Pertussis, also known as whooping cough, is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. It is a cyclical and worldwide endemic disease, with waves occurring every three to five years. The disease affects all ages—infants less than 3 months of age are at highest risk of severe complications and death from whooping cough, but it is also severe for vulnerable adults.[3–6]
In children, pertussis disease is classically characterised by a paroxysmal (sudden and convulsive) cough followed by a ‘whoop’, caused by hard inhalation effort. Older patients may have mild or atypical symptoms, such as a persistent or prolonged cough, which may disturb sleep,[1,5,6] and this milder presentation can contribute to underdiagnosis of disease in adults. While the disease can be less severe in older children, adolescents and adults than in infants, B. pertussis infection concomitant with underlying conditions can lead to complications of those diseases and potentially to increased morbidity and mortality.[4,6,7]
Pertussis is a vaccine-preventable disease but is still not sufficiently controlled even in countries with high vaccine coverage in children. In recent years the disease has resurged in both low- and high-income countries.[7,8–10]
Neither natural infection-induced nor vaccine-induced immunity to pertussis disease is retained over a long period of time. Increased recognition that older children, adolescents and adults are at risk of infection and may transmit B. pertussis to younger people as vectors (including pre-vaccination neonates) (Figure 1) has driven interest in the role of waning immunity following childhood vaccination (Box 1),[1,12] and drawn attention to optimising the vaccination schedule.
Figure 1. Transmission of pertussis between adults and infants.
Adapted from Wirsing von König et al, 2002.
|Box 1. The history of pertussis vaccine development|
Disease transmission: waning immunity and adults as a vector
The change of transmission going from adolescents and adults to infants too young to be vaccinated (Box 1) is likely due to low vaccination coverage and waning immunity, rather than the change of from pertussis whole cell (wP) vaccines to pertussis acellular (aP) vaccines, according to a model using incidence data from Massachusetts. Furthermore, in studies performed in countries that kept wP for the primary vaccination in children and the first booster, the same change of transmission was observed.[21–25]
The pool of undiagnosed pertussis cases in adults, for whom any immunity has waned, provides a reservoir for transmission of potentially serious infections to very young infants who are either unvaccinated or whose vaccinations are not yet fully protective. Adults (mainly parents and grandparents) have been identified as the source of pertussis in infants and children in up to half of the cases investigated, and most infants acquire their infection from adults in their own households.[12,19] Pertussis passes frequently in the population, regardless of age.
To stop transmission from adults, since the mid-2000s, several high-income countries have added boosters for adolescents, for healthcare workers in contact with infants, and a cocooning strategy. Since 2011, vaccination in pregnancy has also been adopted in some countries to protect infants too young to be vaccinated. This was possible because of the development of aP vaccines containing reduced quantities of antigens. Coverage, however, is still not high enough across all these categories of individuals, and transmission to infants can still occur.[26–27]
Pertussis booster vaccinations for adults with chronic conditions or older people are still not widely recommended worldwide, although appropriate vaccines are available. This is particularly important in the context of recent research that estimated that 60% of older people in Europe have two or more chronic, comorbid conditions. In this older and ‘at-risk’ population, the severity both of pertussis and of comorbid disease symptoms can be worsened, leading to poor outcomes and increased healthcare costs.[4,29] Despite emerging evidence supporting the benefits of adult vaccination in terms of healthcare resource use and patient wellness, the World Health Organization (WHO) has no current recommendation for vaccination against pertussis specifically for older adults, prioritising vaccination programmes for infants and young children.
|Box 2. Pertussis and healthcare professionals and public facility workers|
Healthcare professionals and people in public service or facility provision are more exposed to pertussis than the general population and are at risk of both infection and of acting as a transmission vector to other people, potentially including infants, with whom they interact.
Some countries mandate that healthcare professionals and those in nurseries, day care centres or schools must be suspended from duty if they have pertussis and may return no sooner than 5 days after initiation of antibiotic treatment for pertussis.
This Medscape Expert Guidance article
This Expert Guidance discusses what can be done to improve the control of pertussis through:
improved uptake of adult vaccination
better surveillance of the disease.
It also looks at the impact of pertussis on different patient groups and healthcare systems.
Key elements of effective surveillance are clinical suspicion and accurate diagnosis. In routine practice, there are meaningful challenges in diagnosis of pertussis in adults: in many cases there will be missed opportunity (late presentation, lack of clinical suspicion), or inappropriate test choice may give a false negative result. Access to the appropriate diagnostic tools (for example, PCR and serology) is often limited, which can also lead to underdiagnosis of pertussis.
The catarrhal phase presents with non-specific symptoms, including rhinorrhoea (runny nose), sneezing and coughing, but usually without fever.
The paroxysmal phase presents with specific symptoms of pertussis: coughing spasms (often worsening at night), inspiratory whooping, and post-tussive vomiting.
The convalescent phase sees the frequency of coughing episodes gradually decrease.
In adolescents, adults and elderly people, the symptoms of pertussis can vary greatly at each stage of disease progression and depend on their immune status. Symptomatic reinfections of B. pertussis are common in adolescents and adults.
The American College of Chest Physicians (CHEST) notes that “the decision to treat a suspected case of pertussis with antibiotics is usually based on a clinical diagnosis rather than waiting for laboratory confirmation” and has issued guidance on when to suspect pertussis in adults:
In ruling in or out a clinical diagnosis of pertussis, adult patients complaining of acute cough (<3 weeks in duration) or subacute cough (3–8 weeks) should be specifically assessed for the four key characteristics of:
paroxysmal cough, increasing at night
absence of fever
It is suggested to not consider pertussis in adult patients complaining of acute or subacute cough that is not paroxysmal in nature, or if the patient has a fever
Cough is likely to be caused by pertussis if there is post-tussive vomiting or an inspiratory whooping sound.
The WHO, Centers for Disease Control and Prevention (CDC), Public Health England (PHE), the Robert Koch Institute, the European Centre for Disease Prevention and Control (ECDC), and the French Haute Autorité de Santé (HAS) all recommend that an attempt to confirm a clinical diagnosis of pertussis be made, utilising a biological diagnosis.[34–39]
Direct diagnosis needs a nasopharyngeal aspirate or nasopharyngeal swab sampled during the first 3 weeks of the cough. This sample is used for either laboratory culture of isolates or polymerase chain reaction (PCR) detection:
Culture is the gold standard as it is the most specific; however, it is a delicate process that takes 5–7 days and the cultures are sensitive to collection and handling. It is still useful to analyse antibiotic resistance and to perform phylogenetic studies, but is now only performed in some reference laboratories
PCR detection is more sensitive than culture and the result can be obtained within hours. PCR kits are available to detect only B. pertussis (and often also B. parapertussis), but multiplex kits enable the detection of both B. pertussis and other viral agents, allowing the detection of co-infections
If a patient has been coughing for more than 3 weeks, a PCR can be performed on a sample from a secondary case, as the disease is highly contagious
Indirect diagnosis: serology allows a retrospective diagnosis that can be performed in patients with a cough duration of more than 3 weeks, when culture and PCR are unlikely to yield positive results (Box 3). A positive serology test (anti-PT-IgG, performed with an ELISA kit, purified PT antigen, and a reference serum) confirms B. pertussis infection (although it may produce a false positive result if the patient was vaccinated less than 1 year ago).
|Box 3. Practical guidance on the biological diagnosis of pertussis|
The timing of specimen collection in relation to the onset of illness is of critical importance when ordering diagnostic tests for pertussis.
There is an increasing understanding of the burden and complications associated with non-childhood pertussis, such as insomnia, weight loss, urinary incontinence, sinusitis, syncope, and rib fracture.
Pertussis in older people
Both ‘adult’ and ‘elderly’ populations have increased pertussis-related morbidity associated with advancing age (Box 4).
A study in 664 adolescent and adult patients with pertussis found that the burden of disease increases with age. Complications were more frequent in adults than in adolescents (28% vs 16%), with pneumonia and urinary incontinence (in women) occurring more frequently with increasing age.
Potentially serious respiratory complications have been reported in older patients hospitalised with pertussis, including admission diagnoses that required a higher level of care (for example, respiratory distress or failure, hypoxia, apnoea), high rates of pneumonia, and concomitant viral infection (for example, respiratory syncytial virus, influenza), that could further exacerbate pertussis infection severity.
|Box 4. Elderly and frail patients|
Research in a large Australian population cohort study found that adults ≥65 years are more likely to be hospitalised for pertussis than those aged 45–64 years.
The duration of hospitalisation also increases with age, with those over 50 years staying for an average of 8.7 days and younger patients an average of 6.3 days.
For older people, a booster dose of Tdap (tetanus, diphtheria and acellular pertussis combination) vaccine could be readily integrated into a routine vaccination schedule in this age group.
The two key goals in implementing effective vaccination of elderly and frail patients should be:
Pertussis and pregnancy
Recent guidance on the use of Tdap (tetanus, diphtheria and acellular pertussis combination) vaccine suggests that all pregnant women should have immunisation histories reviewed and a vaccine offered to protect both the mother and their baby.[1,30]
Vaccination during pregnancy is particularly important, because over 80% of pertussis-related deaths occur in infants <3 months of age,[3,43,44] and because mothers can be the most common vectors of infection for infants.
Vaccination during pregnancy provides additional protection over naturally acquired maternal antibodies; passive protection by transplacentally acquired maternal IgG antibodies is relatively short-lasting and will not mitigate pertussis-associated morbidity beyond the first few months of life; therefore, infants of vaccinated mothers should be immunised in a timely fashion at the recommended age, which is usually 6–8 weeks.
Ideally, Tdap vaccination during pregnancy should be given between 28 and 36 weeks of gestation to optimise transplacental antibody transfer and to allow protection of preterm-born infants. Tdap vaccination needs to be performed for each pregnancy. This strategy is efficacious and is well tolerated by the mother and infant.[48–50] A case-control evaluation in the US reported that Tdap vaccination during the third trimester of pregnancy prevented more than three out of four (78%) cases of pertussis in babies younger than two months.
Pre-existing conditions and pertussis: the ‘at-risk’ patient
chronic inflammatory diseases
These patients should be considered ‘at risk’ for pertussis and severe complications. It is important to not only recognise, diagnose and treat pertussis, but also to protect them against pertussis through vaccination.
Patients with asthma have been shown to be more likely to develop pertussis during a disease outbreak than those without asthma, even in areas with high vaccine coverage.[6,52] Vaccine protection may wane so even when patients are considered to be up to date with vaccination, they may be poorly protected, and it has been hypothesised that asthma status could influence the durability of humoral immunity against pertussis, increasing the risk of pertussis among patients with asthma.
Comorbid asthma is associated with higher frequency of hospitalisation in adults with pertussis, and pertussis may also worsen the underlying condition: asthma exacerbation secondary to pertussis infection is often the trigger for an emergency room visit.[6,40]
For people with asthma, revisiting the frequency of vaccine boosters may be appropriate.
Similar to patients with asthma, COPD is both associated with more severe pertussis and is potentially exacerbated by B. pertussis infection; concomitant COPD in people with pertussis is associated with more frequent hospitalisation.[6,29]
High body mass index (BMI) has been linked to hospitalisation in patients with pertussis. Patients with obesity (BMI ≥30) and aged >45 years required emergency treatment more frequently than those with a lower BMI and younger age.
Immunocompromising and metabolic conditions
These conditions, including type 2 diabetes mellitus, Wegener’s granulomatosis, multiple myeloma, renal transplantation, and acquired immune deficiency syndrome have been reported at a higher prevalence in adults with pertussis than in the general (US) population.
Pertussis infection can also precipitate cardiac symptoms. Chest pain is a common symptom affecting about 60% of those infected and can lead to expensive diagnostic evaluations especially in older patients. Syncope (up to 40%) and cardiac arrhythmia (up to 60%) are also reported. Many infectious diseases like influenza are connected to myocardial infarction which has been reported to occur in even young infants as a complication of pertussis.[53,54]
The cost burden of pertussis in patients with pre-existing conditions
An economic burden study (2017) in the US found that patients with pre-existing COPD or asthma generate an increased cost burden after diagnosis with pertussis, compared with those with pertussis and no respiratory comorbidity, and observed that patients with pre-existing conditions benefit from targeted combination acellular pertussis vaccination strategies. A cost burden study (2021) in the UK similarly found that both health care resource utilisation and direct medical costs were significantly increased in people with COPD when they had a B. pertussis infection.
A cost-modelling exercise found that increasing uptake of Tdap in ‘at-risk’ patients to help manage resource use was “economically reasonable, and perhaps cost saving, strategy for protecting the health of adults aged < 65 years with high-risk medical conditions”.
Preventing pertussis in people with pre-existing conditions can provide meaningful benefit in patient outcomes and resource sparing. Regular community vaccination could increase immunity sufficiently to the point that fewer resources need allocating to identifying, monitoring, and treating specific patient groups, such as those with chronic conditions.
Vaccination against pertussis is effective in preventing disease, with acellular vaccines being over 90% efficacious. The most common acellular pertussis vaccines are combination vaccines of tetanus, diphtheria and pertussis either with (Tdap/IPV) or without (Tdap) inactivated poliomyelitis virus types 1–3.
While there is evidence to support the use of acellular pertussis vaccines in adults and adolescents to enhance the control of the disease, the most recent (2015) WHO position paper gives priority to vaccination programmes for infants and young children – with insufficient evidence to support the addition of booster doses in adolescents and adults with the aim of reducing severe pertussis in infants. The WHO position paper does, however, take the view that when a country implements a pertussis vaccination programme for adults, healthcare workers should be prioritised.
Because older adults can be both a source of pertussis transmission and adversely impacted by infection themselves, there needs to be greater understanding of, and guidance on, pertussis booster vaccinations in the adult population.
An idealised vaccination schedule might see the majority of the population vaccinated against pertussis every five years to maintain the highest level of immunity. A pragmatic approach might be to have boosters at a 10-year interval (as in Italy59 and the US,60 for example), coordinated alongside other vaccination schedules in the adult and elderly populations.
A recent (2021) large-scale seroprevalence study across 18 participating European counties found that pertussis was circulating at high population levels; in 13 countries, the proportion of sera with a PT antibody of ≥100 IU/mL was 2.7–5.8%. This suggests circulation of B. pertussis in the adult population, despite comprehensive childhood vaccination programmes. Further insight from a coverage assessment in France suggests that these is suboptimal vaccine coverage for diphtheria, tetanus, poliomyelitis, and pertussis, and reinforces the need for an adult booster vaccine schedule.
There is also a high degree of vaccine hesitancy—exacerbated in the general public following COVID-19—and this is also being seen in healthcare professionals, who are an important potential vector. A study into perceptions of vaccines among healthcare students in France found that while vaccines were considered safe and effective, less than half of the students were well vaccinated. Similarly, in a study in Switzerland, despite existing national recommendation, only a low number of pregnant women had received advice from their physicians to be immunised against pertussis and many declined if such a recommendation was given.
Improving vaccine uptake
A recent (2022) position paper suggested that measures to increase pertussis vaccine uptake could include:
strengthening and harmonising immunisation guidelines
supporting healthcare professionals in taking a more active role in recommending pertussis vaccination
enhanced involvement of vaccination centres and pharmacies in the vaccination process
improving knowledge of pertussis burden and vaccine efficacy among the general population.
Appointing vaccination ‘champions’ may also be effective in specific populations, for example at an asthma clinic, in HCP training, or at childcare centres.
Inclusion of enhanced vaccine education in medical curricula may help encourage wider discussion and increased awareness of the benefits of pertussis vaccination at more stages of patient pathways.
Figure 2 highlights the key discussion points for different groups when considering pertussis vaccination, with the aim of achieving several key goals:
Limit transmission of B. pertussis to infants
Protect the elderly and frail population from exposure to B. pertussis
Limit exposure in adults who have pre-existing conditions that might be worsened by pertussis or increase the severity of pertussis
Overcome any misconception that childhood vaccination is providing lifelong immunity to pertussis
Increase pertussis vaccination uptake in HCPs and people in childcare or public-facing roles.
Readers are advised to check local recommendations regarding the frequency of pertussis vaccination.
Figure 2. An algorithm to guide pertussis vaccination discussions.
Efficacy and cost effectiveness
A cost-effectiveness analysis of adults aged 19 years and older in the US found the incremental cost-effectiveness rations for the use of Tdap vaccine in adults ranged from $248,000 per quality-adjusted life year (QALY) to $900,000 per QALY. The lowest costs per QALY were $248,000 for the age 65 cohort, $332,000 for the age 19 cohort, and $477,000 for the age 50 cohort.
Further research into the burden of pertussis in adults and the effectiveness of the adult Tdap vaccination is needed to better estimate the cost-effectiveness of adult vaccination programmes – particularly in specific populations, such as patients with pre-existing conditions, or healthcare workers. It should also be noted that the cost of vaccination, disease diagnosis and treatment varies by country.
Even in countries with high pertussis vaccination coverage in infants and young children, pertussis remains sub-optimally controlled. Pertussis is a cyclical disease; if a system is in place, surveillance can help healthcare systems to prepare for upcoming ‘outbreaks’ as a cycle peaks, confirming cases as rapidly as possible and monitoring treatment outcomes. Improving disease surveillance can help accurately assess incidence rates, define the burden of disease, and develop vaccination strategies. There are several methods for effective disease surveillance.
Hospital surveillance captures admissions for disease and would typically record patients with severe, life-threatening or fatal illness. In the case of pertussis, this type of monitoring is suited to paediatric illness, where very young patients are most likely to present with severe symptoms. Adult patients are less likely to present to a hospital with pertussis as the primary complaint, so may not be captured in this type of surveillance. Adult patients presenting to hospital who have respiratory conditions may not be tested for pertussis, so pertussis could be more common than currently recognised.
Sentinel surveillance requires a functional network where participating physicians can share and record cases of several diseases. While networks are often effective in monitoring several respiratory diseases in adults (for example, influenza, respiratory syncytial virus, asthma or chronic obstructive pulmonary disease), few record adult pertussis cases due to potential lack of awareness or clinical suspicion of the disease. However, there are networks now monitoring pertussis in the population in some countries:
The Swiss SENTINELLA, the French Sentinelle network and the German KRESH pertussis sentinel systems are examples of recent initiatives in monitoring adult pertussis.[67–70]
In the UK, an enhanced surveillance form is used in primary care when patients have a laboratory-confirmed pertussis infection.
In the US, the CDC records reported pertussis cases.
Sero-epidemiology measures specific anti-PT antibodies to assess circulation of B. pertussis in a population. In practice, sero-prevalence initiatives are suited to investigation in select age or comorbidity groups, and for enhancing pertussis awareness in healthcare professionals. Without additional information (vaccination status, symptoms of disease), sero-prevalence data may have limited appeal to practising physicians.
Almost all surveillance methods rely on healthcare professionals or the public to suspect pertussis when its symptoms present; therefore, education is key to improving surveillance of pertussis. Increasing awareness of the potential dangers associated with pertussis in adults, the elderly and those with comorbidities may help address underdiagnosis or under-reporting of the disease and inform the general public of the risks and impact of pertussis. This could be improved with:
greater disease awareness in primary care and across multidisciplinary teams who manage complicated patients
thorough testing in at-risk populations, including asking people who present with an exacerbation of an existing respiratory illness if there are persistent coughs in the close family
the inclusion of pertussis testing in patients presenting with COVID-19-like symptoms or other respiratory tract infections
greater visibility of pertussis as an important vaccine-preventable disease during medical and pharmaceutical studies and in public communications.
Dr CG Griffin (Griffin Scientific Ltd), independent medical writer, helped draft this Expert Guidance article.
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Cite this: Recognition and Prevention of Pertussis Disease in Adults, Particularly in Those at Increased Risk - Medscape - Aug 18, 2023.