Lassa virus: characterization of infectious agent, biological models for pathogenesis studies and variants of vaccine
Bibliographic record
Abstract
Lassa virus (LASV) is classified into genus Mammarenavirus of Arenaviridae family. This virus is etiological agent of Lassa fever (LF) which is widespread in Africa. On average, in four out of five infected people, LF occurs without symptoms. The annual incidence ranges from 100,000 to 500,000 registered clinical cases, at a mortality rate of 1-2%. Among hospitalized patients with severe symptoms of hemorrhagic fever, this figure may be from 14 to 89.5%. Signs of an adverse outcome in LF are open bleeding and disorders of CNS (convulsions, tremor, disorientation and coma). Death occurs from multiple organ failure. Severely ill people recover slowly and may have relapses and complications such as pneumonia, myocarditis, psychosis, and hearing loss. Transmission of the virus in endemic territories occurs by alimentary way, air-dust and airborne droplets from a zoonotic source – rodents of the species African multimammate rat (Mastomys natalensis), by accidental contacts of people with their secretions (urine, feces, saliva) as well as when butchering carcasses and eating rodents. These animals are characterized by asymptomatic carrier and life-long persistence of the virus. Cases of transmission of the virus from person to person through the blood or other body fluids of patients are described. A sick person is contagious for two months, because the virus circulates in the blood despite high levels of antibodies. Infection of medical staff occurs during emergency surgical operations, or when the rules of contact precautions are not observed. Currently, with the ongoing LF outbreak in Nigeria, since 2016, hospitals have registered mortality rates of 22 and 8% for patients and health workers, respectively. During 1969-2016, 33 imported cases of this disease were described from West Africa to non-endemic territories (in the USA, Canada, Great Britain, the Netherlands, Germany, Israel and Japan). The mortality rate among these patients was 39%. The lack of prophylactic vaccines and specific therapeutic drugs is the major challenge for the prevention of LF. Thus, this review considers biological models (cell cultures and animals) that are suitable for studying the pathogenesis of this disease, preclinical studies of the specific activity and harmlessness of candidate vaccines, as well as options for these developments based on the platforms such as inactivated LASV and its DNA, the reassortant of Mopeia arenavirus, and measles virus attenuated strains, recombinant and replication-defective viruses (smallpox vaccine, Venezuelan equine encephalitis, bovine vesicular stomatitis, adenovirus of chimpanzee) and virus-like particles.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".