The Middle East’s Mystery Virus

Physician Islam Hazameh was used to treating people with Middle East respiratory syndrome (MERS). He knew what patients could expect, when the fevers might hit, and what types of people it stalked. What he didn’t foresee was that he would become one of them.

Late in 2014, a woman with a bad cough and a high fever had come to the hospital clinic where Hazameh worked in the Jordanian city of Zarqa, some 12 miles northeast of the capital Amman. It was the winter, and suspecting the woman had a bad case of influenza, Hazameh treated her for the seasonal virus. Shortly after, he woke up with the chills, a rising fever, and a cough just like he’d seen in his patient. “I thought I had just a flu,” Hazameh recalls. But it kept getting worse.

Patients await treatment in a waiting room at the government-owned Prince Hamza Hospital in Amman, Jordan, on August 10, 2015. The clinic housed one of 10 confirmed MERS patients in Jordan in 2014.

Another doctor took a nasal swab from Hazameh, which showed he’d been infected not with influenza, but with MERS, a viral respiratory illness endemic to the region that’s associated with a 40% fatality rate.

As a reasonably healthy 37-year old at the time, Hazameh was an unlikely MERS patient. Typically, elderly or immunodeficient people are at the greatest risk for serious complications from MERS, as are those with pre-existing conditions like poor kidney function, lung disease, and diabetes. Yet days after his first cough, he found himself lying in a hospital bed in Amman, surrounded by weary family members. He was hooked up to an antibiotic drip in an intensive care unit isolation room at the Jordan University Hospital and remained like that for the better part of a week before he recovered enough to go home. Since Hazameh’s patient was never tested for MERS, he will never know for certain whether she passed it to him.

That mystery is just one of many that shrouds the disease. MERS belongs to the coronavirus family that includes the common cold and severe acute respiratory syndrome (SARS), which caused global panic when it killed almost 800 people worldwide in 2002–2003. Because—like SARS—symptoms for MERS mirror influenza, it’s easy to misdiagnose and difficult to catch early enough to protect others from infected patients.

Researchers are only just beginning to understand how MERS infects humans, with lingering questions about why certain populations that should be at high risk for the disease remain unscathed by it.

AR Promo DSC_0649WEB
Bedouin farmer Ibrahim al-Mazana, 44, walks near his village in southern Jordan's Wadi Rum, where he raises six camels, some 40 miles west of a porous border with Saudi Arabia.

Last month, in neighboring Saudi Arabia, health officials recorded a fresh outbreak in the capital of Riyadh with new cases occurring each day. Hospital rolls ballooned despite measures to contain infected patients. The spread soon spilled across the border into Jordan, sparking renewed fears of contagion. The World Health Organization (WHO) reports that MERS has infected some 1,400 people worldwide and killed at least 500 since the virus was first identified in 2012. Most of these cases have been concentrated in Saudi Arabia, though epidemiologists tracking the virus say the data that leaves the country has been difficult to authenticate.

The timing of Saudi Arabia’s most recent outbreak has public health officials especially nervous—it started right before millions of Muslims descend on Mecca for the annual Hajj pilgrimage this week. Arriving by air, land and sea, pilgrims share tight spaces during the five days of the Hajj—the timing and location of the rites is dictated by religious tradition, creating an environment where infectious disease can spread with ease.

Yet with business people, vacationers, pilgrims and nomadic people entering Saudi Arabia’s ports daily, there’s ample opportunity for MERS to cross into countries like Jordan all year round. With symptoms easily brushed aside as a cold or flu, patients can slip through the cracks even when doctors are vigilant.

“It was Saturday…”

The first case of MERS surfaced in Hazameh’s home city of Zarqa. It was the spring of 2012, and a 40-year-old nurse at the government-run Zarqa Hospital, known as patient zero, had come down with an unusual and life-threatening case of pneumonia. More hospital workers soon fell ill with similar symptoms.

“I remember, it was Saturday. I was informed that there was unexplained pneumonia among three healthcare workers in Zarqa,” recalls Mohammad Abdallat, the director of infection control for the Jordanian Ministry of Health. “This was very unusual. Nobody knew how it happened.”

Though he wasn’t sure what was causing the cluster, Abdallat had a well-established infection control system in place partially developed with help from U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Department of Defense through its Cairo-based overseas unit for biomedical research, NAMRU-3. The relationship began in 2008 when Jordanian officials accepted an invitation from NAMRU-3 to collaborate on control protocols and testing sites to combat the looming threat of avian influenza. Together they created a method to monitor a family of infections known as severe acute respiratory infections (SARI), under which both avian flu and MERS fall. Deployed that spring in Zarqa, the SARI system followed a strict protocol to track respiratory illnesses—define the symptoms, quarantine those Jordanians affected, and alert other hospitals to look out for similar cases. With continued monitoring of birds entering Jordanian ports, the country’s officials have not recorded a single case of avian flu since 2006.

Dr. Moutaz al-Batoosh works at a rudimentary clinic in the Wadi Rum village of al-Desea which cares for some 100,000 Bedouin residents in surrounding villages. Batoosh says the facility is not equipped to isolate or diagnose MERS or other serious infectious illnesses.

Within weeks of the 40-year-old nurse’s infection in April, 13 healthcare workers in Zarqa Hospital were also infected with the mysterious illness; two of them died. Jordan’s tight control measures meant the virus didn’t spread further, even as the disease went unexplained. “We did our best to contain that outbreak, but even after a lot of examination, we still didn’t know its cause,” Abdallat says. It wasn’t until November, when a patient in Saudi Arabia died of renal complications from a respiratory illness, that researchers in the country identified the novel coronavirus, MERS. Stored cell samples from the two fatalities in the Zarqa outbreak were later tested, confirming the same strain of the newly defined coronavirus.

Three years later, Jordan’s infection control protocol is still in place. Abdallat has been sending out intermittent reminders of MERS’ symptoms to the country’s hospitals since that first Zarqa outbreak. One such notice went out only four days before a fresh outbreak hit Jordan last month, putting the country’s control system to the test again after eight months of being MERS-free.

Following the new case on August 25, the Ministry of Health sprang into action, scrutinizing the travel history and health status of every confirmed patient. The 60-year-old patient at the heart of the outbreak had fallen ill after traveling to Jeddah, Saudi Arabia. He visited two hospitals in Amman before testing positive for MERS. A small cluster of the virus soon sprung up, and within a week, six more people were infected. Ministry teams then began fanning out and tracking down who MERS patients were in close contact with since becoming infected. Between healthcare workers, family, and friends, every positive MERS sample means some 20 people need to be tested and monitored. Patients may seem fine one day and then dependent on a breathing machine the next.

The Ministry of Health’s Central Lab in Amman runs MERS tests for the entire country. The antiquated building in the capital’s downtown houses a tidy lab. Using swab samples taken either from the patient’s nose or throat, the seven technicians use polymerase chain reaction, or PCR, to amplify the genetic material in the sample to detectable levels. It’s the only method accepted by the WHO to identify MERS and other SARI cases. With real-time PCR, the technicians can identify a positive MERS case within four hours. The CDC and NAMRU-3 regularly test the facility’s accuracy by sending them samples to run through PCR, says Jordanian Ministry of Health Laboratory Director Aktham Haddadin.

Processes like these were established in Jordanian labs to try and stem MERS once it emerges, and ensuring that a few cases don’t balloon into hundreds depends on strict adherence to the protocols. But even the most rapid and rigorous detection methods can’t stop a disease whose origins are still a mystery.

While most of the world’s cases have so far spread in hospital settings, scientists believe the virus first began when bat populations infected camels roaming the Arabian Peninsula. Infected camels then theoretically passed it on to their herders. But no one knows for sure.

A Porous Border

Jordan’s Bedouins are surrounded by camels and trade with Saudi Arabia every day. They should be the deadly virus’s most obvious victims, but they’re not.

Ibrahim al-Mazana is a 44-year-old farmer living in southern Jordan’s Wadi Rum desert, a harsh patch of sand and rock some 200 miles south of Amman and just a few paces from a porous section of the Saudi border. Some 100,000 Bedouins like al-Mazana live here. He has a small collection of camels that he treats like family. “The camel is our history and heritage,” he says. “It’s our life story.”

Ibrahim al-Mazana greets one of the six camels he keeps penned behind his home in one of several villages in southern Jordan's Wadi Rum desert on August 6, 2015.

To al-Mazana, the idea that camels could be behind MERS is not a welcome one. Bedouin communities throughout the Middle East have lived for centuries among these animals. They drink camel milk and sometimes even camel urine, believing it can cure everything from baldness to cancer. “I never stopped drinking camel milk,” he says. “We are convinced that since we milk the camels, drink their milk, and eat their meat, and no one is sick—this is all propaganda.”

Drive far enough across the vast Wadi Rum and you could end up in Saudi Arabia without even passing a checkpoint or signpost. It’s an invisible border that al-Mazana says is crossed by wandering camels and traveling Bedouins all the time. “It’s illegal to bring camels through the regular border, but from here, it’s 40 miles to Saudi Arabia,” he says. “Our camels will go there for three or four days and return. They go across as they please. No one stops them.”

At the rudimentary health clinic that serves Wadi Rum’s Bedouin villages, the doctor in charge, Moutaz al-Batoosh, says he’s never seen a confirmed case of MERS. Patients see him for ailments as minor as a headache, he says. “If the virus was here, I would know.”

More so than people in Jordan’s northern cities, where all of the county’s MERS outbreaks have occurred so far, southern Bedouin communities have all the risk factors outlined by the WHO. They live and work among camels. They cross into Saudi Arabia unfazed by growing infection rates. They consume milk and meat from both Jordanian and imported Saudi camels. Yet no MERS cases have been recorded there, according to Jordanian Ministry of Health official Abdallat.

Um Hussein al-Mazana mixes fresh camel milk into a glass of traditional Bedouin tea in Jordan's Wadi Rum desert on August 6, 2015.

More than three years after MERS appeared, even epidemiologists aren’t entirely sure of the animal’s role in transferring the virus. “It’s a big mystery,” says Dr. Daniel Lucey, a physician and expert on global viral outbreaks at Georgetown University who consulted with regional doctors combating MERS back in 2013. He believes the camel connection is there, but he can’t quite put his finger on the specifics. “It’s a contagious disease where lots of camels have had it, but people who have worked their whole lives with the animals haven’t gotten this disease.”

Lucey’s view is shared by others who study respiratory illnesses, like Dr. Sue Gerber, a medical epidemiologist at the CDC who has worked closely with Jordan’s Ministry of Health since the country’s first MERS outbreak. “We have learned some about the ability of camels to have similar viruses to humans, and it appears camels play a role in transmission,” Gerber says. Still, understanding the lack of infection among groups like the Bedouins is still a long way off. “We’ve only known about this virus for a few years,” she says. “So to really answer questions about populations is tough.”

Gerber thinks the more pressing point is to know what to do once the virus arrives. “Infection control can stop MERS,” she says. “Jordan’s controls have made it able to manage the virus and that’s good news because it speaks to good surveillance—but we’re still learning about why some countries are affected more than others.”

A Wake-Up Call

MERS remained relatively unknown outside the region before this summer’s spate of infections in the South Korean capital, Seoul, left 186 people infected and 36 dead, the largest outbreak ever recorded outside the Middle East. Sparked by one local man returning from a Middle East business trip, MERS’ sudden, distant spread roused public anxiety and spurred ramped up attention toward the disease.

As the number of Seoul infections climbed, the WHO said in June the outbreak should serve as “a wake-up call” for other countries to prepare for possible cases of their own, since the ultra-mobile modern world means infectious diseases like MERS could strike anywhere.

In August, researchers from the University of Pennsylvania finally got the funding and publicity they needed to publish a study on a synthetic DNA vaccine they say has already shown promise in guarding both humans and camels against MERS. Dr. David B. Weiner, a professor of pathology and laboratory medicine at the University of Pennsylvania and one of the study’s authors, says the vaccine could eventually be used to safeguard healthcare workers from the virus or be deployed in camel populations to curb its transmission path before it begins. Weiner estimates field tests of the vaccine on camels could start within the next few months with human tests following by the end of the year.

The village of Wadi Mousa sits just above the historical site of Petra in southern Jordan. Bedouins who live inside the site and its surrounding villages keep camels and other livestock for farming, milk production, and to attract and serve tourists.

According to Georgetown infectious disease scholar Lucey, studies on the presence of MERS antibodies in populations who aren’t currently sick is another research focus. For example, Mohammad Abdallat of the Jordanian Ministry of Health partnered with Gerber and other CDC physicians to look for MERS antibodies in some 50 close contacts of the two Zarqa fatalities in 2012. Their findings, published in May 2014, indicate that seven more people were likely infected but recovered during that first outbreak. While only PCR-confirmed MERS infections are recognized in the WHO count, finding antibodies of the virus in healthy people could help identify whether some gain long-term immunity. Still, that knowledge only scratches the surface. In the meantime, MERS outbreaks like the one Jordan has experienced since August keep popping up. Jordan’s 2015 caseload now has passed ten.

With Jordanians traveling to and from Saudi Arabia all the time, Abdallat says MERS cases are somewhat inevitable. Keeping a lid on the disease means acting quickly and decisively. “We understand many things about MERS but what is still holding us back is specific treatment,” Abdallat says. “Now it’s about management.” But even the most extensive infection control measures can’t prevent the coronavirus from spilling over from animals, leaving Middle East health workers baffled by how else to prepare.

During a quiet week night just before the August outbreak in Amman, Abdallat is resolute in Jordan’s MERS defenses. “Jordan is ready. We faced this virus before we even knew what it was with a well-developed infection control and surveillance program,” he says. Still, a palpable uncertainty lingers in the air. Abdallat adjusts his glasses and shrugs. “How do you face a monster you don’t really know yet?”

This article is part of the “Next Outbreak” series, a collaboration between NOVA Next and The GroundTruth Project in association with WGBH Boston.