eMedicine Specialties > Infectious Diseases > Viral Infections

Parainfluenza Virus

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine

Updated: Jul 24, 2008

Introduction

Background

Parainfluenza viruses (PIVs) are paramyxoviruses. Over the last decade, both the nomenclature and the taxonomic relationships of human parainfluenza viruses (HPIVs) have changed considerably.

The first HPIV discovered was the Sendai virus in 1952 in Japan. In 1955, HPIV type 2 (HPIV-2) was isolated from children with acute laryngotracheobronchitis (croup). In 1985, HPIV type 3 (HPIV-3) was isolated from children with respiratory tract infection. In 1960, HPIV type 4 (HPIV-4) was isolated from children with mild respiratory tract infections. HPIV-4 consists of A and B subtypes. Thus, HPIVs are now classified under 2 genera: the genus Respirovirus (HPIV-1, HPIV-3) and the genus Rubulavirus (HPIV-2, HPIV-4).

HPIVs are pathogens that primarily affect young children, in whom the pathogenic spectrum includes upper and lower respiratory tract infections. HPIVs are responsible for 30-40% of all acute respiratory tract infections in infants and children. These conditions include common cold with fever, croup, bronchiolitis, and pneumonia. HPIVs are also a cause of community-acquired respiratory tract infections of variable severity in adults. HPIV-1 is most commonly associated with croup. HPIV-2 is also associated with croup. HPIV-3 is second only to respiratory syncytial virus (RSV) as a cause of pneumonia and bronchiolitis in infants and young children. HPIV-4 is detected in patients less often, perhaps because HPIV-4 causes less severe disease.

Reinfection with HPIV can occur throughout life, with elderly and immunocompromised persons being at a greater risk of serious complications of infections.

The seasonal patterns of HPIV-1, HPIV-2, and HPIV-3 are curiously interactive. HPIV-1 causes the largest, most defined outbreaks, which are marked by sharp biennial rises in croup cases in the autumn of odd-numbered years. Outbreaks of infection with HPIV-2, although erratic, usually follow HPIV-1 outbreaks. Outbreaks of HPIV-3 infections occur yearly, mainly in spring and summer, and last longer than outbreaks of HPIV-1 and HPIV-2. HPIV-4 is infrequently isolated and, hence, relatively unknown and uncharacterized.¹

The following are clinical conditions caused by the various HPIV types:

• Croup - HPIV-1, HPIV-2, HPIV-3
• Bronchitis - HPIV-1, HPIV-3
• Minor upper respiratory tract disease - HPIV-1, HPIV-3, HPIV-4

In recent years, various aspects of the viruses, such as genomic organization, replication, and host immunity evasion mechanisms have been the subjects of intense study, as this knowledge will be crucial for development of intervening strategies (including vaccines) in the future.

Taxonomy

As noted above, the taxonomy of HPIVs has recently changed. HPIVs are now composed of 5 serotypes—HPIV-1, HPIV-2, HPIV-3, HPIV-4a, and HPIV-4b. These serotypes display substantial serologic cross-reactivity. Presently, these viruses are included in the order Mononegavirales, the family Paramyxoviridae, and the subfamily Paramyxovirinae. They belong to 2 different genera: HPIV-1 and HPIV-3 belong to the Respirovirus genus, and HPIV-2 and HPIV-4 belong to the Rubulavirus genus.

Pathophysiology

Structural organization

HPIVs are pleomorphic viruses whose envelope is derived from the host cell they last infected. These viruses are 150-200 nm in diameter and possess a single-stranded, nonsegmented, negative-sense RNA genome with nucleoprotein P and L proteins. A lipid bilayer covered with glycoprotein spikes surrounds a helical nucleocapsid that measures 12-17 nm in diameter. These glycoproteins are hemagglutinin-neuraminidase (HN) and fusion (F) proteins, which play a major role in the pathogenesis of the disease caused by the viruses.

Pathogenesis

Viral transmission occurs via direct inoculation of contagious secretions from the hands or via large-particle aerosols into the eyes and nose. Prolonged survival of HPIV on skin, cloth, and other objects emphasizes the importance of fomites in nosocomial spread. Respiratory epithelium appears to be the major site of virus binding and subsequent infection. The viruses attach to the host cells through hemagglutinin, which specifically combines with neuraminic acid receptors in the host cells. Subsequently, the viruses enter the cell via fusion with the cell membrane mediated by F1 and F2 receptors.

When HPIV infects a cell, the first observable morphologic changes may include focal rounding and growing of the cytoplasm and nucleus and decreased host-cell mitotic activity. Other observable changes include single or multilocular cytoplasmic vacuoles, basophilic or eosinophilic inclusions, and formation of multinucleated giant cells. These giant cells (fusion cells) usually develop late in the infection, and each giant cell contains between 2 and 7 nuclei.

Mechanisms of airway inflammation

HPIV infection in the respiratory tract leads to secretion of high levels of inflammatory cytokines such as interferon (IFN)–alpha, interleukin (IL)–2, IL-6, and tumor necrosis factor (TNF)–alpha. The peak duration of secretion is 7-10 days after initial exposure. Increasing levels of certain chemokines such as RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein (MIP)–K are detected in the nasal secretion of pediatric patients. These are responsible for pathological changes in the respiratory tract and clinical manifestations of this condition.

The chief pathological features include airway inflammation, necrosis and sloughing of respiratory epithelium, edema, excessive mucus production, and interstitial infiltration of lung. Edema of the mucus layer causes swelling in the vocal cords, larynx, trachea, and bronchi. These changes lead to obstruction of the airway inflow and subsequent stridor, which is characteristic of croup.

In animal models, increased levels of histamine and eosinophils are detected in bronchoalveolar lavage (BAL) samples following infection with HPIV, suggesting a state of hyperresponsiveness of the respiratory tract.

HPIV-2 and HPIV-3 infection in humans is known to induce expression of intercellular adhesion molecule-1 (ICAM-1) in tracheal and other cells of the respiratory tract. These molecules serve as receptors for rhinoviruses, thus paving the way for rhinoviral superinfection.

The virus continues to be excreted in respiratory exudates for 3-16 days following primary infection and 1-4 days following infection.

Immunology

Host defense against HPIVs is mediated largely by humoral immunity to both surface glycol proteins of the virus—HN and F. Most children are born with neutralizing antibodies to all 4 types of HPIV, but these titers quickly fall during the first 6 months of life. Most antibody response appears to involve serum immunoglobulin G1 (IgG1), but levels of serum immunoglobulin G3 (IgG3), immunoglobulin G4 (IgG4), serum immunoglobulin A (IgA), and immunoglobulin M (IgM) rise significantly in 30% of adults. Secretory IgA plays an important but not fully defined role in the protection against natural HPIV infections.

After natural infection with HPIV, most children and adults develop measurable levels of these antibodies in the serum; these antibodies have been shown to be correlated with disease prevention and amelioration in adults. Local interferon production has been noted in about 30% of children with HPIV infection. Although immunity to HPIV infection is long-lasting, reinfection may occur many times throughout life and at variable intervals, even in the presence of neutralizing antibodies. This cannot be explained merely based on the relatively stable antigenic determinants of HPIVs; thus, more research is needed.

In recent years, interesting facts regarding cell-mediated immunity have emerged. HPIV infections tend to be more severe in individuals with defective cell-mediated immunity, indicating that T cells may have a greater role in containing the disease.

Epidemiology

Respiratory secretions from infected humans are the source of infection. Transmission is via respiratory droplets or via direct person-to-person contact with infected secretions. The inoculating dose is very small.

HPIVs are common community-acquired respiratory pathogens without ethnic, socioeconomic, gender, age, or geographic boundaries. Many factors have been found that predispose individuals to these infections, including malnutrition, overcrowding, vitamin A deficiency, lack of breastfeeding, and environmental smoke or toxins.

Frequency

United States

Infections with HPIV-1 and HPIV-2 occur during autumn months. Infections with HPIV-3 occur throughout the year but appear to peak in the spring. HPIV-3 is the second most common cause of lower respiratory tract infections treated in the United States, second only to RSV. HPIV-4 infection patterns are not well-defined.

HPIV-3 infections occur earliest and most frequently. Based on seroepidemiological studies, 50% of US children aged 1 year and almost all US children aged 6 years have been infected by HPIV-3 . Antibodies against HPIV-1 and HPIV-2 develop less rapidly, but 80% of children have antibodies against these types by age 10 years. HPIV-4 induces few clinical illnesses, but infections with this type are common nonetheless, as 70-80% of children aged 10 years have antibodies against HPIV-4.

International

Internationally, HPIV-1, HPIV-2, HPIV-3, and HPIV-4 have worldwide distribution, and epidemics are known to occur, particularly with HPIV-1.

Parainfluenza viruses are responsible for disease throughout the year, but winter outbreaks of respiratory tract infections, especially croup, in children throughout the temperate zones of the northern and southern hemispheres represent peak periods of prevalence. Most infections are endemic, but sharp small epidemics involving HPIV-1 and HPIV-2 occasionally occur. The first reported outbreak of HPIV-4 infection occurred in Hong Kong in autumn of 2004. The outbreak involved 38 institutionalized children and 3 staff members during a 3-week period in a developmental disabilities unit.²

Mortality/Morbidity

Mortality induced by HPIV is unusual in developed countries and occurs almost exclusively in young infants or immunocompromised or elderly people. However, the preschool population in developing countries is at considerable risk for HPIV-induced death. Whether because of primary viral disease or because of facilitating secondary bacterial infections in malnourished children, lower respiratory tract infection causes 25-30% of the death in this age group, and HPIV causes at least 10% of lower respiratory tract infections.

Race

HPIVs have no predilection for any race.

Sex

HPIVs have no predilection for either sex.

Age

HPIV-1 can cause lower respiratory tract infection in young infants but is rare in those younger than 1 month. The full burden of HPIV-1 in adults and elderly persons has not been determined, but studies have shown that this virus causes yearly hospitalizations in healthy adults and may play a role in bacterial pneumonias and death in nursing-home residents.

HPIV-2 accounts for 60% of all infections that develop in children younger than 5 years, with peak incidence between ages 1 and 2 years.

Young infants (<6 mo) are particularly vulnerable to infection with HPIV-3. Unlike other HPIVs, 40% of HPIV-3 infections occur in the first year of life.

Clinical

History

Human parainfluenza viruses (HPIVs) have been associated with every type of upper and lower respiratory tract illness. However, all HPIV types strongly correlate with specific clinical syndromes, age, and time of year. Lack of epidemiological data on HPIV-4 has so far prevented a clear understanding of the true clinical significance of the virus.

• Croup: Croup is a generic term that encompasses a heterogeneous group of illnesses that affect the larynx, the trachea, and the bronchi. HPIV-1, HPIV-2, and HPIV-3 are the most frequent causes of croup, accounting for almost 75% of all cases. HPIV-1 is the most common and is estimated to cause 18% of all croup cases. Symptoms of croup include fever, hoarse barking cough, laryngeal obstruction, and inspiratory stridor.
• Bronchiolitis: All 4 types of HPIV can cause bronchiolitis, but HPIV-1 and HPIV-3 have been reported most commonly. Each of these 2 groups appears to cause 10-15% of bronchiolitis cases in nonhospitalized children. The peak incidence of bronchiolitis occurs during the first year of life (81% of cases during this period) and then dramatically declines until it virtually disappears by school age. Predominant symptoms include fever, expiratory wheezing, tachypnea, retractions, rales, and air trapping.
• Pneumonias: HPIV-1 and HPIV-3 each cause about 10% of outpatient pneumonia cases, but, similar to bronchiolitis, HPIV-3 causes a larger percentage of cases in hospitalized patients. HPIV-2 and HPIV-4 can both cause pneumonia, but the incidence of disease is not well described. HPIV-1 infection has been associated with secondary bacterial pneumonias in elderly persons. Symptoms of pneumonias include fever, rales, and evidence of pulmonary consolidation.
• Tracheobronchitis: More than 25% of the agents identified to cause tracheobronchitis have been HPIVs. (HPIV-3 is more commonly associated with tracheobronchitis than HPIV-1 or HPIV-2.) Tracheobronchitis is the most common feature seen in persons with HPIV-4 infections.
• Other infections: HPIVs routinely cause otitis media, pharyngitis, and conjunctivitis coryza, and these can occur singly or in combination with a lower respiratory tract infection. HPIV-3 is the most frequently reported HPIV associated with otitis media.
• Infections in immunocompromised patients: The increasing number of patients who receive intense immunosuppression after undergoing transplantation of bone marrow and solid organs has highlighted the role of HPIVs as potential opportunistic pathogens. HPIV-2 causes giant cell pneumonia in persons with severe combined immunodeficiency diseases (SCIDs), and HPIV-3 has been found in persons with SCIDS and acute myeloid leukemia (AML) and in patients who have undergone bone marrow transplantation (BMT). The natural history of HPIV in patients infected with HIV is generally less severe than that in transplant recipients.

Physical

A broad range of findings is observed and may include fever, nasal congestion, pharyngeal erythema, nonproductive to minimally productive cough, inspiratory stridor, rhonchi, rales, and wheezing.

• The epiglottis is sometimes grossly swollen and reddened because of viral infection. Severe airway obstruction may ensue, requiring emergency tracheotomy.
• In serious cases, children should be quickly hospitalized (generally within 3-24 h). In immunocompromised hosts, upper respiratory tract symptoms are similar to those observed in healthy hosts, but the incidence of lower respiratory tract symptoms and sinusitis is much higher. In these groups, especially bone marrow transplant recipients, lower respiratory tract infection can lead to respiratory failure and death.

Causes

HPIV infection is acquired through inhalation of infected droplet nuclei or indirectly through contact with infected secretions. The incubation period is generally 2-6 days. See Pathophysiology.

Differential Diagnoses

Adenoviruses
Chlamydial Pneumonias
Coxsackieviruses
Influenza
Mycoplasma Infections

Other Problems to Be Considered

Bacterial superinfections
Bronchiolitis
Coronavirus
Foreign body aspiration (if croup or bronchiolitis is present)
Epiglottitis
Pneumonia
Respiratory syncytial virus
Retropharyngeal abscess
Rhinovirus

Workup

Laboratory Studies

• The CBC count is usually within the reference range. Lymphocytosis may be present.
• Virus antigen detection and isolation
  • Collection and preparation of clinical specimens: Nasopharyngeal aspirations, nasal washings, and nasal aspirations are optimum specimens for collection. Throat swabs and nasal swabs can also be used. Specimens should be collected and placed in viral transport media (VTM), preferably at 4°C; if a delay of more than 24 hours is anticipated, specimens should be frozen. Nonrespiratory specimens such as CSF, rectal swabs, and stool, though rare, can be used. Paired sera (acute and convalescent phase) should be collected, separated quickly, and stored at either -20°C or -70°C; both samples should be tested simultaneously.
  • Electron microscopy: Microdrops of secretions or garglings are placed directly on carbon-coated electron microscopy grids and stained with phosphotungstic acid. Virions typical of the Paramyxoviridae may be observed. However, this study yields poor sensitivity.
  • Immunofluorescence: Indirect immunofluorescence is normally used with antisera against each serotype of parainfluenza virus. However, immunofluorescence findings cannot be used as the sole diagnostic criterion, as it also yields poor sensitivity. A study carried out in Arizona between 1983 and 1985 showed that immunofluorescence revealed HPIV-1 in only 63% of throat specimens from which this serotype was isolated in tissue cultures. HPIV-3 was revealed in only 31% of virus-culture–positive throat secretions.
  • Direct detection of viral antigens: HPIV antigen can be detected with enzyme-linked immunoassay (ELISA), radioimmunoassay, fluoroimmunoassay, and immunofluorescence. Synthesized recombinant HPIV-1 and HPIV-3 nucleocapsid proteins in the yeast Saccharomyces cerevisiae are used as a source of antigens.³ The latter two tests are both rapid and specific. Shell vial assay is another method for rapid identification of HPIV. Shell vials have yielded an average sensitivity of 84% in testing against standard tissue culture–positive HPIV cases.
  • Virus isolation: HPIV grows best in primary monkey kidney (PMK) cells (rhesus monkey kidney cells, cynomolgus, and African green monkeys). The LLC-MK2 strain is also excellent for continued passage and is almost as good as PMK cells for primary isolation. Trypsin (2-3 mg/mL) must be added to the maintenance medium of LLC-MK2 cells to recover all HPIV serotypes. Proteases are necessary for parainfluenza virus to replicate, and it is hypothesized that proteases present in primary cell cultures are absent in continuous cell lines.
  • Detection and typing: Cytopathic effects (CPEs) are rarely demonstrated during primary isolation of HPIV in tissue culture except with HPIV-2, which, when cultured, shows syncytia formation. All HPIVs demonstrate greater cytopathic effects upon adaptation to a particular cell line, with HPIV-3 being the most aggressive, destroying more than 50% of tissue culture monolayer by the third day. Virus growth is detected with hemadsorption inhibition using guinea pig erythrocytes within 3-10 days of incubation. However, the prolonged incubation time (3-10 d) required for virus isolation severely restricts the usefulness of virus isolation in short-term management.
  • Serologic diagnosis: A 4-fold rise or drop in titer is generally thought to signify acute infection if the testing is performed at the same time on paired acute- and convalescent-phase serum pimples. Hemagglutination inhibition, neutralization, complement fixation, ELISA, radioimmune assays, and Western blotting are frequently used antibody-based serological tests for diagnosis of HPIV infections.
  • Genomic detection: HPIV RNA can be detected directly with Northern hybridization or a dot blot analysis using virus-specific DNA probes. Polymerase chain reaction (PCR) assay is sensitive and specific in detecting HPIV. A multiplex reverse-transcriptase PCR (RT-PCR) assay for detecting HPIV-1, HPIV-2, and HPIV-3 has been developed. RT-PCR enzyme hybridization assay (RT-PCR-EHA) is available for detecting HPIV types 1-4, respiratory syncytial viruses A and B, and influenza A and B virus, with a reported sensitivity of 95-100% and specificity of 97-100% when compared with results of tissue culture. The RT-PCR-EHA yields results in approximately 7 hours. A multiplex RT-PCR assay kit under dual priming oligonucleotide system (DPO) that is used to detect 12 common viruses causing respiratory tract infections in children has recently become available.⁴

Imaging Studies

• Radiographs of the neck or chest are important if epiglottitis, croup, or pneumonia is a possibility.
• Anteroposterior views of the neck may demonstrate subglottic swelling with narrowing of the air shadow of the trachea (steeple sign) with croup; in patients with epiglottitis, lateral views may demonstrate enlargement of the epiglottis and ballooning of the hypopharynx.

Histologic Findings

The epithelium of the respiratory tract may show inflammation and necrosis. Subglottic tissues in particular may appear to be involved.

Treatment

Medical Care

• Supportive care is mandatory. Antiviral agents are of uncertain benefit. Anecdotal reports of possible benefit have been published, but controlled studies are lacking.
• Treatment of croup
  • Prehospital care
    • It is paramount to control fever and to relieve respiratory symptoms.
    • Respiratory symptoms are improved by exposing children to cool night air or by inhalation of vapor droplets to soothe inflamed airways.
    • Antipyretics may be administered to control fever.
    • Moderate or severe croup requires medical evaluation in the office or ED.
  • ED care
    • Mild croup: Cool oxygen mist and control of fever are effective in the treatment of mild croup.
    • Moderate croup: Therapy includes cool oxygen mist and, possibly, orally administered glucocorticoids. If patients fail to improve, racemic epinephrine nebulization has been shown to be beneficial. Hydration must be maintained with oral fluids or with intravenous fluids, when necessary.
    • Severe croup: In cases of impending respiratory failure, intensive-care monitoring is required in addition to repeat racemic epinephrine nebulization at 1- to 2-hour intervals. Endotracheal intubation followed by a tracheotomy may be required in patients with severe respiratory obstruction.

Consultations

Consultations may include pulmonologists and infectious diseases specialists.

Medication

Ribavirin is a broad-spectrum antiviral agent that has been shown to be effective against HPIV-3 infection in vitro and possibly in vivo. Although results are mixed, ribavirin aerosol or systemic therapy has been used to treat HPIV infections in children and adults who are severely immunocompromised. Use at this time is of uncertain clinical benefit.

Antibiotics are used only if bacterial complications (eg, otitis, sinusitis) develop. Corticosteroids and nebulizers are used to treat respiratory symptoms and to help reduce the inflammation and airway edema of croup.

Corticosteroids

Prednisone, prednisolone, and dexamethasone are commonly used glucocorticoids. Dexamethasone, because of its high potency and prolonged intramuscular half-life, is the preferred anti-inflammatory drug for croup.

Dexamethasone (Decadron, Solurex, Dexasone)

Decreases airway inflammation by inhibiting migration of phagocytes and reversing capillary permeability, thereby reducing edema occurring in croup.

Dosing

Adult

10 mg/d PO/IV/IM

Pediatric

0.6 mg/kg/d PO/IM

Interactions

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; decreases effect of salicylates and vaccines used for immunization

Contraindications

Documented hypersensitivity; active untreated bacterial or fungal infection

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with tuberculosis or ocular herpes simplex infection; increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications

Budesonide (Pulmicort Respules, Turbuhaler)

Nebulized, this agent is useful to reduce inflammation and edema in patients with croup. Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators. Turbuhaler is used for adults; Pulmicort Respules is used only for children aged 1-8 y.

Dosing

Adult

Not to exceed 1.6 mg/d nebulized

Pediatric

<6 years: Not established for Pulmicort Turbuhaler
>6 years: Not to exceed 400 mcg bid of Pulmicort Turbuhaler
1-8 years: Not to exceed 1 mg/d of Pulmicort Respules; not for use in children > 8 y

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not used to abort acute asthmatic episodes

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

5-60 mg/kg/d PO; taper as symptoms resolve

Pediatric

0.14-2 mg/kg/d PO; taper as symptoms resolve

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, and untreated fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Prednisolone (Delta-Cortef, Articulose-50, Econopred)

Decreases inflammation by suppressing migration of PMN leukocytes and reducing capillary permeability.

Dosing

Adult

5-60 mg/kg/d PO; taper as symptoms resolve

Pediatric

0.14-2 mg/kg/d PO; taper as symptoms resolve

Interactions

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids

Contraindications

Documented hypersensitivity; viral, untreated fungal, or tubercular skin lesions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis

Sympathomimetics

Epinephrine is highly effective when delivered via nebulizer. Nebulizers are air- or oxygen-powered devices that deliver medications directly to mucosal surfaces of respiratory tract and smooth muscles.

Epinephrine (AsthmaNefrin, microNefrin, S-2)

Racemic epinephrine solution causes alpha-adrenergic receptor–mediated vasoconstriction of edematous tissues, thereby reversing upper airway edema. Provides short-term relief.

Dosing

Adult

3 mL isotonic NaCl solution mixed with 0.5 mL epinephrine solution and nebulized q1-2h prn

Pediatric

Administer as in adults

Interactions

Increases toxicity of beta- and alpha-blocking agents and that of halogenated inhalational anesthetics

Contraindications

Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma; during labor (may delay second stage of labor)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly persons, individuals with prostatic hypertrophy, hypertension, cardiovascular disease, tachycardia (especially with HR >200 bpm), diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Follow-up

Further Inpatient Care

• Indications for hospitalization
  • Respiratory distress
  • Dehydration
  • Stridor at rest, even after receiving therapy

Further Outpatient Care

• Bed rest
• Use of vaporizers producing moist air

Deterrence/Prevention

• Field trials of formalin-killed whole HPIV-1, HPIV-2, and HPIV-3 vaccines failed to protect children against natural infections in the late 1960s. Current approaches to HPIV vaccines include intranasal administration of live attenuated strains, subunit strategies using HN and F proteins, recombinant bovine human viruses, and strains engineered using reverse genetics.
• At present, antigenically and genetically stable attenuated stains of HPIV-3 have been developed with cold adaptation (CA), whose stability is enhanced because of multiple markers of attenuation in tissue culture. Cold adaptation strains of HPIV-1 and HPIV-2 have been developed, and attenuation in tissue culture and animal models has been demonstrated.
• Reverse genetics has produced an attenuated chimeric HPIV-1 that contains type 3 internal proteins with type 1 surface glycoproteins F and HN.⁵

Complications

• Adult respiratory distress syndrome and exacerbation of nephritic syndrome
• Serious morbidity in immunocompromised hosts (eg, transplant recipients)
• Rare complications, including Guillain-Barré syndrome and meningitis

Prognosis

• HPIV infections in older children and adults are generally mild. Occasionally, bronchiolitis or viral pneumonia in children and tracheobronchitis in adults has been reported.

Miscellaneous

Medicolegal Pitfalls

• Clinically distinguishing pneumonia caused by HPIV from pneumonia caused by bacteria is difficult; hence, patients with pneumonia are sometimes inappropriately treated with antibacterial antibiotics.

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Keywords

parainfluenza virus, human parainfluenza virus, HPIV, HPIV-1, HPIV-2, HPIV-3, HPIV-4, croup, laryngotracheobronchitis, PIV, paramyxoviruses, croup-associated virus, CA virus, Sendai virus, croup, bronchitis, bronchopneumonia, pharyngitis, tracheobronchitis, bronchiolitis, acute respiratory tract infections, pneumonia, respiratory syncytial virus, RSV

Contributor Information and Disclosures

Author

Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India
Subhash Chandra Parija, MBBS, MD, PhD, FRCPath is a member of the following medical societies: Indian Academy of Tropical Parasitology, Indian Association of Biomedical Scientists, Indian Association of Medical Microbiologists, Indian Association of Pathologists and Microbiologists, Indian Medical Association, Indian Society for Parasitology, National Academy of Medical Sciences, India, and Royal College of Pathologists
Disclosure: Jawaharlal Institute of Postgraduate Medical education & Research , Pondicherry , India Salary Employment

Coauthor(s)

Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine
Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey D Band, MD, Clinical Professor of Medicine, Wayne State University School of Medicine; Director, Division of Infectious Diseases and International Medicine, William Beaumont Hospital Corporation
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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