ESPID REPORTS

AND

REVIEWS

CONTENTS
Pertussis
Thrombocytosis and Infections in Childhood

EDITORIAL BOARD
Co-Editors: Delane Shingadia and Irja Lutsar
Board Members
David Burgner (Victoria, Australia)
Luisa Galli (Rome, Italy)
Christiana Nascimento-Carvalho
(Bahia, Brazil)
Ville Peltola (Turku, Finland)

Nicol Ritz (Basel Switzerland)

Irah Shah (Mumbai, India)
Matthew Snape (Oxford, UK)
George Syrogiannopoulos
(Larissa, Greece)

Tobias Tenenbaum (Manheim, Germany)

Marc Trebruegge (Southampton, UK)
Mareceline van Furth (Amsterdam,
The Netherlands)
Anne Vergison

Pertussis
What the Pediatric Infectious Disease Specialist Should Know
Ulrich Heininger, MD
Abstract: Pertussis is a bacterial disease that is
transmitted very efficiently from human to human
by droplets. It occurs at any age, is endemic in any
population, and can cause outbreaks in highly
variable frequencies. Hallmark of the disease is
cough with or without paroxysms, whoop, and
vomiting. Diagnosis relies on clinical suspicion followed by laboratory confirmation (PCR, Serology)
and should be followed by prompt antibiotic treatment to stop spread of the bacteria to contact persons.
Control of pertussis by acellular vaccines is possible
to some extent if immunization coverage is high and
booster doses are given lifelong. However new vaccines with higher efficacy rates are warranted.
Key Words: pertussis, Bordetella, epidemiology
(Pediatr Infect Dis J 2012;31: 78 79)

lmost all cases of pertussis (or whooping

cough) are caused by Bordetella pertussis
(Bp) or, less frequently, Bordetella parapertussis (Bpp) infection.1 In rare cases, Bordetella
bronchiseptica (which causes kennel cough in
dogs) or Bordetella holmesii is found as the
cause of cough in a patient. Bordetella species
are fimbriated Gram-negative rods that express
a variety of virulence factors, including pertus-

From the Division of Pediatric Infectious Diseases, University Childrens Hospital Basel, Switzerland.
The author is a member of the Global Pertussis
Initiative (supported with an unrestricted grant by
SPMSD) and the Consensus on Pertussis in Europe (C.O.P.E.) working group (supported with an
unrestricted grant by GSK).
Copyright 2012 by Lippincott Williams & Wilkins
ISSN: 0891-3668/12/3101-0078
DOI: 10.1097/INF.0b013e31823b034e

sis toxin (PT, expressed by Bp only), which is

the cause of leukocytosis in unimmunized patients, filamentous hemagglutinin (FHA), and
pertactin (PER).

TRANSMISSION
Bp and Bpp are effectively transmitted
from human to human by droplets. Pertussis is
highly contagious with an R0 in the range of 15
to 17, that is, 1 primary case can cause as many
as 17 secondary cases. This scenario assumes
that the primary case transmits large amounts
of bacteria and that exposed contact persons
are fully susceptible. However, dynamics of
contagiousness are influenced by pertussis-specific preexisting immunity of both the primary
case and exposed contact persons.2

EPIDEMIOLOGY
The variable contagiousness of Bp explains why pertussis occurs in what appear to
be single cases (Bp or Bpp); localized outbreaks (almost exclusively Bp) in families,
day-care centers, schools, hospitals, and other
institutions; and epidemics (Bp only) like most
recently in the United States.3,4 Pertussis is not
an exclusive childhood disease but has long
been known to affect individuals of any age,
including newborns, and can truly be called a
family affair.5 Notably, young infants are
frequently exposed to this potentially devastating disease by their family members, that is,
parents, siblings, or even grandparents.6 Pertussis leads to individually variable degrees of
specific immunity; however, immunity wanes
over time leading to more or less symptomatic
reinfections life long.

DISEASE
Pertussis is a chameleon that can present as anything from rhinitis and unspecific
mild cough (often not leading to a physician
visit or not recognized as pertussis in daily
practice) to classic textbook presentation
with paroxysmal coughing spells, post-tussive whooping, and vomiting. Any of these
cough manifestations can last between a few
days to several weeks or even months.7 Pertussis is at least unpleasant for the patient, as
these symptoms frequently interfere with
daily activities and can cause significant
sleep disturbances. Fever occurs in less than
20% of cases. Type and frequency of complications are dependent on age and immunity. They most commonly present as bronchoalveolar pneumonia (any age) or apnea
(newborns and young infants) and more
rarely as respiratory distress syndrome, seizures, and other signs of encephalopathy.8
Pertussis in young infants can be fatal.9

DIAGNOSIS
Typical pertussis disease can be diagnosed clinically, but this manifestation is only
the tip of the iceberg. More often, pertussis
presents in a child or adolescent as an unexplained prolonged cough that does not appear
to improve after 7 to 14 days duration. Even in
typical disease, clinicians are unable to distinguish Bp from Bpp infection; this distinction
requires laboratory confirmation. Traditionally,
bacterial culture from nasopharyngeal secretions (NPS, aspirated or obtained by a swab)
has been the diagnostic gold standard. However, sensitivity of culture is low, especially in
breakthrough disease (despite previous immu-

The ESPID Reports and Reviews of Pediatric Infectious Diseases series topics, authors and contents are chosen and approved
independently by the Editorial Board of ESPID.

78

| www.pidj.com

The Pediatric Infectious Disease Journal Volume 31, Number 1, January 2012

The Pediatric Infectious Disease Journal Volume 31, Number 1, January 2012

nization) and in reinfections where the number

of bacteria in the NPS is typically low.10
Therefore, today, NPS from patients with suspected pertussis are most commonly analyzed
by specific polymerase chain reaction (PCR).11
Depending on PCR primers used in your laboratory, specific Bp can not only be distinguished from Bpp but also from other rare
Bordetella species. Although PCR (or culture)
is most promising in the early phases of the
disease (weeks 1 and 2), serology is the preferred diagnostic tool thereafter. It is important
that enzyme-linked immunosorbent assays
based on specific antigens such as PT (specific
for Bp) and FHA rather than sonicated bacteria
are used. Unlike with other infectious diseases,
sensitivity of IgM antibodies is low, and diagnosis mainly relies on detection of specific and
IgA and/or IgG antibodies. Unfortunately, serologic tests are poorly standardized, and most
laboratories do not take immunization status of
patients into account. This is important, as tests
cannot discriminate vaccine induced antibodies
from those elicited by wild-type bacterial infection. However, in the absence of recent
pertussis immunization (within previous 6
months), an anti-PT antibody value 27
IU/mL is sensitive and specific for pertussis.12

TREATMENT
Bordetellae are susceptible to a variety
of antibiotics among which macrolides are
most commonly used. When given early during the disease, symptoms may become ameliorated, but this is unlikely when initiated
during the progressed paroxysmal stage.13 The
main indication for treatment is interruption of
the infection chain by eliminating contagiousness within 5 to 7 days after onset of treatment
compared with up to several weeks in untreated patients. Preferred antibiotics are clarithromycin (if 1 month of age, 7.5 mg/kg bid
for 7 days; maximum, 1 g per day) or azithromycin (6 months of age: 10 mg/kg as a
single dose for 5 days; 6 months of age: day
1, 10 mg/kg as a single dose; days 25, 5
mg/kg as a single dose; maximum, 250 mg/
d).14 Other medications including beta mimetics, steroids, and cough-relieving drugs are not
of proven benefit. In patients with lung failure,
aggressive treatment such as extracorporeal
membrane oxygenation (ECMO) is indicated.8

PREVENTION
Postexposure antibiotic prophylaxis
(same drugs, dosages, and duration as for
treatment) may be considered in the most
vulnerable individuals, that is, young infants,
and as a supplementary measure in addition to active immunization to control outbreaks. There is 1 controlled trial that
demonstrated efficacy of antibiotic prophylaxis, and clinical observations also support its recommendation.14,15
2012 Lippincott Williams & Wilkins

Most developed countries today use

multicomponent (PT FHA pertactin
fimbriae) so-called acellular vaccines
(ACV), whereas most resource-limited countries still use the older whole-cell vaccines
(WCV) consisting of inactivated whole Bp
bacteria. Both types of vaccines have been
shown to be safe, immunogenic (although
substantial lot to lot variability has been
demonstrated for WCV), and efficacious,
with efficacy estimates against typical disease caused by Bp ranging from 78% to 85%
for ACV and 38% to 92% for WCV in
infants and young children after 3 to 4
doses.16 Vaccine efficacy against Bpp is
lower (50% for ACV in one study17) and that
against other Bordetellae is not known. National recommendations in almost all countries
recommend 2 or 3 doses in infants, followed
by booster doses at highly variable numbers
and time points. Of note, protection against
complicated pertussis is already demonstrable
after the first dose of vaccine, underlining
timely initiation of the immunization series.18
Furthermore, it is important to achieve high
immunization coverage in the population for
herd protection, given that vaccine efficacy on
an individual level is suboptimal.19
Few countries, mainly in Europe,
America, and Australia, have introduced universal booster doses for adolescents and even
fewer a universal booster dose in adults.1
Because there are no monovalent pertussis
vaccines available, it is important to note that
a single tetanus diphtheriaacellular pertussis combination vaccines with reduced antigen contents (Tdap) can be given regardless of the interval from the last diphtheria
and/or tetanus vaccine.20 Two studies in 387
adults aged 18 to 76 years have demonstrated
that intervals as short as 3 weeks do not lead
to an increased risk for local reactions when
compared with intervals longer than 2 years,
and no serious adverse events occurred.21,22
This is encouraging information when rapid
protection from pertussis in an adult with a
recent history of diphtheria- and/or tetanus
immunization is warranted.
REFERENCES
1. Heininger U. Update on pertussis in children.
Expert Rev Anti Infect Ther. 2010;8:163173.
2. Long S, et al. Serologic evidence of subclinical
pertussis in immunized children. Pediatr Infect
Dis J. 1990;9:700 705.
3. Crameri S, Heininger U. Successful control of a
pertussis outbreak in a university childrens hospital. Int J Infect Dis. 2008;12:e85 e87.
4. Cherry JD, et al. Defining pertussis epidemiology: clinical, microbiologic and serologic perspectives. Pediatr Infect Dis J. 2005;24(suppl
5):S25S34.
5. Mortimer EA. Pertussis and its prevention: a
family affair. J Infect Dis. 1990;161:473 479.
6. de Greeff SC, et al. Pertussis disease burden in
the household: how to protect young infants. Clin
Infect Dis. 2010;50:1339 1345.

ESPID Reports and Reviews

7. Heininger U, et al. Clinical findings in Bordetella

pertussis infections: results of a prospective multicenter surveillance study. Pediatrics. 1997;100:
E10.Availableat:www.pediatrics.org/cgi/content/
full/100/6/e10.
8. Halasa NB, et al. Fatal pulmonary hypertension
associated with pertussis in infants: does extracorporeal membrane oxygenation have a role?
Pediatrics. 2003;112:1274 1278.
9. Crowcroft NS, et al. Deaths from pertussis are
underestimated in England. Arch Dis Child.
2002;86:336 338.
10. Schlapfer G, et al. Polymerase chain reaction
identification of Bordetella pertussis infections in
vaccinees and family members in a pertussis
vaccine efficacy trial in Germany. Pediatr Infect
Dis J. 1995;14:209 214.
11. Templeton KE, et al. Evaluation of real-time PCR
for detection of and discrimination between Bordetella pertussis, Bordetella parapertussis, and
Bordetella holmesii for clinical diagnosis. J Clin
Microbiol. 2003;41:4121 4126.
12. Mertens PL, et al. Sensitivity and specificity of
single IgA and IgG antibody concentrations for
early diagnosis of pertussis in adults: an evaluation for outbreak management in public health
practice. BMC Infect Dis. 2007;7:53.
13. Bergquist S, et al. Erythromycin in the treatment
of pertussis: a study of bacteriologic and clinical
effects. Pediatr Infect Dis J. 1987;6:458 461.
14. Centers for Disease Control Prevention. Recommended antimicrobial agents for the treatment
and postexposure prophylaxes of pertussis: 2005
CDC guidelines. Morb Mortal Wkly Rep. 2005;
54(RR-14):116.
15. Halperin SA, et al. A randomized, placebo-controlled trial of erythromycin estolate chemoprophylaxis for household contacts of children with
culture-positive Bordetella pertussis infection.
Pediatrics. 1999;104:e42. Available at: http://
www.pediatrics.org/cgi/content/full/104/4/e42.
16. Cherry JD. Comparative efficacy of acellular pertussis vaccines: an analysis of recent trials. Pediatr Infect Dis J. 1997;16:S90 S96.
17. Heininger U, et al. Evidence of efficacy of the
Lederle/Takeda acellular pertussis component
diphtheria and tetanus toxoids and pertussis vaccine but not the Lederle whole-cell component
diphtheria and tetanus toxoids and pertussis vaccine against Bordetella parapertussis infection.
Clin Infect Dis. 1999;28:602 604.
18. Juretzko P, et al. Effectiveness of acellular pertussis vaccine assessed by hospital-based active
surveillance in Germany. Clin Infect Dis. 2002;
35:162167.
19. Zepp F, et al. Rationale for pertussis booster
vaccination throughout life in Europe. Lancet
Infect Dis. 2011;11:557570.
20. Centers for Disease Control and Prevention
(CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory
Committee on Immunization Practices, 2010.
Morb Mortal Wkly Rep. 2011;60:1315.
21. Beytout J, et al. Safety of Tdap-IPV given 1
month after Td-IPV booster in healthy young
adults: a placebo-controlled trial. Hum Vaccin.
2009;5:315321.
22. Talbot EA, et al. The safety of immunizing with
tetanus-diphtheria-acellular pertussis vaccine
(Tdap) less than 2 years following previous tetanus vaccination: experience during a mass vaccination campaign of healthcare personnel during a
respiratory illness outbreak. Vaccine. 2010;28:
8001 8007.

www.pidj.com |

79