Respiratory Illness In Young Children Research Articles

2608. Circulating Respiratory Syncytial Virus Genotypes in Hospitalized Children with Bronchiolitis in the United Arab Emirates

Abstract Background Respiratory syncytial virus (RSV) is a major cause of acute respiratory illness in young children and elderly people worldwide. It has a complex molecular epidemiology with multiple strains cocirculating during a single epidemic. Whole genome sequencing is a valuable tool for monitoring genetic diversity and providing genomic information essential for antiviral and vaccine development. In the United Arab Emirates (UAE), little is known about the RSV circulating genotypes, their evolution, and transmission dynamics. Using next-generation sequencing, this study aims to identify RSV genotypes circulating among young children with bronchiolitis in Al Ain City, UAE. Methods This cross-sectional study involved 100 children under two years of age who were hospitalized at a tertiary care facility between April and December 2021 with RSV-positive bronchiolitis. Nasopharyngeal samples were obtained, within 24 hours of hospitalization, for RSV genotyping. MinION nanopore sequencer was used to analyze the whole viral genome. We only sequenced samples with cycle threshold (Ct) < 30 (n=70). After sequencing, 7 samples were not analyzed due to long gaps and small lengths. The remaining 63 samples included 59 RSV-A and 4 RSV-B isolates. Results The median age of the studied children was 4.3 months, interquartile range (2.1-10.4), with 56% below the age of 6 months. There was no significant difference in the clinical characteristics of children having RSV-A compared to those infected with RSV-B. Phylogenetic analysis showed that out of the 59 RSV-A sequences, 58 clustered with the NA1 genotype, and 1 sequence clustered with the GA1 genotype. All RSV-B sequences were classified as BA2 genotypes. The amino acid sequence alignment of the G gene revealed that all 58 NA1 genotypes had 24 amino acid duplication regions from 247 to 282 amino acid positions. We also found four substitutional changes at L248I, H258Q, L274P, and P276Q. Conclusion Phylogenetic analysis revealed that the subtype A NA1 genotype was the dominant strain among the studied children in Al Ain, UAE during the 2021 season. As vaccine development advances, further sequencing of RSV is needed to better understand viral origin, transmission, and genetic recombination, particularly in under-studied populations. Disclosures All Authors: No reported disclosures

Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus

Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within nucleoproteins (N). An essential interaction between N and a C-terminal region of P tethers the L/P polymerase to the template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how the polymerase component P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to activity assays and imaging of inclusion bodies in cells. We report a 2.9 Å resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template.

Spatial resolution of virus replication: RSV and cytoplasmic inclusion bodies.

Respiratory Syncytial Virus (RSV) is a major cause of respiratory illness in young children, elderly and immunocompromised individuals worldwide representing a severe burden for health systems. The urgent development of vaccines or specific antivirals against RSV is impaired by the lack of knowledge regarding its replication mechanisms. RSV is a negative-sense single-stranded RNA (ssRNA) virus belonging to the Mononegavirales order (MNV) which includes other viruses pathogenic to humans as Rabies (RabV), Ebola (EBOV), or measles (MeV) viruses. Transcription and replication of viral genomes occur within cytoplasmatic virus-induced spherical inclusions, commonly referred as inclusion bodies (IBs). Recently IBs were shown to exhibit properties of membrane-less organelles (MLO) arising by liquid-liquid phase separation (LLPS). Compartmentalization of viral RNA synthesis steps in viral-induced MLO is indeed a common feature of MNV. Strikingly these key compartments still remain mysterious. Most of our current knowledge on IBs relies on the use of fluorescence microscopy. The ability to fluorescently label IBs in cells has been key to uncover their dynamics and nature. The generation of recombinant viruses expressing a fluorescently-labeled viral protein and the immunolabeling or the expression of viral fusion proteins known to be recruited in IBs are some of the tools used to visualize IBs in infected cells. In this chapter, microscope techniques and the most relevant studies that have shed light on RSV IBs fundamental aspects, including biogenesis, organization and dynamics are being discussed and brought to light with the investigations carried out on other MNV.

Combined blockade of TNF-a and IFN-I receptors in experimental RSV infection: analysis of STAT protein modulation

Abstract Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness in young children. Two cytokines key to RSV pathogenesis are tumor necrosis factor (TNF)-a and type-I interferon (IFN-I). Using a dual receptor antibody blockade of IFNAR1 with either TNFR1 or TNFR2, we previously reported that IFN-I and TNF-a synergistically contribute to clinical disease while also controlling peak lung viral replication in RSV-infected Balb/c mice. The objective of the current study was to investigate the possible effect of TNF-a/IFN-I on prolonged viral shedding and to dissect canonical signaling pathways that would likely mediate the above-described activity. We found that viral titer in the lung of all treatment groups was comparable to the RSV control mice at days six and seven post-infection, indicating that lack of these cytokine receptor signaling was not involved in prolonged viral shedding. We then determined expression levels of total lung STAT1, STAT2, STAT3 and their phosphorylated forms as well as IRF1, pIRF3, IRF7, and IRF9 by western blot. Though RSV/IFNAR1, RSV/TNFR1, and RSV/TNFR2 demonstrated variations in protein expression for several of these signaling molecules, none of these proteins were uniquely modulated by the dual receptor blockade. These findings collectively demonstrate that while TNF-a/IFN-I receptor signaling controls peak viral replication in the lung, they have no effect on extended viral shedding and that STAT1, STAT2, and STAT3 signaling appears to be dispensable for the enhanced viral replication observed in the dual receptor blockade treated mice. Supported by grants from AI062885, AI25434, Clinical and Translational Science Award [(NRSA (TL1) Training Core TL1TR001440)],Supported by UTMB McLaughlin Fellowship

Household Bird Ownership is Associated with Respiratory Illness among Young Children in Urban Bangladesh (CHoBI7 Program).

There is limited evidence on the association between animal ownership and respiratory illness among young children in low- and middle-income countries. In this study, we examined the association between animal ownership and respiratory illness among children younger than 5 years of age enrolled in a prospective cohort study in urban Bangladesh. This prospective cohort study enrolled 884 participants younger than 5 years of age in Dhaka, Bangladesh. At baseline, trained research assistants administered caregivers of children younger than 5 years of age a questionnaire on household animal ownership. Animal ownership was defined as owning chickens, birds other than chickens, cats, and dogs. Respiratory surveillance was conducted monthly for children based on caregiver-reported coughing, rapid breathing, and difficulty breathing in the past 2 weeks during the 12-month study period. At baseline, 48% of children (424 of 884) had reports of coughing, 5% (40 of 884) had difficulty breathing, 3% (25 of 884) had rapid breathing, and 49% (431 of 884) had reports of any of these three respiratory symptoms. Seventeen percent of children (151 of 884) resided in a household that owned an animal. Children residing in households reporting bird ownership had a significantly greater odds of coughing (odds ratio, 1.14; 95% CI, 1.02-1.28) and any of the three respiratory symptoms in the past 2 weeks (odds ratio, 1.14; 95% CI, 1.02-1.28). Household bird ownership was associated with respiratory illness in young children. These findings suggest that interventions aiming to reduce young children's exposure to domestic animals should extend to include birds other than chickens.

Chloroquine and pyrimethamine inhibit the replication of human respiratory syncytial virus A.

Human respiratory syncytial virus (hRSV) is a major cause of respiratory illness in young children and can cause severe infections in the elderly or in immunocompromised adults. To date, there is no vaccine to prevent hRSV infections, and disease management is limited to preventive care by palivizumab in infants and supportive care for adults. Intervention with small-molecule antivirals specific for hRSV represents a good alternative, but no such compounds are currently approved. The investigation of existing drugs for new therapeutic purposes (drug repositioning) can be a faster approach to address this issue. In this study, we show that chloroquine and pyrimethamine inhibit the replication of human respiratory syncytial virus A (long strain) and synergistically increase the anti-replicative effect of ribavirin in cellulo. Moreover, chloroquine, but not pyrimethamine, inhibits hRSV replication in the mouse model. Our results show that chloroquine can potentially be an interesting compound for treatment of hRSV infection in monotherapy or in combination with other antivirals.

Whole genome sequencing of human metapneumoviruses from clinical specimens using MinION nanopore technology

Human metapneumovirus (HMPV), a member of the Pneumoviridae family, is a causative agent of respiratory illness in young children, the elderly, and immunocompromised individuals. Globally, viruses belonging to two main genetic lineages circulate, A and B, which are further divided into four genetic sublineages (A1, A2, B1, B2). Classical genotyping of HMPV is based on the sequence of the fusion (F) and attachment (G) glycoprotein genes, which are under direct antibody-mediated immune pressure. Whole genome sequencing provides more information than sequencing of subgenomic fragments and is therefore a powerful tool for studying virus evolution and disease epidemiology and for identifying transmission events and nosocomial outbreaks. Here, we report a robust method to obtain whole genome sequences for HMPV using MinION Nanopore technology. This assay is able to generate HMPV whole genome sequences from clinical specimens with good coverage of the highly variable G gene and is equally sensitive for strains of all four genetic HMPV sublineages. This method can be used for studying HMPV genetics, epidemiology, and evolutionary dynamics.

Nasopharyngeal colonization with pathobionts is associated with susceptibility to respiratory illnesses in young children.

Some children are more susceptible to viral and bacterial respiratory infections in the first few years of life than others. However, the factors contributing to this susceptibility are incompletely understood. In a retrospective analysis of clinical samples collected from a prospectively-enrolled cohort of 358 children we sought associations between physician-attended illness visits and bacterial colonization in the first five years of life. A subset of children was identified by unsupervised clustering analysis as infection and allergy prone (IAP). Several respiratory infection- and allergy-mediated illnesses co-occurred at higher rates in IAP children, while the rates of other illnesses were not significantly different between the groups. Analyses of nasopharyngeal (NP) pathobionts and microbiota commensals showed that early age of first colonization with pathobionts Streptococcus pneumonia, non-typeable Haemophilus influenzae, and Moraxella catarrhalis was associated with IAP children, and particularly Moraxella abundance was negatively associated with NP microbiome diversity. We conclude that mucosal pathobiont exposures in early life can influence susceptibility to respiratory illnesses in children.

Capturing respiratory syncytial virus season in Belgium using the influenza severe acute respiratory infection surveillance network, season 2018/19.

BackgroundRespiratory syncytial virus (RSV) is a common cause of severe respiratory illness in young children (< 5 years old) and older adults (≥ 65 years old) leading the World Health Organization (WHO) to recommend the implementation of a dedicated surveillance in countries.AimWe tested the capacity of the severe acute respiratory infection (SARI) hospital network to contribute to RSV surveillance in Belgium.MethodsDuring the 2018/19 influenza season, we started the SARI surveillance for influenza in Belgium in week 40, earlier than in the past, to follow RSV activity, which usually precedes influenza virus circulation. While the WHO SARI case definition for influenza normally used by the SARI hospital network was employed, flexibility over the fever criterion was allowed, so patients without fever but meeting the other case definition criteria could be included in the surveillance.ResultsBetween weeks 40 2018 and 2 2019, we received 508 samples from SARI patients. We found an overall RSV detection rate of 62.4% (317/508), with rates varying depending on the age group: 77.6% in children aged < 5 years (253/326) and 34.4% in adults aged ≥ 65 years (44/128). Over 90% of the RSV-positive samples also positive for another tested respiratory virus (80/85) were from children aged < 5 years. Differences were also noted between age groups for symptoms, comorbidities and complications.ConclusionWith only marginal modifications in the case definition and the period of surveillance, the Belgian SARI network would be able to substantially contribute to RSV surveillance and burden evaluation in children and older adults, the two groups of particular interest for WHO.

Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17.

Respiratory syncytial virus (RSV) circulates worldwide, occurring seasonally in communities, and is a leading cause of acute respiratory illness in young children. There is paucity of genomic data from purposively sampled populations by which to investigate evolutionary dynamics and transmission patterns of RSV. Here we present an analysis of 295 RSV group B (RSVB) genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in nine health facilities across a defined geographical area (∼890 km2), over two RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple virus introductions into the area and co-circulation of distinct genetic clusters, which transmitted and diversified locally with varying frequency. Increase in relative genetic diversity paralleled seasonal virus incidence. Importantly, we identified a cluster of viruses that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel nonsynonymous change (K68Q) in antigenic site ∅ in the Fusion protein. RSVB diversity was additionally marked by signature nonsynonymous substitutions that were unique to particular genomic clusters, some under diversifying selection. Our findings provide insights into recent evolutionary and epidemiological behaviors of RSVB, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic strategies in development.

Rhinovirus C Is Associated With Severe Wheezing and Febrile Respiratory Illness in Young Children.

Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus species and respiratory illness severity. This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3-23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008. Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing. Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.

Effect of Improved Water Quality, Sanitation, Hygiene and Nutrition Interventions on Respiratory Illness in Young Children in Rural Bangladesh: A Multi-Arm Cluster-Randomized Controlled Trial.

.Acute respiratory infections cause mortality in young children. We assessed the effects of water, sanitation, hygiene (WASH) and nutritional interventions on childhood ARI. Geographic clusters of pregnant women from rural Bangladesh were randomly assigned to receive 1) chlorinated drinking water and safe storage (W); 2) upgraded sanitation (S); 3) handwashing promotion (H); 4) combined water, sanitation, and handwashing (WSH); 5) nutrition intervention including lipid-based nutrient supplements; 6) combined WSH plus nutrition (WSHN); or 7) no intervention (control). Masking of participants was not possible. Acute respiratory illness was defined as caregiver-reported persistent cough, panting, wheezing, or difficulty breathing in the past 7 days among index children, those born to enrolled women. We assessed outcomes at 12 and 24 months of intervention using intention to treat. Compared with children in the control group (ARI prevalence, P: 8.9%), caregivers of index children reported significantly lower ARI in the water (P: 6.3%, prevalence ratio (PR): 0.71; 95% CI: 0.53, 0.96), sanitation (P: 6.4%, PR: 0.75, 95% CI: 0.58, 0.96), handwashing (P: 6.4%, PR: 0.68, 95% CI: 0.50, 0.93), and the combined WSH+N arms (P: 5.9%, PR: 0.67, 95% CI: 0.50, 0.90). Those in the nutrition (P: 7.4%, PR: 0.84, 95% CI: 0.63, 1.10) or the WSH arm (P: 8.9%, PR: 0.99, 95% CI: 0.76, 1.28) reported similar ARI prevalence compared with control children. Single targeted water, sanitation, and hygiene interventions reduced reported respiratory illness in young children. There was no apparent respiratory health benefit from combining WASH interventions.

Whole genome sequencing and phylogenetic analysis of human metapneumovirus strains from Kenya and Zambia

BackgroundHuman metapneumovirus (HMPV) is an important cause of acute respiratory illness in young children. Whole genome sequencing enables better identification of transmission events and outbreaks, which is not always possible with sub-genomic sequences.ResultsWe report a 2-reaction amplicon-based next generation sequencing method to determine the complete genome sequences of five HMPV strains, representing three subgroups (A2, B1 and B2), directly from clinical samples. In addition to reporting five novel HMPV genomes from Africa we examined genetic diversity and sequence patterns of publicly available HMPV genomes. We found that the overall nucleotide sequence identity was 71.3 and 80% for HMPV group A and B, respectively, the diversity between HMPV groups was greater at amino acid level for SH and G surface protein genes, and multiple subgroups co-circulated in various countries. Comparison of sequences between HMPV groups revealed variability in G protein length (219 to 241 amino acids) due to changes in the stop codon position. Genome-wide phylogenetic analysis showed congruence with the individual gene sequence sets except for F and M2 genes.ConclusionThis is the first genomic characterization of HMPV genomes from African patients.

The impact of influenza infection on young children, their family and the health care system.

BackgroundInfluenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies.ObjectivesTo describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system.MethodsPreschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes.ResultsAmong 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012).ConclusionsInfluenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.

Live Respiratory Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized Temperature-Sensitivity Mutations Is Highly Attenuated in RSV-Seronegative Infants and Children

Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation. RSV-seronegative 6-24-month-old children received an intranasal dose of 105.3 plaque-forming units (PFU) of RSVcps2 (n = 34) or placebo (n = 16) (International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1114 and companion protocol CIR285). RSV serum neutralizing antibody titers before and 56 days after vaccination, vaccine virus infectivity (defined as vaccine virus shedding detectable in nasal wash and/or a ≥4-fold rise in serum antibodies), reactogenicity, and genetic stability were assessed. During the following RSV transmission season, participants were monitored for respiratory illness, with serum antibody titers measured before and after the season. A total of 85% of vaccinees were infected with RSVcps2 (median peak titer, 0.5 log10 PFU/mL by culture and 2.9 log10 copies/mL by polymerase chain reaction analysis); 77% shed vaccine virus, and 59% developed a ≥4-fold rise in RSV-serum neutralizing antibody titers. Respiratory tract and/or febrile illness occurred at the same rate (50%) in the vaccine and placebo groups. Deattenuation was not detected at either of 2 stabilized mutation sites. RSVcps2 was well tolerated and moderately immunogenic and had increased genetic stability in 6-24-month-old RSV-seronegative children. NCT01852266 and NCT01968083.

Chest radiographic features of human metapneumovirus infection in pediatric patients.

Human metapneumovirus (HMPV) was identified in 2001 and is a common cause of acute respiratory illness in young children. The radiologic characteristics of laboratory-confirmed HMPV acute respiratory illness in young children have not been systematically assessed. We systematically evaluated the radiographic characteristics of acute respiratory illness associated with HMPV in a prospective cohort of pediatric patients. We included chest radiographs from children <5years old with acute respiratory illness who were enrolled in the prospective New Vaccine Surveillance Network (NVSN) study from 2003 to 2009 and were diagnosed with HMPV by reverse transcription-polymerase chain reaction (RT-PCR). Of 215 HMPV-positive subjects enrolled at our tertiary care children's hospital, 68 had chest radiographs obtained by the treating clinician that were available for review. Two fellowship-trained pediatric radiologists, independently and then in consensus, retrospectively evaluated these chest radiographs for their radiographic features. Parahilar opacities were the most commonly observed abnormality, occurring in 87% of children with HMPV. Hyperinflation also occurred frequently (69%). Atelectasis (40%) and consolidation (18%) appeared less frequently. Pleural effusion and pneumothorax were not seen on any radiographs. The clinical presentations of HMPV include bronchiolitis, croup and pneumonia. Dominant chest radiographic abnormalities include parahilar opacities and hyperinflation, with occasional consolidation. Recognition of the imaging patterns seen with common viral illnesses like respiratory syncytial virus (RSV) and HMPV might facilitate diagnosis and limit unnecessary antibiotic treatment.

Costs of hospitalization with respiratory syncytial virus illness among children aged

BackgroundRespiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children <5 years and associated financial impact on households in Bangladesh. Data of this study could be useful for RSV vaccine development and also the value of various preventive strategies, including use of an RSV vaccine in children if one becomes available.MethodsFrom May through October 2010, children aged <5 years with laboratory–confirmed RSV were identified from a sentinel influenza program database at four tertiary hospitals. Research assistants visited case–patients’ homes after hospital discharge and administered a structured questionnaire to record direct medical costs (physician consultation fee, costs for hospital bed, medicines and diagnostic tests); non–medical costs (costs for food, lodging and transportation); indirect costs (caregivers’ productivity loss), and coping strategies used by families to pay for treatment. We used WHO–Choice estimates for routine health care service costs. We added direct, indirect and health care service costs to calculate cost–per–episode of severe RSV illness. We used Monte Carlo simulation to estimate annual economic burden for severe RSV illness.FindingsWe interviewed caregivers of 39 persons hospitalized for RSV illness. The median direct cost for hospitalization was US$ 62 (interquartile range [IQR] = 43–101), indirect cost was US$ 19 (IQR = 11–29) and total cost was US$ 94 (IQR = 67–127). The median out–of–pocket cost was 24% of monthly household income of affected families (US$ 143), and >50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV–associated hospitalization in children aged <5 years in Bangladesh was US$ 10 million (IQR: US$ 7–16 million), the median indirect cost was US$ 3.0 million (IQR: 2–5 million) in 2010.ConclusionRSV–associated hospitalization among children aged <5 years represents a substantial economic burden in Bangladesh. Affected families frequently incurred considerable out of pocket and indirect costs for treatment that resulted in financial hardship.

Nasopharyngeal Pneumococcal Density and Evolution of Acute Respiratory Illnesses in Young Children, Peru, 2009-2011.

We examined nasopharyngeal pneumococcal colonization density patterns surrounding acute respiratory illnesses (ARI) in young children in Peru. Pneumococcal densities were dynamic, gradually increasing leading up to an ARI, peaking during the ARI, and decreasing after the ARI. Rhinovirus co-infection was associated with higher pneumococcal densities.

Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia

Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics.

Estimates of Parainfluenza Virus-Associated Hospitalizations and Cost Among Children Aged Less Than 5 Years in the United States, 1998-2010.

Parainfluenza virus (PIV) is the second leading cause of hospitalization for respiratory illness in young children in the United States. Infection can result in a full range of respiratory illness, including bronchiolitis, croup, and pneumonia. The recognized human subtypes of PIV are numbered 1-4. This study calculates estimates of PIV-associated hospitalizations among U.S. children younger than 5 years using the latest available data. Data from the National Respiratory and Enteric Virus Surveillance System were used to characterize seasonal PIV trends from July 2004 through June 2010. To estimate the number of PIV-associated hospitalizations that occurred annually among U.S. children aged <5 years from 1998 through 2010, respiratory hospitalizations from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample were multiplied by the proportion of acute respiratory infection hospitalizations positive for PIV among young children enrolled in the New Vaccine Surveillance Network. Estimates of hospitalization charges attributable to PIV infection were also calculated. Parainfluenza virus seasonality follows type-specific seasonal patterns, with PIV-1 circulating in odd-numbered years and PIV-2 and -3 circulating annually. The average annual estimates of PIV-associated bronchiolitis, croup, and pneumonia hospitalizations among children aged <5 years in the United States were 3888 (0.2 hospitalizations per 1000), 8481 per year (0.4 per 1000 children), and 10,186 (0.5 per 1000 children), respectively. Annual charges for PIV-associated bronchiolitis, croup, and pneumonia hospitalizations were approximately $43 million, $58 million, and $158 million, respectively. The majority of PIV-associated hospitalizations in young children occur among those aged 0 to 2 years. When vaccines for PIV become available, immunization would be most effective if realized within the first year of life.