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PICORNAVIRUSES: INTRODUCTION Picornaviruses are small (20–30 nm) nonenveloped viruses composed of an icosahedral nucleocapsid and a single-stranded RNA genome. The genome RNA has positive polarity; i.e., on entering the cell, it functions as the viral mRNA. The genome RNA is unusual because it has a protein on the 5' end that serves as a primer for transcription by RNA polymerase. Picornaviruses replicate in the cytoplasm of cells. They are not inactivated by lipid solvents, such as ether, because they do not have an envelope. The picornavirus family includes two groups of medical importance: the enteroviruses and the rhinoviruses. Among the major enteroviruses are poliovirus, coxsackieviruses, echoviruses, and hepatitis A virus (which is described in Chapter 41). Enteroviruses infect primarily the enteric tract, whereas rhinoviruses are found in the nose and throat (rhino = nose). Important features of viruses that commonly infect the intestinal tract are summarized in Table 40–1. Enteroviruses replicate optimally at 37°C, whereas rhinoviruses grow better at 33°C, in accordance with the lower temperature of the nose. Enteroviruses are stable under acid conditions (pH 3–5), which enables them to survive exposure to gastric acid, whereas rhinoviruses are acid-labile. This explains why rhinovirus infections are restricted to the nose and throat. Table 40–1. Features of Viruses Commonly Infecting the Intestinal Tract. Virus Nuclei c Acid Disease Number Lifelong Vaccine Antivira of Immunit Availabl l Serotype y to e Therap s Disease y Poliovirus RNA Poliomyeliti 3 s Yes (type- + specific) – Echoviruses RNA Meningitis, etc Many No – – Coxsackieviruse RNA s Meningitis, Many carditis, etc No – – Hepatitis A virus (enterovirus 72) Hepatitis Yes + – RNA 1 Rotavirus RNA Diarrhea Several1 No –2 – Norwalk virus (Norovirus) RNA Diarrhea Unknown No – – Adenovirus DNA Diarrhea 41; of which 2 cause diarrhea Unknown – – Exact number uncertain. 1 Rotavirus vaccine was released but was withdrawn because of side effects (see text). 2 ENTEROVIRUSES Poliovirus Disease This virus causes poliomyelitis. Important Properties The host range is limited to primates, i.e., humans and nonhuman primates such as apes and monkeys. This limitation is due to the binding of the viral capsid protein to a receptor found only on primate cell membranes. However, note that purified viral RNA (without the capsid protein) can enter and replicate in many nonprimate cells—the RNA can bypass the cell membrane receptor; i.e., it is "infectious RNA." There are three serologic (antigenic) types based on different antigenic determinants on the outer capsid proteins. Because there is little cross-reaction, protection from disease requires the presence of antibody against each of the three types. Summary of Replicative Cycle The virion interacts with specific cell receptors on the cell membrane and then enters the cell. The capsid proteins are then removed. After uncoating, the genome RNA functions as mRNA and is translated into one very large polypeptide called noncapsid viral protein 00. This polypeptide is cleaved by a virus-encoded protease in multiple steps to form both the capsid proteins of the progeny virions and several noncapsid proteins, including the RNA polymerase that synthesizes the progeny RNA genomes. Replication of the genome occurs by synthesis of a complementary negative strand, which then serves as the template for the positive strands. Some of these positive strands function as mRNA to make more viral proteins, and the remainder become progeny virion genome RNA. Assembly of the progeny virions occurs by coating of the genome RNA with capsid proteins. Virions accumulate in the cell cytoplasm and are released upon death of the cell. They do not bud from the cell membrane. Transmission & Epidemiology Poliovirus is transmitted by the fecal–oral route. It replicates in the oropharynx and intestinal tract. Humans are the only natural hosts. As a result of the success of the vaccine, poliomyelitis caused by naturally occurring "wild-type" virus has been eradicated from the United States and, indeed, from the entire Western hemisphere. The rare cases in the United States occur mainly in (1) people exposed to virulent revertants of the attenuated virus in the live vaccine and (2) unimmunized people exposed to "wild-type" poliovirus while traveling abroad. Before the vaccine was available, epidemics occurred in the summer and fall. The World Health Organization set the eradication of paralytic polio by 2005 as a goal. Unfortunately, as of 2007, paralytic polio still exists in 16 countries, but its incidence is greatly reduced. In 1988, there were 388,000 cases of paralytic polio worldwide, whereas in 2005 there were fewer than 2000. Thus far, smallpox is the only infectious disease that has been eradicated, a consequence of the worldwide use of the smallpox vaccine. Pathogenesis & Immunity After replicating in the oropharynx and small intestine, especially in lymphoid tissue, the virus spreads through the bloodstream to the central nervous system. It can also spread retrograde along nerve axons. In the central nervous system, poliovirus preferentially replicates in the motor neurons located in the anterior horn of the spinal cord. Death of these cells results in paralysis of the muscles innervated by those neurons. Paralysis is not due to virus infection of muscle cells. The virus also affects the brain stem, leading to "bulbar" poliomyelitis (with respiratory paralysis), but rarely damages the cerebral cortex. In infected individuals, the immune response consists of both intestinal IgA and humoral IgG to the specific serotype. Infection provides lifelong type-specific immunity. Clinical Findings The range of responses to poliovirus infection includes (1) inapparent, asymptomatic infection; (2) abortive poliomyelitis; (3) nonparalytic poliomyelitis; and (4) paralytic poliomyelitis. Asymptomatic infection is quite common. Roughly 1% of infections are clinically apparent. The incubation period is usually 10–14 days. The most common clinical form is abortive poliomyelitis, which is a mild, febrile illness characterized by headache, sore throat, nausea, and vomiting. Most patients recover spontaneously. Nonparalytic poliomyelitis manifests as aseptic meningitis with fever, headache, and a stiff neck. This also usually resolves spontaneously. In paralytic poliomyelitis, flaccid paralysis is the predominant finding, but brain stem involvement can lead to life-threatening respiratory paralysis. Painful muscle spasms also occur. The motor nerve damage is permanent, but some recovery of muscle function occurs as other nerve cells take over. In paralytic polio, both the meninges and the brain parenchyma (meningoencephalitis) are often involved. If the spinal cord is also involved, the term meningomyeloencephalitis is often used. A post-polio syndrome that occurs many years after the acute illness has been described. Marked deterioration of the residual function of the affected muscles occurs many years after the acute phase. The cause of this deterioration is unknown. No permanent carrier state occurs following infection by poliovirus, but virus excretion in the feces can occur for several months. Laboratory Diagnosis The diagnosis is made either by isolation of the virus or by a rise in antibody titer. Virus can be recovered from the throat, stool, or spinal fluid by inoculation of cell cultures. The virus causes a cytopathic effect (CPE) and can be identified by neutralization of the CPE with specific antisera. Treatment There is no antiviral therapy. Treatment is limited to symptomatic relief and respiratory support, if needed. Physiotherapy for the affected muscles is important. Prevention Poliomyelitis can be prevented by both the killed vaccine (Salk vaccine, inactivated vaccine, IPV) and the live, attenuated vaccine (Sabin vaccine, oral vaccine, OPV) (Table 40–2). Both vaccines induce humoral antibodies, which neutralize virus entering the blood and hence prevent central nervous system infection and disease. Both the killed and the live vaccines contain all three serotypes. At present, the inactivated vaccine is preferred for reasons that are described below. Table 40–2. Important Features of Poliovirus Vaccines. Attribute Killed (Salk) Live (Sabin) Prevents disease Yes Yes Interrupts transmission No Yes Induces humoral IgG Yes Yes Induces intestinal IgA No Yes Affords secondary protection by spread to others No Yes Interferes with replication of virulent virus in gut No Yes Reverts to virulence No Yes (rarely) Coinfection with other enteroviruses may impair immunization No Yes Can cause disease in the immunocompromised No Yes Route of administration Injection Oral Requires refrigeration No Yes Duration of immunity Shorter Longer The current version of the inactivated vaccine is called enhanced polio vaccine, or eIPV. It has a higher seroconversion rate and induces a higher titer of antibody than the previous IPV. eIPV also induces some mucosal immunity IgA, making it capable of interrupting transmission, but the amount of secretory IgA induced by eIPV is significantly less than the amount induced by OPV. OPV is therefore preferred for eradication efforts. The only version of polio vaccine currently produced in the United States is eIPV. In certain countries where polio remains endemic (e.g., India), a monovalent oral polio vaccine is used because the rate of seroconversion is higher with the monovalent vaccine than with the trivalent one. In the past, the live vaccine was preferred in the United States for two main reasons. (1) It interrupts fecal–oral transmission by inducing secretory IgA in the gastrointestinal tract. (2) It is given orally and so is more readily accepted than the killed vaccine, which must be injected. The live vaccine has four disadvantages: (1) Rarely, reversion of the attenuated virus to virulence will occur, and disease may ensue (especially for the type 3 virus); (2) it can cause disease in immunodeficient persons and therefore should not be given to them; (3) infection of the gastrointestinal tract by other enteroviruses can limit replication of the vaccine virus and reduce protection; and (4) it must be kept refrigerated to prevent heat inactivation of the live virus. Outbreaks of paralytic polio caused by vaccine-derived poliovirus (VDPV) continue to occur, especially in areas where there are large numbers of unimmunized people. These VDPV strains have lost their attenuation by acquiring genes from wild type enteroviruses by recombination. Outbreaks of VDPV-associated paralytic polio have been contained by campaigns to immunize people in the affected area with the oral (Sabin) vaccine that interrupts fecal–oral transmission. The duration of immunity is thought to be longer with the live than with the killed vaccine, but a booster dose is recommended with both. The currently approved vaccine schedule consists of four doses of inactivated vaccine administered at 2 months, 4 months, 6–18 months, and upon entry to school at 4–6 years. One booster (lifetime) is recommended for adults who travel to endemic areas. The use of the inactivated vaccine should prevent some of the approximately 10 cases per year of vaccine-associated paralytic polio that arise from reversion of the attenuated virus in the vaccine. In the past, some lots of poliovirus vaccines were contaminated with a papovavirus, SV40 virus, which causes sarcomas in rodents. SV40 virus was a "passenger" virus in the monkey kidney cells used to grow the poliovirus for the vaccine. Fortunately, no increase in cancer occurred in persons inoculated with the SV40 virus–containing polio vaccine. However, there is some evidence that SV40 DNA can be found in certain human cancers such as non-Hodgkin's lymphoma; the role of SV40 as a cause of cancer in persons immunized with early versions of the polio vaccine is unresolved. At present, cell cultures used for vaccine purposes are carefully screened to exclude the presence of adventitious viruses. Passive immunization with immune serum globulin is available for protection of unimmunized individuals known to have been exposed. Passive immunization of newborns as a result of passage of maternal IgG antibodies across the placenta also occurs. Quarantine of patients with disease is not effective, because fecal excretion of the virus occurs in infected individuals prior to the onset of symptoms and in those who remain asymptomatic. Coxsackieviruses Coxsackieviruses are named for the town of Coxsackie, NY, where they were first isolated. Diseases Coxsackieviruses cause a variety of diseases. Group A viruses cause, for example, herpangina, acute hemorrhagic conjunctivitis, and hand-foot-andmouth disease, whereas group B viruses cause pleurodynia, myocarditis, and pericarditis. Both types cause nonspecific upper respiratory tract disease (common cold), febrile rashes, and aseptic meningitis. Important Properties Group classification is based on pathogenicity in mice. Group A viruses cause widespread myositis and flaccid paralysis, which is rapidly fatal, whereas group B viruses cause generalized, less severe lesions of the heart, pancreas, and central nervous system and focal myositis. At least 24 serotypes of coxsackievirus A and 6 serotypes of coxsackievirus B are recognized. The size and structure of the virion and the nature of the genome RNA are similar to those of poliovirus. Unlike poliovirus, they can infect mammals other than primates. Summary of Replicative Cycle Replication is similar to that of poliovirus. Transmission & Epidemiology Coxsackieviruses are transmitted primarily by the fecal–oral route, but respiratory aerosols also play a role. They replicate in the oropharynx and the intestinal tract. Humans are the only natural hosts. Coxsackievirus infections occur worldwide, primarily in the summer and fall. Pathogenesis & Immunity Group A viruses have a predilection for skin and mucous membranes, whereas group B viruses cause disease in various organs such as the heart, pleura, pancreas, and liver. Both group A and B viruses can affect the meninges and the motor neurons (anterior horn cells) to cause paralysis. From their original site of replication in the oropharynx and gastrointestinal tract, they disseminate via the bloodstream. Immunity following infection is provided by type-specific IgG antibody. Clinical Findings GROUP A–SPECIFIC DISEASES Herpangina is characterized by fever, sore throat, and tender vesicles in the oropharynx. Hand-foot-and-mouth disease is characterized by a vesicular rash on the hands and feet and ulcerations in the mouth, mainly in children. GROUP B–SPECIFIC DISEASES Pleurodynia (Bornholm disease, epidemic myalgia, "devil's grip") is characterized by fever and severe pleuritic-type chest pain. Myocarditis and pericarditis are characterized by fever, chest pain, and signs of congestive failure. Dilated cardiomyopathy with global hypokinesia of the myocardium is a feared sequel that often requires cardiac transplantation to sustain life. Diabetes in mice can be caused by pancreatic damage as a result of infection with coxsackievirus B4. This virus is suspected to have a similar role in juvenile diabetes in humans. DISEASES CAUSED BY BOTH GROUPS Both groups of viruses can cause aseptic meningitis, mild paresis, and acute flaccid paralysis similar to poliomyelitis. Upper respiratory infections and minor febrile illnesses with or without rash can occur also. Laboratory Diagnosis The diagnosis is made either by isolating the virus in cell culture or suckling mice or by observing a rise in titer of neutralizing antibodies. A rapid (2.5 hour) PCRbased test for enteroviral RNA in the spinal fluid is useful for making a prompt diagnosis of viral meningitis because culture techniques typically take days to obtain a result. Treatment & Prevention There is neither antiviral drug therapy nor a vaccine available against these viruses. No passive immunization is recommended. Echoviruses The prefix ECHO is an acronym for enteric cytopathic human orphan. Although called "orphans" because they were not initially associated with any disease, they are now known to cause a variety of diseases such as aseptic meningitis, upper respiratory tract infection, febrile illness with and without rash, infantile diarrhea, and hemorrhagic conjunctivitis. The structure of echoviruses is similar to that of other enteroviruses. More than 30 serotypes have been isolated. In contrast to coxsackieviruses, they are not pathogenic for mice. Unlike polioviruses, they do not cause disease in monkeys. They are transmitted by the fecal–oral route and occur worldwide. Pathogenesis is similar to that of the other enteroviruses. Along with coxsackieviruses, echoviruses are one of the leading causes of aseptic (viral) meningitis. The diagnosis is made by isolation of the virus in cell culture. Serologic tests are of little value, because there are a large number of serotypes and no common antigen. There is no antiviral therapy or vaccine available. Other Enteroviruses In view of the difficulty in classifying many enteroviruses, all new isolates have been given a simple numerical designation since 1969. Enterovirus 70 is the main cause of acute hemorrhagic conjunctivitis, characterized by petechial hemorrhages on the bulbar conjunctivas. Complete recovery usually occurs, and there is no therapy. Enterovirus 71 is one of the leading causes of viral central nervous system disease, including meningitis, encephalitis, and paralysis. It also causes diarrhea, pulmonary hemorrhages, hand-foot-and-mouth disease, and herpangina. Enterovirus 72 is hepatitis A virus, which is described in Chapter 41. RHINOVIRUSES Disease These viruses are the main cause of the common cold. Important Properties There are more than 100 serologic types. They replicate better at 33°C than at 37°C, which explains why they affect primarily the nose and conjunctiva rather than the lower respiratory tract. Because they are acidlabile, they are killed by gastric acid when swallowed. This explains why they do not infect the gastrointestinal tract, unlike the enteroviruses. The host range is limited to humans and chimpanzees. Summary of Replicative Cycle Replication is similar to that of poliovirus. The cell surface receptor for rhinoviruses is ICAM-1, an adhesion protein located on the surface of many types of cells. Transmission & Epidemiology There are two modes of transmission for these viruses. In the past, it was accepted that they were transmitted directly from person to person via aerosols of respiratory droplets. However, now it appears that an indirect mode, in which respiratory droplets are deposited on the hands or on a surface such as a table and then transported by fingers to the nose or eyes, is also important. The common cold is reputed to be the most common human infection, although data are difficult to obtain because it is not a well-defined or notifiable disease. Millions of days of work and school are lost each year as a result of "colds." Rhinoviruses occur worldwide, causing disease particularly in the fall and winter. The reason for this seasonal variation is unclear. Low temperatures per se do not predispose to the common cold, but the crowding that occurs at schools, for example, may enhance transmission during fall and winter. The frequency of colds is high in childhood and tapers off during adulthood, presumably because of the acquisition of immunity. A few serotypes of rhinoviruses are prevalent during one season, only to be replaced by other serotypes during the following season. It appears that the population builds up immunity to the prevalent serotypes but remains susceptible to the others. Pathogenesis & Immunity The portal of entry is the upper respiratory tract, and the infection is limited to that region. Rhinoviruses rarely cause lower respiratory tract disease, probably because they grow poorly at 37°C. Immunity is serotype-specific and is a function of nasal secretory IgA rather than humoral antibody. Clinical Findings After an incubation period of 2–4 days, sneezing, nasal discharge, sore throat, cough, and headache are common. A chilly sensation may occur, but there are few other systemic symptoms. The illness lasts about 1 week. Note that other viruses such as coronaviruses, adenoviruses, influenza C virus, and coxsackieviruses also cause the common cold syndrome. Laboratory Diagnosis Diagnosis can be made by isolation of the virus from nasal secretions in cell culture, but this is rarely attempted. Serologic tests are not done. Treatment & Prevention No specific antiviral therapy is available. Vaccines appear impractical because of the large number of serotypes. Paper tissues impregnated with a combination of citric acid (which inactivates rhinoviruses) and sodium lauryl sulfate (a detergent that inactivates enveloped viruses such as influenza virus and respiratory syncytial virus) limit transmission when used to remove viruses from fingers contaminated with respiratory secretions. High doses of vitamin C have little ability to prevent rhinovirus-induced colds. Lozenges containing zinc gluconate are available for the treatment of the common cold, but their efficacy remains unproved. CALICIVIRUSES: INTRODUCTION Caliciviruses are small, nonenveloped viruses with single-stranded RNA of positive polarity. Although they share those features with picornaviruses, caliciviruses are distinguished from picornaviruses by having a larger genome and having distinctive spikes on the surface. There are two human pathogens in the Calicivirus family: Norwalk virus and hepatitis E virus. Hepatitis E virus is described in Chapter 41. NORWALK VIRUS (NOROVIRUS) Disease Norwalk virus (also known as Norovirus) is one of the most common causes of viral gastroenteritis in adults worldwide. It is named for an outbreak of gastroenteritis in a school in Norwalk, Ohio, in 1969. Important Properties Norwalk virus has a nonsegmented, single-stranded, positive-polarity RNA genome. It is a nonenveloped virus with an icosahedral nucleocapsid. There is no virion polymerase. In the electron microscope, 10 prominent spikes and 32 cupshaped depressions can be seen. The number of serotypes is uncertain. Summary of Replicative Cycle Norwalk virus has not been grown efficiently in cell culture, so its replicative cycle has been difficult to study. It is presumed to replicate in a manner similar to that of picornaviruses. Transmission & Epidemiology Norwalk virus is transmitted by the fecal–oral route, often involving the ingestion of contaminated seafood or water. Outbreaks typically occur in group settings such as cruise ships (especially in the Caribbean region), schools, camps, hospitals, and nursing homes. Person-to-person transmission also occurs, especially in group settings. There are many animal caliciviruses, but there is no evidence that they cause human infection. Infection is enhanced by several features of the virus: low infectious dose, excretion of virus in the stool for several weeks after recovery, and resistance to inactivation by chlorination and to drying in the environment. It is thought to remain infectious for several days on environmental surfaces such as door handles. Pathogenesis & Immunity Norwalk virus infection is typically limited to the mucosal cells of the intestinal tract. Watery diarrhea without red cells or white cells occurs. Many asymptomatic infections occur, as determined by the detection of antibodies. Immunity following infection appears to be brief and reinfection can occur. Clinical Findings Disease is characterized by sudden onset of vomiting and diarrhea accompanied by low-grade fever and abdominal cramping. Neither the emesis nor the stool contain blood. The illness typically lasts several days and there are no long-term sequelae, except in certain immunocompromised patients in whom a prolonged infection can occur. In some outbreaks, certain patients manifest signs of central nervous system involvement such as headache, meningismus, photophobia, and obtundation. Laboratory Diagnosis The diagnosis is primarily a clinical one. A polymerase chain reaction (PCR)-based test on the stool is performed primarily when there are public health implications. Treatment & Prevention There is no antiviral therapy or vaccine available. Dehydration and electrolyte imbalance caused by the vomiting and diarrhea may require intravenous fluids. Personal hygiene, such as hand washing, and public health measures, such as proper sewage disposal, are likely to be helpful. REOVIRUSES: INTRODUCTION REO is an acronym for respiratory enteric orphan; when the virus was discovered, it was isolated from the respiratory and enteric tracts and was not associated with any disease. Rotaviruses are the most important human pathogens in the reovirus family. ROTAVIRUS Disease Rotavirus is the most common cause of viral gastroenteritis in young children. Important Properties Reoviruses, including rotavirus, are composed of a segmented,1 doublestranded RNA genome surrounded by a double-layered icosahedral capsid without an envelope. The virion contains an RNA-dependent RNA polymerase. A virion polymerase is required because human cells do not have an RNA polymerase that can synthesize mRNA from a double-stranded RNA template. Many domestic animals are infected with their own strains of rotaviruses, but these are not a source of human disease. There are at least six serotypes of human rotavirus. The outer surface protein (also known as the viral hemagglutinin) is the type-specific antigen and elicits protective antibody. Summary of Replicative Cycle Reoviruses attach to the cell surface at the site of the -adrenergic receptor. After entry of the virion into the cell, the RNA-dependent RNA polymerase synthesizes mRNA from each of the 10 or 11 segments within the cytoplasm. The 10 or 11 mRNAs are translated into the corresponding number of structural and nonstructural proteins. One of these, an RNA polymerase, synthesizes minus strands that will become part of the genome of the progeny virus. Capsid proteins form an incomplete capsid around the minus strands, and then the plus strands of the progeny genome segments are synthesized. The virus is released from the cytoplasm by lysis of the cell, not by budding. Transmission & Epidemiology Rotavirus is transmitted by the fecal–oral route. Infection occurs worldwide, and by age 6 years most children have antibodies to at least one serotype. Pathogenesis & Immunity Rotavirus replicates in the mucosal cells of the small intestine, resulting in the excess secretion of fluids and electrolytes into the bowel lumen. The consequent loss of salt, glucose, and water leads to diarrhea. No inflammation occurs, and the diarrhea is nonbloody. It is thought that this watery diarrhea is caused primarily by stimulation of the enteric nervous system. The virulence of certain reoviruses in mice has been localized to the proteins encoded by several specific genome segments. For example, one gene governs tissue tropism, whereas another controls the inhibition of cell RNA and protein synthesis. Immunity to rotavirus infection is unclear. It is likely that intestinal IgA directed against specific serotypes protects against reinfection and that colostrum IgA protects newborns up to the age of 6 months. Clinical Findings Rotavirus infection is characterized by nausea, vomiting, and watery, nonbloody diarrhea. Gastroenteritis is most serious in young children, in whom dehydration and electrolyte imbalance are a major concern. Adults usually have minor symptoms. Laboratory Diagnosis Although the diagnosis of most cases of viral gastroenteritis does not involve the laboratory, a diagnosis can be made by detection of rotavirus in the stool by using radioimmunoassay or ELISA. This approach is feasible because there are large numbers of virus particles in the stool. The original demonstration of rotavirus in the stool was done by immunoelectron microscopy, in which antibody aggregated the virions, allowing them to be visualized in the electron microscope. This technique is not feasible for routine clinical use. In addition to antigen detection, the diagnosis can be made by observation of a 4-fold or greater rise in antibody titer. Although the virus can be cultured, this procedure is not routinely done. Treatment & Prevention In 2006, the FDA approved a live rotavirus vaccine (RotaTeq) that contains five human rotavirus strains. The immunogen in the vaccine virus is the outer surface protein. The vaccine is given orally and the vaccine virus replicates in the small intestine. The five rotaviruses in the vaccine are reassortants in which the gene for the human outer surface protein is inserted into a bovine strain of rotavirus. (Recall that rotavirus has a segmented genome.) The bovine strain is nonpathogenic for humans, but the human outer surface protein in the vaccine virus elicits protective (IgA) immunity in the GI tract. A previously approved vaccine (Rotashield) was withdrawn when a high rate of intussusception occurred in vaccine recipients. Hygienic measures such as proper sewage disposal and hand washing are helpful. There is no antiviral therapy. Rotaviruses have 11 segments; other reoviruses have 10. 1