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INTRODUCTION
Measles is an acute febrile exanthematous infection caused by the measles virus, which is an RNA virus belonging to the Morbillivirus genus of the Paramyxoviridae family. Human beings are the only hosts of the measles virus. Measles is usually transmitted via respiratory droplets and direct contact, and airborne transmission is possible.1 The typical clinical presentation includes rash with erythematous maculopapular lesions, accompanied by fever, cough, rhinorrhea, and conjunctivitis. The incubation period ranges from 7 to 21 days after exposure to rash onset, and transmission can occur from 4 days before and 4 days after rash onset.23
With the widespread distribution of attenuated live measles vaccine since the 1980s, both the incidence and mortality rates of measles have significantly decreased.4 The World Health Organization (WHO) recommends two doses of measles-containing vaccine and vaccination coverage of at least 95% to eliminate measles globally.5 However, during the coronavirus disease 2019 pandemic, the global first-dose measles vaccination coverage declined from 86% in 2019 to 81% in 2021. This decline in vaccine coverage was more significant in low-income countries, where the vaccination rate decreased from 71% in 2019 to 66% in 2022.6 This decrease in measles vaccination coverage might have contributed to an 18% increase in the number of measles cases worldwide in 2022 compared to 2021, and the number of deaths increased by 43%.7
In 2014, the Republic of Korea was certified by the WHO as a measles-eliminated country.8 As of 2022, the second-dose measles vaccination coverage for six-year-olds in Korea was 95.6%, and the first-dose vaccination coverage for two-year-olds was 97.3%. These statistics were higher than that reported in the United States and United Kingdom.9 From 2015 to 2023 except the year 2019, the annual number of measles cases in Korea remained below 20.10 In 2019, 190 (97.9%) out of the 194 confirmed measles cases were identified as imported cases or cases linked to imported cases, which could have been influenced by the global measles outbreak in 2018.11
On April 6, 2024, an international student from Uzbekistan enrolled at University A in Korea was identified as a confirmed measles cases. Subsequently, on April 15, 2024, four additional measles cases were confirmed amongst the Uzbek student’s residents at the same dormitory (Dormitory B) as the index case. An epidemiological investigation was conducted to contain the spread of the measles outbreak and to identify the transmission route.
METHODS
Case definition and case finding
An epidemiological investigation team was established on April 15, 2024, after the measles outbreak was identified. This epidemiological investigation involved a joint response from the Division of Infectious Disease Control of Gyeongsangbuk-Do Provincial Government, the Gyeongbuk Regional Center for Disease Control and Prevention, the Gyeongbuk Center for Infectious Disease Control and Prevention, and the Gyeongsan City Health Center. A measles case was defined as an individual who tested positive for the measles virus through real-time reverse transcription polymerase chain reaction (RT-PCR). Case finding was conducted among students and faculty members of University A in Gyeongsan City, Gyeongsangbuk-Do Province. Dormitory B residents on the second and third floors were instructed to reside within Dormitory B to prevent measles transmission to University A (cohort isolation), and their body temperature was monitored two-times on a daily basis as active surveillance. Passive surveillance was implemented for other students and faculty members from University A. A temporary screening clinic to collect respiratory specimens from symptomatic individuals was established beside Dormitory B.
Data collection and study design
Cases were investigated using an investigation form from the Measles Response Guidelines by the Korea Disease Control and Prevention Agency (KDCA).12 The form documented personal information, clinical symptoms, locations visited during the infectious period, and contact information. All cases were foreign nationals, and information was gathered through interviews with the assistance of an international student from University A. Other symptoms such as rash, were checked thoroughly until the students were discharged. No additional information on the measles vaccination history was available. As the index case might have been exposed to measles during the entry to Korea on March 20, 2024, relevant information on passengers on the same flight as the index case was collected. The presence of measles cases among them was confirmed through the KDCA’s Integrated Disease Control Information System.
A retrospective cohort study was conducted in the residents of Dormitory B. Information including sex, age, nationality, grades, departments, and dormitory room assignments was obtained through administrators from University A. Due to the language barrier, a survey questionnaire could not be administered to those students.
Contact tracing and management
Contacts were defined as individuals who had face-to-face interactions or shared indoor spaces with the cases during their infectious period (4 days before and 4 days after rash onset). Contacts who were not previously vaccinated for measles were administered measles vaccines, and passive surveillance was conducted for 21 days following their last exposure to the infection. Contacts who were not vaccinated were recommended to be in home quarantine.1314 Before the outbreak recognition, measles vaccines were administered to contacts of the index case. Following identification of the outbreak in Dormitory B, mass vaccination for all residents (due to a lack of information on measles vaccination records) was implemented after April 17. Further, cohort isolation was initiated for the second-floor residents on April 16, and was expanded to the third-floor residents on April 17. During cohort isolation, any individuals who tested positive were transferred to other places out of Dormitory B to prevent transmission.
Laboratory testing
Real-time RT-PCR and measles antibody testing were conducted by the Gyeongsangbuk-Do Government Public Institute of Health and Environment. RT-PCR testing was performed using PowerChek™ MeV/MeVA Multi Real-time PCR Kit (KOGENE BIOTECH, Seoul, Korea), with cycle threshold (Ct) values of 37.3 or lower considered positive for measles. Suspected measles cases with fever were tested using RT-PCR with nasopharyngeal and oropharyngeal specimens regardless of rash, although national diagnostic guidelines in Korea recommend that specimens should be collected within five days from rash onset.15 The RT-PCR test was conducted solely for case diagnosis.
Dormitory B residents were recommended to perform measles antibody testing before implementing cohort isolation. From the collected blood samples, serum was separated and analyzed for anti-measles immunoglobulin G (IgG) using enzyme-linked immunosorbent assay (EUROIMMUN AG, Lübeck, Germany). The PCR-positive specimens were forwarded to the Division of Viral Diseases of the KDCA for measles virus isolation and genotyping.
Statistical analysis
To evaluate the risk factors for measles transmission within the dormitory, relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Fisher’s exact test was used for analysis. The significance level was set at 0.05. Statistical analyses were conducted using R software version 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria).
Ethics statement
This study was approved by the Institutional Review Board (IRB) of the Korea Disease Control and Prevention Agency (KDCA) (IRB No. KDCA-2024-10-05-P-01). As the research relies on secondary data provided by the Gyeongsangbuk-Do Provincial Government for public health response purposes, informed consent was not required.
RESULTS
Investigation of the index case
The index case was a 19-year-old male who arrived in Korea on March 20, 2024, via flight HY511 from Uzbekistan and had no symptoms of measles. No additional measles cases were identified among non-University A flight passengers. The group comprised 44 students who arrived at University A in Gyeongsan City via two buses provided by the university. The index case’s mother in Uzbekistan was diagnosed with measles. Her symptoms appeared after the index case entered Korea. The index case had attended a family gathering prior to entering Korea.
Epidemic curve and transmission in the dormitory
A total of 22 measles cases were reported in University A. All the cases were residents at Dormitory B. The attack rate at the dormitory was 5.3% (22/418). A total of 493 individuals (141 domestic and 352 international students) and 579 individuals (165 domestic residents and 414 foreign residents) were university (except Dormitory B) and community contacts, respectively. The community contacts comprised 122 individuals who were residents of Gyeongsangbuk-Do, and 457 were residents of Daegu Metropolitan City. No additional measles cases were reported.
The index case, a resident on the second-floor of Dormitory B, developed a fever (38.0°C) on April 1 followed by a rash on April 4. The symptoms for other students began on April 9. All the cases, except one, occurred among the second and third floor residents (Fig. 1). Cohort isolation was implemented for second floor residents on April 16, and third floor residents on April 17, which lasted until May 3. Measles vaccines were administered to 397 out of 412 residents (96.4%, six were excluded due to diagnosis of measles) between April 17 and April 25. The last two measles infections were reported on April 19, with no further cases reported afterward.
Fig. 1
Epidemic curve of measles outbreak in University A. (A) Based on symptom onset date; (B) Based on rash onset date. Case numbers were assigned based on the date of diagnosis.
Dormitory B consisted of four floors, with international student residents on each level. Sixteen cases resided on the second-floor along with the index case. Five cases were male and resided on the third-floor of the dormitory. On the third floor, male and female residents were separated by a door, which divided the area into two sections. The index case, who developed a rash on April 6, visited room 326 on the third floor approximately four times between March 29 and April 5 (Fig. 2). Additionally, the index case frequently accessed shared facilities, including the dormitory lounge and dining hall, which may have contributed to further transmission. One female case on the fourth-floor stated that she did not have direct contact with the index case or other cases. In the dormitory, many shared facilities were available, such as the first-floor lounge, laundry room, study room, and table tennis room.
Demographic and clinical characteristics of cases
The average age of cases was 19.5 years (range: 18.0–23.0 years), and 63.6% (14/22) of cases were under 19 years old. The majority were from Uzbekistan (77.3%, 17/22), followed by Kyrgyzstan (18.2%, 4/22) and Vietnam (4.5%, 1/22). Approximately 54.5% (12/22) of cases were affiliated with the Korean Language Institute, and 22.7% (5/22) were affiliated with the Global Business Department, to which the index case was affiliated. Eight out of 12 Korean Language Institute students were from Uzbekistan. Most (95.5%, 21/22) of the affected students were Muslim. Although the index case was Muslim, he rarely visited the prayer room on the second-floor (Table 1).
Table 1
Demographic characteristics of the measles cases at University A
All cases experienced rash, and 15 (68.2%) exhibited rash at the time of diagnosis. Generalized rash (36.4%, 8/22) was less frequent than localized rash (63.6%, 14/22), which predominantly appeared on the trunk (22.7%, 5/22), face (18.2%, 4/22), and neck (18.2%, 4/22) (Supplementary Fig. 1). Subjective febrile sense was reported in 19 cases (86.4%). Seven cases (31.8%) reported a temperature ≥ 38.0°C. Other symptoms included sore throat (40.9%, 9/22), conjunctivitis (22.7%, 5/22), and cough (18.2%, 4/22).
One case (4.5%), the index case, was hospitalized. Measles IgG antibody testing showed 2 (14.3%) positive cases among 14 cases tested for measles. The mean duration from symptom onset to rash onset and from symptom onset to sampling date were 2.5 days (range: 0.0–7.0 days) and 2.1 days (range: 0.0–7.0 days), respectively. The mean duration from rash onset to the sampling date was −0.4 days (range: −4.0 to 4.0 days) (Table 2). The proportion of specimen collection preceding rash onset was reported in 36.4% (8/22) cases.
Table 2
Clinical characteristics of the measles cases at University A
Risk factors for measles transmission in the dormitory
Among dormitory residents, the majority were Vietnamese students (58.1%, 243/418), followed by Uzbek students (27.8%, 116/418) and Kyrgyzstani students (10.8%, 45/418). Uzbek students had a significantly higher RR of 8.85 (95% CI, 3.34–23.44) than other international students. The RRs of males (11.63; 95% CI, 1.58–85.62) and teenagers (3.55; 95% CI, 1.53–8.26) were significantly higher than females and students aged ≥ 20 years, respectively. Students in the Global Business Department and residents of the second and third floors had significantly elevated RRs at 2.78 (95% CI, 1.08–7.13) and 25.4 (95% CI, 3.45–187.42), respectively. The RR of students with positive IgG antibodies (0.36; 95% CI, 0.08–1.54) was low but not statistically significant (Table 3).
Table 3
Analysis of risk factors for measles transmission at Dormitory B
Laboratory findings
The mean Ct value of the 22 cases was 28.75 (range: 18.96–37.03), and the index case showed the lowest Ct value of 18.96. The mean Ct values per day dropped below 30.00 after three days from symptom onset and after rash onset (Fig. 3). The mean interval between symptom onset and rash onset was 2.5 days. Genotyping analysis of the measles virus was conducted for 19 out of 22 cases, while three cases were excluded due to insufficient sample quantity. All 19 cases, including a Vietnamese female student residing on the 4th floor, were confirmed to be infected with the same measles virus (genotype B3, Fig. 4).
Fig. 3
Mean cycle threshold values during the measles outbreak. (A) Based on symptom onset date; (B) Based on rash onset date.
Fig. 4
Genotyping of measles virus isolated during the measles outbreak at University.
MV = Measles virus, MVi = measles virus isolate.
Of 418 residents in Dormitory B, 139 (33.3%) participated in measles antibody testing. Among the participants, 31.7% (44/139) tested positive, 10.1% (14/139) were indeterminate, and 58.3% (81/139) tested negative. The seropositivity rate of Uzbek residents (26.5%, 22/83) was lower than that of the Vietnamese (36.8%, 7/19) and Kyrgyzstani residents (41.7%, 15/36, Table 4).
Table 4
Results of measles immunoglobulin G antibody testing among residents at Dormitory B
DISCUSSION
The measles outbreak in University A was initiated by an index case who arrived from Uzbekistan. Subsequently, the outbreak primarily affected Dormitory B, and 22 out of 418 dormitory residents (5.3%) were infected. All cases, apart from the index case, were assumed to be secondary. The measles attack rate was significantly higher among males, teenagers, students from Uzbekistan, Global Business students, and residents of the second and third floors of the dormitory. In response to the measles outbreak, cohort isolation measures were implemented on the second and third floors, and mass vaccination was conducted for all dormitory residents. As a result of this, no tertiary cases were reported.
The index case arrived in Korea on March 20 and exhibited symptoms on April 1, 2024. Considering the incubation period of measles, it is plausible that the infection occurred either in Uzbekistan or in Korea.1314 Measles is endemic in Uzbekistan since 2023.16 The index case’s mother contracted measles around the same time. Thus, the index case might have been infected in Uzbekistan before arrival in Korea. Moreover, the measles strain detected in the cases was identified as genotype B3, one of the strains currently circulating in the European Region.17
Dormitory B residents were international students, most of whom spent a significant time in the dormitory. The dormitory is highly populated and closed, posing a heightened risk for measles transmission compared to other places.1819 The statistical significance of male students, teenagers, students from Uzbekistan, and Global Business majors among the dormitory residents suggests that the outbreak was originated from the index case. Additionally, while the index case primarily resided on the second floor, he visited the third floor more than four times, thus leading to the emergence of infections in room 326. One female case who was a resident on the fourth floor might have come in contact with the other cases using the shared dormitory facilities.
In University A, measles cases occurred among international students (Uzbekistan, Kyrgyzstan, and Vietnam) and not Korean students. All three countries conducted two rounds of measles vaccination.20 However, the measles IgG seropositivity rate among Uzbek students was the lowest (26.5%) with highest attack rate. The measles IgG seropositivity rate in 2014 for individuals aged 13 to 24 years in Korea was reported to be between 48.5% and 69.6%, respectively,21 which is higher than that of the other three countries. This study aligns with the previous findings that immunity status varies in environments where multinational students live in close proximity.2223
All measles cases presented a rash, and eight (36.4%) were confirmed before the rash developed. Cases were identified up to four days before rash onset through dormitory cohort isolation measures and active surveillance. As soon as the cases were confirmed, they were relocated outside Dormitory B. The mean Ct values of the measles virus, which indicate higher transmissibility at lower values,242526 demonstrated lower values after the rash appeared. Considering the time required for diagnosis, it might be possible to conduct proactive testing from the early stages of symptom onset in densely populated environments, such as dormitories, to reduce the potential for transmission.
In this outbreak, a faint measles rash appeared, which was more commonly present in localized forms. Although measles testing is typically performed based on the presence of a rash,131427 individuals who are vaccinated against measles might present with a mild rash or, in some cases, no rash at all.22829 This variability can make identifying measles infections challenging. However, during this outbreak, measles was primarily suspected based on symptoms such as febrile sense, even without a rash. Although secondary cases in this outbreak showed symptoms since April 9, the outbreak was not recognized until April 15. This delay may have resulted from the mild symptoms of initial cases and the lack of a proactive surveillance system in the dormitory, emphasizing the need for routine health monitoring in such settings.
Verification of prior vaccination is necessary to determine the administration of a vaccine for measles. However, such information was not available for international students in this outbreak. Susceptibility could be estimated based on the antibody results for those who underwent measles IgG antibody testing. Immunity acquired through vaccination may be relatively weaker and shorter than immunity acquired through natural infection.30 Considering that 2 out of 14 cases contracted measles in this outbreak, the suggested approach based on the antibody testing results is partly limited.
This study had several limitations. First, the sample size was relatively small, which may limit the generalizability of our findings. Second, the participation rate for the measles IgG test was 33.3%, potentially introducing selection bias. Third, the absence of vaccination records for international students hindered a comprehensive analysis of the relationship between vaccination status and susceptibility. Finally, the reliance on RT-PCR testing alone for case confirmation may have excluded mild or asymptomatic cases.
Vaccination and home quarantine for individuals without immunity have recommended in Korea to control measles infection.12 However, based on these outbreak results, the 2024 measles response guidelines in Korea were revised to include cohort isolation of susceptible individuals in spatially dense environments such as dormitories.13 Measles cases in Korea are primarily associated with imported infections,10 and the number of international visitors is steadily increasing.31 Considering the ongoing measles outbreaks abroad,17 measures to reduce the risk of imported cases are essential. To mitigate future outbreaks, we recommend developing a centralized vaccination registry for international students and conducting mandatory pre-entry health screenings. Additionally, universities should implement routine health monitoring and proactive surveillance systems in dormitory settings to enable early detection and response to infectious disease outbreaks.
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