Human metapneumovirus infection among children, Bangladesh.We confirmed circulation of human metapneumovirus (HMPV) among children with febrile febrile /feb·rile/ (feb´ril) pertaining to or characterized by fever. feb·rile adj. Of, relating to, or characterized by fever; feverish. and respiratory illness Noun 1. respiratory illness - a disease affecting the respiratory system respiratory disease, respiratory disorder adult respiratory distress syndrome, ARDS, wet lung, white lung - acute lung injury characterized by coughing and rales; inflammation of the in an urban slum in Dhaka, Bangladesh, during active surveillance in 2001, HMPV was the most common single virus identified among febrile children and appears to contribute to the high rates of illness in this population. ********** Human metapneumovirus (HMPV) is the newest member of the family Paramyxoviridae, in the subfamily subfamily /sub·fam·i·ly/ (sub´fam-i-le) a taxonomic division between a family and a tribe. sub·fam·i·ly n. A taxonomic category ranking between a family and a genus. Pneumovirinae, shared with respiratory syncytial virus respiratory syncytial virus (sĭnsĭsh`əl): see cold, common. (RSV RSV respiratory syncytial virus; Rous sarcoma virus. RSV abbr. respiratory syncytial virus RSV 1 Respiratory syncytial virus, see there 2 Rous sarcoma virus, see there ) (1). It appears to have 2 distinct genetic subgroups (2,3). HMPV was first described in a population of children in the Netherlands in 2001 (1) and has subsequently been linked with lower respiratory tract Noun 1. lower respiratory tract - the bronchi and lungs lung - either of two saclike respiratory organs in the chest of vertebrates; serves to remove carbon dioxide and provide oxygen to the blood illness (LRTI LRTI Lower respiratory tract infection ) in children and adults (2,4). Although HMPV independently contributes to LRTI, some studies report more severe cases when HMPV is a coinfectant with RSV (5, 6) or influenza (7); other studies have found no synergy (3). The Study As previously reported (8), we undertook fever surveillance in Kamalapur, an urban community in Dhaka used by the International Center for Diarrheal Disease Research, Bangladesh (ICDDR ICDDR International Centre for Diarrhoeal Disease Research (Bangladesh) ,B) as a field site since 1998. The site has 7 geographic strata and 379 clusters. We randomly selected clusters within strata and enrolled all households within those clusters for surveillance, after obtaining informed written consent. Field research assistants (FRAs) screened for fever across all ages among 5,000 households once weekly using standardized calendar questionnaires. FRAs referred children < 13 years of age who reported fever for any duration, or anyone [greater than or equal to] 13 years who reported fever for [greater than or equal to] 3 days, to our onsite clinic where study physicians conducted standardized history and physical examinations. If an axillary ax·il·lar·y n. Relating to the axilla. Axillary Located in or near the armpit. Mentioned in: Mastectomy axillary of or pertaining to the armpit. temperature of [greater than or equal to] 38[degrees]C was confirmed, physicians collected 3-5 mL of blood from children <5 years and persons [greater than or equal to] 5 years, respectively, as well as convalescent con·va·les·cent adj. Relating to convalescence. n. A person who is recovering from an illness, an injury, or a surgical operation. convalescent 1. pertaining to or characterized by convalescence. 2. blood samples 14 days later. Blood samples were allowed to clot and then centrifuged to obtain serum. We retrospectively selected serum samples to test for respiratory viruses from patients <13 years of age who had cough for 1-3 days and fever of [greater than or equal to] 38.5[degrees]C; we also selected paired serum samples negative for dengue dengue or breakbone fever or dandy fever Infectious, disabling mosquito-borne fever. Other symptoms include extreme joint pain and stiffness, intense pain behind the eyes, a return of fever after brief pause, and a characteristic rash. by immunoglobulin M immunoglobulin M n. Abbr. IgM The class of antibodies found in circulating body fluids and the first antibodies to appear in response to an initial exposure to an antigen. antibody capture (MAC)-ELISA. These samples were sent to the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. (CDC See Control Data, century date change and Back Orifice. CDC - Control Data Corporation ; Atlanta, Georgia, USA) for testing by hemagglutination hemagglutination /he·mag·glu·ti·na·tion/ (he?mah-gloo-ti-na´shun) agglutination of erythrocytes. he·mag·glu·ti·na·tion n. inhibition for influenza and enzyme immunoassay Immunoassay An assay that quantifies antigen or antibody by immunochemical means. The antigen can be a relatively simple substance such as a drug, or a complex one such as a protein or a virus. for RSV; parainfluenza parainfluenza Infectious disease A virus that causes URIs–up to 50% of croup and 10–15% of bronchiolitis, bronchitis, pneumonias in toddlers Clinical Rhinorrhea, cold-like Sx Risk factors Preschool children; by school age most children have been exposed types 1, 2, and 3; 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. ; and HMPV by using standard methods (9,10). A positive acute HMPV infection was defined as a [greater than or equal to] 4-fold rise in titer titer /ti·ter/ (ti´ter) the quantity of a substance required to react with or to correspond to a given amount of another substance. between acute-phase and convalescent-phase samples. Statistical analysis was performed by using StataSE Release 9.2 (StataCorp, College Station, TX, USA). We compared continuous variables between groups by using analysis of variance. For univariate analysis of categorical variables, we used 2 x 2 tables; for multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. , we used conditional logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. to determine strength of association between HMPV infection and potential explanatory covariates to obtain relative odds (RO) and 95% confidence intervals (CIs); p values were obtained by using the Fisher exact test. This study was approved by the research review and ethical review committees of ICDDR,B and the Institutional Review Board of CDC. From December 6, 2000, through December 5, 2001, 889 persons came to our clinic with fever, and blood samples were collected from 888 (99.9%). Of the 889, 775 (84.9%) were self-referred; 114 (93.4%) of 122 were referred by FRAs during the same period. Of the 888 sampled patients, we selected serum samples from 128 children <13 years of age who had paired samples, documented fever >38.5C, cough for 1-4 days before first blood collection, and negative test results for dengue antibodies by MAC-ELISA. These samples were tested by hemagglutination inhibition against influenza virus influenza virus n. Any of three viruses of the genus Influenzavirus designated type A, type B, and type C, that cause influenza and influenzalike infections. A (H1N1 and H3N2) and influenza type B. Among these, 107 paired samples had sufficient remaining serum to be tested for other respiratory viruses, including HMPV. Table 1 shows the distribution of all virus infections detected by serologic testing of 107 paired specimens. Of 60 infections detected among these children, 20 (33.3%) were caused by HMPV, the largest single group after influenza (although more than either influenza A influenza A n. 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'; or B alone). HMPV was detected in the dry premonsoon season from January through the end of June (Figure). We found no demographic differences in subgroup analysis by age group (<5 years and [greater than or equal to] 5 years) or between children with acute HMPV infection and noninfected children (Table 2). Also, no differences were found in the reported history of fever duration or other complaints associated with febrile or respiratory illness in this population before treatment. [FIGURE OMITTED] Clinical findings (Table 2) showed no differences in mean fever or proportion of children with high fever ([greater than or equal to] 39[degrees]C). However, compared with non-HMPV infection, acute HMPV infection was 3.5 times more likely (95% CI 1.02-11.24) to be associated with clinical pneumonia in all children and 4.8 times more likely (95% CI 0.90-23.86) to be associated with altered mental status (irritability/lethargy) in children <5 years old (Table 2). Only 1 child with acute HMPV infection had coinfection with another virus (influenza A). Conclusions To our knowledge, ours is the first reported finding of HMPV in Bangladesh demonstrating substantial contribution of HMPV to febrile and lower respiratory tract illness in children <13 years of age. Our report substantiates that of a study from India (11). In a hospital study conducted in Bangladesh, a virus was isolated in only 33.3% of children with LRTI (12). Although HPMV was unknown at that time, and thus would not have been reported, the contribution of viruses to LRTI in children is often underreported by studies that have focused on bacterial infection identification or that did not include collection of paired serum samples to detect viral infections (3). HMPV has likely been a major factor in pneumonia and bronchiolitis Bronchiolitis Definition Bronchiolitis is an acute viral infection of the small air passages of the lungs called the bronchioles. Description Bronchiolitis is extremely common. in this population, as it has in others (1,2,11). In this study, HMPV was not only significantly associated with pneumonia, but with lethargy, an indicator of severe pneumonia in young children. Given the high rates of illness and death from pneumonia in this population (8), this association has important implications for disease control strategies. HMPV was also found in the dry pre-Monsoon season, when incidence of pneumonia peaks in this population. Similarly, parainfluenza peaks from March-April. In contrast, influenza occurs before and during the Monsoon season (March-August). Our pilot study to assess the possible effects of HMPV on LRTI in children in Bangladesh had the following limitations: 1) healthy control patients were not included in the study; 2) the study was not originally designed to look for respiratory viruses; 3) fever was a main selection criterion and may have biased selection of more severe illnesses (a previous pneumonia study indicated that <33% of children in this environment with severe pneumonia have fever (13), perhaps substantially underestimating HMPV prevalence); 4) the observation period of 1 year may not represent the typical seasonal pattern; 5) case identification was based on serologic test results, and some children may have had a subclinical subclinical /sub·clin·i·cal/ (sub-klin´i-k'l) without clinical manifestations. sub·clin·i·cal adj. Not manifesting characteristic clinical symptoms. Used of a disease or condition. immune response immune response n. An integrated bodily response to an antigen, especially one mediated by lymphocytes and involving recognition of antigens by specific antibodies or previously sensitized lymphocytes. or acute-phase samples may have been collected too late to observe a significant rise in titer, thus underestimating prevalence of disease; and 6) the study included insufficient cases to analyze viral interaction. To more clearly define the role of HMPV and other respiratory viruses in this population, and to improve disease control strategies, fever surveillance targeting a broader range of clinical syndromes over a sustained period is needed. This study was funded by the International Center for Tropical Disease Research of the National Institutes of Health, Bethesda, Maryland, USA; by a cooperative agreement from the US Agency for International Development (HRN-A-00-96-90005-00); and by core donors to ICDDR,B. References (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 n. 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.) Crowe JE Jr. Human metapneumovirus as a major cause of human respiratory tract disease. Pediatr Infect Dis J. 2004;23(Suppl):S215-21. (3.) Williams JV, Harris PA, Tollefson SJ, Halburnt-Rush LL, Pingsterhaus JM, Edwards KM, et al. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. 2004;350:443-50. (4.) Williams JV. Human metapneumovirus: an important cause of respiratory disease in children and adults. Curr Infect Dis Rep. 2005;7:204-10. (5.) Greensill J, McNamara PS, Dove W, Flanagan B, Smyth RL, Hart CA. Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerg Infect Dis. 2003;9:372-5. (6.) Semple MG, Cowell A, Dove W, Greensill J, McNamara PS, Half-hide C, et al. Dual infection of infants by human metapneumovirus and 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. is strongly associated with severe bronchiolitis. J Infect Dis. 2005;191:382-6. (7.) Bosis S, Esposito S, Niesters HG, Crovari P, Osterhaus AD, Principi N. Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses. J Med Virol. 2005;75:1014. (8.) Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M, et al. Effect of weekly zinc supplements on incidence of pneumonia and diarrhea in children younger than 2 years in an urban, low-income population in Bangladesh: randomized controlled trial A randomized controlled trial (RCT) is a scientific procedure most commonly used in testing medicines or medical procedures. RCTs are considered the most reliable form of scientific evidence because it eliminates all forms of spurious causality. . Lancet. 2005;366(9490):999-1004. (9.) Smith NM, Bresee JS, Shay shay n. Informal A chaise. [Back-formation from chaise (taken as pl. )] Noun 1. DK, Uyeki TM, Cox N J, Strikas RA. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices The Advisory Committee on Immunization Practices (ACIP) consists of fifteen advisors to the Centers for Disease Control and Prevention (CDC), selected by the Secretary of the United States Department of Health and Human Services, to provide advice and guidance on the most effective (ACIP ACIP Cardiology A clinical trial–Asymptomatic Cardiac Ischemia Pilot Study that evaluated 3 therapeutic strategies2 for ↓ myocardial ischemia during exercise testing. ). MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg, Recomm Rep. 2006;55(RR-10):1-42. (10.) Falsey AR, Erdman D, Anderson LJ, Walsh EE. Human metapneumovirus infections in young and elderly adults. J Infect Dis. 2003;187:785-90. (11.) Rao BL, Gandhe SS, Pawar SD, Arankalle VA, Shah SC, Kinikar AA. First detection of human metapneumovirus in children with acute respiratory infection in India: a preliminary report. J Clin Microbiol. 2004;42:5961-2. (12.) Huq F, Rahman M, Nahar N, Alam A, Haque M, Sack DA, et al. 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. due to virus among hospitalized children in Dhaka, Bangladesh. Rev Infect Dis. 1990;12(Suppl 8):S982-7. (13.) Brooks WA, Yunus M, Santosham M, Wahed MA, Nahar K, Yeasmin S, et al. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet. 2004;363:1683-8. W. Abdullah Brooks, * ([dagger]) Dean Erdman, ([double dagger]) Pauline Terebuh, ([section]) Alexander Klimov, ([double dagger]) Doli Goswami, * Amina Tahia Sharmeen, * Tasnim Azim, * Stephen Luby, * Carolyn Bridges, ([double dagger]) and Robert Breiman ([paragraph] * ICDDR,B, Dhaka, Bangladesh; ([dagger]) Johns Hopkins University Johns Hopkins University, mainly at Baltimore, Md. Johns Hopkins in 1867 had a group of his associates incorporated as the trustees of a university and a hospital, endowing each with $3.5 million. Daniel C. , Baltimore, Maryland, USA; ([double dagger]) Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([section]) Georgia Department of Human Resources, Atlanta, Georgia, USA; and ([paragraph]) Centers for Disease Control and Prevention, Nairobi, Kenya Address for correspondence: W. Abdullah Brooks, ICDDR,B Division of Health Systems and Infectious Diseases, GPO Box 128 Mohakhali, Dhaka 1000, Bangladesh; email: abrooks@icddrb.org Dr Brooks is a specialist in pediatrics and preventive medicine preventive medicine, branch of medicine dealing with the prevention of disease and the maintenance of good health practices. Until recently preventive medicine was largely the domain of the U.S. , head of the Infectious Diseases Unit in the Division of Health Systems and Infectious Diseases at ICDDR,B in Dhaka, Bangladesh, and a faculty member of the Bloomberg School of Public Health at Johns Hopkins University in Baltimore, Mary land, USA. His interests involve surveillance and intervention studies intervention studies, n.pl the epidemiologic investigations designed to test a hypothesized cause and effect relation by modifying the supposed causal factor(s) in the study population. on infectious diseases such as acute respiratory diseases, typhoid fever typhoid fever acute, generalized infection caused by Salmonella typhi. The main sources of infection are contaminated water or milk and, especially in urban communities, food handlers who are carriers. , and dengue.
Table 1. Viruses detected in children <13 years of age by
serology, Kamalampur, Bangladesh, December 2000-December 2001
Virus No. infections % (N = 60) Cumulative %
Human metapneumovirus 20 33.3 33.3
Respiratory syncytial
virus 3 5.0 38.3
Adenovirus 4 6.7 45.0
Parainfluenza virus 3 9 15.0 60.0
Influenza (H1N1) 8 13.3 73.3
Influenza (H3N2) 2 3.3 76.6
Influenza B 14 23.3 99.9
Table 2. Demographic and clinical characteristics of children < 13
years of age presenting with fever, Kamalampur, Bangladesh, December
2000-December 2001 *
HMPV positive HMPV negative
Variables ([dagger]) (N = 20) (N = 87)
Mean age, y
([section]) (SID,
95% CI) 4.5 (2.6; 3.2-5.7) 4.5 (3.1; 3.9-5.2)
Mean age for 0-4 age
range, y ([section])
(SID, 95% CI) 2.9 (1.4; 2.1-3.8) 2.3 (1.2, 2.0-2.7)
Mean age for 5-12 age
range, y ([section])
(SID, 95% CI) 7.3 (1.9; 5.5-9.0) 7.7 (l.8, 7.1-8.4)
Children <5 y, no. (%) 13 (65.0) 52 (59.8)
Male gender, no. (%) 9 (45.0) 49 (56.3)
Duration of fever
prior to clinic,
([section]) d (SID,
95% CI) 3.1 (0.8; 2.7-3.5) 3.1 (1.7; 2.7-3.4)
Symptoms
Headache,no. (%) 8 (40.0) 34 (39.1)
Body pain, no. (%) 4 (20.0) 25 (28.7)
Rhinorrhea, no. (%) 16 (80.0) 60 (69.0)
Difficulty breathing,
no. (%) 3 (15.0) 4 (4.6)
Normal activity/
behavior, no. (%) 15 (75.0) 64 (73.6)
Fever, ([section])
[degrees]C (SID,
95% CI) 39.2 (0.6; 39.0-39.5) 39.1 (0.6; 39.0-39.2)
High fever ([greater
than or equal to]
39[degrees]C), no.
(%) 10 (50.0) 49 (56.3)
Respiratory rate
([section]) (SID,
95% CI) 42 (11; 36-47) 41 (9; 39-43)
Crepitations (rales)
or wheezing, no. (%) 11 (55.0) 28 (32.1)
Altered mental status,
([paragraph]) no.
(%) 5 (25.0) 8 (9.2)
Altered mental status
([paragraph]) if <5
y (#), no. (%) 5 (38.5) 6 (11.5)
Pneumonia/LRTI
diagnosis, no. (%) 8 (40.0%) 14 (16.1)
Relative odds p value
Variables ([dagger]) (95% Cl) ([double dagger])
Mean age, y
([section]) (SID,
95% CI) -- 0.951
Mean age for 0-4 age
range, y ([section])
(SID, 95% CI) -- 0.113
Mean age for 5-12 age
range, y ([section])
(SID, 95% CI) -- 0.556
Children <5 y, no. (%) 1.25 (0.41-4.08) 0.801
Male gender, no. (%) 0.63 (0.21-1.89) 0.457
Duration of fever
prior to clinic,
([section]) d (SID,
95% CI) -- 0.983
Symptoms
Headache,no. (%) 1.04 (0.33-3.10) 1.000
Body pain, no. (%) 0.62 (0.14-2.20) 0.580
Rhinorrhea, no. (%) 1.80 (0.51-8.06) 0.419
Difficulty breathing,
no. (%) 3.66 (0.48-23.48) 0.119
Normal activity/
behavior, no. (%) 0.73 (0.22-2.20) 0.620
Fever, ([section])
[degrees]C (SID,
95% CI) -- 0.899
High fever ([greater
than or equal to]
39[degrees]C), no.
(%) 0.78 (0.26-2.32) 0.627
Respiratory rate
([section]) (SID,
95% CI) -- 0.808
Crepitations (rales)
or wheezing, no. (%) 2.57 (0.85-7.86) 0.072
Altered mental status,
([paragraph]) no.
(%) 3.29 (0.73-13.19) 0.065
Altered mental status
([paragraph]) if <5
y (#), no. (%) 4.79 (0.90-23.86) 0.035
Pneumonia/LRTI
diagnosis, no. (%) 3.48 (1.02-11 ~ 24) 0.029
* HPMV, human metapneumovirus; CI, confidence interval; SD, standard
deviation; LRTI, lower respiratory tract illness.
([dagger]) Categorical variables report N persons (percent of persons
with characteristic in each group). Compared by 2 x 2 table, odds
ratio with 95% CI.
([double dagger]) 2-tailed Fisher exact text.
([section]) Continuous variables. Means compared by using Student t
test.
([paragraph]) Irritability, lethargy.
(#) N = 65 children <5 y.
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