Pediatrics

Pertussis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has pertussis? What are the typical findings for this disease?

Pertussis or whooping cough is a highly contagious respiratory tract infection caused by the gram-negative bacillus, Bordetella pertussis. Humans are the only known hosts of the disease. Transmission occurs by close contact with cases via aerosolized droplets. The disease remains a public health problem in persons of all ages, socioeconomic classes and ethnicities.

The incidence of disease in the adolescent and adult populations has significantly increased over the last several decades with waning of vaccine and naturally induced immunity being one of the major contributing factors.

Adolescents and adults serve as the major transmitters of the illness to others in the community with young infants who are too young to be immunized or who are incompletely immunized being at the greatest risk for complications, hospitalizations and deaths from the disease.

Symptoms and their severity of pertussis differ depending on the age of the patient; however, prolonged paroxysmal cough that lasts for weeks to months is the hallmark of disease. Symptoms are more severe in young infants and children and milder in adolescents. The disease has three stages.

1. Catarrhal stage (lasts up to 2 weeks)

  • - Low grade to no fever

  • - Rhinorrhea with no pharyngitis

  • - Mild cough

  • - Conjunctival injection

2. Paroxysmal stage (lasts up to 6 weeks)

  • - Paroxysmal coughing episodes (worse at night, triggered by eating or drinking)

  • - Inspiratory whoop (may be mild in adolescents)

  • - Posttussive vomiting

  • - Apnea (may be the only presenting symptom in very young infants)

  • - Trouble catching breath during coughing episode

  • - Cyanosis

3. Convalescent stage (lasts up to 6 weeks)

  • - coughing paroxysms are less frequent and their intensity is decreased

Specific questions to ask that will aid in making diagnosis:

This is especially important in older children and adolescents in whom disease symptoms may be milder and more non-specific.

Duration of cough?

Has cough worsened over time?

Has person had preceding upper respiratory tract illness?

Has person had exposure to individuals with upper respiratory tract infection with protracted coughing?

Have any close contacts had a persistent cough lasting for more than 2 weeks?

Has there been an outbreak of a cough illness in their neighborhood, school, daycare etc?

Do you have trouble sleeping at night due to cough illness?

Do you have trouble catching your breath between cough episodes?

Physical examination findings that may be seen:

Findings during coughing episodes include -

Restlessness and agitation due to prolonged coughing episode with difficulty catching breath.

Tachycardia or bradycardia (young infants), tachypnea or apnea (young infants)

Perioral cyanosis

Subconjunctival hemorrhages

Coryza

Tympanic membrane rupture

Paroxysmal cough with inspiratory whoop

Chest exam - retractions, rib tenderness, asymmetric or decreased breath sounds, rhonchi, wheezing or crackles

Abdominal exam and inguinal exam for development of hernia

Neurologic exam for level of consciousness and presence of seizure activity (seizures and encephalopathy may develop as a complication of disease)

What other disease/condition shares some of these symptoms?

Infectious:

Adenovirus

Aspiration pneumonia

Bronchiolitis

Bacterial pneumonia

Chlamydia trachomatis

Chlamydophilia pneumoniae

Chronic sinusitis

Coronavirus

Human metapneumovirus

Human parainfluenza viruses

Influenza viruses A and B

Mycoplasma pneumoniae

Respiratory syncytial virus

Rhinovirus

Tuberculosis

Inflammatory:

Allergic rhinitis

Asthma

Chronic bronchitis

Bronchiectasis

Interstitial pneumonitis

Postnasal drip

Other:

Gastoesophageal reflux disease

Cystic fibrosis

What caused this disease to develop at this time?

Pertussis is caused by the fastidious Gram negative, pleomorphic bacillus, Bordatella pertussis. The frequency of infection has been significantly reduced in developed countries by the use of pertussis vaccine, but its incidence has increased in recent years.

Major contributing factors to resurgence of pertussis in the United States include:

- waning of vaccine induced and natural immunity in adolescents and adults

- improved recognition

- disease in infants who are too young to be immunized or who are incompletely immunized.

Organism is highly transmissible from person with active disease to close household and community contacts.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Complete blood count with platelets and differential: increased absolute white blood cell count with an absolute lymphocytosis of 10,000 or greater may be seen in young infants and children who are unimmunized or underimmunized. It is uncommon to see significant lymphocytosis in older child or adolescent.

Detection of the organism:

It is critically important to obtain specimen for testing from posterior nasopharynx (NOT throat or sputum). This posterior nasophayrngeal specimen can be sent for both pertussis culture and polymerase chain reaction (PCR). Culture and PCR have their greatest yield during first 3-4 weeks of cough illness. The diagnosis is confirmed if culture and/or PCR are positive.

The ability to isolate the organism by culture is influenced by several factors including the technique used to obtain the specimen, the method by which specimen is transported to the lab, and how the specimen is handled in the lab. Similarly, PCR accuracy may be reduced if specimen collected is not from the posterior nasopharynx and if sample is not transported to lab within 24 to 48 hours of collection. Negative results do exclude the diagnosis of pertussis if clinical symptoms and/or exposure history is compatible with the disease.

After 4 weeks of illness, pertussis single sample serology is a more accurate laboratory test to help confirm the diagnosis. Single-sample serology involves one acute antibody titer determination with no convalescent titer. It is an enzyme-linked immunosorbent assay (ELISA) which measures immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin (PT). High antibody titers of >100 EU/mL are highly suggestive of a current or recent infection. If the patient has been recently immunized or recently completed a course of antibiotics, the immune response may be blunted. IgG titers are more sensitive than IgA titers, however, elevation of both IgG and IgA together is most suggestive of an acute infection.

Would imaging studies be helpful? If so, which ones?

Chest radiograph may be indicated in patients with respiratory distress and abnormal findings on chest examination, however, it is not necessary in routine cases.

Confirming the diagnosis

CDC case definitions:

1. Clinical case: Cough for 14 days or more and at least one of the following symptoms: 1) paroxsymal cough; 2) inspiratory whoop; 3) posttussive vomiting or 2 or more weeks of cough in an outbreak setting.

2. Probable case: Meets clinical case definition, is not laboratory confirmed, and is not epidemiologically linked to a laboratory-confirmed case.

3. Confirmed case: Positive laboratory finding by either culture or PCR; or the patient must meet the clinical case definition for pertussis and have had direct contact with a person with laboratory-confirmed pertussis.

WHO case definitions:

Case definition: Paroxysmal cough of 21 days or longer and one or more of the following: 1) positive culture for B. pertussis; 2) significant increase in the rates of specific antibodies (IgG and IgA against FHA, AGG-2 and 3 or PT); 3) proven contact with culture-confirmed case.

Laboratory Criteria for Diagnosis:

1) Isolation of B. pertussis from a clinical specimen

2) Positive PCR reaction assay for B. pertussis

The case definitions that exist should only be used as a guideline and may not be helpful in all situations to confirm diagnosis of disease. This is especially true for adolescent and adult cases, which may have milder and more non-specific symptoms that don't fit case definitions. Disease expression is heterogenous.

If you are able to confirm that the patient has pertussis, what treatment should be initiated?

Antibiotic therapy should be initiated as soon as possible for all patients with suspected or known pertussis to prevent disease transmission. If antibiotic therapy is initiated during the catarrhal stage, symptoms may be ameliorated or reduced in duration. Antibiotics initiated during the cough stage of illness have no significant effect on the severity or duration of symptoms, but antibiotic should be prescribed in an effort to prevent further spread of infection to susceptible contacts. All close and household contacts should receive antibiotic prophylaxis.

1. Antibiotics in the macrolide class of (erythromycin, azithromycin and clarithromycin) are recommended for both treatment and prophylaxis of pertussis. Azithromycin is the drug of choice for all age groups. Erythromycin therapy is contraindicated in infants under 4 weeks of age due to the risk of hypertrophic pyloric stenosis.

2. For patients that are unable to tolerate or who are allergic to the macrolide class of antibiotics, trimethoprim sulfamethoxazole (TMP/SMX) is the alternative drug that may be used in all age groups.

(See Table I)

Table I.

Antibiotics used in the Treatment and Chemoprophylaxis of Pertussis
Drug Class Agent Dosage
Macrolides Azithromycin Infants < 6 months: 10 mg/kg/day for 5 daysInfants ≥ 6 months and children: 10 mg/kg/day on day 1 (max 500 mg), followed by 5 mg/kg/day on days 2-5 (max 250 mg)Adolescents & Adults: 500 mg on day 1, followed by 250 mg per day on days 2-5
  Erythromycin Infants > 1 month and children:  40-50 mg/kg/day in 3-4 divided doses for 14 daysAdolescents & Adults: 2 grams per day in four divided doses for 14 days
Clarithromycin Infants > 1 month and children:  15 mg/kg/day in 2 divided doses (max 1 gram per day) for 7 daysAdolescents & Adults: 1 gram per day in 2 divided doses for 7 days
Trimethoprim sulfonamide combination Trimethoprim-sulfamethoxazole (TMP-SMX) Infants and children 2 months and older: TMP 8 mg/kg per day, SMX 40 mg/kg per day in two divided doses for 14 daysAdolescents & adults: TMP 320 mg per day, SMX 1,600 mg per day in two divided doses for 14 days

What are the adverse effects associated with each treatment option?

Macrolide antibiotics may cause gastrointestinal irritation including epigastric distress, abdominal cramps, nausea, vomiting and diarrhea. Hypersensitivity reactions include skin rashes, drug fever, cholestatic hepatitis and sensorineural hearing loss.

Most common adverse effects with TMP-SMX are gastrointestinal and hypersensitivity skin reactions. Rare adverse effects include Steven-Johnson syndrome, toxic epidermal necrolysis, blood dyscrasias, and hepatic dysfunction and necrosis.

What are the possible outcomes of pertussis?

1. Resolution of cough illness after prolonged period of time (3-4 months)

2. Development of sequelae and complications

3. Death

What causes this disease and how frequent is it?

Pertussis is a highly transmissible respiratory illness caused primarily by the Gram-negative bacteria Bordetella pertussis (95% of cases) with small portion of cases caused by Bordetella bronchiseptica. Transmission occurs via droplets from a coughing person with attack rates in susceptible household contacts ranging from 70% to 100%. The true disease burden of pertussis is unknown but studies suggest that reported cases represent only 15% to 25% of the cases that are actually occurring.

In the general population, the attack rate is estimated to be about 9 cases per 100,000 population. This rate may be significantly increased in areas experiencing pertussis outbreaks and the rate of disease in the young infant population under 4 months of age is estimated to be 19 times that of the general population.

Pertussis epidemics tend to occur at 2 to 5 year intervals. The disease occurs worldwide and generally has no seasonal pattern, although more cases seem to be seen in the summer and fall months. Disease occurs in both males and females with no predilection for either gender. The incidence of disease in the adolescent and adult populations has significantly increased over the last several decades.

How do these pathogens/genes/exposures cause the disease?

Infected individuals spread the disease via respiratory droplets that either contaminate the environment, with the hands of a potential host making contact with the infected secretions and then inoculating their respiratory tract, or the droplets from a coughing persons reach the upper respiratory tract of a susceptible person.

Other clinical manifestations that might help with diagnosis and management

What complications might you expect from the disease or treatment of the disease?

1. Pneumonia

2. Seizures

3. Encephalopathy

4. Fractured ribs

5. Hearing loss from ruptured typanic membranes

6. Aspiration pneumonia

7. Pneumothoraces

8. Abdominal wall and inguinal hernias

9. Intracranial bleeding (in elderly population)

Are additional laboratory studies available; even some that are not widely available?

How can pertussis be prevented?

Preventative vaccines for infants, children, adolescents and adults are the best way to prevent the disease.

What is the evidence?

Bisgard, KM, Pascual, FB, Ehresmann, KR. "Infant pertussis: Who was the source?". Pediatr Infect Dis J. vol. 23. 2004. pp. 985-989.

CDC. MMWR. vol. 51. 2002. pp. 73-75.

CDC. MMWR. vol. 60. 2011. pp. 13-15.

"Recommended antimicrobial agents for the treatment and postexposure prophylaxes of pertussis: 2005 CDC guidelines". MMWR Morb Mortal Wkly Rep. vol. 54. 2005. pp. 1-16.

Cherry, JD. "Pertussis vaccines for adolescents and adults". Pediatrics. vol. 116. 2005. pp. 755-756.

Cherry, JD, Grimprel, E, Guiso, N. "Defining pertussis epidemiology: clinical, microbiologic and serologic perspectives". Pediatr Infect Dis J. vol. 24. 2005. pp. S25-S34.

Cherry, JD, Tan, TQ, VonKonig, CHW. "Clinical Definition of Pertussis: Summary of a Global Pertussis Initiative (GPI) Roundtable Meeting February 2011". Clin Infect Dis. vol. 54. 2012. pp. 1756-1764.

Christie, CDC, Baltimore, RS. "Pertussis in neonates". Am J Dis Child. vol. 143. 1989. pp. 1199-1202.

Cortese, MM, Baughman, AL, Brown, K, Srivastava, P. "A "new age" in pertussis prevention new opportunities through adult vaccination". Am J Prev Med. vol. 32. 2007. pp. 177-185.

Crowcroft, NS, Booy, R, Harrison, T. "Severe and unrecognized: Pertussis in UK infants". Arch Dis Child. vol. 88. 2002. pp. 802-806.

De Serres, G, Shadmani, R, Duval, B. "Morbidity of pertussis in adolescents and adults". J Infect Dis. vol. 182. 2000. pp. 174-179.

Hallander, HO, Reizenstein, I, Renemar, B. "Comparison of nasopharyngeal aspirates with swabs for culture of Bordetella pertussis". J Clinic Microbiol. vol. 31. 1993. pp. 50-52.

Jenkinson, D. "Whooping cough: What proportion of cases is notified in an epidemic?". BMJ. vol. 287. 1983. pp. 183-185.

Mattoo, S, Cherry, JD. "Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and Bordetella subspecies". Clin Microbiol Rev. vol. 18. 2005. pp. 326-382.

Olin, P, Rasmussen, F, Gustafsson, L. "Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine". Lancet. vol. 350. 1997. pp. 1569-1577.

Schlapfer, G, Senn, HP, Berger, R. "Use of the polymerase chain reaction to detect Bordetella pertussis in patients with mild or typical symptoms of infection". Eur J Clin Microbiol Infect Dis. vol. 12. 1993. pp. 459-463.

Strebel, PM, Cochi, SL, Farizo, KM. "Pertussis in Missouri: Evaluation of nasopharyngeal culture, direct fluorescent antibody testing, and clinical case definitions in the diagnosis of pertussis". Clin Infect Dis. vol. 16. 1993. pp. 276-285.

Tan, TQ, Gerbie, MV. "Pertussis Disease in New Mothers: Impact on Young Infants and Strategies for Prevention". Obstet Gynecol. vol. 113. 2009. pp. 399-401.

Tan, TQ, Gerbie, MV. "Pertussis and Patient Safety: Implementing Tdap Vaccine Recommendations in Hospital Settings". Joint Comm J Qual Pat Safety. vol. 36. 2010. pp. 173-178.

"The Global Pertussis Initiative". Pediatr Infect Dis J. vol. 24. 2005. pp. S5-S98.

Ongoing controversies regarding etiology, diagnosis, treatment

There are ongoing studies to improve the diagnostic criteria of pertussis in different age groups and in the laboratory diagnosis of the disease.

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