++
The World Health Organization estimated
in 2002 that nearly 300,000 children died from pertussis.1 In
the United States, in spite of widespread vaccination there has
been a steady rise in the number of pertussis cases reported to
the Centers for Disease Control and Prevention (CDC) over the past
the last decade, punctuated by several statewide outbreaks in 2004
and 2005.2-5
++
Pertussis occurs year-round in the United States, although the
disease peaks in the summer and fall in most locations. Humans are
the only reservoir for Bordetella pertussis, and
transmission from person to person occurs via respiratory droplets.
Attack rates following household exposure have been reported as
high as 90% for unimmunized children.6-8 Attack
rates in adult household contacts are at least 30%.6 Communicability
is highest early in the disease, but may persist for weeks in some
individuals.8 Unrecognized disease serves as a
reservoir for spread of infection.
++
Infants younger than 6 months of age have the highest burden
of disease.9 Hospitalizations and mortality from
pertussis are highest in infants under 3 months of age.10 Passively
acquired transplacental antibodies afford little protection, and
vaccine-induced immunity requires multiple immunizations. Based
on CDC surveillance data from 2000 to 2003, 86% of hospitalizations
for pertussis occur in infants less than 3 months of age.10 Apnea
and respiratory distress were the most frequent complications, followed
by pneumonias. Mortality is greatest in infants less than 3 months
of age. The frequency of complications decline with increasing age;
however, protracted cough (> 3 months), sleep disturbances, and weight
loss are common in adults with pertussis; subcutaneous emphysema,
pulled muscles, and even broken ribs may occur in adults following paroxysmal
coughing.11,12
++
In 2006 in the United States, infants younger than 6 months old
had the highest reported rate of pertussis (84.21 per 100,000 population),
but adolescents aged 10 to 19 years and adults older than 20 years
contributed the greatest number of reported cases.4 The
characteristic “whoop” is often absent in older
individuals. It is not until the nagging, forceful cough has persisted
for 2 or more weeks that adolescents and adults come to medical
attention. Even then, diagnosis may be delayed or disease may go
unrecognized because of a low index of suspicion.13 Adult caretakers
with undiagnosed pertussis are frequently found to be the source
for pertussis in infants.14 Nosocomial spread by
health care workers has been well documented.15,16
++
Bordetella are small, fastidious, aerobic gram-negative
coccobacilli that require enriched media for isolation. B
pertussis is a respiratory pathogen of humans only and
is the sole cause of epidemic pertussis. B parapertussis is
a closely related species that accounts for less than 5% of
clinical pertussis.17B bronchiseptica occasionally causes
disease in the immunocompromised host but is better recognized as
a veterinary pathogen.18 Only B pertussis elaborates
pertussis toxin.17,19 A variety of other components
of B pertussis are biologically active as well
as antigenic.
++
B pertussis attaches to ciliated epithelial
cells of the respiratory tract, induces toxin-mediated ciliary paralysis
and local inflammation, and decreases clearance of secretions. B
pertussis is not invasive. Disease is mediated through
a variety of bacterial components and toxins. Pertussis toxin formerly
designated as lymphocyte-promoting factor, is secreted by the bacteria
and induces lymphocytosis by preventing migration of lymphocytes
to the area of infection. In addition, pertussis toxin inhibits
the function of neutrophils, macrophages, monocytes, and lymphocytes.
Bacterial adenylate cyclase toxin acts on immune cells that contact the
bacteria, inducing high levels of cyclic AMP, which, in turn, downregulate many immune
cell functions. Other cell-surface proteins, including filamentous
hemagglutinin, pertactin (a 69-kd nonfimbrial protein), and fimbrial
agglutinogens (FIM2, FIM3), are important in bacterial attachment
to ciliated respiratory epithelium. Tracheal cytotoxin selectively destroys
ciliated epithelial cells. Surface lipooligosaccharide has endotoxin-like properties,
whereas cytoplasmic heat-labile toxin may contribute to local cell
damage.19
+++
Clinical Manifestations
++
The incubation period of pertussis is usually 5 to 10 days but
may be up to 3 weeks. Clinical pertussis is a protracted illness
with 3 identifiable stages: the catarrhal, the paroxysmal,
and the convalescent stages. The catarrhal stage
is the most contagious phase and is indistinguishable from a common
cold. During this stage, fever is minimal or absent: rhinorrhea,
sneezing, mild cough, and sometimes mild conjunctival suffusion
last from a few days to a couple of weeks. In the young infant,
signs and symptoms may be minimal or absent in the catarrhal stage.
++
Apnea, choking, or gasping may herald the paroxysmal stage in
young infants.20-22 Observation in a setting in
which assisted ventilation is available is prudent in the very young
infant who presents with these features. Seemingly insignificant
stimuli may provoke frightening episodes of coughing in the young
infant, which may be sufficiently protracted to result in hypoxia
and cyanosis. Forceful coughing can result in subconjunctival and
scleral hemorrhages,23 upper-body petechiae, umbilical
and inguinal hernias, subcutaneous emphysema, rib fractures, and even
central nervous system hemorrhages.24 The characteristic
inspiratory “whoop” of pertussis occurs in toddlers
and older children at the end of a paroxysm as air is finally sucked
in through a partially closed glottis. Posttussive emesis is common
at all ages. Feeding becomes a major problem for the young infant
and may actually provoke the paroxysm; the immediate postparoxysmal
period may provide a refractory period during which feeding is possible.
The severity of the child's paroxysms contrasts sharply with the lack
of distress seen between coughing spells. Most of the complications
from pertussis occur in the paroxysmal stage, which may last from
1 to 6 weeks. Infectivity decreases during this period, although
some patients may still be culture-positive 3 weeks after the onset
of cough.
++
During the convalescent period, coughing in the young infant
may actually become louder, although generally less distressing.
Overall, the paroxysmal coughing gradually lessens in severity and
frequency during convalescence. Paroxysms may disappear, only to reappear
in a milder form during a subsequent respiratory illness over the
ensuing year.
++
In addition to the immediate complications already mentioned,
infectious and noninfectious complications of pertussis are numerous.
Uncomplicated pertussis is usually an afebrile disease, so fever
should prompt evaluation for a secondary bacterial infection. Otitis
media and pneumonia are the most common secondary infections.12,25 Other
pulmonary complications include atelectasis, emphysema, and pneumothorax.
Coughing and vomiting may result in esophageal tears with hematemesis
and melena. Neurologic complications include hypoxic encephalopathy,
seizures, and intracranial bleeds.24-27 Nutritional compromise
and resultant failure to thrive is common in young infants recovering
from pertussis. Risk of death in the young infant is between 0.04% and
1%.28
++
Classical pertussis should be readily diagnosed based on clinical
features. The presence of absolute peripheral lymphocytosis (> 10,000
lymphocytes/mm3) is supportive evidence for systemically
active pertussis toxin. Absolute lymphocyte counts of more than
20,000 cells/mm3 are not uncommon, and total WBC
counts more than 100,000 cells/mm3 have been reported.
++
The chest x-ray in pertussis is often normal, although shagginess
along the cardiac border, peribronchial consolidation, and atelectasis may
be seen. The presence of a focal infiltrate in a febrile child with
pertussis may indicate a secondary bacterial process.
++
Classic pertussis in the nonimmune host is difficult to confuse
with other illnesses. In the immunized individual, symptoms are
less likely to be characteristic. A coughing illness for more than
2 weeks and/or posttussive emesis should arouse suspicion.
In infants presenting with apnea, respiratory syncytial virus infection
and serious bacterial illness need to be excluded.
++
B pertussis is the cause of epidemic pertussis as
well as of most sporadic pertussis. B parapertussis may
cause a similar syndrome, which is less severe and of shorter duration.
Protracted coughing illness mimicking pertussis may also be seen
with adenovirus, mycoplasma, and chlamydia.29 Ancillary
features of the illness such as sore throat, headache, or swollen lymph
nodes, as well as knowledge of epidemiologically significant local
pathogens, will aid diagnostically.
++
Recovery of B pertussis in culture has long been
the gold standard for the diagnosis of pertussis. Nasopharyngeal
specimens should ideally be obtained within the first 2 to 3 weeks
of illness, but cultures may be positive even weeks after the onset
of paroxysms.8 Although the yield is less, cultures
beyond 3 weeks are sometimes useful, because culture confirmation
may guide public health initiatives.
++
Because of the fastidious growth requirements for B pertussis, cultures
are most accurate in a laboratory experienced in B pertussis isolation.
Nasopharyngeal samples should be obtained by inserting a small,
flexible Dacron or calcium alginate swab through the nose into the
posterior nasopharynx and leaving it there for a few seconds during
a cough in order to gather respiratory epithelial cells.19,30-32 The best
bacteriologic yield occurs when the swab is plated on selective Bordetella media
at the bedside. If this is not possible, the swab should be placed
in Bordetella-specific transport media for delivery
to the laboratory. Fresh Bordet-Gengou media, Regan-Lowe charcoal agar,
or modified Stainer-Scholte agar and 7 or more days of incubation
may be required for isolation of B pertussis. Prior
antibiotic therapy will markedly reduce the isolation rate. Asymptomatic
carriage of B pertussis is extremely rare. (Health-care
workers collecting the specimens should use appropriate masks and
eyewear to avoid becoming infected.)
++
A direct fluorescent antibody (DFA) test on secretions from a
nasopharyngeal swab can be used for rapid presumptive diagnosis.30,32,33 Currently
available reagents can distinguish between B pertussis and B
parapertussis, but the technique requires significant technical expertise. Inexperience
in performing this test results in numerous false-positive and false-negative
results, and thus DFA is not recommended by the CDC.30
++
Following infection, antibodies develop to several B
pertussis antigens. These responses wane in 7 to 20 years.34 Serologic
responses following immunization with pertussis vaccines last at
least 6 to 12 years.35,36 Previous natural infection
as well as immunization thus pose challenges to the serologic diagnosis
of pertussis. However, quantitative and qualitative differences
between IgA, IgM, IgG, and IgE responses to pertussis toxin; filamentous hemagglutinin;
pertactin; and FIM2/3 have been used in clinical trials
to allow distinction between immunization and disease.19,37 Standardized
tests for routine serologic diagnosis are not widely available. Currently,
the most generally accepted serologic criterion for diagnosis of
pertussis is the use of an enzyme-linked immunosorbent assay to
demonstrate a significant increase in IgG serum antibody concentrations
against pertussis toxin between acute and convalescent specimens.19,37,38 Results
may not correlate with clinical disease and can be difficult to
interpret in a highly immunized population.
++
Polymerase chain reaction (PCR) testing on nasopharyngeal swab
specimens for pertussis is becoming the most widely used diagnostic
procedure; however, techniques are not standardized.30,37 PCR
has proven to be sensitive and specific for the diagnosis of pertussis
and is an accepted alternative to culture for case confirmation
of B pertussis infection when performed in experienced laboratories.31,39 Routine
use of 2 PCR targets may help eliminate the false-positive results
from less-experienced laboratories that might overestimate the incidence
of disease and induce inappropriate consumption of public health
resources.30,40
++
Treatment for clinical pertussis is primarily supportive. Hospitalization
is indicated for all infants with severe paroxysms associated with cyanosis
or apnea. Infants with potentially fatal pertussis may appear to
be amazingly well between paroxysms. Caution should be exercised when
suctioning these young, exhausted infants because it may precipitate
a paroxysm. Admission to an intensive care setting is indicated
if emergent response to paroxysms cannot be managed on the ward.
Supplemental oxygen, intravenous fluids, and nutritional support
are frequently required in severe and protracted disease. Cough
suppressants, expectorants, mucolytic agents, bronchial dilators,
and sedatives are not beneficial in treating pertussis. Young infants
should remain hospitalized until nutrition is adequate, no supportive
intervention is required during paroxysms, disease is unchanged
or improved for at least 48 hours, and the infant's care can be
safely managed at home.
++
Antibiotic therapy has no discernible effect on the course of
the illness once the paroxysms are well established;7 however,
treatment may ameliorate disease expression for those few who are
treated in the catarrhal phase. All suspected and
confirmed cases of pertussis should be treated in order to minimize
secondary spread.41 Macrolides are the drugs of
choice for the treatment of pertussis. Studies have demonstrated
that both azithromycin and clarithromycin are as effective as erythromycin
at eliminating B pertussis from the nasopharynx,42 although
there are no data in infants younger than 1 month of age. Erythromycin
at a dose of 40 to 50 mg/kg/day in 4 divided doses
for 14 days (maximum, 250 mg 4 times a day); clarithromycin 15 mg/kg/day in
2 divided doses for 7 days; or azithromycin 10 mg/kg/day
as single daily dose for 5 days are all recommended treatments.43 There
are data demonstrating that 7 days of erythromycin estolate are
as effective as 14 days, which may reflect the improved penetration
of this erythromycin formulation over others.44 Stomach
upset is the most commonly reported side effect of erythromycin
and frequently is a reason for patient noncompliance. β-Lactam antibiotics
are not effective against B pertussis.8 Resistance
to erythromycin has been reported but is believed to be limited
at this time.
++
Household and daycare contacts of confirmed pertussis patients
should receive antibiotic prophylaxis for 14 days after the last contact.
Prophylaxis is indicated regardless of prior immunization status.
Macrolides are the drugs of choice at the same dosages used for therapy.43 Efficacy
of trimethoprim/sulfamethoxazole as a chemoprophylactic
agent has not been evaluated.
++
B pertussis is highly contagious and has been recovered
from the nasopharynx of infected individuals after 5 days of macrolide
therapy. Therefore, hospitalized patients should be managed in respiratory
isolation (droplet precautions) until 5 days after the initiation
of macrolide therapy.30 A private room is preferred;
however, culture-positive cases may be cohorted. Untreated patients
should remain in isolation until 3 weeks after the onset of paroxysms.
Local health officials should be notified of all cases in order
to assist in outbreak control within the community. Immunization is
the principal method of prevention. Immunization of infants, along
with booster doses in preschool children, have been the mainstay
of prevention. Recent introduction of routine immunization of adolescents
and adults should have an impact on infant disease as well. Immunizations
are discussed further in Chapter 244.