Global Alert and Response (GAR)

Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update – as of 20 September 2013

Since April 2012, 130 laboratory-confirmed and 17 probable cases of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to WHO. Affected countries in the Middle East include Jordan, Kingdom of Saudi Arabia (KSA), the United Arab Emirates (UAE), and Qatar; in Europe countries affected include: France, Germany, the United Kingdom (UK) and Italy; and in North Africa: Tunisia. Infections presumably acquired through exposure to non-human sources have all occurred in the Middle East; limited transmission in the countries of Europe and North Africa has occurred in close contacts of recent travellers from the Middle East. No new countries have reported MERS-CoV cases since the last update; the last exported case to a country outside the Middle East was in June 2013.

Since the last update, 37 new laboratory-confirmed cases of MERS-CoV have been reported; these include 34 cases from KSA and three cases from Qatar. In addition, one previously reported probable case in Tunisia has now been confirmed as a result of additional laboratory testing. Two cases previously counted as confirmed have been reclassified as probable on the basis of further clarifications of the case definition. Of the 130 confirmed cases, 58 (45%) have died. Seventy-seven of 124 confirmed cases (63%) for which sex is known were male and the median age of the 125 confirmed cases with known age is 50 years (range, 14 months to 94 years).

Nine new cases were reported to be sporadic, i.e. cases that were reported to have no prior contact with another known case and including cases that were the first case within a cluster. Of these, 56% were female; the median age was 53 years; and 89% had at least one underlying condition reported. Eighty-nine percent were severely ill or died. Eight of these cases were probably exposed to the virus in KSA (six in Riyadh, one in Medina, one in Hafr Al Batin) and one in Qatar. The median age and gender balance of these nine new cases represents a shift compared with earlier cases. Up until mid-July 2013, the median age of sporadic cases was 59.5 years and 83% were male.

Three recent outbreaks are described below:

  • Five cases were reported in Medina. The first Saudi case reported was a 55-year-old male who had probable contact with a 59-year-old Qatari male, who was in Medina at the time of onset of illness. The remaining cases were contacts of confirmed cases and included two asymptomatic health care workers identified through contact tracing. One additional health care worker, who died in the course of his illness, was reported without information about contact with other confirmed cases. None of the cases was reported to have performed pilgrimage while in Medina.
  • Two clusters were reported in Riyadh. In a cluster of six cases, one male index case aged 53 years is thought to have infected five other cases, including two health care workers. Both health care workers experienced mild illness. In the second cluster, all three cases were health care workers. A 41 year old Filipino healthcare worker who did not have any contact to confirmed cases of MERS-CoV infections acquired the disease from an unknown source and is thought to have transmitted it to two more healthcare workers. During this same period of time, an additional four sporadic cases were reported (mentioned above) with no contact with known cases, and five with no information on exposure.
  • The first case of the cluster in Hafr Al Batin was a 38-year-old male with onset of illness in early August. Five family members ranging in age from 7 to 79 years subsequently became infected. Two children aged 3 and 18 years and one 74 year-old female were also reported as contacts of a known case but their connection with this family was not reported.

For further details regarding the cases please refer to:

Recent guidelines

On 16 September, WHO published updated interim laboratory testing recommendations for MERS-CoV. WHO continues to emphasize the use of two different PCR assays to confirm the presence of the virus. Patients with positive serological tests in the absence of PCR or sequencing data continue to be classified as probable cases, pending more work on the validation of serological tests.
http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf

Recent peer-reviewed literature

Several scientific investigations have been published in peer-reviewed journals since the last update:

Italian investigators have described the management of a case in Italy that had been imported from Jordan. Further transmission occurred from the case to 2 close contacts (one family and one professional contact), both of whom tested positive for MERS-CoV by real-time polymerase chain reaction (PCR) for the upE gene. Additional contacts (144) were followed clinically and none developed any symptoms; of these, 70 had a respiratory sample taken and all tested negative.
Reference: S. Puzelli et al. Investigation of an imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Florence, Italy, May to June 2013. Eurosurveillance 2013;18.

Investigators in KSA searched for coronavirus infection in bats collected near the home and workplace of the first confirmed case. Samples collected from seven species of bats, including faecal samples from roost sites, were tested for coronaviruses by PCR amplification and sequencing. A 190-nucleotide sequence fragment of the RNA-dependent RNA polymerase gene, recovered from a faecal pellet of one bat, showed 100% identity with the CoV of the case from that area. The authors note that “although RdRp is a conserved portion of the CoV genome, there is no precedent for 100% identity of a bat sequence with a human MERS CoV sequence.”
Reference: Z. Memish et al. Middle East Respiratory Syndrome Coronavirus in bats, Saudi Arabia. Ahead of Print - Emerging Infectious Disease 2013;19.

Camels in Egypt were found to have a very high seroprevalence of antibody reactive to MERS-CoV by two methods (93.6% by MERS conventional neutralization test, and 98.2% by pseudoparticle neutralization assay). Other animals in Egypt (water buffaloes, cows, sheep and goats), reference animals in Hong Kong (swine, wild northern pintails, Eurasian widgeons), as well as human sera (Cairo, Nile Delta region, and Hong Kong) were all negative. The positive camels had been imported from Sudan and other East African countries.
Reference: RA. Perera et al. Seroepidemiology for MERS Coronavirus using microneutralisation assays and pseudoparticle virus neutralization reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Eurosurveillance 2013; 18.

MERS-CoV genetic sequences were from 21 cases in KSA have been pooled with 9 previously published MERS-CoV genomes for the most complete phylogenetic analysis to date. Results estimate an emergence of MERS-CoV in July 2011, consistent with earlier estimates. The analysis supports a geographically dispersed reservoir of MERS-CoV with movement of virus among geographic locations through movement of an animal reservoir, animal products, or possibly infected humans, though movement of animals was thought to be the most likely explanation. Phylogenetic analysis is consistent with sporadic introductions into humans as well as some human-to-human transmission. Focused analysis of a hospital cluster in Al-Hasa indicates that more than one virus introduction in that cluster was likely, rather than the entire outbreak originating from a single introduction.
Reference: M. Cotton et al. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet 2013; 382.

Summary assessment

Although new cases continue to occur in the Arabian Peninsula, including in the area around the pilgrimage sites, no cases have been reported in pilgrims to Saudi Arabia performing Umra during Ramadan. It is notable that only one previously reported case, a resident of the United Kingdom, became ill after a pilgrimage in January 2013.

The recent upsurge in case reporting is of concern and represents both an increase in sporadic cases and several coincident clusters of infection in contacts. These clusters are under close observation by health authorities to detect signs of further onward transmission. The reason for the increase in sporadic cases is unknown but could be the result of increased surveillance, an expansion of the virus in the unknown reservoir, seasonal variation, or a change in exposure patterns.

Sporadic cases continue to experience a severe course of disease and most have a pre-existing medical condition. However, some changes in demographic characteristics of sporadic cases are observed. The median age of sporadic cases has decreased slightly in the most recent group, though the numbers are small; but the shift in gender balance has been more pronounced and persistent. Although the severity observed in sporadic cases is likely to result from surveillance bias, the reason for the changes in age and gender distribution are unclear.

The continued occurrence of clusters in both households and health care facilities highlights the importance of infection prevention control measures in both places to prevent further spread of the virus. Health care providers should be reminded of the need for universal precautions and the use of infection control measures even before the cause of a patient’s illness has been determined. Infection control guidelines for both home care settings and health care facilities can be found on the WHO MERS-CoV website.

Three recent cases have now been reclassified. The discovery of virus, in a stored serum specimen from the first case reported by Tunisia, illustrates that the detection of virus may require specialized studies that are available only at a few reference labs. Countries that detect suspect cases may want to consider partnering with an external lab for further testing when initial specimens test negative. The two contact cases reported by the government of Italy in the Eurosurveillance article serve as a reminder of the current case definitions for reporting. Currently, a laboratory-confirmed case requires testing positive on at least two gene targets by PCR or sequence data that identify the MERS-CoV. Cases not meeting these criteria should be classified as probable and reported as such to WHO. The WHO case definition for probable cases is designed to identify cases that are highly likely to have been infected with the MERS-CoV but which do not meet the current, restrictive standard for confirmation.

The discovery of antibodies reactive with MERS-CoV in Egyptian camels imported from Sudan and other East African countries is consistent with the previous report by a lab in the Netherlands (see last update). These studies, and the report of a partial MERS-CoV genome in a Saudi bat, provide important clues as to potential reservoirs for MERS-CoV and deserve further investigation. However, the possibility of cross-reactivity between antibodies for MERS-CoV and a closely related virus circulating in camels cannot be ruled out definitively without finding the virus itself in an animal. It is also unclear whether camels, even if they are infected with the virus, play a role in transmission to humans. The analysis of additional virus genetic sequences from KSA supports the premise that current observations are the result of sporadic introductions of virus into human populations from an animal source, with subsequent limited human-to-human transmission but does not give any clues as to the animal source or route of transmission. The critical question that remains to be answered concerns the exposures and activities that place humans in contact with the virus and result in infection. Countries in the region with sizable populations of camels, however, may want to consider enhanced surveillance among humans and further studies to identify the virus in animal species.

Countries outside of the affected region should maintain a high level of vigilance, especially those with large numbers of travellers or guest workers returning from the Middle East. Surveillance should be enhanced in these countries according to WHO guidelines along with infection control procedures in health care facilities. 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 the critical features of MERS-CoV infection.

WHO provides guidance and tools for carrying out investigations into human cases of MERS-CoV.

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