Theres only one serotype, so one infection will create lifelong immunity, and a live attenuated vaccine exists.

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1 GIT Viral Infections To start things off, Dr. Azmi rarely ever asks about anything that isn't in his slides. So the usefulness of this sheet is debatable. Last years slides are missing some things that have been added this year. Dr. Azmi will be giving us this years slides after he finishes all the lectures related to them. Introduction: Any part of the GI Tract can be infected with fungi, parasites, bacteria, or viruses. This course will be concerned with Viruses, and will be divided according to the region of the body infected. The first region we'll be talking about is the Salivary Glands. Salivary Glands: The most iconic virus that infects the salivary glands is the Mumps Virus. Mumps is a paramyxovirus, named for the facial expression such an infection causes. To "mump" means to grimace (to make a twisted facial expression meant to express pain, disgust, or wry amusement), and Mumps virus swells your parotid glands making you look like you're grimacing. The virion is nm in diameter. It is an enveloped virus that contains the V (viral) and S (soluble) proteins in addition to the six major proteins of paramyxoviruses. Theres only one serotype, so one infection will create lifelong immunity, and a live attenuated vaccine exists. Mumps is a systemic disease that causes viremia. It enters the body via the respiratory tract (usually in childhood). From the respiratory tract, it gains access to lymphoid tissue and then the blood stream, causing transient viremia. The viremia disseminates virus to many organs especially the parotid salivary glands (giving it the name of epidemic parotitis).

2 Mumps virus also reaches and infects other organs, which are: - The pancreas (causing pancreatitis) - The testis (causing orchitis) - The CNS (causing aspetic meningitis, encephalitis, or meningoencephalitis) - The ovaries (causing oophoritis) The ovaries have no membranes so they can swell without causing much pain. But the testis is limited by the Tunica Albuginea, which will cause the testis pain when it swells, and will cause pressure necrosis. However, the necrosis is spotty and the affected area is usually unilateral. That along with the fact that mumps usually infects children means that mumps does NOT lead to sterility, no matter how many grandma's will tell you otherwise. 25% of cases of mumps lead to ovary/testis infections. The most important target organ is the Parotid Gland. The virus is shed in saliva for about 15 days, which is 6 days before enlargement of parotid and 9 days after, meaning that the end of the incubation period of the disease is associated with shedding of the virus in saliva. The presence of the virus in saliva is not clinically dependent on viral parotitis, meaning that patients can be infectious without developing parotitis. However, 95% of symptomatic cases are associated with parotid enlargement. One third of mumps patients are subclinical. They develop immunity without showing clinical manifestations. Parotid enlargement is usually the first sign but thats not compulsory. The first manifestation can be anything else, like meningitis. Parotid enlargement is caused by periductal interstitial edema and local inflammation. The duct of the gland is surrounded by inflamed tissue. This causes stenosis (abnormal narrowing of a passageway of the body). This stenosis may be severe. For such individuals, salivation is accompanied by severe excruciating pain. One of the most refined and effective torture methods for such patients is to suck a lemon in front of them because it stimulates salivation.

3 The virus disseminates to the CNS. CNS involvement is very common. Pleocytosis (increased cell number) of CSF occurs in about 50% of mumps cases with CNS involvement. When that happens, the virus can reach the brain via the choroid plexus. Other organs can be involved, as we mentioned earlier. Pancreatic involvement, for example, can be mild or hemorrhagic, and can lead to Acute Abdomen (a sudden, severe abdominal pain of unclear etiology that is less than 24 hours in duration). Diagnosis is made by an elevation of the enzyme Amylase (lipase can also be increased but amylase increase is the diagnostic feature). Clinical Features of mumps virus infections: Incubation period of the infection is 2-3 weeks. There may be a prodromal phase (nonspecific manifestations of viral infection due to interferons and other cytokines). Clinical features of mumps reflect the pathogenesis of the infection. Approximately one third of all mumps virus infections occur without recognized symptoms. The featured characteristic of mumps virus infection is salivary gland swelling, especially enlargement of the parotid salivary gland. This enlargement is maximal within 48 hours from when the gland starts to swell. The parotid feels painful 2-4 days before swelling. Diagnosis is made on clinical grounds. Differential diagnosis is stones or tumor of the parotid. A famous person with a parotid tumor is some Barcelona coach that I couldn't catch the name of. Sucks for him (and Barcelona fans) because parotid tumors have really bad prognosis.

4 The virus is best isolated from saliva, although urine also works. Cerebrospinal Fluid works in cases of meningitis only. Cell cultures that can be used to culture the virus are Primary Monkey Kidney or Human Embryonic Kidney. Serological tests showing absence of IgA specific to Mumps and presence of IgG specific to Mumps indicates past infection. Infection can be pyogenic (forms pus) if it is related to involvement of pyogenic bacteria. If its not pyogenic we say that the infection is aseptic. Mumps has a worldwide distribution, although incidence has dropped since the introduction of the vaccine in Mumps vaccine was recommended to be given in a single dose at the age of 16 months in the past, and this would infer solid immunity in more than 95% of individuals for 20 years. But recently, since its given as a part of the Mumps Measles Rubella vaccine, it is being administered in 2 doses. 1 at the age of 1 year, and the second at the age of school entry or sometimes even college entry. In unvaccinated communities, mumps exhibits cyclic epidemics once every 3 years. Jordan has been vaccinated since 2005 as part of the expanded vaccination program. The virus requires a certain number of individuals (200000) to sustain circulation of itself. In smaller populations the virus can t maintain spread. Sustained coverage of 85% or greater is required to stop epidemics. Less coverage is worse than no coverage at all since the infection will be delayed until adulthood, which exhibits more severe symptoms. And thats all we'll be saying about Mumps in this course.

5 Viral Gastroenteritis Viral Gastroenteritis is virally caused infection of the gastrointestinal tract. Infective Diarrhea is viral in 75% of cases. Therefore antibiotics for diarrhea are not needed in most cases. Viral Gastroenteritis is the second most common viral illness after upper respiratory tract infection, and is a major killer of undernourished infants in developing countries. Rotavirus kills a lot of children this way, due only to dehydration from diarrhea. Viruses known to be associated with Viral Gastroenteritis - rotavirus - adenovirus 40 and 41 - Caliciviruses - norwalk like viruses (or small round structured viruses) - astroviruses - coronaviruses - noroviruses Viruses that multiply in the GIT but spread elsewhere - poliovirus - coxsackie A (except A24) - coxsackie B - echoviruses - enteroviruses - hepatitis A and E - adenoviruses 1-39 and reoviruses (except rotavirus)

6 Opportunistic viruses in the GIT - Cytomegalovirus - Herpes simplex virus - Varicella Zoster Virus - Human Immunodeficiency Virus Most important causative viruses - infants (do not infect adults because this infection is common in infants so individuals will be immune by the time they become adults) - Rotavirus A - Adenoviruses 40 and 41 - Coxsackie A24 - infants children and adults - Norwalk Viruses - Astroviruses - Rotavirus B Rotavirus Rotavirus can be divided into 5 groups, termed Group A B C D and E. Group A is the most important human GIT virus. Rotavirus A is the most common cause of diarrhea in infants, especially Rotavirus A1. 73% of infantile diarrhea cases are caused by Rotavirus A1. Rotavirus A can also infect monkeys. Rotavirus Group B primarily infects animals, although it can also infect human adults. Rotavirus Group C mainly infects piglets (baby pigs), although it can also infect humans. It does not cause epidemics in either humans or animals, however. Rotavirus Group D infects bears, and Rotavirus Group E infects pigs.

7 Rotavirus is a major cause of viral gastroenteritis and is a major killer of infants. They are naked viruses that behave like enveloped viruses. They are 70nm in size and are round in shape. They're double-shelled (they have an outer capsid and an inner capsid) and the outer capsid must be gotten rid of for an infection to take place. It can still enter the cell with the outer capsid though. Cleavage of outer capsid results in ISVP (Intermediate/Infectious SubViral Particle) formation. Genome is Double-Stranded RNA. It was first identified as a cause of gastroenteritis in It is the main cause of diarrhea in infants and children, but by 5 years of age, all children will have been infected. This does not mean immunity is established, however, since mild reinfection is possible. Rotavirus is responsible for half a million cases of deaths annually worldwide. The viruses are very stable and may remain viable for weeks or months if not disinfected (since they're naked viruses and naked viruses are strong). They are capable of gene reassortment, so if 2 rotaviruses infect the same cell a new strand of the virus will be created which will be a mixture of the two. Rotaviruses resemble enveloped viruses, in that they acquire an envelope during replication but then lose it upon leaving. They are stable at room temperature. Treatment with detergents does not work that well because they're stable at ph s They are also resistant to freeze-thaw cycles so infected food is lost forever. Proteolytic enzymes will cause shedding of outer capsid which will increase infectivity/create the ISVP. Viral particles are acquired through consumption of contaminated food, water, or other beverages, or from contaminated fingers.

8 Diarrhea is caused by the following: First, the virus is consumed. It then travels to the small intestine where it replicates in the brush border. Infection of microvilli will then take place, causing them to shorten and lump together. This will prevent absorption of water, resulting in a net secretion of water, causing isotonic watery diarrhea. Individuals may lose 20 L of fluid per day as a result. Thats why fluids and electrolytes MUST be replaced. But otherwise, the virus is self limited, with the infection lasting usually only a few days. Clinically speaking, the incubation period is short at only 1-3 days.the extent of clinical manifestations depend on whether or not there was a previous infection. The first infection after the age of 3 months is the most severe form. Rotavirus infection may be asymptomatic or may result in severe diarrhea. Gastroenteritis symptoms generally resolve within 3-7 days. Complications include - severe diarrhea - dehydration - electrolyte imbalance - metabolic acidosis Immunodeficient children may have more severe persistent disease due to failure to resolve infection Immunity develops but its type specific. The protective antigens are VP7 and VP4. First infection usually does not lead to permanent immunity, as reinfection can occur at any age. However, reinfection is usually less severe. Reservoir is the human gastrointestinal tract. Transmission takes place by the fecal-oral route. Season of spread is usually fall or winter, in other words, the colder months. Communicability lasts 2 days before and 10 days after onset of clinical manifestations

9 Rotavirus exhibits a worldwide distribution. Outbreaks take place, especially in nursery's, hospitals, day-care centers and other places where lots of children get grouped together. Most children are infected by the age of 4 years. Groups at risk of developing infection are - children in child care centers - children in hospital wards (nosocomial rotavirus) - caretakers, parents of these children - patients with immunodeficiency related diseases, regardless of there age Prevention of disease has been via vaccination. The first vaccine was tried for 2-3 months. 15 cases of intussusception (telescoping of the small intestine) were reported out of the 1.5 million people vaccinated, leading to the vaccine being banned. Intussusception leads to acute abdomen. Later on, new vaccines were developed. The first was RotaTeq, which was made of 5 forms of the virus. This one contains no mercury-containing preservatives so that anti-vaccine people can t whine about it causing autism (there is no clinical evidence that any vaccines at all cause autism, but uneducated activists seem to think that mercury found in vaccines will cause autism or something). The second vaccine was Rotarix, which contains only 1 strain of rotavirus (group A1). This vaccine is given in 2 oral doses, one at 2 months, and one at 4 months of age. This vaccine has proven to do its job, exact numbers will be in the slides when we get those. Vaccine is recommended for all infants who don t have contraindications, such as severe combined immunodeficiency. Intussusception has been proven to be unrelated to the vaccine.

10 Adverse effects to the vaccine: - Vomiting - Diarrhea - Nasopharyngitis - Fever Diagnosis of Rotavirus: Rotavirus does not grow in cell culture. It has to be demonstrated by electron microscopy or immune electron microscopy, or its antigens or antibodies to the virus should be detected via immunological means such as agglutination, ELISA, or immunofluorescence, or the viral genome can be detected via PCR. Dedicated to all of us "normal human beings" who are finding it hard to stay up-to-date with Dr. Muhtaseb's lectures. Done by, Khaled Al-Juwhari