Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study

Background By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fl uid, including clearance parameters. Methods In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fl uid at follow-up every 3–6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodefi cient mice to test for infectivity. We used a linear mixed-eff ect model to analyse the dynamics of virus persistence in seminal fl uid over time. Findings We enrolled 26 participants and tested 130 seminal fl uid specimens; median follow up was 197 days (IQR 187–209 days) after enrolment, which corresponded to 255 days (228–287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73–181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fl uid of –0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fl uid at 115 days (90% prediction interval 72–160) and 294 days (212–399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in aff ected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. Interpretation Time to clearance of Ebola virus RNA from seminal fl uid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks

Persistence and clearance of Ebola virus RNA from seminal fluid of Ebola virus disease survivors: a longitudinal analysis and modelling study.

BACKGROUND: By January, 2016, all known transmission chains of the Ebola virus disease (EVD) outbreak in west Africa had been stopped. However, there is concern about persistence of Ebola virus in the reproductive tract of men who have survived EVD. We aimed to use biostatistical modelling to describe the dynamics of Ebola virus RNA load in seminal fluid, including clearance parameters. METHODS: In this longitudinal study, we recruited men who had been discharged from three Ebola treatment units in Guinea between January and July, 2015. Participants provided samples of seminal fluid at follow-up every 3-6 weeks, which we tested for Ebola virus RNA using quantitative real-time RT-PCR. Representative specimens from eight participants were then inoculated into immunodeficient mice to test for infectivity. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. FINDINGS: We enrolled 26 participants and tested 130 seminal fluid specimens; median follow up was 197 days (IQR 187-209 days) after enrolment, which corresponded to 255 days (228-287) after disease onset. Ebola virus RNA was detected in 86 semen specimens from 19 (73%) participants. Median duration of Ebola virus RNA detection was 158 days after onset (73-181; maximum 407 days at end of follow-up). Mathematical modelling of the quantitative time-series data showed a mean clearance rate of Ebola virus RNA from seminal fluid of -0·58 log units per month, although the clearance kinetic varied greatly between participants. Using our biostatistical model, we predict that 50% and 90% of male survivors clear Ebola virus RNA from seminal fluid at 115 days (90% prediction interval 72-160) and 294 days (212-399) after disease onset, respectively. We also predicted that the number of men positive for Ebola virus RNA in affected countries would decrease from about 50 in January 2016, to fewer than 1 person by July, 2016. Infectious virus was detected in 15 of 26 (58%) specimens tested in mice. INTERPRETATION: Time to clearance of Ebola virus RNA from seminal fluid varies greatly between individuals and could be more than 13 months. Our predictions will assist in decision-making about surveillance and preventive measures in EVD outbreaks. FUNDING: This study was funded by European Union's Horizon 2020 research and innovation programme, Directorate-General for International Cooperation and Development of the European Commission, Institut national de la santé et de la recherche médicale (INSERM), German Research Foundation (DFG), and Innovative Medicines Initiative 2 Joint Undertaking

Case Report: COVID-19 and Lassa Fever Coinfection in an Ebola Suspected Patient in Guinea

ABSTRACT. In this case report, we describe a clinical presentation and therapeutic history of a unique case diagnosed with Lassa fever and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 23-year-old man from Yomou prefecture in southeast Guinea identified with suspected Ebola Virus Disease (EVD) in the midst of an ongoing outbreak of that disease in the same region. On May 3, 2021, he was admitted to the Nzérékoré Epidemic disease treatment center where his clinical condition deteriorated significantly. Laboratory testing performed on the same day reveals a negative EVD polymerase chain reaction (PCR). Three days later, the patient was tested positive for SARS-CoV-2 and Lassa fever by reverse transcriptase PCR (RT-PCR) assays. Laboratory examination also indicated severe hematological and biochemical deteriorations in the patient. This case substantiates the need for systematic differential diagnosis during epidemic-prone disease outbreaks to better manage severely unwell patients.</jats:p

Intégrer la recherche clinique dans la réponse aux épidémies

Au cours de l’épidémie de maladie à virus Ebola qui a affecté l’Afrique de l’ouest entre 2013 et 2016, la mise en place d’essais cliniques en vue de l’évaluation de stratégies thérapeutiques et de vaccins prometteurs, mais non homologués, est apparue comme une composante emblématique de la réponse globale à l’épidémie. En 2017, aucun agent antiviral n’a pu prouver une efficacité définitive chez les patients. Deux produits, la combinaison d’anticorps monoclonaux ZMapp et l’antiviral direct favipiravir, testés au cours d’essais cliniques de preuve de concept ou contrôlés avec randomisation, présentent un profil de sécurité ou d’efficacité préliminaire encourageant la poursuite de leur évaluation lors de la prochaine résurgence épidémique. Ces enjeux sont portés aux scénarios à construire et anticiper au cours de la période inter-épidémique inaugurée en 2016

Anosmie sans agueusie chez des patients COVID-19: à propos de 2 cas

Dans la pandémie actuelle, l'anosmie associée ou non à une agueusie semble être un symptôme fréquent en cas d'infection par le SRAS-CoV-2 responsable de COVID-19. Nous rapportons deux cas d´anosmies sans agueusies chez des patients COVID-19 adultes. L´installation a été brutale et a persisté quelques semaines après leur guérison. Ils consultèrent dans notre service ORL où ils bénéficièrent d´une abstention thérapeutique et d´une surveillance en ambulatoire. Au bout de 5 semaines, ils ont déclaré avoir récupéré leur odorat. Nous avons constaté que l´anosmie peut exister sans agueusie et persister après la guérison au COVID-19. La récupération de l´odorat est possible au bout de quelques semaines sans traitement médical. C´est pourquoi, nous recommandons un suivi des malades guéris du COVID-19 pour mieux appréhender les symptômes persistants

Des trypanosomes dans la peau

Le trypanosome africain Trypanosoma brucei gambiense, parasite responsable de la trypanosomiase humaine africaine, est transmis à l'homme par la piqûre d'une mouche tsé-tsé infectée, puis il prolifère dans le sang et la lymphe et enfin dans le système nerveux central. Le diagnostic de trypanosomiase implique deux étapes : un dépistage sérologique suivi de la détection de parasites vivants dans un fluide biologique. Cependant, les parasites peuvent rester indétectables chez certains individus qualifiés de séropositifs non confirmés qui restent alors sans traitement. Dans différents modèles de laboratoire, des chercheurs ont récemment démontré l'existence de réservoirs anatomiques de parasites extravasculaires, en particulier la peau, qui pourraient expliquer les infections latentes. Récemment, la présence de trypanosomes extravasculaires dermiques a également été démontrée chez l'homme, soulignant l'importance des individus séropositifs non confirmés comme réservoir de parasites qui pourrait compromettre l'élimination de la maladie. Les impacts cliniques et épidémiologiques de ces trypanosomes dermiques sont ici discutés

Des trypanosomes dans la peau

Le trypanosome africain Trypanosoma brucei gambiense, parasite responsable de la trypanosomiase humaine africaine, est transmis à l'homme par la piqûre d'une mouche tsé-tsé infectée, puis il prolifère dans le sang et la lymphe et enfin dans le système nerveux central. Le diagnostic de trypanosomiase implique deux étapes : un dépistage sérologique suivi de la détection de parasites vivants dans un fluide biologique. Cependant, les parasites peuvent rester indétectables chez certains individus qualifiés de séropositifs non confirmés qui restent alors sans traitement. Dans différents modèles de laboratoire, des chercheurs ont récemment démontré l'existence de réservoirs anatomiques de parasites extravasculaires, en particulier la peau, qui pourraient expliquer les infections latentes. Récemment, la présence de trypanosomes extravasculaires dermiques a également été démontrée chez l'homme, soulignant l'importance des individus séropositifs non confirmés comme réservoir de parasites qui pourrait compromettre l'élimination de la maladie. Les impacts cliniques et épidémiologiques de ces trypanosomes dermiques sont ici discutés

Extravascular dermal trypanosomes in suspected and confirmed cases of gambiense Human African Trypanosomiasis

International audienceBackground: The diagnosis of gambiense human African trypanosomiasis (gHAT) typically involves 2 steps: a serological screen, followed by the detection of living trypanosome parasites in the blood or lymph node aspirate. Live parasites can, however, remain undetected in some seropositive individuals, who, we hypothesize, are infected with Trypanosoma brucei gambiense parasites in their extravascular dermis.Methods: To test this hypothesis, we conducted a prospective observational cohort study in the gHAT focus of Forecariah, Republic of Guinea. Of the 5417 subjects serologically screened for gHAT, 66 were enrolled into our study and underwent a dermatological examination. At enrollment, 11 seronegative, 8 unconfirmed seropositive, and 18 confirmed seropositive individuals had blood samples and skin biopsies taken and examined for trypanosomes by molecular and immunohistological methods.Results: In seropositive individuals, dermatological symptoms were significantly more frequent, relative to seronegative controls. T.b. gambiense parasites were present in the blood of all confirmed cases (n = 18) but not in unconfirmed seropositive individuals (n = 8). However, T. brucei parasites were detected in the extravascular dermis of all unconfirmed seropositive individuals and all confirmed cases. Skin biopsies of all treated cases and most seropositive untreated individuals progressively became negative for trypanosomes 6 and 20 months later.Conclusions: Our results highlight the skin as a potential reservoir for African trypanosomes, with implications for our understanding of this disease's epidemiology in the context of its planned elimination and underlining the skin as a novel target for gHAT diagnostics