Friday, June 14, 2013

The Lancet: MERS-CoV: in search of answers

Volume 381, Issue 9883, Page 2069, 15 June 2013
Anna Petherick

In recent weeks, researchers have uncovered key molecular and clinical details about this novel virus, but fundamental questions remain about how it spreads. Anna Petherick reports.
Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been a cause for concern for months, with a steady trickle of new cases, often fatal, dating back to April, 2012. Until March of this year there were fewer than five confirmed infections per month, but April and May each saw 19 new cases, driven up by a cluster in the Al-Ahsa region in eastern Saudi Arabia. Most people now known to have caught MERS-CoV have done so from another human being.
Efforts to understand the infection have consequently been stepped up. A WHO team of experts tasked with trawling through the existing Saudi data has just returned from the country. It hopes to publish a report this month. Saudi Arabia's Ministry of Health has also agreed to send samples from animals that seem likely candidates to harbour the virus to the USA for analysis. This marks a positive shift in tone: last autumn, the same ministry stood accused of ordering the sacking of Ali Mohamed Zaki, the virologist who alerted the medical community to this new threat by posting an entry on proMED (an infectious disease news website), and who sent a sample abroad to find out what it could be.
The little acts of diplomatic progress of late could have a substantive public health benefit, by enabling researchers to answer the most important question about this virus: what non-human source acts as a conduit from which MERS-CoV can infect people? “It could be a food, an animal, or a contaminated product with virus on it from contact with an animal”, suggests Tony Mount, WHO's technical lead on this virus. “If we can stop that, if we can somehow manage to interrupt that transmission, then the outbreaks won't happen.” A close genetic relative of coronaviruses carried by pipistrelle bats, MERS-CoV is thought to have jumped from bats to something else, and from that something else to humans, repeating a pattern shared by other novel human viruses. The severe acute respiratory syndrome (SARS) pandemic of 2003 arose when a coronavirus hopped from bats to civet cats to people. And Nipah virus, which has caused many deaths in Bangladesh over the past 2 years, moved from bats to humans via date palm sap, a popular local drink.
The intermediary for MERS-CoV has proven surprisingly elusive. A group of Dutch researchers that identified the DPP4 receptor on the surface of lung cells as the foothold by which MERS-CoV enters the body, have struggled to infect other mammals, such as ferrets, mice, and hamsters. “We could show that the virus recognises a similar receptor in bats, and because bats and humans are genetically quite far apart you would expect many species in between to have a conserved receptor that allows the virus to enter”, explains Bart Haagmans, of the Erasmus University Medical Center in Rotterdam. Only rhesus macaques have succumbed—a fact of limited use in explaining outbreaks in the Middle East.
With greater political will where it counts, more widespread surveillance could be underway. At least four institutions have developed serological assays that do not seem to have been picked up by some of the places experiencing the greatest burden. These tests could be deployed to search for the animal conduit in markets and among Saudi Arabia's existing sentinel herds of goats, cattle, and sheep that are already monitored for tick-borne viruses in circulation.
Moreover, the assays could reveal whether infected individuals displaying only mild symptoms, with the potential to disseminate the virus, are more common than currently imagined. To date, two cases in Tunisia and one in the UK have not required admission to hospital. Representatives of Jordan's Ministry of Health and of the US Centers for Disease Control and Prevention are retrospectively probing the shadow of an outbreak in Amman to offer a response to this question, but it would be more pertinently answered in Al-Ahsa. “I think the Saudis have been a little bit reluctant to use one of these tests”, says Mount. “I hope they will very soon because I think that even in their current state [of verification], the assays are actually very useful.”
Perhaps MERS-CoV is of most concern where it is silent. That it has been picked up in travellers heading west from the Arabian Peninsula, but not in those heading east, is more likely a product of the relative intensity of surveillance in different countries, than it is a reflection of the underlying epidemiology. Most of the foreigners who comprise a third of Saudi Arabia's population emanate from Pakistan, India, the Philippines, and Indonesia—countries where large extended families often live in close quarters and hygiene can be poor. The international cooperation to combat MERS-CoV has been lauded. Now, say experts, it is time to take it up a notch.
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