A rapid diagnostic test (RDT) for the dangerous Lassa fever virus developed by Broomfield, Colorado based Corgenix Medical in collaboration with its Viral Hemorrhagic Fever Consortium (VHFC) research partners, has demonstrated effectiveness in quickly detecting the virus that causes Lassa fever, an infectious disease responsible for the deaths of thousands and infection of hundreds of thousands in West Africa each year.
A multi-year study conducted primarily at the Kenema Government Hospital (KGH) in Kenema, in the western African nation of Sierra Leone, investigated the clinical utility of several VHFC diagnostic products, including Corgenix’s recently CE marked ReLASV Antigen Rapid Test for Lassa virus.
A research paper recently published in the PLOS Neglected Tropical Diseases Journal (PNTD) titled “Lassa Fever in Post-Conflict Sierra Leone” (March 20, 2014DOI: 10.1371/journal.pntd.0002748) reports results of the five-year trial.
The Viral Hemorrhagic Fever Consortium (VHFC) is a collaboration of academic research institutes and industry members headed by Tulane University in New Orleans, Louisiana, and partially funded with support from the National Institutes of Health (NIH). Established as a result of a five-year $15 million contract awarded to Tulane University by the National Institute of Allergy and Infectious Diseases (NIAID), a NIH agency, in 2010, to support Tulane’s ongoing efforts focused on development of new recombinant proteins for Lassa virus and diagnostic products to treat and prevent Lassa Fever. The NIH award enabled research to move to the next level, allowing for focus to be shifted towards better treatment and ultimately prevention of Lassa fever altogether.
The VHFC’s mission has been expanded to promotion of global health and safety by creating new products to diagnose, treat and significantly reduce the incidence and mortality rate of a range of viral hemorrhagic fevers including Lassa fever, Ebola fever, Marburg fever, and and other Arenaviruses that are of great concern to public health and bioterrorism. The VHF Consortium’s goal is to undertand mechanisms related to the human immune response to Lassa virus infection and other VHF diseases — specifically, by understanding what parts of the virus are recognized by the immune system so that the mechanisms of antibody-mediated protection or pathogenesis in humans with can be better understood.
Lassa fever (LF), is an often-fatal hemorrhagic disease caused by the Lassa virus (LASV), and a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital, which is located in a region with the world’s highest incidence of the disease.
Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically, and recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF.
The PNTD paper notes that Kenema Government Hospital was reestablished after the civil war ended as a center for Lassa fever treatment and research, with over 500 suspected cases presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict, provisionally attributed to application of different criteria for defining LF stages and differences in sensitivity of assays.
The highest incidence of LF in Sierra Leone is observed during the dry season, and LF cases were observed in ten of Sierra Leone’s thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients as well. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects.
Researchers using the Corgenix Recombinant Lassa Virus (ReLASV) Diagnostic products were able to diagnose and treat patients earlier, a capability that may reduce the fatality rate for Lassa fever cases. The ReLASV Antigen Rapid Test for Lassa Fever is the first commercialized diagnostic test developed by Corgenix, Tulane U., and the other VHFC members.
“This major trial validates the ability of rapid Lassa fever testing to quickly identify cases for immediate treatment,” says Corgenix President and CEO Douglass Simpson. “The trial also established new standards for rapid field and laboratory identification of Lassa fever and other viral hemorrhagic fevers, which include the Ebola virus. This type of investigation is critical in resource limited laboratory and clinical settings.”
“Getting to the patients early is critical,” says Matt Boisen, trial co-author and Corgenix Medical Project Director – Infectious Diseases. “The data indicates that if the patient is diagnosed early enough, the potential for successful treatment is improved, and point-of-care testing with RDTs is the ideal method for rapid diagnosis.”
Lassa fever is characterized by bleeding and coagulation abnormalities, with mortality rates as high as 70 percent, with children and pregnant women being the highest risk groups. According to the Centers for Disease Control and Prevention (CDC), the illness was discovered in 1969 when two missionary nurses died in Nigeria, West Africa. The cause of the illness was found to be Lassa virus, named after the town in Nigeria where the first cases originated. The virus, a member of the virus family Arenaviridae, is a single-stranded RNA virus and is zoonotic, or animal-borne. The Lassa virus is considered a Category A (highest risk) pathogen and potential bioterrorism agent by the National Institute of Allergy and Infectious Diseases (NIAID).
Areas of Africa where the disease is recognized as endemic include Guinea, Liberia, Sierra Leone, and Nigeria. However because the rodent species that carry the virus, the “multimammate rat” of the genus Mastomys, found throughout West Africa, the actual geographic range of the disease may extend to other countries in the region. Lassa fever is a significant cause of morbidity and mortality, and while about 80% of people who become infected with the virus exhibit mild or no observable symptoms, the remaining 20% develop a severe multisystem disease. Lassa fever is also associated with occasional epidemics, during which the case-fatality rate can reach 50%. Mastomys rodents breed very frequently, produce large numbers of offspring, and are numerous in the savannas and forests of West, Central, and East Africa. In addition, Mastomys generally readily colonize human homes — all factors that contribute to relatively efficient spread of Lassa virus from infected rodents to humans.
The CDC estimates the number of Lassa virus infections per year in West Africa is estimated at 100,000 to 300,000, with approximately 5,000 deaths, but cautions that such estimates are crude, because surveillance for cases of the disease is not uniformly performed, noting that some areas of Sierra Leone and Liberia, it is known that 10%-16% of people admitted to hospitals have Lassa fever, which indicates the serious impact of the disease on the region’s population.
Signs and symptoms of Lassa fever typically occur 1-3 weeks after the patient comes into contact with the virus, and include fever, retrosternal pain (pain behind the chest wall), sore throat, back pain, cough, abdominal pain, vomiting, diarrhea, conjunctivitis, facial swelling, proteinuria (protein in the urine), and mucosal bleeding. Neurological problems have also been described, including hearing loss, tremors, and encephalitis. Because the symptoms of Lassa fever are so varied and nonspecific, clinical diagnosis is often difficult.
Traditionally, Lassa fever is most often diagnosed by using enzyme-linked immunosorbent serologic assays (ELISA), which detect IgM and IgG antibodies as well as Lassa antigen. The virus itself may be cultured in 7 to 10 days. Immunohistochemistry performed on tissue specimens can be used to make a post-mortem diagnosis. The virus can also be detected by reverse transcription-polymerase chain reaction (RT-PCR); however, this method is primarily a research tool.
However, conventional Lassa virus testing is costly, time-consuming and requires specialized handling in high-level biohazard laboratories, all of which can result in delays of up to several days before diagnosis can be confirmed and treatment started. ReLASV Antigen Rapid Test is a highly accurate, 15-minute test that detects Lassa virus antigen in serum, plasma or blood, leading to early acute-stage treatment. Patients with a definitive Lassa fever virus diagnosis are treated with the anti-viral drug ribavirin.
Dr. Robert F. Garry, Ph. D., a Professor of Microbiology and Immunology at The Tulane University School of Medicine and a Principal Investigator for the VHFC, says the trial conducted at the Kenema Government Hospital demonstrates how important it is for the test to match the environment.
“In a difficult resource environment such as Sierra Leone, where the testing mechanisms are very different than in the U.S. or other developed countries, properly configured tests can be highly successful,” says Dr. Garry. “A testing program in coordination with a health care system aligned with local authorities, the federal government, and community outreach can provide an organized system that addresses these life-threatening diseases.”
The VHFC is continuing its Sierra Leone research to address Lassa fever, Ebola fever and other severe, high-mortality tropical diseases in West Africa. The Consortium is a collaboration among Tulane, Scripps Research Institute, Broad Institute, Harvard University, University of California at San Diego, University of Texas Medical Branch, Autoimmune Technologies LLC, Corgenix Medical Corporation, Kenema Government Hospital (Sierra Leone), Irrua Specialist Teaching Hospital (Nigeria) and various other partners in West Africa. Together the VHFC partners work on evaluating antibodies from patients who have been infected by Lassa virus and have subsequently recovered, to see if those antibodies might play a role in the development of a vaccine or treatment for the illness.
The Tulane University School of Medicine provides both scientific (laboratory, clinical and international) resources and contract management. Their facilities include fully equipped immunology and virology laboratories run by Dr. Robert Garry, TUSM professor of pediatrics Dr. James Robinson, and their colleague Dr. Daniel Bausch, an Associate Professor in the Department of Tropical Medicine and Section of Infectious Diseases, Department of Internal Medicine, at the Tulane University Health Sciences Center. Formerly with the CDC Special Pathogens Branch, Dr. Bausch has extensive experience in sub-Saharan Africa, Latin America, and Asia combating pathogens such as Ebola and Lassa viruses, hantavirus, and SARS coronavirus. He serves as a frequent consultant for the World Health Organization, United Nations, and National Institutes of Health. Dr. Bausch places a strong emphasis on capacity building in all his research projects, which include epidemiology and control of viral hemorrhagic fevers and emerging pathogens; building research capacity in developing countries and he also has a keen interest in the role of the scientist in promoting health and human rights.
Dr. Garry also serves in the Tulane University administration as Assistant Dean for Graduate Studies in Biomedical Sciences, directing a large multidisciplinary training program. Research in the Garry Laboratory focuses on a number of aspects of viral pathogenesis. He was involved in collaborative studies that lead to the determination that entry proteins of enveloped viruses form at least three distinct structural classes.
The Corgenix ReLASV Antigen Test Kit is CE marked for diagnostic use in the EU and other international markets. It has not been cleared or approved for diagnostic use in the United States by the FDA. Corgenix Ebola products have not yet been cleared or approved for diagnostic use by any worldwide regulatory authority.
Corgenix develops and manufactures specialized diagnostic kits for various immunology disorders, vascular diseases (including the world’s only non-blood-based test for aspirin effect), bone and joint disorders and a line of unique detection products for viral hemorrhagic disease. Corgenix diagnostic products are commercialized for use in clinical laboratories throughout the world. The company currently sells over 50 diagnostic products through a global distribution network and has significant experience in product submissions to the FDA and other worldwide regulatory authorities. Additionally, Corgenix contract develops and manufactures products for key medical and life science companies in state-of-the-art facilities in Colorado. The company operates under a Quality Management System that is ISO 13485:2012 certified and compliant with FDA regulations.
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Viral Hemorrhagic Fever Consortium
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The Centers for Disease Control and Prevention
Kenema Government Hospital
Corgenix Medical Corporation
The Viral Hemorrhagic Fever Consortium
Kenema Government Hospital