Publications of Marie-Pierre HAYETTE
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See detailClinical course and challenging management of early COVID-19 infection after heart transplantation: case report of two patients
TCHANA-SATO, Vincent ULiege; ANCION, Arnaud ULiege; TRIDETTI, Julien ULiege et al

in BMC Infectious Diseases (2021)

Background: There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series ... [more ▼]

Background: There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series described so far. Heart transplant recipients may be at particular high risk due to their comorbidities and immunosuppressed state. Case presentation: This report describes the clinical course and the challenging management of early COVID-19infection in two heart transplant recipients who tested positive for the SARS-CoV-2 virus in the perioperative period of the transplant procedure. The two patients developed a severe form of the disease and ultimately died despite the initiation of an antiviral monotherapy with hydroxychloroquine coupled with the interruption of mycophenolate mofetil. Conclusions: These two cases illustrate the severity and poor prognosis of COVID-19 in the perioperative period of a heart transplant. Thorough screening of donors and recipients is mandatory, and the issue of asymptomatic carriers needs to be addressed. [less ▲]

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See detailThe lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC)
Yobi, Doudou; Kayiba, Nadine; Mvumbi, Dieudonné et al

in PLoS ONE (2020), 15(8),

Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since ... [more ▼]

Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since 2005 in Democratic Republic of Congo (DRC) and a regular surveillance of the ACT efficacy is required to ensure the treatment effectiveness. Mutations in the propeller domain of the pfk13 gene were identified as molecular markers of artemisinin resistance (ART-R). This study investigated the pfk13-propeller gene polymorphism in clinical isolates of P. falciparum collected in the DRC. In 2017, ten geographical sites across DRC were selected for a cross-sectional study that was conducted first in Kinshasa from January to March, then in the nine other sites from September to December. Dried blood samples were collected from patients attending health centers for fever where diagnosis of Malaria was first made by rapid diagnostic test (RDT) available on site (SD Bioline malaria Ag Pf or CareStart Malaria Pf) or by thick blood smear and then confirmed by a P. falciparum real-time PCR assay. A pfk13-propeller segment containing a fragment that codes for amino acids at positions 427-595 was amplified by conventional PCR before sequencing. In total, 1070 patients were enrolled in the study. Real-time PCR performed confirmed the initial diagnosis of P. falciparum infection in 806 samples (75.3%; 95% CI: 72.6%- 77.9%). Of the 717 successfully sequenced P. falciparum isolates, 710 (99.0%; 95% CI: 97.9% - 99.6) were wild-type genotypes and 7 (1.0%; 95% CI: 0.4% - 2.1%) carried non-synonymous (NS) mutations in pfk13-propeller including 2 mutations (A578S and V534A) previously detected and 2 other (M472I and A569T) not yet detected in the DRC. Mutations associated with ART-R in Southeast Asia were not observed in DRC. However, the presence of other mutations in pfk13-propeller gene calls for further investigations to assess their implication in drug resistance. [less ▲]

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See detailEvaluation of the new Id-Fungi plates from Conidia for MALDI-TOF MS identification of filamentous fungi and comparison with conventional methods as identification tool for dermatophytes from nails, hair and skin samples
SACHELI, Rosalie ULiege; Henri, Anne-Sophie ULiege; SEIDEL, Laurence ULiege et al

in Mycoses (2020)

Objectives: We first compare the efficiency of mould/dermatophytes identification by MALDI-TOF MS using a new medium called Id-Fungi plates (IDFP) from Conidia® and two different databases. For the second ... [more ▼]

Objectives: We first compare the efficiency of mould/dermatophytes identification by MALDI-TOF MS using a new medium called Id-Fungi plates (IDFP) from Conidia® and two different databases. For the second purpose, we evaluated a new version of the medium supplemented with cycloheximide, Id-Fungi plates Plus (IDFPC) for the direct inoculation of nails, hair and skin samples and compared the efficiency of MALDI-TOF MS identification of dermatophytes to classical methods based on culture and microscopy. Methods: A total of 71 strains have been cultured IDFP and Sabouraud gentamicin plates (SGC2) and were identified by MALDI-TOF MS. For the evaluation of the combination IDFPC/ MALDI-TOF MS as a method of identification for dermatophytes, 428 samples of hair nails and skin were cultivated in parallel on IDFPC and Sabouraud + cycloheximide medium (SAB-ACTI ). Results: For Aspergillus sp. and non-Aspergillus moulds, the best performances were obtained on IDFP after maximum 48h growth, following protein extraction. For dermatophytes, the best condition was using the IDFP at 72h, after extended direct deposit. Regarding the direct inoculation of nails, hair skin on IDFPC, 129/428 (30.1%) showed a positive culture against 150/428 (35%) on SAB-ACTI medium. Among the 129 positive strains the identification by MALDI-TOF MS was correct for 92/129 (71.4%). Conclusion: The IDFP allows the generation of better spectra by MALDI-TOF MS compared to SGC2. It facilitates sampling and deposit. Regarding the use of IDFPC, this medium seems less sensitive than SAB-ACTI but among positive strains, the rate of correct identification, by MALDI-TOF MS is satisfactory. [less ▲]

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See detailA phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages
Dellicour, Simon; Durkin, Keith ULiege; Hong, Samuel et al

E-print/Working paper (2020)

Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of the causative virus (SARS-CoV-2) have been publicly released. The resulting volume of available genetic data ... [more ▼]

Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of the causative virus (SARS-CoV-2) have been publicly released. The resulting volume of available genetic data presents a unique opportunity to gain real-time insights into the pandemic, but also a daunting computational hurdle if analysed with gold-standard phylogeographic methods. We here describe and apply an analytical pipeline that is a compromise between fast and rigorous analytical steps. As a proof of concept, we focus on Belgium, one of the countries with the highest spatial density of sequenced SARS-CoV-2 genomes. At the global scale, our analyses confirm the importance of external introduction events in establishing transmission chains in the country. At the country scale, our spatially-explicit phylogeographic analyses highlight an impact of the national lockdown of mid-March on the dispersal velocity of viral lineages. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement. [less ▲]

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See detailVariability and target attainment of fluconazole in critically ill patients
Van Daele, Ruth; Wauters, Joost; Brüggemann, Roger J. et al

Poster (2020, April 21)

Background: Fluconazole is an antifungal drug frequently used in the intensive care unit (ICU) but few data are available regarding its exposure in this population. A subanalysis of the DALI-study raised ... [more ▼]

Background: Fluconazole is an antifungal drug frequently used in the intensive care unit (ICU) but few data are available regarding its exposure in this population. A subanalysis of the DALI-study raised some concerns considering variability in exposure and inadequate target attainment in critically ill patients. We aimed to determine fluconazole variability and target attainment at the ICU. Materials/methods: All adult, critically ill patients treated with intravenous fluconazole between May and September 2019 were included, provided that the DNR code was <2 and written informed consent was obtained. The administered dose was left at the discretion of the treating clinician. Trough samples were collected during a maximum period of 15 days. Samples were analysed using an UPLC-DAD analytic method. The intra-and intersubject variability of fluconazole trough concentrations was calculated by dividing the standard deviation by the mean*100. Moreover, the difference between the maximum and minimum fluconazole concentration within each patients was determined. For target attainment, the fAUC/MIC from clinical data amounts to 100 corresponding with trough levels >10-15 mg/L, as recommended by EUCAST and ECIL-6. The limit for toxicity was set on 50 mg/L. Results: Seventeen patients were included, resulting in 95 fluconazole trough levels. Patients had a median APACHE-II score of 18 [16-23] and administered dose of 5.1 [4.1-7.5] mg/kg/day. The median fluconazole trough level was 26.6 [19.7-35.3] mg/L. In Figure 1, fluconazole trough concentrations are depicted in function of the dose. The mean intra-and intersubject variability (CV%) were 18,4% and 34,5%, respectively. The median difference between the maximum and minimum concentration for the 14 patients with >1 measured fluconazole level, was 14,8 [6,6-18,9] mg/L. In two patients, this difference was more than 2-fold. All trough levels were >10mg/L and 85/95 (89%) samples were >15mg/L. None of the levels exceeded the upper limit of 50 mg/L. Conclusions: As shown in the DALI-study, a considerable intra-and intersubject variability in fluconazole levels was observed at the ICU. Despite this variability, all fluconazole trough levels were above the lower limit of 10 mg/L and most of them >15 mg/L. No toxic concentrations were observed. [less ▲]

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See detailMulticentre validation of a EUCAST method for the antifungal susceptibility testing of microconidia-forming dermatophytes
Arendrup, Maiken; Jorgensen, Karin; Guinea, Jesus et al

Poster (2020, April)

Background: Terbinafine resistance is increasingly reported in Trichophyton rubrum and Trichophyton interdigitale rendering susceptibility testing important particularly in non-responding cases. We ... [more ▼]

Background: Terbinafine resistance is increasingly reported in Trichophyton rubrum and Trichophyton interdigitale rendering susceptibility testing important particularly in non-responding cases. We performed a multicentre evaluation of a recently proposed modified EUCAST method implementing medium supplemented with chloramphenicol and cycloheximide (CC) to avoid contamination. Materials/methods: A blinded panel of wild-type and squalene epoxidase (SQLE) target gene mutant T. rubrum and T. interdigitale strains were distributed to 10 European laboratories. Susceptibility to terbinafine, itraconazole, voriconazole and amorolfine) were performed according to the E.Def 9.3.1 method with and without addition of chloramphenicol and cycloheximide (final concentrations 50 mg/L and 300 mg/L, respectively). Plates were incubated at 25 °C (one laboratory used 30 °C) for 5-7 days until sufficient growth. MICs were determined visually (ignoring trailing growth for itraconazole) and spectrophotometrically with 90% and 50% endpoints yielding a total of 7,829 MICs. A. flavus ATCC 204304 and A. flavus CNM-CM1813 were included as controls. Results: 100%/96% (voriconazole) and 84%/84% (itraconazole) MIC determinations fell within the QC ranges for the two QC strains, respectively, and 96%/92% terbinafine MICs fell in a 0.25-1 mg/L 3 two-fold-dilution range suggesting a high interlaboratory reproducibility. Across the six methods, the number of terbinafine MEs varied from 2 (2.6%) to 5 (6.6%) for T. rubrum and between 0 and 2 (2.0%) for T. interdigitale (lowest for the CC-method (2.6%-4.4%/ 0-1% for T. rubrum/T. interdigitale). The difference between the modes for the wt and mutant population were ≥7 two-fold-dilutions in all cases (Table). If excluding a I121M/V237I T. rubrum mutant, and two mixed T. interdigitale strains, the number of VMEs were CC visual: T. rubrum: 1/77 (1.3%), CC spec-90%: 3/68 (4.4%) and CC spec-50%: 1/76 (1.3%), and none for T. interdigitale. The activity of voriconazole, itraconazole and amorolfine were quite uniform against T. rubrum and T. interdigitale, but unacceptably wide MIC ranges were found for the visual and spec-90% inhibition methods for itraconazole (data not shown). Conclusions: Although none of the laboratories perform dermatophyte testing at a regular basis an acceptable interlaboratory agreement and good separation between SQLE wt and mutants were found, suggesting a robust performance of the proposed method. [less ▲]

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See detailMolecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance
Yobi, Doudou; Kayiba, Nadine; Mvumbi, Dieudonné et al

in Malaria Journal (2020), 19(121),

Background: The loss of chloroquine (CQ) efectiveness has led to its withdrawal from national policies as a frst-line treatment for uncomplicated malaria in several endemic countries, such as the ... [more ▼]

Background: The loss of chloroquine (CQ) efectiveness has led to its withdrawal from national policies as a frst-line treatment for uncomplicated malaria in several endemic countries, such as the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identifed as a marker of CQ resistance and the SVMNT haplotype in codons 72–76 on the same gene has been associated with resistance to amodiaquine (AQ). In the DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of this study was to determine the prevalence of K76T mutations in circulating strains of Plasmodium falciparum, 16 years after CQ withdrawal in the DRC and to investigate the presence of the SVMNT haplotype. Methods: In 2017, ten geographical sites across the DRC were selected. Dried blood samples were collected from patients attending health centres. Malaria was frst detected by a rapid diagnostic test (RDT) available on site (SD Bioline Malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confrmed by a P. falciparum species-specifc real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72–76 was amplifed by conventional PCR before sequencing. Results: A total of 1070 patients were enrolled. Of the 806 PCR-confrmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 samples (28.5%; 95% CI 25.4%–31.9%), mainly (96%) with the CVIET haplotype. Prevalence of CQ resistance marker was unequally distributed across the country, ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. Conclusion: Overall, the frequency of the P. falciparum CQ resistance marker has decreased signifcantly and no resistance marker to AQ was detected in the DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for continuous monitoring of the CQ resistance level for its prospective re-use in malaria management. The absence of the AQ resistance marker is in line with the use of this drug in the current DRC malaria treatment policy. [less ▲]

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See detailBelgian national survey on tinea capitis: epidemiological considerations and highlight of terbinafine resistant T. mentagrophytes with a mutation on SQLE gene
SACHELI, Rosalie ULiege; Harag, Saadia; Dehavay, Florence et al

in Journal of Fungi (2020)

Background: In this last decade, a huge increase in African anthropophilic strains causing tinea capitis has been observed in Europe. The Belgian National Reference Center for Mycosis (NRC) conducted a ... [more ▼]

Background: In this last decade, a huge increase in African anthropophilic strains causing tinea capitis has been observed in Europe. The Belgian National Reference Center for Mycosis (NRC) conducted a surveillance study on tinea capitis in 2018 to learn the profile of circulating dermatophytes. Methods: Belgian laboratories were invited to send all dermatophyte strains isolated from the scalp with epidemiological information. Strain identification was confirmed by ITS (Iinternal Ttranscribed Sspacer) sequencing. Mutation in the squalene epoxidase (SQLE) gene was screened by PCR. Results: The main population affected by tinea capitis was children from 5–9 years. Males were more affected than females. The majority of the strains were collected in the Brussels area followed by the Liege area. Among known ethnic origins, African people were more affected by tinea capitis than European people. The major aetiological agent was Microsporum audouinii, followed by Trichophyton soudanense. One strain of Trichophyton mentagrophytes has been characterized to have a mutation on the squalene epoxidase gene and to be resistant to terbinafine. Conclusions: African anthropophilic dermatophytes are mainly responsible for tinea capitis in Belgium. People of African origin are most affected by tinea capitis. The monitoring of terbinafine resistance among dermatophytes seems necessary as we have demonstrated the emergence of resistance in T. mentagrophytes. [less ▲]

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See detailClassification of dermatophytes by a multilocus phylogenetic approach based on Tef-1α, beta tubulin and ITS genes
SACHELI, Rosalie ULiege; Tomé, Carolina; ADJETEY BAHUN, Akolé ULiege et al

in Mycoses (2019, October)

Objectives: Identification of dermatophytes to the species level is epidemiologically, ecologically and therapeutically significant. The use of phylogenetic species concepts based on rDNA internal ... [more ▼]

Objectives: Identification of dermatophytes to the species level is epidemiologically, ecologically and therapeutically significant. The use of phylogenetic species concepts based on rDNA internal transcribed spacer (ITS) regions have improved the taxonomy of dermatophytes. However, it has been shown that for some species, confirmation and refinement using other genes are needed. Indeed, there are problems with accurate definition and characterization of dermatophytes especially among the Trichophyton mentagrophytes series. Intra- and interspecies variations of the translation elongation factor 1-α (Tef-1α) gene were evaluated as a new identification marker in a wide range of dermatophytes. The aim of this study was to evaluate the discriminatory power of a phylogenetic tool based on concatenated sequences of three genomic regions including Tef-1α, ITS (ITS1 to ITS2) and beta-tubulin to differentiate: 1/ the anthropophilic Trichophyton interdigitale species from the zoophilic Trichophyton mentagrophytes 2/ the two closely related African anthropophilic species Trichophyton violaceum from Trichophyton soudanense. Methods: 26 well characterized strains of T. interdigitale/mentagrophytes have been selected including 3 IHEM reference strains; 30 well characterized strains of T. soudanense/T.violaceum including 2 IHEM reference strains were also included. All strains were submitted to ITS, beta-tubulin and Tef-1α PCR/sequencing. Moreover, identification was completed by real time PCR DermaGenius® (PathoNostics). Alignments were performed using MUSCLE in Seaview. The alignments for each of the three genes were then concatenated together based on the name of the sample and gaps were added between genes. Phylogenies were then inferred on the concatenated alignment using PhyML. Results: After generation of the phylogenetic tree by concatenation of the three sequence genes, the differentiation between T. interdigitale and T. mentagrophytes was clear. The 16 strains of T. interdigitale were well classified into one distinct group on the dendrogram. The 10 strains of zoophilic T. mentagrophytes were well distinct of the anthropophilic group and defined by another clade on the dendrogram. Reference strains were correctly classified into the two previously defined groups. Regarding the differentiation between T. soudanense and T. violaceum, the concatenation permitted to define two well distinct clades on the dendrogram. One clade containing 10 T. violaceum tested and the other containing 20 T. soudanense included in the study and one strain previously identified as T. violaceum . Reference strains were correctly classified into each corresponding clade. Conclusion: The concatenation of ITS, beta-tubulin and Tef-1α genes sequences allows the generation of a discriminating dendrogram between the zoophilic T. mentagrophytes and the anthropophilic T. interdigitale. This is less powerfull between the two closely related African anthropophilic species T. violaceum and T. soudanense. Anyway This multilocus phylogenetic approach allows to better define the species boundaries between these dermatophytes and facilitates the molecular characterization of these species in routine diagnostic. [less ▲]

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See detailBelgian national survey on tinea capitis: epidemiology and molecular investigations
SACHELI, Rosalie ULiege; Menatong, Xavière; Labarbe, Chloé et al

in Mycoses, Supplement (2019, October)

Objectives: Tinea capitis (TC) is a superficial infection of the scalp caused by dermatophyte fungi which affects mainly prepubescent children. This last decade, a huge increase of African anthropophilic ... [more ▼]

Objectives: Tinea capitis (TC) is a superficial infection of the scalp caused by dermatophyte fungi which affects mainly prepubescent children. This last decade, a huge increase of African anthropophilic strains causing tinea capitis, has been observed in Europe, probably due to immigration waves from African countries. The Belgian National Reference Center for Mycosis (NRC) has conducted a surveillance study about TC in 2018. This work presents final results of the study for the epidemiological part and preliminary results for the molecular part. Methods: Belgian laboratories were invited to send all dermatophytes strains isolated from the scalp from January to December 2018. Dermatologists were involved and were asked to fill a form containing several epidemiological information about the patient. Strains identification was confirmed by ITS sequencing. A multiplex pan-dermatophyte real time PCR assay (DermaGenius®, PathoNostics) was applied if necessary. Typing of the M.audouinii strains was done using rep-PCR method (Diversilab, BioMérieux). Results: A total of 337 strains have been collected from 337 patients. The main population concerned by TC was children from 5-9 years (165/337, 49,01%). Males (214/337, 63,5%) were more affected than females (123/337, 36,5%), the sex ratio M/F was of 1,74. The majority of the strains was collected in Brussels area (181/337, 53,8%), followed by Liege area (73/337; 21,7%). Other Belgian cities were less concerned by TC. Among known ethnical origins (n=119), African people (114/119, 96,2%) were more concerned by TC than European people (5/119, 3,8%), (p<0,0001). The majority of patients were from Guinea (26/119, 21,8%), followed by Cameroun (14/119, 11,8%) and RDC (14/119, 11,8%), many other African nationalities were represented (12 different countries, all over Africa). The main transmission mode of TC was the familial way (83,3% among known cases n=126, 105/126). The major etiological agent was Microsporum audouinii (118/337, 35%) followed by Trichophyton soudanense (83/337, 24,6%), T. tonsurans (27/337, 17%), M. canis (36/337, 10,7%), T. violaceum (28/337, 8,3%), T. benhamiae (7/337, 2,1%), T. mentagrophytes (5/337, 1,48%) and M. incurvatum (1/337, 0,3%). This last rare dermatophyte has never been reported as responsible for TC in Belgium before. M. audouinii strains have been genotyped by rep-PCR and three genotypic variants have been characterized, one of them circulating mainly in Brussels area. No link with a particular ethnical origin could be found among genotypic groups. Conclusion: African anthropophilic dermatophytes such as M.audouinii and T. soudanense are mainly responsible for tinea capitis in Belgium. Large cosmopolitan cities like Brussels and Liege are the most concerned. People from African origin are mostly affected by TC. Among the M. audouinii strains circulating in Belgium, a genotypic diversity has been characterized. [less ▲]

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See detailMalaria risk assessment and mapping using satellite imagery and boosted regression trees in the Peruvian Amazon
Solano Villarreal, Elisa Yoan ULiege; Valdivia, Walter; Pearcy, Morgan et al

in Scientific Reports (2019)

This is the first study to assess the risk of co-endemic Plasmodium vivax and Plasmodium falciparum transmission in the Peruvian Amazon using boosted regression tree (BRT) models based on social and ... [more ▼]

This is the first study to assess the risk of co-endemic Plasmodium vivax and Plasmodium falciparum transmission in the Peruvian Amazon using boosted regression tree (BRT) models based on social and environmental predictors derived from satellite imagery and data. Yearly cross-validated BRT models were created to discriminate high-risk (annual parasite index API > 10 cases/1000 people) and veryhigh-risk for malaria (API > 50 cases/1000 people) in 2766 georeferenced villages of Loreto department, between 2010–2017 as other parts in the article (graphs, tables, and texts). Predictors were cumulative annual rainfall, forest coverage, annual forest loss, annual mean land surface temperature, normalized difference vegetation index (NDVI), normalized difference water index (NDWI), shortest distance to rivers, time to populated villages, and population density. BRT models built with predictor data of a given year efficiently discriminated the malaria risk for that year in villages (area under the ROC curve (AUC) > 0.80), and most models also effectively predicted malaria risk in the following year. Cumulative rainfall, population density and time to populated villages were consistently the top three predictors for both P. vivax and P. falciparum incidence. Maps created using the BRT models characterize the spatial distribution of the malaria incidence in Loreto and should contribute to malaria-related decision making in the area. [less ▲]

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See detailGroup B streptococcus neonatal invasive infections in Belgium 2010-2017, and characterization of isolated strains.
Melin, Pierrette ULiege; SACHELI, Rosalie ULiege; Lambotte, Olivia et al

in INMIS, International Committee (Ed.) INMIS 2019 Abstract book (2019, September)

Introduction/Background & Aims: Where intrapartum antibiotic-prophylaxis (IAP) is given to pregnant women colonized with Group B Streptococcus (GBS), the incidence of neonatal early-onset disease (EOD ... [more ▼]

Introduction/Background & Aims: Where intrapartum antibiotic-prophylaxis (IAP) is given to pregnant women colonized with Group B Streptococcus (GBS), the incidence of neonatal early-onset disease (EOD) has been successfully reduced; nevertheless, GBS is still the leading cause of severe disease among newborns, notably because the incidence of GBS late-onset disease (LOD) is not affected by IAP. Another strategy such as maternal immunization for prevention of both EOD/LOD is highly desirable worldwide. Aiming to describe GBS epidemiology and characterization of relevant epidemiological markers for vaccine development, surveillance of isolates causing neonatal disease is needed. We provide here results from the Belgian surveillance organized by the National Reference Centre(NRC). Methods: A total of 292 strains of GBS isolated from blood culture/cerebro-spinal fluid of newborns with invasive disease (149 EOD; 143 LOD) were sent to NRC by laboratories of a surveillance network, through years 2010-2017. Capsular-polysaccharide (CPS)-typing and pili-typing were performed with multiplex PCR assays. Multilocus sequence-typing and assignment to the hypervirulent clonal-complex (CC)17 was determined. Results: CPS type III isolates were responsible for 38.9% (n=58) of EOD cases, followed mainly by types Ia, V and II (22.1%, 18.1%, 8.1%). LOD cases were mainly caused by type III isolates (n=107, 74.8%), followed by types Ia (12.6%), V, Ib, IV and II (4.2%, 3.5%,2.8%, 2.1%). These distributions did not vary during the study period. A pili type was assigned to all isolates: at least one pili gene, PI2a, PI2b, or a combination of genes PI1-PI2a and PI1-PI2b. In 2016-2017, the hypervirulent-clone CC17 accounted for 33.3% of EOD (70.4% of type III) and 67% of LOD (89% of type III). Conclusions: The Belgian CPS distributions of isolates from EOD/LOD were similar to European data. One or 2 of 3 pilus-genes were detected in all isolates. CPS type III was predominant in both EOD/LOD and was mainly represented by CC-17 strains. [less ▲]

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See detailCharacterization of the treatment trajectory and assessment of the disease weight during uncomplicated malaria in the Democratic Republic of Congo
KAYIBA, Nadine; YOBI, Doudou; Devleesschauwer, Bart et al

Conference (2019, September)

Introduction: The emergence of Plasmodium falciparum (Pf) resistance to artemisinin (PfART-R) in Africa is a worrisome situation that would annihilate the progress made in reducing the global burden of ... [more ▼]

Introduction: The emergence of Plasmodium falciparum (Pf) resistance to artemisinin (PfART-R) in Africa is a worrisome situation that would annihilate the progress made in reducing the global burden of malaria. The discovery of mutations occurring in portions of the Pf gene sequence encoding kelch 13 (PfK13) – propeller domain and inducing PfART-R, has provided unprecedented opportunities for monitoring such resistance at large scale. Aim: This study aimed to review the PfK13 allelic polymorphism and its spatial distribution in Africa for drawing a baseline for subsequent epidemiological surveillance and containment efforts of PfART-R. Methods: A systematic review was performed according to PRISMA guidelines through six electronic databases consulted up to December 2018. Studies assessing the PfK13 gene in any of the 54 African countries were explored and data related to individual single nucleotide polymorphisms from each report and sampling location were geo-referenced and locus-referenced to be uploaded on maps displaying spatial and molecular patterns. Results: From 8,678 screened records, 50 reports were identified as eligible providing 22,739 Pf isolates successfully sequenced for the PfK13 and originating from 109 sites surveyed in 41 African countries. Overall 619 nonsynonymous (NS) mutants (2.7% of sequenced isolates) were reported at varied relative frequencies (0.5 to 50%) most often being K189T and A578S.Intermediate proportions (30 to 50%) of NS mutants were found in Western and Eastern Africa, moderate proportions (10 to 20%) in Middle Africa and low to very low proportions (<5%), elsewhere. NS mutations were not detected in 11 of 41 sampling countries. A total of 8 PfK13 NS mutations (F446I, C469Y, R515K, S522C, P553L, V568G, P574L, and A675V) out of 24 known as “associated molecular markers” for PfART-R were noticed at relative frequencies from 0.08 to 10.2%. One NS mutation (M476I) out of 6 established as “validated molecular markers” for PfART-R was reported at a relative frequency of 0.42%. Possible foci of NS mutations were noticed in Eastern, Western, and Middle Africa. Conclusion: Africa has noticed rare but alarming signals of possible emergence of Pf-ART-R. Proactive surveillance strategies are needed to be established in different African regions to refrain from massive development of resistance. [less ▲]

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See detailEvaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context
Bontems, Sébastien ULiege; BOREUX, Raphaël ULiege; CAPRARO, Valérie ULiege et al

in Journal of Virological Methods (2019), 270

Real-time PCR are often used for the diagnosis and monitoring of Cytomegalovirus (CMV)and Epstein-Barr virus (EBV)infections in susceptible populations. In this context, we evaluated the analytical ... [more ▼]

Real-time PCR are often used for the diagnosis and monitoring of Cytomegalovirus (CMV)and Epstein-Barr virus (EBV)infections in susceptible populations. In this context, we evaluated the analytical performances of the Abbott RealTime CMV/EBV maxCycle protocol automated on the m2000 platform (Abbott). It was compared to our routinely-used procedure consisting of a NucleoMag® DNA extraction automated on a STARlet platform followed by manually processed CMV and EBV quantitative real-time PCR (Diagenode). In this study, we showed that both EBV assays exhibited a similar sensitivity but with a better precision for the EBV Abbott RealTime assay. For the CMV performances, the Abbott assay was more sensitive and more precise than our routine method. The use of WHO International Standards also indicated a slight underestimation of the viral loads (−0.25 log10 IU/mL and −0.21 log10 IU/mL for CMV and EBV assays respectively)while these were rather overestimated with the Starlet/Diagenode method (0.48 log10 IU/mL and 0.19 log10 IU/mL for CMV and EBV assays respectively). These trends were confirmed using relevant whole-blood clinical samples and external quality controls. The workflows were also compared and we highlighted a significant technician hands-on time reduction (−63%)using the Abbott CMV/EBV maxCycle automated protocol. © 2019 Elsevier B.V. [less ▲]

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