View source for Biology:Human parainfluenza viruses

{{Short description|Viruses that cause human parainfluenza}}
{{Paraphyletic group
| name = Human parainfluenza viruses
| image = Parainfluenza virus TEM PHIL 271 lores.jpg
| image_alt = Transmission electron micrograph of a parainfluenza virus. Two intact particles and free filamentous nucleocapsid
| image_caption = Transmission electron micrograph of a parainfluenza virus. Two intact particles and free filamentous nucleocapsid
| auto = virus
| parent = Paramyxoviridae
| includes =
* ''[[Biology:Respirovirus|Respirovirus]]'' (part)
** ''Human respirovirus 1'' (formerly ''Human parainfluenza virus 1'')
** ''Human respirovirus 3'' (formerly ''Human parainfluenza virus 3'')
* ''[[Biology:Rubulavirus|Rubulavirus]]'' (part)
** ''Human rubulavirus 2'' (formerly ''Human parainfluenza virus 2'')
** ''Human rubulavirus 4'' (formerly ''Human parainfluenza virus 4'')<ref>{{cite web |title=Virus Taxonomy: 2018 Release |url=https://ictv.global/taxonomy |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=25 January 2019 |language=en |date=October 2018}}</ref>
| excludes =
* ''[[Biology:Aquaparamyxovirus|Aquaparamyxovirus]]''
* ''[[Biology:Avulavirus|Avulavirus]]''
* ''[[Biology:Ferlavirus|Ferlavirus]]''
* ''[[Biology:Henipavirus|Henipavirus]]''
* ''[[Biology:Morbillivirus|Morbillivirus]]''
* ''[[Biology:Respirovirus|Respirovirus]]'' (part)
** ''Bovine respirovirus 3''
** ''[[Biology:Murine respirovirus|Murine respirovirus]]''
** ''Porcine respirovirus 1''
* ''[[Biology:Rubulavirus|Rubulavirus]]'' (part)
** ''Achimota rubulavirus 1''
** ''Achimota rubulavirus 2''
** ''Bat mumps rubulavirus''
** ''Mammalian rubulavirus 5''
** ''Mapuera rubulavirus''
** ''Menangle rubulavirus''
** ''Mumps rubulavirus''
** ''Porcine rubulavirus''
** ''Simian rubulavirus''
** ''Sosuga rubulavirus''
** ''Teviot rubulavirus''
** ''Tioman rubulavirus''
** ''Tuhoko rubulavirus 1''
** ''Tuhoko rubulavirus 2''
** ''Tuhoko rubulavirus 3''
* ''[[Biology:Pneumoviridae|Pneumoviridae]]''
* ''[[Biology:Rhabdoviridae|Rhabdoviridae]]''
* ''[[Biology:Sunviridae|Sunviridae]]''
* ''Xinmoviridae''
}}
'''Human parainfluenza viruses''' ('''HPIVs''') are the viruses that cause '''human parainfluenza'''. HPIVs are a [[Biology:Paraphyly|paraphyletic]] group of four distinct single-stranded [[Biology:RNA|RNA]] [[Biology:Virus|virus]]es belonging to the ''[[Biology:Paramyxoviridae|Paramyxoviridae]]'' family. These viruses are closely associated with both human and veterinary disease.<ref>{{cite journal |vauthors=Vainionpää R, Hyypiä T |title=Biology of parainfluenza viruses |journal=Clin. Microbiol. Rev. |volume=7 |issue=2 |pages=265–275 |date=April 1994 |pmid=8055470 |pmc=358320 |doi=10.1128/CMR.7.2.265}}</ref> Virions are approximately 150–250&nbsp;nm in size and contain negative sense [[Biology:RNA|RNA]] with a [[Biology:Genome|genome]] encompassing about 15,000 [[Biology:Nucleotide|nucleotide]]s.<ref name="Henrickson">{{cite journal|last=Henrickson|first=KJ|title=Parainfluenza viruses|journal=Clinical Microbiology Reviews|date=April 2003|volume=16|issue=2|pages=242–264|pmid=12692097|pmc=153148|doi=10.1128/CMR.16.2.242-264.2003}}</ref>

[[File: 1ztm.jpg|thumb|300 px|Fusion glycoprotein trimer, Human parainfluenza virus 3 (HPIV3).]]
The viruses can be detected via [[Biology:Cell culture|cell culture]], [[Biology:Immunofluorescence|immunofluorescent]] [[Biology:Microscopy|microscopy]], and [[Biology:Polymerase chain reaction|PCR]].<ref name="CDC hPIV">{{cite web|title=Human Parainfluenza Viruses|url=https://www.cdc.gov/ncidod/dvrd/revb/respiratory/hpivfeat.htm|publisher=Centers for Disease Control and Prevention (2011)|access-date=21 March 2012|url-status=dead|archive-url=https://web.archive.org/web/20120320192506/http://www.cdc.gov/ncidod/dvrd/revb/respiratory/hpivfeat.htm|archive-date=20 March 2012}}</ref> HPIVs remain the second main cause of hospitalisation in children under 5 years of age for a respiratory illness (only [[Biology:Respiratory syncytial virus|Respiratory syncytial virus (RSV)]] causes more respiratory hospitalisations for this age group).<ref>{{cite journal|last=Schmidt|first=Alexander |author2=Anne Schaap-Nutt |author3=Emmalene J Bartlett |author4=Henrick Schomacker |author5=Jim Boonyaratanakornkit |author6=Ruth A Karron |author7=Peter L Collins|title=Progress in the development of human parainfluenza virus vaccines|journal=Expert Review of Respiratory Medicine|date=1 February 2011|volume=5|issue=4|pages=515–526|doi=10.1586/ers.11.32|pmc=3503243 |pmid=21859271}}</ref>

==Classification==
The first HPIV was discovered in the late 1950s. The taxonomic division is broadly based on antigenic and [[Biology:Genetics|genetic]] characteristics, forming four major serotypes or clades, which today are considered distinct viruses.<ref name="urlParainfluenza Viruses">{{cite book |chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.3128 |title=Parainfluenza Viruses |access-date=2009-03-15|isbn=9780963117212 |chapter=Paramyxoviruses |publisher=University of Texas Medical Branch at Galveston |year=1996 |pmid=21413341 |last1=Baron |first1=S. |last2=Enders |first2=G. }}</ref> These include:
{| class="wikitable"
|-
! Virus
! GenBank acronym
! NCBI taxonomy
! Notes
|-
|Human parainfluenza virus type 1 
|HPIV-1
|[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=12730 12730]
|Most common cause of [[Medicine:Croup|croup]]
|-
|Human parainfluenza virus type 2
|HPIV-2
|[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11212 11212]
|Causes [[Medicine:Croup|croup]] and other upper and lower respiratory tract illnesses
|-
|Human parainfluenza virus type 3
|HPIV-3
|[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11216 11216]
|Associated with [[Medicine:Bronchiolitis|bronchiolitis]] and [[Medicine:Pneumonia|pneumonia]]
|-
|Human parainfluenza virus type 4
|HPIV-4
|[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11203 11203]
|Includes subtypes 4a and 4b
|}

HPIVs belong to two genera: ''[[Biology:Respirovirus|Respirovirus]]'' (HPIV-1 & HPIV-3) and ''[[Biology:Rubulavirus|Rubulavirus]]'' (HPIV-2 & HPIV-4).<ref name="Henrickson"/>

===Viral structure and organisation===
HPIVs are characterised by producing enveloped virions and containing single stranded negative sense [[Biology:RNA|RNA]].<ref name="Henrickson"/> Non-infectious virions have also been reported to contain [[Biology:RNA|RNA]] with positive polarity.<ref name="Henrickson"/> HPIV genomes are about 15,000 nucleotides in length and encode six key structural [[Biology:Proteins|proteins]].<ref name="Henrickson"/>

The [[Biology:Structural gene|structural gene]] sequence of HPIVs is as follows: '''3′-NP-P-M-F-HN-L-5′''' (the protein prefixes and further details are outlined in the table below).<ref>{{cite web|last=Hunt|first=Dr. Margaret|title=PARAINFLUENZA, RESPIRATORY SYNCYTIAL AND ADENO VIRUSES|url=http://pathmicro.med.sc.edu/virol/para-rsv-aden-ver2.htm|publisher=Reference.MD|access-date=21 March 2012}}</ref>

{| class="wikitable"
|-
! Structural protein
! Location
! Function
|-
|[[Medicine:Hemagglutinin|Hemagglutinin]]-[[Biology:Neuraminidase|neuraminidase]] (HN)
|Envelope
|Attachment and cell entry
|-
|Fusion Protein (F)
|Envelope
|Fusion and cell entry
|-
|[[Biology:Viral matrix protein|Matrix Protein]] (M)
|Within the envelope
|Assembly
|-
|[[Biology:Nucleoprotein|Nucleoprotein]] (NP)
|Nucleocapsid
|Forms a complex with the RNA genome
|-
|Phosphoprotein (P)
|Nucleocapsid
|Forms as part of [[Biology:RNA polymerase|RNA polymerase]] complex
|-
|[[Biology:RNA polymerase|Large Protein]] (L)
|Nucleocapsid
|Forms as part of [[Biology:RNA polymerase|RNA polymerase]] complex
|}

With the advent of [[Biology:Reverse genetics|reverse genetics]], it has been found that the most efficient human parainfluenza viruses (in terms of replication and transcription) have a genome [[Biology:Nucleotide|nucleotide]] total that is divisible by the number 6. This has led to the "rule of six" being coined. Exceptions to this rule have been found and its exact advantages are not fully understood.<ref>{{cite journal|last=Vulliémoz|first=D|author2=Roux, L|title='Rule of six': how does the Sendai virus RNA polymerase keep count?|journal=Journal of Virology|date=May 2001|volume=75|issue=10|pages=4506–4518|pmid=11312321|doi=10.1128/JVI.75.10.4506-4518.2001|pmc=114204}}</ref>

[[Biology:Electrophoresis|Electrophoresis]] has shown that the [[Physics:Molecular weight|molecular weight]] (MW) of the proteins for the four HPIVs are similar (with the exception of the phosphoprotein, which shows significant variation).<ref name="Henrickson"/><ref>{{cite journal |doi=10.1128/CMR.16.2.242-264.2003 |pmid=12692097 |pmc=153148 |title=Parainfluenza Viruses |journal=Clinical Microbiology Reviews |volume=16 |issue=2 |pages=242–264 |year=2003 |last1=Henrickson |first1=K. J }}</ref>

===Viral entry and replication===
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 [[Medicine:Hemagglutinin|hemagglutinin]]–[[Biology:Neuraminidase|neuraminidase]] (HN) is involved with viral attachment and thus hemadsorption and [[Medicine:Hemagglutination|hemagglutination]]. Furthermore, the fusion (F) protein is important in aiding the fusion of the host and viral cellular membranes, eventually forming syncytia.<ref name="Rep">{{cite journal|last=Moscona|first=A|title=Entry of parainfluenza virus into cells as a target for interrupting childhood respiratory disease|journal=The Journal of Clinical Investigation|date=July 2005|volume=115|issue=7|pages=1688–1698|pmid=16007245|doi=10.1172/JCI25669|pmc=1159152}}</ref>

Initially the F protein is in an inactive form (F<sub>0</sub>) but can be cleaved by [[Biology:Proteolysis|proteolysis]] to form its active form, F<sub>1</sub> and F<sub>2</sub>, linked by di-sulphide bonds. Once complete, this is followed by the HPIV nucleocapsid entering the [[Biology:Cytoplasm|cytoplasm]] of the cell. Subsequently, genomic transcription occurs using the viruses own 'viral RNA-dependent [[Biology:RNA polymerase|RNA polymerase]]' (L protein). The cell's own ribosomes are then tasked with [[Biology:Translation|translation]], forming the viral proteins from the viral [[Biology:MRNA|mRNA]].<ref name="Rep"/>

Towards the end of the process, (after the formation of the viral proteins) the replication of the viral genome occurs. Initially, this occurs with the formation of a positive-sense RNA (intermediate step, necessary for producing progeny), and finally, negative-sense RNA is formed which is then associated with the [[Biology:Nucleoprotein|nucleoprotein]]. This may then be either packaged and released from the cell by budding or used for subsequent rounds of transcription and replication.<ref name="SUMM">{{cite book|vauthors = Chambers R, Takimoto T|title=Encyclopedia of Life Sciences|chapter=Parainfluenza Viruses|year=2011|doi=10.1002/9780470015902.a0001078.pub3 |journal=eLS |publisher=Wiley|isbn=978-0470016176}}</ref>

The observable and morphological changes that can be seen in infected cells include the enlargement of the [[Biology:Cytoplasm|cytoplasm]], decreased mitotic activity and 'focal rounding', with the potential formation of multi-nucleate cells (syncytia).<ref name="eMed hPIV">{{cite web|title=Parainfluenza Virus: Epidemiology|url=http://emedicine.medscape.com/article/224708-overview#a0199|publisher=eMedicine|access-date=21 March 2012}}</ref>

The pathogenicity of HPIVs is mutually dependent on the viruses having the correct accessory proteins that are able to elicit anti-[[Biology:Interferon|interferon]] properties. This is a major factor in the [[Biology:Clinical significance|clinical significance]] of disease.<ref name="SUMM"/>

===Host range===
The main host remains the human. However, infections have been induced in other animals (both under natural and experimental situations), although these were always [[Medicine:Asymptomatic|asymptomatic]].<ref name="Canada"/>

==Clinical significance==
It is estimated that there are 5 million children with lower respiratory infections (LRI) each year in the United States alone.<ref name="Henrickson2">{{cite journal|last=Henrickson|first=KJ |author2=Kuhn, SM |author3=Savatski, LL|title=Epidemiology and cost of infection with human parainfluenza virus types 1 and 2 in young children|journal=Clinical Infectious Diseases|date=May 1994|volume=18|issue=5|pages=770–9|pmid=8075269|doi=10.1093/clinids/18.5.770}}</ref>  HPIV-1, HPIV-2 and HPIV-3 have been linked with up to a third of these infections.<ref>{{cite journal|last=Denny|first=FW|author2=Clyde WA, Jr|title=Acute lower respiratory tract infections in nonhospitalized children|journal=The Journal of Pediatrics|date=May 1986|volume=108|issue=5 Pt 1|pages=635–46|pmid=3009769|doi=10.1016/S0022-3476(86)81034-4}}</ref>  Upper respiratory infections (URI) are also important in the context of HPIV, however, they are caused to a lesser extent by the virus.<ref>{{cite web|title=Acute Respiratory Infections|url=https://www.who.int/vaccine_research/diseases/ari/en/index2.html|archive-url=https://web.archive.org/web/20060324134018/http://www.who.int/vaccine_research/diseases/ari/en/index2.html|url-status=dead|archive-date=March 24, 2006|publisher=WHO|access-date=21 March 2012}}</ref> 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.{{citation needed|date=June 2022}}

For infants and young children, it has been estimated that about 25% will develop "clinically significant disease".<ref name="Karron">{{cite journal|last=Durbin|first=AP|author2=Karron, RA|title=Progress in the development of respiratory syncytial virus and parainfluenza virus vaccines|journal=Clinical Infectious Diseases|date=December 15, 2003|volume=37|issue=12|pages=1668–1677|pmid=14689350|doi=10.1086/379775|s2cid=41967381 |doi-access=}}</ref>

Repeated infection throughout the life of the host is not uncommon and symptoms of later breakouts include upper respiratory tract illness, such as [[Medicine:Common cold|cold]] and a sore throat.<ref name="Henrickson"/> The [[Medicine:Incubation period|incubation period]] for all four serotypes is 1 to 7 days.<ref>{{cite web|title=General information: human parainfluenza viruses|date=27 August 2008 |url=http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/HumanParainfluenzaViruses/GeneralInformation/|publisher=Health Protection Agency|access-date=21 March 2012}}</ref> In [[Biology:Immunosuppression|immunosuppressed]] people, parainfluenza virus infections can cause severe [[Medicine:Pneumonia|pneumonia]], which can be fatal.<ref>{{cite journal |vauthors=Sable CA, Hayden FG |title=Orthomyxoviral and paramyxoviral infections in transplant patients |journal=Infect. Dis. Clin. North Am. |volume=9 |issue=4 |pages=987–1003 |date=December 1995 |doi=10.1016/S0891-5520(20)30712-1 |pmid=8747776}}</ref>

HPIV-1 and HPIV-2 have been demonstrated to be the principal causative agent behind [[Medicine:Croup|croup]] (laryngotracheobronchitis), which is a viral disease of the upper airway and is mainly problematic in children aged 6–48 months of age.<ref name="urlCDC - Human Parainfluenza Viruses: Common cold and croup">{{cite web |url=https://www.cdc.gov/ncidod/dvrd/revb/respiratory/hpivfeat.htm |title=CDC - Human Parainfluenza Viruses: Common cold and croup |access-date=2009-03-15 |url-status=dead |archive-url=https://web.archive.org/web/20090303090517/http://www.cdc.gov/NCIDOD/dvrd/revb/respiratory/hpivfeat.htm |archive-date=2009-03-03 }}</ref><ref name="eMed CCC">{{cite web|title=Croup Background|url=http://emedicine.medscape.com/article/962972-overview|website=Medscape Reference|access-date=21 March 2012}}</ref> Biennial epidemics starting in Autumn are associated with both HPIV-1 and 2; however, HPIV-2 can also have yearly outbreaks.<ref name="Henrickson2"/> 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.{{cn|date=March 2023}}

HPIV-3 has been closely associated with [[Medicine:Bronchiolitis|bronchiolitis]] and [[Medicine:Pneumonia|pneumonia]] and principally targets those aged <1 year.<ref>{{cite web|title=Parainfluenza Virus Review|url=http://misc.medscape.com/pi/android/medscapeapp/html/A224708-business.html|website=Medscape|access-date=21 March 2012}}</ref>

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 seropositive for HPIV-4 infection which may be indicative of a large proportion of [[Medicine:Asymptomatic|asymptomatic]] or mild infections.<ref name="Henrickson"/>

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.<ref name="Canada">{{cite web|title=HUMAN PARAINFLUENZA VIRUS|url=http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/parainfluenza-eng.php|publisher=Public Health Agency of Canada|access-date=21 March 2012|date=2011-04-19}}</ref>  Associations between HPIVs and neurologic disease are known; for example, hospitalisation with certain HPIVs has a strong association with febrile seizures.<ref>{{cite web|author1=Stephen B Greenberg |author2=Robert L Atmar |title=Parainfluenza Viruses—New Epidemiology and Vaccine Developments|url=http://www.touchinfectiousdisease.com/articles/parainfluenza-viruses-new-epidemiology-and-vaccine-developments-0?page=0,2|publisher=Touch Infectious Disease|access-date=21 March 2012}}</ref> HPIV-4B has the strongest association (up to 62%) followed by HPIV-3 and -1.<ref name="Henrickson"/>

HPIVs have also been linked with rare cases of viral [[Medicine:Meningitis|meningitis]]<ref>{{cite journal|last=Arguedas|first=A |author2=Stutman, HR |author3=Blanding, JG|s2cid=25043753 |title=Parainfluenza type 3 meningitis. Report of two cases and review of the literature|journal=Clinical Pediatrics|date=March 1990|volume=29|issue=3|pages=175–178|pmid=2155085|doi=10.1177/000992289002900307}}</ref> and [[Medicine:Guillain–Barré syndrome|Guillain–Barré syndrome]].<ref name="eMed hPIV"/>

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.{{citation needed|date=June 2022}}

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.{{cn|date=March 2023}}
===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 [[Biology:Interferon type I|IFN–α]], various other interleukins (IL–2, IL-6) and [[Biology:Tumor necrosis factor|TNF–α]]. Various chemokines and inflammatory proteins are also believed to be associated with the common symptoms of HPIV infection.<ref name="eMed hPIV"/>

Recent evidence seems to suggest that virus-specific antibodies (IgE) may be responsible for mediating large-scale releases of [[Chemistry:Histamine|histamine]] in the trachea, which are believed to cause [[Medicine:Croup|croup]].<ref name="eMed hPIV"/><ref>{{cite web |title=Human Parainfluenza Viruses (HPIV) and Other Parainfluenza Viruses: Background, Pathophysiology, Etiology |url=https://emedicine.medscape.com/article/224708-overview#showall |access-date=18 March 2023 |date=17 October 2021}}</ref>

===Immunology===

The body's primary defense against HPIV infection is [[Biology:Adaptive immune system|adaptive immunity]] involving both [[Biology:Humoral immunity|humoral]] and [[Biology:Cell-mediated immunity|cellular immunity]]. With humoral immunity, antibodies that bind to the surface viral proteins HN and F protect against later infection.<ref>{{Cite journal |last1=Branche |first1=Angela |last2=Falsey |first2=Ann |date=2016-08-03 |title=Parainfluenza Virus Infection |journal=Seminars in Respiratory and Critical Care Medicine |language=en |volume=37 |issue=4 |pages=538–554 |doi=10.1055/s-0036-1584798 |issn=1069-3424 |pmc=7171724 |pmid=27486735}}</ref> Patients with defective cell-mediated immunity also experience more severe infection, suggesting that T cells are important in clearing infection.<ref name="eMed hPIV"/>

==Diagnosis==
Diagnosis can be made in several ways, encompassing a range of multi-faceted techniques:<ref name="CDC hPIV"/>
* Isolation and detection of the virus in [[Biology:Cell culture|cell culture]].
* Detection of viral antigens directly within bodily [[Medicine:Respiratory tract|respiratory tract]] secretions using [[Biology:Immunofluorescence|immunofluorescence]], enzyme immunoassays or fluoroimmunoassays.
* [[Biology:Polymerase chain reaction|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, [[Biology:Hemagglutination assay|hemagglutination assay]] (HA) or hemadsorption inhibition (HAdI) processes are often used. Both complement fixation, [[Biology:Neutralizing antibody|neutralisation]], and enzyme linked immunosorbent assays – ELISA, can also be used to aid in the process of distinguishing between viral serotypes.<ref name="Henrickson"/>

==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 remodeling and are believed to be a significant cause of morbidity.<ref>{{cite journal|last=Dimopoulos|first=G|author2=Lerikou, M |author3=Tsiodras, S |author4=Chranioti, A |author5=Perros, E |author6=Anagnostopoulou, U |author7=Armaganidis, A |author8=Karakitsos, P |title=Viral epidemiology of acute exacerbations of chronic obstructive pulmonary disease|journal=Pulmonary Pharmacology & Therapeutics|date=February 2012|volume=25|issue=1|pages=12–8|pmid=21983132|doi=10.1016/j.pupt.2011.08.004|pmc=7110842}}</ref> The exact associations between HPIVs and diseases such as [[Medicine:Chronic obstructive pulmonary disease|chronic obstructive pulmonary disease]] (COPD) are still being investigated.<ref>{{cite journal|last=Beckham|first=JD|author2=Cadena, A |author3=Lin, J |author4=Piedra, PA |author5=Glezen, WP |author6=Greenberg, SB |author7=Atmar, RL |title=Respiratory viral infections in patients with chronic, obstructive pulmonary disease|journal=The Journal of Infection|date=May 2005|volume=50|issue=4|pages=322–30|pmid=15845430|doi=10.1016/j.jinf.2004.07.011|pmc=7132437}}</ref>

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 [[Medicine:Malnutrition|malnutrition]] and other deficiencies, may further elevate the chances of mortality associated with infection.<ref name="eMed hPIV"/>

Overall, LRIs cause approximately 25–30% of total deaths in preschool children in the developing world. HPIVs are believed to be associated with 10% of all LRI cases, thus remaining a significant cause of mortality.<ref name="eMed hPIV"/>

===Risk factors===

Numerous factors have been suggested and linked to a higher risk of acquiring the infection, inclusive of [[Medicine:Malnutrition|malnutrition]], [[Medicine:Vitamin A deficiency|vitamin A deficiency]], absence of breastfeeding during the early stages of life, environmental pollution and overcrowding.<ref>{{cite journal|last=Berman|first=S|title=Epidemiology of acute respiratory infections in children of developing countries|journal=Reviews of Infectious Diseases|date=May–Jun 1991|volume=13|issue=Suppl 6|pages=S454–62|pmid=1862276|doi=10.1093/clinids/13.supplement_6.s454}}</ref>

==Prevention==
Despite decades of research, no vaccines currently exist.<ref name="pmid18820572">{{cite journal |vauthors=Sato M, Wright PF |title=Current status of vaccines for parainfluenza virus infections |journal=Pediatr. Infect. Dis. J. |volume=27 |issue=10 Suppl |pages=S123–5 |date=October 2008 |pmid=18820572 |doi=10.1097/INF.0b013e318168b76f |doi-access=free }}</ref>

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.<ref name="Karron"/>

Vaccine techniques which have been used against HPIVs are not limited to intranasal forms, but also viruses [[Medicine:Attenuated vaccine|attenuated]] by cold passage, host range attenuation, chimeric construct vaccines and also introducing mutations with the help of reverse genetics to achieve attenuation.<ref>{{cite web|title=Parainfluenza Viruses|url=http://www.els.net/WileyCDA/ElsArticle/refId-a0001078.html|publisher=eLS|access-date=21 March 2012}}</ref>

Maternal [[Biology:Antibodies|antibodies]] may offer some degree of protection against HPIVs during the early stages of life via the [[Biology:Colostrum|colostrum]] in breast milk.<ref>{{cite web|title=Definition of Human parainfluenza virus|url=http://www.medterms.com/script/main/art.asp?articlekey=31631|publisher=MedicineNet|access-date=21 March 2012|archive-date=5 January 2012|archive-url=https://web.archive.org/web/20120105180604/http://www.medterms.com/script/main/art.asp?articlekey=31631|url-status=dead}}</ref>

== Medication ==

[[Chemistry:Ribavirin|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).<ref name="eMed hPIV"/> Ribavirin is a broad-spectrum [[Biology:Antiviral drug|antiviral]], and as of 2012, was being administered to those who are severely immuno-compromised, despite the lack of conclusive evidence for its benefit.<ref name="eMed hPIV"/> Protein inhibitors and novel forms of medication have also been proposed to relieve the symptoms of infection.<ref name="Canada"/>

Furthermore, antibiotics may be used if a secondary bacterial infection develops. [[Biology:Corticosteroid|Corticosteroid]] treatment and [[Medicine:Nebulizer|nebulizer]]s are also a first line choice against [[Medicine:Croup|croup]] if breathing difficulties ensue.<ref name="eMed hPIV"/>

== Interactions with the environment ==
Parainfluenza viruses last only a few hours in the environment and are inactivated by soap and water. Furthermore, the virus can also be easily destroyed using common hygiene techniques and detergents, disinfectants and antiseptics.<ref name="CDC hPIV"/>

Environmental factors which are important for HPIV survival are [[Chemistry:PH|pH]], [[Physics:Humidity|humidity]], [[Physics:Temperature|temperature]] and the medium within which the virus is found. The optimal pH is around the physiologic pH values (7.4 to 8.0), whilst at high temperatures (above 37&nbsp;°C) and low humidity, infectivity reduces.<ref>{{cite journal|last=HAMBLING|first=MH|journal=British Journal of Experimental Pathology|date=December 1964|volume=45|pages=647–55|pmid=14245166|pmc=2093680|issue=6|title=Survival of the Respiratory Syncytial Virus During Storage Under Various Conditions}}</ref>

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 [[Medicine:Fomite|fomite]]s (contaminated surfaces).<ref>{{cite web|title=Common Cold, Croup and Human Parainfluenza Viruses: Symptoms and Prevention.|url=http://www.newsflu.com/tag/cold/|publisher=NewsFlu|access-date=21 March 2012}}</ref>

The exact infectious dose remains unknown.<ref name="Canada"/>

==Economic burden==
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|extrapolation]]) in the region of $200 million per annum.<ref name="Henrickson"/>

==References==
{{Reflist}}

==Further reading==
* {{cite journal |vauthors=Henrickson KJ |title=Parainfluenza viruses |journal=Clin. Microbiol. Rev. |volume=16 |issue=2 |pages=242–64 |year=2003 |pmid=12692097 |pmc=153148 |doi=10.1128/cmr.16.2.242-264.2003}}
* [https://www.cdc.gov/parainfluenza/index.html Human Parainfluenza Viruses (HPIVs)]

==External links==
* [https://www.cdc.gov/parainfluenza/index.html Human Parainfluenza Viruses] – information provided by the CDC

{{Medical resources
|  DiseasesDB     = 30631
|  ICD10          = {{ICD10|B|34|8}}, {{ICD10|J|12|2}}, {{ICD10|J|20|4}}
|  ICD9           = {{ICD9|480.2}}
|  ICDO           =
|  OMIM           =
|  MedlinePlus    = 001370
|  eMedicineSubj  =
|  eMedicineTopic =
|  MeshID         = D018184
}}

{{Viral diseases}}
{{Common Cold}}

{{DEFAULTSORT:Human Parainfluenza Viruses (hPIV)}}
[[Category:Respiratory diseases]]
[[Category:Paramyxoviridae]]

{{Sourceattribution|Human parainfluenza viruses}}