Consecutive Epidemic Seasons Research Articles

Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?

Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis. We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O 2 supplementation and the admission at the pediatric intensive care unit. A total of 166 were hospitalized with bronchiolitis in 2017-2018, 97 in 2018-2019, 69 in 2019-2020, 0 in 2020-2021, 129 in 2021-2022 and 176 in 2022-2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020-2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021-2022 season registered a less severe clinical presentation, O 2 supplementation and pediatric intensive care unit admissions increased in 2022-2023 with respect to the prepandemic seasons ( P < 0.001). This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.

Factors Associated With the Development of Bacterial Pneumonia Related to Seasonal Influenza Virus Infection: A Study Using a Large-scale Health Insurance Claim Database.

Influenza-related bacterial pneumonia is a leading complication of influenza infection. However, the differences in the incidence rates and risk factors associated with concomitant viral/bacterial pneumonia (CP) and secondary bacterial pneumonia following influenza (SP) remain unclear. This study aimed to clarify the incidence rates of CP and SP following seasonal influenza and identify factors associated with their development. This retrospective cohort study was conducted using the JMDC Claims Database, a health insurance claims database in Japan. All patients aged <75 years who developed influenza during 2 consecutive epidemic seasons, 2017/2018 and 2018/2019, were analyzed. CP was defined as bacterial pneumonia diagnosed between 3 days before and 6 days after the date of influenza diagnosis, and SP was defined as pneumonia diagnosed 7-30 days after the date of diagnosis. Multivariable logistic regression analyses were performed to identify factors associated with the development of CP and SP. Among the 10 473 014 individuals registered in the database, 1 341 355 patients with influenza were analyzed. The average age at diagnosis (SD) was 26.6 (18.6) years. There were 2901 (0.22%) and 1262 (0.09%) patients who developed CP and SP, respectively. Age 65-74 years, asthma, chronic bronchitis/emphysema, cardiovascular disease, renal disease, malignant tumor, and immunosuppression were significant risk factors for both CP and SP, whereas cerebrovascular disease, neurological disease, liver disease, and diabetes were risk factors specific to CP development. The results determined the incidence rates of CP and SP and identified their risk factors, such as older age and comorbidities.

Bronchiolitis phenotypes identified by latent class analysis may influence the occurrence of respiratory sequelae.

The heterogeneity of bronchiolitis may imply or reflect a different predisposition to respiratory sequelae. Our aim was to investigate whether, among infants hospitalized with bronchiolitis, different clinical profiles extracted by latent class analysis (LCA) are associated with different risks of wheezing. Over 15 consecutive epidemic seasons (2004-2019), we prospectively enrolled infants <1 year hospitalized for the first episode of bronchiolitis in a single tertiary hospital. A detailed clinical questionnaire was filled for each infant. LCA was applied to differentiate bronchiolitis phenotypes, and after hospital discharge, a phone interview was performed annually to record the presence of wheezing episodes. Adjusted multivariate regression analyses were run to investigate the risk of wheezing during 7 years follow-up according to clinical phenotypes. LCA performed on 1312 infants resulted in a three-class model. Profile 1 (65.5%): moderate bronchiolitis; Profile 2 (6.1%): severe bronchiolitis; and Profile 3(28.4%): bronchiolitis infants with high eosinophils blood count. At 1 year of follow up, about 50% of children presented wheezing in each profile. Compared to Profile 1, the adjusted odds ratio (OR) of having wheezing episodes was significantly higher in Profile 2 at 2, 3, and 4 years of follow-up. At 7 years, Profile 3 had an adjusted OR = 2.58, higher than Profile 2 (adjusted OR = 2.29). LCA clearly identified a "moderate", "severe," and "high eosinophils blood count" bronchiolitis. During the first 4 years after bronchiolitis, the "severe" profile showed the higher risk of wheezing, but after 7 years this risk seems higher in the "high eosinophils blood count" group.

Age Limit in Bronchiolitis Diagnosis: 6 or 12 Months?

Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0–6 months and 6–12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up.Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12–24–36 months after discharge, parents were interviewed seeking information on recurrent wheezing.Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score (p = 0.011) and the use of intravenous fluids (p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing (p = 0.149).Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis.

Phylogenetic variability of Human Metapneumovirus in patients with acute respiratory infections in Cameroon, 2011–2014

BackgroundIdentified in 2001, Human Metapneumovirus (HMPV) is a Pneumovirus associated with acute lower and upper respiratory infections in all age groups and especially in newborns, elderly and immunocompromised subjects. Data are still limited in sub-Saharan African countries genetic characterization of this respiratory virus. This study reports the genetic variability of HMPV strains in Cameroonian children for 3 consecutive epidemic seasons (September 2011–October 2014). MethodsA prospective surveillance was conducted to identify inpatient and outpatient children less than 15 years with respiratory symptoms ≤5 days. The nasopharyngeal samples were tested for HMPV using a multiplex polymerase chain reaction. Viral distribution and demographic data were analyzed statistically. Positive samples for HMPV were amplified by semi-nested polymerize chain reaction and then partially sequenced at the G gene. Phylogenetic analyzes were performed on the partial nucleotide and protein sequences of the G gene. ResultsFrom September 2011 to October 2014, 822 children under 15 years were enrolled in the study. HMPV was identified in each of 3.9% (32/822) of children. HMPV were detected throughout the year. HMPV-A (73.3%; 11/15) was predominant compared to HMPV-B (26.7; 4/15). Cameroonian HMPV strains are grouped among the members of genotype A2b (for HMPV-A), B1 and B2 (for HMPV-B). ConclusionThis study suggests that about 4% of ARI recorded in children in Cameroon are caused by HMPV. The present study is also the first report on the genetic variability of the G gene of HMPV strains in the region. Although this work partially fills gaps for some information, additional studies are required to clarify the molecular epidemiology and evolutionary pattern of HMPV in sub-Saharan Africa in general and more particularly in Cameroon.

Molecular epidemiology of G12 rotavirus strains during eight consecutive epidemic seasons in the Basque Country (North of Spain), 2010–2018

G12 rotaviruses were first detected in Spain (Gipuzkoa province) in December 2004. After four years with no detections, G12 strains re-emerged in the 2010–2011 epidemic season, when the first European epidemic circulation of this genotype was observed in Gipuzkoa. G12 rotaviruses were also the dominant strains in 2011–2012, 2014–2015 and 2015–2016 epidemic seasons and were sporadically detected in the remaining periods (2012–2014 and 2016–2018). The most frequently detected G-type between 2010 and 2018 was G12 (29.9%) rather than G1 rotavirus (17.8%), which historically had been the dominant genotype in our setting (1989–2009 period) and globally. Phylogenetic analysis of the VP4 and VP7 genome segments showed chronologically ordered clades, which spanned between two to four consecutive seasons. Overall, the circulating G12 rotavirus strains in Gipuzkoa between 2010 and 2018 belonged to four clades, which emerged in early 2009 potentially due to at least four importations from other regions followed by local evolution. Whole genome analysis of 16 G12 strains detected from 2010 to 2018 revealed a Wa-like genotype constellation, G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, and also showed that G12 strains from Gipuzkoa were similar to those identified in other countries. These findings suggest circulation of G12 rotavirus strains in different parts of the world leading to high genetic diversity.

Genetic diversity of human respiratory syncytial virus isolated among children with acute respiratory infections in Southern Cameroon during three consecutive epidemic seasons, 2011\u20132013

BackgroundHuman respiratory syncytial virus (HRSV) is the main viral cause of severe lower respiratory tract disease in infants and young children. The aim of this study was to describe for the first time the genetic variability of HRSV in Cameroonian patients living in Yaounde for three consecutive epidemic seasons.MethodsHRSV-positive nasopharyngeal samples detected in children less than 15 years in Yaounde were collected from September 2011 to December 2013. Semi-nested RT-PCR, sequencing, and phylogenetic analyses of the second hypervariable region of the G gene were performed.ResultsA total of 57 HRSV-positive samples were collected during the study period. Among these, 46 (80.7%) could be amplified in the G gene. HRSV group A (HRSV-A) and group B (HRSV-B) co-circulated in this population at 17.4 and 82.6%, respectively. HRSV-A strains clustered in the NA-1 genotype while HRSV-B strains clustered in the BA-9 genotype. HRSV-A strains accounted for 33.3% (2/6), 4.3% (1/23), and 29.4% (5/17) of the viruses isolated in 2011, 2012, and 2013, respectively.ConclusionsThis study reports molecular epidemiology data of HRSV in Cameroon for the first time. Additional studies are required to clarify evolutionary patterns of HRSV throughout sub-Saharan Africa to support antiviral and vaccine development.

Acute bronchiolitis: Influence of viral co-infection in infants hospitalized over 12 consecutive epidemic seasons.

Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12‐24‐36 months of follow‐up. We reviewed the clinical records for 486 full‐term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O2 supplementation or admission to the intensive care unit. Single virus was associated with higher serum C‐reactive protein (C‐RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C‐RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C‐RP levels than hRV co‐infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co‐infection, was associated with lower neutrophil count and lower C‐RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co‐infections can occur, without influence in the clinical severity of the disease. Infants with co‐infection seems to mount a lower inflammatory response.

National Laboratory Surveillance of Influenza in Macedonia during Four Seasons.

The aim of the study is to comprehend results of the influenza lab surveillance system in the Republic of Macedonia after the 2009 pandemic and to determine the main characteristics of four consecutive epidemic seasons (from 2010/2011 until 2013/2014). As part of the universal surveillance system, nasal and throat specimens were collected from patients. After extraction of RNA, the CDC real-time RT-PCR assays for the detection of influenza types and subtypes were performed. Out of 920 tested samples, 406 (44.1%) laboratory confirmed cases of influenza were found. Influenza activity begins as early as December and continues until the end of April with peaks in January or February with predominant influenza A and A/H1N1pdm. Influenza A viruses start their activity at week 49 to 52 and subside at week 17. Usually two peaks appear, the first one between week 2 and 4 and the second one between week 6 and 9. Subtype A/H1N1pdm was dominant among influenza A types in the 2010/2011 and 2012/2013 seasons. A/H3N2 was the only circulating influenza virus in the 2011/2012 season. Influenza B season is shorter and has only one peak, between weeks 2-5. Usually the influenza B viruses emerge in later stages than influenza A viruses, except for the first post-pandemic season. Results revealed that post-pandemic influenza seasons in Macedonia were rather different. Although the influenza season pattern is similar to patterns in some countries of the WHO European region, some unique characteristics were observed.

Effectiveness of seasonal influenza vaccination in patients with diabetes: protocol for a nested case–control study

IntroductionSeasonal influenza vaccination (SIV) is recommended for people with diabetes, but its effectiveness has not been demonstrated. All of the available studies are observational and marred with the healthy vaccine...

Prevalence and seasonality of six respiratory viruses during five consecutive epidemic seasons in Belgium

BackgroundAcute Respiratory Infections (ARIs) are a major health problem, especially in young children and the elderly. ObjectivesInsights into the seasonality of respiratory viruses can help us understand when the burden on society is highest and which age groups are most vulnerable. Study designWe monitored six respiratory viruses during five consecutive seasons (2011–2016) in Belgium. Patient specimens (n=22876), tested for one or more of the following respiratory viruses, were included in this analysis: Influenza viruses (IAV & IBV), Human respiratory syncytial virus (hRSV), Human metapneumovirus (hMPV), Adenovirus (ADV) and Human parainfluenza virus (hPIV). Data were analysed for four age categories: <6y, 6–17y, 18–64y and ≥65y. ResultsChildren <6y had the highest infection rates (39% positive vs. 20% positive adults) and the highest frequency of co-infections. hRSV (28%) and IAV (32%) caused the most common respiratory viral infections and followed, like hMPV, a seasonal pattern with winter peaks. hRSV followed an annual pattern with two peaks: first in young children and ±7 weeks later in elderly. This phenomenon has not been described in literature so far. hPIV and ADV occurred throughout the year with higher rates in winter. ConclusionsChildren <6y are most vulnerable for respiratory viral infections and have a higher risk for co-infections. hRSV and IAV are the most common respiratory infections with peaks during the winter season in Belgium.

клещевой риккесиоз у детей иркутской области за период пяти эпидемических сезонов

The article discusses the clinical and laboratory characteristics of tick-borne rickettsiosis in children in the Irkutsk region on the results of the retrospective study of 65 patients admitted to the Regional Infectious Hospital over the period of five consecutive epidemic seasons. It has been found that among hospitalized children with tick-borne rick-ettsiosis dominating proportion (64.6 %) is of rural residents (mean age – 5 years old). The main clinical symptoms in children borne rickettsiosis were rash (96.9 %) and fever (96.9 %), which in one third of observations associated with lymphadenopathy (38.5%). About one third of patients (30.8 %) had pronounced symptoms of intoxication. It has been noted that the laboratory diagnosis of tick-borne rickettsiosis needs to be improved: DGC reaction should replace ELISA detection of specific immunoglobulin M in the blood in combination with PCR for genetic identification of rickettsiae. The development of emergency preventive treatment of tick-borne rickettsiosis is required, taking into account the sensitivity of rickettsiae to antibiotics. All children with tick-borne rickettsial diseases were provided with timely and effective treatment, with favorable prognosis.

A study of genetic variability of human parainfluenza virus type 1 in Croatia, 2011-2014.

Molecular epidemiology of human parainfluenza viruses type 1 (HPIV1) was investigated. Samples were collected from patients hospitalized in Croatia during the three consecutive epidemic seasons (2011-2014). Results indicated co-circulation of two major genetic clusters of HPIV1. Samples from the current study refer to clades II and III in a phylogenetic tree of haemagglutinin-neuraminidase (HN) gene. Additional phylogenetic trees of fusion (F) and phosphoprotein (P) genes confirmed the topology. Analysis of nucleotide diversity of entire P, F and HN genes demonstrated similar values: 0.0255, 0.0236 and 0.0237, respectively. However, amino acid diversity showed F protein to be the most conserved, while P protein was the most tolerant to mutations. Potential N- and O-glycosylation sites suggested that HPIV1 HN protein is abundantly glycosylated, and a specific N-glycosylation pattern could distinguish between clades II and III. Analysis of potential O-glycosylation sites in F protein indicated that samples from this study have two potential O-glycosylation sites, while publicly available sequences have five potential sites. This study provides data on the molecular characterization and epidemic pattern of HPIV1 in Croatia.

Bronchiolitis: Analysis of 10 consecutive epidemic seasons.

SummaryBronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non‐peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, “Sapienza” University of Rome over the period 2004–2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co‐infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December–January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non‐peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330–1335. © 2016 Wiley Periodicals, Inc.

İki Ardışık Epidemik Sezonda Ülkemizde Dolaşımda Olan İnsan Metapnömovirus Suşlarının Filogenetik Çeşitliliği

Human metapneumovirus (HMPV), classified in Paramyxoviridae family, phylogenetically consists of two major groups namely A and B, with genetic lineages of A1, A2 (comprises of sublineages A2a and A2b) and B1, B2. Although detailed evaluation on phylogenetic analysis of HMPV has been described in other countries, there are no data from Turkey on this subject. The aim of this study was to demonstrate for the first time, the phylogenetic diversity of HMPV strains circulating in Turkey during two consecutive epidemic seasons. A total of 2900 upper respiratory tract samples collected from patients with respiratory illness were evaluated between January 2011 and December 2013, without any special selection criteria. The presence of respiratory viruses in the samples were detected by real-time multiplex polymerase chain reaction (FTD® Respiratory Pathogens 21 Multiplex RT-PCR, Fast Track Diagnostics, Luxemburg), and 76 (2.6%) samples positive for HMPV were included in the study. HPMV nucleocapsid (N) (nt: 454-878) and fusion (F) (nt: 3624-4130) genes were selected for phylogenetic analysis. In sequence analysis, F and N gene sequences could only be obtained successfully from 46 out of 76 HMPV positive samples. According to sequences obtained, 54.3% belonged to B2, 17.4% to B1, 4.3% to A1, 4.3% to A2a, and 20% to A2b. In 2011, the A2b sublineage was predominant, while in 2012 and 2013, B2 lineages were predominant together with the B1 lineage. The A1 lineage was observed only in 2013. For the F gene fragment, nucleotide distance between group A and B was in the range of 0.138-0.168, however aminoacid distance amongst Turkish HMPV sequences were in the range of 0.028-0.042. For the N gene fragment, nucleotide distance between group A and B was in the range of 0.141-0.163, but aminoacid distance between group A and B was in the range of 0.037-0.050. Nucleotide diversity was higher than aminoacid diversity between and within lineages found in this study. This result indicated that the functional constraints on F and N genes prevent dramatic aminoacid changes, and indicated that the evolution of HMPV was slow. The seasonal peaks were observed from April to July in 2011, from January to June in 2012 and from January to May in 2013. In addition, our data emphasized that the HMPV prevalence was high in children 0-5 years old, and coinfections were common with the other respiratory viruses such as respiratory syncytial virus, coronavirus, parainfluenza virus 3, rhinovirus and enterovirus. In conclusion, this study showed that HMPV strains circulating in Turkey were similar to those circulating in Europe.

Two years of experience in hospital surveillance for the severe influenza like illnesses in St. Petersburg: etiology, clinical characterization of diseases, antigenic and genetic properties of isolated influenza viruses

ABSTRACT In this paper, we analyze the etiology of the diseases occurring during two consecutive influenza epidemic seasons in St. Petersburg, Russian Federation. The analysis is based on the results of the PCR diagnostics of the clinical samples collected from patients hospitalized in three St. Petersburg hospitals with influenza like illnesses (ILI). It was shown that the influenza virus A(H1N1)pdm09 was the dominant causative agent during the 2012-2013 epidemic season while, in the 2013-2014 season, A(H3N2) virus was predominant among adults and children. The influenza B virus activity was high in the 2012-2013 season and low in the 2013-2014 season. During both seasons, the main causative agent for the hospitalization of young children was respiratory syncytial virus (RSV), followed by rhinovirus and influenza virus. The rate of involvement of parainfluenza, adenovirus, metapneumovirus and coronavirus was low and was negligible for bocavirus. Children 0-2 and 3-6 years old formed the group of patients that was affected by acute respiratory infection agents the most. Children younger than 3 months old were the major group of the intensive care unit (ICUs) patients and only 27.5% of them were adults. RSV and rhinovirus were the leading cause of ILI among the children admitted to ICU. Among the adult patients admitted to the ICU, only influenza A(H1N1)pdm09, A(H3N2) and B viruses were detected during both influenza seasons. According to the results of the antigenic and genetic analysis, most influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in St. Petersburg matched the vaccine strains recommended by the WHO for vaccine composition in the 2012-2013 and 2013-2014 seasons.

Antibody responses against influenza A(H1N1)pdm09 virus after sequential vaccination with pandemic and seasonal influenza vaccines in Finnish healthcare professionals

Background Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine‐induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross‐reactivity. Objectives Influenza vaccine‐induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age‐dependent responses were also analyzed. Methods Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009–2010 and 2010–2011. Serum samples from vaccinated volunteers, age 20–64 years, were collected before and after vaccination with AS03‐adjuvanted pandemic and non‐adjuvanted trivalent seasonal influenza vaccine that was given 1 year later. Results Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14–75% of vaccinated had reached antibody titers (≥1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57–98%. After primary immunization, younger individuals (20–48 years) had significantly higher antibody titers against all tested viruses than older persons (49–64 years) but this difference disappeared after the seasonal booster vaccination. Conclusions Even a few amino acid changes in influenza A HA may compromise the vaccine‐induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.

Human metapneumovirus‐associated hospital admissions over five consecutive epidemic seasons: Evidence for alternating circulation of different genotypes

Human metapneumovirus (hMPV) is a pathogen of the respiratory tract with a worldwide distribution. The purpose of this study was to identify hMPV as the cause of acute respiratory diseases in children admitted at Spedali Civili, a public hospital in Brescia, Italy. Eight hundred forty‐six nasopharyngeal aspirate samples negative for the presence of other common respiratory viruses were tested for the presence of hMPV RNA by reverse transcription‐polymerase chain reaction. Of the 846 samples, 79 (9.3%) were positive for hMPV. Polymerase chain reaction products, obtained by amplification of the partial nucleotide sequence of gene F, were sequenced and compared with sequences deposited in GenBank. All four hMPV subtypes were identified, including the proposed subtype A2 sublineages “A” and “B”. In successive epidemic seasons, large outbreaks of hMPV alternated with small outbreaks in a biannual pattern. This local study provides further evidence that hMPV infection should be considered as a reason for hospital admission for acute respiratory disease in children. J. Med. Virol. 84:511–516, 2012. © 2011 Wiley Periodicals, Inc.

Genetic Variability of Group A Human Respiratory Syncytial Virus Strains Circulating in Germany from 1998 to 2007

The variability between respiratory syncytial virus (RSV) strains is one of the features of RSV infections that might contribute to the ability of the virus to infect people repeatedly and cause yearly outbreaks. To study the molecular epidemiology of RSV, more than 1,400 RSV isolates from human nasopharyngeal aspirates or nasal or throat swabs from patients with respiratory illness were identified and differentiated by TaqMan reverse transcription-PCR into groups A and B. RSV group A was dominant in seven out of nine epidemic seasons. Phylogenetic analysis revealed that RSV group A genotypes GA2 and GA5 circulated from 1998 to 2007. Genotype GA7 was present in only two seasons (1999 to 2000 and 2002 to 2003). Comparison of the synonymous mutation/nonsynonymous mutation ratios showed greater evidence for selection pressure for genotype GA2 (1.18) than for GA5 (4.34). Partial protein sequences were predicted to encode G proteins of 298 amino acids in length and in a few cases of G proteins of 297 amino acids in length. Amino acid analysis also revealed genotype-specific amino acid substitutions: two substitutions for genotype GA2, seven for GA5, and three for GA7. Two to four putative, genotype-specific N-linked glycosylation sites were determined. Predicted O-glycosylation sites included 22 to 34 residues. This study provides for the first time data on the circulation pattern of RSV group A genotypes and their molecular characterization in Germany during nine consecutive epidemic seasons.

Genetic drift of norovirus genotype GII-4 in seven consecutive epidemic seasons in Hungary

Background Noroviruses are common pathogens in human gastroenteritis outbreaks worldwide. They belong to a genetically diverse group of RNA viruses with multiple genogroups (G) and genotypes. Genotype GII-4 norovirus (Lordsdale) is the predominant agent in epidemics. Objectives To investigate the genetic variation in GII-4 strains isolated during seven epidemic seasons in Hungary from November 2000 to June 2007. Study design Using the prospective epidemiological surveillance of norovirus outbreaks in Hungary, GII-4 strains were selected for further genetic analysis. After phylogenetic analysis, RNA-polymerase (open reading frame 1; ORF1), capsid (ORF2) and the ORF1/ORF2 junction were analysed by RT-PCR and sequencing. Results Three hundred and seventy-seven (76.8%) of 491 confirmed norovirus outbreaks were caused by genotype GII-4. GII-4 was the predominant genotype in six of the seven epidemic seasons. Four main GII-4 variants – epidemic point mutants – (GII-4-2000, GII-4-2002, GII-4-2004 and GII-4-2006b) were detected, with each variant predominating in two consecutive epidemic seasons. Conclusions Genotype GII-4 was confirmed as the predominant genetic type in epidemic norovirus seasons in Hungary. Genetic drift successfully promotes the re-emergence of GII-4 variants in the population. The elevated number of norovirus outbreaks in the population predicts the emergence of new GII-4 genetic variants as part of an international epidemic.