Invasive Disease In Children Research Articles

Comment pédiatres et généralistes envisagent-ils l’introduction d’une vaccination contre le méningocoque B en France ?

To assess the acceptability of a vaccine against meningococcus B by pediatricians and GP and to analyze how the vaccine could be implemented in France, InfoVac-France has set up a national survey. An email explained the purpose of this study and the practitioners of InfoVac-France network answered an online questionnaire (e-CRF). Of the 6905 pediatricians and GP who saw the mail sent by InfoVac-France between 11 and 24 January, 2012, 1351 (13.5 %) completed the e-CERF : 361 GP (26.7%), 797 pediatricians (59%) and 193 other doctors (14.3%). The majority of practitioners (96.1%) believe that is important to implement a vaccine against meningococcus B in the French immunization schedule. In 80.5% of cases, practitioners do not want to vaccine three times routinely during a single consultation and more than half (53.5%) would prefer to use this vaccine alone. The best schedule of primary vaccination (80.6%) is the injection at 3, 5 and 6 months. The arguments considered likely to encourage parents to accept the vaccination would be the incidence of the disease, severity of meningitis (82.1%) and the rapid mortality (82.8%). This survey by InfoVac-France shows that the practitioners know the epidemiology of meningococcal B invasive disease in children. They would support the implementation of this vaccine for children under 2 years with a primary vaccination at 3, 5 and 6 months.

Extended-spectrum β-lactamase producing bacilli in a paediatric hospital

Enterobacteriaceae are a common cause of invasive disease in children. The production of extended-spectrum ß-lactamase (ESBL) by these bacteria and consequent resistance to several antibiotics has increased. The paediatric data are scarce. To identify children infected with ESBL-producing bacilli, determining their prevalence in health care related infection and community-acquired disease. To analyse demographic, clinical, laboratory, therapeutic and follow-up data. To identify potential risk factors for infection by ESBL-producing organisms. A case-control study, conducted in a level III paediatric hospital, from July 2007 to December 2009. All patients were identified from the microbiology database. Children infected by ESBL-producing bacilli were compared with a group with infection by non-ESBL producers, selected in a systematic way, given the bacteria, product and date of isolation. Statistical data analysis was performed using SPSS® 17.1. The ESBL-producing phenotype was detected in 0.5% of Escherichia coli and 16.4% of Klebsiella spp identified. These bacteria were isolated in 23 children: 7 Escherichia coli (30.4%), 15 Klebsiella pneumoniae (65.2%) and 1 Klebsiella oxytoca (4.3%). The most common diagnosis was urinary tract infection (39%). Hospital admission was required in 70% of the cases versus 50% controls (p=0.141), with mean duration stay of 69 days for cases and 36 days for controls (p=0.235). The mean time between admission and infection was 32 days in both (p=0.978). Health care related infections were identified in 70% of cases versus 25% of controls (p=0.001). Infections due to ESBL producing organisms occurred in the community setting particularly in the last year of the study (n=4). The presence of chronic disease (p=0.022) and previous hospitalization (p=0.025), antibiotic use (p=0.008) and invasive ventilation (p=0.002) were more common in infection caused by ESBL-producing bacteria. Surgery (p=0.175) and the presence of a central venous catheter (p=0.189) were not risk factors. In a multivariate analysis, only prior invasive ventilation was an independent risk factor for infection by ESBL-producing bacteria (p=0.002, OR=7). The ESBL-producing phenotype was detected in 0.5% Escherichia coli and 16.4% Klebsiella spp identified; mainly in health care related infections. The presence of chronic disease and previous hospitalization, invasive ventilation and antibiotic intake were more common in infections caused by these bacteria. Prior invasive ventilation was an independent risk factor.

Molecular analysis of Streptococcus pneumoniae clones causing invasive disease in children in Singapore

Streptococcus pneumoniae remains a leading cause of serious paediatric disease. However, there are few published epidemiological data regarding invasive pneumococcal disease (IPD) in many countries in South East Asia, including Singapore. Baseline data for IPD are essential to inform policy regarding pneumococcal conjugate vaccine (PCV) use in Singapore. To our knowledge, this is the first study to use multilocus sequence typing (MLST) to investigate clonal relationships among Singaporean IPD isolates. We characterized 86 invasive pneumococci isolated from Singaporean children between 2001 and 2006 using serotyping and MLST. The objectives were to compare Singaporean MLST data to worldwide data and to assess serotype distribution in relation to current PCV formulations. We observed 50 sequence types (STs), a high proportion of which (n = 16) were novel STs. Despite the presence of these novel STs, serotype distribution was similar to that observed elsewhere. Serotypes 14, 6B, 19A and 19F accounted for 85 % of IPD cases. PCV7, PCV10 and PCV13 covered 85 %, 86 % and 97 % of IPD isolates, respectively. We have demonstrated a pressing need for larger studies to determine the molecular epidemiology and antibiotic susceptibility of circulating pneumococcal clones from both carriage and disease in Singapore.

Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study

We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7) programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. Nasopharyngeal swabs were taken from children <5 y old and family members (n=400) 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs) were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT) carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49). The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.

Infantile orbital cellulitis secondary to community-associated methicillin-resistant Staphylococcus aureus

Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized as a cause of invasive disease in children. Orbital cellulitis typically occurs in older children, but it can occasionally affect infants and neonates. We report 2 infants with sepsis and orbital cellulitis caused by community-associated MRSA and review the relevant literature.

Serotypes and antibiotic susceptibility of Streptococcus pneumoniae isolates causative of invasive diseases in Mexican children

Streptococcus pneumoniae is a worldwide leading cause of morbidity and mortality, while susceptibility towards penicillin and macrolides can be less than 50% in many regions. A total of 150 isolates of S. pneumoniae causative of invasive diseases in children were characterized, of which 24.6% had a fatal outcome. The most prevalent serotypes were 19F, 6B, 23F and 14. Resistance to penicillin, erythromycin (mostly of macrolide-lincosamide-streptogramin resistance phenotype) or trimethoprim-sulfamethoxazole was found in more than 40% of the isolates, but no resistance phenotype appeared linked to lethality. Serotype 3 isolates, which were seldom resistant, had a twofold lethality rate compared to the total sample. Serotyping could provide a better outcome-predicting tool than susceptibility testing. The seven-valent vaccine does not include the most prevalent serotypes found in Mexico.

A case of fatal pneumococcal 19A meningoencephalitis despite administration of seven-valent pneumococcal conjugate vaccines

Streptococcus pneumoniae is a major cause of serious invasive diseases in children, especially in young infants, but seven- valent pneumococcal conjugate vaccine (PCV7) is believed to prevent invasive pneumococcal pneumonia and meningitis in young children. However, recently, the incidence of non-PCV7 serotype has increased after PCV7 vaccination. A 14-month- old female patient presented at our emergency room with mental change and lethargy. Three days previously, she had developed fever and vomiting. After being admitted, she rapidly progressed to coma and brain death despite prompt and extensive supportive treatment. She expired 20 days after admission with a final diagnosis of pneumococcal 19A (non-PCV7 serotype) meningoencephalitis despite having received PCV7 (Prevenar ) vaccinations on three occasions. The author reports this first fatality due to pneumococcal 19A meningoencephalitis in Korea and provides a brief review of the literature.

Non-typhoidal salmonellae: a management challenge for children with community-acquired invasive disease in tropical African countries

Although a single species, more than 2000 serovars of Salmonella enterica have been identified, including Typhi, Typhimurium, and Enteritidis. S enterica var Typhi (or S typhi) causes invasive disease, which is particularly common in Asia, whereas non-typhoidal salmonellae are important causes of food-borne infections and cause mainly gastroenteritis in developed countries.1 Far less recognised is the disease burden in tropical African countries. Non-typhoidal salmonellae (mainly S typhimurium and S enteritidis) have long been a common cause of invasive disease in children, especially during rainy seasons, consistently associated with young age (most cases present between 6 months and 3 years of age), anaemia, malnutrition, and of late with HIV infection.

Pneumococcal Invasive Disease in Children

In Brief Streptococcus pneumoniae is one of the major bacterial causes of invasive disease with significant morbidity and mortality. The ability of pneumococci to cause disease is directly related to the production of a capsule that promotes evasion of the host immune system of the patient. A large variety of capsular types can be produced by pneumococci but only a small number of these cause the majority of invasive disease. In February 2000, a protein-polysaccharide conjugate vaccine against the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F (PCV7) was licensed for use in infants and young children. This vaccine has to be safe, immunogenic, and effective in preventing pneumococcal disease in children. The pneumococcal conjugate vaccine also prevents asymptomatic colonization of the nasopharynx by PCV7 serotypes. It was expected that the broad usage of the vaccine would significantly reduce the incidence of invasive pneumococcal disease and the levels of pneumococcal resistance significantly because of the high prevalence of antimicrobial resistance of the PCV7 serotypes. Good results for this vaccine have led the World Health Organization to recommend the introduction of PCV7 into national immunization programs worldwide. However, important questions have recently been raised regarding the effectiveness of PCV7, especially if serotype replacement limits the efficacy of this vaccine. Recently, several authors have reported an increase in infections caused by non-PCV7 serotypes. In addition, resistance to commonly used antimicrobials has significantly increased among nonvaccine serotypes. Virulent pneumococcal serotypes not covered by the PCV7 vaccine and serotype replacement make it essential that there be continued monitoring and surveillance of pneumoccocal colonization and invasive disease. In February 2000, a protein-polysaccharide conjugate vaccine against the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F (PCV7) was licensed for use in infants and young children. After 7 years of use, there is evidence that the vaccine prevents pneumococcal disease for included serotypes. However, important questions have recently been raised regarding the effectiveness of PCV7, especially if serotype replacement limits the efficacy of this vaccine.

Epidemiology ofHaemophilus influenzaeSerotype a, North American Arctic, 2000–2005

Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of invasive H. influenzae disease among indigenous people of the North American Arctic were among the highest in the world. Routine vaccination reduced rates to low levels; however, serotype replacement with non-type b strains may result in a reemergence of invasive disease in children. We reviewed population-based data on invasive H. influenzae in Alaska and northern Canada from 2000-2005; 138 cases were reported. Among 88 typeable isolates, 42 (48%) were H. influenzae type a (Hia); 35 (83%) occurred in indigenous peoples. Among Hia patients, median age was 1.1 years; 62% were male; 1 adult died. Common clinical manifestations included meningitis, pneumonia, and septic arthritis. Overall annual incidence was 0.9 cases per 100,000 population. Incidence among indigenous children <2 years of age in Alaska and northern Canada was 21 and 102, respectively. Serotype a is now the most common H. influenzae serotype in the North American Arctic; the highest rates are among indigenous children.

Incidence of Pneumococcal Disease Due to Non–Pneumococcal Conjugate Vaccine (PCV7) Serotypes in the United States during the Era of Widespread PCV7 Vaccination, 1998–2004

Widespread use of pneumococcal conjugate vaccine (PCV7) resulted in decreases in invasive disease among children and elderly persons. The benefits may be offset by increases in disease due to serotypes not included in the vaccine (hereafter, "nonvaccine serotypes"). We evaluated the effect of PCV7 on incidence of disease due to nonvaccine serotypes. Cases of invasive disease were identified in 8 geographic areas through the Centers for Disease Control and Prevention's Active Bacterial Core surveillance. Serotyping and susceptibility testing of isolates were performed. We calculated the incidence of disease for children aged <5 years and adults aged > or =65 years. We compared rates of serotype-specific disease before and after PCV7 was licensed for use. The annual incidence of disease due to nonvaccine serotypes increased from an average of 16.3 cases/100,000 population during prevaccine years (1998-1999) to 19.9 cases/100,000 population in 2004 for children aged <5 years (P=.01) and from 27.0 cases/100,000 population during prevaccine years to 29.8 cases/100,000 population in 2004 for adults aged > or =65 years (P=.05). Significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period (P<.05 for each serotype); serotype 19A has become the predominant cause of invasive disease in children. The incidence of disease due to these serotypes also increased among elderly persons. The incidence of pneumococcal disease caused by nonvaccine serotypes is increasing. Ongoing surveillance is needed to monitor the magnitude of disease caused by nonvaccine serotypes, to ensure that future vaccines target the appropriate serotypes.

P1426 Microbiological aspects of a Streptococcus pyogenes outbreak causing invasive disease in children attending a day care centre in Cantabria, Spain

P1426 Microbiological aspects of a Streptococcus pyogenes outbreak causing invasive disease in children attending a day care centre in Cantabria, Spain

Infecciones invasoras por Haemophilus influenzae tipo b después de la incorporación de la vacuna conjugada al Programa Ampliado de Inmunizaciones en Chile

After almost a decade since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines in Chile (in a 2-4-6 month schedule), Hib invasive infections have dramatically decreased, albeit they remain to occasionally produce disease in pediatric patients. We report our experience with children whom developed Hib invasive disease in children since 2000 to 2004. Medical records of children with Hib were reviewed in order to describe the epidemiology, main clinical and laboratory findings, management and complications. Twenty three patients (17 male), between 1 and 71 months (median 30 months) were identified: pneumonia (7), meningitis (4), pleuropneumonia (2), empyema (2), sepsis (2), cellulitis (2), meningitis and pleuropneumonia (1), purpura fulminans (1), miositis (1) and epiglottitis (1). No deaths were observed and four patients presented severe sequelae at hospital discharge. Twenty patients were considered vaccine failures. Hib remains as a sporadic cause of severe disease in Chile and thus for physicians should still keep it in mind. Case analysis and active surveillance are necessary to monitor the current immunization regimen.

Serotypes and Clonal Types of Penicillin-SusceptibleStreptococcus pneumoniaeCausing Invasive Disease in Children in Five Latin American Countries

We used multilocus sequencing typing (MLST) to determine the genetic backgrounds of 185 recent penicillin susceptible Streptococcus pneumoniae isolates with serotypes that most frequently cause invasive disease in preschool age children in five Latin American countries-Argentina, Brazil, Colombia, Mexico, and Uruguay. Most of the isolates were associated with pneumonia (90/185), meningitis (74/185), and bacteremia (17/185). The collection of strains included seven serotypes-14, 6B, 5, 1, 23 F-which represent the serotypes of S. pneumoniae most frequently associated with sterile site infections in children. Also included were strains expressing serotypes 7F and 3. Comparison of serotype and multilocus sequence type allowed division of the isolates into two groups: strains expressing serotypes 1, 5, 3, and 7 were represented by a relatively few sequence types while strains expressing serotypes 6B, 14, and 23 F showed great genetic diversity. The genetic diversity of serotypes 14, 6B, and 23 F may be related to the capacity of these serotypes to colonize the nasopharynx of healthy carriers during which opportunities for diversification through genetic exchanges can occur. The findings present an interesting contrast with the results of an earlier study in which over 80% of invasive penicillin- resistant serotype 14 and 23 isolates from the same countries were found to belong to as few as two pandemic clones of S. pneumoniae.

Epidemiology of Invasive Haemophilus influenzae Type A Disease among Navajo and White Mountain Apache Children, 1988-2003

Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of H. influenzae disease among Navajo and White Mountain Apache (WMA) children were among the highest reported worldwide. Routine Hib vaccination has significantly reduced rates of Hib disease in these populations. As Hib disease rates decrease to very low levels, there are concerns that non-type b strains of H. influenzae may emerge as more prevalent causes of invasive disease in children. We reviewed population-based, active laboratory surveillance data from the period of 1988-2003 for invasive H. influenzae type a (Hia) disease among Navajo and WMA children aged <5 years. Clinical information on cases was collected by chart review. A sample of Hia isolates from Navajo children was typed by pulsed-field gel electrophoresis (PFGE). During 1988-2003, a total of 76 reported cases of invasive Hia disease occurred among Navajo and WMA children. The overall annual incidence was 20.2 cases per 100,000 population aged <5 years. There was no increase in Hia disease rates after Hib vaccination was introduced. The median age of patients was 12 months. Meningitis (50% of cases) was the most common presentation, followed by pneumonia (27.6%). Two children with Hia disease died. PFGE analysis revealed a limited genetic diversity of Hia strains in this population. Active surveillance data showed high rates of invasive Hia disease among Navajo and WMA children but no increase in the incidence after Hib vaccination was introduced. The presentation of Hia disease is similar to that of Hib disease in the prevaccine era.

Invasiveness of Serotypes and Clones of Streptococcus pneumoniae among Children in Finland

Streptococcus pneumoniae (the pneumococcus) causes diseases from otitis media to life-threatening invasive infection. The species is extremely antigenically and clonally diverse. We wished to determine odds ratios (ORs) for serotypes and clones of S. pneumoniae that cause invasive disease in Finland. A total of 224 isolates of S. pneumoniae from cases of invasive disease in children <2 years of age in Finland between 1995 and 1999 were serotyped, and sequence types (STs) were determined by multilocus sequence typing. These STs were compared with a previously published carriage data set. STs from invasive disease were significantly less diverse than those from carriage (invasive disease, 0.038 +/- 0.01; carriage, 0.019 +/- 0.005). The ORs of serotypes 14, 18C, 19A, and 6B were significantly greater than 1, indicating association with invasive disease. The ORs of 6A and 11A were significantly less than 1. The difference between 6A and 6B is significant, which suggests that relatively subtle changes in the capsule may have a dramatic effect upon disease potential. We found that ST 156, the Spain(9V)-3 clone which mainly expressed serotype 14 in Finland, is strongly associated with invasive disease (OR, 10.1; 95% confidence interval, 1.3 to 79.5). Significant associations with invasive disease were also detected for STs 482, 191, 124, and 138, and associations with carriage were detected for STs 485 and 62. These results demonstrate the invasive phenotype of the serotype 14 variant of the Spain(9V)-3 clone and differences between members of the same serogroup in invasive disease potential.

Enfermedad invasiva por Streptococcus pneumoniae y Haemophilus influenzae serotipo b. Estudio retrospectivo de 12 años

Streptococcus pneumoniae and Haemophilus influenzae serotype b (Hib) are two of the most common causes of invasive bacterial disease in children. The introduction of a successful Hib vaccine and the emergence of penicillin-resistant pneumococci have changed the epidemiology of these bacteria over the last few years. To evaluate the incidence of S. pneumoniae and Hib invasive disease in children (0-15 years) admitted to our hospital during a 12-year period (January 1991-December 2002). We retrospectively reviewed the medical records of 101 children with isolation of S. pneumoniae and Hib in blood, cerebrospinal fluid (CSF) or synovial fluid samples during the study period. SP was isolated in 81 samples (72 in blood and nine in CSF) from 73 children (72.6 % were aged < 2 years). The annual incidence per 100,000 children aged 0-2 years was 53.76 cases (95 % CI: 40.7-70.9). The most common clinical diagnosis was bacteremia (67 %). The percentage of penicillin-resistant strains was 44 %. Hib was isolated in 38 samples (26 in blood, 10 in CSF and two in synovial fluid) from 28 children (82.1 % were aged < 2 years). The most common clinical diagnosis was meningitis (35.7 %). The annual incidence per 100,000 children aged between 0-5 years dropped from 21.52 cases (95 % CI: 14.4-32) to 1.7 cases (95 % CI: 0.1-10.8) after systematic vaccination. The percentage of ampicillin-resistant strains was 63.1 %. The incidence of invasive pneumococcal disease and the increased antimicrobial resistance rates of pneumococcus are two major reasons to support the routine use of pneumococcal conjugate vaccination in children. Systematic Hib vaccination since October 1998 has dramatically reduced the incidence of this disease.

ANOTHER GOOD YEAR FOR IMMUNIZATIONS

Immunization continues to be one of the most rapidly evolving areas in pediatrics. For vaccines to fulfill their potential, a complex interplay is required among basic science, public health, and societal acceptance: Results from several studies in the public health realm were reported in 2002. The pneumococcal vaccine has had quite an effect since it was approved for use in infants in early 2000: One group of researchers reported an almost 90% decrease in vaccine-specific pneumococcal invasive disease in children younger than 1 year …

Impact of a regional Hib vaccination programme in Italy

In the Veneto region of Italy, a coverage of 26% for Haemophilus influenzae type b (Hib) primary vaccination in 1-year-old children plus a 31–53% catch-up coverage in children 1–4 years of age resulted in a 91% reduction of Hib invasive disease in children <5 years of age. These data suggest that vaccination of older children can contribute substantially to herd immunity, even in settings where primary vaccination is low. Since a single Hib vaccine dose is efficacious in preventing Hib invasive disease in children over 1 year of age, and the costs of vaccination are reduced, catch-up should always be considered when introducing Hib vaccine in routine immunization programmes.

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999. PAHO Sireva-Vigía Study Group. Pan American Health Organization.

Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.