Adequate immune responses to vaccines after chemotherapy for leukaemia diagnosed in childhood.

AIM: The survival rate after treatment for childhood leukaemia has greatly improved, but could result in protracted immune deficiency. This study examined the immune status of children after chemotherapy and evaluated their responses to immunisation. METHODS: Subjects who had completed their treatment for acute lymphoblastic leukaemia at The Children's Hospital Reykjavík, Iceland, during 2011-2020 had blood drawn and were then immunised for influenza in October 2021. Blood was drawn again 4 weeks later and their humoral and cellular responses were measured with a haemagglutination inhibition assay and lymphocyte stimulation test. Antibodies to other immunisations were also evaluated. RESULTS: We studied 18 patients (10 male) who had completed their treatment at 3.7-20.3 years of age (mean 9.1), 11-84 months (mean 36.9) before enrolment. Conventional immunological evaluation did not reveal notable abnormalities. The responses to several childhood vaccinations, including the pneumococcal conjugate vaccination, were adequate in most patients. Humoral responses to the influenza vaccine confirmed adequate reactions in all but one patient. Considerable variations were observed in the lymphocyte stimulations tests. CONCLUSION: Most patients reacted adequately to immunisation, especially against annual influenza and Streptococcus pneumoniae, reiterating the usefulness of vaccinations. The most appropriate timing for vaccination after treatment still needs to be determined.

Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Meningococcal carriage in children and young adults: a cross-sectional and longitudinal study, Iceland, 2019 to 2021.

BackgroundNeisseria meningitidis is a commensal bacterium which can cause invasive disease. Colonisation studies are important to guide vaccination strategies.AimThe study's aim was to determine the prevalence of meningococcal colonisation, duration of carriage and distribution of genogroups in Iceland.MethodsWe collected samples from 1 to 6-year-old children, 15-16-year-old adolescents and 18-20-year-old young adults. Carriers were sampled at regular intervals until the first negative swab. Conventional culture methods and qPCR were applied to detect meningococci and determine the genogroup. Whole genome sequencing was done on groupable meningococci.ResultsNo meningococci were detected among 460 children, while one of 197 (0.5%) adolescents and 34 of 525 young adults (6.5 %) carried meningococci. Non-groupable meningococci were most common (62/77 isolates from 26/35 carriers), followed by genogroup B (MenB) (12/77 isolates from 6/35 carriers). Genogroup Y was detected in two individuals and genogroup W in one. None carried genogroup C (MenC). The longest duration of carriage was at least 21 months. Serial samples from persistent carriers were closely related in WGS.ConclusionsCarriage of pathogenic meningococci is rare in young Icelanders. Non-groupable meningococci were the most common colonising meningococci in Iceland, followed by MenB. No MenC were found. Whole genome sequencing suggests prolonged carriage of the same strains in persistent carriers.

Simplified antibiotic treatment for paediatric osteoarticular infections achieved good outcomes.

AIM: Early diagnosis of osteoarticular infections (OAI) in children and effective treatment prevents complications. The objective of this study was to evaluate effectiveness and safety of shortened intravenous antibiotic treatment of OAI. Incidence, diagnostics and pathogens of paediatric OAI were assessed. METHODS: This retrospective study included all paediatric OAI admissions to The Children's Hospital Iceland in 2006-2020. The treatment was evaluated by dividing the study cohort into two groups. The simplified treatment group received intravenous antibiotics for less than 7 days. The longer intravenous group received intravenous antibiotics for a minimum of 7 days. RESULTS: In total, 205 cases of OAI were included: 106 osteomyelitis, 83 septic arthritis and 16 with both. Age standardised incidence was 17 per 100,000 children and decreased over the study period (p = 0.004). A pathogen was identified in 37% (75/205) of cases of which 65% (49/75) were Staphylococcus aureus and 12% (9/75) Kingella kingae. Simplified treatment was not associated with increased risk of complications. CONCLUSION: This study supports claims that simplified treatment for OAI is safe and effective. Further simplification of treatment might be viable. For uncertain reasons the incidence of OAI was decreasing in Iceland, predominantly in young children.

Longitudinal asthma and allergy study showed that childhood symptoms frequently persisted into adulthood.

AIMS: The prevalence of allergic diseases is high and increasing in many countries. The aim of this study was to describe the prevalence of allergic diseases and changes in clinical expression in a birth cohort followed for three decades. METHODS: We followed Icelandic citizens born in 1987 for allergic diseases when they were 2, 4, 8, 15, 21 and 29 years of age. These were diagnosed using standardised questionnaires, physical examinations and skin-prick tests. RESULTS: Just under half (46%) of the 112 who took part at 29 years of age had one or more allergic diseases, usually mild. Eczema was confirmed in 14% and was highest at the age of 2 years (31%). The prevalence of asthma was 23% and was highest at the age of 4 years (28%). Allergic rhinitis affected 30% at 29 years of age but was not found before the age of 2 years. In addition, 34% had a positive skin-prick test at 29 years of age. CONCLUSION: The results show that 46% of Icelandic adults diagnosed with allergic diseases during childhood still had symptoms at the age of 29, usually mild, developing from eczema in infancy to asthma and allergic rhinitis in adulthood.

HSCT in two brothers with CGD arising from mutations in CYBC1 corrects the defect in neutrophil function.

Homozygous mutations in cytochrome b-245 chaperone 1 (CYBC1) have been recently described as causing recurrent infections and inflammatory disease in an Icelandic cohort and a patient from Saudi Arabia, by destabilising the dimerisation of gp91phox with p22phox, manifesting as phenotypic chronic granulomatous disease (CGD). Haematopoietic stem cell transplantation is the treatment of choice in CGD, though experience of transplantation in this subtype of CGD is limited to a brief description in one patient. We provide clinical and transplant data for two Icelandic brothers with CGD due to homozygous p.Tyr2Ter mutations in CYBC1, demonstrating maintained cure of the immune defect 11 years post-transplant in one brother, and death in the peri-transplant period for the other.

Hematopoietic Stem Cell Transplantation Resolves the Immune Deficit Associated with STAT3-Dominant-Negative Hyper-IgE Syndrome.

Autosomal dominant hyper-IgE syndrome caused by dominant-negative loss-of-function mutations in signal transducer and activator of transcription factor 3 (STAT3) (STAT3-HIES) is a rare primary immunodeficiency with multisystem pathology. The quality of life in patients with STAT3-HIES is determined by not only the progressive, life-limiting pulmonary disease, but also significant skin disease including recurrent infections and abscesses requiring surgery. Our early report indicated that hematopoietic stem cell transplantation might not be effective in patients with STAT3-HIES, although a few subsequent reports have reported successful outcomes. We update on progress of our patient now with over 18 years of follow-up and report on an additional seven cases, all of whom have survived despite demonstrating significant disease-related pathology prior to transplant. We conclude that effective cure of the immunological aspects of the disease and stabilization of even severe lung involvement may be achieved by allogeneic hematopoietic stem cell transplantation. Recurrent skin infections and abscesses may be abolished. Donor TH17 cells may produce comparable levels of IL17A to healthy controls. The future challenge will be to determine which patients should best be offered this treatment and at what point in their disease history.

Children may need higher vancomycin doses to achieve therapeutic levels.

AIM: Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10-20 mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used. METHODS: All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012 and 2016 were included. Vancomycin trough levels were registered. Student t test, Wilcoxon test and regression models were used for statistical analysis. RESULTS: A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4 mg/kg/day and 38.4 mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were <10mg/L in 52.4% and <15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p = 0.09). CONCLUSIONS: In more than half of the cases, trough drug levels were <10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.

The Effect of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine on H. influenzae in Healthy Carriers and Middle Ear Infections in Iceland.

Vaccinations with the 10-valent pneumococcal conjugated vaccine (PHiD-CV) started in Iceland in 2011. Protein D (PD) from H. influenzae, which is coded for by the hpd gene, is used as a conjugate in the vaccine and may provide protection against PD-positive H. influenzae We aimed to evaluate the effect of PHiD-CV vaccination on H. influenzae in children, both in carriage and in acute otitis media (AOM). H. influenzae was isolated from nasopharyngeal swabs collected from healthy children attending 15 day care centers in 2009 and from 2012 to 2017 and from middle ear (ME) samples from children with AOM collected from 2012 to 2017. All isolates were identified using PCR for the hpd and fucK genes. Of the 3,600 samples collected from healthy children, 2,465 were culture positive for H. influenzae (68.5% carriage rate); of these, 151 (6.1%) contained hpd-negative isolates. Of the 2,847 ME samples collected, 889 (31.2%) were culture positive for H. influenzae; of these, 71 (8.0%) were hpd negative. Despite the same practice throughout the study, the annual number of ME samples reduced from 660 in 2012 to 330 in 2017. The proportions of hpd-negative isolates in unvaccinated versus vaccinated children were 5.6% and 7.0%, respectively, in healthy carriers, and 5.4% and 7.8%, respectively, in ME samples. The proportion of hpd-negative isolates increased with time in ME samples but not in healthy carriers. The number of ME samples from children with AOM decreased. The PHiD-CV had no effect on the proportion of the hpd gene in H. influenzae from carriage, but there was an increase in hpd-negative H. influenzae in otitis media. The proportions of hpd-negative isolates remained similar in vaccinated and unvaccinated children.

Vaccination of Icelandic Children with the 10-Valent Pneumococcal Vaccine Leads to a Significant Herd Effect among Adults in Iceland.

The introduction of pneumococcal conjugate vaccines (PCVs) into childhood vaccination programs has reduced carriage of vaccine serotypes and pneumococcal disease. The 10-valent PCV was introduced in Iceland in 2011. The aim of this study was to determine PCV impact on the prevalence of serotypes, genetic lineages, and antimicrobial-resistant pneumococci isolated from the lower respiratory tract (LRT) of adults. Pneumococci isolated between 2009 and 2017 at the Landspitali University Hospital were included (n = 797). The hospital serves almost three-quarters of the Icelandic population. Isolates were serotyped and tested for antimicrobial susceptibility, and the genome of every other isolate collected between 2009 and 2014 was sequenced (n = 275). Serotypes and multilocus sequence types (STs) were extracted from the genome data. Three study periods were defined, 2009 to 2011 (PreVac), 2012 to 2014 (PostVac-I), and 2015 to 2017 (PostVac-II). The total number of isolates and vaccine-type (VT) pneumococci decreased from PreVac to PostVac-II (n = 314 versus n = 230 [p = 0.002] and n = 170 versus n = 33 [p < 0.001], respectively), but non-vaccine-type (NVT) pneumococci increased among adults 18 to 64 years old (n = 56 versus n = 114 [p = 0.008]). Serotype 19F decreased in the PostVac-II period; these isolates were all multidrug resistant (MDR) and were members of the Taiwan19F-14 PMEN lineage. Serotype 6A decreased among adults ≥65 years old in the PostVac-II period (p = 0.037), while serotype 6C increased (p = 0.021) and most serotype 6C isolates were MDR. Nonencapsulated Streptococcus pneumoniae (NESp) isolates increased among adults 18 to 64 years old in the PostVac-II period, and the majority were MDR (p = 0.028). An overall reduction in the number of LRT samples and pneumococcus-positive cultures and significant changes in the serotype distribution became evident within 4 years, thereby demonstrating a significant herd effect.

Abdominal pain is a common and recurring problem in paediatric emergency departments.

AIM: Abdominal pain is a frequent reason for paediatric emergency department visits, but specific research is lacking. Our aim was to obtain information on the diagnosis of abdominal pain and what healthcare services children with this condition need. METHODS: This retrospective study focused on patients visiting the emergency department of the Children's Hospital Iceland in 2010 with abdominal pain and any subsequent visits up to 1 January 2015. RESULTS: There were 11 340 visits to the emergency department in 2010 and 1118 children made 1414 (12%) visits due to abdominal pain. The majority (58%) with abdominal pain were girls (p < 0.001) and they were older than the boys, with an average age of 12 versus 10 years (p < 0.001). The most common diagnoses were non-specific abdominal pain (40%), constipation (22%) and viral infections (13%). During the follow-up period, 423/1118 children (38%) visited the emergency department 883 times, 58% were girls and the most common diagnosis was non-specific abdominal pain (37%). Of the 436 children initially diagnosed with non-specific abdominal pain, 154 (35%) revisited the emergency department during the follow-up period. CONCLUSION: Abdominal pain was a common reason for visits to the paediatric emergency room and a third paid more than one visit.

Increase in tympanostomy tube placements despite pneumococcal vaccination, a population-based study.

AIM: The aim was to estimate the impact of the 10-valent pneumococcal vaccine (PHiD-CV) on tympanostomy tube placements (TTP) in children under five years of age in Iceland. METHODS: This population-based observational cohort study followed 11 consecutive birth-cohorts 2005-2015 from birth until their fifth birthday. Population registries were merged using national identification numbers. The risk of TTP was compared between birth-cohorts adjusted for the number of previous otitis media diagnoses and antimicrobial prescriptions. A Cox regression model was applied and the hazard ratio (HR) of TTP was estimated between each birth-cohort and the last vaccine non-eligible birth-cohort. The vaccine impact of PHiD-CV10 on TTP was estimated as 1-HR ×100%. RESULTS: In total, 51 247 children were followed for 210 724 person-years, of which 14 351 underwent 20 373 procedures. The estimated vaccine impact on TTP was -6% (95% CI -16% to 2.7%). Children in the vaccine-eligible cohorts had fewer previous otitis media diagnoses and had been prescribed fewer antimicrobials prior to the procedure than children in the vaccine non-eligible cohorts. CONCLUSION: Despite high uptake of PHiD-CV10, tympanostomy procedures increased in Iceland during the study period. Vaccine-eligible children had milder disease prior to the procedure. The reason underlying these findings are speculative.

Reduction in All-Cause Acute Otitis Media in Children <3 Years of Age in Primary Care Following Vaccination With 10-Valent Pneumococcal Haemophilus influenzae Protein-D Conjugate Vaccine: A Whole-Population Study.

Background: The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced in Iceland in 2011, without catch-up. The aim of this study was to estimate vaccine impact (VI) on acute otitis media (AOM). Methods: In this whole-population study, all primary care visits due to AOM from 2005 to 2015 in children <3 years of age were included. Birth cohorts were grouped as vaccine noneligible (VNEC) or vaccine eligible (VEC). Crude incidence rates (IRs) were compared between the VNEC and VEC. A Cox regression model for repeated events was used to model the individual-level data. VI was calculated as (hazard ratio [HR] - 1) × 100%. Results: Included were 53150 children, with 140912 person-years of follow-up and 58794 AOM episodes. Both IR and the mean number of episodes differed significantly between VNEC and VEC; 43 compared to 38 episodes per 100 person-years and 1.61 episodes per child compared to 1.37. IR was significantly reduced in all age brackets, with the largest reduction in children <4 months of age (40% [95% confidence interval {CI}, 31%-49%). The VI on all-cause AOM was 22% (95% CI, 12%-31%). The impact was mediated through its effect on the first (HR, 0.84 [95% CI, .82-.86]) and second (HR, 0.95 [95% CI, .93-.98]) episodes. Conclusions: The impact of PHiD-CV10 on all-cause AOM was considerable, mediated mainly by preventing the first two episodes of AOM. A decrease in the IR of AOM in children too young to receive direct vaccine protection was demonstrated, suggesting herd effect.

Effect of Vaccination on Pneumococci Isolated from the Nasopharynx of Healthy Children and the Middle Ear of Children with Otitis Media in Iceland.

Vaccination with pneumococcal conjugate vaccines (PCVs) disrupts the pneumococcal population. Our aim was to determine the impact of the 10-valent PCV on the serotypes, genetic lineages, and antimicrobial susceptibility of pneumococci isolated from children in Iceland. Pneumococci were collected between 2009 and 2017 from the nasopharynges of healthy children attending 15 day care centers and from the middle ears (MEs) of children with acute otitis media from the greater Reykjavik capital area. Isolates were serotyped and tested for antimicrobial susceptibility. Whole-genome sequencing (WGS) was performed on alternate isolates from 2009 to 2014, and serotypes and multilocus sequence types (STs) were extracted from the WGS data. Two study periods were defined: 2009 to 2011 (PreVac) and 2012 to 2017 (PostVac). The overall nasopharyngeal carriage rate was similar between the two periods (67.3% PreVac and 61.5% PostVac, P = 0.090). Vaccine-type (VT) pneumococci decreased and nonvaccine-type (NVT) pneumococci (serotypes 6C, 15A, 15B/C, 21, 22F, 23A, 23B, 35F, and 35B) significantly increased in different age strata post-PCV introduction. The total number of pneumococci recovered from ME samples significantly decreased as did the proportion that were VTs, although NVT pneumococci (6C, 15B/C, 23A, and 23B) increased significantly. Most serotype 6C pneumococci were multidrug resistant (MDR). Serotype 19F was the predominant serotype associated with MEs, and it significantly decreased post-PCV introduction: these isolates were predominantly MDR and of the Taiwan19F-14 PMEN lineage. Overall, the nasopharyngeal carriage rate remained constant and the number of ME-associated pneumococci decreased significantly post-PCV introduction; however, there was a concomitant and statistically significant shift from VTs to NVTs in both collections of pneumococci.

Impact of the 10-valent pneumococcal conjugate vaccine on antimicrobial prescriptions in young children: a whole population study.

BACKGROUND: Antimicrobial resistance is a public-health threat and antimicrobial consumption is the main contributor. The ten-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic vaccination program in 2011. The aim was to estimate the vaccine impact of PHiD-CV10 on outpatient antimicrobial prescriptions in children. METHODS: Eleven Icelandic birth-cohorts (2005-2015) were followed from birth until three years of age or to the end of the study period (December 31, 2016). Birth-cohorts were grouped as vaccine non-eligible (VNEC, 2005-2010) or vaccine eligible (VEC, 2011-2015). Data on primary care visits for respiratory infections and antimicrobial prescriptions were extracted from two national registers. Using national identification numbers, prescriptions were linked to physician visits if filled within three days of the visit. Incidence rates and incidence rate ratios between VNEC and VEC were calculated. An Andersen-Gill model was used to model the individual level data, accounting for repeated events and censoring. Vaccine impact was calculated as (1 - Hazard Ratio) × 100%. RESULTS: Included were 53,510 children who contributed 151,992 person-years of follow-up and filled 231,660 antimicrobial prescriptions. The incidence rate was significantly lower in the VEC compared to the VNEC, 144.5 and 157.2 prescriptions per 100 person-years respectively (IRR 0.92, 95%CI 0.91-0.93). Children in VEC were more likely to have filled zero (IRR 1.16 (95%CI 1.10-1.23) and 1-4 (IRR 1.08 95%CI 1.06-1.11) prescriptions compared to children in VNEC. The vaccine impact of PHiD-CV10 against all-cause antimicrobial prescriptions was 5.8% (95%CI 1.6-9.8%).When only considering acute otitis media-associated prescriptions, the vaccine impact was 21.8% (95%CI 11.5-30.9%). CONCLUSION: The introduction of PHiD-CV10 lead to reduced antimicrobial use in children, mainly by reducing acute otitis media episodes. This intervention therefore reduces both disease burden and could slow the spread of antimicrobial resistance.

Ataxia-telangiectasia: Immunodeficiency and survival.

Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.

Epidemiology of Primary Immunodeficiency in Iceland.

PURPOSE: Primary immunodeficiencies (PID) are rare heterogeneous diseases. Little is known about the prevalence of PID in Iceland and no national registry exists. The aim of the study was to describe the epidemiology of PID in Iceland. METHODS: Using The European Society's for Immunodeficiencies (ESID) criteria for PID, information about individuals with a known PID between 1990 and 2010 in Iceland were collected from inpatient registries of the National University Hospital of Iceland, the Department of Immunology and from clinical immunologists. Selective IgA deficiency, mannan binding lectin deficiency and secondary immunodeficiencies were excluded RESULTS: Sixty six individuals met the study criteria, 35 of them (53%) were females. Four patients died during the study period from PID- or treatment related complications and two moved abroad. In the beginning of 2011 there were 60 individuals living in Iceland with a known PID diagnosis meeting ESID's criteria. Estimated prevalence for PID in the Icelandic population of 318.452 habitants was 18.8 for 100.000 inhabitants. Predominantly antibody disorders comprised the largest category of PID in Iceland. CONCLUSIONS: The prevalence of PID is high in Iceland compared to reports from other nations. Our patient data are easily accessible and a central laboratory measures the immune parameters. This high prevalence may indicate that PID is more common than generally recognized.

Genomics Reveals the Worldwide Distribution of Multidrug-Resistant Serotype 6E Pneumococci.

The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity.

Decreased postural control in adolescents born with extremely low birth weight.

The survival rates of infants born preterm with extremely low birth weight (ELBW ≤ 1000 g) have gradually improved over the last decades. However, these infants risk to sustain long-term disorders related to poor neurodevelopment. The objective was to determine whether adolescents born with ELBW have decreased postural control and stability adaptation. Twenty-nine ELBW subjects performed posturography with eyes open and closed under unperturbed and perturbed standing by repeated calf vibration. Their results were compared with twenty-one age- and gender-matched controls born after full-term pregnancy. The ELBW group had significantly decreased stability compared with controls in anteroposterior direction, both during the easier quiet stance posturography (p = 0.007) and during balance perturbations (p = 0.007). The ELBW group had similar stability decrease in lateral direction during balance perturbations (p = 0.013). Statistically, the stability decreases were similar with eyes closed and open, but proportionally larger with eyes open in both directions. Both groups manifested significant adaptation (p ≤ 0.023) to the balance perturbations in anteroposterior direction, though this adaptation process could not compensate for the general stability deficits caused by ELBW on postural control. Hence, adolescent survivors of ELBW commonly suffer long-term deficits in postural control, manifested as use of substantially more recorded energy on performing stability regulating high-frequency movements and declined stability with closed and open eyes both in anteroposterior and lateral direction. The determined relationship between premature birth and long-term functional deficits advocates that interventions should be developed to provide preventive care in neonatal care units and later on in life.