Адам параинфлюэнца вирустары: сипаттамасы мен аурулары

Viruses that cause human parainfluenza

Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single stranded RNA viruses belonging to the Paramyxoviridae family. These viruses are closely associated with both human and veterinary disease. Virions are approximately 150–250 nm in size and contain negative sense RNA with a genome encompassing about 15,000 nucleotides. The viruses can be detected via cell culture, immunofluorescent microscopy, and PCR. HPIVs remain the second main cause of hospitalisation in children under 5 years of age for a respiratory illness (only respiratory syncytial virus (RSV) causes more respiratory hospitalisations for this age group).

Viral replication is initiated only after successful entry into a cell by attachment and fusion between the virus and the host cell lipid membrane. Viral RNA (vRNA) is initially associated with nucleoprotein (NP), phosphoprotein (P) and the large protein (L). The hemagglutinin–neuraminidase (HN) is involved with viral attachment and thus hemadsorption and hemagglutination. Furthermore, the fusion (F) protein is important in aiding the fusion of the host and viral cellular membranes, eventually forming syncytia. Initially the F protein is in an inactive form (F0) but can be cleaved by proteolysis to form its active form, F1 and F2, linked by di sulphide bonds. Once complete, this is followed by the HPIV nucleocapsid entering the cytoplasm of the cell. Subsequently, genomic transcription occurs using the viruses own 'viral RNA dependent RNA polymerase' (L protein). The cell's own ribosomes are then tasked with translation, forming the viral proteins from the viral mRNA. The observable and morphological changes that can be seen in infected cells include the enlargement of the cytoplasm, decreased mitotic activity and 'focal rounding', with the potential formation of multi nucleate cells (syncytia). The pathogenicity of HPIVs is mutually dependent on the viruses having the correct accessory proteins that are able to elicit anti interferon properties. This is a major factor in the clinical significance of disease. HPIV 1, HPIV 2 and HPIV 3 have been linked with up to a third of these infections. Upper respiratory infections (URI) are also important in the context of HPIV, however, they are caused to a lesser extent by the virus. The highest rates of serious HPIV illnesses occur among young children, and surveys have shown that about 75% of children aged 5 or older have antibodies to HPIV 1. For infants and young children, it has been estimated that about 25% will develop "clinically significant disease". Repeated infection throughout the life of the host is not uncommon and symptoms of later breakouts include upper respiratory tract illness, such as cold and a sore throat. In immunosuppressed people, parainfluenza virus infections can cause severe pneumonia, which can be fatal. HPIV 1 and HPIV 2 have been demonstrated to be the principal causative agent behind croup (laryngotracheobronchitis), which is a viral disease of the upper airway and is mainly problematic in children aged 6–48 months of age. Biennial epidemics starting in autumn are associated with both HPIV 1 and 2; however, HPIV 2 can also have yearly outbreaks. HPIV 4 remains infrequently detected. It is now believed to be more common than previously thought but less likely to cause severe disease. By the age of 10, the majority of children are seropositive for HPIV 4 infectionthis may be indicative of a large proportion of asymptomatic or mild infections. Associations between HPIVs and neurologic disease are known. For example, hospitalisation with certain HPIVs has a strong association with febrile seizures. HPIV 4b has the strongest association (up to 62%) followed by HPIV 3 and 1. and Guillain–Barré syndrome.

The body's primary defense against HPIV infection is adaptive immunity involving both humoral and cellular immunity. With humoral immunity, antibodies that bind to the surface viral proteins HN and F protect against later infection. Patients with defective cell mediated immunity also experience more severe infection, suggesting that T cells are important in clearing infection. The exact associations between HPIVs and diseases such as chronic obstructive pulmonary disease (COPD) are still being investigated. In developing regions of the world, preschool children remain the highest mortality risk group. Mortality may be a consequence of primary viral infection or secondary problems, such as bacterial infection. Predispositions, such as malnutrition and other deficiencies, may further elevate the chances of mortality associated with infection.

Despite decades of research, no vaccines currently exist. Recombinant technology has however been used to target the formation of vaccines for HPIV 1, 2 and 3 and has taken the form of several live attenuated intranasal vaccines. Two vaccines in particular were found to be immunogenic and well tolerated against HPIV 3 in phase I trials. HPIV 1 and 2 vaccine candidates remain less advanced. Maternal antibodies may offer some degree of protection against HPIVs during the early stages of life via the colostrum in breast milk.

Ribavirin is one medication which has shown good potential for the treatment of HPIV 3 given recent in vitro tests (in vivo tests show mixed results). The majority of transmission has been linked to close contact, especially in nosocomial infections. Chronic care facilities and doctors' surgeries are also known to be transmission 'hotspots' with transmission occurring via aerosols, large droplets and also fomites (contaminated surfaces). The exact infectious dose remains unknown.

In economically disadvantaged regions of the world, HPIV infection can be measured in terms of mortality. In the developed world where mortality remains rare, the economic costs of the infection can be estimated. Estimates from the US are suggestive of a cost (based on extrapolation) in the region of $200 million per annum.