The current state of pertussis vaccination in pregnancy around the world, with recommendations for improved care: Consensus statements from the Global Pertussis Initiative.

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers.

Pertussis in India: Past, Present, and Future.

While vaccines have markedly reduced the incidence of pertussis, a resurgence has occurred in many countries. Until recently, pertussis has not been recognized as an important public health challenge in India due to its successful infant immunization program. However, India still accounts for a large proportion of the world's cases, and increasing reports of pertussis in other countries and in neonates have regenerated interest in pertussis among Indian authorities. The Global Pertussis Initiative (GPI) Annual Meeting was held virtually in October 2020, in part, to gain a better understanding of the epidemiology and disease burden of pertussis and to explore opportunities to improve its prevention in India. There was a consensus that pertussis cases are being underestimated in India due to multiple factors, such as a reliance on passive surveillance and diagnostic challenges. India offers both whole-cell pertussis and acellular pertussis vaccines, but vaccine coverage is inconsistent across regions due to differences in vaccine availability, access to health care, and regional administrative challenges. This report summarizes the outcomes and considers the key clinical implications of this meeting. The GPI agreed that active surveillance of pertussis in India would be optimal and recommended several studies, including serosurveillance among women of reproductive age to assess the prevalence of recent pertussis infection and to enable policy changes that will enhance the rational use of acellular and whole-cell vaccines. It also recommended engagement with nongovernmental organizations in order to encourage pregnancy immunization in the public sector. To achieve effective control of pertussis in the future, the GPI recognizes there are opportunities to characterize the burden of pertussis in India appropriately and increase vaccination coverage in multiple age groups.

Vaccination in Pregnancy against Pertussis: A Consensus Statement on Behalf of the Global Pertussis Initiative.

Infants are at high risk for severe morbidity and mortality from pertussis disease during early infancy. Vaccination against pertussis in pregnancy has emerged as the ideal strategy to protect infants during these early, vulnerable, first months of life. On 30 November and 1 December 2021, the Global Pertussis Initiative held a meeting that aimed to discuss and review the most up-to-date scientific literature supporting vaccination against pertussis in pregnancy and outstanding scientific questions. Herein, we review the current and historically published literature and summarize the findings as consensus statements on vaccination against pertussis in pregnancy on behalf of the Global Pertussis Initiative.

Pertussis vaccination in mixed markets: Recommendations from the Global Pertussis Initiative.

The Global Pertussis Initiative is an expert scientific forum that publishes consensus recommendations concerning pertussis for many regions of the world. Here, we give recommendations for the primary vaccination of infants in those countries where whole-cell pertussis (wP)- and acellular pertussis (aP)-containing combination vaccines are used in parallel. A selective literature review was performed concerning the influence on safety, immunogenicity, and effectiveness of mixing wP- and aP-containing vaccines for primary immunization of infants. In addition, local data were collected from various countries and the results discussed in a face-to-face meeting. Very few data addressing issues of mixing combination vaccines were identified, and no data were available concerning the effectiveness or duration of protection. It was also found that pharmacovigilance data are scarce or lacking in those countries where they would be needed the most. We then identified frequent problems occurring in low- and middle-income countries (LMICs) where both vaccine types are used. Relying on local knowledge, we give practical recommendations for a variety of situations in different settings. Specific needs for additional data addressing these issues were also identified. International bodies, such as the World Health Organization (WHO), as well as vaccine producers should try to find ways to highlight the problems of mixing wP- and aP-containing combination vaccines with robust data. Countries are urged to improve on their pharmacovigilance for vaccines. For practicing physicians, our recommendations offer guidance when wP- and aP-containing vaccines are used in parallel during primary immunization.

Global Gaps in Training Opportunities for Pediatricians and Pediatric Subspecialists.

OBJECTIVE: A comprehensive, well-trained pediatric workforce is needed to ensure high-quality child health interventions around the globe. Further understanding of pediatric workforce training capacity would assist planning at the global and country level. The purpose of this study was to better understand the availability and process of training programs for pediatricians and pediatric subspecialists worldwide, as well as in-country presence of subspecialists. METHODS: A survey was developed and distributed by e-mail to national pediatric leaders across the globe. The survey asked about the number of pediatric training programs, duration and logistics of training, and whether practicing pediatric subspecialists and subspecialty training programs were available in their country. RESULTS: We received responses from 121 of the 166 countries contacted (73%). Of these, 108 countries reported the presence of one or more general pediatric postgraduate training programs, ranging from 1 to 500 programs per country. The number of training programs did not vary significantly by gross domestic product but did vary by region, with the fewest in Africa (P < .001). Most countries identified national guidelines for training (82% of countries) and accreditation (84% of countries). Availability of pediatric subspecialists varied significantly by income and region, from no subspecialties available in 4 countries to all 26 queried subspecialties available in 17 countries. Neonatology was most common, available in 88% of countries. Subspecialty training programs were less available overall, significantly correlating with country income. CONCLUSION: Education for general pediatrics and pediatric subspecialties is quite limited in many of the countries surveyed, particularly in Africa. The creation of additional educational capacity is a critical issue challenging the adequate provision of pediatrics and pediatric subspecialty services.

Medical student selection criteria and junior doctor workplace performance.

BACKGROUND: Medical school selection decisions have consequences beyond graduation. With generally low attrition rates, most medical students become junior doctors. Universities are therefore not just selecting students into a medical course; they are choosing the future medical workforce. Understanding the relationship between selection criteria and outcomes beyond the successful completion of a medical degree may inform approaches to student selection. METHODS: A retrospective data matching study was conducted involving 39 interns employed by a South Australian local health network in 2017 who had originally entered Flinders University's medical school through a graduate pathway. Student selection data were matched with internship workplace performance scores (measured by supervising consultants' reports across five clinical rotations using a standardised assessment). Correlational analyses then examined associations between these two sets of variables. RESULTS: An overall selection rank (equal thirds of weighted Grade Point Average from a prior degree, a panel interview, and a national selection test) was moderately associated with all performance measures, accounting for up to 25% of variance. Both weighted Grade Point Average and the interview had multiple and mostly moderate correlations with performance. An increasing number of years taken to complete the course was associated with poorer workplace performance across multiple outcome measures (moderate to strong negative associations with 31 to 62% of shared variance), as was age to a lesser extent (7 to 14%). The national selection test contributed a single and small relationship accounting for 5% of variance with one outcome measure. CONCLUSIONS: Selection into medicine is a critical assessment given that most students become doctors. This study found multiple associations between selection scores and junior doctor workplace performance measures in the internship year, with weighted Grade Point Average from a prior degree and an interview appearing more important than the national selection test. Future collaborative research should map desired workplace performance outcomes to initial student selection and explore the impact of changes to selection which focus on assessment of these domains. The association between slower course progression and poorer workplace performance should also be examined.

Pertussis in Latin America: Recent epidemiological data presented at the 2017 Global Pertussis Initiative meeting.

The Global Pertussis Initiative (GPI) is an expert scientific forum that publishes consensus recommendations for pertussis monitoring, prevention, and treatment across many regions of the world. Here, we report on the regional 2017 GPI meeting on the Americas, focusing on Latin America. Information on current pertussis epidemiology, surveillance, vaccine strategies, diagnostic capabilities, disease awareness, and major local obstacles was presented by researchers from Argentina, Brazil, Colombia, Costa Rica, El Salvador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela. Pertussis outbreaks have occurred during the last decade in the majority of participant countries and have been followed by improvements in surveillance. In the countries that introduced maternal immunization during pregnancy, a reduction in the infant case fatality rate has been detected. All countries need to maintain and improve pertussis surveillance to reach primary vaccination coverage >90%. Moreover, countries without maternal immunization programs should strongly consider them.

Immune biomarkers predicting bronchiolitis disease severity: A systematic review.

Bronchiolitis is one of the leading causes of hospitalisation in infancy, with highly variable clinical presentations ranging from mild disease safely managed at home to severe disease requiring invasive respiratory support. Identifying immune biomarkers that can predict and stratify this variable disease severity has important implications for clinical prognostication/disposition. A systematic literature search of the databases Embase, PubMed, ScienceDirect, Web of Science, and Wiley Online Library was performed. English language studies that assessed the association between an immune biomarker and bronchiolitis disease severity among children aged less than 24 months were included. 252 distinct biomarkers were identified across 90 studies. A substantial degree of heterogeneity was observed in the bronchiolitis definitions, measures of disease severity, and study designs. 99 biomarkers showed some significant association with disease severity, but only 18 were significant in multiple studies. However, all of these candidate biomarkers had comparable studies that reported conflicting results. Conclusion: The heterogeneity among included studies and the lack of a consistently significant biomarker highlight the need for consensus on bronchiolitis definitions and severity measures, as well as further studies assessing their clinical utility both in isolation and in combination.

Where are the paediatricians? An international survey to understand the global paediatric workforce.

OBJECTIVE: Our primary objective was to examine the global paediatric workforce and to better understand geographic differences in the number of paediatricians globally. Secondary objectives were to describe paediatric workforce expectations, who provides children with preventative care and when children transition out of paediatric care. DESIGN: Survey of identified paediatric leaders in each country. SETTING: Paediatric association leaders worldwide. MAIN OUTCOME MEASURES: Paediatrician numbers, provision of primary care for children, age of transition to adult care. RESULTS: Responses were obtained from 121 countries (73% of countries approached). The number of paediatricians per 100 000 children ranged from a median of 0.5 (IQR 0.3-1.4) in low-income countries to 72 (IQR 4-118) in high-income countries. Africa and South-East Asia reported the lowest paediatrician density (median of 0.8 paediatricians per 100 000 children, IQR 0.4-2.6 and median of 4, IQR 3-9, respectively) and fewest paediatricians entering the workforce. 82% of countries reported transition to adult care by age 18% and 39% by age 15. Most countries (91%) but only 64% of low-income countries reported provision of paediatric preventative care (p<0.001, Cochran-Armitage trend test). Systems of primary care provision varied widely. A majority of countries (63%) anticipated increases in their paediatric workforce in the next decade. CONCLUSIONS: Paediatrician density mirrors known inequities in health provider distribution. Fewer paediatricians are entering the workforce in areas with already low paediatrician density, which may exacerbate disparities in child health outcomes. In some regions, children transition to adult care during adolescence, with implications for healthcare training and delivery. Paediatrician roles are heterogeneous worldwide, and country-specific strategies should be used to address inequity in child health provision.

Recommendations to control pertussis prioritized relative to economies: A Global Pertussis Initiative update.

Pertussis is a vaccine-preventable disease that causes morbidity and mortality, particularly in infants and children <5 years of age. The Global Pertussis Initiative (GPI) recommendations represent a systematic evaluation and prioritization of strategies to prevent pertussis-related infant and child deaths, reduce global disease burden and prevent resurgence through vaccination strategies and public health policies at national, regional and local levels. The GPI recommendations are based on clinical trials and observational and surveillance data, which are essential in the planning, implementation and evaluation of vaccination practices and best use of available resources. Many low- and middle-income countries (LMIC) continue to use whole-cell pertussis (wP) vaccines for primary vaccination, while most high-income countries have replaced wP with the less-reactogenic acellular pertussis (aP) vaccines. This present manuscript pertains to discussions held during the GPI's meeting on November 11-13, 2016, in Cape Town, Republic of South Africa. The GPI recommends that LMIC aim for high coverage of infant series pertussis vaccines as a priority. In LMIC and countries with constrained vaccine funding, if wP vaccines are currently used, wP should continue to be used. Furthermore, given that protection against disease and death due to pertussis in neonates is a key priority of the GPI, it recommends that ap immunization in pregnancy should be implemented as a priority in all countries if resources allow. Given that surveillance and epidemiology data on which to base vaccine decisions are important, the GPI also suggests that, in areas where wP vaccines are implemented, standardization and calibration of wP vaccines are checked, considering the many different manufacturers and variable standards of production and quality control. In addition, as immunity to pertussis wanes following the primary infant series of vaccination, the GPI further recommends that toddlers, adolescents, healthcare and childcare workers receive booster vaccine doses, where resources allow.

Pertussis in Africa: Findings and recommendations of the Global Pertussis Initiative (GPI).

Pertussis remains a major cause of morbidity and mortality, particularly in infants and young children, and despite the availability of vaccines and pertinent national and international guidelines. The disease burden is more severe in low- and middle-income countries (LMICs), especially in the African continent. Pertussis is more prevalent among young infants in Africa. Poor or no pertussis surveillance, lack of disease awareness, diagnostic limitations, and competing health priorities are considered key contributory factors for this high pertussis burden in Africa. Most African countries use whole-cell pertussis (wP) vaccines, but coverage with three primary doses of diphtheria-tetanus-pertussis vaccines falls short of the World Health Organization's recommended goal of >90%. The Global Pertussis Initiative (GPI) works toward developing recommendations through systematic evaluation and prioritization of strategies to prevent pertussis-related infant and child deaths, as well as reducing global disease burden to acceptable national, regional, and local levels. For countries using wP vaccines, the GPI recommends continuing to use wP to improve primary and toddler booster vaccination coverage. Vaccination during pregnancy is the next priority when acellular pertussis (aP) vaccines and other resources are available that directly protect newborns too young to be vaccinated, followed by, in order of priority, booster doses in older children, adolescents, healthcare workers and finally, all adults. Improved surveillance should be a high priority for African LMICs assessing true disease burden and vaccine effectiveness to inform policy. More research is warranted to evaluate the safety and efficacy of wP and aP vaccines and strategies, and to determine their optimal use.

The heterogeneity of viral bronchiolitis: A lack of universal consensus definitions.

Viral bronchiolitis is one of the most common hospital presentations in infancy and as such represents a major healthcare burden worldwide. However despite this, there are currently no effective targeted therapies nor can those infants at highest risk for developing severe disease or subsequent respiratory morbidity be predicted on initial hospital presentation. Current definitions of bronchiolitis in the published literature vary significantly in terms of the age range at presentation, specific clinical symptoms, causative virus, and the inclusion or exclusion of infants with previous presentations and/or various comorbidities. In this review, we highlight how this heterogeneity among definitions contributes to a lack of clarity on this condition and its likely multiple endotypes. We argue that without a new universal consensus definition or sets of definitions, progress into bronchiolitis will continue to be stalled.

Neutrophil infiltration and activation in bronchiolitic airways are independent of viral etiology.

BACKGROUND: Hospitalization with bronchiolitis is linked to the development of early childhood chronic wheeze and asthma. Viral etiology and severity of inflammation are potential contributing factors. Previously we observed reduced airway neutrophil infiltration in breastfed bronchiolitic infants, with a corresponding reduction in disease severity. This study aimed to examine whether respiratory viral etiology and co-infection alters the pattern of neutrophil influx, and the inflammatory mediator profile, resulting in epithelial damage in bronchiolitis. METHODS: Nasopharyngeal aspirates (NPAs) collected from hospitalized infants were assessed for viruses, soluble protein, cellular infiltrate, interleukin (IL)-6, -8, and myeloperoxidase (MPO). RESULTS: NPAs were collected from 228 bronchiolitic and 14 non-bronchiolitic infants. In the bronchiolitic cohort, human rhinovirus was most prevalent (38%), followed by respiratory syncytial virus (36%), adenovirus (10%), and human metapneumovirus (6%), with 25% positive for viral co-infections and 25% negative for all screened viruses. Viral-induced bronchiolitis was associated with increased cellular infiltrate and protein, above control, and virus-negative infants (P < 0.05). Cellular infiltrate correlated to IL-6, -8, and MPO (r = 0.331, 0.669, and 0.661; P < 0.01). Protein, IL-6, -8, and MPO differed significantly between viral groups; however, the majority of marker values for all groups fall within an overlapping, indistinguishable range, precluding their use as biomarkers of viral etiology. No significant difference was found between single and viral co-infections for any parameter. CONCLUSION: Bronchiolitic infants presenting with a detectable respiratory virus during hospitalization demonstrated elevated markers of airway tissue inflammation and injury. In this cohort, viral etiology did not discernibly modulate chemokine-mediated neutrophil infiltration and activation. Pediatr Pulmonol. 2017;52:238-246. © 2016 Wiley Periodicals, Inc.

Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013.

Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization regions were also reviewed. Findings are confounded not only by the lack of systematic and comparable observations in many areas of the world but also by the cyclic nature of pertussis with peaks occurring every 3-5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country.

Strategies to decrease pertussis transmission to infants.

The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be vaccinated. Older infants are at risk when their vaccination schedules are incomplete. Infants also bear the greatest disease burden owing to their high risk for pertussis-related complications and death; therefore, protecting them is a high priority. Two vaccine strategies have been proposed to protect infants. The first involves vaccinating pregnant women, which directly protects through the passive transfer of pertussis antibodies. The second strategy, cocooning, involves vaccinating parents, caregivers, and other close contacts, which indirectly protects infants from transmission by preventing disease in those in close proximity. The goal of this review was to present and discuss evidence on these 2 strategies. Based on available data, the GPI recommends vaccination during pregnancy as the primary strategy, given its efficacy, safety, and logistic advantages over a cocoon approach. If vaccination during pregnancy is not feasible, then all individuals having close contact with infants <6 months old should be immunized consistent with local health authority guidelines. These efforts are anticipated to minimize pertussis transmission to vulnerable infants, although real-world effectiveness data are limited. Countries should educate lay and medical communities on pertussis and introduce robust surveillance practices while implementing these protective strategies.