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This award-winning blog supplements the articles in Hospital Infection Control & Prevention.

Invasion of the Body Snatchers: Is MERS Silently Spreading from Asymptomatic Cases?

June 17th, 2015

In a troubling finding, investigators have found 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 seroprevelance 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 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 has established that dromedary camels are an intermediary host for the Middle East Respiratory Syndrome (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 maximum exposure to camels.

In the cross-sectional serosurvey, they tested serum samples obtained from healthy individuals older than 15 years who attended primary health-care 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 sacrifice traditions. Samples were screened by recombinant ELISA and MERS seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralization tests, the authors report.

Between Dec 1, 2012, and Dec 1, 2013, the researchers obtained individual serum samples from 10,009 people. Anti-MERS antibodies were confirmed in 15 people in six 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 increased by 15 times in shepherds (two of 87) and by 23 times in slaughterhouse workers (five of 140).

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

“I believe this 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 paper – says that concern is not supported by the current research.2

“There is no evidence so far of the virus establishing itself in the human population,” he tells HIC. “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 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]." 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 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 popular method was putting four or five civets in a cage and lowering it into water to drown them.

If the Saudis refuse to cull camels, one would expect they would continue to see MERS transmission but also increase the population of people with antibodies. One theory about the explosion of cases in Korea is that -- like Native Americans exposed to Smallpox -- they have no camel exposures and thus absolutely no natural immunity to MERS. As a precaution, camels in Korean zoos are being placed in isolation.

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;15(5):495-497.

For a special report on the dramatic resurgence of MERS see the July 2015 issue of Hospital Infection Control & Prevention