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Parainfluenza viruses in adults

Parainfluenza viruses in adults
Author:
Michael G Ison, MD, MS
Section Editor:
Thomas M File, Jr, MD
Deputy Editor:
Sheila Bond, MD
Literature review current through: Jan 2024.
This topic last updated: Aug 21, 2023.

INTRODUCTION — Parainfluenza viruses (PIVs) are important respiratory pathogens in adults and children. Although parainfluenza viruses are commonly recognized as a significant cause of morbidity and mortality in children, their impact in adults is less well characterized [1]. In adults, parainfluenza viruses usually cause mild upper respiratory infections (URIs) but can lead to life-threatening lower respiratory tract infections, particularly in immunocompromised patients [2,3].

The virology, clinical manifestations, diagnosis, and treatment of parainfluenza viruses in adults will be reviewed here. Infection with parainfluenza viruses in children is discussed separately. (See "Parainfluenza viruses in children".)

VIROLOGY — PIVs are single-stranded, enveloped RNA viruses belonging to the genus Paramyxovirus in the Paramyxoviridae family [4]. This family also includes mumps, measles, respiratory syncytial viruses, human metapneumovirus, and Nipah and Hendra viruses [5-7].

Structure — Parainfluenza virions are pleomorphic, range in diameter from 150 to 200 nanometers, and contain approximately 15,500 nucleotides [5]. The single strand of negative-sense RNA encodes the following viral proteins: nucleocapsid protein (N), phosphoprotein (P), matrix protein (M), fusion glycoprotein (F), hemagglutinin-neuraminidase glycoprotein (HN), and polymerase (L) (figure 1) [5]. In addition, serotype PIV-3 encodes C, D, and V proteins, PIV-1 encodes a C protein, and PIV-2 encodes a V protein.

The HN and F proteins project through the lipid envelope and form the major antigenic targets for neutralizing antibody [8].

The nucleocapsid core is composed of N, P, and L proteins in association with viral RNA. N proteins bind tightly to the viral genome, creating a template for the RNA polymerase composed of the P and L proteins [9].

The HN glycoproteins are involved in attachment of the virus to the host cell via interactions with sialic acid residues on the cell surface [10]. This interaction allows the F protein to mediate virus-cell membrane fusion, which is required for nucleocapsid entry and infection of the host cell. The neuraminidase portion of the HN protein mediates budding of progeny virions from the surface of infected cells [10,11].

The HN glycoproteins of PIVs are more antigenically stable than those of influenza A viruses. However, the development of antigenic differences over time has been reported [12], and this may hinder production of an effective vaccine. (See "Influenza: Epidemiology and pathogenesis".)

Serotypes — Four major serotypes of human PIVs (PIV-1, -2, -3, and -4) have been described [1,6,7]. PIV-1 and -3 are members of the Respirovirus genera, whereas PIV-2 and -4 are members of the Rubulavirus genera [7]. The classification of the PIVs into two genera is based upon genetic characteristics [5].

In a surveillance study of PIVs in children and adults in the United States from 1990 to 2004 in which more than 40,000 cases were detected, the serotypes were found in the following proportions [13]:

PIV-3 – 52 percent

PIV-1 – 26 percent

PIV-2 – 12 percent

PIV-4 – 2 percent

Uncharacterized serotype – 8 percent

Clinical manifestations vary by serotype and the site of viral replication. (See 'Pathogenesis' below and 'Clinical manifestations' below.)

PATHOGENESIS — PIVs initially infect epithelial cells of the nose and oropharynx and can spread distally to the large and small airways [14]. Viral replication rises significantly in the first 24 hours following initial infection, peaking at approximately two to five days [15]. Viral antigen can be detected in the apical portion of respiratory epithelial cells from days 1 to 6 of infection with a decrease on day 7 [16].

The severity of infection appears to correlate with the sites of viral replication and the infecting PIV serotype [17-20]. PIV-1 and PIV-2 replicate efficiently in the upper airway epithelium and are typically associated with upper respiratory infections (URIs) and croup (which results from laryngeal and upper tracheal inflammation) [15,19,20]. PIV-3 replicates in the lower respiratory tract, and infection can lead to bronchiolitis and pneumonia [15]. However, these correlations are not strict; PIV-1 and -2 can cause severe lower tract disease, and PIV-3 can cause self-limited mild URIs.

Pathologic examination of infected tissues in animal models of PIV infection suggests that minimal cellular damage results from direct viral effects [16]. As is the case with other respiratory viruses, the host immune response is likely to play an important role in the pathogenesis of PIV infection [15]. The increase in airway responsiveness (eg, bronchospasm) that is often associated with PIV-3 infection (and other respiratory viruses such as respiratory syncytial virus) may result from increased stromal interleukin-11 production, enhanced acetylcholine release, and increased release of leukotrienes [20-23].

EPIDEMIOLOGY

Prevalence — Human PIVs are among the most common causes of respiratory tract infections worldwide [24-26].

The burden and severity of illness vary with age and the infecting PIV serotype. The majority of PIV-associated illnesses that come to clinical attention occur in young children [27]. Although upper respiratory infections (URIs) are the most common form of PIV infection in children, croup and lower respiratory tract infections account for substantial disease burden. In a surveillance study in the United States, PIV-associated croup, bronchiolitis, and pneumonia accounted for 1.1 hospitalization per 1000 children aged <5 years old [28]. PIV-3 accounted for the majority of cases, followed by PIV-1 and PIV-2. (See "Parainfluenza viruses in children".)

By adulthood, >90 percent of individuals have antibodies to PIVs [6]. However, these antibodies are only partially protective and reinfection can occur [6]. Among adults, URIs and pneumonia are the most common clinical manifestations; PIV-3 is the predominant infecting serotype [19]. Likewise, PIV-3 is most frequently detected among adults hospitalized with PIV with peak incidence in the late spring and early summer [29].

In a large epidemiologic survey of over 2000 patients with community-acquired pneumonia in the United States, PIVs were detected in approximately 3 percent of cases [25]. Similar prevalence rates have been reported in other studies [30-32]. The severity of illness is greatest in older adults (particularly residents of long-term care facilities) and immunocompromised adults [33]. (See 'Risk factors for severe disease' below.)

Trends in PIV infections in the United States are monitored by the National Respiratory and Enteric Virus Surveillance System and can be found on the United States Centers for Disease Control and Prevention website [24]. Like other respiratory viral infections, the incidence of PIV infection dropped during the COVID-19 pandemic when infection control practices were in place and has since rebounded.

Transmission

Route of transmission — PIVS are transmitted from person to person, primarily via inhalation of large droplets or fomites [34]. Virus can be transmitted from patients with symptomatic infections or from those with subclinical infections [35-37]. The latter population is presumed to play a role in the development of outbreaks and can make infection control in health care facilities challenging. (See 'Outbreaks' below and 'Infection control' below.)

Seasonality — PIV infections occur throughout the world and throughout the year, with certain serotypes predominating during the spring or fall [27,38]. In the United States, peak seasonal activity for PIV-1 seems to occur biennially during the fall of odd-numbered years (figure 2) [13,39]. PIV-2 transmission tends to peak annually each fall [13]. PIV-3 is endemic and its transmission patterns are least predictable, though seasonal activity tends to peak in the spring and early summer [6,13,29]. Seasonal patterns of PIV-4 infections have not been established since the disease is usually mild and the virus is difficult to detect. In tropical countries, PIVs do not exhibit seasonal variation [40].

Outbreaks — Although most PIV infections are community acquired, outbreaks can occur within health care facilities and other close-contact settings and can be particularly severe when older individuals and immunocompromised patients are affected. [33,41-48].

As an example, an outbreak involving 26 patients on an inpatient hematology unit was traced to a single admission from the community and persisted over a two-month period [44]. The majority of affected patients developed lower respiratory tract infections, and the case-fatality rate was 38 percent. In one retrospective review of >100 immunocompromised patients in a hematology and stem cell transplantation (SCT) unit, nosocomial transmission was prominent, occurring in 63 percent of SCT recipients [49].

Although few studies have been performed in homeless shelters, one study found PIV transmission to be common and that shelter-specific prevention may be needed to mitigate infections [50].

Risk factors for severe disease — Factors associated with the development of lower respiratory tract infection and severe disease in adults include [30,38,51-54]:

Immunocompromise (particularly hematopoietic stem cell and lung transplantation)

Older age

Cardiac and pulmonary comorbidities

Infection with PIV serotype 3 (PIV-3)

Among immunocompromised patients, the highest morbidity and mortality has been described in hematopoietic cell transplant (HCT) recipients, patients with leukemia, and lung transplant recipients [51,55-59]. In these patient populations, glucocorticoid (≥1 mg/kg/day prednisone equivalent) use has been linked to the development of lower respiratory tract infections and mortality [51,60-62]. Whether glucocorticoids play a direct role in driving disease severity or whether their use is a marker for a sicker patient population (eg, patients with graft-versus-host disease, organ rejection) is unclear. Among solid organ transplantation, clinically significant disease is most common among lung transplant recipients [54].

Secondary bacterial or fungal pneumonia complicating PIV lower respiratory tract infection is also a significant contributor to morbidity and mortality, particularly in immunocompromised hosts [51,62]. As an example, in a cohort of 253 HCT recipients with PIV infection, infection with a second pulmonary pathogen occurred in 29 of 55 patients (53 percent) with PIV-3 pneumonia [51]. The 30-day mortality was higher among those with pulmonary copathogen when compared with those without copathogens (48 versus 19 percent; p = 0.024). A similar trend was observed at 180 days, with a mortality rate of 96 percent in those with pulmonary copathogen compared with 50 percent in those without copathogens.

Among hospitalized adults overall, death is uncommon (5.1 percent) with bacterial coinfection, fungal coinfection, decreased body mass index, and increased respiratory rate being most strongly associated with mortality [29].

CLINICAL MANIFESTATIONS — The clinical manifestations of PIV infections in adults vary based on the patient's age and immune status as well as the infecting PIV serotype. The spectrum ranges from asymptomatic infections and mild upper respiratory infections (URIs) to severe and fatal pneumonia.

URI and acute bronchitis — Upper respiratory infections (URIs) and acute bronchitis are the most common clinical manifestation of PIV infection in adults. The clinical features associated with URI and acute bronchitis caused by PIVs are similar to those caused by other pathogens.

Signs and symptoms of PIV-associated URI include fever, rhinorrhea, cough, and/or sore throat [41]. Other upper respiratory tract manifestations of PIV infection, such as croup, occur more commonly in children. (See "Parainfluenza viruses in children", section on 'Clinical presentation'.)

As with other forms of acute bronchitis, prolonged cough is typically a dominant symptom of PIV-associated acute bronchitis. Wheezing and mild dyspnea may accompany the cough. (See "Acute bronchitis in adults".)

Most cases of URI and acute bronchitis caused by PIV are self-limited. Rarely, infection progresses to involve the lower respiratory tract, particularly in older and immunocompromised adults [51,56,62,63].

Pneumonia — Lower respiratory tract infections can evolve from URIs or may be the initial presenting manifestation of PIV infection [29,51,60]. Pneumonia and acute bronchitis are the most common PIV-associated lower tract infection in adults. Bronchiolitis occurs more commonly in children and is discussed separately. (See "Bronchiolitis in infants and children: Clinical features and diagnosis".)

As with other forms of pneumonia, the most common symptoms and signs associated with pneumonia due to PIV include fever, cough, sputum production, and dyspnea [29]. Wheezing due to bronchospasm is common. PIV pneumonia can be severe. In a retrospective review of 550 adults hospitalized with PIV infection, over 50 percent required supplemental oxygen, approximately 10 percent intensive care, and approximately 7 percent ventilatory support [29]. Severe disease tends to occur more commonly in older and immunocompromised adults.

Radiographic findings are nonspecific, similar to other viral pneumonias, and include tree-in-bud opacities, interstitial infiltrates, ground-glass opacities, bronchial wall thickening, and peribronchial consolidation (image 1) [36,64,65].

Bacterial and fungal coinfection — Secondary bacterial and fungal coinfections are not uncommon in patients with PIV pneumonia and are major contributors to mortality [29,51,66]. Coinfection should be suspected if imaging is not consistent with a purely viral pneumonia (ie, lobar or nodular pneumonia) or if there is a biphasic illness with initial improvement followed by clinical or radiologic worsening.

In one retrospective review of hospitalized patients with PIV infection, coinfection with any pathogen occurred in 136 of 550 patients (25 percent) [29]. The majority of coinfections involved the respiratory tract (83 percent). Of those, approximately 40 percent were bacterial, 13 percent fungal, and the remainder viral. Mortality was higher in patients with bacterial and fungal coinfection when compared with patients without coinfections. The severity of illness was higher in patients with viral coinfections compared with those without, but mortality was not significantly increased.

Bacterial respiratory pathogens are similar to those that cause community-acquired and hospital-acquired pneumonia and include Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and gram-negative rods [3,29,51]. Fungal coinfections are more common in immunocompromised hosts; the most common fungal coinfection is aspergillosis, followed by infection with Candida spp. Viral respiratory copathogens, such as influenza, rhinovirus, adenovirus, respiratory syncytial virus, and human metapneumovirus, typically are present initially and are generally associated with more severe courses.

Other manifestations — Otitis media and sinusitis can occur as either primary PIV infections or secondary bacterial superinfections [67]. Nonrespiratory complications of PIV are rarely reported but include meningitis [68], myocarditis and/or pericarditis [69], and Guillain-Barré syndrome [70].

Chronic airway diseases

Asthma and COPD exacerbations — PIV infection is associated with exacerbations of asthma and chronic obstructive pulmonary disease (COPD) [23,71,72]. In patients with asthma, PIV infections are common triggers for exacerbations and may also play a role in asthma pathogenesis. (See "Role of viruses in wheezing and asthma: An overview", section on 'Asthma exacerbations' and "Role of viruses in wheezing and asthma: An overview", section on 'Development of asthma'.)

In patients with COPD, PIV account for approximately 8 percent of acute exacerbations [73]. As with asthma, PIV infections have a putative role in COPD pathogenesis [19]. (See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease".)

Pulmonary dysfunction in transplant recipients — PIV infections have been associated with significant short- and long-term pulmonary dysfunction in both lung transplant and hematopoietic cell transplant (HCT) recipients [53].

In lung transplant recipients, PIV infections (particularly lower respiratory tract infections) have been associated with lung allograft dysfunction (chronic lung rejection) and graft loss [56,57,74-77]. As an example, in a cohort study evaluating 139 lung transplant recipients, pneumonia caused by community-acquired respiratory viruses was associated with an increased risk of chronic lung allograft dysfunction (CLAD; hazard ratio [HR] 1.64, 95% CI 1.17-2.28). Among respiratory viruses, the risk was highest among those with adenoviral infection followed by PIV infections (HR 13.42, 95% CI 2.81-64.59 and HR 2.18, 95% CI 1.34-3.56, respectively). A recent meta-analysis of available studies demonstrated that PIV was associated with relatively low pooled 30-day mortality (0 to 3 percent), but CLAD progression 180 to 360 days postinfection was substantial (pooled incidences 19 to 24 percent). Progression to CLAD is associated with more severe infections involving the lower respiratory tract [78]. While the pathogenesis is not well understood, both direct viral cytopathic effects and resultant inflammation within the allograft are thought to contribute to development of rejection and chronic graft dysfunction. (See "Chronic lung allograft dysfunction: Bronchiolitis obliterans syndrome", section on 'Etiology and risk factors'.)

Similarly, PIV and other respiratory viral infections have been associated with chronic pulmonary impairment in HCT recipients, characterized by persistent airflow obstruction based on spirometry [79,80]. This chronic impairment has been associated with increased mortality, particularly among HCT recipients with graft-versus-host disease.

DIAGNOSIS — The need to pursue a specific microbiologic diagnosis of PIV infection varies with severity of illness, patient immune status, and treatment setting.

For most immunocompetent outpatients with mild respiratory tract infections (ie, upper respiratory infection [URI], acute bronchitis, or mild community-acquired pneumonia [CAP]), testing for PIV or other pathogens is not necessary, as results generally do not change management.

For hospitalized patients with CAP, we generally include testing for PIV in our initial diagnostic evaluation during respiratory virus season (late fall to early spring in the northern hemisphere) and during known outbreaks.

For most immunocompromised patients presenting with fever or symptoms of upper or lower respiratory tract infection, we generally test for PIV and other respiratory viruses as part of our evaluation regardless of treatment setting.

Polymerase chain reaction (PCR) is the preferred testing method [81,82]. Usually, we obtain a nasopharyngeal swab for testing. However, PCR can also be performed on nasal washings (which may enhance sensitivity) and lower respiratory tract specimens, such as bronchoalveolar lavage fluid [83]. PCR for PIV can be performed directly as a single assay or as part of a multiplex panel [84-87]. The availability of each assay varies from institution to institution.

In general, PCR has higher sensitivity than culture or antigen detection assays [84,88-90]. Most PCR assays detect serotypes 1, 2, and 3 reliably. However, both the overall sensitivity and the sensitivity for certain PIV serotypes may be reduced when using multiplex assays [91-95]. As a practical note, not all multiplex assays include PIV in their panels, so it is important to select one that does or use an adjunct single assay when diagnosis is needed.

A positive PCR result confirms the diagnosis of PIV infection. However, because PIV infection can be asymptomatic or occur concurrently with other respiratory pathogens, we perform a thorough evaluation for other contributors of the patient's symptoms and signs as part of our diagnostic approach. This is particularly important for severely ill and immunocompromised patients who are at higher risk for bacterial and fungal coinfections and/or when radiology suggests possible coinfection. (See 'Bacterial and fungal coinfection' above.)

Other tests have limited value for the diagnosis of PIV infection. Culture and serology are not widely available and have long turnaround times. Rapid antigen testing kits are also not routinely available and have only moderate sensitivity [6,96].

TREATMENT — There are no antiviral agents with proven efficacy for the treatment of PIV infections [3]. Fortunately, most immunocompetent patients with parainfluenza virus infections have mild, self-limited illnesses and recover with supportive care alone.

For adults with pneumonia caused by PIV, the cornerstones of treatment include:

Supportive care Supplemental oxygen and/or ventilatory support may be needed for patients with severe pneumonia. Use of inhaled bronchodilators (eg, albuterol) can help with airway hyper-responsiveness and wheezing [29]. Because airway hyper-responsiveness can be profound, corticosteroids are sometimes used to help reduce inflammation, though this is controversial, particularly in immunocompromised patients [97].

Reduction of immunosuppression (if immunocompromised) – For immunocompromised patients with severe disease, immunosuppression should be reduced when feasible [2]. Because glucocorticoid use has been associated with the development of severe PIV infections, we generally discontinue or taper glucocorticoid use when possible. However, the best approach to reducing immunosuppression varies from patient to patient and needs to be individualized.

Close monitoring and prompt treatment for secondary infections – Patients with PIV are at increased risk of bacterial and fungal infections. Thus, we monitor patients closely for any clinical or radiographic worsening (eg, development of progressive dyspnea or new consolidations on chest imaging). Our threshold for pursuing a thorough diagnostic evaluation (eg, serum fungal markers and/or bronchoscopy) and initiating empiric antibiotics for secondary bacterial and fungal pneumonia is low, particularly in immunocompromised patients. Antifungal prophylaxis is not routinely recommended for patients at risk for secondary fungal infections; however, some experts do use antifungal prophylaxis (with anti-mold activity) for 30 to 90 days after diagnosis of viral lower respiratory tract infections for severely immunocompromised individuals.

We generally do not use ribavirin for the treatment of PIV infections because of lack of proven efficacy and the high side effect profile of this drug [53]. Case reports and small case series have shown variable results for the use of aerosolized, oral, or intravenous ribavirin for the treatment of PIV infection in hematopoietic cell transplant (HCT) and solid organ transplant recipients [51,63,98-102]. Ribavirin is often considered for treatment of PIV infection in lung transplant recipients because of the association between PIV infection and chronic lung allograft dysfunction (CLAD). However, evidence supporting its use is limited. While some individual observational studies suggest benefit, in a systematic review of observational studies in lung transplant recipients, ribavirin did not appear to prevent progression to CLAD (OR 0.61 [0.27-1.18], P = 0.16) [78].

The use of intravenous immune globulin (IVIG) for treatment of severe PIV infections is controversial. We generally do not use IVIG for treatment, as there are insufficient data to support its use [51,103]. However, some experts favor IVIG use for patients with severe infections, particularly in patients with hypogammaglobulinemia [104,105].

DAS181 (an inhaled recombinant sialidase fusion protein) is a promising investigational agent for the treatment of parainfluenza infections. In vitro, DAS181 has been shown to inhibit PIV infection by enzymatically removing the sialic acid moiety of the PIV receptor [106]. Case reports and case series in HCT and solid organ transplant recipients suggest that DAS181 is well tolerated and may improve symptoms, pulmonary function, and need for supplemental oxygen as well as reduce PIV viral loads [97,107-109]. In a posthoc analysis of a randomized trial comparing DAS181 versus placebo in immunocompromised patients, DAS181 was associated with improved oxygenation in a selected group of severely immunocompromised patients with lower respiratory tract infections; however, a statistically significant improvement in oxygenation was not found in the total trial population [110]. Further study is underway. Additional agents under investigation include hemagglutinin neuraminidase inhibitors [111,112] and short interfering RNAs [113].

PREVENTION

Vaccine development — There is no licensed vaccine to prevent infection with PIVs, although vaccine development is underway [3,114-116]. Natural immunity to PIV is incomplete, and reinfection is common. Thus, a protective PIV vaccine may have value, particularly among children and immunocompromised individuals. Vaccine development is discussed in detail separately. (See "Parainfluenza viruses in children", section on 'Vaccine development'.)

Infection control — The United States Centers for Disease Control and Prevention (CDC) recommends that infants and young children hospitalized with PIV infection should be placed on standard and contact precautions and should have a private room when possible [117]. Standard precautions alone are recommended for adults [117]. However, to minimize nosocomial spread, we generally use standard and contact precautions plus isolation for PIV-infected adults as well [44,118]. Respiratory precautions are not considered necessary because the droplets that spread virus are large and do not aerosolize. (See "Infection prevention: Precautions for preventing transmission of infection".)

There are also instances in which an immunocompromised patient may be in close proximity to a contact with PIV infection (ie, an immunocompromised parent exposed to an infected child). In these cases, minimizing exposure would be ideal but is not always feasible. When exposure is unavoidable, both careful hand hygiene and face masks should be used to minimize the risk of transmission.

SUMMARY AND RECOMMENDATIONS

Background – In adults, parainfluenza viruses (PIVs) usually cause mild upper respiratory infections (URIs) but can lead to life-threatening lower respiratory tract infections, particularly in immunocompromised and older adult patients. (See 'Introduction' above and 'Clinical manifestations' above.)

Virology – PIVs are single-stranded, enveloped RNA viruses belonging to the genus Paramyxovirus. (See 'Virology' above.)

Pathogenesis – The extent of infection correlates well with the severity of disease: mild upper respiratory tract infections are associated with limited infection of the nasopharynx, whereas more severe disease involves spread of infection to the large and small airways. (See 'Pathogenesis' above.)

Epidemiology – In the United States, serotype PIV-1 usually causes outbreaks biennially during the fall of odd-numbered years. In contrast, PIV-2 and PIV-3 occur in annual epidemics in the fall and spring, respectively. In tropical countries, PIVs do not exhibit seasonal variation. (See 'Epidemiology' above.)

Diagnosis

Immunocompetent patients – For most immunocompetent outpatients with mild respiratory tract infections (ie, URI, acute bronchitis, or mild community-acquired pneumonia [CAP]), testing for PIV or other pathogens is not necessary, as results generally do not change management. (See 'Diagnosis' above.)

Immunocompromised patients – We generally test any immunocompromised patient with fever and respiratory tract symptoms and signs as infection can quickly progress. In addition, we test most hospitalized patients with CAP for PIV as part of our initial evaluation, particularly during respiratory virus season and/or during known outbreaks. (See 'Diagnosis' above.)

PCR preferred – Polymerase chain reaction (PCR) is the preferred testing method. A positive PCR result confirms the diagnosis of PIV infection. However, because coinfection is common, we perform a thorough evaluation for other contributors to the patient's symptoms as part of our diagnostic approach. This is particularly important for severely ill and immunocompromised patients who are at higher risk for bacterial and fungal coinfection. (See 'Diagnosis' above.)

Treatment

Supportive care – Supportive care (eg, supplemental oxygen, bronchodilators), reduction of immunosuppressive medications (for immunocompromised patients), and close monitoring for the development of secondary bacterial and fungal infections are the cornerstones of management. (See 'Treatment' above.)

Limited efficacy for other therapies – There are no antiviral agents with proven efficacy for PIV infections. We generally do not use ribavirin for the treatment of PIV infections because of lack of proven efficacy and the adverse effects of this drug. Use of intravenous immune globulin is controversial. (See 'Treatment' above.)

Vaccine development – There is no licensed vaccine to prevent infection with parainfluenza viruses, although vaccine development is underway. (See 'Vaccine development' above.)

Infection control – Hospitalized patients with PIV infection should be placed on standard and contact precautions and should have a private room whenever possible. (See 'Infection control' above.)

ACKNOWLEDGMENT — The views expressed in this topic do not necessarily represent the views of the National Institutes of Health or the United States government.

  1. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001; 344:1917.
  2. Ison MG. Respiratory viral infections in transplant recipients. Antivir Ther 2007; 12:627.
  3. Russell E, Ison MG. Parainfluenza Virus in the Hospitalized Adult. Clin Infect Dis 2017; 65:1570.
  4. Lambert DM, Barney S, Lambert AL, et al. Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc Natl Acad Sci U S A 1996; 93:2186.
  5. Karron RA, Collins PL. Parainfluenza viruses. In: Fields Virology, 5th ed, Knipe D, Howley P (Eds), Lippincott Williams and Wilkins, Philadelphia 2006. p.1497.
  6. Piedra PA, Glezen WP. Respiratory syncytial virus and parainfluenza viruses. In: Clinical Virology, 2nd ed, Richman DD, Whitley RJ, Hayden FG (Eds), ASM Press, Washington, DC 2002. p.763.
  7. Wright PF. Parainfluenza viruses. In: Principles and Practice of Infectious Diseases, 6th ed, Mandell GL, Bennett JE, Dolin R (Eds), Elsevier Churchill Livingstone, Philadelphia 2005. p.1998.
  8. 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.
  9. 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.
  10. Moscona A. Interaction of human parainfluenza virus type 3 with the host cell surface. Pediatr Infect Dis J 1997; 16:917.
  11. Huberman K, Peluso RW, Moscona A. Hemagglutinin-neuraminidase of human parainfluenza 3: role of the neuraminidase in the viral life cycle. Virology 1995; 214:294.
  12. Henrickson KJ, Savatski LL. Genetic variation and evolution of human parainfluenza virus type 1 hemagglutinin neuraminidase: analysis of 12 clinical isolates. J Infect Dis 1992; 166:995.
  13. 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.
  14. 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.
  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. 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.
  18. Welliver RC, Wong DT, Sun M, McCarthy N. Parainfluenza virus bronchiolitis. Epidemiology and pathogenesis. Am J Dis Child 1986; 140:34.
  19. Pawełczyk M, Kowalski ML. The Role of Human Parainfluenza Virus Infections in the Immunopathology of the Respiratory Tract. Curr Allergy Asthma Rep 2017; 17:16.
  20. Schaap-Nutt A, Liesman R, Bartlett EJ, et al. Human parainfluenza virus serotypes differ in their kinetics of replication and cytokine secretion in human tracheobronchial airway epithelium. Virology 2012; 433:320.
  21. 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.
  22. 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.
  23. Matsuse H, Kondo Y, Saeki S, et al. Naturally occurring parainfluenza virus 3 infection in adults induces mild exacerbation of asthma associated with increased sputum concentrations of cysteinyl leukotrienes. Int Arch Allergy Immunol 2005; 138:267.
  24. Centers for Disease Control and Prevention. Parainfluenza Types 1-3 National Trends. http://www.cdc.gov/surveillance/nrevss/human-paraflu/natl-trend.html (Accessed on November 24, 2008).
  25. Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med 2015; 373:415.
  26. Wang Y, Dong T, Qi G, et al. Prevalence of Common Respiratory Viral Infections and Identification of Adenovirus in Hospitalized Adults in Harbin, China 2014 to 2017. Front Microbiol 2018; 9:2919.
  27. Álvarez-Argüelles ME, Rojo-Alba S, Pérez Martínez Z, et al. New clinical and seasonal evidence of infections by Human Parainfluenzavirus. Eur J Clin Microbiol Infect Dis 2018; 37:2211.
  28. 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.
  29. Russell E, Yang A, Tardrew S, Ison MG. Parainfluenza Virus in Hospitalized Adults: A 7-Year Retrospective Study. Clin Infect Dis 2019; 68:298.
  30. Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest 2008; 134:1141.
  31. Angeles Marcos M, Camps M, Pumarola T, et al. The role of viruses in the aetiology of community-acquired pneumonia in adults. Antivir Ther 2006; 11:351.
  32. Diederen BM, Van Der Eerden MM, Vlaspolder F, et al. Detection of respiratory viruses and Legionella spp. by real-time polymerase chain reaction in patients with community acquired pneumonia. Scand J Infect Dis 2009; 41:45.
  33. Parainfluenza infections in the elderly 1976-82. Br Med J (Clin Res Ed) 1983; 287:1619.
  34. 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.
  35. Peck AJ, Englund JA, Kuypers J, et al. Respiratory virus infection among hematopoietic cell transplant recipients: evidence for asymptomatic parainfluenza virus infection. Blood 2007; 110:1681.
  36. Ferguson PE, Sorrell TC, Bradstock K, et al. Parainfluenza virus type 3 pneumonia in bone marrow transplant recipients: multiple small nodules in high- resolution lung computed tomography scans provide a radiological clue to diagnosis. Clin Infect Dis 2009; 48:905.
  37. Muchmore HG, Parkinson AJ, Humphries JE, et al. Persistent parainfluenza virus shedding during isolation at the South Pole. Nature 1981; 289:187.
  38. Maykowski P, Smithgall M, Zachariah P, et al. Seasonality and clinical impact of human parainfluenza viruses. Influenza Other Respir Viruses 2018; 12:706.
  39. 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.
  40. Chew FT, Doraisingham S, Ling AE, et al. Seasonal trends of viral respiratory tract infections in the tropics. Epidemiol Infect 1998; 121:121.
  41. Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis 2006; 42:518.
  42. Parainfluenza outbreaks in extended-care facilities -- United States. MMWR Morb Mortal Wkly Rep 1978; 27:475.
  43. Glasgow KW, Tamblyn SE, Blair G. A respiratory outbreak due to parainfluenza virus type 3 in a home for the aged--Ontario. Can Commun Dis Rep 1995; 21:57.
  44. Jalal H, Bibby DF, Bennett J, et al. Molecular investigations of an outbreak of parainfluenza virus type 3 and respiratory syncytial virus infections in a hematology unit. J Clin Microbiol 2007; 45:1690.
  45. Smielewska A, Pearson C, Popay A, et al. Unrecognised Outbreak: Human parainfluenza virus infections in a pediatric oncology unit.  A new diagnostic PCR and virus monitoring system may allow early detection of future outbreaks. Wellcome Open Res 2018; 3:119.
  46. 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.
  47. Nichols WG, Erdman DD, Han A, et al. Prolonged outbreak of human parainfluenza virus 3 infection in a stem cell transplant outpatient department: insights from molecular epidemiologic analysis. Biol Blood Marrow Transplant 2004; 10:58.
  48. Zambon M, Bull T, Sadler CJ, et al. Molecular epidemiology of two consecutive outbreaks of parainfluenza 3 in a bone marrow transplant unit. J Clin Microbiol 1998; 36:2289.
  49. Tabatabai J, Schnitzler P, Prifert C, et al. Parainfluenza virus infections in patients with hematological malignancies or stem cell transplantation: Analysis of clinical characteristics, nosocomial transmission and viral shedding. PLoS One 2022; 17:e0271756.
  50. Chow EJ, Casto AM, Sampoleo R, et al. Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA. Emerg Infect Dis 2022; 28:2343.
  51. Nichols WG, Corey L, Gooley T, et al. Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome. Blood 2001; 98:573.
  52. Jornist I, Muhsen K, Ram D, et al. Characterization of human parainfluenza virus-3 circulating in Israel, 2012-2015. J Clin Virol 2018; 107:19.
  53. Ison MG, Hirsch HH. Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs. Clin Microbiol Rev 2019; 32.
  54. Mombelli M, Lang BM, Neofytos D, et al. Burden, epidemiology, and outcomes of microbiologically confirmed respiratory viral infections in solid organ transplant recipients: a nationwide, multi-season prospective cohort study. Am J Transplant 2021; 21:1789.
  55. Kim YJ, Boeckh M, Englund JA. Community respiratory virus infections in immunocompromised patients: hematopoietic stem cell and solid organ transplant recipients, and individuals with human immunodeficiency virus infection. Semin Respir Crit Care Med 2007; 28:222.
  56. Vilchez RA, Dauber J, McCurry K, et al. Parainfluenza virus infection in adult lung transplant recipients: an emergent clinical syndrome with implications on allograft function. Am J Transplant 2003; 3:116.
  57. 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.
  58. 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.
  59. Weinberg A, Lyu DM, Li S, et al. Incidence and morbidity of human metapneumovirus and other community-acquired respiratory viruses in lung transplant recipients. Transpl Infect Dis 2010; 12:330.
  60. Seo S, Xie H, Leisenring WM, et al. Risk Factors for Parainfluenza Virus Lower Respiratory Tract Disease after Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2019; 25:163.
  61. 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.
  62. Chemaly RF, Hanmod SS, Rathod DB, et al. The characteristics and outcomes of parainfluenza virus infections in 200 patients with leukemia or recipients of hematopoietic stem cell transplantation. Blood 2012; 119:2738.
  63. Wendt CH, Weisdorf DJ, Jordan MC, et al. Parainfluenza virus respiratory infection after bone marrow transplantation. N Engl J Med 1992; 326:921.
  64. Herbst T, Van Deerlin VM, Miller WT Jr. The CT appearance of lower respiratory infection due to parainfluenza virus in adults. AJR Am J Roentgenol 2013; 201:550.
  65. Kim MC, Kim MY, Lee HJ, et al. CT findings in viral lower respiratory tract infections caused by parainfluenza virus, influenza virus and respiratory syncytial virus. Medicine (Baltimore) 2016; 95:e4003.
  66. Hanada S, Pirzadeh M, Carver KY, Deng JC. Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia. Front Immunol 2018; 9:2640.
  67. Gwaltney JM Jr, Scheld WM, Sande MA, Sydnor A. The microbial etiology and antimicrobial therapy of adults with acute community-acquired sinusitis: a fifteen-year experience at the University of Virginia and review of other selected studies. J Allergy Clin Immunol 1992; 90:457.
  68. 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.
  69. Wilks D, Burns SM. Myopericarditis associated with parainfluenza virus type 3 infection. Eur J Clin Microbiol Infect Dis 1998; 17:363.
  70. Román G, Phillips CA, Poser CM. Parainfluenza virus type 3: isolation from CSF of a patient with Guillain-Barré syndrome. JAMA 1978; 240:1613.
  71. Johnston NW. The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations. Proc Am Thorac Soc 2007; 4:591.
  72. Hansbro NG, Horvat JC, Wark PA, Hansbro PM. Understanding the mechanisms of viral induced asthma: new therapeutic directions. Pharmacol Ther 2008; 117:313.
  73. Djamin RS, Uzun S, Snelders E, et al. Occurrence of virus-induced COPD exacerbations during four seasons. Infect Dis (Lond) 2015; 47:96.
  74. Vilchez R, McCurry K, Dauber J, et al. Influenza and parainfluenza respiratory viral infection requiring admission in adult lung transplant recipients. Transplantation 2002; 73:1075.
  75. Billings JL, Hertz MI, Savik K, Wendt CH. Respiratory viruses and chronic rejection in lung transplant recipients. J Heart Lung Transplant 2002; 21:559.
  76. Garbino J, Gerbase MW, Wunderli W, et al. Respiratory viruses and severe lower respiratory tract complications in hospitalized patients. Chest 2004; 125:1033.
  77. Allyn PR, Duffy EL, Humphries RM, et al. Graft Loss and CLAD-Onset Is Hastened by Viral Pneumonia After Lung Transplantation. Transplantation 2016; 100:2424.
  78. de Zwart A, Riezebos-Brilman A, Lunter G, et al. Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies. Clin Infect Dis 2022; 74:2252.
  79. Erard V, Chien JW, Kim HW, et al. Airflow decline after myeloablative allogeneic hematopoietic cell transplantation: the role of community respiratory viruses. J Infect Dis 2006; 193:1619.
  80. Sheshadri A, Chemaly RF, Alousi AM, et al. Pulmonary Impairment after Respiratory Viral Infections Is Associated with High Mortality in Allogeneic Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant 2019; 25:800.
  81. Charlton CL, Babady E, Ginocchio CC, et al. Practical Guidance for Clinical Microbiology Laboratories: Viruses Causing Acute Respiratory Tract Infections. Clin Microbiol Rev 2019; 32.
  82. Miller JM, Binnicker MJ, Campbell S, et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis 2018; 67:813.
  83. Sung RY, Chan PK, Choi KC, et al. Comparative study of nasopharyngeal aspirate and nasal swab specimens for diagnosis of acute viral respiratory infection. J Clin Microbiol 2008; 46:3073.
  84. 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.
  85. Liolios L, Jenney A, Spelman D, et al. Comparison of a multiplex reverse transcription-PCR-enzyme hybridization assay with conventional viral culture and immunofluorescence techniques for the detection of seven viral respiratory pathogens. J Clin Microbiol 2001; 39:2779.
  86. Templeton KE, Scheltinga SA, Beersma MF, et al. Rapid and sensitive method using multiplex real-time PCR for diagnosis of infections by influenza a and influenza B viruses, respiratory syncytial virus, and parainfluenza viruses 1, 2, 3, and 4. J Clin Microbiol 2004; 42:1564.
  87. Li PQ, Yang ZF, Chen JX, et al. Simultaneous detection of different respiratory virus by a multiplex reverse transcription polymerase chain reaction combined with flow-through reverse dot blotting assay. Diagn Microbiol Infect Dis 2008; 62:44.
  88. Kuypers J, Wright N, Ferrenberg J, et al. Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children. J Clin Microbiol 2006; 44:2382.
  89. Mahony JB. Detection of respiratory viruses by molecular methods. Clin Microbiol Rev 2008; 21:716.
  90. Fan J, Henrickson KJ. Rapid diagnosis of human parainfluenza virus type 1 infection by quantitative reverse transcription-PCR-enzyme hybridization assay. J Clin Microbiol 1996; 34:1914.
  91. Pabbaraju K, Wong S, Tokaryk KL, et al. Comparison of the Luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections. J Clin Microbiol 2011; 49:1738.
  92. Pierce VM, Elkan M, Leet M, et al. Comparison of the Idaho Technology FilmArray system to real-time PCR for detection of respiratory pathogens in children. J Clin Microbiol 2012; 50:364.
  93. Krunic N, Merante F, Yaghoubian S, et al. Advances in the diagnosis of respiratory tract infections: role of the Luminex xTAG respiratory viral panel. Ann N Y Acad Sci 2011; 1222:6.
  94. Endimiani A, Hujer KM, Hujer AM, et al. Are we ready for novel detection methods to treat respiratory pathogens in hospital-acquired pneumonia? Clin Infect Dis 2011; 52 Suppl 4:S373.
  95. Bruning AHL, Leeflang MMG, Vos JMBW, et al. Rapid Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review and Meta-analysis. Clin Infect Dis 2017; 65:1026.
  96. Leland DS. Parainfluenza and mumps viruses. In: Manual of Clinical Microbiology, Murray PR, Baron EJ, Jorgensen JH, et al (Eds), ASM Press, Washington, DC 2007. p.1352.
  97. 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.
  98. 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.
  99. Chakrabarti S, Collingham KE, Holder K, et al. Parainfluenza virus type 3 infections in hematopoetic stem cell transplant recipients: response to ribavirin therapy. Clin Infect Dis 2000; 31:1516.
  100. Cobian L, Houston S, Greene J, Sinnott JT. Parainfluenza virus respiratory infection after heart transplantation: successful treatment with ribavirin. Clin Infect Dis 1995; 21:1040.
  101. Wright JJ, O'driscoll G. Treatment of parainfluenza virus 3 pneumonia in a cardiac transplant recipient with intravenous ribavirin and methylprednisolone. J Heart Lung Transplant 2005; 24:343.
  102. Casey J, Morris K, Narayana M, et al. Oral ribavirin for treatment of respiratory syncitial virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 2013; 48:1558.
  103. Seo S, Xie H, Campbell AP, et al. Parainfluenza virus lower respiratory tract disease after hematopoietic cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis 2014; 58:1357.
  104. Waghmare A, Englund JA, Boeckh M. How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation. Blood 2016; 127:2682.
  105. Hirsch HH, Martino R, Ward KN, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis 2013; 56:258.
  106. Moscona A, Porotto M, Palmer S, et al. A recombinant sialidase fusion protein effectively inhibits human parainfluenza viral infection in vitro and in vivo. J Infect Dis 2010; 202:234.
  107. 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.
  108. 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.
  109. 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.
  110. 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.
  111. Alymova IV, Portner A, Takimoto T, et al. The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae. Antimicrob Agents Chemother 2005; 49:398.
  112. Alymova IV, Taylor G, Takimoto T, et al. Efficacy of novel hemagglutinin-neuraminidase inhibitors BCX 2798 and BCX 2855 against human parainfluenza viruses in vitro and in vivo. Antimicrob Agents Chemother 2004; 48:1495.
  113. Bitko V, Musiyenko A, Shulyayeva O, Barik S. Inhibition of respiratory viruses by nasally administered siRNA. Nat Med 2005; 11:50.
  114. Karron RA, San Mateo J, Thumar B, et al. Evaluation of a Live-Attenuated Human Parainfluenza Type 1 Vaccine in Adults and Children. J Pediatric Infect Dis Soc 2015; 4:e143.
  115. 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.
  116. Englund JA, Karron RA, Cunningham CK, et al. Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children. Vaccine 2013; 31:5706.
  117. Siegel JD, Rhinehart E, Jackson M, et al. 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings. Am J Infect Control 2007; 35:S65.
  118. 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.
Topic 7009 Version 32.0

References

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