Virus World

The patient is a soldier who had recently returned from abroad. People who may be at risk through contact with him are being traced. A case of Lassa fever - endemic to West Africa and spread by rats - has been reported in the Paris region. The patient, a soldier who had recently returned from abroad, is now in the Bégin military hospital in Saint-Mandé (Val-de-Marne).  The Ministry of Health has said that an “in-depth epidemiological investigation is under way to determine the persons who may have been in contact with him”. It said his condition “does not give cause for concern”.

What is Lassa fever?

The fever takes its name from the town where it was first identified and isolated - Lassa in Nigeria, West Africa - and where it killed a nurse in 1969. It is now common in Nigeria, Guinea, Liberia, and Sierra Leone, and cases have also been reported in Cote d’Ivoire and Burkina Faso. There have been two epidemics in Benin in recent years; one in 2014 and another in 2016. The virus kills between 5,000 and 6,000 people per year in West Africa, and infects between 100,000 and 300,000 people. Its incubation period - from infection to symptoms - varies from two to 21 days. “The virus circulates almost constantly, especially in Nigeria, which is the worst-affected country,” said Sylvain Baize, head of the emerging viral infections unit at the Institut Pasteur, to BFMTV. “In all, it is estimated that 160 to 180 million people are potentially at risk.”

How does Lassa fever spread?

The virus is spread by rat faeces from the Natal rat (Mastomys natalensis), which is native to West Africa. The World Health Organization states: “The virus can also be transmitted from human to human by direct contact with the blood, urine, excrement or other bodily secretions of a contaminated person.”

What are the symptoms of Lassa fever?

In 80% of cases, it causes no symptoms. However, in the remaining 20%, symptoms come on gradually and become increasingly severe. They include fever, vomiting, nausea, stomach pain, and headaches.  In 15% of cases, symptoms are worse, and include oedema (fluid build-up); pleurisy (inflammation of the lung lining); and oral, nasal or vaginal haemorrhage. The fever is fatal in around 1% of cases, as it goes on to cause organ failure. Of those who develop serious symptoms and do survive, some will have lasting heart problems, and 25% will become deaf. Only half of these will recover their hearing after one to three months.

It is especially dangerous for pregnant women.

What is the treatment for Lassa fever?

So far, only one treatment has been identified. This is the antiviral agent ribavirin. This must be given very soon after infection to be effective.  However, because the symptoms of the fever typically appear similar to other conditions (including malaria and dysentery), by the time the condition is confirmed, it is usually too late to give the drug. There is no vaccine yet available, although the Institut Pasteur released promising results to an international phase one trial in April. After-effects sometimes appear in those who survive this fever: 25% become deaf. Only half recover their hearing after one to three months.

May 3, 2024

A new study, published in the August 8, 2019, issue of Cell by a team of researchers led by Instructor Kathryn Hastie, Ph.D., and Professor Erica Ollmann Saphire, Ph.D., at La Jolla Institute for Immunology (LJI),  identified and then reverse engineered the molecular properties shared by antibodies that are particularly efficient at inactivating or “neutralizing” the virus. The team’s findings also revealed that most neutralizing antibodies bind to the same spot on the surface of Lassa virus, providing a map for rational vaccine design.As this year's Lassa fever outbreak in Nigeria is finally ebbing, the total tally came to more than 600 infected people, one-quarter of them dead. Thousands more die each year, uncounted in rural villages throughout West Africa. With an annual wave of infections and new viral strains emerging, it has never been more important to understand the characteristics of a broadly protective immune response in order to develop effective treatments, or better yet, a vaccine.

“The beauty of structural biology is that it gives you the ability to dissect the molecular details at high resolution to explain precisely how something works,” says structural immunologist Ollmann Saphire. “Once you do, you have a blueprint to engineer potent immunotherapeutics or a vaccine that elicits the desired immune response.”

Identified 50 years ago and named for the town in Nigeria where the first known cases cropped up, Lassa virus is endemic in West Africa where it infects hundreds of thousands of people every year. For the majority of infected people, symptoms are mild and the infection mostly goes undiagnosed. But in 20 percent of patients, the disease causes a more serious illness including neurological symptoms and hemorrhage, which can result in multi-organ failure and death.

For the current study, Hastie compared the structure of three different neutralizing antibodies of varying potency—high, moderate and low—bound to the glycoprotein. The side-by-side comparison highlighted specific amino acid residues that drive high potency and enabled the researchers to precision-engineer mediocre antibodies to turn them into highly effective ones.

“Not only were we able to increase the antibody’s potency, which means you can deliver much less antibody, we were also able to make it pan-Lassa. It can hit every Lassa virus lineage characterized so far,” says Hastie.  But few naturally infected people generate neutralizing antibodies and current vaccine efforts focus on eliciting T cell immunity. “Historically, researchers have found that development of antibodies is not a good correlate of protection in natural Lassa infections,” says Hastie. “It is actually very difficult to induce neutralizing antibodies.” 

The study was published in Cell on August 8, 2019:

https://doi.org/10.1016/j.cell.2019.07.020