Parainfluenza 3 Respiratory Infection Associated with Pericardial Effusion in a Very Low Birthweight Infant

Parainfluenza 3 virus is a frequent cause of respiratory infections in the pediatric population although it is uncommonly diagnosed in neonates, being usually reported as neonatal intensive care unit microepidemics. We report a case of parainfluenza 3 respiratory infection associated with pericardial effusion in a very low birthweight infant.


Case Report
We present the case of a male neonate born at week 25 of gestational age and weighed 720 grams. During pregnancy follow-up, the mother received labetalol because of gestational hypertension. Ultrasound controls during pregnancy were normal, and routine serologies were negative.
At week 25 of gestation, severe preeclampsia was diagnosed. Fetal ultrasound showed intrauterine growth retardation type 1 and redistribution in Doppler ow. Caesarean delivery was indicated due to severe preeclampsia after sulfate magnesium administration for neuronal protection and complete pulmonary maturation. e newborn needed intubation in the delivery room with 100% fraction of inspired oxygen (FiO 2 ) and intratracheal instillation of surfactant. en, he was extubated and connected to nasal continuous positive airway pressure (CPAPn). When FiO 2 was decreased to 30%, the patient was transferred to the neonatal intensive care unit (NICU).
At 29 week postconceptional age, the infant was stable with noninvasive ventilation (mean airway pressure (MAP) 6 cmH 2 O, FiO 2 0.40). Suddenly, clinical deterioration occurred, involving respiratory distress, increased needs of oxygen therapy, tachypnea, bradycardia, desaturations, and frequent apnea episodes, that required intubation and mechanical ventilation (MAP 12 cmH 2 O, FIO 2 0.50). Laboratory tests evidenced lymphocytosis and hypertransaminasemia. Blood culture, urine culture, and cerebrospinal uid culture were negative (Table 1). Chest X-ray showed bilateral pulmonary in ltrates and signi cant cardiomegaly (Figure 1(a)). Echocardiography revealed di use pericardial e usion involving predominantly right chambers ( Figure 2). Contractility and right and left cardiac outputs were preserved as shown in Table 1.
Polymerase chain reaction (PCR) in nasopharyngeal swab was requested the day after the clinical deterioration and was positive for parain uenza 3 virus (PIV3). e multiplex PCR used was CLART-PneumoVir. It detects 17 respiratory viruses: respiratory syncytial viruses (RSV); RSV group-A; RSV group-B; PIV1; PIV2; PIV3; PIV4; coronaviruses; human metapneumovirus; adenoviruses; enteroviruses; in uenza A (including H3N2 and both seasonal and pandemic H1N1), B, and C viruses; rhinoviruses; and bocavirus. Because newborn family members and neonatal intensive care unit sta were asymptomatic before, during or after the episode, nasopharyngeal swabs could not be obtained from the contacts. Other infectious causes of pericardial e usion were incompatible with the clinical picture: the patient was not treated with drugs that may had caused pericardial e usion, there was no possible traumatic cause (central venous catheter perforation and penetrating trauma), and there were not clinical, analytical, or radiological signs of other causes (tuberculosis, fungal infections, collagen diseases, etc.). Blood culture for other microorganisms, including bacteria and fungi, was negative. Because of this, PIV3 may have been the trigger for the pericardial pathology.
Due to the hemodynamic stability of the patient, a conservative approach was adopted. e patient did not require anti-in ammatory or diuretic therapy to reduce pericardial e usion. Serial echocardiograms and chest X-ray con rmed its reduction until its complete resolution within 5 days (Figure 1(b)). Figure 1 shows the cardiomegaly at the clinical deterioration, with near complete resolution. At 36 weeks postconceptional age, the patient developed severe bronchopulmonary dysplasia (BPD), requiring high-ow nasal cannulae and 40% oxygen supplementation.

Discussion
To our knowledge, there are only two cases reported of pericardial e usion associated with parain uenza viruses in children and none of them in the neonatal period. e rst one describes an 8-month-old boy diagnosed with pneumonia and severe combined immunode ciency. Parain uenza 3 was isolated in respiratory secretions and pericardial and cerebrospinal uids. Postmortem evaluation con rmed the presence of the pathogen in the lung, brain, and pericardial samples [1]. e second case is a 9-year-old immunocompetent patient with pericardial e usion in whom parain uenza 4 was isolated in nasopharyngeal aspirate. e patient was successfully treated with ibuprofen [2]. ere are two other cases reported in adults. In the rst one, parain uenza 3 viral infection was considered to be the cause of a fulminant myocarditis with pericardial e usion in a 35-year-old woman with diabetic ketoacidosis and type 1 diabetes [3]. e second one described a 62-year-old woman with pneumonia and pericardial e usion as a result of infection with parain uenza virus type 4 and thrombotic thrombocytopenic purpura [4].
Parain uenza virus is an RNA virus belonging to the Paramyxoviridae family, with four types described. It is a prevailing cause of viral respiratory infection in the pediatric population after respiratory syncytial virus, enteroviruses, or human metapneumovirus. Although respiratory viral infections are usual among hospitalized newborns, they are not clinically suspected because the signs and symptoms of infection are nonspeci c or too subtle. For this reason, they are seldom diagnosed in the neonatal intensive care unit. ere are scarce reports presenting isolated cases like this one as most of the published data refer to neonatal intensive care unit microepidemics in which parain uenza 3 was just one of the di erent viruses detected [5]. ose outbreaks are thought to be related to longer stay in the neonatal intensive care unit. As the main route of transmission of this pathogen is through infected secretions, respiratory and contact isolation is essential to prevent disease outbreaks.
Premature infant population may develop parain uenza virus infection with atypical or even clinically unapparent signs and symptoms [6] as in our patient. Clinical signs are nonspeci c (mainly respiratory with increased secretions, Leukocytes 9.8 cells/mm 3 (74.4% lymphocytes, 15% neutrophils); hemoglobin 13.1 g/dl and platelet count 255/mm 3 . ALT 89 U/L/AST 73 U/L, C-reactive protein (CRP) 1.7 mg/dl; procalcitonine 0.07 ng/ml 2 Case Reports in Infectious Diseases respiratory distress, coughing, tachypnea, pneumonia, or apnea episodes). Diagnosis requires a high index of suspicion in the presence of suggestive symptoms, since other infecting viruses such as respiratory syncytial viruses, enteroviruses, rhinoviruses, or coronaviruses may induce similar clinical pictures con rmation. Diagnosis is based on the detection of virus-speci c RNA using nucleic acid ampli cation techniques from a respiratory sample such as a nasopharyngeal swab. is technique has been a breakthrough in the diagnosis as it could decrease unnecessary use of empirical antibiotic therapy. Other diagnostic methods are viral culture, usually less available and with longer turnaround time results, and direct viral detection in respiratory secretions by immuno uorescence or enzyme immunoassay, which shows lower sensitivity and speci city than PCR. Currently, there is no speci c treatment against parain uenza virus infections. Management of the infected patient is based on supportive therapy according to the clinical condition. e main limitation of our case report is the uncon rmed etiological presence of parain uenza virus in pericardial e usion. Detection of parain uenza 3-speci c RNA from pericardial uid or blood would o er direct evidence that PIV3 caused the e usion. Pericardial uid was not obtained due to the invasiveness of the technique in the context of clinical and hemodynamic stability of our patient and spontaneous resolution in 5 days.
In conclusion, parain uenza 3 infection should be considered during the diagnostic evaluation of neonatal pericarditis. is may prevent possible severe complications and reduce unnecessary use of antibiotics. High index of suspicion is required for rapid diagnosis and appropriate management.

Ethical Approval
Compliance with ethical standards.

Consent
Informed consent was obtained from the patient's parents.

Conflicts of Interest
e authors declare that there are no con icts of interest regarding the publication of this case report.