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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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever.

Horton, Lucy E / Cross, Robert W / Hartnett, Jessica N / Engel, Emily J / Sakabe, Saori / Goba, Augustine / Momoh, Mambu / Sandi, John Demby / Geisbert, Thomas W / Garry, Robert F / Schieffelin, John S / Grant, Donald S / Sullivan, Brian M

Emerging infectious diseases

2021 Volume 26, Issue 11, Page(s) 2625–2637

Abstract: Lassa fever (LF) causes multisystem disease and has a fatality rate <70%. Severe cases exhibit abnormal coagulation, endothelial barrier disruption, and dysfunctional platelet aggregation but the underlying mechanisms remain poorly understood. In Sierra ... ...

Abstract	Lassa fever (LF) causes multisystem disease and has a fatality rate <70%. Severe cases exhibit abnormal coagulation, endothelial barrier disruption, and dysfunctional platelet aggregation but the underlying mechanisms remain poorly understood. In Sierra Leone during 2015-2018, we assessed LF patients' day-of-admission plasma samples for levels of proteins necessary for coagulation, fibrinolysis, and platelet function. P-selectin, soluble endothelial protein C receptor, soluble thrombomodulin, plasminogen activator inhibitor 1, ADAMTS-13, von Willebrand factor, tissue factor, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were more elevated in LF patients than in controls. Endothelial protein C receptor, thrombomodulin, intercellular adhesion molecule 1, plasminogen activator inhibitor 1, D-dimer, and hepatocyte growth factor were higher in fatal than nonfatal LF cases. Platelet disaggregation occurred only in samples from fatal LF cases. The impaired homeostasis and platelet dysfunction implicate alterations in the protein C pathway, which might contribute to the loss of endothelial barrier function in fatal infections.
MeSH term(s)	Adolescent ; Adult ; Aged ; Blood Coagulation ; Blood Platelets/pathology ; Child ; Child, Preschool ; Endothelium/physiopathology ; Female ; Fibrinolysis ; Humans ; Infant ; Lassa Fever/diagnosis ; Lassa Fever/epidemiology ; Male ; Middle Aged ; Sierra Leone ; Young Adult
Language	English
Publishing date	2021-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2611.191694
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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: Building diagnostic systems in Sierra Leone: The role of point-of-care devices in laboratory strengthening.

Ansumana, Rashid / Bah, Fatmata / Biao, Kan / Harding, Doris / Jalloh, Mohamed B / Kelly, Ann H / Koker, Francess / Koroma, Zikan / Momoh, Mambu / Rogers, Mohamed H / Rogers, James / Street, Alice / Vernooij, Eva / Wurie, Isatta

African journal of laboratory medicine

2020 Volume 9, Issue 2, Page(s) 1029

Language	English
Publishing date	2020-04-01
Publishing country	South Africa
Document type	Journal Article
ZDB-ID	2708535-1
ISSN	2225-2010 ; 2225-2002
ISSN (online)	2225-2010
ISSN	2225-2002
DOI	10.4102/ajlm.v9i2.1029
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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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Data set on Lassa fever in post-conflict Sierra Leone.

Shaffer, Jeffrey G / Schieffelin, John S / Grant, Donald S / Goba, Augustine / Momoh, Mambu / Kanneh, Lansana / Levy, Danielle C / Hartnett, Jessica N / Boisen, Matt L / Branco, Luis M / Garry, Robert F

Data in brief

2019 Volume 23, Page(s) 103673

Abstract: Lassa fever is a rodent-borne illness that is endemic to parts of sub-Saharan Africa, including Sierra Leone, Nigeria, and Guinea. The disease is named after the town of Lassa, Nigeria where it was discovered in 1969. This data article focuses on the ... ...

Abstract	Lassa fever is a rodent-borne illness that is endemic to parts of sub-Saharan Africa, including Sierra Leone, Nigeria, and Guinea. The disease is named after the town of Lassa, Nigeria where it was discovered in 1969. This data article focuses on the epidemiology of Lassa fever in Sierra Leone following a decade-long civil war that ended in 2002. The data were collected at Kenema Government Hospital (KGH) in Kenema, Sierra Leone, which maintains the country׳s only Lassa fever treatment facility and a biosafety level 3 (BSL-3) laboratory. The key data set variables include Lassa fever serostatus determined using antigen (Ag), immunoglobulin M (IgM), and immunoglobulin G (IgG) ELISA diagnostic techniques; and patient demographics, survival outcome, and treatment (ribavirin) status. The individual data used to generate the graphs and tables in the corresponding research manuscript published in
Language	English
Publishing date	2019-01-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.01.021
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Article: Data set on Lassa fever in post-conflict Sierra Leone

Shaffer, Jeffrey G. / Schieffelin, John S. / Grant, Donald S. / Goba, Augustine / Momoh, Mambu / Kanneh, Lansana / Levy, Danielle C. / Hartnett, Jessica N. / Boisen, Matt L. / Branco, Luis M. / Garry, Robert F.

Data in Brief. 2019 Apr., v. 23

2019

Institution	the Viral Hemorrhagic Fever Consortium
Abstract	Lassa fever is a rodent-borne illness that is endemic to parts of sub-Saharan Africa, including Sierra Leone, Nigeria, and Guinea. The disease is named after the town of Lassa, Nigeria where it was discovered in 1969. This data article focuses on the epidemiology of Lassa fever in Sierra Leone following a decade-long civil war that ended in 2002. The data were collected at Kenema Government Hospital (KGH) in Kenema, Sierra Leone, which maintains the country׳s only Lassa fever treatment facility and a biosafety level 3 (BSL-3) laboratory. The key data set variables include Lassa fever serostatus determined using antigen (Ag), immunoglobulin M (IgM), and immunoglobulin G (IgG) ELISA diagnostic techniques; and patient demographics, survival outcome, and treatment (ribavirin) status. The individual data used to generate the graphs and tables in the corresponding research manuscript published in PLOS Neglected Tropical Diseases in 2014 and its coding guide are provided as Supplementary material (Shaffer et al., 2014) [1].
Keywords	Lassa virus fever ; antigens ; biosafety ; data collection ; demographic statistics ; hospitals ; immunoglobulin G ; patients ; Guinea ; Nigeria ; Sierra Leone
Language	English
Dates of publication	2019-04
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.01.021
Database	NAL-Catalogue (AGRICOLA)

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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
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Lassa Fever among Children in Eastern Province, Sierra Leone: A 7-year Retrospective Analysis (2012-2018).

Samuels, Robert J / Moon, Troy D / Starnes, Joseph R / Alhasan, Foday / Gbakie, Michael / Goba, Augustine / Koroma, Veronica / Momoh, Mambu / Sandi, John Demby / Garry, Robert F / Engel, Emily J / Shaffer, Jeffrey G / Schieffelin, John S / Grant, Donald S

The American journal of tropical medicine and hygiene

2020 Volume 104, Issue 2, Page(s) 585–592

Abstract: Pediatric Lassa fever (LF) usually presents as a nonspecific febrile illness, similar to other endemic diseases in countries like Sierra Leone, where LF is considered to be hyperendemic. The nonspecificity of presentation and lack of research have made ... ...

Abstract	Pediatric Lassa fever (LF) usually presents as a nonspecific febrile illness, similar to other endemic diseases in countries like Sierra Leone, where LF is considered to be hyperendemic. The nonspecificity of presentation and lack of research have made it difficult to fully understand best practices for pediatric management. We aim to describe clinical characteristics of hospitalized pediatric patients suspected or diagnosed with LF and assess factors associated with hospital outcomes among those with LF antigen-positive results. We conducted a 7-year retrospective cohort study using routine data for all children younger than 18 years admitted at the Kenema Government Hospital's LF ward. A total of 292 children with suspected or confirmed LF were analyzed. Overall, mortality was high (21%). Children with antigen-positive results had a high case fatality rate of 63% (P < 0.01). In univariate analyses, children who presented with unexplained bleeding (odds ratio [OR]: 3.58; 95% CI: 1.08-11.86; P = 0.040) and confusion (altered sensorium) (OR: 5.37; 95% CI: 1.34-21.48; P = 0.020) had increased odds of death. Abnormal serum levels of alanine aminotransferase (P = 0.001), creatinine (P = 0.004), and potassium (P = 0.003) were associated with increased likelihood of death in these children. Treatment with ribavirin was not significantly associated with survival (P = 0.916). Our findings provide insights into current pediatric LF clinical presentation and management. More evidence-based, high-quality research in creating predictive algorithms of antigen-positivity and hospital outcomes is needed in the management of pediatric LF.
MeSH term(s)	Adolescent ; Antibodies, Viral/blood ; Antigens, Viral/blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Lassa Fever/epidemiology ; Lassa Fever/immunology ; Lassa virus/immunology ; Lassa virus/pathogenicity ; Male ; Retrospective Studies ; Sierra Leone/epidemiology ; Time Factors
Chemical Substances	Antibodies, Viral ; Antigens, Viral
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2942-7
ISSN	1476-1645 ; 0002-9637
ISSN (online)	1476-1645
ISSN	0002-9637
DOI	10.4269/ajtmh.20-0773
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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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