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Infant Pertussis
Who Was the Source?
Kristine M. Bisgard, DVM, MPH,* F. Brian Pascual, MPH,* Kristen R. Ehresmann, RN, MPH,†
Claudia A. Miller, MS,† Christy Cianfrini, MPH,* Charles E. Jennings, BS,‡
Catherine A. Rebmann, MPH,§ Julie Gabel, DVM, MPH,§ Stephanie L. Schauer, PhD,储 and
Susan M. Lett, MD, MPH储
Key Words: pertussis, infant, source of infection, epidemiology,
United States
(Pediatr Infect Dis J 2004;23: 985–989)
Background: In the United States in the 1990s, the incidence of
reported pertussis in adults, adolescents and infants increased; infants younger than 1 year of age had the highest reported incidence.
Methods: In 4 states with Enhanced Pertussis Surveillance, we
examined the epidemiology of reported pertussis cases to determine
the source of pertussis among infants. A source was defined as a
person with an acute cough illness who had contact with the
case-infant 7–20 days before the infant’s onset of cough.
Results: The average annual pertussis incidence per 100,000 infants
younger than 1 year of age varied by state: 22.9 in Georgia; 42.1 in
Illinois; 93.0 in Minnesota; and 35.8 in Massachusetts. Family
members of 616 (80%) of 774 reported case-infants were interviewed; a source was identified for 264 (43%) of the 616 caseinfants. Among the 264 case-infants, mothers were the source for 84
(32%) and another family member was the source for 113 (43%). Of
the 219 source-persons with known age, 38 (17%) were age 0 – 4
years, 16 (7%) were age 5–9 years, 43 (20%) were age 10 –19 years,
45 (21%) were age 20 –29 years and 77 (35%) were age ⱖ30 years.
Conclusions: The variation in reported pertussis incidence in the 4
states might have resulted from differences in awareness of pertussis
among health care providers, diagnostic capacity and case classification. Among case-infants with an identifiable source, family
members (at any age) were the main source of pertussis. Understanding the source of pertussis transmission to infants may provide
new approaches to prevent pertussis in the most vulnerable infants.
Accepted for publication September 8, 2004.
From the *Bacterial Vaccine Preventable Diseases Branch, National Immunization Program, Centers for Disease Control and Prevention, Atlanta,
GA; the †Minnesota Department of Health, Minneapolis, MN; the
‡Illinois Department of Public Health, Springfield, IL; the §Georgia
Division of Public Health, Atlanta, GA; and the 㛳Massachussetts Department of Public Health, Jamaica Plain, MA
Supported by the National Immunization Program, U.S. Centers for Disease
Control and Prevention.
Ms. Cianfrini’s current affiliation: élan Pharmaceuticals, Inc., 7475 Lusk
Boulevard, San Diego, CA 92121.
Reprints not available.
Copyright © 2004 by Lippincott Williams & Wilkins
ISSN: 0891-3668/04/2311-0985
DOI: 10.1097/01.inf.0000145263.37198.2b
lthough pertussis incidence declined after the widespread
use of whole cell pertussis vaccines in the mid-1940s,
pertussis continues to be an important cause of morbidity in
the United States, especially among infants younger than 1
year of age who have not received 3 doses of diphtheria and
tetanus toxoids and acellular pertussis vaccine.1–5 Most
young infants with pertussis are hospitalized, and some cases
are fatal.1–5 From 1976 to 2002, the crude incidence of
reported pertussis increased.4 – 6 When the reported average
annual incidence of pertussis in the 1980s was compared with
the incidence in the 1990s, the increase was largest among
infants ⱕ4 months of age (63/100,000 to 89/100,000),5 adolescents 10 –19 years of age (0.8/100,000 to 3.2/100,000) and
among adults (0.2/100,000 to 0.5/100,000) (CDC, unpublished data, 2001). Given the increase and severity of pertussis among young infants, the paucity of data on source of
pertussis among infants and to help direct future prevention
efforts, we examined the age distribution and characteristics
of reported pertussis cases in 4 states and sought to determine
the source of pertussis among infants younger than 1 year of
Pertussis is a notifiable disease in every state in the
United States. Cases are reported by physicians, laboratories,
hospital infection control personnel and other health care
professionals to local and state health departments.1,4,5,7
Since 1998, several states have participated in Enhanced
Pertussis Surveillance (EPS). In these areas, Bordetella pertussis isolates are stored for further laboratory evaluation, and
additional epidemiologic information is obtained during the
The Pediatric Infectious Disease Journal • Volume 23, Number 11, November 2004
"Unauthorized duplication of this content is a copyright infringement and subject to strict penalties."
The Pediatric Infectious Disease Journal • Volume 23, Number 11, November 2004
Bisgard et al
case investigations. For each reported pertussis case in an
infant younger than 1 year of age during 1999 –2002, state
and local health department personnel in 4 participating EPS
states (Georgia, Illinois, Massachusetts and Minnesota) obtained information about the possible source of pertussis.
The pertussis clinical case definition for reporting purposes is an acute cough illness lasting ⱖ14 days with at least
1 pertussis-associated symptom (paroxysmal cough, posttussive vomiting or inspiratory whoop), or ⱖ14 days of cough in
an outbreak setting.1,4,5 A confirmed case is a cough illness of
any duration with isolation of B. pertussis or a case that meets
the clinical case definition and is confirmed by polymerase
chain reaction (PCR) or by epidemiologic linkage to a laboratory-confirmed case. In Massachusetts, persons age ⱖ11
years with a clinical case of pertussis can be confirmed by a
positive serologic test performed by the Massachusetts State
Laboratory Institute.6 A probable case meets the clinical case
definition but is not laboratory-confirmed or epidemiologically linked to a laboratory-confirmed case. In Illinois and
Minnesota confirmed and probable pertussis cases are reported to the Centers for Disease Control and Prevention
(CDC); in Georgia and Massachusetts only confirmed pertussis cases are reported to CDC.
After a report of pertussis in an infant, the parents or
guardians were interviewed during the routine case investigation about cough illnesses among contacts that preceded
the infant’s cough onset. A known or suspected source of the
infant’s pertussis was defined as a person with an acute cough
illness who had contact with the case-infant 7–20 days before
the infant’s cough onset. B. pertussis infection in the source
was not necessarily confirmed by laboratory studies. When
multiple family members or close contacts had an acute
cough illness preceding the illness in the case-infant, the
person who spent the most time with the case-infant was
assigned as the source-case. The sex, age and relationship of
the source for the infant’s illness were also obtained. Because
young infants have the highest incidence of pertussis1–5 and
the age or relationship of the source could differ by the age of
the infant, we also examined characteristics of the source by
age of the case-infant (0 –3 months compared with 4 –11
Pertussis Epidemiology in the 4 EPS States. From 1999 –
2002 in the 4 participating EPS states, 774 infants with
pertussis were reported. Of these 774 cases, 463 (60%) were
confirmed by isolation of B. pertussis, 102 (13%) were
confirmed by PCR, 39 (5%) were confirmed by epidemiologic-link and 170 (22%) infants had an illness that met the
probable case definition. Infants 0 –3 months of age (620
cases during the 4-year period) had the highest average
annual incidence of 102.5/100,000, compared with infants
4 –11 months of age (154 cases during the 4-year period) with
an average annual incidence of 12.7/100,000.
During the 4-year period, the proportion and average
annual incidence of cases among infants younger than 1 year
of age varied by site (Table 1). During the 4-year period,
infants in Minnesota had the highest reported average annual
incidence, and infants in Georgia had the lowest average
annual incidence. Among older age groups, the average
annual incidence of reported pertussis also differed by state.
Ethnicity data were available for 692 (89%) of 774
infants. The average annual incidence of pertussis was 1.7fold higher 关95% confidence interval (CI): 1.4, 2.0兴 among
Hispanic infants (59.9/100,000) than among non-Hispanic
infants (35.6/100,000) (P ⬍ 0.001).
The proportion of infants with complications from
pertussis differed by age. Infants 0 –3 months of age were
significantly more likely to have been hospitalized or to have
apnea than infants 4 –11 months of age (Table 2). Between
the 2 age groups, similar proportions of case-infants had
pneumonia (14%), had seizures (1%) or died (1%). Six of the
7 infants who died were aged 0 –3 months. Of the 7 deceased
infants, 4 were male, 3 were Hispanic and only 1 infant had
an identified source; a mother 28 years of age. Among the
569 infants 0 –3 months of age with known vaccination
information, 378 (66%) had not been vaccinated, 187 (33%)
had received 1 pertussis vaccination and 4 (1%) had received
2 pertussis vaccinations. Of the 146 infants 4 –11 months of
age with known vaccination information, 30 (21%) had not
been vaccinated, 28 (19%) had received one pertussis vacci-
TABLE 1. Total Number and Average Annual Incidence of Reported Pertussis Cases by Age and Site
No. of Cases in the 4-yr Period by Age Group
0 –3 mo
103 (59.50)
93 (87.65)
258 (107.16)
166 (195.40)
4 –11 mo
All aged ⬍1 yr
1–9 yr
10 –19 yr
20 –29 yr
30⫹ yr
All Ages*
16 (4.62)
21 (9.90)
46 (9.55)
71 (41.79)
119 (22.91)
114 (35.81)
304 (42.09)
237 (92.99)
19 (0.43)
75 (2.60)
110 (1.70)
450 (18.68)
9 (0.19)
2073 (62.44)
122 (1.70)
538 (17.97)
1 (0.02)
203 (6.08)
33 (0.48)
65 (2.52)
4 (0.02)
720 (4.65)
129 (0.45)
296 (2.58)
152 (0.46)
3185 (12.56)
698 (1.40)
1586 (8.05)
*Excludes 10 cases in persons with unknown age.
Only confirmed pertussis cases were reported.
Numbers in parentheses, average annual incidence per 100,000.
Confirmed and probable pertussis were reported.
© 2004 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 23, Number 11, November 2004
TABLE 2. Complications from Pertussis Among Infants
by Age
No. With Reported Complication
and No. With Data Available
Age 0 –3 mo
Age 4 –11 mo
416/583 (71)*
346/577 (60)
73/524 (14)
40/140 (29)
57/144 (40)
21/137 (15)
*Numbers in parentheses, percent.
nation, 53 (36%) had received 2 pertussis vaccinations and 35
(24%) had received 3 pertussis vaccinations.
Source of Infant Pertussis. We interviewed the parents or
guardians for 616 (80%) of the 774 case-infants to ascertain
the source-case; we were unable to interview parents or
guardians for 158 (20%) case-infants. A known or suspected
source-case was identified for 264 (43%) of the 616 infant
cases; a source-case could not be identified for 352 (57%)
case-infants. Confirmed pertussis cases in infants were 2.9
times (95% CI 1.3, 2.4) more likely to have had a source
identified than probable infant-cases 关228 (38%) of 604
confirmed cases versus 36 (21%) of 170 probable cases; P ⬍
0.001兴. By state, among interviewed parents/guardians, the identification of a source-case ranged from 33 to 66% (Table 3).
Family members or relatives were the suspected source
of pertussis for 159 (75%) of 212 case-infants 0 –3 months of
age and for 38 (73%) of 52 case-infants 4 –11 months of age
(Table 4). Mothers were the source of 75 (35%) of 212
TABLE 3. Identification of Infant Pertussis Source-Case
by Site
No. of Cases
Known or
Unable to
31 (45)*
61 (66)
80 (33)
92 (43)
38 (55)
32 (34)
161 (67)
121 (57)
*Numbers in parentheses, percent.
Source of Infant Pertussis
case-infants 0 –3 months of age and for 9 (17%) of 52
case-infants 4 –11 months of age; mothers were 2.0 times
(95% CI 1.1, 3.8) more likely to have been the identified
source for case-infants 0 –3 months of age than case-infants
4 –11 months of age (P ⫽ 0.01). Among the 264 case-infants,
fathers were the source for 15% case-infants; siblings were
the source for 20% of case-infants; neighbors, friends or
others were the source for 24% case-infants; and child daycare contacts were the source for 2% case-infants. Of the 219
source-persons with known age, 38 (17%) were 0 – 4 years of
age, 16 (7%) were 5–9 years of age, 43 (20%) were 10 –19
years of age, 45 (21%) were 20 –29 years of age and 77 (35%)
were ⱖ30 years of age.
Results from this study demonstrate the difficulty in
identifying the source of B. pertussis infection in infants; only
43% of case-infants had a potential source identified. Caseinfants without an identifiable source could have been exposed to persons with mild or unrecognized pertussis or to
persons with highly infectious pertussis who had only brief or
unrecognized contact with the infant. Our findings on the
difficulty in identifying a source-case were similar to those in
a Canadian study.8 In Canada, among 1082 hospitalized
pertussis cases in children younger than 2 years of age, a
suspected source was identified for only 40% of patients.
Among the 264 case-infants with a known or suspected
source, a majority (75%) were in a family member. A cough
illness preceding the infant’s cough in a family member could
have been severe enough for that family member to warrant
seeking health care. However, a health care provider might
not have recognized the cough illness as pertussis.8 Pertussis
is a challenging diagnosis to confirm because of the insensitivity of available diagnostic tests.9 –11 Recognition, diagnosis
and treatment of persons with pertussis and chemoprophylaxis of close contacts likely could have prevented some cases
of pertussis in infants who were in this study.10
Previous reports have documented the role of adolescents and adults in transmitting pertussis to infants.12–19
Mothers have been implicated as the source of infant pertussis in many case reports.14 –20 Izurieta et al20 identified adolescent mothers and mothers with 7 days or more of anteced-
TABLE 4. Relationship and Age of the Source-Case to the Pertussis Case-Infant
No. of Case-Infants by Age Group of Source
0 – 4 yr
5–9 yr
10 –14 yr
15–19 yr
20 –29 yr
30⫹ yr
© 2004 Lippincott Williams & Wilkins
Bisgard et al
The Pediatric Infectious Disease Journal • Volume 23, Number 11, November 2004
ent cough illness associated with infant pertussis. In our
study, a mother was the identified source-case for 32% of
case-infants; an adolescent mother was identified as the
source for 5% of case-infants (Table 4). Overall a slight
majority (56%) of source-cases were adults. Adolescents and
adults can become susceptible to B. pertussis infection because of waning immunity that may occur 5–15 years after
the last pertussis vaccination.4,6,13
In this study, 25% of suspected source-cases were
young children (ⱕ9 years of age); young children have been
identified as the source of pertussis for other household
members in another study.21 Although pertussis vaccines are
imperfect and vaccinated children can manifest clinical pertussis and transmit to others, many infants in this study were
not vaccinated or were undervaccinated (had received fewer
vaccinations than recommended); undervaccinated infants
could be a marker for undervaccinated siblings. Pertussis
vaccination protects a child from developing severe pertussis5,22,23 and also helps to decrease the likelihood of transmission to household members.24
As demonstrated by data in Table 1, the reported
pertussis incidence varied considerably by state and by age
group. Although infant incidences varied by state, infants
4 –11 months of age consistently had a lower incidence than
infants 0 –3 months of age, corroborating the effectiveness of
pertussis vaccines that are scheduled to be given to infants at
2, 4 and 6 months of age.22–25 In studies of adolescents and
adults, pertussis has been shown to be much more common
than has been recognized through disease surveillance.12,13,21,26 In older age groups, differences in the reported pertussis incidence may have been caused by factors
such as the knowledge and awareness of pertussis among
health care providers; healthcare-seeking behavior by persons
with an acute cough illness; timeliness of specimen collection
for testing; the likelihood of false negative results (because of
the low sensitivity of diagnostic tests); access to free or
subsidized diagnostic tests; and surveillance for additional
cases after an index case (eg, a case in an infant) is identified.
For example, in Massachusetts, the availability of free laboratory testing and a serologic test with an estimated specificity of 99% and sensitivity of 63% has helped to identify cases
of pertussis in adolescents and adults.6
In the 4 EPS sites, infants of Hispanic ethnicity had a
higher incidence rate than non-Hispanic infants, similar to a
finding in a study of pertussis-associated fatalities.3 Although
“Hispanic” ethnicity is an ambiguous term, Hispanic ethnicity was hypothesized to be a risk marker for higher rates of
exposure to pertussis.
This study presented several limitations pertaining to
the difficulty in ascertaining pertussis disease in the sourcecase. The use of a clinical source-case definition may have
missed persons who had asymptomatic B. pertussis infection
or a mild acute cough illness. Persons who had a cough
illness not caused by B. pertussis infection could have been
misclassified as a source-case. Recall bias may have been a
factor if the parents/guardians did not recall persons with an
acute cough illness who were in contact with the infant or
when an exposure to an acute cough illness occurred. Additionally, parents/guardians may have been reluctant to identify the source to avoid stigmatizing him/her. We chose not to
attempt laboratory confirmation of B. pertussis infection in
suspected source-persons because of the elapsed interval
from cough onset to interview and the lack of sensitivity of
diagnostic tests. Another potential limitation might have
occurred because multiple persons in the 4 states conducted
investigations and there may have been differences in sourcecase ascertainment. Determining the exact source of an infant’s pertussis was problematic when multiple family members had a cough illness. The person who first brought
pertussis into a household (eg, a sibling) may not have been
the person (eg, the mother) who transmitted pertussis to the
infant. Therefore we assigned the person who spent the most
time with the infant within the incubation period for pertussis
as the source-case. Lastly, the likelihood of B. pertussis
transmission by an infant’s brief contact with an infectious
pertussis case-patient is unknown, but such contact may be an
important factor for those cases where a source-case could
not be ascertained.
Documented increases in pertussis among young infants and persons ⱖ10 years of age has generated increasing
interest in vaccinating adolescents and adults with a pertussiscontaining vaccine to attempt to decrease morbidity in these
age groups and reduce circulation of B. pertussis throughout
the entire population. The potential for reducing the incidence
of infant pertussis by vaccinating adolescents and/or adults is
unknown and no pertussis vaccine is currently licensed in the
United States for persons 7 years of age and older. Although
data from our study may be useful for pertussis modeling
studies, these data do not allow predictions about the effect of
vaccinating adolescents and/or adults on protecting infants
from pertussis.
Despite the difficulties in identifying a source-case, this
evaluation highlights the role of children, adolescents and
adults in pertussis transmission to infants. In the absence of a
licensed vaccine for adolescents and adults, early detection
and prophylaxis of close contacts can help to reduce household spread and transmission to infants. Vaccination of infants and children according the childhood immunization
schedule27 remains the most effective method of preventing
pertussis in these age groups.
We thank Drs. Greg Wallace, Marty Roper, Trudy
Murphy, Margaret Cortese and John Moran for their helpful
comments and suggestions on the manuscript. We thank the
health care providers and disease surveillance and control
© 2004 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 23, Number 11, November 2004
personnel in the 4 states for making this study possible.
Special thanks go to disease investigators Kae Hunt, Jill S.
Sheets, MPH, Kristin M. Sullivan, MPH, and Cynthia L.
Kenyon, MPH and to Kim Moore for data collection, entry
and tracking.
1. CDC. Epidemiology of pertussis: United States, 1997–2000. MMWR
2. CDC. Pertussis deaths: United States, 2000. MMWR 2001;51:616 – 618.
3. Vitek C, Pascual FB, Baughman A, et al. Increase in deaths from
pertussis among very young infants in the Unites States in the 1990s.
Pediatr Infect Dis J. 2003;22:628 – 634.
4. Güris D, Strebel PM, Bardenheier B, et al. Changing epidemiology of
pertussis in the United States: increasing reported incidence among
adolescents and adults, 1990 –1996. Clin Infect Dis. 1999;28:1230 –
5. Tanaka M, Vitek C, Pascual FB, et al. Trends in pertussis among infants
in the United States, 1980 –98. JAMA. 2003;290:2968 –2975.
6. Yih WK, Lett SM, des Vignes FN, et al. The increasing incidence of
pertussis in Massachusetts adolescents and adults, 1989 –1998. J Infect
Dis. 2000;182:1409 –1416.
7. Council of State and Territorial Epidemiologists (CSTE). 1997 Position
Statements. Presented at the CSTE National Meeting, Saratoga Springs,
NY. Position Statement 9. Available at
1997-id-09. htm. Accessed June 1, 2004.
8. Halperin SA, Wang EEL, Law B, et al. Epidemiological features of
pertussis in hospitalized patients in Canada, 1991–1997: report of the
Immunization Monitoring Program-Active (IMPACT). Clin Infect Dis.
1999;28:1238 –1243.
9. Cherry JD. Epidemiological, clinical, and laboratory aspects of pertussis
in adults. Clin Infect Dis. 1999;28(suppl 2):S112–S117.
10. CDC. Guidelines for the control of pertussis outbreaks. Atlanta, GA:
Centers for Disease Control and Prevention; 2000. Available at: http:// Accessed Dec. 30, 2003.
11. Lievano FA, Reyolds MA, Waring AL, et al. Issues associated with
using PCR to detect outbreaks of pertussis. J Clin Microbiol. 2002;40:
© 2004 Lippincott Williams & Wilkins
Source of Infant Pertussis
12. Biellik RJ, Patriarca PA, Mullen JR, et al. Risk factors for communityand household-acquired pertussis during a large-scale outbreak in central
Wisconsin. J Infect Dis. 1988;157:1134 –1141.
13. Lambert HJ. Epidemiology of a small pertussis outbreak in Kent County,
Michigan. Public Health Rep. 1965;80:365–369.
14. Nelson J. The changing epidemiology of pertussis in young infants. Am J
Dis Child. 1978;132:371–373.
15. McGregor J, Ogle J, Curry-Kane G. Perinatal pertussis. Obstet Gynecol.
16. Christie C, Baltimore R. Pertussis in neonates. Am J Dis Child. 1989;
143:1199 –1202.
17. Beiter A, Lewis K, Pineda E, et al. Unrecognized maternal peripartum
pertussis with subsequent fatal neonatal pertussis. Obstet Gynecol.
1993;82:691– 693.
18. MacLean D, Calder M. Pertussis in pregnancy. Scott Med J. 1981;26:
250 –253.
19. Granstrom G, Granstrom M, Sterner G. Whooping cough in late pregnancy. Scand J Infect Dis. 1990;71(suppl):27–29.
20. Izurieta HS, Kenyon TA, Strebel PM, et al. Risk factors for pertussis in
young infants during an outbreak in Chicago in 1993. Clin Infect Dis.
21. Wirsing von König CH, Halperin S, Rifflemann M, et al. Pertussis of
adults and infants. Lancet Infect Dis. 2002;2:744 –750.
22. CDC. Pertussis vaccination: use of acellular pertussis vaccines among
infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(RR-7):1–25.
23. Güris D, Strebel PM, Tachdjian R, et al. Effectiveness of the pertussis
vaccination program as determined by use of the screening method:
United States, 1992–1994. J Infect Dis. 1997;176:456 – 463.
24. Préziosi MP, Halloran ME. Effects of pertussis vaccination on transmission: vaccine efficacy for infectiousness. Vaccine. 2003;21:1853–1861.
25. Bisgard KM, Rhodes P, Connelly BL, et al. Pertussis vaccine effectiveness among children aged 6 –59 months in the United States, 1998 –2001
关abstract兴. In: Abstracts of the 41st Annual Meeting of the Infectious
Diseases Society of America, 2003, San Diego, CA. Abstract 901.
26. Strebel P, Nordin J, Edwards K, et al. Population-based incidence of
pertussis among adolescents and adults, Minnesota, 1995–1996. J Infect
Dis. 2001;183:1353–1359.
27. CDC. Recommended Childhood Immunization Schedule, January–June,
2004. MMWR. 2004;53:Q1–Q4.