The paper is devoted to the Middle East Respiratory Syndrome Coronavirus, which has recently become known due to the severe symptoms and consequences. The paper concerns the general information on the virus (its size, classification, etc.), the causes of its emergence and spread. Along with this, the paper is full of the information of the possible diagnostic and preventative measures, which are to keep a person from getting infected with the Middle East Respiratory Syndrome Coronavirus. The relevance of Middle East Respiratory Syndrome Coronavirus had been mainly associated with the intensification of migration processes, including increasing the labor migration’s level, tourism, and business travels, particularly in the regions that were previously – due to limited transport services – not available, or the journey lasted for several weeks or months, etc. This facilitates the rapid movement of the sources of infectious agents (i.e. infected people) across the globe, delivery agents in the territory of non-endemic for a particular infectious disease. None the less, the conditions for the implementation of microorganism transmission mechanism is the emergence of epidemic outbreaks, epidemics, and even pandemics.
Keywords: Middle East Respiratory Syndrome Coronavirus, infection, disease’s environment, treatment, mortality.
Success in the fight against infectious diseases, which was achieved in the middle of the 20th century, has created the illusion of emergency to eliminate them. However, in the following decades, this misconception was refuted due to the reason that it showed that infectious diseases continued to cause enormous economic losses to society. In all countries, regardless of their level of economic development, there has been a marked increase in the incidence of infectious diseases and epidemics recorded. The end of 20th century and the beginning of the 21st century were characterized by the appearance of several new pathogens to human viral infectious diseases.
The original and initial source of the virus still remains unknown, but the nature of transmission of the virus and virological studies indicate that the reservoir of the virus in nature are dromedaries of the Middle East. The mode of transmission is airborne and food (by consuming infected camel’s milk or insufficiently heat-treated meat in endemic regions). Coronaviruses can also be detected in the feces and urine. Therefore, the purpose of this paper is to investigate the nature, prevention, causes and possible treatment of the Middle East Respiratory Syndrome. In order to achieve this goal it is extremely important to review the most recent investigation on this issue.
Middle East Respiratory Syndrome Coronavirus: Background information
The Signs and Symptoms of the Disease
The clinical manifestations of the Middle East Respiratory Syndrome are generally similar to other clinical manifestations of acute respiratory diseases, so the differential diagnosis is to be based on laboratory methods (primarily in the polymerase chain reaction) and epidemiological data. The incubation period is researched to be usually 5-6 days, but may be in the range of 2 – 14 days (Song & Sutter, 2014). Middle East Respiratory Syndrome Coronavirus is clinically characterized by such symptoms are fever, cough, shortness of breath, difficulty breathing, and in the majority of clinically confirmed cases quickly become severe primary viral pneumonia. Patients suffer from chronic diseases of respiratory and cardiovascular systems, metabolic syndrome and immunodeficiency states of various origins, in the foreground may be nominated by symptoms of the gastrointestinal tact (diarrhea) and renal failure.
In this case, the World Health Organization (WHO) recommends considering as a possible Middle East Respiratory Syndrome Coronavirus require appropriate laboratory confirmations, sanitary measures and hospital monitoring of all the cases of acute respiratory illness in the presence of epidemiological evidence (if a person stays in the Middle East for 14 days before the onset of clinical manifestations).
All the described light and asymptomatic cases of Middle East Respiratory Syndrome Coronavirus are currently worrying the experts because of the possibility of hidden spread of the disease, although the real assessment of the likelihood of such a scenario is still uncertain. Almost 95% of all cases of diagnosed Middle East Respiratory Syndrome Coronavirus appear in the Middle East, including a wide margin in the lead of Saudi Arabia and the United Arab Emirates (948 and 74 observations, respectively) (Song & Sutter, 2014). There is the appearance of alertness of the Middle East Respiratory Syndrome Coronavirus in Egypt, where, as this is located in the Arabian Peninsula, there are significant populations of bats and camels that determine the possibility of the formation of secondary natural foci.
The Middle East Respiratory Syndrome Coronavirus is not limited to its natural foci of the base area, and as an imported infection is registered in Africa (Algeria, Egypt, Tunisia), Europe (Austria, France, Germany, Greece, Italy, Netherlands, Turkey, France), Asia (Malaysia, Philippines), America (USA).
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Data on the Virus
The virus of the Middle East Respiratory Syndrome Coronavirus has a spheroid shape (120-140 nm), is provided with a lipid envelope with clearly distinguishable peplomerami on electron micrographs, whose club-length is 5 – 10 nm with the formed trimers of protein S (~ 200 kDa) (Song & Sutter, 2014). The appearance of the virus is showed on the picture (Fig. 1).
Middle East Respiratory Syndrome Coronavirus has attracted particular attention of experts in the field of biological safety, as its known natural foci are found in the Middle East – in the region, with increasing political, social and economic tensions that could also provoke a “flare-up” and “smoldering” epidemic situation.
The discovery of the Middle East Respiratory Syndrome Coronavirus took place in June and September 2012, when in the hospital in Jeddah (Saudi Arabia), a 60-year-old man died. Nasopharyngeal wash was sent to a laboratory (Song & Sutter, 2014). A model of African green monkey (Vero) and makakirezus (LLC-MK-2) cell lines transplanted kidney was obtained from the virus with an isolate pronounced cytopathic effect. Polymerase chain reaction with universal coronavirus primers allowed the identification of primary Coronaviridae pathogen as a representative of the family.
Currently, the status of Middle East Respiratory Syndrome Coronaviru is as follows: a squad of nidovirales, a family of Coronaviridae, a subfamily of Coronavirinae, born as Betacoronavirus, subgenus. Nidovirales contains infectious enveloped viruses with a single segment of the linear single-stranded RNA of positive polarity, which has a number of common features of genome organization, replication, and its expression. This group, in addition to Coronaviridae, includes two other families: Arteriviridae and Roniviridae. The first combines the mammalian viruses, but not the human-related (including virus of arteritis virus, reproductive and respiratory syndrome), the second one is only presented by the viruses of arthropods.
The Pathogenesis of Infection
The virus is transmitted by airborne droplets and through contact with body fluids of the patient. There is information about the presence of the virus in secretions of sweat glands and the possibility of transmission through contact with sweat. Given the presence of the virus in faeces, clarifies the possibility of implementing the fecal-oral mechanism of transmission.
However, today more and more researchers believe that animal coronaviruses of Middle East Respiratory Syndrome Coronavirus fecal-oral transmission mechanism are no big deal for distribution. In hospitals, the factors of transmission may be subject to common use, artificial respiration apparatus, other medical instruments that touched to mucous membranes of humans (Berger, 2015). The period of contagiousness is at the beginning of clinical manifestations and lasts during the height of the disease, some patients may be observed in the phase of recovery. Professional groups at risk of infection are health workers, who provide assistance to the injured people, as well as the personnel of diagnostic and research laboratories.
The results of molecular genetic studies showed that the natural reservoir of the pathogen is bats. There is a possibility of transmission to humans through products of bats living in the attics of apartment buildings. There is a possibility of transmission from a person to a person in close contact (including health care workers).
The clinical picture of Middle East Respiratory Syndrome Coronavirus is an acute viral respiratory disease (spreading of respiratory desists), which is accompanied by fever, cough, shortness of breath, wheezing and, in most clinically confirmed cases, quickly turns into severe primary viral pneumonia (Berger, 2015). Patients suffer from chronic respiratory diseases and cardiovascular, metabolic syndrome and immunodeficiency of the various origins, to the fore as leading symptoms appear lesions gastrointestinal (diarrhea) and renal failure.
The recent research study on Middle East Respiratory Syndrome Coronavirus
Volz et al. (2015, p. 8651) have a conviction that “Middle East respiratory syndrome coronavirus (Middle East Respiratory Syndrome Coronavirus) emerged as the causative agent of severe human respiratory disease in Saudi Arabia.” Thus, the purpose of their study was to prove the fact that antibody elaborated is to contribute to the disease treatment. The hypothesis of the investigation is the fact that mice who have been intentionally infected obtain a positive treatment by the usage of the antibody.
In this connection, the WHO has developed and proposed a questionnaire to be used for the initial investigation of the Middle East Respiratory Syndrome Coronavirus. When a special relevance diagnosis with laboratory methods research is inserted, the samples of body fluids with lower respiratory tract should be a priority for the collection and study of real-time reverse transcriptase polymerase chain reaction (PCR Roth). Mouth-PCR testing samples of the lower airways are more sensitive to detect coronavirus of the Middle East Respiratory Syndrome Coronavirus, than the test samples of the upper respiratory tract.
The major finding of the investigation by Volz et al. (2015) consist in the fact that the authors believe, the priorities include respiratory samples from the lower parts of the respiratory system. Serum sample should be obtained for serological testing. Data from the selected cases to date indicate that the lower respiratory tract samples (Sputum, tracheal aspirate, bronchoalveolar lavage fluid (BLF)) are more sensitive for detection of Middle East Respiratory Syndrome Coronavirus using mouth-PCR tests than those, which have been collected from the upper respiratory tract (in conjunction with the nasopharynx and oropharynx, nasal aspirate).
WHO and the US Centers CDC published recommendations for the prevention and control of Middle East Respiratory Syndrome Coronavirus infection in hospitals. The increase of the level of infection control measures is recommended in caring for patients with the alleged or confirmed cases of Middle East Respiratory Syndrome Coronavirus infection (Berger, 2015). WHO recommends that standard precautions for infection prevention droplet can be used when caring for patients with acute respiratory tract infections.
The importance of the study by Volz et al. (2015) consists in the fact that protective equipment should be added in the care of alleged or confirmed cases of Middle East Respiratory Syndrome Coronavirus infection. Barrier precautions should be used for the performance of medical procedures. Temporary home care and isolation are possible in some cases, as CDC recommends, so that patients who are currently rated as a possible case of Middle East Respiratory Syndrome Coronavirus infection and do not require hospitalization, they can be isolated in their home in the community.
The recommendations of WHO stated that individuals at high risk of severe disease (immunodeficiency, diabetes, chronic lung disease, signs of kidney failure) should not visit farms, sheds, markets, places where there are camels. The preventive measures include avoiding contact with camels, evolving the personal hygiene, stopping consuming raw camel milk as well as the raw and insufficiently heat-treated meat.
One of the most interesting points of the article by Volz et al. (2015) is that clinically, severe respiratory syndrome manifests itself with the development of renal failure. The main symptoms are fever, malaise, weakness, headache, cough, shortness of breath and myalgias. In 1/3 of patients, gastrointestinal symptoms (diarrhea, vomiting, abdominal pain) may develop.
Volz et al. (2015) have a conviction that Middle East Respiratory Syndrome Coronavirus should also involve patients with acute respiratory disease of any severity, which during the previous 14 days of the disease were in close contact with patients with suspected or confirmed case of the Middle East Respiratory Syndrome Coronavirus.
Mortality in severe Middle East Respiratory Syndrome Coronavirus, as the most recent investigations show, is 35-40% higher in patients, who are older than 65 years and with severe comorbidities (Song & Sutter, 2014). Specific prevention and treatment is heliotrope. For laboratory diagnosis of disease, the PCR material of the lower respiratory tract (sputum, endotracheal aspirate, bronchoalveolar lavage) and serum are expected to be performed. If the patient has no signs or symptoms of lower respiratory tract infection and sampling of the lower respiratory tract is not possible or is not clinically indicated, it is necessary to take a sample of nasopharyngeal or oropharyngeal. These two samples can be combined in one container and be tested together. If a patient with a probable case of infection caused by Middle East Respiratory Syndrome Coronavirus, initial testing of nasopharyngeal sample was negative, the patient should be evaluated by using a sample from the lower respiratory tract or repeat nasopharyngeal specimen with additional oropharyngeal sample (if it is impossible to take a sample from the lower respiratory tract) (Rossi & Hui, 2016).
In health care organizations to comply with sanitary and anti-epidemic mode (mode of ventilation, air disinfection, control over the patients visiting relatives, and others) there is a timely transmission of information about probable or confirmed case of infection caused by Middle East Respiratory Syndrome Coronavirus (Rossi & Hui, 2016). There should be a laboratory examination of patients with a probable case of infection caused by Middle East Respiratory Syndrome Coronavirus, laboratory examination of all health workers, who become ill with severe acute respiratory infection (hereinafter – SARI), who provided care for patients with SARI.
There should be a raising awareness among all health care workers of the possibility of cases among people infection caused Middle East Respiratory Syndrome Coronavirus and requirements for the notification of such cases; conducting outreach with the public about the possibility of Middle East Respiratory Syndrome Coronavirus infection when visiting the Middle East, South Korea, paying attention to the fulfillment of prevention rules.
It is important to see the way the Middle East Respiratory Syndrome Coronavirus produces the antibody response. The investigation which has been conducted by Volz et al. (2015, p. 8653) shows that “repeated i.m. immunization further increased the levels of Middle East Respiratory Syndrome Coronavirus-neutralizing antibodies to higher titers than those obtained upon s.c. immunization. However, the peak antibody titers elicited by s.c. and i.m. immunizations did not differ significantly.” This is illustrated on the graph, which is located below.
Fig. 1 (Volz et al., 2015)
Additional investigation on the nature of Middle East Respiratory Syndrome Coronavirus has been conducted on mice by Volz et al. (2015). This investigation showed particularly significant results which concern glycoprotein of Middle East Respiratory Syndrome Coronavirus. Thus, the authors state that “an examination of the efficacy of MVA-MERS-S vaccination in a mouse model of Middle East Respiratory Syndrome Coronavirus lung infection revealed that all of the immunized mice exhibited little or no replication of Middle East Respiratory Syndrome Coronavirus” (Volz et al., 2015). This means that the vaccination is likely to serve as a curing (and probably preventative) tool for the disease treatment. This result is regarded as positive.
In addition to this, the authors mention the fact that “these data confirm that the S glycoprotein of Middle East Respiratory Syndrome Coronavirus… is an important and safe vaccine antigen” (Volz et al., 2015, p. 8655). Thus, it is possible to conclude that the antibody used can help in the disease treatment and save human beings’ lives. As a consequence, the scholars “found no evidence of an increased inflammatory response or the potential enhancement of Middle East Respiratory Syndrome Coronavirus infection through S-antigen-specific antibody induction” (Volz et al., 2015, p. 8655), which helps recall the previous investigation, where “as has been previously speculated for SARS-CoV infections” (Volz et al., 2015, p. 8655). Finally, Volz et al. (2015, p. 8655) make a conclusion that “thus, the MVAMERS-S vector merits further development as a candidate vaccine against Middle East Respiratory Syndrome Coronavirus for potential human use.” It means that the usage of antibody, from both theoretical and empiric points of view, stimulate the disease’s stop and make a contribution to the positive results of treatment.
Description and discussion on either environmental or other factors contributing to the emergence of Middle East Respiratory Syndrome Coronavirus
Middle East Respiratory Syndrome Coronavirus is known to be caused by a new coronavirus, Beta-identified as Middle East Respiratory Syndrome Coronavirus. Clinical manifestations are characterized by high fever, lesions of both upper and lower respiratory symptoms of pneumonia, development of acute respiratory distress syndrome (ARDS). Frequently, there is enough observed exacerbation of chronic somatic diseases. These two properties are the main causes of fatal consequences.
Humanity is facing new diseases mainly viral etiology characterized by the occurrence of unpredictable and difficult course. This often leads doctors around the world to a scientific dead end, figuratively speaking. Here, it is possible to recall, for example, a disease caused by the Ebola virus. The emergence of diseases are caused by unpredictable antigenic variability of the virus, which is associated with spontaneous or emerging population immunity under the influence of qualitative changes antigenic determinants.
A clear confirmation of the above-mentioned facts was cases of fatal diseases caused by coronavirus of Middle East respiratory syndrome. The relevance of infectious disease is associated with increasing migration, the number of tourist and business voyages, particularly in those regions that were previously impossible.
During the period September 2012 – June 2015 the World Health Organization officially informed of the 1289 laboratory confirmed Middle East respiratory syndrome cases caused by the Middle East respiratory syndrome in the world, 455 cases were fatal of which (Song & Sutter, 2014). The mortality rate is 35.3% (Song & Sutter, 2014). The largest outbreak of Middle East respiratory syndrome has been fixed outside the Arabian Peninsula in South Korea. The first report to WHO was received May 21, 2015. As of 15/06/2015, 150 registered cases, of which 17 (11.3%) are deaths (Song & Sutter, 2014). Medical observation is made on more than 5 thousand people who were in contact with laboratory confirmed to the Middle East respiratory syndrome individuals.
The natural environment for the Middle East respiratory syndrome are bats (Chiroptera: Microchiroptera). The bats naturally infected Weaver (Viverridae), which are the inhabitants of the South-Eastern Asia looked after as pets and are often used in food. The most likely way of penetration of Middle East respiratory syndrome in human populations is as follows,
→ bats, small wild mammals (Himalayan civet, a raccoon-like dogs, badgers birmenski) → Meat defective heat treatment restaurants → people (Song & Sutter, 2014).
The natural environment of the coronavirus is the results of the molecular genetic analysis, which found that the main transporters of the disease are bats. Studies in Europe, Africa and Asia, including the Middle East have shown that a similar coronavirus of RNA sequence is often found in samples of feces of bats and that some of these sequences which are closely associated with the sequence of Middle East Respiratory Syndrome Coronavirus. Bats can be a reservoir of Middle East Respiratory Syndrome Coronavirus, but it is unlikely that they are the direct source for Middle East respiratory syndrome disease, because human contact with bats is frequently uncommon.
Possible sources and routes of transmission are likely to be camels (dromedary) – the main owner of Middle East Respiratory Syndrome Coronavirus in animals. Convincing evidence of transmission of Middle East Respiratory Syndrome Coronavirus camel to man had been studied in Saudi Arabia. In the process of complete genome sequencing revealed that the viruses isolated from man and his camel were identical.
The studies show that the Middle East Respiratory Syndrome Coronavirus can be transmitted from a camel to a camel and from them – to people in close contact. Availability of the thematic clusters, which have been epidemiologically confirmed, suggests the transmission of the virus from person to person through close contact occurs, especially in the provision of care to such patients.
The following terms are to be defined for the better understanding of the topic issue.
Middle East Respiratory Syndrome is mainly regarded as a zoonotic virus, which is transmitted from animals to humans. The origin of this virus is not known to a full extent; however, according to the analysis of various virus genomes, it is frequently believed that it originated among the bats and was handed over to the camels in the remote past (“MedlinePlus – Health Information from the National Library of Medicine”, 2016).
Fever is an abnormal rise of the body temperature. This term is a key symptom during the Middle East Respiratory Syndrome (“MedlinePlus – Health Information from the National Library of Medicine”, 2016).
Middle East Respiratory Syndrome Coronavirus infection can occur as virtually asymptomatic, and with the defeat of the upper respiratory tract, with the rapid development of pneumonia, respiratory failure, acute respiratory distress syndrome, as well as with the development of septic shock and multiple organ failure. Most often, Middle East Respiratory Syndrome Coronavirus infection is recorded in adults, although there are cases of the disease in children.
For the diagnosis of Middle East Respiratory Syndrome Coronavirus primarily epidemiological history data is used. It is important to know, whether the patient visited endemic areas of the Middle East and other countries where cases have been recorded Middle East Respiratory Syndrome Coronavirus. Furthermore, it is important to know whether there was contact with the patients, who visited the country of the Arabian Peninsula, or those who suspected Middle East Respiratory Syndrome Coronavirus. All patients who are suspected of Middle East Respiratory Syndrome Coronavirus, in accordance with the instructions on the management of patients, are examined for the presence of bacterial infection. It is recommended that sampling has to be prior to antibiotic therapy. Material for the study is to be taken as from the upper and lower respiratory tract of a nasal swab, nasal and / or throat; sputum, tracheal aspirate, bronchoalveolar lavage.
It is important to keep ot of traveling to Saudi Arabia, Qatar, the United Arab Emirates without any urgent need. When leaving in these countries, if necessary, it is recommended to use the protective masks and refrain from visiting crowded places and contact with sick people with fever. When leaving the country in the Middle East region people should avoid contacts with camels and eating raw foods derived from camels (milk, meat). If experiencing respiratory symptoms, wear a mask and immediately seek medical attention. When a fever or flu-like symptoms when returning from a trip need time to consult a doctor, providing information about the countries visited and the duration of bacterial infection. It is recommended that sampling prior to antibiotic therapy. Material for the study was taken as from the upper and lower respiratory tract of: nasal swab, nasal and / or throat; sputum, tracheal aspirate, bronchoalveolar lavage.
In order to prevent infection of coronavirus infection is recommended to refrain from traveling to Saudi Arabia, Qatar, the United Arab Emirates without urgent need. When leaving in these countries, if necessary, recommend the use of protective masks and refrain from visiting crowded places and contact with sick people with fever. When leaving the country in the Middle East region should be avoided contacts with camels and eating raw foods derived from camels (milk, meat). If experiencing respiratory symptoms, wear a mask and immediately seek medical attention. When a fever or flu-like symptoms when returning from a trip need time to consult a doctor, providing information about the countries visited and the duration of stay.