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Early neonatal acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales in Madagascar and Cambodia: clonal and plasmid-level contributions of maternal gut carriage
No full textInternational audienceAbstract Early neonatal infections caused by extended-spectrum-beta-lactamase-producing Enterobacterales (ESBL-PE) are prevalent in low- and middle-income countries, posing significant treatment challenges. This study investigated ESBL-PE colonization in 499 mother-neonate pairs from Madagascar and Cambodia, with stool samples collected at delivery and from neonates before day three. Using short- and long-read sequencing, identical isolates or plasmids were identified within each pair to assess neonatal acquisition from maternal source. Multinomial regression identified associated risk factors. Maternal gut carriage accounted for only 16.5% of neonatal ESBL-PE acquisition, suggesting that most cases originated from other sources. Primiparity and wet season were associated with an increased risk of acquisition from the mother, while cesarean delivery, neonatal resuscitation, and wet season were associated with acquisition from other sources. These findings challenge the paradigm that maternal carriage is the primary source of early neonatal ESBL-PE colonization, highlighting the need for further research into alternative sources to inform targeted interventions
Plasmacytoid dendritic cell sensing of hepatitis E virus is shaped by both viral and host factors
No full textInternational audienceType I and III interferons critically protect the host against viral infection. Previous studies showed that IFN responses are suppressed in cells infected by hepatitis E virus (HEV). Here, we studied the anti-HEV function of IFN secreted by plasmacytoid dendritic cells (pDCs), specialized producers of IFNs. We showed that pDCs co-cultured with HEV-replicating cells secreted IFN in a cell contact–dependent manner. This pDC response required the endosomal nucleic acid sensor TLR7 and adhesion molecules. IFNs secreted by pDCs reduced viral spread. Intriguingly, ORF2, the capsid protein of HEV, can be produced in various forms by the infected cells, and we wanted to study their role in anti-HEV immune response. During infection, a fraction of ORF2 localizes into the nucleus, and glycosylated forms of ORF2 are massively secreted by infected cells. We showed that glycosylated ORF2 potentiates the recognition of infected cells by pDCs, by regulating cell contacts. On the other hand, nuclear ORF2 triggers immune response by IRF3 activation. Together, our results suggest that pDCs may be essential to control HEV replication
Comparison of GLI-2021 standards with ECSC standards for static lung volume interpretation in patients with respiratory diseases.
No full textInternational audienceBackgroundIn 2021, the Global Lung Function Initiative (GLI) has published new reference equations for static lung volumes (GLI-2021). Many learned societies recommend the use of GLI reference values for interpreting pulmonary function tests (PFT), while pointing out the need for clinicians to be aware of the consequences for their routine practice. We aimed to compare the GLI-2021 reference values and the 1993 European Coal and Steel Community (ECSC) standards on the interpretation of static lung volume data in patients with a probable static hyperinflation or a probable restrictive ventilatory disorder.MethodsWe analyzed plethysmographic PFT data from 2 groups of patients: a group of patients with symptoms compatible with chronic bronchitis (CB) and a group of patients with symptoms compatible with interstitial lung disease (ILD). We investigated discrepancies in the evaluations of static lung volumes when using the ECSC vs. the GLI-2021 reference values.Results2897 sets of PFT results (including 1598 in men) were included. In the CB group, the proportion of hyperinflation was higher for both sexes with the GLI-2021 standards. In the ILD group, the proportion of restrictive ventilatory disorders was higher in women but lower in men with the GLI-2021 standards.ConclusionA move from use of the ECSC standards for static lung volumes to the GLI-2021 standards might lead to a higher estimated proportion of hyperinflation (particularly in participants with CB), together with changes in the proportion of restrictive ventilatory disorders (a lower value in men and a higher value in women with ILD)
The Global Influenza Hospital Surveillance Network: A Multicountry Public Health Collaboration
No full textInternational audienceRespiratory viruses represent a significant public health threat. There is the need for robust and coordinated surveillance to guide global health responses. Established in 2012, the Global Influenza Hospital Surveillance Network (GIHSN) addresses this need by collecting clinical and virological data on persons with acute respiratory illnesses across a network of hospitals worldwide. GIHSN utilizes a standardized patient enrolment and data collection protocol across its study sites. It leverages pre-existing national infrastructures and expert collaborations to facilitate comprehensive data collection. This includes demographic, clinical, epidemiological, and virologic data, and whole genome sequencing (WGS) for a subset of viruses. Sequencing data are shared in the Global Initiative on Sharing All Influenza Data (GISAID). GIHSN uses financing and governance approaches centered around public-private partnerships. Over time, GIHSN has included more than 100 hospitals across 27 countries and enrolled more than 168,000 hospitalized patients, identifying 27,562 cases of influenza and 44,629 of other respiratory viruses. GIHSN has expanded beyond influenza to include other respiratory viruses, particularly since the COVID-19 pandemic. In November 2023, GIHSN strengthened its global impact through a memorandum of understanding with the World Health Organization, aimed at enhancing collaborative efforts and data sharing for improved health responses. GIHSN exemplifies the value of integrating scientific research with public health initiatives through global collaboration and public-private partnerships governance. Future efforts should enhance the scalability of such models and ensure their sustainability through continued public and private support
The Role of Ruminants as Sentinel Animals in the Circulation of the West Nile Virus in Tunisia
No full textInternational audienceOutbreaks of the West Nile Virus (WNV) have increased significantly in recent years in the Mediterranean region, including Tunisia. To understand the risks for animal and human health and to mitigate the impact of future outbreaks, comprehensive viral surveillance in vertebrate hosts and vectors is needed. We conducted the first serosurvey for the WNV in ruminants in southern Tunisia using the ELISA test and confirmed it with the micro-virus neutralization test (VNT). Antibodies were detected by the ELISA test in camels (38/112), sheep (9/155), and goats (7/58), and six samples were doubtful (five camels and one sheep). The ELISA positive and doubtful sera (n = 60) were further analyzed to confirm the presence of specific anti-WNV and anti-Usutu virus (USUV) antibodies using the micro-virus neutralization test (VNT). Out of the 60 sera, 33 were confirmed for specific WNV antibodies, with an overall seroprevalence of 10.15% [95% CI: 7.09–13.96]. The high seroprevalence observed in camels (22.3%) suggests their potential use as sentinel animals for WNV surveillance in southern Tunisia. The viral genome, and consequently active circulation, could not be detected by real-time RT-qPCR in blood samples. Ongoing surveillance of the WNV in animals, including camels, sheep, and goats, may be used for the early detection of viral circulation and for a rapid response to mitigate potential outbreaks in horses and humans
Detection of abortifacient agents in domestic ruminants, with a specific focus on Coxiella burnetii
No full textV1-First publishedInternational audienceQ fever is a widespread zoonotic disease caused by the bacterium, Coxiella burnetii. In ruminants, C. burnetii can cause abortions, stillbirths, premature births, and weak offspring. As part of the EUfunded Q-Net-Assess International Coordination of Research on Infectious Animal Diseases (ICRAD)-project, aimed at generating the most comprehensive understanding of C. burnetii genetic variation to date and determining the implications of this genetic variation for zoonotic risk, pathogenicity and control of C. burnetii infection, we have reviewed the protocols reported by the different project partners and/or countries to diagnose abortion in domestic ruminants. As a result of this review, we have developed guidelines for the detection of abortifacient agents in domestic ruminants, with a special focus on C. burnetii. They include a description of the essential and complementary samples needed for a definitive diagnosis, the analytical techniques to be used, and the interpretation and validity of each type of sample and technique. The most comprehensive diagnostic approach to identify an infectious agent as the cause of abortion in ruminants would include histopathology, including immunohistochemistry (IHC), on the fetus and placental membranes, complemented by bacteriology, serology, and real-time PCR analyses of different types of samples. For the specific diagnosis of C. burnetii Open Peer Review Approval Status AWAITING PEER REVIEWAny reports and responses or comments on the article can be found at the end of the article</div
Anti-GAD Antibodies as an Etiology of Cerebral Cortical Encephalitis: 2 Case Reports.
No full textInternational audienceIntroduction: Cerebral cortical encephalitis (CCE) has been recently described as an entity associated with anti-MOG antibod-ies and, in some cases, of anti- GABA A R encephalitis. No clear association with other antibodies has been reported to date. Wedescribe two cases of patients presenting clinical and radiological features of diffuse cortical encephalitis associated with anti-GAD antibodies.Method: In two patients with CCE, screening for the presence of anti- GAD and other antibodies was performed, along with acomplete workup for alternative diagnoses.Results: Two patients showing clinical and radiological features of CCE were tested positive for anti- GAD antibodies. MRI scanrevealed multiple bilateral areas of cortico-subcortical FLAIR hyperintensities. They were both tested negative for anti-MOG,anti-NMDAr, and anti- GABA A R antibodies. An ovarian teratoma was discovered in patient 1. Clinical and radiological evolutionwas favorable in both patients after cumulated therapies in the acute phase.Discussion: CCE could be a new manifestation of anti- GAD antibodies, with distinct features compared to anti-MOG antibodiesrelated to CCE. We recommend screening for anti- GAD antibodies in the context of CCE, especially in case of atypical featuresfor MOG antibodies-associated disease (MOGAD)
High circulation of pertussis in infants and close contacts in Antananarivo, the capital of Madagascar in Africa, and Cambodia in Asia
No full textInternational audienceBackgroundReliable data on whooping cough, a highly contagious disease sometimes fatal for infants, are largely lacking in low- and middle-income countries.MethodsWe conducted a hospital-based prospective study (PS) on infants, and a household contact-case investigation (CCI) for positive cases throughout Cambodia and in the city of Antananarivo, Madagascar, between 2017 and 2019. The PS, in which Bordetella diagnostics (qPCR) were performed, included infants aged ≤6 months presenting with ≥5 days of cough associated with one pertussis-like symptom. CCI was performed using qPCR and serology regardless of clinical signs.ResultsIn this study, 207 and 173 participants from Cambodia and Antananarivo were respectively enrolled. Respectively 26.1% (54/207) and 22.0% (38/173) of the infants were infected in the cohorts from Cambodia and Antananarivo. Cough longer than 10 days appeared as a risk factor in both countries, as well as coughing spells, apnea and normal pulmonary auscultation, having a coughing contact in Cambodia. In Antananarivo, being clinically well between coughing spells appeared as a risk factor. Five infants, all positive, died during the study. In Cambodia and Antananarivo respectively, 50.9% (118/232) and 67.8% (82/121) of the contact cases were positive. Respectively 94.4% (51/54) and 90.3% (28/31) of the households had at least one positive contact case.ConclusionThe data show that pertussis circulates at high levels among infants and in their households both in Cambodia and in Antananarivo. Given the vulnerability of youngest infants, who are too young to receive fully primary vaccination, they need to be protected through boosters breaking transmission chains. Molecular diagnosis, as well as trained medical human resources to detect the disease early, are absolutely key to protect populations
Ixazomib, pomalidomide and dexamethasone in relapsed or refractory multiple myeloma characterized with high-risk cytogenetics: the IFM 2014-01 study
No full textInternational audienc
Decavanadate Compound Displays In Vitro and In Vivo Antitumor Effect on Melanoma Models
No full textInternational audienceThe efficacy of available treatments for melanoma is limited by side effects and the rapidly emerging resistance to treatment. In this context, the decavanadate compounds represent promising tools to design efficient therapeutic agents. In our study, we synthesized a dimagnesium disodium decavanadate icosahydrate compound (Mg2Na2V10O28·20H2O) and investigated its structure stability as well as its antimelanoma effects. Results showed that the Mg2Na2V10O28·20H2O compound is structured in a monoclinic system with the space group C2/c, stabilized by oxygen vertices, hydrogen bonds, and van der Waals interactions. Interestingly, we found that this newly synthesized compound reduced the viability of human (IGR39, IGR37, and SKMEL28) and murine (B16-F10) melanoma cells in a dose-dependent manner. The IC50 values ranged from 7.3 to 18 μM after 24 h and decreased to 1.4 μM after 72 h of treatment. Notably, this effect was more important than that of cisplatin (IC50 = 3 μM after 72 h of treatment), a chemotherapeutic agent, commonly used in the treatment of malignant melanoma. Furthermore, the cytotoxicity of the decavanadate compound was relatively weak on normal human keratinocytes (HaCaT), with a light effect (IC50 >> 70 μM) observed after 24 h of treatment. Thus, the Mg2Na2V10O28·20H2O compound displayed an advantage over cisplatin, which was reported to be much more aggressive to the keratinocyte cell line (IC50 = 23.9 μM). Moreover, it inhibited dose-dependently the adhesion of IGR39 cells to collagen (IC50 = 2.67 μM) and fibronectin, as well as their migration with an IC50 value of 2.23 μM. More interestingly, its in vivo administration to B16-F10 allografted mice, at the nontoxic dose of 50 μg (2.5 mg/kg), prevented and suppressed by 70% the tumor growth, compared to the nontreated mice. Moreover, this compound has also allowed a recovery against inflammation induced in mice by a mixture of DMBA and croton oil. Thus, all our results showed the potential of the Mg2Na2V10O28·20H2O compound to prevent and efficiently treat the growth and metastasis of melanoma