Feature Articles

Pertussis: Severe clinical presentation in pediatric intensive care

and its relation to outcome*
Poongundran Namachivayam, MRCPCH; Kazuyoshi Shimizu, MD; Warwick Butt, FRACP, FJFICM

Objective: To describe our institutional experience in the man-
agement of infants and children with pertussis admitted during a
20-yr period (January 1985 through December 2004) and also to
study the relation between method of presentation and outcome.
Setting: Pediatric intensive care unit in a university-affiliated
tertiary pediatric hospital in Melbourne, Australia.
Design/Methods: Retrospective review of medical records and
radiology reports of patients with a diagnosis of pertussis iden-
tified from the pediatric intensive care unit database.
Results: A total of 49 patients (median age, 6 wks; interquartile
range, 4 – 8 wks) required 55 admission episodes to the pediatric
intensive care unit. Main reasons for admission were apnea with
or without cough paroxysms (63%), pneumonia (18%), and sei-
zures (10%). None of the infants had completed the primary
course of immunization, and 94% had not received a single dose
of pertussis vaccine. Infants presenting with pneumonia pre-
sented earlier (p ⴝ .001), had longer intensive care stay (p ⴝ
.007), higher white cell count (p < .001), lower PaO2 at admission
(p ⴝ .020), and higher mortality. Six infants out of seven needing
circulatory support died (including all four treated with extracor-
poreal membrane oxygenation), and all deaths (n ⴝ 7) occurred in
infants who had pneumonia at presentation.
Conclusion: Patients with pertussis, presenting as apnea (with
or without cough paroxysms), treated in the pediatric intensive
care unit had 100% survival. However, pneumonia as the main
reason for admission and the need for circulatory support is
associated with a very poor outcome. A deeper understanding of
the molecular basis of Bordetella pertussis and its relation to the
human host might offer means for future therapies. (Pediatr Crit
Care Med 2007; 8:207–211)
KEY WORDS: pertussis; intensive care; children; outcome; pre-
sentation; ventilation

P ertussis continues to be a sig-
nificant cause of childhood
morbidity and mortality, giv-
ing rise to 200,000 – 400,000
deaths every year, mostly in developing
countries (1). The recent increase in the
rate of pertussis is related to short-lived
infection and vaccine-induced immunity,
rendering adolescents and adults suscep-
tible to reinfection (2). This reservoir of
infection maintained in the adolescent
population subsequently causes infection
in susceptible infants, who are too young
to be fully vaccinated. More than half of
the severe cases requiring intensive care
manifests in infants too young to be vac-
*See also p. 288.
From the Intensive Care Unit, The Royal Children’s
Hospital, Melbourne, Australia (PN, KS, WB); and the
Department of Pediatrics, University of Melbourne,
Australia (WB).
The authors have not disclosed any potential con-
flicts of interest.
For information regarding this article, E-mail:
siva.namachivayam@rch.org.au
Copyright © 2007 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000265499.50592.37
cinated (3, 4). Most of the serious com-
plications and deaths related to pertussis
are seen in this age group (5). There is
general agreement that the disease is
toxin mediated, and antibiotics limit the
severity of illness only when started early
in the disease process (6). Pertussis toxin
damages the respiratory epithelium and
can also produce profound systemic and
neurotoxicity.
Infants needing intensive care pre-
dominantly present with apneas with or
without cough paroxysms, pneumonia,
and seizures, and a small proportion
progress to severe respiratory failure,
complicated by pulmonary hypertension
(7). Younger infants may also present
with a rapid progression of disease that is
so compressed and severe that the classic
stages may not be evident. Intensive care
management of pertussis is mainly sup-
portive (suction, oxygen, nasal continu-
ous positive airway pressure, intermittent
positive pressure ventilation). A recent
nationwide survey in Australia (8) showed
that intensive care was provided for 18%
of infants diagnosed with pertussis, and
56% of these infants needed intubation
and ventilation. Two previous reviews re-
port mechanical ventilation rates at 54%
and 42%, respectively (4, 9), and recent
articles highlight poor outcome for pa-
tients with severe pertussis needing ex-
tracorporeal membrane oxygenation
(ECMO) (10, 11). Understanding the
mode of presentation could be crucial in
the subsequent management and even-
tual outcome of these children. In this
article, we offer a single intensive care
unit’s experience of the management and
outcome of severe pertussis based on a
review of children during a 20-yr period.
METHODS AND PATIENTS
Infants and children admitted with a diag-
nosis of pertussis to the pediatric intensive
care unit (PICU) in Royal Children’s Hospital,
Melbourne, during a 20-yr period (January
1985 through December 2004) were included
in the study. Royal Children’s Hospital is a
specialized pediatric hospital serving a popu-
lation of 5 million in the states of Victoria,
Tasmania, and southern New South Wales. All
patients with PICU admission or discharge di-
agnosis of pertussis were identified from the
PICU database using the Australian and New
Zealand pediatric intensive care diagnostic
codes. Case histories were studied in detail by

Pediatr Crit Care Med 2007 Vol. 8, No. 3 207

the authors (PN, KS). Additional information
was also obtained from the PICU database and
from radiology reports. Cases with either con-
firmed pertussis or clinical pertussis (typical
presentation plus a family member positive for
pertussis) were included. Patient demograph-
ics, neonatal history and any preexisting ill-
ness, immunization status, method of presen-
tation, laboratory data, duration and type of
respiratory or circulatory support, complica-
tions, and outcome were recorded. Of note,
there were no major changes in mechanical
ventilation, sedation, and muscle paralysis
guidelines during the study period. ECMO
therapy was introduced in our unit in 1987–
1988 and inhaled nitric oxide therapy in 1993.
This retrospective review was approved as an
audit with our institutional review board.
Based on the method of presentation sub-
jects were divided into three groups. Group 1
(31 of 49 patients, 63%) consisted of patients
who mainly presented with apnea (with or
without cough paroxysms). Group 2 (9 of 49
patients, 18%) patients presented with respi-
ratory insufficiency or respiratory failure due
to pneumonia. The diagnosis of pneumonia was
made based on the clinical presentation and
chest radiography. All patients in this group had
evidence of either focal (3) or diffuse multilo-
bar (6) consolidation on chest radiographs at
admission. Group 3 patients (5 of 49 patients,
10%) presented with seizures. Four children
with pertussis were not included in the groups
either because of different methods of presen-
tation or due to presence of other underlying
illnesses: two with complete lung collapse due
to secretions, one with congenital diaphrag-
matic hernia, and one infant with bilateral
diffuse bronchomalacia.
Statistics. Data are expressed as absolute
values (percentage) or as median (interquar-
tile range); significance testing was made us-
ing one-way analysis of variance with Bonfer-
roni t-test for all pair-wise comparisons after
log transformation of original data, and Fisher
exact test was used in computing relation be-
tween mortality and presentation.
RESULTS
A total of 49 infants and children (24
male patients) with pertussis were admit-
ted to intensive care 55 times. The me-
dian age at admission was 6 wks (inter-
quartile range, 4 – 8 wks), and 46 patients
(94%) were ⬍6 months of age. A total of
45 infants (92%) were of white, and there
were no aboriginal children in our pa-
tient population. There was no significant
difference in age between the three
groups (Table 1). Of the patients, 26% (13
of 49) had been premature infants. Al-
most all children (46 of 49, 94%) were
unimmunized at the time of admission,
and the remaining (6%) had received one
dose of pertussis vaccine. Three children
who presented at an older age (7, 71⁄2, 21
months) had an underlying, unrecog-
nized respiratory condition at admission.
The first had diffuse bilateral bronchoma-
lacia, the second patient had co-existent
adenovirus pneumonia, and the third pa-
tient was diagnosed with congenital dia-
phragmatic hernia. Two thirds of the pa-
tients (34 of 49) were directly admitted to
PICU from the emergency department or
from another referring hospital, and the
remaining patients were admitted from
the hospital ward. Diagnosis was made by
a combination of immunofluorescence
and culture on nasopharyngeal aspirate
in 90% of the subjects (44 of 49). In
three, a diagnosis of clinical pertussis was
made, and one patient each tested posi-
tive for immunoglobulin A antibody and
polymerase chain reaction from nasopha-
ryngeal aspirate.
Table 1 displays patient characteristics
within groups. The median duration of
illness preadmission was 7 days (inter-
quartile range, 5–14 days), but on com-
parison, pneumonia subjects had signifi-
cantly shorter preadmission illness (p ⫽
.001). The PICU length of stay in the
apnea group was considerably shorter
in comparison with the pneumonia
group (p ⫽ .007). Children in group 1
(apnea) and group 3 (seizure) had longer
duration of hospital stay after discharge
from the PICU, and this was related to a
protracted illness due to coughing and
associated feeding difficulties. The PICU
and hospital length of stay for the pneu-
monia group tended to be similar. This
reflects the severity of illness among
these patients, as most of them (seven of
nine patients) subsequently died in the
PICU. Infants presenting with pneumonia
had raised white cell counts (p ⱕ .001)
and lower PaO2 (p ⫽ .020) in comparison
with the apnea group. Eighteen patients
(40%) needed tracheal intubation for re-
spiratory support (Table 2), and the indi-
cations were: severe hypoxic respiratory
failure (n ⫽ 7), progressive hypercapnia
(n ⫽ 2), respiratory arrest after pro-
longed apneas (n ⫽ 5), and seizures (n ⫽
4). The median duration of ventilation
was 84 hrs (interquartile range, 33.5–120
hrs). All patients who did not require
mechanical ventilation survived, and
38% of children (7 of 18) needing intu-
bation died.
Seven infants in the pneumonia group
(15.5%) needed vasoactive support for
progressive circulatory failure (manifest-
ing as worsening perfusion, tachycardia,
and hypotension), and four among them
were eventually placed on ECMO. Echo-
cardiographic data were available for six
of these infants and showed one or
more of the following findings: severe
pulmonary hypertension (all six pa-
tients), dilated and poorly contracting
right ventricle (three patients), and
global myocardial dysfunction (one pa-
tient). Durations of support for the four
infants placed on ECMO were 80, 133,
345, and 408 hrs. Six out of the seven
needing circulatory assistance died,

Table 1. Patient characteristics compared within groups

Apnea Pneumonia Seizure

Variable, Median (IQR) (Group 1) n ⫽ 31, 63% (Group 2) n ⫽ 9, 18% (Group 3) n ⫽ 5, 10% p Valuea

Age, wks 5.5 (4–8) 6 (3.7–10) 5 (3.7–11.5) .837

Illness duration before PICU, days 10 (7–4) 4 (3.7–6.2) 7 (4.7–8.5) .001
ICU length of stay, hrs 39 (26.2–68.5) 186 (57–244.2) 110 (92–129) .007
Hospital length of stay, hrs 294 (208–443) 186 (76.5–382) 454 (282–577.5) .081
White cell count, ⫻109/L 25.2 (16.5–34.5) 76.5 (62.1–108.5) 64 (19.7–74.1) ⬍.001
PaO2 at admission, mm Hg 97 (71–130) 61.5 (54–75) 106 (86.5–121) .020
PaCO2 at admission, mm Hg 48 (42–59.5) 69 (56.5–91) 46.5 (44–72.5) .044
Mortality, n 0 7 0 ⬍.001b

IQR, interquartile range; PICU, pediatric intensive care unit; ICU, intensive care unit.
a
Comparison between groups 1 and 2; bFisher exact test.

208 Pediatr Crit Care Med 2007 Vol. 8, No. 3

which included all patients on ECMO. A hyponatremia in two children, and re- indication for PICU admission is pertussis
detailed description of these patients is lated to hypoxic episodes in two children. pneumonia. The majority of children
given in Table 3. Three infants received One child with severe developmental de- (seven of nine) in the pneumonia group
continuous venovenous hemofiltration lay (due to pertussis encephalopathy) died, and no deaths were seen in other
for renal support, and one patient was died at the age of 14 yrs due to worsening groups.
given both exchange transfusion and cardiac failure secondary to palliated The reported rate of pertussis pneu-
plasmapheresis for toxin clearance. All heart disease. Seven (15.5%) had feeding monia varies around 25% (12, 13). In our
seven children who died had pneumonia difficulties related to coughing episodes study, 18 patients (36%) developed pneu-
as the dominant presentation (Table 3). and needed parenteral nutrition and long monia, and in half of them, it was the
Complications occurred in 30 children hospital stay. All children after discharge presenting illness. Pneumonia evolving
(61%), and most had more than one from PICU were under the care of a re- later in the illness is associated with less
problem. Viral studies (nasopharyngeal spiratory physician. severe disease progression and often re-
aspirate for immunofluorescence and lated to secondary viral infections. Per-
culture) were available in all subjects. DISCUSSION haps the most important feature of our
The frequency and type of viral infections study is the classification of our patients
are shown in Table 4. Pneumonia was This review represents the largest into groups based on the main presenting
identified in 18 patients (36%), and half group of infants and children with per- illness, which enabled us to compare and
of these had pneumonia as initial presen- tussis treated in intensive care. The most
correlate different aspects of treatment
tation. Seizures (9) were thought to be important finding is the poor outcome
and outcome. For example, most patients
toxin induced in five children, caused by associated with this condition if the main
in the apnea group were managed with
supplemental oxygen or nasopharyngeal
Table 2. Respiratory support for different patient groups continuous positive airway pressure as
apposed to infants in the pneumonia
Apnea Pneumonia Seizure Total
(Group 1) n ⫽ 31 (Group 2) n ⫽ 9 (Group 3) n ⫽ 5 n ⫽ 45 group, who needed intubation. This is in
marked contrast to previous literature
IPPV 5 9a 4 18 (4), which report apnea as the main indi-
NCPAP 8 0 1 9 cation for mechanical ventilation. Previ-
Oxygen 18 0 0 18 ous reports (5, 14) identified prematurity
IPPV, intermittent positive pressure ventilation; NCPAP, nasopharyngeal continuous positive as a risk factor for mortality in infantile
airway pressure. pertussis. A total of 13 patients (26%) in
a
Three children initially receiving NCPAP were subsequently intubated for worsening hypoxic our study were born at ⬍37 wks of ges-
respiratory failure. tation, but only one presented with se-

Table 3. Characteristics of children who died of pertussis infection

Duration of ICU
Age, Illness, Length of Highest
Pt Wks Days Stay, Hrs Main Presentation P(A-a)O2/OI Vasoactive Infusionsa Support Cause of Death

1 3 4 21 Pneumonia 554/42 None IPPV Severe pertussis pneumonia,

PHT, severe cardiovascular
compromise; treatment
withdrawn for poor
prognosis
2 6 4 235 Pneumonia 213/17 AD 0.5, NA 0.5, IPPV, HFO, iNO, Severe pertussis pneumonia,
VASO VA-ECMO PHT
3 5 5 96 Pneumonia 454/31 DOB 10, NA 0.5, AD IPPV, HFO, iNO, Treatment withdrawn for poor
bolus, VASO, CA VA-ECMO neurological prognosis;
infusion severe pertussis
encephalopathy
4 7 3 19 Pneumonia 539/30 DOP 15, AD 3, and IPPV Severe pertussis pneumonia,
bolus circulatory failure
5 13 7 369 Pneumonia, shock 626/59 DOB 20, AD 0.4, and IPPV, VA-ECMO Multiorgan failure
bolus
6 4 14 69 Pneumonia 627/31 DOP 20, AD 2, and IPPV Multiorgan failure
bolus
7 10 4 186 Pneumonia 578/63 AD10 and bolus, IPPV, VA-ECMO Severe pertussis pneumonia,
NA1, DOP15, CA PHT, multiorgan failure
infusion

Pt, patient; ICU, intensive care unit; P(A-a)O2/OI, alveolar-arterial oxygen gradient and oxygenation index; IPPV, intermittent positive pressure
ventilation; PHT, pulmonary hypertension; AD, adrenaline; NA, noradrenaline; VASO, vasopressin; HFO, high-frequency oscillation; iNO, inhaled nitric
oxide; VA-ECMO, venoarterial extracorporeal membrane oxygenation; DOB, dobutamine; CA, calcium; DOP, dopamine.
a
Numbers indicate highest dose in micrograms per kilogram per minute.

Pediatr Crit Care Med 2007 Vol. 8, No. 3 209

Table 4. Complications seen in study patients
Complications n (%)
Pneumonia 18 (36)
Seizures 9 (18)
Encephalopathy 5 (10)
Hyponatremia 10 (20)
Acute renal failure
Lung collapse
Pleural effusion
Pneumothorax
Pulmonary hemorrhage
Pneumomediastinum
Pneumoperitoneum
Feeding difficulties 7 (14.2)
Developmental delay
Disseminated intravascular
coagulation
Associated/secondary
infections
Adenovirus
Rhino virus
Respiratory syncytial virus
Parainfluenza
Influenza A
Pseudomonas sepsis
Coagulase-negative sepsis
Candida sepsis
vere disease (pneumonia at presentation)
and eventually died. A previous study
conducted in Australia (8) also did not
identify prematurity as a risk factor for
mortality.
Pertussis is a toxin-mediated disease
associated with several virulence factors,
including pertussis toxin (most widely
studied of all), accounting for the wide-
spread variation in disease severity (15).
Pertussis toxin has multiple proven bi-
ological activities, some of which may
account for the systemic manifestations
of the disease. Severe and fatal pertussis
has been correlated with the degree of
lymphocytosis, a clear manifestation of
pertussis toxin. ECMO has benefited
children with refractory septic shock
(16, 17), and the role of plasmapheresis
in sepsis is currently under evaluation
(18, 19). Both these therapies, with
ECMO in particular, have shown disap-
pointing results in pertussis in our ex-
perience and in published literature
(10, 11, 20). We identified several risk
factors for mortality, such as shorter
preadmission illness, pneumonia at
presentation, leucocytosis, and the
need for circulatory support. Most of
these factors have been reported in pre-
vious literature (5), and moreover,
identifying risk factors does not neces-
sarily offer a solution to the problem.
Severe and refractory pulmonary hyper-
tension often evolves very rapidly and,
210
despite various rescue measures, can be
very difficult to treat. The mechanism
of pulmonary hypertension in pertussis
remains undetermined; however, the
demonstration of leukocyte thrombi in
the pulmonary vein of a fatal case (11)
and the correlation between leukocyto-
2 3. Ranganathan S, Tasker R, Booy R, et al: Per-
sis and mortality (7) lead one to believe
2
2 that therapies aimed at reducing the
2 degree of leukocytosis could be benefi-
1 cial. Exchange transfusion (21) and leu-
1 kopheresis therapy (22) by producing
1
cytoreduction have led to patient sur-
vival, and we suggest these therapies
1
1 should be considered in this high-risk
group.
Disease among adolescents and
adults represent an important reservoir
4
4 of pertussis, and administering booster
2 doses of vaccine to this population
2 might prevent transmission and disease
1 burden in younger infants (23). The
2
1
clinical course of pertussis in immu-
nized children tends to be milder (24),
1
and speeding up the current immuni-
zation schedule to deliver the first dose
earlier (⬍2 months of age) could be
beneficial; moreover, a deeper under-
standing of the molecular basis of Bor-
detella pertussis infection might offer
means for further therapies. Valuable
information obtained from the more re-
cently completed Bordetella genome
project (25, 26) might help in a better
understanding of this organism and its
relation with the human host.
The retrospective nature of our study
is clearly the most important limiting
factor, but dividing our subjects into
groups based on their presentation has
enabled us to more clearly outline the
management and outcome. Infants in our
study represent severe cases with serious
consequences, such as pneumonia, sei-
zures, encephalopathy, multiorgan dys-
function, and death. Most pertussis is a
relatively benign but persistent illness,
and the full effect of the disease on the
community cannot be assessed based on
our results.
In conclusion, pertussis pneumonia as
the main reason for PICU admission is
associated with a very poor outcome. The
need for circulatory support implies a
very poor prognosis. Well-established in-
tensive care therapies like ECMO have
been associated with poor outcome in the
management of pertussis in our experi-
ence. A deeper understanding of the mo-
lecular mechanisms underlying pertussis
infection could be vital for the develop-
ment of future therapies.
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