New animal model for Lassa fever

Scientists at the Southwest Foundation for Biomedical Research have developed a new tool in the battle against a potential biological weapon, Lassa fever, which kills several thousand people each year and leaves thousands more with disabilities such as deafness and liver damage.

In an article in the June 2007 issue of the Journal of Virology (Vol. 81, Issue 12), SFBR scientists Jean Patterson and Ricardo Carrion Jr. and colleagues detail the development of a new animal model, the marmoset monkey, for use in Lassa fever research.

The marmoset is a small primate that weighs about one pound when fully grown, but it has many genetic and physiological similarities to humans. An advantage of using marmosets is that the animal's response to Lassa infection completely mimics the response found in people who develop symptoms.

The availability of the marmoset for this research is expected to speed the testing of potential vaccines against Lassa fever, including a number of candidate vaccines that already have been developed and are waiting on a model like this for testing, said Patterson, chairman of the Department of Virology and Immunology at SFBR.

Already, Patterson and Carrion have been working with marmosets at SFBR to test a promising Lassa fever vaccine developed at the University of Maryland Biotechnology Institute.

A shortage of animals available for testing new vaccines has hindered such research in the past, causing many scientists around the United States to encounter lengthy waits to conduct testing,

“Having this model will allow investigators to test their vaccines more quickly than they would be able to without it,” Carrion said. “And because it mimics the human response to Lassa more faithfully than existing models, it might become the preferred model.”

Collaborators with Patterson and Carrion on the study detailed in the Journal of Virology article include Dr. Kathleen Brasky of the Southwest National Primate Research Center, located at SFBR; Curtis Johnson, Monica Gonzales, and Anysha Ticer of SFBR; Keith Mansfield of the New England Primate Research Center at Harvard Medical School in Southborough, Mass.; Igor Lukashevich of the Institute of Human Virology at the University of Maryland Biotechnology Institute in Baltimore; and Suzette Tardif of the Sam and Ann Barshop Center for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio.

Lassa fever is a viral illness that occurs in West Africa, spread by the “multimammate rat,” known for frequent breeding and a tendency to colonize where people live.

The virus is seen as a potential bioterror weapon because one of the ways that people become infected is via airborne particles contaminated with rodent excretions, known as aerosol or airborne transmission. The virus also can be acquired in other ways, including eating food contaminated with it, through cuts or sores, or by coming into contact with the blood, tissue, secretions, or excretions of an infected person.

Only about 20 percent of people infected with Lassa develop severe symptoms. Of those who get sick, the mortality rate is from 15-20 percent, but the mortality rate rises to 60 percent for those who are pregnant. Like humans, marmosets that die from the disease do so within 20 days of becoming ill.

Of those people who recover, 30-40 percent suffer hearing loss and liver damage.

Lassa fever also causes a marked suppression of the immune system, an aspect of the disease that the researchers are tracking with the current marmoset vaccine study. “Pregnant women have such a high mortality rate from Lassa because pregnancy already causes immunosuppression, and Lassa compounds it,” Patterson said.

In addition to its similarity to humans in response to the disease, marmosets also are valuable in this type of research because they are smaller and take up less space in a laboratory and require lower doses. They also are far more readily available than more traditional research primates, such as rhesus macaques.

“We had a study that was delayed for four or five months because we couldn't get any rhesus macaques,” Carrion said.

He said other dangerous pathogens that the scientists intend to study with the help of marmosets include Ebola, a hemorrhagic fever virus, and Marburg, a relative of Ebola, both of which have up to a 90 percent mortality rate.