#Molecular confirmation and #phylogeny of #Lassa fever virus in #Benin Republic 2014-2016 (Afr J Lab Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Afr J Lab Med. 2019 Aug 22;8(1):803. doi: 10.4102/ajlm.v8i1.803. eCollection 2019.

Molecular confirmation and phylogeny of Lassa fever virus in Benin Republic 2014-2016.

Salu OB1,2, James AB2,3, Bankolé HS4,5, Agbla JM5, Da Silva M5, Gbaguidi F5,6, Loko CF7, Omilabu SA1,2.

Author information: 1 Department of Medical Microbiology and Parasitology, College of Medicine, University of Lagos, Lagos, Nigeria. 2 Centre for Human and Zoonotic Virology, Central Research Laboratory, College of Medicine, University of Lagos, Lagos, Nigeria. 3 Department of Biochemistry, College of Medicine, University of Lagos, Lagos, Nigeria. 4 Department of Applied Microbiology and Pharmacology of Natural Sciences, University of Abomey-Calavi, Abomey-Calavi, Benin, Benin. 5 National Laboratory of Public Health, Ministry of Health, Benin, Benin. 6 Department of Pharmacognosy and Pharmaceutical Organic Chemistry, University of Abomey-Calavi, Abomey-Calavi, Benin. 7 De la Pharmacie, du Medicament et des Explorations Diagnostiques, Ministére de la Santé, Cotonou, Benin.

 

Abstract

BACKGROUND:

The changing epidemiology of the Lassa virus from endemic areas to other parts of West Africa has been reported. However, there have been no documented Lassa fever transmission chains in the Benin Republic. Two outbreaks of Lassa fever (November 2014 and January 2016) in the Benin Republic were characterised by a high number of deaths (more than 50%) among 27 confirmed and other unconfirmed cases.

OBJECTIVES:

We report the detection, confirmation and relatedness of the Lassa virus strains from the Benin Republic with other isolates within the West African Sub-region.

METHODS:

A total of 70 blood samples (16 from 2014 and 54 from 2016) from suspected cases with signs and symptoms suggestive of viral haemorrhagic fever were received for molecular analysis at the Centre for Human and Zoonotic Virology, College of Medicine, University of Lagos and the Lagos University Teaching Hospital. With the detection of the Lassa virus RNA by reverse transcriptase polymerase chain reaction, sequencing and phylogenetic analyses were performed using the Sanger dideoxy sequencing technology platform and the MEGA6 software.

RESULTS:

S segments of the Lassa virus RNA genome were detected in 5 (7.1%) of the 70 samples analysed. Sequencing and a phylogenetic tree construction confirmed that the strain of Lassa virus had close relationships with strains previously isolated from Nigeria.

CONCLUSION:

We confirmed the presence of the Lassa virus in the Benin Republic, with 2 strains having molecular epidemiological links with Lineage I and II strains from Nigeria. To reduce the likelihood of outbreaks, there is a need for heightened awareness and strengthened surveillance systems about Lassa fever, particularly in the sub-region.

KEYWORDS: Benin Republic; Lassa virus; West Africa; phylogeny; surveillance

PMID: 31534915 PMCID: PMC6739551 DOI: 10.4102/ajlm.v8i1.803

Keywords: Lassa fever; Benin; Nigeria.

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A review of #Lassa fever #vaccine candidates (Curr Opin Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Curr Opin Virol. 2019 Aug 28;37:105-111. doi: 10.1016/j.coviro.2019.07.006. [Epub ahead of print]

A review of Lassa fever vaccine candidates.

Salami K1, Gouglas D2, Schmaljohn C3, Saville M4, Tornieporth N5.

Author information: 1 R & D Blueprint for the Prevention of Epidemics, Room 3170, World Health Organization Headquarters, 20, Avenue Appia, Geneva 1211, Switzerland. 2 Coalition for Epidemic Preparedness Innovations, Marcus Thranes Gate 2, 0473 Oslo, Norway. 3 U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD 21702, USA. 4 Coalition for Epidemic Preparedness Innovations, Gibbs Building, 215 Euston Rd, Bloomsbury, London NW1 2BE, UK. Electronic address: Melanie.saville@cepi.net. 5 Coalition for Epidemic Preparedness Innovations, Gibbs Building, 215 Euston Rd, Bloomsbury, London NW1 2BE, UK.

 

Abstract

Lassa fever is a zoonotic disease caused by the Lassa virus, a rodent-borne arenavirus endemic to West Africa. Recent steady increase in reported cases of the disease in Nigeria, where 123 deaths occurred in 546 confirmed cases in 2019 has further underlined the need to accelerate the development of vaccines for preventing the disease. Intensified research and development of Lassa fever medical countermeasures have yielded some vaccine candidates with preclinical scientific plausibility using predominantly novel technology. The more advanced candidates are based on recombinant measles, Vesicular Stomatitis Virus or Mopiea and Lassa virus reassortants expressing Lassa virus antigens, and the deoxyribonucleic acid platform. However, the Lassa fever portfolio still lags behind other neglected tropical diseases’, and further investments are needed for continued development and additional research, such as the safety and efficacy of these vaccine candidates in special populations.

Copyright © 2019. Published by Elsevier B.V.

PMID: 31472333 DOI: 10.1016/j.coviro.2019.07.006

Keywords:  Lassa fever, Vaccines.

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A Single Dose of Modified #Vaccinia Ankara Expressing #Lassa #VLPs Protects Mice from Lethal Intra- #cerebral Virus Challenge (Pathogens., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pathogens. 2019 Aug 28;8(3). pii: E133. doi: 10.3390/pathogens8030133.

A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge.

Salvato MS1, Domi A2, Guzmán-Cardozo C1, Medina-Moreno S1, Zapata JC1, Hsu H1, McCurley N3, Basu R4, Hauser M2, Hellerstein M2, Guirakhoo F5.

Author information: 1 Institute of Human Virology, University of Maryland, Baltimore, MD 21201, USA. 2 GeoVax, Inc., Smyrna, GA 30080, USA. 3 Office of Technology Licensing and Commercialization, Georgia State University, Atlanta, GA 30303, USA. 4 Department of Biology, Georgia State University, Atlanta, GA 30302, USA. 5 GeoVax, Inc., Smyrna, GA 30080, USA. fguirakhoo@geovax.com.

 

Abstract

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.

KEYWORDS: Lassa vaccine; VLP formation; cell-mediated immunity; replication-deficient MVA vector; single-dose efficacy

PMID: 31466243 DOI: 10.3390/pathogens8030133

Keywords: Lassa fever; Vaccines; Animal models.

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#Lassa Fever in #Pregnancy with a Positive #Maternal and #Fetal Outcome: A Case Report (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2019 Aug 26. pii: S1201-9712(19)30349-2. doi: 10.1016/j.ijid.2019.08.023. [Epub ahead of print]

LASSA FEVER IN PREGNANCY WITH A POSITIVE MATERNAL AND FETAL OUTCOME: A CASE REPORT.

Agboeze J1, Nwali MI2, Nwakpakpa E2, Ogah OE2, Onoh R2, Eze J2, Ukaegbe C2, Ajayi N2, Nnadozie UU2, Orji ML2, Ojide CK2, Unigwe US2, Chika-Igwenyi N2, Nwidi UD2, Clement UC3, Kalombo C3, Makwe C3, Tshiang J3.

Author information: 1 Alex-Ekwueme University Federal Teaching Hospital Abakaliki, Ebonyi, Nigeria. Electronic address: jagboeze@gmail.com. 2 Alex-Ekwueme University Federal Teaching Hospital Abakaliki, Ebonyi, Nigeria. 3 Medecins sans Frontieres, Nigeria.

 

Abstract

BACKGROUND:

Lassa fever is a rodent-borne zoonosis that clinically manifests as an acute haemorrhagic fever. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented to date. It is treated using ribavirin.

CASE PRESENTATION:

We report a case of a 25-year old multigravida at 29weeks gestational age with fever who was initially thought to have malaria in pregnancy. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. She subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved and she made full recovery. Her close contacts showed no evidence of Lassa virus infection.

CONCLUSION:

This report adds to the body of literature that individuals may survive Lassa fever during pregnancy with good maternal and fetal outcome.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Abakaliki; Diagnosis; Lassa fever; Pregnancy; Survival

PMID: 31465848 DOI: 10.1016/j.ijid.2019.08.023

Keywords: Lassa Fever; Pregnancy; Nigeria.

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#Knowledge, #Misperceptions, #Preparedness, and #Barriers towards #Lassa Fever #Control among #HCWs in a Tertiary Institution in #Enugu, #Nigeria (J Health Care Poor Underserved., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Health Care Poor Underserved. 2019;30(3):1151-1164. doi: 10.1353/hpu.2019.0079.

Knowledge, Misperceptions, Preparedness, and Barriers towards Lassa Fever Control among Health Care Workers in a Tertiary Institution in Enugu, Nigeria.

Ndu AC, Kassy WC, Ochie CN, Arinze-Onyia SU, Okeke TA, Aguwa EN, Okwor TJ, Chinawa A.

 

Abstract

BACKGROUND:

Lassa fever outbreaks are common in Nigeria. The study aimed to assess knowledge, misperception, preparedness and barriers towards Lassa fever among health care workers (HCWs) in a tertiary hospital in Enugu.

METHODS:

A descriptive cross-sectional study among 400 HCWs of a Teaching Hospital in Nigeria.

RESULTS:

The study showed that 56.5% had fair knowledge while 42.0% and 1.5% had poor and good knowledge, respectively. Over 84% had good risk perception of acquiring Lassa fever while 15.8% had poor risk perception. Only 13% received training on emergency preparedness while 90.3% desired this training. Associations between occupation and knowledge were significant. Barriers to Lassa fever control were non-availability of infection control tools, lack of training on preparedness, absence of local laboratory, and non-availability of ribavirin.

CONCLUSION:

The study showed poor level of preparedness for Lassa fever and recommended routine training of HCWs on emergency preparedness.

PMID: 31422994 DOI: 10.1353/hpu.2019.0079

Keywords: HCW; Lassa fever; Nigeria.

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#Phylogeography of #Lassa virus in #Nigeria (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Phylogeography of Lassa virus in Nigeria

Deborah U. Ehichioya, Simon Dellicour, Meike Pahlmann, Toni Rieger, Lisa Oestereich, Beate Becker-Ziaja, Daniel Cadar, Yemisi Ighodalo, Thomas Olokor, Emmanuel Omomoh,Jennifer Oyakhilome, Racheal Omiunu, Jacqueline Agbukor, Benevolence Ebo, John Aiyepada, Paulson Ebhodaghe, Blessing Osiemi, Solomon Ehikhametalor, Patience Akhilomen,Michael Airende, Rita Esumeh, Ekene Muoebonam, Rosemary Giwa, Anieno Ekanem, Ganiyu Igenegbale, George Odigie, Grace Okonofua, Racheal Enigbe, Edna Omonegho Yerumoh,Elisa Pallasch, Sabrina Bockholt, Liana E. Kafetzopoulou, Sophie Duraffour, Peter O. Okokhere, George O. Akpede, Sylvanus A. Okogbenin, Ikponmwosa Odia, Chris Aire, Nosa Akpede,Ekaete Tobin, Ephraim Ogbaini-Emovon, Philippe Lemey, Donatus I. Adomeh, Danny A. Asogun, Stephan Günther

DOI: 10.1128/JVI.00929-19

 

ABSTRACT

Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatio-temporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian States. The final dataset, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 States. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while few sequences formed a new cluster related to Lassa virus strains from Hylomyscus pamfi. Within lineages II and III, seven and five sub-lineages, respectively, were distinguishable. The phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal towards the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast towards Taraba and Adamawa and south towards Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sub-lineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at higher resolution. In addition, we estimated the direction and timeframe of virus dispersal in the country.

 

IMPORTANCE

Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sub-lineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows predicting into which geographical areas the virus might spread in future and prioritizing areas for Lassa fever surveillance. Our study not only aimed at generating Lassa virus sequences from across Nigeria, but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.

Copyright © 2019 Ehichioya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Lassa fever; Nigeria.

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#Antibody #therapy for #Lassa fever (Curr Opin Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Curr Opin Virol. 2019 Aug 8;37:97-104. doi: 10.1016/j.coviro.2019.07.003. [Epub ahead of print]

Antibody therapy for Lassa fever.

Cross RW1, Hastie KM2, Mire CE1, Robinson JE3, Geisbert TW1, Branco LM4, Ollmann Saphire E2, Garry RF5.

Author information: 1 Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA. 2 La Jolla Institute for Immunology, La Jolla, CA 92037, USA. 3 Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. 4 Zalgen Labs, LLC, Germantown, MD 20876, USA. 5 Zalgen Labs, LLC, Germantown, MD 20876, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA. Electronic address: rfgarry@tulane.edu.

 

Abstract

Serum from convalescent Lassa fever patients was previously shown to be ineffective as a source of protective antibodies in some early studies. Subsequently, monoclonal antibodies (MAbs) to the Lassa virus (LASV) glycoprotein produced by memory B cells of West African patients who survived Lassa fever were identified. Development of MAbs as potential Lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of the LASV glycoprotein. Human mAbs were screened for reactivity to different neutralizing epitopes, potency, and broad reactivity against multiple lineages of LASV. MAbs were downselected in a guinea pig model of Lassa fever. A cocktail of three human MAbs designated Arevirumab-3 rescued 100% of Cynomolgus macaques at advanced stages of disease more than a week post-infection. Antibody therapeutics may be further developed in clinical trials in endemic areas potentially offering a key treatment option for Lassa fever.

Copyright © 2019 Elsevier B.V. All rights reserved.

PMID: 31401518 DOI: 10.1016/j.coviro.2019.07.003

Keywords: Serotherapy; Monoclonal antibodies; Lassa fever.

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