Approach Considerations
Because it is often difficult to distinguish pneumonia caused by HPIV from pneumonia caused by bacteria, patients with viral pneumonia are sometimes inappropriately treated with antibacterial antibiotics. In the setting of HPIV infection, antibiotics are used only if bacterial complications (eg, otitis and sinusitis) develop. Antiviral agents are of uncertain benefit for treatment of HPIV infection.
It is important to document an examination at time of discharge—for example, “Patient is breathing comfortably and is alert and consolable, without tachypnea, stridor, or retractions.” A pulse oximetry reading can also be included if available. If there are any concerns about the patient’s stability for discharge, always err on the side of admission.
Initial Management
Prehospital care includes fever control and attempts to alleviate respiratory symptoms and patient anxiety.
Respiratory symptoms commonly improve with benign measures such as sitting in a bathroom with a steaming shower and allowing vapor droplets to soothe inflamed airways. Another option includes exposing the child to the cool night air. Often, the patient’s symptoms resolve en route to the hospital. Attempts at calming or distracting the child can be beneficial.
Antipyretics may assist with fever control. Moderate or severe croup requires medical evaluation in the office or emergency department (ED). Consultations may include pulmonologists and infectious disease specialists.
Indications for hospitalization in patients with HPIV infection include the following:
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Respiratory distress
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Dehydration
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Stridor at rest, even after receiving therapy
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Need for repeated doses of racemic epinephrine
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Rebound laryngospasm in patients who receive racemic epinephrine
A common issue in pediatric ED charts concerns variations in patient assessments. All notes on the chart (eg, from triage, nurses, and residents) should be examined. If any of these assessments differ from the physician’s assessment, the physician should address the differences in his or her notes. At discharge, ensure that proper discharge instructions, both written and oral, are given to the patient.
Supportive Care and Pharmacologic Therapy
Supportive care is mandatory. Oxygen mist is often helpful. Corticosteroids and nebulizers may be used to treat respiratory symptoms and to help reduce the inflammation and airway edema of croup.
Management of croup caused by HPIV infection depends on the severity of disease.
Mild croup
Management of mild croup consists of cool blow-by oxygen mist, fever control, and observation to determine whether the airway appears compromised.
Moderate croup
Cool oxygen mist and steroids are common therapies for moderate croup. Controlled trials of steroids for the palliation of croup symptoms have yielded conflicting results, and routine use of dexamethasone in this disease remains controversial. Traditionally, dexamethasone was administered intramuscularly (IM); however, some studies have documented the use of oral steroids.
In patients who fail to improve, administration of racemic epinephrine with a nebulizer has been beneficial. If racemic epinephrine alleviates symptoms, observe the patient for a minimum of 3 hours to ensure that his or her condition does not worsen (eg, because of possible rebound laryngospasm as the racemic epinephrine dose wears off). If the patient is asymptomatic at the end of the observation period, he or she can be discharged with proper follow-up care.
In moderate croup, oral intake may be lacking; therefore, it is essential to evaluate the patient’s hydration status. Intravenous (IV) fluids may be required.
Severe croup
The same measures are indicated for severe croup as for moderate croup. Observe the patient for signs of impending respiratory failure.
Repeat racemic epinephrine nebulization may be needed, in addition to intensive care monitoring. Racemic epinephrine nebulizations can be repeated at 1-hour to 2-hour intervals as needed. Endotracheal intubation followed by a tracheotomy may be required in patients with severe respiratory obstruction. Fortunately, fewer than 5% of patients who are admitted require artificial airway support.
Antiviral therapy
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.
Prevention
Passively acquired maternal antibodies may play a role in protection from HPIV-1 and HPIV-2 in the first few months of life, an observation that highlights the importance of breastfeeding.
Currently, there are no effective vaccines for prevention of infections by HPIVs. Among the HPIVs, the HPIV-3 is the most virulent with ability to cause bronchioloitis and pneumonia in infants. Therefore, attempts are being made for the development of human vaccine against the HPIV-3.
In the late 1960s, field trials of formalin-killed whole HPIV-1, HPIV-2, and HPIV-3 vaccines failed to protect children against natural infections. Subsequent approaches to the development of HPIV vaccines have included intranasal administration of live attenuated strains, subunit strategies using hemagglutinin-neuraminidase (HN) and fusion (F) proteins, recombinant bovine human viruses, and strains engineered by means of reverse genetics.
Antigenically and genetically stable attenuated strains of HPIV-3 have been developed with cold adaptation (CA); their stability is enhanced because of multiple markers of attenuation in tissue culture. CA strains of HPIV-1 and HPIV-2 have been developed, and attenuation in tissue culture and animal models has been demonstrated.
HPIV3cp45 vaccine candidate has undergone a phase 1 clinical trial and has been found to be highly infectious and well-tolerated. Different dosing schedules, 1 month apart and 3 months apart, have been tested, and viral shedding is less when vaccine doses are given 1 month apart. [32]
BCX 2798 and BCX 2855 were found to be effective inhibitors of HPIV-3 HN in a mouse model, as well as potentially promising candidates for prophylaxis and treatment of HPIV-3 infection in humans. [33] A live attenuated vaccine against respiratory syncytial virus (RSV) and HPIV-3 was found to be safe and immunogenic in a phase 1 study. [34] Reverse genetics produced an attenuated chimeric HPIV-1 that contains type 3 internal proteins in conjunction with type 1 HN and F surface glycoproteins. [35]
Some of the potential vaccine candidates are the HPIV-3 cp45 nasal vaccine, which is derived from the JS wild-type strain of HPIV-3 and the rB/HPIV3b vaccine, which is a cDNA-derived chimeric HPIV-3. An intranasal vaccine has been developed against HPIV-3. The investigators determined that the vaccine is appropriately attenuated and immunogenic in infants as young as 1 month. Further development of this vaccine is warranted. [36, 37] .
Two vaccines against HPIV-3 were determined to be safe and immunogenic in phase I trials involving HPIV-3–seronegative infants and children; vaccines against HPIV1 and HPIV2 were found to be less advanced. [36]
Bovine PIV (BPIV) has also been used as a live vaccine candidate against HPIV-3. Phase 1 clinical trials found the vaccine candidate to be highly infectious, safe, and immunogenic; however, the mean geometric titers for BPIV were lower against HPIV-3 than against BPIV-3. Phase 2 clinical trials of the same candidate demonstrated that the vaccine was well–tolerated, and fever was the only adverse effect observed. [32]
Combined RSV and HPIV-3 vaccines have also been attempted. The aforementioned BPIV/HPIV-3 virus has been modified to express RSV F protein alone or both the F and G proteins. This bivalent virus contains proteins from both RSV and HPIV-3. Preclinical studies have indicated good tolerance and adequate seroconversion. [32]
Murine PIV-1/Sendai virus vaccine has also been evaluated as a live attenuated xenotropic vaccine candidate. Intranasal formulation of the candidate strain was well-tolerated in a phase 1 trial.
HPIV-1 has also been evaluated as a vector for RSV. In animal studies (hamster model), vaccination with an attenuated RSV strain followed by HPIV-1–expressing RSV F protein showed better immunogenicity than two doses of attenuated RSV. [32]
Development of an HPIV-2 vaccine is being attempted; in preclinical studies, L protein has been identified as the major target for mutagenesis to develop attenuated HPIV-2. [32]
However, the major limitation of these vaccines is their potential to cause actual infection in immunocompromised hosts and children. In order to overcome this limitation, subunit vaccines that target the HPIV-3 HN and F proteins are being investigated. In a recent study, intranasal coadministration of oligomannose-coated liposome-encapsulated HN with the poly(I:C) adjuvant was found to induce adequate viral-specific immunity against HPIV-3 in a mouse model. [3]
Strict attention to infection control should decrease or prevent spread of infection. Frequent handwashing and avoidance of sharing items such as cups, glasses, and utensils with an infected person should decrease the spread of viruses to others. In a hospital setting, the spread of HPIVs can and should be prevented by strict attention to contact precautions, such as handwashing and wearing of protective gowns and gloves.
Long-Term Monitoring
If the patient has a pediatrician or other primary care provider, attempt to contact the provider to ensure proper follow-up care. The pediatrician can also be consulted on management issues if the treating physician has concerns or doubts.
Helpful long-term measures may include the following:
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Bed rest
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Use of vaporizers producing moist air
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Administration of acetaminophen or ibuprofen for fever
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Increased oral fluid intake
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Transmission electron micrograph of parainfluenza virus. Two intact particles and free filamentous nucleocapsid.
