Clinical Pertussis Research Articles

Maternal Pertussis Immunization and Immunoglobulin G Levels in Early- to Late-Term and Preterm Infants

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination protects newborns against severe pertussis. Data on transplacental antibody transfer on Tdap vaccination before 24 weeks' gestation remain scarce and are particularly relevant for preterm infants to increase the time interval for maternal antibody transfer. To assess noninferiority of anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) antibody levels at age 2 months in early- to late-term infants following Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation and compared with preterm infants. This prospective, multicenter cohort study included pregnant women aged 18 years or older in birthing centers and hospitals in the Netherlands between August 2019 and November 2021 who received Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation. Women with imminent premature birth were recruited if they had received maternal Tdap vaccination between 20 and 24 weeks' gestation. Blood samples were collected from mothers at delivery, from the umbilical cord, and from infants at age 2 months. Data from infants' blood samples at age 2 months were compared with a reference cohort (recruited between January 2014 and February 2016) of early- to late-term infants of the same age whose mothers had received Tdap vaccination between 30 0/7 and 33 0/7 weeks' gestation. Maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation or 30 0/7 and 33 0/7 weeks' gestation. The primary outcome was the geometric mean concentration (GMC) of anti-PT IgG antibodies in early- to late-term infants (≥37 0/7 weeks' gestation) at age 2 months, comparing maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' vs 30 0/7 and 33 0/7 weeks' gestation (reference cohort). Anti-PT GMC in 2-month-old infants born preterm (<35 0/7 weeks' gestation) compared with early- to late-term infants after maternal Tdap vaccination between 20 and 24 weeks' gestation was a secondary outcome. In total, 221 women who delivered 239 offspring were enrolled in the study; 66 early- to late-term infants (median gestational age [GA], 40.6 weeks [IQR, 39.8-41.0 weeks]; 38 [57.6%] male) and 73 preterm infants (median GA, 32.1 weeks [IQR, 29.5-33.0 weeks]; 42 [54.5%] female) had blood samples collected at 2 months of age. Anti-PT GMC was 14.7 IU/mL (95% CI, 10.6-20.4 IU/mL) in early- to late-term infants following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 27.3 IU/mL (95% CI, 20.1-37.1 IU/mL) in 55 infants in the reference group (median GA, 40.3 [IQR, 39.1-41.0]; 33 [60.0%] female). The mean anti-PT GMC in preterm infants in the study group was 11.2 IU/mL (95% CI, 8.1-15.3 IU/mL) (P = .23 compared with early- to late-term infants). In this cohort study, 2-month-old preterm and early- to late-term infants showed significantly lower anti-PT antibody levels following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation; preterm and early- to late-term infants had similar anti-PT antibody levels, but both groups showed significantly lower antibody levels compared with the reference group. Epidemiological research should investigate whether maternal Tdap vaccination before 24 weeks' gestation provides sufficient protection against clinical pertussis, particularly in preterm infants, as long as no correlate of protection is available.

Non-primate animal models for pertussis: back to the drawing board?

Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an evolution of concerns with acellular component vaccination have both sparked a renewed interest. Although simian models of infection best correlate with the observed attributes of human infection, several animal models have been used for decades and have positively contributed in many ways to the related science. Nevertheless, there is yet the lack of a reliable small animal model system that mimics the combination of infection genesis, variable upper and lower respiratory infection, systemic effects, infection resolution, and vaccine responses. This narrative review examines the history and attributes of non-primate animal models for pertussis and places context with the current use and needs. Emerging from the latter is the necessity for further such study to better create the optimal model of infection and vaccination with use of current molecular tools and a broader range of animal systems.Key points • Currently used and past non-primate animal models of B. pertussis infection often have unique and focused applications. • A non-primate animal model that consistently mimics human pertussis for the majority of key infection characteristics is lacking. • There remains ample opportunity for an improved non-primate animal model of pertussis with the use of current molecular biology tools and with further exploration of species not previously considered. Graphical abstract

Immunogenicity of a Candidate DTacP-sIPV Combined Vaccine and Its Protection Efficacy against Pertussis in a Rhesus Macaque Model.

The research and development of a pertussis-combined vaccine using a novel inactivated poliovirus vaccine made from the Sabin strain (sIPV) is of great significance in the polio eradication project and to address the recent resurge in pertussis. In the present study, we compared the immunogenicity and efficacy of a candidate DTacP-sIPV with those of a commercial DTacP-wIPV/Hib, DTaP/Hib, pertussis vaccine, and aluminum hydroxide adjuvant control in the rhesus macaque model with a 0-, 1-, and 2-month immunization schedule. At day 28 after the third dose, rhesus macaques were challenged with aerosol pertussis and the antibody and cellular response together with pertussis clinical symptoms were determined. The production of anti-PT, anti-PRN, anti-FHA, anti-DT, anti-TT, and polio type I, II, III antibodies was induced by the candidate DTacP-sIPV, which was as potent as commercial vaccines. In comparison with the control group that showed typical pertussis symptoms of humans after the aerosol challenge, the DTacP-sIPV group did not exhibit obvious clinical pertussis symptoms and had higher neutralization titers of anti-PT, anti-PRN, and anti-FHA. In conclusion, the DTacP-sIPV vaccine was able to induce immunity in rhesus macaques to prevent pertussis infections after immunization. The developed vaccine was as efficient as other commercial vaccines.

Evolutionary genomics of recent clinical Bordetella pertussis isolates from Iran: wide circulation of multiple ptxP3 lineages and report of the first ptxP3 filamentous hemagglutinin-negative B. pertussis.

Here we investigated nationwide clinical Bordetella pertussis isolated during 2005-2017 from different provinces of Iran, a country with more than 50years whole cell vaccine immunisation history. Our results revealed the ongoing increase in the population of ptxP3/fim3-2 B. pertussis isolates in different provinces which were differentiated into nine clades. The largest clade (clade 8) which was previously found to be prevalent in Tehran was also prevalent across the country and clade 5 with ptxP3/prn9 genotype has also increased in frequency (14% of all ptxP3 isolates) in recent years. Furthermore, we detected the first ptxP3 B. pertussis isolates that does not express filamentous hemagglutinin (FhaB) as one of the major antigens of the pathogen and a key component of the acellular pertussis vaccine.

Circulation of Bordetella pertussis in the Caribbean Netherlands: a population-based seroepidemiological study

ObjectivesPertussis is a respiratory infectious disease caused by Bordetella pertussis. In the Caribbean Netherlands (CN), comprising the islands Bonaire, St Eustatius, and Saba, registration of cases is mandatory for disease surveillance. However, insufficient laboratory facilities hamper case confirmation, and circulation persists. The aim of this seroepidemiological study was to gain insight into B. pertussis circulation in CN, and to investigate what factors contribute to the risk of infection. MethodsBlood samples and questionnaires were collected for 1829 participants aged 0–90 years. Concentrations of B. pertussis toxin-specific IgG antibodies (anti-Pt) were determined using a bead-based immunoassay to indicate infections within the previous 12 months (based on anti-Pt ≥ 50 IU/mL) in participants without detectable vaccine-induced humoral immunity. Risk factors for recent infection were analyzed using logistic regression models. ResultsAn estimated 8.2% (95% CI 6.6–10.1) of CN residents aged ≥ 9 years were found to have been recently infected by B. pertussis. Risk factors for a recent infection were age 12–29 years (13.8–14.6%) and Dutch Caribbean or Surinamese origin (10.7%). ConclusionsB. pertussis infections occur frequently among CN residents aged ≥ 9 years, although few clinical pertussis cases are reported. Transmission to vulnerable individuals seems likely and should be taken into account in optimizing vaccination programs.

Pertussis immunity in pregnant women and factors associated with seronegative status

Despite high level of vaccination coverage, pertussis remains a serious problem of modern medicine. Pertussis cases are registered among infants, adolescents, and adults. Infants younger than three months of age have the highest rate of serious clinical pertussis course. Transplacental transfer of pertussis-specific antibodies induce protection against infection. The available data regarding anti-pertussis antibody level in pregnant women in Russia remain sparce. To evaluate the humoral immunity to Bordetella pertussis in pregnant women and factors associated with seronegative status, we performed a cross-sectional study with 388 participants. SeroPertussis IgG (Israel) ELISA kit was used to quantitate antibodies against pertussis toxin/hemagglutinin. Binary logistic regression analysis was performed to assess factors associated with seronegative status. The median age of the subjects was 30 years old, more than half of which (51.3%) provided no verified pertussis vaccination data so that their children will not receive transplacental anti-infectious immunity. Gestational age was significantly associated with seronegative status. Compared to women tested during the first trimester, participants in the third trimester of pregnancy were more likely to be seronegative against pertussis. The odds of being susceptible rose with increased gestational period (p 0.01 for linear trend). Age, number of pregnancies and vaccination status revealed no impact on significant differences between seropositive and seronegative subjects. Pertussis booster vaccinations for preschool children, adolescents and healthcare workers dealing with pregnant women and neonates as well as cocoon vaccination strategy and vaccination during pregnancy were necessary to be implemented to protect infants against pertussis.

Comparative genomics of clinical Bordetella pertussis strains against vaccine reference strains of India reveals genomic structural heterogeneity

Background: Pertussis, also known as whooping cough, caused by Bordetella pertussis, is a highly contagious, vaccine-preventable respiratory disease causing neonatal morbidity and mortality worldwide. Pertussis continues to be a serious public health problem in India. Data on incidence of pertussis and molecular epidemiology is scarce in India. The present study investigated the diversity of clinical B. pertussis strains against vaccine reference strains of India at genome structural level. Methods and materials: B. pertussis strains, BPD1 and BPD2 isolated from nasopharyngeal swabs of pediatric patients were included in the study. Swabs were plated in charcoal blood agar and incubated at 37 °C with CO2 for 48 h. Isolates were confirmed by standard biochemical tests and real-time PCR for the targets IS481 and ptxS1 genes. Genomic DNA was extracted and whole genome sequencing was performed using hybrid assembly approach with Ion torrent and MinION reads. Annotation was done using PATRIC and NCBI pipeline. MLST was analyzed through CGE database. Results: Genome comparison of clinical B. pertussis against 5 whole-cell pertussis vaccine reference strains of India and 1 global reference strains, showed novel insertion of repeat region (∼150 kb) flanked by IS481 in one strain and insertion of known ∼128 kb repeat region in another strain. The clinical strains has shown to undergone genome reduction due to insertion or deletion of IS481 repeat regions comparable to vaccine strains. These isolates harboured multiple virulence traits and ptxS toxin subunits. In addition, the isolates harboured pertactin adhesion (prn) gene, dermonecrotic, hemolysin and cytolysin toxins, and genes involved in type II toxin-antitoxin systems. Other virulence genes identified include virB2, B3, B6, B7, B8, B9, B10 and B11. Both these isolates belonged to sequence type, ST2. Conclusion: The comparative analysis showed genome re-arrangement due to insertions, deletions, and inversions in B. pertussis strains resulting in genome structural diversity. The significance of these genome re-arrangement among clinical strains in response to vaccination needs to be studied. Continues monitoring of changes in vaccine strains at genome level is essential. Further, comprehensive studies on whole genomes are required to understand the genome evolution of B. pertussis.

Comparison of whole-cell versus acellular pertussis vaccine effectiveness in school clusters of pertussis, France, 2013

Objectives and methodWe conducted a prospective study in 2013 to compare the whole-cell versus acellular pertussis vaccines effectiveness and duration of protection, following the occurrence of pertussis clusters. ResultsDuring seven school outbreaks, we identified 102 clinical pertussis cases, including 10 cases biologically confirmed by Bordetella pertussis specific PCR, among a cohort of 305 children in 2nd to 6th grade. The risk of pertussis when vaccinated with an acellular vaccine alone was 1.6 (RR=1.6; 95% CI=1.1–2.5) times higher than when vaccinated with a whole-cell vaccine or using a combined schedule. ConclusionsThe limited duration of protection conferred by the acellular vaccine reinforces the 2013 introduction of the pertussis booster at six years old.

Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons.

Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.

Pertussis diagnostic practices of general practitioners in the Netherlands: A survey study

Background: Pertussis testing is most important when transmission to vulnerable groups is likely. Patients with signs and symptoms suggestive of pertussis are prevalent in primary care, yet general practitioners’ (GPs) reasons (not) to test for pertussis are largely unknown.Objectives: To evaluate GP-reported diagnostic practices for pertussis, reasons for (not) testing and intentions towards testing among GPs.Methods: A total of 594 Dutch GPs were invited by email to participate in a survey study including a questionnaire reflecting on their pertussis diagnostic practices, reasons for (not) testing and the intention to test for pertussis in the year of 2013. Intention to test was measured as the likelihood to test for eight clinical vignettes.Results: In total, 122 GPs (21%) completed the online questionnaire. Most GPs reported having diagnosed at least one pertussis case (84%) in the previous year. Of all GPs, 14% did not perform any pertussis tests in the last year. The most reported reason for testing was to confirm the clinical pertussis diagnosis (70%); the most reported reason for not testing was that the diagnostic test result does not influence treatment (70%). Overall, judging from the clinical vignettes, GPs reported being more likely to perform diagnostic testing based on symptoms than based on vulnerable groups at risk.Conclusion: In contrast to national guidelines, our results suggest that GPs report to test for pertussis mainly based on clinical symptoms rather than based on protecting vulnerable groups at risk.

Pertussis detection in children with cough of any duration

BackgroundThe diagnosis of pertussis in clinical practice continues to be a challenge worldwide as the symptoms are variable. We aimed to determine the prevalence of pertussis in Chinese children irrespective of cough duration and explore the clinical characteristics of children with pertussis with different cough durations.MethodsThis was a prospective study of children 1 month to 11 years of age with different cough durations in one large Chinese hospital. Bilateral deep posterior nasopharyngeal swabs and venepuncture for full blood count, CRP and serology and sputum were obtained when possible for investigation. E-test strips were used for testing the susceptibility of the B.pertussis isolates against erythromycin, azithromycin, sulphamethoxazole/trimethoprim, levofloxacin, amoxicillin and doxycycline. Demographic, clinical and laboratory information on culture and antimicrobial susceptibility testing was collected from children, and analyzed using SAS v.10 (SAS Institute Inc., USA).ResultsAfter exclusions we analyzed 312 children. Ninety-seven (31.1%) children had laboratory evidence of pertussis. When grouped by cough duration, few characteristics were significant between children with and without pertussis. Of the 36 isolates, 72.2% (26/36)could not be inhibited by erythromycin and azithromycin at all. The MIC50 and MIC90 to amoxicillin were 0.75 mg/L and 1 mg/L respectively, sensitive to amoxicillin by the EUCAST points.ConclusionsThe “one-size-fits-all” clinical pertussis case definition is no longer optimal to recognize this disease. A large comprehensive study of children with all types of cough is required to make substantial inroads into increasing both the sensitivity and specificity in pertussis diagnosis, which will have a beneficial impact on public health. Amoxicillin maybe an alternative for children with marolide-resistant B.pertussis infection; however, local sensitivities are required to inform clinical practice.

Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination offers protection for neonates against clinical pertussis until primary vaccinations, but maternal antibodies also interfere with infants' immune responses to primary vaccinations. We investigated the effect of maternal Tdap vaccination on the pertussis antibody responses of infants starting primary vaccinations at age 3 months. In an open-label, parallel, randomised, controlled trial, pregnant women aged 18-40 years with a low risk of pregnancy complications were recruited through independent midwives at 36 midwife clinics in the Netherlands and received Tdap vaccination either at 30-32 weeks of pregnancy (maternal Tdap group) or within 48 h after delivery (control group). All term-born infants were vaccinated with the diphtheria, tetanus, and pertussis-inactivated poliomyelitis-Haemophilus influenzae type B-hepatitis B six-in-one vaccine and a ten-valent pneumococcal vaccine at 3 months, 5 months, and 11 months. Randomisation was done using a number generator in a 1:1 ratio and with sealed envelopes. Participants and clinical trial staff were not masked, but laboratory technicians were unaware of study group assignments. The primary endpoint was serum IgG pertussis toxin antibody concentrations at age 3 months. Cord blood and infant blood samples were collected at age 2 months, 3 months, 6 months, 11 months, and 12 months. Analysis was done by modified intention to treat with all randomly assigned participants in case a laboratory result was available. This trial is registered with ClinicaltTrialsRegister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314). The trial is now closed to new participants. Between Jan 16, 2014, and March 4, 2016, 118 pregnant women were enrolled into our study, with 58 in the maternal Tdap group and 60 in the control group. The geometric mean concentration (GMC) of pertussis toxin antibodies were higher in infants in the maternal Tdap group than in the control group infants at age 3 months (GMC ratio 16·6, 95% CI 10·9-25·2) and also significantly higher compared with control infants at age 2 months. After primary vaccinations, antibody concentrations for pertussis toxin, filamentous haemagglutinin, and pertactin were significantly lower at all timepoints in infants of the maternal Tdap group than in infants in the control group. No safety issues after maternal Tdap vaccination were encountered. In view of the high pertussis toxin antibody concentrations at age 3 months, maternal vaccination supports a delay of the first pertussis vaccination in infants until at least age 3 months. Maternal antibody interference affects antibody concentrations after primary and booster vaccinations. The clinical consequences of this interference remain to be established. The Dutch Ministry of Health, Welfare, and Sport.

Genomic Survey of Bordetella pertussis Diversity, United States, 2000-2013.

We characterized 170 complete genome assemblies from clinical Bordetella pertussis isolates representing geographic and temporal diversity in the United States. These data capture genotypic shifts, including increased pertactin deficiency, occurring amid the current pertussis disease resurgence and provide a foundation for needed research to direct future public health control strategies.

Whole-Cell or Acellular Pertussis Primary Immunizations in Infancy Determines Adolescent Cellular Immune Profiles.

Pertussis is re-emerging worldwide, despite effective immunization programs for infants and children. Epidemiological studies show a more limited duration of protection against clinical pertussis in adolescents primed with acellular pertussis (aP) vaccines during infancy than those who have been primed with whole-cell pertussis (wP) vaccines. This study aimed to determine whether memory immune responses to aP, diphtheria, and tetanus vaccine antigens following booster vaccinations at 4 and 9 years of age differ between wP- versus aP-primed children. In a cross-sectional study, blood was collected of DTwP- or diphtheria, tetanus, and aP (DTaP)-primed children before, 1 month, and 2 years after the preschool DTaP booster administered at 4 years of age (n = 41-63 per time point). In a longitudinal study, blood was sampled of DTwP- or DTaP-primed children before, 1 month, and 1 year after a preadolescent Tdap booster at 9 years of age (n = 79-83 per time point). Pertussis, diphtheria, and tetanus vaccine antigen-specific IgG levels, B-cell and T-cell responses were determined. After the preschool booster vaccination, IgG levels were significantly higher in aP-primed as compared with wP-primed children until 6 years of age. Before the preadolescent Tdap booster vaccination, humoral and cellular immune responses were similar in aP- and wP-primed children. However, the Tdap booster vaccination induced lower vaccine antigen-specific humoral, B-cell, and T-helper 1 (Th1) cell responses resulting in significantly lower Th1/Th2 ratios in aP-primed compared with wP-primed children. The memory immune profiles at preadolescent age to all DTaP vaccine antigens are already determined by the wP or aP combination vaccines given in infancy, showing a beneficial Th1-dominated response after wP-priming. These immunological data corroborate epidemiological data showing that DTaP-primed adolescents are less protected against clinical pertussis than DTwP-primed children.

Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections

Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17–109 days, 64. 1% boys), hospitalized in the Pediatric Departments at “Sapienza” University Rome and Bambino Gesù Children’s Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found. Policlinico Umberto I: protocol 213/14, 3085/13.02.2014, retrospectively registered. Bambino Gesù Children’s Hospital: protocol n. RF-2010-2317709.

Pertussis disease and transmission and host responses: insights from the baboon model of pertussis

Whooping cough is a highly contagious, acute respiratory disease, caused by the Gram-negative bacterium Bordetella pertussis (Bp). Despite the introduction and widespread use of vaccines starting in the 1950s pertussis cases continue to be reported, with a significant global impact. The role of specific virulence factors in disease and the immune mechanisms associated with protection following natural infection or vaccination are still not completely understood. The recently-developed baboon model of clinical pertussis provides a valuable tool for the study of pertussis. Baboons infected with B. pertussis exhibit all of the manifestations of human pertussis including paroxysmal coughing, mucus production, leukocytosis and transmission. The establishment of this model provides the opportunity to address unanswered questions about the natural progression of this disease and host responses to infection and vaccination in a very relevant model. In this review, we present an overview of our knowledge of pertussis along with recent advances resulting from use of the baboon model. Remaining questions and future research directions are discussed. We hope that the knowledge gained through use of the baboon model of pertussis and clinical studies will allow the development of more efficacious vaccines, conferring long lasting protection against disease and transmission.

Pertussis incidence rates in Novi Sad (Serbia) before and during improved surveillance

Introduction/Objective. The Global Pertussis Initiative (GPI) proposed clinical case definitions for pertussis diagnosis in three different age cohorts in order to improve surveillance of pertussis especially in older children, adolescents, and adults. The main goal of this research was to compare the burden of pertussis in the city of Novi Sad before and after the introduction of improved surveillance using the GPI clinical case definitions of pertussis. Methods. Baseline data on pertussis were obtained from routine (non-sentinel) reporting before improved surveillance was introduced. From September 16, 2012, clinical case definitions proposed by GPI were applied within improved (sentinel and hospital) surveillance, while surveillance clinical case definitions were not introduced within non-sentinel. To confirm the suspected diagnosis, sampling of nasopharyngeal swab and/or blood was obtained from all cases. The choice of laboratory method (PCR or ELISA) depended on the duration of coughing and the age of the patients. Data were statistically processed by SPSS Statistics, version 22. Results. During the 12-year period before the introduction of improved surveillance, only two clinical pertussis cases were registered. In contrast, during the two-year period of improved surveillance, a total of 14 (season 2012/13) and 146 (season 2013/2014) confirmed pertussis cases were reported. Significant differences were determined in distribution of pertussis according to the type of surveillance and the level of health care. Conclusion. Introduction of clinical case definitions proposed by GPI improved the quality of surveillance and enabled an insight in the distribution of pertussis in all age groups and at all levels of health care.

Incidence of Severe and Nonsevere Pertussis Among HIV-Exposed and -Unexposed Zambian Infants Through 14 Weeks of Age: Results From the Southern Africa Mother Infant Pertussis Study (SAMIPS), a Longitudinal Birth Cohort Study.

Background. Maternal vaccination with tetanus, reduced-dose diphtheria, and acellular pertussis vaccine (Tdap) could be an effective way of mitigating the high residual burden of infant morbidity and mortality caused by Bordetella pertussis. To better inform such interventions, we conducted a burden-of-disease study to determine the incidence of severe and nonsevere pertussis among a population of Zambian infants.Methods. Mother–infant pairs were enrolled at 1 week of life, and then seen at 2- to 3-week intervals through 14 weeks of age. At each visit, nasopharyngeal (NP) swabs were obtained from both, and symptoms were catalogued. Using polymerase chain reaction (PCR) to identify cases, and a severity scoring system to triage these into severe/nonsevere, we calculated disease incidence using person-time at risk as the denominator.Results. From a population of 1981 infants, we identified 10 with clinical pertussis, for an overall incidence of 2.4 cases (95% confidence interval [CI], 1.2–4.2) per 1000 infant-months and a cumulative incidence of 5.2 cases (95% CI, 2.6–9.0) per 1000 infants. Nine of 10 cases occurred within a 3-month window (May–July 2015), with highest incidence between birth and 6 weeks of age (3.5 cases per 1000 infant-months), concentrated among infants prior to vaccination or among those who had only received 1 dose of Diphtheria Tetanus whole cell Pertussis (DTwP). Maternal human immunodeficiency virus (HIV) modestly increased the risk of infant pertussis (risk ratio, 1.8 [95% CI, .5–6.9]). Only 1 of 10 infant cases qualified as having severe pertussis. The rest presented with the mild and nonspecific symptoms of cough, coryza, and/or tachypnea. Notably, cough durations were long, exceeding 30 days in several cases, with PCRs repeatedly positive over time.Conclusions. Pertussis is circulating freely among this population of Zambian infants but rarely presents with the classical symptoms of paroxysmal cough, whooping, apnea, and cyanosis. Maternal HIV appears to increase the risk, while lack of effective exposure to DTwP increased the risk.

Potential Role of Bordetella Pertussis in Celiac Disease

We discuss the correlation between the incidence of acute clinical Bordetella pertussis infection and celiac disease in children < 2 years of age during the Swedish celiac disease epidemic of the 1980s and 1990s.

The "100 Days Cough" Was Not Originally Whooping Cough.

The "100 Days Cough" Was Not Originally Whooping Cough.