Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox.

BACKGROUND: Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects. METHODS: To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio. RESULTS: A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm2 in the MVA group and 76.0 mm2 in the ACAM2000-only group, resulting in an area attenuation ratio of 97.9% (95% CI, 96.6 to 98.3). There were fewer adverse events or adverse events of grade 3 or higher after both MVA vaccination periods in the MVA group than in the ACAM2000-only group (17 vs. 64 participants with adverse events of grade 3 or higher, P<0.001). CONCLUSIONS: No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).

Spatio-temporal patterns of the minimum rest time for outdoor workers exposed to summer heat stress in South Korea.

In this study, the spatio-temporal characteristics of the minimum rest time for the safety of South Korean outdoor workers during hot summer months (June to August) are examined based on the hourly wet-bulb globe temperature (WBGT) across 27 weather stations in South Korea. The WBGT thresholds in the work-rest recommendation of the Korea Occupational Safety and Health Agency (KOSHA 2017) for the quantification of the minimum rest time are evaluated through a comparison of the given thresholds with the occurrences of occupational heat-related illness patients due to outdoor work during hot summer months in South Korea. The long-term (2009-2018) average of the hourly WBGT values during summer months shows that outdoor workers with a moderate workload are exposed to heat stress during approximately 30% of the entire daytime working hours (06:00-18:00). According to the WBGT thresholds modified from the KOSHA (2017) guidelines, the daily minimum rest time for a moderate workload noticeably increases up to 18% (11 min/h) in mid-summer (late July and early August). During mid-summer, the minimum rest time for a continuous moderate outdoor workload even increases up to 31% (18 min/h) between 12:00 and 13:00 and is regionally higher in the southwestern than in the southeastern regions of the Korean Peninsula. These results suggest that in summertime high-heat environments, a mandatory rest time must be provided according to appropriate heat management programs for the safety of workers.

Plasmodium vivax malaria among U.S. forces Korea in the Republic of Korea, 1993-2007.

Malaria is a significant health threat to U.S. combat forces that are deployed to malaria-endemic regions. From 1979, when the Republic of Korea (ROK) was declared malaria free, malaria did not present a health threat to U.S. forces deployed to Korea until the early 1990s. In 1993, a temperate strain of vivax malaria expressing both latent (long prepatent incubation periods of usually 6-18 months after infection) and nonlatent (short prepatent incubation periods < 30 days after infection) disease reemerged near the demilitarized zone (DMZ) and once again presented a primary health threat to U.S. military populations in the ROK. Following its reemergence, malaria rates increased dramatically through 1998 and accounted for > 44% of all malaria cases among U.S. Army soldiers from 1997 to 2002. More than 60% of all Korean-acquired malaria among U.S. soldiers was identified as latent malaria. Nearly 80% of all latent malaria attributed to exposure in Korea was diagnosed in the U.S. or other countries where soldiers were deployed. These data illustrate the requirement for a comprehensive malaria education program, especially for those soldiers residing or training in malaria high-risk areas, to inform soldiers and providers of the risk of developing malaria after leaving Korea.

Malaria in the Republic of Korea, 1993-2007. Variables related to re-emergence and persistence of Plasmodium vivax among Korean populations and U.S. forces in Korea.

Malaria was eradicated and the Republic of Korea (ROK) declared "malaria free" in 1979. However, in 1993, a temperate strain of vivax malaria, expressing both latent and nonlatent disease populations, re-emerged near the demilitarized zone (DMZ), rapidly spread to civilian sectors near the DMZ, and increased exponentially in ROK military, veteran, and civilian populations through 1998. Malaria among all ROK populations decreased 5-fold from a high of 4142 cases in 2000 to a low of 826 cases in 2004, before increasing again to 2180 cases by 2007. Each malaria case in the ROK is reported in the metropolitan area/province where the diagnosis is made, which may be at some distance from the area where infection occurred. Therefore, it is difficult to ascertain transmission sites since approximately 60% of vivax malaria in Korea is latent with symptoms occurring >1 month to 24 months after infection. A review of case diagnosis for civilian, veteran, and military populations shows that nearly all malaria south of Gyeonggi and Gangwon Provinces is the result of veterans exposed in malaria high-risk areas along the DMZ and returning to their hometowns where they later develop malaria. Thus, malaria currently remains localized near the DMZ with limited transmission in provinces south of Seoul and has not spread throughout Korea as previously hypothesized. This report describes the reemergence of vivax malaria cases in civilian and military ROK populations and U.S. military personnel and assesses variables related to its transmission and geographic distribution.

Outbreak of sandfly fever in central Iraq, September 2007.

An outbreak of nonspecific febrile illnesses occurred among U.S. Army troops in September 2007 at a remote, newly established, rural-situated patrol base, south of Baghdad, Iraq. Soldiers displayed an acute flu-like syndrome with symptoms of fever, headache, malaise, and myalgia. A total of 14 cases was identified and treated presumptively as query fever. Subsequent convalescent serum specimens confirmed 13 (92.9%) positive for sandfly Sicilian virus and 3 (21.4%) positive for Coxiella burnetii, with two positive for both. One sandfly Sicilian virus case tested positive for Brucella spp. This outbreak emphasizes the potential for multiple simultaneous disease exposures to endemic diseases in nonindigenous military personnel at remote military locations in Iraq. Recommendations include increased theater disease surveillance, medical training, and vector control.

The war on severe acute respiratory syndrome: United States Forces Korea's campaign plan.

A mysterious new respiratory illness known as severe acute respiratory syndrome (SARS) has become the most perplexing infectious disease to emerge in the 21st century. From March to May 2003, it competed daily with the war in Iraq as the most sensational media event of the moment. U.S. personnel serving in the Republic of Korea represented the largest U.S. military population at risk for SARS. With tensions growing between Pyongyang and Washington, the United States/Republic of Korea alliance could not afford to be rendered combat ineffective by SARS. To remain mission ready, the U.S. Forces Korea (USFK) commander declared a "War on SARS" and directed his medical staff to develop a plan to prevent a SARS outbreak among USFK personnel. This article outlines the USFK campaign plan for the SARS epidemic and documents lessons learned for future outbreaks of highly infectious diseases.

The Combined Effect of Sleep Duration and Quality on Mental Health Among Republic of Korea Armed Forces.

Sleep problems in the Republic of Korea Armed Forces have increased. This study analyzed the mental health impact of sleep duration and quality on personnel of the Republic of Korea Armed Forces. Data from the 2014 Military Health Survey were used. Degree of sleep duration and quality were measured by this self-reported questionnaire. Analysis of variance was carried out to compare Kessler Psychological Distress Scale 10 (K10) scores. Multiple logistic regression analysis identified associations between sleep duration, quality, and K10 scores. Among the personnel studied, 2.5% reported severe sleep difficulties. The average sleep duration was 6.83 ± 1.12 hours. Short sleep duration and sleep difficulty were associated with poorer K10 scores. Higher K10 scores among individuals with short sleep duration and low sleep quality were identified in the isolated military area group, the over 53 working hours/week group, and the enlisted soldier group. The factors listed were not by themselves associated with poorer mental health scores. Rather, specific workplaces and specific rank groups were more prone to poorer mental health. These results provide helpful information to minimize the negative psychological effects of sleep factors and to promote a sleep problem prevention and management policy.

Medical needs of tsunami disaster refugee camps.

BACKGROUND AND OBJECTIVES: In response to the massive tsunami disaster in South Asia, two Korean medical relief teams provided emergency medical care in the southern coastal area of Sri Lanka. Their findings are reported here to provide a realistic picture of medical needs created by the tsunami disaster and to enable a better-prepared medical response to future disasters of this type. METHODS: All victims of the tsunami in the area of operation of the two medical relief teams were encouraged to receive medical care. Care provided to each victim was documented in individual medical records. All medical records were reviewed and classified by age, gender, and diagnosis. RESULTS: A total of 4,710 people were treated by the two Korean medical relief teams for 9 days of operation in southern Sri Lanka. Respiratory problems were common, but diarrhea was diagnosed in an average of only 4.3 patients per day. Minor skin trauma and wound infection in the extremities were frequent as long as 3 weeks after the disaster. The proportion of skin trauma in relation to total trauma decreased as days elapsed from the disaster. CONCLUSIONS: Because of the provision of adequate quantities of potable water, the likelihood of waterborne diarrhea was low. Acute respiratory problems and chronic problems were prevalent in tsunami refugee camps. Despite concerted international relief efforts, inadequate treatment of minor skin trauma and skin infections was evident.

Field-user acceptability of new camouflage face paint formulations in the Republic of Korea.

New formulations of camouflage face paint (CFP), one with 30% N,N-diethyl-3-methylbenzamide (DEET) and the other without DEET, were evaluated for soldier-user acceptability during a military field-training exercise in the Republic of Korea. Soldiers testing the CFP formulations were members of one of four U.S. Army infantry companies (A, B, C, or D). The formulations were evaluated while soldiers participated in simulated combat exercises for 5 days during hot, humid summer weather in Korea. Results showed that soldiers found both of the new formulations easier to apply (91.3% of respondents who used CFP without DEET and 87.9% of respondents who used CFP with DEET) and remove (82.6% without DEET and 81.2% with DEET) than the previous standard military-issue CFP. Soldier acceptability was higher for the new CFP formulation with 30% DEET (70.5%) than for the formulation without 30% DEET (52.9%). Soldiers recommended it more frequently (70.5%) than the formulation without 30% DEET (50.0%). The new CFP formulation with 30% DEET was rated more often (79.5%) as either good or excellent than the new formulation without 30% DEET (67.4%). Soldiers reported that the CFP formulation with 30% DEET more successfully camouflaged the face (92.7%) than the formulation without 30% DEET (80.0%).

Molecular epidemiological study for tick-borne disease (Ehrlichia and Anaplasma spp.) surveillance at selected U.S. military training sites/installations in Korea.

Vector-borne diseases are a potential public health threat to U.S. Forces Korea (USFK). Ehrlichia and Anaplasma spp., transmitted by ticks, are only two of several diseases that may affect military readiness and operations. Rodents were collected at selected U.S. military installations and training sites in the Republic of Korea. DNA was extracted from spleen tissues and assayed by PCR methods for Ehrlichia and Anaplasma species. From rodents and mustelids collected during 1999 and 2000, a total of 196 Apodemus agrarius (striped field mouse), 2 Mustela sibirica (weasel), and 1 Cricetulus triton nestor (Korean greater long-tailed hamster) were assayed for Ehrlichia and Anaplasma species-specific DNA fragments. Rodent surveillance indicated a very high prevalence of Ehrlichia and Anaplasma spp. at selected training sites. Ehrlichia/Anaplasma DNA were identified from spleen tissue from 157 Apodemus agrarius, 1 Mustela sibirica, and 1 Cricetulus riton nestor. Species-specific DNA fragments of E. canis (45), E. ewingii (16), A. phagocytophila (5), and A. platys (62) were amplified by PCR techniques. Seventy-one striped field mice had single infections, while 24 had mixed infections of 2 (17 specimens), 3 (7 specimens), or 4 (1 specimen) pathogens. The striped field mouse plays a role as a reservoir for latent infections of various Ehrlichia or Anaplasma species.

Vivax malaria: a continuing health threat to the Republic of Korea.

Vivax malaria reemerged in the Republic of Korea in 1993. Most of the cases occurred among soldiers in the region adjacent to the Demilitarized Zone (DMZ) until 1995. To determine the rate of dispersion of vivax malaria, we evaluated its epidemiologic characteristics. Of 13,903 cases of vivax malaria reported in 2000, 40.1% (5,577) were reported among Republic of Korea military personnel, 26.2% (3,641) among veterans discharged less than two years from the military, and 33.7% (4,685) among civilians. Cases of vivax malaria have rapidly increased annually among counties bordering the DMZ, and have spread to approximately 40 km south of the DMZ. Chemoprophylaxis administered to military personnel may have been responsible for the decreasing number of cases among the Republic of Korea military population. The first mosquito-transmitted cases appeared in early June. Therefore, chemoprophylaxis should be instituted in early April to reduce the number of infected mosquitoes. Extensive intervention is warranted to reduce the spread of vivax malaria in the Republic of Korea.

A preliminary investigation of early smoking initiation and nicotine dependence in Korean adults.

BACKGROUND: Few studies have investigated the association between age at smoking initiation and Fagerström test for nicotine dependence (FTND) in adulthood. The goal of this study was to develop the Korean version of FTND (FTND-K) and to examine the relationship between age at smoking initiation and nicotine dependence. METHODS: This investigation used data from 268 current smokers who visited the Center for Cancer Prevention and Early Detection in the National Cancer Center, Korea. The internal consistency of the FTND-K was assessed by Cronbach's coefficient alpha. Pearson's correlation coefficients were used to assess the relationships between the FTND-K sum scores and urinary cotinine levels. One-way analysis of variance (ANOVA) and t-tests were used to assess differences in the FTND-K sum score between groups. Factor associated with nicotine dependence were identified through stepwise multiple logistic regression analysis. RESULTS: The standardized Cronbach's alpha of FTND-K was 0.72. A significant positive correlation was seen between the FTND-K sum score and urinary cotinine level (correlation coefficient = 0.49, P < 0.05). Age at smoking initiation had a significant association with the FTND-K sum score in univariate analysis. In multivariate analysis, nicotine dependence was higher in smokers that started smoking cigarettes at 19 years or earlier than in those that started at 25 years or later (OR = 11.25, 95% CIs, 1.46-97.10). CONCLUSIONS: The FTND-K is a valid assessment tool of nicotine dependence with acceptable levels of internal consistency and close correlation to urinary cotinine level. The finding that those who initiate smoking at an early age tend to be more nicotine dependent underscores and reinforces the public health significance of delaying smoking onset.

Hantavirus infection in an active duty U.S. Army soldier stationed in Seoul, Korea.

Hemorrhagic fever with renal syndrome has been described among the U.S. and the U.N. troops assigned to the Republic of Korea since the Korean War. However, this appears to be the first case in which infection was acquired during garrison duty in an urban environment.