immunization is among the most important public health measure to control and eliminate infectious diseases .
however , safety of the vaccines and immunization is not perfect ; therefore occurrence of adverse events following immunization ( aefi ) is inevitable .
although most aefis are mild and does not cause serious health outcomes , some may cause substantial degree of disease and complication .
moreover , because immunization is given to the large population , the occurrence of serious aefi , which is seen less in other medications which are used in treating disease , is expected .
most vaccines that we use nowadays are not replaceable to another ; therefore impetuous judgment on causality between certain vaccine and its aefi may lead to negative impact on public health management on infectious diseases .
furthermore , false causality assessment of aefi can cause misunderstanding of the public and lower their confidence on immunization safety . on another hand , disapproving such aefi with ample amount of evidence is not acceptable in the practices of modern medicine .
therefore , scrupulous causality assessment between vaccine , immunization and aefi should be conducted ; and the investigation on the magnitude of safety of such vaccine ; and considering its cost - benefit in the scope of public health should be in place in order to operate the national immunization program .
the aefi can be classified as follows : by frequency ( rare or common aefi ) ; by locality ( local or systemic aefi ) ; by disease severity ( mild or severe aefi ) ; and by pathophysiology .
the stabilizers , immune potentiators , or antibiotics which are included in the vaccines may cause adverse reaction to susceptible vaccinees .
generally , these hyperreactive responses are postulated to occur because of egg - related antigen ( measles , mumps , and rubella [ mmr ] and influenza vaccine ) , mercury ( hepatitis b vaccine , diphtheria , tetanus , pertussis vaccine [ dtap ] , japanese encephalitis vaccine , and influenza vaccine ) , vaccine stabilizer ( mmr ) , or antibiotics included in the live - attenuated virus vaccine ( mmr ) ; however , these mechanisms are not clearly explained , often [ 1 - 4 ] .
most vaccines result in local reactions following vaccination such as pain , swelling and redness in some population ; this frequency slightly increases following dtap or tetanus - containing vaccines .
after 2 - 3 weeks of receiving bacillus calmette - gurin ( bcg ) vaccine , localized inflammation and ulceration forms , then heal within few months .
systemic reactions such as fever and malaise may occur in some population ; the frequency is higher in dtap , which may also result in irritability and decreased oral intake in infants .
following mmr vaccination , systemic reactions such as measles - like illness due to vaccine - strain virus may occur on more than 5 - 10% of vaccinees .
this vaccine - related measles is generally mild in immune - competent persons ; however , may result in severe disease in immune - compromised hosts , therefore mmr and other live - attenuated vaccines are contraindicated in such population .
the attenuated mumps virus included in mmr may result arthralgia and lymphadenitis on less than 1% of those who are vaccinated .
the advances in vaccines and immunization practices have led to decline in the incidence of vaccine - preventable diseases worldwide .
however , the increase in reported cases of aefi has been noted recently , probably following increased utilization of vaccines ; increased vaccinees who are susceptible to such complications ; and increased awareness and notification . in the united states with long - standing history of aefi surveillance system
, the number of reported aefi cases has exceeded the number of reported vaccine - preventable diseases ; therefore the increase in public awareness on aefi may occur , consequently . in order to maintain the public confidence and to ensure political support on national immunization program , the public health sector must ensure the safety of vaccines and immunization practices . before the introduction of aefi surveillance system in the 1980s , neurologic adverse event such as seizure was reported following whole - cell pertussis vaccination in multiple countries . in response to the media coverage ,
immunization coverage decreased and then consequent resurgence of pertussis was observed in many countries such as japan , sweden , and uk . in the us , lawsuits against vaccine manufacturers has resulted in renunciation of vaccine production , and therefore led to inadequate procurement of essential vaccines . in order to minimize the unnecessary conflicts and arguments , and to achieve adequate level of immunization coverage in the population , the need for aefi management system was raised .
the national aefi management system was meant to distinguish between the true vaccine reactions and the coincidental events following immunization in timely manner , therefore to ensure safety of the vaccinees and to improve the confidence in national immunization program .
most of other medications are intended to use for treatment purposes , however , vaccines are given to healthy people , especially children , to prevent the future or potential occurrence of infectious diseases .
the unhealthy patients who are receiving the medications such as chemotherapeutic agents or antibiotics may tolerate the occurrence of adverse event .
however , the vaccinees , who are mostly healthy without having any diseases , may not tolerate on reactions after they receive the vaccines .
furthermore , vaccines are forcibly given in some instances , therefore high level of safety should be guaranteed .
in addition , most vaccines utilized by national immunization program are given to general populations in a large amount ; therefore safety should be heavily reviewed .
in the republic of korea , aefi management system began since 1994 , after the two deaths following japanese encephalitis vaccine immunization was reported . in 2000 , the system that included report of aefi through electronic document interchange was introduced , and all systems were computerized before 2001 . in 2001 , the communicable disease control act has mandated healthcare professionals to report all noticed aefi to the public health centers , and in 2005 , the system has introduced an internet - based reporting system , which made the reporting more handy .
currently , vaccine safety management system in korea is composed of four parts : rapid response system , aefi surveillance system , aefi investigation system , and vaccine injury compensation program ( vicp ) ( fig .
the division of vaccine preventable disease control and national immunization program at korea centers for disease control and prevention ( kcdc ) operates routine and ad - hoc surveillance measures on aefi in korea ; performs epidemiological investigation on certain aefis such as serious adverse reactions or clustered aefis ; and operates vicp .
since 1994 , when 11 aefis were reported , the reported numbers for aefi has increased to 741 in 2010 ( table 1 ) .
there were two surges in 2001 ( n=141 ) and 2009 ( n=2,380 ) , when there were nationwide immunization campaign for measles and h1n1 influenza took place , respectively . among 5,339
reported aefis between 1994 and 2010 , 97 deaths and 10 disabled cases were notified . when classified according to vaccine types ( table 2 ) , bcg was the vaccine with most aefi cases reported in 2008 with 38.59 cases per 1,000,000 vaccinees . however , this rate decreased down to 10.38 in 2009 and 8.1 in 2010 , when the government changed the vaccine - strain from pasteur - strain to danish - strain , because of the reactogenicity . in 2010 ,
mmr and tetanus diphtheria vaccine ( td ) were recognized as the second and third common vaccine to be reported as cause of aefi . when an aefi has occurred , the vaccinees or their guardians may report the suspected aefi through telephone to the local public health center ; or by accessing website at http://nip.cdc.go.kr ; and the healthcare professionals may report through telephone to the local public health center ; or by accessing website at http://is.cdc.go.kr .
when the local public health center receives the notification of suspected aefi , then they report to the kcdc through website or by telephone .
kcdc then compile the nationally - collected aefi data , analyze the unexpected pattern of aefi , and conducts overall management of vaccine safety in korea .
however , the quality of data collected by the routine surveillance system is limited because data collected do not include detailed epidemiological or clinical information regarding aefi . in 2011 , kcdc initiated to retrospectively investigate the vaccination - related serious aefi of seasonal trivalent influenza in korea from 2003 to 2010 . during the period ,
nine guillain - barr syndrome ( gbs ) , eighteen other neurologic events , eight local events , and seven miscellaneous events were included ( table 3 ) .
when classified according to causality assessment made by korea advisory committee on vaccine injury compensation for gbs , three were considered to be potentially associated to vaccination , whereas five were assessed as unlikely related .
all of the three cellulitis cases had their injury sites that are not within 20 cm apart from the injection site , and two of the three cases had their symptoms onset after more than 2 weeks after vaccination .
approximately two third of localized events were assessed to have potential association with vaccination ( 62.5% , 5/8 ) , whereas more than half of neurologic events ( 14/18 ) were considered to have no association with vaccination ( unlikely ) . in addition
, ascertainment of each investigated cases is also important . in 2009 - 2010 season , mass vaccination for h1n1 pandemic influenza raised concern in a particular aefi : the gbs . in 2011 , kcdc investigated the data of reported cases of gbs following receipt of pandemic influenza vaccine in korea .
all cases were reviewed under case definition developed by brighton collaboration working group , in order to ascertain a clear and precise case definition for aefi data analysis .
of 29 reported cases during 2009 - 2010 season , 22 were confirmed to meet brighton criteria level 1 , 2 , or 3 for gbs . of those , 2 ( 9.1% ) met level 1 , 9 ( 40.9% ) met level 2 , and 11 ( 50.0% ) met level 3 .
the brighton case definition was used to improve the quality of aefi data , and was applicable in retrospective review of medical records in cases with gbs after influenza a ( h1n1 ) vaccination .
the compensation of vaccine injury was meant to decrease the negative public awareness on vaccine safety may decrease the population vaccination coverage , which then consequently decreases the population immunity .
the korea national vaccine injury compensation program ( kvicp ) , which was established in 1994 , compensates individuals who experience certain aefi for vaccines that are recommended by the government .
the program was first became a legal entity under the prevention of contagious disease act in 1994 , and consists of committee with a chairperson and specialists in pediatric , neurology , cardiology , epidemiology , forensic medicine , and pharmaceutical engineering . in order to be eligible for compensation , a claim
must be filed within 5 years after occurrence of aefi , and the patient must have spent more than krw300,000 ( approximately us$300 ) on health care expenses .
table 4 depicts the annual number of potential adverse reactions that filed claim on vicp , and the number of cases compensated .
the proportion of compensation ranged from 25% ( 1996 ) to 100% ( 2004 ) .
although the number of reported cases of aefi has gradually increased during the last 10 years , the number of claims remained relatively constant during the same time - period ( table 4 ) .
when a patient places a claim for compensation , the aefi investigation team jointly operated by kcdc and local health authority starts an investigation .
determination of causal association between the injury and influenza vaccination is assessed by korea advisory committee on vaccine injury compensation , who use the simplified world health organization ( who ) categories of likelihood of causality : 1 ) definite , 2 ) probable , 3 ) possible , and 4 ) unlikely .
compensations are made for cases that are classified as definite , probable , or possible .
the data collection and analysis of information on aefi from the korean aefi surveillance system are continuously done .
however , low reporting rate and limited data have prompted the introduction of supplementary surveillance measures to complete the data required to ensure vaccine safety in korea .
further efforts will be needed to provide adequate data to ensure the safety of vaccines and immunizations currently practiced in the country .
many surveillance measures that are routinely performed or ad - hoc surveillance had showed the safety of vaccines currently utilized .
continual monitoring for aefi is necessary to ensure the long - term safety of the vaccines , and to further contribute to vaccine policy for control of vaccine - preventable diseases and its complications in korea .
 although vaccination is regarded as one of the most effective public health measure to prevent and control infectious diseases , no vaccine is perfectly safe . 
 therefore , safety management is an essential component in running national immunization program . here 
 , we review the current issues and suggest future perspectives of korean vaccine safety management system . 
Introduction
Adverse Events Following Immunization
Vaccine Safety Management
Vaccine Safety Management in Korea
Case-Based AEFI Investigation
Vaccine Injury Compensation Program
Conclusion