In April 2012, a 60-year-old male citizen of Bisha, located in southeast Saudi Arabia, became seriously ill with pneumonia. After his condition deteriorated, he was transported to a hospital in Jeddah, where he eventually died. He became the index case of a hitherto unknown corona infection, later to be coined Middle East respiratory syndrome coronavirus, or MERS-CoV.
Since then, the epidemic has undergone striking development, with most cases reported from Saudi Arabia and the United Arab Emirates. The other countries in the Middle East with MERS-CoV cases suspected to be acquired locally include Jordan, Kuwait, Oman, Qatar and Yemen. The virus has been found since to be circulating widely throughout the Arabian Peninsula. All cases that have been reported outside the Middle East first developed infection within the region and were then exported. These travel-related cases have, so far, rarely infected others in the destination countries.
MERS-CoV has already been reported from four continents: Africa (Egypt and Tunisia); Europe (France, Germany, Greece, Italy, the Netherlands and the United Kingdom); Asia (Iran, Malaysia and Philippines); and North America (United States). As of early June, the global number of laboratory confirmed cases was 681, including 204 deaths. As of May 9, 65.6% of cases were male, and the median age was 49 years (range, 9 months to 94 years).
Bats and camels serve as reservoirs
Since the latter part of 2013, several international research centers have intensified their efforts to unravel the epidemiology of MERS-CoV, particularly to identify the animal reservoir of the virus and its mode of transmission. Obviously, the severe acute respiratory syndrome (SARS) experience in 2003, when coronavirus disease from animal origin caused rather similar symptoms in humans (but with lower fatality rates and higher inter-human infectivity), was taken into consideration. The reservoir of the SARS virus was found to be bats; thus bats were the initial candidate suspects in relation to MERS-CoV epidemiology. So far, there is one report on the detection of MERS coronavirus genetic material in a bat (Taphozous perforatus, the Egyptian tomb bat, in Saudia), but no isolate could be obtained from this or any other bat-derived sample.
The initial suspicion of camels being involved in the event was raised on March 26, 2013, when it became known that a MERS patient from the United Arab Emirates who died in a hospital in Munich, Germany, had been around a sick camel shortly before falling ill. But that animal was not tested. Incidentally, the index case kept four camels as pets in his yard. These observations encouraged researchers to focus attention to camels, though surveillance addressed other species of domestic animals as well. This led to several isolations of a virus closely related to the human MERS-CoV from camels, in Qatar, Oman and Saudi Arabia.
Two countries, Qatar and Oman, have subsequently officially reported to the World Organization for Animal Health (OIE) the isolation of MERS-CoV from four (three in October 2013, one in February 2014) and five (in December 2013) camels, respectively. In Qatar, the virus was detected on a farm where a human case had been confirmed. The infected camels, in both countries, reportedly did not show clinical disease.
There is a steadily growing evidence that the virus, or its close relatives, may have been circulating in dromedary camels longer and wider than initially suspected. Recent serosurveillance, undertaken in the dromedary populations of Ethiopia, Nigeria and Tunisia, sampled from 2009 to 2011 discovered a high percentage of the tested animals to be seropositive. Notably, the overall seropositivity was higher in adult animals than in animals younger than 2 years. The authors raised the question whether human cases occur outside the Arabian Peninsula and if such cases are currently underdiagnosed in Africa. In addition, for the whole region, they ask about the possibility that MERS-CoV illness occurred before its discovery in 2012 and that such infection has been overlooked in the areas with evidence for virus circulation among animals during the past 10 years. In another paper, the authors showed that camels sampled in different regions in Kenya during 1992-2013 had MERS antibodies; high densities of camel populations correlated with increased seropositivity and was suggested to possibly be a factor in predicting long-term virus maintenance.
Regarding the camel demography, the global number of heads increased regularly between 1961 and 2011, and in 2011, the world dromedary camel population was estimated to be about 25 million. The main concentrations were in the Horn of Africa and the Sahelian countries. The dromedary population of Saudi Arabia (2012 OIE data) is 213,320. Other statistics are significantly (up to threefold) higher. The camel farming there has and still is undergoing significant changes, in tandem with the country’s urbanization. Papers in the 1960s were forecasting the disappearance of camels from industrializing Saudi Arabia; the opposite happened. Six types of camel farms are currently seen in Saudi Arabia: commercial farms (dairy and meat); racing farms; camel farms for leisure (weekend farm); camel farms for renting; traditional farms; and camels for prestige. There are also other typologies, and they share the similar trend of intensification.
Australia is the country with the world’s largest population of feral dromedary camels (currently, about 300,000 head). It has been reported that surveillance for coronviruses is being underway.
According to a recent statement from WHO, the full picture on the source is not yet clear. Human and camel genetic sequence data demonstrate a close link between the virus found in camels and that found in people. It is possible that other reservoirs exist. Other animals, including goats, cows, sheep, water buffalo, swine and wild birds, have been tested for antibodies to MERS-CoV, but so far none have been found in these animals. Serosurveillance in humans, potentially exposed to infected camels, has yet to be performed.
“These studies combined support the premise that camels are a likely source of infection in humans.” The apparent seasonal increase in primary cases occurring for unknown reasons “may be related to the weaning of young camels from their mothers in the spring of each year,” the WHO statement read.
Although camels are suspected to be the primary source of infection for humans, the routes of direct or indirect transmission remain unknown and investigations are ongoing.
Sharp increase in human cases
The number of laboratory-confirmed MERS-CoV cases reported to WHO has sharply increased since mid-March 2014, essentially in Saudi Arabia and UAE, where health care-associated outbreaks have been described. The number of individuals who acquired the infection presumably from nonhuman sources has also increased since mid-March. These cases have not reported contacts with other laboratory-confirmed cases, and some have reported contacts with animals, including camels. A WHO mission found that the upsurge in cases in Jeddah could be explained by an increase in the number of primary cases, amplified by several hospital-acquired outbreaks that resulted from a lack of systematic implementation of infection prevention and control measures.
Advice for infection prevention
WHO published guidelines for the public, which have been adopted by health authorities in the Arabian Peninsula and elsewhere in the region. As a general precaution, visitors to farms, markets, barns or other places where animals are present are advised to practice general hygiene measures, including regular hand-washing before and after touching animals, and avoiding contact with sick animals. The public is warned against the consumption of raw or undercooked animal products, including milk and meat. Animal products processed appropriately through cooking or pasteurization are regarded safe for consumption, but should also be handled with care to avoid cross-contamination with uncooked foods.
Most of the required knowledge about the source and transmission of MERS-CoV is still subterranean. The OIE recently published its updated opinion on the investigations required to develop a more complete understanding of the potential role of camels (and other animals) in the epidemiology of MERS, including:
1. Epidemiological studies which aim to determine the risk factors and potential exposure sources for camel infection and clarify its relatedness to human cases of MERS; this includes genetic analyses of MERS-CoV.
2. Animal infection studies (including experimental challenges) to determine the behavior of MERS-CoV in camels (and other animals) and how the virus may be shed from infected camels.
3. Diagnostic tests used for MERS-CoV surveillance in camels (and other animals) should be assessed for the reliability of their results in these species.
WHO. Middle East respiratory syndrome coronavirus (MERS‐CoV) summary and literature update–as of 9 May 2014. Available at: www.who.int/csr/disease/coronavirus_infections/archive_updates/en/. Last updated May 9, 2014. Accessed May 19, 2014.
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Arnon Shimshony, DVM, is associate professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail animal diseases zoonoses moderator. Shimshony was chief veterinary officer, State of Israel, from 1974 to 1999. He is also a member of the Infectious Disease News Editorial Board.
Disclosure: Shimshony reports no relevant financial disclosures.