It is estimated that there are 5 million children with lower respiratory infections (LRI) each year in the United States alone. 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. The incubation period for all four serotypes is 1 to 7 days. In immunosuppressed people,<unk>  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. Additionally, HPIV-1 tends to cause biennial outbreaks of croup in the Fall. In the United States, large peaks have presently been occurring during odd-numbered years. HPIV-3 has been closely associated with bronchiolitis and pneumonia and principally targets those aged <1 year. HPIV-4 remains infrequently detected. However, it is now believed to be more common than previously thought, but is less likely to cause severe disease. By the age of 10, the majority of children are sero-positive for HPIV-4 infection which may be indicative of a large proportion of asymptomatic or mild infections. Important epidemiological factors that are associated with a higher risk of infection and mortality are those who are immuno-compromised and may be taken ill with more extreme forms of LRI. 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. HPIVs have also been linked with rare cases of virally caused meningitis and Guillain–Barré syndrome. HPIVs are spread from person to person ('horizontal transmission') by contact with infected secretions through respiratory droplets or contaminated surfaces or objects. Infection can occur when infectious material contacts mucous membranes of the eyes, mouth, or nose, and possibly through the inhalation of droplets generated by a sneeze or cough. HPIVs can remain infectious in airborne droplets for over an hour. Overall, HPIVs remain best known for its effects on the respiratory system and this appears to be where the majority of the focus has been upon. Airway inflammation The inflammation of the airway is a common attribute of HPIV infection. It is believed to occur due to the large scale up-regulation of inflammatory cytokines. Common cytokines, expected to be up-regulated, include IFN–α, various other interleukins (IL–2, IL-6) and TNF–α. Various chemokines and inflammatory proteins are also believed to be associated with the common symptoms of HPIV infection. Recent evidence seems to suggest that<unk> pecific antibodies (IgE) may be responsible for mediating large-scale releases of histamine in the trachea, which are believed to cause croup. More detail on the pathways and interactions can be found here. Immunology The body's primary defense against HPIV infection remains humoral immunity. This is mainly directed against surface proteins which can be found on the virus. In particular the proteins HN and F prove to be most immunogenic in terms of stimulating the immune system. Recently the importance of the 'cell mediated immune system' has been scrutinized. Reports have shown that those with defective adaptive immune responses are at a higher risk of severe infection.
Human parainfluenza viruses
Influenza A virus
Influenza B virus
Influenza D virus
Respiratory syncytial virus
Rhinovirus
Novel coronavirus
Chinese coronavirus