Human metapneumovirus, Australia, 2001-2004.We examined 10,025 respiratory samples collected for 4 years (2001-2004) and found a 7.1% average annual incidence of human metapneumovirus. The epidemic peak of infection was late winter to spring, and genotyping showed a change in predominant viral genotype in 3 of the 4 years.
Human metapneumovirus (HMPV) is now recognized as a substantial cause of acute respiratory infection, particularly in children; it has phenotypic and clinical characteristics that are similar to those of respiratory syncytial virus respiratory syncytial virus (sĭnsĭsh`əl): see cold, common. (RSV RSV respiratory syncytial virus; Rous sarcoma virus.
respiratory syncytial virus
RSV 1 Respiratory syncytial virus, see there 2 Rous sarcoma virus, see there ) (1,2). HMPV is ubiquitous; it infects most children at an early age, and distinct epidemic peaks are reported in the winter months (1,3-6). However, many of theses studies were conducted in the Northern Hemisphere and involved samples collected during a relatively short period; few data exist from extended studies over several years that involve populations in other parts of the world.
Although 2 main HMPV types are recognized (A and B) (1,3,7), each with 2 subtypes (A1, A2; B1, B2) (8), the extent of genetic variation of circulating HMPV subtypes over time has not been extensively examined. We sought to determine the incidence and seasonal distribution of HMPV in an Australian population from 2001 to 2004 and to establish the pattern of genotype distribution during those 4 years by examining the genetic variability of the P gene in 640 of 707 HMPV-positive samples.
The necessary ethics approval for this study was obtained from the Royal Children's Hospital The Royal Children's Hospital in Melbourne, Australia is the major specialist paediatric hospital for Victoria offering a full range of clinical services, tertiary care and health promotion and prevention programs for children and adolescents. ethics committee ethics committee A multidisciplinary hospital body composed of a broad spectrum of personnel–eg, physicians, nurses, social workers, priests, and others, which addresses the moral and ethical issues within the hospital. See DNR, Institutional review board. . We collected nasopharyngeal nasopharyngeal
pertaining to the nasal and pharyngeal cavities.
see nasopharyngeal meatus.
see reverse sneeze. aspirate as·pi·rate
To take in or remove by aspiration.
A substance removed by aspiration.
The removal by suction of a fluid from a body cavity using a needle. (NPA (1) (Numbering Plan Area) The Bellcore/Telcordia telephone area code system in use in the U.S., Canada, Alaska, Hawaii and islands in the Caribbean. See NPA code.
(2) (Network Professional Association, San Diego, CA, www.npanet. ) specimens from January 2001 through December 2004 from patients with acute lower respiratory tract infection While often used as a synonym for pneumonia, the rubric of lower respiratory tract infection can also be applied to other types of infection including lung abscess, acute bronchitis, and emphysema. in Queensland, Australia. Patients were from 3 months to 93 years of age (mean 8.2 years, median 1.37 years), and 78.1% of specimens were from children <5 years of age. Nucleic acids Nucleic acids
The cellular molecules DNA and RNA that act as coded instructions for the production of proteins and are copied for transmission of inherited traits. were extracted from 0.2 mL of each NPA specimen by using the High Pure Viral Nucleic Acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis. kit (Roche Diagnostics, Mannheim, Germany), according to the manufacturer's instructions. Extracts were analyzed for HMPV sequences by reverse transcriptase PCR RT-PCR is a one or two-step process for converting RNA to DNA and the subsequent amplification of the reversely-transcribed DNA.
In the first step of RT-PCR, called the “first strand reaction,” complementary DNA (cDNA) is made from an mRNA template using (9). For samples collected during 2001 and 2002, other viral respiratory pathogens were detected by using a direct fluorescent antibody Direct fluorescent antibody (DFA or dFA) is a laboratory test that uses antibodies tagged with fluorescent dye to detect the presence of microorganisms. This is the main test used to detect rabies in animals and requires the examination of brain tissue. assay (DFA DFA - Deterministic Finite-state Automaton. See Finite State Machine. ) in combination with a culture-augmented DFA method (10). For samples collected in 2003 and 2004, these pathogens were detected by multiplex PCR PCR polymerase chain reaction.
polymerase chain reaction
Polymerase chain reaction (PCR) (10).
Of 10,025 NPA specimens tested, 707 were positive for HMPV, for an overall incidence of 7.1% during the 4 years. The youngest HMPV-positive patient was 4 months old, and the oldest was 79 years. In children (<18 years of age) the incidence of virus was 7.4%, and 91.9% of HMPV-positive children were <5 years of age. The seasonal distribution of HMPV infection showed a distinctive pattern for each of the 4 years studied (Figure 1). In 2001, HMPV showed broad seasonal activity; incidence was >5% in 3 consecutive seasons (autumn, winter, and spring) and peaked at 10.6% in the spring (September--November). In 2002 and 2004, most HMPV activity was in spring, (incidence of 13.6% and 15.4%, respectively), with little evidence during autumn (March-May). In 2003, the peak incidence of 9.0% occurred in winter (June--August) and persisted into spring (5.4%). In all years, virus was present well into summer (December--February), with an incidence ranging from 2.5% to 5.2%. On examination of those samples collected in 2003 and 2004, which were all previously analyzed for common respiratory viruses by PCR, HMPV was the most frequently detected respiratory virus in children during the spring of each year. Expressed as an annual average over the 4 years studied, the predominant viral pathogen was RSV (9.2%), followed by HMPV (7.1%), influenza A influenza A
Influenza caused by infection with a strain of influenza virus type A.
influenza A Infectious disease An avian virus, especially of ducks–which in China live near the pig reservoir and 'vector'; (3.5%), parainfluenza virus parainfluenza virus
Any of five types of viruses of the genus Paramyxovirus that are associated with various respiratory infections, especially in children. 3 (2.3%), and adenovirus adenovirus
Any of a group of spheroidal viruses, made up of DNA wrapped in a protein coat, that cause sore throat and fever in humans, hepatitis in dogs, and several diseases in fowl, mice, cattle, pigs, and monkeys. (1.3%). In 6.8% of HMPV-positive cases, evidence of co-infection with another respiratory virus was seen; 20 patients were concurrently infected with an adenovirus, 10 with influenza A virus, 8 with RSV, 9 with parainfluenza virus 3, and 1 with parainfluenza virus 2.
[FIGURE 1 OMITTED]
Amplification products generated directly from 640 HMPV-positive NPA specimens were genotyped as previously described (11) (GenBank accession nos. DQ112292-DQ112320 and DQ121378-DQ121384). Data showed that all 4 viral subtypes cocirculated during each of the 4 years studied (Table 1, Figure 2). However, a different subtype (programming) subtype - If S is a subtype of T then an expression of type S may be used anywhere that one of type T can and an implicit type conversion will be applied to convert it to type T. predominated during 3 of the 4 years: HMPV subtype A1 was dominant in 2001, subtype A2 in 2002 and 2003, and subtype B1 in 2004 (Table 1).
[FIGURE 2 OMITTED]
Clinical records from 273 patients who were positive for HMPV were scrutinized, and data describing clinical features and length of hospital stay were recorded. Of these patients, 203 (74.4%) were admitted to hospital with a median length of admission of 3 days and a mean of 6.5 days. The predominant clinical features were cough (63%), rhinorrhea (61%), respiratory crackles/crepitations (60%), and fever (57%) (Table 2). Ninety (33.9%) of the 273 patients had a chest radiograph radiograph /ra·dio·graph/ (-graf?) the film produced by radiography.
n. , and 77 (85.6%) patients showed bilateral parahilar peribronchial infiltrates consistent with a lower respiratory tract infection. Disease severity of the 273 HMPV-positive patients was classified as mild (46.8%), moderate (42.5%), and severe (10.7%), based on the use of supplemental oxygen and fluids and length of hospital stay.
This study of HMPV infection is the largest so far reported. The results of recent, similar studies suggested that peak periods of infection with HMPV predominate during winter in the Northern Hemisphere. However, this finding has not been extensively examined over an extended period with a large, continuous sample. Our study found that the peak period of HMPV infection in Queensland, Australia, occurs predominantly in spring (August--October) but that HMPV can be detected in every month. This finding suggests that HMPV activity, like RSV activity, occurs in the community throughout the year, and peaks of infection are a result of seasonal environmental factors.
Although RSV predominated in all years, HMPV was the second most frequently detected virus in each year studied. The low rate of co-infection of HMPV with other respiratory viruses (including RSV) suggests that co-infection may not be common in our community. When analyzing disease severity in this sample with a 2-sided test of proportions, we saw no significant difference between patients with a co-infection and those without. Therefore, our data did not support the suggestion by others that co-infection of HMPV with RSV or other viral respiratory pathogens is a risk factor for severe disease (6).
The shift in predominant HMPV genotype observed in this study was similar to those reported for RSV and influenza viruses (6) and can be attributed to changes in immunity of the population in response to antigenic differences between the predominant circulating strains (12,13). However, a relationship between genotype and disease severity, as previously established for RSV (14,15), did not appear to apply for HMPV, but we plan to examine this relationship further.
The clinical features associated with HMPV infection in this study were not sufficiently distinctive to clinically differentiate it from other respiratory viral infections in children, particularly those attributed to RSV. In addition, few patients (10.6%) had severe disease, but most (76%) were sufficiently ill to be admitted and treated in the hospital for [greater than or equal to] 3 days, which represents a substantial amount in healthcare costs.
Finally, this comprehensive study, conducted for 48 months, is the first one aimed at establishing an accurate estimate of the incidence and seasonal distribution of HMPV infection and to determine the genetic variation of HMPV circulating in our population. The clinical spectrum of infection in a substantial proportion of HMPV-positive patients has been described, and studies are continuing to fully elucidate the clinical effect of infection with this virus in our community.
We thank the staff of the Microbiology Division of the Queensland Health Pathology Service, Royal Brisbane and Women's Hospital The Royal Brisbane and Women's Hospital is a hospital located in the suburb of Herston in Brisbane, Queensland, Australia.
The hospital currently has a total of 948 beds. It is estimated that 65% of the patients served come from 15 kilometres of the hospital. . We also acknowledge the Directors of Paediatrics, Queensland Health, who gave permission to review the medical records of HMPV-positive patients.
This study was supported by the Royal Children's Hospital Foundation grants I 922-034 and R 912-009, the Woolworths Fresh Futures Appeal, and the National Health and Medical Research Council The National Health and Medical Research Council (NHMRC) is Australia's peak funding body for medical research, with a budget of nearly A$500M a year . The Council was established to develop and maintain health standards and is responsible for implementing the , Australia, project grant 243702.
Dr Sloots is the director of the research section of the Queensland Paediatric Adj. 1. paediatric - of or relating to the medical care of children; "pediatric dentist"
pediatric Infectious Diseases Laboratory at Sir Albert Sakzewski Virus Research Centre. His main research interests are in pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. infectious diseases, particularly viral respiratory disease.
(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 respiratory tract
The air passages from the nose to the pulmonary alveoli, including the pharynx, larynx, trachea, and bronchi.
Respiratory tract disease. Nat Med. 2001;7:719-24.
(2.) Nissen MD, Siebert DJ, Mackay IM, Sloots TP, Withers withers
the region over the backline where the neck joins the thorax and where the dorsal margins of the scapulae lie just below the skin.
see fistulous withers. SJ. Evidence of human metapneumovirus in Australian children. Med J Aust. 2002; 176:188.
(3.) Bastien N, Ward D, van Caeseele P, Brandt K, Lee SH, McNabb G, et al. Human metapneumovirus infection in the Canadian population. J Clin Microbiol. 2003;41:4642-6.
(4.) Freymouth F, Vabret A, Legrand L, Eterradossi N, Lafay-Delaire F, Brouard J, et al. Presence of the new human metapneumovirus in French children with bronchiolitis Bronchiolitis Definition
Bronchiolitis is an acute viral infection of the small air passages of the lungs called the bronchioles.
Bronchiolitis is extremely common. . Pediatr Infect Dis J. 2003;22:92-4.
(5.) Peiris JS, Tang WH, Chan KH, Khong PL, Guan guan: see curassow. Y, Lau YL, et al. Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerg Infect Dis. 2003;9:628-33.
(6.) Robinson JL, Lee BE, Bastien N, Li Y. Seasonality and clinical features of human metapneumovirus infection in children in northern Alberta. J Med Virol. 2005;76:98-105.
(7.) van den Hoogen BG, Bestebroer TM, Osterhaus AD, Fouchier RA. Analysis of the genomic sequence of a human metapneumovirus. Virology virology, study of viruses and their role in disease. Many viruses, such as animal RNA viruses and viruses that infect bacteria, or bacteriophages, have become useful laboratory tools in genetic studies and in work on the cellular metabolic control of gene expression . 2002;295:119-32.
(8.) Boivin G, Mackay IM, Sloots TP, Madhi S, Freymuth F, Wolf D, et al. Global genetic diversity of human metapneumovirus fusion gene. Emerg Infect Dis. 2004; 10:1154-7.
(9.) Mackay IM, Bialasiewicz S, Jacob KC, McQueen E, Arden KA, Nissen MD, et al. Genetic diversity of human metapneumovirus over 4 consecutive years in Australia. J Infect Dis. 2006; 193:160-3.
(10.) Syrmis MW, Whiley DM, Thomas M, Mackay IM, Williamson J, Siebert DJ, et al. A sensitive, specific, and cost-effective multiplex reverse transcriptase-PCR assay for the detection of seven common respiratory viruses in respiratory samples. J Mol Diagn. 2004;6:125-31.
(11.) Mackay IM, Bialasiewicz S, Waliuzzaman Z, Chidlow GR, Fegredo DC, Laingam S, et al. Genotyping of the human metapneumovirus using the P gene identifies four viral subtypes. J Infect Dis. 2004;190:1913-8.
(12.) Peret TC, Hall CB, Schnabel KC, Golub JA, Anderson LJ. Circulation patterns of genetically distinct group A and B strains of human respiratory syncytial virus Human respiratory syncytial virus (RSV) is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae, which includes common respiratory viruses such as those causing measles and mumps. in a community. J Gen Virol. 1998;79:2221-9.
(13.) Cane PA, Pringle CR. Evolution of subgroup A respiratory syncytial virus: evidence for progressive accumulation of amino acid changes in the attachment protein. J Virol. 1995;69:2918-25.
(14.) Kneyber MC, Brandenburg AH, Rothbarth PH, de Groot R, Ott A, van Steensel-Moll HA. Relationship between clinical severity of respiratory syncytial virus infection Respiratory Syncytial Virus Infection Definition
Respiratory syncytial virus (RSV) is a virus that can cause severe lower respiratory infections in children under the age of two, and milder upper respiratory infections in older children and adults. and subtype. Arch Dis Child. 1996;75:137-40.
(15.) Walsh EE, McConnochie KM, Long CE, Hall CB. Severity of respiratory syncytial virus infection is related to virus strain. J Infect Dis. 1997;175:814-20.
Address for correspondence: Theo P. Sloots, Queensland Paediatric Infectious Diseases Laboratory, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital and Health Service District, Herston Rd, Herston, Queensland, Australia 4029; email: email@example.com
Theo P. Sloots,* ([dagger]) ([double dagger]) ([section]) (1) Ian M. Mackay,* ([dagger]) ([double dagger]) (1) Seweryn Bialasiewicz, * ([dagger]) Kevin C. Jacob, * ([dagger] [double dagger]) Emily McQueen, * ([dagger]) Gerald B. Harnett, ([paragraph]) David J. Siebert, ([section]) I. Brent Masters, * Paul R. Young, ([double dagger]) and Michael D. Nissen * ([dagger]) ([double dagger]) ([section])
* Royal Children's Hospital and Health Service District, Brisbane, Queensland, Australia; ([dagger]) Clinical Medical Virology Centre at University of Queensland The University of Queensland (UQ) is the longest-established university in the state of Queensland, Australia, a member of Australia's Group of Eight, and the Sandstone Universities. It is also a founding member of the international Universitas 21 organisation. , Brisbane, Queensland, Australia; ([double dagger]) University of Queensland, Brisbane, Queensland, Australia; ([section]) Queensland Health Pathology Service, Brisbane, Queensland, Australia; and ([paragraph]) PathWest Laboratory Medicine, Perth, Western Australia This article is about the metropolitan area of Perth, Western Australia. For the local government area, see City of Perth.
Perth is the capital of the Australian state of Western Australia. , Australia
(1) These authors contributed equally to this study.
Table 1. Distribution of human metapneumovirus (HMPV) subtypes in Queensland, Australia, 2001-2004 HMPV subtype Total samples Year tested A1 A2 B1 B2 2001 59 58 24 8 10 2002 122 20 51 12 17 2003 189 10 36 30 24 2004 270 1 23 59 17 Table 2. Signs and symptoms noted with human metapneumovirus infection (N = 273) Clinical feature % Cough 63 Rhinorrhea 61 Crackles/crepitations 60 Fever 57 Respiratory distress 48 Anorexia 45 Vomiting 39 Wheezing 38 Irritability 31 Tachypnea 30 Lethargy 26 Pharyngitis/tonsillitis 24 Dry mouth 23 Diarrhea 18 Otitis media 15 Noisy breathing 14 Rash 10 Conjunctivitis 7 Cyanosis 4 Apnea 2 Hoarseness 1