Summary An international group of multidisciplinary experts on middle-ear and paediatric infections met to explore where consensus exists on the management of acute otitis media. After informal ...discussions among several specialists of paediatric infectious disease, the group was expanded to include a larger spectrum of professionals with complementary expertise in middle-ear disease. Acute otitis media is a very common bacterial infection in children worldwide, leading to excessive antibiotic consumption in children in most countries and to a substantial burden of deafness and suppurative complications in developing countries. The group attempted to move beyond the existing controversies surrounding guidelines on acute otitis media, and to propose to clinicians and public health officials their views on the actions needed to be taken to reduce the disease burden caused by acute otitis media and the microbial antibiotic resistance from the resulting use of antibiotics. Definition of acute otitis media and diagnostic accuracy are crucial steps to identify children who will potentially benefit from treatment with antibiotics and to eliminate unnecessary prescribing. Although the group agreed that antibiotics are distributed indiscriminately, even to children who do not seem to have the disease, no consensus could be reached on whether antibiotics should be given to all appropriately diagnosed children, reflecting the wide range of practices and lack of convincing evidence from observational studies. The major unanimous concern was an urgent need to reduce unnecessary prescribing of antibiotics to prevent further increases in antibiotic resistance. Prevention of acute otitis media with existing and future viral and bacterial vaccines seems the most promising approach to affect disease burden and consequences, both in developed and developing countries.
Objective To assess rotavirus vaccine and pneumococcal conjugate vaccines (PCVs) cumulative impact on the pediatric emergency department visits and hospitalization rates in children <2 years of age ...in southern Israel between April 2006 and March 2014. Study design This prospective, population-based observational study calculated the rates of rotavirus gastroenteritis (RVGE), non-RVGE, community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory tract infection, and all-cause hospital visits. PCV7, PCV13, and rotavirus vaccination programs were implemented in Israel in July 2009, November 2010, and January 2011, respectively. Results From 2006-2009 to 2013-2014, the rates of hospitilizations for RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection decreased by 78%, 21%, 46%, and 7%, respectively. In outpatients, the respective decreases were 80%, 16%, 67%, and 14%. All-cause outpatient pediatric emergency department visits and hospitalization rates were reduced by 12% and 11%, respectively. During the peak season (October through March), RVGE, non-RVGE, CAAP, and nonalveolar lower respiratory tract infection hospitalization rates decreased significantly by 86%, 44.6%, 23.3%, and 10.5%, respectively. In outpatients, the respective decreases were 81.7%, 73.5%, 13.8%, and 10.7%. The proportion of RVGE and CAAP (grouped) of all-cause hospitalizations and outpatient pediatric ED visits decreased from 19.9% to 12.3% and from 6.9% to 1.8%, respectively. Conclusions Rotavirus vaccine and PCV introduction cocontributed to a rapid, considerable reduction in hospital burden in children <2 years of age. Because seasonalities of both diseases overlap, this reduction is particularly helpful in relieving burdens of disease and care during the most cumbersome morbidity season.
Objectives To determine the involvement of human metapneumovirus (HMPV) in childhood community-acquired alveolar pneumonia (CAAP) and compare the demographic, clinical, and laboratory features of ...HMPV-associated CAAP and CAAP associated with other respiratory viruses. Study design Nasopharyngeal wash specimens obtained prospectively over a 4-year period from children age < 5 years evaluated in the emergency department with radiologically diagnosed CAAP and from healthy controls were tested for HMPV by reverse-transcriptase polymerase chain reaction and for respiratory syncytial virus (RSV), adenovirus, influenza and parainfluenza viruses by direct immunofluorescence and culture. Results HMPV was detected in 108 of 1296 patients (8.3%) versus RSV in 23.1%, adenovirus in 3.4%, influenza A virus in 2.9%, and parainfluenza viruse in 2.9%. During the period of peak activity (November to May), HMPV was detected in 95 of 1017 patients (9.3%) and in 3 of 136 controls (2.2%) ( P = .005). The patients with HMPV were older than those with RSV ( P < .001) with a more common history of acute otitis media requiring tympanocentesis ( P = .032), wheezing ( P = .001) and gastrointestinal symptoms ( P < .001) and a lower hospitalization rate ( P = .005). Conclusions The high detection rate suggests an important role for HMPV in childhood CAAP. Our findings identify demographic and clinical features of HMPV-positive CAAP and its age-related impact on hospital admissions.
Background Data are scarce with regard to risk factors for acute community-acquired alveolar pneumonia (CAAP) in children, but it is known that children with sleep-disordered breathing (SDB) ...experience more respiratory infections. We aimed to assess whether SDB is a risk factor for CAAP in early childhood. Methods We conducted a prospective, nested, case-control study assessing children < 5 years old who had been given a diagnosis of CAAP based on World Health Organization radiographic criteria. Demographic and clinical data were collected. SDB symptoms were documented using a structured questionnaire. CAAP study and retrospective sleep laboratory databases were compared. SDB presence and severity were determined by questionnaire and polysomnography (PSG). Results A total of 14,913 children underwent chest radiography during the study period; 1,546 children with radiographically proven CAAP (58% boys) and 441 control subjects (54% boys) were prospectively enrolled. Frequent snoring was reported in 18.6% vs 2.9% subjects with CAAP and control subjects, respectively ( P < .001). The respective figures for subjects with CAAP and control subjects for restless sleep, nocturnal breathing problems, abnormal behavior, and chronic rhinorrhea were 21.6% vs 5.3%, 5% vs 1.4%, 6.4% vs 0.2%, and 12.9% vs 1.8%, ( P < .001 for each). Fifty children (3.3%) with CAAP vs three control subjects (0.7%) underwent adenoidectomy ( P < .001). PSG diagnosis of obstructive sleep apnea had been established previously in 79 patients (5%) with CAAP vs six (1.3%) of the control subjects (OR, 3.7 95% CI, 1.6-10.0; P < .001), with higher severity in patients with CAAP than in control subjects. Conclusions SDB is common in children with CAAP and is possibly a predisposing risk factor for CAAP in children < 5 years old. We recommend considering SDB in young children who are given a diagnosis of CAAP.
While there have been initial concerns about the efficacy of the PCV7 in the developing world, the 9-valent pneumococcal conjugate vaccine (containing serotypes 1 and 5 in addition to those of PCV7), ...has demonstrated high levels of effectiveness in field studies. In 2010, with the support of the Bill & Melinda Gates Foundation, The Global Alliance for Vaccines and Immunization (GAVI) - a global health partnership between the private and public sectors committed to increasing access to immunization in developing countries - launched the Advance Market Commitment (AMC), a program designed to reduce existing cost-barriers to expanding vaccination programs where the disease burden is highest.
Summary Otitis media is a common childhood infection of the middle ear and a major cause of morbidity. This multifactorial disease manifests as a spectrum of clinical syndromes from uncomplicated ...acute otitis media to more complex recurrent and chronic cases (frequently polymicrobial), with the major pathogens involved being Streptococcus pneumoniae and non-typeable Haemophilus influenzae . Pneumococcal conjugate vaccines (PCVs) target only a few serotypes that cause otitis media; however, results from studies suggest that existing PCVs can prevent early episodes of disease associated with vaccine serotypes, resulting in a reduction of subsequent complex cases caused by non-vaccine serotypes and other otopathogens, which contribute considerably to the disease burden. In this Review, we discuss the role of pneumococcus in the disease continuum and assess clinical evidence showing the effect of prevention of early episodes on the complex interplay between bacterial species implicated in otitis media.
BACKGROUND:We compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and ...influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity.
METHODS:Nasal wash specimens were prospectively obtained from 516 children hospitalized for LRI during a 1-year period and tested for the presence of HMPV by reverse transcription-polymerase chain reaction and for RSV and influenza A by direct immunofluorescence.
RESULTS:HMPV was detected in 68 (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV-positive children (24%) had coinfection with other respiratory viruses (HMPVco).HMPV patients were older than RSV patients (17.6 ± 16.8 months versus 10.5 ± 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%, P < 0.05 for each). HMPV infection was more often associated with a diagnosis of pneumonia than RSV and influenza A and was more often associated with a diagnosis of asthma and less often associated with a diagnosis of bronchiolitis than RSV infection (P < 0.05 for each), even when corrected for age. Children with HMPVco had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture.
CONCLUSIONS:The clinical pattern of HMPV more closely resembles that of RSV than that of influenza A LRI, yet the differences in age, radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.
Abstract
Objectives
We reported tet(S/M) in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.
Methods
We whole-genome sequenced 12 254 ...pneumococcal isolates from 29 countries on an Illumina HiSeq sequencer. Serotype, multilocus ST and antibiotic resistance were inferred from genomes. An SNP tree was built using Gubbins. Temporal spread was reconstructed using a birth–death model.
Results
We identified tet(S/M) in 131 pneumococcal isolates and none carried other known tet genes. Tetracycline susceptibility testing results were available for 121 tet(S/M)-positive isolates and all were resistant. A majority (74%) of tet(S/M)-positive isolates were from South Africa and caused invasive diseases among young children (59% HIV positive, where HIV status was available). All but two tet(S/M)-positive isolates belonged to clonal complex (CC) 230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sublineage predicted to exhibit resistance to penicillin, co-trimoxazole, erythromycin and tetracycline. The birth–death model detected an unrecognized outbreak of this sublineage in South Africa between 2000 and 2004 with expected secondary infections (effective reproductive number, R) of ∼2.5. R declined to ∼1.0 in 2005 and <1.0 in 2012. The declining epidemic could be related to improved access to ART in 2004 and introduction of pneumococcal conjugate vaccine (PCV) in 2009. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sublineage.
Conclusions
The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognized outbreak of CC230 in South Africa. Capsular switching in this MDR sublineage highlighted its potential to continue to cause disease in the post-PCV13 era.
Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France ...and place these findings into a global context.
Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590).
Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain.
Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases.
Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.
Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs ...to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (
,
,
) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.
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