Publications by authors named "Valentin Greigert"

15 Publications

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Ancylostoma ceylanicum as the second most frequent hookworm species isolated in France in travellers returning from tropical areas.

J Travel Med 2021 Jan 28. Epub 2021 Jan 28.

Institut de Parasitologie et Pathologie Tropicale, Université de Strasbourg, 67000 Strasbourg, France.

Ancylostoma ceylanicum is the second most common hookworm species infecting humans in Southeast Asia and Oceania. We performed a three years multicenter study to assess its frequency in hookworm infecting patients returning from tropical areas to France and found that A. ceylanicum was the second most frequent hookworm species isolated.
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http://dx.doi.org/10.1093/jtm/taab014DOI Listing
January 2021

Pathophysiology of ocular toxoplasmosis: Facts and open questions.

PLoS Negl Trop Dis 2020 12 31;14(12):e0008905. Epub 2020 Dec 31.

Institut de Parasitologie et Pathologie Tropicale, UR 7292, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.

Infections with the protozoan parasite Toxoplasma gondii are frequent, but one of its main consequences, ocular toxoplasmosis (OT), remains poorly understood. While its clinical description has recently attracted more attention and publications, the underlying pathophysiological mechanisms are only sparsely elucidated, which is partly due to the inherent difficulties to establish relevant animal models. Furthermore, the particularities of the ocular environment explain why the abundant knowledge on systemic toxoplasmosis cannot be just transferred to the ocular situation. However, studies undertaken in mouse models have revealed a central role of interferon gamma (IFNγ) and, more surprisingly, interleukin 17 (IL17), in ocular pathology and parasite control. These studies also show the importance of the genetic background of the infective Toxoplasma strain. Indeed, infections due to exotic strains show a completely different pathophysiology, which translates in a different clinical outcome. These elements should lead to more individualized therapy. Furthermore, the recent advance in understanding the immune response during OT paved the way to new research leads, involving immune pathways poorly studied in this particular setting, such as type I and type III interferons. In any case, deeper knowledge of the mechanisms of this pathology is needed to establish new, more targeted treatment schemes.
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http://dx.doi.org/10.1371/journal.pntd.0008905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774838PMC
December 2020

The BASIC Score: A Useful Tool to Identify Patients at High Risk of Early Progression to Severe Coronavirus Disease 2019.

Open Forum Infect Dis 2020 Oct 1;7(10):ofaa405. Epub 2020 Sep 1.

CHU de Strasbourg, Department of Infectious and Tropical Diseases, Strasbourg, France.

We developed a score, with easily accessible data (age, sex, body mass index, dyspnea, inflammatory parameters), to predict the risk of rapid progression to severe coronavirus disease 2019. Using a cutoff of >6 points, the negative predictive value was 87%.
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http://dx.doi.org/10.1093/ofid/ofaa405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499730PMC
October 2020

Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in North-Eastern France, March 2020.

Euro Surveill 2020 12;25(48)

CHU de Strasbourg, Department of Infectious and Tropical Diseases; Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.

BackgroundIn March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization.AimOur objective was to identify risk factors predictive of severe disease and death in France.MethodsIn this prospective cohort study, we included patients ≥ 18 years old with confirmed COVID-19, hospitalised in Strasbourg and Mulhouse hospitals (France), in March 2020. We respectively compared patients who developed severe disease (admission to an intensive care unit (ICU) or death) and patients who died, to those who did not, by day 7 after hospitalisation.ResultsAmong 1,045 patients, 424 (41%) had severe disease, including 335 (32%) who were admitted to ICU, and 115 (11%) who died. Mean age was 66 years (range: 20-100), and 612 (59%) were men. Almost 75% of patients with body mass index (BMI) data (n = 897) had a BMI ≥ 25 kg/m2 (n = 661). Independent risk factors associated with severe disease were advanced age (odds ratio (OR): 1.1 per 10-year increase; 95% CrI (credible interval): 1.0-1.2), male sex (OR: 2.1; 95% CrI: 1.5-2.8), BMI of 25-29.9 kg/m2 (OR: 1.8; 95% CrI: 1.2-2.7) or ≥ 30 (OR: 2.2; 95% CrI: 1.5-3.3), dyspnoea (OR: 2.5; 95% CrI: 1.8-3.4) and inflammatory parameters (elevated C-reactive protein and neutrophil count, low lymphocyte count). Risk factors associated with death were advanced age (OR: 2.7 per 10-year increase; 95% CrI: 2.1-3.4), male sex (OR: 1.7; 95% CrI: 1.1-2.7), immunosuppression (OR: 3.8; 95% CrI: 1.6-7.7), diabetes (OR: 1.7; 95% CrI: 1.0-2.7), chronic kidney disease (OR: 2.3; 95% CrI: 1.3-3.9), dyspnoea (OR: 2.1; 95% CrI: 1.2-3.4) and inflammatory parameters.ConclusionsOverweightedness, obesity, advanced age, male sex, comorbidities, dyspnoea and inflammation are risk factors for severe COVID-19 or death in hospitalised patients. Identifying these features among patients in routine clinical practice might improve COVID-19 management.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.48.2000895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716399PMC
December 2020

CT lung lesions as predictors of early death or ICU admission in COVID-19 patients.

Clin Microbiol Infect 2020 Oct 24;26(10):1417.e5-1417.e8. Epub 2020 Jul 24.

Department of Infectious Disease, Strasbourg University Hospital, Strasbourg, France.

Objective: The main objective of this study was to investigate the prognostic value of early systematic chest computed tomography (CT) with quantification of lung lesions in coronavirus disease 2019 (COVID-19) patients.

Methods: We studied 572 patients diagnosed with COVID-19 (confirmed using polymerase chain reaction) for whom a chest CT was performed at hospital admission. Visual quantification was used to classify patients as per the percentage of lung parenchyma affected by COVID-19 lesions: normal CT, 0-10%, 11-25%, 26-50%, 51-75% and >75%. The primary endpoint was severe disease, defined by death or admission to the intensive care unit in the 7 days following first admission.

Results: The mean patient age was 66.0 ± 16.0 years, and 343/572 (60.0%) were men. The primary endpoint occurred in 206/572 patients (36.0%). The extent of lesions on initial CT was independently associated with prognosis (odds ratio = 2.35, 95% confidence interval 1.24-4.46; p < 0.01). Most patients with lung involvement >50% (66/95, 69.5%) developed severe disease compared to patients with lung involvement of 26-50% (70/171, 40.9%) and ≤25% (70/306, 22.9%) (p < 0.01 and p < 0.01, respectively). None of the patients with normal CT (0/14) had severe disease.

Conclusion: Chest CT findings at admission are associated with outcome in COVID-19 patients.
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http://dx.doi.org/10.1016/j.cmi.2020.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378475PMC
October 2020

The Good, the Bad, and the Hoax: When Publication Instantaneously Impacts Treatment Strategies for COVID-19.

Antimicrob Agents Chemother 2020 07 22;64(8). Epub 2020 Jul 22.

CHU de Strasbourg, Service de Maladies Infectieuses et Tropicales, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1128/AAC.01127-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526849PMC
July 2020

Locally acquired infection with Dibothriocephalus nihonkaiense (=Diphyllobothrium nihonkaiense) in France: the importance of molecular diagnosis.

Parasitol Res 2020 Feb 17;119(2):513-518. Epub 2019 Dec 17.

Institut de Parasitologie et Pathologie Tropicale, EA 7292, Fédération de Médecine Translationnelle, Université de Strasbourg, 3 rue Koeberlé, F-67000, Strasbourg, France.

Diphyllobothriasis is a parasitic fish-borne disease caused by tapeworms of the genus Dibothriocephalus (=Diphyllobothrium). The majority of reported cases are attributed to D. latum, based on morphological identification of eggs or proglottids. However, numerous reports in recent years suggested that other Dibothriocephalus species could be involved in human infections, mainly after consumption of salmonid fish. Among these, D. nihonkaiense has been predominantly reported from Eastern Asia and probably underestimated in the rest of the world. We report here a clinical case of D. nihonkaiense in a French patient (without history of travel abroad) after consumption of salmon. Suspected on morphological characteristics, the final identification of D. nihonkaiense was performed using molecular methods by sequencing nad1, cox1, and 5.8S rRNA (containing ITS1 and 2) genes sequences. The patient was successfully treated by a single dose of praziquantel. Reports of diphyllobothriasis due to D. nihonkaiense are rare outside Asia, but worldwide demand of seafood could lead to the globalization of cases and reflect the need to monitor the distribution of Dibothriocephalus species. Thus, clinical parasitologists should be aware of this risk and able to raise the possibility of infections by non-endemic Dibothriocephalus species in order to use the proper molecular tools.
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http://dx.doi.org/10.1007/s00436-019-06566-6DOI Listing
February 2020

The Trick of the Hedgehog: Case Report and Short Review About Archaeopsylla erinacei (Siphonaptera: Pulicidae) in Human Health.

J Med Entomol 2020 01;57(1):318-323

Institut de Parasitologie et Pathologie Tropicale, Université de Strasbourg, Strasbourg, France.

Fleas are ectoparasites of various animals, including Homo sapiens Linnaeus, 1758 (Primates: Hominidae). Among the species relevant to the human health field, either due to their dermatopathological potential or because of their role as vectors of microorganisms responsible for infectious diseases, such as plague or murine typhus, are the human flea, oriental rat flea, closely related cat and dog fleas, and chigoe flea. However, other species can accidentally infest humans. We have herein reported two unusual cases of humans infested and bitten by Archaeopsylla erinacei, the hedgehog flea. This species has been identified using stereomicroscopy, on the base of key characteristics. Furthermore, a brief literature review has revealed that hedgehog fleas could carry human-infectious agents, such as Rickettsia felis Bouyer et al. 2001 (Rickettsiales: Rickettsiaceae) or Bartonella henselae Regnery et al.1992 (Rhizobiales: Bartonellaceae). Using molecular biology, we thus tested nine A. erinacei specimens taken from these patients, for several bacteria species commonly associated with hematophagous arthropods, implicated in human pathology. However, all our samples were proven negative. The role of A. erinacei in human epidemiology has never been evaluated to date. This report sought to remind us that these fleas can be accidental parasites in humans. In addition, recent findings pertaining to bacteria of medical interest that are present in these insects should be brought to the fore, given that the question of their role as vectors in human infections remains unanswered and deserves further investigation.
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http://dx.doi.org/10.1093/jme/tjz157DOI Listing
January 2020

Biological Diagnosis of Ocular Toxoplasmosis: a Nine-Year Retrospective Observational Study.

mSphere 2019 09 25;4(5). Epub 2019 Sep 25.

Institut de Parasitologie et Pathologie Tropicale, Université de Strasbourg, Strasbourg, France.

Ocular toxoplasmosis (OT), i.e., the ocular manifestation of infection, is one of the leading causes of posterior uveitis. While ocular lesions are often typical, atypical forms often require biological confirmation of the diagnosis. Our study sought to review the biological OT diagnoses made in our laboratory to further assess the role of each test in the diagnostic procedure. All ocular samples sent to our laboratory over the last 9 years for OT diagnosis were included. These samples were analyzed using PCR and antibody detection by means of immunoblotting and Candolfi coefficient (CC) determinations, either alone or in combination. Since serum analysis is required to interpret both the CC and immunoblotting, blood serology for was also performed in most cases. Of the 249 samples analyzed, 80 (32.1%; 95% confidence interval [95%CI], 26.3 to 37.9) were positive for OT. Of these 80 cases, 52/80 (65.0%; 54.6 to 74.5) displayed a positive PCR, 15/80 (18.8%; 10.2 to 27.3) a positive CC, and 33/80 (41.3%; 95%CI, 30.5 to 52.0) a positive immunoblot result. Overall, 63 of the 80 OT diagnoses (78.8%; 95%CI, 69.8 to 87.7) were made on the basis of a single positive test result. Our study results remind us that current biological diagnostic tools for OT must be employed in combination to obtain an optimal diagnosis based on the precious ocular fluids sampled by ophthalmologists. Clinicobiological studies that are focused on correlating the performances of the different tests with clinical features are critically needed to improve our understanding of the pathophysiology and diagnosis of OT. Ocular toxoplasmosis (OT), a parasitic infection of the eye, is considered to be the most important infectious cause of posterior uveitis worldwide. Its prevalence is particularly high in South America, where aggressive strains are responsible for more-severe presentations. The particular pathophysiology of this infection leads, from recurrence to recurrence, to potentially severe vision impairment. The diagnosis of this infection is usually exclusively based on the clinical examination. However, the symptoms may be misleading and are not always sufficient to confirm a diagnosis of OT. In such cases, biological tests performed by means of several techniques on blood and ocular samples may facilitate the diagnosis. In this study, we analyzed the tests that were performed in our laboratory over a 9-year period every time OT was suspected. Our report highlights that the quality of ocular sampling by ophthalmologists and combinations of several techniques are critical for a reliable biological OT diagnosis.
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http://dx.doi.org/10.1128/mSphere.00636-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763772PMC
September 2019

Positive Impact of a Point-of-Care Molecular Influenza Test in the Emergency Department During the 2017-2018 Seasonal Influenza Epidemic.

Open Forum Infect Dis 2019 Jul;6(7)

Emergency Department, Hôpitaux Civils de Colmar, Colmar, France.

During the 2017-2018 flu epidemic, the point-of-care Alere-i (n = 72) and reverse transcription polymerase chain reaction (n = 106) tests were compared. Patients in the point-of-care group were administered oseltamivir significantly more rapidly (9 hours vs 23 hours), they spent less time in the emergency department, and they had lower rates of antibiotic administration and hospitalization.
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http://dx.doi.org/10.1093/ofid/ofz312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667710PMC
July 2019

When biology supports clinical diagnosis: review of techniques to diagnose ocular toxoplasmosis.

Br J Ophthalmol 2019 07 14;103(7):1008-1012. Epub 2019 May 14.

Institut de Parasitologie et Pathologie Tropicale, Université de Strasbourg, Strasbourg, France.

Toxoplasmosis is a common infection whose worldwide prevalence is estimated at 30%, with large disparities across the world. Among infected subjects, the prevalence of ocular toxoplasmosis (OT) is, however, limited to about 2% in Europe and 17% in South America. In France, it is estimated that about 1 000 000 patients present either active OT or subsequent chorioretinal scars. is the first cause of posterior uveitis worldwide, responsible for retinochoroiditis, at times associated with anterior uveitis. To date, there is no consensus yet on how to diagnose OT, which is often based only on clinical presentation. Nevertheless, OT-associated symptoms are often atypical and misleading. Over the last 20 years, tremendous progress has been made in biological tools, enabling parasitologists to confirm the diagnosis in most suspected cases of OT. Using anterior chamber puncture, a safe and fast procedure, ophthalmologists sample aqueous humour for analysis using multiple techniques in order to reach high specificity and sensitivity in OT diagnosis. In this article, we present the different techniques available for the biological diagnosis of OT, along with their characteristics, and propose a diagnostic algorithm designed to select the best of these techniques if clinical examination is not sufficient to ascertain the diagnosis.
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http://dx.doi.org/10.1136/bjophthalmol-2019-313884DOI Listing
July 2019

Cestode infections in non-human primates suggest the existence of zoonotic cycles in the area surrounding the Strasbourg primatology center.

Parasite 2019 1;26:25. Epub 2019 May 1.

Institut de Parasitologie et de Pathologie Tropicale, EA 7292, Fédération de Médecine Translationnelle, Université de Strasbourg, 67000 Strasbourg, France - Laboratoire de Parasitologie et Mycologie Médicales, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France.

Background: Several cases of infections due to Echinococcus multilocularis, Taenia martis and Taenia crassiceps were recently described in various species of captive non-human primates (NHPs) harbored in the Strasbourg Primate Center (SPC). Furthermore, one of the first cases of human cysticercosis due to T. martis was described in the Strasbourg region. These data suggest the existence of zoonotic cycles of tapeworm infections in the direct environment of the SPC. The aim of our study was to assess the prevalence of larval cestode infections among intermediate and definitive hosts in the close neighborhood of the center. We analyzed carnivore mammal fecal samples as well as rodent carcasses, collected inside or near the SPC, using PCR. Furthermore, we performed serology for Echinococcus spp. and Taenia spp. on NHP sera.

Results: We found that 14.5% (95% CI [8.6; 20.4]) of 138 carnivore feces were positive for E. multilocularis-DNA, as well as 25% (95% CI [5.5; 57.2]) of 12 rodent carcasses, and 5.1% (95% CI [1.4; 8.7]) for T. martis or T. crassiceps. Of all NHPs tested, 10.1% (95% CI [3.8; 16.4]) were seropositive for Echinococcus spp. and 8.2% (95% CI [1.3; 15.1]) for Taenia spp.

Conclusions: Our data support the existence of zoonotic cycles of larval cestode infections in the direct environment of the primatology center affecting NHPs harbored in the SPC, potentially threatening the human population living in this area. Since this zoonotic risk is borne by local wildlife, and given the severity of these infections, it seems necessary to put in place measures to protect captive NHPs, and further studies to better assess the risk to human populations.
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http://dx.doi.org/10.1051/parasite/2019025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492538PMC
August 2019

Type I ROP16 regulates retinal inflammatory responses during ocular toxoplasmosis.

PLoS One 2019 22;14(3):e0214310. Epub 2019 Mar 22.

Institut de Parasitologie et Pathologie Tropicale, EA, Fédération de Médecine Translationnelle, Université de Strasbourg, Strasbourg, France.

Ocular toxoplasmosis (OT), mostly retinochorioditis, is a major feature of infection with the protozoan parasite Toxoplasma gondii. The pathophysiology of this infection is still largely elusive; especially mouse models are not yet well developed. In contrast, numerous in vitro studies showed the highly Toxoplasma strain dependent nature of the host-parasite interactions. Some distinct polymorphic virulence factors were characterized, notably the rhoptry protein ROP16. Here, we studied the strain-dependent pathophysiology in our OT mouse model. Besides of two wild type strains of the canonical I (RH, virulent) and II (PRU, avirulent) types, we used genetically engineered parasites, RHΔROP16 and PRU ROP16-I, expressing the type I allele of this virulence factor. We analyzed retinal integrity, parasite proliferation and retinal expression of cytokines. PRU parasites behaved much more virulently in the presence of a type I ROP16. In contrast, knockout of ROP16 in the RH strain led to a decrease of intraocular proliferation, but no difference in retinal pathology. Cytokine quantification in aqueous humor showed strong production of Th1 and inflammatory markers following infection with the two strains containing the ROP16-I allele. In strong contrast, immunofluorescence images showed that actual expression of most cytokines in retinal cells is rapidly suppressed by type I strain infection, with or without the involvement of its homologous ROP16 allele. This demonstrates the particular immune privileged situation of the retina, which is also revealed by the fact that parasite proliferation is nearly exclusively observed outside the retina. In summary, we further developed a promising OT mouse model and demonstrated the specific pathology in retinal tissues.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430381PMC
December 2019

Human intestinal parasites in Mahajanga, Madagascar: The kingdom of the protozoa.

PLoS One 2018 10;13(10):e0204576. Epub 2018 Oct 10.

Laboratoire de Parasitologie-Mycologie, CHU Clermont-Ferrand, Clermont-Ferrand, France.

Introduction: Intestinal parasitic infections are a major public health problem in inter-tropical areas. The aim of our study was to describe the situation in Mahajanga, Madagascar with a particular focus on two protozoa, Dientamoeba fragilis and Blastocystis sp.

Methods: This was a prospective study from February to June 2015. Stool samples from symptomatic hospitalized patients and asymptomatic volunteers were submitted to microscopy and molecular assays in order to detect parasites.

Results: A wide panel of intestinal parasites were identified among the 265 included subjects, protozoa being the most prevalent with 72.8% whereas the prevalence of helminths and microsporidia was of 7.9% and 4.5%, respectively. Blastocystis sp. was the most prevalent protozoa (64.5% of the entire cohort) followed by various amoebas (35.5%) and flagellates (27,5%). We only detected subtypes 1, 2 and 3 of Blastocystis sp. Among the patients positive for D. fragilis (9.4%), 23 carried genotype 1 and 1 genotype 2. For the first time, we detected in 4 human stools the DNA of a recently described protozoon, Simplicimonas similis. Interestingly, subjects living in urban areas harbored significantly more different parasitic species than subjects living in rural areas with a correlation between sanitary level of neighborhood and protozoan infection. However, there was no difference in prevalence of digestive symptoms between parasite-free and parasite-infected subjects, except for Giardia intestinalis which had more symptomatic carriers.

Discussion: Our study reveals a high overall parasite prevalence, similar to what had been found in 2003 in the same city and to other prevalence studies conducted in Africa. The poor access of the population to sanitary infrastructures may explain this result. Data from our study provide valuable key for sanitation programs and prevention of fecal-related infectious diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204576PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179227PMC
March 2019

Intestinal microsporidiosis in Strasbourg from 2014 to 2016: emergence of an Enterocytozoon bieneusi genotype of Asian origin.

Emerg Microbes Infect 2018 Jun 6;7(1):97. Epub 2018 Jun 6.

Institute of Parasitology and Tropical Diseases, EA 7292, University of Strasbourg, 3 rue Koeberlé, Strasbourg, France.

Microsporidia cause opportunistic infections in highly immunodeficient individuals. Few studies on the epidemiology of these infections have been conducted in France. Between 2014 and 2016, we undertook a study to estimate the prevalence and circulating genotypes of this fungus-related micro-organism among the population of Strasbourg University Hospital. Samples were collected from hospitalized patients and analyzed using microscopy and molecular assays. Strains from positive subjects were sequenced for genotyping. Only 7/661 patients (1.1%) were positive for microsporidia, and the only species identified was Enterocytozoon bieneusi. Two patients presented immunodeficiency linked to AIDS, and five transplant recipients presented immunodeficiency linked to immunosuppressive therapies. Only five patients received specific antimicrosporidial treatment, but clinical outcomes were good in all cases. We identified four genotypes: A and D in patients with AIDS, and C and S9 in transplant recipients. To date, genotype S9 has been described only once. This genotype is similar to those found in farm animals in China. Because some of these animals have been introduced to Central Europe, we postulate that this genotype might be of Asian origin. Thus, genotyping microsporidial strains may be of epidemiological and clinical interest to identify potential outbreak sources depending on the infecting strains.
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http://dx.doi.org/10.1038/s41426-018-0099-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988701PMC
June 2018