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Article ; Online: Expansion of CD8+ T cell population in Lassa virus survivors with low T cell precursor frequency reveals durable immune response in most survivors.

LaVergne, Stephanie M / Sakabe, Saori / Momoh, Mambu / Kanneh, Lansana / Bond, Nell / Garry, Robert F / Grant, Donald S / de la Torre, Juan Carlos / Oldstone, Michael B A / Schieffelin, John S / Sullivan, Brian M

PLoS neglected tropical diseases

2022 Volume 16, Issue 11, Page(s) e0010882

Abstract: Introduction: Lassa virus is a priority pathogen for vaccine research and development, however the duration of cellular immunity and protection in Lassa fever (LF) survivors remains unclear.: Methods: We investigated Lassa virus specific CD8+ T cell ... ...

Abstract	Introduction: Lassa virus is a priority pathogen for vaccine research and development, however the duration of cellular immunity and protection in Lassa fever (LF) survivors remains unclear. Methods: We investigated Lassa virus specific CD8+ T cell responses in 93 LF survivors. Peripheral blood mononuclear cells from these individuals were infected with recombinant vesicular stomatitis virus encoding Lassa virus antigens and virus specific T cell responses were measured after 18-hour incubation. Participants who had undetectable CD8+ T cell response underwent further analysis using a 10-day T cell proliferation assays to evaluate for low T cell precursor frequency. Results: Forty-five of the 93 LF survivors did not have a Lassa virus specific CD8+ T cell response. Of those with responses and a known date of onset of LF (N = 11), 9 had LF within the last ten years. Most participants without a measurable CD8+ T cell response were more than 10 years removed from a clinical history of LF (N = 14/16). Fourteen of 21 patients (67%) with undetectable CD8+ T cell response had a measurable Lassa virus specific CD8+ T cell response with the 10-day assay. Discussion: Despite reports of strong CD8+ T cell responses during acute Lassa virus infection, circulating Lassa virus-specific CD8+ T cells declined to undetectable levels in most Lassa fever survivors after ten years when evaluated with an 18-hour T cell stimulation. However, when Lassa virus-specific T cells were expanded prior to restimulation, a Lassa virus-specific CD8+ T cell response could be detected in many if the samples that were negative in the 18-hour stimulation assay, suggesting that prolonged cellular immunity does exist in Lassa fever survivors at low frequencies.
MeSH term(s)	Humans ; Lassa virus ; Lassa Fever ; Leukocytes, Mononuclear ; Precursor Cells, T-Lymphoid ; Immunity ; CD8-Positive T-Lymphocytes
Language	English
Publishing date	2022-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010882
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Article ; Online: Immunomodulatory potential of

Bond, Nell G / Fahlberg, Marissa D / Yu, Shan / Rout, Namita / Tran, Dollnovan / Fitzpatrick-Schmidt, Taylor / Sprehe, Lesli M / Scheef, Elizabeth A / Mudd, Joseph C / Schaub, Robert / Kaur, Amitinder

iScience

2022 Volume 25, Issue 3, Page(s) 103889

Abstract: Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, ... ...

Abstract	Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103889
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Article ; Online: Pericytes as novel targets for HIV/SIV infection in the lung.

Stephenson, Sarah E / Wilson, Carole L / Bond, Nell G / Kaur, Amitinder / Alvarez, Xavier / Midkiff, Cecily C / Schnapp, Lynn M

American journal of physiology. Lung cellular and molecular physiology

2020 Volume 319, Issue 5, Page(s) L848–L853

Abstract: Antiretroviral therapy in HIV patients has lengthened lifespan but led to an increased risk for secondary comorbidities, such as pulmonary complications characterized by vascular dysfunction. In the lung, PDGFRβ+ mesenchymal cells known as pericytes ... ...

Abstract	Antiretroviral therapy in HIV patients has lengthened lifespan but led to an increased risk for secondary comorbidities, such as pulmonary complications characterized by vascular dysfunction. In the lung, PDGFRβ+ mesenchymal cells known as pericytes intimately associate with endothelial cells and are key for their survival both structurally and through the secretion of prosurvival factors. We hypothesize that in HIV infection there are functional changes in pericytes that may lead to destabilization of the microvasculature and ultimately to pulmonary abnormalities. Our objective in this study was to determine whether lung pericytes could be directly infected with HIV. We leveraged lung samples from macaque lungs with or without SIV infection and normal human lung for in vitro experiments. Pericytes were isolated based on the marker platelet-derived growth factor receptor-β (PDGFRβ). We determined that lung PDGFRβ-positive (PDGFRβ+) pericytes from both macaques and humans express CD4, the primary receptor for SIV/HIV, as well as the major coreceptors CXCR4 and CCR5. We found cells positive for both PDGFRβ and SIV in lungs from infected macaques. Lung pericytes isolated from these animals also harbored detectable SIV. To confirm relevance to human disease, we demonstrated that human lung pericytes are capable of being productively infected by HIV in vitro, with the time course of infection suggesting development of viral latency. In summary, we show for the first time that SIV/HIV directly infects lung pericytes, implicating these cells as a novel target and potential reservoir for the virus in vivo.
MeSH term(s)	CD4-Positive T-Lymphocytes/virology ; Endothelial Cells/virology ; HIV Infections/virology ; Humans ; Lung/immunology ; Lung/virology ; Macrophages/immunology ; Macrophages/virology ; Receptors, CXCR4/immunology ; Simian Immunodeficiency Virus/pathogenicity ; Virus Latency/physiology ; Virus Replication
Chemical Substances	CXCR4 protein, human ; Receptors, CXCR4
Language	English
Publishing date	2020-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00296.2020
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Article ; Online: The prevalence of Post-Ebola Syndrome hearing loss, Sierra Leone.

Ficenec, Samuel C / Grant, Donald S / Sumah, Ibrahim / Alhasan, Foday / Yillah, Mohamed S / Brima, Jenneh / Konuwa, Edwin / Gbakie, Michael A / Kamara, Fatima K / Bond, Nell G / Engel, Emily J / Shaffer, Jeffrey G / Fischer, William A / Wohl, David A / Emmett, Susan D / Schieffelin, John S

BMC infectious diseases

2022 Volume 22, Issue 1, Page(s) 624

Abstract: Background: Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world's population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in ... ...

Abstract	Background: Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world's population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa. Following the 2014 West African Ebola Outbreak, disease survivors began to describe hearing loss as part of the constellation of symptoms known as Post-Ebola Syndrome. The goal of this study was to more fully characterize hearing loss among Ebola Virus Disease (EVD) survivors. Methodology and principal findings: EVD survivors and their household contacts were recruited (n = 1,12) from Eastern Sierra Leone. Each individual completed a symptom questionnaire, physical exam, and a two-step audiometry process measuring both air and bone conduction thresholds. In comparison to contacts, EVD survivors were more likely to have complaints or abnormal findings affecting every organ system. A significantly greater percentage of EVD survivors were found to have hearing loss in comparison to contacts (23% vs. 9%, p < 0.001). Additionally, survivors were more likely to have bilateral hearing loss of a mixed etiology. Logistic regression revealed that the presence of any symptoms of middle or inner ear (p < 0.001), eye (p = 0.005), psychiatric (p = 0.019), and nervous system (p = 0.037) increased the odds of developing hearing loss. Conclusions and significance: This study is the first to use an objective and standardized measurement to report hearing loss among EVD survivors in a clinically meaningful manner. In this study it was found that greater than 1/5th of EVD survivors develop hearing loss. The association between hearing impairment and symptoms affecting the eye and nervous system may indicate a similar mechanism of pathogenesis, which should be investigated further. Due to the quality of life and socioeconomic detriments associated with untreated hearing loss, a greater emphasis must be placed on understanding and mitigating hearing loss following survival to aid in economic recovery following infectious disease epidemics.
MeSH term(s)	Disease Outbreaks ; Hearing Loss/epidemiology ; Hemorrhagic Fever, Ebola/complications ; Hemorrhagic Fever, Ebola/epidemiology ; Humans ; Prevalence ; Sierra Leone/epidemiology ; Survivors/statistics & numerical data
Language	English
Publishing date	2022-07-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-022-07604-y
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Article: Novel Tools for Lassa Virus Surveillance in Peri-domestic Rodents.

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Lassa fever (LF) is a rodent-borne disease endemic to West Africa. In the absence of licensed therapeutics or vaccines, rodent exclusion from living spaces remains the primary method of preventing LF. Zoonotic surveillance of Lassa virus ( ... ...

Abstract	Background: Lassa fever (LF) is a rodent-borne disease endemic to West Africa. In the absence of licensed therapeutics or vaccines, rodent exclusion from living spaces remains the primary method of preventing LF. Zoonotic surveillance of Lassa virus (LASV), the etiologic agent of LF, can assess the burden of LASV in a region and guide public health measures against LF. Methods: In this study, we adapted commercially available LASV human diagnostics to assess the prevalence of LASV in peri-domestic rodents in Eastern Sierra Leone. Small mammal trapping was conducted in Kenema district, Sierra Leone between November 2018-July 2019. LASV antigen was detected using a commercially available LASV NP antigen rapid diagnostic test. LASV IgG antibodies against LASV nucleoprotein (NP) and glycoprotein (GP) were tested by adapting a commercially available semi-quantitative enzyme linked immunosorbent assay (ELISA) for detection of mouse-related and rat-related species IgG. Findings: Of the 373 tested specimens, 74 (20%) tested positive for LASV antigen. 40 (11%) specimens tested positive for LASV NP IgG, while an additional 12 (3%) specimens only tested positive for LASV GP IgG. Simultaneous antigen presence and IgG antibody presence was linked in Interpretation: The tools developed in this study can aid in the generation of valuable public health data for rapid field assessment of LASV burden during outbreak investigations and general LASV surveillance. Funding: Funding for this work was supported by the National Institute of Allergy and Infectious Diseases National Institute of Health, Department of Health and Human Services under the following grants: International Collaboration in Infectious Disease Research on Lassa fever and Ebola - ICIDR - U19 AI115589, Consortium for Viral Systems Biology - CViSB - 5U19AI135995, West African Emerging Infectious Disease Research Center - WARN-ID - U01AI151812, West African Center for Emerging Infectious Diseases: U01AI151801.
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.17.23287380
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Article ; Online: Ophthalmic manifestations and vision impairment in Lassa fever survivors.

Li, Alexa L / Grant, Donald / Gbakie, Michael / Kanneh, Lansana / Mustafa, Ibrahim / Bond, Nell / Engel, Emily / Schieffelin, John / Vandy, Matthew J / Yeh, Steven / Shantha, Jessica G

PloS one

2020 Volume 15, Issue 12, Page(s) e0243766

Abstract: The purpose of this study was to describe the ocular findings, structural ocular complications, and vision impairment in a cohort of Lassa fever survivors in Kenema, Sierra Leone. A retrospective, uncontrolled, cross-sectional study of 31 Lassa fever ... ...

Abstract	The purpose of this study was to describe the ocular findings, structural ocular complications, and vision impairment in a cohort of Lassa fever survivors in Kenema, Sierra Leone. A retrospective, uncontrolled, cross-sectional study of 31 Lassa fever survivors (62 eyes) who underwent an ophthalmic evaluation in January 2018 at the Kenema Government Hospital in Kenema, Sierra Leone was performed. Data collection included demographic information, ocular/systemic symptoms, visual acuity (VA), and ophthalmic examination findings. Main outcome measures included anterior and posterior segment ophthalmic manifestations and level of VA impairment in Lassa fever survivors. Anterior segment findings included cataract (18%) and pterygium (2%), while posterior segment manifestations consisted of glaucoma (6%), preretinal hemorrhage (2%), and lattice degeneration (2%). Findings suggestive of prior sequelae of uveitis included chorioretinal scarring (5%), retinal fibrosis (3%), and vitreous opacity (2%). Visual acuity was normal/mildly impaired in 53 eyes (85%), moderately impaired in 6 eyes (10%), and 3 eyes (5%) were considered blind by the World Health Organization (WHO) criteria. Median VA was worse in Lassa fever survivors with ophthalmic disease findings (p<0.0001) for both anterior segment (p<0.0001) and posterior segment disease (p<0.013). Untreated cataract was a significant cause of visual acuity impairment (p<0.0001). Lassa fever survivors in this cohort were found to have cataract and posterior segment findings that potentially represent sequelae of uveitis associated with visual impairment. Future studies are warranted to improve our understanding of the spectrum of ocular disease in this emerging infectious disease of public health consequence.
MeSH term(s)	Adult ; Cross-Sectional Studies ; Female ; Humans ; Lassa Fever/complications ; Male ; Middle Aged ; Retrospective Studies ; Survivors/statistics & numerical data ; Vision Disorders/complications ; Young Adult
Language	English
Publishing date	2020-12-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0243766
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Article ; Online: Post-Ebola Syndrome Presents With Multiple Overlapping Symptom Clusters: Evidence From an Ongoing Cohort Study in Eastern Sierra Leone.

Bond, Nell G / Grant, Donald S / Himmelfarb, Sarah T / Engel, Emily J / Al-Hasan, Foday / Gbakie, Michael / Kamara, Fatima / Kanneh, Lansana / Mustapha, Ibrahim / Okoli, Adaora / Fischer, William / Wohl, David / Garry, Robert F / Samuels, Robert / Shaffer, Jeffrey G / Schieffelin, John S

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 73, Issue 6, Page(s) 1046–1054

Abstract: Background: Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome >2.5 years after ... ...

Abstract	Background: Following the 2013-2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome >2.5 years after resolution of disease. Additionally, we report subphenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone. Methods: Participants in Eastern Sierra Leone were identiﬁed by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical examination. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified presentation of incredibly complex evaluations (SPICE), correlation analysis, logistic regression, and principal component analysis (PCA) were performed to explore the relationships between symptom clusters. Results: Three hundred seventy-five EVD survivors and 1040 contacts were enrolled into the study. At enrollment, EVD survivors reported signiﬁcantly more symptoms than their contacts in all categories (P < .001). Symptom clusters representing distinct organ systems were identified. Correlation and logistic regression analysis identified relationships between symptom clusters, including stronger relationships between clusters including musculoskeletal symptoms (r = 0.63, P < .001; and P < .001 for correlation and logistic regression, respectively). SPICE and PCA further highlighted subphenotypes with or without musculoskeletal symptoms. Conclusions: This study presents an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors >2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.
MeSH term(s)	Cohort Studies ; Disease Outbreaks ; Ebolavirus ; Hemorrhagic Fever, Ebola/complications ; Hemorrhagic Fever, Ebola/epidemiology ; Humans ; Sierra Leone/epidemiology ; Syndrome
Language	English
Publishing date	2021-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab267
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Article ; Online: Seroprevalence of anti-Lassa Virus IgG antibodies in three districts of Sierra Leone: A cross-sectional, population-based study.

Grant, Donald S / Engel, Emily J / Roberts Yerkes, Nicole / Kanneh, Lansana / Koninga, James / Gbakie, Michael A / Alhasan, Foday / Kanneh, Franklyn B / Kanneh, Ibrahim Mustapha / Kamara, Fatima K / Momoh, Mambu / Yillah, Mohamed S / Foday, Momoh / Okoli, Adaora / Zeoli, Ashley / Weldon, Caroline / Bishop, Christopher M / Zheng, Crystal / Hartnett, Jessica /

Chao, Karissa / Shore, Kayla / Melnik, Lilia I / Mucci, Mallory / Bond, Nell G / Doyle, Philip / Yenni, Rachael / Podgorski, Rachel / Ficenec, Samuel C / Moses, Lina / Shaffer, Jeffrey G / Garry, Robert F / Schieffelin, John S

PLoS neglected tropical diseases

2023 Volume 17, Issue 2, Page(s) e0010938

Abstract: Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The ... ...

Abstract	Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown. This cross-sectional study aimed to establish a baseline point seroprevalence of IgG antibodies to LASV in three administrative districts of Sierra Leone and identify potential risk factors for seropositivity and LASV exposure. Methodology and principal findings: Between 2015 and 2018, over 10,642 participants from Kenema, Tonkolili, and Port Loko Districts were enrolled in this cross-sectional study. Previous LASV and LF epidemiological studies support classification of these districts as "endemic," "emerging," and "non-endemic", respectively. Dried blood spot samples were tested for LASV antibodies by ELISA to determine the seropositivity of participants, indicating previous exposure to LASV. Surveys were administered to each participant to assess demographic and environmental factors associated with a higher risk of exposure to LASV. Overall seroprevalence for antibodies to LASV was 16.0%. In Kenema, Port Loko, and Tonkolili Districts, seroprevalences were 20.1%, 14.1%, and 10.6%, respectively. In a multivariate analysis, individuals were more likely to be LASV seropositive if they were living in Kenema District, regardless of sex, age, or occupation. Environmental factors contributed to an increased risk of LASV exposure, including poor housing construction and proximity to bushland, forested areas, and refuse. Conclusions and significance: In this study we determine a baseline LASV seroprevalence in three districts which will inform future epidemiological, ecological, and clinical studies on LF and the LASV in Sierra Leone. The heterogeneity of the distribution of LASV and LF over both space, and time, can make the design of efficacy trials and intervention programs difficult. Having more studies on the prevalence of LASV and identifying potential hyper-endemic areas will greatly increase the awareness of LF and improve targeted control programs related to LASV.
MeSH term(s)	Animals ; Humans ; Sierra Leone/epidemiology ; Cross-Sectional Studies ; Seroepidemiologic Studies ; Lassa Fever/epidemiology ; Lassa virus ; Virus Diseases ; Murinae ; Antibodies, Viral ; Immunoglobulin G
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2023-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010938
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Article: Space-Time Trends in Lassa Fever in Sierra Leone by ELISA Serostatus, 2012–2019

Microorganisms. 2021 Mar. 12, v. 9, no. 3

2021

Abstract: Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) ... ...

Abstract	Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) maintains one of only a few LF isolation facilities in the world with year-round diagnostic testing. Here we focus on space-time trends for LF occurring in Sierra Leone between 2012 and 2019 to provide a current account of LF in the wake of the 2014–2016 Ebola epidemic. Data were analyzed for 3277 suspected LF cases and classified as acute, recent, and non-LF or prior LF exposure using enzyme-linked immunosorbent assays (ELISAs). Presentation rates for acute, recent, and non-LF or prior LF exposure were 6.0% (195/3277), 25.6% (838/3277), and 68.4% (2244/3277), respectively. Among 2051 non-LF or prior LF exposures, 33.2% (682/2051) tested positive for convalescent LF exposure. The overall LF case-fatality rate (CFR) was 78.5% (106/135). Both clinical presentations and confirmed LF cases declined following the Ebola epidemic. These declines coincided with an increased duration between illness onset and clinical presentation, perhaps suggesting more severe disease or presentation at later stages of illness. Acute LF cases and their corresponding CFRs peaked during the dry season (November to April). Subjects with recent (but not acute) LF exposure were more likely to present during the rainy season (May to October) than the dry season (p < 0.001). The findings here suggest that LF remains endemic in Sierra Leone and that caseloads are likely to resume at levels observed prior to the Ebola epidemic. The results provide insight on the current epidemiological profile of LF in Sierra Leone to facilitate LF vaccine studies and accentuate the need for LF cohort studies and continued advancements in LF diagnostics.
Keywords	Lassa virus fever ; diagnostic techniques ; disease severity ; dry season ; hospitals ; mortality ; space and time ; vaccines ; wet season ; Sierra Leone
Language	English
Dates of publication	2021-0312
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9030586
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Article: Space-Time Trends in Lassa Fever in Sierra Leone by ELISA Serostatus, 2012-2019.

Microorganisms

2021 Volume 9, Issue 3

Abstract	Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) maintains one of only a few LF isolation facilities in the world with year-round diagnostic testing. Here we focus on space-time trends for LF occurring in Sierra Leone between 2012 and 2019 to provide a current account of LF in the wake of the 2014-2016 Ebola epidemic. Data were analyzed for 3277 suspected LF cases and classified as acute, recent, and non-LF or prior LF exposure using enzyme-linked immunosorbent assays (ELISAs). Presentation rates for acute, recent, and non-LF or prior LF exposure were 6.0% (195/3277), 25.6% (838/3277), and 68.4% (2244/3277), respectively. Among 2051 non-LF or prior LF exposures, 33.2% (682/2051) tested positive for convalescent LF exposure. The overall LF case-fatality rate (CFR) was 78.5% (106/135). Both clinical presentations and confirmed LF cases declined following the Ebola epidemic. These declines coincided with an increased duration between illness onset and clinical presentation, perhaps suggesting more severe disease or presentation at later stages of illness. Acute LF cases and their corresponding CFRs peaked during the dry season (November to April). Subjects with recent (but not acute) LF exposure were more likely to present during the rainy season (May to October) than the dry season (
Language	English
Publishing date	2021-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9030586
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