Vaccination plans:- The first-ever detailed estimate of the real damage done by Lassa fever, a virus endemic to West Africa, has found that it infects 2.7 million people a year, ten times more than health agencies had assumed.

In 2016 the World Health Organization (WHO) designated Lassa – a disease with no licensed vaccines or specific treatments – a top pandemic threat.

After that warning, research intensified and four candidate vaccines are now being tested in people, one of which started advanced trials last week.

Now a team of 16 scientists, in Nigeria and at the University of Oxford in England, have for the first time calculated what may be the true burden of the disease – and how best to use vaccination to reduce it.

Their study, published in Nature Medicine, found vaccinating high-risk populations could avert up to 4,400 deaths in West Africa and save societal costs, including labour losses and healthcare, of almost US$129 million a year.

Cases of the virus occur in all 15 countries of continental West Africa, but most often in Nigeria, Guinea, Liberia and Sierra Leone. The WHO now considers Benin, Ghana, Mali and Togo endemic for the disease as well.

It was thought to live only in some multimammate rats, the most common rodent in Sub-Saharan Africa. Nearly all human infections of Lassa fever come from animals, and people very rarely infect other people, mostly healthcare workers. But the virus has now been found in other rodent species – and more places.

“It seems the at-risk area is expanding, particularly with climate change,” says Robert Garry of Tulane University in New Orleans, USA, a leading Lassa expert not involved in the study.

Changes in land use bring more people into contact with infected rodent droppings and Lassa has been ranked the most likely animal virus to spill over into humans – even ahead of Ebola.

But it has been hard to assess its full impact. Disease surveillance is limited in West Africa and cheap, simple tests for the virus have not been available, although one is now being used in Sierra Leone, says Garry.

The commonly cited statistic, up to 300,000 cases a year and 5,000 deaths, are based on one study done almost 40 years ago.

One problem has been that the main symptoms of Lassa – fever and vomiting – are similar to other local diseases, so misdiagnosis is common. Response to the Ebola epidemic of 2014 was delayed when early cases were mistaken for Lassa.

Additionally, the vast majority of infections cause mild or even no symptoms. The new study found that only 0.9 per cent become severe, says David Smith at Oxford, a lead author.

However, 16 per cent of hospitalised cases die, while many survivors become deaf.

The researchers say they did the study because, if vaccines become available in the near future, more understanding of how they affect numbers of infections is needed if countries are to deploy them effectively.

Extrapolating data

Smith and team mapped the data they had onto a computerised, geographic model of the region, starting with local rainfall, vegetation and temperatures, which affect rodent numbers.

Then they added the percentage of people and rats found in various local studies that had evidence in their blood of previous infection with Lassa. This gave a more accurate picture of the infection in people than doctors’ reports, as many mild cases are never recognised.

It also revealed the relationship between geography and known infections, which was then used to predict the risk of infection throughout the region, including where it had not been measured directly. Then a standard model of epidemics was used to calculate the actual number of infections that would result from that risk.

Adding data on hospitalisations and deaths from places that track this closely, such as Ondo in Nigeria, says Smith, allowed them to extrapolate the number of deaths that would result from these infections in all of West Africa.

That gave 2.7 million infections a year – more than half in Nigeria – and almost 4,000 deaths.

As experts have suspected, says Smith, there are far more mild cases than previously thought. These pose a risk, both of becoming severe and of the virus adapting to people.

Yet we have few direct measurements of how many such cases there are, says Smith. “Mali reports virtually no cases,” he says, yet a recent survey for blood markers of infection by researchers in Bamako found them in up to 44 per cent of people per village.

Vaccination strategies

The team then used the model to predict the effects of different patterns of vaccination. Just vaccinating people living amidst recognised outbreaks – as is done for some other diseases – didn’t cut case numbers much overall.

But vaccinating 80 per cent of people in the zones of highest risk, and five per cent elsewhere in the region, with a vaccine that stopped 70 per cent of cases, prevented 3,300 deaths a year – ten times as many as only vaccinating around outbreaks, according to the model. It also kept 14,000 people from being driven below the poverty line by medical costs.

Moreover the “monetary value” of the lives saved was up to US$1.9 billion, showing how the burden of otherwise unhindered disease adds to poverty and stymies development.

The team also calculated the cost to the region if a more frequently severe variant of Lassa emerged that also spread more readily between people, as happened with mpox.

“We have no evidence whatsoever regarding how likely this is to occur,” cautions Smith. But in the model, an explosive outbreak led to a death toll just in West Africa of 25 million, with 100,000 pushed into poverty.

The risk of this happening is real. At least eight viruses in Lassa’s family, the arenaviruses, are known to cause disease in humans, and many more are unknown, Garry warns. “One of these could emerge and if it happens to spread a bit more easily than Lassa, that would be a problem.” AlphaGalileo/SP