Asst. Prof. Dr. Dalya Basil Hanna Paramyxoviruses Asst. Prof. Dr. Dalya Basil Hanna

Paramyxoviridae a. Measles – rubeola b. Mumps c. Parainfluenza d. RSV – respiratory syncytial virus

Paramyxoviruses 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. The morphology of Paramyxoviridae is pleomorphic, with particles 150 nm or more in diameter, occasionally ranging up to 700 nm.

Properties of Paramyxoviruses Virion: Spherical, pleomorphic, 150 nm or more in diameter (helical nucleocapsid, 13–18 nm) Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate (6%)  Genome: Single-stranded negative RNA, linear, nonsegmented, about 15 kb  Proteins: Six to eight structural proteins  Envelope: Contains viral glycoprotein (G, H, or HN) (which sometimes carries hemagglutinin or neuraminidase activity) and fusion (F) glycoprotein  Replication: Cytoplasm; particles bud from plasma membrane  Outstanding characteristics:   Antigenically stable  Particles are labile yet highly infectious

Paramyxovirus Replication Attachment, Penetration, & Uncoating Paramyxoviruses attach to host cells via the hemagglutinin glycoprotein (HN, H, or G protein). Next, the virion envelope fuses with the cell membrane by the action of the fusion glycoprotein. If the F precursor is not cleaved, it has no fusion activity; virion penetration does not occur; and the virus particle is unable to initiate infection.

Transcription, Translation, & RNA Replication Messenger RNA transcripts are made in the cell cytoplasm by the viral RNA polymerase, and viral proteins are synthesized in the cytoplasm. Maturation The virus matures by budding from the cell surface. Progeny nucleocapsids form in the cytoplasm and migrate to the cell surface.

Measles

Measles (Rubeola) 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. The introduction of an effective live-virus vaccine has dramatically reduced the incidence of this disease.

Pathogenesis & Pathology Humans are the only natural hosts for measles virus. 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.

Pathogenesis & Pathology 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.

Pathogenesis & Pathology The described events occur during the incubation period, which typically lasts 8– 12 days but may last up to 3 weeks in adults. Involvement of the central nervous system is common in measles. Because infectious virus is rarely recovered from the brain, it has been suggested that an autoimmune reaction is the mechanism responsible for this complication.

Clinical Findings Infections in nonimmune hosts are almost always symptomatic. After an incubation period of 8–12 days, measles is typically a 7-11days 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 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.

Clinical Findings Koplik spots are small, bluish-white ulcerations on the buccal mucosa opposite the lower molars. These spots contain giant cells and viral antigens and appear about 2 days before the rash. The fever and cough persist until the rash appears and then subside within 1–2 days.

Clinical Findings 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. Pulmonary complications account for more than 90% of measles-related deaths. Pneumonia develops in 3–15% of adults with measles, but most cases are due to the virus itself rather than bacteria.

Laboratory Diagnosis Antigen & Nucleic Acid Detection Measles antigens can be detected directly in epithelial cells from respiratory secretions, the nasopharynx, conjunctiva, and urine. Antibodies to the nucleoprotein are useful because that is the most abundant viral protein in infected cells. Detection of viral RNA by RT-PCR is a sensitive method that can be applied to a variety of clinical samples for measles diagnosis.

Laboratory Diagnosis Isolation & Identification of Virus Nasopharyngeal and conjunctival swabs, blood samples, respiratory secretions, and urine collected from a patient during the febrile period are appropriate sources for viral isolation. Serology Serologic confirmation of measles infection depends on a fourfold rise in antibody titer between acute-phase and convalescent- phase

Treatment, Prevention, & Control 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.

Treatment, Prevention, & Control It is recommended that all children, health care workers, and international travelers be vaccinated. Contraindications to vaccination include pregnancy, immune compromise (except that due to infection with human immunodeficiency virus). The use of killed measles virus vaccine was discontinued by 1970, as certain vaccinees became sensitized and developed severe atypical measles when infected with wild virus.

Mumps

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 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.

Pathogenesis & Pathology About one-third of infected individuals do not exhibit obvious symptoms (inapparent 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. Mumps is a systemic viral disease with a propensity to replicate in epithelial cells in various visceral organs. Virus frequently infects the kidneys and can be detected in the urine of most patients. Viruria may persist for up to 14 days after the onset of clinical symptoms. The central nervous system is also commonly infected and may be involved in the absence of parotitis.

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. cases is swelling of the salivary glands, which The most characteristic feature of symptomatic occurs in about 50% of patients.

Clinical Findings Central nervous system involvement is common (10–30% of cases). The testes and ovaries may be affected, especially after puberty. Twenty to fifty percent of men who are infected with mumps virus develop orchitis (often unilateral). Because of the lack of elasticity of the tunica albuginea, which does not allow the inflamed testis to swell, the complication is extremely painful. Atrophy of the testis may occur as a result of pressure necrosis, but only rarely does sterility result.

Laboratory Diagnosis Isolation & Identification of Virus The most appropriate clinical samples for viral isolation are saliva, cerebrospinal fluid, and urine collected within a few days after onset of illness. Virus can be recovered from the urine for up to 2 weeks. Nucleic Acid Detection RT-PCR is a very sensitive method that can detect mumps genome sequences in clinical samples. It can detect the virus in many clinical samples that are negative in virus isolation attempts.

Laboratory Diagnosis Serology Simple detection of mumps antibody is not adequate to diagnose an infection. Rather, an antibody rise can be demonstrated using paired sera: a fourfold or greater rise in antibody titer is evidence of mumps infection. The ELISA or HI test is commonly used. Antibodies against the HN protein are neutralizing. ELISA can be designed to detect either mumps-specific IgM antibody or mumps-specific IgG antibody. Mumps IgM is uniformly present early in the illness and seldom persists longer than 60 days. Therefore, demonstration of mumps- specific IgM in serum drawn early in illness strongly suggests recent infection. Heterotypic antibodies induced by parainfluenza virus infections do not cross-react in the mumps IgM ELISA.

Treatment, Prevention, & Control There is no specific therapy. Immunization with attenuated live mumps virus vaccine is the best approach to reducing mumps- associated morbidity and mortality rates. Attempts to minimize viral spread during an outbreak by using isolation procedures are futile because of the high incidence of asymptomatic cases and the degree of viral shedding before clinical symptoms appear; however, students and health care workers who acquire mumps illness should be excluded from school and work until 5 days after the onset of parotitis.

Treatment, Prevention, & Control An effective attenuated live-virus vaccine made in chick embryo cell culture was licensed in the United States in 1967. 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 78–95% of vaccinees. There is no increased risk of aseptic meningitis after MMR vaccination. Other live attenuated mumps virus vaccines have been developed in Japan, Russia, and Switzerland.

Treatment, Prevention, & Control Two doses of MMR vaccine are recommended for school entry. Because of the 2006 outbreak of mumps, updated vaccination recommendations for prevention of mumps transmission in settings with high risk for spread of infection were released. Two doses of vaccine should be given to health care workers born before 1957 without evidence of mumps immunity, and a second dose of vaccine should be considered for those who had received only a single dose.

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