Effect of COVID-19 Pandemic on Invasive Pneumococcal Disease in Children, Catalonia, Spain.

We analyzed the effect of COVID-19 on healthcare demand and invasive pneumococcal disease in children in Catalonia, Spain. Compared with 2018-2019, we noted large reductions in healthcare activities and incidence of invasive pneumococcal disease in 2020. These changes likely resulted from nonpharmaceutical measures implemented during the COVID-19 pandemic.

The impact of COVID-19 lockdown on children with recurrent wheezing and asthma in Spain.

AIM: The rapid spread of a novel human coronavirus SARS-CoV-2 led to drastic measures world-wide. Most countries were forced to declare a national lockdown. We studied the effect of lockdown measures on the level of asthma control and maintenance treatment in children with recurrent wheezing and asthma during the first wave of COVID-19 in Spain. METHODS: We analysed children with recurrent wheezing or asthma before and after the implementation of the lockdown, by using a questionnaire aimed to examine pre-existing respiratory disorders, step treatment and level of asthma control before/after lockdown, COVID history and laboratory testing including IgG SARS-CoV-2. RESULTS: We enrolled 475 asthmatic and pre-school wheezers (60.6% males), mean age 5.6 years. There were no differences in asthma treatment comparing both periods: 81.7% maintained the same treatment (P = 0.103). According to child asthma-control questionnaire, 87.7% remained well controlled during confinement. Nearly, a third of children (34.9%) needed reliever treatment, mainly in older children. Determination of IgG SARS-CoV-2 was performed in 233 children (49.1%) of whom 17 (7.3%) tested positive. Seven patients positive to IgG SARS-CoV-2 were assisted in the emergency department and two required hospital admission. CONCLUSIONS: During COVID-19 lockdown in Spain, most children with recurrent wheezing and asthma remained well controlled from their underlying disease and did not modify greatly their maintenance treatments. Unexpectedly, we also observed that those children who tested positive to SARS-CoV-2 IgG showed a significant increase in paediatric hospital admissions and attendances to urgent care settings.

Changes in Invasive Pneumococcal Disease in the Paediatric Population in the Second COVID-19 Pandemic Year.

Incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020, coinciding with the implementation of measures to reduce COVID-19 transmission. We evaluated the impact of the COVID-19 pandemic on healthcare demand and IPD in children in 2021 compared to the pre-pandemic period (2018-2019) and the early pandemic period (2020) in a study carried out during 2018-2021 in Catalonia. Incidence rates were compared by calculating the incidence rate ratio (IRR), and expressing percentage changes in IRR as (1-IRR)x100. Compared to 2018-2019, emergency room (ER) visits declined by 21% in 2021 (p < 0.001), mainly in the first quarter (-39%), and compared to 2020, ER visits increased by 22% in 2021 (p < 0.001), except in the first quarter. IPD incidence overall was 11.0 in 2018-2019 and 4.6 in 2021 (-58%, p < 0.001); the reduction in incidence was similar in the 0-4 age group and was higher in the first quarters. Compared to 2020, in 2021, IPD incidence decreased during the first quarter (-86%, p < 0.001), but increased from 0.0 to 1.2 in the second quarter (p = 0.02) and from 0.6 to 2.1 (p=0.03) in the fourth quarter. The decreased IPD incidence observed in 2021 compared to 2018-2019 (most especially in the first quarter) was greater than the decrease in healthcare demand and PCR test requests. Compared to 2020, IPD incidence decreased in the first quarter when a second state of alarm was in force. In 2021, compared to 2018-2019, there was a greater reduction in PCV13 serotypes than in non-PCV13 serotypes.

Pediatric Gaucher disease with intermediate type 2-3 phenotype associated with parkinsonian features and levodopa responsiveness.

INTRODUCTION: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid ß-glucosidase encoded by the GBA gene. In patients with GD, childhood onset parkinsonian features have been rarely described. METHODS: Twin siblings with GD are described, including clinical follow-up and treatment response. Bone marrow, enzyme activity studies and genotyping were performed. RESULTS: By age 9 months, symptoms at onset were thrombocytopenia and splenomegaly. By age 2, hypokinesia, bradykinesia and oculomotor apraxia were observed. By age 5 a complete rigid hypokinetic syndrome was stablished in both patients, including bradykinesia, tremor and rigidity. Treatment with imiglucerase, miglustat, ambroxol and levodopa were performed. Levodopa showed a good response with improvement in motor and non-motor skills. Foamy cells were found in the bone marrow study. Glucocerebrosidase activity was 28% and 26%. Sanger sequencing analysis identified a missense mutation and a complex allele (NP_000148: p.[(Asp448His)]; [(Leu422Profs*4)]) in compound heterozygosity in GBA gene. CONCLUSIONS: Two siblings with neuronopathic GD with an intermediate form between type 2 and 3, with a systemic and neurological phenotype are described. The complex neurological picture included a hypokinetic-rigid and tremor syndrome that improved with levodopa treatment. These conditions together have not been previously described in pediatric GD. We suggest that in children with parkinsonian features, lysosomal storage disorders must be considered, and a levodopa trial must be performed. Moreover, this report give support to the finding that GBA and parkinsonian features share biological pathways and highlight the importance of lysosomal mechanisms in parkinsonism pathogenesis, what might have therapeutic implications.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

[Characteristics of patients with invasive pneumococcal disease requiring admission to intensive care units]. / Características de los pacientes con enfermedad neumocócica invasora que requieren ingreso en la unidad de cuidados intensivos.

INTRODUCTION: Patients with invasive pneumococcal disease (IPD) may require admission into paediatric intensive care units (PICU). The aim of this study is to analyse the epidemiological, clinical, and microbiological characteristics associated with IPD that may require admission to the PICU. MATERIAL AND METHODS: A prospective study was conducted on cases of IPD diagnosed in three Paediatric Hospitals in Barcelona between January 2012 and June 2016. An analysis was made of the associations between the admission to PICU and the epidemiological, clinical, and microbiological variables. RESULTS: A total of 263 cases with IPD were included, of which 19% (n = 50) required admission to PICU. Patients with septic shock (7; 100%), meningitis (16; 84.2%), and those with complicated pneumonia (23; 15.2%) were admitted to the PICU. The most frequent complications were pulmonary (35.2%) and neurological (39.5%). The ratio between admission and non-admission to PICU was 4.7 times higher in subjects with an underlying disease. The serotypes associated with PICU admission were 19A (23% of the total of this serotype), serotype 14 (20%), serotype 3 (17%), and serotype 1 (12.5%). CONCLUSIONS: IPD required PICU admission in cases of septic shock and meningitis, and less so with complicated pneumonia. The percentage of admissions is greater in children with an underlying disease. Admission into the PICU involves a longer stay, complications during the acute phase, as well as sequelae, particularly neurological ones. The serotypes of the patients that were admitted to PICU were predominantly vaccine serotypes.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

Serotype and clonal distribution dynamics of invasive pneumococcal strains after PCV13 introduction (2011-2016): Surveillance data from 23 sites in Catalonia, Spain.

BACKGROUND: The objective of this study is to describe incidence and shifts of serotype and clonal distribution of invasive Streptococcus pneumoniae strains in four different age groups (<5 years, 5-17 years, 18-64 years and >65 years) during a period of intermediate PCV13 vaccination coverage (2011-2016) in Catalonia, Spain. METHODS: We included all pneumococcal strains systematically sent to the Catalan support laboratory for molecular surveillance of invasive pneumococcal disease (IPD) located at Hospital Sant Joan de Deu, Barcelona. Two study periods were considered: 2011-13, early PCV13 vaccination period (EVP) and 2014-2016, late vaccination period (LVP). RESULTS: A total of 2142 strains were included in the study. Five years after intermediate introduction of PCV13 in our population, a significant decrease of overall incidence of IPD in children <5 years was observed (incidence rate ratio 0.5, 95% confidence interval 0.4-0.8). However, in seniors older than 65 years, a significant increase of overall incidence of IPD was observed (IRR 1.4, 95% CI 1.1-1.7). The contribution of PCV13 vaccine serotypes to IPD declined significantly in all age groups: from 59% to 38.1% in <5 years; 82.7% to 59% in 5-17 years, 47.8% to 34.1% in 18-64 years and 48.2% to 37% in >65 years. Results found when comparing both periods were consistent with IRRs observed year by year. In children <5 years, the three major serotypes detected were 1, 24F and 19A in EVP vs 24F, 14 and 10A in LVP. Among patients 5-17 years the first three serotypes were 1, 12F and 14 both in EVP and LVP. Among adults 18-64, the three major serotypes detected were 1, 12F and 8 vs 8, 12F and 3, respectively. Finally, in patients >65 years the most frequently isolated serotypes were 3, 19A and 7F vs 3, 14 and 12F, respectively. Regarding clonal complexes (CCs) expressing mainly PCV13 serotypes, significant decreases of the proportions of CC306, CC191 and CC320 were observed, while CC156 showed a significant increase. As for CCs expressing mostly non-PCV13 serotypes, significant increases in ST989, CC53 and CC404 were showed. CONCLUSIONS: Despite low vaccine coverage in our setting a significant decrease of incidence of IPD was observed in children younger than 5 years. The modest indirect protection against vaccine serotypes causing IPD in elderly indicate the need for the inclusion of more serotypes in future high-valent PCV and vaccinating old adults should be considered.

Complicated pneumococcal pneumonia with pleural effusion or empyema in the 13-valent pneumococcal conjugate vaccine era.

AIM: The aim was to analyze the epidemiological, microbiological and clinical characteristics of patients with complicated pneumococcal pneumonia with pleural effusion (PE) or empyema. METHOD: Prospective study in three Catalan hospitals in persons aged <18 years diagnosed with complicated pneumonia with PE or empyema with isolation of Streptococcus pneumoniae in blood or pleural fluid by culture or real-time PCR between January 2012 and June 2016. Patients were divided into <2 years and 2-17 years age groups. Epidemiological, microbiological, and clinical data of patients were compared annually in both groups. PCV13 vaccination coverage increased from 48.2% in 2012 to 74.5% in 2015. RESULTS: We included 143 patients. The incidence of pneumococcal pneumonia was 6.83 cases × 10-5 persons/year in cases with PE or empyema and 2.09 cases × 10-5 person-years in cases without (rate ratio [RR]: 3.27; 2.25-4.86; P < 0.001). Empyema was more frequent than PE (79.7% vs 20.3%, P < 0.005). Of 143 cases studied, 93 (65.0%, P < 0.001) were diagnosed by real-time-PCR, 43 (30.1%) by culture and RT-PCR and 7 (4.9%) by culture only. PCV13 serotypes were more frequent in complicated than in uncomplicated pneumonia (116/142, 81.7% vs 27/45, 60.0%; P = 0.003), especially serotype 1 (41/142, 28.9% vs 6/45, 13.3%, P : 0.036). From 2012 to 2015 there was a significant reduction in serotype 1 (16/43, 37.2% vs 3/27, 11.1%, P = 0.026), and a trend to an increase in non-PCV13 serotypes (6/43, 14% vs 9/27, 33.3%, P = 0.054). CONCLUSIONS: A directly proportional relationship was observed between the reduction in pneumonia complicated with PE or empyema and a significant reduction in PCV13 serotypes, especially serotype 1, coinciding with increased PCV13 coverage.

Vaccine Failures in Patients Properly Vaccinated with 13-Valent Pneumococcal Conjugate Vaccine in Catalonia, a Region with Low Vaccination Coverage.

Vaccine failures occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in 3 pediatric hospitals in Barcelona (2012-2013) are described. PCV13 vaccine failure was defined as the occurrence of an invasive pneumococcal infection in children properly vaccinated by PCV13. Among 84 patients with invasive pneumococcal infection, 32 had received at least one dose of PCV13. Seventeen of them had invasive pneumococcal infection produced by a PCV13 serotype. Among those, 9 patients were considered to have a PCV13 vaccine failure. Serotype 3 was isolated in 6 patients, serotype 19A in 2 and serotype 6B in 1.