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MERS: The limping epidemic on steroids
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One year ago — 18 months into the outbreak of the Middle East respiratory syndrome, or MERS, coronavirus — we prepared an editorial on the status of the MERS epidemic. As of mid-February, we are now 31 months into the outbreak.
In the past year, the number of cases has more than quadrupled from fewer than 200 to more than 950, with a global estimated case fatality rate (CFR) of about 40%. The CFR is undoubtedly lower as mild or asymptomatic cases are probably more common and may be missed. Diagnosis usually depends on reverse-transcription PCR studies, with the highest yield from lower as opposed to upper respiratory tract samples; these specimens are unlikely to be obtained in mildly ill patients. Unfortunately, large-scale serosurveys designed to identify the prevalence of MERS coronavirus (MERS-CoV) antibodies in residents of one or more of the countries in the Middle East have not been published yet so as to permit a tentative assessment of the background rate of asymptomatic or mildly symptomatic infections. The disease has remained centered in the Arabian Peninsula, with the great majority of cases in Saudi Arabia (825 laboratory confirmed cases reported as of Jan. 1 2015, or 88% of all cases reported to WHO), followed by the United Arab Emirates (UAE; 73 cases or 8% of the global reported cases). All confirmed cases to date owe their origin to the Arabian Peninsula. There have been at least 20 cases in which infected individuals have traveled from that region during the incubation period to become sick elsewhere, and there have been limited secondary cases occurring in relationship to these cases.
Severe disease and mortality primarily has been seen in older individuals with comorbidities, whereas young, healthy individuals tend to have asymptomatic to mild disease. In 2014, the average age of reported fatal cases from Saudi Arabia was 60 years, whereas the average age of those reported to have recovered was 44 years, and of those who were asymptomatic contacts, 36 years.
Health care workers (HCWs) continue to be at high risk for infection. In an analysis presented by WHO on 402 cases reported during April and May where details were known, HCWs represented more than 25% of cases, although 58% of those infected HCWs were reported as asymptomatic or having mild disease. Of all reported MERS-CoV cases in Saudi Arabia, 63% have been in men. This male predominance possibly may suggest either an occupational or cultural relationship.
Marjorie P. Pollack
Seasonality of MERS-CoV activity continues to reflect increases in transmission during the spring and fall months for the Northern Hemisphere (April to June and September to November). In 2013, there were slightly more than 60 newly confirmed MERS-CoV infections during the April-June period. In contrast, there were about 515 cases reported by Saudi Arabia alone during the April-June period of 2014. A smaller but similar pattern was observed during the September-November period in 2013, with slightly more than 50 newly confirmed cases reported and about 100 cases reported during the same months in 2014. During both periods, according to the Saudi Arabia Ministry of Health, nosocomial transmission accounted for approximately 70% of the identified cases. With the majority of transmission of MERS-CoV occurring in Saudi Arabia, earlier fears of significant international spread associated with the pilgrimages to Saudi Arabia (the hajj and umrah) have not been realized, with fewer than 20 confirmed cases of MERS-CoV identified in pilgrims to date.
While much has been learned about MERS-CoV, there are many unanswered questions, primarily related to epidemiology. We know that bats are probably the original source of MERS-CoV. Infection likely jumped species from bats to camels. Serological studies of stored camel sera have demonstrated that MERS-CoV has been circulating in camels in North Africa and the Middle East for at least 20 years. Camels have been shown to excrete virus from their nostrils and may well serve as an important reservoir for some of the human cases. High percentages of camels in the Arabian Peninsula have antibody titers against MERS-CoV demonstrating past or present infection. We also know that human-to-human spread occurs especially in family clusters and nosocomial outbreaks. However, there are many unknowns. We still do not know what events happen during the spring and fall months in the Northern Hemisphere to explain the major increases in transmission. We know the major camel breeding season is in the winter months, and so calving occurs 15 months later in the springtime; studies have shown that juvenile camels (aged younger than 2 years) are the primary seroconverters. As the virus is genetically similar to CoVs identified in bats, we still do not understand how and when the species jump occurred.
Donald Kaye
There are many cases in the community with no known relationship to exposure to patients with MERS-CoV or to bats, camels or camel products. Using the Saudi Arabia Ministry of Health reports from 2014, information was available on 392 reported cases of MERS-CoV infection, of whom 60% had an identifiable high risk exposure to either confirmed or suspected MERS-CoV cases in either the health care environment or in the community, or they had probable evidence of nosocomial exposure. Another 9% gave a history of high-risk exposure to camels or camel products during the incubation period. This leaves 31% with no apparent source of infection. The source of infection in these cases remains a mystery.
While it would be expected that camel handlers, butchers and others who have intense contact with the animals and their bodily fluids would be at risk for MERS-CoV, these groups appear no more likely to acquire the disease than people with no contact at all. Limited studies available on these individuals have found lower rates of seropositivity than one might expect. Camels from countries outside of the Arabian Peninsula, such as in North, East and West Africa (Egypt, Tunisia, Nigeria and Ethiopia), as well as other countries (eg, Pakistan), also have been demonstrated to have a high prevalence of antibodies against MERS-CoV, but no human cases have been reported from these countries. It could be argued that the lack of reported human disease in these countries could be related to poor case finding, but in a country such as Egypt, where avian influenza has been repeatedly diagnosed, it is highly likely that MERS-CoV infection would have been detected if present.
Unfortunately, our statement in last year’s editorial is still applicable today: “From the experience thus far, it seems likely that the MERS outbreak will continue to limp along with sporadic cases occurring primarily in the Arabian Peninsula followed by nosocomial outbreaks when first introduced into a health care facility. This may change when the routes of transmission to the sporadic cases are clearly identified, or if there is a change in the virus leading to the super spreader phenomenon observed with SARS or a change in virulence of the virus.”
The experience in 2014 with MERS-CoV saw many more nosocomial enhanced outbreaks in both Saudi Arabia and the UAE, and significantly larger outbreaks, resulting in the quadrupling of confirmed cases during the course of the year.
*Data presented in this editorial were synthesized by the authors from the original reports issued by the Saudi Arabia Ministry of Health, WHO and the European Centre for Disease Prevention and Control.
References:
Corman VM. Emerg Infect Dis. 2014;20:1319-1322.
Memish ZA. Influenza Other Respir Viruses. 2014;doi:10.1111/irv.12287.
Nowotny N. Euro Surveill. 2014;19:20781.
For more information:
Donald Kaye, MD, is a professor of medicine at Drexel University College of Medicine, associate editor of ProMED-mail, section editor of news for Clinical Infectious Diseases and an Infectious Disease News Editorial Board member.
Marjorie P. Pollack, MD, is deputy editor of ProMED-mail and an independent consultant medical epidemiologist with a focus on developing world issues following CDC training. She is based in New York.
Disclosure: Kaye and Pollack report no relevant financial disclosures.