Researchers at The University of Texas Medical Branch (UTMB), funded by a National Institutes of Health grant, have published findings in Nature showing that antiviral medicine successfully treated non-human primates infected with the virus that causes Lassa fever.
Lassa fever remains a global health threat
Lassa fever is a hemorrhagic disease for which there is currently no treatment. It is estimated to cause 100,000 to 300,000 infections and 5,000 deaths annually in West Africa with Nigeria accounting for a significant portion of cases. Infections have also been regularly detected in travelers returning to North America or Europe after traveling through the region. Mortality rates are unusually high in pregnant women.
UTMB study shows promising antiviral results
In the publication, UTMB researchers described treating five African green monkeys with 4′-fluorouridine six days after infection with the virus. Four of the five animals cleared the virus rapidly and completely.
The broad-spectrum antiviral drug used in this study was administered orally. Using oral medications can lead to more timely treatment with improved compliance since no special medical supplies or special training are required. Speed of deployment is critical when addressing a viral outbreak in the field, according to Dr. Thomas Geisbert, professor of microbiology and immunology at UTMB and the study’s senior investigator.
In a real clinical setting, patients may not come in until they have significant illness, so the team reflected that reality in their study. Some antiviral drugs, like those often given to treat influenza, are only effective if used very soon after exposure. Being able to treat sicker patients would be significant as this could increase chances of survival.
Next steps to improving outbreak response and research models
Using African green monkeys is a novel approach, Geisbert said. In fact, using these monkeys in the research was an important point of the study.
“Macaque monkeys are the primates most used in such research, but the cost to procure them has increased significantly over the last few years,” Geisbert said.
This research allows Galveston National Lab (GNL) scientists at UTMB to investigate new options for animal models. Although scientific advances aim to minimize the use of animals as research subjects, animal models are still necessary in some scenarios, including the study of infectious disease transmission. Human trials are difficult to conduct during an outbreak.
Dr. Robert Cross, associate professor of microbiology and immunology and the study’s lead author, said developing new animal models is still important.
“AI and alternative testing approaches, such as organoids and organ-on-a-chip technologies, are very promising,” Cross said. “However, it’s still too early to replace some animal research, especially when studying how much immune response is needed to ensure a drug works in advanced disease or in highly susceptible populations, such as the elderly or pregnant individuals. It is an aspirational goal; but there are major limitations, and, in the meantime, non-human primate subjects are offering convincing data resulting in saved lives.”
Geisbert said GNL researchers are also investigating developing technologies that will help reduce the number of animals needed for such research.
“We’re trying to get into the new approaches like organ-chip technologies as well,” Geisbert said. “We want to compare the data we get from monkeys and Lassa-infected humans. We want to compare all of that to make sure the organ chips really are giving the right answers. We’re just not quite there yet.”
Other authors are Jacquelyn Turcinovic, Abhishek N. Prasad, Viktoriya Borisevich, Krystle N. Agans, Daniel J. Deer, Rachel O’Toole, Natalie S. Dobias, Courtney Woolsey, and Karla A. Fenton, all of UTMB.