Kate Johnson

May 12, 2014

BARCELONA, Spain — A team from the European Centre for Disease Prevention and Control (ECDC) just back from Jeddah, Saudi Arabia, reports that there appears to be no change in either the virulence of Middle East respiratory syndrome coronavirus (MERS-CoV) or its transmissibility.

The "dramatic" spike in the number of MERS-CoV cases reported in the past 3 weeks is related to a seasonal increase in primary cases, combined with a "huge spillover and amplification" of secondary cases caused by in-hospital transmission to healthcare workers and other patients, said Denis Coulombier, MD, head of the unit for surveillance and response support at the EDCD.

Confirming the source of the virus and its means of transmission and improving infection-control efforts in Saudi Arabia are international priorities, he said.

The World Health Organization (WHO) just issued a caution about exposure to camels, a suspected source of the infection, and have called an emergency meeting on the issue that will begin tomorrow.

Concern has arisen because there were more cases of confirmed MERS-CoV in April alone than there were in the 2-year period from March 2012 to March 2014 (288 vs 207), Dr. Coulombier reported.

Just today, the Florida Department of Health confirmed the second imported case of MERS-CoV in the United States.

Dr. Coloumbier provided an update on the situation in Saudi Arabia in a late-breaking teleconference from Stockholm here at the 24th European Congress of Clinical Microbiology and Infectious Diseases.

As of May 7, there were 518 confirmed cases — all connected to the Middle East — and 145 deaths.

In the initial 2-year period, asymptomatic patients, identified because of contact with a primary case, made up 14% of cases. In April, asymptomatic patients made up 24% of cases, "which certainly illustrates that enhanced screening and contact tracing has resulted in the identification of more asymptomatic and milder cases," explained Dr. Coulombier.

Early identification has also lowered the mortality rate — from about 60% in the initial 2-year period to 25% in April.

The "Spike" in Jeddah

"The situation of most concern is in Jeddah, where there were 4 cases in the past 2 years and 135 cases in April," said Dr. Coulombier.

Analysis of the Jeddah spike, which began around week 12 of this year, shows that primary cases were predominantly men 50 years and older. This is consistent with the hypothesis that camels are a source of the virus, because camel farming is largely practiced by "young retirees," he explained.

Secondary infections are seen in younger patients, where the distribution between the sexes is more even.

"What we learned in the hospital cluster last year in Al Ahsa is that effective infection-control measures are sufficient to control an outbreak. That's really the priority now for Jeddah," said Dr. Coulombier.

The inconsistent use of protective gear, combined with a mid-March influx of MERS-CoV patients for which Jeddah emergency departments were not prepared, likely played a key role in the spike.

It has been reported that symptomatic patients stayed in the emergency department for up to 1 week. "Part of the increase in secondary cases that we saw in the hospital were potentially acquired while attending the emergency room at that time," he explained.

Disease Presentation

"Most primary cases of MERS-CoV present initially with fever and signs of respiratory infection. During the course of the disease, other organs become involved. Up to one-third of patients will present with diarrhea, and the disease may evolve into renal or other organ failure or acute respiratory distress syndrome," Dr. Coulombier reported.

Primary cases are predominantly symptomatic and lead to high rates of admission to the hospital or intensive care unit and death. Secondary infections lead to lower rates of symptomatic illness and death, except in already-hospitalized patients.

Patients with comorbidities tend to present with more severe disease, and the few immunosuppressed patients who have been infected have presented with fever and diarrhea early in the course of the disease, he said.

A system of triage and quarantine, which has now been implemented in Jeddah, is associated with early signs of improvement, he added.

In week 14 of this year, secondary infections peaked in hospitalized patients; in week 15, they peaked in healthcare workers. "In the past 2 weeks, there has been a marked decrease in these cases," said Dr. Coulombier.

"Primary cases continue to increase," he said, "although we have to be a bit cautious in interpreting the most recent week because there may be delays in reporting."

Understanding the Source of Infection a Priority

The source of the infection and how it is transmitted remain unclear. "Camels are indeed playing a role, but it's still unclear what that role is," said Dr. Coulombier, noting that only a few of the patients with primary infection had direct contact with camels.

"There are probably multiple modes of transmission, including foodborne," he said, explaining that camel meat and milk are commonly consumed in the area.

As with the SARS coronavirus, it is suspected that "superspreaders" play a role in transmission. Studies should focus on risk factors for MERS-CoV infection and on modes of transmission, especially in the hospital setting, he added.

In an editorial published in the April 24 issue of Eurosurveillance, Dr. Coulombier and a colleague suggest that WHO should declare MERS-CoV a public health emergency of international concern (2014;19:20783).

Still, "I do think that WHO has done a good job in handling this situation. There have been 4 meetings and very appropriate recommendations to fill the gap in knowledge about MERS," Dr. Coulombier told Medscape Medical News.

"The current MERS-CoV outbreak in the Kingdom of Saudi Arabia requires intensive, global, collaborative scientific investigation," said Scott McNabb, PhD, research professor at Emory University, Rollins School of Public Health, managing partner at Public Health Practice, and senior consultant at Global Strategies in Atlanta.

"It points out the urgent need for WHO to develop an enhanced governance document addressing data sharing, collaborative research, and public health surveillance strengthening," he explained.

"Certainly, the major efforts now underway to improve hospital infection prevention and control are critical in Saudi Arabia. The preventive measures undertaken by the Kingdom of Saudi Arabia Ministry of Health will pay great dividends, both in containment now and in the future as general healthcare services are improved and modernized," he said.

Dr. McNabb and his team from the Rollins School of Public Health are currently working with academic scientists at King Saud University in Riyadh to conduct the epidemiologic and laboratory studies necessary to understand the mode of transmission and risk factors for MERS-CoV exposure, infection, and disease.

"While the genomic sequence of the virus has remained stable since its recognition 2 years ago and there have been no observed changes in the virulence or transmissibility of the virus, we remain cautious and watchful about this epidemiologic feature," he told Medscape Medical News.

Additionally, he said, the age distribution of patients is an important observation. "If proven a risk factor for disease, this may hold a key for future preventive measures, like vaccine administration recommendations or basic pathogenesis investigation."

Dr. Coulombier and Dr. McNabb have disclosed no relevant financial relationships.

24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Presented May 11, 2014.

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