID-19 (coronavirus disease 2019) patients, with no information on lung exposure in this population. The aim of our study was to evaluate HCQ concentrations in the lung epithelial lining fluid (ELF) in patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19. This was a retrospective, observational, multicentre, pharmacokinetic study of HCQ in critically ill COVID-19 patients. No additional interventions or additional samples compared with standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed HCQ tablets, regardless of the dosage administered by nasogastric tube. Blood and bronchoalveolar lavage samples (n = 28) were collected from 22 COVID-19 patients and total HCQ concentrations in ELF were estimated. Median (interquartile range) HCQ plasma concentrations were 0.09 (0.06–0.14) mg/L and 0.07 (0.05–0.08) mg/L for 400 mg × 1/day and 200 mg × 3/day, respectively. Median HCQ ELF concentrations were 3.74 (1.10–7.26) mg/L and 1.81 (1.20–7.25) for 400 mg × 1/day and 200 mg × 3/day, respectively. The median ratio of ELF/plasma concentrations was 40.0 (7.3–162.7) and 21.2 (18.4–109.5) for 400 mg × 1/day and 200 mg × 3/day, respectively. ELF exposure is likely to be underestimated from HCQ concentrations in plasma. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because lung exposure may already be high.
SUMMARY
In places where sedimentation and erosion compete at fast rates, part of the record of past earthquakes on faults may be buried, hence hidden, in the first few metres below the surface. We ...developed a novel form of palaeoseismology, of geophysical type, based on the use of a dense pseudo‐3‐D Ground Penetrating Radar (GPR) survey to investigate such possible buried earthquake traces, on a long, fast‐slipping strike‐slip fault (Hope fault, New Zealand), at a site (Terako) where marked alluvial conditions prevail. We first used LiDAR data to analyse the ground surface morphology of the 2 km2 site at the greatest resolution. Nineteen morphological markers were observed, mainly alluvial terrace risers and small stream channels that are all dextrally offset by the fault by amounts ranging between 3 and 200 m. The measurements document about 10 past earthquake slip events with a mean coseismic slip of 3.3 ± 1 m, with the most recent earthquake event having a slip of 3 ± 0.5 m. We then investigated a detailed area of the site (400 × 600 m2) with pseudo‐3‐D GPR. We measured 56, ≈ 400 m long, 5–10 m spaced GPR profiles (250 MHz), parallel to the fault and evenly distributed on either side. The analysis revealed the existence of a palaeosurface buried at about 3 m depth, corresponding to the top of alluvial terraces of different ages. That buried surface is incised by a dense network of stream channels that are all dextrally offset by the fault. We measured 48 lateral offsets in the buried channel network, more than twice than at the surface. These offsets range between 6 and 108 m, as observed at the surface, yet provide a more continuous record of the fault slip. The similarity of the successive slip increments suggests a slip per event averaging 4.4 ± 1 m, fairly similar to that estimated from surface data. From the total ‘surface and buried’ 67 offset collection, we infer that a minimum of 30 large earthquakes have broken the Hope fault at the Terako site in the last about 6–7 kyr, with an average coseismic slip of 3.2 ± 1 m, a minimum average recurrence time of about 200 yr, and a magnitude of at least Mw 7.0–7.4. Our study therefore confirms that part of the record of past earthquakes may indeed reside in the first few metres below the surface, where it may be explored with geophysical, GPR‐based palaeoseismology. Developing such a new palaeoseismological tool should provide rich information that may complement surface observations and help to document the past earthquakes on faults.
Recent evidence has supported welding fume (WF)-derived ultrafine particles (UFP) could be the driving force of their adverse health effects. However, UFP have not yet been extensively studied and ...are currently not included in present air quality standards/guidelines. Here, attention was focused on the underlying genetic and epigenetic mechanisms by which the quasi-UFP (Q-UFP, i.e., ≤ 0.25 μm) of the WF emitted by gas metal arc welding-stainless steel (GMAW-SS) exert their toxicity in human bronchial epithelial BEAS-2B cells. The Q-UFP under study showed a monomodal size distribution in number centered on 104.4 ± 52.3 nm and a zeta potential of −13.8 ± 0.3 mV. They were enriched in Fe > Cr > Mn > Si, and displayed a relatively high intrinsic oxidative potential. Dose-dependent activation of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B signaling pathway, glutathione alteration, and DNA, protein and lipid oxidative damage were reported in BEAS-2B cells acutely (1.5 and 9 μg/cm2, 24 h) or repeatedly (0.25 and 1.5 μg/cm2, 3 × 24 h) exposed to Q-UFP (p < 0.05). Alterations of the Histone H3 acetylation were reported for any exposure (p < 0.05). Differentially regulated miRNA and mRNA indicated the activation of some critical cell signaling pathways related to oxidative stress, inflammation, and cell cycle deregulation towards apoptosis. Taken together, these results highlighted the urgent need to better evaluate the respective toxicity of the different metals and to include the Q-UFP fraction of WF in current air quality standards/guidelines relevant to the occupational settings.
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•Better knowledge of the critical role of WF-derived Q-UFP-induced lung toxicity.•ROS overproduction triggered by Q-UFP activates NRF2-ARE signaling pathway.•Alterations of the histone H3 acetylation triggered by Q-UFP.•New insights into the miRNA and mRNA profiles induced by Q-UFP.•Cell signaling pathways related to oxidative, inflammatory, and apoptotic events.
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