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. Diagnosis Diagnosis can be made in several ways, encompassing a range of multi-faceted techniques: Isolation and detection of the virus in cell culture. Detection of viral antigens directly within bodily respiratory tract secretions using immunofluorescence, enzyme immunoassays or fluoroimmunoassays. Polymerase chain reaction (PCR). Analysis of specific IgG antibodies showing a subsequent rise in titre following infection (using paired serum specimens). Because of the similarity in terms of the antigenic profile between the viruses, hemagglutination assay (HA) or hemadsorption inhibition (HAdI) processes are often used. Both complement fixation, neutralisation and enzyme linked immunosorbent assays – ELISA, can also be used to aid in the process of distinguishing between viral serotypes. Morbidity and mortality Mortality caused by HPIVs in developed regions of the world remains rare. Where mortality has occurred, it is principally in the three core risk groups (very young, elderly and immuno-compromised). Long term changes can however be associated with airway remodelling and are believed to be a significant cause of morbidity. 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. Overall, LRI's cause approximately 25–30% of total deaths in preschool children in the developing world. HPIVs is believed to be associated with 10% of all LRI cases, thus remaining a significant cause of mortality. Risk factors Numerous factors have been suggested and linked to a higher risk of acquiring the infection, inclusive of malnutrition, vitamin A deficiency, absence of breastfeeding during the early stages of life, environmental pollution and overcrowding. Prevention 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