11 research outputs found
Resurgence of Ebola Virus Disease in Guinea Linked to a Survivor With Virus Persistence in Seminal Fluid for More Than 500 Days.
We report on an Ebola virus disease (EVD) survivor who showed Ebola virus in seminal fluid 531 days after onset of disease. The persisting virus was sexually transmitted in February 2016, about 470 days after onset of symptoms, and caused a new cluster of EVD in Guinea and Liberia
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
LCOs (luminescent conjugated oligothiophenes) als neue β-Amyloid-bindende Substanzen zur Diagnose und Therapie der Alzheimer´schen Erkrankung
Luminescent conjugated oligothiophenes (LCOs) are novel molecular amyloid
binding agents, which identify their targets with high sensitivity and
specificity, and additionally provide structural information about bound
amyloid lesions due to changing emission spectra. The pentameric LCO pFTAA
readily crosses the blood brain barrier (BBB) after intravenous injection and
efficiently labels cerebral Aβ plaques in Alzheimer´s disease (AD) transgenic
APPPS1 mice. Within the present thesis, LCOs were investigated as in vivo
tracers for detecting cerebral Aβ deposits and as potential pharmacophores in
APPPS1 mice, a model of early and robust cerebral amyloidosis. To test LCOs
for neuroimaging of cerebral Aβ deposits using magnetic resonance imaging
(MRI), they were attached by distinct spacer components to magnetic
nanoparticles (MNPs), resulting in coupled probes termed LCO-MNPs. LCO-MNPs
were peripherally applied to APPPS1 mice and BBB passing as well as labeling
of cerebral Aβ plaques was investigated using optical imaging and MRI. Results
revealed a specific optical signal of LCO labeled cerebral Aβ plaques after
peripheral administration of LCO-MNPs, however no significant MRI and
transmission electron microscopic signals were detected so far. Since
different amyloid dyes showed anti-amyloid effects by preventing Aβ
fibrillogenesis or by inhibition of Aβ toxicity, pFTAA was further
investigated as potential pharmacophores in AD. After crossing the BBB of
APPPS1 mice following peripheral application, pFTAA binds deposited fibrillar
Aβ plaques but possibly also pre-fibrillar toxic oligomers, which were
described to primarily cause impairments in memory and cognition. To analyze
the effect of cerebral bound pFTAA on AD pathology, APPPS1 mice were treated
with pFTAA, and cerebral Aβ plaque load and hippocampal synaptic transmission
were determined. Although no functional impact on synaptic transmission was
observed after peripheral pFTAA treatment, an influence on Aβ plaque pathology
in APPPS1 mice was detected. The overall cerebral Aβ plaque burden was not
changed, however pFTAA treated APPPS1 mice revealed more numerous and smaller
plaques when compared to PBS treated controls, which could in addition be
structurally distinguished from Aβ plaques of control animals. Thus in vivo
pFTAA binding to cerebral amyloid deposits in APPPS1 mice slows Aβ plaque
growth and maturation. The significant increase of cortical Aβ plaque number
might be explained by elevated amyloid seeding through pFTAA binding to
cerebral Aβ. The results of the present thesis show, that pFTAA or LCOs have
the potential to be further investigated for human AD diagnostic, since they
caused no obvious toxic side effects in long term treated APPPS1 mice and did
not substantially alter cerebral plaque burden.LCOs sind neuartige, konformations-sensitive optische Amyloid-Marker, die je
nach Struktur der gebundenen, pathologischen Amyloid-Ablagerungen
Fluoreszenzlicht unterschiedlicher Wellenlänge emittieren. Nach einer
intravenösen Injektion in dem transgenen Alzheimer Mausmodell APPPS1 sind
bestimmte LCOs, beispielsweise pFTAA, in der Lage die Blut-Hirn-Schranke (BHS)
zu passieren und zerebrale β-Amyloid-Plaques sowohl langfristig als auch
spezifisch zu markieren. Im Rahmen dieses Promotionsprojektes wurden LCOs zum
einen auf ihre Verwendbarkeit als neuartige diagnostische Marker zur Detektion
von zerebralen β-Amyloid und zum anderen als potentielle therapeutische
Substanzen im transgenen Alzheimer Mausmodell APPPS1 untersucht. Innerhalb des
diagnostischen Versuchsansatzes wurde analysiert, ob an magnetische
Nanopartikel gekoppelte LCO-Derivate (LCO-MNPs) für den Einsatz als
Kontrastmittel nach einer intravenösen Injektion ebenfalls in der Lage sind,
die BHS zu passieren und an zerebrale β-Amyloid-Ablagerungen in APPPS1 Tieren
zu binden. Nach intravenöser Applikation der LCO-MNPs wurden mittels
Fluoreszenz-Mikroskopie in APPPS1 Tieren LCO-markierte β-Amyloid-Plaques
detektiert. Magnetische Nanopartikel konnten bisher mittels der
Magnetresonanztomographie und Elektronenmikroskopie allerdings nicht im Hirn
der behandelten Tiere nachgewiesen werden. Verschiedene Amyloid-spezifische
Marker wie beispieslwesie Kongo Rot oder Methoxy-XO4 wiesen zuvor anti-
amyloidogene Eigenschaften in vitro und in transgenen Alzheimer Tier-Modellen
in vivo auf. Auch LCPs (luminescent conjugated polythiophenes) als Vorläufer
von LCOs reduzieren die Ausbreitung von Prion-Proteinen in vitro und wiesen
somit einen Amyloid-hemmenden Effekt auf. Innerhalb des vorliegenden
Promotionsprojektes wurde weiterhin untersucht, ob die langfristige in vivo
Bindung von pFTAA an zerebrale β-Amyloid-Plaques in APPPS1 Tieren einen
Einfluss auf die Plaque-Pathologie in kortikalen Hirnregionen hat und LCOs
somit möglicherweise als neue therapeutische Substanzen eingesetzt werden
können. Nach einer in vivo Behandlung von transgenen APPPS1 Tieren, wurden
keine toxischen Nebenwirkungen beobachtet und Analysen der Gesamt-Plaque-
Belastung im Hirn der behandelten Tiere zeigten im Vergleich zu Kontrolltieren
keine signifikanten Unterschiede. Allerdings wiesen pFTAA-behandelte APPPS1
Tiere signifikant mehr kleinere β-Amyloid Plaques und geringere
durchschnittliche Flächen pro Plaque auf. Zusätzlich wurden signifikante
morphologische Unterschiede zwischen pFTAA gebundenen und unbehandelten
zerebralen β-Amyloid Plaques aufgezeigt, die auf eine langsamere β-Amyloid
Plaque-Reifung hinweisen. Die erhöhte Anzahl an kortikalen Plaqes könnte auch
auf eine mögliche, verstärkte Nukleation der Amyloidablagerungen auf Grund der
pFTAA Bindung hinweisen. Zusammenfassend könnten diese beiden Ergebnisse die
unveränderte Gesamt-Plaque-Belastung im Hirn pFTAA behandelter Tiere erklären.
Da pFTAA auch pre-fibrilläre, toxisch wirkende Aβ-Oligomere bindet, wurde
ausserdem der Effekt einer pFTAA Behandlung auf die synaptische Transmission
in APPPS1 Tieren untersucht. Es wurde jedoch kein signifikanter Einfluss der
pFTAA Behandlung in APPPS1 Tieren auf die synaptische Transmission im
Hippokampus nachgewiesen. Zusammenfassend demonstrieren die Ergebnisse keinen
substantiellen therapeutischen Effekt während einer Langzeit-Behandlung von
transgenen Alzheimer Tieren mit pFTAA. Allerdings unterstützen die generierten
Daten die Anwendung von pFTAA beziehungsweise LCOs in der humanen in vitro
Diagnostik und potentiell auch in der in vivo Diagnostik
Whole genome sequencing and phylogenetic classification of Tunisian SARS-CoV-2 strains from patients of the Military Hospital in Tunis
In the present work, two complete genome sequences of SARS-CoV-2 were obtained from nasal swab samples of Tunisian SARS-CoV-2 PCR-positive patients using nanopore sequencing. The virus genomes of two of the patients examined, a Tunisian soldier returning from a mission in Morocco and a member of another Tunisian family, showed significant differences in analyses of the total genome and single nucleotide polymorphisms (SNPs). Phylogenetic relationships with known SARS-CoV-2 genomes in the African region, some European and Middle Eastern countries and initial epidemiological conclusions indicate that the introduction of SARS-CoV-2 into Tunisia from two independent sources was travel-related
Viral and Bacterial Zoonotic Agents in Dromedary Camels from Southern Tunisia: A Seroprevalence Study
The rapid spread of SARS-CoV-2 clearly demonstrated the potential of zoonotic diseases to cause severe harm to public health. Having limited access to medical care combined with severe underreporting and a lack of active surveillance, Africa carries a high burden of neglected zoonotic diseases. Therefore, the epidemiological monitoring of pathogen circulation is essential. Recently, we found extensive Middle East respiratory syndrome coronavirus (MERS-CoV) prevalence in free-roaming dromedary camels from southern Tunisia. In this study, we aimed to investigate the seroprevalence, and thus the risk posed to public health, of two additional viral and two bacterial pathogens in Tunisian dromedaries: Rift Valley fever virus (RVFV), foot-and-mouth disease virus (FMDV), Coxiella burnetii and Brucella spp. via ELISA. With 73.6% seropositivity, most animals had previously been exposed to the causative agent of Q fever, C. burnetii. Additionally, 7.4% and 1.0% of the dromedaries had antibodies against Brucella and RVFV, respectively, while no evidence was found for the occurrence of FMDV. Our studies revealed considerable immunological evidence of various pathogens within Tunisian dromedary camels. Since these animals have intense contact with humans, they pose a high risk of transmitting serious zoonotic diseases during active infection. The identification of appropriate countermeasures is therefore highly desirable
Prevalence of Middle East Respiratory Syndrome Coronavirus in Dromedary Camels, Tunisia
Free-roaming camels, especially those crossing national borders, pose a high risk for spreading Middle East respiratory syndrome coronavirus (MERS-CoV). To prevent outbreaks, active surveillance is necessary. We found that a high percentage of dromedaries in Tunisia are MERS-CoV seropositive (80.4%) or actively infected (19.8%), indicating extensive MERS-CoV circulation in Northern Africa
Two-Photon Fluorescence and Magnetic Resonance Specific Imaging of Aβ Amyloid Using Hybrid Nano-GdF 3 Contrast Media
International audienceReal time in vivo detection of Amyloid β (Aβ) deposits at an early stage may lead to faster and more conclusive diagnosis of Alzheimer’s disease (AD) and can facilitate the follow up of the effect of therapeutic interventions. In this work, the capability of new hybrid nanomaterials to target and detect Aβ aggregates using magnetic resonance (MRI) and fluorescence imaging is demonstrated. These smart contrast agents contain paramagnetic nanoparticles surrounded by luminescent conjugated oligothiophenes (LCOs) known to selectively bind to Aβ aggregates, with emission spectra strongly dependent on their conformations, opening the possibilities for several fluorescence imaging modes for AD diagnostics. Relaxivity is evaluated in vitro and ex vivo. The capability of these contrast media to link to Aβ fibrils in stained sections is revealed using transmission electron microscopy and fluorescence microscopy. Preliminary in vivo experiments show the ability of the contrast agent to diffuse through the blood–brain barrier of model animals and specifically stain amyloid deposits
Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer's disease-like mice
Although central nervous system-resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), a major pathological hallmark of Alzheimer's disease (AD), it has been suggested that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ-clearing capabilities. Here, we demonstrate that the conditional ablation of resident microglia in CD11b-HSVTK (TK) mice is followed by a rapid repopulation of the brain by peripherally derived myeloid cells. We used this system to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology and therefore depleted and replaced the pool of resident microglia with peripherally derived myeloid cells in Aβ-carrying APPPS1 mice crossed to TK mice (APPPS1;TK). Despite a nearly complete exchange of resident microglia with peripheral myeloid cells, there was no significant change in Aβ burden or APP processing in APPPS1;TK mice. Importantly, however, newly recruited peripheral myeloid cells failed to cluster around Aβ deposits. Even additional anti-Aβ antibody treatment aimed at engaging myeloid cells with amyloid plaques neither directed peripherally derived myeloid cells to amyloid plaques nor altered Aβ burden. These data demonstrate that mere recruitment of peripheral myeloid cells to the brain is insufficient in substantially clearing Aβ burden and suggest that specific additional triggers appear to be required to exploit the full potential of myeloid cell-based therapies for AD
Evidence for Age-Dependent <i>in Vivo</i> Conformational Rearrangement within Aβ Amyloid Deposits
Deposition
of aggregated Aβ peptide in the brain is one of the major hallmarks
of Alzheimer’s disease. Using a combination of two structurally
different, but related, hypersensitive fluorescent amyloid markers,
LCOs, reporting on separate ultrastructural elements, we show that
conformational rearrangement occurs within Aβ plaques of transgenic
mouse models as the animals age. This important mechanistic insight
should aid the design and evaluation of experiments currently using
plaque load as readout