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Frontiers in Immunology 2021Current vaccination strategies against pertussis are sub-optimal. Optimal protection against , the causative agent of pertussis, likely requires mucosal immunity....
BACKGROUND
Current vaccination strategies against pertussis are sub-optimal. Optimal protection against , the causative agent of pertussis, likely requires mucosal immunity. Current pertussis vaccines consist of inactivated whole cells or purified antigens thereof, combined with diphtheria and tetanus toxoids. Although they are highly protective against severe pertussis disease, they fail to elicit mucosal immunity. Compared to natural infection, immune responses following immunization are short-lived and fail to prevent bacterial colonization of the upper respiratory tract. To overcome these shortcomings, efforts have been made for decades, and continue to be made, toward the development of mucosal vaccines against pertussis.
OBJECTIVES
In this review we systematically analyzed published literature on protection conferred by mucosal immunization against pertussis. Immune responses mounted by these vaccines are summarized.
METHOD
The PubMed Library database was searched for published studies on mucosal pertussis vaccines. Eligibility criteria included mucosal administration and the evaluation of at least one outcome related to efficacy, immunogenicity and safety.
RESULTS
While over 349 publications were identified by the search, only 63 studies met the eligibility criteria. All eligible studies are included here. Initial attempts of mucosal whole-cell vaccine administration in humans provided promising results, but were not followed up. More recently, diverse vaccination strategies have been tested, including non-replicating and replicating vaccine candidates given by three different mucosal routes: orally, nasally or rectally. Several adjuvants and particulate formulations were tested to enhance the efficacy of non-replicating vaccines administered mucosally. Most novel vaccine candidates were only tested in animal models, mainly mice. Only one novel mucosal vaccine candidate was tested in baboons and in human trials.
CONCLUSION
Three vaccination strategies drew our attention, as they provided protective and durable immunity in the respiratory tract, including the upper respiratory tract: acellular vaccines adjuvanted with lipopeptide LP1569 and c-di-GMP, outer membrane vesicles and the live attenuated BPZE1 vaccine. Among all experimental vaccines, BPZE1 is the only one that has advanced into clinical development.
Topics: Humans; Immunity, Mucosal; Pertussis Vaccine; Whooping Cough
PubMed: 34211481
DOI: 10.3389/fimmu.2021.701285 -
Expert Review of Vaccines Jul 2021Pertussis is a highly contagious respiratory disease that results in disproportionate morbidity and mortality in infants who have yet to receive the primary...
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 began 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 remain 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 OPINION
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.
Topics: Diphtheria-Tetanus-Pertussis Vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Infant; Pertussis Vaccine; Pregnancy; Vaccination; Whooping Cough
PubMed: 34129416
DOI: 10.1080/14760584.2021.1940146 -
Infectious Diseases and Therapy Sep 2021Pertussis is a highly contagious disease of the respiratory tract caused by Bordetella pertussis. Although the burden of pertussis is highest in children, available data... (Review)
Review
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.
PubMed: 34117998
DOI: 10.1007/s40121-021-00465-z -
BMC Pediatrics Jun 2021For evidence-based decision making, primary care physicians need to have specific and reliable information on the pre-test probabilities of underlying diseases and a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For evidence-based decision making, primary care physicians need to have specific and reliable information on the pre-test probabilities of underlying diseases and a symptom's course. We performed a systematic review of symptom-evaluating studies in primary care, following three research questions: (1) What is the prevalence of the symptom cough in children consulting primary care physicians? (2) What are the underlying aetiologies of cough and the respective frequencies? (3) What is the prognosis of children with cough?
METHODS
Following a pre-defined algorithm and independent double reviewer ratings we searched MEDLINE and EMBASE. All quantitative original research articles in English, French or German were included if they focused on unselected study populations of children consulting a primary care physician for cough. We used the random effects model for meta-analysis in subgroups, if justifiable in terms of heterogeneity.
RESULTS
We identified 14 eligible studies on prevalence, five on aetiology and one on prognosis. Prevalence estimates varied between 4.7 and 23.3% of all reasons for an encounter, or up to estimates of 60% when related to patients or consultations. Cough in children is more frequent than in adults, with lowest prevalences in adolescents and in summer. Acute cough is mostly caused by upper respiratory tract infections (62.4%) and bronchitis (33.3%); subacute or chronic cough by recurrent respiratory tract infection (27.7%), asthma (up to 50.4% in cough persisting more than 3 weeks), and pertussis (37.2%). Potentially serious diseases like croup, pneumonia or tuberculosis are scarce. In children with subacute and chronic cough the total duration of cough ranged from 24 to 192 days. About 62.3% of children suffering from prolonged cough are still coughing two months after the beginning of symptoms.
CONCLUSION
Cough is one of the most frequent reasons for an encounter in primary care. Our findings fit in with current guideline recommendations supporting a thoughtful wait-and-see approach in acute cough and a special awareness in chronic cough of the possibility of asthma and pertussis. Further evidence of aetiological pre-test probabilities is needed to assess the diagnostic gain based on patient history and clinical signs for differential diagnoses of cough in children.
Topics: Adolescent; Adult; Child; Cough; Family Practice; Humans; Prevalence; Primary Health Care; Prognosis
PubMed: 34088294
DOI: 10.1186/s12887-021-02739-4 -
Infectious Diseases and Therapy Sep 2021Cyclic epidemics of pertussis (whooping cough) have been observed globally over the past twenty years despite high infant vaccine coverage. The resurgence of pertussis... (Review)
Review
Cyclic epidemics of pertussis (whooping cough) have been observed globally over the past twenty years despite high infant vaccine coverage. The resurgence of pertussis in high-income countries is partly due to waning vaccine immunity in older children and adults, as well as better surveillance and diagnostics. Moreover, in adolescents and adults, pertussis symptoms are mild and similar to common cough syndromes, meaning that it is under-diagnosed in older populations. 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 Asia. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible due to the mix of methodologies used. The results showed that in East Asia, including Japan, South Korea, China, and Taiwan, pertussis is circulating in older children and adults. Diphtheria-tetanus-pertussis (DTP4) coverage is high in East Asia, yet outbreaks observed in Japan and South Korea suggest that vaccine-acquired immunity had waned in adolescents and adults. Several school outbreaks in China show that pertussis is circulating in young children, with continued circulation in adolescents and adults. There was a lack of information from Southeast/South Asian countries, although pan-Asian serosurveys showed that recent pertussis infection was common in adolescents and in adults with persistent cough. To conclude, the circulation of pertussis in Asian countries with high DTP4 coverage supports the expansion of routine vaccination to include booster doses for children at school entry and adolescents. However, surveillance is weak or absent in many countries, meaning that the true burden of pertussis, particularly among older populations, is unknown.
PubMed: 33928533
DOI: 10.1007/s40121-021-00439-1 -
Infectious Diseases and Therapy Jun 2021Despite modern diphtheria-tetanus-pertussis (DTP) vaccines and high vaccine coverage, a resurgence of pertussis (whooping cough) has been observed globally. In North... (Review)
Review
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.
PubMed: 33905101
DOI: 10.1007/s40121-021-00440-8 -
Infectious Diseases and Therapy Sep 2021The Global Pertussis Initiative recommends diphtheria-tetanus-pertussis (DTP3) vaccination of infants aged < 1 year for all African countries, and recommends the... (Review)
Review
The Global Pertussis Initiative recommends diphtheria-tetanus-pertussis (DTP3) vaccination of infants aged < 1 year for all African countries, and recommends the vaccination of pregnant women as a primary prevention strategy. However, the role of older children and adults in the transmission of pertussis in Africa is not clear. 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 Africa. Studies identified for inclusion were reviewed narratively because a statistical comparison was not possible because of the mix of methodologies used.Studies from North Africa (Morocco, Tunisia, and Algeria) reported that although DTP4 vaccine coverage is high, severe pertussis-related complications persist in young children, vaccine-acquired immunity wanes in adolescents, and household contacts are important transmitters of infection. A serosurvey in Gambia showed that 6% of the general population had pertussis antibody levels suggesting recent infection, and studies from Senegal showed that pertussis infection was endemic despite high DTP3 coverage. During a pertussis outbreak in Ethiopia, the case fatality rate was 3.7% overall, and 6.3% among children aged 5-9 years. In a case-surveillance study in South Africa, the incidence of pertussis among hospitalized children was 526/100,000, and infection rates were higher in HIV-exposed and -infected children compared with uninfected children. In conclusion, the highest burden of pertussis in Africa is among infants, and surveillance is lacking in many African countries meaning that the burden of pertussis among infants and infection rates among older children and adults are not well reported, and likely underestimated.
PubMed: 33881713
DOI: 10.1007/s40121-021-00442-6 -
Human Vaccines & Immunotherapeutics Jun 2021We aimed to describe the impact of pertussis on adolescents, adults, and older adults over 2007-2018 in selected Latin American countries by reviewing the literature. We...
We aimed to describe the impact of pertussis on adolescents, adults, and older adults over 2007-2018 in selected Latin American countries by reviewing the literature. We searched the Medline, Embase, Scopus, LILACS, Scielo, Google Scholar, CAPES Journals Web-portal, and Cochrane databases for observational epidemiological studies, clinical trials, and systematic reviews of primary studies. Data were extracted and analyzed for all individuals aged ≥10 years. Of 6,891 studies identified only 25 were eligible. Studies were conducted in Brazil (14), Argentina (4), Colombia (4), Mexico (2) and Chile (1). Epidemiological data among target population were limited. No studies clearly assessed the status of asymptomatic or oligosymptomatic carriers in these age groups. Among all pertussis cases identified, the percentage of patients ≥10 years-old ranged between 2.1% and 66.7% depending on country and sample characteristics. The definition of cases, diagnostic methods, and age groups were not consistent across studies.
Topics: Adolescent; Aged; Argentina; Brazil; Child; Chile; Colombia; Humans; Latin America; Mexico; Whooping Cough
PubMed: 33734002
DOI: 10.1080/21645515.2020.1827613 -
Journal of Preventive Medicine and... Dec 2020In industrialized countries, the routine use of Bordetella pertussis vaccines has shifted the burden of Bordetella pertussis disease from children to infants,... (Review)
Review
Immunogenicity and antibody persistence of diphteria-tetanus-acellular pertussis vaccination in adolescents and adults: a systematic review of the literature showed different responses to the available vaccines.
INTRODUCTION
In industrialized countries, the routine use of Bordetella pertussis vaccines has shifted the burden of Bordetella pertussis disease from children to infants, adolescents and adults, leading to the necessity for booster doses.
MATERIALS AND METHODS
We prepared a review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) with the aims of: a) describing the immunogenicity of the main available vaccines for adolescents and adults; b) describing antibody persistence after immunization with the main vaccines available in childhood and adults and, also, possible co-administration; and c) identifying the gold standard for adolescent and adult immunizations.
RESULTS
We identified 6906 records. After removing duplicate records, we included 12 RCT (Randomized Controlled Trial) (people aged 11-73): 7 of these studies had only 1 control group, 4 had 2 control groups and 1 had 5 control groups; moreover, of the 12 studies included, only 2 regarded co-administration, while all concerned immunogenicity. Nine of the 12 studies had a Jadad score above 3 points, and 10 out of 12 met the criteria of Cochrane Back Review Group Criteria List for Methodological Quality Assessment.
DISCUSSION AND CONCLUSION
We found a limited number of good-quality RCTs investigating our object. The 5-component vaccines, although containing a lower dose of antigen, proved more effective than the 1-component vaccine. Evidence supports the use of 5-component vaccines for booster sessions in adolescence and adulthood.
Topics: Adolescent; Adult; Antibodies, Bacterial; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Humans; Immunization, Secondary; Immunogenicity, Vaccine; Randomized Controlled Trials as Topic; Tetanus; Vaccination; Whooping Cough
PubMed: 33628957
DOI: 10.15167/2421-4248/jpmh2020.61.4.1832 -
The Cochrane Database of Systematic... Aug 2020Reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global priority. Contact tracing identifies people who were recently in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global priority. Contact tracing identifies people who were recently in contact with an infected individual, in order to isolate them and reduce further transmission. Digital technology could be implemented to augment and accelerate manual contact tracing. Digital tools for contact tracing may be grouped into three areas: 1) outbreak response; 2) proximity tracing; and 3) symptom tracking. We conducted a rapid review on the effectiveness of digital solutions to contact tracing during infectious disease outbreaks.
OBJECTIVES
To assess the benefits, harms, and acceptability of personal digital contact tracing solutions for identifying contacts of an identified positive case of an infectious disease.
SEARCH METHODS
An information specialist searched the literature from 1 January 2000 to 5 May 2020 in CENTRAL, MEDLINE, and Embase. Additionally, we screened the Cochrane COVID-19 Study Register.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-RCTs, quasi-RCTs, cohort studies, cross-sectional studies and modelling studies, in general populations. We preferentially included studies of contact tracing during infectious disease outbreaks (including COVID-19, Ebola, tuberculosis, severe acute respiratory syndrome virus, and Middle East respiratory syndrome) as direct evidence, but considered comparative studies of contact tracing outside an outbreak as indirect evidence. The digital solutions varied but typically included software (or firmware) for users to install on their devices or to be uploaded to devices provided by governments or third parties. Control measures included traditional or manual contact tracing, self-reported diaries and surveys, interviews, other standard methods for determining close contacts, and other technologies compared to digital solutions (e.g. electronic medical records).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened records and all potentially relevant full-text publications. One review author extracted data for 50% of the included studies, another extracted data for the remaining 50%; the second review author checked all the extracted data. One review author assessed quality of included studies and a second checked the assessments. Our outcomes were identification of secondary cases and close contacts, time to complete contact tracing, acceptability and accessibility issues, privacy and safety concerns, and any other ethical issue identified. Though modelling studies will predict estimates of the effects of different contact tracing solutions on outcomes of interest, cohort studies provide empirically measured estimates of the effects of different contact tracing solutions on outcomes of interest. We used GRADE-CERQual to describe certainty of evidence from qualitative data and GRADE for modelling and cohort studies.
MAIN RESULTS
We identified six cohort studies reporting quantitative data and six modelling studies reporting simulations of digital solutions for contact tracing. Two cohort studies also provided qualitative data. Three cohort studies looked at contact tracing during an outbreak, whilst three emulated an outbreak in non-outbreak settings (schools). Of the six modelling studies, four evaluated digital solutions for contact tracing in simulated COVID-19 scenarios, while two simulated close contacts in non-specific outbreak settings. Modelling studies Two modelling studies provided low-certainty evidence of a reduction in secondary cases using digital contact tracing (measured as average number of secondary cases per index case - effective reproductive number (R )). One study estimated an 18% reduction in R with digital contact tracing compared to self-isolation alone, and a 35% reduction with manual contact-tracing. Another found a reduction in R for digital contact tracing compared to self-isolation alone (26% reduction) and a reduction in R for manual contact tracing compared to self-isolation alone (53% reduction). However, the certainty of evidence was reduced by unclear specifications of their models, and assumptions about the effectiveness of manual contact tracing (assumed 95% to 100% of contacts traced), and the proportion of the population who would have the app (53%). Cohort studies Two cohort studies provided very low-certainty evidence of a benefit of digital over manual contact tracing. During an Ebola outbreak, contact tracers using an app found twice as many close contacts per case on average than those using paper forms. Similarly, after a pertussis outbreak in a US hospital, researchers found that radio-frequency identification identified 45 close contacts but searches of electronic medical records found 13. The certainty of evidence was reduced by concerns about imprecision, and serious risk of bias due to the inability of contact tracing study designs to identify the true number of close contacts. One cohort study provided very low-certainty evidence that an app could reduce the time to complete a set of close contacts. The certainty of evidence for this outcome was affected by imprecision and serious risk of bias. Contact tracing teams reported that digital data entry and management systems were faster to use than paper systems and possibly less prone to data loss. Two studies from lower- or middle-income countries, reported that contact tracing teams found digital systems simpler to use and generally preferred them over paper systems; they saved personnel time, reportedly improved accuracy with large data sets, and were easier to transport compared with paper forms. However, personnel faced increased costs and internet access problems with digital compared to paper systems. Devices in the cohort studies appeared to have privacy from contacts regarding the exposed or diagnosed users. However, there were risks of privacy breaches from snoopers if linkage attacks occurred, particularly for wearable devices.
AUTHORS' CONCLUSIONS
The effectiveness of digital solutions is largely unproven as there are very few published data in real-world outbreak settings. Modelling studies provide low-certainty evidence of a reduction in secondary cases if digital contact tracing is used together with other public health measures such as self-isolation. Cohort studies provide very low-certainty evidence that digital contact tracing may produce more reliable counts of contacts and reduce time to complete contact tracing. Digital solutions may have equity implications for at-risk populations with poor internet access and poor access to digital technology. Stronger primary research on the effectiveness of contact tracing technologies is needed, including research into use of digital solutions in conjunction with manual systems, as digital solutions are unlikely to be used alone in real-world settings. Future studies should consider access to and acceptability of digital solutions, and the resultant impact on equity. Studies should also make acceptability and uptake a primary research question, as privacy concerns can prevent uptake and effectiveness of these technologies.
Topics: Botswana; COVID-19; Cohort Studies; Contact Tracing; Coronavirus Infections; Disease Outbreaks; Hemorrhagic Fever, Ebola; Humans; Mobile Applications; Models, Theoretical; Patient Isolation; Privacy; Quarantine; Secondary Prevention; Sierra Leone; Tuberculosis; United States; Whooping Cough
PubMed: 33502000
DOI: 10.1002/14651858.CD013699