Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France.

An indirect in-house immunofluorescent assay was developed in order to assess the serological status of COVID-19 patients in Marseille, France. Performance of IFA was compared to a commercial ELISA IgG kit. We tested 888 RT-qPCR-confirmed COVID-19 patients (1302 serum samples) and 350 controls including 200 sera collected before the pandemic, 64 sera known to be associated with nonspecific serological interference, 36 sera from non-coronavirus pneumonia and 50 sera from patient with other common coronavirus to elicit false-positive serology. Incorporating an inactivated clinical SARS-CoV-2 isolate as the antigen, the specificity of the assay was measured as 100% for IgA titre ≥ 1:200, 98.6% for IgM titre ≥ 1:200 and 96.3% for IgG titre ≥ 1:100 after testing a series of negative controls. IFA presented substantial agreement (86%) with ELISA EUROIMMUN SARS-CoV-2 IgG kit (Cohen's Kappa = 0.61). The presence of antibodies was then measured at 3% before a 5-day evolution up to 47% after more than 15 days of evolution. We observed that the rates of seropositivity as well as the titre of specific antibodies were both significantly higher in patients with a poor clinical outcome than in patients with a favourable evolution. These data, which have to be integrated into the ongoing understanding of the immunological phase of the infection, suggest that detection anti-SARS-CoV-2 antibodies is useful as a marker associated with COVID-19 severity. The IFA assay reported here is useful for monitoring SARS-CoV-2 exposure at the individual and population levels.

Clinical efficacy of chloroquine derivatives in COVID-19 infection: comparative meta-analysis between the big data and the real world.

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020. The keywords 'hydroxychloroquine', 'chloroquine', 'coronavirus', 'COVID-19' and 'SARS-Cov-2' were used in the PubMed, Google Scholar and Google search engines without any restrictions as to date or language. Twenty studies were identified involving 105 040 patients (19 270 treated patients) from nine countries (Brazil, China, France, Iran, Saudi Arabia, South Korea, Spain and the USA). Big data observational studies were associated with conflict of interest, lack of treatment dosage and duration, and absence of favourable outcome. Clinical studies were associated with favourable outcomes and details on therapy. Among clinical studies, three of four randomized controlled trials reported a significant favourable effect. Among clinical studies, a significant favourable summary effect was observed for duration of cough (OR 0.19, p 0.00003), duration of fever (OR 0.11, p 0.039), clinical cure (OR 0.21, p 0.0495), death (OR 0.32, p 4.1 × 10-6) and viral shedding (OR 0.43, p 0.031). A trend for a favourable effect was noted for the outcome 'death and/or intensive care unit transfer' (OR 0.29, p 0.069) with a point estimate remarkably similar to that observed for death (∼0.3). In conclusion, a meta-analysis of publicly available clinical reports demonstrates that chloroquine derivatives are effective to improve clinical and virological outcomes, but, more importantly, they reduce mortality by a factor of 3 in patients with COVID-19. Big data are lacking basic treatment definitions and are linked to conflict of interest. The retraction of the only big data study associated with a significantly deleterious effect the day after (June 5, 2020) the acceptance of the present work (June 4, 2020) confirms the relevance of this work.

Nullane salus extra ecclesiam.

Randomized clinical trials are not relevant for infectious disease outbreaks due to a new pathogen, for which public health decisions have to be made urgently. An approach based on group comparisons, in silico, may provide valuable results in a reasonably short period of time for a negligible amount of money.

New guidelines for the prevention of imported malaria in France.

Prevention of malaria is based on personal vector-control measures (PVCMs) to avoid mosquito bites at night and chemoprophylaxis if justified by the risk of contracting the disease. The most effective PVCM is the use of insecticide-treated mosquito nets. The decision to prescribe chemoprophylaxis, mainly to prevent Plasmodium falciparum infection, depends on the benefit-risk ratio. Overall, the risk of contracting malaria is 1,000-fold lower during a stay in the tropical regions of Asia or the Americas than in sub-Saharan Africa. For "conventional" stays (less than one month with nights spent in urban areas) in low-risk settings in tropical Asia and America, the risk of being infected with Plasmodium parasites (≤1/100,000) is equivalent or lower than that of experiencing serious adverse effects caused by chemoprophylaxis. Preventive medication is therefore no longer recommended. By contrast, in other settings and particularly in sub-Saharan Africa, chemoprophylaxis is the most effective measure against malaria. However, it is worth noting that no single preventive measure provides full protection. Regardless of the level of risk or chemoprophylaxis-related indication, protection against mosquito bites and rapid management of febrile illness after returning from an endemic area are also critical to prevent malaria. Finally, migrants of sub-Saharan origin visiting friends and relatives in their country of origin form a high-risk group who should be recommended chemoprophylaxis in the same way as any other travelers-with a preference for the least expensive molecules (doxycycline).

The University Hospital Institute Mediterrannée Infection from Marseille to Dakar.

In Senegal, we have developed technology-driven research based on observation and technology transfer especially in molecular biology, genomics, culturomics, and proteomics with the use of the first Maldi-TOF mass spectrometer in clinical microbiology in Africa. This strategy is associated with a policy of training students from the South and helping them to return back. This technology transfer and expertise has enabled us to explore the causes of non-malarial fevers of unknown causes, with the study of the repertoire of infectious pathogens in humans and arthropod vectors, to diagnose infectious diseases in rural areas with Point of Care laboratories, to isolate new bacteria, and to study pathologies linked to mass gatherings. They have also allowed us to develop transdisciplinary research including the study of the microbiota in malnourished children. We wish to continue this technological development, which provides the foundation for high-level research in Senegal.

Epidemiology of respiratory pathogen carriage in the homeless population within two shelters in Marseille, France, 2015-2017: cross sectional 1-day surveys.

OBJECTIVES: To assess risk factors for respiratory tract infection symptoms and signs in sheltered homeless people in Marseille during the winter season, including pathogen carriage. METHODS: Data on 479 male participants within two shelters who completed questionnaires and a total of 950 nasal and pharyngeal samples were collected during the winters of 2015-2017. Respiratory pathogen carriage including seven viruses and four bacteria was assessed by quantitative PCR. RESULTS: The homeless population was characterized by a majority of individuals of North African origin (300/479, 62.6%) with a relatively high prevalence of chronic homelessness (175/465, 37.6%). We found a high prevalence of respiratory symptoms and signs (168/476, 35.3%), a very high prevalence of bacterial carriage (313/477, 65.6%), especially Haemophilus influenzae (280/477, 58.7%), and a lower prevalence of virus carriage (51/473, 10.8%) with human rhinovirus being the most frequent (25/473, 5.3%). Differences were observed between the microbial communities of the nose and throat. Duration of homelessness (odds ratio (OR) 1.77, p 0.017), chronic respiratory diseases (OR 5.27, p <0.0001) and visiting countries of origin for migrants (OR 1.68, p 0.035) were identified as independent risk factors for respiratory symptoms and signs. A strong association between virus (OR 2.40, p 0.012) or Streptococcus pneumoniae (OR 2.32, p 0.014) carriage and respiratory symptoms and signs was also found. CONCLUSIONS: These findings allowed identification of the individuals at higher risk for contracting respiratory tract infections to better target preventive measures aimed at limiting the transmission of these diseases in this setting.

Endocarditis in the Mediterranean Basin.

Infective endocarditis is a severe disease with high mortality. Despite a global trend towards an increase in staphylococcal aetiologies, in older patients and a decrease in viridans streptococci, we have observed in recent studies great epidemiologic disparities between countries. In order to evaluate these differences among Mediterranean countries, we performed a PubMed search of infective endocarditis case series for each country. Data were available for 13 of the 18 Mediterranean countries. Despite great differences in diagnostic strategies, we could classify countries into three groups. In northern countries, patients are older (>50 years old), have a high rate of prosthetic valves or cardiac electronic implantable devices and the main causative agent is Staphylococcus aureus. In southern countries, patients are younger (<40 years old), rheumatic heart disease remains a major risk factor (45-93%), viridans streptococci are the main pathogens, zoonotic and arthropod-borne agents are frequent and blood culture-negative endocarditis remains highly prevalent. Eastern Mediterranean countries exhibit an intermediate situation: patients are 45 to 60 years old, the incidence of rheumatic heart disease ranges from 8% to 66%, viridans streptococci play a predominant role and zoonotic and arthropod-borne diseases, in particular brucellosis, are identified in up to 12% of cases.

Mobile populations across the Mediterranean Sea and beyond: travel medicine, mass gathering medicine and homeless health.

The Méditerranée Infection institute is internationally recognized for its expertise in infectious diseases and tropical medicine, and is one of the most active research centres for infectious diseases in Europe. Surveillance and research addressing infectious diseases in globally mobile populations is one of the strong components of the research conducted at the institute. A significant amount of clinical, microbiologic and epidemiologic works have been conducted in international travellers, pilgrims participating in large international religious gatherings, economic migrants and homeless migrant people over the last decades by our group. Our strong anchoring in several countries around the Mediterranean Sea and beyond, as well as the pivotal role of Marseille in the EuroTravNet and GeoSentinel international networks that monitor travel-associated diseases, reinforce our leading position in the fields of travel and tropical medicine, mass gathering medicine and homeless health.

Evaluation of visual triage for screening of Middle East respiratory syndrome coronavirus patients.

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 in Saudi Arabia had attracted the attention of the global health community. In 2017 the Saudi Ministry of Health released a visual triage system with scoring to alert healthcare workers in emergency departments (EDs) and haemodialysis units for the possibility of occurrence of MERS-CoV infection. We performed a retrospective analysis of this visual score to determine its sensitivity and specificity. The study included all cases from 2014 to 2017 in a MERS-CoV referral centre in Riyadh, Saudi Arabia. During the study period there were a total of 2435 suspected MERS cases. Of these, 1823 (75%) tested negative and the remaining 25% tested positive for MERS-CoV by PCR assay. The application of the visual triage score found a similar percentage of MERS-CoV and non-MERS-CoV patients, with each score from 0 to 11. The percentage of patients with a cutoff score of ≥4 was 75% in patients with MERS-CoV infection and 85% in patients without MERS-CoV infection (p 0.0001). The sensitivity and specificity of this cutoff score for MERS-CoV infection were 74.1% and 18.6%, respectively. The sensitivity and specificity of the scoring system were low, and further refinement of the score is needed for better prediction of MERS-CoV infection.

A Hydrothermal-Sedimentary Context for the Origin of Life.

Critical to the origin of life are the ingredients of life, of course, but also the physical and chemical conditions in which prebiotic chemical reactions can take place. These factors place constraints on the types of Hadean environment in which life could have emerged. Many locations, ranging from hydrothermal vents and pumice rafts, through volcanic-hosted splash pools to continental springs and rivers, have been proposed for the emergence of life on Earth, each with respective advantages and certain disadvantages. However, there is another, hitherto unrecognized environment that, on the Hadean Earth (4.5-4.0 Ga), would have been more important than any other in terms of spatial and temporal scale: the sedimentary layer between oceanic crust and seawater. Using as an example sediments from the 3.5-3.33 Ga Barberton Greenstone Belt, South Africa, analogous at least on a local scale to those of the Hadean eon, we document constant permeation of the porous, carbonaceous, and reactive sedimentary layer by hydrothermal fluids emanating from the crust. This partially UV-protected, subaqueous sedimentary environment, characterized by physical and chemical gradients, represented a widespread system of miniature chemical reactors in which the production and complexification of prebiotic molecules could have led to the origin of life. Key Words: Origin of life-Hadean environment-Mineral surface reactions-Hydrothermal fluids-Archean volcanic sediments. Astrobiology 18, 259-293.

Genome sequence of "Leucobacter massiliensis" sp. nov. isolated from human pharynx after travel to the 2014 Hajj.

"Leucobacter massiliensis" strain 122RC15T sp. nov. is a new species within the genus Leucobacter. The genome of this strain is described here. It was isolated from the pharynx of a 76-year-old Algerian female after travelling from the 2014 Hajj. "Leucobacter massiliensis" is a Gram-positive, aerobic bacillus. Here we describe the features including complete genome and annotation of this strain. The 3 136 406-bp long genome contains 2797 protein-coding genes and 49 RNA genes.

Mineralization and Preservation of an extremotolerant Bacterium Isolated from an Early Mars Analog Environment.

The artificial mineralization of a polyresistant bacterial strain isolated from an acidic, oligotrophic lake was carried out to better understand microbial (i) early mineralization and (ii) potential for further fossilisation. Mineralization was conducted in mineral matrixes commonly found on Mars and Early-Earth, silica and gypsum, for 6 months. Samples were analyzed using microbiological (survival rates), morphological (electron microscopy), biochemical (GC-MS, Microarray immunoassay, Rock-Eval) and spectroscopic (EDX, FTIR, RAMAN spectroscopy) methods. We also investigated the impact of physiological status on mineralization and long-term fossilisation by exposing cells or not to Mars-related stresses (desiccation and radiation). Bacterial populations remained viable after 6 months although the kinetics of mineralization and cell-mineral interactions depended on the nature of minerals. Detection of biosignatures strongly depended on analytical methods, successful with FTIR and EDX but not with RAMAN and immunoassays. Neither influence of stress exposure, nor qualitative and quantitative changes of detected molecules were observed as a function of mineralization time and matrix. Rock-Eval analysis suggests that potential for preservation on geological times may be possible only with moderate diagenetic and metamorphic conditions. The implications of our results for microfossil preservation in the geological record of Earth as well as on Mars are discussed.

What is the experience from previous mass gathering events? Lessons for Zika virus and the Olympics 2016.

All previous experiences from different mass gathering show that vaccine preventable diseases is the most important infections like influemza, hepatitis A, polio and meningitis. Three mass gathering held in Africa during the Ebola outbreak accepted participants from West Africa and was able to handle the theoretical risk without any incident. Therefore we believe that the Olympc games in Rio de Janeiro should not be canceled. The number of visitors to the games is a tine fraction (1%) of other visitors to Zika endemic con tries and it will have no measurable effect on the risk of spreading Zika virus, if the games was cancelled.

Risk perceptions of MSF healthcare workers on the recent Ebola epidemic in West Africa.

Healthcare workers (HCW) in general are considered to be at high risk during epidemics. Their training for Ebola provided by Médecins sans frontières (MSF) is presently based on imparting factual information, which does not necessarily translate into knowledge or appropriate practices. We aimed to understand the importance of risk perception during training. A total of 130 MSF-trained HCW traveling to Africa during the Ebola epidemic of 2014-2015 participated in this longitudinal cohort study. Their baseline knowledge was good but did not significantly increase after training except for minor symptoms, case fatality rate and wearing personal protective equipment as a preventive measure. Additionally, they underestimated their likelihood for contracting Ebola compared to their colleagues of same age and sex, and despite their high-risk status, they showed little concern about contracting Ebola during their mission. Our findings suggest that the use of individualized risk feedback during training in appraising erroneous perceptions will increase adherence to preventive measures.

Molecular dynamics of Staphylococcus aureus nasal carriage in Hajj pilgrims.

During the 2012 Hajj season, the risk of acquisition of Staphylococcus aureus nasal carriage in a cohort of French pilgrims was 22.8%, and was statistically associated with the acquisition of viral respiratory pathogens (p 0.03). The carriage of S. aureus belonging to the emerging clonal complex 398 significantly increased following the pilgrimage (p < 0.05).