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Pertussis, or whooping cough, is an ancient
disease that continues to cause signifcant
morbidity and mortality.
1
Tere has been a
dramatic resurgence of pertussis in the past
several years. Tis was most evident in
2012, when the highest number of cases in
50 years was reported in the United States.
2

Large outbreaks have occurred in multiple
states, and infant deaths have drawn the
attention of not only health-care providers
but also the media. Despite the advent of
polymerase chain reaction (PCR) tests, the
disease remains underdiagnosed, likely
because of a lack of recognition and consid-
eration for testing. Treatments are mainly
aimed at preventing spread and have little
impact on the course of the disease. New
vaccination strategies have been imple-
mented across diferent age groups and
patient populations, to include pregnant
women and the elderly, but vaccine cov-
erage remains dismally low.
3-6
Acellular vac-
cines, although safe, may not aford the
same long-lasting immunity as the previ-
ously used whole-cell vaccine. Unless we
can improve vaccine ef cacy and coverage,
Whooping Cough in 2014 and Beyond
An Update and Review
Joshua D. Hartzell , MD ; and Jason M. Blaylock , MD
Pertussis, or whooping cough, has had a dramatic resurgence in the past several years and
is the most common vaccine-preventable disease in the world. The year 2012 marked the
most cases in the United States in . 50 years. Large outbreaks have occurred in multiple
states, and infant deaths have drawn the attention of not only health-care providers but also
the media. Although the disease is theoretically preventable by vaccination, it remains a
challenge to control. New vaccination strategies have been implemented across dierent age
groups and populations of patients, but vaccine coverage remains dismally low. Acellular
vaccines, although safe, do not aord the same long-lasting immunity as the previously used
whole-cell vaccine. Ultimately, improvements in the development of vaccines and in vaccina-
tion coverage will be essential to decrease the burden of pertussis on society. This article
provides a review of pertussis infection and discusses advances related to the epidemiology,
diagnosis, treatment, and prevention of infection, as well as continued areas of uncertainty.
CHEST 2014; 146(1):205- 214
ABBREVIATIONS: CDC 5 Centers for Disease Control and Prevention; DTaP 5 diphtheria-tetanus toxoids,
acellular pertussis; PCR 5 polymerase chain reaction; Tdap 5 tetanus toxoid, reduced diphtheria toxoid,
and acellular pertussis
[ Recent Advances in Chest Medicine ]
Manuscript received December 13, 2013; revision accepted February 16,
2014.
AFFILIATIONS: From the Infectious Diseases Clinic, Walter Reed
National Military Medical Center, Bethesda, MD.
CORRESPONDENCE TO: Jason M. Blaylock, MD, Infectious Diseases
Clinic, Walter Reed National Military Medical Center, 8960 Brown Dr,
Bethesda, MD 20889-5629; e-mail: jason.m.blaylock.mil@mail.mil
2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of
this article is prohibited without written permission from the American
College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.13-2942
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206 Recent Advances in Chest Medicine [ 1 4 6 # 1 CHEST J ULY 2 0 1 4 ]
pertussis will continue to be a signifcant health threat
worldwide. Tis article reviews advances in the epidemi-
ology, diagnosis, treatment, and prevention of pertussis
infection and highlights areas of uncertainty ( Table 1 ).
Defnition
Multiple case defnitions for pertussis exist worldwide,
making it dif cult to defne the disease from a clinical
perspective and to determine the true epidemiologic
burden of disease.
7
Most defnitions are categorized as
confrmed or probable and vary depending on the con-
text in which they are used (ie, vaccine trials, outbreaks,
and so forth). Te US Centers for Disease Control and
Prevention (CDC) defnition is provided in Table 2 and
can serve as the working case defnition at this time.
8

Similar to the CDC defnition, most defnitions world-
wide are a decade old and based largely on the clinical
presentation in infants and children. With an increasing
burden of disease in adolescents and adults, new defni-
tions have been proposed in an attempt to improve the
sensitivity and specifcity of diagnosis. Te increased use
of PCR testing and its inclusion in updated defnitions is
being evaluated, with hope of providing more accurate
defnitions of clinical disease. Studies are needed to vali-
date these defnitions and determine their usefulness. A
thorough review of the topic, including the proposed
defnitions and their scientifc basis, was recently
published.
7

Microbiology
Pertussis is primarily caused by the gram-negative coc-
cobacillus, Bordetella pertussis. However, other species
of Bordetella , most notably Bordetella parapertussis and
Bordetella bronchiseptica , can cause mild or moderate
pertussis-like symptoms.
9

-11
Of interest to pet owners,
B bronchiseptica is the cause of kennel cough. More
recently, cases of Bordetella holmesii have been identi-
fed during pertussis outbreaks that have particularly
afected adolescents. In a community outbreak in Ohio,
60% of B holmesii case patients had received tetanus
toxoid, reduced diphtheria toxoid, and acellular per-
tussis (Tdap) vaccine, thus questioning the efectiveness
of the vaccine in prevention of illness secondary to this
particular species.
11,12
Te emergence of B holmesii has
been observed in other countries as well.
13

-15

Variation in the expression of pertussis virulence factors
has been reported in recent years, prompting questions
regarding the ef cacy of the Tdap vaccine in the pres-
ence of these novel strains. Pertactin, a highly immuno-
genic virulence factor of B pertussis , is currently one of
the main components of the acellular vaccine. To our
knowledge, pertactin-negative strains were frst reported
in France,
16
and researchers in Philadelphia described
pertactin-negative strains in 11 isolates for the frst time
in the United States in 2013.
17
Other countries had pre-
viously reported similar results, thus highlighting the
need for ongoing research into the diferent variants of
pertussis, in particular those isolated from previously
vaccinated patients who develop disease.
18
Te long-
term consequences of these changes are unknown, but a
recent study from France reported no clinical diference
in infants (aged , 6 months) when comparing pertactin-
positive and pertactin-negative isolates.
19

Pertussis is an acute airway infection that is localized to
the airway and does not commonly enter the circulation
and disseminate. Although pertussis harbors a multi-
tude of toxins, including pertussis toxin, adenylate
cyclase toxin, and tracheal toxin, the mechanism of the
paroxysmal cough is not known. Te most accepted
explanation is that respiratory cilia are damaged by both
the toxins and the resultant host immune response,
resulting in irritation and subsequent coughing spells.
20

Tere is no long-term human carriage or animal reser-
voir, and B pertussis does not survive for long periods in
the environment. Tese characteristics should in theory
TABLE 1 ] Key Updates for Pertussis
Update
There were more pertussis cases in 2012 compared with any other year in the past 50 years.
Consider testing for pertussis in any patient with cough lasting . 2 wk who meets the pertussis clinical case denition.
Pertussis testing with culture, polymerase chain reaction, and serology should be performed based on the clinical stage
of disease.
Treatment of pertussis remains limited, as antibiotics are mainly used to prevent spread.
In the United States and worldwide, pertussis vaccination rates are dismally low.
Pertussis vaccination is recommended for all adults, and methods for increasing vaccination coverage should be explored.
Pregnant women need to be vaccinated against pertussis with each pregnancy.
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journal.publications.chestnet.org 207
limit transmission; however, pertussis remains very
contagious, afecting 40% to 80% of susceptible con-
tacts.
21
It is this highly infectious nature that has con-
tributed in large part to the resurgence of disease in the
past several years.
Epidemiology
Te World Health Organization reported 200,868 cases
of pertussis in 2012.
22
Te majority (approximately 95%)
of infections occurred in developing countries, with
most deaths attributed to young infants who were either
unvaccinated or incompletely vaccinated.
23,24
Case
fatality rates in developing countries are estimated to be
as high as 3% in infants.
25
Pertussis burden is underesti-
mated in resource-limited countries because of a
number of factors, including misdiagnosis, lack of rec-
ognition, and absent reporting requirements. Realistic
global disease burden models estimate that there are
closer to 30 to 50 million pertussis cases and about
300,000 deaths per year.
26
In developed countries,
implementation of vaccination programs and contact
tracing remains problematic in susceptible populations
because of social and cultural diferences.
27

Before the introduction of the whole-cell pertussis vac-
cine, B pertussis infection was responsible for . 200,000
cases and nearly 7,000 deaths per year in the United
States.
28
Beginning in the late 1940s, vaccination mark-
edly reduced the overall incidence and mortality of
disease. Pertussis cases reached a historic low in the
1970s following implementation of large-scale vaccina-
tion strategies throughout the industrialized world
during the 1950s and 1960s. Despite these vaccination
strategies, pertussis historically has been endemic and
cyclical within the United States, with outbreaks occur-
ring every 3 to 5 years; however, a grad ual increase has
been observed over the past few decades. Tere were
48,277 cases of pertussis in the United States in 2012.
29

Approximately 50% of the cases were in children . age
11 years and adults, yet 15 of the 18 deaths occurred in
children , 1 year of age.
2
Te US military health-care
system has reported a shif in the epidemiologic profle
of pertussis to include more members of the adolescent
and young adult pop ulation. In a report of nearly
3,500 pertussis cases among US military members and
their benefciaries from 2005 to 2012, infants , 1 year
and adolescents aged 11 to 15 years accounted for the
highest num bers of confrmed cases (16.7% and 16.4%,
respec tively).
30
Although localized outbreaks of pertussis
are not uncommon and occur throughout the year,
marked rises in outbreak activity were identifed in sev-
eral states in 2012.
2,31
Of particular importance is that,
over the past several years, schools have been identifed
as signifcant venues for transmission of pertussis among
the adolescent and young adult age groups.
32,33
Mirroring
the United States, there is a global increase in the num-
ber of cases among adolescents and adults. In New Zea-
land, 86% of diagnosed pertussis cases in 2007 were in
groups . 25 years of age.
34
In Australia, 60% of pertussis
cases occurred in adults . 20 years of age in 2008.
35

TABLE 2 ] CDC Case Denition of Pertussis
8

Case Denition
Clinical case denition
a

A cough illness lasting at least 2 wk with one of the following: paroxysms of coughing, inspiratory whoop, or
posttussive vomiting, without other apparent cause (as reported by health-care provider)
Laboratory criteria for diagnosis
b

Isolation of Bordetella pertussis from clinical specimen in culture
Positive PCR for B pertussis
Case classication
Conrmed
Meets clinical case denition and is conrmed by PCR, culture, or is epidemiologically linked to a case that was
conrmed by culture or PCR
Probable
Meets the clinical case denition but is neither conrmed by culture or PCR or epidemiologically linked to case
conrmed by culture or PCR
CDC 5 Centers for Disease Control and Prevention; PCR 5 poly merase chain reaction.

a
The denition is for endemic or sporadic cases. In outbreak settings, a clinical case may be dened as a cough illness lasting at least 2 wk.

b
Serologic testing can be used clinically to aid in diagnosis but is not part of the o cial CDC case denition because serologic testing is not
standardized.
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208 Recent Advances in Chest Medicine [ 1 4 6 # 1 CHEST J ULY 2 0 1 4 ]
Infants too young to have completed their primary vac-
cination series account for the majority of pertussis-
related complications, hospitalizations, and deaths. In a
multinational study, approximately 75% of infants hos-
pitalized with pertussis had received less than or equal
to one dose of pertussis vaccine.
36
In a 2010 epidemic in
California, household coughing contacts were reported
in 75% of patients with pertussis; the mother was the
contact in 42% and siblings in 46% of cases.
37
Given the
diminished duration of protection aforded by the cur-
rent childhood acellular pertussis vaccines, it is apparent
that adolescents and adults with waning immunity and
unrecognized pertussis are the most important source of
infection for infants. Te concern over adult transmis-
sion of pertussis to unprotected infants resulted in the
Advisory Committee on Immunization Practices and
CDC making successive changes to the Tdap immuniza-
tion schedule in recent years ( Table 3 ).
38

Tere are several proposed reasons for the changes in
the epidemiology of pertussis infection. More press
reports and recent published scientifc literature, as well
as reports of pertussis vaccine trials and subsequent
licensures of acellular vaccines for use in adults, have all
contributed to increased clinician awareness and report-
ing.
39,40
Growing use of PCR testing for B pertussis has
improved the ability to make the diagnosis.
41
It has been
hypothesized that genetic changes in circulating strains
of B pertussis might be contributing to vaccine failures.
42

A diminished duration of protection aforded by the
acellular vaccine compared with the whole-cell pertussis
vaccine is also contributing to the increase in pertussis
cases and is discussed in further detail in the Vaccina-
tion section.
43-47

Clinical Presentation
Te incubation period for B pertussis is longer (approxi-
mately 7-10 days) than most viral upper respiratory
tract infections (1-3 days); therefore, exposure to a per-
son with a cough illness 1 to 2 weeks prior to the devel-
opment of upper respiratory symptoms may be more
suggestive of pertussis. Classic infection with B pertussis
is characterized by three stages: catarrhal, paroxysmal,
and convalescent. Te catarrhal stage is marked by a
1- to 2-week period of generalized malaise, rhinorrhea,
and mild cough. Fevers, if present, are generally low
grade and not incapacitating. Symptoms during this
stage are nonspecifc and overlap with other more
common viral infections. A diagnosis of pertussis is
rarely considered unless there is a clear contact. It is
important to ask if other family members have had a
prolonged cough, as this increases the odds of per-
tussis.
21
Te presence of nonpurulent conjunctival
injection or excessive lacrimation might prompt the
astute clinician to consider a diagnosis of pertussis
during this stage.
48

Te paroxysmal stage usually commences during the
second week of illness and consists of paroxysms, or a
series of coughs during a single expiration. In severe
cases, patients may have 30 or more paroxysms per day.
Low lung volumes caused by the paroxysmal cough lead
to vigorous inspiration that, particularly in infants and
children with a smaller caliber trachea, can result in the
TABLE 3 ] CDC DTaP and Tdap Recommendations
38

Age Group (Vaccine) Timing
Birth through age 6 y (DTaP) 2, 4, and 6 mo, at 15-18 mo, and at age 4-6 y
Age 7-10 y (Tdap) Single dose for those not fully vaccinated
a,b

Adolescents aged 11-18 y (Tdap) Single dose for those fully vaccinated, preferably at age 11 or
12 y.
a
If not, then as soon as possible during this period
Adults aged 19 y, including age . 65 y (Tdap) Replace 1 dose of Td at earliest opportunity
c

Pregnant women (Tdap) Give during each pregnancy between 27-36 wk gestation.
Should be given immediately postpartum if not done earlier
Health-care personnel (Tdap) Replace 1 dose of Td at earliest opportunity.
c
Prevents infection
and potential spread, with priority given to those caring
for infants
DTaP 5 diphtheria-tetanus toxoids, acellular pertussis; Tdap 5 tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis. See Table 2 legend for
expansion of other abbreviation.

a
Catch-up schedule should be followed if not fully vaccinated.

b
Five doses of DTaP or four doses of DTaP if the fourth dose was administered on or after the fourth birthday.

c
Administer as soon as possible regardless of when tetanus- or diphtheria toxoid-containing vaccine was last given. Tdap is only given once currently
(either as an adolescent or an adult).
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journal.publications.chestnet.org 209
classically described whoop.
49
Examples of the cough
are available online.
50,51
Paroxysms occur most fre-
quently at night and may be incited by cold air, loud
noises, or other stressors. Te presence of posttussive
emesis and inspiratory whoop is associated with an
increased likelihood of pertussis infection.
48
Patients are
ofen asymptomatic between paroxysms, which should
point toward the diagnosis, as few other respiratory
infections present in this manner. A recent study sug-
gested that cyanosis and a lack of fever and congestion
can be predictive of pertussis in infants.
37
Te presence
of wheezing in children should not dissuade providers
from including pertussis in the diferential, as this might
ultimately delay the diagnosis.
52
Sweating between epi-
sodes of paroxysms has also been indicative of a diagno-
sis of pertussis in adults.
7
At the end of the catarrhal
stage or beginning of the paroxysmal stage, patients may
exhibit signs of systemic disease, such as leukocytosis
with predominant lymphocytosis, which portend a
worse clinical outcome.
53

Severe paroxysms have led to complications includ ing
syncope, subconjunctival hemorrhages, rib fractures,
urinary incontinence, hernias, intracranial hemor-
rhage, and stroke from vertebral artery dissection.
54

Older adults with asthma and obesity are at increased
risk of more severe disease and hospitalization.
55
Com-
plications are more common in nonimmune infants
and include pneumonia, failure to thrive, seizures,
encephalopathy, cerebral hypoxia, secondary bacterial
infections, pulmonary hypertension, and rectal
prolapse.
56

Patients are most infectious during the catarrhal period
and for the frst 2 weeks of spasmodic cough; however,
they can remain infective for up to 6 weeks, especially in
the case of nonimmune infants. A gradual transition to
the convalescent stage (1-6 weeks) occurs afer 1 to
2 months and is characterized by a persistent but
decreasing frequency and severity of cough. It is impor-
tant to note that children who have had pertussis may
have a recurrence of coughing paroxysms when exposed
to new respiratory viral infections.
49

Te clinical presentation of pertussis in previously
immunized or infected adolescents and adults is vari-
able and ofen atypical. Te predominant, and some-
times sole, symptom is persistent cough. Pertussis was
the cause of 12% to 32% of prolonged cough illnesses in
adolescents and adults in one study.
57
Te mean dura-
tion of cough in adults is 36 to 48 days. Recurrences of
paroxysmal cough are not uncommon and may occur
up to 1 year following infection.
58
In a recent outbreak
of pertussis infection in Ohio, paroxysmal cough was
noted in 82% of infections, but posttussive vomiting and
a whooping cough were only noted in 42% and 20% of
cases, respectively.
11
Tese atypical presentations and
subsequent lack of recognition ofen lead to delays in
diagnosis, thus eliminating the chance to initiate timely
and efective treatment.
Diagnosis
Clinical suspicion is paramount in the diagnosis of per-
tussis. If a case meets the clinical case defnition criteria
as defned in Table 2 , then it should be confrmed via
either an epidemiologic link or with appropriate labora-
tory testing (ie, culture or PCR assay). Even during
infuenza season, pertussis should be considered in the
diferential for a patient presenting with a chronic
cough. Timely diagnosis prevents unnecessary evalua-
tions and allows for early treatment to prevent spread.
Current recommendations from the CDC support a
combination of diagnostic tests based on the duration of
symptoms ( Table 4 ).
59

Culture is the gold standard because it is 100% specifc
for identifcation of B pertussis and allows for specifc
strain identifcation and antimicrobial resistance
testing. Sensitivity has ranged from 10% to 60%
depending upon the timing of specimen collection as
it relates to symptom onset.
60,61
Sensitivity markedly
decreases when culture is obtained . 2 weeks afer
symptom onset.
61,62
Various factors contribute to this
low sensitivity, including the fastidious nature of the
organism, recent antibiotic use, the type of specimen
collected, the method of collection, prolonged trans-
port to the laboratory and delayed specimen plating,
and the specifc collection media.
63
Te CDC provides
an overview for providers on testing strategies as well
as sample collection.
64
Specimens for culture should be
obtained via nasopharyngeal aspirate or posterior
nasopharyngeal swab, as these specimens contain the
ciliated respiratory epithelial cells for which the
organism has an af nity. Te specimens should be col-
lected via calcium alginate or Dacron swabs; however,
Dacron is optimal, as calcium alginate may interfere
with PCR assays. Cotton or rayon swabs should not
be used, as they contain fatty acids that are toxic to
B pertussis . Specimens should be immediately placed
in Regan-Lowe media for transport or directly onto
Regan-Lowe agar or Bordet-Gengou agar, which usu-
ally reveals growth in 7 to 10 days.
49
Sample collection
is variable and should be discussed with your local
laboratory.
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210 Recent Advances in Chest Medicine [ 1 4 6 # 1 CHEST J ULY 2 0 1 4 ]
PCR is the most sensitive method for rapid detection of
pertussis. PCR is generally not afected by pre vious anti-
biotic use, and results are available within 1 to 2 days.
Compared with culture, PCR may increase the diagnos-
tic yield threefold to fvefold and can detect very small
numbers of viable and nonviable organisms.
11
PCR is
most sensitive during the frst 3 weeks of cough, when
bacterial DNA is still present in the nasopharynx.
65

Tereafer, sensitivity markedly declines. A recent study
during a pertussis outbreak found that PCR sensitivity
was 64% and 56% in the third and fourth weeks afer
symptom onset, respectively.
41
PCR test ing is not with-
out its faws. PCR is costly, not available in all settings,
and can produce both false-negative and false-positive
results (especially during outbreaks). It is not recom-
mended afer 5 days of antibiotic use.
66
Pseudo-
outbreaks due to false-positive results of assays have
highlighted the need for defned cutof values based on
analytical sensitivity and clinical relevance.
67
Tere is no
standardized or US Food and Drug Administration-
approved, commercially available PCR test for
B pertussis . PCR methodologies and results may vary
signifcantly between laboratories. Among several chro-
mosomal regions used for real-time PCR detection of
B pertussis , the multicopy insertion sequence IS481 is
ofen the target of choice because it is found in multiple
copies in B pertussis . However, IS481 is found in other
Bordetella species, to include B holmesii and B bronchi-
septica .
68
Novel real-time PCR assays that include mul-
tiple targets for speciation among Bordetella species
have improved the specifcity of diagnosis in pertussis-
like illnesses.
69

Serological testing is primarily used for epidemiologic
or research purposes but is being incorporated into the
diagnostic approach. Both the CDC and the US Food
and Drug Administration have developed a useful sero-
logic assay for confrming diagnosis during suspected
outbreaks.
59
Many state public health laboratories have
included this assay as part of their pertussis testing algo-
rithm. Commercial assays should be used cautiously, as
they have diferent antigen composition and quality
without proven clinical accuracy. Serologic diagnosis is
useful for adults and adolescents who present late in the
course of their illness, when both culture and PCR are
likely to be negative. Paired sera demonstrating a two-
fold rise is the gold standard for serological diagnosis,
but in clinical practice a probable diagnosis of pertussis
can be based on single-sample serology.
70
For the CDC
single-point serology, the optimal timing for specimen
collection is 2 to 8 weeks following cough onset, when
antibody titers are at their peak; however, serology may
be performed on specimens collected up to 12 weeks
following cough onset.
59
Importantly, a recent study
demonstrated that antibody responses to the vaccine
will not afect serologic results if the vaccine was given
at least 6 months prior to the testing.
71

Direct fuorescent antibody testing of nasopharyngeal
specimens is inexpensive and provides rapid results but
is not recommended based on its poor sensitivity and
specifcity. In addition, cross-reactivity has been dem-
onstrated with other organisms, such as B bronchisep-
tica , Haemophilus infuenza , and diphtheroids.
72

Pulse-feld gel electrophoresis is a DNA fngerprinting
technique that may be useful for epidemiologic pur-
poses; however, availability is limited.
Treatment
Te treatment of pertussis consists of treating the bacte-
rial infection and, maybe more importantly to the
patient, the symptoms. Treatment ef cacy is largely
based on the immediacy of treatment. Unfortunately,
treatment is rarely given early enough to impact the
clinical course of the disease. A recent Cochrane Review
concluded that short-term treatment with macrolides
was as efective as long-term treatment in eradication
of B pertussis , with fewer side efects.
73
Azithromycin for
TABLE 4 ] Clinical Stages of Pertussis and Diagnostic Approach Over Time
58

Clinical Stage Symptoms (Duration of Phase) Time Since Onset of Illness Test of Choice
Catarrhal Malaise, rhinorrhea, mild
cough, fever (1-2 wk)
1-2 wk PCR and culture
Paroxysmal Severe paroxysms of cough.
Paroxysms are most common
at night (1-2 mo)
2 wk to 1 mo PCR
a
and serology
Convalescent Persistent but decreasing frequency
and severity of cough (1-6 wk)
. 1 mo Serology
See Table 2 legend for expansion of abbreviation.

a
PCR sensitivity decreases markedly after 2 wk; 64% and 56% in the third and fourth weeks after symptom onset, respectively.
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journal.publications.chestnet.org 211
3 to 5 days is the preferred treatment based on ease of
administration and side efect profle. Resistance to
macrolides is rare but has been reported.
74
Trimetho-
prim/sulfamethoxazole for 7 days is an alternative. It is
always important to consider both the age of the patient
and possible antibiotic side efects when initiating
treatment.
Te most distressing issue for patients is the paroxysmal
cough; unfortunately, antibiotics have no beneft on
symptoms in this stage. No proven treatments exist to
decrease the severity or frequency of symptoms. A
Cochrane Review on the topic concluded that there is
insuf cient evidence to make conclusions regarding
treatments for the cough.
75
Te majority of studies were
of poor quality, and in general symptomatic treatment
was not benefcial. Steroids, pertussis immunoglobulin,
and exchange transfusion may provide beneft in severe
cases but should not be used routinely.
75,76

Prevention
Prevention remains the key in controlling pertussis, as
delays in recognition and treatment signifcantly ham-
per providers ability to otherwise impact the course of
the illness and transmission. Multiple strategies have
been used to control pertussis, with the main eforts
focusing on vaccination. Antibiotics have a minimal
role in preventing disease and should be limited to those
who are identifed as having close contact (within 91 cm
[3 feet ] or direct contact with oral/nasal secretions) of
someone with pertussis. Prophylactic treatment of con-
tacts has not been demonstrated to have a meaningful
impact on the number of cases that occur or the sever ity
of symptoms if disease does develop.
77
Te CDC is
expected to publish a new set of recommendations on
prevention within the year. Currently, each case should
be considered individually and take into account past
guidance.
77
Important considerations include degree of
exposure, vaccination status, immune status of the
patient, and the risks of antibiotic use. Special consider-
ation for antibiotic prophylaxis should be given to preg-
nant women, infants, and immunosuppressed patients,
given the increased risk of morbidity in these
populations.
Vaccination
Vaccination for pertussis was introduced in the 1950s
and dramatically reduced the incidence of disease, but
success was moderated by side efects. Whole-cell per-
tussis vaccines (ie, diphtheria-tetanus toxoids, whole-
cell pertussis [DTwP]) were associated with fever
(includ ing febrile seizures), local reactions, and hypo-
tonic episodes.
78
Tese concerns resulted in their
replacement with acellular vaccines (ie, diphtheria-
tetanus toxoids, acellular pertussis [DTaP]; Tdap; and so
forth) in the 1990s. Although acellular vaccines have an
improved safety profle, their efectiveness has been
called into question. A Cochrane Review demonstrated
that the efectiveness of acellular vaccines in preventing
typical whooping cough ranges from 59% to 85%.
79
Fur-
thermore, studies demonstrated that having a whole-cell
vaccine as any part of the vaccination series improved
immunity.
43,80
A case-control study of children done by
Kaiser Permanente Northern California reported that
following the ffh dose of DTaP, children were 46%
more likely to develop pertussis in each subsequent
year.
46
Studies in Minnesota children and from 15 Cali-
fornia counties reported similar results of waning
immunity with DTaP.
47,81
Tese recent reports highlight
a clear concern of waning immunity with use of the cur-
rent acellular vaccines.
Tere are multiple possible reasons for the decreased ef -
cacy of acellular vaccines, and a full discussion is beyond
the scope of this paper. A recent review by Cherry
42
high-
lights several of these potential explanations. Others have
discussed the importance of antigenic divergence and
how it may be afecting memory recall and antibody ef -
cacy.
82
It is clear from the available data that there is a
need for newer more immunogenic pertussis vaccines. A
recent review suggested that including new virulence fac-
tors might be the most appropriate approach.
83
Unfortu-
nately, the development and approval of new vaccine
products will take time. In the meantime, the use of the
vaccines that we do have could be improved.
Vaccination timing is an important component of elicit-
ing immunity. A study of pregnant women reported
that passive protection of infants requires vaccination
during the third trimester, and it is short-lived.
84
As a
result, the current Advisory Committee on Immuniza-
tion Practices recommendation for pregnant women is
that vaccination occur between 27 and 36 weeks gesta-
tion during each pregnancy to maximize the maternal
antibody response and passive antibody transfer to the
infant.
6
Future studies should examine the timing of
other patient populations (including infants) to deter-
mine if diferent schedules or more frequent boosters
may improve outcomes.
Ensuring adequate vaccination coverage remains a chal-
lenge. Several studies have demonstrated that there are
gaps in coverage (Tdap coverage ranged from 5.9% to
45.5%) and adherence to recommendations, includ ing
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212 Recent Advances in Chest Medicine [ 1 4 6 # 1 CHEST J ULY 2 0 1 4 ]
Acknowledgments
Financial/nonfnancial disclosures: Te authors have reported to
CHEST that no potential conficts of interest exist with any com-
panies/organizations whose products or services may be discussed in
this article .
Other contributions: Te views expressed in this article are those of
the authors and do not necessarily refect the of cial policy or position
of the Department of the Navy, Department of the Army, Uniformed
Services University, Department of Defense, nor the US Government.
Tis work was prepared as part of our of cial duties. Title 17 U.S.C.
101 defnes a US Government work as a work prepared by a military
service member or employee of the US Government as part of that
persons of cial duties. Reviewed by the WRNMMC public afairs
of ce in February 2014.
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TABLE 5 ] Multipronged Approach to Improve
Pertussis Vaccination
Approach
Screen and vaccinate all hospital admissions
Screen parents of infants and children admitted
to hospital
Screen parents and siblings at pediatrics appointments
Screen all emergency room visits
Standing order sets for administration of Tdap
Vaccinate all pregnant or postpartum women
Incorporate screening with vital signs at routine
health visits
Screen at travel clinic visits
Add pertussis vaccination to annual u drive campaign
Hospital pertussis drives to ensure health-care
worker vaccination
Monthly vaccination clinics (outreach to
low-resource areas)
Electronic medical record review and contact of patients
without pertussis vaccination
See Table 3 legend for expansion of abbreviation.
patients with free access to care and those with adequate
insurance coverage.
85-90
Tere are multiple barriers to vac-
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adverse events.
91
Te problem is amplifed worldwide,
where an estimated 22.6 million children are not com-
pleting the appropriate pertussis vaccination series (three
doses in frst year of life).
92
Unfortunately, this leaves the
most vulnerable patients at risk.
85,86,88
Disappointingly,
health-care workers have low rates of vaccination as well
(26.9% in one study).
93
To improve vaccination, health-
care organizations need to think outside the box and
consider a multipronged approach to vaccination
( Table 5 ).
88,94,95
Te cost of such strategies is a barrier in
many settings, but a grow ing body of evidence suggests
that these approaches may ultimately be cost efective.
96-99

Conclusions
Pertussis continues to be a signifcant health problem
worldwide. Tere are tremendous needs in terms of
improved recognition, diagnosis, treatment of symp-
toms and severe disease, and, most importantly, preven-
tion. Ultimately, the development of new vaccines as
well as improvement in vaccination coverage will be
essential to decreasing the burden of pertussis on soci-
ety. Without a comprehensive approach to the disease,
it is likely that pertussis will be just as, if not more, prev-
alent in another 100 years.
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