Pertussis In Infants Research Articles

Maternal Vaccination and Infant Influenza and Pertussis.

Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants. This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged <2 months, 2 to <6 months, and <6 months combined. Secondary outcomes included infant hospitalization (emergency presentation or admission) and death. Risk ratios and 95% confidence intervals (CIs) were estimated by Poisson regression. Vaccine effectiveness (VE) was estimated as (1 minus the risk ratio) x 100%. Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged <2 months and 35.7% (2.2% to 57.7%) for infants aged 2 to <6 months. Pertussis VE was 80.1% (95% CI, 37.1% to 93.7%) for infants aged <2 months and 31.8% (95% CI, -39.1% to 66.6%) for infants aged 2 to <6 months. Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged <2 months. The findings strengthen the importance of maternal vaccination to prevent these diseases in infants.

Pertussis vaccination in pregnancy - current data on safety and effectiveness.

Whooping cough/pertussis is a respiratory infection caused by the bacteria Bordetella pertussis and Bordetella parapertussis. The World Health Organization (WHO) has identified whooping cough as one of the least controlled diseases in all age groups. Clinically, the catarrhal phase manifests itself as flu-like, nonspecific symptoms: cough, runny nose, mild fever, which, regrettably, makes early diagnosis difficult. The severe course is more specific (an audible inspiratory whoop followed by paroxysmal cough and vomiting). Currently, in Poland the highest percentage of cases is observed in children aged 0-4 years, followed by children over 15 years of age, with peaks among teens and seniors. Notably, hospitalization, morbidity and mortality rates are considerable in children (especially infants). Vaccinating pregnant women against pertussis provides approximately 90% protection to infants in their first two months of life. It is an effective form of preventing pertussis in infants. Moreover, it is safe for pregnant women and their children. The Advisory Committee on Immunization Practices (ACIP) recommends Tdap vaccination to every pregnant woman between 27-36 weeks of pregnancy.

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines.

Pertussis (‘whooping cough’) is a severe respiratory tract infection that primarily affects young children and unimmunised infants. Despite widespread vaccine coverage, it remains one of the least well-controlled vaccine-preventable diseases, with a recent resurgence even in highly vaccinated populations. Although the exact underlying reasons are still not clear, emerging evidence suggests that a key factor is the replacement of the whole-cell (wP) by the acellular pertussis (aP) vaccine, which is less reactogenic but may induce suboptimal and waning immunity. Differences between vaccines are hypothesised to be cell-mediated, with polarisation of Th1/Th2/Th17 responses determined by the composition of the pertussis vaccine given in infancy. Moreover, aP vaccines elicit strong antibody responses but fail to protect against nasal colonisation and/or transmission, in animal models, thereby potentially leading to inadequate herd immunity. Our review summarises current knowledge on vaccine-induced cellular immune responses, based on mucosal and systemic data collected within experimental animal and human vaccine studies. In addition, we describe key factors that may influence cell-mediated immunity and how antigen-specific responses are measured quantitatively and qualitatively, at both cellular and molecular levels. Finally, we discuss how we can harness this emerging knowledge and novel tools to inform the design and testing of the next generation of improved infant pertussis vaccines.

The Effect of Tetanus-Diphtheria-Acellular-Pertussis Immunization During Pregnancy on Infant Antibody Responses: Individual-Participant Data Meta-Analysis.

BackgroundImmunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in pregnancy is increasingly recommended. We determined the effect of Tdap immunization in pregnancy on infants’ vaccine responses.MethodsIndividual-participant data meta-analysis of ten studies (n=1884) investigating infants’ antibody response to routine immunizations following Tdap immunization in pregnancy was performed. Geometric mean ratios (GMRs) of antigen-specific immunoglobulin G (IgG) levels were calculated using mixed-effects models. Seroprotection rates were compared using chi-squared tests.ResultsInfants of Tdap-immunized women had significantly lower IgG against pertussis toxin (GMR 0.65; 95%CI 0.57-0.74), filamentous haemagglutinin (FHA) (0.68; 0.53-0.87), pertactin (0.65; 0.58-0.72) and fimbria 2/3 (FIM2/3) (0.41; 0.32-0.52) after primary immunization, compared with infants of unimmunized women. These lower levels persisted after booster immunization for FHA (0.72; 0.61-0.84) and FIM2/3 (0.53; 0.29-0.96). After primary immunization, infants of Tdap-immunized women had lower seroprotection rates against diphtheria (90% [843/973] vs 98% [566/579]; p<0.001) and invasive pneumococcal disease (IPD) caused by 5 Streptococcus pneumoniae (SPN) serotypes (SPN5, SPN6B, SPN9V, SPN19A, SPN23F), and higher seroprotection rates against Haemophilus influenzae type b (short-term and long-term seroprotection rates, 86%[471/547] vs 76%[188/247] and 62%[337/547] vs 49%(121/247), respectively, all p=0.001). After booster immunization, seroprotection rates against diphtheria and tetanus were 99% (286/288) and (618/619) in infants of Tdap-immunized women, respectively.ConclusionsInfants of Tdap-immunized women in pregnancy had lower IgG levels against pertussis, diphtheria and some SPN serotypes after their immunization compared with infants of unimmunized women. Enhanced surveillance of pertussis, diphtheria and IPD in infants is needed to determine the clinical significance of these findings.Systematic Review RegistrationCRD42017079171.

Hospital-based prospective study of pertussis in infants and close contacts in Tehran, Iran

BackgroundPertussis 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.MethodsHospital-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.ResultsA 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 < 3 months old (79.9%; 157/199) and unvaccinated (62.3%; 124/199), 20.1% (40/199) of them were confirmed having B. pertussis infection. Greater cough duration and lymphocyte counts were the only symptoms associated to positivity. Half of the contact cases (51.0%; 53/104) had a B. pertussis infection, median age was 31 years old. A proportion of 28.3% (15/53) positive contacts did not report any symptom. However, 67.9% (36/53) and 3.8% (2/53) of them reported cough at inclusion or during the study, including 20.8% (11/53) who started coughing ≥7 days before infant cough onset. Overall, only five samples were successfully cultured.ConclusionThese data evidenced the significant prevalence of pertussis infection among paucy or poorly symptomatic contacts of infants with pertussis infection. Widespread usage of molecular testing should be implemented to identify B. pertussis infections.

The impact of pertussis in infants: insights from a hospital-based enhanced surveillance system, Lazio region, Italy, 2016 to 2019.

BackgroundRoutine surveillance systems for pertussis often suffer from under-recognition and under-reporting.AimOur aim was to describe the epidemiology and the clinical features of pertussis in children younger than 1 year in an Italian region, detected through an enhanced hospital surveillance system.MethodsFrom 2016 to 2019, we monitored the incidence and the clinical characteristics of hospitalised pertussis cases younger than 1 year in two paediatric hospitals involved in the PERTINENT project.ResultsWe detected 141 pertussis cases, corresponding to an estimated incidence of 105.8 per 100.000 in 2016, 91.7 per 100.000 in 2017, 64.5 per 100.000 in 2018 and 40.9 per 100.000 in 2019, based on the hospitals’ catchment area, roughly corresponding to the Lazio region. A total of 101 cases (77.1%) had a household member with cough or other respiratory symptoms. The most frequent combination of symptoms was paroxysmal cough with apnoea in the absence of fever. Almost 40% had been prescribed an antibiotic treatment before hospitalisation, and the median time from symptom onset to contact with the hospital was 8 days. Thirty-one (22.0%) had complications.ConclusionAn enhanced surveillance system showed a high incidence of pertussis among infants in the Lazio region, where the impact of this disease may still be underestimated. Increasing the coverage of pertussis immunisation among pregnant women and improving the capacity for early detection in primary care may contribute to reducing the impact of pertussis among infants.

Exchange transfusion in the management of critical pertussis in young infants: a case series.

It is proposed that severe leucocytosis mainly contributes to pulmonary hypertension by blocking pulmonary capillaries and restricting blood flow. Exchange transfusion (ET) in pertussis has been demonstrated as a safe and useful technique for depleting the leucocyte mass. We aim to discuss four cases of pertussis-induced respiratory distress and the effectiveness of ET in such a setting. We conducted a retrospective case series at the Infectious Disease Department of Children's Hospital 2 in Ho Chi Minh City, Vietnam, and included four pertussis patients that were confirmed by PCR tests on respiratory secretions, presented with severe leucocytosis and respiratory distress and required mechanical ventilation. Among the included patients, three underwent a double volume ET for leucodepletion, two of whom were discharged after the procedure with proper vitals and laboratory test results. On the other hand, one patient died despite ET, performed late in the course of the disease. Exchange transfusion was not performed in the last patient who died as well. Early ET may be a useful and rapid life-saving treatment in children with critical pertussis and severe leucocytosis before cardiopulmonary complications appear.

Malignant pertussis in infants: factors associated with mortality in a multicenter cohort study

BackgroundMalignant pertussis (MP) affects young infants and is characterized by respiratory distress, perpetual tachycardia and hyperleukocytosis up to 50 G/l, leading to multiple organ failure and death in 75% of cases. Leukodepletion may improve prognosis. A therapeutic strategy based on leukodepletion and extracorporeal life support (ECLS) according to different thresholds of leucocytes has been proposed by Rowlands and colleagues. We aimed at identifying factors associated with death and assess whether the respect of the Rowlands’ strategy is associated with survival.MethodsWe reviewed all MP infants hospitalized in eight French pediatric intensive care units from January 2008 to November 2013. All infants younger than 3 months of age, admitted for respiratory distress with a diagnosis of pertussis and WBC count ≥ 50 G/l were recorded. Evolution of WBC was analyzed and an optimal threshold for WBC growth was obtained using the ROC-curve method. Clinical and biological characteristics of survivors and non-survivors were compared. Therapeutic management (leukodepletion and/or ECLS) was retrospectively assessed for compliance with Rowlands’ algorithm (indication and timing of specific treatments).ResultsTwenty-three infants were included. Nine of 23 (40%) died: they presented more frequently cardiovascular failure (100% vs 36%, p = 0.003) and pulmonary hypertension (PHT; 100% vs 29%, p = 0.002) than survivors and the median [IQR] WBC growth was significantly faster among them (21.3 [9.7–28] G/l/day vs 5.9 [3.0–6.8] G/l/day, p = 0.007).WBC growth rate > 12 G/l/day and lymphocyte/neutrophil ratio < 1 were significantly associated with death (p = 0.001 and p = 0.003, respectively).Ten infants (43%) underwent leukodepletion, and seven (30%) underwent ECLS. Management following Rowlands’ strategy was associated with survival (100% vs 0%; p < 0.001, relative risk of death = 0.18, 95%-CI [0.05–0.64]).ConclusionsA fast leukocyte growth and leukocytosis with neutrophil predominance during acute pertussis infection were associated with death. These findings should prompt clinicians to closely monitor white blood cells in order to early identify infants at risk of fatal outcome during the course of malignant pertussis. Such an early signal in infants at high risk of death would increase feasibility of compliant care to Rowlands’ strategy, with the expectation of a better survival.

Clinical repercussions in pertussis infants post-Tdpa vaccination of pregnant woman: An immunization success?

IntroductionIn 2014, there was an epidemic of pertussis in Brazil that caused the death of 129 infants. To control the disease amongst infants under 6 months of age, and especially those under 2 months, the Brazilian Ministry of Health introduced Tdap immunization for all pregnant women. MethodsThis study aimed to describe the morbidity and mortality variables of pertussis cases in 969 infants aged under 6 months, comparing the periods before and after the introduction of Tdap vaccine in pregnant women. Data was extracted from the Information System on Notifiable Diseases (SINAN) including every case of pertussis that occurred in the metropolitan region of Recife-Brazil in infants under 6 months from January 2009 to October 2018. In order to analyze the variables, patients were divided into two groups Pre-Tdap(2009–2014), and Post-Tdap (2016–2018). ResultsThere were no significant differences between the age groups and gender distribution in the period compared. In the Post- Tdap group compared with the Pre-Tdap group, the clinical presentation of pertussis in infants differed with more paroxysmal cough, and more vomiting, less apnea, and cyanosis. During this period, there were fewer complications and no deaths occurred. ConclusionsMaternal immunization with Tdap decreased disease severity, complication rates, and no deaths occurred in infants under 6 months of age diagnosed with pertussis.

Pertussis infant morbidity and mortality trends after universal maternal immunisation in Mexico: An ecological database study with time-series analysis

IntroductionPertussis is a highly contagious infectious disease caused by Bordetella pertussis and a leading cause of infant mortality in Mexico. The Tetanus-diphtheria-acellular pertussis (Tdap) vaccine was recommended in the Mexican Immunisation Programme for pregnant women in 2013. We describe pertussis morbidity and mortality trends in infants ≤2 and ≤12 months of age), before and after maternal Tdap immunisation implementation in Mexico. MethodsAn ecological retrospective database study was performed in the Mexican National and Workers Social Security Institutes (IMSS; ISSSTE). Data were collected on confirmed pertussis ambulatory cases, hospitalisations, and deaths, plus vaccination coverage (Tdap; Diphtheria-tetanus-acellular pertussis [DTPa]) and population estimates. Descriptive and regression time-trend analyses were performed for pertussis morbidity and mortality in infants between pre- (2010–2012) and post- (2014–2018) maternal Tdap immunisation periods. ResultsAround 1 million infants a year are covered in IMSS/ISSSTE databases. Average full primary infant DTPa vaccine coverage was 71.4%-72.7% nationally. Since 2013, annual maternal Tdap vaccine coverage ranged from 70%-93%. Between 2010-2018, 2,024 pertussis cases, 2,518 hospitalisations and 71 deaths were reported in infants. Among infants 0–2 months old (maternal immunisation target group), there was a significant decrease, post-maternal vaccination, in pertussis incidence (49.9%, p < 0.000), hospitalisation (70.0%, p < 0.000) and mortality (82.4%, p = 0.003). In infants 0–12 months old, pertussis hospitalisations (28.9%, p = 0.000) and mortality (36.2%, p = 0.059) decreased, but incidence increased (61.8%, p = 0.000). ConclusionAfter maternal immunisation was implemented, there was a decreasing trend in incidence, hospitalisation and death due to pertussis in infants 0–2 months old. Increases in incidence reported in 0–12-month-olds are likely due to major changes in diagnosis and reporting introduced during the study period as well as limited vaccination and health coverage in some states. These findings confirm the important contribution of the Tdap maternal immunisation programme in reducing pertussis disease burden, particularly severe disease, among infants in Mexico.

Infant pertussis and maternal immunity: The curious case of Canada

BackgroundThe United Kingdom (UK) and Canada use the same acellular pertussis vaccine and both experienced large pertussis outbreaks in the past, occurring in the 1980s in the UK and 1990s in Canada, yet current epidemiology differs. A national outbreak with infant deaths occurred in the UK in 2012, yet outbreaks remain localized and death from pertussis rare in Canada. AimWe explored whether past outbreaks in children may influence future risk when those children become parents. MethodsWe conducted an ecological within-country birth cohort analysis in women of childbearing age of the relative risk of ever having pertussis infection by two points in time, 2002 and 2012, comparing with 1992 as the baseline. We used notified cases of pertussis in England and Wales and Canada to compare trends in relative risk. We projected forward to 2022 in Canada assuming incidence remained stable. ResultsIn Canada, the cumulative risk of previous pertussis was similar in 2002 and 2012 and, in both periods, was higher than in 1992. In England and Wales, the cumulative risk of pertussis fell stepwise from 1992 to 2012. Projecting forwards, the pattern of risk in Canada becomes similar to England and Wales in 2022. ConclusionsWidespread pertussis outbreaks in children may reduce the risk of pertussis in infants when those children become parents. Further research is needed to determine the mechanism. As birth cohorts that experienced outbreaks grow past childbearing age, pertussis burden in infants in Canada may increase, following trends observed in England and Wales.

Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Pertussis in the Newborn in Publicly and Privately Insured Mother-infant Pairs in the United States.

In the United States, pertussis circulation persists and primarily infects infants and children, despite routine vaccinations. To minimize infant morbidity and mortality from the disease before the first DTaP dose, the Advisory Committee on Immunization Practices recommends maternal Tdap vaccination in weeks 27-36 of pregnancy. Cohorts of mother-infant pairs in the Medicaid Analytic eXtract (MAX) (2010-2014) and IBM MarketScan (2011-2015) databases were analyzed to estimate the effectiveness of prenatal Tdap vaccination compared with no vaccination to prevent infant pertussis in the first 6 months. Hazard ratios were estimated with Cox proportional hazards models and adjusted for potential confounders via inverse probability weights. The impact of preterm delivery on the risk of pertussis was analyzed. Results from the 2 databases were pooled. In MarketScan, women received Tdap vaccination before delivery in 114,067 (25.6%) of 445,638 pregnancies and in MAX, 33,286 (4.8%) of 695,262 pregnancies. Among pregnancies with preterm delivery, only 21.2% and 3.8% in MarketScan and MAX had been vaccinated. The risk of pertussis in unvaccinated term infants was 3.5 (MarketScan) and 17 (MAX) per 10,000; and in preterm infants, it was 8.4 (MarketScan) and 19.8 (MAX) per 10,000. The pooled hazard ratio for Tdap vaccination any time before delivery versus no vaccination was 0.64 [95% confidence interval (CI): 0.41-1.00]. The hazard ratio was 0.11 (95% CI: 0.03-0.36) for preterm and 0.78 (95% CI: 0.48-1.29) for term infants vaccinated before 37 weeks. The incidence of pertussis was higher and the protective hazard ratio stronger during pertussis outbreaks. Prenatal Tdap vaccination reduces the risk of pertussis infections in the infants' first 6 months by 36%. Vaccination soon after 27 weeks of pregnancy, before when deliveries began, ensures vaccination includes those born preterm, who are at highest risk for pertussis and benefit particularly from this vaccination.

Pertussis in infants in Nordic countries.

A life-course immunisation approach is required to prevent and control pertussis. We aimed at reviewing pertussis incidence among infants in Denmark, Finland, Norway and Sweden, and at putting these data in the context of national surveillance systems and vaccination schedules. We collected 2014-2018 data on pertussis incidence, on pertussis vaccination schedules and on coverage of the third dose of the diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine from publicly available sources. We gathered opinions on national surveillance systems from public health and paediatrics experts of the relevant countries. The pertussis vaccination schedules and coverage in infancy were similar across countries. All countries except Denmark recommended an additional booster vaccine dose for adolescents. None of the countries had maternal immunisation recommendation. Mean pertussis incidence in Denmark, Sweden and Finland was 168, 76 and 35 per 100,000 infant-years, respectively. Data were insufficient to derive a mean incidence in Norway. There were no systematic differences in the national surveillance systems across the countries. The higher mean pertussis incidence in Denmark may be explained by the lack of recommendations for adolescent pertussis booster vaccination. Further investigations are warranted.

Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study

BackgroundThe incidence of pertussis shows an increasing trend in recent years, but some clinicians often lack sufficient understanding of the clinical characteristics and risk factors for severe pertussis, and more effective measures should be taken to reduce the incidence and mortality of pertussis in young infantsMethodsA retrospective study was conducted, and 184 infants and children with pertussis who had been hospitalized in the Department of Pediatrics of Beijing Ditan Hospital affiliated with Capital Medical University from January 2016 to December 2017 were included. Clinical data of the patients were collected and the clinical characteristics were statistically analyzedResultsAmong the 184 patients, 41.85% were infants < 3 months of age, and 65.22% of the total patients were not vaccinated against pertussis. There were 22 critically ill children, among whom 4 died, and compared with mild cases, they had a higher proportion of children younger than 3 months of age and infants not vaccinated against pertussis (63.64% vs. 38.89% and 100% vs. 60.49%, respectively); a higher proportion of children with severe pneumonia (100% vs. 0%); higher leukocyte count(× 109/L , 35.80 ± 20.53 vs 19.41 ± 8.59); and a higher proportion of children with severe hyperleukocytosis (18.18% vs. 0%, respectively) (P<0.05)Conclusions1. Infants aged <3 months not vaccinated for pertussis appear more likely to become infected and have more severe disease. 2. Severe pneumonia and hyperleukocytosis are the main mechanisms underlying severe pertussis.

Health Belief Model efficacy in explaining and predicting intention or uptake pertussis vaccination during pregnancy.

Pertussis is a highly contagious respiratory disease and vaccination of pregnant women seems to be the most effective strategy to prevent pertussis in infants. The aim of this study is to assess the acceptance by women of pertussis vaccination during pregnancy based on Health Belief Model (HBM) constructs. A multicentre observational study was carried out with a convenience sample of 300 respondents. Most women were worried to contract or to transmit pertussis during the first months of the infant's life and perceived pertussis contracted in the first months of life as very serious. Parity appears to be a factor predicting this health behaviour, as nulliparous women tend to get more vaccinated or have a higher intention to get vaccinated (ORa 2.8 CI 95% 1.5-5.2 p<0.01). HBM is an effective tool for identifying facilitators and barriers to health behaviours. Strategies to promote vaccination during pregnancy are needed, including educational interventions and communication campaigns.

Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil

BackgroundThis paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. MethodsWe defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models’ different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. ResultsThe dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90–95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models’ estimates over their different time horizons are compared at infant coverage < 90–95%, their projections fall in the same range. ConclusionsStatic models may serve to explore an intervention’s cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally. Clinical Trial registryClinical Trial registry name and registration number: Not applicable.

Pertussis (Keuchhusten)

Pertussis wird durch das gramnegative Bakterium Bordetella pertussis verursacht. Die Krankheitsmanifestationen reichen von unspezifischem Husten bis zu lebensbedrohlichen Verläufen mit Hyperleukozytose und respiratorischer Insuffizienz, v.a. bei jungen Säuglingen. Die Diagnose basiert auf klinischer Symptomatik und mikrobiologischen Nachweisverfahren. Die Therapie besteht aus Makrolidantibiotika; bei Apnoen kann Koffein versucht werden. Die Inzidenz beträgt 10–40 Fälle/100.000 Bevölkerung und Jahr, bei Säuglingen ist sie am höchsten (ca. 50), gefolgt von Jugendlichen (30–35). Mehr als 50 % der in den ersten 5 Lebensmonaten an Pertussis erkrankten Kinder werden hospitalisiert. Die Impfprävention umfasst Grundimmunisierung und regelmäßige Auffrischimpfungen mit azellulären Impfstoffen. Um schwere Verläufe bei jungen Säuglingen zu verhindern, ist die Impfung schwangerer Frauen am erfolgversprechendsten. Säuglinge geimpfter Mütter sollen zeitgerecht ab dem Alter von 2 Monaten für den Eigenschutz immunisiert werden.

Interference With Pertussis Vaccination in Infants After Maternal Pertussis Vaccination.

* Abbreviations: aP — : acellular pertussis DTaP — : diphtheria-tetanus-acellular pertussis DTwP — : diphtheria, tetanus, and whole-cell pertussis HIC — : high-income country LMICs — : low- and middle-income countries WHO — : World Health Organization Pertussis is a major public health concern. In 2014, 24 million cases and 160 000 deaths from pertussis in children <5 years were estimated worldwide, with nearly one-third of the cases occurring in Africa.1 Vaccination with an acellular pertussis (aP)–containing vaccine in pregnancy prevents severe pertussis in young infants and has been recommended in an increasing number of high-income countries (HICs). We have recently discussed optimal strategies for vaccination in pregnancy to maximize protection against infections in infancy.2 However, pertussis vaccination in pregnancy reduces infants’ primary immune responses to diphtheria-tetanus-acellular pertussis (DTaP) vaccines, leading to lower antibody levels to some pertussis antigens, when compared with infants of unvaccinated mothers.3 This is termed “interference” and has been shown primarily in studies from HICs that used DTaP formulations for infant immunization, but its clinical implications are unknown. Fewer data are available on the potential interference with diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccines for infant immunization, the vaccines used almost exclusively in low- and middle-income countries (LMICs). An earlier study that we conducted in the United States revealed interference with DTwP vaccines, but not with DTaP vaccines, in infants with higher maternally derived antibody levels before primary vaccination.4 In a recent study conducted in Pakistan, the authors found no correlation between preexisting anti-pertussis antibody levels at delivery and infants’ anti-pertussis antibody levels after primary vaccination with DTwP vaccines.5 However, women in these 2 studies did … Address correspondence to Bahaa Abu-Raya, MD, British Columbia Children’s Hospital Research Institute, The University of British Columbia, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. E-mail: baburaya{at}bcchr.ubc.ca

Cytotoxicity of the effector protein BteA was attenuated inBordetella pertussisby insertion of an alanine residue.

Bordetella bronchiseptica and Bordetella pertussis are closely related respiratory pathogens that evolved from a common bacterial ancestor. While B. bronchiseptica has an environmental reservoir and mostly establishes chronic infections in a broad range of mammals, B. pertussis is a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity of B. bronchiseptica, the cytotoxicity induced by B. pertussis BteA (Bp BteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression in B. pertussis. We show that the presence of an alanine residue inserted at position 503 (A503) of Bp BteA accounts for its strongly attenuated cytotoxic potency. The deletion of A503 from Bp BteA greatly enhanced the cytotoxic activity of B. pertussis B1917 on mammalian HeLa cells and expression of Bp BteAΔA503 was highly toxic to Saccharomyces cerevisiae cells. Vice versa, insertion of A503 into B. bronchiseptica BteA (Bb BteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, the production of Bp BteAΔA503 increased virulence of B. pertussis B1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effector Bp BteA may represent an evolutionary adaptation that fine-tunes B. pertussis virulence and host immune response.

A data driven clinical algorithm for differential diagnosis of pertussis and other respiratory infections in infants.

Clinical criteria for pertussis diagnosis and clinical case definitions for surveillance are based on a cough lasting two or more weeks. As several pertussis cases seek care earlier, a clinical tool independent of cough duration may support earlier recognition. We developed a data-driven algorithm aimed at predicting a laboratory confirmed pertussis. We enrolled children <12 months of age presenting with apnoea, paroxistic cough, whooping, or post-tussive vomiting, irrespective of the duration of cough. Patients underwent a RT-PCR test for pertussis and other viruses. Through a logistic regression model, we identified symptoms associated with laboratory confirmed pertussis. We then developed a predictive decision tree through Quinlan's C4.5 algorithm to predict laboratory confirmed pertussis. We enrolled 543 children, of which 160 had a positive RT-PCR for pertussis. A suspicion of pertussis by a physician (aOR 5.44) or a blood count showing leukocytosis and lymphocytosis (aOR 4.48) were highly predictive of lab confirmed pertussis. An algorithm including a suspicion of pertussis by a physician, whooping, cyanosis and absence of fever was accurate (79.9%) and specific (94.0%) and had high positive and negative predictive values (PPV 76.3% NPV 80.7%). An algorithm based on clinical symptoms, not including the duration of cough, is accurate and has high predictive values for lab confirmed pertussis. Such a tool may be useful in low resource settings where lab confirmation is unavailable, to guide differential diagnosis and clinical decisions. Algorithms may also be useful to improve surveillance for pertussis and anticipating classification of cases.