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The paramyxoviruses include the most important agents of respiratory infections of infants and young children (respiratory syncytial virus and the parainfluenza viruses) as well as the causative agents of two of the most common contagious diseases of childhood (mumps and measles). All members of the Paramyxoviridae family initiate infection via the respiratory tract. Replication of the respiratory pathogens is limited to the respiratory epithelia, whereas measles and mumps become disseminated throughout the body and produce generalized disease. Virion: Spherical, pleomorphic, RNA (1%), protein (73%), lipid (20%), carbohydrate (6%), Single-stranded RNA, linear, nonsegmented, noninfectious, Envelope: Contains viral glycoprotein (G, H, or HN) (which sometimes carries hemagglutinin or neuraminidase activity) and fusion (F) glycoprotein; very fragile Replication: Cytoplasm; particles bud from plasma membrane Outstanding characteristics: Antigenically stable Particles are labile yet highly infectious
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Three proteins participate in the formation of the viral envelope. A matrix (M) protein underlies the viral envelope; it has an affinity for both the N and the viral surface glycoproteins and is important in virion assembly. The nucleocapsid is surrounded by a lipid envelope that is studded with 8- to 12-nm spikes of two different transmembrane glycoproteins. The activities of these surface glycoproteins help differentiate the various genera of the Paramyxoviridae family. The larger glycoprotein (HN or G) may or may not possess hemagglutination and neuraminidase activities and is responsible for attachment to the host cell. It is assembled as a tetramer in the mature virion. The other glycoprotein (F) mediates membrane fusion and hemolysin activities. The pneumoviruses and metapneumoviruses contain two additional small envelope proteins (M2-1 and SH).
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Parainfluenza Virus Infections Parainfluenza viruses are ubiquitous and cause common respiratory illnesses in persons of all ages. They are major pathogens of severe respiratory tract disease in infants and young children. Only respiratory syncytial virus, and perhaps human metapneumovirus, causes more cases of serious respiratory disease in children. Reinfections with parainfluenza viruses are common. Pathogenesis & Pathology Parainfluenza virus replication in the immunocompetent host appears to be limited to respiratory epithelia. Viremia, if it occurs at all, is uncommon. The infection may involve only the nose and throat, resulting in a harmless "common cold" syndrome. However, infection may be more extensive and, especially with types 1 and 2, may involve the larynx and upper trachea, resulting in croup (laryngotracheobronchitis). Croup is characterized by respiratory obstruction due to swelling of the larynx and related structures. The infection may spread deeper to the lower trachea and bronchi, culminating in pneumonia or bronchiolitis, especially with type 3, but at a much lower frequency than that observed with respiratory syncytial virus.
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Duration of parainfluenza virus shedding is about 1 week after onset of illness; some children may excrete virus several days prior to illness. Type 3 may be excreted for up to 4 weeks after onset of primary illness. This persistent shedding from young children facilitates spread of infection. Prolonged viral shedding may occur in children with compromised immune function and in adults with chronic lung disease. Clinical Findings :- Primary infections in young children usually result in rhinitis and pharyngitis, often with fever and some bronchitis. However, children with primary infections caused by parainfluenza virus type 1, 2, or 3 may have serious illness, ranging from laryngotracheitis and croup (particularly with types 1 and 2) to bronchiolitis and pneumonia (particularly with type 3). The severe illness associated with type 3 occurs mainly in infants under the age of 6 months; croup or laryngotracheobronchitis is more likely to occur in older children, between ages 6 months and 18 months. More than one-half of initial infections with parainfluenza virus types 1–3 result in febrile illness. It is estimated that only 2– 3% develop into croup. Parainfluenza virus type 4 does not cause serious disease, even on first infection. The most common complication of parainfluenza virus infection is otitis media.
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Respiratory Syncytial Virus Infections : Respiratory syncytial virus is the most important cause of lower respiratory tract illness in infants and young children, usually outranking all other microbial pathogens as the cause of bronchiolitis and pneumonia in infants under 1 year of age. It is estimated to account for approximately 25% of pediatric hospitalizations due to respiratory disease. Pathogenesis & Pathology :- Respiratory syncytial virus replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia. There is lymphocyte migration, resulting in peribronchiolar infiltration; submucosal tissues become edematous; and plugs consisting of mucus, cellular debris, and fibrin occlude the smaller bronchioles. Viral antigens can be detected in the upper respiratory tract and in shed epithelial cells in the plugs but are seldom detected in the small bronchioles.
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Viremia occurs rarely if at all. The incubation period between exposure and onset of illness is 3–5 days. Viral shedding may persist for 1–3 weeks from infants and young children, whereas adults shed for only 1–2 days. High viral titers are present in respiratory tract secretions from young children. Inoculum size is an important determinant of successful infection in adults (and possibly in children as well). Clinical Findings The spectrum of respiratory illness caused by respiratory syncytial virus ranges from in apparent infection or the common cold through pneumonia in infants to bronchiolitis in very young babies. Bronchiolitis is the distinct clinical syndrome associated with this virus. About one-third of primary respiratory syncytial virus infections involve the lower respiratory tract severely enough to require medical attention. The child may wheeze. Almost 2% of infected babies require hospitalization, with the peak occurrence at 2 months of age. Progression of symptoms may be very rapid, culminating in death. With availability of modern pediatric intensive care, the mortality rate in normal infants is low (about 1% of hospitalized patients). But if a respiratory syncytial virus infection is superimposed on preexisting disease, such as congenital heart disease, the mortality rate may be high.
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Reinfection is common in both children and adults. Although reinfections tend to be symptomatic, the illness is usually limited to the upper respiratory tract, resembling a cold, in healthy individuals. Treatment & Prevention Treatment of serious respiratory syncytial virus infections depends primarily on supportive care (eg, removal of secretions, administration of oxygen). The antiviral drug ribavirin is approved for treatment of lower respiratory tract disease due to respiratory syncytial virus, especially in infants at high risk for severe disease. The drug is administered in an aerosol for 3–6 days. Oral ribavirin is not useful.
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Mumps Virus Infections : Mumps is an acute contagious disease characterized by nonsuppurative enlargement of one or both salivary glands. Mumps virus mostly causes a mild childhood disease, but in adults complications including meningitis and orchitis are fairly common. More than one-third of all mumps infections are asymptomatic. Pathogenesis & Pathology :- Humans are the only natural hosts for mumps virus. Primary replication occurs in nasal or upper respiratory tract epithelial cells. Viremia then disseminates the virus to the salivary glands and other major organ systems. Involvement of the parotid gland is not an obligatory step in the infectious process. The incubation period may range from 2 weeks to 4 weeks but is typically about 14–18 days. Virus is shed in the saliva from about 3 days before to 9 days after the onset of salivary gland swelling. About one-third of infected individuals do not exhibit obvious symptoms (in apparent infections) but are equally capable of transmitting infection. It is difficult to control transmission of mumps because of the variable incubation periods, the presence of virus in saliva before clinical symptoms develop, and the large number of asymptomatic but infectious cases.
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Clinical Findings : The clinical features of mumps reflect the pathogenesis of the infection. At least one-third of all mumps infections are subclinical, including the majority of infections in children under 2 years of age. The most characteristic feature of symptomatic cases is swelling of the salivary glands, which occurs in about 50% of patients. A prodromal period of malaise and anorexia is followed by rapid enlargement of parotid glands as well as other salivary glands. Swelling may be confined to one parotid gland, or one gland may enlarge several days before the other. Gland enlargement is associated with pain. Central nervous system involvement is common (10–30% of cases). Mumps causes aseptic meningitis and is more common among males than females ?. The testes and ovaries may be affected, especially after puberty. Treatment There is no specific therapy.
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Prevention, & Control :- An effective attenuated live-virus vaccine made in chick embryo cell culture is available. It produces a subclinical, noncommunicable infection. Mumps vaccine is available in combination with measles and rubella (MMR) live-virus vaccines. Combination live-virus vaccines produce antibodies to each of the viruses in about 78% to 95% of vaccinees. There is no increased risk of aseptic meningitis after MMR vaccination. Measles (Rubella) Virus Infections :- Measles is an acute, highly infectious disease characterized by fever, respiratory symptoms, and a maculopapular rash. Complications are common and may be quite serious. Pathogenesis & Pathology :- Humans are the only natural hosts for measles virus, although numerous other species, including monkeys, dogs, and mice, can be experimentally infected.
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The virus gains access to the human body via the respiratory tract, where it multiplies locally; the infection then spreads to the regional lymphoid tissue, where further multiplication occurs. Primary viremia disseminates the virus, which then replicates in the reticuloendothelial system. Finally, a secondary viremia seeds the epithelial surfaces of the body, including the skin, respiratory tract, and conjunctiva, where focal replication occurs. Measles can replicate in certain lymphocytes, which aids in dissemination throughout the body. Multinucleated giant cells with intranuclear inclusions are seen in lymphoid tissues throughout the body (lymph nodes, tonsils, appendix). The described events occur during the incubation period, which typically lasts 8–12 days but may last up to 3 weeks in adults. During the prodromal phase (2–4 days) and the first 2–5 days of rash, virus is present in tears, nasal and throat secretions, urine, and blood. The characteristic maculopapular rash appears about day 14 just as circulating antibodies become detectable, the viremia disappears, and the fever falls. The rash develops as a result of interaction of immune T cells with virus-infected cells in the small blood vessels and lasts about 1 week.
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Clinical Findings : Infections in non immune hosts are almost always symptomatic. After an incubation period of 8–12 days, measles is typically a 7- to 11-day illness (with a prodromal phase of 2–4 days followed by an eruptive phase of 5–8 days). The prodromal phase is characterized by fever, sneezing, coughing, running nose, redness of the eyes, Koplik's spots, and lymphopenia. The cough and coryza reflect an intense inflammatory reaction involving the mucosa of the respiratory tract. The conjunctivitis is commonly associated with photophobia. The fever and cough persist until the rash appears and then subside within 1–2 days. The rash, which starts on the head and then spreads progressively to the chest, the trunk, and down the limbs, appears as light pink, discrete maculopapules that coalesce to form blotches, becoming brownish in 5–10 days. The fading rash resolves with desquamation. Symptoms are most marked when the rash is at its peak but subside rapidly thereafter. The most common complication of measles is otitis media (5–9% of cases). Pneumonia is the most common life-threatening complication of measles, caused by secondary bacterial infections, while the central nervous system Complications are the most serious one.
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Immunity : Infection confers lifelong immunity. Most so-called second attacks represent errors in diagnosis of either the initial or the second illness. The presence of humoral antibodies indicates immunity. However, cellular immunity appears to be essential for recovery and protection. Treatment, Prevention, & Control :- Vitamin A treatment in developing countries has decreased mortality and morbidity. Measles virus is susceptible in vitro to inhibition by ribavirin, but clinical benefits have not been proved. A highly effective and safe attenuated live measles virus vaccine has been available since 1963. Measles vaccine is available in monovalent form and in combination with live attenuated rubella vaccine (MR) and live attenuated rubella and mumps vaccines (MMR).
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