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Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Information and Guidance for Clinicians

Moderator:Leticia R. Davila

Presenters:Susan Gerber, MD and Alexander Kallen, MD, MPH

Date/Time:June 13, 2013 2:00 pm ET

NOTE:This transcript has not been reviewed by the presenter and is made available solely for your convenience. A final version of the transcript will be posted as soon as the presenter’s review is complete. If you have any questions concerning this transcript please send an email to coca@cdc.gov

Coordinator:
Welcome and thank you for standing by. For today’s conference all parties will be on listen-only. During the question and answer session please press *1 to ask a question. You will be prompted to record your name. Please unmute your phone and record your name clearly in order to be introduced into the conference with your question. Today’s call is being recorded. If you have any objections you may disconnect at this time. I will now turn the conference over to Leticia Davila. You may begin. Thank you.

Leticia Davila:
Thank you (Denise). Good afternoon. I’m Leticia Davila and I’m representing the Clinician Outreach and Communication Activity, COCA with the Emergency Communications System at the Centers for Disease Control and Prevention. I am delighted to welcome you to today’s COCA Webinar, Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Information and Guidance for Clinicians. We are pleased to have with us today Dr. Susan Gerber and Dr. Alexander Kallen. They will provide an update on MERS-CoV and will discuss the clinical signs, epidemiology and infection control recommendations.

There is no continuing education credit provided for this call. You may participate in today’s presentation by audio only, via Webinar or you may download the slides if you are unable to access the Webinar. The PowerPoint slide set and the Webinar link can be found in our COCA Web page at emergency.cdc.gov/coca, click on COCA Calls. The Webinar link and slide set will be found under the call in number and call passcode.

At the conclusion of today’s session the participant will be able to describe the key components in the surveillance case definition for a patient under investigation for MERS-CoV infection, identify specimens to be obtained and the appropriate laboratory test to diagnose a patient, and list infection control measures appropriate for control of MERS-CoV.

Our first presenter today is Dr. Susan Gerber. She is the Team Lead for the Respiratory Viruses and the Picornavirus Team, in the Division of Viral Diseases at CDC. She received her MD from Loyola University and completed a pediatric residency and Pediatric Infectious Disease Fellowship at the University of Chicago. Dr. Gerber later joined the University of Chicago faculty in the section of Pediatric Infectious

Disease. She has over 13 years of experience in local public health with work on communicable diseases at the Cook County Department of Public Health and the Chicago Department of Public Health.

Our second presenter is Dr. Alexander Kallen. He is a Medical Epidemiologist and Outbreak Response Coordinator in the Division of Healthcare Quality Promotion at the CDC. He works to conduct and coordinate healthcare outbreak investigations and response for the division. Dr. Kallen is also a volunteer attending physician in both the HIV clinic and infectious disease inpatient service at the Atlanta Veteran’s Affairs Medical Center.

In addition to today’s presenters Captain Francisco Alvarado-Ramy from CDC’s Division of Global Migration and Quarantine will be available to answer questions during the Q&A section of today’s COCA call. At the end of the presentation you will have the opportunity to ask the presenters questions. On the phone dialing *1 will put you in the queue for questions. You may submit questions through the Webinar system at any time during the presentation by selecting the Q&A tab at the top of the Webinar screen and typing in your question.

Questions will be limited to clinicians who would like information on clinical guidance related to MERS- CoV. For those who have media questions please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov. At this time please welcome our first presenter, Dr. Gerber.

Dr. Susan Gerber:
Thank you. As we heard the first objectives we are going to discuss in this first part are describe the clinical spectrum of disease caused by MERS-CoV, identify the key components in the surveillance case definition for a patient under investigation for MERS-CoV, identify specimens to be obtained and the appropriate laboratory test to diagnose a patient with MERS-CoV and list infection control measures appropriate for control of MERS-CoV.

First background about coronaviruses, they’re enveloped positive strand RNA viruses. And human coronaviruses were first isolated in the 1960s.

There are six human coronaviruses that have been identified to date. And they are called 229E, OC43, NL63, HKU1, the SARS coronavirus and lastly more recently identified the Middle East Respiratory Syndrome Coronavirus or MERS-CoV.

Coronaviruses are classified into alpha, beta, gamma and delta categories. MERS-CoV is known as a beta coronavirus. Other beta coronaviruses include OC43, HKU1 and the SARS coronavirus.

First some background about human coronaviruses, 229E and NL63, OC43 and HKU1 are most often associated with upper respiratory tract infections in children. Pneumonia and lower tract infections may occur in immunocompromised individuals and the elderly. And they may also play a role in exacerbations of underlying respiratory diseases.

Epidemiologically they are found worldwide and seasonality, they can occur any time in the year but in particular winter and spring in temperate climates. Exposure is common in early childhood and transmission is likely to be droplet, contact and indirect contact. Symptoms and viral loads are high in the first few days of illness, and the incubation period is generally two to five days.

Now moving on to SARS coronavirus, it was characterized as fever, myalgia, headaches and chills for one to two days followed by a nonproductive cough and shortness of breath approximately five to seven days after onset. It was most often - most identified illnesses were recognized in adults. And about 25% had diarrhea, 20% to 30% were managed in intensive care units and had ARDS and were mechanically ventilated. There was about a 10% to 15% mortality rate which was higher in adults more than 60 years of age.

Epidemiologically the SARS coronavirus was first recognized in November 2002 as sporadic cases in Guangdong province, China. The outbreak period for SARS coronavirus was between 2002 and 2003. There was a Hong Kong hotel that contributed to spread of virus to several countries. And in all 8,098 probable SARS cases including 774 deaths.

Remembering the epidemiology of SARS, the incubation period was thought to be somewhere between two to 10 days with a median of four days. Transmission through droplets and possibly aerosol spread, fomites. There seem to be fecal-respiratory transmission in an apartment complex in Hong Kong and transmission was thought to most likely occur during the second week of illness. During the outbreak there were super spreading events or cases that seemed to transmit to more individuals than other cases.

Moving on to MERS coronavirus and in the initial first identification and the first case that was identified -- and we’ll look at the timeline later -- but the first case identified in September, along with the second case, was a 60-year-old Saudi man, presented on June 13th with a seven-day history of fever and cough, and a recent shortness of breath.

The patient had increasing blood urea nitrogen (BUN) and creatinine starting at day three of admission.

The white cell count was normal on admission but there were 92.5% neutrophils. And the white count increased to a peak of 23,800 cells per cubic millimeter on day 10 with neutrophilia, lymphopenia, and progressive thrombocytopenia. And this information is found in Zaki et al. in the New England Journal.

There are two X-rays on this radiograph. A panel is on admission, and the B panel is two days later.

On admission there was thought to be bilateral enhanced pulmonary hilar vascular shadows as seen and accentuated bronchovascular lung markings and multiple patchy opacities in the middle and lower lung fields. In the bottom, two days later the opacities seem more confluent and dense.

The first case outcome the patient developed acute respiratory distress syndrome and multi-organ dysfunction syndrome and died on June 24th. There were no close contacts with severe illnesses that were reported.

The second case that was identified during this time in September when MERS came to light was a 49- year-old Qatari national who had onset of illness September 3rd with mild respiratory symptoms.

On September 9th there was admission to a Qatar hospital with bilateral pneumonia and subsequent intubation.

And on September 12th the patient was admitted to a London intensive care unit with respiratory failure and renal failure. The patient became fully dependent on ECMO. And his - this patient had a history of travel to Saudi Arabia July 31st to August 18th, where was noted to have upper respiratory infection symptoms along with traveling companions, but this resolved.

The patient was known to have a history of farm exposure including camels and sheep but no history of direct contact with these particular animals. This information is found in Euro Surveillance, October 4th.

The management of the second case included airborne precautions, and close contacts were monitored for at least 10 days. There were 64 contacts identified among healthcare personnel, family and friends. No severe acute respiratory illnesses were identified. And 13 healthcare personnel with mild respiratory symptoms, and 10 of which were found to be negative for MERS-CoV.

What was the link between these two cases? Viruses isolated from these two cases were compared to each other. And there was 99.5% identity with the one nucleotide mismatch over regions that were sequenced and compared.

This is a phylogenetic tree of the Middle East Respiratory Syndrome Coronavirus. And as you can see in the beta coronavirus C lineage the MERS coronavirus is most closely related to two bat coronaviruses, HKU4 and HKU5.

This is the timeline of events that occurred concerning MERS coronavirus. We talked about the identification of the two cases in September but retrospectively identified were two fatal cases from a - associated in time with respiratory illnesses described among healthcare workers in April 2012 in Jordan. These cases were retrospectively identified from specimens that were held and saved.

Then the recognition of the MERS coronavirus after the comparison of viruses from the two cases I just described. And I’m going to talk about summaries of events that happened since September 2012 including the first family cluster in Saudi Arabia, November 2012, followed by a United Kingdom family cluster that occurred in February, 2013, an imported United Arab Emirates case into Germany, March 2013, a healthcare facility cluster in Saudi Arabia beginning in April 2013, and a healthcare facility cluster in France, May 2013.

First the Saudi Arabia household cluster - and this is found in Memish ZA et al. in New England Journal, May 29 - a cluster of four respiratory illnesses in a family who lived in an apartment, all males age 16 to 70 years old. All were hospitalized, and three of four were confirmed with MERS-CoV. Three of four patients were found to have gastrointestinal symptoms including diarrhea, abdominal pain and anorexia. And two of the four patients died.

Notably, patient one had a positive bronchial lavage specimen. Patients two and four were found to have positive sputum specimens for this MERS coronavirus.

Patient three’s illness was milder, and no respiratory tract specimens were available. Upper respiratory tract swaps from this patient were found to be negative.

This is a timeline from the same New England Journal article that depicts cases one, two, three and four in time.

There were 124 healthcare workers who remained healthy as of January 2013 that were close contacts of these particular patients.

The exposures of these patients along with different family exposures could have also included hospital exposures as family members took care of other family members.

The Jordan cluster which I mentioned was - these cases were retrospectively identified after the first identification of the MERS coronavirus. And this is from Hijawi et al. in the East Mediterranean Health Journal.

These were two confirmed cases that were reported. And both cases were fatal. One was a healthcare worker and one was not. They occurred at the same time as a cluster of severe respiratory illnesses among healthcare workers at that time associated with a healthcare facility. The total number of illnesses described at that time in that outbreak - it was 13.

The United Kingdom cluster, which was reported in Euro Surveillance by the Public Health England, was an index case who had traveled from Saudi Arabia and Pakistan who had an onset January 24th, 2013. This patient had severe respiratory illness. Later was found that there was transmission to a second patient who had onset February 6th, 2013 and died, and a third patient who had onset February 5th, 2013 who had mild illness and recovered.

This is a timeline from the same Euro Surveillance article. In green you can see when each patient was clinically well, in yellow when the patients were first - had onset of symptoms and were mildly ill.

In orange when two of the three patients were hospitalized and ventilated in intensive care, and red depicts ECMO. The first indexed patient -- this is not depicted on this chart -- subsequently died, as did case two. Case three was described as a mild illness.

Notably contact with case one traveling to and from a family home was the exposure for case two to case one. Also case number three’s contact with case number one included visiting in the hospital.

Public health implications for this United Kingdom cluster was this was really the first clear evidence of person-to-person transmission since the index patient had a history of travel, but case two and case three did not and had exposure to the index patient.

Also there was evidence of coinfections. There was coinfection with influenza in the index case. And both secondary cases also had Parainfluenza type 2.

There were no sustained chains of transmission that were identified. And the incubation period was estimated to possibly be between one and nine days.

Moving on in time to the nosocomial transmission in France, we’ll start with the index patient. This is published in Guery et al. in Lancet 2013.

The index patient was a 64-year-old man who had returned from travel to Dubai five days earlier. This patient had a history of renal transplantation and had onset of symptoms that were described as diarrhea, fever and chills.

An abdominal CT showed pulmonary infiltrates two days after onset. Then the patient developed a cough and dyspnea four days after onset. The initial nasal pharyngeal swab was deemed negative but a bronchoalveolar lavage specimen was positive.

The patient subsequently had respiratory failure, renal failure and death 36 days after onset of illness.

Patient two was - is a 51-year-old man with history of myocardial infarction, arterial hypertension and steroid therapy for histamine-induced angioedema.

This patient also had a history of several episodes of deep venous thrombosis.

He shared a hospital room with the index patient during day four to seven of the index patient’s illness.

The index patient was mostly confined to the bed while patient two was described as moving around.

These two patients shared a bathroom. The nasal pharyngeal swabs from patient two were inconclusive; however, induced sputum was positive for MERS-CoV.

Notably there were no aerosolizing procedures performed for the index patient. And at the time that these two patients shared a room there was no suspicion of MERS-CoV.

These are radiographs, more examples of radiographs from patient two. A is - shows consolidation of the right upper lobe one day after onset of illness.

The B panel is four days after onset of illness, shows the ground-glass opacity and consolidation of the left lower lobe. And panel C and D bilateral ground-glass opacity of consolidation seven and nine days after onset of illness respectively.

This is a timeline of the French cluster from the same article. In red, the heavy red line is the exposure period between the index patient and patient two, and the notable clinical timeline for some of what I just went over.

The French cluster, the public health implications included this was nosocomial transmission. The initial presentation of the index patient was without respiratory symptoms.

The incubation period was estimated to be up to possibly nine to 12 days. And lower respiratory tract specimens may be preferred samples for detection of MERS-CoV, although this is a small sample size.

The MERS coronavirus outbreak in Saudi Arabia, the cluster that was described in April and May of 2013, occurred in the Al-Ahsa Governorate in the Eastern region of the country.

This cluster is still currently being investigated. Including 25 confirmed cases and 14 confirmed deaths, 18 males, seven females ages 14 to 94 years and a median age of 58.

Initial cases were known to be associated with one hospital but now also what has been reported has included family contacts, healthcare workers and some cases with no link to the hospital.

Most of the cases reported in this cluster have been reportedly having comorbidities.

Now the MERS-CoV overall epidemiology has been at approximately 50% mortality rate - onsets between April 2012 and May 29, 2013 from the cases in Jordan to some more recent onset.

The median age over - from the overall epidemiology is 56 years including two pediatric cases reported. There is a male predominance of cases. And most cases that have been reported have been people who have had comorbidities.

These are old numbers, but as of the end of last week there were 40 Saudi Arabia cases - 40 cases reported from Saudi Arabia, three from the United Kingdom, two from Jordan, two from Qatar, one from United Arab Emirates, two from France, two from Tunisia and three from Italy.

Three were returning travelers and three medical transfers. And I would like to stress these are numbers as of June 7th.

This is a map showing confirmed cases of MERS-CoV, again a number from June 7th, n equals 55, and history of travel from the area of the Arabian Peninsula, depicting where cases are in red, cases associated with a cluster, in green cases not associated with a cluster, and in blue cases that were reported from the Saudi Arabia cluster from the Eastern province in that country.

And you can see by the dotted lines travel history associated with cases occurring outside of the Arabian Peninsula in neighboring countries and seeing the either direct or indirect relationships between cases from the four countries of Jordan, Saudi Arabia, Qatar and the United Arab Emirates.

This picture is just to depict that case reports have increased in the last couple of months. This is an epidemic curve of month and year of onset.

Moving on to the CDC case definition, for a patient under investigation - it’s a person who has an acute respiratory infection which may include fever of more than or equal to 38 degrees centigrade or 100.4 degrees Fahrenheit and cough, and suspicion of pulmonary parenchymal disease such as pneumonia or acute respiratory distress syndrome based on clinical or radiological evidence of consolidation, and history of travel from the Arabian Peninsula or neighboring countries within 14 days.

This has recently been a change from the MMWR of June 7 to go from a possible exposure period of 10, to 14 days based on more recent data.

Also, not already explained by any other infection or etiology including all clinically indicated tests for community-acquired pneumonia according to local management guidelines however ruling out other etiologies should not slow - should not slow potential testing.

In addition, persons who develop severe acute lower respiratory illness of known etiology within 14 days after travel from the Arabian Peninsula or neighboring countries but either do not respond to appropriate therapy or do not fit the clinical picture should still be considered for testing for MERS-CoV.

In addition, persons who develop severe acute lower respiratory illness who are close contacts of a symptomatic traveler who developed fever and acute respiratory illness within 14 days after travel from the Arabian Peninsula or neighboring countries.

A close contact is defined as any person who provided care for the patient including a healthcare worker or a family member or a similarly close physical contact; any person who stayed at the same place, lived with or visited, as the patient while the patient was ill.

So surveillance could include an index patient who has within a 14-day history of travel to the Arabian Peninsula or neighboring countries, who has severe acute respiratory infection. Or potentially a close contact such as a household contact who - where the index patient had an acute respiratory infection, may or may not have been hospitalized, who has the travel exposure, and the first patient picked up, is a severe acute respiratory infection patient who came in close contact with the traveler.

All surveillance is aimed at severe acute respiratory infections in persons indirect - directly or indirectly associated with the Arabian - travel to or from the Arabian Peninsula or neighboring countries.

In addition, a probable case is any person who meets the clinical criteria that we described and is a close contact with a laboratory-confirmed case and also has illness not already explained by another infection or etiology, or any severe acute respiratory illness with no known etiology and an epidemic link or close contact to a confirmed MERS-CoV case.

And a confirmed case is a person with laboratory confirmation of infection with MERS-CoV.

Dr. Alexander Kallen:
Thanks. This is Alex Kallen. I’m now just going to briefly review what we have available as our interim infection prevention and control recommendations for hospitalized patients.

So as a kind of summary to get to the bottom line first we’re currently recommending standard, contact, and airborne precautions for the management of hospitalized patients with known or suspected MERS- CoV infection.

These recommendations are consistent with those recommended for the coronavirus that caused severe acute respiratory syndrome, SARS. And as information because available these recommendations will be re-evaluated and updated as needed.

These recommendations are for hospitalized patients who meet the case definition and are based at this point on the following issues:

First is the relatively poorly characterized clinical signs and symptoms, as well as a suspected high rate of mortality and morbidity associated with infected patients.

The second is the unknown modes of transmission of MERS-CoV as it stands now.

Next is a lack of a vaccine or chemoprophylaxis. In addition, the evidence of limited, not sustained, human-to-human transmission. And at this point the absence of confirmed or probable MERS-CoV cases in the United States.

As far as patient placement this would require the use of Airborne Infection Isolation Rooms (AIIR). If an AIIR is not available the patient should be transferred as soon as feasible to a facility where an AIIR is available.

Pending transfer, a face mask should be placed on the patient for source control, and they should be isolated in a single patient room with the door closed.

The patient should not be placed in a room where room exhaust is recirculated without high-efficiency particulate air or HEPA filtration. Once in the AIIR the patient’s facemask may be removed. But when outside of the AIIR patients should wear a facemask to contain secretions.

While the patient is hospitalized efforts should be made to limit the transportation and movement of the patient outside of the AIIR to medically essential purposes. And staffing policies should be implemented to minimize the number of persons who must enter the room.

Personal protective equipment for healthcare personnel would include gowns, gloves, eye protection which include - could be goggles or face shield and respiratory protection that is at least as protected as a fit tested NIOSH-certified disposable N95 filtering facepiece respirator.

PPE should be worn by healthcare personnel upon entry into a patient room or care areas. And upon exit from the patient room or care area the PPE should be removed and either discarded or, for reusable PPE, cleaned and disinfected according to the manufacturer’s reprocessing instructions.

For environmental infection control, at this point we’re recommending that you follow standard procedures per your hospital policy, and the manufacturer’s instructions for cleaning and disinfection of environmental surfaces and equipment, textiles and laundry, and food utensils and dishware.

And now I’ll turn it over to Dr. Gerber to continue her talk.

Dr. Susan Gerber:
Moving on to laboratory testing, lower respiratory tract specimens, such as sputum, bronchoalveolar lavage and endotracheal specimens, are a priority respiratory specimen for real-time reverse transcription polymerase chain reaction or RT-PCR testing.

Respiratory specimens -- and this would also include upper-tract specimens and stool and serum specimens are also recommended to be collected.

Importantly specimen collection at different times may be important. There is still incomplete information about shedding of virus from different sites at different times for several patients. So we recommend different time points including when initially to rule out that possibly at other points in time.

In addition there has been an Emergency Use Authorization. The FDA issued this Emergency Use Authorization or EUA on June 5th, 2013, to authorize use of CDC’s “Novel coronavirus 2012 real-time reverse transcription-PCR assay” to test for MERS-CoV in clinical respiratory, blood, and stool specimens.

This assay has and will be deployed to lab - the Laboratory Response Network or LRN Laboratories in all 50 states over the coming weeks.

This is a depiction of a coronavirus genome with the different genes evidenced by the E gene and nucleocapsid gene and N.

This slide is courtesy of Dean Erdman at CDC which describes an algorithm for testing for the coronavirus by reverse transcription, real-time reverse transcription-PCR which includes first using gene targets aimed at the E gene in a nucleocapsid gene. And then there’s another nucleocapsid gene for comfort that’s considered a confirmation assay - not to go over this entire slide but multiple gene targets being positive for a case to show that a case was positive.

These are electron micrographs of this virus. And you can see the small round circles. And in this particular picture you can see the circle with projections or spikes that are an important protein for attachment to cells for this virus.

There is work in approach to serology at CDC which includes identifying and generating candidate coronavirus antigens using proteins from similar bat viruses in the C lineage of the beta coronavirus - viruses.

This approach includes developing an ELISA-based assay and to - and evaluating this assay and other assays with an extensive panel of negative for specificity and positive sera for sensitivity.

In addition there has been described by Annan et al. in Emerging Infectious Diseases recently of bats that have had similar sequences to the MERS coronavirus. And these bats were located in Ghana and Eurasia. However there is no known reservoir for this MERS-CoV and there are no known animal intermediate hosts at this time.

There have been no vaccines developed as of yet. There are no antivirals identified as of yet but research continues. Currently treatment is supportive.

A snapshot of where we are for MERS-CoV says that the virus may cause mild to severe illness. There has been evidence of person-to-person transmission and nosocomial spread with healthcare personal transmission.

There has been a focus in the Arabian Peninsula and of the reported cases thus far there’s approximately a 50% mortality rate. There have been no cases identified in the United States as of yet.

In conclusion the MERS coronavirus is a different virus than the SARS coronavirus but it is also virulent. There have been more reported cases in the past two months, and persons with underlying health conditions may be at increased risk of disease and may also be at increased risk of transmission.

Continuing issues for the MERS coronavirus include human surveillance for additional cases, availability of laboratory diagnostics. And this would include both PCR and serologies to determine new cases that could be identified and control the transmission addressed quickly.

In addition when an antibody is properly valid - an antibody assay is properly validated serologic assays are needed to describe more of the epidemiologic features of these viral infections.

In addition surveillance for severe acute respiratory infections is important to find a first case and to understand where cases are and not to - and to be able to control transmission by effective infection control precautions as soon as possible.

There is also a need for more investigations to understand human-to-human routes of exposure through more epi-studies.

In addition animal surveillance must continue to potentially identify an animal reservoir for this virus. Many coronaviruses are related to - many coronaviruses are from animals. And perhaps to identify a possible intermediate host.

In addition more work needs to be done on geography and understanding where this virus is coming from and possible - to be on alert for new geography that may be relevant for this virus.

In addition management of patients under investigation, ruling out other etiologies, however for patients under investigation that may be under a high index of suspicion, ruling out other etiologies should not slow the testing for this MERS coronavirus. Also implementing infection control precautions quickly and effectively. And lastly more research on therapeutics is needed to - for both antivirals and vaccines. Thank you.

Leticia Davila:
Thank you, Dr. Gerber and Dr. Kallen, for providing our COCA audience with such a wealth of information. As a reminder Captain Francisco Alvarado-Ramy from CDC is available to answer any questions you may have. We will now open up the lines for the question and answer session. Please remember that questions are limited to clinicians who would like information on MERS-CoV. For those who have media questions, please contact CDC Media Relations at 404-639-3286 or send an email to media@cdc.gov.

We do have some questions that have come through the Webinar system. The first one is what types of comorbidities are common overall?

Dr. Susan Gerber:
Hello, I’ll take that question. We don’t know all the comorbidity information from all of the cases that have been reported thus far. However some comorbidities have included the renal transplantation, malignancy, steroid therapy, and renal failures. However I can stress that we don’t yet have information on all reported cases and all of their comorbidities.

Leticia Davila:
Thank you. One more question. Is there any testing done yet on the viability of the virus outside of the body on surfaces?

Dr. Susan Gerber:
There is no published data on the environmental properties or how long this virus can exist on surfaces. There may be other factors such as pH, temperature, quality of the surface. But there is no real definitive data on this yet.

Leticia Davila:
Thank you. Operator?

Coordinator:
The first question that I have comes from (Archer Cleat DiGiovanni). Your line is now open.

(Archer Cleat DiGiovanni):
Hi. This is (Cleat DiGiovanni). Question in confirmed cases thus far studied has this virus been identified in upper-respiratory tract specimens?

Dr. Susan Gerber:
Yes. There have been nasal pharyngeal swabs that have been positive for this virus. There have been instances where lower tract specimens were positive and nasopharyngeal swabs were negative. But the virus has been detected in upper-respiratory tract specimens as well. And both upper and lower- respiratory tract specimens are recommended to be collected at this time, especially while we are trying to find out more data concerning viral detection from different specimen types at different times.

(Archer Cleat DiGiovanni):
Thank you.

Coordinator:
The next question comes from (Maria). Your line is open.

(Maria):
Hi. My question is we deal with a population of military personnel, and we did have a group of folks that were there within the past several months, returned in May.

I realize the effort now is for control measures in identifying current cases. Is there any effort - worth doing anything in terms of surveying these individuals to see if they had any related sicknesses while they were in that area?

Dr. Susan Gerber:
That question can be answered by, as serologic assays are developed and validated - we’re working on serologic assays here at CDC, but they still need to be validated with more specimens that, more positive from - more specimens from patients who are positive to evaluate sensitivity.

And a validated serologic assay would be very useful to - in different populations such as the that one you described where there might have been respiratory illnesses in the remote past.

So that would be an approach. And if serologic assays become validated and are available these are some of the questions that can be potentially more readily answered.

(Maria):
Thank you.

Coordinator:
The next question comes from (Maureen Balu). Your line is open.

(Maureen Balu):
Hello. My name is (Maureen Balu). And I’m a staff nurse in an emergency department. And I just wanted to ask you a question. It sounds like a number of people who presented, although this is a primarily respiratory disorder, a few of the people it sounds like 25% had diarrhea. I was just wondering did anybody - did any of these cases present them initially with nausea and vomiting, diarrhea, and then later develop the respiratory symptoms?

Dr. Susan Gerber:
Hello, there was one case described by the public health agency in France that I presented of a patient who had an underlying history of renal transplantation whose initial symptoms were diarrhea and GI symptoms without apparent respiratory symptoms.

However we do not know of the - of gastrointestinal symptoms described for every patient who has been reported, and we don’t have information concerning the initial onset of symptoms and what they are for all the patients.

So we’re missing a lot of data to really understand what percentage of patients have gastrointestinal symptoms upon presentations or what percentage of patients do not have apparent respiratory symptoms on initial presentation.

But the - this case has been described. And it may be important to note there might be unusual initial presentations of this virus infection especially perhaps in patients who have underlying illnesses.

(Maureen Balu):
Thank you very much.

Coordinator:
If anyone else would like to ask a question please press *1 on your touch-tone phone.

Leticia Davila:
We do have a couple of questions coming from the Webinar system as we wait for more callers to join on the line. What are the exposures that have been identified in sporadic cases? Is there surveillance data from animals? Surveillance data from ILI cases in KSA?

Dr. Susan Gerber:
First, animal data, there is no - there are no positive results or no published results of extensive animal surveys as of yet.

Those investigations we are aware are ongoing. And in the terms of Influenza-Like Illness or ILI investigations, not - I am not aware of any published data that reflect those kinds of studies. But animal investigations are currently ongoing.

Leticia Davila:
Perfect. Thank you. We have another one. For confirmed patients who have recovered is there consideration for using - I’m sorry this is - I’m not familiar with this terminology – (IGG) from the patients to support the most critically ill acute patients?

Dr. Susan Gerber:
In terms of - I think that’s a question about therapeutics or can therapeutic - can unconfirmed cases of - of antibodies can be used, this would have to be experimental. And there is not a lot of knowledge about this as of yet.

Leticia Davila:
Thank you. Operator?

Coordinator:
Thank you. I do have several questions. The first one is from (Hira Nakasi). Your line is open.

(Hira Nakasi):
Thank you. This is (Hira Nakasi) from FDA. Can you hear me?

Dr. Susan Gerber:
Yes.

(Hira Nakasi):
Okay. So the question I have is was there any attempt made to look at the blood samples from these patients especially when you mentioned there is an asymptomatic period of between nine to 14 days.

So the question therefore especially for us for blood safety if there’s a person who’s got this infection exposed and is asymptomatic for nine to 12 days or 14 days and can they donate blood and then can cause transmission?

Dr. Susan Gerber:
First the 14-day window of how we’re doing surveillance, we’re now referring to as a potential exposure period. We’re looking at exposures within 14 days to possibly travel to the Arabian Peninsula or neighboring countries. The incubation period when we - could be anywhere, has been estimated anywhere from one to 12 days, and we need more information to understand - some - we need more epidemiologic information to really understand the incubation period.

Secondly in terms of transmissibility we have no evidence that people are transmissible before they have symptoms. So far the evidence points to transmissibility while patients are symptomatic, although that information is limited at this time.

(Hira Nakasi):
I see. So the question really if I can ask that it be in follow-up question, I just want to make it clear myself, so between one to 12 days which you think it may be an incubation period was there any (varinia) in the blood or was it tested or attempted to be tested or something like that?

Dr. Susan Gerber:
There have been blood specimens that have been positive for this virus. But we really lack a lot of data to understand how common and during what time we - actually shedding is identified.

But this is after people are already symptomatic...

(Hira Nakasi):
Okay.

Dr. Susan Gerber:
...and have the disease are their specimens positive.

So far there is no published - published information of PCRs or positive bloods that - where there is an RNA detection from PCR that are positive in someone who is completely asymptomatic. There’s no information at this time.

(Hira Nakasi):
Thank you.

Coordinator:
The next question that comes from (Alvaro Mehale). Your line is open.

(Alvaro Mehale):
Thank you. I have actually two questions but the first one is I think I missed any possible discussion that you have had about therapeutics for this infection. Have any antivirals been tried in this infection?

And the second is just an administrative question, are these presentations going to be available for the audience?

Dr. Susan Gerber:
The first question is about therapeutics and antivirals. They’re starting to be investigations to look at potential antivirals.

There are no known antivirals recommended for this viral infection. Information - there is some information from some studies looking at cells, and - but there’s no information about humans and antiviral trials at this time. And I believe this information is available.

(Alvaro Mehale):
So I was just curious so as far as we know the neuroaminidase inhibitors haven’t been tried or there’s no possibility that they would work in this infection?

Dr. Susan Gerber:
Right now there are investigators looking at different potential anti - different therapeutics with antiviral properties such as interferon and ribavirin, for example. But right now there are no known recommendations for particular antivirals. This is all experimental.

(Alvaro Mehale):
Thank you very much.

Leticia Davila:
And I can let you know for the PowerPoint slides they’re available right now at emergency.cdc.gov/coca, C-O-C-A. And you can just follow the call links.

(Leticia Davila):
And also we do have a question on the Webinar system. This is for Captain Alvarado-Ramy. What advice does CDC have for travelers to the Middle East?

Captain Francisco Alvarado-Ramy, MD:
Yes. The CDC Travelers’ Health Web site has three types of travel notices. The travel notice currently posted for travel to the Middle East is the lowest notice level, called a Watch. And it was first posted back in October of 2012. This travel notice essentially says that CDC does not recommend that anyone change their travel plans because of these cases of MERS coronavirus. CDC does recommend that U.S. travelers to countries in or near the Arabian Peninsula monitor their health for two weeks. These travelers should see a physician if they develop fever and symptoms of lower respiratory illness as Dr. Gerber has mentioned, such as cough or difficulty breathing. And if they seek medical attention they should tell their physician - their clinician about recent travel to the region.

Leticia Davila:
Thank you. Operator?

Coordinator:
And the next question comes from (Kerry Berger). Your line is open.

(Kerry Berger):
Hello. The reason why I am calling - I’m from Lehigh Valley Health Network in Pennsylvania. I’m curious to know whether or not you believe that we should begin active screening in all our emergency departments? Do we have a strong sense that this will impact the U.S.? And if so do we have a guesstimate of a timeframe?

Dr. Susan Gerber:
Right now our surveillance recommendations center on trying to identify a patient who has severe acute respiratory infections that are typically cough and fever with pneumonia, and often these patients are hospitalized, plus a travel link from the Arabian Peninsula or neighboring countries.

We’re trying to identify that the - that particular travel epidemiologic history with severe infections. So we’re trying to target individuals who may become ill and fit into those categories.Trying to alert clinicians and public health departments to looking for these features as an astute clinician would be important in possibly identifying a first case.

(Kerry Berger):
So just to piggyback on that, we had put our clinicians on alert more recently prior to this for H7N9 for travelers to China. But it would appear at this point that your concern is much more elevated with the transmissibility for this particular infection. Am I correct?

Dr. Susan Gerber:
Well I’m not comparing H7N9 to MERS-CoV. And really this discussion is just about this new coronavirus, MERS-CoV. And we are concerned that we identify a case if one is in the United States. And timing of that would be important so that infection control recommendations could be recognized, to be implemented and a patient who is potentially infected tested readily. But it is concerning and it is important that we’re reaching out to both healthcare providers and public health entities.

(Kerry Berger):
Okay thank you.

Coordinator:
The next question comes from (Lucy). Your line is open.

(Dan Lucy):
Hi. This is (Dan Lucy) calling from Georgetown University. And I wanted to ask two related questions. One is how many patients are the CDC aware of who’ve had an incubation period between 11, 12 or 13 or 14 days if it was more than 10 days?

Dr. Susan Gerber:
Hi. We do not have incubation period - well it’s difficult to calculate incubation periods especially for these sporadic cases because we don’t yet understand the exposures.

Our best source of possible incubation periods comes from the study of clusters or transmission from person to person.

What we do know, what has been published, has been one to nine days from the United Kingdom cluster, and upwards for an upper limit of nine to 12 days for the French transmission in the healthcare facility.

However there is a large potential exposure period anywhere from one to possibly 12 days, but we need more information and more epidemiologic data to understand what are more - what the most typical incubation period would be like. It may be more like five to six days, for example. But we need more information. And hopefully as these investigations progress elsewhere we will be getting more epidemiologic investigations that could help inform more information about incubation periods.

(Dan Lucy):
Okay. If I could just quickly ask a follow-up related question and if I understand correctly June 7 CDC modified their recommendations for surveillance purposes to extend that to 14 days people for example had been traveling to the Arabian Peninsula. Is that correct?

Dr. Susan Gerber:
Yes. We originally suggested 10 days. And these are all interim recommendations that I would like to stress that these surveillance recommendations for who to test and how to do surveillance are current - are continuously being updated.

So it’s important to check our Web site. And we did just change from 10 to 14 days based on some of the upper limits of potential incubation periods and wanting to go a bit beyond to actually ensure that we identify a potential case quickly and that especially and make sure our case definition for surveillance or how we approach doing surveillance is broad enough that we will include all potential cases.

(Dan Lucy):
Right I think it’s a good idea. And the last related question, why not include Egypt or other parts of the Middle East other than just the Arabian Peninsula and the total of 14 countries that’s a better name in the CDC Web site.

Now the May 18th WHO surveillance recommendations speak of a – I’m just reading that if the person has a history of travel to the Middle East within 10 days before onset of illness, unless another etiology has been identified. And then they have a map of the Middle East which, you know, obviously includes Egypt for example.

So with so many people traveling back and forth every day between Saudi Arabia and Egypt why isn’t the CDC including Egypt as one of the 14 countries?

Dr. Susan Gerber:
Well right now all the cases that have been reported have either a direct or an indirect link to four countries, which are Jordan, Saudi Arabia, Qatar, and the United Arab Emirates. So the data that we have is that all cases as I said are either directly or indirectly linked to those countries so far. And how we have structured travel is looking at those countries and neighboring countries. However as we actually get more data, more investigation is done, that could potentially change. But at this moment that is information that we have.

(Dan Lucy):
Thank you for your comments ma’am.

Coordinator:
The next question comes from (Lory Rubin). Your line is open.

(Lory Rubin):
Hi. This is (Lory Rubin). I work in a Children’s Hospital in a New York metropolitan area. And so my question is do you think that putting in some sort of a screening in our emergency department for patients arriving is warranted at this time given there’s been no cases in the U.S.? And if so what would be the trigger to for example to ask about a travel history?

Dr. Susan Gerber:
First I think it’s important to get a travel history especially for any severe or acute respiratory infections in patients who may enter in an emergency department. Actually ensuring that good travel histories are performed and asking about travel not only in - for the patient within 14 days but also let’s say in close contacts such as households, and if there are any travel in households within 14 days or acute respiratory infections associated with travel.

These are important epidemiologic questions to ask for any severe acute respiratory infections that could actually present at an emergency department. So it’s collecting epidemiologic information that could be important for our surveillance guidance. And I think that that is important way to find case potential cases that may need to be tested.

(Lory Rubin):
All right thank you. And but for the child or adult that for example would meet criteria for an ILI, an Influenza-Like Illness, you know, fever plus cough or sore throat sort of thing, that would be a possibly more sensitive test but very much less specific to then go and get additional history. And I sort of get the sense that probably going using that as criteria is probably not warranted at this time rather sticking with a more severe respiratory syndrome with lower respiratory tract involvement?

Dr. Susan Gerber:
Right now we don’t have any cases in the United States. And right now looking at cases reported there have been mildly ill cases that have been confirmed as being positive for MERS-CoV. The majority of patients identified so far have had severe acute respiratory infections.

Right now our surveillance is focused on severe acute respiratory infections or illnesses. However as data changes or the situation changes it could be different in the future. But right now we don’t have cases and our information suggests that right now this is what we would recommend.

(Lory Rubin):
Thank you.

Leticia Davila:
Operator, do we have any more questions on the line?

Coordinator:
Yes. Our next question comes from (Gides Jomodi). Your line is open.

(Gides Jomodi):
Yes. I want to know whether the emergency rooms in the United States are equipped to detect the MERS-CoV if we have a severe case of respiratory illness?

Dr. Susan Gerber:
Our assays, our real-time reverse transcription PCR assays are becoming more widely available throughout the United States. And this will enable more jurisdictions to be able to test for this virus particularly at health department - at state health department labs and also LRN labs.

So there are more widely available laboratory resources. And if a clinician feels a patient should be tested who presents with severe - with the relevant traveler epidemiologic history as severe acute respiratory infection symptoms and there is no other explanation or there is a high index of suspicion, that patient could be tested. And also if there are any questions, we at CDC are available to answer questions as they come up about testing and surveillance recommendations.

(Gides Jomodi):
Thank you.

Coordinator:
open.

(Robert Vall):
Yes Dr. (Robert Vall), Medical University of South Carolina. Question was asked and answered regarding travel history. Thank you very much also for making the slides available.

Coordinator:
And the next question comes from (Lee Chapman).

(Lee Chapman):
Yes you able to share an estimate number of patients ruled out in the United States and if so is that information available geographically?

Dr. Susan Gerber:
Right now we have calls and assisting state and local public health departments with potential cases, but we haven’t had any cases to date. We have assisted in providing negative results as we have no confirmed cases in the United States with some jurisdictions. In other jurisdictions we’ve been able to answer questions without testing so it has been both, you know, in terms of all of the inquiries that we’ve received.

(Lee Chapman):
Okay great.

Dr. Susan Gerber:
But we have been steadily receiving inquiries since the identification of this virus in September and October of 2012.

(Lee Chapman):
Okay. Thank you very much.

Coordinator:
Okay. Our next question the person did not record their name. So if you did queue up for a question your line is open at this time.

If you did queue up for a question please check your mute feature. Your line is open but I did not get a name.

Again at this time if you do have a question from the phone you may press *1 on your touch-tone phone.

(Leticia Davila):
Operator we will take one more question if there’s a question on the line.

Coordinator:
Okay. I am showing no questions at this time.

Leticia Davila:
Okay, thank you. On behalf of COCA I would like to thank everyone for joining us today with a special thank you to our presenters, Dr. Gerber, Dr. Kallen and Captain Alvarado-Ramy.

If you have additional questions for today’s presenters please email us at coca@cdc.gov. Put June 13 COCA Call in the subject line of your email and we will ensure that your question is forwarded to the presenters for a response.

Again that email address is coca@cdc.gov. A recording of this call and transcript will be posted to the COCA Web site within the next few days.

There are no continuing education credits for this call. MERS-CoV resources for clinicians are available on the COCA call Webpage. Go to emergency.cdc.gov/coca. Click COCA Calls and then follow the links to the MERS-CoV call.

To receive information on upcoming calls subscribe to COCA by sending an email to coca@cdc.gov and write Subscribe in the subject line. CDC launched a Facebook page for HealthPartners.

Like our page at Facebook.com/cdc healthpartnersoutreach to receive COCA updates.

Thank you again for being a part of today’s COCA call. Have a great day!

Coordinator:
Thank you. And that does conclude today’s conference and parties may disconnect at this time.

END

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