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International audience; Background: The Cambodia pertussis immunization schedule includes three doses given at age 6, 10 and 14 weeks using a whole-pertussis vaccine. No booster doses are included. Pertussis biological diagnosis is unavailable in Cambodia and its burden remains unclear. This study aimed to provide accurate data on pertussis serological status of Cambodian children and adolescents, and to evaluate vaccination timeliness. Methods: Fully vaccinated children aged 3-15 years were recruited at the Rabies Prevention Center, Institut Pasteur in Cambodia, Phnom Penh. Capillary blood samples and information on pertussis vaccination history were collected. Anti-pertussis toxin (PT) IgG titers were quantified by ELISA. Results: Compliance with the national immunization schedule was 95.1%. Initiation of vaccination after 8 weeks of age was observed for 29.0% of the children, but was less frequent in the youngest children (13.0%) compared with the oldest ones (46.4%). Rate of children exhibiting anti-PT IgG varied across age groups, and increased from 35.7% to 55.0% in 3-5 and 12-15 years age groups, respectively. Conclusion: Pertussis circulates among vaccinated Cambodian children and adolescents. These data support the need for public health authorities to strengthen pertussis surveillance and use local epidemiological data to make evidence-based decision for the establishment of an optimal vaccination strategy.

Background Bordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough. Aim We aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996–2018). Methods Isolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing. Results The proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p 481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3. Conclusions B. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.

Pertussis is a highly contagious infectious disease and remains an important cause of mortality and morbidity worldwide. Over the last decade, vaccination has greatly reduced the burden of pertussis. Yet, uncertainty in individual vaccination coverage and ineffective case surveillance systems make it difficult to estimate burden and the related quantity of population-level susceptibility, which determines population risk. These issues are more pronounced in low-income settings where coverage is often overestimated, and case numbers are under-reported. Serological data provide a direct characterisation of the landscape of susceptibility to infection; and can be combined with vaccination coverage and basic theory to estimate rates of exposure to natural infection. Here, we analysed cross-sectional data on seropositivity against pertussis to identify spatial and age patterns of susceptibility in children in Madagascar. A large proportion of individuals surveyed were seronegative; however, there were patterns suggestive of natural infection in all the regions analysed. Improvements in vaccination coverage are needed to help prevent additional burden of pertussis in the country.

The genomic sequence data generated in this work were submitted to the European Nucleotide Archive and are available from the International Nucleotide Sequence Database Collaboration (NCBI/ENA/DDBJ) databases under project accession number PRJEB27412 and run data accession numbers ERS2572942 to ERS2572951.; International audience; The recent increase in pertussis cases observed in some countries may have several causes, including the evolution of Bordetella pertussis populations towards escape of vaccine-induced immunity. Most genomic studies of B. pertussis isolates performed so far are from countries that use acellular vaccines. The objective was to analyse genomic sequences of isolates collected during the 2014 whooping cough epidemic in Tunisia, a country where whole-cell vaccines are used. Ten Tunisian isolates and four vaccine strains were sequenced and compared to 169 isolates from countries where acellular vaccines are used. Phylogenetic analysis showed that Tunisian isolates are diverse, demonstrating a multi-strain 2014 epidemic peak, and are intermixed with those circulating in other world regions, showing inter-country transmission. Consistently, Tunisian isolates have antigen variant composition observed in other world regions. No pertactin-deficient strain was observed. The Tunisian B. pertussis population appears to be largely connected with populations from other countries.

The increasing incidence of pertussis in a number of countries, despite good vaccination coverage, is a cause for concern. We used pulsed-field gel electrophoresis (PFGE) typing to examine the genetic diversity of 101 clinical isolates of Bordetella pertussis, recovered during 1999-2001, and circulating in five different European countries to evaluate temporal and geographical distribution. This DNA fingerprinting approach seems to be a more discriminative epidemiological tool than sequencing of individual genes. Despite differences in vaccination policies in the five countries, these European isolates were found to be very similar and fell into the same major PFGE profile groups, with a predominance of one profile group. There was no evidence of geographic clustering, except that one new profile subgroup was predominantly found in one country. This study provides a baseline for continued surveillance of the B. pertussis population in Europe.

International audience; The argument of whether early immunization against infections promotes allergy or protects from it is presently under debate. The relationship between childhood immunization and the development of atopic diseases (asthma, allergic rhinitis and eczema) was examined in a population-based sample of 718 adolescents by taking individual data drawn from personal paediatric records on the schedule and the type of vaccination into account. Atopic diseases were determined using a standardized questionnaire. After adjustment for sex, age, father's socioeconomic status and active smoking, adolescents having been vaccinated (n = 694) had a significant lower risk to suffer from asthma or atopic diseases than non-vaccinated adolescents did (n = 24) [odds ratio (OR) = 0.30; 95% CI: 0.10, 0.92]. The relationship did not depend on the disease against which the vaccine was used as prophylaxis, the observance of the vaccination schedule or the number of inoculations. A higher protection was observed in the case of live attenuated vaccines (oral poliomyelitis and bacilli Camille-Guerin; OR = 0.26; 95% CI: 0.08, 0.83). These results, in agreement with previous ecological data, support the hypothesis that early vaccines could promote Th1 proliferation in response to the infectious agent contained in it, which inhibits the enhancement of atopic manifestations. Further studies are needed to confirm the phenomenon.

Background Compliance with official recommendations can be assessed by evaluating vaccination coverage (VC) in populations. The main objective of our study was to assess VC of adults against diphtheria, tetanus, poliomyelitis and pertussis (dTPaP) according to age. The second objective was to explore if vaccination status could be confirmed by documentation. Methods A cross-sectional study was conducted in 680 adults consulting for biological examination in private laboratories in Lyon (France) to evaluate VC for diphtheria, tetanus, poliomyelitis and pertussis (dTPaP) and enabled reported vaccinations to be compared with documented, confirmed vaccinations. Results Verification of documented, confirmed vaccinations disclosed VC of 78.7% for tetanus, 63.6% for poliomyelitis, 57.8% for diphtheria and 10.7% for pertussis. Comparison of confirmed and self-reported vaccinations revealed that a large percentage of people who thought that they were vaccinated were not. VC significantly decreased with age for diphtheria and poliomyelitis and did not vary by gender. The VC rate for pertussis has increased since the 2008 recommendations were made. Conclusions The main thrust of this study was to compare reported and confirmed data. A significant percentage of people wrongly believed that they were up to date with their vaccination.

We have studied the epidemiology of pertussis in two countries, Argentina and France, which have similar histories of long-term mass vaccination with a whole-cell vaccine. Both countries display a comparable epidemiology, with an increase of the incidence of the disease in non-vaccinated newborns. We used pulsed-field gel electrophoresis (PFGE) analysis and genotyping to compare Bordetella pertussis clinical isolates recovered in Argentina and France in 2001-2004. The majority of the isolates harbors prn2 allele and belongs to PFGE IVbeta group. Isolates were found to be very similar genetically suggesting a common evolution of the disease in these two countries using the same vaccine.

International audience; A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge. IgG1 and IgG2a were stimulated suggesting that the immune response could be modulated to produce Th1 or Th2.

Several vaccines are now routinely used since fifty years in different developed countries. Their principal impact has been to decrease morbidity and mortality of the infectious diseases they are targeting. One disease, smallpox, is eradicated, poliomyelitis will be soon, diphteria is controlled in several countries but pertussis is still endemic although an efficacious vaccine was used. Why? Pertussis is an example of an infection for which the immunity of the population has changed after the introduction of generalized vaccination with killed whole cell pertussis vaccines, from a natural immunity due to infection to different types of vaccine-induced immunity. These different types of immunity have changed the protection against infection, disease and transmission. The impact of the generalized vaccination in a human population has been an important change in the epidemiology of the disease. In fact, a child-to-child transmission observed before the introduction of vaccination is now replaced by an adolescent-adult to infant transmission. The major consequence is an increase in the mortality and morbidity in non vaccinated infants mostly contaminated by their parents. Researches undertaken on the agent of the disease, the bacterium, Bordetella pertussis, conducted to the development of subunits vaccines, efficacious and better tolerated by infants than whole-cell vaccines. Many developed countries decided to change vaccines but also to add vaccine boosters for adolescents and adults in order to stop the transmission of the disease to infants. However, even after 15 years of studies in many countries, pertussis is still underestimated in adults and generalized adult vaccination remains difficult. The new goal now is to give information to medical students and health care workers in general in order to increase adolescent and adult's vaccination coverage.