Picornaviruses PDF

Picornaviruses Dr Rania Talaat Abdel Haleem Lecturer of Medical Microbiology and Immunology Faculty of Medicine Helwan University  Picornaviruses (Pico = small, rna = RNA) They are the smallest RNA viruses; 25-30 nm Picornaviruses tha...

Picornaviruses Dr Rania Talaat Abdel Haleem Lecturer of Medical Microbiology and Immunology Faculty of Medicine Helwan University  Picornaviruses (Pico = small, rna = RNA) They are the smallest RNA viruses; 25-30 nm Picornaviruses that cause human diseases include the following genera: Human Enteroviruses (HEV) Hepatovirus is hepatitis A virus Rhinoviruses Parechoviruses Aphthoviruses  Picornaviruses 1 -Human Enteroviruses (HEV) are stable at pH 3 and they can resist the acidity of the stomach, so they can infect by the oral route. 2- Hepatovirus is hepatitis A virus which was classified as enterovirus type 72. It is now placed in a separate genus. 3- Rhinoviruses; which include more than 150 antigenic types. These infect by the respiratory route and are acid-labile at pH 3. 4- Parechoviruses 14 serotypes; they cause common cold, gastroenteritis, neonatal sepsis, aseptic meningitis, encephalitis and myocarditis. 5- Aphthoviruses cause foot and mouth disease in cattle, sheep and goats, which may be transmitted to man by contact or ingestion of infected meat.  Human Enteroviruses They include 5 species and several serotypes. The following is the new classification:- a-Polioviruses types 1-3 b- HEV-A includes coxsackieviruses A-12 types. c- HEV-B includes coxsackieviruses B-7 types and echo viruses 33 types. d- HEV-C includes coxsackieviruses A-12 types. e- Enteroviruses type 68-116 Polioviruses Polioviruses  Polioviruses They cause poliomyelitis, which in its full blown picture affects the CNS, destroys the motor neurons in the spinal cord, causing flaccid paralysis. Fortunately, most poliovirus infections are subclinical. Man is the only natural host or reservoir of infection.  Properties of Polioviruses It is an icosahedral non-enveloped virus, the genome is a positive sense single stranded RNA, 25-30 nm in diameter. There are 3 antigenic types. The virus infects only primates, e.g. man and monkeys as they possess specific receptors for viral attachment. They are grown in primary or continuous cell lines derived from man or monkey tissues causing characteristic cytopathogenic effects (CPE).  Pathogenesis of poliovirus Infection occurs by the ingestion of food or drink contaminated by stools of cases or carriers. Incubation period is 7-14 days Polioviruses  Pathogenesis of poliovirus Inapparent infection. Abortive infection Aseptic meningitis (non-paralytic poliomyelitis) Paralytic poliomyelitis  Pathogenesis of poliovirus Inapparent infection. The organism multiplies in the oropharynx (tonsils) and the peyer's patches in the intestine and is excreted in stools. Infection may stop at this stage Abortive infection Infection may continue and the virus passes to the deep cervical and deep mesenteric lymph nodes. Then it invades the blood stream Viraemia is associated with mild symptoms of fever, malaise, headache, nausea, and vomiting. The disease may be stopped at this stage Pathogenesis of poliovirus  Pathogenesis of poliovirus Aseptic meningitis (non-paralytic poliomyelitis) may occur and manifests by stiffness and pain in the back and neck. It usually recovers but it may progress to paralysis. Paralytic poliomyelitis occurs only in 0.1-1% of cases. The virus affects the anterior horn cells of the spinal cord leading to flaccid paralysis. In severe cases, it may affect the posterior horn cells, the vestibular nuclei and motor cortex. Death may occur due to respiratory paralysis.  Pathogenesis of poliovirus No permanent carrier state occurs, but virus excretion in stools can occur for several months. Immunity is permanent to the type of poliovirus causing the infection  Diagnosis Isolation of the virus from stools or throat washings is done on tissue culture. CPEs are identified by neutralization, immunofluorescence or by PCR. Paired serum samples are tested to demonstrate a rising antibody titre by neutralization or complement fixation tests. PCR is used for rapid detection of viral RNA in blood  Prophylaxis Active immunization: There are two vaccines that contain the three types of virus and produce neutralizing antibodies and prevent CNS infection Salk inactivated polio-vaccine (IPV) Sabin living attenuated oral polio-vaccine (OPV) Passive immunization: Gamma globulins given early to susceptible unimmunized contacts may be effective in preventing paralytic poliomyelitis.  I- Salk inactivated polio-vaccine (IPV) It is a formalin inactivated vaccine prepared from the three types of the virus grown in monkey kidney cell cultures. It is given in 4 subcutaneous doses at 2, 4 and 6 months and a booster injection is given at 4-6 years. The vaccine produces neutralizing antibodies (IgG and IgM) and prevents infection of the CNS. However, it does not prevent virus replication in the intestine. So, the vaccine protects against paralytic poliomyelitis but not against non-paralytic forms of infection. The vaccine can be safely given to immunosuppressed children and pregnant mothers, in whom Sabin vaccine is contraindicated.  II- Sabin living attenuated oral polio- vaccine (OPV) It is a living attenuated vaccine prepared from non-paralytogenic mutants of the three types of poliovirus grown on human diploid cell cultures and stabilized by MgCl2. Four doses are given orally at the age of 2, 4 and 6 months and a booster dose is given at 4- 6 years.  II- Sabin living attenuated oral polio- vaccine (OPV) The vaccine has the following advantages: 1- It is easily administered i.e. orally. 2- The live vaccine virus multiplies locally in the intestine, thus leads to production of serum neutralizing antibodies (IgG and IgM) and local immunity in the intestine by IgA and interferon. Hence, it prevents intestinal infection with the wild virus, thus preventing both paralytic and non- paralytic poliovirus infections. 3- The vaccine strains pass with the stools and are disseminated in the environment and can be transmitted to non-immunized children by faeco-oral route. This leads to spread of immunity in the community called "herd immunity" which may eventually lead to eradication of the wild poliovirus.  Disadvantages of Sabin vaccine: 1- Failure of vaccination which may be due to:  Loss of the potency of the vaccine due to improper refrigeration during transport or storage  Interference with replication of the virus in the intestine if the child is already infected with another enterovirus. 2- The vaccine may cause paralytic disease in immunodeficient children. Salk vaccine is recommended for these children. 3- Rarely (1/million), vaccine-associated paralytic poliomyelitis (VAPP) may occur due to reversion of the attenuated virus to the virulent type during its replication in vaccinated children (particularly type 2 and 3).  II- Sabin living attenuated oral polio- vaccine (OPV) In USA they use IPV and not OPV for the 4 doses of vaccination of children to avoid occurrence of VAPP. The current version of the inactivated vaccine used in USA in 2007 is the enhanced polio-vaccine elPV which proved to be as immunogenic as OPV and is not associated with the development of VAPP. A major campaign is under way by the WHO using OPV mass vaccination to eradicate poliovirus from the world as was done with smallpox. Coxsackieviruses  Coxsackieviruses Coxsackieviruses are classified into A and B based on their pathogenicity in newborn suckling mice: Coxsackieviruses A 12 types in HEV-A species and 12 types in HEV- C species They produce wide spread myositis and flaccid paralysis which is rapidly fatal without other observable lesions Coxsackieviruses B (7 types) in HEV-B species They produce focal myositis and other generalized mild lesions of the CNS, heart and pancreas. Coxsackieviruses They cause several disease syndromes in man. They are transmitted by the faeco-oral or respiratory route. They multiply in the GIT or oropharynx and disseminate via the blood stream. Pathogenesis and Pathology Virus has been recovered from the blood in the early stages of natural infection in humans. Virus is also found in the throat for a few days early in the infection and in the stools for up to 5–6 weeks. Virus distribution is similar to that of the other enteroviruses. Clinical Findings The incubation period of coxsackievirus infection ranges from 2 to 9 days. The clinical manifestations of infection with various coxsackieviruses are diverse and may present as distinct disease entities. They range from mild febrile illness to CNS, skin, cardiac, and respiratory diseases. The examples shown are not all-inclusive; different serotypes may be associated with a particular outbreak. The syndromes include: 1- Herpangina caused by group A affects children mainly and is characterized by fever, sore throat, anorexia, dysphagia, vomiting and abdominal pain. Vesicles appear on the throat and tongue. It is a self limited disease. The syndromes include: 2- Acute haemorrhagic conjunctivitis caused by group A 24. The syndromes include: 3- Hand foot and mouth disease caused mainly by group A. The disease is characterized by a vesicular rash on the hands and feet and ulceration in the mouth mainly in children The syndromes include: 4- Pleurodynia caused by group B , and is characterized by fever and chest pain. Abdominal pain may occur in some cases. The syndromes include: 5- Myocarditis and pericarditis caused by group B, infection may be fatal in neonates or may cause permanent heart damage and cardiomyopathy. 6- Diabetes mellitus: Coxsackievirus B 3.4 is suspected to have a role in type I diabetes mellitus. 7- Aseptic meningitis; caused by groups A and B. It is characterized by fever, malaise, headache, nausea and vomiting, stiff neck or back. 8- Minor febrile illness and upper respiratory infections with or without rash is caused by both groups A and B. 9- Diarrhea and hepatitis caused by group A and B.  Echoviruses There are 33 serotypes in HEV-B species. They are transmitted by the faeco-oral route. Diseases caused by echoviruses are; aseptic meningitis, encephalitis, febrile illness with or without rash, common cold, diarrhea, hepatitis, pleurodynia, myocarditis and pericarditis  Human enterovirus types 68-116 Enterovirus 68 causes pneumonia in children. Enterovirus 70 causes acute haemorrhagic conjunctivitis, and encephalitis. Enterovirus 71 causes meningitis, encephalitis and paralysis resembling poliomyelitis. They cause also hand-foot-and-mouth disease, and herpangina.  Rhinoviruses More than 150 types are known. These cause upper respiratory tract infections specially, common cold. They are responsible for about half of asthma exacerbations. They grow better at a temperature of 33°C which is the temperature of the nasopharynx. Infection is transmitted by contact or by airborne particles.  Rhinoviruses The virus enters via the respiratory tract and multiplies locally in the mucous membrane of the nasopharynx. Incubation period is short 2-4 days followed by headache, nasal discharge, mild cough and malaise. There is no blood invasion and the disease is self-limited. Immunity is due to local IgA and interferon. That is why immunity is short lived and several attacks may be acquired during one season. This is also due to multiplicity of antigenic types. Secondary bacterial infections may cause otitis media, sinusitis, bronchitis or pneumonitis, especially in children.