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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.

Background Pertussis remain a global health concern, especially in infants too young to initiate their vaccination. Effective vaccination and high coverage limit the circulation of the pathogen, yet duration of protection is limited and boosters are recommended during a lifetime. In Iran, boosters are given at 18 months and 6 years old using whole pertussis vaccines for which efficacy is not known, and pertussis surveillance is scant with only sporadic biological diagnosis. Burden of pertussis is not well understood and local data are needed. Methods Hospital-based prospective study implementing molecular laboratory testing in infants aged ≤6 months and presenting ≥5 days of cough associated to one pertussis-like symptom in Tehran. Household and non-household contact cases of positive infants were evaluated by comprehensive pertussis diagnosis (molecular testing and serology) regardless of clinical signs. Clinical evaluation and source of infection were described. Results A total of 247 infants and 130 contact cases were enrolled. Pertussis diagnosis result was obtained for 199 infants and 104 contact cases. Infant population was mostly

International audience; Purpose. Pertussis remains a public health concern in most countries. Our study aimed to prospectively explore the epidemiology of pertussis in the Tunis area of Tunisia between 2007 and 2016, and to characterize the virulence-associated genes of the collected Bordetella pertussis isolates.Methodology. Infants and children hospitalized at the Children’s Hospital of Tunis, Tunisia, between 2007 and 2016 for suspicion of pertussis were enrolled in the study. Culture and real-time PCR (qPCR) assays targeting IS481, IS1001, recA, H-IS1001 and ptxP were used to confirm the pertussis diagnosis. Phenotypic and genotypic characterization of recovered isolates was performed.Results/Key findings. A total of 1844 children were included in the study. Overall, 306 children (16.6 %) with Bordetella infection were confirmed by qPCR. Among them, 265 (86.6 %) were confirmed as having B. pertussis (IS481+, ptxP+, H-IS1001−), 18 (5.9 %) as having Bordetella parapertussis (IS481−, IS1001+) and 11 (3.6 %) as having Bordetella spp. (IS481+, ptxP−, H-IS1001−). No Bordetella holmesii (IS481+, IS1001−, H-IS1001+) was identified. The estimated pertussis incidence in the Tunis area was 134/100 000 in children aged less than 5 years. Two epidemic peaks were observed in 2009 and 2014. Ten B. pertussis isolates were cultured and characterized. Deficiency in pertactin expression was not observed, and genotyping of the isolates revealed a predominant allelic profile: ptxP3-ptxA1-prn2-fim2-1-fim3-2.Conclusion. This study demonstrated that pertussis is still present as a cyclical disease in Tunisia, despite high primo-vaccination coverage with a pertussis whole-cell vaccine. The predominant genotype of Tunisian B. pertussis isolates is similar to isolates circulating in countries using the acellular vaccine.

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.

Pertussis remains a life-threatening disease in children under 3 months of age without vaccination. Cardio-respiratory failures and pulmonary hypertention in severe pertussis are believed to be linked to white blood cell aggregates in lung microvasculature. Leukodepletion, by fighting against this accumulation, seems to improve those patients survival rate in various publications. The purpose of this retrospective monocentric study is to assess the tolerance of leukodepletion and the risk factor of death among patients hospitalized in Kremlin Bicêtre ICU for pertussis from 2001 to 2018. 60 children were hospitalized for pertussis during this period. 8 died, representing a mortality rate of 13.3%. The main risk factors for deaths were young age (p=0.006), small weight (p=0.025), tachycardia (p=0.024), peripheral hypoperfusion (p

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.

International audience; BACKGROUND INFORMATION:The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown.RESULTS:In this study, we use a recently proposed multiple bond force spectroscopy (MFS) with an atomic force microscope to assess the early phase of cell adhesion (maximal detachment and local rupture forces) and cell rigidity (Young's modulus) in alveolar epithelial cells (A549) for toxin exposure 95%) at CyaA concentration of 0.5 nM, but a significant effect (≈81%) at 10 nM. MFS performed on A549 for three different concentrations (0.5, 5 and 10 nM) demonstrates that CyaA toxin significantly affects both cell adhesion (detachment forces are decreased) and cell mechanics (Young's modulus is increased). CyaA toxin (at 0.5 nM) assessed at three indentation/retraction speeds (2, 5 and 10 μm/s) significantly affects global detachment forces, local rupture events and Young modulus compared with control conditions, while an enzymatically inactive variant CyaAE5 has no effect. These results reveal the loading rate dependence of the multiple bonds newly formed between the cell and integrin-specific coated probe as well as the individual bond kinetics which are only slightly affected by the patho-physiological dose of CyaA toxin. Finally, theory of multiple bond force rupture enables us to deduce the bond number N which is reduced by a factor of 2 upon CyaA exposure (N ≈ 6 versus N ≈ 12 in control conditions).CONCLUSIONS:MFS measurements demonstrate that adhesion and mechanical properties of A549 are deeply affected by exposure to the CyaA toxin but not to an enzymatically inactive variant. This indicates that the alteration of cell mechanics triggered by CyaA is a consequence of the increase in intracellular cAMP in these target cells.SIGNIFICANCE:These results suggest that mechanical and adhesion properties of the cells appear as pertinent markers of cytotoxicity of CyaA toxin.

International audience; Background: Pertussis, a vaccine preventable disease, is still responsible of significant morbidity and mortality around the world, mostly in newborns. The aim of the present study was (1) to introduce pertussis surveillance in the major pediatric hospital of Casablanca (2) to analyze the prevalence of pertussis among children under 14 years of age and their entourage in Casablanca, Morocco. Methods: This is a prospective and non-case controlled study, including children suspected of Pertussis admitted at the Abderrahim Harouchi Pediatric Hospital in Casablanca, from January 2013 to June 2015. Nasopharyngeal samples were obtained for Bordetella spp. culture and Real time PCR detection (RT-PCR) with specific primers of Bordetella spp., B. pertussis, B. parapertussis and B. holmesii. The detection of Bordetella spp. was also performed in some household contacts of the children suspected of pertussis. Results: During the 2.5-years period, a total of 282 samples were collected from hospitalized children (156) and in some of their contacts (126). Among 156 samples from the children (from whom 57% were under 2 month of age), Bordetella DNA was detected in 61% (96/156) by RT-PCR. Among these positive samples, 91.7% (88/96) corresponded to B. pertussis DNA. Furthermore, in 39.5% (38/96) of the Bordetella positive samples, B. holmesii DNA was also detected. B. parapertussis DNA was detected in only one sample (1/156). Out of the 156 samples collected from the hospitalized children, only 48 were tested by culture, and 4 B. pertussis were isolated (8.3%). Among the 126 samples from the contacts of the children, mostly mothers (115 cases), Bordetella DNA was detected in 47% (59/126), 90% (53/59) being B. pertussis DNA. Moreover, B. holmesii DNA was also detected in 18.6% (11/59) of the Bordetella positive samples, and coexistence of B. pertussis and B. holmesii DNA in 36.5% (35/96). Two B. pertussis were isolated by culture performed on 43 samples of the contacts of the children (4.6%).Conclusions: This study highlights the circulation of B. pertussis but also of B. holmesii in Casablanca-Morocco with a high proportion of co-infections B. holmesii/B. pertussis in infants and their mothers, indicate that infection of non-vaccinated infants could be more associated with young parents. Moreover, the RT- PCR provides a sensitive and specific diagnosis of B. pertussis infections and distinguishes it from other Bordetella species, and is therefore suitable for implementation in the diagnostic laboratory.

En France, les objectifs de couverture vaccinale sont fixés par le plan de Santé Publique à 95 %. Cette étude s’est intéressée aux motifs de refus vaccinal chez des enfants âgés de 11 à 15 ans en Ile-de-France Ouest pour la rougeole, la coqueluche, l’hépatite B et le papillomavirus humain. Nous avons remis un questionnaire comprenant des données administratives et un panel de propositions de motifs de non vaccination pour ces maladies. Au total, 301 enfants ont été inclus entre avril et décembre 2014 dans 5 centres hospitaliers, ainsi que 3 cabinets médicaux de médecins généralistes. Nos résultats rejoignent pour une part les objectifs nationaux avec un taux de couverture vaccinale de 95,3 % contre la rougeole et 94,3 % contre la coqueluche ; en revanche, nous avons retrouvé une couverture de 67,1 % contre l’hépatite B et 4,4 % contre le papillomavirus humain. Les principaux motifs évoqués de non vaccination contre l’hépatite B étaient le fait d’avoir « entendu parler de problèmes liés au vaccin » et la « peur qu’il ne déclenche une maladie ». Pour le vaccin contre le papillomavirus, les principaux motifs étaient l’âge trop jeune de l’enfant, le manque d’information et le fait d’avoir « entendu parler de problèmes liés au vaccin ». Une meilleure information des parents mais également des médecins traitants apparaît comme l’une des principales solutions. Ainsi, un effort ciblé dans ma pratique future sur ces interrogations parentales, mais également à l’échelon national avec un débat de qualité au sein des instances de santé, pourraient permettre de mieux promouvoir la vaccination contre ces maladies

Objective : New-borns and toddlers suffer from the most severe cases of whooping cough. An adult, most of the time one of the parents, usually transmits the disease to them. The cocooning policy was introduced ten years ago to face this problem. However, few data exist regarding its execution. The aim of this study is to determine the proportion of adults, close to a child enrolled in the first year of preschool in the 13th district of Paris, correctly vaccinated against whooping cough according to the cocooning policy. Method : This is an observational, descriptive, transversal study. The study population consisted of adults living with a child enrolled in the first year of preschool. Two questionnaires were handed out for each child through the teacher. Results : The data were collected between September and December 2014. 532 questionnaires were handed out, 114 questionnaires were returned. 55 adults possessed an immunisation card, 59 did not. Among the adults possessing an immunisation card, 32.5% were up to date with their whooping cough vaccination according to the cocooning policy. Among the adults who did not have an immunisation card, 64% thought that they received a vaccination shot in the last 10 years. Only 31% of the adults could record having had a medical advice regardingthis vaccination around their child’s birth. Conclusion : The cocooning policy remains insufficiently put into practise. This can be partly explained by a lack of medical advice given to the parents around their child’s birth.; Objectif : Les nouveaux-nés et les nourrissons contractent les formes les plus sévères de coqueluche. La maladie leur est habituellement transmise par un adulte, la plupart du temps par un des parents. La politique du cocooning a été mise en place il y a dix ans pour pallier ce problème. Cependant, très peu de données existent sur sa mise en application. L’objectif de cette étude est de déterminer la proportion d’adultes, proches d’un enfant scolarisé en petite section de maternelle dans le 13e arrondissement de Paris, correctement vaccinés contre la coqueluche dans le cadre du cocooning.Méthode : Il s’agit d’une étude observationnelle, descriptive, transversale. La population d’étude était constituée des adultes vivant sous le même toit que les enfants scolarisés en petite section de maternelle. L’enseignant concerné a distribué deux questionnaires à chaque enfant.Résultats : Les données ont été recueillies entre septembre et décembre 2014. 532 questionnaires ont été distribués, 114 questionnaires ont été rendus. 55 adultes possédaient un carnet de vaccination, 59 n’en possédaient pas. Parmi les adultes possédant un carnet de vaccination, 32.5% avaient effectué une vaccination coqueluche dans le cadre du cocooning. Parmi les adultes ne possédant pas de carnet de vaccination, 64% pensaient avoir reçu un vaccin depuis moins de 10 ans. Seulement 31% des adultes se souvenaient avoir reçu un conseil vaccinal autour de la naissance de leur enfant.Conclusion : Le cocooning coqueluche reste à l’heure actuelle trop peu mis en œuvre. Ceci peut être en partie expliqué par un manque de conseils donnés par les professionnels de santé aux parents autour de la naissance.

Pertussis is a bacterial disease, benign in adults, but with a high morbidity and mortality index in newborn infants. Early diagnosis and treatment, using appropriate antibiotics and hospital care, enabled to reduce the seriousness of the disease. However, the bacteria keeps on circulating with recurrent epidemic peaks.Since 2004, the Cocoon Strategy aims to vaccinate the relatives of newborn infants, so as to protect them before they get their first vaccines.We made a descriptive transversal epidemiologic study, in order to evaluate the prevalence of the pertussis booster vaccine in a particular population : grandparents. We collected datas from september 2014 to march 2015, using a survey completed by general practitioners in their respective offices, in the french region of Ile-de-France. It applied to patients aged 43 and 46 or more, men or women, who had at least one grandchild. 101 surveys were collected during this time.The number of cocooning found (defined by a vaccine booster in the 10 years before or in the 6 months after the infant’s birth) was 31%. The only factor, in our study, significantly associated with a more frequent booster shot was the advice given to the patient. This number of vaccinated adults is not high enough to lead to an effective protection of infants.From this study and from datas in recent publications, we have to note that the Cocoon Strategy, 10 years after its establishment, is insufficiently known and applied. We must pursue our efforts to develop it with doctors, maternity wards and families, and consider new vaccination strategies, e.g. vaccination during pregnancy or in the first-two months of life, in order to avoid new peak incidence in the years to come.; La coqueluche est une maladie bactérienne, bénigne chez l’adulte mais source d’une morbi-mortalité importante chez le nourrisson. Le diagnostic précoce et la prise en charge thérapeutique, notamment par une antibiothérapie et une prise en charge hospitalière adaptée ont permis d’en réduire la gravité mais la bactérie continue à circuler, avec des pics épidémiologiques récurrents. Depuis 2004, la stratégie du cocooning vise à vacciner l’entourage des nourrissons pour les protéger avant qu’ils n’aient reçu les 1ères doses vaccinales.Nous avons mené une étude épidémiologique descriptive transversale, afin d’évaluer la prévalence du rappel vaccinal anti coquelucheux dans une population donnée : les grands-parents. Le recueil s’est déroulé entre septembre 2014 et mars 2015, à l’aide d’un hétéro questionnaire, au sein de cabinets de médecins généralistes franciliens. Il visait une population âgée de plus de 43 ans ou 46 ans, homme et femme, et ayant au minimum un petit enfant. 101 questionnaires ont pu être recueillis durant cette période.Le cocooning effectif retrouvé (répondant à la définition d’un rappel vaccinal dans les 10 ans précédant ou les 6 mois suivant la naissance du nourrisson) était de 31%. Le seul facteur, dans notre étude, significativement associé à un rappel vaccinal plus fréquent était le conseil donné au patient. Ce pourcentage d’adulte vacciné ne s’avère pas assez élevé pour engendrer une protection efficace des nourrissons.D’après notre étude et les données de la littérature récente, force est de constater que la stratégie du cocooning, 10 ans après sa mise en place, est encore insuffisamment connue et appliquée. Il faut donc poursuivre nos efforts pour la développer auprès des principaux intéressés, médecins, maternité, famille, et envisager de nouvelles stratégies de politique vaccinale, vaccination durant la grossesse, vaccination avant 2 mois, afin d’éviter de nouveaux pics d’incidence dans les années à venir.

We used pulsed-field gel electrophoresis analysis and genotyping to compare clinical isolates of Bordetella pertussis recovered since the early 1990s in Finland and France, 2 countries with similar histories of long-term mass vaccination with whole-cell pertussis vaccines. Isolates from both countries were similar genetically but varied temporally.

International audience; Macromolecular crowding affects most chemical equilibria in living cells, as the presence of high concentrations of macromolecules sterically restricts the available space. Here, we characterized the influence of crowding on a prototypical RTX protein, RC(L). RTX (Repeat in ToXin) motifs are calcium-binding nonapeptide sequences that are found in many virulence factors produced by Gram-negative bacteria and secreted by dedicated type 1 secretion systems. RC(L) is an attractive model to investigate the effect of molecular crowding on ligand-induced protein folding, as it shifts from intrinsically disordered conformations (apo-form) to a stable structure upon calcium binding (holo-form). It thus offers the rare opportunity to characterize the crowding effects on the same polypeptide chain under two drastically distinct folding states. We showed that the crowding agent Ficoll70 did not affect the structural content of the apo-state and holo-state of RC(L) but increased the protein affinity for calcium. Moreover, Ficoll70 strongly stabilized both states of RC(L), increasing their half-melting temperature, without affecting enthalpy changes. The power law dependence of the melting temperature increase (ΔT(m)) on the volume fraction (φ) followed theoretical excluded volume predictions and allowed the estimation of the Flory exponent (ν) of the thermally unfolded polypeptide chain in both states. Altogether, our data suggest that, in the apo-state as found in the crowded bacterial cytosol, RTX proteins adopt extended unfolded conformations that may facilitate protein export by the type I secretion machinery. Subsequently, crowding also enhances the calcium-dependent folding and stability of RTX proteins once secreted in the extracellular milieu.

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 evaluated the performances of 4 commercial real-time PCR kits for Bordetella pertussis IS 481 sequence detection in nasopharyngeal aspirates by comparison with an in-house real-time PCR assay. Among them, the Simplexa Bordetella pertussis/parapertussis assay (Focus Diagnostics), the SmartCycler Bordetella pertussis / parapertussis assay (Cepheid), and Bordetella R-gene (Argene) present sensitivities over 90%. One kit proved unsuitable for routine clinical use.

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; BACKGROUND:Pertussis vaccination has reduced the number of notified cases in industrialized countries from peak years by more than 95%. The effect of recently recommended adult and adolescent vaccination strategies on infant pertussis depends, in part, on the proportion of infants infected by adults and adolescents. This proportion, however, remains unclear, because studies have not been able to determine the source case for 47%-60% of infant cases.METHODS:A prospective international multicenter study was conducted of laboratory confirmed infant pertussis cases (aged

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.

We describe a case of nosocomial maternal transmission of Bordetella pertussis to a very-low-birth-weight (VLBW) neonate in whom treatment was unsuccessful. This case underscores the need for rapid and sensitive PCR diagnosis in VLBW neonates and in parents with clinical signs of pertussis and suggests that standard treatment may not be appropriate for VLBW neonates.

The global epidemiology of pertussis has recently been reviewed (12, 15). Bordetella pertussis continues to circulate even in populations where high vaccination coverage of infants and children is achieved (15, 23), because the protection after natural infection wanes after 10 to 15 years and protection after vaccination lasts for 6 to 10 years (15). A significant increase of pertussis cases was observed in the United States, in Europe, and in other countries with high vaccination coverage, making pertussis a reemerging disease. Transmission of the disease in highly vaccinated populations occurs mainly from adolescents and adults to infants or among older vaccinated children, adolescents, and adults (15). Thus, most cases of pertussis are now observed in unvaccinated infants, older schoolchildren, adolescents, and adults. In outbreak situations asymptomatic carriage has been observed in up to ∼50% (12).