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CORONA VIRUSES COLD AND SARS 1 Coronaviruses are the largest RNA viruses They infect humans and animals in which they cause respiratory and enteric diseases. Coronaviruses cause about one third of "common colds" and the newly recognized Severe acute respiratory syndrome (SARS). 2 Epidemiology Most people harbor anti-coronavirus antibodies but reinfection is common indicating that there are many circulating serotypes of the virus in the human population. Major outbreaks occur every few years with a cycle that depends on the type of virus involved. 3 Pathogenesis Coronaviruses cause respiratory and enteric disease in a variety of animals. In humans, the major site of virus replication is the epithelial cells of the respiratory tract about one-third of colds are caused by coronaviruses. 4 The symptoms are (runny nose, sore throat, cough, headache, fever, chills etc.) incubation period 3 days. Viral spread is limited by the immune response of most patients but this immunity is short-lived. 5 Symptoms may last about a week with considerable variation between patients. Often there are no apparent symptoms but the patient still sheds infectious virus Transmission is by transfer of nasal secretions such as in aerosols caused by sneezes. Viruses that infect epithelial cells of the enteric tract cause diarrhea. 6 In humans, these viruses have been implicated in infections of the middle ear, and some pneumonias in immunosuppressed patients 7 Diagnosis Most coronavirus infections go undiagnosed and the disease is self-limiting. Diagnosis can be carried out using immunoelectron microscopy and serology. There are no anti-viral for routine coronavirus infections but over-the-counter remedies to alleviate symptoms are useful 8 Severe acute respiratory syndrome (SARS ) In late 2002, a new syndrome was observed in southern China (Guangdong Province). It was named severe acute respiratory syndrome (SARS). This disease, has now been reported in Asia, North America, Africa and Europe. 9 The SARS coronavirus causes severe respiratory disease. The incubation period averages about 6 days. Common early symptoms include fever above 380C, malaise, chills, headache, dizziness, cough, and sore throat, followed a few days later by shortness of breath. 10 Many patients have abnormal chest radiographs. Some cases progress rapidly to acute respiratory distress, requiring ventilatory support. Death from progressive respiratory failure occurs in almost 10% of cases, with the death rate highest among the elderly. 11 It has been shown that SARS coronavirus can be airborne in a health care setting, suggesting that airborne transmission might occur. SARS contamination of frequently touched surfaces, such as a bed table (fomites), has been observed also. 12 Laboratory Diagnosis Antigen and Nucleic Acid Detection Coronavirus antigens in cells in respiratory secretions may be detected using the ELISA test if a high-quality antiserum is available. Enteric coronaviruses can be detected by examination of stool samples by electron microscopy. 13 Polymerase chain reaction (PCR) assays are useful to detect coronavirus nucleic acid in respiratory secretions and in stool samples. 14 SARS virus RNA was detectable in plasma by PCR, with viremia most readily detectable between days 4 and 8 of infection. Isolation of human coronaviruses in cell culture has been difficult. However, the SARS virus was recovered from oropharyngeal specimens using Vero monkey kidney cells. 15 Serology Because of the difficulty of virus isolation, serodiagnosis using acute and convalescent sera is the practical means of confirming coronavirus infections. ELISA and hemagglutination tests may be used. 16 Treatment, Prevention, & Control There is no proven treatment for SARS other than management of symptoms. Drugs are under development There is no vaccine against the SARS virus or any other human corona virus. A major problem with live virus vaccine is antigenic shift and unpredictable outcomes. 17 Control measures that were effective in stopping the spread of SARS included isolation of patients, quarantine of those who had been exposed, and travel restrictions, as well as the use of gloves, gowns, goggles, and respirators by health care workers. 18 Slow virus & Prions 19 Slow virus infections The term " Slow virus infections " refers to the tempo of the DISEASE, not to the growth rate of the virus. Such diseases have a prolonged incubation period (which can be months or years), and a protracted, progressive clinical course. 20 Slow virus diseases may be caused by conventional or unconventional viruses. The symptoms associated with slow viral/prion diseases of the central nervous system tend to have multiple neurological symptoms and different patients may present with different symptoms 21 CONVENTIONAL VIRUSES Progressive multifocal leukoencephalopathy (PML) This is a rare, fatal, demyelinating disease of the CNS which kills oligodendrocytes It results in memory loss, loss of coordination, mental problems, and vision problems. Patients who develop PML frequently have some abnormality of the immune system. PML develops in up to 5% of patients with AIDS. 22 Subacute sclerosing panencephalitis (SSPE) This disease is a rare complication of measles virus infection and develops approximately 1 to 10 years after the initial infection. It is progressive and fatal and is characterized by mental and motor deterioration. Risk factors include acquiring primary measles at early age. SSPE is associated with defective forms of the virus in the brain and so it is difficult to isolate infectious virus from patients. Incidence has decreased since the introduction of anti-measles vaccination. 23 Progressive rubella panencephalitis (PRP) PRP is a very rare consequence of rubella virus infection results in mental and motor deterioration. the onset of PRP occurs at 8 to 19 years of age. 24 UNCONVENTIONAL VIRUSES :PRIONS These are very small, filterable agents that require host cells to grow. They have no capacity for energy generation or protein synthesis. In some ways, however, they are rather different from viruses for we cannot see any evidence of virus particles in infected tissues or purified preparations of infectious material. 25 These unconventional viruses or agents are often called 'prions' - since protein is present in purified preparations of infectious material No-one has been able to prove that these agents contain nucleic acid. These agents are resistance to treatments commonly used to inactivate viruses 26 These agents cause diseases which are confined to the CNS have a prolonged incubation period show a slow, progressive, fatal course of disease show a spongiform encephalopathy characteristically result in vacuolation of neurons 27 These diseases (transmissible spongiform encephalopathies) are relatively rare in man. They may be acquired, inherited, or occur sporadically. but there is speculation that they may be more common than previously thought and they may have implications in the study of other CNS degenerative diseases 28 Kuru Kuru is a disease of man. It causes tremors and ataxia (failure of muscle coordination) and, in later stages, dementia. It is transmitted by rites for the dead which included autopsy and cannibalism in Fore people in Papua/New Guinea. 29 No one born since these practices ceased has acquired Kuru. There is no evidence for transmission to fetus, transmission via milk or intimate social contact. 30 Creutzfeldt-Jakob disease (CJD) CJD is a disease of man resulting in dementia and also tremors and lack of motor co-ordination. The disease can be transmitted to animals in the laboratory. disease have been observed to develop at ages 16 to 80+ years 31 CJD can be transmitted by medical manipulations: eg. cornea transplants, dura mater transplants, use of improper sterilized equipment in neurosurgery. 32 New variant CJD disease (human BSE) This is a form of CJD has been reported in the United Kingdom in patients who are usually younger (frequently under 40; average age at death: 28 years) than is the case for most CJD patients (average age of death: 68 years) This disease is also different from the usual CJD in that patients tend to present with psychiatric problems and in that the course of the disease tends to be more protracted. 33 Sufferers may eventually show any or all of the symptoms described above for other human prion diseases. The disease was first seen in 1996 and there is strong evidence to suggest that it is associated with exposure to BSEcontaminated beef. Strong BSE control measures have now been implemented. Autopsy reveals a distinctive neuropathological appearance and more PrP (prion protein) 34 This raises questions about sterilization of surgical instruments etc. and the possibility of iatrogenic spread. There is a possibility that vCJD agents may have been transmitted by blood transfusion it is thought leuko-depletion might decrease the chances of transmission by blood transfusion. 35