Publications by authors named "Sarah Winnicki"

22 Publications

  • Page 1 of 1

The limits of egg recognition: testing acceptance thresholds of American robins in response to decreasingly egg-shaped objects in the nest.

R Soc Open Sci 2021 Jan 27;8(1):201615. Epub 2021 Jan 27.

Department of Biological Sciences; Rutgers, The State University of New Jersey, Newark, NJ, USA.

Some hosts of avian brood parasites reduce or eliminate the costs of parasitism by removing foreign eggs from the nest (rejecter hosts). In turn, even acceptor hosts typically remove most non-egg-shaped objects from the nest, including broken shells, fallen leaves and other detritus. In search for the evolutionary origins and sensory mechanisms of egg rejection, we assessed where the potential threshold between egg recognition and nest hygiene may lie when it comes to stimulus shape. Most previous studies applied comparisons of egg-sized objects with non-continuous variation in shape. Here, instead, we used two series of three-dimensional-printed objects, designed to increasingly diverge from natural eggs along two axes (width or angularity) of shape variation. As predicted, we detected transitions from mostly acceptance to mostly rejection in the nests of American robins along each of the two axes. Our methods parallel previous innovations in egg-rejection studies through the use of continuous variation in egg coloration and maculation contrast, to better understand the sensory limits and thresholds of variation in egg recognition and rejection in diverse hosts of avian brood parasites.
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http://dx.doi.org/10.1098/rsos.201615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890492PMC
January 2021

Real-time Metagenomic Analysis of Undiagnosed Fever Cases Unveils a Yellow Fever Outbreak in Edo State, Nigeria.

Sci Rep 2020 02 21;10(1):3180. Epub 2020 Feb 21.

African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Osun State, Nigeria.

Fifty patients with unexplained fever and poor outcomes presented at Irrua Specialist Teaching Hospital (ISTH) in Edo State, Nigeria, an area endemic for Lassa fever, between September 2018 - January 2019. After ruling out Lassa fever, plasma samples from these epidemiologically-linked cases were sent to the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Ede, Osun State, Nigeria, where we carried out metagenomic sequencing which implicated yellow fever virus (YFV) as the etiology of this outbreak. Twenty-nine of the 50 samples were confirmed positive for YFV by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), 14 of which resulted in genome assembly. Maximum likelihood phylogenetic analysis revealed that these YFV sequences formed a tightly clustered clade more closely related to sequences from Senegal than sequences from earlier Nigerian isolates, suggesting that the YFV clade responsible for this outbreak in Edo State does not descend directly from the Nigerian YFV outbreaks of the last century, but instead reflects a broader diversity and dynamics of YFV in West Africa. Here we demonstrate the power of metagenomic sequencing for identifying ongoing outbreaks and their etiologies and informing real-time public health responses, resulting in accurate and prompt disease management and control.
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http://dx.doi.org/10.1038/s41598-020-59880-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035389PMC
February 2020

Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018.

N Engl J Med 2018 11 17;379(18):1745-1753. Epub 2018 Oct 17.

From the Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard University (K.J.S., K.G.B., S.M., S.F.S., S.M.W., R.R.S., J.Q., S.W., P.B., S.Y., B.C., D.K., A.C., A.G.-Y., C.A.F., D.J.P., N.L.Y., B.L.M., P.C.S.), the Center for Systems Biology, Department of Organismic and Evolutionary Biology (K.J.S., K.G.B., S.F.S., S.W., B.C., D.K., C.A.F., N.L.Y., P.C.S.), and the Faculty of Arts and Sciences (M.N.), Harvard University, Harvard University Extension School (R.R.S.), and Harvard-MIT Health Sciences and Technology, MIT (S.Y., P.C.S.), Cambridge, and the Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health (K.G.B., S.F.S., B.L.M., P.C.S., C.T.H.), and Beth Israel Deaconess Medical Center, Division of Infectious Diseases (S.M.), Boston - all in Massachusetts; the African Center of Excellence for Genomics of Infectious Diseases (P.E., J.U.O., E.U., T.K., F.A., J.U., A.G., M.M., I.N., P.O., O.T., O.A.F., C.T.H.) and the Department of Biological Sciences, College of Natural Sciences (J.U.O., E.U., T.K., F.A., J.U., P.O., O.A.F., C.T.H.), Redeemer's University, Ede, the Institute of Lassa Fever Research and Control (I.O., C. Iruolagbe, J.A., E.U., P.A., G.O., O.O., B.O., E.B.M., M.A., R.E., B.E., E.O.-E., G.A., S.O., P.O.O., C.T.H.) and the Department of Medicine (P.O.O.), Irrua Specialist Teaching Hospital, Irrua, the Nigeria Center for Disease Control, Abuja (C. Ihekweazu), and the Department of Medicine, Faculty of Clinical Sciences, Ambrose Alli University, Ekpoma (P.O.O.) - all in Nigeria; the Laboratory of Parasitology/Mycology HALD, Cheikh Anta Diop University of Dakar, Dakar, Senegal (A.G.); Kenema Government Hospital, Kenema, Sierra Leone (M.M.); Tulane Health Sciences Center, Tulane University, New Orleans (R.F.G.); the Departments of Immunology and Microbial Science and Integrative Structural and Computational Biology, Scripps Research Institute, and the Scripps Translational Science Institute, La Jolla, CA (K.G.A.); and Howard Hughes Medical Institute, Chevy Chase, MD (P.C.S.).

During 2018, an unusual increase in Lassa fever cases occurred in Nigeria, raising concern among national and international public health agencies. We analyzed 220 Lassa virus genomes from infected patients, including 129 from the 2017-2018 transmission season, to understand the viral populations underpinning the increase. A total of 14 initial genomes from 2018 samples were generated at Redeemer's University in Nigeria, and the findings were shared with the Nigerian Center for Disease Control in real time. We found that the increase in cases was not attributable to a particular Lassa virus strain or sustained by human-to-human transmission. Instead, the data were consistent with ongoing cross-species transmission from local rodent populations. Phylogenetic analysis also revealed extensive viral diversity that was structured according to geography, with major rivers appearing to act as barriers to migration of the rodent reservoir.
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http://dx.doi.org/10.1056/NEJMoa1804498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181183PMC
November 2018

Field validation of recombinant antigen immunoassays for diagnosis of Lassa fever.

Sci Rep 2018 04 12;8(1):5939. Epub 2018 Apr 12.

Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Ede, Osun State, Nigeria.

Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient's clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR. The ReLASV rapid diagnostic test (RDT), a lateral flow immunoassay based on paired monoclonal antibodies to the Josiah strain of LASV (lineage IV), performed with 90% sensitivity and 100% specificity. ReLASV immunoassays performed better than the most robust qPCR currently available, which had 82% sensitivity and 95% specificity. The performance characteristics of recombinant antigen-based Lassa virus immunoassays indicate that they can aid in the diagnosis of LASV Infection and inform the clinical management of Lassa fever patients.
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http://dx.doi.org/10.1038/s41598-018-24246-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897328PMC
April 2018

Zika virus evolution and spread in the Americas.

Nature 2017 06 24;546(7658):411-415. Epub 2017 May 24.

Bureau of Public Health Laboratories, Division of Disease Control and Health Protection, Florida Department of Health, Tampa, Florida, USA.

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.
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http://dx.doi.org/10.1038/nature22402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563848PMC
June 2017

Genomic epidemiology reveals multiple introductions of Zika virus into the United States.

Nature 2017 06 24;546(7658):401-405. Epub 2017 May 24.

The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.
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http://dx.doi.org/10.1038/nature22400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536180PMC
June 2017

Virus genomes reveal factors that spread and sustained the Ebola epidemic.

Nature 2017 04 12;544(7650):309-315. Epub 2017 Apr 12.

Institute of Infection and Global Health, University of Liverpool, Liverpool L69 2BE, UK.

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.
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http://dx.doi.org/10.1038/nature22040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712493PMC
April 2017

In vivo Ebola virus infection leads to a strong innate response in circulating immune cells.

BMC Genomics 2016 09 5;17:707. Epub 2016 Sep 5.

Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.

Background: Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90 %. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entirely understood. In this study, we analyze RNA sequencing data to determine the host response to Ebola virus infection in circulating immune cells.

Results: Approximately half of the 100 genes with the strongest early increases in expression were interferon-stimulated genes, such as ISG15, OAS1, IFIT2, HERC5, MX1 and DHX58. Other highly upregulated genes included cytokines CXCL11, CCL7, IL2RA, IL2R1, IL15RA, and CSF2RB, which have not been previously reported to change during Ebola virus infection. Comparing this response in two different models of exposure (intramuscular and aerosol) revealed a similar signature of infection. The strong innate response in the aerosol model was seen not only in circulating cells, but also in primary and secondary target tissues. Conversely, the innate immune response of vaccinated macaques was almost non-existent. This suggests that the innate response is a major aspect of the cellular response to Ebola virus infection in multiple tissues.

Conclusions: Ebola virus causes a severe infection in humans that is associated with high mortality. The host immune response to virus infection is thought to be an important aspect leading to severe pathology, but the components of this overactive response are not well characterized. Here, we analyzed how circulating immune cells respond to the virus and found that there is a strong innate response dependent on active virus replication. This finding is in stark contrast to in vitro evidence showing a suppression of innate immune signaling, and it suggests that the strong innate response we observe in infected animals may be an important contributor to pathogenesis.
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http://dx.doi.org/10.1186/s12864-016-3060-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011782PMC
September 2016

Unbiased Deep Sequencing of RNA Viruses from Clinical Samples.

J Vis Exp 2016 07 2(113). Epub 2016 Jul 2.

Broad Institute of MIT and Harvard; Harvard University.

Here we outline a next-generation RNA sequencing protocol that enables de novo assemblies and intra-host variant calls of viral genomes collected from clinical and biological sources. The method is unbiased and universal; it uses random primers for cDNA synthesis and requires no prior knowledge of the viral sequence content. Before library construction, selective RNase H-based digestion is used to deplete unwanted RNA - including poly(rA) carrier and ribosomal RNA - from the viral RNA sample. Selective depletion improves both the data quality and the number of unique reads in viral RNA sequencing libraries. Moreover, a transposase-based 'tagmentation' step is used in the protocol as it reduces overall library construction time. The protocol has enabled rapid deep sequencing of over 600 Lassa and Ebola virus samples-including collections from both blood and tissue isolates-and is broadly applicable to other microbial genomics studies.
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http://dx.doi.org/10.3791/54117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993327PMC
July 2016

Ebola Virus Epidemiology and Evolution in Nigeria.

J Infect Dis 2016 10 4;214(suppl 3):S102-S109. Epub 2016 Jul 4.

Department of Biological Sciences African Center of Excellence for Genomics of Infectious Diseases, Redeemer's University, Ede, Osun State.

Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050462PMC
http://dx.doi.org/10.1093/infdis/jiw190DOI Listing
October 2016

Direct Identification of Hundreds of Expression-Modulating Variants using a Multiplexed Reporter Assay.

Cell 2016 Jun;165(6):1519-1529

Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA. Electronic address:

Although studies have identified hundreds of loci associated with human traits and diseases, pinpointing causal alleles remains difficult, particularly for non-coding variants. To address this challenge, we adapted the massively parallel reporter assay (MPRA) to identify variants that directly modulate gene expression. We applied it to 32,373 variants from 3,642 cis-expression quantitative trait loci and control regions. Detection by MPRA was strongly correlated with measures of regulatory function. We demonstrate MPRA's capabilities for pinpointing causal alleles, using it to identify 842 variants showing differential expression between alleles, including 53 well-annotated variants associated with diseases and traits. We investigated one in detail, a risk allele for ankylosing spondylitis, and provide direct evidence of a non-coding variant that alters expression of the prostaglandin EP4 receptor. These results create a resource of concrete leads and illustrate the promise of this approach for comprehensively interrogating how non-coding polymorphism shapes human biology.
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http://dx.doi.org/10.1016/j.cell.2016.04.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957403PMC
June 2016

Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

Cell 2015 Aug;162(4):738-50

FAS Center for Systems Biology, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA.

The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2015.07.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537774PMC
August 2015

Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.

Cell 2015 Jun;161(7):1516-26

Kenema Government Hospital, Kenema, Sierra Leone.

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.
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http://dx.doi.org/10.1016/j.cell.2015.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503805PMC
June 2015

Discovery of novel rhabdoviruses in the blood of healthy individuals from West Africa.

PLoS Negl Trop Dis 2015 Mar 17;9(3):e0003631. Epub 2015 Mar 17.

Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria; Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Redemption City, Ogun State, Nigeria.

Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen's nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.
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http://dx.doi.org/10.1371/journal.pntd.0003631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363514PMC
March 2015

Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples.

Genome Biol 2014 ;15(11):519

We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies.
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http://dx.doi.org/10.1186/PREACCEPT-1698056557139770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262991PMC
July 2015

Clinical illness and outcomes in patients with Ebola in Sierra Leone.

N Engl J Med 2014 Nov 29;371(22):2092-100. Epub 2014 Oct 29.

The authors' affiliations are listed in the Appendix.

Background: Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014.

Methods: We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase-polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients.

Results: Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness (in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient.

Conclusions: The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.).
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http://dx.doi.org/10.1056/NEJMoa1411680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318555PMC
November 2014

Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak.

Science 2014 Sep 28;345(6202):1369-72. Epub 2014 Aug 28.

Kenema Government Hospital, Kenema, Sierra Leone.

In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.
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http://dx.doi.org/10.1126/science.1259657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431643PMC
September 2014

Early host-pathogen interactions in a marine bivalve: Crassostrea virginica pallial mucus modulates Perkinsus marinus growth and virulence.

Dis Aquat Organ 2013 Jun;104(3):237-47

School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY, USA.

Perkinsus marinus is an important protistan parasite of the eastern oyster Crassostrea virginica. Recent findings showed that oyster pallial organs (mantle, gills) are a major portal of entry for the parasite. Therefore, mucus covering these organs represents the first host effectors encountered by P. marinus. This study consisted of several experiments designed to investigate the effect of oyster pallial mucus on the growth, protease production and infectivity of P. marinus. In each experiment, P. marinus performance in cultures supplemented with pallial mucus (mantle, gill, or both) was compared to that of parasite cells grown in unsupplemented media or in cultures supplemented with oyster plasma or digestive extracts. P. marinus grown in media supplemented with C. virginica mantle mucus showed a significantly higher growth rate than cultures enriched with the other supplemental extracts, while cultures grown in gill mucus promoted higher protease production. Conversely, P. marinus grown in cultures supplemented with pallial mucus of the non-compatible host Crassostrea gigas (Pacific oyster) were dramatically inhibited. Challenge experiments showed a significant increase in P. marinus virulence in cultures supplemented with C. virginica pallial mucus as compared to unsupplemented cultures or to those supplemented with digestive extract or plasma. These results suggest that C. virginica mucus plays a significant role in the pathogenesis of P. marinus by enhancing the proliferation and the infectivity of this devastating parasite. The contrasting results obtained with both oyster species indicate that P. marinus host specificity may begin in the mucus.
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http://dx.doi.org/10.3354/dao02599DOI Listing
June 2013

Identifying recent adaptations in large-scale genomic data.

Cell 2013 Feb;152(4):703-13

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Although several hundred regions of the human genome harbor signals of positive natural selection, few of the relevant adaptive traits and variants have been elucidated. Using full-genome sequence variation from the 1000 Genomes (1000G) Project and the composite of multiple signals (CMS) test, we investigated 412 candidate signals and leveraged functional annotation, protein structure modeling, epigenetics, and association studies to identify and extensively annotate candidate causal variants. The resulting catalog provides a tractable list for experimental follow-up; it includes 35 high-scoring nonsynonymous variants, 59 variants associated with expression levels of a nearby coding gene or lincRNA, and numerous variants associated with susceptibility to infectious disease and other phenotypes. We experimentally characterized one candidate nonsynonymous variant in Toll-like receptor 5 (TLR5) and show that it leads to altered NF-κB signaling in response to bacterial flagellin. PAPERFLICK:
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674781PMC
http://dx.doi.org/10.1016/j.cell.2013.01.035DOI Listing
February 2013

Early host-pathogen interactions in marine bivalves: evidence that the alveolate parasite Perkinsus marinus infects through the oyster mantle during rejection of pseudofeces.

J Invertebr Pathol 2013 May 27;113(1):26-34. Epub 2012 Dec 27.

School of Marine and Atmospheric Sciences, Stony Brook University, Stony Brook, NY 11794-5000, USA.

Parasites have developed myriad strategies to reach and infect their specific hosts. One of the most common mechanisms for non-vector transmitted parasites to reach the internal host environment is by ingestion during feeding. In this study, we investigated the mechanisms of oyster host colonization by the alveolate Perkinsus marinus and focused on how oysters process infective waterborne P. marinus cells during feeding in order to determine the portal(s) of entry of this parasite to its host. We also compared the infectivity of freely-suspended cells of P. marinus with that of cells incorporated into marine aggregates to link changes in particle processing by the feeding organs with infection success and route. Finally, we evaluated the effect of oyster secretions (mucus) covering the feeding organs on P. marinus physiology because these host factors are involved in the processing of waterborne particles. The ensemble of results shows a unique mechanism for infection by which the parasite is mostly acquired during the feeding process, but not via ingestion. Rather, infection commonly occurs during the rejection of material as pseudofeces before reaching the mouth. The pseudofeces discharge area, a specialized area of the mantle where unwanted particles are accumulated for rejection as pseudofeces, showed significantly higher parasite loads than other host tissues including other parts of the mantle. Aggregated P. marinus cells caused significantly higher disease prevalence and infection intensities when compared to freely-suspended parasite cells. Mucus covering the mantle caused a quick and significant increase in parasite replication rates suggesting rapid impact on P. marinus physiology. A new model for P. marinus acquisition in oysters is proposed.
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http://dx.doi.org/10.1016/j.jip.2012.12.011DOI Listing
May 2013