In a troubling finding, investigators have discovered that MERS is now one step removed from its reservoir in camels.

There appear to be thousands of asymptomatic or mild MERS cases — primarily young men who have frequent contact with camels — who may be transmitting the virus to those with underlying medical conditions in Saudi Arabia, according to a recently published seroprevalence study.1

“Seroprevalence of MERS antibodies was significantly higher in camel-exposed individuals than in the general population,” the authors reported. “By simple multiplication, a projected 44,951 individuals older than 15 years might be seropositive for MERS in Saudi Arabia. These individuals might be the source of infection for patients with confirmed MERS who had no previous exposure to camels.”

The study may actually be an underestimate of the situation, the lead author tells Hospital Infection Control & Prevention.

“Our approach was very conservative as we are fully aware of cross-reactive antibodies against other commonly circulating coronaviruses,” says Marcel Muller, PhD, a researcher at the Institute of Virology in Bonn, Germany. “However, this means that the actual numbers could be much higher as some people might have been infected but lost their neutralizing antibodies already.”

Previous research suggests that dromedary camels are the intermediary host for the MERS coronavirus, which likely arose in bats. However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such contact.

The authors undertook a nationwide serosurvey in Saudi Arabia to establish the prevalence of MERS antibodies, both in the general population and in populations of individuals who have ongoing exposure to camels.

In the cross-sectional serosurvey, they tested serum samples obtained from healthy individuals older than 15 years who attended primary healthcare centers or participated in a national burden-of-disease study in all 13 provinces of Saudi Arabia. In addition, they tested serum samples from shepherds and slaughterhouse workers with occupational exposure to camels. Camels may be slaughtered to eat or as part of ritual sacrifices.

Samples were screened by recombinant ELISA and MERS seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralization tests, the authors report.

Between December 1, 2012, and December 1, 2013, the researchers obtained individual serum samples from 10,009 people. Anti-MERS antibodies were confirmed in 15 people in 6 of the 13 provinces.

The mean age of seropositive individuals was significantly younger than that of patients with reported laboratory-confirmed MERS. Men had a higher antibody prevalence than did women (11 of 4,341 vs. two of 4,378). Compared with the general population, seroprevalence of MERS antibodies was 15 times higher in shepherds (two of 87) and 23 times higher in slaughterhouse workers (five of 140).

Small numbers, big implications

While those numbers are small, the implications could be big.

“I believe these data strongly support the hypothesis that young people exposed to camels are getting infected with MERS — whether asymptomatically or with mild symptoms — and are transmitting the virus to their contacts in the general population of whom the most susceptible, with underlying conditions, become severely sick and are hence detected by the surveillance system in Saudi Arabia,” says Ghazi Kayali, PhD, MPH staff scientist in the department of infectious diseases at St. Jude Children’s Research Hospital in Memphis, TN.

Some have questioned whether the findings suggest that eventually MERS could establish an endemic presence in humans, but Kayali — who co-authored a commentary on the research paper2 — says that concern is not supported by the current research.

“There is no evidence so far of the virus establishing itself in the human population,” he tells Hospital Infection Control & Prevention. “I believe that the index case would always have contact with camels.”

The presence of antibodies should not be confused with having active infection, but if present trends continue, the pattern of asymptomatic or mild infection and subsequent antibody production would be similar.

“Having antibodies means that at one point in time, those people were exposed to the virus,” he explains. “It does not necessarily mean that all those had an active infection with MERS; exposure to virus could lead to having antibodies without an active infection. However, a good proportion of those would have had a MERS infection and at that time would be capable of infecting others.”

As the threat of camels became clear, the Saudi Agriculture Ministry urged people who come in contact with the animals to exercise caution and “wear protective gloves, especially when dealing with births or sick or dead [camels].”3 That may be a practical alternative to attempting a camel cull, which would be a non-starter with Saudis deeply attached to the central animal in their culture.

Indeed, attempts to point an epidemiological finger at camels for causing MERS have been met by a strange act of defiant affection by Saudi camel owners: kissing the beasts of burden right on lips.

Chickens don’t inspire much sentiment. When H5N1 avian flu emerged as a major public health threat in 1997, officials in Hong Kong eliminated its suspected animal reservoir by killing more than 1 million chickens.

Similarly, when SARS hit China in 2002-2003, more than 10,000 masked palm civets — cat-like animals sold as a delicacy in public markets — were culled with extreme prejudice. One method was putting four or five civets in a cage and lowering it in water to drown them.

As with many aspects of MERS, there are questions about the camel connection that trouble epidemiologists and researchers.

“We think this comes from camels, but look at the serology: Camels have been positive for MERS since 1990 or so and this disease didn’t enter the human population until 2012,” says Stanley Perlman, MD, PhD, a microbiology professor who studies coronavirus pathogenesis at the University of Iowa in Iowa City.

Similarly, given their prolonged exposure to camels, one might think that the virus would have taken a greater toll on those who have close contact with the animals. Instead, MERS exploded when it got to hospital patients with underlying illness that compromises their immune system. Going back out into the community, MERS stalls out again.

“This is a funky virus. We don’t know exactly where it came from — we have bats and then all these camels — but it’s not as though we had a huge epidemic and all the camel owners, herders and breeders [became infected]. Isn’t that weird?” says veteran epidemiologist William Schaffner, MD, chairman of preventive medicine at Vanderbilt University Medical Center in Nashville.

REFERENCES

1. Muller MA, Meyer B, Corman VM, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: A nationwide, cross-sectional, serological study Lancet Infect Dis 2015;15 (5)559–564.

2. Kayali G, Peiris M. A more detailed picture of the epidemiology of Middle East respiratory syndrome coronavirus. Lancet Infect Dis. 2015 May;15(5):495-7. doi: 10.1016/S1473-3099(15)70128-3. Epub 2015 Apr 8.

3. Saudi Arabia warns of MERS risk from camels. Al Jazeera May 11, 2014: http://bit.ly/1nDyP9k.