NIAID Scientists Recommend Favipiravir for Human Trials of Lassa Fever Virus
NIAID scientists have successfully treated cynomolgus macaques infected with Lassa fever virus using the broad-protection antiviral drug favipiravir, and, subsequently, have recommended that testing for the investigational antiviral proceed to human clinical trials. The study findings, published online June 11 in Emerging Infectious Diseases, add support to discussions the World Health Organization has had on the subject.
A 2012 study estimated that 300,000 people—mostly in West Africa where the virus is endemic—become infected with Lassa each year, about 5,000 of whom die. A Lassa outbreak began in January 2018 in Nigeria and remained a concern into mid-June. According to the International Society for Infectious Diseases, Nigeria had reported 1,999 suspected cases, 437 of which were confirmed, with 109 deaths. To the west of Nigeria, Liberia and Sierra Leone also have experienced cases of Lassa fever in 2018. Liberia has reported 112 suspected and 18 confirmed cases with 13 deaths. Sierra Leone has reported 18 cases and seven deaths.
Lassa, discovered in 1969, is transmitted by Mastomys rats, which usually spread the virus through saliva, urine and feces that contact food or household items. Person-to-person transmission is possible by contact with body fluids of an infected person.
Favipiravir, also known as also known as T-705 and Avigan, is approved in Japan for influenza treatment and is being tested against influenza in the United States. It is thought to have broad potential for treating several RNA-based viruses. During the 2014-16 Ebola outbreak in West Africa, favipiravir was used to treat some patients, but its effectiveness was unclear.
In 2015 researchers at NIAID’s Rocky Mountain Laboratories used favipiravir to successfully treat guinea pigs infected with Lassa, and they quickly followed up with the cynomolgus macaque study. The monkeys, infected with a lethal dose of Lassa fever virus, began favipiravir treatments four days after infection. At the end of the study, none of the treated animals had Lassa fever virus in their blood or tissue, and their livers—which usually show severe disease from the virus—were normal.
Unlike some of the cold-chain logistical challenges of distributing drug treatments in Africa, favipiravir is stable at room temperature and only requires protection from light.
Also of interest, the same research group on June 21 published a study showing favipiravir was effective in treating mice against Crimean-Congo hemorrhagic fever virus. CCHF virus, spread by ticks, is found in Eastern Europe, throughout the Mediterranean, in northwestern China, central Asia, southern Europe, Africa, the Middle East, and the Indian subcontinent. That work appears online in Antiviral Research. The group has concluded additional studies of favipiravir against CCHF virus in monkeys and is analyzing the data.
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