Molecular epidemiology of a Parainfluenza Type 3 virus outbreak: Informing infection control measures on adult hematology wards.

OBJECTIVES: Parainfluenza virus type 3 (PIV3) outbreaks among hematology patients are associated with high morbidity and mortality. Prompt implementation of infection prevention (IP) measures has proven to be the most efficacious approach for controlling PIV3 outbreaks within this patient population. The most suitable IP measures can vary depending on the mode of virus transmission, which remains unidentified in most outbreaks. We describe the molecular epidemiology of an outbreak of PIV3 among hematology patients and the development of a new method that allows for the differentiation of outbreak and community strains, from which a closed outbreak could be inferred. METHODS: Patients were screened for respiratory viruses using multiplex-PCR. PIV3 positive samples with a cycle threshold (Ct)-value of <31 underwent a retrospective characterization via an in-house developed sequence analysis of the hemagglutinin-neuraminidase (HN) gene. RESULTS: Between July and September 2022, 31 hematology patients were identified with PIV3. Although infection control measures were implemented, the outbreak persisted for nine weeks. Sequencing the HN gene of 27 PIV3 strains from 27 patients revealed that all outbreak strains formed a distinct cluster separate from the control strains, suggestive of a nosocomial transmission route. CONCLUSIONS: Sequencing the HN gene of PIV3 strains in an outbreak setting enables outbreak strains to be distinguished from community strains. Early molecular characterization of PIV3 strains during an outbreak can serve as a tool in determining potential transmission routes. This, in turn, enables rapid implementation of targeted infection prevention measures, with the goal of minimizing the outbreak's duration and reducing associated morbidity and mortality.

Phylogenetic lineage dynamics of global parainfluenza virus type 3 post-COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks of parainfluenza virus type 3 (PIV-3) decreased due to infection control measures. However, a post-pandemic resurgence of PIV-3 has recently been observed. Nonetheless, the role of viral genetic epidemiology, possibly influenced by a genetic bottleneck effect, remains unexplored. We investigated the phylogenetic structure of the publicly available PIV-3 whole-genome and hemagglutinin-neuraminidase (HN) gene sequences spanning the last 65 years, including the COVID-19 pandemic. Sequences were retrieved from the nucleotide database of the National Center for Biotechnology Information using the search term "Human respirovirus 3." Sequence subsets covering all six genes of PIV-3 or the HN gene were designated as the whole-genome and HN surveillance data sets, respectively. Using these data sets, we constructed maximum-likelihood phylogenetic trees and performed a time-scaled analysis using a Bayesian SkyGrid coalescent prior. A total of 455 whole-genome and 1,139 HN gene sequences were extracted, revealing 10 and 11 distinct lineages, respectively, with >98% concurrence in lineage assignments. During the 2020 COVID-19 pandemic, only three single-lineage clusters were identified in Japan, Korea, and the USA. The inferred year of origin for PIV-3 was 1938 (1903-1963) for the whole-genome data set and 1955 (1930-1963) for the HN gene data set. Our study suggests that PIV-3 epidemics in the post-COVID era are likely influenced by a pandemic-driven bottleneck phenomenon and supports previous hypotheses suggesting s that PIV-3 originated during the early half of the 20th century.IMPORTANCEUsing publicly available parainfluenza virus type 3 (PIV-3) whole-genome sequences, we estimated that PIV-3 originated during the 1930s, consistent with previous hypotheses. Lineage typing and time-scaled phylogenetic analysis revealed that PIV-3 experienced a bottleneck phenomenon in Korea and the USA during the coronavirus disease 2019 pandemic. We identified the conservative hemagglutinin-neuraminidase gene as a viable alternative marker in long-term epidemiological studies of PIV-3 when whole-genome analysis is limited.

Emergence of swine influenza A virus, porcine respirovirus 1 and swine orthopneumovirus in porcine respiratory disease in Germany.

Respiratory disease is a significant economic issue in pig farming, with a complex aetiology that includes swine influenza A viruses (swIAV), which are common in European domestic pig populations. The most recent human influenza pandemic in 2009 showed swIAV's zoonotic potential. Monitoring pathogens and disease control are critical from a preventive standpoint, and are based on quick, sensitive, and specific diagnostic assays capable of detecting and distinguishing currently circulating swIAV in clinical samples. For passive surveillance, a set of multiplex quantitative reverse transcription real-time PCRs (mRT-qPCR) and MinION-directed sequencing was updated and deployed. Several lineages and genotypes of swIAV were shown to be dynamically developing, including novel reassortants between human pandemic H1N1 and the avian-derived H1 lineage of swIAV. Despite this, nearly 70% (842/1216) of individual samples from pigs with respiratory symptoms were swIAV-negative, hinting to different aetiologies. The complex and synergistic interactions of swIAV infections with other viral and bacterial infectious agents contribute to the aggravation of pig respiratory diseases. Using a newly developed mRT-qPCR for the combined detection of swIAV and the recently described porcine respirovirus 1 (PRV1) and swine orthopneumovirus (SOV) widespread co-circulation of PRV1 (19.6%, 238/1216 samples) and SOV (14.2%, 173/1216 samples) was evident. Because of the high incidence of PRV1 and SOV infections in pigs with respiratory disease, these viruses may emerge as new allies in the porcine respiratory disease syndrome.

Human parainfluenza virus type 3 infections in a haemato-oncology unit: social distancing measures needed in outpatient clinics.

BACKGROUND: Human parainfluenza virus type 3 (HPIV3) infections are associated with high mortality in immunocompromised settings, especially in bone marrow transplant recipients. Asymptomatic infection and lack of effective antiviral treatment makes HPIV3 prevention and treatment a real challenge. AIM: To retrospectively investigate the epidemiological characteristics, clinical characteristics and outcomes of 51 haematology patients with confirmed HPIV3 infections, detected between February and May 2019 in the haematology unit at King's College Hospital, London. METHODS: Between February and May 2019, HPIV3 RNA was detected in combined nose and throat swab samples collected from 51 symptomatic haematology patients, 41 of whom attended the haematology outpatient unit. Clinical data were reviewed retrospectively and a timeline of patients' appointments drawn up to investigate transmission. Sequencing analysis was performed on 14 stored samples. FINDINGS: Fifty-one patients were identified with HPIV3 infection. Mean age was 54 years (SD: 12; range: 19-72) and 60% (31/51) were male. There were 41 (80%) bone marrow transplant recipients, 24 had an allograft, and 17 an autograft. Thirty-day and 3-month mortality post HPIV3 was 6% and 14%, respectively. Lower respiratory tract infection and inpatient acquisition were associated with higher mortality (6/7 vs 1/7, P = 0.010; and 5/7 vs 2/7, P = 0.031). Onset of HPIV3 infection in patients within 6 days of attending the clinic was associated with the clusters identified in phylogenetic analysis (64% (9/14) vs 21% (8/37); odds ratio: 6.5 (confidence interval: 95% 1.7-25); P = 0.006). CONCLUSION: Timelines suggested community transmission, but also possible transmission patterns within the outpatients and subsequent nosocomial transmission within the same ward. Early recognition of HPIV3 infection and the use of polymerase chain reaction and sequence analysis is fundamental in identifying respiratory virus outbreaks and person-to-person transmission. Careful planning of outpatient clinic attendance is required to minimize contact and prevent respiratory virus transmission in immunosuppressed patients.

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.

Pathogenicity and transmissibility of a novel respirovirus isolated from a Malayan pangolin.

The identification of SARS-CoV-2-like viruses in Malayan pangolins (Manis javanica) has focused attention on these endangered animals and the viruses they carry. We successfully isolated a novel respirovirus from the lungs of a dead Malayan pangolin. Similar to murine respirovirus, the full-length genome of this novel virus was 15 384 nucleotides comprising six genes in the order 3'-(leader)-NP-P-M-F-HN-l-(trailer)-5'. Phylogenetic analysis revealed that this virus belongs to the genus Respirovirus and is most closely related to murine respirovirus. Notably, animal infection experiments indicated that the pangolin virus is highly pathogenic and transmissible in mice, with inoculated mice having variable clinical symptoms and a fatality rate of 70.37 %. The virus was found to replicate in most tissues with the exception of muscle and heart. Contact transmission of the virus was 100 % efficient, although the mice in the contact group displayed milder symptoms, with the virus mainly being detected in the trachea and lungs. The isolation of a novel respirovirus from the Malayan pangolin provides new insight into the evolution and distribution of this important group of viruses and again demonstrates the potential infectious disease threats faced by endangered pangolins.

Prevalence of human respiratory syncytial virus, parainfluenza and adenoviruses in East Africa Community partner states of Kenya, Tanzania, and Uganda: A systematic review and meta-analysis (2007-2020).

BACKGROUND: Viruses are responsible for a large proportion of acute respiratory tract infections (ARTIs). Human influenza, parainfluenza, respiratory-syncytial-virus, and adenoviruses are among the leading cause of ARTIs. Epidemiological evidence of those respiratory viruses is limited in the East Africa Community (EAC) region. This review sought to identify the prevalence of respiratory syncytial virus, parainfluenza, and adenoviruses among cases of ARTI in the EAC from 2007 to 2020. METHODS: A literature search was conducted in Medline, Global Index Medicus, and the grey literature from public health institutions and programs in the EAC. Two independent reviewers performed data extraction. We used a random effects model to pool the prevalence estimate across studies. We assessed heterogeneity with the I2 statistic, and Cochran's Q test, and further we did subgroup analysis. This review was registered with PROSPERO under registration number CRD42018110186. RESULTS: A total of 12 studies met the eligibility criteria for the studies documented from 2007 to 2020. The overall pooled prevalence of adenoviruses was 13% (95% confidence interval [CI]: 6-21, N = 28829), respiratory syncytial virus 11% (95% CI: 7-15, N = 22627), and parainfluenza was 9% (95% CI: 7-11, N = 28363). Pooled prevalence of reported ARTIs, all ages, and locality varied in the included studies. Studies among participants with severe acute respiratory disease had a higher pooled prevalence of all the three viruses. Considerable heterogeneity was noted overall and in subgroup analysis. CONCLUSION: Our findings indicate that human adenoviruses, respiratory syncytial virus and parainfluenza virus are prevalent in Kenya, Tanzania, and Uganda. These three respiratory viruses contribute substantially to ARTIs in the EAC, particularly among those with severe disease and those aged five and above.

Dynamics of nosocomial parainfluenza virus type 3 and influenza virus infections at a large German University Hospital between 2012 and 2019.

Nosocomial virus infections cause significant morbidity and mortality. Besides influenza viruses, the disease burden of parainfluenza virus type 3 (PIV-3) is comparatively high among hospitalized patients and severe disease courses can occur. PIV-3 showed the highest rates of nosocomial infections of a panel of respiratory viruses. Therefore, a retrospective observational study was conducted among patients with either PIV-3 or influenza viruses, which served as reference pathogen. The aim was to compare the seasonal dynamics and clinical characteristics of nosocomial infections with these highly transmittable viruses. Nosocomial infection occurred in 15.8% (n = 177) of all influenza cases, mainly in the first half of a season. About 24.3% (n = 104) of the PIV-3 cases were nosocomial and occurred mainly in the second half of a season. Both nosocomial rates of influenza and nosocomial rates of PIV-3 varied between the seasons. Community acquired and nosocomial cases differed in underlying medical conditions and immunosuppression. Knowledge of the baseline rates of nosocomial infections could contribute to the implementation of appropriate infection control measures.

Phylogenetic and antigenic analysis of bovine parainfluenza virus type 3 isolated in Japan between 2002 and 2019.

Bovine parainfluenza virus type 3 (BPIV3) is one of the most important viral respiratory pathogens of cattle. In addition to the classical BPIV3 genotype A (BPIV3a), new genetic groups, genotype B (BPIV3b) and C (BPIV3c), have been identified and isolated in certain parts of the world. The present study aimed to investigate the genetic and antigenic characteristics of BPIV3 circulating in Japan. Seventy-three BPIV3 field strains were isolated from nasal samples of cattle between 2002 and 2019. Phylogenetic analysis of the phosphoprotein and hemagglutinin-neuraminidase genes showed that the isolates clustered into two genotypes, BPIV3a (49 %) and BPIV3c (51 %). The BPIV3a strains had more wide genetic variation than the rest of the genotypes. Additionally, new variants were obtained and designated them tentatively as subgroup 4 of the BPIV3a. The first Japanese BPIV3c was isolated in 2012, but here the BPIV3c NM2 strain was isolated from a sample collected four years earlier than the previous report. The antigenicity of ten BPIV3 strains including all three genotypes was assessed with a viral cross-neutralization test. Anti-sera against BPIV3a and BPIV3b cross-reacted well with both homologous and heterologous viruses. On the other hand, anti-sera against BPIV3c had reduced cross-reactivity to the heterologous viruses. Overall, our findings showed that genetically and antigenically divergent BPIV3 is prevalent in cattle in Japan. These results could provide a reference for molecular epidemiological characterization of BPIV3 and vaccine development.

Human coronavirus OC43 and other respiratory viruses from acute respiratory infections of Egyptian children.

Respiratory infections have a significant impact on health worldwide. Viruses are major causes of acute respiratory infections among children. Limited information regarding its prevalence in Egypt is available. This study investigated prevalence of 10 respiratory viruses; Adenovirus, influenza A, B, respiratory syncytial virus (RSV), Parainfluenza virus (PIV)type 1-4, enterovirus, and human coronavirus OC43 (HCoV-OC43) among children in Alexandria, Egypt presenting with acute lower respiratory tract infections.The study was conducted on children <14 years of age selected from ElShatby Pediatric Hospital, Alexandria University, Egypt. One hundred children presenting during winter season with influenza-like illness were eligible for the study. Oropharyngeal swabs were collected and subjected to viral RNA and DNA extraction followed by polymerase chain reaction.Viral infections were detected in 44% of cases. Adenovirus was the most common, it was found in 19% of the patients. Prevalence of PIV (3 and 4) and enterovirus was 7% each. Prevalence of RSV and HCoV-OC43 was 5% and 3% respectively. Two percentage were Influenza A positive and 1% positive for influenza B. Mixed viral infection was observed in 7%.To the best of our knowledge, this is the first report of the isolation of HCoV-OC43 from respiratory infections in Alexandria, Egypt.

Human parainfluenza virus circulation, United States, 2011-2019.

BACKGROUND: Human parainfluenza viruses (HPIVs) cause upper and lower respiratory tract illnesses, most frequently among infants and young children, but also in the elderly. While seasonal patterns of HPIV types 1-3 have been described, less is known about national patterns of HPIV-4 circulation. OBJECTIVES: To describe patterns of HPIVs circulation in the United States (US). STUDY DESIGN: We used data from the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary passive laboratory-based surveillance system, to characterize the epidemiology and circulation patterns of HPIVs in the US during 2011-2019. We summarized the number of weekly aggregated HPIV detections nationally and by US census region, and used a subset of data submitted to NREVSS from public health laboratories and several clinical laboratories during 2015-2019 to analyze differences in patient demographics. RESULTS: During July 2011 - June 2019, 2,700,135 HPIV tests were reported; 122,852 (5 %) were positive for any HPIV including 22,446 for HPIV-1 (18 %), 17,474 for HPIV-2 (14 %), 67,649 for HPIV-3 (55 %), and 15,283 for HPIV-4 (13 %). HPIV testing increased substantially each year. The majority of detections occurred in children aged ≤ 2 years (36 %) with fluctuations in the distribution of age by type. CONCLUSIONS: HPIVs were detected year-round during 2011-2019, with type-specific year-to-year variations in circulation patterns. Among HPIV detections where age was known, the majority were aged ≤ 2 years. HPIV-4 exhibited an annual fall-winter seasonality, both nationally and regionally. Continued surveillance is needed to better understand national patterns of HPIV circulation.

Assessing exhibition swine as potential disseminators of infectious disease through the detection of five respiratory pathogens at agricultural exhibitions.

Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.

Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China.

BACKGROUND: No comparison data have been reported on viral and epidemiological profiles of hospitalized children with severe acute respiratory infection (SARI) in Beijing or Shanghai, China. METHODS: We collected 700 nasopharyngeal aspirates (NPA) from hospitalized children with SARI in Beijing (northern China) and Shanghai (southern China). Multiple respiratory viruses (including 15 common viruses) were screened by validated polymerase chain reaction (PCR) or real-time reverse transcription-PCR assays and confirmed by sequencing. Demographic data and the distribution of viral infections were also examined. RESULTS: Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1-3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai. CONCLUSIONS: Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.

Molecular epidemiology of an outbreak of human parainfluenza virus 3 among oncology patients.

A hospital outbreak of human parainfluenza virus type 3 (HPIV-3) in haematologic oncology patients is described in 12 patients over a four-week period. Exposure histories and molecular analysis of HPIV-3 isolates suggest that both community-acquired and nosocomially transmitted infections occurred during this outbreak. Molecular analysis of HPIV-3 isolates indicated that a chain of transmission occurred among multiple patients in an oncology ward. This transmission was later determined to be associated with the movement of fomites, visitors, and activities in the unit. The infection prevention team stopped nosocomial spread of HPIV-3 through interventions including advanced cleaning procedures.

Epidemiological investigation and phylogenetic analysis of caprine parainfluenza virus type 3 in sheep of China.

Caprine parainfluenza virus type 3 (CPIV3) is a new member of the Respirovirus genus in the Paramyxivirudae family, mainly causing respiratory disease. Up to now, accumulating evidence has focused on CPIV3 infection in goats, with little understood about its epidemiology in sheep. To that end, we collected 1,163 sheep sera samples from nine provinces/autonomous regions in 2012 and 1,863 samples from six provinces/autonomous regions during 2016-2017, with serological prevalence of 50.3% (95% CI: 47.5, 53.3) and 64.9% (95% CI: 62.9, 67.2), respectively. Pathogenic detection by qRT-PCR was also performed on serum samples collected in 2016-2017, and the percentage of CPIV3 positive samples was 21.5% (95% CI: 19.7, 23.5). Sequence alignment and phylogenetic analyses revealed 11 novel CPIV3 strains based on the M gene sequences. The M gene and full-length sequences of CPIV3 strains derived from sheep shared high nucleotide similarity with goat-origin strains, indicating conserved genome characteristics between the viruses. Furthermore, sequence evolution and epidemiological analysis show that CPIV3 is widespread throughout China. This is the first report describing CPIV3 infection in sheep in China, showing a high sero-prevalence and contributes to the assessment of the epidemiology of CPIV3 in China.

Respiratory Pathogens in Infants Diagnosed with Acute Lower Respiratory Tract Infection in a Tertiary Care Hospital of Western India Using Multiplex Real Time PCR.

OBJECTIVE: To determine the frequency of respiratory pathogens in infants diagnosed with acute lower respiratory tract infections. METHODS: A prospective cross-sectional observational study was conducted in infants hospitalized with a diagnosis of acute lower respiratory tract infection (ALRTI), in a tertiary care hospital in a metropolitan city of Western India. Nasopharyngeal swabs were analyzed by multiplex real time polymerase chain reaction, for 18 viruses and 3 bacteria (H. influenzae type b, C. pneumoniae and M. pneumoniae). The entire data was entered in Microsoft excel sheet and frequencies were determined. RESULTS: One hundred eligible infants were enrolled. Pathogens were detected in 82 samples, which included Respiratory syncytial viruses (RSV) A / B (35.4%), Human rhinovirus (25.6%), Adenovirus (22%), Human Parainfluenza viruses (11%), Human bocavirus (9.8), Human metapneumovirus A / B (8.5%), Influenza A (H1N1) pdm 09 (6.1%), Parechovirus (3.7%), Human coronaviruses (3.66%), Haemophilus influenzae type b (6.1%), Chlamydia pneumoniae (2.4%) and Mycoplasma pneumoniae (2.4%). Influenza A (other than H1N1), Influenza B, Human Coronavirus 229E and Enterovirus were not detected. The rate of coinfection was 34% and rhinovirus was the most common of the multiple pathogens. CONCLUSIONS: Spectrum of viral etiologies of ALRTI is highlighted. Etiological diagnosis of ALRTI would enable specific antiviral therapy, restrict antibiotic use and help in knowing burden of disease.

Identfication of viral and bacterial etiologic agents of the pertussis-like syndrome in children under 5 years old hospitalized.

BACKGROUND: Acute respiratory infections (ARIs) represent an important cause of morbidity and mortality in children, remaining a major public health concern, especially affecting children under 5 years old from low-income countries. Unfortunately, information regarding their epidemiology is still limited in Peru. METHODS: A secondary data analysis was performed from a previous cross-sectional study conducted in children with a probable diagnosis of Pertussis from January 2010 to July 2012. All samples were analyzed via Polymerase Chain Reaction (PCR) for the following etiologies: Influenza-A, Influenza-B, RSV-A, RSV-B, Adenovirus, Parainfluenza 1 virus, Parainfluenza 2 virus, Parainfluenza 3 virus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 288 patients were included. The most common pathogen isolated was Adenovirus (49%), followed by Bordetella pertussis (41%) from our previous investigation, the most prevelant microorganisms were Mycoplasma pneumonia (26%) and Influenza-B (19.8%). Coinfections were reported in 58% of samples and the most common association was found between B. pertussis and Adenovirus (12.2%). CONCLUSIONS: There was a high prevalence of Adenovirus, Mycoplasma pneumoniae and other etiologies in patients with a probable diagnosis of pertussis. Despite the presence of persistent cough lasting at least two weeks and other clinical characteristics highly suspicious of pertussis, secondary etiologies should be considered in children under 5 years-old in order to give a proper treatment.

Characterization of human parainfluenza virus-3 circulating in Israel, 2012-2015.

BACKGROUND: Human parainfluenza virus 3 (hPIV-3) causes respiratory tract infection. OBJECTIVES: The objective of this study was to describe the epidemiology of hPIV-3 infection among hospitalized patients and characterize the circulating strains. STUDY DESIGN: A cross-sectional study was conducted using respiratory samples of 15,946 hospitalized patients with respiratory symptoms in 2012-2015 in Israel. All samples were subjected to q-PCR and q-RT-PCR to determine the presence of hPIV-3 and other respiratory viruses. Samples positive for hPIV-3 were subjected to molecular typing and phylogenetic analysis. RESULTS: Overall, 547 samples 3.4% (95% CI 3.2-3.7) were positive for hPIV-3. Of these 87 (15.9%) were mixed infections; 41.4% with adenovirus, 40.2% with RSV (40.2%) and 19.5% influenza A viruses. The prevalence of hPIV-3 was highest (5.1%) in children aged 0-4 years. Hospitalization in oncology department was associated with increased likelihood of hPIV-3 infection: adjusted odds ratio [aOR] 2.29 (95% confidence intervals [CI] 1.78-2.96), as well as hospitalization in organ transplantation department: aOR 3.65 (95% CI 2.80-4.76). The predominant lineages were C3c (62.3%) and C1b (24.6%), followed by sub-lineages C5 (8.7%) and C3b (2.9%). A new sub-lineage emerged in our analysis, named C1d, which was 17 (1.5%) nucleotide different from C1a, 25 (2.2%) nucleotide different from C1b and 24 (2.1%) nucleotide different from C1c. DISCUSSION: Young children and immunocompromised patients are likely the risk groups for severe respiratory infections with hPIV-3. Strains belonging to lineages C3c and C1b, which are present worldwide, should be targeted in vaccine development. The emergence of new lineage might have public health implications and on vaccine development.

New clinical and seasonal evidence of infections by Human Parainfluenzavirus.

Human Parainfluenzaviruses (PIVs) account for a significant proportion of viral acute respiratory infections (ARIs) in children, and are also associated with morbidity and mortality in adults, including nosocomial infections. This work aims to describe PIV genotypes and their clinical and epidemiological distribution. Between December 2016 and December 2017, 6121 samples were collected, and submitted to viral culture and genomic quantification, specifically Parainfluenza 1-4 (PIV1-4), Influenza A and B, Respiratory Syncytial Virus (RSV) A and B, Adenovirus, Metapneumovirus, Coronavirus, Rhinovirus, and Enterovirus. Normalized viral load, as (log10) copies/103 cells, was calculated as virus Ct, determined by multiple qRT-PCR, as a function of the Ct of ß-globin. PIV was confirmed in 268 cases (4.37%), and linked to both upper and lower respiratory tract disease, being more frequent in children than in adults (5.23 and 2.43%, respectively). PIV1 and PIV3 were most common (31 and 32.5%, of total PIV positive samples, respectively), with distribution being similar in children and adults, as was viral load. PIV type was correlated with seasonality: PIV3 being more frequent in winter and spring, PIV1 in summer, and PIV 4 in fall. No correlation between vial load and clinical severity was found. Novel findings were that PIV viral load was higher in fall than in other seasons, and PIV4, classically linked to mild respiratory symptoms, was circulating, in children and adults, at all levels of symptoms throughout the year.