While I was working on the "H1N-What?" post, I also knew there would soon be questions about MERS (Middle East Respiratory Syndrome), just as there were about SARS. So here are the essentials of what we know and don't know about MERS—which has just been reported in the U.S.—as well as intriguing tidbits that remain an unsolved mystery.
What is MERS?
MERS is a respiratory virus, known initially as novel coronavirus (CoV). Until now, it has largely been confined to the Middle East, having been first discovered in Saudi Arabia in 2012. Isolated cases were found in Europe earlier this spring—one case each in France, Italy, and Greece—a warning that things would soon get interesting here as well.
SARS (Severe acute respiratory syndrome coronavirus), which is a cousin to MERS, caused a major worldwide epidemic in 2003, infecting more than 8000 and killing almost 10%. SARS caused major infections in China, Hong Kong and Toronto, among others, before being contained by unprecedented multinational cooperation and careful infection control, within only about a year.
Where did MERS come from?
Short answer—we don’t know. It’s quite curious. We do know that many camels have antibodies to the virus, but we don’t know how they were infected or how the disease (if any symptoms) manifests itself in camels. Further, although most camels have antibodies, there is no similar evidence of antibodies among abattoir workers. The live virus has recently been isolated from nasal swabs of camels as well, and has shown to have identical whole genome sequences as that found in humans. How transmission occurs between camels and people is unknown; most of the people infected have not had contact with camels. One possibility is that camel meat or raw camel milk might be one route of transmission.
Similarly, SARS was linked to live animal markets, and specifically to civets; here, antibodies were found in the blood of animal handlers. Fruit bats were found to be the likely reservoir for infection, transmitting the SARS-CoV to civets at crowded animal markets.
As with SARS, fruit bats are increasingly thought to be the reservoir for MERS—specifically, the Egyptian tomb bat. The most intriguing hypothesis I’ve read is that infected bats contaminate date palms, thus exposing farm workers who have to climb the trees to pollinate them and then perform further work up in the trees to maximize yields of the fruit. Laurie Garrett likens this to the transmission of Nipah virus by bats in Bangladesh, via palm oil collected near the tree tops.
Animals are often the hidden source of outbreaks, known as zoonoses. For example, birds and live animal markets have been the source of recent influenza outbreaks (see "H1N-What?" and Epidemiology table, below), as well.
While the origin of MERS is still a bit of a mystery, what is known is that the number of cases has been suddenly increasing recently—though again, we don’t know why.
Subterfuge, rivalry, and profit
As with China and SARS early on, one of the current problems is that the Saudi government has been less than forthcoming about the number of MERS cases. A new report says that the government directed physicians to misreport the cause of death of patients. This is worrisome for many reasons—and it cannot be emphasized enough that what stopped SARS was candor and cooperation—scientists sharing specimens and governments being more transparent than usual.
Obviously, governments are loathe to admit that they have problems—especially ones that can have a serious economic impact. David L. Heymann, former executive director of communicable diseases at the World Health Organization, recalls that an epidemic of cholera in the 1990s cost Peru more than $770 million; later, India lost more than $1 billion due to a plague outbreak.
There has also been a longstanding reluctance to share samples because of patent considerations. For example, in 2007, Indonesia, the country most affected by H5N1, decided to stop sending viral isolates to WHO (World Health Organization), seriously hampering efforts to study the newly emerging virus. Indonesia argued that the samples they freely provided would be exploited by wealthy countries to develop a vaccine that would be too costly for developing countries. Ultimately, they did agree to a proposal with WHO that would allow sharing the viruses and the profits.
There has been similar bickering over the MERS virus. A virus sample was sent for identification from a virologist, Ali Mohamed Zaki, to Albert Osterhaus and Ron Fouchier at Erasmus Medical Center in the Netherlands. The virologist who discovered the virus, was promptly fired for sending the sample to try to help diagnose a patient’s illness, and for posting his concerns about the emergence of a new viral pathogen on an infectious disease alert bulletin board, ProMed—a compelling reading. That listing on ProMed alerted London physicians to the possible coronavirus diagnosis in a Qatari man they were caring for—and prompted an immediate global alert from the WHO.
In the meantime, Erasmus promptly patented the “use of the sequence and host receptor data" for MERS and insisted on material transfer agreements, or MTAs, claiming they had an “ethical obligation” to do so, to speed development of therapies. While the Saudis were understandably miffed, Osterhaus and Erasmus have said that the viral samples were being made freely available for public health research.
But the Saudis are seriously hampering study of MERS, particularly now by hiding cases and not sharing epidemiologic information that might lead to understanding of how MERS is being transmitted, and help stopping this growing global pandemic. This is unconscionable.
Who has been affected? Who is at risk?
It appears that there is limited person-to-person transmission, so cases have primarily occurred in those with close contact to an index patient—family or health care workers, the latter of whom have been affected quite disproportionately. In hospital transmission was nicely illustrated in a 2013 outbreak. Reassuringly, the rate of transmission to household members was low. One of the intriguing findings is that, as with SARS, there appear to be “superspreaders,” individuals who spread an unusually large amount of illness to others (like “Typhoid Mary”). More recently, more cases of hospital acquired transmission, including to other patients, have been reported.
Only people with close contact to a case, who then become ill with a respiratory infection within two weeks, are advised to be tested. The CDC has a rRT-PCR test available through state health departments.
The apparent need for close contact for transmission is why the CDC has not sounded great alarms yet over the first case to be reported in the U.S., a healthcare worker who just traveled back from Saudi Arabia. They are, however, monitoring his travel contacts.
Should MERS-CoV infections become established in the US, the CDC has infection control advice for families and in-home caretakers available here. It’s pretty standard, with additional recommendations for gowns, masks, and gloves for caretakers.
For in-hospital care, contact and airborne precautions are recommended, based on experience with SARS, including eye protection. Meticulous infection control practices are required, as SARS was transmitted through lapses in technique, contaminating surfaces and healthcare workers.
Respiratory failure occurs more rapidly with MERS than with SARS. The death rate is roughly 1/3 now, though last year the mortality was listed as ~56%. Note that this is far higher than SARS. The MERS virus seems to disproportionately affect people with serious co-morbidities, such as kidney failure, diabetes, serious lung or cardiac diseases.
There aren’t any, except for the usual supportive care, with mechanical ventilation and extracorporeal membrane oxygenation, as with severe H1N1 flu. There is no specific antiviral therapy. And don’t expect to see any for years. It takes about a decade for most drugs to be developed and tested enough to be able to get regulatory approval. That process will only occur if a pharmaceutical company decides it is likely profitable enough to warrant the research—and if the antibiotic pipeline is any indicator, development of a coronavirus treatment is highly unlikely. If illnesses are confined to poorer regions of the world, like Ebola or neglected tropical infections, prospects for work on a treatment are even bleaker. After all, infections just aren’t as profitable as chronic diseases, like diabetes, vaccines for common childhood infections, or made up ailments, like “Low T.”
A speedier route would be to develop a vaccine for animals that are found to be significant transmitters, such as camels. That might be achieved in just a couple of years.
One other potential treatment is immunotherapy, based on antibodies developed in response to infection, but this is also a long way off.
What might the US expect?
An interesting report from the Institute of Gulf Affairs suggests upcoming waves of visitors who may be bringing MERS with them:
First will be Saudi students and expats coming to the US for their summer vacation. Next will be students returning to the US or Europe for universities in the fall, after being home during the summer and Ramadan (a month-long period of daytime fasting and reflection). The end of Ramadan also marks a period of pilgrimage, the Umrah, though not as large as Hajj, the major Islamic time of pilgrimage. Finally, there may be a wave in October, when travelers return from Hajj pilgrimages to Mecca and Medina—though no confirmed cases were reported after last year’s Hajj, two recent cases were recently seen among religious pilgrims.
As I noted in my post about the Sochi Olympics , pilgrimages (or any similarly large gatherings) are well known for transmitting infections. For the Hajj pilgrimage, ~3 million people from more than 183 countries go to Saudi Arabia each year. In 2000-2001, Hajj led to the global spread of meningococcal meningitis; now vaccination against this bacterial infection is required of attendees. Last year, Saudi Arabia discouraged many at risk (elderly, those with chronic illnesses) from making the pilgrimage.
The recent surge in cases in Saudi Arabia is concerning, and there is no clear reason for the uptick. On the other hand, we now have diagnostic tests available and (if used reliably) better infection control capabilities than we did when SARS hit a decade ago. What we still lack is transparency and better cooperation between countries, which proved essential in stopping SARS.
MERS-Corona map: http://coronamap.com/
Garrett, Laurie Stay Away from Camel Milk and Egyptian Tomb Bats
Memish ZA et al. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med, 2013, 368(26):2487-94. (free)
Assiri, A et al. Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus. N Engl J Med 2013, 369;5. (free)
Helen Branswell (@HelenBranswell)
Laurie Garrett (@Laurie_Garrett)
Crawford Kilian (@crof)
Ian M Mackay, PhD (@MackayIM) and Virology Down Under
MERS coronavirus image - NIAID
"Molecules to Medicine" banner Michele Banks