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1. Characterization and analytical validation of a new antigenic rapid diagnostic test for Ebola virus disease detection.

Author

Céline Couturier, Atsuhiko Wada, Karen Louis, Maxime Mistretta, Benoit Beitz, Moriba Povogui, Maryline Ripaux, Charlotte Mignon, Bettina Werle, Adrien Lugari, Delphine Pannetier, Sabine Godard, Anne Bocquin, Stéphane Mely, Ismaël Béavogui, Jean Hébélamou, David Leuenberger, Philippe Leissner, Takeshi Yamamoto, Patrick Lécine, Christophe Védrine, and Julie Chaix

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Hemorrhagic fever outbreaks are difficult to diagnose and control in part because of a lack of low-cost and easily accessible diagnostic structures in countries where etiologic agents are present. Furthermore, initial clinical symptoms are common and shared with other endemic diseases such as malaria or typhoid fever. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need, particularly in outbreak settings. Therefore, rapid diagnostic tests such as lateral flow can be broadly deployed and are typically well-suited to rapidly diagnose hemorrhagic fever viruses, such as Ebola virus. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect very low amount of virus in blood. Here, we developed and characterized an immunoassay test based on immunochromatography coupled to silver amplification technology to detect the secreted glycoprotein of EBOV. The glycoprotein is among the first viral proteins to be detected in blood. This strategy aims at identifying infected patients early following onset of symptoms by detecting low amount of sGP protein in blood samples. The limit of detection achieved by this sGP-targeted kit is 2.2 x 104 genome copies/ml in plasma as assayed in a monkey analytical cohort. Clinical performance evaluation showed a specificity of 100% and a sensitivity of 85.7% when evaluated with plasma samples from healthy controls and patients infected with Zaire Ebola virus from Macenta, Guinea. This rapid and accurate diagnostic test could therefore be used in endemic countries for early detection of infected individuals in point of care settings. Moreover, it could also support efficient clinical triage in hospitals or clinical centers and thus reducing transmission rates to prevent and better manage future severe outbreaks.

Published
2020
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2. Wide Diversity of Coronaviruses in Frugivorous and Insectivorous Bat Species: A Pilot Study in Guinea, West Africa

Author

Audrey Lacroix, Nicole Vidal, Alpha K. Keita, Guillaume Thaurignac, Amandine Esteban, Hélène De Nys, Ramadan Diallo, Abdoulaye Toure, Souana Goumou, Abdoul Karim Soumah, Moriba Povogui, Joel Koivogui, Jean-Louis Monemou, Raisa Raulino, Antoine Nkuba, Vincent Foulongne, Eric Delaporte, Ahidjo Ayouba, and Martine Peeters

Subjects
bat, coronavirus, Guinea, virus diversity, Africa, Microbiology, QR1-502
Abstract

Zoonoses can constitute a threat for public health that can have a global importance, as seen with the current COVID-19 pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV2). Bats have been recognized as an important reservoir of zoonotic coronaviruses (CoVs). In West Africa, where there is a high diversity of bat species, little is known on the circulation of CoVs in these hosts, especially at the interface with human populations. In this study, in Guinea, we tested a total of 319 bats belonging to 14 genera and six families of insectivorous and frugivorous bats across the country, for the presence of coronaviruses. We found CoVs in 35 (11%) of the tested bats—in three insectivorous bat species and five fruit bat species that were mostly captured close to human habitat. Positivity rates varied from 5.7% to 100%, depending on bat species. A wide diversity of alpha and beta coronaviruses was found across the country, including three sequences belonging to SarbeCoVs and MerbeCoVs subgenera known to harbor highly pathogenic human coronaviruses. Our findings suggest that CoVs are widely spread in West Africa and their circulation should be assessed to evaluate the risk of exposure of potential zoonotic CoVs to humans.

Published
2020
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3. Resurgence of Ebola Virus in 2021 in Guinea Suggests a New Paradigm for Outbreaks

Author

Fodé B. Sako, Jacob Camara, Amadou A. Sall, Ariane Düx, Giuditta Annibaldis, Meike Pahlmann, Abdoulaye Toure, Ousmane Faye, Mamadou Condé, Haby Diallo, Steven T. Pullan, Amadou Sidibe, Moriba Povogui, Fara Raymond Koundouno, Christophe Peyrefitte, Liana E. Kafetzopoulou, Alpha Kabinet Keita, Saa L. Millimono, Mandiou Diakite, Ahmadou Doré, Karla Pietro, N'. Faly Magassouba, Fabian H. Leendertz, Nicole Vidal, Stephan Günther, Anke Thielebein, Julia Hinzmann, Dembo Diakite, Ahidjo Ayouba, Cheikh Loucoubar, Kaka Kourouma, Martin Faye, Philippe Lemey, Moussa Moïse Diagne, Mamadou D. Barry, Fodé Y. Soumah, Annick Renevey, Georges Ki-Zerbo, Kékoura Ifono, Andrew Rambaut, Abdoul K. Soumah, Miles W. Carroll, Mamadou S. Bah, Joseph Akoi Bore, Ibrahima Camara, Mamadou S. Sow, Sébastien Calvignac-Spencer, Fodé A. Traore, Sophie Duraffour, Assaïtou Bah, John T. McCrone, Nathalie J. Vielle, Joshua Quick, Noël Tordo, Moussa Baldé, Mamadou Diop, Youssouf Sidibé, Martine Peeters, Madeleine Kourouma, Sakoba Keita, Mamadou B. Keita, Frédéric Le Marcis, Cé D. Saouromou, Anais Legand, Amadou Diallo, Pierre Formenty, Almudena Mari-Saez, Michael R. Wiley, Karifa Kourouma, Eric Delaporte, Barré Soropogui, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Robert Koch Institute [Berlin] (RKI), German Center for Infection Research - Partner Site Hamburg-Lübeck-Borstel-Riems, German Centre for Infection Research (DZIF), Centre de Recherche et de Formation en Infectiologie de Guinée [Conakry, Guinée] (CERFIG), Triangle : action, discours, pensée politique et économique (TRIANGLE), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Hôpital National Donka, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Epidemiology of Highly Pathogenic Microorganisms, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), CEA Tech Grand-Est (DGDE), CEA Tech en régions (CEA-TECH-Reg), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Santé Publique [Conakry, Guinée] (INSP), Ministère de la Santé [Conakry, Guinea], Laboratoire de Physique de l'Atmosphère et de l'Océan Siméon Fongang (LPAO-SF), École Supérieure Polytechnique de Dakar (ESP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Public Health England, University of Birmingham [Birmingham], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organization [Geneva], The University of Texas Medical Branch (UTMB), University of Nebraska Medical Center, University of Nebraska System, Institut Pasteur de Guinée, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), University of Edinburgh, Division Prévention et Lutte contre la Maladie, Ministère de la Santé et de l’Hygiène Publique, Ecole Nationale Superieure de Lyon, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Infectious and Tropical Diseases Department [Montpellier], Institut de Recherche pour le Développement (IRD)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Max Planck Institute for Evolutionary Anthropology [Leipzig], Max-Planck-Gesellschaft, ANR-16-IDEX-0006,MUSE,MUSE(2016), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), University of Oxford [Oxford], Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CEA Tech Alsace Champagne-Ardenne Lorraine, École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Sciences Po Lyon - Institut d'études politiques de Lyon (IEP Lyon), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Michel de l'Hospital : laboratoire de recherche en sciences juridiques et politiques (CMH ), and Université Clermont Auvergne (UCA)

Subjects
Male, Zaire ebolavirus, Time Factors, viruses, Disease, Biology, medicine.disease_cause, Disease cluster, Models, Biological, Viral Zoonoses, Virus, Disease Outbreaks, 03 medical and health sciences, Ebola virus, 0302 clinical medicine, medicine, Animals, Humans, Survivors, 030212 general & internal medicine, Clade, Phylogeny, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Transmission (medicine), Guinea-2021, High-Throughput Nucleotide Sequencing, Outbreak, Hemorrhagic Fever, Ebola, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, Ebolavirus, Virology, 3. Good health, Democratic Republic of the Congo, Female, Persistent Infection, epidemiology, Guinea, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak—between 14 February and 19 June 2021—near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization. The viral lineage responsible for the February 2021 outbreak of Ebola virus disease in Guinea is nested within a clade that predominantly consists of genomes sampled during the 2013–2016 epidemic, suggesting that the virus might have re-emerged after a long period of latency within a previously infected individual.

Published
2021

4. Characterization and analytical validation of a new antigenic rapid diagnostic test for Ebola virus disease detection

Author

Julie Chaix, Stéphane Mély, Adrien Lugari, Atsuhiko Wada, Philippe Leissner, Karen Louis, Maxime Mistretta, Takeshi Yamamoto, Moriba Povogui, Céline Couturier, Maryline Ripaux, Sabine Godard, Jean Hébélamou, Delphine Pannetier, Charlotte Mignon, Anne Bocquin, Christophe Védrine, Patrick Lécine, Benoit Beitz, Bettina Werle, David Leuenberger, Ismaël Béavogui, Bodescot, Myriam, BIOASTER Microbiology Technology Institute [Lyon], FUJIFILM [Kaisei, Ashigarakami, Kanagawa, Japon], Centre de Recherche et de Formation en Infectiologie de Guinée [Conakry, Guinée] (CERFIG), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Spécialisé de Macenta [Guinée] (CHRS Macenta), and The work performed by BIOASTER received funding from the French Government as part of the 'Programme des Investissements d’Avenir' (grant n˚ANR-10-AIRT-03) and from FUJIFILM.

Subjects
0301 basic medicine, RNA viruses, Viral Diseases, Physiology, RC955-962, Molecular Diagnostic Method, Monkeys, medicine.disease_cause, Pathology and Laboratory Medicine, 0302 clinical medicine, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Enzyme-Linked Immunoassays, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Antigens, Viral, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mammals, Immunoassay, Rapid diagnostic test, Mammalian Genomics, Eukaryota, Genomics, Ebolavirus, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Body Fluids, Blood, Infectious Diseases, Medical Microbiology, Filoviruses, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, Vertebrates, Public aspects of medicine, RA1-1270, Anatomy, Pathogens, Ebola Virus, Research Article, Neglected Tropical Diseases, Primates, Point-of-Care Systems, 030231 tropical medicine, Research and Analysis Methods, Microbiology, Ebola Hemorrhagic Fever, Typhoid fever, Virus, Blood Plasma, 03 medical and health sciences, Diagnostic Medicine, medicine, Genetics, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Immunoassays, Microbial Pathogens, Viral Hemorrhagic Fevers, Ebola virus, business.industry, Hemorrhagic Fever Viruses, Public Health, Environmental and Occupational Health, Organisms, Outbreak, Biology and Life Sciences, Reproducibility of Results, Hemorrhagic Fever, Ebola, medicine.disease, Tropical Diseases, Virology, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Animal Genomics, Amniotes, Immunologic Techniques, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Malaria
Abstract

Hemorrhagic fever outbreaks are difficult to diagnose and control in part because of a lack of low-cost and easily accessible diagnostic structures in countries where etiologic agents are present. Furthermore, initial clinical symptoms are common and shared with other endemic diseases such as malaria or typhoid fever. Current molecular diagnostic methods such as polymerase chain reaction require trained personnel and laboratory infrastructure, hindering diagnostics at the point of need, particularly in outbreak settings. Therefore, rapid diagnostic tests such as lateral flow can be broadly deployed and are typically well-suited to rapidly diagnose hemorrhagic fever viruses, such as Ebola virus. Early detection and control of Ebola outbreaks require simple, easy-to-use assays that can detect very low amount of virus in blood. Here, we developed and characterized an immunoassay test based on immunochromatography coupled to silver amplification technology to detect the secreted glycoprotein of EBOV. The glycoprotein is among the first viral proteins to be detected in blood. This strategy aims at identifying infected patients early following onset of symptoms by detecting low amount of sGP protein in blood samples. The limit of detection achieved by this sGP-targeted kit is 2.2 x 104 genome copies/ml in plasma as assayed in a monkey analytical cohort. Clinical performance evaluation showed a specificity of 100% and a sensitivity of 85.7% when evaluated with plasma samples from healthy controls and patients infected with Zaire Ebola virus from Macenta, Guinea. This rapid and accurate diagnostic test could therefore be used in endemic countries for early detection of infected individuals in point of care settings. Moreover, it could also support efficient clinical triage in hospitals or clinical centers and thus reducing transmission rates to prevent and better manage future severe outbreaks., Author summary Ebola virus disease is a severe disease caused by Ebola virus, a member of the filovirus family, which occurs in humans and other primates. Ebola is believed to be zoonotic, however the natural reservoir is unknown. Overlapping symptoms with other endemic diseases, such as malaria and cholera, make accurate diagnostic challenging. Outbreaks of Ebola have been widespread as the consequence of the absence of available rapid, sensitive, specific, robust, and affordable licensed diagnostic test in remote areas, where outbreaks usually start. Here we have established and validated a rapid diagnostic test, which is fast, sensitive, specific, efficient, affordable, and user-friendly. Its analytical characteristics make it suitable for clinical management during Ebola virus outbreaks in remote areas. Of interest, this rapid diagnostic test detects the presence of an early viral antigen, the secreted glycoprotein, found in blood of patients shortly after infection, suggesting that it could be used to identify infected patients shortly after onset of symptoms.

Published
2020

5. Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study

Author

Bernard Taverne, Eric Delaporte, Ahidjo Ayouba, Muriel Rabilloud, Thierno Alimou Barry, Aboubacar Hawa Sylla, Charlotte Laniece-Delaunay, Mariama Djouldé Sall, Alseny Balde, Moriba Povogui, Ibrahima Camara, Yazdan Yazdanpanah, Amara Bamba, Cécé Kpamou, Fabien Subtil, Emile Souro Kamano, Christelle Butel, Amadou Yalla Camara, Martine Peeters, Alpha Kabinet Keita, Guillaume Thaurignac, Maou Sakouvogui, Mamadou Saliou Diallo, Saran Doumbouya, Mamadou Saliou Sow, Philippe Msellati, Abdoulaye Touré, Amadou Bailo Diallo, Jean Louis Monemou, Aboubacar Mamy Conte, René Ecochard, Joel Balle Koivogui, Yves Levy, Abdoul Karim Soumah, Jean-François Etard, Jean-François Delfraissy, Sandrine Leroy, Ibrahima Balde, Diaby Aboubacar, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université Gamal Abdel Nasser de Conakry, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université de Lyon, Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CCSD, Accord Elsevier, and Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI)

Subjects
Male, Cross-sectional study, viruses, medicine.disease_cause, Antibodies, Viral, 0302 clinical medicine, Risk Factors, Seroepidemiologic Studies, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, Medicine, 030212 general & internal medicine, Child, Aged, 80 and over, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Environmental exposure, Middle Aged, Ebolavirus, 3. Good health, Infectious Diseases, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Population study, Female, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, Asymptomatic, 03 medical and health sciences, Young Adult, Internal medicine, Disease Transmission, Infectious, Humans, Aged, Retrospective Studies, Ebola virus, business.industry, Retrospective cohort study, Odds ratio, Environmental Exposure, Hemorrhagic Fever, Ebola, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Asymptomatic Diseases, Guinea, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Funding Institut National de la Santé et de la Recherche Médicale, Reacting, the French Ebola Task Force, Institut de Recherche pour le Développement, and Montpellier University Of Excellence-University of Montpellier.; International audience; BACKGROUND : The prevalence of Ebola virus infection among people who have been in contact with patients with Ebola virus disease remains unclear, but is essential to understand the dynamics of transmission. This study aimed to identify risk factors for seropositivity and to estimate the prevalence of Ebola virus infection in unvaccinated contact persons.METHODS : In this retrospective, cross-sectional observational study, we recruited individuals between May 12, 2016, and Sept 8, 2017, who had been in physical contact with a patient with Ebola virus disease, from four medical centres in Guinea (Conakry, Macenta, N'zérékoré, and Forécariah). Contact persons had to be 7 years or older and not diagnosed with Ebola virus disease. Participants were selected through the Postebogui survivors' cohort. We collected self-reported information on exposure and occurrence of symptoms after exposure using a questionnaire, and tested antibody response against glycoprotein, nucleoprotein, and 40-kDa viral protein of Zaire Ebola virus by taking a blood sample. The prevalence of Ebola virus infection was estimated with a latent class model.FINDINGS : 1721 contact persons were interviewed and given blood tests, 331 of whom reported a history of vaccination so were excluded, resulting in a study population of 1390. Symptoms were reported by 216 (16%) contact persons. The median age of participants was 26 years (range 7-88) and 682 (49%) were male. Seropositivity was identified in 18 (8·33%, 95% CI 5·01-12·80) of 216 paucisymptomatic contact persons and 39 (3·32%, 5·01-12·80) of 1174 (2-4) asymptomatic individuals (p=0·0021). Seropositivity increased with participation in burial rituals (adjusted odds ratio [aOR] 2·30, 95% CI 1·21-4·17; p=0·0079) and exposure to blood or vomit (aOR 2·15, 1·23-3·91; p=0·0090). Frequency of Ebola virus infection varied from 3·06% (95% CI 1·84-5·05) in asymptomatic contact persons who did not participate in burial rituals to 5·98% (2·81-8·18) in those who did, and from 7·17% (3·94-9·09) in paucisymptomatic contact persons who did not participate in burial rituals to 17·16% (12·42-22·31) among those who did.INTERPRETATION : This study provides a new assessment of the prevalence of Ebola virus infection among contact persons according to exposure, provides evidence for the occurrence of paucisymptomatic cases, and reinforces the importance of closely monitoring at-risk contact persons.

Published
2019

6. A 40-Month Follow-Up of Ebola Virus Disease Survivors in Guinea (PostEbogui) Reveals Long-Term Detection of Ebola Viral Ribonucleic Acid in Semen and Breast Milk

Author

Keita, Alpha Kabinet, Vidal, Nicole, Toure, Abdoulaye, Diallo, Mamadou Saliou Kalifa, Magassouba, N’fally, Baize, Sylvain, Mateo, Mathieu, Raoul, Herve, Mely, Stephane, Subtil, Fabien, Kpamou, Cécé, Koivogui, Lamine, Traore, Falaye, Sow, Mamadou Saliou, Ayouba, Ahidjo, Etard, Jean Francois, Delaporte, Eric, Peeters, Martine, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG), Université Gamal Abdel Nasser de Conakry, Institut National de Santé Publique [Conakry, Guinée] (INSP), Ministère de la Santé [Conakry, Guinea], Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire P4 Jean Mérieux-Inserm [Lyon] (Unité de service 3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Européen de Recherche en Virologie et Immunologie [Lyon] (Tour Inserm CERVI), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital National Donka, This work was funded in part by grants from the Institut National de la Santé et de la Recherche Médicale/Ebola Task Force, REACTing (REsearch and ACTion targeting emerging infectious diseases) and the Institut de Recherche pour le Développement and Montpellier Université d’Excellence (EBOHEALTH, I-Site MUSE, ANR-16-IDEX-0006). A. K. K. was supported by a postdoctoral fellowship from Montpellier Université d’Excellence (I-Site MUSE, ANR-16-IDEX-0006)., We thank the PostEbogui team for their daily work, all of the survivors, the Guinean survivors’ associations for their help in identifying and tracing survivors, the laboratory staff of Institut National de Santé Publique and Centre de Recherche et de Formation en Infectiologie (CERFIG) (Moriba Povogui, Jean-louis Monemou, Joel Ballè Koivogui, Abdoul Karim Soumah, Amara Bamba, and Saran Doumbouya), the laboratory facility from Macenta (Guillain Mikaty), and European West African Mobile Laboratory (Brunel Joanna, Belarbi Essia, Martinez Prudencio, Pannetier Delphine, Picard Caroline, Escudero Beatriz, Mengardi Chloe, Nguyen Xuan-Nhi, Tracqui Elodie, Hamied Lola, Olausson Mikaela, Verner-Carlsson Jenny, Godard Sabine, Moroso Marie, Thomas Damien, Ottmann Michele, Bernard Sandra, Yonga Wansi Gide Martial, Sylla Yahaya, Bocquin Anne, Sautter Carmen-Alexandra, Rittaud Adeline, Carbonnelle Caroline, Mundweiler Stephanie, Calland Noemie, Chevillard Eve, and Juven Fabienne)., PostEbogui Study Group, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-16-IDEX-0006,MUSE,MUSE(2016), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Donka National Hospital

Subjects
Editor's Choice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ebola, Major Article, breast milk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Guinea, semen, body fluids
Abstract

Background With the increasing frequency and impact of Ebola virus disease (EVD) outbreaks illustrated by recent epidemics, a good understanding of the extent of viral persistance or ribonucleic acid (RNA) detection in body fluids from survivors is urgently needed. Methods Ebola viral RNA shedding was studied with molecular assays in semen (n = 1368), urine (n = 1875), cervicovaginal fluid (n = 549), saliva (n = 900), breast milk (n = 168), and feces (n = 558) from EVD survivors in Guinea (PostEbogui cohort, n = 802) at a regular base period until 40 months after inclusion. Results Twenty-seven of 277 (9.8%) male survivors tested positive for Ebola RNA in at least 1 semen sample. The probability of remaining positive for Ebola RNA in semen was estimated at 93.02% and 60.12% after 3 and 6 months. Viral RNA in semen was more frequent in patients with eye pain (P = .036), joint pain (P = .047), and higher antibody levels to Ebola virus antigens (nucleoprotein [P = .001], glycoprotein [P = .05], and viral protein-40 [P = .05]). Ebola RNA was only rarely detected in the following body fluids from EVD survivors: saliva (1 of 454), urine (2 of 593), breast milk (2 of 168), cervicovaginal secretions (0 of 273), and feces (0 of 330). Ribonucleic acid was detected in breast milk 1 month after delivery but 500 days after discharge of Ebola treatment unit (ETU) in 1 woman who became pregnant 7 months after discharge from the ETU. Conclusions The frequency and potential long-term presence of viral RNA in semen confirmed that systematic prevention measures in male survivors are required. Our observation in breast milk suggests that our knowledge on viral reservoir in immune-privileged sites and its impact are still incomplete., On 5,400 body fluid samples from Ebola Virus Disease (EVD) survivors, during 40 months follow-up in Guinea, RNA was observed in semen and breast milk for up to 500 days, illustrating the complexity of the viral reservoir and management of survivors.

Published
2019

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