Global Alert and Response (GAR)

Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update – as of 9 July 2013

Since April 2012, 80 laboratory-confirmed cases of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to WHO. Forty-five of the confirmed cases have died (56%). Forty-nine of 75 cases (65%) for which the sex is known were male and the median age of the cases with known age is 51 years (range, 14 months to 94 years). Affected countries in the Middle East include Jordan, Qatar, Saudi Arabia and the United Arab Emirates (UAE); in Europe countries affected include France, Germany, the United Kingdom (UK) and Italy; and in North Africa, Tunisia. No new countries have reported MERS-CoV cases since the last update. All the European and North African cases have had a direct or indirect connection to the Middle East. However, in France, Italy, Tunisia and UK, there has been limited local transmission among close contacts that had not been to the Middle East.

Since the last update, 16 new laboratory-confirmed cases of MERS-CoV were reported by Saudi Arabia. Eight of the new cases were reported to be asymptomatic. Of the eight asymptomatic cases four were female health care workers, two from the Ta’if governorate and two from the Eastern Province of Saudi Arabia. The other four asymptomatic cases were children aged 7 to 15 years from Riyadh and the Eastern Province of Saudi Arabia who had contact with confirmed cases.

WHO MERS-CoV related activities and upcoming guidance

WHO is currently preparing travel and health advice for travellers to forthcoming mass gatherings.

Recommendations for infection prevention and control for MERS-CoV patients in hospital are under review. Advice on infection prevention for patients being cared for at home is under development.

WHO is convening an Emergency Committee meeting, as described in the International Health Regulations (2005), to review the current MERS-CoV outbreak, discuss whether the outbreak constitutes a Public Health Emergency of International Concern (PHEIC), and advise the Director General on temporary recommendations for any necessary public health actions.

WHO is also coordinating the collection of a panel of clinical serum specimens, which will include both MERS-CoV positive and negative specimens, to standardize serological assays. This activity is being done in collaboration with an international network of public health and research laboratories.

Recent guidelines

On 5 July, WHO published a guideline for investigation of MERS-CoV cases. It provides recommendations for early case investigation including further case finding, surveillance enhancements, and studies that need to be done around new cases.

On 3 July, WHO published revised case definitions for MERS-CoV confirmed and probable cases based on new epidemiological and clinical information. The document also contains recommendations on further evaluation for cases with inconclusive tests and asymptomatic infections.

On 27 June, WHO published interim surveillance recommendations for human infection with MERS-CoV. The two major changes include a stronger recommendation for the use of lower respiratory tract specimens in addition to nasopharyngeal swabs for diagnostic testing and a longer observation period for contacts of cases.

Recent papers in the scientific literature

Several MERS-CoV scientific investigations have been published in journals:

Hospital outbreak of Middle East respiratory syndrome coronavirus

The Saudi Arabian Ministry of Health provided an in-depth analysis of 25 (23 confirmed and 2 probable) MERS-CoV cases associated with an outbreak in Al-Hasa region of Saudi Arabia. The outbreak involved patients, their family members and health care workers from four different hospitals, including a haemodialysis unit, an intensive care unit and other inpatient units. Human-to-human-transmission was considered the likely source of infection for most of the cases. The estimated median incubation period was 5.2 days (95% confidence interval 1.9 to 14.7 days).

Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection

German investigators published a viral load profile of a patient infected with MERS-CoV treated in Germany in March 2013. They found very high viral loads in lower respiratory tract samples from the patient compared with upper respiratory samples, and low concentrations of the virus in stool, urine and blood.

Transmission scenarios for Middle East respiratory syndrome coronavirus (MERS-CoV) and how to tell them apart

A recent paper describes three possible transmission scenarios for MERS-CoV, detailing the implications for risk assessment and control for each. The scenarios include subcritical outbreaks where the reproduction number (R0) is less than 1, supercritical outbreaks where R0 is greater than 1 but the epidemic has not become self-sustaining in human populations, and a self-sustaining epidemic where R0 is greater than one. The authors stress the importance of adequate data collection in order to permit rigorous assessment of the severity and transmission characteristics of MERS-CoV.

Summary assessment

With recent reports of asymptomatic and mild cases, the proportion of confirmed cases that have died of MERS-CoV infections is lower than previously reported, as is the average age, and the proportion of patients who are female has increased. It is noteworthy that these cases have been detected as part of contact investigations around severe cases. These severe cases were discovered as a result of surveillance activities that focus on finding severely affected patients. Index cases, the first cases occurring in a cluster, presumably are more likely to have had a non-human exposure as their source of infection and continue to be predominantly older males, perhaps providing a clue to the exposure that resulted in their infection. Whether the relative mildness of illness in contact cases is an artifact of surveillance and case-finding activities or represents a difference in virulence between sporadic infections acquired from non-human exposures and those acquired from human-to-human transmission is unknown.

The recent mild and asymptomatic cases raise concerns about the possibility of large numbers of milder cases going undetected. While it is clear that human-to-human transmission does occur, it is not clear whether transmission is sustained in the community. The currently observed pattern of disease occurrence could be consistent either with ongoing transmission in an animal reservoir with sporadic spillover into humans resulting in non-sustained clusters, or unrecognized sustained transmission among humans with occasional severe cases. Detailed case contact investigations, increased surveillance in other countries of the region, and formal studies of non-human exposures of index cases are urgently needed to answer these questions. A new guideline for these case investigations has recently been published (see above).

The public health importance of asymptomatic cases is uncertain. More information is needed about the virus excretion patterns in persons without symptoms to understand the risk they may pose to non-infected persons. Experience from the Severe Acute Respiratory Syndrome (SARS) outbreak in 2003 suggests that very little if any transmission occurred from asymptomatic individuals. In addition, in the absence of symptomatic illness, the burden of proof must be higher because of the possibility of misclassification from false positive tests that result from laboratory contamination. In most viral infections, an immunological response, such as development of specific antibodies, would be expected even with mild or asymptomatic infection; as such, serological testing may be useful as additional confirmation of the diagnosis. Additional steps to reconfirm asymptomatic cases, or any case in which the diagnosis is suspect, could also include re-extraction of RNA from the original clinical specimen and testing for different virus target genes, ideally in an independent laboratory.

WHO continues to request that Member States report all confirmed and probable cases along with information about their exposures, testing, and clinical course to inform the most effective international preparedness and response. WHO strongly recommends detailed case investigations for every case, case-control-studies for index cases and intensive follow up of contacts with serological testing to improve knowledge of critical features of the MERS-CoV infection.

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