ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Parainfluenza viruses in children

Parainfluenza viruses in children
Authors:
Flor M Munoz, MD, MSc
Morven S Edwards, MD
Section Editor:
Sheldon L Kaplan, MD
Deputy Editor:
Mary M Torchia, MD
Literature review current through: Jun 2022. | This topic last updated: Jul 28, 2021.

INTRODUCTION — Parainfluenza viruses (PIV) are important respiratory pathogens in children and adults. Parainfluenza viruses cause a variety of upper and lower respiratory tract illnesses, ranging from mild cold-like syndromes to life-threatening pneumonia, particularly in immunocompromised patients.

The virology, clinical manifestations, diagnosis, and treatment of PIV in children will be reviewed here. The clinical syndromes caused by PIV in children and PIV in adults are discussed separately:

(See "Croup: Clinical features, evaluation, and diagnosis" and "Management of croup".)

(See "The common cold in children: Clinical features and diagnosis" and "The common cold in children: Management and prevention".)

(See "Bronchiolitis in infants and children: Clinical features and diagnosis" and "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)

(See "Pneumonia in children: Epidemiology, pathogenesis, and etiology" and "Community-acquired pneumonia in children: Clinical features and diagnosis".)

(See "Parainfluenza viruses in adults".)

VIROLOGY — Parainfluenza viruses (PIV) belong to the Paramyxoviridae family, which includes mumps, measles, and henipaviruses [1].

Four major human serotypes have been described based upon complement fixation and hemagglutinating antigens: PIV-1, PIV-2, PIV-3, and PIV-4 [2]. PIV-1 and PIV-3 belong to the Respirovirus genus; PIV-2 and PIV-4 belong to the Rubulavirus genus [1]. In national surveillance for PIV infections in children and adults, PIV-3 were detected most frequently (approximately 55 percent of PIV-positive tests), followed by PIV-1 (18 percent), PIV-2 (14 percent), and PIV-4 (13 percent) [3]. The clinical manifestations vary with serotype. (See 'Clinical presentation' below.)

PIV are single stranded, enveloped RNA viruses [4]. The virions are pleomorphic and range in diameter from 150 to 200 nm. The single strand of negative-sense RNA is approximately 15,500 nucleotides in length and encodes six structural viral proteins [1]:

The hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins project through the lipid envelope and form the major antigenic targets for neutralizing antibody [5]. Their hydrophobic tails project into the virion, where they interact with the matrix (M) protein to aid in virus assembly [6].

The nucleocapsid core is composed of the nucleocapsid protein (NP), the phosphoprotein (P), and RNA polymerase (L) proteins in association with viral RNA. NP proteins bind tightly to the viral genome, creating a template for the RNA-dependent RNA polymerase composed of the P and L proteins [7].

Each PIV also expresses at least one nonessential protein [8,9]:

PIV-1 and PIV-3 RNA encode short C proteins, which inhibit the host innate immune response; PIV-3 also expresses a D protein, the function of which is unknown.

PIV-2 RNA encodes a V protein, which inhibits the host innate immune response.

PATHOGENESIS — Parainfluenza viruses (PIV) initially infect the epithelial cells of the nose and oropharynx [10] and can spread distally to the large and small airways [11]. The extent of infection correlates with disease severity: Limited infection of the nasopharynx is associated with mild upper respiratory infection; spread of infection to the large and small airways is associated with more severe disease [12]. Progression to the lower respiratory tract and severity of disease are related to virus load in the upper respiratory tract, previous exposure to the specific virus, and genetic susceptibility [4,13,14].

In an animal model, viral replication increases during the first day of infection and peaks at two to five days [15]. Viral antigen was detected in respiratory epithelial cells from days 1 to 6 of infection, with a decrease on day 7 [16].

Direct viral effects of PIV appear to cause minimal cellular or tissue damage [8,11,16,17]. As with other respiratory viruses, the host immune response plays an important role in the pathogenesis of PIV infection. PIV induce innate immune responses, CD8+ and CD4+ T cell responses, interferon production, and local and systemic immunoglobulin (Ig)A and IgG responses, which contribute to the clearing of the virus [15,18]. The increase in airway responsiveness that often is associated with PIV-3 infection (and other respiratory viruses, such as respiratory syncytial virus) may result from IgE, increased stromal interleukin-11 production, and enhanced acetylcholine release [19-21].

NATURAL IMMUNITY — Natural immunity to parainfluenza virus is incomplete, and reinfection is common. In immunocompetent children, reinfections tend to be milder than initial infection and restricted to the upper respiratory tract [22].

Although antibodies are produced to all viral proteins, only antibodies to the surface proteins (ie, hemagglutinin-neuraminidase and fusion proteins) are neutralizing [4]. T cell immunity contributes to viral clearance and confers transient resistance to reinfection [8,23].

EPIDEMIOLOGY

Prevalence — Parainfluenza viruses (PIV) are most commonly recovered in children younger than five years of age with upper respiratory infections [24,25].

In surveillance in the United States from 1998 to 2010, the annual estimated PIV-associated hospitalization rates in children <5 years of age were 0.2 per 1000 children for bronchiolitis, 0.4 per 1000 children for croup, and 0.5 per 1000 children for pneumonia [26]. The majority of PIV-associated hospitalizations occurred in children younger than two years.

In separate population-based studies, PIV accounted for 7 percent of pneumonia-related hospitalizations in children [24,27]. Most of the hospitalizations occurred in children younger than two years. PIV-3 accounted for approximately one-half of PIV-associated hospitalizations [24].

The age at first infection varies with serotype. In serologic studies, as many as 50 percent of children have been infected with PIV-3 by their first birthday [28]. PIV-1, PIV-2, and PIV-4 typically affect children at three to five years of age [22,28-30].

Seasonality — PIV infections occur throughout the world and throughout the year. In tropical countries, PIV do not exhibit seasonal variation [31]. In countries with temperate climates, certain serotypes predominate during the spring or fall [32,33].

PIV-1 usually causes biennial outbreaks during the fall of odd-numbered years (figure 1).

PIV-2 occurs in annual epidemics in the fall.

PIV-3 occurs in annual epidemics in the spring.

During years in which PIV-1 is not circulating, there is an increase in PIV-3 activity, manifested either as a longer spring PIV-3 season or as a second smaller peak in the fall.

PIV-4 is most commonly seen during the fall, peaking in winter of each year [3].

Transmission and incubation period — PIV are transmitted by direct person-to-person contact and exposure to aerosolized respiratory secretions and fomites [34]. Spread within families is extensive [35].

The incubation period ranges from two to six days [34].

Risk and protective factors

Risk factors for severe infection – Immunocompromised patients are at increased risk for severe infection; this includes children with:

HIV infection [36].

Severe T cell deficiencies [37].

Hematologic malignancy (particularly acute lymphoblastic leukemia) and leukopenia [38-40].

In a retrospective study of children with hematologic malignancies, PIV were detected in 10 percent of children tested for respiratory infections (second only to influenza) [41]; 90 percent of PIV infections were community associated. PIV-3 accounted for 61 percent of PIV infections. Although 80 percent of children had upper respiratory tract illness, children who were young (median age 27 months) and presented with fever, severe neutropenia, or lymphopenia were at increased risk for lower respiratory tract infection.

Hematopoietic cell transplantation recipients; these patients are at particular risk of severe PIV-associated pneumonia, with prolonged shedding and mortality rates of up to 30 percent [37,42-46].

Solid organ transplant recipients.

In a multicenter retrospective study of acute respiratory virus infections in the six months after solid organ transplant, PIV occurred in 16 percent and was the third most frequently identified virus (following rhinovirus and respiratory syncytial virus) [47]. PIV-related complications included fever, lower respiratory tract disease, and at least one death. Complications such as bronchiolitis obliterans and acute and chronic rejection have been reported in lung transplant patients with PIV and other respiratory viral infections [48,49].

Protective factors – In observational studies, breastfeeding and pneumococcal vaccination have been associated with reduced risk of severe infection [12,50]. Pneumococcal vaccination has been associated with decreased risk of pneumonia in infants with PIV and other respiratory virus infections, suggesting that pneumococcus may play a role in the pathogenesis of virus-associated pneumonia. (See "Pneumococcal vaccination in children", section on 'Pneumonia and empyema'.)

CLINICAL PRESENTATION

Respiratory tract illness — Parainfluenza viruses (PIV) cause a variety of upper and lower respiratory tract illnesses, ranging from mild cold-like syndromes to life-threatening pneumonia. They cause a greater proportion of acute respiratory infections in outpatients than in hospitalized children. Immunocompromised patients are at increased risk for severe infection. (See 'Risk and protective factors' above.)

In children, more than 50 percent of PIV infections are upper respiratory infections (URIs), of which 30 to 50 percent are complicated by otitis media [51,52]. Approximately 15 percent of PIV infections in children involve the lower respiratory tract.

Specific PIV serotypes are strongly associated with certain clinical syndromes in children [53,54]:

PIV-1 is the leading cause of laryngotracheitis (croup), which is characterized by hoarseness, barking cough, and stridor. (See "Croup: Clinical features, evaluation, and diagnosis", section on 'Clinical presentation'.)

PIV-2 also is associated with croup, although the illness generally is milder than with PIV-1.

PIV-3, which is isolated from children more frequently than other serotypes [25,32], is associated with lower respiratory tract infection (eg, bronchiolitis, pneumonia), particularly in young infants. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Clinical features' and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clinical presentation'.)

PIV-4 typically causes only mild URI symptoms [29]. However, PIV-4 has been isolated in cases of bronchiolitis, pneumonia, croup, apnea, and paroxysmal cough in young infants and in children with underlying conditions (eg, developmental disabilities, chronic cardiopulmonary disease, immunosuppression) [55-57].

PIV causes approximately 60 to 75 percent of cases of croup and 10 to 20 percent of cases of confirmed viral bronchiolitis [54]. PIV also may cause conjunctivitis and pharyngitis [54].

In patients with underlying asthma, PIV may cause acute exacerbations that can be refractory to standard asthma therapy [58]. (See "Role of viruses in wheezing and asthma: An overview", section on 'Specific viruses'.)

Otitis media and sinusitis can result from either primary viral infections or secondary bacterial superinfection. (See "Acute otitis media in children: Epidemiology, microbiology, and complications" and "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis".)

Other manifestations — Nonrespiratory complications of PIV are rare but include:

Meningitis [59] (see "Viral meningitis in children: Clinical features and diagnosis", section on 'Clinical features')

Myocarditis and pericarditis [60,61] (see "Clinical manifestations and diagnosis of myocarditis in children")

Guillain-Barré syndrome [62] (see "Guillain-Barré syndrome in children: Epidemiology, clinical features, and diagnosis")

Acute disseminated encephalomyelitis [63,64] (see "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis")

DIAGNOSIS — Most immunocompetent children who present with clinical syndromes that typically are caused by parainfluenza viruses (PIV) or other respiratory viruses (eg, croup, bronchiolitis) do not require microbiologic testing. In these children, knowing the causative pathogen does not affect management.

Laboratory confirmation may be helpful in excluding other infections in children who are hospitalized with community-acquired pneumonia, seriously ill, and/or immunocompromised. In such patients, knowing the etiologic pathogen may affect management (eg, antimicrobial therapy). Laboratory confirmation also may be helpful in evaluating the possibility of a community outbreak.

When laboratory confirmation is necessary, detection of viral RNA with polymerase chain reaction (PCR) of nasopharyngeal and/or oropharyngeal specimens is the preferred diagnostic test [54]. PCR has high sensitivity, high specificity, and rapid turn-around time [65]. Some multiplex respiratory panels include PIV. Although PCR does not differentiate noninfectious genomic particles from infection, PIV are more frequently detected in children with acute respiratory symptoms than in children who are asymptomatic [66,67].

Multiplex PCR assays permit the detection of PIV and other respiratory viruses in nasopharyngeal and oropharyngeal secretions with reported sensitivities of 95 to 100 percent and specificity of >97 percent [1,65,68-71]. Collection of paired oropharyngeal and nasopharyngeal samples may increase the sensitivity [72,73]. The yield of detection of PIV-3 is greater with PCR than with viral culture [74].

If PCR is not available, rapid antigen detection or viral culture may establish the diagnosis.

Rapid immunofluorescence antigen detection of PIV-1 to PIV-3 is specific, but the reported sensitivity is generally lower than that of PCR [75-78].

Viral culture of nasopharyngeal samples (nasopharyngeal swabs, aspirates, or washes) is also available but not clinically practical because cell culture may take up to seven days [34]. Specimens should be placed in viral transport media and kept at 4°C because the virus loses infectivity at room temperature [79]. Hemadsorption and immunofluorescence typing are routinely used for identification, as observed cytopathic effects can be variable.

Serology is not routinely used for the diagnosis of PIV [34]. It is not practical in the clinical setting because it is time consuming and may be confounded by heterotypic antibody response [1].

TREATMENT — Parainfluenza virus (PIV) infections usually are self-limited, and immunocompetent children are treated with supportive measures. There are no licensed antiviral agents with proven clinical efficacy.

Supportive care for specific clinical syndromes is discussed separately:

Common cold (see "The common cold in children: Management and prevention", section on 'Supportive care')

Croup (see "Management of croup")

Bronchiolitis (see "Bronchiolitis in infants and children: Treatment, outcome, and prevention")

Community-acquired pneumonia (see "Community-acquired pneumonia in children: Outpatient treatment", section on 'Supportive care' and "Pneumonia in children: Inpatient treatment", section on 'Supportive care')

Immunocompromised patients (primarily hematopoietic transplant and solid organ transplant recipients) may benefit from reduction of immune suppression in addition to supportive care.

Although ribavirin inhibits PIV in in vitro studies, proven benefit in controlled trials is lacking. Ribavirin and other agents that have been used to treat PIV in immunocompromised hosts are discussed separately. (See "Parainfluenza viruses in adults", section on 'Treatment'.)

DAS181 (an inhaled sialidase fusion protein) is an investigational agent for the treatment of PIV infections. It cleaves the sialic acid containing receptors of PIV in respiratory cells. It has in vitro antiviral activity against influenza and PIV. In case reports and clinical trials, DAS181 has been reported to successfully treat PIV in patients with hematopoietic cell and lung transplantation and/or decrease viral load [80-87]. DAS181 has been evaluated for the treatment of PIV in children and adults who received it through compassionate use and in various clinical trials, but it is not available for clinical use [87-89].

PREVENTION

Infection control

All patients – Hand hygiene, respiratory hygiene, and cough etiquette may help to prevent parainfluenza virus (PIV) transmission in all settings [90]. (See "Infection control in the outpatient setting".)

Children who are hospitalized – For infants and children who are hospitalized with documented PIV infection, contact precautions are recommended for the duration of illness (in addition to standard precautions) [90]. (See "Infection prevention: Precautions for preventing transmission of infection".)

Pending results of microbiologic testing or if microbiologic testing is not performed, droplet precautions are also recommended; droplet precautions can be discontinued if influenza and adenovirus have been excluded [90]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Droplet precautions'.)

Vaccine development — There is no licensed vaccine for PIV [54]. However, studies of vaccine candidates are ongoing.

Several live attenuated intranasal vaccine candidates have been developed using cell culture passage or chemical mutagenesis for viral attenuation and reverse genetics technology:

Bovine PIV-3 (BPIV-3), a virus that is antigenically related to human PIV-3 (hPIV-3), has been evaluated in clinical trials as a vaccine candidate to protect against PIV-3 in children and infants. However, seroconversion rates to hPIV-3 have been modest [91-93].

Sendai virus (SeV) is a mouse PIV-1 candidate vaccine for hPIV-1, as well as a vector for other respiratory viruses [94,95]. An SeV-based vaccine carrying the respiratory syncytial virus (RSV) F gene demonstrated safety and transient viral genome detection in a phase 1 study in adults, an initial step toward developing a combination RSV and hPIV-1 vaccine for children [95].

A live attenuated, cold-adapted PIV-3 vaccine candidate, hPIV-3-cp45, the cp45 derivative of the JS strain of wild-type hPIV-3, was safe and immunogenic in a phase 2 trial in healthy seropositive and seronegative infants and children [96]. A combined hPIV-3-cp45/RSV experimental vaccine has been studied in 6- to 18-month-old seronegative children, showing antibody responses similar to the monovalent vaccine components [97].

Reverse genetics technology has contributed to the development of additional vaccines with promising results, including a complementary DNA (cDNA) derived live attenuated recombinant virus vaccine, recombinant hPIV-3-cp45 [8,98], monovalent cDNA-derived chimeric B/hPIV-3 virus vaccine (rB/hPIV-3) [99], bivalent chimeric rB/hPIV-3 and RSV vaccine [100], and PIV-1 and PIV-2 vaccines [8,91,101-103].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Croup" and "Society guideline links: Bronchiolitis in infants and children" and "Society guideline links: Pediatric pneumonia".)

SUMMARY AND RECOMMENDATIONS

Virology – Parainfluenza viruses (PIV) are single stranded, enveloped RNA viruses belonging to the Paramyxoviridae family. Four major serotypes of human PIV (PIV-1, PIV-2, PIV-3, PIV-4) have been described. (See 'Virology' above.)

Natural immunity – Natural immunity to PIV is incomplete, and reinfection is common. In immunocompetent children, reinfections tend to be milder than initial infection. (See 'Natural immunity' above.)

Epidemiology and transmission – PIV are most commonly recovered in children younger than five years of age with upper respiratory infections. Immunocompromised children are at increased risk for severe infection. (See 'Epidemiology' above.)

PIV are transmitted through direct person-to-person contact and exposure to aerosolized respiratory secretions and fomites. The incubation period ranges from two to six days. (See 'Transmission and incubation period' above.)

Clinical presentation – PIV cause a variety of upper and lower respiratory tract illnesses, ranging from mild cold-like syndromes to life-threatening pneumonia. PIV-1 and PIV-2 generally are associated with croup, PIV-3 with pneumonia and bronchiolitis, and PIV-4 with mild upper respiratory tract illness. (See 'Respiratory tract illness' above.)

Laboratory confirmation – Most immunocompetent children who present with clinical syndromes that typically are caused by PIV or other respiratory viruses (eg, croup, bronchiolitis) do not require microbiologic testing. Laboratory confirmation may be helpful in excluding other infections in children who are hospitalized with community-acquired pneumonia, seriously ill, and/or immunocompromised. (See 'Diagnosis' above.)

When laboratory confirmation is necessary, detection of viral RNA with polymerase chain reaction (PCR) testing is preferred, given its high sensitivity, high specificity, and rapid turn-around time. If PCR is not available, rapid antigen detection or viral culture may establish the diagnosis. (See 'Diagnosis' above.)

Management – PIV infections usually are self-limited, and immunocompetent children are treated with supportive measures. There are no licensed antiviral agents with proven clinical efficacy. Supportive care for children with specific clinical syndromes is discussed separately (see 'Treatment' above):

Common cold (see "The common cold in children: Management and prevention", section on 'Supportive care')

Croup (see "Management of croup")

Bronchiolitis (see "Bronchiolitis in infants and children: Treatment, outcome, and prevention")

Community-acquired pneumonia (see "Community-acquired pneumonia in children: Outpatient treatment", section on 'Supportive care' and "Pneumonia in children: Inpatient treatment", section on 'Supportive care')

  1. Welliver RC. Parainfluenza viruses. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry JD, Harrison G, Kaplan SL, et al (Eds), Elsevier, Philadelphia 2018. p.1745.
  2. Wendt CH, Hertz MI. Respiratory syncytial virus and parainfluenza virus infections in the immunocompromised host. Semin Respir Infect 1995; 10:224.
  3. DeGroote NP, Haynes AK, Taylor C, et al. Human parainfluenza virus circulation, United States, 2011-2019. J Clin Virol 2020; 124:104261.
  4. Karron RA, Colling PL. Parainfluenza viruses. In: Fields Virology, Knipe DM, Howley PM (Eds), Lippincott Williams & Wilkins, Philadelphia 2007. p.1497.
  5. Tao T, Durbin AP, Whitehead SS, et al. Recovery of a fully viable chimeric human parainfluenza virus (PIV) type 3 in which the hemagglutinin-neuraminidase and fusion glycoproteins have been replaced by those of PIV type 1. J Virol 1998; 72:2955.
  6. Patterson S, Gross J, Oxford JS. The intracellular distribution of influenza virus matrix protein and nucleoprotein in infected cells and their relationship to haemagglutinin in the plasma membrane. J Gen Virol 1988; 69 ( Pt 8):1859.
  7. Hamaguchi M, Yoshida T, Nishikawa K, et al. Transcriptive complex of Newcastle disease virus. I. Both L and P proteins are required to constitute an active complex. Virology 1983; 128:105.
  8. Bartlett EJ, Cruz AM, Boonyaratanakornkit J, et al. A novel human parainfluenza virus type 1 (HPIV1) with separated P and C genes is useful for generating C gene mutants for evaluation as live-attenuated virus vaccine candidates. Vaccine 2010; 28:767.
  9. Boonyaratanakornkit J, Bartlett E, Schomacker H, et al. The C proteins of human parainfluenza virus type 1 limit double-stranded RNA accumulation that would otherwise trigger activation of MDA5 and protein kinase R. J Virol 2011; 85:1495.
  10. Castleman WL, Brundage-Anguish LJ, Kreitzer L, Neuenschwander SB. Pathogenesis of bronchiolitis and pneumonia induced in neonatal and weanling rats by parainfluenza (Sendai) virus. Am J Pathol 1987; 129:277.
  11. Zhang L, Bukreyev A, Thompson CI, et al. Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium. J Virol 2005; 79:1113.
  12. Welliver RC, Wong DT, Sun M, McCarthy N. Parainfluenza virus bronchiolitis. Epidemiology and pathogenesis. Am J Dis Child 1986; 140:34.
  13. Wilson J, Rowlands K, Rockett K, et al. Genetic variation at the IL10 gene locus is associated with severity of respiratory syncytial virus bronchiolitis. J Infect Dis 2005; 191:1705.
  14. Crowe JE Jr, Williams JV. Immunology of viral respiratory tract infection in infancy. Paediatr Respir Rev 2003; 4:112.
  15. Porter DD, Prince GA, Hemming VG, Porter HG. Pathogenesis of human parainfluenza virus 3 infection in two species of cotton rats: Sigmodon hispidus develops bronchiolitis, while Sigmodon fulviventer develops interstitial pneumonia. J Virol 1991; 65:103.
  16. Prince GA, Porter DD. Treatment of parainfluenza virus type 3 bronchiolitis and pneumonia in a cotton rat model using topical antibody and glucocorticosteroid. J Infect Dis 1996; 173:598.
  17. Schaap-Nutt A, Scull MA, Schmidt AC, et al. Growth restriction of an experimental live attenuated human parainfluenza virus type 2 vaccine in human ciliated airway epithelium in vitro parallels attenuation in African green monkeys. Vaccine 2010; 28:2788.
  18. Schmidt AC, Schaap-Nutt A, Bartlett EJ, et al. Progress in the development of human parainfluenza virus vaccines. Expert Rev Respir Med 2011; 5:515.
  19. Welliver RC, Wong DT, Middleton E Jr, et al. Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection. J Pediatr 1982; 101:889.
  20. Einarsson O, Geba GP, Zhu Z, et al. Interleukin-11: stimulation in vivo and in vitro by respiratory viruses and induction of airways hyperresponsiveness. J Clin Invest 1996; 97:915.
  21. Jacoby DB, Xiao HQ, Lee NH, et al. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons. J Clin Invest 1998; 102:242.
  22. Glezen WP, Frank AL, Taber LH, Kasel JA. Parainfluenza virus type 3: seasonality and risk of infection and reinfection in young children. J Infect Dis 1984; 150:851.
  23. Takamura S, Roberts AD, Jelley-Gibbs DM, et al. The route of priming influences the ability of respiratory virus-specific memory CD8+ T cells to be activated by residual antigen. J Exp Med 2010; 207:1153.
  24. Weinberg GA, Hall CB, Iwane MK, et al. Parainfluenza virus infection of young children: estimates of the population-based burden of hospitalization. J Pediatr 2009; 154:694.
  25. Steffens A, Finelli L, Whitaker B, Fowlkes A. Population-based Surveillance for Medically Attended Human Parainfluenza Viruses From the Influenza Incidence Surveillance Project, 2010-2014. Pediatr Infect Dis J 2016; 35:717.
  26. Abedi GR, Prill MM, Langley GE, et al. Estimates of Parainfluenza Virus-Associated Hospitalizations and Cost Among Children Aged Less Than 5 Years in the United States, 1998-2010. J Pediatric Infect Dis Soc 2016; 5:7.
  27. Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med 2015; 372:835.
  28. PARROTT RH, VARGOSKO AJ, KIMHW, et al. Acute respiratory diseases of viral etiology. III. parainfluenza. Myxoviruses. Am J Public Health Nations Health 1962; 52:907.
  29. Fairchok MP, Martin ET, Kuypers J, Englund JA. A prospective study of parainfluenza virus type 4 infections in children attending daycare. Pediatr Infect Dis J 2011; 30:714.
  30. Ren L, Gonzalez R, Xie Z, et al. Human parainfluenza virus type 4 infection in Chinese children with lower respiratory tract infections: a comparison study. J Clin Virol 2011; 51:209.
  31. Chew FT, Doraisingham S, Ling AE, et al. Seasonal trends of viral respiratory tract infections in the tropics. Epidemiol Infect 1998; 121:121.
  32. Fry AM, Curns AT, Harbour K, et al. Seasonal trends of human parainfluenza viral infections: United States, 1990-2004. Clin Infect Dis 2006; 43:1016.
  33. Marx A, Török TJ, Holman RC, et al. Pediatric hospitalizations for croup (laryngotracheobronchitis): biennial increases associated with human parainfluenza virus 1 epidemics. J Infect Dis 1997; 176:1423.
  34. American Academy of Pediatrics. Parainfluenza viral infections. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barrett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.555.
  35. Ansari SA, Springthorpe VS, Sattar SA, et al. Potential role of hands in the spread of respiratory viral infections: studies with human parainfluenza virus 3 and rhinovirus 14. J Clin Microbiol 1991; 29:2115.
  36. Cohen AL, Sahr PK, Treurnicht F, et al. Parainfluenza Virus Infection Among Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Children and Adults Hospitalized for Severe Acute Respiratory Illness in South Africa, 2009-2014. Open Forum Infect Dis 2015; 2:ofv139.
  37. Taylor CE, Osman HK, Turner AJ, et al. Parainfluenza virus and respiratory syncytial virus infection in infants undergoing bone marrow transplantation for severe combined immunodeficiency. Commun Dis Public Health 1998; 1:202.
  38. Shah DP, Shah PK, Azzi JM, Chemaly RF. Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review. Cancer Lett 2016; 370:358.
  39. Lehners N, Tabatabai J, Prifert C, et al. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders. PLoS One 2016; 11:e0148258.
  40. Richardson L, Brite J, Del Castillo M, et al. Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy. Clin Microbiol Infect 2016; 22:380.e1.
  41. Srinivasan A, Wang C, Yang J, et al. Parainfluenza virus infections in children with hematologic malignancies. Pediatr Infect Dis J 2011; 30:855.
  42. Srinivasan A, Wang C, Yang J, et al. Symptomatic parainfluenza virus infections in children undergoing hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2011; 17:1520.
  43. Elizaga J, Olavarria E, Apperley J, et al. Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment. Clin Infect Dis 2001; 32:413.
  44. Piralla A, Percivalle E, Di Cesare-Merlone A, et al. Multicluster nosocomial outbreak of parainfluenza virus type 3 infection in a pediatric oncohematology unit: a phylogenetic study. Haematologica 2009; 94:833.
  45. Maziarz RT, Sridharan P, Slater S, et al. Control of an outbreak of human parainfluenza virus 3 in hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2010; 16:192.
  46. Campbell AP, Chien JW, Kuypers J, et al. Respiratory virus pneumonia after hematopoietic cell transplantation (HCT): associations between viral load in bronchoalveolar lavage samples, viral RNA detection in serum samples, and clinical outcomes of HCT. J Infect Dis 2010; 201:1404.
  47. Danziger-Isakov L, Steinbach WJ, Paulsen G, et al. A Multicenter Consortium to Define the Epidemiology and Outcomes of Pediatric Solid Organ Transplant Recipients With Inpatient Respiratory Virus Infection. J Pediatric Infect Dis Soc 2019; 8:197.
  48. Vu DL, Bridevaux PO, Aubert JD, et al. Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies. Am J Transplant 2011; 11:1071.
  49. Kumar D, Husain S, Chen MH, et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation 2010; 89:1028.
  50. Madhi SA, Klugman KP, Vaccine Trialist Group. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004; 10:811.
  51. Reed G, Jewett PH, Thompson J, et al. Epidemiology and clinical impact of parainfluenza virus infections in otherwise healthy infants and young children < 5 years old. J Infect Dis 1997; 175:807.
  52. Vesa S, Kleemola M, Blomqvist S, et al. Epidemiology of documented viral respiratory infections and acute otitis media in a cohort of children followed from two to twenty-four months of age. Pediatr Infect Dis J 2001; 20:574.
  53. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001; 344:1917.
  54. Branche AR, Falsey AR. Parainfluenza Virus Infection. Semin Respir Crit Care Med 2016; 37:538.
  55. Slavin KA, Passaro DJ, Hacker JK, et al. Parainfluenza virus type 4: case report and review of the literature. Pediatr Infect Dis J 2000; 19:893.
  56. Lau SK, To WK, Tse PW, et al. Human parainfluenza virus 4 outbreak and the role of diagnostic tests. J Clin Microbiol 2005; 43:4515.
  57. Frost HM, Robinson CC, Dominguez SR. Epidemiology and clinical presentation of parainfluenza type 4 in children: a 3-year comparative study to parainfluenza types 1-3. J Infect Dis 2014; 209:695.
  58. Merckx J, Ducharme FM, Martineau C, et al. Respiratory Viruses and Treatment Failure in Children With Asthma Exacerbation. Pediatrics 2018; 142.
  59. Arisoy ES, Demmler GJ, Thakar S, Doerr C. Meningitis due to parainfluenza virus type 3: report of two cases and review. Clin Infect Dis 1993; 17:995.
  60. Wilks D, Burns SM. Myopericarditis associated with parainfluenza virus type 3 infection. Eur J Clin Microbiol Infect Dis 1998; 17:363.
  61. Romero-Gómez MP, Guereta L, Pareja-Grande J, et al. Myocarditis caused by human parainfluenza virus in an immunocompetent child initially associated with 2009 influenza A (H1N1) virus. J Clin Microbiol 2011; 49:2072.
  62. Román G, Phillips CA, Poser CM. Parainfluenza virus type 3: isolation from CSF of a patient with Guillain-Barré syndrome. JAMA 1978; 240:1613.
  63. Olivares F, Salinas M, Soto A, et al. [Severe acute disseminated encephalomyelitis associated with parainfluenza 3 infection: Case report]. Rev Chilena Infectol 2015; 32:476.
  64. Voudris KA, Vagiakou EA, Skardoutsou A. Acute disseminated encephalomyelitis associated with parainfluenza virus infection of childhood. Brain Dev 2002; 24:112.
  65. Leber AL, Everhart K, Daly JA, et al. Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples. J Clin Microbiol 2018; 56.
  66. Shi T, McLean K, Campbell H, Nair H. Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta-analysis. J Glob Health 2015; 5:010408.
  67. Self WH, Williams DJ, Zhu Y, et al. Respiratory Viral Detection in Children and Adults: Comparing Asymptomatic Controls and Patients With Community-Acquired Pneumonia. J Infect Dis 2016; 213:584.
  68. Osiowy C. Direct detection of respiratory syncytial virus, parainfluenza virus, and adenovirus in clinical respiratory specimens by a multiplex reverse transcription-PCR assay. J Clin Microbiol 1998; 36:3149.
  69. Fan J, Henrickson KJ, Savatski LL. Rapid simultaneous diagnosis of infections with respiratory syncytial viruses A and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 by multiplex quantitative reverse transcription-polymerase chain reaction-enzyme hybridization assay (Hexaplex). Clin Infect Dis 1998; 26:1397.
  70. Puppe W, Weigl JA, Aron G, et al. Evaluation of a multiplex reverse transcriptase PCR ELISA for the detection of nine respiratory tract pathogens. J Clin Virol 2004; 30:165.
  71. Selvaraju SB, Selvarangan R. Evaluation of xTAG Respiratory Viral Panel FAST and xTAG Human Parainfluenza Virus Analyte-Specific Reagents for detection of human parainfluenza viruses in respiratory specimens. Diagn Microbiol Infect Dis 2012; 72:278.
  72. Kim C, Ahmed JA, Eidex RB, et al. Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays. PLoS One 2011; 6:e21610.
  73. Hammitt LL, Kazungu S, Welch S, et al. Added value of an oropharyngeal swab in detection of viruses in children hospitalized with lower respiratory tract infection. J Clin Microbiol 2011; 49:2318.
  74. Weinberg GA, Erdman DD, Edwards KM, et al. Superiority of reverse-transcription polymerase chain reaction to conventional viral culture in the diagnosis of acute respiratory tract infections in children. J Infect Dis 2004; 189:706.
  75. Ray CG, Minnich LL. Efficiency of immunofluorescence for rapid detection of common respiratory viruses. J Clin Microbiol 1987; 25:355.
  76. Terlizzi ME, Massimiliano B, Francesca S, et al. Quantitative RT real time PCR and indirect immunofluorescence for the detection of human parainfluenza virus 1, 2, 3. J Virol Methods 2009; 160:172.
  77. Ivaska L, Niemelä J, Heikkinen T, et al. Identification of respiratory viruses with a novel point-of-care multianalyte antigen detection test in children with acute respiratory tract infection. J Clin Virol 2013; 57:136.
  78. Sadeghi CD, Aebi C, Gorgievski-Hrisoho M, et al. Twelve years' detection of respiratory viruses by immunofluorescence in hospitalised children: impact of the introduction of a new respiratory picornavirus assay. BMC Infect Dis 2011; 11:41.
  79. Frank AL, Couch RB, Griffis CA, Baxter BD. Comparison of different tissue cultures for isolation and quantitation of influenza and parainfluenza viruses. J Clin Microbiol 1979; 10:32.
  80. Moss RB, Hansen C, Sanders RL, et al. A phase II study of DAS181, a novel host directed antiviral for the treatment of influenza infection. J Infect Dis 2012; 206:1844.
  81. Chen YB, Driscoll JP, McAfee SL, et al. Treatment of parainfluenza 3 infection with DAS181 in a patient after allogeneic stem cell transplantation. Clin Infect Dis 2011; 53:e77.
  82. Guzmán-Suarez BB, Buckley MW, Gilmore ET, et al. Clinical potential of DAS181 for treatment of parainfluenza-3 infections in transplant recipients. Transpl Infect Dis 2012; 14:427.
  83. Chalkias S, Mackenzie MR, Gay C, et al. DAS181 treatment of hematopoietic stem cell transplant patients with parainfluenza virus lung disease requiring mechanical ventilation. Transpl Infect Dis 2014; 16:141.
  84. Drozd DR, Limaye AP, Moss RB, et al. DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient. Transpl Infect Dis 2013; 15:E28.
  85. Waghmare A, Wagner T, Andrews R, et al. Successful Treatment of Parainfluenza Virus Respiratory Tract Infection With DAS181 in 4 Immunocompromised Children. J Pediatric Infect Dis Soc 2015; 4:114.
  86. Dhakal B, D'Souza A, Pasquini M, et al. DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation. Case Rep Med 2016; 2016:8503275.
  87. Salvatore M, Satlin MJ, Jacobs SE, et al. DAS181 for Treatment of Parainfluenza Virus Infections in Hematopoietic Stem Cell Transplant Recipients at a Single Center. Biol Blood Marrow Transplant 2016; 22:965.
  88. Chemaly RF, Marty FM, Wolfe CR, et al. DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study. Clin Infect Dis 2021; 73:e773.
  89. Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study. ClinicalTrials.gov Identifier: NCT03808922. Available at: https://clinicaltrials.gov/ct2/show/NCT03808922 (Accessed on June 28, 2021).
  90. Siegel JD, Rhinehart E, Jackson M, et al, 2007 Guideline for isolation precautions: Preventing transmission of infectious agents in healthcare settings. Updated July 2019. Available at: https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html (Accessed on March 03, 2020).
  91. Schmidt AC. Progress in respiratory virus vaccine development. Semin Respir Crit Care Med 2007; 28:243.
  92. Lee MS, Greenberg DP, Yeh SH, et al. Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and human PIV3 infection in young infants. J Infect Dis 2001; 184:909.
  93. Greenberg DP, Walker RE, Lee MS, et al. A bovine parainfluenza virus type 3 vaccine is safe and immunogenic in early infancy. J Infect Dis 2005; 191:1116.
  94. Slobod KS, Shenep JL, Luján-Zilbermann J, et al. Safety and immunogenicity of intranasal murine parainfluenza virus type 1 (Sendai virus) in healthy human adults. Vaccine 2004; 22:3182.
  95. Scaggs Huang F, Bernstein DI, Slobod KS, et al. Safety and immunogenicity of an intranasal sendai virus-based vaccine for human parainfluenza virus type I and respiratory syncytial virus (SeVRSV) in adults. Hum Vaccin Immunother 2021; 17:554.
  96. Belshe RB, Newman FK, Tsai TF, et al. Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old. J Infect Dis 2004; 189:462.
  97. Belshe RB, Newman FK, Anderson EL, et al. Evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children. J Infect Dis 2004; 190:2096.
  98. Bernstein DI, Falloon J, Yi T. A randomized, double-blind, placebo-controlled, phase 1/2a study of the safety and immunogenicity of a live, attenuated human parainfluenza virus type 3 vaccine in healthy infants. Vaccine 2011; 29:7042.
  99. Karron RA, Thumar B, Schappell E, et al. Evaluation of two chimeric bovine-human parainfluenza virus type 3 vaccines in infants and young children. Vaccine 2012; 30:3975.
  100. Bernstein DI, Malkin E, Abughali N, et al. Phase 1 study of the safety and immunogenicity of a live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine in seronegative children. Pediatr Infect Dis J 2012; 31:109.
  101. Bartlett EJ, Amaro-Carambot E, Surman SR, et al. Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys. Vaccine 2005; 23:4631.
  102. Nolan SM, Surman SR, Amaro-Carambot E, et al. Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses. Vaccine 2005; 23:4765.
  103. Bartlett EJ, Castaño A, Surman SR, et al. Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes. Virol J 2007; 4:67.
Topic 5975 Version 19.0

References