Pertussis infection in adolescents and adults: Treatment and prevention
Pertussis, also known as "whooping cough," is a highly contagious acute respiratory illness caused by Bordetella pertussis. In the prevaccine era, the disease predominantly affected children <10 years of age and usually manifested as a prolonged cough illness with one or more of the classical symptoms including inspiratory whoop, paroxysmal cough, and post-tussive emesis [1].
Since the introduction of pertussis vaccines, the epidemiology of reported pertussis infections has changed. In the United States in the 1990s, more than one-half of cases occurred in adolescents and adults [2]. In 2015, the greatest proportion of cases was amongst adolescents aged 11 to 19 (32 percent) [3].These infected adolescents and adults serve as a reservoir for infection of infants and children, who more often experience serious pertussis-related morbidity and mortality. Because symptoms and signs in adolescents and adults are often nonspecific, clinicians may not consider the diagnosis of pertussis in patients presenting with a cough illness.
Issues related to treatment and prevention of pertussis in adolescents and adults will be reviewed here. Issues related to treatment and prevention of pertussis in infants and children are discussed separately. (See "Pertussis infection in infants and children: Treatment and prevention".)
The pathogenesis, epidemiology, clinical manifestations, and diagnosis of this infection are discussed separately. (See "Pertussis infection: Epidemiology, microbiology, and pathogenesis" and "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis" and "Pertussis infection in infants and children: Clinical features and diagnosis".)
TREATMENTThe United States Centers for Disease Control and Prevention (CDC) has published recommendations for treatment and postexposure prophylaxis of pertussis [4]. Our approach is consistent with these recommendations.
Antibiotic therapy
Indications
Within three weeks of cough onset — We recommend antibiotic therapy for all patients with a clinical or microbiologic diagnosis of pertussis who present within three weeks of cough onset, particularly because this is the highest risk period of transmission. This includes patients who present during the catarrhal phase (typically the first one to two weeks of illness) whose cough may not have paroxysmal features; although the diagnosis of pertussis is rarely established, or even considered, during this phase among adolescents and adults, it may be suspected in symptomatic individuals in outbreak settings or following contact with a patient with pertussis infection. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis", section on 'Approach to diagnosis'.)
Although antibiotic treatment at this stage in the illness (particularly after the catarrhal phase) may not affect the course of symptoms, it is effective in eradicating B. pertussis [5], and thereby can reduce the spread of the infection to others. A small number of trials have evaluated antibiotic therapy for pertussis infection in children, mainly in the paroxysmal phase of illness. In a systematic review of these trials, antibiotic therapy was effective in eradicating B. pertussis from the nasopharynx, but did not alter the course of the disease [5]. Observational studies, however, have suggested that treatment of pertussis is associated with a lower rate of secondary spread (eg, among households or institutions) [6-8].
After three weeks of cough onset — Since persistent cough is related to local tissue damage from B. pertussis rather than an ongoing infection, we do not routinely prescribe antibiotic therapy after three weeks of cough onset in patients with clinical or microbiologic diagnosis of pertussis. An exception is pregnant women, particularly those who are near term, in whom antibiotic therapy up to six weeks after cough onset is appropriate to prevent transmission to neonates [9]. Additionally, we favor antibiotic therapy up to six weeks after cough onset for patients with asthma, chronic obstructive pulmonary disease, or immunocompromising condition, and for those over 65 years old. Although limited, emerging data indicate that pertussis-related morbidity, including the risk for hospitalization, is highest in these specific subgroups [10-13], and thus, we feel that such treatment is appropriate although the benefit remains uncertain.
Antibiotic therapy is not warranted after six weeks of cough onset for any adolescent or adult. Based on limited data, most individuals appear to clear pertussis infection within six weeks, even without antibiotic treatment [14].
Timing — Given the highly contagious nature of the disease and the delay in availability of culture test results (up to 7 to 10 days), in accordance with CDC recommendations, we suggest initiating empiric antibiotic therapy once there is sufficient clinical suspicion for pertussis without awaiting diagnostic testing results.
The clinical case definition of pertussis is a cough illness lasting at least two weeks without an apparent cause, with at least one of the following symptoms: paroxysms of coughing, inspiratory whoop, or post-tussive emesis [15,16]. Patients with a history of potential exposure to pertussis may warrant clinical suspicion despite less characteristic symptoms. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis".)
Regimen selection — Either azithromycin or clarithromycin is the recommended antibiotic regimen for pertussis infection in adolescents and adults [4,9]. In patients unable to take these macrolide agents, trimethoprim-sulfamethoxazole (TMP-SMX) is an acceptable alternative. The antibiotic regimens for treatment and postexposure prophylaxis are identical. (See 'Postexposure prophylaxis' below.)
Doses for adults and adolescents are:
●Azithromycin orally for five days (500 mg day 1, followed by 250 mg days 2 through 5)
●Clarithromycin 500 mg orally twice daily for seven days
●TMP-SMX one double-strength tablet orally twice daily for 14 days
Macrolides are highly effective at eradicating B. pertussis from the nasopharynx [4,17]. A small number of trials have evaluated antibiotic therapy for pertussis infection in children, mainly in the paroxysmal phase of illness. In a systematic review of antibiotic trials in children, short-term macrolide therapy (azithromycin for three to five days or clarithromycin or erythromycin for seven days) was as effective at eradicating B. pertussis as long-term treatment (erythromycin for 10 to 14 days) [5].
Azithromycin and clarithromycin are the preferred agents given both their relative stability at gastric acid pH levels and high oral bioavailability. Erythromycin is no longer recommended because it requires four times daily dosing and is more frequently associated with gastrointestinal toxicity (abdominal cramping, nausea, vomiting, and diarrhea). In the systematic review of trials among children, when treatment with azithromycin or clarithromycin was compared with erythromycin, there was no difference in rates of microbial eradication but fewer side effects with azithromycin and clarithromycin [5].
Azithromycin is contraindicated for persons with a prior history of cholestatic jaundice or hepatitis specifically associated with its use [18]. Like all macrolide antibiotics, azithromycin has also been associated with electrocardiographic QT prolongation, as well as a small absolute increase in cardiovascular deaths, particularly in those at high baseline risk [19]. Because clarithromycin and erythromycin inhibit the cytochrome P450 enzyme system, concomitant use of any other drug metabolized by this system may result in increased macrolide levels with resultant toxicity, including QT interval prolongation and sudden cardiac death [20]. In these situations, alternative therapy with TMP-SMX may be preferable. Drug interactions can be checked through the Lexicomp drug interactions program within UpToDate.
While in vitro susceptibility of B. pertussis to other antibiotic agents including fluoroquinolones and tetracyclines has been demonstrated [21-25], there are no clinical data to support their use. It is reasonable to use these in patients who have contraindications or intolerance to macrolides and TMP-SMX. Although amoxicillin has in vitro activity against B. pertussis, we do not recommend using it as it does not effectively eradicate the organism from the nasopharynx [26].
Routine antimicrobial susceptibility testing is not needed for B. pertussis since macrolide resistance is relatively uncommon [4]. However, in cases of apparent clinical failure with macrolide therapy, it may be useful to test any cultured isolates of B. pertussis for macrolide susceptibility. This can be done using standard methodology, including E-test and disk diffusion assays [27].
A Finnish study including 148 B. pertussis strains isolated between 2006 and 2017 found no resistant organisms, or any increase in resistance levels, to either macrolides or quinolones [28]. Similarly, among isolates in the Czech Republic from 1967 to 2015, the minimum inhibitory concentrations of erythromycin, clarithromycin, azithromycin, ciprofloxacin, and TMP-SMX to B. pertussis were unchanged over time [29].
Cough management — The paroxysmal cough of pertussis may be severe and protracted, representing the main cause of associated morbidity. The cough likely results from destruction of upper respiratory ciliated cells by pertussis toxins; this leads to trickling of secretions from the nasopharynx into the larynx, triggering the cough reflex. Cough resolution requires regrowth of these cells, which typically takes many weeks.
Because of its more favorable side effect profile, we feel that dextromethorphan is a reasonable therapy for patients particularly bothered by the cough. We avoid prescribing other agents, particularly opioids, as the risk of adverse effects most likely outweighs benefit and the cough, although troublesome and protracted, is self-limited. Untested home remedies that may offer relief to some include keeping well hydrated, using a mist vaporizer, avoiding cough triggers (eg, smoke, strong chemicals, allergens), and eating frequent small meals to help avoid vomiting.
A systematic review, including 12 trials of various treatments, concluded that there is insufficient evidence to allow recommendations for symptomatic treatment of cough in the setting of pertussis [30].
PREVENTIONPreventive measures against pertussis include vaccination, postexposure prophylaxis, and isolation of patients with known or suspected pertussis.
Vaccination — Initial vaccines developed following the isolation of the B. pertussis organism in the early 1900s contained killed whole-cell B. pertussis organisms. Subsequently, acellular pertussis vaccines containing purified components of the organism were developed. The acellular vaccines have a more favorable side effect profile, though the whole-cell vaccine may induce more durable immunity [31-34]. Countries with universal childhood vaccination programs have observed dramatic reductions in the incidence of pertussis.
Acellular vaccines were first licensed for use in the United States in 1991 [35,36]. Routine childhood vaccination in the United States is performed with the diphtheria, tetanus toxoids, and pertussis (DTaP) vaccine ("a" designating acellular pertussis vaccine combined with tetanus and diphtheria toxoids) [37]. In the United States, standard vaccination for pertussis is recommended for all children, followed by routine booster dosing in adolescence and adulthood. Vaccination in infants and children is discussed elsewhere. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age".)
Previously unvaccinated individuals — For adolescents (up to 18 years old) who have not been fully immunized with DTaP, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) should be given as the first dose of the “catch-up series;” additional doses of tetanus diphtheria vaccine (Td) and the interval of administration depend on the prior vaccination history (table 1) [37]. For unvaccinated adults, a three-vaccine series is recommended; the preferred vaccination schedule is Tdap followed by Td at least four weeks later, then Td again in 6 to 12 months [37].
Tdap booster for previously vaccinated individuals — Immunity to pertussis infection wanes 5 to 10 years after completing the childhood vaccination series. Because of steadily increasing cases of pertussis in adolescents and adults, in 2005 the United States Advisory Committee on Immunization Practices (ACIP) recommended booster vaccination for all adolescents and adults [38,39]. This is particularly important for those with close contacts with infants, as well as for health care workers and pregnant women during each pregnancy (figure 1).
Adolescents aged 11 to 18 years — A single booster immunization with Tdap (Boostrix or Adacel [brand names]) should be administered, preferably at 11 or 12 years of age [37]. The use of Tdap for adolescents is discussed in detail separately. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age".)
Nonpregnant adults 19 years or older — A single Tdap booster dose should be administered to adults older than 19 years who have not previously received Tdap (ie, after age 11 years), as recommended by the ACIP [40]. Vaccination is particularly important in those adults who have close contact with infants (eg, grandparents or childcare providers), health care workers, and those who are obese or who have pre-existing asthma [41]. Tdap booster vaccination is appropriate even for patients who have had a recent clinical episode of pertussis.
Tdap should be administered regardless of the interval since the last dose of Td. This represents a change from previous ACIP guidelines, which recommended that Tdap be given a minimum of two years after the last dose of Td in most cases. If it is not possible to determine whether an adult has had a Tdap booster, it is reasonable to administer a dose and ensure that it is appropriately documented. Subsequent tetanus booster doses, in the form of Td, should be given at 10-year intervals throughout adulthood. (See "Tetanus-diphtheria toxoid vaccination in adults", section on 'Routine adult immunization'.)
The US Food and Drug Administration (FDA) has approved Boostrix for individuals ≥10 years of age and approved Adacel for individuals 10 to 64 years of age [42]. While either of the available Tdap formulations (Boostrix or Adacel [brand names]) may be administered to a person ≥65 years, Boostrix is preferred because it has FDA approval for this age group [43]. However, to avoid missing an opportunity to vaccinate an individual ≥65 years, providers should administer whichever Tdap vaccine is available. Based on review of published and unpublished data, the ACIP 2012 recommendations noted that the safety and immunogenicity of Boostrix and Adacel in adults ≥65 years are comparable [43]. Available data have confirmed that immunization of adults aged ≥65 years did not have untoward safety consequences [44,45].
Booster vaccination with Tdap is recommended because childhood pertussis vaccination does not provide lifelong immunity and the incidence of pertussis infection has been rising among adolescents and adults. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age", section on 'Duration of immunity' and "Pertussis infection: Epidemiology, microbiology, and pathogenesis", section on 'Evolving epidemiology'.)
The safety and immunogenicity of acellular pertussis vaccines in adolescents and adults have been demonstrated in randomized, placebo-controlled trials [40,46-52]. In the largest randomized controlled trial, which included 4480 adolescents and adults (aged 11 through 64 years), Tdap elicited a robust immune response with an overall safety profile similar to that of Td [51]. The efficacy of acellular pertussis vaccine (without Td) among adolescents and adults has also been demonstrated in a randomized trial [52]. Among healthy individuals between the ages of 15 and 65 years who received acellular pertussis vaccine (rather than the control hepatitis A vaccine), the efficacy was 92 percent (95% CI 32-99).
In the United States, only a single Tdap is recommended in nonpregnant patients older than 11 years since there is no evidence that additional Tdap vaccination will reduce the overall burden of pertussis or be cost-effective [37]. However, several European countries recommend booster Tdap doses every 10 years for adults [53]. The rationale for this is that the effectiveness of the Tdap vaccine in adolescents has been shown to wane within two to four years after administration [33]. This likely contributes to the increased incidence of pertussis observed in adolescents. Administration of a second Tdap dose to young adults 10 years after the first dose appears to be safe and immunogenic [54]. As an example, in a randomized controlled trial in 1330 adults aged 18 to 65 years of age who had received a dose of Tdap 8 to 12 years previously, administration of Tdap or Td resulted in similar rates of adverse events; those in the Tdap group had robust antibody responses to the pertussis antigens [55].
Rates of Tdap coverage among adults with children in their household appear to be low but are substantially higher for patients whose providers recommend the vaccine, highlighting the important role of the provider [56].
Health care personnel (HCP) are at risk for exposure to pertussis and for exposing vulnerable patients when they are infectious. Numerous nosocomial outbreaks of pertussis have been attributed to HCP exposure, with considerable associated morbidity and occasional mortality [38,57-59]. Tdap vaccination in adult health care workers is effective in controlling nosocomial outbreaks of pertussis and is less costly than a hospital outbreak [38,57].
Pregnant women — Issues related to pertussis vaccination in pregnancy are discussed separately. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)
Contraindications — Contraindications to the Tdap vaccine include prior severe allergic reaction (anaphylaxis) after a vaccine dose or to a vaccine component or a history of encephalopathy (not attributable to an alternate cause) that occurred within seven days of a pertussis-containing vaccination. Individuals with an apparent severe allergic reaction to a vaccine should be referred to an allergist to determine the responsible allergen and for advice regarding future vaccination [60].
International strategies — An international collaboration, the Global Pertussis Initiative (GPI), has assessed various vaccination strategies including routine childhood immunizations, universal adolescent, adult, and preschool booster vaccination, as well as selective vaccination of health care workers, childcare workers, new mothers, and close contacts of newborns ("cocooning") [61]. Providing indirect protection through Tdap vaccination to adults is the premise for the “cocooning” strategy to prevent pertussis in young infants at highest risk for severe pertussis, but evidence suggests that vaccination with acellular pertussis vaccines does not prevent transmission [37].
Given the global variability in pertussis epidemiology and health care resources, a uniform set of guidelines for all countries is not feasible. The GPI does, however, offer some region-specific strategies [62-67].
Postexposure prophylaxis — We suggest that all household contacts of a person with pertussis receive postexposure antibiotics, regardless of their vaccination history. Prior Tdap booster is not sufficiently protective to eliminate the need for antibiotic prophylaxis [4]. Even young, healthy adults who have been fully vaccinated (including with a booster dose within five years) can become infected during an outbreak [68]. For others who have close contact with a person with pertussis, postexposure prophylaxis is recommended for those who are at high risk for severe pertussis illness or have close contact with persons at high risk. The United States Centers for Disease Control and Prevention defines high-risk persons as: infants, women in the third trimester of pregnancy, and those with chronic health conditions that may increase the likelihood of pertussis-related morbidity (eg, immunocompromising condition, chronic lung disease) [69]. Exposed individuals, especially those with an incomplete vaccination history, should be closely observed for symptoms and signs of pertussis for three weeks after contact.
Close contact is defined as:
●Face-to-face exposure within three feet of a symptomatic patient
●Direct contact with respiratory, nasal, or oral secretions
Regimens for postexposure prophylaxis are the same as for treatment. (See 'Regimen selection' above.)
Administration of postexposure antibiotic therapy to an asymptomatic person who has had contact with a person with pertussis who is within 21 days of onset of cough can potentially prevent symptomatic infection [70]. In one retrospective analysis, implementation of postexposure prophylaxis as part of an institutional protocol was associated with termination of a pertussis outbreak [68].
Postexposure immunization, either passive with immunoglobulin [71] or active with pertussis vaccine, does not protect contacts from infection [72]. For adolescents and adults with prior pertussis infection or exposure, subsequent vaccination should be administered based on standard recommendations [37].
Infection control — Hospitalized patients with B. pertussis should be placed on droplet precautions (in addition to standard precautions). (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Droplet precautions'.)
As above, postexposure prophylaxis is recommended for health care workers who have been exposed to pertussis and are either at high risk for severe pertussis illness or have close contact with persons who are at high risk [69] (see 'Postexposure prophylaxis' above). Other exposed health care workers who do not meet those criteria or have less direct contact may be closely monitored for 21 days after exposure and treated if they develop signs or symptoms of pertussis. If health care workers develop symptoms of pertussis, they should be excluded from work for at least the first five days of antimicrobial therapy.
Patients with B. pertussis infection should avoid contact with young children and infants, particularly those who are unimmunized or incompletely immunized, until they have completed at least five days of appropriate antibiotic therapy.
In addition, patients with B. pertussis infection working in schools, daycare centers, or health care facilities should not return to work until completing at least five days of appropriate antibiotic therapy [9,17].
SOCIETY GUIDELINE LINKSLinks to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pertussis" and "Society guideline links: Immunizations in children and adolescents" and "Society guideline links: Immunizations in adults".)
INFORMATION FOR PATIENTSUpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Tdap vaccine (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Adolescents and adults with pertussis serve as a reservoir for infection of infants and young children, who have the highest risk of serious pertussis-related morbidity and mortality. Antibiotic treatment probably does not substantially affect the course of symptoms but may be useful to reduce the spread of the infection. (See 'Treatment' above.)
●For adolescents or adults with suspected or documented pertussis and cough duration of three weeks or less, we suggest antibiotic therapy (Grade 2C). This is the period of highest risk for transmission. Following three weeks cough duration, we do not routinely prescribe antibiotic therapy. However, shedding of Bordetella pertussis has been described up to six weeks after onset of illness. Thus, for pregnant women near term, we suggest antibiotic therapy up to six weeks following cough onset to prevent exposure to neonates (Grade 2C). We also suggest antibiotic therapy for up to six weeks following cough onset for adolescents or adults with asthma or chronic obstructive pulmonary disease, immunocompromising conditions, and for adults over 65 years old (Grade 2C). Pertussis-related morbidity appears highest in these subgroups, and we feel treatment is appropriate despite the uncertain benefits. (See 'Treatment' above.)
●For patients who warrant antibiotic therapy for pertussis, we suggest azithromycin or clarithromycin (Grade 2B). For patients who cannot tolerate macrolide antibiotics, trimethoprim-sulfamethoxazole is an acceptable alternative. Dosing is outlined in the table (table 2). (See 'Regimen selection' above.)
●In the United States, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is routinely recommended at age 11 through 12 years. For nonpregnant adolescents and adults who have not previously received Tdap at that time, we recommend booster vaccination with Tdap (Grade 1B). Vaccination is particularly important for individuals who have close contact with infants aged younger than one year (such as grandparents, childcare providers, and health care providers). (See 'Tdap booster for previously vaccinated individuals' above.)
●Tdap vaccination in pregnant individuals is discussed in detail elsewhere. (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination'.)
●We suggest postexposure antibiotic prophylaxis for the following individuals (Grade 2C):
•Household contacts of patients with pertussis
•Individuals who had close contact to a patient with pertussis and are at risk for severe pertussis illness (eg, infants, women in the third trimester of pregnancy, and those with chronic health conditions such as an immunocompromising condition or chronic lung disease)
•Individuals (including health care personnel) who had close contact to a patient with pertussis and have close contact with individuals at risk for severe pertussis illness
The prophylaxis regimen is the same as the treatment regimen (table 2). Prior vaccination with Tdap should not be considered sufficiently protective to eliminate the need for chemoprophylaxis. (See 'Postexposure prophylaxis' above.)
●Patients with B. pertussis infection should avoid contact with young children and infants until they have completed at least five days of effective antibiotic therapy. Similarly, patients working in schools, daycare centers, or health care facilities should not return to work until they have received five days of antibiotic treatment. (See 'Infection control' above.)
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