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Pertussis: Reappearing, and tricky to diagnose
By Sanjeev Sharma, MD, Sumanth Punukollu, MD, Christi Anderson, PharmD, Poonam Sharma, MD, and Donald Frey, MD
December 11, 2009
Known more familiarly to patients as whooping cough, pertussis is an acute, highly contagious respiratory infection, characterized by spells of uncontrollable spasmodic coughing followed by an inspiratory whoop or post-tussive vomiting. Prior to the vaccine era, pertussis was one of the major communicable diseases in children, with high mortality in infants. Following extensive use of vaccines, pertussis incidence decreased, but recently, a resurgence has been noted in the United States. What is causing this surge, and do we need to revisit our customary prevention and treatment measures?
Pathology
Pertussis is caused by the aerobic gram-negative bacteria Bordetella pertussis and is primarily toxin-mediated. Individuals become infected by inhaling contaminated droplets from an infected person's cough or sneeze. Once inside the airways, bacteria attach to cilia in the respiratory epithelial tract and release numerous antigenic and biologically active components. These include pertussis toxin, filamentous hemagglutinin, agglutinogens, adenylate cyclase, pertactin, and tracheal cytotoxin. The presence of these agents results in local inflammation and tissue damage, the combination of which interferes with the clearance of the pulmonary secretions. It also allows the organism to evade the host's defense mechanisms and causes lymphocytosis and impairment of chemotaxis.
Epidemiology
Pertussis is endemic in the United States, with approximately 5,000-7,000 cases reported each year. The disease affects all age groups, with higher incidence in infants less than 6 months of age (in 2002, 24% of all reported cases) and children between 10 and 19 years of age (in 2002, 33% of all reported cases). The bacteria cause disease only in humans; there are no known animal or insect vectors involved in transmission. Transmission is by close contact, (i.e., spending more than 10 hours a week in close proximity to an infected person) or being face-to-face during coughing or sneezing (regardless of the duration of exposure).
Pertussis is highly contagious, and up to 80% of susceptible household contacts may develop clinical disease following exposure to an index case.1 The infectious period lasts approximately three weeks. The patient is infectious during the catarrhal stage, two weeks from the onset of cough, and for five days following the start of antibiotics.2
In the United States, pertussis is a reportable disease. State health departments must be notified?at the time the clinician suspects the disease pending laboratory confirmation and again when confirmed by the laboratory.3
Page 2 of 5
Changing epidemiology
Despite uniform vaccination strategies across the world, pertussis has reappeared globally. In the United States, the incidence of pertussis has increased in the past 15 years (from one case per 100,000 population during 1980-1990 to 8.9 cases per 100,000 in 2004).4,5 There has also been a shift in age distribution, as increasing numbers of adults and adolescents are being diagnosed with the disease. The CDC data from 2004 indicate a 19-fold increase in 10- to 19-year-olds and a 16-fold increase in persons older than 20. In 2004-2005, 60% of all reported cases were in this age group, i.e., 11 years and older.6 There are several reasons for this recent change in age distribution:
Waning immunity Neither pertussis vaccination nor natural infection results in lifelong immunity. Instead, immunity generally wanes within 5-10 years.7. Adolescents and adults who acquire this infection after their immunity begins to wane usually present with milder atypical symptoms. Until recently, these patients were often underdiagnosed or misdiagnosed and went untreated. Such patients are also the primary source of infection for vulnerable infants and children, posing a significant community health concern as the disease may be transmitted unnoticed.1,4,7,8.
Increased awareness Physicians have become increasingly aware of the need for early recognition, diagnosis, and reporting of the disease.
Enhanced surveillance Surveillance is increased through the national electronic transmittal system and the supplementary pertussis surveillance system.
Available technology Improved laboratory diagnostic techniques, such as polymerase chain reaction (PCR), are widely available.
Past use of whole-cell pertussis vaccine In the 1990s, whole-cell pertussis vaccine was used in the United States, with variable efficacy and reduced immunity.
Incomplete immunization Children who miss one or two doses of primary immunization reduce herd immunity.
The current estimates are still thought to underrepresent the true incidence of pertussis. This could be explained by heterogeneity of disease expression, modification of disease by immunization, mixed infections, insensitive or nonstandardized tests, or poorly performed or unavailable laboratory tests.9-12.
Clinical presentation
The clinical course of pertussis is described in three stages: catarrhal, paroxysmal, and convalescent (Table 1). The incubation period is usually 7-10 days (range 5-21 days).
Atypical presentation
Vaccinated adolescents and adults may experience less severe paroxysmal symptoms, and the disease generally runs a milder course.13,14. Symptoms can resemble those of chronic bronchitis, and the paroxysmal cough and whoop may be absent. (A list of symptoms and their incidence appears in Table 2.) Pertussis should be kept in the differential diagnosis of adults and adolescents who experience acute nonimproving cough of more than one week's duration and who fail to improve with OTC medicines.
In infants younger than 6 months of age, the coughing paroxysms and characteristic whoop are often absent. Gagging, gasping or apnea, bradycardia, prolonged cough, and poor feeding are the main symptoms.2,10 In infants only, a clue to diagnosis is an elevated WBC count (>15,000/?L) with a preponderance of lymphocytes. The most contagious stages, catarrhal and early paroxysmal, may be missed, especially with atypical presentation, and could result in unknowing exposure of susceptible infants.15
(Page 3 of 5)
Diagnosis
Laboratory tests Bacterial culture is the gold standard for the diagnosis of pertussis. Additional methods include polymerase chain reaction (PCR), serology, and direct fluorescent antibody (DFA) testing.
Bacterial culture is the gold standard for the diagnosis of pertussis. Additional methods include polymerase chain reaction (PCR), serology, and direct fluorescent antibody (DFA) testing.
Bacterial culture is the gold standard for the diagnosis of pertussis. Additional methods include polymerase chain reaction (PCR), serology, and direct fluorescent antibody (DFA) testing.
Culture requires collection of a specimen from the posterior nasopharynx (not the anterior nares) using Dacron or calcium alginate (not cotton) swabs (Figure 1). Bordetella pertussis is a fastidious organism requiring special media for isolation, so the specimen should be collected and transported in either Lowe agar or Bordet-Gengou medium.
Obtaining results from the B. pertussis culture may take up to 10 days. Overall sensitivity of this test is low (15%)16 but is best during the catarrhal stage. Sensitivity decreases as the disease progresses10 and in previously immunized patients. Specificity is 100%.16 A negative culture does not exclude pertussis, and the CDC recommends using culture results along with PCR.
PCR is quick, with results available the same day.1,5,17,18 PCR can detect pertussis up to six weeks after onset of symptoms12,19 and is not affected by antimicrobial therapy.20 Sensitivity and specificity are 94% and 97%, respectively.16 Because of high numbers of false-positive results, the CDC recommends using PCR in addition to and not as replacement for culture.2 PCR is not standardized or FDA-licensed.
Serologic studies are used primarily in epidemiologic studies. The CDC does not recommend serology because it is not nationally standardized.2,16 Sensitivity and specificity of serology are variable.16
The DFA test requires specially trained personnel. It has high specificity (98%)16 and provides rapid results, but its sensitivity (52%)16 is lower than that of PCR. The CDC does not recommend DFA testing.2
Figure 1. The swab should be held in place for up to 10 seconds or until a paroxysmal cough is elicited (or ask patient to cough). After obtaining a sample, the swab should be shaken vigorously in saline solution and plated immediately in a selective medium.
Case definitions The CDC defines a clinical case of pertussis as a cough illness lasting at least two weeks with one of the following:
The CDC defines a clinical case of pertussis as a cough illness lasting at least two weeks with one of the following:
The CDC defines a clinical case of pertussis as a cough illness lasting at least two weeks with one of the following:
* Paroxysmal cough OR
* Inspiratory ?whoop? OR
* Post-tussive vomiting.2
A patient is considered to have confirmed pertussis if he has
* Acute cough illness of unspecified duration with isolation of B. pertussis OR
* Illness that fulfills the criteria for clinical pertussis and is confirmed by PCR OR
* Illness that fulfills the criteria for clinical pertussis and is epidemiologically linked to a culture- or PCR-confirmed case of pertussis.
A cough illness that fulfills the criteria for a clinical case but is not confirmed by laboratory testing or epidemiologically linked to a laboratory-confirmed case is classified by the CDC as probable pertussis.
(Page 4 of 5)
Treatment
The CDC recommends treating patients who have clinical, confirmed, or probable pertussis regardless of test results.9
Antibiotic therapy started early in the catarrhal stage can decrease the symptoms of the disease. However, once pertussis has progressed to the paroxysmal stage, the antibiotic serves only to reduce communicability and is less likely to impact the disease's course and duration. Infants may remain culture-positive for several weeks. There is no chronic carrier state.
First-line agents for the treatment of pertussis include erythromycin, clarithromycin, or azithromycin. Trimethoprim-sulfamethoxazole (TMP-SMX) can also be used in patients who cannot tolerate macrolides or who have erythromycin-resistant strains of B. pertussis. (See Table 3 for medications and the dosages used to treat pertussis.)
The FDA has not yet approved clarithromycin or azithromycin for use in infants younger than 6 months, and an association between orally administered erythromycin and infantile hypertrophic pyloric stenosis (IHPS) has been reported in infants younger than 1 month. Available data on the use of azithromycin in this population does not show a similarly increased risk. Until additional information is available, azithromycin is the drug of choice for treatment or prophylaxis of pertussis in infants younger than 1 month of age. However, all infants younger than 1 month who receive any macrolides should be monitored for development of IHPS for one month after completing the antibiotic course.
**TMP-SMX Contraindicated in infants <2 months.
Adapted from the CDC. Recommended antimicrobial agents for treatment and postexposure prophylaxis for pertussis. 2005 CDC Guidelines. MMWR. 2005;54(RR-14):1-20 and American Pediatric Society. Pertussis (whooping cough). In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009;504-519.
Infants younger than 6 months and older individuals with underlying conditions often require hospitalization for supportive care, including assessment of self-rescue following paroxysms and control of apnea, hypoxia, feeding difficulties, or other complications. Intensive-care facilities may be required.
Deaths and serious complications of pertussis (Table 4) occur mainly in infants and the elderly.
Postexposure prophylaxis
Postexposure prophylaxis depends upon the probable infectiousness of the patient, intensity of the exposure, potential consequences of severe pertussis in the contact, and the possibility for secondary exposure. Chemoprophylaxis is recommended for all household contacts and all other close contacts, such as children in day care and adults in close contact with high-risk children.2 Patients with pertussis should be excused from school and work until they have completed five days of recommended treatment; droplet precautions are recommended for five days after initiation of antibiotic therapy. Health-care professionals should observe standard precautions and wear respiratory masks. Prophylaxis medications and dosing are the same as for treatment.
(Page 5 of 5)
Vaccination
Routine vaccination of children and adolescents is the most important preventive strategy against pertussis. The Global Pertussis Initiative (GPI) recommends a primary series including five doses of diphtheria, tetanus toxoids, and acellular pertussis (DTaP) at ages 2, 4, 6, and 15-18 months, with a fifth dose at 4-6 years of age. Children younger than 7 years who have been in close contact with pertussis and have not completed the primary series should complete the series on a minimal-interval schedule. Currently there is no pertussis vaccine approved for children between 7 and 9 years of age in the United States. Children with a documented pertussis infection do not need an additional dose of pertussis vaccine and should complete the vaccine series with diphtheria and tetanus toxoids, adsorbed, pediatric strength.2
However, since natural immunity wanes, booster doses of tetanus toxoid and reduced diphtheria and acellular pertussis vaccine (Tdap) are recommended at the appropriate ages. With increased recognition of pertussis infection in adolescents and adults, the CDC and the American Academy of Pediatrics now recommend a single dose of Tdap for adolescents 11-18 years of age, as well as replacing a single dose of tetanus and diphtheria toxoids (adult type) (Td) at any vaccination site with Tdap for adults younger than 65. The interval between Td and Tdap vaccinations for adults and adolescents is five years. Adacel is the only vaccine available for adults (11-64 years), while Boostrix can be given only to children between 10 and 18 years of age. (See Table 5 for a list of currently available vaccines and their indications.)
Preterm birth, pregnancy, lactation, and HIV infection are not contraindications for either chemoprophylaxis or vaccination with Tdap or Td. In children with a prior history of a seizure disorder or other neurologic disorders, vaccine should be postponed and the patient's neurologic condition assessed. Seizures within three days of vaccination and inconsolable screaming or crying for three or more hours, collapse or shocklike state, hypotonic/hyporesponsive state, or body temperature reaching 104.8?F, any of which occurs within 48 hours following immunization, are contraindications for future pertussis vaccinations.
Adapted from prescribing information of each vaccine.
DTaP=diphtheria, tetanus, acellular pertussis; Hep B=hepatitis B; Hib=Hemophilus influenzae type B; IPV=inactivated polio vaccine; Tdap=tetanus, diphtheria, pertussis antigens
<hr>
Conclusion
Despite the widespread availability of vaccines, pertussis is making a comeback. Among the possible reasons behind the resurgence are waning immunity and improving diagnostic abilities. Once pertussis is diagnosed, effective antimicrobials include erythromycin, clarithromycin, and azithromycin, as well as TMP-SMX in patients intolerant of the macrolide antibiotics. Prevention is still the best medicine, though, with the appropriate vaccine for the patient's age at the appropriate dose. Up-to-date information is available from the CDC (www.cdc.gov) and the current edition of the American Academy of Pediatrics' Red Book: 2006 Report of the Committee on Infectious Diseases.21
Dr. Sanjeev Sharma is assistant professor, Department of Family Medicine, Creighton University Medical Center, Omaha, where Dr. Punukollu is a third-year resident in the Department of Family Medicine; Dr. Anderson is assistant professor, Department of Pharmacy; Dr Poonam Sharma is assistant professor, Department of Pathology; and Dr Frey is associate professor and chair, Department of Family Medicine.
References
1. Cherry JD, Grimprel E, Guiso N, et al. Defining pertussis epidemiology: Clinical, microbiologic and serologic perspectives. Pediatr Infect Dis J. 2005;24(5 Suppl):S25-S34.
2. Centers for Disease Control and Prevention. Guidelines for the Control of Pertussis Outbreaks. Available at www.cdc.gov/vaccines/pubs/pertussis-guide/guide.htm. Published 2000. Updated 2006.
3. Roush S, Birkhead G, Koo D, et al. Mandatory reporting of diseases and conditions by health care professionals and laboratories. JAMA. 1999;282:164-170. Available at jama.ama-assn.org/cgi/content/full/282/2/164.
4. Cherry JD. Epidemiology of pertussis. Pediatr Infect Dis J. 2006;25:361-362.
5. Greenberg DP. Pertussis in adolescents: increasing incidence brings attention to the need for booster immunization of adolescents. Pediatr Infect Dis J. 2005;24:721-728.
6. Edwards K, Freeman DM. Adolescent and adult pertussis: disease burden and prevention. Curr Opin Pediatr. 2006;18:77-80.
7. Wendelboe AM, Van Rie A, Salmaso S, Englund JA. Duration of immunity against pertussis after natural infection or vaccination. Pediatr Infect Dis J. 2005;24(5 Suppl):S58-S61.
8. Wheeler JG, Simmons AL. Pertussis update. Pediatr Infect Dis J. 2005;24:829-830.
9. Sutter RW, Cochi SL. Pertussis hospitalizations and mortality in the United States, 1985-1988. Evaluation of the completeness of national reporting. JAMA. 1992;267:386-391. Available
10. Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev. 2005;18:326-382. Available at http://cmr.asm.org/cgi/reprint/18/2/326.
11. Pertussis--United States, 2001-2003. MMWR. 2005;54:1283-1286. Available at www.cdc.gov/mmwr/preview/mmwrhtml/mm5450a3.htm.
12. Loeffelholz MJ, Thompson CJ, Long KS, Gilchrist MJ. Comparison of PCR, culture, and direct fluorescent-antibody testing for detection of Bordetella pertussis. J Clin Microbiol. 1999;37:2872-2876. Available at jcm.asm.org/cgi/content/full/37/9/2872?view=long&pmid=10449467.
13. Yaari E, Yafe-Zimerman Y, Schwartz SB, et al. Clinical manifestations of Bordetella pertussis infection in immunized children and young adults. Chest. 1999;115:1254-1258. Available at www.chestjournal.org/content/115/5/1254.long.
14. Heininger U, Klich K, Stehr K, Cherry JD. Clinical findings in Bordetella pertussis infections: results of a prospective multicenter surveillance study. Pediatrics. 1997;100(6):E10. Available at pediatrics.aappublications.org/cgi/reprint/100/6/e10.
15. Deen JL, Mink CA, Cherry JD, et al. Household contact study of Bordetella pertussis infections. Clin Infect Dis. 1995;21:1211-1219.
16. Gregory DS. Pertussis: a disease affecting all ages. Am Fam Physician. 2006;74:420-426. Available at www.aafp.org/afp/20060801/420.html.
17. van Kruijssen AM, Templeton KE, van der Plas RN, et al. Detection of respiratory pathogens by real-time PCR in children with clinical suspicion of pertussis. Eur J Pediatr. 2007;166:1189-1191.
18. Wendelboe AM, Van Rie A. Diagnosis of pertussis: a historical review and recent developments. Expert Rev Mol Diagn. 2006;6:857-864.
19. Heininger U, Schmidt-Schl?pfer G, Cherry JD, Stehr K. 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. Pediatrics. 2000;105(3):E31. Available at pediatrics.aappublications.org/cgi/reprint/105/3/e31.
20. Edelman K, Nikkari S, Ruuskanen O, et al. Detection of Bordetella pertussis by polymerase chain reaction and culture in the nasopharynx of erythromycin-treated infants with pertussis. Pediatr Infect Dis J. 1996;15:54-57.
21. Pertussis (whooping cough). In: Pickering LK, American Academy of Pediatrics, Committee on Infectious Diseases, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2006.
All electronic documents accessed September 1, 2009.
Authors' Information
Corresponding Author:
Dr Sanjeev Sharma MD Assistant Professor, Department of Family Medicine, Creighton University Medical Center, Omaha, NE
Mailing Address: 6709 N 30th Street, Omaha, NE 68112.
Ph: Office 402 2804734, Cell 402 2038544
Fax 402 2804785
Email: ssharma@creighton.edu
Other Authors:
Dr Sumanth Punukollu MD, 3rd year Resident, Department of Family Medicine, Creighton University Medical Center. Omaha, NE
Christi Anderson PharmD Asssitant Professor, Department of Pharmacy, Creighton University Medical Center. Omaha, NE
Dr Poonam Sharma MD, Assistant Professor, Department of Pathology, Creighton University Medical Center. Omaha, NE
Dr Donald Frey MD, Associate Professor and Chair, Department of Family Medicine, Creighton University Medical Center. Omaha, NE
Pertussis: Reappearing, and tricky to diagnose
By Sanjeev Sharma, MD, Sumanth Punukollu, MD, Christi Anderson, PharmD, Poonam Sharma, MD, and Donald Frey, MD
December 11, 2009
Known more familiarly to patients as whooping cough, pertussis is an acute, highly contagious respiratory infection, characterized by spells of uncontrollable spasmodic coughing followed by an inspiratory whoop or post-tussive vomiting. Prior to the vaccine era, pertussis was one of the major communicable diseases in children, with high mortality in infants. Following extensive use of vaccines, pertussis incidence decreased, but recently, a resurgence has been noted in the United States. What is causing this surge, and do we need to revisit our customary prevention and treatment measures?
Pathology
Pertussis is caused by the aerobic gram-negative bacteria Bordetella pertussis and is primarily toxin-mediated. Individuals become infected by inhaling contaminated droplets from an infected person's cough or sneeze. Once inside the airways, bacteria attach to cilia in the respiratory epithelial tract and release numerous antigenic and biologically active components. These include pertussis toxin, filamentous hemagglutinin, agglutinogens, adenylate cyclase, pertactin, and tracheal cytotoxin. The presence of these agents results in local inflammation and tissue damage, the combination of which interferes with the clearance of the pulmonary secretions. It also allows the organism to evade the host's defense mechanisms and causes lymphocytosis and impairment of chemotaxis.
Epidemiology
Pertussis is endemic in the United States, with approximately 5,000-7,000 cases reported each year. The disease affects all age groups, with higher incidence in infants less than 6 months of age (in 2002, 24% of all reported cases) and children between 10 and 19 years of age (in 2002, 33% of all reported cases). The bacteria cause disease only in humans; there are no known animal or insect vectors involved in transmission. Transmission is by close contact, (i.e., spending more than 10 hours a week in close proximity to an infected person) or being face-to-face during coughing or sneezing (regardless of the duration of exposure).
Pertussis is highly contagious, and up to 80% of susceptible household contacts may develop clinical disease following exposure to an index case.1 The infectious period lasts approximately three weeks. The patient is infectious during the catarrhal stage, two weeks from the onset of cough, and for five days following the start of antibiotics.2
In the United States, pertussis is a reportable disease. State health departments must be notified?at the time the clinician suspects the disease pending laboratory confirmation and again when confirmed by the laboratory.3
Page 2 of 5
Changing epidemiology
Despite uniform vaccination strategies across the world, pertussis has reappeared globally. In the United States, the incidence of pertussis has increased in the past 15 years (from one case per 100,000 population during 1980-1990 to 8.9 cases per 100,000 in 2004).4,5 There has also been a shift in age distribution, as increasing numbers of adults and adolescents are being diagnosed with the disease. The CDC data from 2004 indicate a 19-fold increase in 10- to 19-year-olds and a 16-fold increase in persons older than 20. In 2004-2005, 60% of all reported cases were in this age group, i.e., 11 years and older.6 There are several reasons for this recent change in age distribution:
Waning immunity Neither pertussis vaccination nor natural infection results in lifelong immunity. Instead, immunity generally wanes within 5-10 years.7. Adolescents and adults who acquire this infection after their immunity begins to wane usually present with milder atypical symptoms. Until recently, these patients were often underdiagnosed or misdiagnosed and went untreated. Such patients are also the primary source of infection for vulnerable infants and children, posing a significant community health concern as the disease may be transmitted unnoticed.1,4,7,8.
Increased awareness Physicians have become increasingly aware of the need for early recognition, diagnosis, and reporting of the disease.
Enhanced surveillance Surveillance is increased through the national electronic transmittal system and the supplementary pertussis surveillance system.
Available technology Improved laboratory diagnostic techniques, such as polymerase chain reaction (PCR), are widely available.
Past use of whole-cell pertussis vaccine In the 1990s, whole-cell pertussis vaccine was used in the United States, with variable efficacy and reduced immunity.
Incomplete immunization Children who miss one or two doses of primary immunization reduce herd immunity.
The current estimates are still thought to underrepresent the true incidence of pertussis. This could be explained by heterogeneity of disease expression, modification of disease by immunization, mixed infections, insensitive or nonstandardized tests, or poorly performed or unavailable laboratory tests.9-12.
Clinical presentation
The clinical course of pertussis is described in three stages: catarrhal, paroxysmal, and convalescent (Table 1). The incubation period is usually 7-10 days (range 5-21 days).
Atypical presentation
Vaccinated adolescents and adults may experience less severe paroxysmal symptoms, and the disease generally runs a milder course.13,14. Symptoms can resemble those of chronic bronchitis, and the paroxysmal cough and whoop may be absent. (A list of symptoms and their incidence appears in Table 2.) Pertussis should be kept in the differential diagnosis of adults and adolescents who experience acute nonimproving cough of more than one week's duration and who fail to improve with OTC medicines.
In infants younger than 6 months of age, the coughing paroxysms and characteristic whoop are often absent. Gagging, gasping or apnea, bradycardia, prolonged cough, and poor feeding are the main symptoms.2,10 In infants only, a clue to diagnosis is an elevated WBC count (>15,000/?L) with a preponderance of lymphocytes. The most contagious stages, catarrhal and early paroxysmal, may be missed, especially with atypical presentation, and could result in unknowing exposure of susceptible infants.15
(Page 3 of 5)
Diagnosis
Laboratory tests Bacterial culture is the gold standard for the diagnosis of pertussis. Additional methods include polymerase chain reaction (PCR), serology, and direct fluorescent antibody (DFA) testing.
Bacterial culture is the gold standard for the diagnosis of pertussis. Additional methods include polymerase chain reaction (PCR), serology, and direct fluorescent antibody (DFA) testing.
Bacterial culture is the gold standard for the diagnosis of pertussis. Additional methods include polymerase chain reaction (PCR), serology, and direct fluorescent antibody (DFA) testing.
Culture requires collection of a specimen from the posterior nasopharynx (not the anterior nares) using Dacron or calcium alginate (not cotton) swabs (Figure 1). Bordetella pertussis is a fastidious organism requiring special media for isolation, so the specimen should be collected and transported in either Lowe agar or Bordet-Gengou medium.
Obtaining results from the B. pertussis culture may take up to 10 days. Overall sensitivity of this test is low (15%)16 but is best during the catarrhal stage. Sensitivity decreases as the disease progresses10 and in previously immunized patients. Specificity is 100%.16 A negative culture does not exclude pertussis, and the CDC recommends using culture results along with PCR.
PCR is quick, with results available the same day.1,5,17,18 PCR can detect pertussis up to six weeks after onset of symptoms12,19 and is not affected by antimicrobial therapy.20 Sensitivity and specificity are 94% and 97%, respectively.16 Because of high numbers of false-positive results, the CDC recommends using PCR in addition to and not as replacement for culture.2 PCR is not standardized or FDA-licensed.
Serologic studies are used primarily in epidemiologic studies. The CDC does not recommend serology because it is not nationally standardized.2,16 Sensitivity and specificity of serology are variable.16
The DFA test requires specially trained personnel. It has high specificity (98%)16 and provides rapid results, but its sensitivity (52%)16 is lower than that of PCR. The CDC does not recommend DFA testing.2
Figure 1. The swab should be held in place for up to 10 seconds or until a paroxysmal cough is elicited (or ask patient to cough). After obtaining a sample, the swab should be shaken vigorously in saline solution and plated immediately in a selective medium.
Case definitions The CDC defines a clinical case of pertussis as a cough illness lasting at least two weeks with one of the following:
The CDC defines a clinical case of pertussis as a cough illness lasting at least two weeks with one of the following:
The CDC defines a clinical case of pertussis as a cough illness lasting at least two weeks with one of the following:
* Paroxysmal cough OR
* Inspiratory ?whoop? OR
* Post-tussive vomiting.2
A patient is considered to have confirmed pertussis if he has
* Acute cough illness of unspecified duration with isolation of B. pertussis OR
* Illness that fulfills the criteria for clinical pertussis and is confirmed by PCR OR
* Illness that fulfills the criteria for clinical pertussis and is epidemiologically linked to a culture- or PCR-confirmed case of pertussis.
A cough illness that fulfills the criteria for a clinical case but is not confirmed by laboratory testing or epidemiologically linked to a laboratory-confirmed case is classified by the CDC as probable pertussis.
(Page 4 of 5)
Treatment
The CDC recommends treating patients who have clinical, confirmed, or probable pertussis regardless of test results.9
Antibiotic therapy started early in the catarrhal stage can decrease the symptoms of the disease. However, once pertussis has progressed to the paroxysmal stage, the antibiotic serves only to reduce communicability and is less likely to impact the disease's course and duration. Infants may remain culture-positive for several weeks. There is no chronic carrier state.
First-line agents for the treatment of pertussis include erythromycin, clarithromycin, or azithromycin. Trimethoprim-sulfamethoxazole (TMP-SMX) can also be used in patients who cannot tolerate macrolides or who have erythromycin-resistant strains of B. pertussis. (See Table 3 for medications and the dosages used to treat pertussis.)
The FDA has not yet approved clarithromycin or azithromycin for use in infants younger than 6 months, and an association between orally administered erythromycin and infantile hypertrophic pyloric stenosis (IHPS) has been reported in infants younger than 1 month. Available data on the use of azithromycin in this population does not show a similarly increased risk. Until additional information is available, azithromycin is the drug of choice for treatment or prophylaxis of pertussis in infants younger than 1 month of age. However, all infants younger than 1 month who receive any macrolides should be monitored for development of IHPS for one month after completing the antibiotic course.
**TMP-SMX Contraindicated in infants <2 months.
Adapted from the CDC. Recommended antimicrobial agents for treatment and postexposure prophylaxis for pertussis. 2005 CDC Guidelines. MMWR. 2005;54(RR-14):1-20 and American Pediatric Society. Pertussis (whooping cough). In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009;504-519.
Infants younger than 6 months and older individuals with underlying conditions often require hospitalization for supportive care, including assessment of self-rescue following paroxysms and control of apnea, hypoxia, feeding difficulties, or other complications. Intensive-care facilities may be required.
Deaths and serious complications of pertussis (Table 4) occur mainly in infants and the elderly.
Postexposure prophylaxis
Postexposure prophylaxis depends upon the probable infectiousness of the patient, intensity of the exposure, potential consequences of severe pertussis in the contact, and the possibility for secondary exposure. Chemoprophylaxis is recommended for all household contacts and all other close contacts, such as children in day care and adults in close contact with high-risk children.2 Patients with pertussis should be excused from school and work until they have completed five days of recommended treatment; droplet precautions are recommended for five days after initiation of antibiotic therapy. Health-care professionals should observe standard precautions and wear respiratory masks. Prophylaxis medications and dosing are the same as for treatment.
(Page 5 of 5)
Vaccination
Routine vaccination of children and adolescents is the most important preventive strategy against pertussis. The Global Pertussis Initiative (GPI) recommends a primary series including five doses of diphtheria, tetanus toxoids, and acellular pertussis (DTaP) at ages 2, 4, 6, and 15-18 months, with a fifth dose at 4-6 years of age. Children younger than 7 years who have been in close contact with pertussis and have not completed the primary series should complete the series on a minimal-interval schedule. Currently there is no pertussis vaccine approved for children between 7 and 9 years of age in the United States. Children with a documented pertussis infection do not need an additional dose of pertussis vaccine and should complete the vaccine series with diphtheria and tetanus toxoids, adsorbed, pediatric strength.2
However, since natural immunity wanes, booster doses of tetanus toxoid and reduced diphtheria and acellular pertussis vaccine (Tdap) are recommended at the appropriate ages. With increased recognition of pertussis infection in adolescents and adults, the CDC and the American Academy of Pediatrics now recommend a single dose of Tdap for adolescents 11-18 years of age, as well as replacing a single dose of tetanus and diphtheria toxoids (adult type) (Td) at any vaccination site with Tdap for adults younger than 65. The interval between Td and Tdap vaccinations for adults and adolescents is five years. Adacel is the only vaccine available for adults (11-64 years), while Boostrix can be given only to children between 10 and 18 years of age. (See Table 5 for a list of currently available vaccines and their indications.)
Preterm birth, pregnancy, lactation, and HIV infection are not contraindications for either chemoprophylaxis or vaccination with Tdap or Td. In children with a prior history of a seizure disorder or other neurologic disorders, vaccine should be postponed and the patient's neurologic condition assessed. Seizures within three days of vaccination and inconsolable screaming or crying for three or more hours, collapse or shocklike state, hypotonic/hyporesponsive state, or body temperature reaching 104.8?F, any of which occurs within 48 hours following immunization, are contraindications for future pertussis vaccinations.
Adapted from prescribing information of each vaccine.
DTaP=diphtheria, tetanus, acellular pertussis; Hep B=hepatitis B; Hib=Hemophilus influenzae type B; IPV=inactivated polio vaccine; Tdap=tetanus, diphtheria, pertussis antigens
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Conclusion
Despite the widespread availability of vaccines, pertussis is making a comeback. Among the possible reasons behind the resurgence are waning immunity and improving diagnostic abilities. Once pertussis is diagnosed, effective antimicrobials include erythromycin, clarithromycin, and azithromycin, as well as TMP-SMX in patients intolerant of the macrolide antibiotics. Prevention is still the best medicine, though, with the appropriate vaccine for the patient's age at the appropriate dose. Up-to-date information is available from the CDC (www.cdc.gov) and the current edition of the American Academy of Pediatrics' Red Book: 2006 Report of the Committee on Infectious Diseases.21
Dr. Sanjeev Sharma is assistant professor, Department of Family Medicine, Creighton University Medical Center, Omaha, where Dr. Punukollu is a third-year resident in the Department of Family Medicine; Dr. Anderson is assistant professor, Department of Pharmacy; Dr Poonam Sharma is assistant professor, Department of Pathology; and Dr Frey is associate professor and chair, Department of Family Medicine.
References
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2. Centers for Disease Control and Prevention. Guidelines for the Control of Pertussis Outbreaks. Available at www.cdc.gov/vaccines/pubs/pertussis-guide/guide.htm. Published 2000. Updated 2006.
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13. Yaari E, Yafe-Zimerman Y, Schwartz SB, et al. Clinical manifestations of Bordetella pertussis infection in immunized children and young adults. Chest. 1999;115:1254-1258. Available at www.chestjournal.org/content/115/5/1254.long.
14. Heininger U, Klich K, Stehr K, Cherry JD. Clinical findings in Bordetella pertussis infections: results of a prospective multicenter surveillance study. Pediatrics. 1997;100(6):E10. Available at pediatrics.aappublications.org/cgi/reprint/100/6/e10.
15. Deen JL, Mink CA, Cherry JD, et al. Household contact study of Bordetella pertussis infections. Clin Infect Dis. 1995;21:1211-1219.
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17. van Kruijssen AM, Templeton KE, van der Plas RN, et al. Detection of respiratory pathogens by real-time PCR in children with clinical suspicion of pertussis. Eur J Pediatr. 2007;166:1189-1191.
18. Wendelboe AM, Van Rie A. Diagnosis of pertussis: a historical review and recent developments. Expert Rev Mol Diagn. 2006;6:857-864.
19. Heininger U, Schmidt-Schl?pfer G, Cherry JD, Stehr K. 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. Pediatrics. 2000;105(3):E31. Available at pediatrics.aappublications.org/cgi/reprint/105/3/e31.
20. Edelman K, Nikkari S, Ruuskanen O, et al. Detection of Bordetella pertussis by polymerase chain reaction and culture in the nasopharynx of erythromycin-treated infants with pertussis. Pediatr Infect Dis J. 1996;15:54-57.
21. Pertussis (whooping cough). In: Pickering LK, American Academy of Pediatrics, Committee on Infectious Diseases, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2006.
All electronic documents accessed September 1, 2009.
Authors' Information
Corresponding Author:
Dr Sanjeev Sharma MD Assistant Professor, Department of Family Medicine, Creighton University Medical Center, Omaha, NE
Mailing Address: 6709 N 30th Street, Omaha, NE 68112.
Ph: Office 402 2804734, Cell 402 2038544
Fax 402 2804785
Email: ssharma@creighton.edu
Other Authors:
Dr Sumanth Punukollu MD, 3rd year Resident, Department of Family Medicine, Creighton University Medical Center. Omaha, NE
Christi Anderson PharmD Asssitant Professor, Department of Pharmacy, Creighton University Medical Center. Omaha, NE
Dr Poonam Sharma MD, Assistant Professor, Department of Pathology, Creighton University Medical Center. Omaha, NE
Dr Donald Frey MD, Associate Professor and Chair, Department of Family Medicine, Creighton University Medical Center. Omaha, NE