Ebola Lying in Wait

The New York Times
By Pam Belluck and William J. Broad
April 20, 2015

(Click here to view the original article.)

A growing body of scientific clues — some ambiguous, others substantive — suggests that the Ebola virus may have lurked in the West African rain forest for years, perhaps decades, before igniting the deadly epidemic that swept the region in the past year, taking more than 10,000 lives.

Until recently, Ebola had been considered a threat mostly to Central African nations. Yet studies tell of possible Ebola antibodies in human blood samples drawn in West Africa long before the current outbreak. And genetic analysis suggests the West African virus broke off from a parent strain in Central Africa at least 10 years ago, possibly as long as 150 years ago.

“My gut feeling,” said Dr. Peter Piot, the director of the London School of Hygiene and Tropical Medicine, who helped discover the Ebola virus in 1976, is that the evidence points to “infection before the current epidemic.”

Medical detectives in West Africa are now seeking to establish whether the virus had previously infected people there. The research is part of a broader push to better understand where Ebola might strike next, and to strengthen surveillance and health systems in hopes of preventing future outbreaks.

Beyond the known outbreaks in Central and West African nations, scientists have found signs in human blood that suggest immune reactions to Ebola in 14 other countries: 12 in Africa, as well as Panama and the Philippines.

Zeroing in on African rain forests, a team of scientists from Oxford University, Harvard and other institutions recently used ecological data and patterns of known human and animal outbreaks to construct a detailed prediction of other likely Ebola danger zones.

It stretches across 22 nations from West Africa as far east as Madagascar. The team stressed the low probability of humans picking up the virus, which can be transmitted only by direct contact with bodily fluids like blood and vomit.

But the scientists also warned of new dangers because of encroachments on primal forests and sharp rises in populations and mobility.

Stuart Nichol, the chief of the viral special pathogens branch at the National Center for Emerging and Zoonotic Infectious Diseases, said there was a growing consensus “that in this broad area of Africa, we should be doing all we can to improve surveillance.”

The World Health Organization and the Centers for Disease Control and Prevention have been working to prepare African countries considered at high risk for Ebola epidemics. The nations are prioritized by their proximity to the current outbreak zone and the fragility of their health systems, among other factors.

Many, though not all, of the countries on the C.D.C.’s and W.H.O’s lists overlap with countries in the scientific studies. Dr. Thomas Frieden, the C.D.C. director, said that ideally, every nation in need should receive preparedness assistance, but that agencies have given priority to “countries that have a lot of people and a lot of travel.”

For decades, scientists have searched for the presence of Ebola in West Africa, though few outside experts knew of their detective work. It is generally assumed that the virus survives in an animal host, perhaps bats, from which it is periodically transmitted to humans.

But the host has never been identified, and researchers have struggled to understand how often humans have been exposed.

In 1982, German scientists, examining blood from hundreds of Liberians, reported antibodies to the Ebola virus in 6 percent of the samples. Four years later, Dutch scientists found the antibodies in 13 percent of blood samples from Liberia.

Similar rates were found in samples from Guinea and Sierra Leone. But doubts arose because of diagnostic imprecision.

World health authorities had long promoted a test known as indirect fluorescence because it was fast, sensitive and relied on inexpensive microscopes. By the early 1990s, experts had concluded that its reliability was overly dependent on skilled interpretation.

Then, in 1994, came the first and — until the current outbreak — only confirmed human Ebola case in West Africa: a Swiss scientist who had examined a dead chimpanzee in an Ivory Coast rain forest near the Liberian border. She was flown to Switzerland for treatment and survived.

More than 10 years later, a team of American scientists and West African medical personnel working at the Kenema Government Hospital in eastern Sierra Leone made a strange find. They had been treating people suspected of having Lassa fever, with its swelling,vomiting and bleeding. But more accurate tests showed that only about a third of patients actually had that disease.

Led by Randal J. Schoepp, the head of diagnostics at the United States Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md., the team sought to solve the puzzle by analyzing blood drawn from more than 200 patients at the hospital from October 2006 to October 2008. They found antibodies for a range of diseases, including what appeared to be Ebola antibodies in nearly 9 percent of the blood samples.

“That sort of blew our minds,” Dr. Schoepp said.

The scientists were also surprised to learn that the possible strain of Ebola in the samples bore little similarity to the one that had sickened the Swiss woman in Ivory Coast. Instead, it resembled one from the continent’s interior, more than a thousand miles away: the Zaire strain, the deadliest of all, the one that would later spark West Africa’s catastrophic epidemic.

The scientists appealed to American groups, including the United States Agency for International Development, for money to expand and verify their results. Dubious officials expressed skepticism. Years passed, and no significant funds materialized.

In August 2013, the team submitted its findings to a journal published by the C.D.C. After the Zaire strain had been identified as the cause of the current outbreak, the C.D.C. journal published the team’s report online in June.

In July, Dr. Sheik H. Khan, the chief physician of the Lassa ward in Kenema, Sierra Leone, exhausted after treating waves of Ebola patients, died of the infection that he and other team members believed they had identified in the blood samples.

In January, another virology team at the Kenema hospital reported Ebola antibodies in blood samples of patients who entered the Lassa ward from June 2011 to March 2014. The team, led by Robert F. Garry, a virologist at Tulane University, found the antibodies in up to 22 percent of 242 patients.

He said “a lot more validation” is needed to confirm that Ebola was indeed present before the current outbreak.

Several experts cautioned that antibody evidence from the blood studies — so far, the only direct sign of early Ebola infections in West Africans — is especially murky given that some antibodies can react more widely than intended with blood tests and produce misleading clues.

“You have to take those with more than a pinch of salt,” Dr. Nichol said. He and other experts said one possibility was that tests were picking up antibodies to an unknown nonlethal filovirus, the group that includes Ebola.

“I think we’re still locked in uncertainty,” said Dr. Daniel G. Bausch, a tropical medicine expert with Tulane and the United States Navy, who helped start Kenema’s Lassa research program but was not involved in the new research.

Although the investigators took steps to limit false reactions, antibody tests can be imprecise. Dr. Thomas Ksiazek, an Ebola expert at the University of Texas Medical Branch at Galveston, who has long worked with such blood tests, said people in poor African countries often carried “all kinds of bad infections” and may produce a host of confusing antibodies.

But clues that Ebola might have been hiding in forests throughout Africa does not come just from blood tests. Scientists have sequenced the genes of the virus in the current epidemic and compared it to the Zaire strain responsible for most Central African Ebola outbreaks.

The researchers identified hundreds of genetic mutations that, taken together, suggest that the West African Ebola variant diverged from the Central African strain and settled into a distinct ecological niche 25 to 150 years ago, perhaps even earlier.

In September, 58 researchers from Harvard, M.I.T. and the Broad Institute, among other institutions, reported sequencing results from a much larger group of Ebola viruses in the West Africa outbreak. The genetic split, they contended, occurred more recently, around 2004.

“There’s evidence that these things have been around for a while,” said Dr. Pardis C. Sabeti, a Harvard geneticist who led the team.

Dr. Ksiazek said he considered the gene analysis much more reliable, but noted that the genetic findings do not prove the virus infected people in West Africa before this outbreak. It is possible the virus was present only in animals like chimpanzees and other apes.

Still, the scientific clues through the decades should not be discounted, several experts said. Ebola may be more deeply rooted in the African landscape than anyone guessed.

Jens H. Kuhn, a virologist at the National Institutes of Health, pointed to the detection of possible Ebola antibodies in the Democratic Republic of Congo in the 1980s, saying those sketchy findings now seem prescient. That nation, once called Zaire, has since had eight Ebola outbreaks, most recently last year.

“These are hints that need to be followed,” Dr. Kuhn said. “They should raise the level of vigilance.”

And Stephen S. Morse, an infectious disease expert at the Mailman School of Public Health at Columbia University, said it now seemed likely that Ebola had long smoldered in the West African jungle.

Perhaps, he said, years of limited encounters between people and the virus had produced a relatively small number of human cases that were never identified and never spread: “None of the embers reached the stage of a fire.”