As the Hajj Unfolds in Saudi Arabia, A Deep Look Inside the Battle Against MERS

For more than a year, Saudi Arabia has struggled to control the new disease MERS. Now, with millions of Muslim pilgrims descending on the country, the challenge will get that much tougher.

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Fayez Nureldine / AFP / Getty Images

A Muslim pilgrim wears a mask as she walks to Mecca's Grand Mosque to perform evening prayers on Oct. 8, five days before the start of the annual Hajj pilgrimage.

In the sci-fi thriller Contagion, a new virus emerges from wildlife and jumps into human beings, wreaking havoc around the world. Millions die and society all but shuts down. The plot is frightening because it’s realistic—there are viruses out there in the animal population that, with the right genetic mutation, can jump the species barrier and infect us. If virulent enough and able to spread easily between people, we might find ourselves living in a real-life horror movie.

The film is loosely based on what the deadly but limited Nipah virus—the bat-to-pig-to-human infection identified 14 years ago in Malaysia—would look like if it could have easily spread around the world. Now we’re seeing a sequel of sorts. Some scientists who tackled that virus are battling a new coronavirus called Middle East Respiratory Syndrome (MERS-CoV). The symptoms appear gastrointestinal (abdominal pain, diarrhea) or flu-like (fever, shortness of breath, heavy cough), but can worsen into severe pneumonia. It has killed 60 of 138 laboratory-confirmed patients since it first emerged in Jordan in April 2012. The majority of cases and deaths have appeared in Saudi Arabia; others were reported in Qatar, Tunisia, the United Arab Emirates and Western Europe, where some patients sought better care or returned from visits to the region.

The world’s top virologists have struggled to uncover the origin of MERS and predict its path. Many believe it’s carried by bats—the reservoir for a number of new pathogens, including its distant cousin SARS. But since people rarely interact with bats, it may be introduced to humans through an intermediary animal. In August, European investigators suggested in the Lancet that camels could be the middlemen after blood tests of retired racing dromedaries in Oman and ones used for tourism in the Canary Islands found antibodies—proteins made by the immune system to fight infection—that indicate prior exposure to MERS or a close relative. A  Eurosurveillance report weeks later stoked that suspicion, as most of the dromedaries sampled from Egypt had similar results. They earned equal parts promise and skepticism.

So did an Emerging Infectious Diseases study in late August that named bats as the likely ultimate source of the virus. “Finally, we nailed it,” says Peter Daszak, president of the EcoHealth Alliance, a New York-based organization that patrols the animal-human health border. EcoHealth collaborated on the study with the Saudi Ministry of Health and Columbia University’s Center for Infection and Immunity. Researchers matched a fragment of viral RNA from a fecal pellet of the insect-eating Egyptian tomb bat to a sample from the first human case in Saudi Arabia. One problem: the genetic fragment was too small to be certain that it was indeed from the MERS virus. Researchers in Sydney added to that lead in October with a report in Virology Journal that suggested bats haven’t just fought the virus, but evolved a way to escape it. It’s all the strongest evidence scientists have yet about the source of this new disease—and it still doesn’t add up to much.

Saudi Arabia has been criticized for its slow response to MERS, but so far the world has been lucky. The disease has yet to really break out of the Middle East and threaten the world like the H1N1 flu in 2009 and SARS six years earlier. SARS, which killed 744 of the 8,098 people who contracted it, earned a rare global travel warning to affected hotspots like Hong Kong and caused some $40 billion in economic damages. But that could change this week with the Hajj, the world’s largest annual gathering, which typically draws millions of Muslims to Saudi Arabia to trace the footsteps of the Prophet Mohammed between holy sites in Mecca, Mina, Mount Arafat and Medina.

The journey is a notorious hotbed of infectious disease, as pilgrims from every corner of the planet often trek around barefoot in demonic heat and share tight sleeping quarters. On Oct. 15, the Kingdom announced there are 1.38 million pilgrims from 188 countries, down 21% from last year due to health concerns and a steep reduction in visa quotas as the expansion of the Grand Mosque in Mecca continues. There are 57% fewer domestic pilgrims, too, tallied at about 600,000. But while the ministry claims it’s more prepared than ever, with 22,500 health-care workers offering free medical care to those in need, it’s the aftermath that has experts worried.


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In a conference call with reporters on Sept. 25, Keiji Fukuda, the World Health Organization’s (WHO) assistant director-general for health security and environment, said the current level of surveillance for MERS was “suboptimal.” The average MERS incubation period of five days to two weeks leaves plenty of time for pilgrims to return home infected but not yet obviously ill, potentially seeding the virus internationally. The WHO’s emergency committee expressed concern that nations in sub-Saharan Africa lack the proper lab facilities and ability to track cases and infection patterns if the virus appears there.

We still don’t know exactly how the virus is contracted, or whether it has adapted to our bodies well enough to pass efficiently between us, or how to stop it. Those answers could have enormous impacts on humans, and they’re certain to involve wildlife. In his book Spillover: Animal Infections and the Next Human Pandemic, the writer David Quammen described the relationship well, calling animal and human diseases “strands of one braided cord.” HIV, Nipah virus, SARS—they all jumped from wildlife to people. And we’re just getting started.

A recent EcoHealth study in mBio estimates there are at least 320,000 viruses in mammals awaiting discovery. About 70% of these are believed to be zoonoses, or ones that cross from animals to humans. That’s why independent laboratories, universities and governments are investing so heavily in early detection programs, to stop emerging pathogens like MERS before they become global killers. When each new virus can set off a pandemic, Daszak says, “we’re in a race against evolution.”

The Outbreak Begins

In June 2012, a Saudi businessman died at the Dr. Soliman Fakeeh Hospital in Jeddah, an urban hub on the bank of the Red Sea. His physician, Egyptian microbiologist Ali Mohamed Zaki, couldn’t identify the man’s respiratory infection and sent a sample to the Saudi Ministry of Health. But dissatisfied with its negative tests for flu and other viruses, he mailed another sample to Ron Fouchier, a virologist at Erasmus Medical Center in Rotterdam. The lab grew the virus’s full genome sequence and the two researchers concluded it was a new coronavirus. On Sept. 20 that year, Zaki—unable to report the finding to the WHO without going through government channels—posted to ProMED-mail, an Internet forum that tracks emerging diseases. That prompted a London hospital to test a Qatari patient, who had recently visited Saudi Arabia. He was positive for a closely related virus.

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One case tosses up a flag, but when there are at least two cases, three months apart, in two different countries, “then you know there is trouble,” says Fouchier. The ministry was enraged with Zaki for sending a sample outside the country unauthorized and reportedly forced hospital brass to fire him, sending him back to Egypt. But within days of Zaki’s post, Ziad Memish, the Saudi deputy minister of public health, reached out to W. Ian Lipkin, the epidemiologist and famed ‘virus-hunter’ at Columbia. (It was Lipkin who was hired as a consultant to help make Contagion realistic.) Within days, Lipkin was on the ground in Bisha, the arid town in the southwest where the businessman had lived. Vishal Kapoor, a senior researcher and colleague at Columbia, joined him. So did two members of EcoHealth: Kevin Olival, a bat specialist, and Jonathan Epstein, a veterinarian and its associate vice president for conservation medicine.

Bisha was desolate but more modern than the desert outpost they expected. The group met the man’s family, seeking to learn about his health and lifestyle, and to gauge his interaction with wildlife like bats. None, they were told. That wasn’t surprising. Bats typically roost in non-descript cracks or crevices and emerge after dusk. If you don’t know to look for them, you may never see them. They also visited the man’s hardware store. The eureka moment, Epstein recalls, came when they found bats foraging around the sheds out back. This was a critical contradiction of the family’s claim, and a welcome clue. Now they just needed to catch the bats.

The researchers were eventually led to abandoned ruins on the hem of town, where Epstein says they found the “needle in the haystack”—a roost with hundreds of bats. Over three weeks at various roosts, they caught and released 96 bats, each sampled for their blood, saliva, feces and urine—the four conventional ways a virus can escape their bodies. Plastic tarps were also placed at roosts to collect their pellets. The samples were stored in liquid nitrogen, then packed in dry nitrogen and sent back to the U.S. for testing.

They would later preliminarily find that the virus, thought to travel through bats’ gastrointestinal tracts, might be found in the pellets and that a human or another animal could inhale the pathogen if the pellets were crushed and aerosolized. But the researchers couldn’t say for certain. Since the virus was found in feces, a bat might have dropped infected pellets on another animal, or it could have been ingested from another source altogether. It didn’t help that the samples were delayed leaving Saudi Arabia and that U.S. border protection officers ended up opening the containers, causing them to thaw. Still, Lipkin’s lab subjected the degraded samples to polymerase chain reaction, a biochemical tool that quickly copies RNA millions of times and sows them into a segment. But the output wasn’t long enough. “You need big chunks of RNA to start out with in order to get big chunks later,” says Olival.

In April, Lipkin, Kapoor and Olival returned to Saudi Arabia to collect more pellets, sample other domestic animals and widen their ground search. By then, a cluster of cases from a Jordanian hospital a year earlier had been linked to the virus and there was a new hospital outbreak in Al-Hasa, in the oil-rich eastern province. The infection would spread to three other hospitals as patients went elsewhere, sickening others. Memish, in charge of the response, invited in Western academics and clinicians—including SARS veterans—to help with the epidemiology.

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Around their arrival in May, the International Committee on Taxonomy of Viruses—yes, it exists—decided on a name that was catchy, informative and geographically sensitive: MERS. Three members of that international team said most of their work involved streamlining clinical chart reviews, aiding health care workers with infection control practices and working to define which patients needed to be tested for MERS. Writing in the New England Journal of Medicine, they found that the infection had moved between patients in hemodialysis units.

Medical tests in general are skewed toward the seriously ill, who are more likely to have higher concentrations of a virus and therefore more likely to turn up positive. Only “unexplained” cases of pneumonia were being examined and patients must have hailed from (or visited) the Arabian Peninsula to qualify for MERS testing. That’s why the mortality rate hovered around an alarming 50%—doctors were likely only catching the sickest of the sick. But the experts urged for an expanded spectrum of symptoms worthy of testing to spot milder cases, who could conceivably still transmit the virus. That would eventually happen. And when they looked harder, they found more.

Since April, the number of cases has more than doubled and other outbreaks—one included a Filipino health care worker—have blossomed throughout Saudi Arabia. In Hafr al-Batin, a remote town in the northeast where 11 cases were confirmed, there were four deaths in one family. The brothers of Fahd al-Sahly, 39, a government employee and part-time camel trader, told the Wall Street Journal he fell ill in August after buying a young camel that became sick. He cared for the animal, then sold it. Thirteen days later, he was dead. His mother and two other relatives would die, too. One brother, Jawal, recalled hospital workers told Fahd “you’re making a big deal out of nothing.” Memish, who coauthored a study that found several strains of the virus had been swirling as a common ancestor as early as mid-2011, insists the ministry has appropriately increased its information campaign with television and newspaper ads. Jawal said the family wasn’t aware MERS had even existed, let alone how to avoid it.

Blaming the Host

No search for an emerging disease is free of criticism, and Saudi Arabia has received a lot of it. In June, Tareq Madani, an infectious medicine professor at King Abdul Aziz University in Jeddah, accused the ministry of poorly informing citizens about how MERS spreads. In September, Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, called the lack of epidemiology surrounding the outbreaks “absolutely unacceptable.” Larry Anderson, the scientist who led the SARS response for the Centers for Disease Control and Prevention and who now teaches at Emory University, recently told the Canadian Press it’s “concerning and sad” that more was known about SARS just weeks after it was found than what’s known now about MERS.

Memish has pushed back, asking critics to put the virus into the perspective of something like the seasonal flu, which annually kills between 250,000 to 500,000 people worldwide. He says case information, while limited, is posted online before being sent to the WHO and that testing has been expanded to anyone who’s been in contact with known MERS carriers. On Oct. 2, he said hospitals along the Hajj route are screening pneumonia patients for MERS using tests that produce results in six hours. He also confirmed that pilgrims have been advised to wear surgical facemasks and a case-control study, which compares sick and healthy people to look for possible sources of infection, would begin at a future date. Critics have wanted this standard for months*. “It’s not that we don’t have resources and it’s not that we don’t have brains, and it’s not that we don’t have the capacity,” Memish told TIME, “but there’s always the critic[s] who say we should know in a day what’s going on.”

That never happens. Laurie Garrett, a senior fellow at the Council on Foreign Relations, says the blame isn’t Saudi Arabia’s alone. The exorbitant cost of ground-level research and surveillance, in desolate parts of a country that tends to be hostile to non-academic Westerners but which lacks scientific resources of its own, at a time when funding is low and millions of foreigners could become carriers and return home to countries incapable of combatting it, has created “a perfect storm.” By the end of the month, we could see a menial rise in the number of regional infections, or we could see the bloom of the next big pandemic.

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Like Garrett, William Karesh, executive vice president for health and policy at EcoHealth, says there aren’t any “bad guys.” He believes the Saudis were right to be cautious and avoid the possibility of mass hysteria. “There’s a lot of potential risk in saying the wrong thing and then, of course, there’s a potential risk of not doing the right thing,” he adds. “There’s a dilemma, and that’s not uncommon.”

Karesh recently returned from Saudi Arabia as part of a two-week mission with the U.N.’s Food and Agriculture Organization. At the invitation of the Ministry of Agriculture, the country’s legal authority for domestic animals, the team was asked to strategize how to identify the virus in animals. To date, not one has been found sick with it. Karesh recognizes that Saudi officials haven’t prioritized animal testing the way they have for human cases—now ramped up to hundreds of samples each week—but insists there’s a desire for it.

New cases, and sometimes deaths, are being reported as testing widens and researchers try to define the elusive path of transmission. There’s still no vaccine, either, which isn’t surprising—they’re not typically made for viruses with few cases due to the immense time and money needed to create, test and distribute one. The ministry hasn’t reported Hajj-related cases, but if they do appear the international response could shift into overdrive when the WHO emergency committee meets again in November. Until then, we wait. “There’s nothing to suggest at present that we need to go on high alert,” says Lipkin. “We’re yellow, not red.”

Flying Blind

We’re still new at this. We may beat back one pathogen, but another can reappear and take its place. Several SARS cases have popped up since the outbreak a decade ago, and an alert was recently issued in Madagascar amid new cases of the bubonic plague. Much of today’s health research is fueled by the need to respond to new outbreaks, rather than averting a crisis before it hits. With MERS, scientists at the CDC have aimed to remedy this by developing and distributing molecular diagnostics to state agencies so they can tell whether any of the estimated 11,000 Hajj pilgrims from the U.S. return infected. None have yet, but this regional strategy shows that we’re running out of time to change our global approach.

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EcoHealth’s Daszak likens the response to what happens in the wake of earthquakes: “We go in there, we deal with it after it’s happened, we dig people out of the rubble.” Karesh agrees: with so many unknown infectious diseases out there, medicine needs the equivalent of tougher building codes and the technologies to predict outbreaks before they hit so we’re not spending crucial time and resources to rebuild. Preemption, not reaction, would go a long way.

So why hasn’t that changed? We have the technology needed to identify most emerging viruses and their origins, speeding up recognition and intervention, but we stall. The answer is simple: politics and money. In Wired, the writer Maryn McKenna explains that governments almost always seek to evade blame for global health threats within their borders rather than promote transparency: “Information can outrun deadly new diseases, but only if it’s allowed to spread.” These threats are expensive to find, test and contain. And even if labs have the time, they’re short on personnel and cash.

Sequestration in the U.S. hasn’t helped. Automated federal spending cuts in 2012 reduced the National Institutes of Health’s annual budget by 5.5%, to $29.1 billion. Labs have felt the pinch of fewer research grants, with directors ending half-completed projects, foregoing others altogether and trying to keep their staffs relatively intact. That was all worsened by the government shutdown on Oct. 1, which also marked the start of flu season. About 9,000 of the CDC’s 15,000 workers have been furloughed. Thomas Frieden, the CDC’s director, tells TIME that several staffers are still working in Saudi Arabia, but the lack of resources back home is inhibiting their research.

Frieden’s tone is anguished. The shutdown hasn’t just “derailed” the agency’s capacity to find, stop and prevent health problems, but “undermined” its ability to work with local and state authorities. Bi-weekly calls with state health agencies about global threats have stopped and concern is high that should an emergency come up, any response would be delayed. Illustrating the impact, he likens the CDC to a ship lost at sea. “You can go a day or two without your navigation system—you won’t get too far off-track,” he says. “If you go a week or two, you could end up in very dangerous waters.” Now his biggest worry is what they’re missing: “We can respond to emergencies, but we don’t have our systems to find them reliably.”

Lipkin, who advises the NIH director, puts it bluntly: “There’s no money for science in the United States.” It’s hard to see effects on his office-lab setup at Columbia—the floors buzz with white coats handling vials or waiting for costly machines to spit out results as others slog away on computers. Sequestration forced him to reallocate other funding to MERS research and pushed back the hire of another researcher, but the shutdown means new tests on ungulate samples—he says the surveillance focus should shift to livestock and wildlife—will be outsourced through mobile labs he’s helping send to Saudi Arabia. “We’re wrestling with these challenges of trying to find ways to do as much, if not more, with less,” he says. “And it’s tough.”

In the meantime, doctors are keeping up with threats as best they can. This virus isn’t a pandemic yet, and some believe that MERS may lack the ability to truly threaten the world. But the potential is there. “If it does,” says Connie Price, the infectious disease chief at Denver Health Medical Center who aided epidemiology efforts in Al-Hasa, “I guess it’s on us.” And the generations that come after us.

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*[UPDATE: The original version of this story reported that Ziad Memish confirmed a case-control study had begun. Memish hasn't provided a start date and couldn't be reached for comment on this matter.]

4 comments
TomMengel
TomMengel

It seems history may yet repeat itself.  We have many destabilizing events going on in the middle east and Africa as well as mass deforestation and global warming that seem to mirror the same destabilizing situations seen during and after WWI (1914-1918) that led up to the Spanish Flu (est. 50 to 100 million dead)  Then as now there were large populations under huge stresses that would weaken the populations with many people migrating home after the war.  Even if there has been no formal connection to those past events to support the idea of that disease spreading vector it would seem to this layman that having a large population in poor health kept in very close quarters would easily be a prelude to a bigger disaster.  We have already seen this in SARS and the bird flu in south China.  Maybe in the not so near future we will come to realize that in a tightly knit and interdependent world the biggest danger as to war and mass population migration will not be the political changes involved, but rather may be the plagues unleashed by those events as "collateral damage".

powerandprivilege
powerandprivilege

The Muslim pilgrims to holy Mecca probably do not realize that they practice ancient Vedic customs:  shaving their heads, taking a dip in 'holy water,' wear white robes [called dhoti in Sanskrit], and circum-ambulate around the Kaaba.  Islam forbids idolatry.  So, what is the significance of pilgrimage to Mecca about? If Allah/God/Divine is everywhere, has the original purpose of the rituals in Mecca been lost or suppressed through history?  Perhaps the Imaams ought to give this some thought and seek what binds us all on this small planet - a common ancestry. 

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BabuG.Ranganathan

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