Pertussis 

Updated: May 02, 2019
Author: Joseph J Bocka, MD; Chief Editor: Russell W Steele, MD 

Overview

Practice Essentials

Pertussis (whooping cough) is a respiratory tract infection characterized by a paroxysmal cough. The most common causative organism is Bordetella pertussis (see the image below), though Bordetella parapertussis has also been associated with this condition in humans. Pertussis remains a significant cause of morbidity and mortality in infants younger than 2 years.

A photomicrograph of the bacterium Bordetella pert A photomicrograph of the bacterium Bordetella pertussis, using Gram stain technique.

Signs and symptoms

Pertussis is a 6-week disease divided into catarrhal, paroxysmal, and convalescent stages, each lasting 1-2 weeks.

Stage 1 – Catarrhal phase

  • Nasal congestion

  • Rhinorrhea

  • Sneezing

  • Low-grade fever

  • Tearing

  • Conjunctival suffusion

Stage 2 – Paroxysmal phase

  • Paroxysms of intense coughing lasting up to several minutes, occasionally followed by a loud whoop

  • Posttussive vomiting and turning red with coughing

Stage 3 – Convalescent stage

  • Chronic cough, which may last for weeks

See Clinical Presentation for more detail.

Diagnosis

The diagnosis of pertussis is made by isolation of B pertussis in culture. A polymerase chain reaction (PCR) test can also be performed.

  • The culture specimen should be obtained during the first 2 weeks of cough by using deep nasopharyngeal aspiration

  • For PCR testing, nasopharyngeal specimens should be taken at 0-3 weeks following cough onset

  • The CDC recommends a combination of culture and PCR assay if a patient has a cough lasting longer than 3 weeks

  • Early serial monitoring of white blood cell (WBC) counts is warranted

See Workup for more detail.

Management

Goals of treatment

  • Limit the number of paroxysms

  • Observe the severity of cough and provide assistance when necessary

  • Maximize nutrition, rest, and recovery

Pharmacologic therapy

  • Antimicrobial agents and antibiotics can hasten the eradication of B pertussis and help prevent spread

  • Erythromycin, clarithromycin, and azithromycin are the preferred agents for patients aged 1 month or older

Immunization

Prevention through immunization remains the best defense in the fight against pertussis. CDC recommendations for vaccination are as follows:

  • DTaP vaccine: Recommended at the ages of 2, 4, 6, and 15-18 months and at age 4-6 years; it is not recommended for children aged 7 years or older

  • Tdap vaccine: Recommended for children aged 7-10 years who are not fully vaccinated; as a single dose for adolescents 11-18 years of age; for any adult 19 years of age or older; and for pregnant woman regardless of vaccination history, including repeat vaccinations in subsequent pregnancies[1, 2]

See Treatment and Medication for more detail.

Background

Pertussis, commonly known as whooping cough, is a respiratory tract infection characterized by a paroxysmal cough. It was first identified in the 16th century. In 1906, Bordet isolated the most common causative organism, Bordetella pertussis.Bordetella parapertussis has also been associated with whooping cough in humans (see the image below). (See Etiology and Pathophysiology.)

A photomicrograph of the bacterium Bordetella pert A photomicrograph of the bacterium Bordetella pertussis, using Gram stain technique.

In the prevaccination era, pertussis (ie, whooping cough) was a leading cause of infant death. As a result of vaccination, however, the number of cases reported decreased by more than 99% from the 1930s to the 1980s. Nonetheless, because of many local outbreaks, the number cases reported in the United States increased by more than 2300% between 1976 and 2005. (See Epidemiology.)[3]

The disease is still a significant cause of morbidity and mortality in infants younger than 2 years. Pertussis should be included in the differential diagnosis of protracted cough with cyanosis or vomiting, persistent rhinorrhea, and marked lymphocytosis. (See Prognosis, DDx, Presentation, and Workup.)[4]

Complications of pertussis can include the following (see Prognosis, Treatment, and Medication):

  • Pneumonia

  • Hypoxic encephalopathy

  • Otitis media

  • Tuberculosis activation

  • Epistaxis, hemoptysis

  • Hernia

  • Reinduction of paroxysmal coughing with upper respiratory infections

  • Seizures

  • Cerebral hemorrhage

  • Coma and death

Etiology and Pathophysiology

Humans are the sole reservoir for B pertussis and B parapertussis. B pertussis, a gram-negative pleomorphic bacillus, is the main causative organism for pertussis. (B parapertussis is less common than B pertussis and produces a clinical illness that is similar to, but milder than, that produced by B pertussis.) B pertussis spreads via aerosolized droplets produced by the cough of infected individuals, attaching to and damaging ciliated respiratory epithelium. B pertussis also multiplies on the respiratory epithelium, starting in the nasopharynx and ending primarily in the bronchi and bronchioles.[5]

Pertussis is highly contagious, developing in approximately 80-90% of susceptible individuals who are exposed to it. Most cases occur in the late summer and early fall.

A mucopurulent sanguineous exudate forms in the respiratory tract. This exudate compromises the small airways (especially those of infants) and predisposes the affected individual to atelectasis, cough, cyanosis, and pneumonia. The lung parenchyma and bloodstream are not invaded; therefore, blood culture results are negative.

Transmission of pertussis can occur through direct face-to-face contact, through sharing of a confined space, or through contact with oral, nasal, or respiratory secretions from an infected source. In a study of pertussis in 4 US states, out of 264 infants with the disease, the infant’s mother was the source of pertussis in 32% of cases, and another family member was the source in 43% of cases.[6]

Although mothers have historically been the most common source of transmission of pertussis to their infant, data from a study found that the most common source of transmission to infants is through their siblings.[7, 8]

Young infants, especially those born prematurely, and patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk for contracting the disease and for complications.

Risk factors for pertussis include the following:

  • Nonvaccination in children

  • Contact with an infected person

  • Epidemic exposure

  • Pregnancy

An Australian study of adult risk factors for pertussis found not only that persons aged 65 years or older were more likely than those aged 45-64 years to be hospitalized for pertussis, but that adults with obesity or preexisting asthma had a greater likelihood of being diagnosed with pertussis. (The investigators did not see a link between the pertussis incidence and age.) The population-based, prospective, cohort study involved 263,094 adults aged 45-64 years.[9]

Epidemiology

Occurrence in the United States

Since the early 1980s, pertussis incidence has cyclically increased, with peaks occurring every 2-5 years.[10] Most cases occur between June and September. Neither acquisition of the disease nor vaccination provides complete or lifelong immunity. Protection against typical disease wanes 3-5 years after vaccination and is not measurable after 12 years.[11, 12, 13]

The rate of pertussis peaked in the 1930s, with 265,269 cases and 7518 deaths reported in the United States. This rate decreased to a low of 1010 cases in the United States, with 4 deaths, in 1976. Starting in the 1980s, however, the reported incidence of US pertussis cases dramatically increased across all age groups. Although the largest increase in pertussis cases has been among adolescents and adults, the annual reported incidence has been highest among infants younger than 1 year.[14]

In 2010, according to the Centers for Disease Control and Prevention (CDC), the US pertussis rate reached 27,550 cases (the highest number since 1959), with 27 related deaths.[15, 16]

In 2011, according to preliminary statistics from the CDC, adolescents (ages 11-19 years) and adults together accounted for 47% of pertussis cases, while children aged 7-10 years accounted for 18% of cases.[16, 17]

According to the CDC, during the first half of 2012, most states had reported either increased pertussis activity or outbreaks of the disease. By July 5 of that year, 37 states had reported increases in pertussis cases over those reported during the same period in 2011.

For example, as listed by the CDC and the states’ health departments, the number of reported cases in Washington State (where a pertussis epidemic was declared), Minnesota, and Wisconsin in 2012 were as follows[16] :

  • Washington State - 2012: 3400 cases reported through Aug 4; 2011: 287 cases reported through Aug 4

  • Minnesota - 2012: 2039 cases reported as of Aug 2; 2011 (entire year): 661 cases reported

  • Wisconsin - 2012: 3496 confirmed or probable cases reported through July 31, 2012; 2011 (entire year): 1192 confirmed or probable cases reported

The CDC listed a provisional national figure of 17,000 pertussis cases between Jan 1 and July 21, 2012, including 9 pertussis-related deaths. The reasons that pertussis cases peak in some years is not completely understood, according to the CDC.[16]

The CDC has estimated that 5-10% of all cases of pertussis are recognized and reported. Pertussis remains the most commonly reported vaccine-preventable disease in the United States in children younger than 5 years. In studies, 12-32% of adults with prolonged (1-4 wk) cough have been found to have pertussis.

Between January 1, 2014 and June 10, 2014 California's public health department reported 3,458 cases of pertussis. The department declared the outbreak to have reached epidemic proportions, with 800 cases reported in the span of just 2 weeks.[18] A study that examined a similar outbreak in California in 2010 determined that nonmedical vaccine exemptions played a role.[19]

Nationally, the CDC stated that the 4,838 cases of pertussis reported from January 1, 2014 to April 14, 2014 represented a 24% increase over the same period in 2013.[20]

The CDC reports that during January 1–November 26, 2014, a total of 9,935 cases of pertussis with onset in 2014 were reported in California. Severe and fatal disease occurs almost exclusively in infants who are too young to be vaccinated against pertussis. Therefore, pregnant women are encouraged to receive tetanus, diphtheria, and acellular pertussis vaccine (Tdap) during the third trimester of each pregnancy to provide placental transfer of maternal antibodies to the infant.[21, 22]

International occurrence

The annual worldwide incidence of pertussis is estimated to be 48.5 million cases, with a mortality rate of nearly 295,000 deaths per year.[23] The case-fatality rate among infants in low-income countries may be as high as 4%.[24]

In England, the percentage of people vaccinated for pertussis over the last 4 decades has decreased to less than 30%. This decline has resulted in thousands of recently reported cases of the disease, with the incidence rate approaching that of the prevaccination era. Similar epidemic outbreaks have recently occurred in Sweden, Canada, and Germany. Nearly 300,000 deaths from pertussis are thought to have occurred in Africa over the last decade.

Race- and sex-related demographics

With regard to race, the CDC reported that among individuals with pertussis between 2001 and 2003, 90% were white, 7% were black, 1% were Asian/Pacific Islander, and 1% were American Indian/Alaska Native, and 1% were identified as “other race”. From 2001-2003, females accounted for 54% of pertussis cases in the United States.[25]

Age-related demographics

From 2001-2003, of patients with pertussis, 23% were younger than 1 year, 12% were aged 1-4 years, 9% were aged 5-9 years, 33% were aged 10-19 years, and 23% were older than 20 years.[26, 25]

Because of the lack of maternal immunity transfer, 10-15% of all cases of pertussis occur in infants younger than 6 months; more than 90% of all deaths occur in this same age group. However, the growing majority of cases are now in persons aged 10 years and older, which has led to increased booster recommendations.

Prognosis

Prognosis for full recovery from pertussis is excellent in children over 3 months of age. In those less than 3 months the mortality is 1-3%.

Complications of pertussis in older infants and children are usually minimal, and most patients make a gradual, but full, recovery with supportive care and antibiotics. Minor complications during the illness include epistaxis, nausea and vomiting, subconjunctival hemorrhages, and ulcers of the frenulum.

Patients with certain comorbid conditions, however, have a higher risk of morbidity and mortality and should be evaluated on an individual basis.

In addition, compared with older children and adults, infants younger than 6 months with pertussis are more likely to have severe disease, to develop complications, and to require hospitalization. From 2001-2003, 69% of infants younger than 6 months with pertussis required hospitalization.[14]

Reported deaths due to pertussis in young infants have increased substantially since the late 20th century. Between 2004 and 2008, out of a total 111 pertussis-related deaths reported to the CDC, 92 (83%) were in infants aged 3 months or less.[27, 28, 15]

Pneumonia, either from Bordetella pertussis infection or from secondary infection with other pathogens, is a relatively common complication, occurring in approximately 13% of infants with pertussis.[26]

Central nervous system (CNS) complications, such as seizures (1-2% of infants) and encephalopathy, are less common and are thought to result from severe, paroxysm-induced cerebral hypoxia and apnea; metabolic disturbances such as hypoglycemia; and small intracranial hemorrhages. Failure to thrive is another possible complication of pertussis.

Leukocytosis, particularly with white blood cell (WBC) counts of more than 100,000, has been associated with fatalities from pertussis. Another study showed that WBC counts of more than 55,000 and pertussis complicated by pneumonia were independent predictors of fatal outcome in a multivariate model.

Infants born prematurely and patients with underlying cardiac, pulmonary, neuromuscular, or neurologic disease are at high risk for complications of pertussis (eg, pneumonia, seizures, encephalopathy, death).

Older children, adolescents, and adults often have mild or atypical illness. Approximately one half of adolescents with pertussis cough for 10 weeks or longer. Complications among adolescents and adults include syncope, sleep disturbance, incontinence, rib fractures, and pneumonia. Seizures occur in 0.3-0.6% of adults.

Control measures should be implemented immediately when 1 or more cases of pertussis are recognized in health care settings such as a hospital, institution, or outpatient clinic. Confirmed and suspected cases should be reported to the local health departments, and their involvement in control measures should be sought.

Patient Education

When a diagnosis of pertussis is made, patient and parent education and individualized supportive treatment are the best options. All parents should receive information regarding the infectious and contagious potential of pertussis, as well as the risks derived from the vaccine.

Prevention of pertussis involves the use of vaccine approved by the US Food and Drug Administration (FDA) and standard infection control precautions.

For patient education information, see the Children's Health Center, as well as Whooping Cough (Pertussis) and Immunization Schedule, Children.

 

Presentation

History

Typically, the incubation period of pertussis ranges from 3-12 days. Pertussis is a 6-week disease divided into catarrhal, paroxysmal, and convalescent stages, each lasting from 1-2 weeks.

Older children, adolescents, and adults may not exhibit distinct stages. Symptoms in these patients include uninterrupted coughing, feelings of suffocation or strangulation, and headaches. Vaccinated adults usually develop only prolonged bronchitis without a whoop, whereas unvaccinated adults are more likely to have whooping and posttussive emesis.

Stage 1 - Catarrhal phase

The initial (catarrhal) phase is indistinguishable from common upper respiratory infections. It includes nasal congestion, rhinorrhea, and sneezing, variably accompanied by low-grade fever, tearing, and conjunctival suffusion. Pertussis is most infectious when patients are in the catarrhal phase, but pertussis may remain communicable for 3 or more weeks after the onset of cough.

Stage 2 - Paroxysmal phase

Patients in the second (paroxysmal) phase present with paroxysms of intense coughing lasting up to several minutes. In older infants and toddlers, the paroxysms of coughing occasionally are followed by a loud whoop as inspired air goes through a still partially closed airway. Infants younger than 6 months do not have the characteristic whoop but may have apneic episodes and are at risk for exhaustion. Posttussive vomiting and turning red with coughing are common in affected children.

Stage 3 - Convalescent phase

Patients in the third (convalescent) stage have a chronic cough, which may last for weeks.

Physical Examination

In patients with uncomplicated pertussis, physical examination findings contribute little to the diagnosis. In all patients with pertussis, fever is typically absent. Most patients do not have signs of lower respiratory tract disease. Conjunctival hemorrhages and facial petechiae are common and result from intense coughing. Dehydration is also common on presentation. Hypoxia should be considered and assessed.

The classic inspiratory gasp or whoop develops primarily in children aged 6 months to 5 years. It is usually absent in patients younger than 6 months and in most older vaccinated children and adults. However, it can often be observed in unvaccinated adults, as can posttussive emesis.

 

DDx

Diagnostic Considerations

Illnesses that mimic clinical pertussis include the following:

  • Adenoviral respiratory infection - Children present with fever, sore throat, and conjunctivitis

  • Mycoplasmal pneumonia - Patients with mycoplasmal infections have more pronounced systemic symptoms, fever and headache may occur, and rales may be appreciated on chest auscultation

  • Chlamydial pneumonia - Young infants with chlamydial infections present with staccato cough, purulent conjunctival discharge, tachypnea, rales, and wheezing

  • Respiratory syncytial virus infection - Patients present with predominantly lower respiratory tract signs (eg, wheezing, rales)

Other conditions to consider in the differential diagnosis of pertussis include the following:

  • Common cold

  • Influenza

  • Cystic fibrosis

  • Interstitial pneumonitis

  • Bronchiolitis

  • Croup (Laryngotracheobronchitis)

  • Dehydration

  • Febrile Seizures

  • Fever

  • Gastroenteritis

  • Intussusception

  • Tachycardia

  • Aspiration pneumonia

  • Bacterial pneumonia

  • Viral pneumonia

  • Tuberculosis

Differential Diagnoses

 

Workup

Approach Considerations

The criterion standard for diagnosis of pertussis is isolation of B pertussis in culture. However, laboratory confirmation of pertussis is difficult and delayed. Therefore, clinicians need to make the diagnosis of pertussis presumptively in patients with a history of intense paroxysmal coughing with or without whooping, color changes, posttussive vomiting, incomplete or absent pertussis vaccination, and a finding of lymphocytosis on laboratory examination.

A clinical case of pertussis is defined as one of the following:

  • An acute coughing illness that lasts at least 14 days in a person with at least one characteristic pertussis symptom (ie, paroxysmal cough, posttussive vomiting, or inspiratory whoop)

  • A cough that lasts at least 14 days in an outbreak setting

A confirmed case is defined as one of the following:

  • Any cough illness in which B pertussis is isolated and cultured (see the image below)

  • A case consistent with the clinical case definition confirmed by polymerase chain reaction (PCR) assay findings or epidemiologic linkage to a laboratory-confirmed case

    A photomicrograph of the bacterium Bordetella pert A photomicrograph of the bacterium Bordetella pertussis, using Gram stain technique.

Imaging studies typically add little to the diagnosis of pertussis but should be obtained when clinically indicated, based on examination or if the patient requires supplemental oxygen.

Serologic antibody titer testing is available, but often needs to be compared with results 1-2 weeks later and thus is not commonly helpful. The Centers for Disease Control and Prevention (CDC) also performs characterization of B pertussis isolates by serologic and molecular subtyping methods for outbreak support and other public health concerns. Laboratory testing is provided only upon prior communication with the Pertussis and Diphtheria Laboratory, indicating the reason for this service.

The use of direct fluorescent assay (DFA) of nasopharyngeal secretions is not recommended by the CDC; although the results can be available within minutes, the test has low sensitivity and specificity.

Chest radiography

Chest radiography may reveal perihilar infiltrates or edema with variable degrees of atelectasis. Consolidation is indicative of secondary bacterial infection or, rarely, pertussis pneumonia. Occasionally, pneumothorax, pneumomediastinum, or air in the soft tissues may be seen.

Blood Work

Leukocytosis (15,000-50,000/µL) with absolute lymphocytosis occurs during the late catarrhal and paroxysmal phases. It is a nonspecific finding but correlates with the severity of the disease. One study showed that among infants suspected of having pertussis, an absolute leukocyte count lower than 9400/μL excluded almost all infants who had a negative pertussis test finding.[29] In adults, especially those who have been vaccinated, lymphocytosis is rare.

In infants aged 90 days or younger, early serial monitoring of white blood cell (WBC) counts is crucial for identifying risk and determining the prognosis of infants with pertussis. A retrospective study of 31 infants with pertussis found that WBC counts higher than 30,000/μL (within a mean of 5.1 days after cough onset), rapid heart rates, and hyperventilation were indicators of severe B pertussis infection.[30, 31]

In this study, WBC counts in infants with severe disease tended to elevate more rapidly than those in infants with less severe disease.[30, 31] Moreover, WBC counts reached higher peaks in patients with severe pertussis than in those with less severe pertussis (mean, 74,200/μL vs 26,900/μL; median, 74,100/μL vs 24,200/μL).

Cultures

The results of blood culture are uniformly negative because B pertussis grows solely in the respiratory epithelium. The culture specimen should be obtained by using deep nasopharyngeal aspiration or by holding a flexible swab (Dacron or calcium alginate) in the patient's posterior nasopharynx for 15-30 seconds or until a cough is produced.

The sample special media (preferred media include Regan-Lowe or Bordet-Gengou agar and modified Stainer-Scholte media) should be promptly inoculated. B pertussis usually grows after 3-4 days; however, culture findings cannot be considered negative for pertussis until after 10 days.

Recovery rates are highest during the catarrhal or early paroxysmal phase and are low after the fourth week of illness.

See the following pertussis guideline pages from the CDC:

  • Laboratory Information

  • Diagnosis Confirmation

  • Best Practices for Health Care Professionals on the use of Polymerase Chain Reaction (PCR) for Diagnosing Pertussis

Culture findings may be negative in patients who were previously immunized, have received antimicrobial therapy, or have been coughing for more than 3 weeks. A negative culture finding does not exclude the diagnosis of pertussis.

PCR Assay and ELISA

PCR assays and antigen detection are increasingly used to assist in diagnosing pertussis. Advantages include greater sensitivity, more rapidly available results, and use later in the disease course or after antimicrobial therapy because the tests do not rely on the isolation of viable organisms.[32] Their use is limited by lack of standardization and incomplete understanding of the correlation between test results and the course of the illness.

A PCR assay may reveal 10 organisms per swab sample, and its sensitivity may be greater than that of culturing.

However, false-positive results have been a problem, with some reports of more than 50%. Although this or a positive culture is the case definition for reporting pertussis to the CDC or the World Health Organization (WHO), some are now recommending confirmation with enzyme-linked immunosorbent assay (ELISA) before declaring an epidemic. (Many now consider serologic testing with ELISA to be the criterion standard.)

The CDC recommends a combination of culture and PCR assay if a patient has a cough lasting longer than 3 weeks.

 

Treatment

Approach Considerations

Supportive therapy is the mainstay of treatment in patients with active pertussis infection.[23] The goals of therapy include limiting the number of paroxysms, observing the severity of cough, providing assistance when necessary, and maximizing nutrition, rest, and recovery. Oxygenation, breathing treatments, and mechanical ventilation should be provided as necessary. Infants should be carefully observed for apnea, cyanosis, or hypoxia.

Inpatient care is required for patients with pertussis who have intractable nausea and vomiting, failure to thrive, seizures, or encephalopathy or for patients with sustained hypoxemia during coughing paroxysms who require supplemental oxygen.

Hospitalization should be strongly considered for patients at risk for severe disease and complications, including infants younger than 3 months; infants aged 3-6 months, unless observed paroxysms are not severe; premature young infants; and infants or children with underlying pulmonary, cardiac, or neuromuscular disease.

Patients with pneumonia, apneic or cyanotic spells, hypoxia, or moderate to severe dehydration should also be considered for admission. Patients who are severely ill may require treatment in an intensive care unit (ICU).

For the hospitalized patient, in addition to standard precautions, droplet precautions are recommended for 5 days after initiation of effective therapy or until 3 weeks after the onset of paroxysms if appropriate antimicrobial therapy is not given.

Continuously monitor the heart rate, respiratory rate, and oxygen saturation of hospitalized patients, especially in relation to coughing paroxysms. Coughing, feeding, vomiting, and weight changes should be recorded. Pay attention to the young infant's hydration and nutritional status.

Diet and activity

No special diet is indicated, although a clinically age-appropriate diet should be maintained. Infants who cannot tolerate oral feedings may require intravenous fluids.

Activity for patients with pertussis should be guided by clinical course. In general, patients engage in activity as tolerated.

Consultations

Consultation with subspecialists is usually not indicated; however, if the diagnosis is unclear or the clinical course warrants, infectious disease specialists or other subspecialists should be consulted.

Transfer

Transfer of patients is not usually indicated unless inpatient therapy and monitoring are warranted and facilities for these are not available at the original institution. Need for transfer should be evaluated on an individual basis. Standard monitoring and transfer protocols should be followed.

Monitoring

Most patients older than 1 year can be treated on an outpatient basis if they do not fulfill the criteria for hospital admission. Frequent outpatient reevaluations are required; frequency of observation should be individualized based on the patient's age, disease severity, and presence of comorbid conditions.

Pharmacologic Therapy

Although antimicrobial agents initiated during the paroxysmal stage do not affect the duration and severity of illness, they can hasten the eradication of Bpertussis in the respiratory tract and help to prevent spread. Antibiotics may also prevent or alleviate secondary bacterial infection.

For patients of all ages azithromycin is the preferred agent.

Erythromycin and clarithromycin are not recommended in infants younger than 1 month, because their use has been associated with increased risk of infantile hypertrophic pyloric stenosis (IHPS). Azithromycin is the recommended agent for the youngest patients, although it also carries some risk of IHPS. Patients who are aged 2 months or older with hypersensitivity to macrolides may be treated with trimethoprim-sulfamethoxazole.

Prophylaxis

The effectiveness of prophylaxis for exposed, susceptible persons has not been determined; however, it is recommended for household and close contacts of the patient. Regimens include the following:

  • Azithromycin (5 d)

  • Erythromycin (14 d)

  • Alternative regimen - Clarithromycin 7.5 mg/kg twice daily for 14 days (the effectiveness of clarithromycin has not been proven but is inferred)

Immunization

Prevention through immunization remains the best defense in the fight against pertussis. However, because nearly all of the fatal cases of pertussis occur in infants who are too young to have been immunized, novel strategies must be explored to protect these patients.

An option may be to immunize neonates with acellular pertussis vaccine. However, immunogenicity of the vaccine in newborns and possible induction of tolerance to B pertussis antigens need to be investigated.

Evidence is overwhelming that parents and older siblings are the primary source of infection in young infants. The incidence of pertussis in preadolescents, adolescents, and adults has increased and may be responsible for the increasing number of cases observed in young infants in some countries. A study from the Netherlands concluded that 35-55% of pertussis cases in infants could be prevented if immunity to pertussis in parents were maintained or boosted.[33]

In December 2005, the American Academy of Pediatrics approved recommendations from the Committee on Infectious Diseases (COID) for universal vaccination of adolescents at the 11- or 12-year visit to boost protection against pertussis.[34, 35] The FDA has licensed 2 tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) products for use in children aged 10-18 years (Boostrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) and for patients aged 11-64 years (Adacel; Sanofi Pasteur, Toronto, Canada). Tdap has replaced tetanus in the childhood and adult immunization schedules. It has been shown to be effective in outbreaks in the short term. Long-term effectiveness studies are ongoing.

Whole-cell vaccination

This vaccine, used from the 1940s until the mid-1990s in the United States and from the 1940s until the 1980s in Europe, consisted of a whole cell with endotoxin given in 4 doses. About 80% of recipients acquired effective protection with this regimen. Two doses provided some immunity, whereas 1 dose provided little protection.

It was found that about 50% of patients who received the vaccine had a local reaction to it, 1 patient in 1750 had a seizure without fever, and 10.5 patients per million developed encephalitis; permanent brain damage was rare. Concern about CNS adverse effects is a major reason why many individuals chose not to be vaccinated.

Acellular vaccination

Vaccination is now recommended with acellular pertussis vaccine plus diphtheria and tetanus toxoids (DTaP) at the ages of 2, 4, 6, and 15-18 months and at age 4-6 years. A booster with Tdap (DTaP is not recommended for children aged 7 years or older) is recommended instead of 1 diphtheria-tetanus toxoid (Td) booster from age 19 years and up. Ideally, Tdap is recommended before pregnancy, but it may be given during pregnancy after 20 weeks’ gestation.[36] Additionally, the CDC recommends that all adults receive 1 dose of Tdap in order to decrease pertussis transmission in children.

After immunization, fever is reported in 3-5% of patients, persistent crying in 12 patients per 100,000, febrile seizures in 5 patients per 100,000, afebrile seizure in 2 patients per 100,000, and hyporesponsive episodes in 5 patients per 100,000. Severe neurologic sequelae have not been reported. This is about the same as it is for Td alone.

A randomized, controlled study by Pitisuttithum et al that included 450 adolescents reported that a monovalent and a combined recombinant acellular pertussis vaccine containing PTgen produced antibody responses that were greater and more sustained compared to Tdap.[51]

A study by McNamara et al that included 9801 pertussis patients 3 months of age and older reported a 60% reduction in odds of severe disease in children 7 months to 6 years of age when they received the recommended pertussis vaccine. The study also found a 30% reduction in posttussive vomiting in children and adult patients who received the age-appropriate vaccine.[37]

A study found that the pertussis vaccine did not increase the risk of adverse birth outcomes in an observational study of 123,494 women who gave birth to a live singleton infant, including 26,229 who received the acellular pertussis vaccine (Tdap) during pregnancy.[38, 39]  Crude estimates for preterm delivery were 6.3% among vaccinated women and 7.8% among unvaccinated women (adjusted risk ratio [RR] 1.03). Estimates for small for gestational age birth were 8.4% in vaccinated women and 8.3% in unvaccinated woman (adjusted RR, 1.00). Women who received Tdap before 20 weeks were not at increased risk for hypertensive disorder of pregnancy (adjusted RR, 1.09). The study did find a small but statistically significant increased risk of chorioamnionitis with Tdap vaccination during pregnancy. Chorioamnionitis was diagnosed in 6.1% of vaccinated women and 5.5% of unvaccinated women, for an adjusted risk ratio of 1.19.[38, 39]

A case-control evaluation by Skoff et al on 240 pertussis cases in newborns under months old reported that the vaccine effectiveness estimate for Tdap administered during the third trimester of pregnancy was 77.7% (95% confidence interval [CI], 48.3%-90.4%) and vaccine effectiveness increased to 90.5% when looking at just the serious cases of pertussis that required hospitalization (95% CI, 65.2%-97.4%).[40]

A study by Kent et al found that maternal vaccination administered early in the third trimester may provide protection against pertussis and other pathogens for infants born prematurely. In the study, mothers of 31 (19%) of 160 premature infants received combined tetanus, diphtheria, 5-component acellular pertussis, inactivated polio vaccine in pregnancy. The study reported that compared with infants of unvaccinated mothers, those born to vaccinated mothers had significantly higher antibody concentrations at 2 months for all measured vaccine antigens.[41]  Another study that included 66 mothers of infants with pertussis < 4 months of age reported that only 30% of the pregnant mothers received Tdap vaccine as recommended during their routine prenatal visit.[50]

A CDC survey reported that 48.8% of pregnant women in the US received the Tdap vaccine in 2016, an increase from 42.1% in 2015.[42]

For the latest childhood and adolescent immunization recommendations, see the CDC immunization schedules.[35, 43]

 

Medication

Medication Summary

Antimicrobial agents given during the catarrhal phase may ameliorate the disease. Once cough is established, antimicrobial agents may not alter the course of the illness but are still recommended to limit the spread of disease.

Pertussis-specific immunoglobulin is an investigational product that may be effective in decreasing paroxysms of cough, although it requires further evaluation.

The use of corticosteroids, albuterol, and other beta2-adrenergic agents for the treatment of pertussis is not supported by controlled, prospective data.

Antibiotics, Other

Class Summary

The Committee on Infectious Diseases (COID) of the American Academy of Pediatrics (Red Book Committee) currently recommends promptly treating all household and other close contacts (eg, children and staff at daycare centers) with erythromycin to limit secondary transmission.[44] This is regardless of the age or immunization status of contacts.

A 14-day course of oral erythromycin is the antimicrobial therapy of choice for patients with pertussis and for close contacts. Typical dosing schedule is 40-50 mg/kg/day (not to exceed 2 g/day) in 4 divided doses. Some experts prefer the estolate preparation in young infants because of more effective absorption, which may lead to decreased dosing and less frequent dosing intervals.

Erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin)

Erythromycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Erythromycin estolate is the antibiotic of choice to prevent interpersonal transfer, because of enhanced absorption, particularly in young infants. (Its effectiveness in prophylaxis for exposed and susceptible persons has not been determined.)

Erythromycin is recommended for household and close contacts (50 mg/kg/day PO qid for 14 days). It is effective in reducing the course and symptoms of pertussis if it is started within the first 10-14 days, but its efficacy has not proven beyond this period.

Azithromycin (Zithromax, Zmax)

Azithromycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It has been shown in several small studies to be effective against pertussis.

Clarithromycin (Biaxin)

Clarithromycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It has been shown in small studies to be effective against pertussis.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)

This agent inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It can be used as an alternative drug, although its efficacy against pertussis has not been unproven.

Vaccines, Inactivated, Bacterial

Class Summary

Active immunization increases resistance to infection. Vaccines consist of microorganisms or cellular components that act as antigens. Administration of the vaccine stimulates the production of antibodies with specific protective properties.

The need for prevention of pertussis through immunization cannot be overemphasized. All children younger than 7 years should receive the pertussis vaccine. In the United States, acellular pertussis vaccine is recommended and usually is combined with diphtheria and tetanus toxoids (DTaP). When possible, the same DTaP vaccine product should be used for the first 3 doses of the pertussis immunization series. Reduced-volume dosing is not recommended. Measurable antibody wanes after 3-5 years and is not measurable 12 years after vaccination has been completed. The vaccine may not prevent the illness entirely, but it has been shown to lessen disease severity and duration.

Adolescents and adults have been identified as the source of pertussis transmission to infants, from household contact studies and outbreak investigations. In February 2012, the CDC Advisory Committee on Immunization Practices (ACIP) recommended the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for all adults, including those aged 65 years or older, and pregnant women.

A Cochrane Database of Systematic Reviews study comparing the safety and efficacy of whole-cell pertussis vaccines with acellular pertussis vaccines in children up to age 6 years found that not only are multi-component acellular pertussis vaccines effective, they show less adverse effects than whole-cell vaccines for primary and booster doses.[45]

The American Academy of Pediatrics approved recommendations from the Committee on Infectious Diseases (COID) for universal vaccination of adolescents at the 11-year or 12-year visit to boost protection against pertussis.[34, 35] The FDA has licensed 2 Tdap vaccines for use in patients aged 10 years or older (Boostrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) and those aged 10-64 years (Adacel; Sanofi Pasteur, Toronto, Canada). Tdap has replaced tetanus in the childhood and adult immunization schedules. It has been shown to be effective in outbreaks in the short term. Long-term effectiveness studies are ongoing.

Compared with children who have been vaccinated, children of parents who refuse pertussis immunizations are at high risk for pertussis infection. A case-control study identified 156 laboratory-confirmed pertussis cases over an 11-year period (matched controls n=595).[46] Among the cases, 18 (12%) children did not receive the pertussis vaccine; among the controls, 3 (0.5%) children did not receive the pertussis vaccine. A secondary case-control analysis confirmed these results.

The study was performed within the Kaiser Permanente system of Colorado, where 11% of all pertussis cases within the system were attributed to parental vaccine refusal. Herd immunity does not seem to completely protect unvaccinated children from pertussis.

The latest vaccine recommendations can be found at the CDC Immunization Schedule Website.[47]

Diphtheria & tetanus toxoids/ acellular pertussis vaccine (Daptacel, Infanrix)

DTaP (Daptacel, Infanrix) promotes active immunity to diphtheria, tetanus, and pertussis by inducing production of specific antibodies and antitoxins.

In children and adults, DTaP may be administered into the deltoid or midlateral thigh muscles. In infants, the preferred site of administration is the mid-thigh, laterally.

Tetanus & reduced diphtheria toxoids/ acellular pertussis vaccine (Adacel, Boostrix, Tdap)

Promotes active immunity to diphtheria, tetanus, and pertussis by inducing the production of specific neutralizing antibodies and antitoxins. It is indicated for active booster immunization for persons aged 10 or older (Adacel approved for aged 10-64 y, Boostrix approved for aged 10 y or older). It is the preferred vaccine for adolescents scheduled for a booster vaccination.

 

Questions & Answers

Overview

What is pertussis (whooping cough)?

How long does pertussis (whooping cough) last?

What are the signs and symptoms of the catarrhal phase (stage 1) pertussis (whooping cough)?

What are the signs and symptoms of the paroxysmal phase (stage 2) pertussis (whooping cough)?

What are the signs and symptoms of the convalescent phase (stage 3) pertussis (whooping cough)?

How is pertussis (whooping cough) diagnosed?

What are the goals of treatment of pertussis (whooping cough)?

Which medications are used in the treatment of pertussis (whooping cough)?

What are the CDC recommendations for vaccination against pertussis (whooping cough)?

What is pertussis (whooping cough)?

How has the vaccination against pertussis (whooping cough) reduced the incidence?

What are the manifestations of pertussis (whooping cough)?

What are the complications of pertussis (whooping cough)?

What causes pertussis (whooping cough)?

What is the pathophysiology of pertussis (whooping cough)?

How is pertussis (whooping cough) transmitted?

Which patients are at a high risk of getting pertussis (whooping cough)?

What are the risk factors for pertussis (whooping cough)?

Is age a risk factor for pertussis (whooping cough) in adults?

How does the incidence of pertussis (whooping cough) in the US vary from year to year?

What is the rate of pertussis (whooping cough) in the US?

What is the rate of pertussis (whooping cough) in older children and adults in the US?

Is the rate of pertussis (whooping cough) increasing in the US?

Which states are the most affected by pertussis (whooping cough)?

What is the incidence of pertussis (whooping cough) in the US?

When was the most recent pertussis (whooping cough) epidemic in the US?

What is the worldwide incidence of pertussis (whooping cough)?

What are the race-related demographics of pertussis (whooping cough)?

Is pertussis (whooping cough) more common in males or females?

What are the age-related demographics of pertussis (whooping cough)?

What is the prognosis of pertussis (whooping cough)?

What are the complications of pertussis (whooping cough) in older infants and children?

Which patients with pertussis (whooping cough) have a higher risk of morbidity?

What is the mortality rate for pertussis (whooping cough)?

How often does pneumonia develop as a complication of pertussis (whooping cough)?

What are the CNS complications of pertussis (whooping cough)?

What is the role of leukocytosis in the prognosis of pertussis (whooping cough)?

Which conditions increase the risk of pertussis (whooping cough)?

How is the course of pertussis (whooping cough) characterized in older children, adolescents, and adults?

When are control measures indicated in cases of pertussis (whooping cough)?

What information on pertussis (whooping cough) should be provided to patients and parents?

Presentation

What is the incubation period of pertussis (whooping cough)?

What are the symptoms of pertussis (whooping cough) in children, adolescents, and adults?

What are the symptoms of the catarrhal phase (stage 1) pertussis (whooping cough)?

What are the symptoms of the paroxysmal phase (stage 2) pertussis (whooping cough)?

What are the symptoms of the convalescent phase (stage 3) pertussis (whooping cough)?

What is the typical presentation of pertussis (whooping cough)?

DDX

Which illnesses mimic clinical pertussis (whooping cough)?

Which conditions are considered in the differential diagnosis of pertussis (whooping cough)?

What are the differential diagnoses for Pertussis?

Workup

What is the criterion standard for the diagnosis of pertussis (whooping cough)?

How is a clinical case of pertussis (whooping cough) defined?

How is a confirmed case of pertussis (whooping cough) defined?

When are imaging studies indicated in the workup of pertussis (whooping cough)?

What is the role of serologic antibody titer testing in the workup of pertussis (whooping cough)?

Is direct fluorescent assay (DFA) useful in the workup of pertussis (whooping cough)?

What is the role of chest radiography in the workup of pertussis (whooping cough)?

What is the role of white blood count (WBC) testing in the workup of pertussis (whooping cough)?

What is the role of blood cultures in the workup of pertussis (whooping cough)?

When are the recovery rates of pertussis (whooping cough) the highest?

What are the CDC guidelines on pertussis (whooping cough)?

What are the culture findings in pertussis (whooping cough)?

What is the role of PCR assays and antigen detection testing in the workup of pertussis (whooping cough)?

What do PCR assays reveal in the workup of pertussis (whooping cough)?

Are PCR assays reliable for a diagnosis of pertussis (whooping cough)?

What are the CDC recommendations for the use of PCR assays in the workup of pertussis (whooping cough)?

Treatment

What is the mainstay of treatment for active pertussis (whooping cough) infection?

When is inpatient care indicated for the treatment of pertussis (whooping cough)?

Which vitals need to be continuously monitored in patients with pertussis (whooping cough)?

What are the dietary restrictions for patients with pertussis (whooping cough)?

Should activity restrictions for used in patients with pertussis (whooping cough)?

Are specialist consultations indicated in the treatment of pertussis (whooping cough)?

When is transfer indicated for patients with pertussis (whooping cough)?

How are patients with pertussis (whooping cough) best monitored on an outpatient basis?

What is the role of antimicrobial agents in the treatment of pertussis (whooping cough)?

What is the preferred antibiotic treatment of pertussis (whooping cough)?

Are erythromycin and clarithromycin used in the treatment of pertussis (whooping cough)?

What prophylaxis is available for people at risk for pertussis (whooping cough)?

What is the best defense against pertussis (whooping cough)?

Is a pertussis (whooping cough) vaccine available for neonates?

How do infants contract pertussis (whooping cough)?

What are the recommendations for vaccination against pertussis (whooping cough)?

What is whole-cell vaccination against pertussis (whooping cough)?

What is the recommended vaccination protocol against pertussis (whooping cough)?

What are the risks of pertussis (whooping cough) vaccination during pregnancy?

How effective is maternal vaccination for infants for the prevention of pertussis (whooping cough)?

Medications

Which medications are used in the treatment of pertussis (whooping cough)?

Which medications in the drug class Vaccines, Inactivated, Bacterial are used in the treatment of Pertussis?

Which medications in the drug class Antibiotics, Other are used in the treatment of Pertussis?