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- 1. Middle East Respiratory Syndrome – Coronavirus (MERS-CoV) PREPARED BY : EMMA LYNN R. MILLENA R.N.
- 2. First Reported Case • 60 year old Saudi man • Presented on June 13th with 7d h/o fever and cough; recent shortness of breath • Increasing blood urea nitrogen (BUN) and creatinine, starting day 3 of admission • White cell count normal on admission(but 92.5% neutrophils) and increased to a peak of 23,800 cells/cumm on day 10 with neutrophilia, lymphopenia, and progressive thrombocytopenia Zaki et al. N Engl J Med 2012 367:1814-20
- 3. First Case: Chest Radiographs A: On admission Zaki et al. N Engl J Med 2012 367:1814-20 Bilateral enhanced pulmonary hilar vascular shadows (more prominent on the left) and accentuated bronchovascular lung markings. Multiple patchy opacities in middle and lower lung fields Opacities more confluent and dense B: 2 days later
- 4. First Case Outcome • Patient developed acute respiratory distress syndrome (ARDS) and multiorgan dysfunction syndrome • Died June 24th • No close contacts with severe illnesses reported Zaki et al. N Engl J Med 2012 367:1814-20
- 5. Second Case Eurosurv, Vol. 17:40,Oct. 4, 2012 • 49 year old Qatari national • Timeline: Onset of illness Onset of illness September 3rd with mild respiratory Sx September 9th- admission to Qatar hospital with bilateral pneumonia- subsequent intubation September 12th admitted to London ICU with respiratory failure and renal failure • Fully dependent on ECMO(extracorporeal membrane oxygenation) • History of travel to Saudi Arabia July 31- Aug. 18, where noted to have URI symptoms (and traveling companions) • History of farm (camels and sheep) exposure, but no history of direct contact with these animals
- 6. Second Case: Management Eurosurv, Vol. 17:40,Oct. 4, 2012 • Airborne precautions • Close contacts monitored for at least 10 days • 64 contacts identified among healthcare personnel (HCP), family, and friends No severe acute respiratory illnesses identified 13 HCP with mild respiratory symptoms 10 HCP negative for MERS-CoV
- 7. Background • Middle East respiratory syndrome (MERS)? MERS is a viral respiratory disease caused by Coronavirus Most people confirmed to have MERS-CoV infection developed severe acute respiratory illness is related to but is not the same as SARS First identified– late 2012 in Saudi Arabia About 30% of people confirmed to have MERS-CoV infection have died. April 30, 2014 2 MERS virus - Image from CDC.gov
- 8. Quick Factoids Middle East respiratory syndrome (MERS)? Mortality has been decreasing 75% of recent cases are in the health care setting 75% are secondary transmissions Only 2 cases known to be tertiary o Anecdotally more Season spike is expected April 30, 2014 2 MERS virus - Image from CDC.gov
- 9. Infection and Transmission • Infectious Period Not clearly established Likely to extend from the onset of fever until 10 days after fever resolves • Incubation Period Symptoms occurred up to 14 days after last exposure
- 11. • Zoonotic Dromedary camel play impt role to human transmisssion o Viral RNA isolated from nasal/fecal specimens o MERS-CoV remains infectious beyond 72 hours after introduction in unpasteurised camel milk Infection and Transmission • Human-to-human Nosocomial transmission o Hemodialysis unit, intensive care unit, medical ward. Risk of community transmission has increased as more human-to-human transmission has been observed. No large numbers of secondary infections among HCP household contact after close monitoring
- 12. • Airborne • The following have been observed: • Can transmit from human to human Seen as clusters and sporadic cases Not sustained Transmission between close contacts Transmission from infected patients to healthcare personnel • Remains stable as an aerosol and at a low temp Infection and Transmission
- 13. Disease Spectrum • Multiple reports of mild disease and asymptomatic • Initial symptoms may not be respiratory o Fever , Cough o Shortness of breath, Myalgia • GI illness can be prominent o Diarrhea, Vomiting o Abdominal pain • Some cases have had atypical presentations: o Initially presented with abdominal pain and diarrhea and later developed respiratory complications
- 14. Comorbidities • Diabetes • Hypertension • Chronic cardiac disease • Chronic renal disease • Co-infection with other respiratory viruses and a few cases of co-infection with community-acquired bacteria at admission has been reported; nosocomial bacterial and fungal infections have been reported in mechanically- ventilated patients TheLancet.com Published Online 7/26/13
- 15. Watch for these symptoms: • Fever (38°C or higher) Take your temperature twice a day. • Coughing • Shortness of breath • Other early symptoms to watch: chills, body aches sore throat, headache, diarrhoea, nausea/vomiting, and runny nose.
- 16. Patient Under Investigation (PUI) Any PUI should be reported to state and local health departments immediately PUI Criteria: 1. Acute respiratory infection, may include fever ≥ 38°C and cough AND 2. Suspicion of pneumonia or acute respiratory distress syndrome based on clinical or radiological evidence AND 3. History of travel to the Arabian Peninsula or neighboring countries within 14 days AND 4. Symptoms not already explained by any other infection or etiology
- 17. Patient Under Investigation (PUI) The following persons may be considered for evaluation of MERS-CoV: Persons who develop severe acute lower respiratory illness of known etiology within 14 days after traveling from the Arabian Peninsula or neighboring countries, but who do not respond to appropriate therapy OR 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 of traveling from the Arabian Peninsula or neighboring countries
- 18. Confirmed Case Definition • A confirmed case is any person with laboratory confirmation of infection with MERS-CoV (PCR)
- 19. Close Contact • Any person who provided care for the patient, including a healthcare worker or family member, or had similarly close physical contact • Any person who stayed at the same place (lived with, visited) as the patient while the patient was ill
- 20. MERS-CoV and Pregnancy • very difficult to draw conclusions on the effect of MERS to pregnancy. • pregnant mother considered high risk group due to the changes in their immune response and the fetal effects of a severe respiratory syndrome.
- 21. Collection of Laboratory Specimens Determine if patient meets PUI criteria Collect: An upper respiratory specimen: Nasopharyngeal AND oropharyngeal swab A lower respiratory specimen: Broncheoalveolar lavage, OR Tracheal aspirate, OR Pleural fluid, OR Sputum Serum for eventual antibody testing Should be collected during acute phase during first week after onset, and again during convalescence ≥ 3 weeks later
- 22. Therapeutics • Minimal evidence to indicate antiviral or adjunctive therapy • Supportive care • Mechanical ventilation • Some studies have shown that interferon may have beneficial effects in the treatment of SARS
- 23. MERS and Travel • NO travel restrictions/ban • Special precautions for travellers to Arabian Peninsula To reduce risk of infection o maintain good personal hygiene wash hands often with soap and water and use antibacterial hand gel regularly; o avoid consuming undercooked meat and unpasteurised milk, especially from camels and food prepared in an unsanitary environment; o wash fruits and vegetables before eating;
- 24. MERS and Travel • NO travel restrictions/ban • Special precautions for travellers to Arabian Peninsula Use appropriate precautions when in close contact with people who are ill Avoid close contact with animal or waste products o Avoid unnecessary contact with farms, domestic and wild animals, especially camels. o Avoid any animal excretions, especially urine and faeces, particularly from camels and bats Seek medical attention when flu-like illness or severe respiratory illness develop during or within 14 days after returning from the Arabian Peninsula o advise healthcare providers of any travel history, possible contact with animals or other sick individuals
- 25. Thank you
Editor's Notes
- The first confirmed case was reported in Saudi Arabia 2012. Egyptian virologist Dr. Ali Mohamed Zaki isolated and identified a previously unknown coronavirus from the man's lungs. Dr. Zaki then posted his findings on 24 September 2012 on ProMED-mail. The isolated cells showed cytopathic effects (CPE), in the form of rounding and syncytia formation.
- A second case was found in September 2012. A 49-year-old male living in Qatar presented similar flu symptoms, and a sequence of the virus was nearly identical to that of the first case.[4] In November 2012, similar cases appeared in Qatar and Saudi Arabia. Additional cases were noted, with deaths associated, and rapid research and monitoring of this novel coronavirus began
- Virus from second case compared to virus isolated from lung tissue of first case 99.5% identity: One nucleotide mismatch over regions (replicase) compared Genome sequence: JX869059.1
- MERS-CoV and Severe Acute Respiratory Syndrome (SARS) are the same family of viruses Coronaviruses are common and are typically associated with mild upper respiratory illness Rarely some types of coronaviruses produce more severe illness May cause mildto severe illness Evidence of person-to-person transmission Nosocomial spread with healthcare personnel transmission Focus in the Arabian Peninsula ~ 50% mortality rate No cases identified in the U.S. This strain of coronavirus that causes MERS was first identified in 2012 in Saudi Arabia. Our understanding of the virus and the disease it causes is continuing to evolve
- All the clusters of cases seen so far have been transmitted between family members or in a health care setting, the WHO said in an update . Human-to-human transmission occurred in at least some of these clusters, however, the exact mode of transmission is unknown. That means it's not yet known how humans contract the virus. But, experts say, there has been no evidence of cases beyond the clusters into communities. The median incubation period for secondary cases associated with limited human-to-human transmission is approximately 5 days (range 2-13 days). In MERS-CoV patients, the median time from illness onset to hospitalization is approximately 4 days.
- Zoonotic transmission There is growing evidence that the dromedary camel is a host species for the MERS-CoV and that camels play an important role in the transmission to humans [2,3]. The first evidence of the implication of dromedary camels in transmission was the detection of high rates of MERS-CoV antibodies in dromedary camels on the Arabian Peninsula [4,5]. Evidence of infection in camels precedes the first evidence of human infection [6,7]. Recently, viral RNA has been detected in different specimens from camels and the virus has been isolated from nasal and faecal samples [6,8-12]. The detection of MERS-CoV in dromedary camels imported from Sudan and Ethiopia for slaughter in Egypt [9], as well as serological evidence of previous MERS-CoV infection in dromedaries in Ethiopia, Kenya [13], Nigeria [14], Tunisia [14] and the Canary Islands (Spain; some originating from Morocco) [5] suggests that the virus could be geographically widespread in the dromedary camel populations on the African continent and that previously undetected transmission to humans may occur outside of the Arabian Peninsula [14]. However, in two studies, the absence of MERS-CoV antibodies was reported respectively in 226 and 179 abattoir workers in Saudi Arabia (from Jeddah and Makkah sampled in October 2012) and in Egypt (June-December 2013), suggesting a the virus is not easily transmitted from camels to humans [9,15]. Among the primary cases reported from Saudi Arabia, only a minority have documented camel contact. A recent study showed that the MERS-CoV remains infectious beyond 72 hours after introduction in unpasteurised camel milk [16]. The consumption of raw camel milk is traditional in the Arabic culture. So far, to our knowledge, no study has looked at the excretion rate of MERS-CoV in camel milk and urine. Raw camel milk may therefore play a role in transmission. In a prospective study of two camel herds in Saudi Arabia from November 2013 to February 2014, nasal, oral, or rectal swabs and blood samples were collected up to five times. The study showed that acute MERS-CoV infections diagnosed with PCR resulted in increased anti MERS-CoV titers. The infection of very young animals (<one month) indicates that maternal antibodies may not fully protect very young animals from infection. There was no evidence of prolonged virus shedding or viraemia among the tested animals [10]. Human-to-human transmission While the source or reservoir of MERS-CoV is unknown, the disease is transmitted from person to person, for example by close contacts or in healthcare facilities [17-24]. Based on information related to the first 77 cases, the basic reproduction number of the infection (R0) was estimated to be 0.69 (95% CI 0.50–0.92) at the time [25], indicating a low pandemic potential [26]. For comparison, the R0 was estimated to be 0.80 (95% CI 0.54–1.13) for SARS-CoV, using the same methodology [25]. However, the small number of confirmed cases used for this calculation, the increasing detection of asymptomatic cases and the potential evolution of the virus will probably modify these figures [27]. An investigation of community transmission among household contacts of 26 clusters with 280 contacts over six months in 2013 showed nine positive cases by serology and PCR revealing an R0 of 0.35 (Memish, personal communication). Nosocomial transmission has been a hallmark of MERS-CoV [28] [29] and has resulted in an upsurge of cases during spring 2014 [30]. A large outbreak was previously documented in Al-Ahsa, Saudi Arabia in 2013. Twenty-three confirmed and 11 probable cases were diagnosed as part of a single outbreak that involved four healthcare facilities [17]. The majority of cases were hospitalised patients but five family members and two healthcare workers were also affected. The haemodialysis unit was the most heavily affected, with nine confirmed cases, but transmission also occurred in the intensive care unit and the medical ward. Sequencing of viral isolates from this outbreak suggested multiple introductions to the facility rather than a single one [17] [30]. Strict infection control measures allowed the containment of outbreaks when implemented e.g. in Al-Ahsa. Virus shedding in urine has been observed in a human case up to 13 days after symptom onset, in stool up to 16 days and from oronasal swabs up to 16 days after onset of symptoms [31]. In another study, a tracheal aspirate sample was shown to be viral nucleotide positive 20 days after onset of disease [21]. However, this does not yet confirm for how long the infectious virus is shed. The detection of MERS-CoV in a sample is obviously affected by the time of sampling with regard to the onset of disease; type of sample; sensitivity and specificity values of the laboratory tests available, and the prevalence of the MERS-CoV in the population to which the test is applied. There is no information available about virus shedding among infected camels. The shedding in urine among humans makes it plausible that this also applies to camels. Therefore, taking into account the occasional use of camel urine as traditional medicine in the Arabic culture, the possibility of urine as a source of infection should not be disregarded [55]. However, to date, no urinary route secondary case has been confirmed. Faecal transmission was indicated as the most likely route for the nosocomial case in France Asymptomatic and mildly symptomatic healthcare workers have been identified. One study reported seven MERS cases in Saudi Arabia (two asymptomatic and five symptomatic) confirmed by RT-PCR. All were women, six had no pre-existing conditions. All had contact with a known MERS case and most were linked to lapses in infection control while taking care of the patients. No secondary cases were identified from these healthcare workers [32]. In Germany and the United Kingdom [20,22,31], a follow-up screening exercise of nearly 200 personal contacts and healthcare workers exposed to two imported confirmed cases found no evidence of human-to-human transmission [20,22,31]. No tertiary cases were identified from these healthcare workers [32]. Limited clusters of close contacts (one or two secondary cases among close contacts) were identified in Tunisia and Saudi Arabia [31]. The risk of community transmission has increased as more human-to-human transmission has been observed. MERS is not only easily transmitted from patient to patient, but also from the transfer of sick patients to other hospitals. in humans, the virus has a strong tropism for nonciliated bronchial epithelial cells, and it has been shown to effectively evade the innate immune responses and antagonize interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells Due to the clinical similarity between MERS-CoV and SARS-CoV, it was proposed that they may use the same cellular receptor; the exopeptidase, angiotensin converting enzyme 2 (ACE2).[14] However, it was later discovered that neutralization of ACE2 by recombinant antibodies does not prevent MERS-CoV infection.
- This has a unique pathogenesis because it causes both upper and lower respiratory tract infections and can also cause Gastroenteristis. Eight clusters of illnesses have been reported by six countries
- common signs and symptoms include fever, chills/rigors, headache, non-productive cough, dyspnea, and myalgia. Other symptoms can include sore throat, coryza, nausea and vomiting, dizziness, sputum production, diarrhea, vomiting, and abdominal pain. Atypical presentations including mild respiratory illness without fever and diarrheal illness preceding development of pneumonia have been reported. Patients who progress to requiring admission to an intensive care unit (ICU) often have a history of a febrile upper respiratory tract illness with rapid progression to pneumonia within a week of illness onset.
- Co-infection with other respiratory viruses and a few cases of co-infection with community-acquired bacteria at admission has been reported; nosocomial bacterial and fungal infections have been reported in mechanically-ventilated patients
- Radiographic findings may include unilateral or bilateral patchy densities or opacities, interstitial infiltrates, consolidation, and pleural effusions. Rapid progression to acute respiratory failure, acute respiratory distress syndrome (ARDS),
- A close contact is defined as a healthcare worker or family member providing direct patient care or anyone who had prolonged (>15 minutes) face-to-face contact with a probable or confirmed symptomatic case in any closed setting. Close contacts should have a baseline serum sample collected and stored, which can be used for comparison of paired sera if required later. Where local epidemiology allows, it is also advisable to collect airway specimens for PCR testing.
- There have been less of a handful cases of confirmed MERS-CoV in pregnancy. So it is very difficult to draw conclusions on the effect of MERS to pregnancy. However traditionally pregnant mother are considered to be in the high risk group for MERS complications due to the changes in their immune response and the fetal effects of a severe respiratory
- use of CDC's 2012 real-time reverse transcription–PCR assay to test for MERS-CoV in clinical respiratory, blood, and stool specimens. PCR testing should be performed with samples from: Lower respiratory tract specimens: Broncheoalveolar lavage, tracheal aspirate, pleural fluid and/or sputum Typically have highest yield Upper respiratory tract specimens Nasopharyngeal and oropharyngeal swabs Serum Stool OCHCA can arrange testing What specimen to collect Nasal washes are not acceptable. Use only synthetic fiber swabs with plastic shafts. To increase the likelihood of detecting infection, please submit specimens from different sites and from different times after symptom onset. Do not use calcium alginate or wooden shaft swabs. State labs were sent materials to test for MERS virus from CDC. For inpatient suspected cases: airborne, droplet and contact precautions. Cases that meet the criteria for “patient under investigation” must be reported to the state and CDC. No travel restrictions or border screening have been announced at this time. Lower respiratory specimens (sputum, bronchoalveolar lavage, endotracheal) are a priority respiratory specimen for real time reverse transcription polymerase chain reaction (RT-PCR) testing Respiratory (lower and upper tracts), stool, and serum specimens Specimen collection at different times
- No vaccines developed as of yet No antivirals identified as of yet Treatment is supportive
- Travellers from the EU/EEA to the Arabian Peninsula and its neighbouring countries need to be aware of the presence of MERS-CoV in this area and of the small risk of infection. Travellers from the EU to the Arabian Peninsula should: • Consult their doctor before travelling if suffering from serious or severe medical conditions (such as diabetes, chronic lung, renal disease or immunodeficiency) that may increase the likelihood of illness including MERS-CoV infection, or the likelihood of contact with healthcare facilities while in the region. • Avoid travelling if ill with an infectious disease. Pilgrims planning to attend the Hajj or Umrah should comply with the Saudi Arabian Ministry of Health’s health regulations from 2013. They recommend that the elderly (over 65 years), pregnant women, children (under 12 years), those with chronic diseases (e.g. heart disease, kidney disease, respiratory disease, diabetes) and pilgrims with immune deficiency postpone the performance of the Hajj and Umrah for their own safety. All EU/EEA visitors to, and EU/EEA citizens residing in the Arabian Peninsula should: • Follow general health travel precautions to lower the risk of infection: – wash hands often with soap and water and use antibacterial hand gel regularly; – maintain good personal hygiene; – avoid consuming undercooked meat and unpasteurised milk, especially from camels; – avoid consuming food prepared in an unsanitary environment; – wash fruits and vegetables before eating; – use appropriate precautions when in close contact with people who are ill, especially those with flu-like symptoms (respiratory illness), diarrhoea (and other gastrointestinal illness) or other potentially infectious diseases. The measures above are especially important when visiting or staying in healthcare facilities in the region, where most of the transmission to humans appears to be occurring. • Avoid unnecessary contact with farms, domestic and wild animals, especially camels. • Avoid any animal excretions, especially urine and faeces, particularly from camels and bats. • Seek medical attention if developing flu-like illness or severe respiratory illness while travelling or within 14 days after returning from the Arabian Peninsula and advise healthcare providers of any travel history, possible contact with animals or other sick individuals. • If ill with a potentially infectious disease: – use appropriate cough etiquette (coughing and sneezing into your elbow and using disposable tissues); – avoid close contact with other people to keep from infecting them; – avoid participating in food production or preparation; – wash hands often with soap and water and use antibacterial hand gel regularly; − maintain good personal hygiene. CDC does not recommend that anyone change their travel plans because of MERS. The current CDC travel notice is an Alert (Level 2), which provides special precautions for travelers. Because spread of MERS has occurred in healthcare settings, the alert advises travelers going to countries in or near the Arabian Peninsula to provide healthcare services to practice CDC’s recommendations for infection control of confirmed or suspected cases and to monitor their health closely. Travellers who are going to the area for other reasons are advised to follow standard precautions, such as hand washing and avoiding contact with people who are ill.
- Travellers from the EU/EEA to the Arabian Peninsula and its neighbouring countries need to be aware of the presence of MERS-CoV in this area and of the small risk of infection. Travellers from the EU to the Arabian Peninsula should: • Consult their doctor before travelling if suffering from serious or severe medical conditions (such as diabetes, chronic lung, renal disease or immunodeficiency) that may increase the likelihood of illness including MERS-CoV infection, or the likelihood of contact with healthcare facilities while in the region. • Avoid travelling if ill with an infectious disease. Pilgrims planning to attend the Hajj or Umrah should comply with the Saudi Arabian Ministry of Health’s health regulations from 2013. They recommend that the elderly (over 65 years), pregnant women, children (under 12 years), those with chronic diseases (e.g. heart disease, kidney disease, respiratory disease, diabetes) and pilgrims with immune deficiency postpone the performance of the Hajj and Umrah for their own safety. All EU/EEA visitors to, and EU/EEA citizens residing in the Arabian Peninsula should: • Follow general health travel precautions to lower the risk of infection: – wash hands often with soap and water and use antibacterial hand gel regularly; – maintain good personal hygiene; – avoid consuming undercooked meat and unpasteurised milk, especially from camels; – avoid consuming food prepared in an unsanitary environment; – wash fruits and vegetables before eating; – use appropriate precautions when in close contact with people who are ill, especially those with flu-like symptoms (respiratory illness), diarrhoea (and other gastrointestinal illness) or other potentially infectious diseases. The measures above are especially important when visiting or staying in healthcare facilities in the region, where most of the transmission to humans appears to be occurring. • Avoid unnecessary contact with farms, domestic and wild animals, especially camels. • Avoid any animal excretions, especially urine and faeces, particularly from camels and bats. • Seek medical attention if developing flu-like illness or severe respiratory illness while travelling or within 14 days after returning from the Arabian Peninsula and advise healthcare providers of any travel history, possible contact with animals or other sick individuals. • If ill with a potentially infectious disease: – use appropriate cough etiquette (coughing and sneezing into your elbow and using disposable tissues); – avoid close contact with other people to keep from infecting them; – avoid participating in food production or preparation; – wash hands often with soap and water and use antibacterial hand gel regularly; − maintain good personal hygiene. CDC does not recommend that anyone change their travel plans because of MERS. The current CDC travel notice is an Alert (Level 2), which provides special precautions for travelers. Because spread of MERS has occurred in healthcare settings, the alert advises travelers going to countries in or near the Arabian Peninsula to provide healthcare services to practice CDC’s recommendations for infection control of confirmed or suspected cases and to monitor their health closely. Travellers who are going to the area for other reasons are advised to follow standard precautions, such as hand washing and avoiding contact with people who are ill.