INTRODUCTION — The clinical presentation, including complications, and the diagnosis of pertussis (whooping cough) infection in infants and children will be discussed here. The treatment and prevention of pertussis in infants and children; the epidemiology, microbiology, and pathogenesis of pertussis infection, and the clinical features, treatment, and prevention of pertussis in adolescents and adults are discussed separately:
●(See "Pertussis infection in infants and children: Treatment and prevention".)
●(See "Pertussis infection: Epidemiology, microbiology, and pathogenesis".)
●(See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis".)
●(See "Pertussis infection in adolescents and adults: Treatment and prevention".)
MICROBIOLOGY — Bordetella pertussis is a human pathogen with no known animal or environmental reservoir. It is a fastidious gram-negative coccobacillus, surviving only a few hours in respiratory secretions outside of the human body. Other Bordetella species, including Bordetella parapertussis, Bordetella bronchiseptica, and Bordetella holmesii, may cause a clinical syndrome similar to whooping cough but are generally less severe. (See "Pertussis infection: Epidemiology, microbiology, and pathogenesis", section on 'Microbiology'.)
Coinfection with other respiratory pathogens (eg, respiratory syncytial virus, adenovirus) may occur [1-5].
EPIDEMIOLOGY
Incidence — Despite widespread vaccination, the incidence of pertussis has been rising since the 1990s, with peaks occurring every three to five years [6]. Although, the rising incidence is particularly concerning for infants younger than one year, who are at the greatest risk of morbidity and mortality [6-11], the rate of pertussis hospitalizations among infants in the United States <2 months appears to have declined following the 2012 Advisory Committee on Immunization Practices recommendation for maternal pertussis immunization during pregnancy [12,13]. Atypical/mild and asymptomatic infections are increasingly recognized in older children and adults but may be underreported [14]. (See "Pertussis infection: Epidemiology, microbiology, and pathogenesis", section on 'Epidemiology' and 'Complications' below.)
Although pertussis occurs year-round, the incidence appears to increase during the summer and fall [15-17].
Transmission — Pertussis is spread by respiratory droplets and can be transmitted by coughing, sneezing, or sharing breathing space for extend periods of time [18,19]. The risk of transmission is greatest during the catarrhal stage [20]. Asymptomatic infection may contribute to transmission between household contacts [21].
When a case of pertussis is identified, exposed individuals should be notified and offered preventive measures, if warranted. (See "Pertussis infection in infants and children: Treatment and prevention", section on 'Postexposure prophylaxis' and "Pertussis infection in adolescents and adults: Treatment and prevention", section on 'Postexposure prophylaxis'.)
Incubation period — The average incubation period for B. pertussis is 7 to 10 days, with a range of 6 to 20 days [22-24].
CLINICAL FEATURES — The clinical presentation of pertussis may vary with age and immunity (from vaccination or previous natural infection).
Classic presentation — The classic presentation of pertussis includes paroxysms of coughing, an inspiratory whoop, and posttussive vomiting. The classic presentation typically occurs as a primary infection in unvaccinated children <10 years of age [14,25-27], but it also may occur in vaccinated children and adults [28].
Classic pertussis ("the cough of 100 days") is divided into three stages:
●Catarrhal stage – The catarrhal stage appears similar to a viral upper respiratory infection with mild cough and coryza. Fever is uncommon; if present, it is usually low grade [29]. In contrast to that in a viral upper respiratory infection, the cough in pertussis gradually increases instead of improving and the coryza remains watery [25].
The catarrhal stage generally lasts one to two weeks [14].
●Paroxysmal stage – During the paroxysmal stage, coughing spells increase in severity. The paroxysmal cough is distinctive: a long series of coughs between which there is little or no inspiratory effort [25]. The child may gag, develop cyanosis, and appear to be struggling for breath (movie 1). Sweating episodes may occur between paroxysms. Paroxysms of coughing can develop spontaneously or be precipitated by external stimuli. They are more bothersome at night. Complications occur most frequently during the paroxysmal stage. (See 'Complications' below.)
The whoop, or noise made by the forced inspiratory effort that follows the coughing attack (movie 2), is not always present (movie 3). In a prospective multicenter surveillance study that included 2137 cases of B. pertussis among unvaccinated patients, whooping occurred in 79 percent of children [29]. In a 2010 outbreak that occurred predominantly in vaccinated children, whooping occurred in 22 to 44 percent; it was more frequent in children <1 year of age (44 percent) [30].
Posttussive vomiting is moderately sensitive and specific for pertussis in children. It is more common in infants younger than 12 months than in older children. In a systematic review and meta-analysis of six studies, posttussive vomiting had a sensitivity of 60 percent (95% CI 40-77 percent) and a specificity of 66 percent (95% CI 53-77 percent) for laboratory-confirmed pertussis in children [31].
The paroxysmal stage may last for two to eight weeks [14]. The coughing spells increase in frequency during the first one to two weeks, remain at the same intensity for two to three weeks, and decrease gradually thereafter.
●Convalescent stage – During the convalescent stage, the cough subsides over several weeks to months. In a prospective multicenter surveillance study (in predominantly unvaccinated children), the total duration of cough was >4 weeks in 62 percent of 1548 patients with follow-up questionnaires [29]. In another study of 62 children (5 to 16 years) with serologic evidence of B. pertussis infection, the median duration of cough was 112 days (range 38 to 191) [32].
Episodic coughing may recur or worsen during convalescence with interval upper respiratory tract infections [14].
Atypical presentations — Atypical presentations of pertussis occur more often in young infants and individuals who have been vaccinated but can occur in any individual regardless of age and vaccination status [1,33]. They also may occur in unvaccinated children [29,34,35]. The atypical features may vary with age and length of time elapsed since the last vaccination (for vaccinated children). Atypical presentations may contribute to the underrecognition of pertussis infection [14].
Infants — The clinical presentation of pertussis in young infants, particularly those younger than four months of age, may include [1,25,36-42]:
●A short or absent catarrhal stage during which the infant can appear deceptively well with a mild cough and no fever, watery coryza, or sneezing
●A paroxysmal stage characterized by gagging, gasping, eye bulging, vomiting, cyanosis, and bradycardia (or tachycardia if illness is severe); the cough may or may not be paroxysmal
●Complications, including apnea, seizures, respiratory distress, pneumonia and pulmonary hypertension, hypotension/shock, renal failure, and death
●A close contact (usually a family member, often the mother or a sibling) with a prolonged cough and no fever [36,43-47]
Pertussis infection in infants may be particularly severe, with increased rates of hospitalization for complications including apnea, seizures, and pulmonary hypertension [10,36,48-50]. The mortality rate in infants is approximately 1 percent [37,44,51,52]. (See 'Complications' below.)
Given the increased morbidity and mortality in infants, pertussis must be considered early in the presentation of respiratory illness but is often difficult to distinguish from other respiratory infections. In pertussis outbreaks, infants who required hospitalization often presented to medical care at least once before pertussis was considered [36,39].
Clinical features that are more suggestive of pertussis than respiratory viruses in infants <3 months of age were described in a case control study of 32 infants hospitalized with pertussis and 92 control infants hospitalized with respiratory syncytial virus or influenza [36]. Pertussis was associated with:
●Paroxysmal cough (approximately 90 versus 5 percent)
●Posttussive vomiting (approximately 40 versus 20 percent)
●Longer mean duration of symptoms (11 versus 3.4 days) and cough (10.7 versus 3.8 days) before admission
●Absence of fever (approximately 80 versus 50 percent)
●Decreased incidence of congestion (approximately 45 versus 85 percent)
●Cyanosis (approximately 65 versus 10 percent)
●Increased acute life-threatening event, apnea, or seizure (approximately 25 versus 5 percent)
●Higher mean white blood cell (WBC) count (20,700 versus 9900 cells/microL)
●Higher absolute lymphocyte count (13,300 versus 4900 lymphocytes/microL)
Vaccinated children — The clinical presentation and course of pertussis infection generally are less severe in children who have been vaccinated [53-56].
The clinical features of pertussis infection in vaccinated and unvaccinated children were described in a study of children who participated in a randomized trial comparing two acellular pertussis vaccines with placebo [54]. All children were actively monitored for pertussis infection until age six years. A total of 788 cases of laboratory-confirmed pertussis were diagnosed. The following findings were noted:
●Vaccination decreased the median duration of pertussis-related cough throughout the six-year follow-up (number of days with two different pertussis vaccines versus placebo group):
•29 and 33 versus 61 days at 6 to 24 months of age
•39 and 31 versus 60 days at 25 to 33 months of age
•35 versus 52 days at 34 to 72 months of age
●Among children 6 to 24 months of age, vaccination also decreased the incidence of pertussis-related apnea (47 and 36 percent versus 85 percent) and cyanosis (31 and 21 percent versus 65 percent)
The efficacy and effectiveness of pertussis vaccination in children are discussed separately. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age", section on 'Efficacy and effectiveness'.)
Older children and adolescents — Older children and adolescents with pertussis infection may be asymptomatic or have a mild cough illness without any of the characteristic features (ie, paroxysms, whoop, posttussive vomiting) [57-60]. Wheezing is another atypical finding. In a 2010 statewide outbreak, wheezing was noted in 8 percent of 501 children (mean age 8.4 years) with polymerase chain reaction (PCR)-confirmed pertussis [57].
Clinical features of pertussis in adolescents and adults are discussed separately. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)
Laboratory findings — The predominant nonspecific laboratory indication of B. pertussis infection is a leukocytosis resulting from lymphocytosis, although the WBC count may be normal [24,61]. The absolute lymphocyte count is often ≥10,000 lymphocytes/microL [36]. In a prospective multicenter surveillance study, 72 percent of patients with culture-proven pertussis had leukocytosis (WBC count above the age-specific mean) and 76 percent had lymphocytosis (lymphocyte count above the age-specific mean) [29]. Clefting of the nuclei of WBCs occurs occasionally in infants and young children and may be a clue to the diagnosis [62-67].
In infants, the WBC count and lymphocyte count are directly correlated with disease severity [37,40,68]. Marked leukocytosis (eg, >60,000 cells/microL) has been associated with increased pertussis severity, including pertussis pneumonia and pulmonary hypertension [68-71]. In a case series of infants <90 days who required intensive care for treatment of pertussis, WBC count ≥30,000 cells/microL at the time of presentation and rapid rise of WBC count to ≥30,000 cells/microL (mean five days after onset of cough) were associated with increased severity and death [40]. (See 'Complications' below.)
Radiographic findings — In uncomplicated pertussis, chest radiographs may be normal or demonstrate subtle abnormalities, such as peribronchial cuffing, perihilar infiltrates, or atelectasis, but these findings are nonspecific.
Complications — The most common complications of pertussis infection include apnea, pneumonia, and weight loss secondary to feeding difficulties and posttussive vomiting [10,14,29]. These complications are more common in infants. Other complications include seizures, encephalopathy, death, difficulty sleeping, pneumothorax, epistaxis, subconjunctival hemorrhage, subdural hematoma, rectal prolapse, urinary incontinence, and rib fracture [10,14,39,72-74].
In a multicenter surveillance study that included 2137 cases of culture-confirmed pertussis in unvaccinated outpatients (80 percent were <6 years), the overall complication rate was 6 percent, but among infants younger than six months, the complication rate was 24 percent [29]. In a retrospective cohort from a single institution, complications occurred in 37 percent of infants younger than six months who were hospitalized with pertussis [75]. Age <60 days, cough duration <7 days, history of color change, parenteral intervention for apnea, and the need for oxygen in the emergency department were associated with increased risk of complications.
●Apnea – Apnea occurs almost exclusively in infants, primarily those younger than six months [29,30,51]. Apnea usually is associated with a paroxysm of coughing but also occurs spontaneously, perhaps related to vagal stimulation [76,77]. In infants, apnea may be the only manifestation of pertussis infection.
In a 2010 outbreak that included 968 cases of probable/confirmed pertussis, apnea occurred in 26 percent of infants <6 months, 14 percent of infants 6 to 12 months, and 8 percent of children 1 to 5 years [30].
●Pneumonia – Pneumonia (infection of the lung parenchyma) is one of the most frequent complications of pertussis [29,39,51,52,78].
•Extreme leukocytosis and pulmonary hypertension – Primary B. pertussis pneumonia is associated with extreme leukocytosis (eg, >60,000 cells/microL), pulmonary hypertension, and increased mortality, particularly in young infants [37,69,79]. The pathologic findings of fatal B. pertussis infection were evaluated in an autopsy study of 15 infants ≤4 months of age who had PCR- or culture-confirmed B. pertussis pneumonia; 12 of the infants had evidence of pulmonary hypertension [69]. Histopathologic examination of respiratory tissue revealed evidence of necrotizing bronchiolitis, intra-alveolar hemorrhage, and fibrinous edema. There were abundant leukocytes and extracellular Bordetella in the cilia of the respiratory tract, and intracellular bacteria and antigens in alveolar macrophages and ciliated epithelium. In a case-control study designed to identify predictors of death in cases of fatal pertussis, pneumonia was more predictive of mortality than apnea [37].
●Seizures and encephalopathy – New-onset seizures occur in 1 to 2 percent of infants and young children with pertussis [51,52,78]. The incidence of encephalopathy is <1 percent. Pertussis appears to be associated with an increased risk of epilepsy, but the absolute risk is low. In a population-based cohort in Denmark, the 10-year cumulative incidence of epilepsy was 1.7 percent (95% CI 1.4-2.1) among children with a hospital diagnosis of pertussis compared with 0.9 percent (95% CI 0.8-1.0) in the matched comparison group without pertussis [80]. (See "Seizures and epilepsy in children: Classification, etiology, and clinical features", section on 'Etiology'.)
In a 2010 outbreak, seizures occurred in 2 of 51 children hospitalized with pertussis (both young infants); one of the infants also had encephalopathy [30].
●Death – Most deaths from pertussis occur in infants younger than six months of age, who are too young to have completed the primary series of pertussis vaccines [39,44,51,52,81,82]. The case fatality rate for pertussis among infants younger than six months of age is approximately 1 percent, with the majority of deaths occurring in those younger than two months [37,44,51,52].
An association between epidemic pertussis and sudden infant death syndrome (SIDS) has been suggested [83]. However, in a multicenter, case-control study to investigate the relationship between pertussis infection and SIDS, pertussis PCR was positive in 5.1 percent of cases and in 5.3 percent of controls [84]. Nonetheless, it is plausible that fatal apnea occurring in an infant with undiagnosed pertussis could present as SIDS. Laboratory testing for pertussis should be considered in cases of apparent SIDS, particularly if the infant or other family members had been coughing. (See "Sudden unexpected infant death including SIDS: Initial management", section on 'Case investigation'.)
DIAGNOSIS
Clinical suspicion
Infants <4 months — Pertussis should be suspected (regardless of vaccination status or wheezing) in infants <4 months with a cough illness, usually without significant fever, who have [25,32,42,57,85]:
●Cough that is not improving (of any duration); the cough may or may not be paroxysmal
●Rhinorrhea in which the nasal discharge remains watery
●Apnea, seizures, cyanosis, vomiting, or poor weight gain
●Leukocytosis with lymphocytosis (white blood cell [WBC] count ≥20,000 cells/microL with ≥50 percent lymphocytes)
●Pneumonia
●Household contact with a prolonged cough
There should be a low threshold to suspect pertussis in young infants, given the risk of serious complications. Clinical suspicion of pertussis in infants, especially those younger than four months, should trigger immediate treatment. Laboratory confirmation should not delay the initiation of treatment. Early diagnosis and prompt treatment, as well as other precautionary measures, are essential to prevention of transmission. (See 'Complications' above and "Pertussis infection in infants and children: Treatment and prevention".)
Hospitalization may be warranted because pertussis can progress rapidly in young infants. Intensive care may be required, especially if apnea, cyanosis, or leukocytosis >30,000 cells/microL (which is associated with significant morbidity) is present, given the potential for rapid, unpredictable deterioration [42,86]. If the admitting hospital cannot provide intensive care, transfer to a hospital with an intensive care unit may be warranted [85].
Infants ≥4 months and children — Pertussis should be suspected (regardless of vaccination status or wheezing) in infants ≥4 months and children with a cough illness, usually without significant fever, who have [25,32,57,85,87]:
●Paroxysmal nonproductive cough of ≥7 days duration (with or without a whoop or posttussive vomiting)
●A cough illness associated with rhinorrhea in which the nasal discharge remains watery
●A cough illness with whoop, apnea, posttussive vomiting, subconjunctival hemorrhage, or sleep disturbance
●Cyanosis
●Sweating episodes between paroxysms
The threshold of suspicion in contacts of young infants should be low, given the risk of serious complications in young infants. Early diagnosis is essential to prevention of transmission. (See 'Complications' above and "Pertussis infection in infants and children: Treatment and prevention".)
Infants ≥4 months of age and children with suspected pertussis should be treated for pertussis. Laboratory confirmation should not delay the initiation of treatment. (See "Pertussis infection in infants and children: Treatment and prevention", section on 'Antimicrobial therapy'.)
Clinical diagnosis — Pertussis is a clinical diagnosis. Clinical case definitions of pertussis may vary from country to country and depend upon the clinical scenario (eg, outbreak setting, routine surveillance, determination of vaccine efficacy, etc) [25]. Most clinical case definitions require two weeks of cough illness with at least one characteristic feature of pertussis (paroxysms, whoop, posttussive vomiting).
We use the case definition for probable pertussis provided by the Centers for Disease Control and Prevention (CDC) [6], which is similar to that provided by the World Health Organization (WHO) [88].
According to the CDC case definition, probable pertussis can be diagnosed without laboratory testing in patients without a more likely diagnosis who have either of the following [6]:
●An acute cough illness of ≥2 weeks and at least one of the following pertussis-associated symptoms:
•Paroxysms of coughing
•Inspiratory whoop
•Posttussive vomiting
•Apnea, with or without cyanosis
●An acute cough illness of any duration, with at least one of the above pertussis-associated symptoms, and contact with a laboratory-confirmed case (ie, epidemiologic linkage)
The sensitivity and specificity of the WHO clinical case definition (which is similar to the CDC definition, except that apnea is not a defining symptom) were evaluated in a study performed in Iran where immunizations, health care, and transmission risks may be different than in other countries [89]. Among 328 children 6 to 14 years of age who presented with ≥2 weeks of cough, 6.4 percent had pertussis confirmed by polymerase chain reaction (PCR). When only one of the characteristic findings (eg, paroxysms, whoop, posttussive vomiting) was required, sensitivity and specificity were 95 and 15 percent, respectively. If two or more characteristic symptoms were required for diagnosis, sensitivity decreased to 81 percent and specificity increased to 60 percent. If all three characteristic symptoms were required, sensitivity decreased to 10 percent and specificity increased to 91 percent.
Laboratory confirmation — Although laboratory testing is not necessary to make a diagnosis of pertussis, we often perform it to confirm the diagnosis, particularly when there is a need for contact prophylaxis. Laboratory testing is beneficial for confirming the diagnosis of pertussis in patients without an exposure history and for public health considerations (eg, in an outbreak setting) [6,88]. However, laboratory confirmation should not delay the initiation of treatment.
When indicated, laboratory testing should be performed as soon as the diagnosis of pertussis is considered. B. pertussis is more difficult to grow/identify from specimens obtained during or after the paroxysmal stage and after antibiotic therapy has been initiated. Microbiologic studies that can confirm the diagnosis of pertussis include bacterial culture, PCR, and serology (table 1).
PCR assays include traditional techniques that detect multiple copies of the insertion sequence gene and a multiplex respiratory panel (BioFire FilmArray Respiratory Panel 2) that detects a single copy target in the toxin promoter region. Traditional PCR is more sensitive than the multiplex panel because multiple copies of the insertion sequence gene are present in B. pertussis [90]. The multiplex panel is generally considered to be more specific than traditional PCR because the toxin promoter target is only present in B. pertussis, whereas the insertion sequence target is present in other Bordetella species, increasing the risk of false positives [91-93]. However, false positive results also may occur with the multiplex panel [94].
In addition, the sensitivity and specificity of the laboratory tests vary depending on age, time from symptom onset, vaccination history, and exposure history (table 1) [14,58]. Among these tests, only culture and PCR meet criteria for laboratory confirmation of a case for national reporting purposes [6]. Direct fluorescent antibody testing can yield false positives and false negatives and should not be used [95].
We suggest the following approach to laboratory diagnosis of pertussis [25,96]:
●Cough <3 weeks duration
•Age <4 months – PCR and culture (if available) of nasopharyngeal specimens.
False negatives may occur with culture and PCR, particularly if the specimen was not adequate. False positives may occur with PCR; this may be due to specimens being contaminated at the time of collection (eg, from environmental vaccine-associated B. pertussis DNA), type of transport medium used, in-lab contamination during specimen handling/processing, or if test validation procedures have too low PCR thresholds [97-99].
•Age ≥4 months – PCR and culture (if available); single-point serology (immunoglobulin G [IgG] to pertussis toxin [PT]) if ≥1 year since last pertussis vaccine and laboratory is able to provide cutoff values in a validated assay for recent infection.
●Cough >3 weeks duration
•Age <4 months – PCR and culture (if available) of nasopharyngeal specimens (serology is not useful).
•Age ≥4 months – Serology (IgG to PT) if ≥1 year since last pertussis vaccine and laboratory is able to provide cutoff values in a validated assay for recent infection.
The CDC provides information regarding best practices on the use of PCR for diagnosing pertussis. These note that traditional PCR may provide accurate results for up to four weeks after cough onset [99]. After the fourth week of illness, diminishing DNA increases the risk of a falsely negative result. The PCR test also lacks sensitivity in previously immunized people.
The diagnosis of pertussis is confirmed in patients of any age with [6,88]:
●Acute cough illness of any duration and either:
•Isolation of B. pertussis from a clinical specimen, or
•PCR positive for B. pertussis
●Elevated IgG antibodies to PT in a person ≥11 years of age, provided that it has been ≥1 year since the last dose of pertussis-containing vaccine
Patients with discordant test results (eg, positive culture with negative PCR, negative culture with positive PCR, or positive serology with negative PCR) should be presumed to have pertussis.
Obtaining specimens — Nasopharyngeal specimens must be collected by swab or aspiration from the ciliated respiratory epithelium of the posterior nasopharynx where B. pertussis resides (picture 1). Aspiration is recommended [100], but supplies for aspiration often are not readily available. Throat swabs and anterior nasal swabs have low rates of recovery and should not be used for the diagnosis of pertussis.
Nasopharyngeal swabs for culture should be obtained with polyethylene terephthalate (PET, better known as Dacron) or calcium alginate swabs with a flexible metal shaft. Cotton or rayon swabs contain fatty acids that are toxic to B. pertussis. Nasopharyngeal swabs for PCR should be obtained with a polyester (eg, PET), rayon, or nylon-flocked swabs. Cotton and calcium alginate may interfere with PCR assays [99].
The patient or caregiver should be educated about the importance of a properly obtained specimen and forewarned about the discomfort of the procedure. Proper specimen collection typically induces cough or sneeze. The person obtaining the specimen should wear gloves and a protective face mask.
The CDC has developed short videos describing the proper collection of nasopharyngeal aspirate and swab specimens [101].
Disease reporting — Probable and confirmed cases of B. pertussis in the United States should be reported to public health authorities.
International outbreaks of pertussis should be reported to the appropriate local authorities as well as to the WHO regional office [88].
DIFFERENTIAL DIAGNOSIS
Infectious diseases — Other Bordetella species, such as B. parapertussis, B. bronchiseptica, and B. holmesii, may cause paroxysmal cough similar to whooping cough [24,102-107]. These agents can be challenging for the laboratory to isolate and differentiate from B. pertussis [94].
Other infectious agents that may cause illnesses with intractable coughing are listed below and discussed separately [108,109]. Respiratory viruses are commonly detected in infants with suspected pertussis, either alone or in combination with other viruses or B. pertussis [109-111]. Microbiologic testing generally differentiates these infections from B. pertussis. Clinical features that are more suggestive of B. pertussis than respiratory viruses in young infants are discussed above. (See 'Infants' above.)
●Mycoplasma pneumoniae (see "Mycoplasma pneumoniae infection in children")
●Chlamydia spp (see "Chlamydia trachomatis infections in the newborn" and "Pneumonia caused by Chlamydia pneumoniae in children")
●Tuberculosis (see "Tuberculosis disease in children")
●Viral pathogens, including:
•Respiratory syncytial virus (see "Respiratory syncytial virus infection: Clinical features and diagnosis")
•Adenovirus (see "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection" and "Diagnosis, treatment, and prevention of adenovirus infection")
•Parainfluenza viruses (see "Parainfluenza viruses in children", section on 'Clinical presentation')
•Influenza A and B viruses (see "Seasonal influenza in children: Clinical features and diagnosis", section on 'Diagnosis')
•Rhinovirus (see "Epidemiology, clinical manifestations, and pathogenesis of rhinovirus infections")
•Human metapneumovirus (see "Human metapneumovirus infections")
Some of these infections also may occur simultaneously with pertussis [1-5]. Thus, the identification of another respiratory pathogen does not exclude the diagnosis of pertussis.
Other conditions — Noninfectious processes to consider in the differential diagnosis of infants and children with persistent cough are listed below and discussed separately. Isolation or identification of B. pertussis through culture, polymerase chain reaction testing, or serology distinguishes pertussis from these conditions.
●Foreign body aspiration (see "Airway foreign bodies in children")
●Reactive airway disease/asthma (see "Wheezing phenotypes and prediction of asthma in young children" and "Asthma in children younger than 12 years: Initial evaluation and diagnosis")
●Allergic or infectious sinusitis (see "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis" and "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis")
●Gastroesophageal reflux (see "Gastroesophageal reflux in infants" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents")
●Aspiration pneumonia (see "Aspiration due to swallowing dysfunction in children")
Additional causes of chronic cough and the approach to the child with chronic cough are discussed separately. (See "Causes of chronic cough in children" and "Approach to chronic cough in children".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pertussis".)
INFORMATION FOR PATIENTS — UpToDate 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 email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topics (see "Patient education: Whooping cough (The Basics)" and "Patient education: Cough in children (The Basics)")
SUMMARY
●Despite widespread vaccination, the incidence of pertussis has been rising, especially since the 1990s, particularly in infants younger than one year. Pertussis is spread by respiratory droplets. The risk of transmission is greatest during the catarrhal stage. The average incubation period is 7 to 10 days (range 6 to 20 days). (See 'Epidemiology' above.)
●Classic pertussis typically occurs in unvaccinated children. It has three stages: a catarrhal stage that lasts one to two weeks and is similar to an upper respiratory infection; a paroxysmal stage that lasts two to eight weeks and is characterized by paroxysms of coughing (movie 1), an inspiratory whoop (movie 2), and posttussive vomiting; and a convalescent stage, during which the cough subsides over several weeks to months. (See 'Classic presentation' above.)
●The presentation of pertussis in infants younger than four months may include (see 'Infants' above):
•A short, mild catarrhal stage during which the infant can appear deceptively well
•A paroxysmal stage characterized by gagging, gasping, eye bulging, vomiting, cyanosis, and bradycardia (or tachycardia if illness is severe); the cough may or may not be paroxysmal
•Complications, including apnea, seizures, respiratory distress, pneumonia and pulmonary hypertension, hypotension/shock, renal failure, and death
•A close contact (usually a family member, often the mother) with a prolonged cough
●Young children who have been vaccinated against pertussis usually have a milder and shorter illness than unvaccinated children. Older children and adolescents with pertussis infection may be asymptomatic or have a mild cough illness without any characteristic features; they also may have wheezing. (See 'Vaccinated children' above and 'Older children and adolescents' above.)
●The predominant laboratory findings of pertussis are nonspecific: Leukocytosis and lymphocytosis (eg, absolute lymphocyte count ≥10,000 lymphocytes/microL). Marked leukocytosis (eg, >60,000 white blood cells/microL) has been associated with increased pertussis severity. (See 'Laboratory findings' above.)
●Pertussis should be suspected (regardless of vaccination status or wheezing) in the following patients (see 'Clinical suspicion' above):
•Infants <4 months with a cough illness, usually without significant fever, who have:
-Cough that is not improving (of any duration); the cough may or may not be paroxysmal (movie 1)
-Rhinorrhea in which the nasal discharge remains watery
-Apnea, seizures, cyanosis, vomiting, or poor weight gain
-Leukocytosis with lymphocytosis (white blood cell count ≥20,000 cells/microL with ≥50 percent lymphocytes)
-Pneumonia
•Infants ≥4 months and children with a cough illness, usually without significant fever, who have:
-Paroxysmal nonproductive cough (movie 1 and movie 3) of ≥7 days' duration (with or without a whoop or posttussive vomiting)
-A cough illness associated with rhinorrhea in which the nasal discharge remains watery
-A cough illness with whoop (movie 2), apnea, posttussive vomiting, subconjunctival hemorrhage, or sleep disturbance
-Cyanosis
-Sweating episodes between paroxysms
●Laboratory testing is beneficial for confirming the diagnosis of pertussis in patients without an exposure history and for public health considerations (eg, in an outbreak setting) (table 1). However, laboratory confirmation should not delay the initiation of treatment. Hospitalization may be warranted for infants <4 months of age because pertussis can progress rapidly in young infants. Intensive care may be required, especially if there is apnea, cyanosis, or leukocytosis >30,000 cells/microL. (See 'Laboratory confirmation' above and "Pertussis infection in infants and children: Treatment and prevention".)
●Probable and confirmed cases of pertussis in the United States should be reported to public health authorities. International outbreaks of pertussis should be reported to the appropriate World Health Organization regional office. (See 'Disease reporting' above.)
●The differential diagnosis of Bordetella pertussis infection includes infection with other Bordetella species (eg, Bordetella parapertussis, Bordetella bronchiseptica, Bordetella holmesii), other respiratory pathogens (eg, Mycoplasma pneumoniae, Chlamydia spp, and respiratory viruses). Microbiologic testing distinguishes these infections from B. pertussis. (See 'Infectious diseases' above.)
●Noninfectious conditions that should be considered in the differential diagnosis of children with persistent or worsening cough include foreign body aspiration, reactive airways disease/asthma, allergic or infectious sinusitis, gastroesophageal reflux, and aspiration pneumonia. Isolation or identification of B. pertussis through culture, polymerase chain reaction testing, or serology distinguishes pertussis from these conditions. (See 'Other conditions' above.)
1 : Severe and unrecognised: pertussis in UK infants.
2 : Bordetella pertussis infection attenuates clinical course of acute bronchiolitis.
3 : Dual infection with Bordetella pertussis and Mycoplasma pneumoniae in three infants: case reports.
4 : Bordetella pertussis infection is common in nonvaccinated infants admitted for bronchiolitis.
5 : Bordetella pertussis and mixed infections.
6 : Bordetella pertussis and mixed infections.
7 : Are pertussis fatalities in infants on the rise? What can be done to prevent them?
8 : Prospective multinational study of pertussis infection in hospitalized infants and their household contacts.
9 : Incidence and Burden of Pertussis Among Infants Less Than 1 Year of Age.
10 : Severe Pertussis Infections in the United States, 2011-2015.
11 : The Epidemiology of Nationally Reported Pertussis in the United States, 2000-2016.
12 : Trends in Infant Pertussis Hospitalizations in the United States, 2009-2017.
13 : Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women--Advisory Committee on Immunization Practices (ACIP), 2012.
14 : Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies.
15 : Eight-Year Review of Bordetella pertussis Testing Reveals Seasonal Pattern in the United States.
16 : Seasonal patterns in time series of pertussis.
17 : Seasonal patterns in time series of pertussis.
18 : Airborne transmission of Bordetella pertussis.
19 : Airborne transmission of Bordetella pertussis.
20 : Report of the task force on pertussis and pertussis immunization - 1988
21 : Asymptomatic Infection and Transmission of Pertussis in Households: A Systematic Review.
22 : Epidemiological, clinical, and laboratory aspects of pertussis in adults.
23 : Whooping cough and its epidemiological anomalies.
24 : Whooping cough and its epidemiological anomalies.
25 : Clinical definitions of pertussis: Summary of a Global Pertussis Initiative roundtable meeting, February 2011.
26 : Pertussis in the preantibiotic and prevaccine era, with emphasis on adult pertussis.
27 : Pertussis outbreak in an Amish community--Kent County, Delaware, September 2004-February 2005.
28 : Comparison of values of antibody to Bordetella pertussis antigens in young German and American men.
29 : Clinical findings in Bordetella pertussis infections: results of a prospective multicenter surveillance study.
30 : The California Pertussis Epidemic 2010: A Review of 986 Pediatric Case Reports From San Diego County.
31 : Clinical Characteristics of Pertussis-Associated Cough in Adults and Children: A Diagnostic Systematic Review and Meta-Analysis.
32 : Whooping cough in school age children with persistent cough: prospective cohort study in primary care.
33 : Neonatal pertussis.
34 : Clinical and laboratory diagnosis of pertussis in the regions of a large vaccine efficacy trial in Germany.
35 : Polymerase chain reaction identification of Bordetella pertussis infections in vaccinees and family members in a pertussis vaccine efficacy trial in Germany.
36 : Clinical and laboratory features of pertussis in infants at the onset of a California epidemic.
37 : Predictors of death in infants hospitalized with pertussis: a case-control study of 16 pertussis deaths in Canada.
38 : Risk factors for pertussis in young infants during an outbreak in Chicago in 1993.
39 : California pertussis epidemic, 2010.
40 : Characteristics of severe Bordetella pertussis infection among infants≤90 days of age admitted to pediatric intensive care units - Southern California, September 2009-June 2011.
41 : Pertussis in Young Infants Throughout the World.
42 : An Observational Study of Severe Pertussis in 100 Infants≤120 Days of Age.
43 : Infant pertussis: who was the source?
44 : Monitoring the Impact of Vaccination on Pertussis in Infants Using an Active Hospital-based Pediatric Surveillance Network: Results from 17 Years' Experience, 1996-2012, France.
45 : Sources of Infant Pertussis Infection in the United States.
46 : Survey of Household Contacts of Infants With Laboratory-confirmed Pertussis Infection During a National Pertussis Outbreak in England and Wales.
47 : Real-Time Polymerase Chain Reaction-Based Detection of Bordetella pertussis in Mexican Infants and Their Contacts: A 3-Year Multicenter Study.
48 : Predictors of disease severity in children hospitalized for pertussis during an epidemic.
49 : Burden and Outcomes of Severe Pertussis Infection in Critically Ill Infants.
50 : Clinical and Epidemiologic Characteristics of Pertussis in Hospitalized Children: A Prospective and Standardized Long-term Surveillance Study.
51 : Epidemiological features of pertussis in hospitalized patients in Canada, 1991-1997: report of the Immunization Monitoring Program--Active (IMPACT).
52 : Pertussis--United States, 2001-2003.
53 : Clinical course of pertussis in immunized children.
54 : Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life.
55 : Vaccinated children and adolescents with pertussis infections experience reduced illness severity and duration, Oregon, 2010-2012.
56 : Reduced Severity of Pertussis in Persons With Age-Appropriate Pertussis Vaccination-United States, 2010-2012.
57 : Wheezing in children with pertussis associated with delayed pertussis diagnosis.
58 : The "how" of polymerase chain reaction testing for Bordetella pertussis depends on the "why".
59 : Clinical validation of a polymerase chain reaction assay for the diagnosis of pertussis by comparison with serology, culture, and symptoms during a large pertussis vaccine efficacy trial.
60 : Bordetella Pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT).
61 : Question 3. Is measurement of the lymphocyte count useful in the investigation of suspected pertussis in infants?
62 : Lymphocytosis in a baby with pertussis.
63 : Peripheral smear clues for Bordetella pertussis.
64 : The morphologic and immunophenotypic assessment of the lymphocytosis accompanying Bordetella pertussis infection.
65 : A 4-year-old girl with progressive cough and abnormal blood smear
66 : "Cleaved Lymphocytes" Could Be Induced by Pertussis Toxin Injection in Mice, and Are Actually Not Lymphocytes.
67 : Marked lymphocytosis and atypical cells with a cleft nucleus in a 1-month-old child.
68 : Is leukocytosis a predictor of mortality in severe pertussis infection?
69 : Pathology and pathogenesis of fatal Bordetella pertussis infection in infants.
70 : Pertussis and fatal pulmonary hypertension: a discouraged entity.
71 : Fatal pulmonary hypertension associated with pertussis in infants: does extracorporeal membrane oxygenation have a role?
72 : Recommended antimicrobial agents for the treatment and postexposure prophylaxis of pertussis: 2005 CDC Guidelines.
73 : Pertussis and bilateral subdural hematomas.
74 : Health burden of pertussis in infants and children.
75 : Risk factors for complications in hospitalized young infants presenting with uncomplicated pertussis.
76 : Pertussis as the cause of recurrent bradycardia in a young infant.
77 : Pertussis requiring intensive care.
78 : Pertussis--United States, 1997-2000.
79 : Fulminant pertussis: a multi-center study with new insights into the clinico-pathological mechanisms.
80 : Hospital-Diagnosed Pertussis Infection in Children and Long-term Risk of Epilepsy.
81 : Infant and maternal risk factors for pertussis-related infant mortality in the United States, 1999 to 2004.
82 : Risk Factors Associated With Infant Deaths From Pertussis: A Case-Control Study.
83 : Sudden infant death and prevalence of whooping cough in the Swedish and Norwegian communities.
84 : A controlled study of the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants.
85 : A controlled study of the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants.
86 : A controlled study of the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants.
87 : Clinically Diagnosing Pertussis-associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report.
88 : Clinically Diagnosing Pertussis-associated Cough in Adults and Children: CHEST Guideline and Expert Panel Report.
89 : Sensitivity and specificity of the World Health Organization pertussis clinical case definition.
90 : Testing implications of varying targets for Bordetella pertussis: comparison of the FilmArray Respiratory Panel and the Focus B. pertussis PCR assay.
91 : Testing implications of varying targets for Bordetella pertussis: comparison of the FilmArray Respiratory Panel and the Focus B. pertussis PCR assay.
92 : Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples.
93 : Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples.
94 : Misdiagnosis of Bordetella bronchiseptica Respiratory Infection as Bordetella pertussis by Multiplex Molecular Assay.
95 : Misdiagnosis of Bordetella bronchiseptica Respiratory Infection as Bordetella pertussis by Multiplex Molecular Assay.
96 : Finnish guidelines for the treatment of community-acquired pneumonia and pertussis in children.
97 : Outbreaks of respiratory illness mistakenly attributed to pertussis--New Hampshire, Massachusetts, and Tennessee, 2004-2006.
98 : Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
99 : Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
100 : Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
101 : Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
102 : Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
103 : Epidemiologic and laboratory features of a large outbreak of pertussis-like illnesses associated with cocirculating Bordetella holmesii and Bordetella pertussis--Ohio, 2010-2011.
104 : Transmission of Bordetella holmesii during pertussis outbreak, Japan.
105 : Occurrence of 3 Bordetella species during an outbreak of cough illness in Ohio: epidemiology, clinical features, laboratory findings and antimicrobial susceptibility.
106 : Widespread Bordetella parapertussis Infections-Wisconsin, 2011-2012: Clinical and Epidemiologic Features and Antibiotic Use for Treatment and Prevention.
107 : Two Distinct Episodes Of Whooping Cough Caused By Consecutive Bordetella Pertussis And Bordetella Parapertussis Infections In A Fully Immunized Healthy Boy.
108 : A serologic study of organisms possibly associated with pertussis-like coughing.
109 : Respiratory Viruses Frequently Mimic Pertussis in Young Infants.
110 : Respiratory viral infections in infants with clinically suspected pertussis.
111 : Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections.