Human metapneumovirus (hMPV) is a single-stranded negative-sense RNA virus. Though first isolated in 2001, studies of archived sera suggest it has been circulating since at least 1958 . Analyses of respiratory tract samples suggest that hMPV associates with illness in HIV-infected cohorts [2,3], but there are no detailed published accounts of hMPV infection in HIV-positive individuals. We describe five HIV-positive patients hospitalized in London, UK, with hMPV respiratory illnesses in Spring 2011.
We retrospectively identified and reviewed the records for all HIV-positive adult inpatients who tested positive for hMPV. For each patient, a combined nose/throat swab for respiratory virus PCR was obtained. In the laboratory, viral nucleic acid was extracted and detected using real-time PCR. Primers to hMPV targeted the viral nucleoprotein gene, as described by Mackay et al.; later adapted to multiplex PCR by Gunson et al..
Our total HIV-positive outpatient cohort is approximately 3800, with 80 admitted during this period. Clinical, laboratory and radiological features of the five patients are summarized in Table 1. Patient 1 was a 29-year-old Caucasian man with a 4-week history of coryza, sore throat and dry cough, and 2 days productive cough, fever and right-sided pleuritic chest pain. Patient 2 was a 31-year-old Caucasian man with a 4-day history of dry cough and a 2-day history of fever. Patient 3 was a 42-year-old Asian man with a 5-day history of coryza, fever, diarrhoea, shortness of breath and a productive cough. Patient 4 was a 40-year-old Caucasian man with a 3-day history of shortness of breath, wheeze, fever and productive cough. Patient 5 was a 57-year-old Caucasian man with a 7-day history of dry cough, fever, night sweats, malaise, myalgia and diarrhoea.
No evidence of bacterial co-infection was identified on blood or sputum culture in any patient. All five patients tested positive for hMPV, and negative for influenza A, influenza B, parainfluenza viruses 1–3, adenovirus and respiratory syncytial virus. Their mean CD4 cell count (cells/μl) was 456 (range 250–620), reflecting relatively low-level immunosuppression. All three patients on antiretroviral therapy (ART) had suppressed viral loads (<50 copies/ml). The mean number of days between first fever and presentation was 4.2 (range 2–7) and presenting symptoms were non-specific. Ground-glass opacities/ground-glass nodular opacities were present in three patients, and ground-glass consolidation was seen in four patients. Bronchial wall thickening and ‘tree in bud’ change was also seen in four patients.
This is the first study to describe detailed clinical and radiological features of hMPV respiratory infection in HIV-positive adults. All five patients made full clinical recoveries from their presenting illness. Among HIV-positive adults, viruses account for a large proportion of respiratory illnesses, with hMPV increasingly recognized as an important cause. In Montreal, Klein et al. undertook a prospective evaluation of HIV-infected outpatients (median CD4 cell count 325 cells/μl) with a documented temperature above 38°C associated with respiratory symptoms. Of 50 patients, 45 (90%) were receiving ART. Viruses accounted for 64% of infections: after influenza, hMPV was most common (six samples) and was associated with wheeze in 50% of patients. By contrast, wheeze was present in 5% of those with influenza. Individuals with hMPV infection were generally less immunosuppressed than those with influenza. In this series, all five patients had CD4 cell counts above 250 cells/μl, and two (40%) had wheeze. As part of the Swiss HIV Cohort Study, Garbino et al. obtained 59 bronchoalveolar lavage specimens from 55 HIV-infected patients undergoing bronchoscopy for evaluation of opportunistic infection. At least one respiratory virus was identified in 11 patients (19%) and one had hMPV.
The radiological findings in our patients were non-specific and similar to those reported in other patient groups with hMPV infection. Franquet et al. reviewed the high-resolution computed tomography (HRCT) findings of five HIV-uninfected haematopoietic stem cell transplant recipients with proven hMPV pneumonia. Bilateral abnormalities were identified in all cases, with patchy asymmetric ground-glass opacification and intra-pulmonary nodules being most common. Wong et al. described a nosocomial outbreak of hMPV pneumonia in Hong Kong. HRCT scans of all four patients showed ground-glass consolidation, parenchymal bands and areas of opacification; three patients had intra-pulmonary nodules.
Extrapolation of the observations from these studies, or our own, is limited by small patient numbers, and further work on the epidemiology and pathology of hMPV infection in both immunocompetent and immunocompromised patients is awaited. However, it is clear that clinicians caring for HIV-positive patients should consider a wide differential of respiratory viruses, and that hMPV can cause significant morbidity. This continues to be the case in the highly active antiretroviral therapy era, when a relative decrease in the incidence of opportunistic pulmonary infection can be expected.
Conflicts of interest
There are no conflicts of interest.
1. van den Hoogen BG, de Jong JC, Groen J, Kuiken T, de Groot R, Fouchier RA, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease
. Nat Med
2. Klein MB, Yang H, DelBaso L, Carbonneau J, Frost E, Boivin G. Viral pathogens including human metapneumovirus are the primary cause of febrile respiratory illness in HIV-infected adults receiving antiretroviral therapy
. J Infect Dis
3. Garbino J, Inoubli S, Mossdorf E, Weber R, Tamm M, Soccal P, et al. Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infections
4. Mackay IM, Jacob KC, Woolhouse D, Waller K, Syrmis MW, Whiley DM, et al. Molecular assays for detection of human metapneumovirus
. J Clin Microbiol
5. Gunson RN, Collins TC, Carman WF. Real-time RT-PCR detection of 12 respiratory viral infections in four triplex reactions
. J Clin Virol
6. Franquet T, Rodriguez S, Martino R, Salinas T, Gimenez A, Hidalgo A. Human metapneumovirus infection in haematopoietic stem cell transplant recipients: high-resolution computed tomography findings
. J Comput Assist Tomogr
7. Wong CK, Lai V, Wong YC. Comparison of initial high resolution computed tomography features in viral pneumonia between metapneumovirus infection and severe acute respiratory syndrome
. Eur J Radiol