Childhood Pertussis Research Articles

The Improvement of Adaptive Immune Responses towards COVID-19 Following Diphtheria-Tetanus-Pertussis and SARS-CoV-2 Vaccinations in Indonesian Children: Exploring the Roles of Heterologous Immunity.

Routine childhood vaccination, e.g., for diphtheria, tetanus, and pertussis (DTP), might provide additional protection against SARS-CoV-2 infection. This concept of heterologous immunity was explored in healthy children receiving both DTP and inactivated SARS-CoV-2 vaccines. A cross-sectional study was performed on 154 healthy children aged 6-8 years old in Jakarta, Indonesia. Their vaccination status for the DTP (including a diphtheria-tetanus booster vaccine at 5 years old) and CoronaVac (from 6 years old) vaccines were recorded. Peripheral blood samples were collected from all participants, in which anti-diphtheria toxoid IgG and anti-SARS-CoV-2 S-RBD antibodies and T cell-derived IFN-γ were measured. The study participants with complete DTP vaccination had significantly higher titers of anti-diphtheria toxoid IgG than the ones without (median = 0.9349 versus 0.2113 IU/mL; p < 0.0001). Upon stratification based on DTP and CoronaVac vaccination statuses, the participants with complete DTP and CoronaVac vaccinations had the highest titer of anti-SARS-CoV-2 S-RBD antibodies (median = 1196 U/mL) and the highest concentration of SARS-CoV-2-specific T cell-derived IFN-γ (median = 560.9 mIU/mL) among all the groups. Healthy children aged 6-8 years old with complete DTP and CoronaVac vaccinations exhibited stronger SARS-CoV-2-specific T cell immune responses. This might suggest an additional benefit of routine childhood vaccination in generating protection against novel pathogens, presumably via heterologous immunity.

Pertussis epidemiology in adults: Retrospective analysis of pertussis incidence and association with comorbidities among adult populations in Aotearoa New Zealand, using national administrative datasets

BackgroundIn New Zealand, approximately half reported pertussis cases are adult. Studies indicate underestimated pertussis burden in this population and probable reservoir for childhood pertussis. Pertussis is linked to chronic obstructive pulmonary disease (COPD) development and increased risk with pre-existing COPD. While acellular pertussis vaccines are available for adults, data on pertussis disease burden in adults and association with COPD remain limited. AimTo estimate pertussis incidence in New Zealand adult health service user (HSU) population aged ≥ 18 between 2008–2019 and inform adult pertussis vaccination strategies by assessing disease burden and risk factors in different adult populations. MethodsRetrospective observational cohort study using an HSU cohort, formed by linking administrative health data using unique National Health Index identifier. For primary analysis, annual incidence rates were calculated using pertussis hospitalisations and notifications. In secondary analysis, Cox proportional hazards survival analyses explored association between pertussis in adults and chronic comorbidities. ResultsThe cohort had 2,907,258 participants in 2008 and grew to 3,513,327 by 2019, with 11,139 pertussis cases reported. Highest annual incidence rate of 84.77 per 100,000 PYRS in 2012, notably affecting females, those aged 30–49 years, and European or Māori ethnicity. Adjusting for sociodemographic variables found no significant risk of prior pertussis notification leading to comorbidity diagnosis (Adjusted-HR: 0.972). However, individuals with prior comorbidity diagnosis had 16 % greater risk of receiving pertussis notification or diagnosis (Adjusted-HR: 1.162). ConclusionsStudy found significant pertussis burden among the HSU adult cohort and highlighted higher risk of pertussis for those with recent comorbidity diagnoses. Vaccination for pertussis should be recommended for individuals with comorbidities to reduce infection risk and disease severity. GPs must have capability to test for pertussis, given it is notifiable disease with implications for individuals, their families, and broader population. High-quality disease surveillance is crucial for informing policy decisions.

Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) — a protocol for two parallel, open-label, randomised controlled trials

BackgroundUniversal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines.MethodsThe OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety.DiscussionThese data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood.Trial registrationsISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).

Humoral immunity against pertussis among healthcare workers

Background. Vaccination is the most effective way to prevent infectious diseases. Inadequate vaccination coverage among healthcare workers is a major concern for healthcare organizations. The lack of specific immunity against pertussis represents the risk for acquiring a healthcare associated infection by medical staff but also of being a source of infection to patients. More than 70% of all healthcare associated infections are vaccine-preventable. Pertussis remains one of the most important vaccine-preventable infections and continues to be a public health concern even in countries with high vaccination coverage among children. Revaccination of adults against pertussis is not included in the National vaccination schedule of the Russian Federation.&#x0D; Aim. To assess the humoral immunity against pertussis among healthcare workers of the infectious disease hospitals.&#x0D; Materials and methods. We conducted a cross-sectional study that included 252 healthcare workers. All study participants were surveyed and tested for antibodies (immunoglobulins G) against Bordetella pertussis by enzyme immunoassay.&#x0D; Results. The proportion of healthcare workers seronegative for pertussis was 46.8%. The healthcare workers with unknown vaccination status amounted to 40.5%. More than half (55.6%) of the participants have been vaccinated and 3.9% of them have had pertussis in childhood. A recent infection was confirmed in 8.0% of participants who had the level of antibodies to Bordetella pertussis greater than 50 U/ml. The largest proportion of participants seronegative to Bordetella pertussis (55.2%) was observed among those under 30 years. The median level of antibodies against pertussis in seropositive health workers was 28.3 U/ml.&#x0D; Conclusion. The significant proportion of seronegative participants (46.8%) and those who had the recent infection underline the necessity of the improvement of pertussis prevention by implementation of vaccination in the risk groups, including healthcare workers to reduce the risk of healthcare associated infections.

Burden of pertussis among young infants in Malaysia: A hospital-based surveillance study

BackgroundThe case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia. MethodsThe study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test. Results441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p < 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents. ConclusionsA high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden.

Pertussis epidemiology including direct and indirect effects of the childhood pertussis booster vaccinations, Norway, 1998–2019

BackgroundThe acellular pertussis vaccine has been used in the Norwegian national immunisation program since 1998. Following an increase in pertussis incidence in all age groups, booster doses were introduced for 7–8-year-olds in 2006, and for 15–16-year-olds in 2013. We assessed the effects of the booster doses on pertussis incidence in different age groups to inform potential changes in vaccination policy. MethodsWe included all pertussis cases notified to the Norwegian Surveillance System for Communicable Diseases in 1998–2019. We calculated annual incidence rates (IR, per 100,000 inhabitants) by age group. We estimated average annual changes in IRs (incidence rate ratios, IRR) for each age group for 2006–2012 and 2013–2019 using Poisson regression. ResultsIn 1998–2019, 74,675 cases of pertussis were notified. Coinciding with booster introduction, between 2006 and 2012 the IR decreased among 8–15-year-olds (from 433 to 199/100,000, IRR 0.89 [95% confidence interval 0.88–0.90]). A similar decrease was seen between 2013 and 2019 among 16–19-year-olds (from 171 to 77/100,000, IRR 0.84 [0.82–0.86]). There was no significant change in IRs among children < 1 year of age between 2006 and 2012 (IRR 0.99 [0.95–1.04]) or 2013–2019 (IRR 0.96 [0.91–1.02]). The IR decreased in both periods among adults aged 20–39 and 40+ (IRR 0.94 [0.93–0.95] and 0.92 [0.91–0.92] in 2006–2012; IRR 0.97 [0.96–0.99] and 0.97 [0.96–0.99] in 2013–2019, respectively). Despite steady, high vaccination coverage, in 2013–2019, there was an increase in the IR among children aged 1–7 (63 to 86/100,000, IRR 1.05 [1.03–1.07]) and 8–15 years (88 to 122/100,000, IRR 1.08 [1.06–1.10]). ConclusionsPertussis booster doses have offered direct protection in the targeted age groups. Our findings suggest indirect protection in adults, while the incidence in infants hasn’t changed. The recent increase in IRs among 1–15-year-olds warrants close monitoring and further evaluation of the vaccination schedule.

Childhood pertussis is still here: An Asian city's perspectives.

Pertussis, or whooping cough, is a highly contagious respiratory infection that is caused by the bacterium Bordetella pertussis. It is one of the most common causes of death in childhood. It is also a frequent cause of chronic cough in children, adolescents, and adults. Global and Hong Kong perspectives of childhood pertussis were described. Hong Kong has prided herself in the city's childhood immunization program. There appear to be no major outbreaks of pertussis since the 1960s. Nevertheless, pediatricians may see isolated cases of pertussis or pertussis-like cases from time to time. Occasionally, infants are severely affected with apneas and managed with ventilator supports in the PICU. Outbreaks of the notifiable disease continue to occur despite a reasonable surveillance system and vaccination program in Hong Kong. Vaccination of mothers, adolescents, and adults are efficacious methods to further reduce the risks of pertussis. Macrolides remain efficacious antibiotics especially used early during the infectious phase. Infants with pertussis may require intensive care support and morbidity is high. Physicians should be reminded from time to time that outbreaks of pertussis still exist in Hong Kong and in many cities globally.

Investigation of immunity against Bordetella pertussis in pregnant women and an overview of the vaccination schedule in Turkey.

Pertussis caused by Bordetella pertussis, is a disease leading to significant morbidity and mortality in neonates and infants. Direct protection of the infant may be achieved by maternal and neonatal vaccination. Despite primary vaccination, infants under six months pose the greatest risk of infection with pertussis. Maternal immunization provides a high level of infant protection from birth until immunity is achieved by active vaccination. There is no routine Tdap vaccination recommendation for pregnant women in Turkey. This study was carried out to determine pertussis antibody levels in pregnant women and provide data for improving vaccine planning. The study was carried out with 133 pregnant women in Turkey. Antibody titers to pertussis toxin (anti-PT) and filamentous hemagglutinin (anti-FHA) were measured by the commercially available ELISA. Among 133 participants, 93 (69.9%) were found to be immune according to anti-PT IgG antibody levels. According to anti-FHA IgG antibody levels, 123 (92.5%) participants were considered to be immune. A positive correlation was observed between PT and FHA and the findings were statistically significant (P < 0.001, r = 0.343). In the study group, the ages of the participants varied between 17 and 44 years. The mean age of those who were immune was 27.3±5.6, the mean age of non-immune patients was 29.1±6.2 and the difference was not statistically significant (P= 0.14). Our results reveal that approximately one-third of pregnant women were not immune to pertussis, reflecting many young infants to be vulnerable to pertussis infection until the onset of primary vaccinations, although childhood pertussis vaccination coverage has been high for a long time. We conclude that Tdap vaccine recommendation for pregnant women regardless of previous immunization history may be beneficial for the protection of infants in their first six months.

Introduction of newer vaccines in Immunization Programme of India: Challenges to be addressed

Small Pox eradication will continue to be regarded as the humanity’s greatest triumph for all times to come. Since then, several health achievements were attained that too made significant contributions towards the goals of human survival and development. Substantial reductions in deaths and disabilities have been observed in diseases like childhood Tuberculosis, Pertussis, Diphtheria, Measles and paralytic Polio. In India, considerable reduction in vaccine preventable disease (VPD) burden was observed following launch of Expanded Programme of Immunization (EPI) in 1978. Reported number of Pertussis cases came down from 320109 (1980) to 25206 (2015). Measles cases reduced from 114036 to 25488 in the same time interval. Maternal and Neonatal Tetanus has been eliminated from most part of the world including India. There were 18975 paralytic Polio cases reported in 1980, which came down to ‘zero’ in 2011, and South-East Asia region including India declared free of WPV in 2014. We are at the end game phase of another great landmark, Polio eradication. In all these successes, immunization was the core intervention.Millennium Development Summit in 2000 focused on intensification of child health interventions for attainment of the MDG-4 of reducing under-five deaths. The benefits of traditional EPI vaccines are already evident. Worldwide, the projected number of deaths averted by Measles vaccine (including SIA rounds) during 2011-2020 will be around 14.1 million. Introduction of newer and less utilized vaccines may further boost the attainment of MDG-4. Universalizing Hepatitis-B vaccine may prevent 6 million child deaths by 2020. Newer vaccine Hib may avert 1.7 million deaths. Sustaining the current vaccines and upscaling the programme with newer vaccines is expected to prevent 25 million child deaths worldwide during 2011-2020. Also, a number of new vaccines, like malaria, dengue, new-generation tuberculosis and typhoid conjugate vaccines are in advanced stages of development and may be available in the coming years.

SEVERE PERTUSSIS IN CHILDHOOD: UPDATE AND CONTROVERSY - SYSTEMATIC REVIEW.

ABSTRACTObjective: Through a systematic review, this essay aimed at revising the concepts of severe pertussis, updating the epidemiology, pathophysiology, clinical presentation, antibiotic therapy and auxiliary therapeutic options for symptomatology and complications.Data sources:This review considered publications from the last 30years in the databases US National Library of Medicine (PubMed), Scientific Electronic Library Online (SciELO), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Cochrane, Google Scholar, as well as protocols of the Ministry of Health and recommendations of the Centers for Disease Control and Prevention, related to childhood pertussis (whooping cough), with emphasis on its severe form. This research was based on keywords derived from the terms “pertussis”, “azithromycin”, “antitussives”, “leukocyte reduction” in Portuguese and English. Duplicate studies and those with unavailable full-text were excluded.Data synthesis:Among 556 records found, 54 were selected for analysis. Pertussis, as a reemerging disease, has affected all age groups, evidencing the transient immunity conferred by infection and vaccination. Severe cases occur in neonates and infants, with secondary viral and bacterial complications and malignant pertussis, a longside hyperleukocytosis, respiratory failure and shock. Macrolides continue to be the chosen antibiotics, while antitussives for coughing remain without efficacy. The prompt treatment in Intensive Care Units improved the prognostic in severe cases, and transfusion was promising among procedures for leukoreduction. Conclusions: Approaching severe pertussis in childhood remains a challenge for diagnostic and therapy, as the available therapeutic options are still unsatisfactory. Strategies of prevention are expected to reduce the occurrence of severe cases, while new studies should confirm the role of auxiliary therapies.

A step beyond the hygiene hypothesis\u2014immune-mediated classes determined in a population-based study

BackgroundComorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables.MethodsLCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35–82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1β, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts.ResultsLCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men.ConclusionsThis is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.

Local Epidemic of Childhood Pertussis in a Rural Area of Akita Prefecture

Local Epidemic of Childhood Pertussis in a Rural Area of Akita Prefecture

Bias due to differential and non-differential disease- and exposure misclassification in studies of vaccine effectiveness.

BackgroundStudies of vaccine effectiveness (VE) rely on accurate identification of vaccination and cases of vaccine-preventable disease. In practice, diagnostic tests, clinical case definitions and vaccination records often present inaccuracies, leading to biased VE estimates. Previous studies investigated the impact of non-differential disease misclassification on VE estimation.MethodsWe explored, through simulation, the impact of non-differential and differential disease- and exposure misclassification when estimating VE using cohort, case-control, test-negative case-control and case-cohort designs. The impact of misclassification on the estimated VE is demonstrated for VE studies on childhood seasonal influenza and pertussis vaccination. We additionally developed a web-application graphically presenting bias for user-selected parameters.ResultsDepending on the scenario, the misclassification parameters had differing impacts. Decreased exposure specificity had greatest impact for influenza VE estimation when vaccination coverage was low. Decreased exposure sensitivity had greatest impact for pertussis VE estimation for which high vaccination coverage is typically achieved. The impact of the exposure misclassification parameters was found to be more noticeable than that of the disease misclassification parameters. When misclassification is limited, all study designs perform equally. In case of substantial (differential) disease misclassification, the test-negative design performs worse.ConclusionsMisclassification can lead to significant bias in VE estimates and its impact strongly depends on the scenario. We developed a web-application for assessing the potential (joint) impact of possibly differential disease- and exposure misclassification that can be modified by users to their own study scenario. Our results and the simulation tool may be used to guide better design, conduct and interpretation of future VE studies.

Assessment of Tdap Vaccination Effectiveness in Adolescents in Integrated Health-Care Systems

PurposeDespite high national vaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines among U.S. adolescents, rates of adolescent pertussis disease are increasing. We estimated the duration of protection after Tdap vaccination and the possible effects of the change from whole-cell to acellular childhood pertussis vaccines in the United States during the 1990s. MethodsWe conducted a retrospective cohort analysis among 11- to 18-year-olds enrolled in two integrated health-care delivery systems during 2005–2012. Cases met the Council of State and Territorial Epidemiologists' confirmed or probable definition or a polymerase chain reaction-positive suspect definition. We estimated vaccine effectiveness (VE) overall and by time since Tdap receipt. We stratified VE estimates by primary series pertussis vaccine received (based on birth year): mixed-vaccine cohort (1987–1997) and acellular vaccine cohort (1998–2001). ResultsThe overall Tdap VE was 57% (95% confidence interval [CI]: 42%–68%); the VE in the mixed-vaccine and acellular cohorts was 65% (95% CI: 44%–78%) and 52% (95% CI: 30%–68%), respectively. Tdap VE within <2 years post vaccination (69%, 95% CI: 54%–79%) was significantly different from VE ≥2 years post vaccination (34%, 95% CI: 1%–55%, p value < .01). VE was significantly higher <2 years post vaccination compared with ≥2 years post vaccination in both mixed-vaccine (87%, 95% CI: 58%–96%, and 52%, 95% CI: 13%–73%; p value = .04) and acellular cohorts (62%, 95% CI: 41%–76%, and 21%, 95% CI: −30% to 52%; p value = .01). ConclusionsAlthough Tdap vaccination remains the best pertussis prevention method for adolescents, protection wanes within 2 years regardless of the type of childhood primary vaccine. Vaccines with longer duration of protection could decrease pertussis burden.

Trends and patterns of pertussis morbidity and mortality in Bauchi State, Nigeria: 2011 - 2015

Introduction: globally, there are estimated 16 million pertussis cases and about 195,000 deaths occur in children every year. Despite generally high coverage with childhood pertussis vaccines globally, pertussis is one of the leading causes of vaccine-preventable deaths worldwide. Most deaths occur in young babies who are either unvaccinated or incompletely vaccinated. In Nigeria national estimate for DPT coverage in 2013 was 38% and state level coverage ranged from 3% - 76% across 20 Northern states. Pentavalent vaccine was the most effective means of preventing Pertussis and is given in three doses at 6 weeks, 10 weeks and 14 weeks of age. We analyzed five-year pertussis morbidity and mortality trend from Bauchi State.

Estimating Pertussis Susceptibility Among 0-23-Month-Old Children in the United States: Using National Immunization Survey (NIS) 2013.

Despite high pertussis-containing vaccine coverage in the United States, children who are unvaccinated or not fully vaccinated remain susceptible to pertussis. Over multiple birth cohorts of incomplete vaccination, the number of children not immune to pertussis will accumulate because of factors such as age-specific vaccination status and dose-specific vaccine effectiveness. The total number of pertussis-susceptible children 0-23 months of age in the United States is unknown. Using data on age-specific pertussis-containing vaccine receipt among children evaluated in the 2013 National Immunization Survey (born between February 2011 and June 2012) and accounting for vaccine effectiveness and maternal transfer of antipertussis antibodies, we estimated the cumulative number of pertussis-susceptible children 0-23 months of age. Of an estimated 7,905,672 children 0-23 months of age in the United States, we estimated that approximately 22% (1,716,429) are susceptible to pertussis. Age was a large factor in susceptibility, with 89% of children less than 2 months of age not immune to pertussis compared with 7% of children 21-23 months of age. In sensitivity analysis, increasing maternal pertussis vaccination coverage from 10% to 42% decreased susceptibility in children less than 2 months of age to 68%. When considering waning immunity after the fourth dose of vaccine, the herd protection threshold was no longer reached. These estimates underscore the need to monitor age-specific pertussis vaccine coverage, to increase childhood and maternal pertussis vaccine coverage, to maintain population-level immunity and to prevent the spread of pertussis among young children.

Risk factors for pertussis in adults and teenagers in England

Pertussis is a vaccine-preventable respiratory infection caused by Bordetella pertussis which can be fatal in infants. Although high vaccine coverage led to prolonged disease control in England, a national outbreak of pertussis in 2011 led to the largest increase in over two decades, including a marked increase in cases aged ⩾15 years. A case-control study in four regions of England was undertaken to investigate risk factors for pertussis in adolescents and adults, specifically employment type and professional and household contact with children. Pertussis cases were laboratory-confirmed and aged ⩾15 years. Controls were recruited through general practitioner nomination. Demographic and risk factor information were collected using an online survey. Multivariable logistic regression was used to estimate independent associations with outcome. Two hundred and thirty-one cases and 190 controls were recruited. None of the four employment variables (social care, education, health sector, patient contact) were significantly associated with pertussis. Professional contact with children aged < 1 year was associated with a significantly reduced odds of pertussis [odds ratio (OR) 0·25, 95% confidence interval (CI) 0·08-0·78, P = 0·017]. Household contact with ⩾1 child aged 10-14 years was associated with significantly increased odds of pertussis (OR 2·61, 95% CI 1·47-4·64, P = 0·001). Occupational contact with very young children was associated with reduced odds of pertussis, probably due to immune boosting by low-level exposures to B. pertussis. Sharing a household with a young adolescent was a significant risk factor for pertussis in adults and older teenagers. The primary focus of the childhood pertussis vaccination programmes is to prevent infant disease. Although evidence is emerging that adolescent vaccination does not provide indirect protection to infants, our results highlight the importance of children aged 10-14 years in pertussis transmission to older adolescents and adults.

Pertussis-Associated Pneumonia in Infants and Children From Low- and Middle-Income Countries Participating in the PERCH Study.

Background. Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.Methods. Children 1–59 months of age hospitalized with World Health Organization–defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.Results. Bordetella pertussis was detected in 53 of 4200 (1.3%) cases and 11 of 5196 (0.2%) controls. In the age stratum 1–5 months, 40 (2.3% of 1721) cases were positive, all from African sites, as were 8 (0.5% of 1617) controls. Pertussis-positive African cases 1–5 months old, compared to controls, were more often human immunodeficiency virus (HIV) uninfected-exposed (adjusted odds ratio [aOR], 2.2), unvaccinated (aOR, 3.7), underweight (aOR, 6.3), and too young to be immunized (aOR, 16.1) (all P ≤ .05). Compared with pertussis-negative African cases in this age group, pertussis-positive cases were younger, more likely to vomit (aOR, 2.6), to cough ≥14 days (aOR, 6.3), to have leukocyte counts >20 000 cells/µL (aOR, 4.6), and to have lymphocyte counts >10 000 cells/µL (aOR, 7.2) (all P ≤ .05). The case fatality ratio of pertussis-infected pneumonia cases 1–5 months of age was 12.5% (95% confidence interval, 4.2%–26.8%; 5/40); pertussis was identified in 3.7% of 137 in-hospital deaths among African cases in this age group.Conclusions. In the postneonatal period, pertussis causes a small fraction of hospitalized pneumonia cases and deaths; however, case fatality is substantial. The propensity to infect unvaccinated infants and those at risk for insufficient immunity (too young to be vaccinated, premature, HIV-infected/exposed) suggests that the role for maternal vaccination should be considered along with efforts to reduce exposure to risk factors and to optimize childhood pertussis vaccination coverage.

Clot or not? An unusual case of false positive CTPA and an approach to diagnosis

The case involves a 69-year-old female with severe, longstanding bronchiectasis secondary to childhood pertussis infection. She presented to the hospital and was thought clinically to have a pulmonary embolus. A CT pulmonary angiogram was performed, which was technically satisfactory. This revealed multiple, bilateral filling defects that were fairly convincing for pulmonary emboli. Further review of the CT scan not only revealed the extent of her bronchiectasis but also a number of enlarged bronchial arteries supplying the diseased lung. The pulmonary arterial filling defects arose suspiciously close to the bronchial arteries and the possibility of bronchial to pulmonary artery anastomoses was considered. Could the admixture of highly contrast-opacified pulmonary arterial blood with partially opacified systemic arterial blood cause the apparent filling defects? After further consideration, a second electrocardiography-gated CT angiogram was performed—this time in the systemic arterial phase but planned with two regions of interest sited over the main pulmonary artery and the aorta with the aim of triggering the scan with maximum contrast in the bronchial arteries, and as much contrast washout as possible in the pulmonary arteries. This study revealed a reversal of the CT pulmonary angiogram appearances with contrast now seen in the bronchial arteries and opacifying the sites of the previous filling defects in the pulmonary arteries. Thus, the filling defects were actually false positives caused by an admixture of highly opacified and part-opacified blood via bronchial artery anastomoses. In the context of a false-positive finding of pulmonary embolus on a background of severe bronchiectasis, unnecessary anticoagulation could have increased the risk of complications such as haemoptysis. This case report illustrates the importance of knowledge of potential false-positive findings in CT pulmonary angiography and describes a novel approach based on cardiac CT techniques to prove this.

Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood

The recent increase in cases of whooping cough among teenagers in the US suggests that the acellular Bordetella pertussis vaccine (aP) that became standard in the mid 1990s might be relatively less effective than the whole-bacteria formulation (wP) previously used since the 1950s. To understand this effect, we compared antibody and T cell responses to a booster immunization in subjects who received either the wP or aP vaccine as their initial priming dose in childhood. Antibody responses in wP- and aP-primed donors were similar. Magnitude of T cell responses was higher in aP-primed individuals. Epitope mapping revealed the T cell immunodominance patterns were similar for both vaccines. Further comparison of the ratios of IFNγ and IL-5 revealed that IFNγ strongly dominates the T cell response in wP-primed donors, while IL-5 is dominant in aP primed individuals. Surprisingly, this differential pattern is maintained after booster vaccination, at times from eighteen years to several decades after the original aP/wP priming. These findings suggest that childhood aP versus wP vaccination induces functionally different T cell responses to pertussis that become fixed and are unchanged even upon boosting.