Index
The most common disease suffered by people of all ages worldwide is an acute respiratory tract infection (RTI).
It is one of the leading causes of mortality and morbidity worldwide. Viruses are responsible for a large proportion of RTIs. A significant part of infections with viral etiology can also be attributed to human metapneumovirus (HMPV) in adults.
HMPV is an important pathogen that causes viral RTI. People at risk are the elderly, immunocompromised patients, and heart or lung disease patients.
Although HMPV infections are mild and self-limited in most adults, the clinical course can be complicated in these risk groups, and the associated morbidity and mortality are considerable.
HMPV was first identified in the Netherlands in 2001. Still, serological studies of antibodies to HMPV indicate that the virus is not new and has been in circulation in humans for at least 50 years.
This article aims to review the current literature on HMPV infections in adults and verify recent developments in treatment and vaccination. Others are for informational purposes only.
Human metapneumovirus was recently identified in 2001 as a significant cause of respiratory disease. However, some serological tests suggest that the virus has spread since 1958.
Notably, metapneumovirus is associated with RSV and influenza during respiratory virus season, but metapneumovirus activity generally peaks in winter than RSV and influenza.
Metapneumovirus Virology
HMPV is the first human member of the genus metapneumovirus in the subfamily Pneumovirinae within the family Paramyxoviridae.
It is an enveloped negative-sense single-stranded RNA virus. The RNA genome includes eight genes that code for nine different proteins. HMPV is identical in genetic order to avian pneumovirus (AMPV), which also belongs to the genus metapneumovirus.
Phylogenetic analysis has identified two HMPV genotypes, namely A and B. Both genotypes can co-circulate simultaneously, but one genotype generally dominates during an epidemic. Two clades are designated within these subgroups (designated A1, A2, B1, and B2).
This classification is based on the sequence variability of the binding (G) and fusion (F) surface glycoproteins. The highly conserved protein F constitutes an antigenic determinant that mediates the neutralization and protection of the cross lineage.
In 2006, two other subgroups, A2a and A2b were described, but this further division was based on limited data and has not been confirmed by other groups. Furthermore, the clinical importance of these subgroups has not yet been demonstrated.
Pathogenesis and susceptibility
For an extensive explanation of the pathogenesis of HMPV and animal models, we refer to the review by Schildgen et al. The pathogenesis of HMPV infections in adults appears to be similar to that in children.
HMPV is associated with a severe infection in patients with lung disease and chronic obstructive pulmonary disease (COPD). HMPV in BALB / c in mice and cotton rats show airway obstruction and hyperresponsiveness after infection.
Initially, HMPV infection in the lung is characterized by interstitial inflammation with alveolitis that begins on day 3, peaks on day 5, and then decreases inflammation.
However, after 2 to 3 weeks, this develops into a more prominent peribronchiolar and perivascular infiltrate. Hamelin et al.
They also show airway obstruction in BALB / c mice after a single challenge, with HMPV peaking on day five but still present until day 70.
In addition, significant hyperresponsiveness was also shown after methacholine exposure up to day 70, indicating long-term lung inflammation after HMPV infection.
In a mouse model, Dario and his colleagues demonstrated that susceptibility to HMPV infection is related to the age of elderly mice that show more severe disease and mortality than young mice.
The aged mice showed more excellent virus replication in the lung; however, viral clearance was not delayed.
In addition, lower levels of virus-specific antibodies, neutralizing antibodies, and gamma interferon with a significant increase in IL4 and CD4 + lymphocytes were observed in elderly mice after HMPV infection.
This suggests a vital role for the cellular immune response in controlling HMPV infection.
This hypothesis is partially confirmed by Ditt et al., who discovered that HMPV infection in aged mice results in decreased expression of TNF-alpha, resulting in low levels of NF-Kb compared to young mice.
Lüsebrink et al. showed that neutralizing antibodies appear to be present in all age groups in humans and that neutralizing capacities remain high, with a lesser decline for people older than 69 years.
Therefore, they hypothesized that the cellular response plays a more critical role in clearing the HMPV infection than the neutralizing humoral immune response.
Sastre et al. used a recombinant fusion protein-linked immunosorbent assay (F-ELISA) on the same set of sera.
Their results support the hypothesis that neutralizing antibodies appear likely to play a minor role in controlling HMPV infections in humans.
Furthermore, Falsey et al. found higher serum antibodies at baseline, a higher binding antibody response, and a trend toward higher neutralizing antibody responses in older adults compared to younger adults with HMPV disease of the same severity.
This suggests immune dysregulation in elderly patients with an HMPV infection.
In general, neutralizing antibodies appear to play a minor role in controlling HMPV infections. Cellular immune responses appear to be more critical for susceptibility to HMPV infections in elderly patients.
Metapneumovirus Epidemiology
HMPV is distributed worldwide and has a seasonal distribution comparable to influenza viruses and RSV.
It tends to attack in late winter and early spring. In young children, HMPV is the second most common cause of lowest RTI after RSV, and children under one year of age show the highest infection rates. The seroprevalence at the age of 5 years is almost 100%.
However, reinfection occurs due to an incomplete protective immune response or infection with a new genotype, especially in elderly and high-risk patients.
Van den Hoogen et al. demonstrated that experimental HMPV infection induces transient protective immunity in cynomolgus macaques.
Walsh et al. found that the proportion of HMPV infections in adults ranged between 3% and 7.1% in four consecutive winters. This is similar to the mean annual RSV infection rate (5.5%) and higher than influenza A (2.4%) in the same cohorts during the same period.
HMPV was identified in 2.2% of patients who visited a general practitioner for an acute community-acquired RTI negative for RSV and influenza virus.
HMPV infection is associated with hospitalization for acute RTI in adults in the study by Walsh et al. The incidence of HMPV disease in this hospitalized adult varied from year to year and ranged from 4.3% to 13.2%.
This is in agreement with the rates for RSV and influenza A. Average annual infection rates for RSV and influenza A were 9.6% and 10.5% in the same cohorts. Two-thirds of these hospitalized patients had an underlying disease.
Twenty percent of these patients had a co-infection with another respiratory virus.
Widmer et al. found that HMPV accounted for 4.5% of acute RTI hospitalizations in adults over 50 years of age during the winter season for three consecutive years.
The RSV and influenza A rates were 6.1% and 6.5%, respectively. Average annual hospitalization rates for HMPV were 1.8 / 10,000 residents in adults 50-65 years and 22.1 / 10,000 residents in adults> 65 years.
Patients with HMPV infections were older, had more cardiovascular disease, and were more likely to be vaccinated with the influenza vaccine compared to patients with influenza.
Boivin et al. found HMPV in 2.3% of respiratory samples during the 2000-2001 winter season. Of the 26 hospitalized patients with HMPV infection, 35% were younger than five years old, and 46% were older than 65.
One-third of hospitalized children younger than five years old, two-thirds of patients 15-65 years old, and all patients more aged than 65 years old had an underlying disease.
Data from our hospital suggest a comparable incidence in adult and pediatric patients. We analyzed all polymerase chain reaction (PCR) tests for respiratory viruses in our hospital for the last 19 months.
A total of 283 adults were tested for HMPV due to RTI symptoms, and nearly five percent of the patients (14 of 283 patients) tested positive for HMPV.
Transmission
HMPV is thought to be transmitted by direct or close contact with contaminated secretions, which may include saliva, droplets, or large particulate aerosols. HMPV RNA is found in excretions five days to two weeks after the onset of symptoms.
However, the degree of contagion is unknown since detecting HMPV RNA in respiratory samples from patients recovering from infection does not per se indicate viable contagious virus particles.
Based on two unique cases of nosocomial HMPV infections, the incubation period for HMPV is estimated to be 4 to 6 days. Another study of nosocomial HMPV disease in a pediatric hemato-oncology ward found an estimated incubation period of 7 to 9 days.
In a retrospective study, HMPV transmission was studied in households in Japan. Of the 15 families learned, all indexed patients were children attending primary, nursery, or nursery schools.
Contact cases developed symptoms a median of five days (range 3-7 days) after the index case developed symptoms.
Since this retrospective study included only symptomatic patients, an exact, reliable number of household transmissions could not be determined.
Two studies found HMPV transport in 4.1% of asymptomatic adults, suggesting that asymptomatic adults could be a neglected source of HMPV transmission.
However, other studies found that the presence of HMPV RNA in the excretions of asymptomatic people is rare.
Clinical manifestations (symptoms)
HMPV infection cannot be distinguished from other respiratory viruses for clinical reasons alone. Adult patients with an HMPV disease may be asymptomatic or have symptoms ranging from mild upper RTI symptoms to severe pneumonia.
Most patients have:
- To.
- Nasal congestion.
- Breathlessness.
Other reported symptoms are:
- To purulent.
- Wheezing
- Throat pain.
- Fever.
- Pneumonia.
- Bronchitis.
- Conjunctivitis.
- Otitis media
Li et al. described an HMPV infection in an immunocompetent adult presenting as a mononucleosis-like disease. Adults with HMPV disorder were less likely to report fever than adults with RSV or influenza infection.
In addition, adults with an HMPV infection were more likely to wheeze than adults with RSV or influenza.
Falsey et al. showed that this is mainly in the elderly population (> 65 years). Elderly patients also showed more dyspnea compared to younger adults. Young adults with HMPV infection had more outstanding complaints of hoarseness.
In frail elderly patients, patients with pulmonary or cardiovascular disease, and immunocompromised patients, infections can be severe.
The lab test may show:
- Linfopenia.
- Neutropenia.
- Elevated transaminases.
Chest X-ray and computed tomography (CT) imaging studies initially show signs of acute interstitial pneumonia (ground-glass opacity and consolidation of the air space) that turn into symptoms of bronchiolitis/bronchitis (thickening of the bronchial wall (ar ) or impact).
Compared to RSV and influenza, similar rates of intensive care unit (ICU) admission, mechanical ventilation, length of hospital stay, and length of ICU stay were observed for HMPV infection in adults.
Diagnosis of metapneumovirus infection
The diagnosis of HMPV infection can be made by several techniques, including culture, nucleic acid amplification tests (NAAT), antigen detection, and serological tests.
Virus culture is tricky because HMPV grows slowly in traditional cell culture and has mild cytopathic effects. The rapid culture technique is known as shell vial amplification.
Detection of viral RNA by NAAT, such as the transcriptase-PCR assay (RT-PCR), is the most sensitive method for diagnosing HMPV infection.
Methods for detecting HMPV antigens, such as enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA), are not commonly used. No commercial immunochromatographic assays are available.
A direct immunofluorescence antibody test (IFA), a rapid test in which labeled antibodies are used to detect specific viral antigens on explicit patient materials, could help diagnose HMPV cluster infections.
The test results are known within two hours. However, the sensitivity of IFA is lower than that of RT-PCR and must be validated before use.
Detection of the immune response against the virus by serological tests is only used for epidemiological studies.
One of the disadvantages of serology is that the interval between the spread of the virus and the detection of HMPV-specific IgM and IgG antibodies is relatively long.
However, a combined approach of serology and RT-PCR have added diagnostic value in diagnosing HMPV infections in the case of investigating the magnitude of an outbreak, for example, in long-term care facilities.
Treatment and prevention
Treatment
To date, the treatment of HMPV infection is primarily supportive. Various treatment regimens have been investigated.
Most of these therapeutic options, such as innovative approaches based on fusion inhibitors and RNA interference, appeared to be effective in vitro and animal studies.
Ribavirin is a nucleoside with broad-spectrum inhibitory activity against various RNA and DNA viruses, including HMPV.
Ribavirin has shown in vitro inhibition of tumor necrosis factor-alpha, interferon-gamma, and interleukin (IL) -10, suggesting decreased Th1 and Th2 cytokine production regulation and increased IL-2 production. by peripheral blood mononuclear cells.
Ribavirin can end immune-mediated damage to T cells caused by viral infections. It limits viral transcription and has been shown to have immunomodulatory effects. The in vitro results are confirmed by an in vivo study in BALB / c mice.
Immunoglobulins for therapeutic purposes can be divided into specific and non-specific.
Palivizumab (Synagis®) contains humanized monoclonal antibodies that can recognize a highly conserved neutralizing epitope on the RSV fusion protein.
It was shown to have preventive effects in infants at high risk for severe RSV infections; monthly injections of palivizumab reduced RSV hospitalizations by 50% compared to placebo.
Motavizumab is another RSV-specific monoclonal antibody preparation developed after the success of palivizumab. It was shown not to be inferior to palivizumab in preventing RSV hospitalization in high-risk children.
These data on the effectiveness of humanized monoclonal Abs against RSV infection have prompted a similar approach to protection against HMPV.
MAb 338 is one of the antibodies developed to attack the HMPV fusion protein.
It appeared effective in animal models. It neutralized the prototypical strains of the four HMPV subgroups, significantly reduced the pulmonary viral titer, limited severe acute manifestations, and limited bronchial hyperresponsiveness.
In mice, it appears to have both prophylactic and therapeutic benefits. Hamelin et al. also showed that it could be helpful after infection and not just as a preventive measure.
Williams et al. tested a fully human monoclonal antibody fragment (Human Fab DS7) with biological activity against HMPV in vivo and in vitro. They demonstrated prophylactic and therapeutic potential against severe HMPV infection.
When Fab DS7 was administered intranasally to cotton rats, a> 1500-fold reduction in viral titer was found in the lungs and a modest 4-fold decrease in nasal tissues. A dose-response relationship was observed between the dose of DS7 and the virus titer.
Wyde et al. showed that standard immunoglobulin preparations (thus without selection for antibodies against a particular microorganism or its toxin), initially used as a preventive measure against hRSV, also inhibit HMPV replication in vitro.
The combination of oral and aerosolized ribavirin with intravenous polyclonal immunoglobulin (IVIG) appears to be an effective treatment for severe HMPV infections. Still, no randomized controlled trials have been performed on humans.
Despite this lack of good human evidence, much experience has been gained in individual cases and small case series.
Both ribavirin and IVIG are expensive and have drawbacks. Ribavirin is a potential teratogen, and administration by nebulization should be through a small particle aerosol generator.
Therefore, ribavirin nebulization is rarely used for HMPV infection in daily practice.
In addition, healthcare providers who are pregnant or trying to become pregnant should avoid contact with patients receiving ribavirin spray.
In addition, IVIG requires large-volume fluid infusions, generates a high protein load, and is associated with adverse side effects in children with congenital heart disease.
Fusion inhibitors target the early stages of the viral replication cycle.
Deffrasnes and colleagues tested nine inhibitory peptides with sequence homology to the HRA and HRB domains of the HMPV fusion protein. They demonstrated potent in vitro viral inhibitory activity of five of these peptides.
One peptide, HRA2, showed very potent activity against all four subgroups of HMPV. BALB / c mice that received the HRA2 peptide and a lethal intranasal HMPV challenge were simultaneously protected from clinical symptoms and mortality.
The study by Miller and colleagues showed that individual HR-1 peptides could lead to effective viral inhibition.
These peptides could prevent severe infections in vulnerable patients after exposure, but the clinical role after infection needs to be investigated.
RNA interference (RNAi) is an exciting approach to treating RNA virus infections.
RNAi is a naturally occurring intracellular inhibitory process that regulates gene expression by silencing specific mRNAs.
Small RNAs, microRNA (miRNA), and interfering small RNA (siRNA) can down-regulate protein production by inhibiting targeted mRNA in a sequence-specific manner.
RNAi therapies are active in vitro and in vivo against respiratory syncytial virus, parainfluenza, and influenza.
Deffrasnes et al. successfully identified two highly efficient siRNAs against HMPV in vitro, targeting essential components of the HMPV replication complex.
Most recently, Preston and his colleagues designed and validated a siRNA molecule that is effective against the hMPV G gene in vitro.
Although a significant reduction in G mRNA did not reduce viral growth in vitro or induce a multiple type I interferon (IFN) response, hMPV G could be a valid target for RNAi, as G is required for replication. Viral in vivo.
Wyde et al. have also shown that both sulfated sialyl lipid (NMSO3) and heparin have antiviral activity against HMPV in vitro. NMSO3 most likely acts by inhibiting virus attachment and penetration and can inhibit cell-to-cell spread.
Vaccination
Several in vitro and animal studies have been conducted to investigate the development of a vaccine against HMPV. However, human studies have not yet been completed, and no vaccines are available yet.
Studies conducted in rodents and non-human primate models appear promising, but very little research is done on human volunteers.
A variety of live, virus-vectorized, virus-inactivated virus-inactivated subunit and virus vaccines have been tested in animal models and shown to have immunogenicity and protective efficacy.
HMPV expresses the major surface glycoproteins F and G. two major genetic virus lineages worldwide have a similar highly conserved F (fusion) protein. Immunization strategies have been directed against these surface proteins.
Immunization with monoclonal antibodies against F protein shows a prophylactic effect.
Several animal studies investigating immunization with a chimeric virus vector using a bovine parainfluenza virus three that expresses HMPV protein F, adjuvant soluble protein F, or protein F DNA show protective immunity after testing for the HMPV.
Immunization with HMPV (G) binding glycoproteins did not show antibody production or protection.
Ryder et al. also showed that HMPV G is not a protective antigen. They evaluated the protective efficacy of immunization with a recombinant form of ectodomain G (GDeltaTM) in cotton rats.
Although the immunized animals developed high serum antibodies to both the native and recombinant G protein, they did not develop neutralizing antibodies. They were not protected against exposure to the virus.
Studies investigating immunization with inactivated HMPV show an enhanced immune response with even lethal results after HMPV infection in animals.
Live attenuated viruses generated by reverse genetics or recombinant proteins, tested in animals, showed encouraging results.
Live vaccines mimic natural infection; however, the natural condition only leads to transient protective immunity. This poses an additional challenge for vaccine development.
The primary strategy is to develop a live attenuated virus for intranasal immunization. Reverse genetics provides a means for developing highly characterized live “designer” vaccines.
Several promising candidate vaccines have been developed, each with a different mode of attenuation.
The first candidate involves the elimination of glycoprotein G, which provides an attenuation that is probably based on the reduction of the efficiency of the coupling.
The second candidate involves the elimination of the M2-2 protein, which participates in the regulation of RNA synthesis and whose elimination has the advantageous property of regulating transcription and increasing antigen synthesis.
A third candidate involves replacing the HMPV P protein gene with its related avian metapneumovirus counterpart, thus introducing attenuation due to its chimeric nature and host range restriction.
Another in vivo vaccine strategy involves using an attenuated parainfluenza virus as a vector to express HMPV protective antigens, providing a bivalent pediatric vaccine.
Infection control measures
As HMPV outbreaks are frequently described, control measures to prevent HMPV transmission in hospitals and long-term care facilities seem justifiable.
When hospitalized patients with HMPV infection, infection control measures similar to those taken for RSV infection should be taken, including isolation of droplets until clinical recovery.
The Dutch Working Group on Infection Prevention advises applying drop isolation to all hospitalized patients with bronchiolitis until clinical recovery.
No specific advice is formulated for HMPV infections. The CDC advises droplet and contact precautions for infants and young children with respiratory diseases; however, no advice is given for adults.
Some other prevention measures
Patients can help prevent the spread of HMPV and other respiratory viruses by following these steps:
- Wash your hands often with soap and water.
- Avoid touching your eyes, nose, or mouth with unwashed hands.
- Avoid close contact with people who are sick.
Patients who have cold-like symptoms should:
- Cover your mouth and nose when coughing and sneezing.
- Wash your hands frequently and adequately (with soap and water for 20 seconds).
- Avoid sharing your cups and kitchen utensils with others.
- Refrain from kissing others.
- Stay home when they are sick.
Additionally, cleaning up potentially contaminated surfaces (such as doorknobs and shared toys) can help stop the spread of HMPV.
Risk groups
HMPV infections can be more severe in older patients or patients with underlying medical conditions.
It is a significant cause of acute respiratory diseases in adults over 65 and adults with comorbid conditions, such as COPD, asthma, cancer, immunosuppressed status, HIV, or subsequent transplantation.
Adults with lung disease or congestive heart disease
Respiratory viruses are a common trigger for COPD exacerbations and have been associated with respiratory failure in patients with cardiopulmonary diseases such as COPD and congestive heart failure.
Walsh et al. conducted a cohort study over four winters to investigate the clinical outcome and incidence of HMPV infections. Serum samples were taken before and after each year’s observation period (November 15 to April 15).
In case of respiratory symptoms, samples were taken from a nasopharyngeal swab to analyze HMPV RNA and serum.
They showed that 71% of HMPV infections were asymptomatic in healthy young adults (19–40 years) compared to 39% in high-risk adults (patients with symptomatic lung disease, COPD, congestive heart failure).
These patients were also more likely to use the health care service. Patients were ill for ten days in young adults compared to 16 days in the high-risk group.
Johnstone et al. investigated the potential role of respiratory viruses in the natural history of community-acquired pneumonia (CAP). A pathogen was identified in 39% of the 193 patients admitted for CAP.
Of these pathogens, 39% were viruses, and efficiently transmissible viruses, such as influenza, HMPV, and RSV, were the most common (24, 24, and 17%, respectively).
There were few clinically significant differences in presentation, and there were no differences in results based on the presence or absence of viral infection.
The patients with viral infection were, compared with bacterial infection, significantly older, more likely to have heart disease, and more fragile.
This agrees with the results of Hamelin et al., who found HMPV in 4.1% of patients with CAP or exacerbation of the chronic obstructive pulmonary disease.
Martinello et al. also showed that HMPV was frequently identified in hospitalized patients due to COPD exacerbation.
HMPV (genotype A and B) was identified in nasopharyngeal samples (by RT-PCR) in 12% of these patients (6/50). RSV, influenza A and parainfluenza type 3 were identified in 8%, 4%, and 2%, respectively.
Together with these results, Williams and colleagues demonstrated that HMPV (by RT-PCR of nasal wash samples) was detected in nearly 7% (7/101) of adults hospitalized for an acute exacerbation of asthma, compared to 1.3% in the follow-up patients (p = 0.03).
Although none of these patients tested positive for HMPV three months after discharge, it seems highly likely that the virus has a direct etiologic role.
We recently reported a case series of adult patients, including two known COPD patients, with severe HMPV infections with respiratory failure and a need for ICU admission.
Healthy elderly patients over 65 years of age
Because adults are not routinely screened for HMPV in hospitals and the clinical course may be asymptomatic or mild, infections in the elderly are likely to be underreported.
The annual incidence reported in adults is between 4 and 11%, and in adults over 50 years of age, hospitalization rates for HMPV were similar to those associated with influenza and RSV.
Walsh et al. showed that severe symptomatic HMPV infection was higher in the elderly. HMPV infection was asymptomatic in 44% of healthy elderly compared to 71% of healthy young adults.
38% of the elderly with HMPV infection used medical care compared to 9% of young adults.
Hospitalization rates in elderly patients older than 65 years were also significantly higher for HMPV infection (22.1 / 10,000 residents) compared to influenza virus (12.3 / 10,000 residents), but similar to those for HMPV infection. RSV (25.4 / 10,000 residents).
Antibody levels before infection were higher in the elderly, suggesting possible immune dysregulation associated with decreased viral clearance in the elderly.
Outbreaks in long-term care facilities
Several studies have reported outbreaks in long-term care facilities for the elderly. Boivin et al. studied a large explosion at a long-term care facility in Canada in which 96 (27%) of 364 residents had respiratory symptoms.
Six of the 13 residents analyzed were positive for HMPV by RT-PCR. Nine patients died, of which three residents tested positive for HMPV.
In a 23-bed ward in a hospital for the elderly in Japan, all eight residents with respiratory symptoms tested positive for HMPV by RT-PCR.
None of these residents died. Tu et al. found that 10 of 13 evaluated residents of a 53-bed psychiatric ward of the armed forces general hospital in Taiwan were HMPV positive by RT-PCR.
In a summer outbreak at a long-term care facility in California, 26 (18%) residents developed respiratory symptoms. Five of the 13 residents evaluated were positive for HMPV.
In an outbreak that the authors of this review described, the attack rate was 13% in a long-term care facility.
Three patients died; however, these were only possible cases. Osbourn et al. found a 16.4% attack rate in HMPV outbreaks in a long-term care facility in Australia, in which two residents died.
Sixteen (36%) of the 44 residents in a long-term care facility in Oregon had respiratory symptoms, of which 6 of the ten residents tested were positive for HMPV by RT-PCR. Another study in England’s community hospital reported an attack rate of 29.4%.
Different settings (residential care facilities for the elderly and hospitals) and different case definitions could partly explain the difference in attack rate and mortality.
Immunocompromised
Several case reports and case series related to HMPV infections in immunocompromised patients have been published, reporting variable morbidity and mortality.
Although immunocompromised patients, including patients with hematologic malignancies and hematopoietic stem cell and solid organ transplantation, appear to acquire HMPV infection with the same frequency as immunocompetent individuals, they seem to be at risk of severe conditions.
This is probably due to poor viral clearance. The clinical course is prolonged and respiratory failure may develop. However, Debiaggi demonstrated that HSCT receptors could frequently develop an HMPV infection without symptoms.
Sumino et al. examined a cohort of 688 patients who underwent bronchoscopy.
Of these patients, 72% were immunocompromised (mainly lung transplant patients), and 30% were patients without acute disease who underwent routine bronchoscopy for surveillance after lung transplantation or follow-up for rejection.
Six cases of HMPV infection were identified using RT-PCR; Four of them were immunocompromised hosts. In asymptomatic individuals, no issues were identified.
Kamboj et al. showed that HMPV is detected in 2.7% of cancer patients with respiratory disease. However, HMPV was associated with mild respiratory illness, and RSV and influenza were found more frequently.
In patients with hematologic malignancies, HMPV was found more frequently.
Dabur et al. showed that HMPV was present in 2.5% of hematologic stem cell transplant recipients with respiratory disease. Most patients had a higher RTI, while 27% had a lower RTA. No patients died.
Englund et al. conducted a retrospective survey to demonstrate the importance of HMPV in hematopoietic stem cell transplant recipients.
HMPV (by RT-PCR) was detected in 3% of these patients who underwent BAL due to LITR. The clinical course in this group was severe, and 80% died from acute respiratory failure.
Williams et al. showed that HMPV is found in the same frequency as RSV, influenza, and parainfluenzavirus in patients with hematological malignancies with acute respiratory disease. All patients had a higher RTI, but 41% progressed to a lower RTI.
One-third (three patients) of these patients died; however, two of them also found potential bacterial pathogens in the BAL fluid.
Cane et al. published a case report on an HSCT receptor who succumbed to progressive respiratory failure after an upper respiratory prodrome and where HMPV was detected as the sole pathogen in the nasopharyngeal aspirate.
In lung transplant patients, HMPV was found in 6% of adults with RTIs. This was significantly less than the most common viral cause, namely the parainfluenza virus (17%). RSV and influenza were found in 12% and 14%, respectively.
The required hospitalization rate and length of hospital stay were not different between HMPV and other respiratory viruses.
In this study, viral RTI was associated with acute graft rejection. However, this rate was significantly higher for RSV infection than for HMPV illness.
Larcher et al. found HMPV in 25% of BAL fluids from lung transplant patients. Not all had respiratory symptoms at the time of lavage.
In this study, HMPV infection appears to be associated with acute graft rejection but not obliterative bronchiolitis development.
However, other studies suggest that viral RTI is associated with the risk of developing bronchiolitis obliterans.
Complications
Bacterial and fungal superinfections may complicate respiratory viral infections.
No specific studies have been done addressing this problem. However, some studies report the presence of potential bacterial pathogens in BAL fluid, sputum, or blood cultures in patients, with sometimes fatal results.
In a mouse model, HMPV infection predisposes to severe bacterial infections.
Higher levels of airway obstruction, pneumococcal replication, and inflammatory cytokines and chemokines were observed in the lungs of superinfected mice, which were challenged with Streptococcus pneumoniae (S. pneumoniae) five days after HMPV infection.
Inactivated HMPV did not result in these changes after the pneumococcal challenge, suggesting that HMPV replication rather than host response to HMPV may be responsible for these effects.
Mice infected with influenza A show a long-term impairment of lung clearance by S. pneumonia, but the mechanism that produces these effects could be different.
In contrast to these findings, Ludwick et al. Demonstrated that HMPV-infected BALB / c mice had average lung bacterial clearance when exposed to S. pneumonia 14 days after HMPV infection.
Discussion
More knowledge has been gained about the importance of HMPV infection in adult patients in recent years.
Thanks to more sensitive diagnostic tools such as CRP, the proportion of known viral etiologies has increased. HMPV is a significant cause of respiratory disease in patients of all ages.
Reported annual incidences in adults are up to 11%, but the true incidence of HMPV infections is difficult to measure or estimate. First, because many HMPV infections are asymptomatic or mild and these patients do not present to the hospital.
Second, most patients with respiratory symptoms who present in our hospital are not screened for viral infections.
Epidemiological studies show that the elderly over 65 years of age, patients with heart or lung disease, and immunocompromised patients are at higher risk of HMPV infection, presenting with more severe disease than younger adults without comorbidity.
Severe outbreaks of HMPV with mortality have been reported in long-term care facilities. Among immunocompromised patients, infection control measures should be taken in case of RTI with HMPV.
These control measures must be taken, mainly because these groups of patients are at higher risk of more severe disease, and there is no proven treatment. And vaccination strategies against HMPV are available until now.
So far, much experience has been gained in treating HMPV in individual cases and small case series.
The combination of ribavirin with IVIG appears to be very promising, although this combination is expensive and has disadvantages. Several other treatment regimens have been investigated and effective in vitro and animal studies.
Both immunoglobulins (such as mAb 338 and Fab DS7) and synthetic fusion inhibitors were efficient against HMPV. The recently discovered approach to RNA interference (RNAi) could be the future technique.
However, until now, no treatment is available that is effective in large clinical trials, and treatment of HMPV infection is primarily supportive.
A VACCINE IS DESIRABLE since HMPV is a significant cause of morbidity and mortality in frail patients. Several in vitro and animal studies have investigated the development of a vaccine for HMPV.
The development of an HMPV vaccine is hampered by natural HMPV infection. It does not elicit complete immunity—studies in which you are vaccinated with inactivated HMPV show an extended immune response with even lethal results.
However, other studies showed promising results, although no vaccines are available.
Bottom line
HMPV is an important pathogen that causes viral RTI in adults.
The elderly, immunocompromised patients, and patients with heart or lung disease risk severe infection.
Clinically distinguishing HMPV from other respiratory viruses is difficult. The diagnosis is mainly based on RT-PCR.
Although a lot of research has been done in recent years, the treatment of HMPV infection is primarily supportive, and no vaccine is available yet.
In severe infections, treatment with ribavirin and IVIG may be considered.
Human metapneumovirus (HMPV) is a relatively recently described virus. It was first isolated in 2001 and currently appears to be one of the most important and common human viral infections.
Retrospective serological studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier.
Although the virus was known primarily as a causative agent of respiratory tract infections in children, HMPV is also a significant cause of respiratory infections in adults.
Almost all children are infected with HMPV under five; Repeated infections throughout life indicate transient immunity.
HMPV infections are usually mild and self-limited, but the clinical course can be complicated in frail elderly and immunocompromised patients.
Since the virus is relatively difficult to grow, the diagnosis relies primarily on a nucleic acid amplification test, such as a reverse transcriptase-polymerase chain reaction. To date, no vaccine is available, and treatment is supportive.
However, ongoing research shows encouraging results. This article aims to review the current literature on HMPV infections in adults and verify recent developments in treatment and vaccination.
Antiviral treatment is not recommended. You can help your patients reduce the risk of respiratory illnesses caused by metapneumovirus and other pathogens by reminding them to wash their hands frequently and practice good hygiene habits.
Because human metapneumovirus is relatively new and not well described, healthcare professionals may not perform routine testing or consider it in their differential diagnosis.
