Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome
Abstract
Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas.
Background
Lassa virus (LASV), a member of the Arenaviridae family, is the etiologic agent of Lassa fever, an acute and often fatal illness endemic to West Africa. There are an estimated 300,000 – 500,000 cases of Lassa fever each year with a mortality rate of 15%-20% for hospitalized patients, which can become as high as 50% during epidemics. Presently, there is no licensed vaccine or immunotherapy available for prevention or treatment of this disease. Although the antiviral drug ribavirin is somewhat beneficial, it must be administered at an early stage of infection to successfully alter disease outcome, thereby limiting its utility. Furthermore, there is no commercially available Lassa fever diagnostic assay, which hampers early detection and rapid implementation of existing treatment regimens (e.g. ribavirin administration). The severity of the disease, its ability to be transmitted by aerosol droplets and the lack of a vaccine or therapeutic drug led to its classification as a National Institutes of Allergy and Infectious Diseases (NIAID) Category A pathogen and biosafety level-4 (BSL-4) agent. Several imported Lassa fever cases have been described since 1973 primarily from foreign nationals displaying signs of the disease upon returning to native countries or having been evacuated after falling ill abroad. To date, and despite the often severe nature of Lassa fever in Western African nations, resources have not been available to perform comprehensive daily analysis of blood samples from suspected and confirmed patients in-country. Continuous infrastructure improvements at the Kenema Government Hospital (KGH) Lassa Fever Laboratory (LFL) by Tulane University, Department of Defense (DoD) and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) since 2005 have allowed for the implementation of sophisticated diagnostic and research capabilities at this location. Currently the KGH LFL diagnoses Lassa fever using ELISA and lateral flow immunoassay (LFI) platforms to detect viral antigen and virus-specific IgM and IgG levels in the serum of every suspected case presented to the LFW. Additionally, the laboratory can assess 14 serum analytes using a Piccolo® blood chemistry analyzer coupled with comprehensive metabolic panel disks. Flow cytometry powered by a 4-color Accuri® C6 cytometer is used to perform immunophenotyping and intracellular and bead-based secreted cytokine analysis. Together, these diagnostic assays and instruments enabled the analysis of metabolic and inflammatory functions in real time utilizing the sera of individuals discussed in this case report with concomitant appropriate medical intervention.
The main patient case discussed in this report was closely monitored for nine days during his hospitalization, during which time his condition stabilized; he began walking with supervision and was nearing the end of ribavirin treatment. These studies herald a new era in real time diagnosis and management of Lassa hemorrhagic fever in resource poor, endemic areas of Western Africa. They represent a novel platform toward more efficient and broader control of the effects of this disease in the population at large.