Human parapneumovirus infection

  In recent years human metapneumovirus (HMPV) has been recognized as a major pathogen causing acute respiratory infections in pediatric patients, along with respiratory syncytial virus and adenovirus. This article provides an overview of the epidemiology, clinical features, virus detection and treatment of HMPV to draw clinicians’ attention to this new member of the viral infection spectrum.  1. epidemiology 1.1. epidemic territory, infection rate HMPV was first isolated from nasopharyngeal secretions of children in 2001 by Van et al. in the Netherlands. since then, HMPV infection has been reported in more than 10 countries in all continents, and the HMPV pathogen has been detected in children with respiratory tract infections in Beijing, Hong Kong, Chongqing and Xi’an in China. This proves that the virus is endemic in the world and throughout China.  The reported HMPV infection rates in various countries range from 2.2% to 11%. The reported HMPV infection rates in China are higher than those in foreign countries. In Beijing, the rate of HMPV positivity was 30% (74/274) among specimens tested negative for common viruses in children aged ≤6 years with respiratory infections in winter and spring of 2002-2003. 16% (12/75) of HMPV infections were reported among acute respiratory patients aged 2-28 years in outpatient clinics in Xuzhou from January to March 2005. Thereafter, Xi’an reported a 12.31% (8/65) HMPV detection rate in nasopharyngeal washings that tested negative for common viruses in children under 14 years of age hospitalized with respiratory infections from November 2006 to February 2007. 26% HMPV detection rate in airway specimens from 799 children hospitalized with respiratory tract in Chongqing area from April 2006 to March 2008. 2007 Feb. ~ October 2007, the detection rate of HMPV in outpatients and hospitalized respiratory patients under 7 years old in Dongguan area was 9.41%. In Hong Kong, the detection rate of HMPV among hospitalized respiratory patients under the age of 18 was 5.5% in 2003.  There are large differences in the reported HMPV infection rates among countries and across China, which are related to many influencing factors such as geographical environmental conditions, sampling time, testing methods, different subjects being tested, and the immune status of the population.  1.2, epidemic season, age distribution HMPV infection can be disseminated throughout the year, but most of them have obvious seasonality. In Hong Kong, the prevalence of HMPV infection is reported in spring and summer, while in most regions it is prevalent in autumn, winter and spring, and its peak is the same as or later than that of respiratory syncytial virus (RSV) infection.  HMPV infection can occur in people of all ages, and studies have shown that HMPV has been detected by RT-PCR in people with respiratory symptoms from 2 months to 87 years of age, but is more common in children, especially infants and young children. Older adults and immunocompromised individuals are also susceptible populations. Infants, the elderly and immunocompromised individuals are more severely infected with HMPV than the general population. However, there have only been reports of death after HMPV infection in adults.  The understanding of the epidemiological characteristics of HMPV is still preliminary and needs to be further elucidated by expanding the scope of detection and conducting controlled prospective studies.  2. Clinical features The clinical manifestations of HMPV are difficult to distinguish from other respiratory viral infections. Cough, runny nose and fever are the main symptoms, but there may also be dyspnea, wheezing, cyanosis, vomiting, diarrhea and other symptoms, and older children may also have myalgia, headache, malaise and other systemic symptoms. The diagnosis is mostly acute upper respiratory tract infection, but also pharyngitis, bronchitis and pneumonia. However, it is worth noting that HMPV is associated with the occurrence of wheezing diseases. In Beijing, 28% of HMPV-positive cases presented with capillary bronchitis; in Chongqing, 12 (48%) of 25 HMPV-positive patients were clinically diagnosed with capillary bronchitis and 4 (16%) with acute asthma attacks. HMPV infection without clinical symptoms is less common in infants and children.  X-rays of children with HMPV infection may show signs of peribronchitis or changes such as pulmonary infiltrates, hyperinflation, pulmonary atelectasis, and pleural infiltrates. The lung tissue is type II epithelial cell hyperplasia with dense chromatin staining of the nucleus and diffuse alveolar destruction. Electron microscopy reveals hyaline membrane formation.  HMPV infection can exist alone or mixed with other viruses such as RSV. The co-infection rate of HMPV and RSV has been reported in foreign countries <10%. However, only 10 (40%) of 25 HMPV-positive cases were reported in Chongqing and 15 (60%) were mixed infections, of which 8 (32%) were HMPV combined with RSV infection. The acute lower respiratory tract infection caused by HMPV alone was less severe than RSV infection alone. Giren-Sill et al. found that co-infection with HMPV and RSV was associated with more severe clinical symptoms and even required intensive care and mechanical ventilation than RSV infection alone. The Lazar study, however, showed that HMPV was not associated with the severity of RSV. The 25 cases of HMPV reported in Chongqing were difficult to distinguish from clinical manifestations alone whether they were HMPV mono-infections or co-infections with other viruses. The clinical features and significance of mixed respiratory virus infections need to be further explored.  3, virus detection The experimental diagnostic methods for HMPV include virus isolation, serological diagnosis, RT-PCR (reverse transcription-polymerase chain reaction), enzyme-linked immuno-amplification hybridization analysis, etc.  HMPV does not proliferate in most cells where respiratory viruses are cultured, and its growth rate is quite slow even in suitable host cells. Therefore, it is difficult to isolate live HMPV virus by cell culture method. The traditional immunofluorescence detection method is simple and rapid, but is limited to detecting HMPV-specific IgG, whose specificity is lower than that of RT-PCR. RT-PCR technology can amplify and sequence the nuclear shell protein gene, matrix gene, fusion gene, and multi-polymerase gene of HMPV virus, and has been the main diagnostic tool at present. The HMPV infections reported in Beijing, Chongqing, Xi'an, Xuzhou, Suzhou, and Dongguan, China, were detected by RT-PCR except for Xi'an, where IFP (indirect immunofluorescence method) was used. ooSteribeert et al. concluded that this technique has a higher diagnostic sensitivity compared with traditional detection methods and can increase the detection rate from 21% to 43%.  4. Treatment There is no specific effective treatment for respiratory viral infections. There are reports of ribavirin and interferon (rIFN) for the treatment of capillary bronchitis caused by human metapneumovirus, showing that the rIFN and ribavirin groups had significantly shorter cough, wheezing and lung rales disappearance times than the control group, and no adverse effects. Ribavirin has broad-spectrum antiviral activity and inhibits the growth of HMPV in cells, as well as HMPV adhesion, invasion and replication. Recombinant human interferon alpha-Ib (rIFN) is a low-molecular glycoprotein with antiviral activity, which has enhanced immune defense and can be used as an adjuvant treatment for HMPV infection as well as for sedated immunoglobulin.  The development of a vaccine is currently considered to be the key to stopping the onset of HMPV. However, the development of a vaccine should be based on an in-depth study of the immunopathogenesis of HMPV. The development of a live recombinant attenuated HMPV vaccine will take a long time.