Parainfluenza Virus Type 3 Infection Research Articles

Parainfluenza Virus Type 3 Co-infection with Other Respiratory Pathogens Among Hospitalized Children with Acute Respiratory Infections in Wuhan, China

Background: Bacterial and viral co-infections are increasingly recognized as the cause of Acute Respiratory Infection (ARI). The role of co-infection in ARI patients with Parainfluenza Virus type 3 (PIV3) infection is unclear. Objectives: This study aimed to determine the prevalence of PIV3 co-infections in hospitalized children and assess the co-infections' role in ARI patients with PIV3 infections. Methods: Between January 2018 and December 2021, children were confirmed to have a PIV3 infection via throat swabs or nasopharyngeal aspirates. Some digital clinical data were analyzed, including demographic, epidemiological, diagnostic, and laboratory data. Results: During the study period from 2018 to 2021, 2,539 patients were hospitalized with ARI caused by PIV3. Of them, 34.0% had co-infection with other pathogens, and 2.4% had co-infection with more than two pathogens. Mycoplasma pneumoniae was the most common co-infecting pathogen (71.3%), followed by other bacteria (13.3%) and viruses (8.2%). A significantly higher proportion of patients with M. pneumoniae co-infection was found in girls (χ2 = 19.233, P < 0.001). Co-infections with M. pneumoniae were observed principally in patients aged 1 – 2 years (χ2 = 202.130, P < 0.001). In contrast, viral (56.3%) and bacterial (66.1%) co-infections occurred mainly in children younger than one year. The diagnosis of PIV3 as a single infection included pneumonia (41.2%), bronchitis (39.9%), upper respiratory tract infections (15.0%), and laryngitis (3.9%), which were distinguished from those with bacterial co-infections (χ2 = 16.424, P = 0.001) and co-infections with more than two pathogens (χ2 = 11.687, P = 0.010). Co-infections of PIV3 with any pathogen were not associated with admissions to intensive care units or ventilator support. However, the mean hospitalization was significantly higher in M. pneumoniae co-infections (t = 2.367, P = 0.018), bacterial co-infections (t = 2.402, P = 0.016), and co-infections with more than two pathogens (t = 2.827, P = 0.006) than in single PIV3 infection. Conclusions: Parainfluenza virus type 3 frequently occurs with other pathogens. The epidemiological and clinical characteristics of co-infections with different pathogens differed. Mycoplasma pneumoniae co-infections, bacterial co-infections, and co-infections with more than two pathogens lengthened the hospitalization. Bacterial co-infections and co-infections with more than two pathogens increased the severity of ARI and worsened the symptoms.

Use of a multiplex polymerase chain reaction assay for the early detection of an outbreak of human parainfluenza virus type 3 infection in a nursery school during the COVID-19 pandemic

SummaryIntroductionAlthough outbreaks of parainfluenza virus type 3 (PIV-3) have been reported in children, to our knowledge none have been reported in a nursery school. As the symptoms of PIV-3 infection are similar to those of COVID-19 infection, accurate diagnosis of PIV-3 and other respiratory viruses is important during the COVID-19 pandemic.AimsWe experienced an outbreak of upper respiratory symptoms at a nursery school in Miyagi Prefecture, Japan, from 29/5/2021 to 13/6/2021 and aimed to determine the causative organism(s).MethodsA multiplex polymerase chain reaction (PCR) assay which enabled rapid detection of a variety of causative microorganisms of respiratory tract infections was used to analyse 13 nasopharyngeal swabs collected during the outbreak. Infection Prevention and control measures were implemented to prevent further spread of infection.ResultsAll 13 samples were positive for PIV-3 infection. 2 of the 13 samples were also positive for rhinovirus/enterovirus and 1 sample was also positive rhinovirus/enterovirus and coronavirus NL 63. No samples were positive for SARS-CoV-2.DiscussionChildren in school settings are especially vulnerable to respiratory viral infections, including COVID-19. Children under two years are unable to wear masks reliably, and the COVID-19 vaccine was approved only for older children. Multiplex PCR assays can be used for the rapid diagnosis of respiratory infections.ConclusionWe identified an outbreak of PIV-3 in a nursery school during the COVID-19 pandemic. The investigation of the outbreak highlighted that it was important not to overlook other respiratory infections including PIV-3 during the COVID-19 pandemic. The multiplex PCR assay provided rapid and accurate diagnosis of the causative organisms in the outbreak and helped to direct appropriate interventions to control the outbreak.

Shift in Clinical Epidemiology of Human Parainfluenza Virus Type 3 and Respiratory Syncytial Virus B Infections in Korean Children Before and During the COVID-19 Pandemic: A Multicenter Retrospective Study.

BackgroundParainfluenza virus type 3 (PIV3) and respiratory syncytial virus (RSV) B epidemics occurred in South Korea in late 2021. We investigated epidemiological changes of PIV3 and RSV B infections in Korean children before and during the coronavirus disease 2019 (COVID-19) pandemic.MethodsIn this multicenter retrospective study, we enrolled patients aged less than 19 years with PIV3 or RSV infection in four university hospitals from January 2018 to January 2022. Demographic and clinical data were extracted from the subject’s medical records and analyzed for each virus.ResultsA total of 652 children with PIV3 were identified including three epidemics: 216 in 2018, 260 in 2019, and 167 in 2021. Among 627 RSV B cases, 169 were identified in 2017/2018, 274 in 2019/2020, and 115 in 2021/2022. The peak circulation of PIV3 and RSV B epidemics were delayed by 6 and 2 months, respectively, in 2021, compared with those in the pre-COVID-19 period. The median age of PIV3 infections increased in 2021 (21.5 months in 2021 vs. 13.0–14.0 in 2018–2019; P < 0.001), whereas that of RSV B infections remained unchanged (3.6–4.0 months). During the COVID-19 pandemic, less frequent hospitalization rates were observed for both PIV3 and RSV B infections, but more children needed respiratory assistance for RSV B infection in 2021/2022 epidemic (32.5%) than before (14.7–19.4%, P = 0.014).ConclusionWe observed changes in the epidemiology and clinical presentation of PIV3 and RSV B infections in Korean children during the COVID-19 pandemic.

A 48-Year-Old Previously Healthy Man Presenting with Acute Respiratory Distress Syndrome (ARDS), Negative Tests for SARS-CoV-2, and Positive Serology for Parainfluenza Virus Type 3 (PIV-3)

Patient: Male, 48-year-old Final Diagnosis: Acute respiratory distress syndrome (ARDS) • parainfluenza virus infection Symptoms: Dyspnea Medication: — Clinical Procedure: — Specialty: Infectious Diseases • Pulmonology Objective: Rare disease Background:Human parainfluenza viruses (PIVs) belong to the Paramyxoviridae family. PIVs cause lower respiratory tract infections in children and the elderly. In addition, severe pneumonia due to PIVs has been reported in immunocompromised adults. However, no reports have described PIV infections leading to acute respiratory distress syndrome (ARDS) in immunocompetent hosts.Case Report:A 48-year-old otherwise healthy man was transported to our hospital due to worsening dyspnea. On arrival, strong effortful breathing was observed and results of arterial blood gas analysis revealed severe hypoxia. On the basis of the clinical presentation, we intubated the patient for mechanical ventilation. However, mechanical ventilation provided inadequate oxygenation. Finally, veno-venous extracorporeal membrane oxygenation was initiated. Pneumonia was considered to be a cause of the ARDS, based on the patient’s history and blood examination. Repeated reverse transcription-polymerase chain reaction tests for the novel coronavirus were performed, and endotracheal aspirate specimens were cultured for bacteria and fungus; however, the results were all negative. On day 2, the PIV-3-specific antibody titer was elevated. Two weeks later, the PIV-3-specific antibody titer had increased 4-fold. On the basis of these results, we diagnosed pneumonia induced by PIV-3 infection.Conclusions:ARDS can occur because of severe pneumonia induced by PIV-3. In cases of unexplained severe pneumonia or ARDS, PIV infection should be included in the differential diagnosis.

Antibodies to parainfluenza virus type 3 in goat population in Poland.

Respiratory diseases constitute a major health problem in small ruminant herds around the world, and parainfluenza virus type 3 (PIV-3) has been shown to play a vital role in their etiology. This cross-sectional study describes the serological status of the non-vaccinated dairy goat popu- lation in Poland with respect to PIV-3 infection and investigates the relationship between the presence of antibodies to PIV-3 and some basic herd-level and animal-level factors, including small ruminant lentivirus (SRLV) infection. Serum samples from 1188 goats from 48 herds were tested for the concentration of antibodies to PIV-3 using a quantitative immunoenzymatic assay. Specific antibodies were detected in all tested goats from all herds. The concentration of PIV-3 antibodies varied from 8.4 to >240 ng/ml (median 95.9 ng/ml) and was significantly higher in goats from larger herds and from these herds in which cough was often observed by farmers. Moreover, it was noted that female goats had higher antibody concentrations than males. On the other hand, the concentration of PIV-3 antibodies did not prove to be significantly linked to the presence of SRLV infection. This study shows that PIV-3 infection in the Polish goat population is widespread and appears to contribute to the occurrence of respiratory diseases in goat herds.

Parainfluenza virus infection enhances NSAIDs–induced inhibition of PGE2 generation and COX-2 expression in human airway epithelial cells

PurposeRespiratory viral infection and nonsteroidal anti-inflammatory drugs (NSAIDs) may affect arachidonic acid (AA) metabolism in the airway epithelium, however their joint effect has not been studied. We hypothesized, that alternations of AA metabolism in human airway epithelial cells (ECs) – induced by Parainfluenza virus type 3 (PIV3) – may be modified by concomitant treatment with NSAIDs. Materials and methodsNasal (RPMI 2650) and bronchial (BEAS-2B) epithelial cells were cultured into confluence and then infected with PIV3. Prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) levels in cell supernatants were measured by ELISA and expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) mRNA in cells was evaluated after reverse transcription with real-time polymerase chain reactions. ResultsPGE2 generation was decreased by PIV3 infection in the upper airway epithelial cells, and increased in the lower airway epithelial cells. Both naproxen and celecoxib induced significant reduction in PGE2 release in both infected and non-infected upper and lower airway epithelial cells. However, in PIV3-infected epithelial cells celecoxib inhibited PGE2 release and COX-2 expression to significantly higher degree as compared to non-infected cells. 15-HETE generation or COX-1, 5-LO and 15-LO expression were not affected by the virus infection or by NSAIDs. ConclusionVirus infection in airway epithelial cells enhances inhibitory effect of NSAIDs on prostaglandin E2 generation.

Impaired virus replication and decreased innate immune responses to viral infections in nasal epithelial cells from patients with allergic rhinitis.

The aim of this study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. NECs were obtained from eight patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR-3 and TLR-7/8 agonists. Interferon (IFN)-λ1, IFN-α, IFN-β and regulated on activation, normal T expressed and secreted (RANTES) release into the cell culture supernatants was assessed at 8, 24 and 48 h upon infection or 8 and 24 h after stimulation with poly(I:C) and R848. mRNA levels of IFNs, RANTES, interferon regulatory transcription factor (IRF)3, IRF7 and viral gene copy number were determined using real-time polymerase chain reaction (RT-PCR). PIV3 but not RV1B replication 48 h after infection was significantly lower (P < 0·01) in NECs from AR patients compared to HC. PIV3 infection induced significantly less IFN-λ1 (both protein and mRNA) in NECs from AR compared to HC. IFN-β mRNA expression and RANTES protein release and mRNA expression tended to be smaller in AR compared HC cells in response to both viruses. Stimulation with TLR-3 agonist [poly (I:C)] induced similar IFN-λ1 and RANTES generation in AR and HC subjects. Viral infections in NECs induced IRF7 expression, which correlated with IFN and RANTES expression. These data suggest that virus proliferation rates and the immune response profile are different in nasal epithelial cells from patients with allergic rhinitis compared to healthy individuals.

Parainfluenza 3 virus induces increased cough sensitivity, tracheal BDNF expression, and vagal sensory TRPV1 expression

Parainfluenza virus type 3 (PIV3) infection causes excessive coughing and croup in children, and is associated with exacerbation of asthma. We infected guinea pigs intranasally with PIV3 and quantified the cough response in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium (control) in response to either capsaicin or bradykinin (P<0.05). In an ex vivo perfused guinea pig tracheal preparation, we found that within 8 hr of infusion PIV3 resulted in a ~10-fold increase in brain-derived neurotrophic factor (BDNF) mRNA (qPCR) in the tissue. We have previously reported that tracheal BDNF is an effective inducer of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) in nodose Aδ tracheal cough neurons that normally do not express this channel (Am J Physiol; 302:L941-8). Consistent with this, PIV3 infection (day 4) increased TRPV1 expression in tracheal-specific nodose Aδ neurons. In vehicle treated animals only 20±10% of the tracheal-specific nodose neurons expressed TRPV1 (single neuron rt-PCR), whereas 4 days after PIV3 infection 60±2% of the neurons expressed TRPV1 (n=6 ganglia ~60 neurons; P<0.05). In summary, PIV3 infection in guinea pigs evokes BDNF expression in the trachea and this increased de novo TRPV1 expression in tracheal specific cough nodose neurons, and a heightened cough response to capsaicin and bradykinin. Supported by NIH.

Parainfluenza virus type 3 Ab in allogeneic hematopoietic cell transplant recipients: factors influencing post-transplant Ab titers and associated outcomes.

Parainfluenza virus type 3 (PIV-3) can cause severe respiratory illness among hematopoietic cell transplantation (HCT) recipients. Factors associated with PIV-3-specific Ab level, and the association between PIV-3 Ab levels and clinical outcomes in HCT recipients who acquire PIV-3 infection, are unknown. We evaluated PIV-3-specific hemagglutination inhibition Ab levels and clinical outcomes among 172 patients with PIV-3 infection following HCT. In a multivariable linear regression model, high post-transplantation Ab levels were independently associated with higher pre-transplantation recipient titer (mean difference 0.38 (95% confidence interval (CI), 0.26, 0.50), P<0.001). Significant associations between pre-HCT Ab titers in both patients and donors and occurrence of lower respiratory tract disease (LRD) after HCT were not observed. In conclusion, low pre-transplantation titers are associated with low Ab levels after HCT. The relationship between PIV-3 Ab levels and outcomes remain uncertain. Further study is needed to prospectively evaluate the dynamics of PIV-3-specific Ab responses and the relative contribution of PIV-3-specific Ab to protection from infection acquisition and progression to LRD.

Parainfluenza virus‐3‐induced cytopathic effects on lung tissue and bronchoalveolar lavage fluid in a bone marrow transplant recipient

Parainfluenza virus type 3(PIV-3) commonly causes respiratory tract infections in hematopoietic stem cell transplant (HSCT) patients. The majority of PIV-3 infections develop in patients who have undergone stem cell transplantation from unrelated donors. From these patients, bronchoalveolar lavage (BAL) fluid and/or lung biopsies are often collected and sent for evaluation of infectious processes. However, cytologic findings associated with a PIV-3 infection in BAL fluid have not been reported in the literature. We describe BAL cytology and lung biopsy findings in a patient who received an HSCT from a related donor and subsequently developed a PIV-3 infection. This patient was noted to have scattered reticular-nodular opacities in both lungs on computed tomogram scan and underwent transbronchial biopsy and BAL of the left lower lobe. Examination of the BAL fluid revealed scattered multinucleated giant cells intermixed with inflammatory cells. The lung biopsy showed organizing pneumonia associated with several multinucleated respiratory epithelial cells containing rare intracytoplasmic inclusions. Gram, periodic acid Schiff, Gomori methenamine silver, and acid fast stains on the biopsy specimen failed to reveal microorganisms. A sample of the BAL fluid sent for respiratory viral culture grew PIV-3. These findings suggest that the presence of giant cells in transplant patients with organizing pneumonia should raise suspicion of a PIV-3 infection.

Epidemiology and clinical characteristics of parainfluenza virus 3 outbreak in a Haemato-oncology unit

We describe molecular investigations of a large hospital outbreak of parainfluenza virus type 3 (PIV3), in which 32 patients became infected. We outline infection control measures that successfully limited further spread of PIV3 in a Haemato-oncology unit. Clinical retrospective review of infected haemato-oncology patients was undertaken. PIV3 haemagglutinin sequences from each case (n = 32) and local epidemiologically unlinked controls (n = 53) were compared to identify potential linkage. PIV3-infected patients presented with upper (n = 18) and lower (n = 11) respiratory tract infections, 3 showed pyrexia only and one was asymptomatic. All symptomatic patients received antibiotics; bacterial co-infection was confirmed in eleven patients. PIV3 infections were associated with lower mortality than documented previously; three of the PIV3-infected patients died (3/32; 9%). All deaths were associated with relapsed malignancies, and PIV3 was not believed to be the primary cause of death in any of these patients. Sequences from 27 cases clustered closely together, consistent with nosocomial infections from PIV3 circulating within the ward. Factors favouring transmission were high patient turnaround between the day treatment unit and in-patient ward, and limited isolation facilities for immunocompromised and infected patients, especially within the day treatment unit. New infections reduced to baseline levels three days after enhanced infection control interventions were introduced. Molecular epidemiological analysis provided evidence for nosocomial transmission of PIV3 infection that facilitated effective implementation of infection control measures. These were instrumental in restricting further spread of the virus among high-risk patients.

Cough reflex sensitivity is increased in guinea pigs with parainfluenza virus infection

ABSTRACTThe purpose of this study was to investigate for the change in cough reflex sensitivity (CRS) caused by parainfluenza virus type 3 (PIV3) infection. Guinea pigs were randomized into a vehicle control, an asthma control, or 1 of 4 PIV3-inoculated groups (referred to as postinfection day [PID] 6, 12, 28, and 42 groups). Evidence of viral protein and nucleic acid within the lung confirmed successful PIV3 infection. Plethysmography was used to assess CRS and airway reaction and airway inflammation was assessed via bronchoalveolar lavage fluid cytology and lung histopathology. Compared with the vehicle control group, CRS was significantly increased in all PID groups (P <.05) in concert with an obvious airway hyperresponsiveness in the PID 6 group. Though a small increase in CRS in the asthma control group was noted, it was not significant compared to the vehicle control group. Total cell counts from the bronchoalveolar lavage fluid of all PIV3-inoculated groups increased markedly and the number of lymphocytes was significantly increased in the PID 6 and PID 12 groups. The lung pathology of PIV3-inoculated animals showed airway inflammation without pneumonia in the acute infectious phase. The temporal and spatial variation of CRS may be the essential mechanism of cough caused by PIV3.

Parainfluenza virus type 3 infections in a hematology unit.

Parainfluenza virus type 3 (PIV3) is associated with a high mortality rate in BMT recipients with lower respiratory tract infections. We describe nine patients with hematological malignancies (five having undergone either allogeneic or autologous stem cell transplantation) identified as having PIV3 infection during a 2-month period in a Hematology Unit. Four patients with infiltrates on chest radiograph received intravenous ribavirin therapy; all survived. The infection was community-acquired in two patients, while nosocomial origin of the disease was evident, or presumed, in the remaining seven. The policy implemented to control the spread of PIV3 was as follows: (1) nasopharyngeal samples for antigen detection were obtained from all patients presenting with respiratory symptoms; (2) all diagnosed (or suspected) PIV3-positive hematological patients were nursed following contact isolation precautions, preferably in the Infectious Diseases Unit; and (3) staff were given further education on hospital hygiene. Our experience shows that it may be possible to avoid mortality for PIV3 lower respiratory tract infection in immunocompromised patients by early commencement of intravenous ribavirin. It is also possible, even without closing the ward, to contain nosocomial spread of PIV3 by implementing systematic nasopharyngeal sampling for rapid diagnostics, and by strict adherence to cohorting and contact isolation precautions.

Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment.

All 456 recipients of hemopoietic stem cell transplants (SCT) at the Hammersmith Hospital, London, from January 1990 through September 1996 were reviewed for parainfluenza virus (PIV) infections. Of the 24 (5.3%) PIV type 3 (PIV3)-infected patients, 10 had upper respiratory tract infection and all survived, but 8 of 14 with pneumonia died. A same-day immunofluorescence test diagnosed PIV3 infection in 20 (83%) of the 24 cases, but virus culture diagnosed only 10 (42%) of the 24 cases after a mean delay of 12 days. Eighteen PIV3-infected patients first received ribavirin at a median of 3 days after onset of symptoms, but, nevertheless, 2 patients shed PIV3 for 4 months. Six of 10 patients with pneumonia died despite early ribavirin therapy. The cause of death was not established by autopsy; 3 patients had concurrent infections, but in 3, only PIV3 was detected. The value of immunofluorescence testing for early diagnosis and treatment of PIV3 infection after SCT is demonstrated, but the outcome was not altered.

Respiratory syncytial virus G and/or SH glycoproteins modify CC and CXC chemokine mRNA expression in the BALB/c mouse.

Chemokine mRNA expression by pulmonary leukocytes following infection of BALB/c mice with two strains of respiratory syncytial virus (RSV) and one strain of parainfluenza virus type 3 (PIV-3) was determined. The results suggest that RSV G and/or SH proteins inhibit early MIP-1alpha, MIP-1beta, MIP-2, MCP-1, and IP-10 mRNA expression. TCA-3 mRNA expression was found to be increased during PIV-3 infection.

Rapid detection of parainfluenza virus type 3 RNA in respiratory specimens: use of reverse transcription-PCR-enzyme immunoassay.

Parainfluenza virus type 3 (PIV-3), an important lower respiratory tract pathogen in young children and immunocompromised individuals, may be underdiagnosed because of the insensitivity of available culturing systems and delay in identification of virus in cell culture. We developed a reverse transcription-PCR-enzyme immunoassay (RT-PCR-EIA) for PIV-3, using primers specific for a highly conserved region of the hemagglutinin-neuraminidase gene. Testing of nasal washes spiked with PIV-3 or other respiratory viruses showed that this assay detected seven strains of PIV-3 but not other respiratory viruses. Of 103 respiratory tract samples obtained from children experimentally infected with a liver PIV-3 vaccine or naturally infected with wild-type PIV-3, 51 were positive by culture and 48 were positive by RT-PCR-EIA. Eleven of the culture-positive samples were negative by RT-PCR-EIA; however, none of these grew virus upon reinoculation into cell culture, indicating that virus was lost or was present at a very low titer. Eight of the culture-negative samples were positive by RT-PCR-EIA: two were obtained from a subject who was culture negative but had a serologic response to PIV-3, four were obtained 7 to 9 days after the first positive culture, and two were obtained 1 day prior to the first positive culture. Thus, this RT-PCR-EIA for PIV-3 is sensitive and specific and can detect viral RNA in samples from which virus cannot be cultivated. This assay could be used for diagnosis late in the course of PIV-3 infection and for accurate detection of disease outbreaks.

Immunization with vaccinia virus recombinants that express the surface glycoproteins of human parainfluenza virus type 3 (PIV3) protects patas monkeys against PIV3 infection.

Patas monkeys (Eryphrocebus patas) were immunized intradermally with two vaccinia virus recombinants that individually express the hemagglutinin-neuraminidase glycoprotein or the fusion glycoprotein of human parainfluenza virus type 3 (PIV3). These immunizations induced a high titer of PIV3 serum-neutralizing antibodies. At 1 month after immunization, monkeys were challenged intratracheally with PIV3. Subsequent virus replication was reduced in these monkeys by 3.2 log10 and 1.9 log10 (mean peak virus titers) in the upper and lower respiratory tracts, respectively, compared with control animals. The average duration of virus shedding was also reduced from 9.0 to 3.4 days in the upper respiratory tract and from 5.3 to 1.2 days in the lower respiratory tract. These findings demonstrate that a single intradermal dose of live recombinant vaccinia viruses can significantly restrict the replication of a virus which primarily infects the epithelial cells of the respiratory tract.