SPECIAL TOPICS IN INFECTIOUS DISEASE DISEASES
Understanding Middle East respiratory syndrome Kenneth V.I. Rolston, MD
CREDIT: SCIENCE SOURCE / COLORIZATION BY: MARY MARTIN
ABSTRACT Middle East respiratory syndrome is an infection caused by a novel coronavirus. The primary source of the virus is infected camels in several countries in the Arabian peninsula. The infection is acquired by coming into contact with infected animals, animal products, or with patients who have the syndrome. Mortality for this syndrome is 30% to 40%, and treatment is supportive because no antiviral therapy exists. Keywords: Middle East respiratory syndrome, coronavirus, Arabian peninsula, dromedary camels, antiviral, MERS-CoV
C
oronaviruses are a large family of viruses that are common pathogens in animals. They have the capacity to mutate and infect new species, including humans. In humans, coronaviruses are primarily respiratory pathogens, although they may occasionally be associated with viral diarrhea. The spectrum of human respiratory disease ranges from asymptomatic infection to severe respiratory insufficiency. In 2003, severe acute respiratory syndrome (SARS) caused by the SARS coronavirus emerged from China and was responsible for a global pandemic. More recently, Middle East respiratory syndrome (MERS), also caused by a coronavirus, has become the focus of global attention. This article describes the initial recognition of MERS, its transmission, clinical features, and management, as well as advice to travelers and healthcare facilities.
GEOGRAPHIC DISTRIBUTION In June 2012, a 60-year-old Saudi Arabian businessman was hospitalized with fever, cough, progressive dyspnea, and renal failure. The illness was fatal and was caused by a novel beta-coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV ) (Figure 1).1 The virus was subsequently linked to several cases of respiratory illnesses in Jordan in early 2012.2,3 By April 2015, the World Kenneth V.I. Rolston is a professor of medicine at M.D. Anderson Cancer Center in Houston, Tex. The author has disclosed no potential conflicts of interest, financial or otherwise. Roy A. Borchardt, PA-C, PhD, department editor DOI: 10.1097/01.JAA.0000466591.41090.5e Copyright © 2015 American Academy of Physician Assistants
52
FIGURE 1. Color-enhanced transmission electron micrograph
showing MERS-CoV.
Health Organization (WHO) had been notified of 1,110 laboratory-confirmed cases of MERS, including at least 422 related deaths.4 This number appears to be an underestimate. To facilitate better surveillance, case recognition, and reporting, the WHO issued a revised case definition that includes delineation of confirmed cases and probable cases.5 Surveillance recommendations and updates can be found on the WHO coronavirus website.5 The virus appears to be circulating widely in the Arabian Peninsula, with most cases reported from Saudi Arabia.6 Other countries that have reported cases among residents include Jordan, United Arab Emirates, Kuwait, Yemen, Qatar, and Oman. Cases have also been described in visitors who have traveled to these areas and have returned to Europe (France, Greece, Germany, Italy, the Netherlands, and the United Kingdom), Africa (Algeria, Egypt, and Tunisia), Asia (Malaysia and the Philippines), and the
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Volume 28 • Number 7 • July 2015
Copyright © 2015 American Academy of Physician Assistants
Understanding Middle East respiratory syndrome
United States. Lebanon and Iran have also reported cases related to travel to Saudi Arabia. Patients with travelrelated MERS have not infected other people in their native countries.6 Coronaviruses can infect multiple species (hosts) and can change rapidly through recombination. These properties have fueled fears that a worldwide epidemic similar to SARS could occur due to the spread of MERS-CoV. Consequently, the WHO and the CDC have issued guidelines for travelers and for healthcare workers to help contain the spread of this infection, although neither agency has issued travel advisories discouraging travel to the Middle East. SOURCE AND MODE OF TRANSMISSION Evidence suggests that the MERS virus has been circulating in bats for several years.7 However, the primary source seems to be dromedary (single-humped) camels in Egypt, Qatar, and Saudi Arabia.8 Genetic sequencing has shown that the camel and human viruses are closely linked.8 The exact mode of transmission of MERS-CoV has not fully been determined. Cases have occurred in patients exposed to infected camels and the communities they live in as well as in healthcare facilities. Cases in the community are thought to arise from contact with infected animals or unprocessed products from infected animals.6 Some evidence to support this has emerged from the increase in cases during the camel breeding season.6 Cases have also been reported in the absence of contact with infected animals or unprocessed products, suggesting human-to-human transmission.9 In the hospital outbreak in Jordan, the transmission rate among exposed healthcare workers was 10%; no specific precautions were in place, as MERS had not yet been described.2,3 Patients at increased risk for MERS include: • Residents of and recent travelers to the Arabian Peninsula • Close contacts of patients with confirmed MERS • Close contacts of ill travelers from the Arabian Peninsula • Healthcare personnel not using recommended infection control precautions • People with exposure to camels and/or ingestion of raw or undercooked camel products such as milk or meat.10 CLINICAL AND LABORATORY FEATURES The clinical manifestations of MERS range from asymptomatic infection to a rapidly progressive respiratory and systemic illness. The most common symptoms include fever, chills, myalgias, sore throat, cough, and dyspnea. Other symptoms include headache, nausea, vomiting, dizziness, and diarrhea. Renal failure may occur as the disease progresses. MERS is more severe in patients who are immunocompromised or have diabetes, chronic lung disease, or renal insufficiency.6 Laboratory findings are nonspecific and include thrombocytopenia, lymphopenia, and elevated lactate
dehydrogenase levels. Radiographic findings include patchy lung infiltrates and, occasionally, pleural effusions.11 Several antibody assays have been developed to detect the presence of the MERS-CoV, which has been detected in various respiratory secretions, urine, serum, and feces. The most recent standard for laboratory confirmation can be found on the WHO coronavirus website. TREATMENT Although no effective antiviral treatment exists for MERS, several agents have indicated in-vitro activity against the virus. Treatment primarily consists of supportive care, including mechanical ventilation and renal replacement when necessary. The survival rate for patients who need ICU care is 42%.6,11 ADVICE TO HEALTHCARE FACILITIES Healthcare providers should observe standard precautions and infection control practices when dealing with patients: hand hygiene before and after patient contact; the use of protective equipment such as gowns, gloves, masks, and goggles when exposure to body fluids is expected; adequate cleaning, disinfection, or sterilization of patient care equipment before use on another patient; and strict adherence to respiratory etiquette, such as placing masks on patients who are coughing. Patients presenting with fever and radiographic findings of pneumonia should be screened for travel to the Arabian Peninsula, or for close contact with patients with confirmed MERS or symptomatic travelers from the Middle East. Patients meeting these criteria should be further evaluated while being placed in airborne and contact precautions. Healthcare providers evaluating these patients should wear protective equipment as indicated above. ADVICE FOR TRAVELERS Travelers to the Middle East should avoid contact with sick people and avoid ingestion of raw or undercooked animal products. They should seek medical attention if, within 2 weeks after returning from the Middle East, they develop symptoms suggestive of MERS, such as fever, cough, and myalgias. Travelers with diabetes, renal insufficiency, chronic lung disease, or immunosuppression should be warned that they are at increased risk for developing severe complications and death if they contract MERS.12 JAAPA REFERENCES 1. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814-1820. 2. Hijawi B, Abdallat M, Sayaydeh A, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J. 2013;19 (suppl 1):S12-S18. 3. Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Jordan MERS-CoV Investigation Team. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic,
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2015 American Academy of Physician Assistants
www.JAAPA.com
53
SPECIAL TOPICS IN INFECTIOUS DISEASE
4.
5.
6.
7.
54
epidemiologic, and clinical description. Clin Infect Dis. 2014;59 (9):1225-1233. World Health Organization. Global alert and response. Middle East respiratory syndrome coronavirus (MERS-CoV)—Saudi Arabia. April 29, 2015. http://www.who.int/csr/don/archive/ disease/coronavirus_infections/en. Accessed May 5, 2015. World Health Organization. Global alert and response. Revised case definition for reporting to WHO—Middle East respiratory syndrome coronavirus. http://www.who.int/csr/disease/coronavirus_infections/case_definition/en. Accessed May 5, 2015. Rasmussen SA, Gerber SI, Swerdlow DL. Middle East respiratory syndrome coronavirus: update for clinicians. Clin Infect Dis. 2015;pii:civ118. Ithete NL, Stoffberg S, Corman VM, et al. Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa. Emerg Infect Dis. 2013;19(10):1697-1699.
8. Haagmans BL, Al Dhahiry SH, Reusken CB, et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014;14(2):140-145. 9. Oboho IK, Tomczyk SM, Al-Asmari AM, et al. 2014 MERSCoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372(9):846-854. 10. Centers for Disease Control and Prevention. Middle East respiratory syndrome (MERS). People who may be at increased risk for MERS. http://www.cdc.gov/coronavirus/mers/risk.html. Accessed April 15, 2015. 11. Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160(6): 389-397. 12. Sampathkumar P. Middle East respiratory syndrome: what clinicians need to know. Mayo Clin Proc. 2014;89(8):1153-1158.
www.JAAPA.com
Volume 28 • Number 7 • July 2015
Copyright © 2015 American Academy of Physician Assistants
Understanding Middle East respiratory syndrome Kenneth V.I. Rolston, MD
CREDIT: SCIENCE SOURCE / COLORIZATION BY: MARY MARTIN
ABSTRACT Middle East respiratory syndrome is an infection caused by a novel coronavirus. The primary source of the virus is infected camels in several countries in the Arabian peninsula. The infection is acquired by coming into contact with infected animals, animal products, or with patients who have the syndrome. Mortality for this syndrome is 30% to 40%, and treatment is supportive because no antiviral therapy exists. Keywords: Middle East respiratory syndrome, coronavirus, Arabian peninsula, dromedary camels, antiviral, MERS-CoV
C
oronaviruses are a large family of viruses that are common pathogens in animals. They have the capacity to mutate and infect new species, including humans. In humans, coronaviruses are primarily respiratory pathogens, although they may occasionally be associated with viral diarrhea. The spectrum of human respiratory disease ranges from asymptomatic infection to severe respiratory insufficiency. In 2003, severe acute respiratory syndrome (SARS) caused by the SARS coronavirus emerged from China and was responsible for a global pandemic. More recently, Middle East respiratory syndrome (MERS), also caused by a coronavirus, has become the focus of global attention. This article describes the initial recognition of MERS, its transmission, clinical features, and management, as well as advice to travelers and healthcare facilities.
GEOGRAPHIC DISTRIBUTION In June 2012, a 60-year-old Saudi Arabian businessman was hospitalized with fever, cough, progressive dyspnea, and renal failure. The illness was fatal and was caused by a novel beta-coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV ) (Figure 1).1 The virus was subsequently linked to several cases of respiratory illnesses in Jordan in early 2012.2,3 By April 2015, the World Kenneth V.I. Rolston is a professor of medicine at M.D. Anderson Cancer Center in Houston, Tex. The author has disclosed no potential conflicts of interest, financial or otherwise. Roy A. Borchardt, PA-C, PhD, department editor DOI: 10.1097/01.JAA.0000466591.41090.5e Copyright © 2015 American Academy of Physician Assistants
52
FIGURE 1. Color-enhanced transmission electron micrograph
showing MERS-CoV.
Health Organization (WHO) had been notified of 1,110 laboratory-confirmed cases of MERS, including at least 422 related deaths.4 This number appears to be an underestimate. To facilitate better surveillance, case recognition, and reporting, the WHO issued a revised case definition that includes delineation of confirmed cases and probable cases.5 Surveillance recommendations and updates can be found on the WHO coronavirus website.5 The virus appears to be circulating widely in the Arabian Peninsula, with most cases reported from Saudi Arabia.6 Other countries that have reported cases among residents include Jordan, United Arab Emirates, Kuwait, Yemen, Qatar, and Oman. Cases have also been described in visitors who have traveled to these areas and have returned to Europe (France, Greece, Germany, Italy, the Netherlands, and the United Kingdom), Africa (Algeria, Egypt, and Tunisia), Asia (Malaysia and the Philippines), and the
www.JAAPA.com
Volume 28 • Number 7 • July 2015
Copyright © 2015 American Academy of Physician Assistants
Understanding Middle East respiratory syndrome
United States. Lebanon and Iran have also reported cases related to travel to Saudi Arabia. Patients with travelrelated MERS have not infected other people in their native countries.6 Coronaviruses can infect multiple species (hosts) and can change rapidly through recombination. These properties have fueled fears that a worldwide epidemic similar to SARS could occur due to the spread of MERS-CoV. Consequently, the WHO and the CDC have issued guidelines for travelers and for healthcare workers to help contain the spread of this infection, although neither agency has issued travel advisories discouraging travel to the Middle East. SOURCE AND MODE OF TRANSMISSION Evidence suggests that the MERS virus has been circulating in bats for several years.7 However, the primary source seems to be dromedary (single-humped) camels in Egypt, Qatar, and Saudi Arabia.8 Genetic sequencing has shown that the camel and human viruses are closely linked.8 The exact mode of transmission of MERS-CoV has not fully been determined. Cases have occurred in patients exposed to infected camels and the communities they live in as well as in healthcare facilities. Cases in the community are thought to arise from contact with infected animals or unprocessed products from infected animals.6 Some evidence to support this has emerged from the increase in cases during the camel breeding season.6 Cases have also been reported in the absence of contact with infected animals or unprocessed products, suggesting human-to-human transmission.9 In the hospital outbreak in Jordan, the transmission rate among exposed healthcare workers was 10%; no specific precautions were in place, as MERS had not yet been described.2,3 Patients at increased risk for MERS include: • Residents of and recent travelers to the Arabian Peninsula • Close contacts of patients with confirmed MERS • Close contacts of ill travelers from the Arabian Peninsula • Healthcare personnel not using recommended infection control precautions • People with exposure to camels and/or ingestion of raw or undercooked camel products such as milk or meat.10 CLINICAL AND LABORATORY FEATURES The clinical manifestations of MERS range from asymptomatic infection to a rapidly progressive respiratory and systemic illness. The most common symptoms include fever, chills, myalgias, sore throat, cough, and dyspnea. Other symptoms include headache, nausea, vomiting, dizziness, and diarrhea. Renal failure may occur as the disease progresses. MERS is more severe in patients who are immunocompromised or have diabetes, chronic lung disease, or renal insufficiency.6 Laboratory findings are nonspecific and include thrombocytopenia, lymphopenia, and elevated lactate
dehydrogenase levels. Radiographic findings include patchy lung infiltrates and, occasionally, pleural effusions.11 Several antibody assays have been developed to detect the presence of the MERS-CoV, which has been detected in various respiratory secretions, urine, serum, and feces. The most recent standard for laboratory confirmation can be found on the WHO coronavirus website. TREATMENT Although no effective antiviral treatment exists for MERS, several agents have indicated in-vitro activity against the virus. Treatment primarily consists of supportive care, including mechanical ventilation and renal replacement when necessary. The survival rate for patients who need ICU care is 42%.6,11 ADVICE TO HEALTHCARE FACILITIES Healthcare providers should observe standard precautions and infection control practices when dealing with patients: hand hygiene before and after patient contact; the use of protective equipment such as gowns, gloves, masks, and goggles when exposure to body fluids is expected; adequate cleaning, disinfection, or sterilization of patient care equipment before use on another patient; and strict adherence to respiratory etiquette, such as placing masks on patients who are coughing. Patients presenting with fever and radiographic findings of pneumonia should be screened for travel to the Arabian Peninsula, or for close contact with patients with confirmed MERS or symptomatic travelers from the Middle East. Patients meeting these criteria should be further evaluated while being placed in airborne and contact precautions. Healthcare providers evaluating these patients should wear protective equipment as indicated above. ADVICE FOR TRAVELERS Travelers to the Middle East should avoid contact with sick people and avoid ingestion of raw or undercooked animal products. They should seek medical attention if, within 2 weeks after returning from the Middle East, they develop symptoms suggestive of MERS, such as fever, cough, and myalgias. Travelers with diabetes, renal insufficiency, chronic lung disease, or immunosuppression should be warned that they are at increased risk for developing severe complications and death if they contract MERS.12 JAAPA REFERENCES 1. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814-1820. 2. Hijawi B, Abdallat M, Sayaydeh A, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J. 2013;19 (suppl 1):S12-S18. 3. Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Jordan MERS-CoV Investigation Team. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic,
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2015 American Academy of Physician Assistants
www.JAAPA.com
53
SPECIAL TOPICS IN INFECTIOUS DISEASE
4.
5.
6.
7.
54
epidemiologic, and clinical description. Clin Infect Dis. 2014;59 (9):1225-1233. World Health Organization. Global alert and response. Middle East respiratory syndrome coronavirus (MERS-CoV)—Saudi Arabia. April 29, 2015. http://www.who.int/csr/don/archive/ disease/coronavirus_infections/en. Accessed May 5, 2015. World Health Organization. Global alert and response. Revised case definition for reporting to WHO—Middle East respiratory syndrome coronavirus. http://www.who.int/csr/disease/coronavirus_infections/case_definition/en. Accessed May 5, 2015. Rasmussen SA, Gerber SI, Swerdlow DL. Middle East respiratory syndrome coronavirus: update for clinicians. Clin Infect Dis. 2015;pii:civ118. Ithete NL, Stoffberg S, Corman VM, et al. Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa. Emerg Infect Dis. 2013;19(10):1697-1699.
8. Haagmans BL, Al Dhahiry SH, Reusken CB, et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014;14(2):140-145. 9. Oboho IK, Tomczyk SM, Al-Asmari AM, et al. 2014 MERSCoV outbreak in Jeddah—a link to health care facilities. N Engl J Med. 2015;372(9):846-854. 10. Centers for Disease Control and Prevention. Middle East respiratory syndrome (MERS). People who may be at increased risk for MERS. http://www.cdc.gov/coronavirus/mers/risk.html. Accessed April 15, 2015. 11. Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160(6): 389-397. 12. Sampathkumar P. Middle East respiratory syndrome: what clinicians need to know. Mayo Clin Proc. 2014;89(8):1153-1158.
www.JAAPA.com
Volume 28 • Number 7 • July 2015
Copyright © 2015 American Academy of Physician Assistants
