Marie-Pierre Hayette

Molecular surveillance of Plasmodium falciparum resistance to artemisinin-based combination therapies in the Democratic Republic of Congo

Malaria is a major public health problem in the Democratic Republic of Congo. Despite progress achieved over the past decade in the fight against malaria, further efforts have to be done such as in the surveillance and the containment of Plasmodium falciparum resistant strains. We investigated resistance to artemisinin-based combination therapies currently in use in Democratic Republic of Congo by surveying molecular polymorphisms in three genes: pfcrt, pfmdr1 and pfk13 to explore possible emergence of amodiaquine, lumefantrine or artemisinin resistance in Democratic Republic of Congo. This study essentially revealed that resistance to chloroquine is still decreasing while polymorphism related to amodiaquine resistance seems to be not present in Democratic Republic of Congo, that three samples, located in the east of the country, harbor Pfmdr1 amplification and that none of the mutations found in South-East Asia correlated with artemisinine resistance have been found in Democratic Republic of Congo. But new mutations have been identified, especially the M476K, occurred in the same position that the M476I previously identified in the F32-ART strain, strongly resistant to artemisinine. Antimalarial first-line treatments currently in use in Democratic Republic of Congo are not associated with emergence of molecular markers of resistance.

Recurrence of visceral and muco-cutaneous leishmaniasis in a patient under immunosuppressive therapy

BackgroundLeishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many other infectious or malignant diseases. The disease can present in three ways: cutaneous, mucocutaneous, or visceral leishmaniasis, which rarely occur together or consecutively.Case presentationThe patient was a 52xa0years old immunosuppressed Belgian woman with a long history of severe rheumatoid arthritis. She underwent bone marrow biopsy to explore thrombocytopenia. Diagnosis of visceral leishmaniasis was made by identification of Leishman Donovan (LD) bodies in macrophages. Treatment with liposomal amphotericin B was successful. She later developed cutaneous leishmaniasis treated with amphotericin B lipid complex. She next presented with relapsing cutaneous lesions followed by rapidly progressing lymphadenopathies. Biopsy confirmed the diagnosis of leishmaniasis. Treatments by miltefosine, amphotericin B, N-methyl-glucamine antimoniate were subsequently initiated. She later presented a recurrent bone marrow involvement treated with intramuscular paromomycin and miltefosine. She died two years later from leukemia. At the time of death, she presented with a mucosal destruction of the nose. A Leishmania-specific PCR (Polymerase Chain Reaction) identified L. infantum as etiological agent.ConclusionsClinicians should be aware of the potential concomitant or sequential involvement of multiple anatomic localizations of Leishmania in immunosuppressed patients.

Clinical evaluation of the DermaGenius Nail real-time PCR assay for the detection of dermatophytes and Candida albicans in nails

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 DermaGenius® (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.

Phylogenetic analysis of the Belgian HIV-1 epidemic reveals that local transmission is almost exclusively driven by men having sex with men despite presence of large African migrant communities

To improve insight in the drivers of local HIV-1 transmission in Belgium, phylogenetic, demographic, epidemiological and laboratory data from patients newly diagnosed between 2013 and 2015 were combined and analyzed. Characteristics of clustered patients, paired patients and patients on isolated branches in the phylogenetic tree were compared. The results revealed an overall high level of clustering despite the short time frame of sampling, with 47.6% of all patients having at least one close genetic counterpart and 36.6% belonging to a cluster of 3 or more individuals. Compared to patients on isolated branches, patients in clusters more frequently reported being infected in Belgium (95.1% vs. 47.6%; pu202f<u202f0.001), were more frequently men having sex with men (MSM) (77.9% vs. 42.8%; pu202f<u202f0.001), of Belgian origin (68.2% vs. 32.9%; pu202f<u202f0.001), male gender (92.6% vs. 65.8%; pu202f<u202f0.001), infected with subtype B or F (87.8% vs. 43.4%; pu202f<u202f0.001) and diagnosed early after infection (55.4% vs. 29.0%; pu202f<u202f0.001). Strikingly, Sub-Saharan Africans (SSA), overall representing 27.1% of the population were significantly less frequently found in clusters than on individual branches (6.0% vs. 41.8%; pu202f<u202f0.001). Of the SSA that participated in clustered transmission, 66.7% were MSM and this contrasts sharply with the overall 12.0% of SSA reporting MSM. Transmission clusters with SSA were more frequently non-B clusters than transmission clusters without SSA (44.4% versus 18.2%). MSM-driven clusters with patients of mixed origin may account, at least in part, for the increasing spread of non-B subtypes to the native MSM population, a cross-over that has been particularly successful for subtype F and CRF02_AG. The main conclusions from this study are that clustered transmission in Belgium remains almost exclusively MSM-driven with very limited contribution of SSA. There were no indications for local ongoing clustered transmission of HIV-1 among SSA.

Alveolar echinococcosis in southern Belgium: retrospective experience of a tertiary center.

Dear Editor, Alveolar Echinococcosis (EA) is a zoonosis due to the larval stage of the fox tapeworm Echinococcus multilocuris. Humans are dead-end hosts and are exposed through sylvatic (fox) or domestic (cat and dog) cycles. Infection is acquired through the fecal-oral route. The metacestodes of E. multilocularis proliferate in the liver, inducing a Btumorlike^ lesion that can invade the neighboring organs or spread away from the primary lesion [1]. Until recently, Belgium was considered as a low-risk country for AE. However, in 2008, Hanosset et al. demonstrated by necropsies of red foxes (Vulpes vulpes), a prevalence of AE at up to 60% in some parts of Wallonia, the Southern part of Belgium [2]. The first indigenous Belgian human AE case was diagnosed in 1999 at the Centre Hospitalier Universitaire (CHU) of Liege, a tertiary university hospital in Wallonia [3]. Since this first case, other patients have been diagnosed with EA and managed by the different departments of the CHU Liege [4]. The aim of this study was to evaluate the overall experience and results of the different teams of the CHU Liege with AE and to better determine the number of indigenous AE cases to provide this information to authorities in charge of public health. After University Hospital Ethical committee approval, the authors retrospectively collecteddata from the laboratoryof clinical microbiology (for Echinococcus serologies and PCR), the hospital pharmacy in charge of supplying albendazole, and by searching through patient files from themedico-economic informationservice. Informationwascollectedfrom1999toFebruary 2018. Belgian regulations do not require patient informed consent for a purely retrospective review of medical files. Between 1999 and February 2018, a total of 22 human indigenous AE cases were recorded and their medical files were studied. In all cases, the diagnosis was established based on Echinococcus sp. serology (inhibition of hemagglutination (Fumouze, France), ELISA specific for E. granulosus (Rbiopharm, Germany) and E. multilocularis (Bordier, Suisse) respectively and Western Blot), clinical imaging, histopathology and in some cases an E. multilocularis specific PCR assay on tissue [5]. According to the criteria of Brunetti et al. [1], 11 possible and 11 confirmed cases were diagnosed. The mean age of the patients at the time of diagnosis was 69 years (ranges: 34–85 years). Sixty-four percent of the patients were male. Some degree of immunosuppression could be identified in 36% of cases (solid or hematologic cancers, chronic inflammatory disease, diabetes, and chronic alcoholism). At least one of the risk factors described by Conraths et al. [6] (owning a dog and/or a cat, living in a rural zone, working as farmer, or forestry worker) was identified in all patients but one (data are missing). Patients lived in rural * Audrey Cambier au.cambier@gmail.com

Hepatic alveolar echinococcosis.

Olivier Detry, Nicolas Meurisse, Jean Delwaide, Jean-Baptiste Giot, Philippe Leonard, Bertrand Losson, Marie-Pierre Hayette, Noella Bletard, Paul Meunier and Pierre Honor e Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Multidisciplinary Unit for Echinococcosis Management and Research of the University of Liege (Echino-Liege), University of Liege, Liege, Belgium; Department of Hepatogastroenterology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Department of Infectious diseases, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Laboratory of Parasitology and Pathology of Parasitic Diseases, Faculty of Veterinary Medicine, University of Liege (ULg), Liege, Belgium; Department of Microbiology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Department of Pathology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium; Department of Radiology, CHU Liege, University of Liege (CHU-ULg), Liege, Belgium

Disseminated histoplasmosis: case report and review of the literature

Abstract Case report We report the case of a young Cameroonian woman who presented with cough, hyperthermia, weight loss, pancytopenia, and hepatosplenomegaly. A positive HIV serology was discovered and a chest radiography revealed a ‘miliary pattern’. Bone marrow aspiration pointed out yeast inclusions within macrophages. Given the morphological aspect, the clinical presentation and immunosuppression, histoplasmosis was retained as a working hypothesis. Antiretroviral and amphotericin B treatments were promptly initiated. Review Given the immigration wave that Europe is currently experiencing, we think it is important to share experience and knowledge, especially in non-endemic areas such as Europe, where clinicians are not used to face this disease. Histoplasmosis is due to Histoplasma capsulatum var. capsulatum, a dimorphic fungus. Infection occurs by inhaling spores contained in soils contaminated by bat or bird droppings. The clinical presentation depends on the immune status of the host and the importance of inoculum, varying from asymptomatic to disseminated forms. AIDS patients are particularly susceptible to develop a severe disease. Antigen detection, molecular biology techniques, and microscopic examination are used to make a rapid diagnosis. However, antigen detection is not available in Europe and diagnosis needs a strong clinical suspicion in non-endemic areas. Because of suggestive imagery, clinicians might focus on tuberculosis. Our case illustrates the need for clinicians to take histoplasmosis in the differential diagnosis, depending on the context and the patient’s past history.