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Tanaka M, Vitek CR, Pascual FB, Bisgard KM, Tate JE, Murphy TV. Trends in Pertussis Among Infants in the United States, 1980-1999. JAMA. 2003;290(22):2968–2975. doi:10.1001/jama.290.22.2968
Author Affiliations: Bacterial Vaccine Preventable Disease Branch, Epidemiology and Surveillance Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Tanaka, Bisgard, and Murphy, and Mr Pascual); Division of HIV/AIDS Prevention, National Centers for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Vitek); Department of Epidemiology, University of North Carolina at Chapel Hill, (Ms Tate).
Context Reported cases of pertussis among adolescents and adults have increased
since the 1980s, despite increasingly high rates of vaccination among infants
and children. However, severe pertussis morbidity and mortality occur primarily
Objective To describe the trends and characteristics of reported cases of pertussis
among infants younger than 12 months in the United States from 1980 to 1999.
Design, Setting, and Participants Cases of pertussis in infants younger than 12 months in the United States
reported to the National Notifiable Disease Surveillance System of the Centers
for Disease Control and Prevention between 1980 and 1999, and detailed case
data from the Supplementary Pertussis Surveillance System.
Main Outcome Measures Incidence and demographic and clinical characteristics of cases.
Results The incidence of reported cases of pertussis among infants increased
49% in the 1990s compared with the incidence in the 1980s (19 798 vs
12 550 cases reported; 51.1 cases vs 34.2 cases per 100 000 infant
population, respectively). Increases in the incidence of cases and the number
of deaths among infants during the 1990s primarily were among those aged 4
months or younger, contrasting with a stable incidence of cases among infants
aged 5 months or older. The proportion of cases confirmed by bacterial culture
was higher in the 1990s than in the 1980s (50% and 33%, respectively); the
proportion of hospitalized cases was unchanged (67% vs 68%, respectively).
Receipt of fewer doses of vaccine was associated with hospitalization, when
cases were stratified by age in months.
Conclusions The incidence of reported cases of pertussis among infants increased
in the 1990s compared with the 1980s. The limited age group affected, the
increased rate of bacteriologic confirmation, and the unchanged severity of
illness suggest that an increase in infant pertussis has occurred apart from
any change in reporting. Strategies are needed to prevent the morbidity and
mortality from pertussis among infants too young to be fully vaccinated, according
to the current recommended schedules of vaccination in the United States.
Pertussis, a respiratory illness caused by Bordetella
pertussis, is characterized by a paroxysmal cough that can last for
several weeks. In the prevaccine era, pertussis was a major cause of morbidity
and mortality among infants and children in the United States, with a mean
of more than 160 000 cases and more than 5000 deaths reported annually
in the 1920s and 1930s.1,2 After
the introduction of whole-cell pertussis vaccine combined with diphtheria
and tetanus toxoids in the 1940s, reported cases of pertussis decreased more
than 99%, reaching a nadir of 1010 cases in 1976.3,4
After 1976, the number of reported cases of pertussis progressively
increased, while maintaining the 3- to 4-year cyclicity characteristic of
the prevaccine era. The incidence of reported cases of pertussis increased
among all age groups, but especially among adolescents and adults.5,6 The relative contributions to the increase
in reports from heightened awareness of pertussis among adolescents and adults,
improved surveillance, and the real increase in disease remain unclear.
Among all age groups, infants (aged <12 months) have had the highest
incidence of pertussis in the vaccine era, and infants account for the overwhelming
majority of hospitalizations, serious complications, and deaths from pertussis.5-7 Because pertussis is
a well-known disease among infants, case ascertainment and disease reporting
may be more consistent among infants than among older age groups. To describe
the trends and characteristics of reported infant pertussis cases in the United
States, we analyzed the national database of cases among infants for the period
of 1980-1999 and determined the characteristics of cases in the 1990s.
Pertussis has been a notifiable disease in the United States since the
1920s. Cases are reported by clinicians, laboratories, and other health care
personnel to local and state health departments. Health department personnel
investigate these reports and determine if they should be reported as cases
of pertussis. Data about these cases are reported by state health departments
to the Centers for Disease Control and Prevention (CDC).
In 1990, case definitions for pertussis were recommended by CDC and
the Council of State and Territorial Epidemiologists (CSTE) for the national
surveillance of pertussis8; minor revisions
were made in 1996.9 The definition of clinical case for an endemic or sporadic case of pertussis
is a cough illness lasting 2 weeks or longer with at least 1 of the following:
paroxysms of coughing, inspiratory "whoop," or post-tussive vomiting, without
other apparent cause. In outbreak settings, a case may
be defined by a cough illness lasting 2 weeks or longer without other criteria.
Isolation of B pertussis was required for laboratory
confirmation in the early 1990s; the test has relatively low yield in routine
use but is the standard for the diagnosis of pertussis.10,11 Some
states began reporting the result of polymerase chain reaction (PCR) for B pertussis DNA in 1995, and a positive result was accepted
by CDC/CSTE as an additional confirmatory test in 1996. The CDC/CSTE does
not recommend the use of direct fluorescent antibody (DFA) test for laboratory
confirmation, because some studies have documented that DFA testing of nasopharyngeal
secretions has low sensitivity and variable specificity,9,11 but
the test is still commonly used in some states.
Although all cases reported through the national surveillance system
were considered to be pertussis by a clinician or public health official,
some were lacking data needed to classify them according to the CDC/CSTE criteria.
For this report, cases of pertussis were reclassified as confirmed or probable
if they met CDC/CSTE criteria for endemic/sporadic cases.9 A confirmed case was defined as a case with an acute cough
illness of any duration that was culture-positive, or a case that met the
clinical case definition and was confirmed by polymerase chain reaction, or
a case that met the clinical case definition and was epidemiologically linked
to a laboratory-confirmed case. A probable case of
pertussis was one that met the clinical case definition, was not laboratory-confirmed,
and was not epidemiologically linked to a laboratory-confirmed case.9,11 Cases with unknown
status were those cases that did not have sufficient information reported
to classify them as confirmed or probable.
In the 1980s and 1990s, CDC maintained a national surveillance system
for pertussis in the United States, the National Notifiable Disease Surveillance
System (NNDSS). The objective of NNDSS was timely passive reporting from state
and local surveillance personnel of pertussis cases with basic information
such as year of disease, age of cases in years, and disease outcome. Data
from NNDSS are published weekly by CDC in the Morbidity
and Mortality Weekly Report (MMWR). The Supplementary
Pertussis Surveillance System (SPSS)12 was
introduced in 1979 to obtain more detailed information about pertussis cases
reported to NNDSS, such as dates of birth and disease onset, vaccination status,
laboratory results, symptoms, and complications. The number of infant cases
for which SPSS information was available was 86% of the number of infant cases
reported to NNDSS in the 1980s and 93% of cases reported to NNDSS in the 1990s.
By 1984, the number of infant cases with supplementary information reported
through SPSS reached a figure comparable with reports through NNDSS. Since
1996, cases from the 2 systems have been reconciled into a single database.
We used the routine schedule for pertussis vaccination recommended by
the Advisory Committee on Immunization Practices (ACIP) to determine whether
infants with pertussis were age-appropriately vaccinated at the onset of pertussis.13 The timing of recommended doses of pertussis vaccine
for infants (2, 4, and 6 months of age) has not changed since 1977; the recommendations
allow the first dose of pertussis-containing vaccine to be given as early
as 6 weeks of age. Subsequent doses are given at a minimum interval of 4 weeks.
In defining the minimum number of doses an infant should have received to
be age-appropriately vaccinated at a given age in months, we allowed a grace
period of 1 month from the recommended schedule.
Infants received either diphtheria and tetanus toxoids and acellular
pertussis vaccines (DTaP) or diphtheria and tetanus toxoids and whole-cell
pertussis vaccines (DTwP) for the first 3 doses. Until mid-1996, DTwP vaccines
were the only licensed preparations for the first 3 doses. In the United States, DTaP vaccines were recommended for the fourth
and fifth dose by the ACIP in 1992. In July 1996, DTaP vaccines were recommended
for infants starting at 2 months of age and subsequently replaced DTwP vaccines.
Data on the type of vaccine received at the individual case level usually
were not available from surveillance reports. For this reason, DTwP and DTaP
vaccines are collectively denoted as diphtheria, tetanus, and pertussis vaccine
(DTP) in this article.
To ensure consistency with previously published analyses,5,6 we
included all nationally reported cases of pertussis among infants younger
than 12 months at the time of disease; we excluded cases reported from Puerto
Rico and other overseas territories. Data from NNDSS were used to determine
the total number of infant cases and deaths by year. For all other analyses,
we used detailed data from the SPSS database. The SPSS data since 1984 were
used for calculations of incidences. The denominator for calculated incidence
rates among specific age or ethnic groups was restricted to the US population
estimate that represented the group of interest. Reporting of race and ethnicity
began in 1995, but was incomplete; we restricted the analysis of race and
ethnicity to cases reported in 1997-1999 when the reporting of the information
improved. Population demographic data were obtained from intercensal estimates
from the National Census Bureau.14 Statistical
analyses were performed using Microsoft Excel 2002 (Microsoft, Redmond, Wash)
and Epi Info (version 6.04, CDC, Atlanta, Ga).
During the 1990s, a total of 19 798 cases of pertussis among infants
younger than 12 months were reported through NNDSS and 12 550 cases were
reported in the 1980s. Cases among infants accounted for 35% of all pertussis
cases reported in the 1990s. The annual number of reported cases of pertussis
among infants increased progressively during the last 2 decades with peaks
every 3 to 4 years (Figure 1). In
the 1990s compared with the 1980s, the mean annual number of cases among infants
reported through NNDSS increased by 58% (1980 cases vs 1255 cases, respectively),
and the mean annual incidence increased by 49% (51.1 vs 34.2 cases per 100 000
infant population, respectively).
During the 1990s, 18 500 infant cases were reported through SPSS;
50.6% were male. Cases among infants 4 months or younger accounted for 77%
(14 311 cases) of all infant cases reported through SPSS and 27% of pertussis
cases of all ages during the 1990s. The mean annual incidence rate among infants
4 months or younger increased from 63.4 cases per 100 000 population
in the 1980s to 88.7 cases per 100 000 in the 1990s; the mean annual
incidence rate among infants aged 2 months or younger increased by 49%, from
72.1 cases in the 1980s to 107.3 cases per 100 000 in the 1990s (Figure 2, Figure 3). The mean annual incidence among infants aged 5 to 11
months changed little (20.2 cases per 100 000 in the 1980s and 18.6 cases
per 100 000 in the 1990s) (Figure 2 and Figure 3).
Among 18 500 infant cases reported through SPSS in the 1990s, 10 161
cases (55%) were confirmed; 9231 (50%) cases were culture-confirmed by isolation
of B pertussis. In contrast, among 10 859 infant
cases reported through SPSS in the 1980s, 3604 (33%) were culture-confirmed.
In the 1990s, 706 (4%) cases were confirmed by a positive polymerase chain
reaction assay, and 224 (1%) were confirmed by epidemiological linkage to
a laboratory-confirmed case. Results of DFA testing of nasopharyngeal secretions
for B pertussis were reported for 6794 (67%) of the
10 161 confirmed cases in the 1990s; 4170 (61%) DFA tests were positive.
Among 5688 cases (31%) classified as probable cases, 3123 (55%) had a positive
DFA test. An additional 2651 cases (14%) were unable to be categorized; 1527
(58%) of these cases had a positive DFA test. This contrasts with 42% of cases
that were unable to be characterized in the 1980s.
The mean annual incidence of culture-confirmed cases among infants increased
in the 1990s compared with the 1980s (24.0 and 13.2 per 100 000 infant
population, respectively). In the 1990s, the proportion of cases that were
culture-tested increased (67% in the 1990s vs 50% in the 1980s; P<.001), and the proportion of cases with a positive result among
those culture-tested also increased (75% in the 1990s vs 66% in the 1980s; P<.001).
In the 1990s, 7387 cases (91%) of the 8116 reported cases among infants
aged 3 to 11 months had information about vaccination with DTP; in the 1980s,
5540 (95%) of cases in this age group had the information. The proportion
of cases age-appropriately vaccinated was higher in the 1990s than in the
1980s (Table 1).
Classic symptoms of pertussis, cough and paroxysm, were common among
infant cases regardless of age in months (Table 2). Among hospitalized cases, the mean length of hospitalization
was 7.0 days in the 1990s. The proportions of cases with whoop and with vomiting
increased with increasing age; the proportions of cases with apnea and cases
hospitalized decreased with increasing age. The proportion of cases hospitalized
was 67% in the 1990s and 68% in the 1980s. We examined the relationship between
age in months and clinical symptoms or hospitalization. For this analysis,
we stratified cases by the number of DTP doses at the onset of pertussis symptoms.
Younger age (2-3 months vs 4-11 months, stratified into 0-dose or 1-dose group)
was found to be a risk factor for apnea (odds ratio [OR], 1.27; 95% confidence
interval [CI], 1.17-1.40) and for hospitalization (OR, 1.85; 95% CI, 1.68-2.04).
We also examined the relationship between the number of DTP doses and
clinical symptoms or hospitalization. For this analysis we stratified by age
in months. Among cases aged 6 to 11 months with known vaccination status,
0 dose compared with 3 doses was a risk factor for whoop (OR, 1.53; 95% CI,
1.24-1.87), apnea (OR, 1.25; 95% CI, 1.02-1.53), and pneumonia (OR, 1.54;
95% CI, 1.12-2.12). Irrespective of age, infants with pertussis who received
fewer DTP vaccinations were significantly more likely to be hospitalized (Table 3).
In the 1990s compared with the 1980s, the mean annual incidence of hospitalized
cases among infants increased by 21% (30.8 vs 25.5 per 100 000 infant
population). Among infants 4 months or younger, the mean incidence of hospitalization
rose by 36% (62.7 vs 46.2 cases per 100 000 population). By contrast,
among infants aged 5 to 11 months, the mean incidence of hospitalization decreased
by 25% (8.1 vs 10.7 cases per 100 000 population).
During the 1990s, 93 (90%) of 103 reported pertussis-related fatalities
were among infants, compared with 61 (79%) of 77 reported pertussis-related
fatalities during the 1980s; the case-fatality rate among infants was 0.5%
in both decades. Among reported pertussis deaths of all ages, the proportion
of infants younger than 4 months increased from 64% in the 1980s to 82% in
the 1990s. In the 1990s, of 25 infant death cases aged 2 months or older (and
therefore who had been eligible for routine vaccination), 15 had received
no pertussis vaccine.
Data on race were available for 4224 (68%) of the 6172 infant cases
reported during 1997-1999; 78% were white and 17% were African American. Of
the 4304 cases with data on ethnicity, 29% were identified as Hispanic. Although
national reporting of ethnicity remains incomplete, 6 states (Arizona, California,
Connecticut, Florida, New Mexico, and Texas) had more than 90% complete reporting
on ethnicity for infant pertussis cases and more than 5% Hispanics among their
infant populations in 1997-1999. In these states, the mean annual incidence
of pertussis among Hispanic infants was 68 per 100 000 infant population,
74% higher than among non-Hispanic infants (39 per 100 000).
In the 1990s, the mean annual incidence of pertussis among infants by
state ranged from 10 to 133 cases per 100 000 in Mississippi and Idaho,
respectively (SPSS data). Substantial year-to-year variation in the incidence
was observed by state, but some states, such as Idaho, New Hampshire, Hawaii,
Minnesota, Colorado, and Washington, consistently reported mean annual incidences
higher than 100 cases per 100 000 infant population. Other states, such
as Mississippi, Alaska, Florida, New Jersey, Louisiana, and South Carolina,
consistently reported low incidences throughout the 1990s (<50% of the
national average of 51 cases per 100 000 infant population). Most states
in the southern Atlantic, eastern south-central, and western south-central
regions reported lower than the national average annual incidences; most states
in New England reported higher than the national average annual incidences
(data not shown).
During the 1990s, 46% of reported infant pertussis cases had an onset
of cough between June and September (Figure
4). For 27% of the cases, the onset was in July and August; the
summer peak was less pronounced for infant cases aged 4 months or younger
compared with infant cases older than 4 months. The peak pattern among infant
cases aged 4 months or younger was similar to cases aged 5 to 9 years and
cases 20 years or older, and the pattern among cases aged 5 to 11 months was
similar to cases aged 1 to 4 years. Nationally, pertussis cases among adolescents
peaked in the fall months of the year, although there was variation by state.
National surveillance data show a progressive increase in reports of
pertussis among infants in the United States from the end of the 1970s through
the 1990s. In the 1990s, the increase occurred exclusively among infants 4
months or younger and contrasted with the absence of a change in the incidence
of reported cases among older infants.
The increase in reported cases of pertussis among young infants may
have resulted from several factors, including a real increase in disease,
increased awareness of pertussis among clinicians, or improved surveillance
activities. We believe that the increase of reported cases among infants reflects
a real increase in B pertussis disease and is not
an artifact from the surveillance system for the following reasons. First,
the increase in infant cases was unlikely to have resulted from greater awareness
among clinicians.15-21 Clinicians,
especially pediatricians, have recognized pertussis as a cause of severe respiratory
disease among infants for decades. Second, introduction of new case definitions
and diagnostic methods contributed little to the increase observed in the
data; the specificity of the reported cases, as shown by the proportion of
cases confirmed by isolation of B pertussis, increased
in the 1990s. Third, no great change in the completeness of reporting was
detected using as a surrogate the stability of the proportion of reported
infant cases who were hospitalized during the 1980s and 1990s, and by a recent
analysis of the completeness of reported pertussis deaths.22 This
stability suggests that reporting of milder cases did not increase. Finally,
reported cases of pertussis among infants aged 5 to 11 months did not increase
in the 1990s; some increase in reported cases among these infants would have
been likely if a change had occurred in case ascertainment or reporting.
Increased rates of pertussis among infants resulted in large numbers
of excess hospitalizations and deaths because infants have the highest age-specific
rates of clinically severe pertussis and its complications. The number of
reported pertussis hospitalizations among infants 4 months or younger in the
1990s increased by more than 4500 during the 1980s; reported deaths increased
at least by 33. The true increase in pertussis hospitalizations and deaths
is probably larger, as previous studies have estimated that only approximately
one third of pertussis hospitalizations were reported to the CDC.23 Severe pertussis and deaths among young infants also
may not have been recognized when the clinical presentation of pertussis was
atypical. Infants, especially neonates, can present with episodes of apnea
and bradycardia, and typical cough can be minimal or absent.18,20,24,25
Among infants aged 5 to 11 months, the age-specific incidence of pertussis
remained stable. Increased immunization coverage in the 1990s is one likely
reason that increased pertussis activity did not cause an increase in reported
cases among infants aged 5 to 11 months and young children. In the United
States, estimated coverage with 3 doses or more of DTP vaccination improved
from less than 68% among children aged 1 to 4 years in the 1980s to greater
than 86% by 13 months of age from 1995 to 1999.26,27 Infants
aged 5 to 6 months may have been too young to have received 3 doses of pertussis
vaccine. However, we believe that the increased level of vaccination coverage
with 2 doses of DTP in this age group in the 1990s26 resulted
in stable rates of pertussis. Our data suggest a protective effect from even
2 doses of DTP in this age group (Table
3), and other reports support this observation.28-30
The Healthy People 2010 initiative of the US Department of Health and
Human Services sets a goal for the year 2010 of less than 2000 pertussis cases
among children younger than 7 years annually. This goal assumes that "pertussis
among children will be reduced by increasing vaccination coverage."31 Our analyses suggest that pertussis is increasing
among very young infants despite high rates of immunization among infants
and preschool children. Since the youngest infants are not directly protected
by immunization using current vaccines and vaccine policies, our analyses
suggest that improved implementation of the current vaccination recommendations
may not substantially reduce the morbidity and mortality of infant pertussis.
New strategies are needed to prevent the morbidity and mortality among infants
too young to be fully vaccinated in the United States.
Developing improved control measures for pertussis among infants will
require a better understanding of the reasons for the increase in infant pertussis,
including the sources of and risk factors for transmission. Increased pertussis
among young infants may reflect either decreased immunity to pertussis or
increased exposure to B pertussis among young infants.
Data are limited on hypotheses for the potential of decreased immunity among
infants.32 Increased exposure of young infants
to B pertussis may have resulted from increased B pertussis circulation among individuals likely to transmit
to infants. The most frequent sources for transmission of pertussis to infants
appear to vary depending on the level of effective immunization coverage33 and possibly other epidemiological factors such as
family structure. The majority of infants studied in the United States in
the 1990s did not have an identified source; the most frequent identified
sources for transmission of pertussis to infants were parents, followed by
patterns were observed in the 1990s in other countries with high vaccination
seasonality of pertussis is likely related to patterns of contacts with infectious
cases,38 and the observed seasonality pattern
among the different age groups in the 1990s also may suggest that pertussis
transmission to young infants (summer peak) is associated more closely with
adults aged older than 20 years and with school-aged children aged 5 to 9
years than with adolescents (fall peak).
Racial and ethnic disparities in infant pertussis appear to exist but
are incompletely understood. As noted earlier, although national data were
limited, Hispanic infants had an increased incidence of pertussis compared
with non-Hispanic infants in states with more complete ethnicity data for
pertussis cases. Hispanic infants also accounted for a disproportionate share
(31 deaths [33%]) of 93 pertussis deaths among infants reported to CDC during
the 1990s22; data in the 1990s from California,
in which detailed case-based information was available for fatal cases, show
that the case-fatality ratio for pertussis cases among Hispanic infants was
not significantly different from that among non-Hispanics.22 These
data may suggest an increased incidence of pertussis among Hispanic infants.
In the late 1990s, the national immunization coverage with 3 doses or more
of DTP vaccines among children of Hispanic ethnicity was very close to that
of non-Hispanic children,26 but the timeliness
of the second and third doses of DTP at the recommended age for Hispanic infants,
as well as for African American infants, was delayed compared with non-Hispanic
white or Asian/Pacific islanders (Emmanuel Maurice, MS, CDC/National Immunization
Program, written communication, April 7, 2003).
It is unclear if this difference in timeliness of vaccination nationally
could explain the suspected increased incidence among Hispanic infants in
the selected states. Hispanic ethnicity could be a marker for other high-risk
factors among infants, such as an increased opportunity for exposure to B pertussis. More information on the reasons for the apparent
disparities would be useful in improving control strategies.
A limitation of our study is the use of data from a passive surveillance
system. The pertussis surveillance relies on the diagnosis of pertussis, which
is generally not sensitive, as well as subsequent reporting from health care
professionals; as a result, pertussis was likely underreported. Also the completeness
of reporting to the surveillance system may vary by reporting units and by
year, although there was no apparent factor causing a change in the completeness
as a whole during the study period. Despite these limitations, the trends
in the reported pertussis incidence among infants should reflect trends in
the true incidence as discussed above.
The potential strategies for improved pertussis control among infants
include both nonvaccine strategies, such as trying to reduce infant exposure
or increase prophylaxis through educational efforts, and vaccine strategies,
such as accelerated vaccination of infants through changes in the recommended
schedule of current pertussis vaccines or the development of improved vaccines.
The use of acellular pertussis vaccines among adults and older children could
potentially become another tool for controlling pertussis among young infants,
if vaccines for these age groups become available in the United States. The
safety of DTaP vaccine among adolescents and adults has been shown in clinical
such vaccines already have been licensed in some countries.
Whatever strategy is used, the incidence of pertussis among young infants
is likely to be a primary marker of a successful intervention and might be
less influenced by changes in case ascertainment or reporting than the incidence
of pertussis in older age groups. Further improvements in the surveillance
of pertussis among young infants and additional data on both transmission
sources and risk factors for pertussis in this age group are needed to guide
the development of new pertussis control strategies and to monitor their success.
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