Human Parainfluenza Virus Infection Research Articles

Clinical characteristics and risk factors of severe human parainfluenza virus infection in hospitalized children

BackgroundHuman parainfluenza viruses (HPIVs) commonly cause childhood respiratory illness requiring hospitalization in Taiwan. This study aimed to investigate clinical severity and identify risk factors predisposing to severe disease in hospitalized children with HPIV infection. MethodsWe included hospitalized patients with lab-confirmed HPIV infection from 2007 to 2018 and collected their demographic and clinical characteristics. Patients with ventilator support, intravenous inotropic agents, and extracorporeal membrane oxygenation were defined as severe cases. ResultsThere were 554 children hospitalized for HPIV infection. The median age was 1.2 years; 518 patients had non-severe HPIV infection, whereas 36 patients (6.5%) had severe HPIV infection. 266 (48%) patients had underlying diseases, and 190 patients (34.3%) had bacterial co-detection. Children with severe HPIV infection were more likely to have bacterial co-detection than those without (52.8% vs 33.0%, p = 0.02). Patients with lung patch or consolidation had more invasive bacterial co-infection or co-detection than those without patch or consolidation (43% vs 33%, p = 0.06). Patients with neurological disease (adjusted OR 4.77, 95% CI 1.94–11.68), lung consolidation/patch (adjusted OR 6.64, 95% CI 2.80–15.75), and effusion (adjusted OR 11.59, 95% CI 1.52–88.36) had significantly higher risk to have severe HPIV infection. ConclusionNeurological disease and lung consolidation/patch or effusion were the most significant predictors of severe HPIV infection.

Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.

This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42-11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05-0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4-23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6-87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups. ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.

Epidemiological Characteristics of Human Parainfluenza Viruses Infections - China, 2019-2023.

A retrospective study based on sentinel surveillance was conducted in 10 provincial-level administrative divisions (PLADs) in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses (HPIVs). From January 2019 to June 2023, respiratory specimens were collected from individuals with acute respiratory infections (ARIs) and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction (PCR). This study analyzed the association of HPIVs infections with seasonal patterns, geographical distribution, demographic profiles, clinical features, and co-infection status. During the study period, a total of 12,866 ARIs were included. The overall detection rate of HPIVs was 6.15%, varying from 5.04% in 2022 to 9.70% in 2020. The median age of HPIVs-infected patients was 3 years. HPIV2 was more prevalent among individuals aged 5-17 years (42.57%), while HPIV4 was more common in those over 65 years (12.24%). HPIV3 (54.16%) and HPIV1 (27.18%) were the predominant serotypes, and their prevalence exhibited significant seasonal fluctuations post- coronavirus disease 2019 (COVID-19) pandemic. The peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak thereafter. Two peaks of HPIV1 were observed in 2021 following the peak of HPIV3. Additionally, co-infections were frequent in HPIVs cases (overall rate: 22.12%), with human rhinovirus being the most common co-infecting virus. The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1, and their seasonal patterns were altered by pandemic restrictions. Hence, continuous surveillance of HPIVs is essential.

Clinical impact of human parainfluenza virus infections before and during the COVID-19 pandemic in Southern China

Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Non-pharmaceutical interventions (NPIs) were widely administered to combat the pandemic of the coronavirus disease 2019 (COVID-19). Respiratory specimens were obtained from 10,454 hospitalized children with ARTIs to detect HPIV. We investigated differences in epidemiological and clinical characteristics of HPIV infections before (2017–2019) and during the COVID-19 pandemic (2020–2022). HPIVs were detected in 392 (3.75%, 392/10,454) patients, of whom 70 (17.86%), 48 (12.24%), and 274 (69.90%) were positive for HPIV1, HPIV2, and HPIV3, respectively. Detection rates of HPIV3 were higher in 2020–2022 than in 2017–2019 (3.38% vs. 2.24%). The seasonal distribution of HPIV1 showed no difference, but HPIV3 peaked between September and December during the COVID-19 pandemic, which differed from previous epidemiological patterns. Compared to the period before the COVID-19 pandemic, there has been a noticeable decrease in the incidence of asthma, moist rales, and emesis in patients infected with HPIV1 and in asthma, expectoration, and severe pneumonia in patients infected with HPIV3 during 2020–2022. The detection rates of HPIV increased in Southern China during the COVID-19 outbreak, which underlines the importance of continuous surveillance of HPIV in the next epidemic season.

Human Parainfluenza Virus (HPIV) Detection in Hospitalized Children with Acute Respiratory Tract Infection in the Western Cape, South Africa during 2014-2022 Reveals a Shift in Dominance of HPIV 3 and 4 Infections.

The epidemiology of human parainfluenza viruses (HPIV), particularly its role as a cause of acute respiratory infection (ARI) in infants, has not been formally studied in South Africa. We evaluated HPIV prevalence in diagnostic samples from hospitalized children from public sector hospitals in the Western Cape between 2014 and 2022. HPIV infection was detected in 2-10% of patients, with the majority of infections detected in children less than 1 year of age. Prior to 2020, HPIV 4 (40%) and HPIV 3 (34%) were the most prevalent types, with seasonal peaks in late winter/spring for HPIV 3 and autumn/winter for HPIV 4. HPIV 4A and 4B co-circulated during the seasonal activity between 2014 and 2017. Pandemic restrictions in 2020 had a profound effect on HPIV circulation and the rebound was dominated by waves of HPIV 3, accounting for 66% of detections and a sustained decline in the circulation of HPIV 1, 2 and 4. An immunity gap could account for the surge in HPIV 3 infections, but the decline in prior HPIV 4 dominance is unexplained and requires further study.

Epidemiological and Clinical Characteristics of Human Parainfluenza Virus Infection in Children of Xianyang Children's Hospital in 2022

The incidence of HPIV infection in children is on the rise, particularly following the emergence of SARS-CoV-2, which presents a potential risk to the health of children.&#x0D; Objective: This study aims to investigate the epidemiological and clinical features of human parainfluenza virus (HPIV) in children admitted to Xianyang Children's Hospital (Xianyang Caihong Hospital) from January 2022 to December 2022.&#x0D; Methods: Out of the 5873 cases of hospitalised children, the ones which had HPIV as the only pathogen and were non-standard cases were excluded, and the rest were analysed for their clinical characteristics, based on the six nucleic acids kits used to detect HPIV in respiratory tract viruses. Results: Among 5873 cases of Nasopharyngeal swab specimens, there were 795 cases of HPIV antigen positive, of which 794 cases of HPIV3（13.52%, 3 cases of HPIV1（0.05%; There were 472 males (13.92%) and 325 females (13.09%) in them(χ2 =0.381, P=0.362).The infection rates in spring, summer, autumn and winter were 8.03%, 55.71%, 28.48% and 7.78%, respectively, and the difference of pairwise comparison were statistically significant (χ2=539.158, P=0).There were 318 cases (19.51%) in infant group and 164 cases (10.86%) in children group (χ2=45.118, P=0). With HPIV as the sole pathogen including 363 cases of bronchopneumonia, 237 cases of bronchitis, 8 cases of pertussis syndrome, 84 cases of bronchiolitis.&#x0D; Conclusion: ⑴. During the period of January to December 2022, Xianyang Children's Hospital has seen a high prevalence of HPIV, a virus causing lower respiratory tract infection, especially HPIV3. ⑵.No statistical evidence showed a difference between men and women in terms of high morbidity during spring and summer, which was more common among infants and young children. ⑶. Among children infected with HPIV, the four most common respiratory illnesses are bronchopneumonia, bronchitis, pertussis syndrome, and bronchiolitis. After undergoing symptomatic treatment, most children showed marked improvement. It is imperative to gain a thorough understanding of HPIV infections in children, enabling timely prevention and symptomatic treatment, identifying critical and serious illnesses, and reducing morbidity and mortality.

Lockdown measures during the COVID-19 pandemic strongly impacted the circulation of respiratory pathogens in Southern China

A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Shenzhen. We examined the effect of these measures on the prevalence of respiratory pathogens in children. Clinical and respiratory pathogen data were collected for routine care from hospitalized children with acute respiratory infections in Shenzhen Children’s Hospital from July 2018 to January 2022. Nasopharyngeal swabs were collected and respiratory pathogens were detected using standardized clinical diagnostics as part of routine care. Data were analyzed to describe the effects of COVID-19 prevention procedures on other common pathogens. A total of 56,325 children under 14 years of age were hospitalized with an acute respiratory infection during the study period, 33,909 were tested from July 2018 to January 2020 (pre-lockdown), 1168 from February 2020 to May 2020 (lockdown) and 21,248 from July 2020 to January 2022 (post-lockdown). We observed a 37.3% decline of routine care in respiratory infection associated hospital admission in the 19 months’ post-lockdown vs. the 19 months’ pre-lockdown. There were 99.4%, 16.0% and 1.26% reductions measured for Mycoplasma pneumoniae, influenza virus A and adenovirus, respectively. However, a 118.7% and 75.8% rise was found for respiratory syncytial virus (RSV) and human para-influenza virus (HPIV) during the 19 months’ post-lockdown in comparison to the pre-pandemic period. The detection of RSV especially increased in toddlers after the lockdown. Lockdown measures during the COVID-19 pandemic led to a significant reduction of Mycoplasma pneumoniae, influenza virus A and adenovirus infection. In contrast, RSV and HPIV infection increased.

PULMONARY TB WITH HUMAN PARAINFLUENZA 3 VIRUS PRESENTING AS SEPTIC SHOCK WITH MULTIORGAN SYSTEM FAILURE

SESSION TITLE: Critical Care Presentations of TBSESSION TYPE: Rapid Fire Case ReportsPRESENTED ON: 10/18/2022 12:25 pm - 01:25 pmINTRODUCTION: Septic shock with Multiple Organ System Failure (MOSF) from Mycobacterium tuberculosis (MTB) is an uncommon, yet well-known clinical syndrome with high rate of in-hospital mortality (79.2%). Most Human Parainfluenza Virus (HPIV) in immunocompetent adults are mild or asymptomatic. However, not much is known about MTB co-infection with HPIV causing septic shock with MOSF. To the best of our knowledge, this is the first case of pulmonary MTB with HPIV infection presenting as septic shock with multiorgan failure reported in literature.CASE PRESENTATION: Patient is a 72 yo Spanish speaking male without significant past medical history, visiting from Mexico, who presented to the ED with cough. He was at baseline health until the day prior to the presentation when he noted cough with streaked hemoptysis, nausea, vomiting with fever. While in the ED, patient developed respiratory distress with hypotension, needing intubation, mechanical ventilation and vasopressors. CT of the chest demonstrated extensive right middle and lower lung consolidation, concerning for pneumonia. Respiratory pathogen panel was positive for HPIV, type 3. Pt developed multiorgan failure including renal failure needing CVVH, biventricular heart failure with EF of 15% and shock liver. Sputum culture was positive for MTB. Pt was started on anti-TB treatment with ethambutol, isoniazid, pyrazinamide, and rifampin. He clinically improved and after 2-week course of hospitalization was discharged home with outpatient follow up with Health Department and Infectious disease.DISCUSSION: Septic shock with multiorgan failure from MTB is rare yet known phenomenon with high rate of in-hospital mortality, however, co-infection of MTB with parainfluenza virus is not well described. The role of HPIV infection in causing respiratory tract illness is likely contributing factor making pulmonary MTB infection more complicated that can lead to septic shock with multiorgan failure.CONCLUSIONS: Pulmonary MTB co-infection with HPIV can present with septic shock with multiorgan failure. Further studies are needed to investigate and support significance of HPIV to pulmonary MTB.Reference #1: https://pubmed.ncbi.nlm.nih.gov/23429859/Reference #2: https://pubmed.ncbi.nlm.nih.gov/28283855/DISCLOSURES: No relevant relationships by Dovile BaniulisNo relevant relationships by Dovile CerkauskaiteNo relevant relationships by Momcilo Durdevic SESSION TITLE: Critical Care Presentations of TB SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Septic shock with Multiple Organ System Failure (MOSF) from Mycobacterium tuberculosis (MTB) is an uncommon, yet well-known clinical syndrome with high rate of in-hospital mortality (79.2%). Most Human Parainfluenza Virus (HPIV) in immunocompetent adults are mild or asymptomatic. However, not much is known about MTB co-infection with HPIV causing septic shock with MOSF. To the best of our knowledge, this is the first case of pulmonary MTB with HPIV infection presenting as septic shock with multiorgan failure reported in literature. CASE PRESENTATION: Patient is a 72 yo Spanish speaking male without significant past medical history, visiting from Mexico, who presented to the ED with cough. He was at baseline health until the day prior to the presentation when he noted cough with streaked hemoptysis, nausea, vomiting with fever. While in the ED, patient developed respiratory distress with hypotension, needing intubation, mechanical ventilation and vasopressors. CT of the chest demonstrated extensive right middle and lower lung consolidation, concerning for pneumonia. Respiratory pathogen panel was positive for HPIV, type 3. Pt developed multiorgan failure including renal failure needing CVVH, biventricular heart failure with EF of 15% and shock liver. Sputum culture was positive for MTB. Pt was started on anti-TB treatment with ethambutol, isoniazid, pyrazinamide, and rifampin. He clinically improved and after 2-week course of hospitalization was discharged home with outpatient follow up with Health Department and Infectious disease. DISCUSSION: Septic shock with multiorgan failure from MTB is rare yet known phenomenon with high rate of in-hospital mortality, however, co-infection of MTB with parainfluenza virus is not well described. The role of HPIV infection in causing respiratory tract illness is likely contributing factor making pulmonary MTB infection more complicated that can lead to septic shock with multiorgan failure. CONCLUSIONS: Pulmonary MTB co-infection with HPIV can present with septic shock with multiorgan failure. Further studies are needed to investigate and support significance of HPIV to pulmonary MTB. Reference #1: https://pubmed.ncbi.nlm.nih.gov/23429859/ Reference #2: https://pubmed.ncbi.nlm.nih.gov/28283855/ DISCLOSURES: No relevant relationships by Dovile Baniulis No relevant relationships by Dovile Cerkauskaite No relevant relationships by Momcilo Durdevic

Epicatechin analogues may hinder human parainfluenza virus infection by inhibition of hemagglutinin neuraminidase protein and prevention of cellular entry.

Human parainfluenza viruses (HPIVs) are ( -)ssRNA viruses belonging to Paramyoviridaie family. They are one of the leading causes of mortality in infants and young children and can cause ailments like croup, bronchitis, and pneumonia. Currently, no antiviral medications or vaccines are available to effectively treat parainfluenza. This necessitates the search for a novel and effective treatment. Computer-aided drug design (CADD) methodology can be utilized to discover target-based inhibitors with high accuracy in less time. A library of 45 phytocompounds with immunomodulatory properties was prepared. Thereafter, molecular docking studies were conducted to characterize the binding behavior of ligand in the binding pocket of HPIV3 HN protein. The physicochemical properties for screened compounds were computed, and the top hits from docking studies were further analyzed and validated using molecular dynamics simulation studies using the Desmond module of Schrodinger Suite 2021-1, followed by MM/GBSA analysis. The compounds CID:72276 (1) and CID:107905 (2) emerged as lead compounds of our in silico investigation. Further in vitro studies will be required to prove the efficacy of lead compounds as inhibitors and to determine the exact mechanism of their inhibition. Computational studies predict three natural flavonoids to inhibit the HN protein of HPIV3.

Seasonal epidemiological and clinical characteristics of pediatric patients with human parainfluenza virus infection by serotype: a retrospective study

BackgroundThe development of the polymerase chain reaction (PCR) test promoted the evaluation of the epidemiological and clinical characteristics of human parainfluenza virus (HPIV) type 4, which has been rarely studied using conventional diagnostic methods. This study aimed to determine the seasonal epidemiological and clinical characteristics of all four HPIV serotypes (HPIV-1, HPIV-2, HPIV-3, and HPIV-4) during the era of PCR testing.MethodsThe medical records of hospitalized pediatric patients diagnosed with HPIV infections by a multiplex PCR test between 2015 and 2021 were retrospectively reviewed to determine the seasonal distributions of each HPIV serotype. For patients with a single HPIV infection, the clinical characteristics of each HPIV serotype were evaluated and compared with one another.ResultsAmong the 514 cases of HPIV infection, HPIV-1, HPIV-2, HPIV-3, and HPIV-4 were identified in 27.2%, 11.9%, 42.6%, and 18.3% of cases, respectively. HPIV-3 was most prevalent in spring, and the other three serotypes were most prevalent in autumn. For patients with a single HPIV infection, those infected by HPIV-1 and HPIV-3 were younger than those infected by HPIV-2 and HPIV-4 (P < 0.001). Croup and lower respiratory tract infection (LRI) were most frequently diagnosed in patients infected by HPIV-1 (P < 0.001) and HPIV-4 (P = 0.002), respectively. During 2020–2021, HPIV-3 was most prevalent in autumn and caused fewer LRIs (P = 0.009) and more seizures (P < 0.001) than during 2015–2019.ConclusionsEach HPIV serotype exhibited a distinct seasonal predominance, and some differences in the clinical characteristics of the HPIV serotypes were observed. HPIV-4 acted as an important cause of LRI. Considering the recent changes in the epidemiological and clinical characteristics of HPIV-3, more time-series analyses should be conducted.

Spatial and Spatio-Temporal Distribution of Human Respiratory Syncytial Virus, Human Parainfluenza Virus, and Human Adenoviruses Cases in Kenya 2007-2013.

Human Respiratory Syncytial Virus (HRSV), Human Parainfluenza Virus (HPIV), and Human Adenovirus (HAdV) epidemics differ in geographical location, time, and virus type. Regions prone to infections can be identified using geographic information systems (GIS) and available methods for detecting spatial and time clusters. We sought to find statistically significant spatial and time clusters of HRSV, HPIV, and HAdV cases in different parts of Kenya. To analyse retrospective data, we used a geographical information system (GIS) and the spatial scan statistic. The information was gathered from surveillance sites and aggregated at the county level in order to identify purely spatial and Spatio-temporal clusters. To detect the presence of spatial autocorrelation, the local Moran's I test was used. To detect the spatial clusters of HRSV, HPIV, and HAdV cases, we performed the purely spatial scan statistic. Furthermore, space-time clusters were identified using space-time scan statistics. Both spatial and space-time analyses were based on the discrete Poisson model with a pre-specified statistical significance levelof p<0.05. The findings showed that HRSV, HPIV, and HAdV cases had significant autocorrelation within the study areas. Furthermore, in the Western region of the country, the three respiratory viruses had local clusters with significant positive autocorrelation (p<0.05). Statistically, the Western region had significant spatial clusters of HRSV, HPIV, and HAdV occurrence. Furthermore, the space-time analysis revealed that the HPIV primary cluster persisted in the Western region from 2007 to 2013. However, primary clusters of HRSV and HAdV were observed in the Coastal region in 2009-11 and 2008-09, respectively. Human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), and human adenovirus (HAdV) hotspots (clusters) occurred in Kenya's Western and Coastal regions from 2007 to 2013. The Western region appeared to be more prone to the occurrence of allthree respiratory viruses throughout the study period. Strategic mitigation should focus on these locations to prevent future clusters of HRSV, HPIV, and HAdV infections that could lead to epidemics.

Climate variability and seasonal patterns of paediatric parainfluenza infections in the tropics: An ecological study in Singapore.

Evidence of the relationship between climate variability, air pollution and human parainfluenza virus (HPIV) infections has been inconsistent. We assessed this in a paediatric population from a highly urbanized tropical city-state. We analysed all reports of HPIV infections in children <5 years old obtained from a major specialist women and children's hospital in Singapore. Assuming a negative binomial distribution and using multivariable fractional polynomial modelling, we examined the relations between climate variability, air quality and the risk of HPIV infections, adjusting for time-varying confounders. We identified 6393 laboratory-confirmed HPIV infections from 2009 to 2019. Every 1°C decline in temperature was associated with a 5.8% increase (RR: 0.943, 95% Confidence Interval [95% CI]: 0.903-0.984) in HPIV infection risk 6 days later. Every 10% decrease in relative humidity was associated with a 15.8% cumulative increase in HPIV risk over the next 6 days (cumulative RR: 0.842, 95% CI: 0.771-0.919). Rainfall was positively associated with HPIV risk 2 days later (RR: 1.021, 95% CI: 1.000-1.043). A within-year seasonal rise of HPIV was driven by HPIV-3 and HPIV-1 and preceded by a seasonal decline in temperature. Gender was an effect modifier of the climate-HPIV relationship. Air quality was not associated with HPIV risk. This study demonstrates a close association between HPIV infection risk and tropical climate variability. The climate dependence and seasonal predictability of HPIV can inform the timing of community campaigns aimed at reducing infection risk and the development of hospital resources and climate adaption plans.

Epidemiology of human parainfluenza virus infection in patients with acute respiratory tract infection in Beijing, 2015–2020

Objective To understand the epidemiological characteristics of human parainfluenza virus (HPIV) infection in patients with acute respiratory tract infections (ARIs) in Beijing, and provide support for the development of prevention and control strategies for respiratory infectious diseases. Methods The throat swabs, sputum, bronchoalveolar lavage fluid, tracheal aspirates and other pathogenic samples were collected from the patients with ARIs in 35 sentinel hospitals in Beijing from 2015 to 2020. Multiple real-time PCR was used to detect HPIV-1, HPIV-2, HPIV-3, HPIV-4 and other common respiratory tract viruses. The results were analyzed with SPSS 20.0 and χ2 test was used to compare the rates between groups. Results During 2015–2020, the positive rate of HPIV was 3.90% (1622/41557). HPIV-3 was the mostly detected pathogen, accounting for 58.45%, followed by HPIV-1 (19.17%), HPIV-2 (12.70%) and HPIV-4 (10.79%). The positive rate of HPIV in 2020 (1.65%, 70/4 234) was significantly lower than that during 2015–2019 (4.52%, 1569/37 323). The HPIV infection arte showed a peak every other year. The infection peak of HPIV was from May to July. The incidence trend of HPIV-3 infection was the similar to other HPIVs. The positive rate of HPIV-1 during summer-autumn was higher than that in other seasons. There was no obvious seasonality of HPIV-2 infection. The positive rate of HPIV-4 in autumn was higher than that in other seasons. The positive rate of HPIV in men was lower than that in women. The positive rate in 0–5 years old group was highest (8.81%, 685/7 776), followed by 6–15 years old group (4.07%, 173/4 247), and ≥ 60 years old group (3.25%, 442/13 582). There was significant differences in the positive rate of HPIV-1 and HPIV-3 between upper and lower respiratory tract infection cases ( χ2=4.449, P=0.039; χ2=17.513, P Conclusion HPIV is a common respiratory pathogens in Beijing. The main affecting population of HPIV infection is children under 15 years old. In 2020, the prevention and control of COVID-19 significantly reduced the incidence of HPIV infection.

Virological Surveillance and Molecular Characterization of Human Parainfluenzavirus Infection in Children with Acute Respiratory Illness: Germany, 2015-2019.

Human parainfluenza viruses (HPIVs) are important causes of respiratory illness, especially in young children. However, surveillance for HPIV is rarely performed continuously, and national-level epidemiologic and genetic data are scarce. Within the German sentinel system, to monitor acute respiratory infections (ARI), 4463 respiratory specimens collected from outpatients < 5 years of age between October 2015 and September 2019 were retrospectively screened for HPIV 1–4 using real-time PCR. HPIV was identified in 459 (10%) samples. HPIV-3 was the most common HPIV-type, with 234 detections, followed by HPIV-1 (113), HPIV-4 (61), and HPIV-2 (49). HPIV-3 was more frequently associated with age < 2 years, and HPIV-4 was more frequently associated with pneumonia compared to other HPIV types. HPIV circulation displayed distinct seasonal patterns, which appeared to vary by type. Phylogenetic characterization clustered HPIV-1 in Clades 2 and 3. Reclassification was performed for HPIV-2, provisionally assigning two distinct HPIV-2 groups and six clades, with German HPIV-2s clustering in Clade 2.4. HPIV-3 clustered in C1, C3, C5, and, interestingly, in A. HPIV-4 clustered in Clades 2.1 and 2.2. The results of this study may serve to inform future approaches to diagnose and prevent HPIV infections, which contribute substantially to ARI in young children in Germany.

The landscape of extrapulmonary manifestations of human parainfluenza viruses: A systematic narrative review.

Human parainfluenza virus (HPIV) infection is associated with every kind of respiratory tract illnesses, including the common cold, laryngotracheobronchitis (i.e. croup), tracheobronchitis, bronchiolitis, and pneumonia, in both children and adults. Although HPIVs are common respiratory pathogens, there are increasing reports about extrapulmonary manifestations of HPIVs infection. Each of the HPIVs could produce infection of other organs (central nervous system, heart, myocardium, etc.) in all age groups who are either immunocompetent or immunocompromised. This review aimed at summarizing the available data on clinical manifestations of HPIV infection outside the respiratory tract from 1961 to 2020. The findings support the possibility of extrapulmonary infections that were thought to be due to rare host genetic or immunologic defects in infected patients. These findings highlight the fact that extrapulmonary dissemination of HPIV can occur, but the association is not clearly demonstrated. Our data support the hypothesis that HPIV infection is one of the possible causes of these alterations and may even be the direct cause in some cases.

A review on disease burden and epidemiology of childhood parainfluenza virus infections in Asian countries.

Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory tract infections (ARTIs) in children less than 5 years, second only to human respiratory syncytial viruses (HRSVs). Generally, patients infected with HPIVs are treated in outpatient clinics, yet also contribute to ARTI-associated hospitalization in children. Although HPIV infections are well studied in developed countries, these infections remain under-investigated and not considered in the routine laboratory diagnosis of childhood ARTI in many developing countries in Asia. We performed an extensive literature search on the prevalence, epidemiology, and burden of HPIV infections in children less than 5 years in Asia using PubMed and PubMed Central search engines. Based on the literature, the prevalence of HPIV infection in Asia ranges from 1% to 66%. According to many studies, HPIV-3 is the major virus circulating among children; however, several studies failed to detect HPIV-4 due to unavailability of diagnostic tools. In Asian countries, HPIV contributes a substantial disease burden in children. The data in this review should assist researchers and public health authorities to plan preventive measures, including accelerating research on vaccines and antiviral drugs.

Sequencing and analysis of globally obtained human parainfluenza viruses 1 and 3 genomes.

Human Parainfluenza viruses (HPIV) type 1 and 3 are important causes of respiratory tract infections in young children globally. HPIV infections do not confer complete protective immunity so reinfections occur throughout life. Since no effective vaccine is available for the two virus subtypes, comprehensive understanding of HPIV-1 and HPIV-3 genetic and epidemic features is important for diagnosis, prevention, and treatment of HPIV-1 and HPIV-3 infections. Relatively few whole genome sequences are available for both HPIV-1 and HPIV-3 viruses, so our study sought to provide whole genome sequences from multiple countries to further the understanding of the global diversity of HPIV at a whole-genome level. We collected HPIV-1 and HPIV-3 samples and isolates from Argentina, Australia, France, Mexico, South Africa, Switzerland, and USA from the years 2003–2011 and sequenced the genomes of 40 HPIV-1 and 75 HPIV-3 viruses with Sanger and next-generation sequencing with the Ion Torrent, Illumina, and 454 platforms. Phylogenetic analysis showed that the HPIV-1 genome is evolving at an estimated rate of 4.97 × 10−4 mutations/site/year (95% highest posterior density 4.55 × 10−4 to 5.38 × 10−4) and the HPIV-3 genome is evolving at a similar rate (3.59 × 10−4 mutations/site/year, 95% highest posterior density 3.26 × 10−4 to 3.94 × 10−4). There were multiple genetically distinct lineages of both HPIV-1 and 3 circulating on a global scale. Further surveillance and whole-genome sequencing are greatly needed to better understand the spatial dynamics of these important respiratory viruses in humans.

Inhibiting Human Parainfluenza Virus Infection by Preactivating the Cell Entry Mechanism.

Paramyxoviruses, specifically, the childhood pathogen human parainfluenza virus type 3, are internalized into host cells following fusion between the viral and target cell membranes. The receptor binding protein, hemagglutinin (HA)-neuraminidase (HN), and the fusion protein (F) facilitate viral fusion and entry into the cell through a coordinated process involving HN activation by receptor binding, which triggers conformational changes in the F protein to activate it to reach its fusion-competent state. Interfering with this process through premature activation of the F protein has been shown to be an effective antiviral strategy in vitro. Conformational changes in the F protein leading to adoption of the postfusion form of the protein-prior to receptor engagement of HN at the host cell membrane-render the virus noninfectious. We previously identified a small compound (CSC11) that implements this antiviral strategy through an interaction with HN, causing HN to activate F in an untimely process. To assess the functionality of such compounds, it is necessary to verify that the postfusion state of F has been achieved. As demonstrated by Melero and colleagues, soluble forms of the recombinant postfusion pneumovirus F proteins and of their six helix bundle (6HB) motifs can be used to generate postfusion-specific antibodies. We produced novel anti-HPIV3 F conformation-specific antibodies that can be used to assess the functionality of compounds designed to induce F activation. In this study, using systematic chemical modifications of CSC11, we synthesized a more potent derivative of this compound, CM9. Much like CSC11, CM9 causes premature triggering of the F protein through an interaction with HN prior to receptor engagement, thereby preventing fusion and subsequent infection. In addition to validating the potency of CM9 using plaque reduction, fusion inhibition, and binding avidity assays, we confirmed the transition to a postfusion conformation of F in the presence of CM9 using our novel anti-HPIV3 conformation-specific antibodies. We present both CM9 and these newly characterized postfusion antibodies as novel tools to explore and develop antiviral approaches. In turn, these advances in both our molecular toolset and our understanding of HN-F interaction will support development of more-effective antivirals. Combining the findings described here with our recently described physiologically relevant ex vivo system, we have the potential to inform the development of therapeutics to block viral infection.IMPORTANCE Paramyxoviruses, including human parainfluenza virus type 3, are internalized into host cells by fusion between viral and target cell membranes. The receptor binding protein, hemagglutinin-neuraminidase (HN), and the fusion protein (F) facilitate viral fusion and entry into cells through a process involving HN activation by receptor binding, which triggers conformational changes in F to activate it to reach its fusion-competent state. Interfering with this process through premature activation of the F protein may be an effective antiviral strategy in vitro We identified and optimized small compounds that implement this antiviral strategy through an interaction with HN, causing HN to activate F in an untimely fashion. To address that mechanism, we produced novel anti-HPIV3 F conformation-specific antibodies that can be used to assess the functionality of compounds designed to induce F activation. Both the novel antiviral compounds that we present and these newly characterized postfusion antibodies are novel tools for the exploration and development of antiviral approaches.

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

Background: Human parainfluenza viruses (HPIVs) are significant causes of both upper and lower respiratory tract infections with type 3 (HPIV3) causing the most severe disease in the immunocompromised cohorts. The objective of this study was to analyse the epidemiological nature of a cluster of cases of HPIV3 in a pediatric oncology unit of a major teaching hospital. Methods: In order to determine whether the activity observed represented a deviation from the norm, seasonal trends of HPIV3 in the surrounding geographical area as well as on the ward in question were analysed. The genetic link between cases was established by the phylogenetic analysis of the non-coding hypervariable region between the M (Matrix) and F (fusion) genes of HPIV3. The 15 cases involved and 15 unrelated cases were sequenced. Transmission routes were subsequently inferred and visualized using Konstanz Information Miner (KNIME) 3.3.2. Results: Of the 15 cases identified, 14 were attributed to a point source outbreak. Two out of 14 outbreak cases were found to differ by a single mutation A182C. The outbreak strain was also seen in 1 out of 15 unrelated cases, indicating that it was introduced from the community. Transmission modeling was not able to link all the cases and establish a conclusive chain of transmission. No staff were tested during the outbreak period. No deaths occurred as a result of the outbreak. Conclusion: A point source outbreak of HPIV3 was recognized post factum on an oncology pediatric unit in a major teaching hospital. This raised concern about the possibility of a future more serious outbreak. Weaknesses in existing systems were identified and a new dedicated respiratory virus monitoring system introduced. Pediatric oncology units require sophisticated systems for early identification of potentially life-threatening viral outbreaks.

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.

Background: Human parainfluenza viruses (HPIVs) are significant causes of both upper and lower respiratory tract infections with type 3 (HPIV3) causing the most severe disease in the immunocompromised cohorts. The objective of this study was to analyse the epidemiological nature of a cluster of cases of HPIV3 in a pediatric oncology unit of a major teaching hospital. Methods: In order to determine whether the activity observed represented a deviation from the norm, seasonal trends of HPIV3 in the surrounding geographical area as well as on the ward in question were analysed. The genetic link between cases was established by the phylogenetic analysis of the non-coding hypervariable region between the M (Matrix) and F (fusion) genes of HPIV3. The 15 cases involved and 15 unrelated cases were sequenced. Transmission routes were subsequently inferred and visualized using Konstanz Information Miner (KNIME) 3.3.2. Results: Of the 15 cases identified, 14 were attributed to a point source outbreak. Two out of 14 outbreak cases were found to differ by a single mutation A182C. The outbreak strain was also seen in 1 out of 15 unrelated cases, indicating that it was introduced from the community. Transmission modeling was not able to link all the cases and establish a conclusive chain of transmission. No staff were tested during the outbreak period. No deaths occurred as a result of the outbreak. Conclusion: A point source outbreak of HPIV3 was recognized post factum on an oncology pediatric unit in a major teaching hospital. This raised concern about the possibility of a future more serious outbreak. Weaknesses in existing systems were identified and a new dedicated respiratory virus monitoring system introduced. Pediatric oncology units require sophisticated systems for early identification of potentially life-threatening viral outbreaks.