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In endemic malaria areas, Plasmodium is currently diagnosed mainly through the use of rapid diagnostic tests (RDTs). However, in Senegal, many causes of fever remain unknown. Tick-borne relapsing fever, an often-neglected public health problem, is the main cause of consultation for acute febrile illness after malaria and flu in rural areas. Our objective was to test the feasibility of extracting and amplifying DNA fragments by quantitative polymerase chain reaction (qPCR) from malaria-negative RDTs for Plasmodium falciparum (malaria Neg RDTs P.f) to detect Borrelia spp. and other bacteria. Between January and December 2019, malaria Neg RDTs P.f were collected on a quarterly basis in 12 health facilities in four regions of Senegal. The DNA extracted from the malaria Neg RDTs P.f was tested using qPCR and the results were confirmed by standard PCR and sequencing. Only Borrelia crocidurae DNA was detected in 7.22% (159/2,202) of RDTs. The prevalence of B. crocidurae DNA was higher in July (16.47%, 43/261) and August (11.21%, 50/446). The annual prevalence was 9.2% (47/512) and 5.0% (12/241) in Ngayokhem and Nema-Nding, respectively, health facilities in the Fatick region. Our study confirms that B. crocidurae infection is a frequent cause of fever in Senegal, with a high prevalence of cases in health facilities in the regions of Fatick and Kaffrine. Malaria Neg RDTs P.f are potentially a good source of pathogen sampling for the molecular identification of other causes of fever of unknown origin, even in the most remote areas.

International audience; Abstract Hedgehogs are small synanthropic mammals that live in rural areas as well as in urban and suburban areas. They can be reservoirs of several microorganisms, including certain pathogenic agents that cause human and animal public health issues. Hedgehogs are often parasitized by blood-sucking arthropods, mainly hard ticks and fleas, which in turn can also carry various vector-born microorganisms of zoonotic importance. Many biotic factors, such as urbanization and agricultural mechanization, have resulted in the destruction of the hedgehog’s natural habitats, leading these animals to take refuge near human dwellings, seeking food and shelter in parks and gardens and exposing humans to zoonotic agents that can be transmitted either directly by them or indirectly by their ectoparasites. In this review, we focus on the microorganisms detected in arthropods sampled from hedgehogs worldwide. Several microorganisms have been reported in ticks collected from these animals, including various Borrelia spp ., Anaplasma spp ., Ehrlichia spp . , and Rickettsia spp. species as well as Coxiella burnetii and Leptospira spp. As for fleas, C. burnetii , Rickettsia spp., Wolbachia spp., Mycobacterium spp. and various Bartonella species have been reported. The detection of these microorganisms in arthropods does not necessarily mean that they can be transmitted to humans and animals. While the vector capacity and competence of fleas and ticks for some of these microorganisms has been proven, in other cases the microorganisms may have simply been ingested with blood taken from an infected host. Further investigations are needed to clarify this issue. As hedgehogs are protected animals, handling them is highly regulated, making it difficult to conduct epidemiological studies on them. Their ectoparasites represent a very interesting source of information on microorganisms circulating in populations of these animals, especially vector-born ones. Graphical abstract

Background The Republic of Djibouti is a malaria endemic country that was in pre-elimination phase in 2006–2012. From 2013, however, malaria has re-emerged in the country, and its prevalence has been increasing every year. Given the co-circulation of several infectious agents in the country, the assessment of malaria infection based on microscopy or histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDT) has shown its limitations. This study, therefore, aimed to assess the prevalence of malaria among febrile patients in Djibouti city using more robust molecular tools. Methods All suspected malaria cases reported to be microscopy-positive were randomly sampled (n = 1113) and included in four health structures in Djibouti city over a 4-year period (2018–2021), mainly during the malaria transmission season (January–May). Socio-demographic information was collected, and RDT was performed in most of the included patients. The diagnosis was confirmed by species-specific nested polymerase chain reaction (PCR). Data were analysed using Fisher’s exact test and kappa statistics. Results In total, 1113 patients with suspected malaria and available blood samples were included. PCR confirmed that 788/1113 (70.8%) were positive for malaria. Among PCR-positive samples, 656 (83.2%) were due to Plasmodium falciparum, 88 (11.2%) Plasmodium vivax, and 44 (5.6%) P. falciparum/P. vivax mixed infections. In 2020, P. falciparum infections were confirmed by PCR in 50% (144/288) of negative RDTs. After the change of RDT in 2021, this percentage decreased to 17%. False negative RDT results were found more frequently (P Conclusions The present study confirmed the high prevalence of falciparum malaria and, to a lesser extent, vivax malaria. Nevertheless, 29% of suspected malaria cases were misdiagnosed by microscopy and/or RDT. There is a need to strengthen the capacity for diagnosis by microscopy and to evaluate the possible role of P. falciparum hrp2 gene deletion, which leads to false negative cases of P. falciparum.

Background Despite being first identified in 1947, Zika virus-related outbreaks were first described starting from 2007 culminating with the 2015 Latin American outbreak. Hypotheses indicate that the virus has been circulating in Asia for decades, but reports are scarce. Methods We performed serological analysis and screened placental samples isolated in 2008 for the presence of Zika virus from pregnant women in Ho Chi Minh City (Vietnam). Results None of the placental samples was positive for Zika virus. Four serum samples out of 176 (2.3%) specifically inhibited Zika virus, with variable degrees of cross-reactivity with other flaviviruses. While one of the four samples inhibited only Zika virus, cross-reactivity with other flaviviruses not included in the study could not be ruled out. Conclusion Our results support the conclusion that the virus was not present among pregnant women in the Vietnamese largest city during the initial phases of the epidemic wave.

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8-Aminoquinoline antimalarial drugs (primaquine, tafenoquine) are required for complete cure of Plasmodium vivax malaria, but they are contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In the absence of spectrophotometry, which is a gold standard for measuring G6PD activity, G6PD genotyping is one of the alternatives to establish a database and distribution map of G6PD enzyme deficiency in Mauritania, which has become a new epicenter of P. vivax malaria in West Africa. The aim of our study was to assess the performance of multiplex allele-specific polymerase chain reaction (PCR) (African-type Diaplex C™ G6PD kit) against PCR–restriction fragment length polymorphism and sequencing. Of 146 mutations associated with G6PD A− genotypes in 177 blood samples from Mauritanian patients, all but two samples were identified correctly using multiplex allele-specific PCR (100% sensitivity and 99% specificity; “almost perfect agreement” between allele-specific PCR and PCR-restriction fragment length polymorphism/sequencing, with a kappa coefficient of 0.977). Despite a suboptimal PCR protocol for dried blood spots and the inability of the commercial assay to predict unequivocally the G6PD enzyme level in heterozygous females, the African-type Diaplex C™ G6PD genotyping kit seemed to be a valuable screening tool for male subjects and for research purposes in resource-limited countries where spectrophotometer and DNA sequencing are not available.

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International audience; Before the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications.

International audience; We report a case of unusual human anaplasmosis in the Amazon rainforest of French Guiana. Molecular typing demonstrated that the pathogen is a novel Anaplasma species, distinct to all known species, and more genetically related to recently described Anaplasma spp. causing infections in rainforest wild fauna of Brazil.

International audience; Objectives: We studied the kinetics of SARS-CoV-2 antibodies and identified the associated risk factors with the presence of these antibodies.Methods: In this longitudinal cohort study, we included all PLWHIV. Samples were tested for IgG targeting the nucleocapsid (N) and all positive samples were tested for IgG targeting the spike (S) and IgA targeting S.Results: 1,901 PLWHIV were included: 64.4% male, median age: 53 years (44-60). At inclusion, 254 (13.4%, 95% CI 11.9, 15.0) had positive IgG anti-N. Levels of IgG anti-N, IgG anti-S and IgA anti-S were 3.95 (standard error: 0.16), 199.4 BAU/mL (21.7) and 3.14 (0.21), respectively. Over one year, levels of IgG anti-N and anti-S decreased significantly (-2.83 p

In the search of new antiplasmodial agents, a multitargeted approach was used in the synthesis of triazolopyrimidine- and 4-aminoquinolines-based hybrids.

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International audience; Abstract Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy. Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.

In this work, we describe, for the first time, the occurrence of carbapenem-resistant bacteria colonizing COVID-19 patients who developed hospital-associated infections with carbapenemase-producing, Gram-negative bacteria at some isolation centers of COVID-19 in the eastern part of Libya. Our results confirmed that the overuse of antimicrobials, such as carbapenem antibiotics, during the COVID-19 pandemic has led to the emergence of multidrug-resistant bacteria, mainly K. pneumoniae and A. baumannii , as well as colistin resistance.

International audience; Background The cutaneous leishmaniasis (CL) incubation period (IP) is defined as the time between parasite inoculation by sandfly bite and the onset of the first CL lesion. IP distribution is difficult to assess for CL because the date of exposure to an infectious bite cannot be accurately determined in endemic areas. IP current estimates for CL range from 14 days to several months with a median around 30–60 days, as established by a few previous studies in both New and Old Worlds. Methodology We estimated CL incubation period distribution using time-to-event models adapted to interval-censored data based on declared date of travels from symptomatic military personnel living in non-endemic areas that were exposed during their short stays in French Guiana (FG) between January 2001 and December 2021. Principal findings A total of 180 patients were included, of which 176 were men (97.8%), with a median age of 26 years. When recorded, the parasite species was always Leishmania guyanensis (31/180, 17.2%). The main periods of CL diagnosis spread from November to January (84/180, 46.7%) and over March-April (54/180, 30.0%). The median IP was estimated at 26.2 days (95% Credible Level, 23.8–28.7 days) using a Bayesian accelerated failure-time regression model. Estimated IP did not exceed 62.1 days (95% CI, 56–69.8 days) in 95% of cases (95 th percentile). Age, gender, lesion number, lesion evolution and infection date did not significantly modify the IP. However, disseminated CL was significantly associated with a 2.8-fold shortening of IP. Conclusions This work suggests that the CL IP distribution in French Guiana is shorter and more restricted than anticipated. As the incidence of CL in FG usually peaks in January and March, these findings suggest that patients are contaminated at the start of the rainy season.

International audience; High concentration of soluble E-cadherin (E-cad) was previously found in sera from Q fever patients. Here, BeWo cells which express a high concentration of E-cad were used as an in vitro model to investigate the expression and function of E-cad in response to infection by Coxiella burnetii , the etiological agent of Q fever. Infection of BeWo cells with C . burnetii leads to a decrease in the number of BeWo cells expressing E-cad at their membrane. A shedding of soluble E-cad was associated with the post-infection decrease of membrane-bound E-cad. The modulation of E-cad expression requires bacterial viability and was not found with heat-inactivated C . burnetii . Moreover, the intracytoplasmic cell concentration of β-catenin (β-cat), a ligand of E-cad, was reduced after bacterial infection, suggesting that the bacterium induces modulation of the E-cad/β-cat signaling pathway and CDH1 and CTNNB1 genes transcription. Finally, several genes operating the canonical Wnt-Frizzled/β-cat pathway were overexpressed in cells infected with C . burnetii . This was particularly evident with the highly virulent strain of C . burnetii , Guiana. Our data demonstrate that infection of BeWo cells by live C . burnetii modulates the E-cad/β-cat signaling pathway.

Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as “ultramicrobacteria” with a cell volume under 0.1 μm(3) and were first associated with the human oral microbiota in 2007. The evolution of technology has been paramount for the study of CPR within the human microbiota. In fact, since these ultramicrobacteria have yet to be axenically cultured despite ongoing efforts, progress in imaging technology has allowed their observation and morphological description. Although their genomic abilities and taxonomy are still being studied, great strides have been made regarding their taxonomic classification, as well as their lifestyle. In addition, advancements in next-generation sequencing and the continued development of bioinformatics tools have allowed their detection as commensals in different human habitats, including the oral cavity and gastrointestinal and genital tracts, thus highlighting CPR as a nonnegligible part of the human microbiota with an impact on physiological settings. Conversely, several pathologies present dysbiosis affecting CPR levels, including inflammatory, mucosal, and infectious diseases. In this exhaustive review of the literature, we provide a historical perspective on the study of CPR, an overview of the methods available to study these organisms and a description of their taxonomy and lifestyle. In addition, their distribution in the human microbiome is presented in both homeostatic and dysbiotic settings. Future efforts should focus on developing cocultures and, if possible, axenic cultures to obtain isolates and therefore genomes that would provide a better understanding of these ultramicrobacteria, the importance of which in the human microbiome is undeniable.

International audience; Introduction Burkholderia thailandensis is a study model for Burkholderia pseudomallei , a highly virulent pathogen, known to be the causative agent of melioidosis and a potential bioterrorism agent. These two bacteria use an (acyl-homoserine lactone) AHL-mediated quorum sensing (QS) system to regulate different behaviors including biofilm formation, secondary metabolite productions, and motility. Methods Using an enzyme-based quorum quenching (QQ) strategy, with the lactonase Sso Pox having the best activity on B. thailandensis AHLs, we evaluated the importance of QS in B. thailandensis by combining proteomic and phenotypic analyses. Results We demonstrated that QS disruption largely affects overall bacterial behavior including motility, proteolytic activity, and antimicrobial molecule production. We further showed that QQ treatment drastically decreases B. thailandensis bactericidal activity against two bacteria ( Chromobacterium violaceum and Staphylococcus aureus ), while a spectacular increase in antifungal activity was observed against fungi and yeast ( Aspergillus niger , Fusarium graminearum and Saccharomyces cerevisiae ). Discussion This study provides evidence that QS is of prime interest when it comes to understanding the virulence of Burkholderia species and developing alternative treatments.

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International audience; Mycoviruses are viruses that selectively infect and multiply in fungal cells. Malassezia is the most abundant fungus on human skin and is associated with a variety of conditions, including atopic eczema, atopic dermatitis, dandruff, folliculitis, pityriasis versicolor, and seborrheic dermatitis. Here, we conducted mycovirome studies on 194 public transcriptomes of Malassezia (2,568,212,042 paired-end reads) screened against all available viral proteins. Transcriptomic data were assembled de novo resulting in 1,170,715 contigs and 2,995,306 open reading frames (ORFs) that were subsequently tracked for potential viral sequences. Eighty-eight virus-associated ORFs were detected in 68 contigs from 28 Sequence Read Archive (SRA) samples. Seventy-five and thirteen ORFs were retrieved from transcriptomes of Malassezia globosa and Malassezia restricta, respectively. Phylogenetic reconstructions revealed three new mycoviruses belonging to the Totivirus genus and named Malassezia globosa-associated-totivirus 1 (MgaTV1); Malassezia restricta-associated-totivirus 1 (MraTV1) and Malassezia restricta-associated-totivirus 2 (MraTV2). These viral candidates extend our understanding of the diversity and taxonomy of mycoviruses as well as their co-evolution with their fungal hosts. These results reflected the unexpected diversity of mycoviruses hidden in public databases. In conclusion, this study sheds light on the discovery of novel mycoviruses and opens the door to study their impact on disease caused by the host fungus Malassezia and globally, their implication in clinical skin disorders.

International audience; Intermittent preventive treatment in pregnancy with sulfadoxine and pyrimethamine (IPTp-SP) is a key component in the malaria control strategy implemented in Africa. The aim of this study was to determine IPTp-SP adherence and coverage, and the impact on maternal infection and birth outcomes in the context of widespread SP resistance in the city of Douala, Cameroon. Clinical and demographic information were documented among 888 pregnant women attending 3 health facilities, from the antenatal care visit to delivery. Positive samples were genotyped for P. falciparum gene (dhfr, dhps, and k13) mutations. The overall IPTp-SP coverage (≥three doses) was 17.5%, and 5.1% received no dose. P. falciparum prevalence was 16%, with a predominance of submicroscopic infections (89.3%). Malaria infection was significantly associated with locality and history of malaria, and it was reduced among women using indoor residual spraying. Optimal doses of IPTp-SP were significantly associated with reduced infection among newborns and women (secundiparous and multiparous), but there was no impact of IPTp-SP on the newborn bodyweight. Pfdhfr-Pfdhps quintuple mutants were over-represented (IRNI-FGKAA, IRNI-AGKAA), and sextuple mutants (IRNI-AGKAS, IRNI-FGEAA, IRNI-AGKGS) were also reported. The Pfk13 gene mutations associated with artemisinin resistance were not detected. This study highlights the role of ANC in achieving optimal SP coverage in pregnant women, the mitigated impact of IPTp-SP on malaria outcomes, and the high prevalence of multiple SP-resistant P. falciparum parasites in the city of Douala that could compromise the efficacy of IPTp-SP.

International audience; Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer's patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.

International audience; BackgroundSuccessive epidemic waves of COVID-19 illustrated the potential of SARS-CoV-2 variants to reshape the pandemic. Detecting and characterising emerging variants is essential to evaluate their public health impact and guide implementation of adapted control measures.AimTo describe the detection of emerging variant, B.1.640, in France through genomic surveillance and present investigations performed to inform public health decisions.MethodsIdentification and monitoring of SARS-CoV-2 variant B.1.640 was achieved through the French genomic surveillance system, producing 1,009 sequences. Additional investigation of 272 B.1.640-infected cases was performed between October 2021 and January 2022 using a standardised questionnaire and comparing with Omicron variant-infected cases.ResultsB.1.640 was identified in early October 2021 in a school cluster in Bretagne, later spreading throughout France. B.1.640 was detected at low levels at the end of SARS-CoV-2 Delta variant’s dominance and progressively disappeared after the emergence of the Omicron (BA.1) variant. A high proportion of investigated B.1.640 cases were children aged under 14 (14%) and people over 60 (27%) years, because of large clusters in these age groups. B.1.640 cases reported previous SARS-CoV-2 infection (4%), anosmia (32%) and ageusia (34%), consistent with data on pre-Omicron SARS-CoV-2 variants. Eight percent of investigated B.1.640 cases were hospitalised, with an overrepresentation of individuals aged over 60 years and with risk factors.ConclusionEven though B.1.640 did not outcompete the Delta variant, its importation and continuous low-level spread raised concerns regarding its public health impact. The investigations informed public health decisions during the time that B.1.640 was circulating.

Two new bacterial strains, Marseille-P2698T (CSUR P2698 = DSM 103,121) and Marseille-P2260T (CSUR P2260 = DSM 101,844 = SN18), were isolated from human stools by the culturomic method. We used the taxonogenomic approach to fully describe these two new bacterial strains. The Marseille-P2698T strain was a Gram-negative, motile, non-spore-forming, rod-shaped bacterium. The Marseille-P2260T strain was a Gram-positive, motile, spore-forming rod-shaped bacterium. Major fatty acids found in Marseille-P2698T were C15:0 iso (63%), C15:0 anteiso (11%), and C17:0 3-OH iso (8%). Those found in Marseille-P2260T strain were C16:00 (39%), C18:1n9 (16%) and C18:1n7 (14%). Strains Marseille-P2698T and Marseille-P2260T had 16S rRNA gene sequence similarities of 91.50% with Odoribacter laneusT, and of 90.98% and 95.07% with Odoribacter splanchnicusT and Eubacterium sulciT, respectively. The exhibited digital DNA-DNA Hybridization values lower than 20.7%, and Orthologous Average Nucleotide Identity values lower than 73% compared to their closest related bacterial species O. splanchnicusT and E. sulciT respectively. Phenotypic, biochemical, phylogenetic, and genomic results obtained by comparative analyses provided sufficient evidence that both of the two studied strains Marseille-P2698T and Marseille-P2260T are two new bacterial species and new bacterial genera for which the names Culturomica massiliensis gen. nov., sp. nov., and Emergencia timonensis gen. nov., sp. nov. were proposed, respectively.

We describe a new targeted sequencing approach that characterizes the PPE gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This approach has direct implications on the understanding of pathogen diversity and natural history and potential therapeutic implications when dealing with obligate and opportunistic pathogens, such as Mycobacterium ulcerans presented here as a prototype.

BackgroundAlthough previous studies have determined limit values of normality for diaphragm excursion and thickening, it would be beneficial to determine the normal diaphragm motion-to-inspired volume ratio that integrates the activity of the diaphragm and the quality of the respiratory system.MethodsTo determine the normal values of selected ultrasound diaphragm motion-volume indices, subjects with normal pulmonary function testing were recruited. Ultrasound examination recorded diaphragm excursion on both sides during quiet breathing and deep inspiration. Diaphragm thickness was also measured. The inspired volumes of the corresponding cycles were systematically recorded using a spirometer. The indices were calculated using the ratio excursion, or percentage of thickening, divided by the corresponding breathing volume. From this corhort, normal values and limit values for normality were determined. These measurements were compared to those performed on the healthy side in patients with hemidiaphragm paralysis because an increase in hemidiaphragm activity has been previously demonstated in such circumstances.ResultsA total of 122 subjects (51 women, 71 men) with normal pulmonary function were included in the study. Statistical analysis revealed that the ratio of excursion, or percentage of thickening, to inspired volume ratio significantly differed between males and females. When the above-mentioned indices using excursion were normalized by body weight, no gender differences were found. The indices differed between normal respiratory function subjects and patients with hemidiaphragm paralysis (27 women, 41 men). On the paralyzed side, the average ratio of the excursion divided by the inspired volume was zero. On the healthy side, the indices using the excursion and the percentage of thickening during quiet breathing or deep inspiration were significantly increased comparedto patients with normal lung function. According to the logistic regression analysis, the most relevant indice appeared to be the ratio of the excursion measured during quiet breathing to the inspired volume.ConclusionThe normal values of the diaphragm motion-volume indices could be useful to estimate the performance of the respiratory system. Proposed indices appear suitable in a context of hyperactivity.

Background International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. Methods Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers’ first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients’ healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. Results A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18–72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108–$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0–$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0–$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0–$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240–1140) and USD $240 (IQR 0–600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200–3600) and USD $1500 (IQR 510–2625), respectively. Conclusion Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.

Background Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust estimates of malaria prevalence and Plasmodium species from studies conducted in Mauritania and published since 2000. Methods The present review followed the PRISMA guidelines. Searches were conducted in various electronic databases such as PubMed, Web of Science, and Scopus. To obtain pooled prevalence of malaria, meta-analysis was performed using the DerSimonian-Laird random-effects model. Methodological quality of eligible prevalence studies was assessed using Joanna Briggs Institute tool. Inconsistency and heterogeneity between studies were quantified by the I2 index and Cochran’s Q test. Publication bias was assessed with funnel plots and Egger’s regression tests. Results A total of 16 studies with a good individual methodological quality were included and analysed in this study. The overall random effects pooled prevalence of malaria infection (symptomatic and asymptomatic) across all included studies was 14.9% (95% confidence interval [95% CI]: 6.64, 25.80, I2 = 99.8%, P 2 = 99.6%, P 2 = 99.7%, P Plasmodium falciparum and Plasmodium vivax was 51.14% and 37.55%, respectively. Subgroup analysis showed significant variation (P = 0.039) in the prevalence of malaria between asymptomatic and symptomatic cases. Conclusion Plasmodium falciparum and P. vivax are widespread in Mauritania. Results of this meta-analysis implies that distinct intervention measures including accurate parasite-based diagnosis and appropriate treatment of confirmed malaria cases are critical for a successful malaria control and elimination programme in Mauritania.

International audience; miRNAs, small non-coding RNAs that regulate gene expression, are involved in various pathological processes, including viral infections. Virus infections may interfere with the miRNA pathway through the inhibition of genes involved in miRNA biogenesis. A reduction in the number and the levels of miRNAs expressed in nasopharyngeal swabs of patients with severe COVID-19 was lately observed by us, pointing towards the potential of miRNAs as possible diagnostic or prognostic biomarkers for predicting outcomes among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The objective of the present study was to investigate whether SARS-CoV-2 infection influences the expression levels of messenger RNAs (mRNAs) of key genes involved in miRNA biogenesis. mRNA levels of AGO2, DICER1, DGCR8, DROSHA, and Exportin-5 (XPO5) were measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal swab specimens from patients with COVID-19 and controls, as well as in cells infected with SARS-CoV-2 in vitro. Our data showed that the mRNA expression levels of AGO2, DICER1, DGCR8, DROSHA, and XPO5 were not significantly different in patients with severe COVID-19 when compared to patients with non-severe COVID-19 and controls. Similarly, the mRNA expression of these genes was not affected by SARS-CoV-2 infection in NHBE and Calu-3 cells. However, in Vero E6 cells, AGO2, DICER1, DGCR8, and XPO5 mRNA levels were slightly upregulated 24 h after infection with SARS-CoV-2. In conclusion, we did not find evidence for downregulation of mRNA levels of miRNA biogenesis genes during SARS-CoV-2 infection, neither ex vivo nor in vitro.

International audience; Following the publication a few months ago of the new WHO guidelines for malaria, the European pharmacist, even out of endemic areas, as a health care professional and advisor, has a major role to play in their effective implementation and in the interest of public health. The pharmacist is central in the health care system to ensure the correct application of these recommendations and to perform a decisive role in the prevention of malaria infections, both in the adapted pharmaceutical advice on personal protection against biting vector insects on the one hand, and in the pharmaceutical analysis and recommendations concerning antimalarial chemoprophylaxis prescriptions on the other hand. Physicians and pharmacist biologists, as well as hospital pharmacists, are also important for the analysis and treatment of effective malaria cases, particularly in the management of the diagnostic and therapeutic emergency that a P. falciparum infection represents.

Borrelia miyamotoi is a tick-borne zoonotic agent that causes hard tick-borne relapsing fever, an emerging disease in humans. Some small mammalian and bird species are reported to be reservoirs of B. miyamotoi. This study aims to examine Borrelia species present in rodents captured from rural areas of Turkey. Blood samples of rodents were initially screened with Borrelia 16S rRNA qPCR. The Borrelia flaB gene was subsequently amplified by conventional PCR, after which all positive samples were sequenced. Borrelia miyamotoi was observed in nine out of 536 blood samples (1.7%) collected from wild rodents. Phylogenetic analysis showed that all positive samples belonged to the European genotype clade of B. miyamotoi. PCR positivity was 5.3%, 3.7%, and 1.8% in Apodemus uralensis, Apodemus flavicollis, and Myodes glareolus, respectively. Borrelia burgdorferi sensu lato that causes Lyme borreliosis in humans could not be detected in the rodents. In this study, presence of B. miyamotoi DNA is reported for the first time in rodents in Turkey.

International audience; The human immune repertoire retains the molecular memory of a very great diversity of target antigens (epitopes) and can recall this upon a second encounter with epitopes against which it has previously been primed. Although genetically diverse, proteins of coronaviruses exhibit sufficient conservation to lead to antigenic cross-reactions. In this review, our goal is to question whether pre-existing immunity against seasonal human coronaviruses (HCoVs) or exposure to animal CoVs has influenced the susceptibility of human populations to SARS-CoV-2 and/or had an impact upon the physiopathological outcome of COVID-19. With the hindsight that we now have regarding COVID-19, we conclude that although antigenic cross-reactions between different coronaviruses exist, cross-reactive antibody levels (titers) do not necessarily reflect on memory B cell frequencies and are not always directed against epitopes which confer cross-protection against SARS-CoV-2. Moreover, the immunological memory of these infections is short-term and occurs in only a small percentage of the population. Thus, in contrast to what might be observed in terms of cross-protection at the level of a single individual recently exposed to circulating coronaviruses, a pre-existing immunity against HCoVs or other CoVs can only have a very minor impact on SARS-CoV-2 circulation at the level of human populations.

International audience; The benefits of SARS-CoV-2 spike mRNA vaccines are well known, including a significant decline in COVID-19 morbidity and a decrease in the mortality rate of SARS-CoV-2 infected persons. However, pharmacovigilance studies have revealed the existence of rare cases of cardiovascular complications after mass vaccination using such formulations. Cases of high blood pressure have also been reported but were rarely documented under perfectly controlled medical supervision. The press release of these warning signals triggered a huge debate over COVID-19 vaccines’ safety. Thereby, our attention was quickly focused on issues involving the risk of myocarditis, acute coronary syndrome, hypertension and thrombosis. Rare cases of undesirable post-vaccine pathophysiological phenomena should question us, especially when they occur in young subjects. They are more likely to occur with inappropriate use of mRNA vaccine (e.g., at the time when the immune response is already very active during a low-noise infection in the process of healing), leading to angiotensin II (Ang II) induced inflammation triggering tissue damage. Such harmful effects observed after the COVID-19 vaccine evoke a possible molecular mimicry of the viral spike transiently dysregulating angiotensin converting enzyme 2 (ACE2) function. Although the benefit/risk ratio of SARS-CoV-2 spike mRNA vaccine is very favorable, it seems reasonable to suggest medical surveillance to patients with a history of cardiovascular diseases who receive the COVID-19 vaccine.

International audience; Microbial ecology is a critical field for understanding the composition, diversity, and functions of microorganisms in various environmental and health-related processes. The discovery of Candidate Phyla Radiation (CPR) through culture-independent methods has introduced a new division of microbes characterized by a symbiotic/parasitic lifestyle, small cell size, and small genome. Despite being poorly understood, CPRs have garnered significant attention in recent years due to their widespread detection in a variety of environmental and clinical samples. These microorganisms have been found to exhibit a high degree of genetic diversity compared to other microbes. Several studies have shed light on their potential importance in global biogeochemical cycles and their impact on various human activities. In this review, we provide a systematic overview of the discovery of CPRs. We then focus on describing how the genomic characteristics of CPRs have helped them interact with and adapt to other microbes in different ecological niches. Future works should focus on discovering the metabolic capacities of CPRs and, if possible, isolating them to obtain a better understanding of these microorganisms.

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.

Background: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers’ health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. Methods: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). Results: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (−5.3%), rabies post-exposure prophylaxis (−2.8%), and dengue (−2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). Conclusions: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.

International audience

International audience

International audience; Midazolam is a benzodiazepine frequently used for sedation in patients hospitalized in the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19). This drug is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes. Several studies have suggested that inflammation, frequently observed in these patients, could modulate CYP3A activity. The objective of this work was to study the impact of inflammation on midazolam pharmacokinetics in patients with COVID-19. Forty-eight patients hospitalized in the ICU for COVID-19 and treated with midazolam administered by continuous infusion were included in this study. Midazolam and α-hydroxymidazolam concentrations were measured and patient data, including the use of CYP3A inhibitors, were collected. Total and unbound concentrations of midazolam and α-hydroxymidazolam were measured in plasma using a validated liquid-chromatography coupled with mass spectrometry method. Inflammatory condition was evaluated by C-reactive protein (CRP) level measurement. Both drug concentrations and CRP measurements were performed on 354 plasma samples. CRP elevation was significantly associated with the α-hydroxymidazolam/midazolam plasma ratio decrease, whether for the unbound fraction or for the total fraction. Conversely, inflammation was not associated with protein binding modifications. Logically, α-hydroxymidazolam/midazolam plasma ratio was significantly reduced when patients were treated with CYP3A inhibitors. In this study, we showed that inflammation probably reduces the metabolism of midazolam by CYP3A. These results suggest that molecules with narrow therapeutic margins and metabolized by CYP3A should be administrated with care in case of massive inflammatory situations.

International audience; Background: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis.Objectives: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A−).Methods: A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).Results: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A− patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A− patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A− had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A− patients (54%) but in none of the MIS-A+ patients.Conclusion: MIS-A+ and MIS-A− fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology

International audience; Ionised active water S-100® has been proposed as an original solution for use in dermocosmetics and for the treatment of wounds such as burns and atopic dermatitis. Among the mechanisms of action that are not completely understood, an antimicrobial activity would appear to be important. In the context of the COVID-19 pandemic, we assessed the inactivating efficacy of this solution on SARS-CoV-2 based on the recommendations of the NF-EN-14476+A2 standard. The tests carried out demonstrated that ionised active water S-100® 40% has a virucidal activity on SARS-CoV-2 which is at least 3.1 log after a contact time of 30 seconds and 3.5 log after two minutes at 20°C under clean conditions. Assays were also performed at 4°C and 37°C, and the results obtained are identical to those obtained at 20°C. This demonstration of the virucidal effect of ionised water against SARS-CoV-2 paves the way for the development of usage as an alternative disinfectant in SARS-CoV-2 control.

Chryxus garcetebarrettisp. nov. from Paraguay is described, taxonomical notes on C. bahianus Gil-Santana, Costa & Marques, 2007 and C. tomentosus Champion, 1899 are provided; the latter species is recorded from French Guiana for the first time; a redescription of the genus Chryxus Champion, 1899 and an updated key for the genera and species of Chryxinae are presented.

Multiple SARS-CoV-2 variants have successively, or concommitantly spread worldwide since summer 2020. A few co-infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co-detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J/AY.4-Omicron 21K/BA.1 “Deltamicron” recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1,163-1,421 reads and mean nucleotide diversity of 0.1-0.6%. It is composed of the near full-length spike gene (from codons 156-179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening qPCR, we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.