Epidemiology and diagnosis technologies of human metapneumovirus in China: a mini review.

Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future.

Clinical comparison of HMPV and RSV infections in hospitalised Malaysian children: A propensity score matched study.

INTRODUCTION: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children. METHODS: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics. RESULTS: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p < 0.001) and had a higher incidence of comorbidities (24.1% vs. 7.5%, p = 0.003). Fever was more common in the hMPV group (97.3% vs. 73.8%, p < 0.001), but the other clinical manifestations were similar. Postmatching analysis showed higher corticosteroid use in the hMPV group (p = 0.01). No significant differences were observed in the use of other resources, PICU admissions, duration of hospitalisation or mortality rates between both groups. CONCLUSION: hMPV and RSV infections in children share similar clinical manifestations and outcomes, with hMPV affecting older children and showing higher corticosteroid usage. These findings emphasise the need for equal clinical vigilance for both hMPV and RSV in paediatric respiratory infections.

Head-to-Head Comparison Between Respiratory Syncytial Virus and Human Metapneumovirus Bronchiolitis in the Setting of Increased Viral Testing.

We compared the epidemiology, severity and management of hospitalized respiratory syncytial virus (n = 305) and human metapneumovirus (n = 39) bronchiolitis in a setting with high respiratory virus testing (95% of admissions tested). Respiratory syncytial virus-positive infants were younger and tended to require more hydration support and longer hospital stays compared to human metapneumovirus-positive infants. Respiratory support requirements were similar between groups despite significant age differences.

[Analysis of parainfluenza virus infection in acute respiratory tract infection adult cases in Shanghai, 2015-2021].

Objective: To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV. Methods: Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR. Results: A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant (χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions: There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.

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.

Development of a duplex real-time RT-PCR assay for the detection and identification of two subgroups of human metapneumovirus in a single tube.

Human metapneumovirus (hMPV) is a common cause of respiratory infections in children. Many genetic diagnostic assays have been developed, but most detect hMPV regardless of the subgroup. In this study, we developed a real-time RT-PCR assay that can detect and identify the two major subgroups of hMPV (A and B) in one tube. Primers and probes were designed based on the sequences of recent clinical isolates in Japan. The assay showed comparable analytical sensitivity to a previously reported real-time RT-PCR assay and specific reactions to hMPV subgroups. The assay also showed no cross-reactivity to clinical isolates of 19 species of other respiratory viruses. In a validation assay using post-diagnosed clinical specimens, 98% (167/170) positivity was confirmed for the duplex assay, and the three specimens not detected were of low copy number. The duplex assay also successfully distinguished the two major subgroups for all 12 clinical specimens, for which the subgroup had already been determined by genomic sequencing analysis. The duplex assay described here will contribute to the rapid and accurate identification and surveillance of hMPV infections.

Burden of human metapneumovirus infections among children with acute respiratory tract infections attending a Tertiary Care Hospital, Kathmandu.

BACKGROUND: Acute respiratory infections (ARIs) are one of the most common causes of mortality and morbidity worldwide. Every year millions of children suffer from viral respiratory tract infections (RTIs) ranging from mild to severe illnesses. Human Metapneumovirus (HMPV) is among the most frequent viruses responsible for RTIs. However, HMPV infections and their severity among children have not been explored yet in Nepal. PURPOSE: Therefore, the study was focused on HMPV infections and other potential viral etiologies or co-infections using multiplex PCR among children attending Kanti Children's Hospital and assessed the clinical characteristics of the infections as well as found the co-infections. A hospital-based cross-sectional study was designed and a convenience sampling method was used to enroll children of less than 15 years with flu-like symptoms from both outpatients and inpatients departments over three months of the study period. RESULTS: HMPV infection (13.3%) was the most predominant infection among the different viral infections in children with ARIs in Kanti Children's Hospital. The HMPV was more prevalent in the age group less than three years (21.8%). Cough and fever were the most common clinical features present in all children infected with HMPV followed by rhinorrhea, sore throat, and wheezing. HMPV-positive children were diagnosed with pneumonia (42.9%), bronchiolitis (28.5%), upper respiratory tract infections (14.3%), and asthma (14.3%). The prevalence of HMPV was high in late winter (14.3%) followed by early spring (13.5%). CONCLUSIONS: This study provides the baseline information on HMPV and associated co-infection with other respiratory viruses for the differential diagnosis based on molecular methods and also the comparison of clinical presentations among the different respiratory syndromes.

Recent Changes in the Human Metapneumovirus Outbreak at a University Hospital in Korea.

BACKGROUND: Although the detection of respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was significantly reduced because of quarantine due to the coronavirus disease (COVID-19) pandemic, an epidemic of several viruses was reported unexpectedly. We also detected a change in the pattern of human metapneumovirus (HMPV) outbreak compared to that before the COVID-19 pandemic. Therefore, the authors intended to identify the incidence and altered distribution pattern of the HMPV outbreak and provide useful information for clinical practice. METHODS: This retrospective study investigated the incidence and distribution of HMPV from March 2020 to December 2022 during the COVID-19 pandemic. Detection of respiratory microorganisms was performed by multiplex polymerase chain reaction using a commercial kit and FilmArray assay. RESULTS: The overall incidence of at least one respiratory microorganism was 50.3% (1,152/2,290). HMPV was not detected between March 2020 and June 2022. However, it was suddenly detected in July 2022 and continued for approximately five months until November 2022. In particular, the detection rate of HMPV was high in September and October 2022, accounting for approximately 76.1% (51/67) of the total HMPV-positive cases. Seasonally, 92.5% (62/67) of HMPV cases were detected in autumn, while the rest of the cases were detected in summer. The HMPV detection rate, according to the age group, was highest in group 4 (3 - 6 years) at 7.4% (27/367), followed by group 3 (4 months to 2 years) at 3.6% (31/861). In HMPV-positive cases, the rate of more than two respiratory pathogens was 46.3% (31/67). An analysis of co-infecting pathogens showed that HMPV with rhinovirus A/B/C/ enteroviruses accounted for the highest percentage (51.6%), followed by HMPV with respiratory syncytial virus (48.4%). CONCLUSIONS: The COVID-19 pandemic has caused several changes in our lives. This study confirmed that the seasonal distribution of HMPV was different from that before the COVID-19 pandemic. Therefore, it can be assumed that the distribution of other respiratory microorganisms could have changed and it appears that changes could occur in previously known viral epidemiology. Clinicians should therefore be alert to this possibility.

A surge in human metapneumovirus paediatric respiratory admissions in Western Australia following the reduction of SARS-CoV-2 non-pharmaceutical interventions.

AIM: Western Australian laboratory data demonstrated a decrease in human metapneumovirus (hMPV) detections through 2020 associated with SARS-CoV-2-related non-pharmaceutical interventions (NPIs), followed by a subsequent surge in metropolitan region in mid-2021. We aimed to assess the impact of the surge in hMPV on paediatric hospital admissions and the contribution of changes in testing. METHODS: All respiratory-coded admissions of children aged <16 years at a tertiary paediatric centre between 2017 and 2021 were matched with respiratory virus testing data. Patients were grouped by age at presentation and by ICD-10 AM codes into bronchiolitis, other acute lower respiratory infection (OALRI), wheeze and upper respiratory tract infection (URTI). For analysis, 2017-2019 was utilised as a baseline period. RESULTS: hMPV-positive admissions in 2021 were more than 2.8 times baseline. The largest increase in incidence was observed in the 1-4 years group (incidence rate ratio (IRR) 3.8; 95% confidence interval (CI): 2.5-5.9) and in OALRI clinical phenotype (IRR 2.8; 95% CI: 1.8-4.2). The proportion of respiratory-coded admissions tested for hMPV in 2021 doubled (32-66.2%, P < 0.001), with the greatest increase in wheeze (12-75% in 2021, P < 0.001). hMPV test percentage positivity in 2021 was higher than in the baseline period (7.6% vs. 10.1% in 2021, P = 0.004). CONCLUSION: The absence and subsequent surge underline the susceptibility of hMPV to NPIs. Increased hMPV-positive admissions in 2021 can be partially attributable to testing, but test-positivity remained high, consistent with a genuine increase. Continued comprehensive testing will help ascertain true burden of hMPV respiratory diseases.

Bronchiolitis Due to RSV and HMPV-Epidemiology, Clinical Course, and Prognosis: Experience of a Single Tertiary Center.

Acute bronchiolitis is a leading cause of hospitalization in infants. In this retrospective study, 645 patients with acute bronchiolitis diagnosed as respiratory syncytial virus (RSV; n = 538) or human metapneumovirus (HMPV; n = 107) were compared in terms of demographic, clinical, and laboratory findings. The HMPV patients presented later in the winter, were older (20 vs 7.55 months; P < .001)), had higher levels of C-reactive protein (4.55 vs 3.03 mg/dL; P = .007), and a higher prevalence of complications (43.9% vs 32.7%; P = .03). This study highlights the similarities and differences between these 2 common respiratory viral pathogens and shows that HMPV has a slightly more severe disease course than RSV. These findings can help guide approaches to these 2 common viruses that cause bronchiolitis.

Metapneumovirus Infections are Uncommon in Infants Younger than 60 Days of Age Admitted for Sepsis Evaluation.

The epidemiology and clinical manifestations of human metapneumovirus are not well studied in infants younger than 60 days of age. In this retrospective review of infants admitted for sepsis evaluation, we identified HMPV less frequently than other viral etiologies via nasopharyngeal multiplex polymerase chain reaction testing; in only 16 (1.9%) infants. Two infants had apneic episodes, but none had wheezing.

Retrospective comparison of respiratory syncytial virus and metapneumovirus clinical presentation in hospitalized children.

Respiratory syncytial virus (RSV) and Human metapneumovirus (hMPV), members of Pneumoviridae family are common causes of acute respiratory tract infections (ARTI) among children. Study material includes routine nasopharyngeal samples obtained during 8-year period for hMPV and one single season for RSV in children hospitalized for ARTI between 0 and 15 years at the Center Hospitalier Universitaire (CHU) Saint Pierre in Brussels. Positive samples for RSV or hMPV identified by viral culture, lateral flow chromatography test for RSV or direct fluorescent assay for hMPV were selected retrospectively. Characteristics of children hospitalized for RSV or hMPV infections were compared. Children hospitalized for RSV infection were significantly younger and requiring more respiratory support, longer hospital stay and transfers in Pediatric intensive Care Units than those hospitalized for hMPV infection. Pneumonia diagnostic and antibiotics therapies were more significantly associated with hMPV infections. In conclusion, despite their genetic similarities, RSV, and hMPV present epidemiological and clinical differences in pediatric infections. Our results should be confirmed prospectively.

Outbreak of Parainfluenza Virus During the COVID-19 Pandemic at a University Hospital in Korea.

BACKGROUND: The incidence of respiratory viral diseases including parainfluenza virus (PIV) infection has decreased noticeably due to strict quarantine measures during the COVID-19 pandemic. However, the recent outbreak of PIV in children occurred unexpectedly and the distribution pattern showed prominent differences from before the COVID-19 pandemic. PIV is one of the major viral pathogens related to acute lower respiratory infection in young children and the elderly. Accordingly, the authors intended to identify the incidence and distribution pattern of PIV outbreaks and to contribute to public health by providing information on it. METHODS: This study was conducted retrospectively to investigate the incidence and distribution of PIV according to age group, gender, month, and season, and to analyze the co-infections from March 2020 to February 2022. The detection for respiratory microorganisms was performed through FilmArray assay. RESULTS: The overall incidence for at least one respiratory pathogen was 45.9% (665/1,450). PIV was not detected at all from March 2020 to August 2021. However, it was first detected in September 2021 and the rate in the month that followed, October, accounted for 60% (114/190) of the total PIV infections during the entire study period. It also accounted for 44.9% (190/423) of patients with respiratory pathogens from September 2021 to February 2022. It reached the highest proportion at 90.5% (114/126) in October 2021. As for the distribution according to the age groups, group 3 (58.4%) accounted for the highest percentage, followed by group 4 (21.1%). In the PIV positive cases, the overall rate of more than two respiratory pathogens was 32.6% (62/190). The most common pattern of co-infection was PIV3 with rhinovirus/enterovirus (67.7%), followed by PIV3 with adenovirus (8.1%) and PIV3 with rhinovirus/enterovirus and adenovirus (8.1%). CONCLUSIONS: The COVID-19 pandemic has brought about many changes in our daily lives. It has been confirmed that the seasonal distribution of PIV was distinctly different from before the COVID-19 pandemic. It is anticipated that this phenomenon will affect the incidence or distribution of other respiratory pathogens and viral epidemiology. Therefore, clinicians should pay attention to these changes in terms of public health.

Outbreaks of Human Metapneumovirus in Western Sydney Aged-Care Facilities in 2018.

Background: Human metapneumovirus (hMPV), first described in 2001, is a cause of acute respiratory tract infection in the elderly, with symptoms ranging from mild to severe, including pneumonia, but outbreaks are rarely described. Methods: Between 1 July and 31 December 2018, there were three outbreaks of Influenza-like Illness (ILI) where hMPV was the primary pathogen observed, among 64 aged-care facilities (ACFs) in Western Sydney. These outbreaks were investigated by the Western Sydney Local Health District (WSLHD) Public Health Unit (PHU); multiplex polymerase chain reaction (PCR) testing was performed on nasopharyngeal swabs collected by the ACF. Results: hMPV was the main causative pathogen in three outbreaks (27, 28, and 15 symptomatic cases, respectively) in late winter and early spring. Fifty-five residents and 15 staff cases (70 total cases) were identified; hMPV was detected in 12 of 63 specimens submitted. Of the cases in residents, eight were hospitalised (8/63; 15%), including five with confirmed hMPV and a further one epidemiologically linked to a positive case. Six residents died (6/63; 11%) during the hMPV outbreaks; four of these had laboratory-confirmed hMPV, with a further case epidemiologically linked to a hMPV case, with a primary diagnosis of pneumonia/viral pneumonia. The sixth death was not epidemiologically linked, nor did this case exhibit any respiratory symptoms during the outbreak; however, it was reported in line with public health guidelines. Conclusion: A major challenge in 2018 was the incompleteness of testing for, and awareness of, hMPV as a viral cause of ILI by facilities, laboratories, and emergency departments, which generally opted for rapid testing for influenza and RSV only. There is no licensed vaccine or approved treatment for hMPV, so efficient infection control measures are most important.

Comparison of sputum specimens and nasopharyngeal swab specimens for diagnosis of acute human metapneumovirus-related lower respiratory tract infections in adults.

BACKGROUND: To detect human metapneumovirus, tests besides reverse transcription-polymerase chain reaction (RT-PCR) on nasopharyngeal swab specimens are less accessible. Immunochromatography assays are rapid and simple without the need of any special equipment but sometimes are insufficiently sensitive. This study describes the usefulness of immunochromatography assays to detect human metapneumovirus in adult patients with human metapneumovirus-related acute lower respiratory tract infection using sputum specimens. METHODS: This prospective single-center study enrolled adults and adolescents aged ≥16 years with signs and symptoms of an acute respiratory illness who were diagnosed with acute lower respiratory tract infection. The presence of human metapneumovirus infection was confirmed by seroconversion. Immunochromatography assays and real-time RT-PCR were performed to compare the efficacy of nasopharyngeal swab specimens and sputum specimens. Comparative results were obtained via McNemar's test. RESULTS: Overall, 337 patients were recruited in this study; 63 (18.7%) patients were seroconverted. Sputum specimens showed significantly higher positivity rates than nasopharyngeal swab specimens with both immunochromatography assays (p = 0.0008) and real-time RT-PCR (p = 0.014). Among 29 patients with pneumonia who had concordant positive real-time RT-PCR results for both nasopharyngeal swab specimens and sputum specimens, 21 (72.4%) had a higher viral load in the sputum specimens. CONCLUSIONS: Sputum specimens are more useful in detecting human metapneumovirus than nasopharyngeal swab specimens in adult patients with acute lower respiratory tract infection.

Human parainfluenza 2 & 4: Clinical and genetic epidemiology in the UK, 2013-2017, reveals distinct disease features and co-circulating genomic subtypes.

BACKGROUND: Human Parainfluenza viruses (HPIV) comprise of four members of the genetically distinct genera of Respirovirus (HPIV1&3) and Orthorubulavirus (HPIV2&4), causing significant upper and lower respiratory tract infections worldwide, particularly in children. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2&4 at a regional UK hospital across four autumn/winter epidemic seasons. METHODS: A retrospective audit of clinical features of all HPIV2 or HPIV4 RT-PCR-positive patients, diagnosed between 1st September 2013 and 12th April 2017 was undertaken, alongside sequencing of viral genome fragments in a representative subset of samples. RESULTS: Infection was observed across all age groups, but predominantly in children under nine and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2&4, but with little variation between each epidemic season or from limited global reference sequences. CONCLUSIONS: Despite being closest known genetic relatives, our data indicates a potential difference in associated disease between HPIV2 and HPIV4, with more hospitalisation seen in HPIV2 mono-infected individuals, but a greater overall number of HPIV4 cases.

Human bocavirus and human metapneumovirus in children with lower respiratory tract infections: Effects on clinical, microbiological features and disease severity .

BACKGROUND: We aimed to compare the clinical findings of human bocavirus (HBoV) and human metapneumovirus (HMPV) infections, and to analyze the effects of coinfections on clinical features and disease severity in children with HBoV and HMPV infections. METHODS: Data were collected from 125 children with lower respiratory tract infections due to HBoV or HMPV, detected from nasal swap by real-time polymerase chain reaction (PCR) during the period from January, 2013 to December, 2017. In total, there were 101 HBoV (group 1) and 23 HMPV (group 2) infections in our data. The patients were further divided into four subgroups according to the coinfection status: HoBV only (subgroup 1, n = 41), HMPV only (subgroup 2, n = 19), HBoV and coinfection with other respiratory viruses (subgroup 3, n = 60), and HMPV and coinfection with other respiratory viruses (subgroup 4, n = 4). RESULTS: The majority (88.8%) of the patients were aged 5 years or younger. Coinfections with other respiratory viruses were significantly more common in group 1 (P = 0.001). Among patients who had nosocomial pneumonia, patients with HBoV infections had significantly longer mean length of hospital stay (LOS) than those with HMPV infections (P = 0.032). The hospitalization and antibiotic requirements were significantly higher in subgroup 1 than subgroup 3 (P = 0.005, 0.039, resp.) According to the logistic regression analyses, the LOS increased by 21.7 times with HBoV infections (P = 0.006). CONCLUSIONS: Human bocavirus and HMPV infections are serious pathogens mostly seen in children and usually requiring hospitalization regardless of co-infection status. The HBoV infections caused longer LOS than the HMPV infections in patients with nosocomial infections.