pertussis , also known as whooping cough , is an acute respiratory tract infection caused by bordetella pertussis . although the incidence rate of pertussis has significantly decreased following the wide use of pertussis vaccine , b. pertussis infection is continuously occurring as a small outbreak even in several developed countries with high vaccination coverage ( 1 - 4 ) .
there has been the resurgence of reported pertussis cases primarily in infants younger than 1 yr old , especially less than 3 months of age , in adolescents and young adults worldwide ( 5 , 6 ) .
the possible causes of increased incidence in adolescents and adults include waning of vaccine immunity , adaptation of circulating b. pertussis strains , development of diagnostic methods , and active surveillance due to increased awareness of pertussis ( 7 - 9 ) .
household contact with infected adolescents and adults also becomes the major source of pertussis infection in infants who are not fully immunized , and this problematic circulation may consequently threaten overall public health ( 10 , 11 ) .
the epidemiological characteristics of pertussis can vary depending on the definition of case , diagnostic method of confirmed case , national reporting system , network organization for epidemiological investigation , and the local vaccination schedule .
national immunization program ( nip ) of korea consists of three primary series of diphtheria - tetanus - acellular pertussis vaccine ( dtap ) at 2 , 4 , and 6 months , followed by a first booster at 15 - 18 months and a second booster between 4 and 6 yr of age .
recently , a tetanus toxoid , reduced diphtheria and acellular pertussis ( tdap ) booster vaccine in adolescents aged 11 - 12 yr is added to korean nip in 2012 .
the vaccination rate of primary dtap continues to be approximately 94% ( 12 , 13 ) , and there is a mandatory notification system in korea .
an annual average of about 11.5 cases of pertussis has been reported to the korea center for disease control and prevention ( kcdc ) , however , the reported cases of pertussis have increased since the 2000s .
in addition , the kcdc reported that the incidence of pertussis was markedly increased ( more than about 5.5 times ) in 2009 , compared to the previous ( 14 ) . also , the incidence of pertussis in 2011 was more than two times compared with the incidence in 2009 ( 15 ) .
we may predict the substantial outbreak in the future in our country . given the importance of accurately determining the epidemiological features of infant pertussis and the lack of reliable existing data in korea
, this study was conducted to describe the clinical characteristics of laboratory confirmed cases less than 1 yr of age and to evaluate the relative importance of family members on infants who are vulnerable to b. pertussis transmission .
a prospective , multicenter , observational study was conducted between january 2009 and september 2011 .
we evaluated all infants clinically suspected of pertussis infection because of a cough lasting at least 2 weeks with at least one of the following symptoms : paroxysmal coughing ; inspiratory whooping ; post - tussive vomiting or apnea without other known cause .
we obtained information on current respiratory manifestations , radiologic findings and immunization status for each infant . diagnostic approaches for pertussis
nasopharyngeal aspirates ( npa ) , or swab samples if aspirates were not possible , and blood samples were collected within 2 days at admission .
laboratory tests were performed at the vaccine bio institute ( vbi ) of the catholic university of korea .
it is determined as the criteria for laboratory - confirmed pertussis case when the subjects is applicable to one of the following criteria : 1 ) positive result of b. pertussis on culture of nasopharyngeal aspirates ( npa ) or swab ; this sample was collected and cultured on regan - lowe culture medium at 37 for more than 1 week ; 2 ) positive result of b. pertussis in pcr or real - time pcr ( rt - pcr ) of npa or swab ; pcr was done by the method glare et al . reported ( 16 ) , and rt - pcr was done by modified method of reischl u. colleagues manual ( 17 ) ; 3 ) positive serology which defined as pertussis toxin ( pt ) antibody in a single serum sample that was higher than cut - off value ( 24 eu / ml ) of enzyme - linked immunosorbent assay ( elisa ) kit ( ibl , hamburg , germany ) or a 4-fold increased change in anti - pt antibody between acute - phase and convalescent - phase serum . after the laboratory confirmation on pertussis
, the parent or legal guardian for registration of index case was contacted as soon as possible , and all infants who are eligible for inclusion criteria were registered to the study immediately upon receipt of the consent form . to all family members if cough started at least 7 days before the onset of symptoms in the index case , it was requested to participate in the study as household contacts .
and they were registered for the study immediately upon receipt of the consent form , and interviewed using the standard questionnaire to collect demographic and clinical data .
also , for all long - term household contacts , it was asked to visit for the study to collect respiratory samples ( for culture , pcr , rt - pcr identification of b. pertussis ) and/or serum samples ( for elisa ) .
student 's t - test and fisher 's exact test were applied for comparing categorical variables between the groups .
data were analyzed using spss statistical software , version 15.0 for windows ( chicago , il , usa ) .
this study was approved by the institutional review boards ( irb ) of seoul st .
mary 's hospital ( irb approval number : xc09tim - i0081k ) and of other 2 hospitals .
a prospective , multicenter , observational study was conducted between january 2009 and september 2011 .
we evaluated all infants clinically suspected of pertussis infection because of a cough lasting at least 2 weeks with at least one of the following symptoms : paroxysmal coughing ; inspiratory whooping ; post - tussive vomiting or apnea without other known cause .
we obtained information on current respiratory manifestations , radiologic findings and immunization status for each infant . diagnostic approaches for pertussis
nasopharyngeal aspirates ( npa ) , or swab samples if aspirates were not possible , and blood samples were collected within 2 days at admission .
laboratory tests were performed at the vaccine bio institute ( vbi ) of the catholic university of korea .
it is determined as the criteria for laboratory - confirmed pertussis case when the subjects is applicable to one of the following criteria : 1 ) positive result of b. pertussis on culture of nasopharyngeal aspirates ( npa ) or swab ; this sample was collected and cultured on regan - lowe culture medium at 37 for more than 1 week ; 2 ) positive result of b. pertussis in pcr or real - time pcr ( rt - pcr ) of npa or swab ; pcr was done by the method glare et al . reported ( 16 ) , and rt - pcr was done by modified method of reischl u. colleagues manual ( 17 ) ; 3 ) positive serology which defined as pertussis toxin ( pt ) antibody in a single serum sample that was higher than cut - off value ( 24 eu / ml ) of enzyme - linked immunosorbent assay ( elisa ) kit ( ibl , hamburg , germany ) or a 4-fold increased change in anti - pt antibody between acute - phase and convalescent - phase serum . after the laboratory confirmation on pertussis
, the parent or legal guardian for registration of index case was contacted as soon as possible , and all infants who are eligible for inclusion criteria were registered to the study immediately upon receipt of the consent form . to all family members if cough started at least 7 days before the onset of symptoms in the index case , it was requested to participate in the study as household contacts .
and they were registered for the study immediately upon receipt of the consent form , and interviewed using the standard questionnaire to collect demographic and clinical data .
also , for all long - term household contacts , it was asked to visit for the study to collect respiratory samples ( for culture , pcr , rt - pcr identification of b. pertussis ) and/or serum samples ( for elisa ) .
student 's t - test and fisher 's exact test were applied for comparing categorical variables between the groups .
data were analyzed using spss statistical software , version 15.0 for windows ( chicago , il , usa ) .
this study was approved by the institutional review boards ( irb ) of seoul st .
mary 's hospital ( irb approval number : xc09tim - i0081k ) and of other 2 hospitals .
of a total of 65 clinically suspected cases , 21 infants ( 32.3% ) were enrolled to be the confirmed cases of b. pertussis infection in this study .
the age range was from 22 to 198 days old with a mean age of 2.5 months old .
nine patients ( 42.9% , average age : 47.4 days ) had not received any dtap vaccinations , 9 ( 42.9% , average age : 77.2 days ) received 1 dose , 2 ( 9.5% , average age : 104.5 days ) received 2 doses , and 1 ( 4.8% , age : 198 days ) received 3 doses of dtap ( table 1 ) .
pertussis occurred mostly in spring , summer and early fall , peaking in april , june , and september .
although paroxysmal cough manifested for more than 1 week in all cases , whooping cough was present in only 3 cases ( 14.3% ) .
there were 4 cases ( 19.0% ) of pneumonic infiltration , 3 cases ( 14.3% ) of hyperinflation on radiologic examinations .
four patients with abnormal chest radiographic finding were not immunized with dtap vaccination , and remaining 3 patients were received with 1 dose of dtap vaccination .
two patients had concomitant infections of rhinovirus and respiratory syncytial virus , respectively , and severity was not increased in these patients .
absolute lymphocytosis was noted in 12 patients ( 57.1% ) . of note , absolute lymphocytosis was found more commonly in patients ( 8/9 , 88.9% , average age : 45.8 days ) who did not receive dtap vaccination than patients ( 4/12 , 33.3% , average age : 88.0 days ) who did receive dtap vaccination ( p = 0.024 , table 2 ) .
however , the mean length of hospitalization for patients without dtap vaccination was 15.4  6.6 days , which was significantly longer than the 8.8  3.8 days of patients with dtap vaccination ( p = 0.009 , table 2 ) .
two patients were admitted to the intensive care unit ( icu ) ; both of them did not receive dtap vaccination , and one of these patients treated with a mechanical ventilator
. there were no deaths due to pertussis during the study period ( table 1 ) . on the result of diagnostic methods ,
pcr had the highest sensitivity showing positivity for all 21 cases ( 100% ) , however , confirmed cases with culture were 9 ( 42.9% ) which showed the lowest sensitivity .
although rt - pcr and serological test were not performed in all patients , high sensitivity was observed in all patients done with these tests .
total of 72 family members and long - term guardians of index infant cases were enrolled in this study for confirming household transmission .
the composition of those members were as followings ; 42 parents , 20 siblings , 10 relatives .
seventy members ( 97.2% ) showed respiratory symptoms , and 42 members ( 60% ) with respiratory symptoms had a history of antibiotics use .
of these 72 family members , 38 members ( 38/72 , 52.8% ) were confirmed with laboratory criteria of pertussis as followings ; all 38 members were positive by pcr , 31 members ( who received elisa assay ) were all positive serology , 12 members were positive culture .
finally , a total of 18 potential family sources ( 18/21 , 85.7% ) were identified for confirmed cases , of which 20 members ( 20/38 , 52.6% , 15 family ) were parents and 8 ( 8/38 , 21.1% , 6 family ) were siblings .
other 10 members ( 6 family ; 6 grandparents , 4 aunts ) accounted for 26.3% ( 10/38 ) .
in particular , mothers provided the highest proportion ( 13/38 , 34.2% ) of presumed sources of infection ( fig .
a resurgence of reported pertussis has been documented in a number of countries with high vaccine coverage since the 1990s ( 1 , 4 , 18 ) .
dtap vaccination coverage in korea is very high , with 94% of the children completing the primary series of pertussis immunization . despite the nationwide vaccination program with high coverage
understanding the epidemiological and clinical features of pertussis in community is important because it remains a major cause of morbidity and mortality worldwide . in this study , we have made the demographic data from confirmed pertussis in an attempt to compare the clinical outcomes according to dtap immunization .
generally , pertussis mostly occurred in young infants under 6 months of age who did not complete the primary series of dtap vaccination . depending on the immunization status of our patients ,
there were significant differences in clinical outcome similar to other studies ( 11 , 19 , 20 ) .
the duration of hospital stay was significantly longer ; and the severe cases admitted to icu were found in patients without pertussis vaccination as compared to those with vaccination .
the absolute lymphocytosis in laboratory findings was shown primarily in patients without the vaccination history .
even though all patients had paroxysmal cough for more than 1 week , whooping cough was present in only 14.3% of the patients .
because the presenting symptoms may be nonspecific , it is important for clinicians to suspect pertussis when there is prolonged cough or absolute lymphocytosis , especially in young infants with no or incomplete dtap vaccination .
the highest numbers of pertussis cases was in april , june , and september , which have relatively warm temperatures in korea .
few patients occurred in winter as other respiratory pathogens are commonly considered in the differential diagnosis .
similar studies from other countries have also shown that the reported pertussis case mostly occurred in a summer months with high temperatures ( 21 , 22 ) .
since the number of patients is too small , it is unclear to know the seasonality of pertussis based only upon this result .
in addition , various factors such as environmental factors , school opening , and climate can affect the seasonal characteristics of pertussis epidemiology .
however , because clinical presentations of pertussis often resemble influenza - like symptoms and those of other respiratory diseases such as mycoplasma pneumoniae and adenovirus , this lack of awareness and nonspecific clinical characteristics may be often associated with underdiagnosed condition of pertussis .
culture of nasopharyngeal secretions is essential for diagnosis , however , the result showed the lowest sensitivity ( 42.9% ) in our patients .
moreover , this result requires a long incubation period up to 10 to 14 days , after which the patient can be delayed in critical treatment and infect other persons with contact .
although rt - pcr and serological test were not performed in all patients , these methods also have higher sensitivity than culture .
serologic testing can help the diagnosis of patients with atypical symptoms , for whom clinical samples are collected at later time from the onset of disease .
this study is , to our knowledge , the first to document the presumed importance of household transmission in korea . in 18 families ( 85.7% ) of our patients where a source of infection was established , parents ( 52.6% ) , grandparents and aunts ( 26.3% ) , or siblings ( 21.1% )
in particular , mothers provided the highest proportions of presumed sources of infection . in our study , the majority of household members showed respiratory symptoms such as prolonged cough and recent history of antibiotics treatment for respiratory infections .
however , none of them did know that pertussis might cause severe or chronic cough in adolescents and adults .
. there has been an increase in the reported number of pertussiss cases in many countries , primarily among adolescents and adults , which is special concern because adolescents and young adults are a recognized reservoir of infection for neonates and infants , who are at high risk for pertussis - related morbidity and mortality ( 23 - 26 ) .
several household studies have noted the predominant role of parents in the transmission of pertussis to susceptible infants ( 27 , 28 ) .
for this reason , the usa advisory committee on immunization practices ( acip ) has recommended the cocooning strategy that tdap vaccine be administered to all caregivers of infants less than 1 yr , in an effort to protect young infants against pertussis since 2006 ( 29 ) .
likewise , the cocooning strategy is important in korea , in keeping with high morbidity and mortality in young infants without immunization ( 30 ) . despite the introduction of tdap vaccine in our country
, vaccine use is only beginning , perhaps because of an incomplete understanding of the burden of pertussis among community population and the lack of national policy and education concerned with the necessity of tdap vaccination .
the immunization policy in korea recently introduced the booster dose of tdap vaccine as part of routine immunization in adolescent .
therefore , the change in the epidemiology of pertussis should be noted carefully . in conclusion , pertussis is still present in korea and remains a major morbidity in young infants .
most infants were too young to have received the primary series of dtap vaccination before infection .
household members were identified as a potential source of pertussis infection , and they should be encouraged to receive booster immunization with tdap to minimize pertussis transmission to this vulnerable group on infants . nationwide pertussis reporting is also urgently required to better understand disease transmission patterns , for early recognition and prevention of outbreak and for the evaluation of vaccination policy .
universal recommendation for pertussis booster vaccination at 11 to 12 yr is expected to decrease the transmission of pertussis in households in korea .
 a recent resurgence of pertussis has raised public health concerns even in developed countries with high vaccination coverage . the aim of this study was to describe the clinical characteristics of infant pertussis , and to determine the relative importance of household transmission in korea . 
 the multicenter study was prospectively conducted from january 2009 to september 2011 . 
 we identified the demographic and clinical data from these patients and performed the diagnostic tests for pertussis in their household contacts . 
 twenty - one patients with confirmed pertussis were included in the analysis . 
 all infections occurred in infants younger than 6 months of age ( mean age , 2.5 months ) who had not completed the primary dtap vaccination except for one patient . 
 infants without immunization history had a significant higher lymphocytosis and longer duration of hospital stay compared to those with immunization . 
 all were diagnosed with pcr ( 100% ) , however , culture tests showed the lowest sensitivity ( 42.9% ) . 
 presumed source of infection in household contacts was documented in 85.7% , mainly parents ( 52.6% ) . 
 pertussis had a major morbidity in young infants who were not fully immunized . 
 household members were responsible for pertussis transmission of infants in whom a source could be identified . 
 the control of pertussis through booster vaccination with tdap in family who is taking care of young infants is necessary in korea . 
INTRODUCTION
MATERIALS AND METHODS
Data sources
Statistical analysis
Ethics statement
RESULTS
DISCUSSION