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

Introduction: 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). Methods: 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. Results: 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. Conclusions: 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.

Design, Synthesis, and Antiviral Evaluation of Sialic Acid Derivatives as Inhibitors of Newcastle Disease Virus Hemagglutinin-Neuraminidase: A Translational Study on Human Parainfluenza Viruses.

Global infections with viruses belonging to the Paramyxoviridae, such as Newcastle disease virus (NDV) or human parainfluenza viruses (hPIVs), pose a serious threat to animal and human health. NDV-HN and hPIVs-HN (HN hemagglutinin-neuraminidase) share a high degree of similarity in catalytic site structures; therefore, the development of an efficient experimental NDV host model (chicken) may be informative for evaluating the efficacy of hPIVs-HN inhibitors. As part of the broad research in pursuit of this goal and as an extension of our published work on antiviral drug development, we report here the biological results obtained with some newly synthesized C4- and C5-substituted 2,3-unsaturated sialic acid derivatives against NDV. All developed compounds showed high neuraminidase inhibitory activity (IC50 0.03-13 µM). Four molecules (9, 10, 23, 24) confirmed their high in vitro inhibitory activity, which caused a significant reduction of NDV infection in Vero cells, accompanied by very low toxicity.

Trends in Hospitalization and Mortality for Influenza and Other Respiratory Viruses during the COVID-19 Pandemic in the United States.

Seasonal epidemics of respiratory viruses, respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses (PIVs), and human metapneumovirus (MPV) are associated with a significant healthcare burden secondary to hundreds of thousands of hospitalizations every year in the United States (US) alone. Preventive measures implemented to reduce the spread of SARS-CoV-2 (COVID-19 infection), including facemasks, hand hygiene, stay-at-home orders, and closure of schools and local/national borders may have impacted the transmission of these respiratory viruses. In this study, we looked at the hospitalization and mortality trends for various respiratory viral infections from January 2017 to December 2020. We found a strong reduction in all viral respiratory infections, with the lowest admission rates and mortality in the last season (2020) compared to the corresponding months from the past three years (2017-2019). This study highlights the importance of public health interventions implemented during the COVID-19 pandemic, which had far-reaching public health benefits. Appropriate and timely use of these measures may help to reduce the severity of future seasonal respiratory viral outbreaks as well as their burden on already strained healthcare systems.

Parainfluenza viruses: A trigger for type 1 diabetes new onset?

Type 1 diabetes (T1DM) ethiopathogenesis is still being studied, since the role of environmental factors , especially viruses, is not yet clear. This study was conducted on 31 paediatric patients with T1DM at onset. We analysed: Coxsackieviruses A (CoxA), Coxsackieviruses B (CoxB), Echoviruses (Echo); Influenzavirus A and B (IV-A and IV-B); Adenovirus (AdV); Parainfluenza viruses 1-2 and 3 (PiV 1-2-3); Cytomegalovirus (CMV) and Respiratory Syncytial Virus (RSV). Enteroviruses, especially CoxB and Echo, are most represented. Unexpectedly, Parainfluenza viruses were detected in seasonal subgroups, with peaks in autumn and spring, and spread homogeneously in different age groups.

Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City.

BACKGROUND: Although the burden of influenza is well characterized, the burden of community-onset non-influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non-influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines. METHODS: From October 2017 to September 2019, a retrospective study was performed in a pre-defined catchment area to estimate the population-based incidence of community-onset respiratory viruses associated with hospitalization. Included patients were ≥18 years old, resided in New York City, were hospitalized for ≥24 hours, and had a respiratory virus detected within 3 calendar-days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in-hospital mortality and compared among those with laboratory-confirmed influenza versus those with laboratory-confirmed non-influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus). RESULTS: During the study period, 4232 eligible patients were identified of whom 50.9% were ≥65 years of age. For each virus, the population-based incidence was highest for those ≥80 years of age. When compared to those with influenza viruses detected, those with non-influenza respiratory viruses detected (combined) had higher population-based incidence, significantly more ICU admissions, and higher in-house mortality. CONCLUSIONS: The burden of non-influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non-influenza respiratory viruses, particularly for older adults.

Epidemiology and seasonality of human parainfluenza serotypes 1-3 in Australian children.

BACKGROUND: Parainfluenza viruses are significant contributors to childhood respiratory illness worldwide, although detailed epidemiological studies are lacking. Few recent Australian studies have investigated serotype-specific PIV epidemiology, and there is a paucity of southern hemisphere PIV reports. We report age-stratified PIV hospitalisation rates and a mathematical model of PIV seasonality and dynamics in Western Australia (WA). METHODS: We used linked perinatal, hospital admission and laboratory diagnostic data of 469 589 children born in WA between 1996 and 2012. Age-specific rates of viral testing and PIV detection in hospitalised children were determined using person time-at-risk analysis. PIV seasonality was modelled using a compartmental SEIRS model and complex demodulation methods. RESULTS: From 2000 to 2012, 9% (n = 43 627) of hospitalised children underwent PIV testing, of which 5% (n = 2218) were positive for PIV-1, 2 or 3. The highest incidence was in children aged 1-5 months (PIV-1:62.6 per 100 000 child-years, PIV-2:26.3/100 000, PIV-3:256/100 000), and hospitalisation rates were three times higher for Aboriginal children compared with non-Aboriginal children overall (IRR: 2.93). PIV-1 peaked in the autumn of even-numbered years, and PIV-3 annually in the spring, whereas PIV-2 had inconsistent peak timing. Fitting models to the higher incidence serotypes estimated reproduction numbers of 1.24 (PIV-1) and 1.72 (PIV-3). CONCLUSION: PIV-1 and 3 are significant contributors towards infant respiratory hospitalisations. Interventions should prioritise children in the first 6 months of life, with respect to the observed autumn PIV-1 and spring PIV-3 activity peaks. Continued surveillance of all serotypes and investigation into PIV-1 and 3 interventions should be prioritised.

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.

Clinical and epidemiological characteristics of human parainfluenza virus infections of children in southern Taiwan.

BACKGROUND: Human parainfluenza viruses (HPIV) 1-4 had been analyzed as being one of the most frequent causes of hospitalizations for young children with respiratory tract illnesses. METHODS: This retrospective study was performed from children virologically confirmed as HPIV infection through throat swab or nasopharyngeal aspirates at a tertiary care university hospital, between January 2012 and December 2014. HPIV4 was not checked and analyzed, due to not include in the commercial kit. The demographic, epidemiological, clinical presentations, diagnosis, treatment, outcomes, and laboratory data were analyzed. RESULTS: Totally 398 cases were enrolled, including 39 (9.8%) of HPIV1, 67 (16.8%) of HPIV2, and 292 (73.4%) of HPIV3. The mean age of HPIV-infected children was 2.9 year-old, and 50.5% were among one to three year-old. A total of 56.8% HPIV3-infected children were among one to three years old, however, no HPIV2-infected children was younger than one year-old. The HPIV1-infected patients were more common to develop wheezing and diagnose as acute bronchiolitis. HPIV2-infected children were more likely to have hoarseness (23.9%), and were associated with croup (25.4%). HPIV3 was isolated from two fatal cases, with neurological underlying diseases. CONCLUSION: The impact caused by HPIVs infections is significant in hospitalized children. In the current study, our results contribute to the epidemiologic, clinical and laboratory information of HPIV infection in children in the important areas of respiratory tract infection that could support the development of optimization management.

The Role of Human Parainfluenza Virus Infections in the Immunopathology of the Respiratory Tract.

Viral infections are leading causes of both upper and lower airway acute illness in all age groups of healthy persons, and have also been implicated in the acute exacerbations of chronic respiratory disorders like asthma and COPD. Human rhinovirus, respiratory syncytial virus, influenza virus and coronavirus have been considered as the most important respiratory pathogens and relatively little attention has been paid to the role of parainfluenza viruses (hPIVs). Human parainfluenza viruses are single-stranded RNA viruses belonging to the paramyxovirus family that may evoke lower respiratory infections in infants, children and immunocompromised individuals. Among non-immune compromised adults, hPIV infection typically causes mild disease manifested as upper respiratory tract symptoms and is infrequently associated with severe croup or pneumonia. Moreover, hPIV infection may be associated with viral exacerbations of chronic airway diseases, asthma or COPD or chronic rhinosinusitis. In this review, we summarized the basic epidemiology and immunology of hPIVs and addressed the more recent data implicating the role of parainfluenza viruses in the exacerbation of chronic airway disorders.

The potential influence of human parainfluenza viruses detected during hospitalization among critically ill patients in Kuwait, 2013-2015.

BACKGROUND: The four types of human parainfluenza viruses (PIV) are important causes of community-acquired pneumonia, particularly in children; however, limited information exists about the incidence of PIV in critically ill patients. The aim of this study is to describe the spectrum, incidence and clinical features of PIV-associated infections diagnosed during the hospital stay of patients admitted to pediatric intensive care unit (PICU) and intensive care unit (ICU) of 5 medical centers across Kuwait. METHODS: This was a population-based, retrospective study from 2013 to 2015. Specimens were analyzed by molecular methods. This analysis was performed using the database of Virology Unit, Mubarak Al-Kabeer Hospital. Data from 1510 admitted patients with suspected respiratory viral infections was extracted. RESULTS: The database contained a total of 39 (2.6%) patients infected with PIV (53.8% male and 46.2% females) and 20 (51.3%) were under 1 year of age. The most frequently isolated type was type 3 (28, 71.8%) followed by type 1 (9, 23.1%). At admission the most common clinical diagnosis was pneumonia in 12 patients (30.8%, p < 0.05) followed by bronchiolitis in 10 patients (25.6%). CONCLUSION: PIV plays an important yet unrecognized role in the outcomes of PIUC and ICU patients. Our results contribute to the limited epidemiologic data of PIV in PIUC and ICU in this region.

Viral influenza-like illnesses: dynamic interrelationships during the 2015-2016 influenza season in hospitalized patients.

In hospitalized children and adults, the temporal relationship of viruses causing influenza-like illnesses (ILIs) and influenza has not been well described. During the 2015-2016 influenza season at our hospital, the dynamic interrelationships between ILI viruses (human metapneumovirus, respiratory syncytial virus, human parainfluenza viruses 3 and 4, rhinoviruses/enteroviruses, and coronaviruses) and influenza A were characterized in 768 hospitalized children and adults.

Distribution and Trends of Human Parainfluenza Viruses in Hospitalised Children.

OBJECTIVE: To study the distribution of Human Parainfluenza viruses (HPIV) 1-4 and their trends in children ≤5 y of age, hospitalised at a tertiary care centre, Jaipur and co-infection with other respiratory viruses. METHODS: Nasopharyngeal aspirate and throat swabs were collected and processed for extraction of nucleic acid using automated extraction system and real time RT-PCR was performed using primers and probes specific to HPIV 1-4 and other respiratory viruses on 743 samples. RESULTS: Total positivity for Parainfluenza viruses 1-4 was found to be 69/743 (9.28 %), of which 50/533 (9.38 %) were boys and 19/210 (9.05 %) girls. Predominance of HPIV- 3 was observed [41/743 (5.52%)] followed by HPIV-1 in 13/743 (1.75%), HPIV-4 in 10/743 (1.34%) and HPIV-2 in 5/743 (0.67%) patients. Maximum positivity was observed in age group 25-36 mo (12.98%) followed by 13-24 mo group (11.96%). HPIVs were found to be circulating round the year and each year. Co-infections with other respiratory viruses were observed in 22/69 (31.88%) of HPIV positive patients. CONCLUSIONS: All the four types of HPIV were found to be circulating in the index population during all the three years, predominantly during post monsoon and winter seasons. HPIV vaccination should be targeted for all types.

An anti-interferon activity shared by paramyxovirus C proteins: inhibition of Toll-like receptor 7/9-dependent alpha interferon induction.

Paramyxovirus C protein targets the host interferon (IFN) system for virus immune evasion. To identify its unknown anti-IFN activity, we examined the effect of Sendai virus C protein on activation of the IFN-α promoter via various signaling pathways. This study uncovers a novel ability of C protein to block Toll-like receptor (TLR) 7- and TLR9-dependent IFN-α induction, which is specific to plasmacytoid dendritic cells. C protein interacts with a serine/threonine kinase IKKα and inhibits phosphorylation of IRF7. This anti-IFN activity of C protein is shared across genera of the Paramyxovirinae, and thus appears to play an important role in paramyxovirus immune evasion.

Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model.

DAS181 is a novel drug in development for the treatment of influenza as well as human parainfluenza viruses (hPIVs). Previous studies demonstrated that DAS181 inhibited laboratory strains of hPIV, but no tests were conducted with primary clinical isolates of hPIV. To fill this gap, we studied six primary isolates including hPIV-2 and hPIV-3. First tests showed that the amplification of all viruses in vitro was reproducibly inhibited with DAS181 drug concentrations ranging between 0.1 and 1nM. An hPIV-3 primary clinical isolate was then tested in a cotton rat model for sensitivity to 0.3-1mg/kg drug treatments. Results showed that virus amplification in the lower respiratory tract was significantly and reproducibly inhibited by drug. Together, experiments demonstrated that DAS181 inhibited primary clinical isolates of hPIV in vitro and in vivo at doses similar to those previously described for inhibition of laboratory hPIV and influenza virus isolates.

Comparación de la línea NCI-H292 con otras líneas continuas para la multiplicación de virus respiratorios

La línea continua NCI-H292 de células mucoepidermoides de pulmón humano ha sido reportada ser de utilidad para la propagación de muchos virus, principalmente Adenovirus y Paramyxovirus. Se plantea la posible sustitución de cultivos primarios de riñón de mono por NCI-H292 para el aislamiento de dichos agentes. En el presente trabajo se evalúa la utilidad de esta nueva línea para la multiplicación de los virus sincitial respiratorio, Adenovirus 3 y 7 y los virus parainfluenza 1, 2 y 3 en comparación con las líneas celulares continuas utilizadas tradicionalmente para la propagación de éstos; para lo cual se inocularon cepas de los virus en cuestión en las líneas Vero, HEp-2 y HeLa, según sus sensibilidades conocidas, y en NCI-H292 paralelamente. La multiplicación viral se detectó por aparición de efecto citopático o por hemadsorción. Como resultado se corroboró la capacidad de multiplicación de la línea NCI-H292 para los Adenovirus 3 y 7 y el parainfluenza 3, siendo más útil para la multiplicación de éstos que las líneas tradicionalmente usadas.

The NCI-H292 continual line of mucoepidermoid cells of the human lungs has been reported to be useful for the propagation of many viruses, mainly Adenovirus and Paraxymovirus. It is stated the possible substitution of primary cultures of monkey kidney for NCI-H292 in order to isolate such agents. In the present paper it is evaluated the utility of this line for multiplying the respiratory syncytial viruses Adenovirus 3 and 7, and the parainfluenza viruses 1, 2, and 3, in comparison with the continual cellular lines traditionally used for the propagation of these viruses, whose strains were inoculated this time in the Vero, HEp-2, and HeLa lines, according to their know sensitivities as well as in NCI-H292 simultaneously. The viral multiplication was detected by the appareance of the cytopathic effect or by hemaadsorption. As a result, it was demostrated the multiplication capacity of the NCI-H292 line for Adenoviruses 3 and 7 and parainfluenza 3, being more useful for their multiplication than the tradicionally used lines.