SUSTAINABLE MEDICAL PREPAREDNESS AND RESPONSE SYSTEM FOR RADIATION EMERGENCIES IN THE REPUBLIC OF KOREA.

This paper provides information about the medical preparedness and response system for radiation emergencies in Republic of Korea. The National Radiation Emergency Medical Center (NREMC) oversees medical affairs in the Korean radiological disaster prevention system since its establishment in 2002. It has dedicated itself to set up a nationwide radiation emergency medicine network with 24 designated radiation emergency hospitals. NREMC, as one division under the Korea Institute of Radiological And Medical Sciences (KIRAMS), provides efficient medical care to patients suspected with radiation exposure by collaborating with professional medical staffs in Korea Cancer Center Hospital (KCCH). For prompt response to radiation accidents, NREMC has offered specialized trainings for medical staffs and first responders. It has also operated the 24-h on-call system to consult public concerns of radiation exposure, which can be switched into an emergency mode upon receiving accident reports. In addition, NREMC has conducted dose assessments of radiation exposure with high level of accuracy and implemented R&D programs for radiation injury therapeutics and low-dose radiation risks evaluation in daily life. NREMC supports global initiatives for strengthening medical preparedness and response for radiation emergencies with international organizations.

Factors associated with severe neurologic complications in patients with either hand-foot-mouth disease or herpangina: A nationwide observational study in South Korea, 2009-2014.

BACKGROUND: In 2009, a nationwide sentinel surveillance for hand-foot-mouth disease (HFMD) and herpangina (HA) with neurologic complications was initiated in South Korea. We used this surveillance system to investigate the clinical characteristics of patients with either HFMD or HA with neurologic complications, with the aim of determining risk factors for severe neurologic complications. METHODS: A retrospective review of medical records was conducted on all cases of HFMD and HA with neurologic complications that were reported in the national system between April 1, 2009 and December 31, 2014. A severe case was defined as having HFMD or HA with encephalitis, polio-like syndrome, or cardiopulmonary failure, and less-severe cases were defined as having HFMD or HA with aseptic meningitis. RESULTS: A total of 138 cases (less-severe: 90/138, 65.2%; severe: 48/138, 24.8%) were included from 28 hospitals; 28 ineligible cases were excluded. Of 48 severe cases, 27 (56.2%) had encephalitis; 14 (29.2%) had polio-like syndrome; and seven (14.6%) had cardiopulmonary syndrome. The median patient age was 36 months (IQR: 18-60) and 63 (45.7%) patients were female. Most patients completely recovered, except for seven cases that were fatal or resulted in long-term symptoms (5.1%, 3 patients with neurologic sequelae and 4 deaths). In a multivariable logistic regression analysis, lethargy (OR = 4.67, 95% CI: 1.37-15.96, P = 0.014), female sex (OR = 3.51, 95% CI: 1.17-10.50, P = 0.025), and enterovirus A71 (OR = 3.55, 95% CI: 1.09-11.57, P = 0.035) were significantly associated with severe neurologic complications in HFMD and HA patients. CONCLUSION: In patients with HFMD and HA, lethargy, female, and enterovirus A71 may predict severe neurologic complications.

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013.

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.

Laboratory-acquired dengue virus infection by needlestick injury: a case report, South Korea, 2014.

BACKGROUND: Dengue fever is one of the most dominant vector-borne diseases, putting approximately 3.9 billion people at risk worldwide. While it is generally vector-borne, other routes of transmission such as needlestick injury are possible. Laboratory workers can be exposed to dengue virus transcutaneously by needlestick injury. This is the first case, to our knowledge, of dengue virus infection by needlestick injury in a laboratory environment. This paper evaluates the risk and related health concerns of laboratory workers exposed to dengue virus. CASE PRESENTATION: We evaluated a 30-year-old female laboratory worker exposed to the dengue virus by needlestick injury while conducting virus filtering. During admission, she showed symptoms of fever, nausea, myalgia, and a characteristic maculopapular rash with elevated aspartate aminotransferase (AST) of 235 IU/L and alanine aminotransferase (ALT) of 269 IU/L. She had been diagnosed by a positive nonstructural protein 1 (NS1) antigen (Ag) rapid test one day prior to symptom onset along with positive immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) on the ninth day of symptom onset. Reverse transcription polymerase chain reaction (RT-PCR), also conducted on the ninth day, was negative. After proper symptomatic treatment, she recovered without any sequelae. As a result of thorough epidemiologic investigation, it was determined that she had tried to recap the needle during the virus filtering procedure and a subsequent needlestick injury occurred. CONCLUSIONS: In the context of health promotion of laboratory workers, we suggest that the laboratory biosafety manual be revised and reinforced, and related prevention measures be implemented. Furthermore, health authorities and health care providers in Korea should be fully informed of proper dengue fever management.

Hepatitis A in Korea from 2011 to 2013: Current Epidemiologic Status and Regional Distribution.

The hepatitis A virus (HAV) has been the leading cause of viral hepatitis in Korea since the 2000s. We aimed to describe the current status and regional differences in hepatitis A incidence. We studied the total number of hepatitis A cases reported to the Korea Centers for Disease Control and Prevention through the National Infectious Diseases Surveillance System between 2011 and 2013. Additionally, National Health Insurance Review and Assessment Service data and national population data from Statistics Korea were used. In total, 7,585 hepatitis A cases were reported; 5,521 (10.9 cases per 100,000 populations), 1,197 (2.3 cases per 100,000 populations), and 867 (1.7 cases per 100,000 populations) in 2011, 2012, and 2013, respectively. Fifty-eight patients were infected outside of the country and 7,527 patients represented autochthonous HAV infection cases. Autochthonous HAV infection occurred more frequently among men than women (4,619 cases, 6.1 cases per 100,000 population vs. 2,908 cases, 3.9 cases per 100,000 population). The incidence rate was higher in the 20-29 yr-old group (2,309 cases, 11.6 cases per 100,000 populations) and 30-39 yr-old group (3,306 cases, 13.6 cases per 100,000 populations). The majority of cases were reported from March to June (53.6%, 4,038/7,527). Geographic analyses revealed a consistently high relative risk (RR) of HAV infection in mid-western regions (2011, RR, 1.25, P=0.019; 2012, RR, 2.53, P<0.001; 2013, RR, 1.86, P<0.001). In summary, we report that hepatitis A incidence has been decreasing gradually from 2011 to 2013 and that some regions show the highest prevalence rates of HAV infection in Korea.

Outbreak of Ciprofloxacin-Resistant Shigella sonnei Associated with Travel to Vietnam, Republic of Korea.

We investigated an October 2014 outbreak of illness caused by Shigella sonnei in a daycare center in the Republic of Korea (South Korea). The outbreak strain was resistant to extended-spectrum cephalosporins and fluoroquinolones and was traced to a child who had traveled to Vietnam. Improved hygiene and infection control practices are needed for prevention of shigellosis.

An Outbreak of Foodborne Illness Caused by Enteroaggregative Escherichia coli in a High School in South Korea.

In June 2013, a diarrheal outbreak occurred among high school students in Incheon, South Korea. We investigated the outbreak to identify the pathogen and mode of transmission. A case-control study using a self-administered questionnaire was conducted by local authorities and the Korean Centers for Disease Control and Prevention. Bacterial cultures of stool samples, environmental samples, and samples of preserved food items were prepared. PCR, serotyping, and pulsed-field gel electrophoresis (PFGE) were used to identify and characterize the outbreak-related pathogen. We identified 54 cases of gastroenteritis, with symptoms including diarrhea, abdominal pain, and nausea. None of the food items served in the high school cafeteria were significantly associated with illness, although the odds ratio for kippered trotters mixed with vegetables was relatively high (odds ratio: 2.92, 95% confidence interval: 0.62-13.69). Enteroaggregative Escherichia coli (EAEC) was isolated from this item and the stool samples from 22 symptomatic students and 4 asymptomatic food handlers. The PFGE patterns of EAEC isolated from these sources were indistinguishable. This outbreak was caused by EAEC, and kippered trotters mixed with vegetables, perhaps contaminated by asymptomatic food handlers, were linked to the outbreak. This case-control study highlights the importance of safe food preparation.

A national cross-sectional study for poliovirus seroprevalence in the Republic of Korea in 2012: implication for deficiency in immunity to polio among middle-aged people.

BACKGROUND: A worldwide poliomyelitis eradication program was initiated in 1988; however, strains of wild poliovirus (WPV) are still endemic in some countries. Until WPV transmission is eradicated globally, importation and outbreaks of WPV are alarming possibilities. This study is the first report to document the polio immunity after 2004, when an inactivated polio vaccine (IPV) was introduced in the Republic of Korea. METHODS: A total of 745 serum samples from randomly selected patients ranging from 6 to 84 years of age were used for neutralization tests, performed in the World Health Organization polio national reference laboratory. RESULTS: Among the 745 tested sera, 439 (58.9%) were seropositive and 19 (2.6%) were seronegative to all PV serotypes. In all age groups, PV3 showed the lowest level of seroprevalence, at 509 cases (68.3%), compared to 616 (82.7%) for PV1 and 685 (91.9%) for PV2. In the 6-10-year age group, which included IPV-immunized children, the highest seropositive rate was observed and the difference in seroprevalence between PV3 and other serotypes was the lowest compared to the other age groups immunized with oral PV vaccines (OPV). In addition, the seronegative rates of all three PV types in children aged 6-10 in this study were found to be lower than those in OPV-immunized children reported in a previous study from the Republic of Korea. Meanwhile, middle-aged subjects (41-60 years) had the lowest seroprevalence and geometric mean titer. CONCLUSIONS: This study indicates a deficiency in immunity to PV in middle-aged individuals, and low seroprevalence to PV3 in all age groups. In addition, due to the ongoing risk of importing PV, middle-aged people should consider PV vaccination before visiting a PV-endemic country. Our findings provide data to assist those involved in deciding future national polio vaccination strategies for the maintenance of a polio-free status in Korea.

Pandemic influenza A vaccination and incidence of Guillain-Barré syndrome in Korea.

BACKGROUND: Many studies have investigated the association between Guillain-Barré syndrome (GBS) and vaccinations during the influenza A H1N1 pandemic of 2009 (pH1N1). Based on a nationally representative sample, we estimated the incidence of GBS during the pandemic period in Korea. MATERIALS AND METHODS: All medical records of GBS cases were reviewed in 28 randomly selected hospitals during 2008-2010, and the number of GBS cases at the national level was extrapolated using emergency care utilization data. The GBS rate per 100,000 person-years was estimated in the reference and pandemic periods. RESULTS: The incidence of GBS was 0.63 (95% CI: 0.37-0.89) per 100,000 person-years in the reference period and 0.87 (0.49-1.26) in the pandemic period. During the vaccination season, the pandemic period GBS incidence rate was not significantly higher than the reference period incidence rate (rate ratio: 1.52; 0.99-2.32), but difference was observed among persons aged 20-34 years. Rate of GBS increased after pH1N1 vaccination compared to the reference period (1.46, 1.26-1.68). DISCUSSION: The incidence of GBS increased slightly but not significantly during the pandemic period, although pH1N1 vaccination increased the GBS rate. Therefore, mass influenza vaccination programs should not be precluded on the basis of GBS.

Imported Melioidosis in South Korea: A Case Series with a Literature Review.

OBJECTIVES: Melioidosis is a potentially fatal infectious disease caused by the environmental anaerobic Gram-negative bacillus Burkholderia pseudomallei. Melioidosis is endemic to areas of northern Australia and Southeast Asia. With increasing international travel and migration, imported cases of melioidosis are being reported regularly. Here, we summarize the 11 cases of melioidosis reported in South Korea from 2003 to 2014. METHODS: Tracing epidemiological investigations were performed on every patient reported to the National Surveillance System since 2011. A systematic literature search was performed to identify melioidosis cases that occurred prior to 2011. RESULTS: The overall fatality rate was 36.4%. All the patients had visited Southeast Asia where melioidosis is endemic. The stay in the endemic region ranged from 4 days to 20 years. Of the seven patients who developed initial symptoms after returning to South Korea, the time interval between returning to South Korea and symptom onset ranged from 1 day to 3 years. The remaining four patients developed symptoms during their stay in the endemic region and were diagnosed with melioidosis in South Korea. Seven (63.6%) patients possessed at least one risk factor, all of whom were diabetic. Pneumonia was the most frequent clinical manifestation, but the patients showed a wide spectrum of clinical features, including internal organ abscesses, a mycotic aneurysm of the aorta, and coinfection with tuberculosis. CONCLUSION: An early diagnosis and initiation of the appropriate antibiotics can reduce the mortality of melioidosis. Consequently, increased awareness of the risk factors and clinical features of melioidosis is required.

Prioritization of the introduction of new vaccines to the national immunization program in the Republic of Korea.

BACKGROUND: This study was performed to determine the priority of vaccine introduction for five vaccine-preventable diseases (VPDs) caused by Haemophilus influenzae type b (Hib), pneumococcus (Spn), hepatitis A virus (HepA), rotavirus (RV), and human papillomavirus (HPV) to the future Korean National Immunization Program (NIP) and to suggest framework programs to assist decision makers on implementation of the NIP. METHODS: Following analysis of the disease burden and economics of the five VPDs by the core team and Korean Advisory Committee on Immunization Practices sub-committee members, a Delphi survey was administered to 94 Korean experts using structured questionnaires that provided the reference data. The two evaluation frameworks for NIP prioritization were (1) a disease-related framework and (2) a vaccine-related framework. After analyzing the responses, a meeting of experts was held to build a consensus for determining how to prioritize NIP implementation. RESULTS: The average scores for relative importance were 63.29 for the disease-related framework and 36.71 for the vaccine-related framework. Within the disease-related framework, the mortality and case fatality rate was the highest scored factor (8.97), whereas within the vaccine-related framework, efficacy of the vaccine was considered the most important factor (9.56). On average, Spn, Hib, and HepA had the highest priority scores. CONCLUSION: The Korean experts suggested that the main factors influencing the decision to adopt new vaccines in the Korean NIP should be disease mortality, case fatality, and the efficacy and effectiveness of the vaccine. Among the five selected VPDs, Spn, Hib, and HepA were considered to be of higher priority than RV and HPV.

Vaccine-associated measles in the low-incidence country of Korea over a 10-year period.

As the incidence of measles decreases, cases reported as suspected measles will increasingly involve rash associated with measles vaccination itself. In this study, we assessed vaccine-associated measles cases reported in Korea between 2002 and 2012 using a standardized assessment and following by the World Health Organization case definition criteria. We retrospectively analyzed data regarding (i) wild-type measles and (ii) vaccine-associated measles in patients aged 12-23 months. The presence or absence of fever, rash, cough, coryza, conjunctivitis, and Koplik spots were reviewed. Males were more likely to be reported with vaccine-associated measles than with wild-type measles (68% vs. 47%, P < 0.05). The number of patients with wild-type measles peaked between April and July, whereas that of patients with vaccine-associated measles remained relatively constant throughout the year. However, after excluding the cases reported during the 2007 outbreak in Korea, the trend was similar between the two groups. Cough, coryza, and conjunctivitis were more likely to be present in patients with wild-type measles (32-61% vs. 10-43%, P < 0.05); conversely, the absence of these symptoms was noted in most patients with vaccine-associated measles. We therefore conclude that cough, coryza, and conjunctivitis may be useful as key positive findings to distinguish between wild-type measles and vaccine-associated measles infection among 12-23-month-old patients in a country with a low incidence of measles.

Timely measles surveillance in the Republic of Korea, 2002-2009: impact of sentinel laboratory surveillance.

In order to sustain the elimination of measles, timely reporting is important. The surveillance data in Korea from 2002-2009 was analyzed to determine the effect of sentinel laboratory surveillance, which was introduced in 2006, on the timeliness of measles reporting. The data were stratified by two surveillance periods, (A) before and (B) after 2006, and by cases confirmed clinically and cases confirmed by laboratory measures. During Period A, 113 suspected cases were reported, and 241 during Period B. There was no difference in the proportion of timely reporting among cases confirmed clinically between the two periods, whereas the proportion of cases confirmed by laboratory measures has increased. The mean notification interval in cases confirmed by laboratory measures was shortened from 39 to 16 days. In Korea, sentinel laboratory surveillance has enhanced earlier detection of suspected cases that had not been reported, improving the timeliness of measles surveillance. Adopting this new method may improve the timely collection of cases in other countries.

Factors related to completed status and seropositivity of hepatitis a immunization among children aged 1-3 years and 6-8 years in South Korea.

This study was designed to identify factors associated with hepatitis A immunization status and seropositivity in Korean children. In-person interviews, reviewing their vaccination cards and testing hepatitis A antibody were conducted with 389 children aged 1-3 years and 544 children aged 6-8 years. In all age groups, earlier birth order was the only significant factor in children receiving either single or both doses of the vaccination. And completion of the second dose of vaccination was a prerequisite for increased seropositivity. Additionally, household income had a positive impact on seropositivity only in children aged 6-8 years. Our findings suggest that presence of an economic barrier is the underlying cause of the decreased hepatitis A vaccination services in Korea. Therefore, hepatitis A vaccine should be included in the essential National Immunization Program.

Revision of the national action plan in response to poliovirus importation in Korea.

The polio outbreak in China in 2011 makes it necessary to revise the 2010 polio National Action Plan (NAP) in Korea. The revised plan was provided after evaluation of the 2010 NAP, literature reviews, and expert advice. It was discussed and confirmed by the Polio National Certificate Committee (NCC). The revised NAP (2012 NAP) has structured the action to take by patient phase and the role of each institution. It also provides the specified classification and management actions on the contacts. It includes a new recommendation of onetime additional immunization for the contacts regardless of the immunization history. The 2012 NAP could provide an effective countermeasure if there are imported poliomyelitis patients in Korea.

Epidemiological features and surveillance performance of measles in the Republic of Korea, 2002-2011.

Measles was declared eliminated from the Republic of Korea in 2006; however, recently the number of reported cases has been gradually increasing. To address this issue, we summarized the measles surveillance data collected during 2002-2011, and aimed to evaluate the performance of the current surveillance system in Korea. We analyzed data from the national surveillance system to describe the occurrence of measles. Surveillance indicators proposed by the World Health Organization were used to evaluate the performance of the current measles surveillance system. Between 2002 and 2005, a gradual decrease in confirmed cases of measles was noted, whereas cyclical increases were noted from 2006 to 2011. Since 2006, confirmed cases of measles were more likely to be identified by laboratory methods. In general, the incidence of confirmed case was less than one per million in Korea; however, this figure increased in 2002 (1.3/million), 2007 (4.0), and 2010 (2.3). Most cases were occurred in the age groups 0-23 months and 12-17 years. Laboratory testing was performed in most suspected cases; however, the proportion of discarded cases was low. Overall, more than half of the reported cases experienced an onset of symptoms from April to June. The incidence of measles is relatively low in Korea, and the laboratory surveillance may have helped in identifying under-diagnosed cases within the country. It remains important to continuously assess the surveillance data to improve the surveillance performance.

Economic analysis of measles elimination program in the Republic of Korea, 2001: a cost benefit analysis study.

BACKGROUND: In this study, we modeled the cost benefit analysis for three different measles vaccination strategies based upon three different measles-containing vaccines in Korea, 2001. We employed an economic analysis model using vaccination coverage data and population-based measles surveillance data, along with available estimates of the costs for the different strategies. In addition, we have included analysis on benefit of reduction of complication by mumps and rubella. METHODS: We evaluated four different strategies: strategy 1, keep-up program with a second dose measles-mumps-rubella (MMR) vaccine at 4-6 years without catch-up campaign; strategy 2, additional catch-up campaign with measles (M) vaccine; strategy 3, catch-up campaign with measles-rubella (MR) vaccine; and strategy 4, catch-up campaign with MMR vaccine. The cost of vaccination included cost for vaccines, vaccination practices and other administrative expenses. The direct benefit of estimated using data from National Health Insurance Company, a government-operated system that reimburses all medical costs spent on designated illness in Korea. RESULTS: With the routine one-dose MMR vaccination program, we estimated a baseline of 178,560 measles cases over the 20 years; when the catch-up campaign with M, MR or MMR vaccines was conducted, we estimated the measles cases would decrease to 5936 cases. Among all strategies, the two-dose MMR keep-up program with MR catch-up campaign showed the highest benefit-cost ratio of 1.27 with a net benefit of 51.6 billion KRW. CONCLUSION: Across different vaccination strategies, our finding suggest that MR catch-up campaign in conjunction with two-dose MMR keep-up program was the most appropriate option in terms of economic costs and public health effects associated with measles elimination strategy in Korea.