Publications of Marie-Pierre HAYETTE
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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 detailEconomic costs analysis of uncomplicated malaria case management in the Peruvian Amazon
Moreno-Gutierrez, Diamantina; Rosas-Aguirre, Angel; Llanos-Cuentas, Alejandro et al

in Malaria Journal (2020), 19(1), 161

Background Case management is one of the principal strategies for malaria control. This study aimed to estimate the economic costs of uncomplicated malaria case management and explore the influence of ... [more ▼]

Background Case management is one of the principal strategies for malaria control. This study aimed to estimate the economic costs of uncomplicated malaria case management and explore the influence of healthseeking behaviours on those costs. Methods A knowledge, attitudes and practices (KAP) survey was applied to 680 households of fifteen communities in Mazan-Loreto in March 2017, then a socio-economic survey was conducted in September 2017 among 161 individuals with confirmed uncomplicated malaria in the past three months. Total costs per episode were estimated from both provider (Ministry of Health, MoH) and patient perspectives. Direct costs were estimated using a standard costing estimation procedure, while the indirect costs considered the loss of incomes among patients, substitute labourers and companions due to illness in terms of the monthly minimum wage. Sensitivity analysis evaluated the uncertainty of the average cost per episode. Results The KAP survey showed that most individuals (79.3%) that had malaria went to a health facility for a diagnosis and treatment, 2.7% received those services from community health workers, and 8% went to a drugstore or were self-treated at home. The average total cost per episode in the Mazan district was US$161. The cost from the provider’s perspective was US$30.85 per episode while from the patient’s perspective the estimated cost was US$ 131 per episode. The average costs per Plasmodium falciparum episode (US$180) were higher than those per Plasmodium vivax episode (US$156) due to longer time lost from work by patients with P. falciparum infections (22.2 days) than by patients with P. vivax infections (17.0 days). The delayed malaria diagnosis (after 48 hours of the onset of symptoms) was associated with the time lost from work due to illness (adjusted mean ratio 1.8; 95%CI 1.3, 2.6). The average cost per malaria episode was most sensitive to the uncertainty around the lost productivity cost due to malaria. Conclusions: Despite the provision of free malaria case management by MoH, there is delay in seeking care and the costs of uncomplicated malaria are mainly borne by the families. These costs are not well perceived by the society and the substantial financial impact of the disease can be frequently undervalued in public policy planning [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 Mainike; Guinea, Jesus et al

in Journal of Antimicrobial Chemotherapy (2020)

OBJECTIVES: Terbinafine resistance is increasingly reported in Trichophyton, rendering susceptibility testing particularly important in non-responding cases. We performed a multicentre evaluation of six ... [more ▼]

OBJECTIVES: Terbinafine resistance is increasingly reported in Trichophyton, rendering susceptibility testing particularly important in non-responding cases. We performed a multicentre evaluation of six EUCAST-based methods. METHODS: Ten laboratories susceptibility tested terbinafine, itraconazole, voriconazole and amorolfine against a blinded panel of 38 terbinafine WT and target gene mutant isolates. E.Def 9.3.1 modifications included: medium with/without addition of chloramphenicol and cycloheximide (CC), incubation at 25°C to 28°C for 5-7 days and three MIC endpoints [visually and spectrophotometrically (90%/50% inhibition)], generating 7829 MICs. Quality control (QC) strains were Aspergillus flavus ATCC 204304 and CNM-CM1813. Eyeball, ECOFFinder (where ECOFF stands for epidemiological cut-off) and derivatization WT upper limits (WT-ULs), very major errors (VMEs; mutants with MICs ≤WT-ULs) and major errors (MEs; WT isolates with MICs >WT-ULs) were determined. RESULTS: MICs fell within the QC ranges for ATCC 204304/CNM-CM1813 for 100%/96% (voriconazole) and 84%/84% (itraconazole), respectively. Terbinafine MICs fell within 0.25-1 mg/L for 96%/92%, suggesting high reproducibility. Across the six methods, the number of terbinafine MEs varied from 2 to 4 (2.6%-5.2%) for Trichophyton rubrum and from 0 to 2 (0%-2.0%) for Trichophyton interdigitale. Modes for WT and mutant populations were at least seven 2-fold dilutions apart in all cases. Excluding one I121M/V237I T. rubrum mutant and two mixed WT/mutant T. interdigitale specimens, the numbers of VMEs were as follows: T. rubrum: CC visual, 1/67 (1.5%); CC spectrophotometric 90% inhibition, 3/59 (5.1%); and CC spectrophotometric 50% inhibition, 1/67 (1.5%); and T. interdigitale: none. Voriconazole and amorolfine MICs were quite uniform, but trailing growth complicated determination of itraconazole visual and spectrophotometric 90% inhibition MIC. CONCLUSIONS: Although none of the laboratories was experienced in dermatophyte testing, error rates were low. We recommend the CC spectrophotometric 50% inhibition method and provide QC ranges and WT-ULs for WT/non-WT classification. [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 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 detailHospital Laboratory Survey for Identification of Candida auris in Belgium
Dewaele, Klaas; Lagrou, Katrien; Frans, Johan et al

in Journal of Fungi (2019), 84

Candida auris is a difficult-to-identify, emerging yeast and a cause of sustained nosocomial outbreaks. Presently, not much data exist on laboratory preparedness in Europe. To assess the ability of ... [more ▼]

Candida auris is a difficult-to-identify, emerging yeast and a cause of sustained nosocomial outbreaks. Presently, not much data exist on laboratory preparedness in Europe. To assess the ability of laboratories in Belgium and Luxembourg to detect this species, a blinded C. auris strain was included in the regular proficiency testing rounds organized by the Belgian public health institute, Sciensano. Laboratories were asked to identify and report the isolate as they would in routine clinical practice, as if grown from a blood culture. Of 142 respondents, 82 (57.7%) obtained a correct identification of C. auris. Of 142 respondents, 27 (19.0%) identified the strain as Candida haemulonii. The remaining labs that did not obtain a correct identification (33/142, 23.2%), reported other yeast species (4/33) or failed to obtain a species identification (29/33). To assess awareness about the infection-control implications of the identification, participants were requested to indicate whether referral of this isolate to a reference laboratory was desirable in a clinical context. Over one-third of all respondents (54/142, 38.0%) stated that they would not send the isolate to a reference laboratory, neither for epidemiological reasons nor for identification confirmation or antifungal susceptibility testing. This comprised 41.5% of the laboratories that submitted an identification of C. auris (34/82). Awareness among Belgian microbiologists, therefore, remains inadequate more than two years after C. auris’ emergence in European clinics. Our data confirm high rates of misidentifications with commonly used identification methods. Programs for raising awareness in European hospitals may be warranted. [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 detailClinical evaluation of the DermaGenius Nail real-time PCR assay for the detection of dermatophytes and Candida albicans in nails
Hayette, Marie-Pierre ULiege; SEIDEL, Laurence ULiege; ADJETEY BAHUN, Akolé ULiege et al

in Medical Mycology (2019)

Onychomycosis represents one of the most frequent mycoses in the world. Causative agents are mainly dermatophytes, but yeasts and nondermatophyte moulds can also be involved. Conventional diagnostic ... [more ▼]

Onychomycosis represents one of the most frequent mycoses in the world. Causative agents are mainly dermatophytes, but yeasts and nondermatophyte moulds can also be involved. Conventional diagnostic methods include direct microscopy (or histology) and culturing. However,molecular methods are becoming increasingly popular in this field. The DermaGeniusR (DG) Nail multiplex assay (PathoNostics, The Netherlands) is a new commercial real-time polymerase chain reaction (PCR) kit, which can detect Trichophyton rubrum, Trichophyton interdigitale and Candida albicans directly in nails. The present study is a retrospective evaluation of the kit applied to 138 finger and toenail clippings in comparison to histology and culture methods. The sensitivity and specificity of the PCR assay are 80% (76/95) and 74.4% (32/43), respectively,when histology and culture are used as reference to define onychomycosis. DG performance is not different from histology combined with culture (P = .11) but the best diagnostic efficacy (88.4%, 122/138) is obtained by the combination of histology and DG. In conclusion, this study emphasizes the clinical usefulness of the DG in diagnostics. The high specificity of this test guarantees a better identification compared to culture that can lead to dermatophyte misidentifications. It is a reliable PCR assay that shortens the time to diagnosis and can unmask the presence of nongrowing fungal pathogens in nails. [less ▲]

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See detailUtilisation de la nystatine dans la candidose oropharyngée au CHU de Liège
Vercheval, Christelle ULiege; GILLET, Manon ULiege; Koch, Nathan ULiege et al

in Journal de Pharmacie de Belgique (2019)

Le Groupe de Gestion de l’Antibiothérapie du Centre Hospitalier Universitaire de Liègea souligné une utilisation importante et nonjustifiée de nystatine sous forme de bain debouche. Devant ce constat ... [more ▼]

Le Groupe de Gestion de l’Antibiothérapie du Centre Hospitalier Universitaire de Liègea souligné une utilisation importante et nonjustifiée de nystatine sous forme de bain debouche. Devant ce constat, nous avons réalisé une revue de la littérature sur l’efficacité et l’innocuité de la nystatine dans la candidose oropharyngée (COP) et nous partageons dans cet article quelques recommandations pratiques institutionnelles. La COP est une infection fongique fréquente avec un bon pronostic si elle est diagnostiquée et traitée de manière appropriée. La nystatine sous forme de pastille ou de suspension buvable est recommandée comme traitement alternatif en cas de COP bénigne par la Société Américaine des Maladies Infectieuses. Néanmoins, la littérature évaluant l’efficacité et la sécurité de la nystatine dans la COP est pauvre. En Belgique, la nystatine est commercialisée sous forme de suspension buvable et sous forme de matière première. Aucun consensus national n’est disponible sur la formulation, le dosage ou encore la durée de traitement de la nystatine en cas de COP. Au CHU de Liège, il a été décidé d’arrêter la préparation de bain de bouche à base de nystatine et de privilégier l’utilisation d’une suspension de nystatine en cas de COP bénigne. [less ▲]

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