Agnes Lepoutre

Pediatric Pneumococcal Serotypes in 4 European Countries

After heptavalent pneumococcal conjugate vaccine (PCV7) was marketed in France, Spain, Belgium, and England and Wales (United Kingdom), invasive disease from non-PCV7 serotypes (NVT) increased. Adjusted serotype-specific incidences among children <15 years of age were compared between 1999-2002 (prevaccine) and 2005-2006 (postmarketing). Vaccine coverage increased to approximately 32%-48% in France, Spain, and Belgium but remained <1% in England and Wales. Serotype 1 incidence rose in all age groups and countries (incidence rate ratio [IRR] 1.3-4.2; p<0.004), independently of PCV7 use, but incidence of serotypes 7F and 19A increased most in France, Spain, and Belgium (IRR 1.9-16.9 in children <5 years; p<0.001), where PCV7 coverage was greater. Vaccine-induced replacement of PCV7 serotypes possibly contributed to NVT increases, as did secular trends. New vaccines targeting these serotypes are available, but serotype dynamics needs further exploration that accounts for underreporting and prevaccine trends.

Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001–2012

CONTEXT AND AIMS Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0-15 years) and adults (>15 years). METHODS IPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001-2002), late PCV7 (2008-2009) and post PCV13 (2012) periods. RESULTS The PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001-2002 and 2008-2009 in children <2 years, but increased in children aged 2-15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5-15 years and 15% in adults from 2008-2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5-15 years. CONCLUSIONS Vaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001-2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.

Introduction of SARS in France, March–April, 2003

We describe severe acute respiratory syndrome (SARS) in France. Patients meeting the World Health Organization definition of a suspected case underwent a clinical, radiologic, and biologic assessment at the closest university-affiliated infectious disease ward. Suspected cases were immediately reported to the Institut de Veille Sanitaire. Probable case-patients were isolated, their contacts quarantined at home, and were followed for 10 days after exposure. Five probable cases occurred from March through April 2003; four were confirmed as SARS coronavirus by reverse transcription–polymerase chain reaction, serologic testing, or both. The index case-patient (patient A), who had worked in the French hospital of Hanoi, Vietnam, was the most probable source of transmission for the three other confirmed cases; two had been exposed to patient A while on the Hanoi-Paris flight of March 22–23. Timely detection, isolation of probable cases, and quarantine of their contacts appear to have been effective in preventing the secondary spread of SARS in France.

Insight Into Resistance Phenotypes of Emergent Non 13-valent Pneumococcal Conjugate Vaccine Type Pneumococci Isolated From Invasive Disease After 13-valent Pneumococcal Conjugate Vaccine Implementation in France

Implementation of 13-valent conjugate pneumococcal vaccine in France has led to an overall antibiotic resistance decrease among invasive pneumococcal isolates. However, among emerging non-PCV13 serotypes, 12F, 24F, 15A and 35B are associated to antibiotic resistance and should be further monitored.

Epidemiology and Antimicrobial Resistance of Streptococcus pneumoniae in France in 2007: Data from the Pneumococcus Surveillance Network

Antimicrobial resistance of Streptococcus pneumoniae in France is closely monitored by the pneumococcus surveillance network, founded in 1995, which collects data from regional observatories (Observatoire Régionaux du Pneumocoque [ORP]). In 2007, 23 ORPs analyzed the antibiotic susceptibility of 5,302 isolates of S. pneumoniae recovered in France from cerebrospinal fluid, blood, middle ear fluid, and pleural fluid, as well as from adult respiratory samples. The study showed that 38.2% of the strains were nonsusceptible to penicillin, 19.3% nonsusceptible to amoxicillin, and 10.5% nonsusceptible to cefotaxime. The percentage of pneumococcus nonsusceptible to penicillin varied according to both the sample and the age of the patient (child/adult): blood (27.8%/32.5%), cerebrospinal fluid (33.7%/34.6%), middle ear fluid (60.2%/27.5%), and pleural fluid (50.0%/31.0%). Between 2003 and 2007, the frequency of penicillin resistance in invasive pneumococcal disease gradually decreased from 46.4% to 29.0% in children and from 43.8% to 32.7% in adults. This decrease coincided with the introduction of a seven-valent pneumococcal conjugate vaccine into immunization programs and with a general reduction in levels of antibiotic consumption in France.

Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study

BACKGROUND The Streptococcus pneumoniae Invasive Disease network (SpIDnet) actively monitors populations in nine sites in seven European countries for invasive pneumococcal disease. Five sites use 13-valent pneumococcal conjugate vaccine (PCV13) alone and four use the ten-valent PCV (PCV10) and PCV13. Vaccination uptake is greater than 90% in six sites and 67-78% in three sites. We measured the effects of introducing high-valency PCVs on the incidence of invasive pneumococcal disease in children younger than 5 years. METHODS We compared the incidence of invasive pneumococcal disease in each of the 4 years after the introduction of PCV13 alone or PCV10 and PCV13 with the average incidence during the preceding period of heptavalent PCV (PCV7) use, overall and by serotype category. We calculated incidence rate ratios (IRRs) and 95% CIs for each year and pooled the values for all sites in a random effects meta-analysis. FINDINGS 4 years after the introduction of PCV13 alone or PCV10 and PCV13, the pooled IRR was 0·53 (95% CI 0·43-0·65) for invasive pneumococcal disease in children younger than 5 years caused by any serotype, 0·16 (0·07-0·40) for disease caused by PCV7 serotypes, 0·17 (0·07-0·42) for disease caused by 1, 5, and 7F serotypes, and 0·41 (0·25-0·69) for that caused by 3, 6A and 19A serotypes. We saw a similar pattern when we restricted the analysis to sites where only PCV13 was used. The pooled IRR for invasive pneumococcal disease caused by non-PCV13 serotypes was 1·62 (1·09-2·42). INTERPRETATION The incidence of invasive pneumococcal disease caused by all serotypes decreased due to a decline in the incidence of vaccine serotypes. By contrast, that of invasive pneumococcal disease caused by non-PCV13 serotypes increased, which suggests serotype replacement. Long-term surveillance will be crucial to monitor the further effects of PCV10 and PCV13 vaccination programmes in young children. FUNDING European Centre for Disease Prevention and Control, Czech National Institute of Public Health, French National Agency for Public Health, Irish Health Services Executive, Norwegian Institute of Public Health, Public Health Agency of Catalonia, Public Health Department of Community of Madrid, Navarra Hospital Complex, Public Health Institute of Navarra, CIBER Epidemiology and Public Health, Institute of Health Carlos III, Public Health Agency of Sweden, and NHS Scotland.

Impact of Haemophilus influenzae type b vaccination on the incidence of invasive Haemophilus influenzae disease in France, 15 years after its introduction

We assessed the impact of Haemophilus influenzae type b (Hib) vaccination, introduced in France in early 1993, on the incidence of invasive Haemophilus influenzae (Hi) disease up to 2008.The incidence of Hi meningitis fell from 0·9/100000 in 1991–1992 to 0·09/100 000 in 1996–2008,with a marked decline (96%) in children aged <5 years, including infants aged <3 months, from 12 to 0·4 /100 000. The incidence of invasive Hi disease also decreased in children aged <15 years from 6 to 0·7 /100 000, remained stable in the 15–64 years age group at about 0·5/100 000,and increased slightly from 2·0 to 2·4 /100 000 in persons aged >64 years. No emergence of non-encapsulated or encapsulated non-vaccine serotypes was observed. These findings confirm the major direct impact of Hib vaccination on the incidence of Hi invasive disease in children and the indirect benefit of vaccination for infants too young to be vaccinated.

Severe group a streptococcus infection after thyroidectomy: report of three cases and review.

BACKGROUND Group A Streptococcus (GAS) is an uncommon cause of infection after clean surgery in non-pregnant adults. METHODS Report of three cases and review of the literature. results: For the first time in France, severe GAS infections were observed in three patients who underwent thyroidectomy at three hospitals. Two of them developed streptococcal toxic shock syndrome. CONCLUSION Better knowledge of physiopathologic mechanisms would help in the detection and prevention of severe GAS infections.

Clonal expansion of the macrolide resistant ST386 within pneumococcal serotype 6C in France.

In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002–2003) to the PCV13 era (2010–2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

Observatoires régionaux du pneumocoque : épidémiologie et résistance aux antibiotiques des souches de Streptococcus pneumoniae isolées en France en 2007

Resume Les observatoires regionaux du pneumocoque (ORP), crees a partir de 1995, participent aux cotes du Centre national de reference des pneumocoques et de l’Institut de veille sanitaire a la surveillance etroite de l’evolution de la resistance du pneumocoque aux antibiotiques. En 2007, les 23 ORP francais ont etudie la sensibilite aux antibiotiques et le serogroupe de 5 302 souches de pneumocoque isolees de liquides cephalo-rachidiens (LCR), d’hemocultures, de pus d’otite moyenne aigue, de liquides pleuraux de l’enfant et de l’adulte (≥ 16 ans) ainsi que de certains echantillons pulmonaires de l’adulte (≥ 16 ans). L’etude a montre que 38,2 % des souches etaient de sensibilite diminuee a la penicilline (PSDP), 19,3 % a l’amoxicilline et 10,5 % au cefotaxime. Le pourcentage de PSDP differait selon les regions, allant de 29 % en Alsace a 50 % a Paris Ile-de-France Ouest. Il etait plus eleve chez l’enfant (50,2 %) que chez l’adulte (33,7 %) et variait selon le prelevement (enfant/adulte) : hemocultures (27,8 %/32,5 %), LCR (33,7 %/34,6 %), pus d’otite moyenne aigue (60,2 %/27,5 %), liquides pleuraux (50 %/31 %). Les PSDP etaient souvent multiresistants avec en particulier un pourcentage eleve de resistance a l’erythromycine (84,2 % contre 12,7 % pour les pneumocoques sensibles a la penicilline). Enfin, le serogroupe majoritairement rencontre etait le serogroupe 19 (25,2 % des isolats).