Table 5 Lassa fever clinical research priorities identified
Clinical phenotype and natural history of disease | RRNA | Expert panel |
|---|---|---|
Which are the populations at risk? | ✓ | ✓ |
What is the true incidence of asymptomatic infection; is the reported 85% of asymptomatic infections true or is there a diversity of clinical presentation? | ✓ | |
What are the clinical characteristics of Lassa fever in different at-risk populations? | ✓ | |
What are the long-term health sequelae and what is their frequency, severity, and duration? | ✓ | ✓ |
What are the underlying pathophysiological mechanisms of death and are these preventable e.g. acute kidney injuries? What is the cause of platelet dysfunction in acutely ill Lassa patients? | ✓ | ✓ |
What is the clinical and epidemiology relevance of Lassa virus sequence heterogeneity? | ✓ | |
Transmission and prevention | ||
What are the risks of person-to-person transmission associated with different types of exposure e.g. to what extent and how does human-human transmissions account for disease transmission? What is the risk of transmission from different body fluids and organs? | ✓ | ✓ |
Does disease severity vary with route of transmission? | ✓ | |
Does genetic differences within and between Lassa virus strains results in differences in transmission and in disease phenotype? | ✓ | |
Who are the target population for a Lassa vaccine, e.g. does asymptomatic infection protect against re-infection? Does presence of antibodies protect from re-infection? | ✓ | ✓ |
Does ribavirin PEP reduce the risk of Lassa virus disease, or more severe disease? | ✓ | |
What is the optimal route and dosing for post-exposure prophylaxis with ribavirin (e.g. oral vs. intravenous)? | ✓ | ✓ |
How diverse does a vaccine need to be to protect against all strains of Lassa virus? | ✓ | |
Diagnostics | ||
Can we develop a diagnostic test that is highly sensitive and specific for all lineages? | ✓ | ✓ |
How does sequence variation/heterogeneity impact diagnostic methods and accuracy? | ✓ | |
What is the optimal sampling time frame for diagnostics using RT-PCR? How many days after symptoms does Lassa virus become detectable by PCR? | ✓ | |
Can we develop a validated point-of-care test for use in different healthcare settings, including rural health posts? | ✓ | ✓ |
Immune response | ||
What are the dynamics of resistance to re-infection? What is the average kinetics of antibody responses following acute Lassa fever virus infection and what is the variability between individuals and by age? | ✓ | ✓ |
In what sites and for how long does virus persist? What are the risk factors for virus persistence? | ✓ | |
Does previous exposure to Lassa virus result in more severe disease upon subsequent re-exposure (e.g. vaccine) as a result of antibody-dependent enhancement of infection, i.e. could a vaccine do harm? | ✓ | |
What immunological end-points should be used for Lassa virus vaccine trials? | ✓ | |
Drug therapy and supportive care | ||
What is the true efficacy and safety of ribavirin for the treatment of Lassa? Can we transition acutely ill Lassa patients to oral ribavirin once viral loads are decreasing? | ✓ | ✓ |
Does the use of ribavirin in acute Lassa fever virus infection improve clinical outcomes compared to supportive care alone? | ✓ | ✓ |
What is the optimal approach to supportive care for acutely ill patients with Lassa and other VHFs? | ✓ | |
What is the target therapeutic plasma and CSF concentrations of ribavirin for the treatment of Lassa fever virus infection? Do current oral and IV treatment regimens achieve these target concentrations? | ✓ | |
Can type 1 interferon therapy boost the efficacy of ribavirin? Is there a role for therapies directed at host immunopathology in the management of Lassa fever? | ✓ | |
Risk factors for more severe disease | ||
Are reported differences in CFR attributable to differences in case mix (e.g. illness severity on presentation to a healthcare facility), differences in the underlying prevalence of risk factors for death, or differences in the care provided? | ✓ | |
Are there clinical features or biomarkers of the risk of progression to severe disease that have clinical utility? | ✓ | |
Do genetic differences within and between Lassa strains results in differences in disease phenotype and disease severity? | ✓ | |