Editor's note: This story was revised on Jun 5, 2014, to explain that another research team previously presented findings concerning a match between MERS-CoV in the same patient and his camels.
In findings that shed more light on the suspected link between camels and humans, an investigation into a fatal human MERS-CoV (Middle East respiratory syndrome coronavirus) infection identified the virus in both the man and his sick camels, with genetic sequencing showing the viruses to be identical.
The study augments earlier findings by a Saudi-European team that studied the same patient and his camels. That group likewise found a close match between the human and camel isolates, but the genetic evidence they presented was not as complete as in the new study.
The 44-year-old man, from Jeddah, Saudi Arabia, kept a herd of nine camels near the city and had had contact with the respiratory secretions of one of the animals that was sick, according to a team of scientists from King Abdulaziz University in Jeddah who reported their findings today in an early online edition of the New England Journal of Medicine.
Previously healthy and retired from the military, the man kept his camels in a barn outside Jeddah. He and three friends visited the animals each day until 3 days before he was admitted the hospital. They reported that four of the camels had been sick with nasal discharge and that the patient had applied topical medicine to one animal's nose 7 days before he started having symptoms.
As his illness worsened and progressed to shortness of breath, the man was hospitalized Nov 3 and died Nov 18. The medical team obtained nasal swabs and blood samples from him four times during his hospitalization.
Five days after he was admitted to the hospital, the researchers began collecting samples from his camels (nasal, blood, milk, urine, rectal), collecting samples from his (asymptomatic) friends who went with him to the camel barn, and monitoring the health of his 18-year-old daughter, who had a mild respiratory infection that resolved on its own.
Samples, sequencing yield connection clues
Nasal swabs collected from the patient were positive for MERS-CoV each of the four times he was tested in the hospital. A nasal sample from the camel the man had contact with that was collected on the first testing day was positive, with a second sample at 28 days showing the animal had cleared the virus.
Tests on the man's daughter found no evidence of MERS or of 2009 H1N1 influenza infection, and no MERS antibodies were detected in the man's three friends.
Serum tests suggested that the man didn't have antibodies to the virus when he was first hospitalized, but they had quadrupled in later sampling. The first serum samples in four of the other camels showed high MERS antibody titers, and tests on four other animals showed rising antibody levels.
The researchers said serology tests suggest that the virus was circulating in the camels and the camels were probably infected before the man got sick.
Full genetic sequencing of the isolates from the man and the ill camels showed that the MERS viruses were identical. The authors wrote that their evidence suggests the direct transmission probably occurred between the camel and the man with no intermediate host.
They also concluded that the camels showed a transient infection pattern, suggesting that they may also be intermediate hosts.
The study partly duplicates an earlier report by Saudi, German, British and Dutch investigators who studied the same human and camel cases. Their report was published in Emerging Infectious Diseases in March.
The team sequenced the nearly complete genome of an isolate from the patient and 15% of an isolate from one of the camels. They found that the sequences yielded "nucleotide polymorphism signatures suggestive of cross-species transmission," but the evidence was not enough to determine if transmission was from camel to human or vice versa. However, serologic findings indicated that the camels were infected before their owner.
Experts see growing evidence of camel-human connection
Two experts who have been involved with coronavirus research weighed in on the significance of today's findings.
Matthew Frieman, PhD, with the University of Maryland School of Medicine's Department of Microbiology and Immunology, told CIDRAP News that the report is the closest yet to showing direct transmission from an infected camel to a human that resulted in illness. He said that there are citizens in the Middle East who are resisting the idea that camels can carry the MERS virus and that people can get sick from their camels.
"The most likely explanation of the data is that camels can carry MERS-CoV and can transmit it to humans," Frieman said. "This should be a wake-up call to camel owners and handlers around the Middle East."
He said culling camels that test positive for the virus isn't a feasible option, adding, "This pushes forward the idea that vaccination of camels with a MERS-CoV vaccine is the most direct way to handle this virus in the reservoir."
Removing the reservoir, combined with better infection control in healthcare settings and quarantine of infected people, is the way to eliminate the spread of MERS, Frieman said.
Marion Koopmans, DVM, PhD, said the report shows the presence of a virus that is essentially identical in a camel and a human in the same location. Koopmans is head of virology at the Laboratory for Infectious Diseases of the National Institute of Public Health and the Environment in the Netherlands.
She said her group reported similar findings based on an outbreak investigation in Qatar. "Through studies like this, direction of transmission is hard to say—camels could have gotten it from people," Koopmans said.
However, she added that the bulk of the evidence, such as MERS-CoV-like antibodies dating back to the 1990s and diverse MERS viruses co-circulating in different countries, shows that the virus is endemic in camels. Koopmans also noted that interspersed animal and human MERS viruses in phylogenetic trees suggest there must be a connection.
"The big issue remains how many of the primary cases (outside the hospital) get infected" by camels, she said. Current suspicions point to more human-to-human transmission, even if not sustained.
If animal workers with mild disease can transmit the virus, that would explain why primary cases don't often report animal contact, Koopmans said, adding that the list of alternatives could include environmental contamination.
Azhar EI, El-Kafrawy SA, Farraj SA, et al. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med 2014 Jun 4 [Abstract]
Dec 16, 2013, CIDRAP News story "Nearly identical MERS-CoV strains found in camels, humans"
Related Mar 21 CIDRAP News item