Human metapneumovirus infection as an emerging pathogen causing acute respiratory distress syndrome

Published on Jan 15, 2011in The Journal of Infectious Diseases5.226
· DOI :10.1093/INFDIS/JIQ045
Luregn J. Schlapbach36
Estimated H-index: 36
,
Philipp Agyeman12
Estimated H-index: 12
+ 3 AuthorsThomas Riedel17
Estimated H-index: 17
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Abstract
To the Editor—Viral respiratory infections represent a frequent cause of intensive care unit (ICU) admissions in children and impose a considerable burden worldwide [1]. The main pathogens are respiratory syncytial virus (RSV) and seasonal influenza. Human metapneumovirus (hMPV) is an emerging pathogen of the Paramyxoviridae family causing acute bronchiolitis-like respiratory illness in children [2]. Williams et al [2] have recently reported an annual rate of hMPV-associated hospitalizations of 1.2 per 1000 hospitalized children <5 years of age in the United States, confirming that hMPV contributes significantly to respiratory morbidity with a similar impact as influenza. In their study, most hMPV-infected children had a relatively mild course, with only 1 participant (3%) requiring ICU admission. We would like to comment on severe hMPV infections and to present the case of a child with fatal acute respiratory distress syndrome (ARDS) due to infection with hMPV. The 20-month-old boy initially presented with a bronchiolitis-like pattern, with rhinitis, cough, and increasing respiratory distress. The child's history was unremarkable except for moderate neurodevelopmental delay of unknown etiology. Because of impending respiratory failure (capillary pH, 7.17; partial carbon dioxide pressure, 86 mm Hg; saturation 83% with 100% oxygen), he was intubated. The oxygenation index was 0.32 and the PaO2/FiO2 ratio resulted 68 (55 mm Hg/0.8). On the basis of radiological findings of bilateral diffuse pulmonary infiltrates, the diagnosis of ARDS was made. Echocardiography demonstrated good biventricular function and no evidence for pulmonary hypertension. The patient was placed on high-frequency oscillatory ventilation (Sensormedics 3100A), with a mean airway pressure of up to 30 cm water. Tests for RSV and H1N1 influenza virus were negative. Results of repeated bacterial blood and tracheal fluid cultures were negative. Therefore, an expanded panel of respiratory viruses (adenovirus, picornaviruses, influenzavirus A/B, parainfluenzaviruses 1–3, RSV, and hMPV) was assessed using direct immunofluorescence. The patient tested positive for hMPV. Viral testing was repeated several times and confirmed only infection with hMPV. Because of the high risk of bacterial superinfection, empirical treatment with cefuroxime and vancomycin was initiated. The patient subsequently developed multi-organ failure, with catecholamine-dependent arterial hypotension, renal failure requiring continuous renal replacement, coagulopathy, thrombocytopenia, leukopenia, and hepatitis. Because oxygenation further deteriorated (oxygenation index, .45), venoarterial extracorporal membrane oxygenation (ECMO) was initiated. After repeated failed attempts to wean from ECMO, the decision to limit treatment was made on day 18 after admission. The patient died after cessation of ECMO. The parents declined an autopsy. To date, lethal hMPV infections have been primarily described in immunosuppressed adults [3]. hMPV was first reported in the Netherlands in 2001, and several studies have shown that the clinical course of hMPV closely resembles RSV infection with bronchiolitis, pneumonia, and asthma exacerbation as the main manifestations [2]. In contrast, the proportion of children with severe hMPV infection requiring ICU admission or respiratory support is small [2, 4]. However, infants with RSV and hMPV coinfection had a 10-fold increased risk of requiring mechanical ventilation when compared with infants with isolated RSV infection [4]. Although ARDS is known to occur in patients with RSV bronchiolitis [5], hMPV-associated pediatric ARDS is very rare. An extensive literature search resulted in only 4 pediatric patients with isolated hMPV infection who developed severe ARDS: a 17-month-old girl receiving chemotherapy for acute leukemia died after a prolonged period of mechanical ventilation [6]. Two other children, both with underlying diseases (prematurity with chronic lung disease in one, transplant-related immunosuppression in the other), required ECMO but ultimately recovered [7, 8]. The fourth reported case concerns a 2 year-old, previously healthy girl without any known immunodeficiency who died of pulmonary hemorrhage soon after admission [9]. It has been suggested that deficiencies in innate immunity pathways, such as Toll-like receptor 4, lead to an increased risk of severe RSV infection [10], but the role of innate immunity in hMPV infections has not been studied thus far. The underlying neurodevelopmental delay may represent a clinical risk factor for severe respiratory disease in the presented case [2]. In conclusion, the summarized cases illustrate that hMPV infection may cause severe ARDS in susceptible children. Considering that testing for hMPV is not routinely performed, it is likely that hMPV-related ARDS is underreported. The mortality of pediatric ARDS remains high and early identification of the causative agent is crucial. We, therefore, suggest early testing for hMPV in patients with presumptive viral ARDS where no other agent can be identified. Additional studies investigating the role of hMPV in severe respiratory infections are needed to improve early and appropriate treatment of high-risk patients.
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#1John V. Williams (Monroe Carell Jr. Children's Hospital at Vanderbilt)H-Index: 63
#2Kathryn M. Edwards (Vandy: Vanderbilt University)H-Index: 115
Last. James E. Crowe (Vandy: Vanderbilt University)H-Index: 94
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Results. Forty-two (3.8%) of 1104 children tested positive for HMPV. The overall annual rate of HMPVassociated hospitalizations per 1000 children !5 years old was 1.2 (95% confidence interval [CI], 0.9‐1.6). This rate was highest among infants 0‐5 months old (4.9 per 1000 [95% CI, 2.9‐7.2]), followed by children 6‐11 months old (2.9 per 1000 [95% CI, 1.4‐4.7]). The annual rate of hospitalization for HMPV infection was less than that for respiratory syncytial virus infection but similar to that f...
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Background The primary role of respiratory syncytial virus (RSV) in causing infant hospitalizations is well recognized, but the total burden of RSV infection among young children remains poorly defined. Methods We conducted prospective, population-based surveillance of acute respiratory infections among children under 5 years of age in three U.S. counties. We enrolled hospitalized children from 2000 through 2004 and children presenting as outpatients in emergency departments and pediatric office...
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This is the first reported case of respiratory failure associated with human metapneumovirus (hMPV) infection in a liver transplant recipient or in a pediatric solid transplant recipient. A 9-month-old female developed respiratory distress 8 days following a liver transplant. hMPV was detected and she required intubation followed by extracorporeal membrane oxygenation for 26 days. Immunosuppressive medications were stopped during the acute infection except for methylprednisolone as treatment for...
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#1John V. WilliamsH-Index: 63
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Human metapneumovirus (hMPV) is a recently described paramyxovirus associated with upper and lower respiratory-tract infection (URI and LRI, respectively). We conducted a prospective study of URI and LRI in adults with hematologic malignancies during a 4-year period. We retrospectively tested samples by reverse-transcription polymerase chain reaction for hMPV and analyzed clinical data. Twenty-two (9%) of 251 episodes of respiratory infection tested positive for hMPV. Sixteen (73%) of the illnes...
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#1Malcolm G Semple (University of Liverpool)H-Index: 39
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The association between severe bronchiolitis and dual infection by human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) was investigated in !2-year-old infants with bronchiolitis who were admitted to the hospital during the 2001–2002 winter season. hMPV in nasopharyngeal aspirate and/or cells and fluid collected by nonbronchoscopic bronchoalveolar lavage was detected by reverse transcriptase–polymerase chain reaction (RT-PCR). hRSV was detected in nasopharyngeal aspirate and...
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We present the first report in the literature of a child with human metapneumovirus pneumonia who required extracorporeal membrane oxygenation for survival. This was a 3-month-old premature boy from British Columbia, Canada, who developed severe respiratory failure, experienced failure of high-frequency oscillatory mechanical ventilation, and required extracorporeal membrane oxygenation support for 10 days. This case illustrates the importance of including this newly discovered pathogen among th...
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#1Gilles Pelletier (Laval University)H-Index: 3
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The human Metapneumovirus (HMPV), a new member of the Paramyxoviridae family, has been recently associated with respiratory tract infections in young children. We report the case of a young, immunocompromised child who had severe lower respiratory tract infections during two consecutive winter seasons caused by genetically distinct HMPV strains.
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Acute respiratory distress syndrome (ARDS) complicating severe respiratory syncytial virus (RSV) infection has been described in only a few infants. In contrast to the low mortality rates usually associated with RSV infections (<5%), mortality rates in the range of 40–70% have been reported in pediatric patients with ARDS. However, studies on patients with ARDS are usually lumped with respect to causation, and the disease course of RSV-induced ARDS has not been previously studied. We examined th...
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Human metapneumovirus (hMPV), a common cause of respiratory illness in children, typically presents with clinical symptoms resembling that of respiratory syncytial virus. The unusual aspect in this case is the presentation of pertussis-like syndrome due to sole hMPV infection. To our knowledge, a case of pertussis-like syndrome caused by hMPV without concomitant Bordetella pertussis infection has not been reported.
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