Repurposing of Drugs as Novel Influenza Inhibitors From Clinical Gene Expression Infection Signatures

Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials. We exploited in vivo global transcriptomic signatures of infection directly obtained from a patient cohort to determine a shortlist of already marketed drugs with newly identified, host-targeted inhibitory properties against influenza virus. The antiviral potential of selected repurposing candidates was further evaluated in vitro, in vivo, and ex vivo. Our strategy allowed the selection of a shortlist of 35 high potential candidates out of a rationalized computational screening of 1,309 FDA-approved bioactive molecules, 31 of which were validated for their significant in vitro antiviral activity. Our in vivo and ex vivo results highlight diltiazem, a calcium channel blocker currently used in the treatment of hypertension, as a promising option for the treatment of influenza infections. Additionally, transcriptomic signature analysis further revealed the so far undescribed capacity of diltiazem to modulate the expression of specific genes related to the host antiviral response and cholesterol metabolism. Finally, combination treatment with diltiazem and virus-targeted oseltamivir neuraminidase inhibitor further increased antiviral efficacy, prompting rapid authorization for the initiation of a Phase II clinical trial. This original, host-targeted, drug repurposing strategy constitutes an effective and highly reactive process for the rapid identification of novel anti-infectious drugs, with potential major implications for the management of antimicrobial resistance and the rapid response to future epidemic or pandemic (re)emerging diseases for which we are still disarmed

Emergence of melioidosis in the Indian Ocean region: Two new cases and a literature review.

Melioidosis is a disease caused by bacteria called B. pseudomallei. Infections can develop after contact with standing water. This disease can reach all the organs and especially the lungs. It is associated with a high mortality rate (up to 50%). Melioidosis is endemic in northern Australia and in Southeast Asia. Nevertheless, B. pseudomallei may be endemic in the Indian Ocean region and in Madagascar in particular, so clinicians and microbiologists should consider acute melioidosis as a differential diagnosis in the Indian Ocean region, in particular from Madagascar

SARS-CoV-2 with Panton-Valentine leukocidin-producing Staphylococcus aureus healthcare-associated pneumonia in the Indian Ocean

At this time, the literature reports only one case of superinfection with Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus in a patient with severe acute respiratory distress syndrome secondary to coronavirus 2 (SARS-CoV-2) pneumonia. Here we report the first two cases of PVL-producing S. aureus healthcareassociated pneumonia in patients hospitalized for SARS-CoV-2 pneumonia in the Indian Ocean region. The two isolated strains of S. aureus were found to belong to the ST152/t355 clone, a known PVL-producing S. aureus clone that circulates in Africa and is responsible for infections imported into Europe. Our two cases reinforce the hypothesis that SARS-CoV-2 infection favors the occurrence of PVL-producing S. aureus pneumonia. Production of PVL should be searched in patients returning from the Indian Ocean region who present with severe SARS-CoV-2 pneumonia complicated by superinfection with S. aureus even in the case of late onset healthcare-associated pneumonia Dear Editor, Bacterial superinfections in patients with severe acute respiratory distress syndrome secondary to coronavirus 2 (SARS-CoV-2) pneumonia are relatively rare and are often caused by Staphylococcus aureus [1]. At this time, the literature reports only one case of superinfection with Panton-Valentine leukocidin (PVL)-producing S. aureus in a patient with SARS-CoV-2 pneumonia[2]. Here we report the first two cases of PVL-producing S. aureus healthcare-associated pneumonia in patients hospitalized for SARS-CoV-2 pneumonia in the Indian Ocean region

Case Report: Emergence of Candida auris in the Indian Ocean Region

International audienceCandida auris is an emerging multidrug-resistant yeast that can cause severe infections and spread easily between hospitalized patients, leading to outbreaks in hospital. Here, we report the first four cases of colonization and invasive infection with C. auris reported in the Indian Ocean region. All cases were observed in the French overseas Reunion Island, a very popular destination for European travelers. Three patients had urinary tract or skin colonization, and one had a fatal invasive infection. In three cases, including that of the infected patient, the yeast was not initially identified as C. auris , preventing specific hygiene measures to be implemented as suggested in the December 2016 clinical alert to European healthcare facilities. The infected patient likely acquired C. auris in the intensive care unit from the first colonized patient. This is the first case of C. auris infection and the first potential case of nosocomial transmission of the pathogen to be reported in the French overseas Reunion Island

Human Papillomavirus (HPV) Infections Among Participants Undergoing Chlamydia trachomatis Testing in Reunion Island (RUN-SurV-HPV Study): Protocol for a Prevalence Study

BackgroundInfection by human papillomavirus (HPV) induces various cancers, mainly cervical cancer but also anal and pharyngeal cancers. Reunion Island is a French department in the Indian Ocean. Due to the history of its settlement, the island’s population has a wide variety of origins, and the population’s sociodemographic characteristics differ from those of the French mainland. These characteristics make the island’s population an original French population in its own right, particularly in terms of health. Cervical cancer incidence and mortality in Reunion Island are 10.4 per 100,000 and 4.4 per 100,000, respectively, both of which are much higher than those in mainland France. There is also a disparity in the prevalence of different HPV types, with types 33 and 52 being overrepresented and type 18 being underrepresented. However, vaccination and screening coverage in Reunion Island is low. It is important to understand the burden of infection and its risk factors in members of the young Reunionese population at risk of HPV infection to promote and evaluate the implementation of future vaccination and screening programs on a larger scale. ObjectiveThe RUN-SurV-HPV study will have the following four objectives: (1) to describe the prevalence of HPV genotypes in a population at risk of sexually transmitted infections in Reunion Island; (2) to describe the prevalence of HPV genotypes by anatomical site, gender, and sexuality; (3) to describe the correlates and risk factors for HPV detection; and (4) to examine HPV genotypes between different anatomical sites. MethodsCross-sectional analyses of 1200 routine vaginal, anal, pharyngeal, and urinary samples collected between October 2020 to December 2022 from female and male patients aged 16 to 30 years undergoing Chlamydia trachomatis testing at a sexually transmitted infection (STI) testing center at Reunion Island will be performed. The population included 333 women who all had vaginal and pharyngeal swabs, with 80 of them also having had an anal swab. There are 167 men who have sex with men who have had anal and pharyngeal swabs, and 120 men who have sex with women who have had a urine swab only. Results will be correlated with sociodemographic and clinical data collected routinely during the consultations. HPV detection and genotyping will be performed using the Anyplex II HPV28 detection assay (Seegene). ResultsThe first polymerase chain reactions should begin in November 2023. The first results should be submitted for publication in 2024. ConclusionsThe study will determine HPV prevalence by age, sex, male sexual preference, human immunodeficiency virus status, and STI co-infection. Collecting data from young patients not usually routinely screened for HPV infection will be a simple and reproducible way of better understanding local specificities, encouraging vaccination campaigns in the short-term, and evaluating their effectiveness in the future. International Registered Report Identifier (IRRID)DERR1-10.2196/4737

Multifocal cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides in an immunocompromised patient: A case report

International audienc

Trametes polyzona, an emerging filamentous basidiomycete in Reunion Island

We describe two serious Trametes polyzona pulmonary infections, which occurred in Reunion Island, in critically ill patients. The identification was performed using sequencing of the internal transcribed spacer region of ribosomal DNA and D1/D2 region of 28S rDNA. In one case, the significance of T.polyzona in the pathological process was certain, proven by histopathological evidence of fungal lung infection. T.polyzona, an emerging filamentous basidiomycete, prevalent in tropical areas, has not been described so far in human infections

Severe community-acquired pneumonia in Reunion Island: Epidemiological, clinical, and microbiological characteristics, 2016–2018

No data are available on severe community-acquired pneumonia (CAP) in the French overseas department of Reunion Island. This is unfortunate as the microorganisms responsible for the disease are likely to differ from those in temperate regions due to a tropical climate and proximity to other islands of the Indian Ocean region. The aim of this study was to assess the epidemiological, clinical, prognosis, and microbiological characteristics of patients with severe CAP in Reunion Island. Materials and methods This retrospective study evaluated all patients with CAP aged >18 years and hospitalized in one of the two intensive care units of Reunion Island between 2016 and 2018. Microorganisms were identified by culture from blood and respiratory samples, multiplex polymerase chain reaction from respiratory samples, urinary antigen tests, and serology. Results Over the study period, 573 cases of severe CAP were recorded, with a mean incidence of 22 per 100,000 person-years. The most frequently isolated microorganism was influenza (21.9%) followed by Streptococcus pneumoniae (12%). The influenza virus was detected in affected patients all year round. Twenty-four patients with severe CAP came from another island of the Indian Ocean region (4.2%), mainly Madagascar (>50%). Two of these patients presented with melioidosis and 4 were infected with Acinetobacter spp

Characteristics of the patients with melioidosis in Indian Ocean region.

<p>Characteristics of the patients with melioidosis in Indian Ocean region.</p