Viruses Infecting GIT 2024/2025 PDF

Damietta University Faculty of Medicine L2 Sem3 A GIT Module Lecture #1  ILOs of the lectures 1. Identify the most common viruses that can cause infections of the GI tract. 2. Compare the major characteristics of specific viral diseases affecting the GI tract and liver....

Damietta University Faculty of Medicine L2 Sem3 A GIT Module Lecture #1  ILOs of the lectures 1. Identify the most common viruses that can cause infections of the GI tract. 2. Compare the major characteristics of specific viral diseases affecting the GI tract and liver.  Contents 1. Viruses infecting the GIT 2. Reoviridae family 3. Rotaviruses: Virology, Infection, Diagnosis, Vaccine and Management. 4. Gastroenteritis caused by Norovirus. 5. Gastroenteritis caused by Astroviruses. 6. Enteroviruses and their family Picornaviridae. 7. Poliovirus and Poliomyelitis. 8. Poliovirus vaccine; Salk vaccine and Sabine vaccine.  Clinical Case Ali is 3-year child from Damietta. Last week he had fever , vomiting and diarrhea. His mother took him to the doctor who diagnosed the case as viral gastroenteritis. The doctor asked the mother about recent booster dose of poliomyelitis vaccine, and if Ali had received Rotavirus vaccine. The doctor prescribed fluids as Ali has dehydration. Few days later Ali was fine, and he visited the doctor again to receive Rotavirus vaccine.  Viruses infecting The GIT and Liver  Viral infections of the GIT and Liver are very common. Viruses causing GIT infection and diarrhea (Reoviruses, Astroviruses, and Norovirus) result in millions of lost working days each year, as well as much discomfort. Viral gastroenteritis results in about 1,000 deaths among children each day, the highest incidence being in developing countries of the world. Viral Hepatitis is affecting many people worldwide and in Egypt it is a major health problem.  Reoviridae Reoviridae is a family of double-stranded RNA viruses. Its name was derived from 3 letters : R (respiratory) , E (entero) and O (orphan). This is because they were isolated from respiratory secretions and from stool without being associated with any known disease in man at that time. The main member in this family with medical importance is called Rotavirus.  Reoviridae Reoviruses are Double-stranded RNA, non- enveloped viruses and have icosahedral capsid. Ultrastructure studies show that virion capsids are composed of two or three separate layer. The core contains the double stranded RNA genome. The genomes contain 10–12 segments which are grouped into three categories corresponding to their size: L (large), M (medium) and S (small).  Rotavirus Rotavirus is the main member of Reoviridae family. It has three shells: an outer capsid, inner capsid and core which surrounds the 11 segments of double-stranded RNA.  Rotavirus Rotavirus infections cause endemic/epidemic gastroenteritis and infantile diarrhea (a major cause of death in the developing world). Rotavirus causes self-limited infections, rare in adults, but may kill infants unless properly treated. The Rotavirus infections are widespread in children, especially in day-care centers.  Diagnosis and Management Infection occurs by feco-oral route. Diagnosis is confirmed by virus detection in stool by E/M or isolation by culture. Treatment : oral rehydration therapy with isotonic glucose/mineral salt solution. No specific antiviral drugs.  Rotavirus vaccine Rotarix is a monovalent, human, live attenuated rotavirus vaccine containing one rotavirus strain. It is administered by mouth in two doses at 2 and 4 months of age. RotaTeq is a live attenuated, oral pentavalent vaccine that contains five rotavirus strains produced by reassortment. RotaTeq (RV5), is given in three doses at 2 months, 4 months, and 6 months of age.  Gastroenteritis Caused by Noroviruses Noroviruses, commonly identified as Norwalk viruses, are Caliciviruses. Several strains can cause gastroenteritis. There are millions of cases a year, predominately in infants, young children, and the elderly.  Noroviruses Noroviruses (NoV) are a genetically diverse group of single-stranded positive-sense RNA, non- enveloped viruses belonging to Caliciviridae. Noroviruses are classified into seven different genogroups (GI, GII, GIII, GIV, GV, GVI, and GVII), which can be further divided into different genetic clusters or genotypes. Most noroviruses that infect humans belong to genogroups GI and GII.  Noroviruses The signs and symptoms of norovirus infection are similar to those for rotavirus, with watery diarrhea, mild cramps, and fever. Sometimes infection causes projectile vomiting. The illness is usually relatively mild, develops 12 to 48 hours after exposure, and clears within 2 days without treatment. However, dehydration may occur.  Noroviruses Norovirus can be diagnosed using PCR or enzyme immunoassay (EIA) testing. RT-qPCR is the preferred approach as EIA is insufficiently sensitive. No medications are available, the illness is usually self-limiting. Rehydration therapy and electrolyte replacement may be used. Good hygiene, hand washing, and careful food preparation reduce the risk of infection.  Astroviruses Astroviruses are single-stranded RNA viruses (family Astroviridae) that can cause severe gastroenteritis, especially in infants and children. Astroviruses are 28–35 nm diameter, icosahedral viruses that have a characteristic five- or six- pointed star-like surface structure when viewed by electron microscopy.  Gastroenteritis Caused by Astroviruses Signs and symptoms include diarrhea, nausea, vomiting, fever, abdominal pain, headache, and malaise. The viruses are transmitted through the fecal-oral route (contaminated food or water). For diagnosis, stool samples are analyzed. Testing may involve enzyme immunoassays and immune electron microscopy. Treatment involves supportive rehydration and electrolyte replacement if needed.  Enteroviruses Enterovirus is a genus of positive-sense single- stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission- route through the intestine. Enteroviruses are members of the family Picornaviridae, a large and diverse group of small RNA viruses.  Picornaviruses Classification 1. Enterovirus: Poliovirus, Coxsackie, echo viruses 2. Rhinovirus: Human rhinovirus A 3. Hepatovirus: HAV. 4. Cardiovirus: Encephalomyocarditis virus 5. Aphthovirus: Foot-and-mouth disease virus. Picornaviruses Classification  Poliovirus Virus: small (30nm) with an icosahedral capsid enclosing a positive-sense, single-stranded RNA genome. Relatively resistant to extremes of pH and temperature, and to lipid solvents and detergents. Antigenic types: 3 serotypes (PV1, PV2 and PV3) that are extremely virulent and produce the same disease symptoms.  Pathogenesis of Poliomyelitis The disease is transmitted via the fecal-oral route, by ingesting contaminated food or water After ingestion, the virus multiplies in the oropharynx and associated lymph nodes, in the gut mucosa and regional lymph nodes. From lymph nodes the virus reaches blood, and the patient may experience a fever about a week after exposure.  Pathogenesis of Poliomyelitis Virus produced and released into the gut (and throat initially) can be isolated from the throat or stools following the incubation period. Most infections are asymptomatic or manifest as a minor transient febrile illness. Occasionally (in 0.1 – 1% of cases) viraemia may lead to CNS involvement.  Poliomyelitis Clinically 4 forms are usually described: 1. Abortive Poliomyelitis 2. Non-paralytic Poliomyelitis (aseptic viral meningitis) 3. Paralytic Poliomyelitis 4. Progressive Post poliomyelitis Muscle Atrophy.  Pathogenesis of Poliomyelitis Damage to the anterior horn motor neurons of the spinal cord may cause paralysis. About 1% of people infected with the most virulent strains experience paralysis (while about 99% have asymptomatic infections). Death is usually due to respiratory failure by paralysis of the intercostal muscles and diaphragm.  Laboratory Diagnosis Viral Isolation Poliovirus may be isolated from the stool or pharynx by cultures on human or monkey cells with recognition of CPE after 3 – 6 days. Isolation of virus from the cerebrospinal fluid (CSF) is rarely accomplished but antibodies may be detected in CSF.  Laboratory Diagnosis Serology: Antibodies to poliovirus are generally detected in the blood of infected patients early in the course of infection. Antibodies are not helpful in providing a positive diagnosis of poliomyelitis but do give the immune status of individuals (need or don't need further vaccination).  Poliovirus Vaccines Inactivated poliovirus vaccine (Salk Vaccine) was licensed in 1955 and was used extensively from that time until the early 1960s. In 1963, live attenuated trivalent oral polio vaccine (OPV) or (Sabine Vaccine) was licensed. Sabine Vaccine was the vaccine of choice in most countries of the world. Poliovirus Vaccines  Sabine Vaccine The 3 serotypes of poliovirus 1, 2 and 3 attenuated to lose neurovirulence (not expensive). It is given as oral drops (easy administration) on 3 doses plus repeated boosters. Live vaccine mimics natural infection and replicates in the gut with good immunity including IgA (advantage).  Sabine Vaccine One strain may interfere with uptake of another (disadvantage); hence it must be given repeatedly to ensure immunity to all 3 types. Cold chain should be maintained during storing and distributing vaccine to keep its potency (disadvantage). It can not be given to immunocompromised infants ( another disadvantage).  Salk Vaccine This vaccine contains the three serotypes of polio vaccine virus. The viruses are grown in a type of monkey kidney tissue culture (Vero cell line) and inactivated with formaldehyde (expensive). It is supplied in a single-dose prefilled syringe and administered by subcutaneous or intramuscular injection (disadvantage).  Salk Vaccine It is given as 3 injections at 3 to 6 months of age with later boosters. Much antigen is required which makes the vaccine expensive (disadvantage). Effective when coverage is good (nearly 100% immunity in people vaccinated but with no local IgA). Can be used in immunocompromized (advantage).  Clinical Case Ali is 3-year child from Damietta. Last week he had fever , vomiting and diarrhea. His mother took him to the doctor who diagnosed the case as viral gastroenteritis. The doctor asked the mother about recent booster dose of poliomyelitis vaccine, and if Ali had received Rotavirus vaccine. The doctor prescribed fluids as Ali has dehydration. Few days later Ali was fine and he visited the doctor again to receive Rotavirus vaccine.  Case Discussion 1. What are viral causes of gastroenteritis in children? 2. To which family does Rotavirus belong? 3. What are Rotavirus vaccines? 4. What is the treatment of Dehydration? 5. What are poliomyelitis vaccines? 6. What are the advantages and disadvantages of each type of polio vaccines?  Summary 1. Some viruses may infect GIT causing gastrodermis. 2. The most common viruses causing gastroenteritis are Rotavirus, Norovirus and Astrovirus. 3. Rotavirus belongs to Reoviridae family. 4. Reoviridae is the only double stranded RNA human virus family. 5. Rotavirus has no envelope but has 3 layers capsid. 6. The double stranded RNA genome is made from 11 segments grouped according to their size into: L , M and S segments.  Summary 7. Noroviruses (NoV) are single-stranded positive- sense RNA, non-enveloped viruses belonging to Caliciviridae. 8. Astroviruses are single-stranded RNA viruses (family Astroviridae) that look like stars in electron microscopic pictures. 9. Viral gastroenteritis is manifested by fever, diarrhea and sometimes vomiting. 10. Infection occurs via fecal-oral route. 11. The diagnosis depends on detection of the virus in stool by electron microscope or by EIA.  Summary 12.No specific treatment is available, but treatment of dehydration is essential. 13.Rotavirus has 2 types of vaccines. 14.Enterovirus is a genus of the family Picornaviridae (positive-sense single- stranded RNA viruses) associated with several human and mammalian diseases. 15.The prototype of enteroviruses is Poliovirus the causative agent of poliomyelitis.  Summary 16. Clinically 4 forms of poliomyelitis are usually described: 1- Abortive Poliomyelitis, 2- Non- paralytic Poliomyelitis (aseptic viral meningitis), 3- Paralytic Poliomyelitis and 4- Progressive Post poliomyelitis Muscle Atrophy. 17. There 2 vaccines for poliomyelitis called Salk and Sabine vaccines ( each of them has advantages and disadvantages) but they could almost prevent new cases.  References 1. Viruses Causing Diarrhoea in the Developing World." Current Opinions in Infectious Diseases 22 (2009) 5: pp. 477–482. 2. "Viral Gastroenteritis." Michael Vincent F Tablang. http://emedicine.medscape.com/article /176515-overview. (2021).