Lassa Fever

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Abstract

Lassa fever outbreaks West Africa have caused up to 10,000 deaths annually. Primary infection occurs from contact with Lassa virus-infected rodents and exposure to their excreta, blood, or meat. Incubation takes 2 to 21 days. Symptoms are difficult to distinguish from malaria, typhoid, dengue, yellow fever, and other viral hemorrhagic fevers. Clinical manifestations range from asymptomatic, to mild, to severe fulminant disease. Ribavirin can improve outcomes. Overall mortality is between 1% and 15%. Lassa fever should be considered in the differential diagnosis with travel to West Africa. There is an urgent need for rapid field-friendly diagnostics and preventive vaccine.

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Most cited references 94

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Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6

Omar Abudayyeh, Max J. Kellner, Julia Joung … (2018)

Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) that combines isothermal pre-amplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCKv2: 1) 4-channel single reaction multiplexing using orthogonal CRISPR enzymes; 2) quantitative measurement of input down to 2 aM; 3) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxilary CRISPR-associated enzyme; and 4) lateral flow read-out. SHERLOCKv2 can detect Dengue or Zika virus ssRNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.

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Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak

L. Kafetzopoulou, S. Pullan, P. Lemey … (2019)

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.

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Mastomys natalensis and Lassa Fever, West Africa

Emilie Lecompte, Elisabeth Fichet-Calvet, Stephane Daffis … (2006)

PCR screening of 1,482 murid rodents from 13 genera caught in 18 different localities of Guinea, West Africa, showed Lassa virus infection only in molecularly typed Mastomys natalensis. Distribution of this rodent and relative abundance compared with M. erythroleucus correlates geographically with Lassa virus seroprevalence in humans.