Mark S. Dworkin, MD, MPHTM, Assistant Professor of Medicine, Rush University; Voluntary Attending Physician, John H. Stroger, Jr, Hospital; and State
Epidemiologist, Illinois Department of Public Health, Chicago, Ill.
Last winter an adult male patient with AIDS presented at his routine follow-up appointment complaining of a nonproductive
cough illness. The cough had lasted for more than 2 weeks, was occurring in spasmodic episodes, and was disturbing his sleep.
I ordered a CBC and differential count along with other routine HIV-related follow-up laboratory measurements, such as a CD4
T-cell count and viral load. Also, because of the description of his cough illness, I obtained a collection kit and transport
medium for pertussis and performed a nasopharyngeal swab for a Bordetella pertussis polymerase chain reaction (PCR) test and culture. The patient recoiled as I attempted to place the swab deep into his nares
and forbade me from reattempting the procedure to collect a better specimen.
I prescribed a 14-day treatment with erythromycin and debated with myself whether this patient should be reported to the local
health department as a suspected case of pertussis. There were no infants or pregnant women in his home, and no one else he
knew was ill with a similar illness. He was educated to avoid others for the first 5 days of antibiotic treatment because
pertussis was a possible diagnosis. Had this case occurred just a few months earlier and been handled by a different physician,
the likelihood would have been low that pertussis would have been in the differential diagnosis, or even that the pertussis
diagnostic collection kit would have been readily available. However, during the summer and fall of 2004, Illinois and many
other states experienced the largest surge in reported cases of pertussis since 1959, including unprecedented media attention
that raised awareness of this disease among some physicians and their patients.
The problem
Many physicians are not aware that childhood vaccinations against pertussis do not provide protective immunity into adulthood.
Whole-cell vaccines have been used in the United States since the late 1940s, and their use has been associated with a remarkable
decline in pertussis. We also know that a decline in pertussis immunization rates in previously well-vaccinated populations
has resulted in substantial pertussis epidemics. In the United Kingdom, when vaccination dropped from 79% (1973) to 40% (1976),
an outbreak of more than 100,000 cases occurred, including more than 30 deaths.1
Pertussis outbreaks generally have occurred not because of vaccine failures but because pertussis immunization programs did
not have a vaccine that could eliminate the disease. Although the vaccine was effective, adequate antibody levels derived
from immunization persist only up to 3 years after the last dose and then appear to decline. The rate of decline in immunity
after receipt of the last dose has varied widely in different studies. Immunity following the full 5-dose regimen has been
shown to wane in some children to the point of susceptibility within only 5 to 10 years.2
As a result, a significant proportion of pertussis infections occur in immunized adolescents and adults whose levels of protective
antibodies have declined. These persons may be susceptible to pertussis infection and may, in turn, infect infants, who are
much more likely to become severely ill and die. Enhanced recognition of pertussis in adolescents and adults thus becomes
crucial.
When to suspect pertussis
Although not rare in adults, pertussis has infrequently been considered in the differential diagnosis of adults with respiratory
tract illness. A cough lasting more than 2 weeks should generally arouse suspicion of it. The CDC's clinical case definition
for pertussis is a cough illness lasting at least 2 weeks with at least 1 of the following symptoms without other apparent
cause: paroxysms of coughing, inspiratory whooping, and posttussive vomiting.3 The distinctive sound of a pertussis cough can be heard on a Texas State Health Services Web site (http://www.tdh.state.tx.us/immunize/pert_cough.htm).4
Unimmunized persons of all ages typically develop more severe disease. In infants, pertussis may result in apnea, pneumonia,
encephalopathy, and death. Complications of pertussis include secondary bacterial infections (for example, otitis media and
pneumonia), especially in infants. Severe coughing may produce conjunctival and scleral hemorrhages, facial and truncal petechiae,
epistaxis, CNS hemorrhages, subcutaneous emphysema, pneumothorax, rib fracture, umbilical and inguinal hernias, and rectal
prolapse. Ulceration of the frenulum, seizures, dehydration from protracted vomiting, and cranial nerve abnormalities have
been reported. Sleep disturbance is common.
Adults, including those who were fully immunized as children, may develop classical pertussis with posttussive vomiting and/or
inspiratory whooping, or they may present with an illness characterized only by prolonged coughing (weeks to months). Some
are relatively asymptomatic. Although adults with pertussis are hospitalized and die much less frequently than infants with
this infection, adult hospitalizations and deaths have occurred both in the United States and abroad.
Disease transmission
Pertussis is highly contagious and spread by respiratory droplets. When a patient with the disease is hospitalized, respiratory
precautions are required to prevent transmission. Pertussis is especially contagious during the first week of illness but
is easily transmitted during the period starting 7 days following exposure and for up to 3 weeks after the onset of spasmodic
coughing. It can develop in up to 90% of susceptible family contacts of an index household case.2 Because the incubation period for pertussis is from 7 to 13 days (range, 6-20 days), transmission within a household may
occur among family members over weeks. Adults may transmit this disease to each other, and outbreaks have been reported in
office settings, hospitals, and even an oil refinery.
Making the diagnosis
Recognizing pertussis can be challenging. Leukocytosis, often with lymphocytosis, may be observed but primarily in unimmunized
persons. Recent infection is suggested by high IgA titers (or, in unimmunized persons, high IgM titers), but, with the exception
of the Massachusetts State Laboratory Institute, most laboratories that perform serology lack a reliable standardized method.
Although a standardized single serum assay for national use is under development, none of the commercial serologic tests for
pertussis have been licensed in this country for routine diagnostic use.5 Because of concerns over false-positive results, the direct fluorescent antibody test tends not to be used much.
The preferred test is the nasopharyngeal aspirate or swab for PCR and culture confirmation. Problems with these techniques
include lack of familiarity with the procedure, patient discomfort (the swab must be inserted fairly deeply), and use of less-than-optimal
swabs. Dacron or calcium alginate swabs are preferred.6 The swab should be inserted through the nostril into the nasopharynx and gently rotated for 15 to 60 seconds, if possible.
While laboratory confirmation is always preferred, B pertussis is a fastidious organism and often does not grow out in culture. The longer after onset of illness that testing with PCR
and culture is done, the lower the yield. Thus, by the time the chronic nature of the cough provides a clue to the diagnosis
of pertussis, the actual yield may be poor. Because of relatively low sensitivity, a negative test result for pertussis does
not rule out the diagnosis and cannot be the only basis for a decision not to treat the disease.
Management
The traditional regimen for treating and prophylaxis of pertussis is erythromycin, given for 14 days, but GI discomfort is
a common adverse effect. The alternative choices of clarithromycin and azithromycin are better tolerated. Though considerably
more expensive, azithromycin may be worth considering because only 5 days of treatment provide effectiveness similar to that
of erythromycin given for 2 weeks.7 For patients with an allergy to macrolide antibiotics, trimethoprim/sulfamethoxazole is an alternative. Although in vitro
studies of the fluoroquinolones have shown promise against B pertussis, in vivo studies have not been performed.
Cough illness may persist despite treatment of the infection with an antimicrobial. Patients should be counseled about this
fact so that they do not have unrealistic expectations about the duration of cough illness and subsequently request additional
treatment with antibiotics. One of the major goals of therapy, however, is to reduce transmission to others.
A reportable disease
Pertussis is reportable to the local health department. Prophylaxis is usually recommended for all close contacts of a pertussis
case, regardless of age and vaccination status, although in some localities, such as Oregon and Canada, a more limited approach
to prophylaxis is used, based on protecting infants.
Newly approved vaccines
In May of this year, the FDA approved a single-dose active booster immunization against tetanus, diphtheria, and pertussis
in individuals aged 10 through 18 years: tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed
(Tdap). This combination vaccine now provides a pertussis component to the tetanus/diphtheria booster currently provided to
teens.
In June, the FDA approved a combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis booster vaccine,
adsorbed (Tdap) for administration as a single dose to individuals aged 11 to 64 years—the first vaccine to be approved as
a pertussis booster for adults. Adverse events included transient pain, swelling or redness at the injection site, and transient
low-grade fever. Systemic events included headache, body ache, and fatigue.
The CDC's Advisory Committee on Immunization Practices recommended on June 30 that adolescents 11 and 12 years of age be given
Tdap in place of the tetanus-diphtheria (Td) booster currently given to adolescents and that Tdap be given to adolescents
aged 13 through 18 who missed the 11- to 12-year dose of Td. Adolescents aged 11 to 18 who have already been vaccinated with
Td are encouraged to receive a dose of Tdap as further protection against pertussis.8
Case outcome
The patient returned for a follow-up visit several weeks later. The results of the nasopharyngeal swab specimen were negative
for PCR and culture. His cough illness persisted, although it had improved. No one else in his home had developed a similar
illness. The CD4 T-lymphocyte count was more than 400 cells/μL and his WBC count and differential were unremarkable. The case was unsatisfying because I had not definitively diagnosed
pertussis, although his recoiling when I was obtaining a specimen, his older age, and time since onset of illness all may
have contributed to a negative result.
Also troubling was the unresolved issue of whether such a patient should be reported to the local health department. Had his
test result been positive, this would have been clearly reportable. Since this was a suspect case, some health departments
would accept such a report. However, the CDC's clinical case definition for pertussis states that in the absence of laboratory
confirmation or epidemiologic linkage to a laboratory-confirmed case, a probable case not only should meet the clinical case
definition but also not be attributable to another cause.3 This case fell in a gray zone, since I considered that the differential diagnosis of this patient included infections with
Mycoplasma pneumoniae, Chlamydia pneumoniae, and TWAR, adenovirus, respiratory syncytial virus, and chronic sinusitis.
Had the patient had a whoop, been in close contact with an infant or pregnant woman, or refused antibiotic treatment with
an effective antimicrobial like erythromycin, I would consider reporting such a case all the more important, despite my clinical
suspicion of other pathogens. Exactly when to report such suspect cases remains ambiguous, especially since doing so may overwhelm
local health departments in the setting of increased awareness of pertussis and record numbers of cases being reported. Once
an FDA-approved diagnostic test using a single blood specimen becomes available, the diagnosis of pertussis in adolescents
and adults will become more certain and the gray zone narrower.
This article was contributed by Dr Dworkin and edited by Peter D'Epiro, PhD.
Dr Dworkin discloses that he has no financial relationship with any manufacturer in this area of medicine.
REFERENCES
1. Cherry JD, Baraff LJ, Hewlett E. The past, present, and future of pertussis: the role of adults in epidemiology and future
control. West J Med. 1989;150:319-328.
2. Hodder SL, Mortimer EA. Epidemiology of pertussis and reactions to pertussis vaccine. Epidemiol Rev. 1992;14:243-267.
3. Case definitions for infectious conditions under public health surveillance. Centers for Disease Control and Prevention.
MMWR Recomm Rep. 1997;46:1-55.
4. Pertussis cough examples. Immunization Division, Texas State Department of Health Services. Available at: http://www.tdh.state.tx.us/immunize/
pert_cough.htm. Accessed August 16, 2005.
5. Baughman AL, Bisgard KM, Edwards KM, et al. Establishment of diagnostic cutoff points for levels of serum antibodies to
pertussis toxin, filamentous hemagglutinin, and fimbriae in adolescents and adults in the United States. Clin Diagn Lab Immunol. 2004;11:1045-1053.
6. Cloud JL, Hymas W, Carroll KC. Impact of nasopharyngeal swab types on detection of Bordetella pertussis by PCR and culture. J Clin Microbiol. 2002;40:3838-3840.
7. Langley JM, Halperin SA, Boucher FD, et al. Azithromycin is as effective as and better tolerated than erythromycin estolate
for the treatment of pertussis. Pediatrics. 2004;114:e96-101.
8. CDC. ACIP recommends adolescent vaccination for tetanus, diphtheria and pertussis vaccine. Available at http://www.cdc.gov/nip/pr/pr_tdap_jun2005.htm. Accessed August 25, 2005.
Drugs mentioned in this article
Azithromycin (Zithromax)
Clarithromycin (Biaxin)
Erythromycin
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine, adsorbed (Tdap) (Boostrix)
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis booster vaccine, adsorbed (Tdap) (Adacel)
Trimethoprim/sulfamethoxazole
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