Search

Background A phase 2 randomized-controlled safety and immunogenicity trial evaluating different doses of recombinant acellular pertussis vaccine containing genetically-inactivated pertussis toxin (PTgen) was conducted in women of childbearing age in Thailand to identify formulations to advance to a trial in pregnant women. Methods A total of 250 women were randomized 1:1:1:1:1 to receive one dose of one of three investigational vaccines including low-dose recombinant pertussis-only vaccine containing 1 μg PTgen and 1 μg FHA (ap1gen), tetanus, reduced-dose diphtheria (Td) combined to ap1gen (Tdap1gen) or combined to recombinant pertussis containing 2 μg PTgen and 5 μg FHA (Tdap2gen), or one dose of licensed recombinant TdaP vaccine containing 5 μg PTgen and 5 μg FHA (Boostagen®, TdaP5gen) or licensed Tdap vaccine containing 8 μg of chemically inactivated pertussis toxoid (PTchem), 8 μg FHA, and 2.5 μg pertactin (PRN) (BoostrixTM, Tdap8chem). Serum Immunoglobulin G (IgG) antibodies against vaccine antigens were measured before and 28 days after vaccination by ELISA. To advance to a trial in pregnant women, formulations had to induce a PT-IgG seroresponse rate with a 95% confidence interval (95% CI) lower limit of ≥ 50%. Results Between 5 and 22 July 2018, a total of 250 women with median age of 31 years were enrolled. Post-vaccination PT-IgG seroresponse rates were 92% (95% CI 81–98) for ap1gen, 88% (95% CI 76–95) for Tdap1gen, 80% (95% CI 66–90) for Tdap2gen, 94% (95% CI 83–99) for TdaP5gen, and 78% (95% CI 64–88) for Tdap8chem. Frequencies of injection site and systemic reactions were comparable between the groups. No serious adverse events were reported during the 28-day post-vaccination period. Conclusions All recombinant acellular pertussis vaccines were safe and immunogenic in women of childbearing age, and all met pre-defined immunogenicity criteria to advance to a trial in pregnant women. Clinical Trial Registration: Thai Clinical Trial Registry, TCTR20180321004.

Pertussis is a highly contagious, vaccine-preventable respiratory tract infection, with high morbidity and mortality and a particularly severe effect on newborns and infants under 2 months. The first pertussis vaccines were introduced in the 1940s. Since 1980, however, the incidence of cases has risen despite the extensive vaccination programmes and antibiotic adjuvant treatments available. Transition from the use of whole-cell vaccines to acellular vaccines and the antigenic modifications of Bordetella pertussis have contributed, among other factors, to a reduction in vaccine-acquired immunity and reemergence of the disease. Today, there are still unmet needs not covered by conventional prevention measures and existing antibiotic treatments. This review aims to update the available data, and to discuss which vaccine strategies might contribute to better disease control and prevention.

Background There are worrying indications that diphtheria-tetanus-pertussis (DTP) vaccine has negative non-specific effects for females. We previously found, in a trial of early-Bacillus Calmette-Guerin (BCG) to low weight (LW) neonates, that receiving early-DTP (before 2 months of age), was associated with increased female mortality compared with no-DTP/delayed-DTP. Within a subsequent LW trial, we aimed to retest this observation. Methods Between 2010 and 2014, in Guinea-Bissau, 2,398 infants were randomised 1:1 to early-BCG (intervention) or delayed-BCG (standard practice for LW neonates) and visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. DTP is recommended at 6 weeks of age. We examined the effect of having “early-DTP” versus “no-DTP” at the time of the 2-month visit on all-cause mortality between the 2- and 6-month visits in Cox models stratified by sex and adjusted for BCG-group and 2-month-weight-for-age (z-scores) providing adjusted mortality rate ratios (aMRRs). We analysed to which extent conditions varied between the present and the previous LW trials and how that might have affected the overall result of comparing the early-DTP and the no-DTP groups. Results At the time of the 2-month visit, 75% (1,795/2,398) had received DTP. Those vaccinated had better anthropometric indices than no-DTP infants at birth and by 2 months of age. Between the 2- and 6-month visits, 29 deaths occurred. The early-DTP/no-DTP aMRR was 1.09 (95% CI: 0.44–2.69); 1.19 (0.45–3.15) for females and 0.77 (0.14–4.19) for males. Compared to the previous study, the present study cohort had 56% (30–72%) lower overall mortality, fewer no-DTP infants, higher BCG vaccination coverage and several more oral polio vaccine campaigns. Conclusion We did not find that early-DTP was associated with increased female mortality as found in a previous study; differences in results may partly be due to a decline in overall mortality and changes in vaccination practices.

PLAIN LANGUAGE SUMMARYPertussis, also called whooping cough, is a common disease in adults. However, how it affects adults in some countries in the Asia-Pacific region is not well understood. In 2019, a panel of experts met to review the available information on adult cases of pertussis in Australia, Hong Kong, New Zealand, Singapore, South Korea, and Taiwan. Here, we present the outcomes of the meeting. Pertussis is increasingly reported in the Asia-Pacific region, including cases diagnosed in adults. The diagnosis may be missed in countries where awareness is still low and/or it is not tested routinely. The experts concluded that physicians should consider recommending pertussis vaccination to older adults (aged 65 or older) on an individual basis, as well as people with asthma or chronic obstructive pulmonary disease, who appear to be at higher risk of severe pertussis. Uptake of pertussis vaccination in adults could be improved by increasing awareness of the vaccines available and vaccination infrastructure for this age-group. Some of the measures proposed were as follows: improved access to vaccination; personalized reminders when vaccines are due; and more education about pertussis in adults for doctors, nursesnurses, and patients. The experts also proposed setting up adult vaccination registries for tracking and evaluation of vaccine uptake. This expert opinion might help the healthcare community build action plans to recognise the burden of the disease and increase rates of vaccination among adults. In addition, better data on the disease burden would help to generate awareness.

Neonatal pertussis can potentially cause severe complications and even death. Mothers have been most frequently identified as the source of neonatal pertussis. Approximately a dozen countries have implemented pertussis vaccination programs for pregnant women to protect neonates; however, in Japan, this has not been implemented. The aim of this questionnaire-based study was to ascertain the willingness of women to be vaccinated during pregnancy and the factors associated with willingness. The subjects were 977 pregnant women who visited either of the two selected hospitals for maternity health checks. Most of the women were in their first pregnancy (96%), and approximately half of them considered a physician to be the most reliable source of information about vaccination (481/977, 49%). "Willingness to receive pertussis vaccination" was significantly associated with the factors "no fear of receiving vaccination" (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 2.21-4.34), "necessary to prevent pertussis" (OR = 8.70, 95% CI: 6.17-12.28), "effective in pregnancy" (OR = 5.46, 95% CI: 3.94-7.56), and "no concern about the side effects after vaccination" (OR = 3.03, 95% CI: 1.66-5.55). Pregnant women are likely to consider vaccination if they have a good understanding of the disease and its outcomes. Physicians are well positioned to improve knowledge and attitudes toward pertussis vaccination during pregnancy.

Relevance. Currently, the national calendar of preventive vaccinations does not provide for revaccination against whooping cough in children over the age of 18 months. At the same time, the epidemiological and economic feasibility of revaccination against whooping cough in children aged 6–7 years, as well as adolescents, has been demonstrated in world practice. Aim. Based on a mathematical model, develop a forecast of pertussis morbidity dynamics and assess the potential socio-economic damage under the current and expanded vaccine prophylaxis algorithms.Methods. Mathematical modeling of the potential effect of revaccination against whooping cough in children aged 6–7 years (scenario 1) and at 6–7 years and 14 years (scenario 2) was carried out within the framework of the national calendar of preventive vaccinations. A simulation dynamic mathematical model is constructed that allows predicting the development of the epidemiological process of whooping cough on the basis of the dynamics of the main indicators of its prevalence in the population that developed in previous years. The model took into account dynamic changes in the preventive effectiveness of vaccinations and the potential level of underestimation of morbidity. The obtained arrays of indicators served as the basis for extrapolating trends in morbidity and mortality until 2034.The calculation of epidemiological benefits was carried out in the metrics of prevented loss of years of life under the two scenarios under consideration in comparison with the current vaccination algorithm. The calculation of the economic effect was carried out on the basis of the obtained indicators of epidemiological benefits in the metrics of the monetary equivalent of the average cost of a year of life, taking into account the projected inflation coefficients until 2034.Results. The projected decrease in the number of years of life lived in a state of illness, in comparison with the current situation, will total 44.5 thousand years for the period 2019–2034 under scenario 1 and 66.7 thousand years under scenario 2. The socio-economic damage from prevented cases of the disease, expressed in the monetary equivalent of the average cost of living, will decrease by 28.6% (scenario 1) or 42.0% (scenario 2).Conclusions. A comparison of the received public benefits with the costs of vaccination shows that the expansion of the NCPP with additional revaccinations against whooping cough (at 6–7 years or at 6–7 and at 14 years) is advisable both in epidemiological and economic aspects.

INTRODUCTION: Despite high vaccination coverage among children and adolescents, pertussis remains a public health problem, with large outbreaks occurring periodically in the US and other developed countries. AREAS COVERED: We examined lessons learned more than 20 years after implementation of programs which use only acellular pertussis vaccines and proposed avenues for possible effective use of acellular pertussis vaccine to prevent large outbreaks. EXPERT OPINION/COMMENTARY: Acellular pertussis vaccines were introduced more than 20 years ago, yet the incidence of pertussis has been increasing the past decade, with periodic large outbreaks marked by notable shifts in disease burden from infants and young children towards fully vaccinated adolescents and young adults. This age shift is mainly driven by waning of vaccine immunity. To better protect adolescents against pertussis, modification of the current acellular pertussis vaccination schedule or adoption of new vaccination strategies should be considered. For infants not yet eligible to be vaccinated, maternal vaccination against pertussis during pregnancy is an effective way to protect infants from infection, severe disease and death. Implementation of maternal vaccination programs should be encouraged in countries without one or efforts to improve coverage should be supported in countries with existing program.

Objective This study aimed to elucidate the effects of early macrolide administration on genetically confirmed pertussis-induced cough in adolescents and adults. Methods This single-center, retrospective cohort study examined the effects of the early administration of macrolides and antitussive agents on cough secondary to pertussis. We divided the patients into two groups based on the median duration from the beginning of the cough to the initiation of macrolide administration: early macrolide administration group (EMAG) and non-early macrolide administration group (NEMAG). The clinical improvement of cough was defined as maintaining a cough awareness score of ≤3 points for 3 consecutive days. Patients The medical records of 40 patients diagnosed with pertussis (≥12 years old) who were able to maintain a cough diary and received no other antibiotics aside from macrolides were included in the study. A diagnosis of pertussis was made using the loop-mediated isothermal amplification (LAMP) test. Results The EMAG (24 patients) showed a significantly shorter total cough period than the NEMAG [16 patients; 20.0 (95% confidence interval (CI), 16-28) vs. 30.5 (95% CI, 27-40) days; log-rank test, p=0.002]. There was no significant difference in the post-administration cough periods between the EMAG and NEMAG [11.0 (95% CI, 7-19) vs. 13.0 (95% CI, 5-23) days; log-rank test, p=0.232]. Antitussive agents did not affect the cough. Conclusion The early administration of macrolides, but not antitussive agents, is effective for treating pertussis. Therefore, macrolides should be administered as soon as possible for this disease.

Vaccination during pregnancy is increasingly adopted worldwide in order to protect the mother and her offspring. We studied the current vaccination programs specifically for pregnant women in 42 European countries. Vaccination programs for pregnant women are in place in 37 countries, as follows: influenza (36 countries), pertussis (28), hepatitis B (12), tetanus (10), pneumococcal disease (10), meningococcal disease (10), rabies (8), tick-borne encephalitis (6), hepatitis A (5), poliomyelitis (4), diphtheria (3), Haemophilus influenzae (2), and human papilloma virus (1). Recommendations for vaccination against influenza and pertussis concern almost exclusively pregnant women regardless of high-risk conditions, however differences between vaccination recommendations are noted in terms of timing. Vaccinations against hepatitis B, hepatitis A, pneumococcal disease, meningococcal disease, poliomyelitis, H. influenzae, rabies, and tick-born encephalitis mainly concern pregnant women at high-risk for exposure or serious illness and post-exposure vaccinations. Overall, five European countries have no vaccination recommendations specifically for pregnant women. In conclusion, there are significant differences in vaccination programs for pregnant women in Europe. Vaccination programs for pregnant women should expand in order to protect maternal and infant health. A consensus-based vaccination program is needed.

Purpose: to investigate the level anti-pertussis IgM, IgG, IgA in pregnant women in the I — II — III trimesters. Materials and methods. A total of 288 pregnant women aged. 17 — 43 years (in the I — II — III trimesters) were examined. A serums samples tested for IgM, IgG, IgA against pertussis by ELISA of RIDASCREEN (Germany). Results. Anti-pertussis IgG concentration below the low limit of detection occurred in 75,7% of pregnant women. The majority of seropositive among pregnant women was in the age group 26 — 35 years (82,9%). The proportion of seronegative among pregnant women increased. with increasing pregnancy periods, as well as depending on age. In III trimester IgG were detected in 18,2% of pregnant women. The most seronegative among pregnant women were in the III trimester and at the age of over 36 years old. The detection of IgM, IgG and IgA made it possible to detect the active infection process in 11 (3,9%) pregnant women by elevated level of IgA. High IgA level only in combination with IgM was in serum sample from 1 pregnant woman, high IgA level in combination with IgG at negative values of IgM was in serum samples from 8 pregnant woman. Only IgA in serum sample from 2 pregnant women (I and III trimesters of pregnancy) were detected. This is probably due to the presence of whooping cough or mucosal contamination with B.pertussis (persisting IgA). Conclusion. The serological studies have shown the need to develop algorithms for protecting newborns — from, the moment pregnant women are registered, to the onset of childbirth. These algorithms will provide information about on the presence of whooping cough and will help prevent infection of the newborn.

Background Some children hospitalized for severe pertussis need intensive care; moreover, some children die because of deterioration alone or in combination with other complications. The purpose of this study was to identify the mortality risk factors among hospitalized children with severe pertussis. Methods This study evaluated the medical records of 144 hospitalized children with severe pertussis at the Guangzhou Women and Children’s Medical Centre between January 2016 and December 2019. Results The median age of patients was 2 months (IQR 1–4 months), with 90.3% of the patients aged 70.0 × 109/L (odds ratio [OR], 230.66; 95% confidence interval [CI], 5.16–10,319.09 P = 0.005) and pulmonary hypertension (PH) (OR 323.29; 95% CI 16.01–6529.42; P Conclusion Severe pertussis mainly occurred in children aged 70.0 × 109/L and PH were the prognostic independent variables associated with death.

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is generally used for booster vaccination of infants in Europe and the United States to avoid increased reactogenicity after diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccination. However, Japan has extended the use of additional DTaP vaccination without reducing the antigen dose for diphtheria and pertussis in adolescents and adults, despite limited reports on its safety in adults. This prospective, observational, questionnaire-based study investigated the occurrence of adverse events (AEs) following DTaP vaccination between June 2018 and June 2019 in participants aged 10 years or older. Of the 250 eligible participants, 235 (94%) responded regarding AEs. Among them, 133 (56.6%) reported AEs, of which 39 reported systemic AEs (16.6%) and 120 reported local AEs (51.1%) attributed to DTaP vaccination. The incidence of local AEs was markedly higher with DTaP vaccination than with non-DTaP vaccination (51.1% vs. 10.5%), and AEs appeared later (P < 0.01) and lasted longer (P < 0.01) with DTaP vaccination. However, more than 75% of these AEs resolved within 7 days. DTaP vaccination was not associated with any serious AEs. These results indicate that the DTaP vaccine can be widely used as a booster in adults as an alternative to the Tdap vaccine.

Azithromycin is an antibiotic, which is usually used to treat infections of the upper and lower respiratory tract in children. Despite its high popularity, concerns have been raised regarding the increasing resistance of respiratory pathogens to this drug in recent years. The pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects, as well as recommendations on the use are considered. Azithromycin is recommended as an antibiotic of choice for empirical therapy and selective therapy of major bacterial pathogens of acute intestinal infections in children, for etiotropic treatment of whooping cough, with Lyme disease and for long-term immunomodulatory therapy of cystic fibrosis.

ObjectiveTo evaluate pertussis antibody status of pregnant women and their newborns, and the impact of antenatal immunisation.DesignObservational study.SettingHospitals in urban western India.ParticipantsPregnant women and their newborns.MethodsPertussis antibody titres in mothers and their newborns were determined. Vaccinated and unvaccinated mothers and their newborns were compared for baseline characteristics, geometric mean titres (GMTs) and placental transfer ratio of antibodies. Multivariate logistic regression was performed to understand the influence of different factors on protective antibody titres.ResultsOf 284 mother–infant pairs, 75 mothers and 73 of their newborns were seropositive for anti-pertussis toxin (PT) IgG antibodies. 94 women were vaccinated in pregnancy; 51 (54.3%) of these mothers and newborns were PT IgG positive, compared with 24 (12.3%) of the women (and 22 newborns) not vaccinated in pregnancy. Women vaccinated in pregnancy and their newborns had higher GMT (30.88 and 32.54 IU/mL), compared with women who were not vaccinated (12.63%, 2.24 IU/mL) and their newborns (11.58%, 2.53 IU/mL). Placental transfer ratios in newborns of mothers vaccinated in pregnancy and those who had childhood immunisation or natural immunity were similar (1.05 and 1.12, respectively). Protective titres of antibodies at birth (>20 IU/mL) were observed in 72.3% vs 21% of newborns of vaccinated and unvaccinated pregnant women, respectively; influenced by mother’s vaccination status and seropositivity.ConclusionProtection against pertussis is low in newborns of mothers who are only immunised during childhood. Vaccination early in pregnancy boosts maternal and neonatal immunity.

Objective To assess the protective effect of exclusive breastfeeding and the effectiveness of maternal vaccination in reducing pertussis-like illness. Method This was a case-control study conducted in sentinel hospitals for pertussis in Recife between July 2016 and July 2018. Cases included children aged under six months with symptoms compatible with pertussis (pertussis-like illness). Controls included children aged under six months, living in the metropolitan region of Recife with no diagnosis of pertussis-like illness and matched by the same hospital and birth date. Results Seventy-three cases and 194 controls were included. The diagnosis of pertussis-like illness was predominantly clinical (97,2%). Amongst the main symptoms, paroxysmal cough was observed in 95.89% of cases and vomiting in 53.4%. There were 29 hospitalized cases and no deaths. Out of the 73 cases, 47 were born to mothers vaccinated against pertussis during pregnancy, and the mothers of 144 of the 194 controls had been vaccinated. The protective effect of breastfeeding was of 74% (95% CI;38%, 89%). Children younger than six months, who were exclusively breastfed and with mothers vaccinated against pertussis during pregnancy were 5 times less likely to develop pertussis-like illness, corresponding to a protection of 79% (95% CI;31%, 94%). The effectiveness of maternal vaccination against pertussis-like illness in children under six months was low (27%) and not statistically significant (CI 95%; −34% a 60%). Conclusions Exclusive breastfeeding protects children under six months from pertussis-like illness and may be enhanced when associated with maternal vaccination. These strategies should be encouraged because they also protect against pertussis-like illnesses.

Background Low vaccination rates and under-detection of pertussis infections in adolescents and young adults have an impact on the transmission of pertussis to infants. In this study, the proportion of adolescents and young adults with IgG antibodies against B. pertussis antigens, representing recent infection or vaccination, was estimated in a population-based probabilistic survey in Mexico. Methods Sera and data from 1,581 subjects, including 1,102 adolescents and 479 young adults (10–19 and 20–25 years old, respectively) randomly selected from Mexico’s 2012 National Health and Nutrition Survey, were analyzed. IgG antibodies against pertussis toxin (PT) were measured with the CDC/FDA ELISA. A subset of 234 samples was additionally tested with Bp-IgG PT ELISA kit (EUROIMMUN AG, Lubeck, Germany). Threshold values from corresponding test kits were used to identify recent infection or vaccination. Results Overall anti-PT IgG seroprevalence was 3.9% (95% CI: 2.3–6.3); 3.1% (95% CI: 1.9–5.0) in adolescents, and 4.9% (95% CI: 2.2–11) in young adults. Seroprevalence did not significantly vary by sex, socioeconomic status, region or rural/urban location. Compared to the CDC/FDA ELISA, the EUROIMMUN test showed a 76% sensitivity and 88% specificity. The weighted estimates represent a considerable burden of recent infection in adolescents and young adults; however, most adolescents and adults were seronegative and, therefore, susceptible to pertussis infection. Conclusion Since booster vaccination to B. pertussis after toddlerhood is not recommended in the Mexican national policy, anti-PT IgG seropositivity may be reasonably attributed to recent infection. Assessing pertussis seroprevalence requires careful consideration of the diagnostic test threshold interpretation and epidemiological model used.

Whooping cough, despite the fact that the disease has long been known, still remains a problem for all countries. Cough attacks can cause not only physical discomfort to the patient, but also a significant negative psycho-emotional load. Existing drug therapy to date does not solve all the problems in the treatment of whooping cough. The aim of our study was to conduct a literature review of pertussis treatment and evaluate the efficacy of inhaled corticosteroids in adult patients with moderate to severe disease.Material and methods. Guidelines for the treatment of whooping cough were studied, and 26 medical records of inpatients with the diagnosis of “Pertussis” were analysed. Conclusion. Antibiotic therapy is a mandatory component of treatment. The effectiveness of inhaled corticosteroids in adult patients with moderate to severe whooping cough has been established.

The purpose of this study is to understand children’s clinical characteristics with pertussis and analyze risk factors on critical pertussis patients. Demographic data from patients with pertussis at Children’s Hospital affiliated to the Capital Institute of Pediatrics between March 2011 and December 2018 were collected. We retrospectively gathered more information with the positive exposure, vaccination, antibiotic usage before diagnosis, clinical manifestation, laboratory tests, therapy, and complications for hospitalized children. We divided the patients into severe and non-severe groups, comparing related factors and clinical characteristics among each group. In particular, we summarize the clinical features of the severe patients before aggravation. A total of 967 pertussis cases were diagnosed, of which 227 were hospitalized. The onset age younger than 3 months old accounted for the highest proportion, and 126 patients received hospitalization. For those patients, the incidence of post-tussive vomiting, paroxysmal cyanosis, post-tussive heart rate decrease, hypoxemia, severe pneumonia, and mechanical ventilation was significantly higher than that in the ≥ 3-month-old group (p

Background Pertussis is an important cause of hospitalization in children. Limited data on pertussis have been reported from China. The aim of this study was to characterize clinically suspected pertussis attributable to Bordetella pertussis among children and determine factors associated with longer duration of hospital stay in B. pertussis infection. Methods Two hundred and seventeen consecutive children with clinically suspected pertussis were prospectively enrolled in the study between Jan 2016 through Aug 2017. Variables assessed included demographics, clinical symptoms and laboratory findings. Cox proportional hazards regression model were used to predict variables associated with longer duration of hospital stay. Results Among the 217 patients with clinically suspected pertussis, B. pertussis was found in 106 (48.8%) patients. Of the 106 children with B. pertussis infection, 63 (59.4%) patients had coinfections with majority due to rhinovirus (HRV) (30.2%), Mycoplasma pneumoniae (29.2%) and human bocavirus (hBoV) (11.3%). Presence of coinfection [odds ratio (OR): 1.73, CI: 1.17–2.54], age ≤ 3 months (OR: 1.51, CI: 1.09 to 2.27), and WBC count ≥30 × 109/L (OR: 1.66, CI: 1.07 to 2.84) were independently associated with a longer hospital stay. Conclusions B. pertussis infection had a high coinfection rate with the majority of coinfections due to HRV, M. pneumoniae and hBoV. Presence of coinfection, Age ≤3 months and WBC count ≥30 × 109/L were associated with a longer hospital stay. Children admitted with pertussis need close monitoring when they had evidence of coinfection, Age ≤3 months, WBC count ≥30 × 109/L.

Conventional pertussis animal models deliver hundreds of thousands of Bordetella pertussis bacteria deep into the lungs, rapidly inducing severe pneumonic pathology and a robust immune response. However, human infections usually begin with colonization and growth in the upper respiratory tract. We inoculated only the nasopharynx of mice to explore the course of infection in a more natural exposure model. Nasopharyngeal colonization resulted in robust growth in the upper respiratory tract but elicited little immune response, enabling prolonged and persistent infection. Immunization with human acellular pertussis vaccine, which prevents severe lung infections in the conventional pneumonic infection model, had little effect on nasopharyngeal colonization. Our infection model revealed that B. pertussis can efficiently colonize the mouse nasopharynx, grow and spread within and between respiratory organs, evade robust host immunity, and persist for months. This experimental approach can measure aspects of the infection processes not observed in the conventional pneumonic infection model.

Background Pertussis, is an infectious respiratory disease caused by Bordetella pertussis. The incidence of pertussis has been increasing in South Korea to due to waning vaccine-induced immunity. Culture has a low sensitivity and a long turnaround time (TAT). Recently, a rapid multi-polymerase chain reaction (mPCR) test with a TAT of about 1 h was developed for the detection of respiratory pathogens (17 viruses and three bacteria), including B. pertussis. This study aimed to investigate the effectiveness of mPCR for early diagnosis and treatment of pertussis. Methods We performed a retrospective study of patients with pertussis diagnosed from May 2017 to June 2019 at a university hospital in South Korea. Nasopharyngeal swab specimens were tested using mPCR. Data were extracted from medical records. Results A total of 27 patients with a median age of 48.9 years (range: 3.3–82.2 years) were diagnosed with pertussis, of whom 9 (33.3%) were male. Eleven (40.7%) had fever, 12 (44.4%) had dyspnea, three (11.1%) had paroxysmal cough, and nine (33.3%) had inspiratory whooping. The median interval from symptom onset to diagnosis was 9.0 days (range: 1–31 days). Twenty-four patients (81.5%) were diagnosed within 2 weeks from symptom onset. All but one patient was prescribed macrolide antibiotics. Twenty-two patients (81.5%) required hospitalization, including three (11.1%) who required intensive care unit care for ventilation. Conclusion Testing patients with respiratory symptoms using mPCR can improve early diagnosis of pertussis, ensure proper treatment, and may help with outbreak control.

The maximum incidence of pertussis in young children confirms the importance of their timely immunization.The goal is – to study the timeliness of vaccination against whooping cough, causes of violation of the vaccination schedule in young children, the effect of recombinant interferon-a on the post-vaccination period.Materials and methods: the vaccination history and data on the course of the post-vaccination period after immunization with DPT and DaPT vaccines of 469 children at the age of 3–24 months were studied.Results. The analysis showed that 14,9% of the observed children were not vaccinated against whooping cough in a timely manner. Of these: 34,3% had a written refusal to vaccinate (5.1% of the total number of observed children), in 32,8% of cases, the vaccination schedule was violated due to late arrival of parents, 32,9% of children by the start of immunization had medical challenges, and only half of them had justified contraindications. Non-serious side effects associated with immunization were observed in 11.3% of cases, statistically more often with DTP (22,0%) compared with DaPT (5.,5%). General and local reactions, in general, were recorded on DPT (6,9% and 15,1%, respectively) and less often developed with the use of DaPT (1,0% and 4,5%, respectively). Within 1 month after immunization, 16,2% of the observed children had an acute respiratory viral infection of varying severity. Those who did not receive antiviral therapy more often carried the disease in a moderate and severe form, which in all cases led to the postponement of the administration of the second and third doses of the vaccine.Conclusion. To increase the timeliness of vaccination of children against whooping cough, medical professionals should persistently remind parents about the timing of turnout for the next vaccination, when making medical withdrawals, be guided by modern methodological documents and instructions for vaccines. The use of antiviral and immunomodulatory effects of IFN-alpha drugs allows us to comply with the recommended schedule for vaccination of children with a high risk of SARS in the post-vaccination period.

Despite ample evidence of the safety and efficacy of the influenza vaccine and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy, two-thirds of pregnant women do not receive these vaccines. Providers have a significant role in increasing prenatal vaccine uptake. It is important to understand how different sources of vaccine prescribing information, such as Food and Drug Administration package inserts, influence provider recommendations. We aimed to examine the role of vaccine package inserts in provider recommendations and perceptions of safety and effectiveness of vaccines during pregnancy. A cross-sectional survey was mailed to a random, weighted sample of American College of Obstetricians and Gynecologists Fellows living in the United States in March 2019. Providers were asked about their attitudes toward package inserts, and to evaluate sample package insert statements following two different labeling rules. Their evaluations of each rule were then compared. Of the 321 respondents, the majority (90%, 288/321) recommended and/or administered maternal vaccinations. Few respondents (7.8%, 25/321) read package inserts for information regarding vaccination. Respondents were less likely to recommend sample vaccines with Pregnancy and Lactation Labeling Rule-complying inserts (46.1%, 148/321) than vaccines with Pregnancy Category inserts (87.5%, 282/321). Although most providers did not actively utilize vaccine package inserts to inform recommendations, the previous Pregnancy Categories rule was preferred compared to the Pregnancy and Lactation Labeling Rule. Collaborative efforts to update inserts with current clinical practices for pregnancy would be valuable in reducing apprehensiveness around package inserts to generate safer and more cogent recommendations for pregnant women.

INTRODUCTION: Pertussis is a highly contagious respiratory disease that results in disproportionate morbidity and mortality in infants who have yet to receive the primary diphtheria-tetanus-pertussis vaccine series. In the preceding decades numerous countries started to pursue either prenatal vaccination of pregnant women or postpartum vaccination of caregivers to protect infants. Despite proven benefit, maternal uptake of pertussis vaccine continues to be suboptimal. AREAS COVERED: Many studies have been conducted to address the suboptimal uptake of maternal pertussis vaccination. This systematic review was undertaken to systematically identify those studies, highlight the most successful strategies and find the knowledge gaps that need to be filled over the coming years to improve vaccine uptake. Twenty-five studies were identified from six different databases. EXPERT COMMENTARY: Five different interventions were shown to be successful in promoting uptake of pertussis vaccination: (1) standing orders, (2) opt-in orders, (3) provider education, (4) on-site vaccination and (5) interactive patient education. Three major knowledge gaps were also identified that need to be filled over the coming years: (1) lack of studies in low- and middle-income countries, (2) lack of studies targeting midwives and/or home birth and (3) lack of studies on the process of vaccine communication.

A case of whooping cough in a moderate form in a child of the first month of life is described in the presented clinical observation. The moderate form was manifested by the duration of the preconvulsive period up to 5 days, the appearance of cyanosis of the face when coughing in the early stages of the disease (1 week), an increase in the number of coughing attacks. The difficulties of treating pertussis in young children are demonstrated by our observation of the course of the disease. There is no vaccination against pertussis in children in the family due to the refusal of parents and children with prolonged coughing were not examined at the outpatient stage. As a result, chemoprophylaxis was not performed on time and the newborn was discharged from the hospital to the center of pertussis infection. The solution to the problem of reducing the incidence in children in the first months of life should be vaccination of pregnant women in the last stages, and vaccination of the environment, including agerelated revaccinations.

Pertussis, caused by Bordetella pertussis, is a reemerging disease that can produce severe disease manifestations in infants, including pulmonary hypertension (PH). B. pertussis-induced PH is a major risk factor for infection-induced death, but the molecular mechanisms promoting PH are unknown and there is no effective treatment. We examined B. pertussis-induced PH in infant and adult mouse models of pertussis by Fulton index, right heart catheterization, or Doppler echocardiogram. Our results demonstrate that B. pertussis-induced PH is age related and dependent on the expression of pertussis toxin by the bacterium. Hence, pertussis toxin-targeting treatments may ameliorate PH and fatal infant infection.

Background Infections caused by Bordetella pertussis are frequent and responsible for cases of huge severity in unvaccinated young infants. However, clinical manifestations vary and mimic other respiratory diseases as respiratory viruses. Methods A prospective cohort study was performed with infants under 1 old, hospitalized with suspected pertussis. All infants were submitted to etiological research to identify Bordetella pertussis (nasopharynx swab for culture and/or PCR) and respiratory viruses (nasopharyngeal aspirate for indirect immunofluorescence). Clinical and demographic data were collected. Results Among 59 infants, an etiological agent was identified in 37 (62.8%). Respiratory virus was identified in 19 (32%) and Bordetella pertussis in 14 (23.7%) as sole agent. Codetection was found in 4 (7%). Younger age, absence of fever, lack of BP immunization, leukocytosis > 20,000/mm3, lymphocytosis >10,000/mm3 were associated to a greater chance of pertussis. Wheezing and living with siblings were associated with viral infection. After adjustment for confounders, the most important predictors were presence of wheezing for respiratory virus and leukocytosis for pertussis. The severity of infections by RV and BP were similar. Conclusion Respiratory virus infections are frequent in cases of clinical suspicion of pertussis and may actually exceed the prevalence of BP. Clinical/laboratory characteristics may suggest the etiology, but they are not pathognomonic, which stresses the need for respiratory virus and Bordetella pertussis research in this clinical situation.

Pertussis is a highly contagious disease of the respiratory tract caused by Bordetella pertussis. Although the burden of pertussis is highest in children, available data suggests that pertussis in the elderly and those with underlying chronic conditions or illnesses can result in significant morbidity, mortality and costs. We undertook a comprehensive review to assess the association between pertussis and chronic conditions/illnesses. A search was undertaken on 17 June 2019 across EMBASE, Medline and BIOSIS. Citations were limited to those in English, in humans and published since 1 January 1990. There were 1179 papers identified with an additional 70 identified through a review of the reference lists. Of these, 34 met the inclusion criteria. Papers included were categorised in groups, those which reported: associations between prior pertussis and subsequent chronic conditions or illnesses; a link between chronic conditions/illnesses and subsequent risk of pertussis; and those which reported on the effect of the chronic conditions/illnesses on pertussis complications or exacerbations. Pertussis appears to increase the likelihood of developing some chronic conditions/illnesses, but also appears to decrease the likelihood of developing some haematological cancers. There were several chronic conditions/illnesses where the study results were mixed, and several studies that found no association with previous pertussis. There were also studies which showed that having some comorbid health condition(s) might increase the risk of developing pertussis. Three studies showed pertussis can lead to increased exacerbations of chronic conditions/illnesses and associated hospitalisations, although one study showed it reduced the effects of chronic bronchitis. Previous pertussis appears to contribute to the increased likelihood of developing some respiratory conditions like asthma, and conversely those with asthma or COPD are at increased risk of severe pertussis requiring further intervention. Further research is required to confirm or disprove these associations, and to characterise the pathophysiological mechanisms behind the potential associations with pertussis., Plain Language Summary Pertussis, or whooping cough as it is more commonly known, is a respiratory disease that mainly affects young children, although it can be caught at any age. An increasing number of cases are being identified in older adults. This is concerning since older people typically have other underlying health conditions that can increase the risk of severe outcomes leading to increased mortality. We assessed 34 published studies that examined the link between whooping cough and some health conditions. Several studies found that prior whooping cough was more likely in those with an underlying health condition, and this was particularly true in those with respiratory conditions like asthma and chronic obstructive pulmonary disease, whilst there were also studies which showed that having some health condition(s) might increase the risk of developing severe whooping cough which might require medical attention or hospitalisation. There was also some evidence that previous whooping cough might be protective against some blood cancers. Whooping cough was shown to exacerbate several underlying health conditions, although a single study found that it may reduce the risk of chronic bronchitis exacerbations. More research is required to corroborate these findings.

Background and objectives 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. Materials and methods 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. Results 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. Conclusion Early ET may be a useful and rapid life-saving treatment in children with critical pertussis and severe leucocytosis before cardiopulmonary complications appear.

Background Limited data exist on the impact of maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccination for preterm born infants. We report its effect at birth and on antibody-mediated immune responses to a DTaP-IPV-HB-PRP~T vaccine in preterm compared with term infants. Methods Women delivering at term or prematurely were either vaccinated with a Tdap vaccine (Boostrix; GSK) during pregnancy or not vaccinated in the last 5 years. Cord and maternal blood were collected at delivery. Infants were vaccinated with DTaP-IPV-HB-PRP~T vaccine (Hexyon; Sanofi Pasteur) and blood collected before and 1 month after primary (8-12-16 weeks) and before and 1 month after booster vaccination (13 or 15 months for preterm and term, respectively). Immunoglobulin G antibodies against all antigens included in DTaP-IPV-HB-PRP~T vaccine were measured (NCT02511327). Results Cord blood geometric mean concentrations (GMCs) in preterm infants from Tdap-vaccinated women were significantly higher than in term and preterm infants from unvaccinated women. A longer time interval between maternal vaccination and delivery resulted in higher cord blood GMCs in preterm infants. Equal GMCs in term and preterm infants from Tdap-vaccinated women were observed after primary vaccination. After boosting, significantly lower GMCs were seen for pertussis toxin, filamentous hemagglutinin, and tetanus toxoid in preterm compared with term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women. Conclusions Preterm infants profit from maternal Tdap vaccination. Prematurity did not influence primary immune responses in the presence of maternal antibodies but was associated with a lower booster immune response.

Active immunization in pregnancy is recommended for the influenza and the tetanus, diphtheria, and acellular pertussis (Tdap) vaccines. Evidence indicates vaccine effectiveness in preventing influenza-related hospitalizations and pertussis in early infancy. We investigate vaccine uptake in pregnant and non-pregnant women through a sample of young women and consultant gynecologists, along with the potential predisposing and/or enabling factors affecting attitudes to vaccination (knowledge, beliefs, barriers). A cross-sectional study was conducted between June and September 2019, with a sample of 251 women and 14 consultant gynecologists at the Local Health Authority (ASL01) of the Abruzzo Region (Italy), using an anonymous, self-report questionnaire survey. Among the participants, 5.6% of women had received influenza vaccination, 16.4% had received Tdap during pregnancy and only 1.2% had received both vaccines. The assessment of the psychometric attitudinal variables has suggested a more positive willingness to receive Tdap than influenza vaccine among women, as the former is considered more important for the maternal and neonatal health. Health care workers have reported vaccine safety concerns, lack of information, and misconceptions about the need for vaccination as barriers to immunization in pregnant women. The results of this study will contribute to defining the goals and strategies to increase vaccine uptake under the current recommendations, through promoting effective training programs for all health care workers involved (gynecologists, obstetricians, public health physicians).

Background The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Rhesus macaques have been shown to be ideal animal models for several infectious diseases, but a model of infectious pertussis has not been established in these organisms. Studies on rhesus macaque models of pertussis were performed in the 1920s–1930s, but limited experimental details are available. Recent monkey pertussis models have not been successful because the typical clinical symptoms and transmission have not been achieved. Methods In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using an aerosol method to evaluate the feasibility of this system as an animal model of pertussis. Results Upon aerosol infection, monkeys infected with the recently clinically isolated B.p strain 2016-CY-41 developed the typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and interanimal transmission of pertussis. Both systemic and mucosal humoral responses were induced by B.p. Conclusion These results demonstrate that a model of pertussis was successfully established in infant rhesus macaques. This model provides a valuable platform for research on pertussis pathogenesis and evaluation of vaccine candidates.

Pertussis, mainly caused by Bordetella pertussis, is a severe respiratory disease that can be fatal, especially in young infants. Vaccines, massively implemented since the middle of the last century, have substantially reduced the pertussis incidence, but have not been able to fully control the disease. One of the shortcomings of current pertussis vaccines is their inability to prevent infection by and transmission of B. pertussis, in contrast to immunity following natural infection. We have developed the live attenuated nasal vaccine BPZE1 and have shown that it prevents both disease and B. pertussis infection in preclinical models. This vaccine is now in clinical development. However, the initial clinical studies have suggested that vaccine take is hampered by pre-existing antibodies to pertactin. Here, we have constructed a pertactin-deficient BPZE1 derivative called BPZE1P in order to overcome this limitation. BPZE1P colonized the murine respiratory tract as efficiently as BPZE1 and induced antibodies at levels similar to those elicited by BPZE1. In the presence of pre-existing antibodies induced by acellular pertussis vaccination, BPZE1P colonized the mouse respiratory tract more efficiently than BPZE1. Both vaccines protected equally well the murine lungs and noses from challenge with laboratory and clinical strains of B. pertussis, including pertactin-deficient strains, against which current acellular pertussis vaccines are less efficient. BPZE1P may thus be an interesting alternative to BPZE1 to overcome vaccine take limitations due to pre-existing antibodies to pertactin.

Background Pertussis is an acute respiratory tract disease caused by Bordetella pertussis. In 2014, 24.1 million pertussis cases, resulting in 160,700 deaths, were estimated to have occurred worldwide. This study aimed to determine the epidemiology of pertussis among patients with clinically compatible illness who visited selected hospitals in the Amhara Regional State of Ethiopia. Methods A cross-sectional study design was used to review pertussis patients with clinically compatible illness. Nasopharyngeal swabs were collected from 515 patients from July 2018 through February 2019. DNA was extracted from all nasopharyngeal swabs and samples were analyzed using real-time (RT-) PCR. Crude and adjusted odds ratios with corresponding 95% confidence intervals were estimated using bivariable and multivariable logistic regression analysis, respectively. Results The overall prevalence of Bordetella species among the study participants was 156 of 515 (30.3%) [95% CI = 26.4–34.6] as determined by Bordetella RT-PCR, including: 65 (41.7%) B. pertussis, 89 (57.1%) indeterminate B. pertussis, one (0.6%) Bordetella holmesii and one (0.6%) Bordetella parapertussis. Conclusions This study found that pertussis is potentially endemic and a common health problem among patients visiting health institutions in the Amhara Regional State of Ethiopia. More data regarding pertussis in Ethiopia could inform development of effective prevention strategies.

Despite modern diphtheria-tetanus-pertussis (DTP) vaccines and high vaccine coverage, a resurgence of pertussis (whooping cough) has been observed globally. In North America and Europe, high vaccine coverage in children has led to a shift in the age-specific peak incidence of infection away from infants and towards older children and adolescents. However, much less is known about the prevalence of pertussis in older children and adults in the Middle East. A systematic search of MEDLINE, EMBASE, and BIOSIS was undertaken to identify studies published between 1 January 1990 and 17 June 2019, with information on pertussis epidemiology, burden of illness, and mortality in school-aged children, adolescents, and adults in the Middle East. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible because of the mix of methodologies used. The results showed that surveillance data are weak or missing in most Middle Eastern countries, and among 24 epidemiological studies identified, most were from Iran (14), Israel (4), and Turkey (3), with single studies from the United Arab Emirates and Iraq. Despite various surveillance periods, clinical definitions, and antibody cut-off values used across the studies, the reported seroprevalence of pertussis antibodies suggested that adolescents and adults are commonly exposed to pertussis in the community and that vaccine-acquired immunity from childhood wanes. Few countries in the Middle East include a diphtheria-tetanus-acellular pertussis (Tdap) booster for adolescents on the national schedule. Israel was the only country with epidemiological data in a population that received Tdap, and the study showed that after the introduction of the adolescent booster dose, there was decrease in pertussis among children aged 5-14 years. To conclude, results from the Middle East suggest that in common with other regions, pertussis is widely circulating and that it might be shifting towards older age groups.

Background Adult vaccinations may reduce risk for dementia. However, it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia. Methods Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were at least 65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of the 2 index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and age subgroups (65–69, 70–74, and ≥75 years). Results VHA patients were, on average, 75.6 (SD ± 7.5) years of age, 4% female, and 91.2% were White. MarketScan patients were 69.8 (SD ± 5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without, Tdap vaccination had a significantly lower risk for dementia in both cohorts (VHA: hazard ratio [HR] = 0.58; 95% confidence interval [CI]:0.54–0.63 and MarketScan: HR = 0.58; 95% CI:0.48–0.70). Conclusions Tdap vaccination was associated with a 42% lower dementia risk in 2 cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.