Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period.

BACKGROUND: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. METHOD: We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. RESULTS: A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. CONCLUSIONS: Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.

Comparison of Waning Neutralizing Antibody Responses Against the Omicron Variant 6 Months After Natural Severe Acute Respiratory Syndrome Coronavirus 2 Infection (With or Without Subsequent Coronavirus Disease 2019 [COVID-19] Vaccination) Versus 2-Dose COVID-19 Vaccination.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, subsequent ChAdOx1 nCoV-19 vaccination induced similar neutralizing antibody levels against the original strain but significantly higher levels against the Omicron variant compared to those who were not vaccinated. Prior SARS-CoV-2 infection exhibited higher neutralization antibody titers than vaccination alone for both original strains and the Omicron variant.

Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea.

We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4-10 days after symptom onset.

Non-polio enteroviruses among healthy children in the Philippines.

BACKGROUND: Enteroviruses (EVs) are most commonly associated with either mild or asymptomatic infections, however, the presence of silent carriers in the community has been proven to play a crucial role in the spread of diseases such as hand, foot, and mouth disease (HFMD) that records high incidence in Asia Pacific region. In the Philippines, limited information is available on the etiology and prevalence of enterovirus outside the Acute Flaccid Paralysis (AFP) surveillance, thus, a study to determine the baseline prevalence of Non-Polio Enteroviruses (NPEVs) among healthy Filipino children was conducted. METHODS: A descriptive, cross-sectional study was performed to determine the prevalence of NPEV among healthy children under 6 years old in the Philippines. Duplicate stool samples were collected from 360 healthy children residing in three major urban cities in the country. Virus isolation and polymerase chain reaction were performed to identify enteroviruses present in the samples. To determine if the results of the study are comparable to the AFP surveillance data, the results of the study were compared to the prevalence and isolation rate among AFP cases of the similar cases collected the same year. RESULTS: Prevalence of enteroviruses among healthy children was found to be at 24.7%. Comparing the NPEV rates from the study and AFP surveillance of similar age and the same year of collection, there was no significant difference in NPEV case prevalence. The study identified a total of 19 different enterovirus serotypes with majority belonging to species Enterovirus B (EV-B). CONCLUSION: The study was able to establish a baseline NPEV case prevalence of 24.7% among healthy children aged under 6 years old in three major urban sites in the Philippines. The high isolation of NPEV among healthy children signifies continuous fecal-oral transmission of enteroviruses in the community.

Influence of anonymous HIV testing on national HIV surveillance in the Republic of Korea (2000 to 2015): a retrospective analysis.

BACKGROUND: Owing to the continuous increase in the number of new human immunodeficiency virus (HIV) infection in Korea, public health centers (PHCs) have performed anonymous tests since 1989. No study has examined the patterns of anonymous HIV testing performed at PHCs and the characteristics of HIV infection detected in those tests. We aimed to assess the influence of anonymous HIV testing on Korea's national HIV surveillance. METHODS: HIV screening test data from 253 PHCs over a 16-year period were classified into 13 groups based on reason for testing. For anonymous HIV test takers (Anonymous), the HIV positivity per 10,000 tests was calculated, as repetitions could not be distinguished. Those with suspected HIV infection voluntarily underwent HIV testing and revealed their identity (Suspected). HIV prevalence was calculated as the number of HIV-positive persons per 10,000 test takers. Analyses were performed using chi-square and Cochran-Armitage trend test with SAS 9.4. RESULTS: Approximately 400,000 HIV screening tests were performed at PHCs annually, which remained unchanged in the past 10 years. The proportion of anonymous testing increased from < 3.0% before 2014 to 4.8% in 2014 and 6.1% in 2015. While the number of HIV cases increased, the number of anonymous HIV-positive test results per 10,000 tests decreased from 68.8 in 2010 to 41.8 in 2015. The HIV prevalence among the suspected was approximately 20.0 per 10,000 test takers before 2014, which steeply increased to 71.6 in 2015. Those with suspected HIV were predominantly men, aged 20 years, foreigners, and metropolitan city dwellers in the last 6 years. The high prevalence of persons with suspected HIV resulted in a doubling of HIV prevalence at PHCs between 2014 and 2015. CONCLUSIONS: Anonymous and Suspected, which were driven by similar motives, impacted each other. Increase in HIV prevalence among the suspected led to a higher HIV prevalence among all test takers in PHCs and higher proportions of HIV infection nationwide, which could be attributed to the increase in the number of anonymous tests performed in PHCs. HIV positivity among the anonymous and HIV prevalence among the suspected are key indexes of the national HIV surveillance in Korea.

Viral and serological kinetics in Zika virus-infected patients in South Korea.

Zika virus is a mosquito-borne flavivirus that causes clinical symptoms similar to those observed in dengue and chikungunya virus infections. The Korea Centers for Disease Control and Prevention initiated laboratory testing using a real-time reverse transcription-polymerase chain reaction in January 2016. More than 1,000 suspected cases of infection were tested and nine were confirmed as imported cases of Zika virus infection from January to July 2016. The travel destinations of the infected individuals were Brazil, Philippines, Viet Nam, Guatemala, Puerto Rico, and the Dominican Republic. Phylogenetic analysis based on the partial envelope gene indicated that the viruses belonged to the Asian genotype circulating in South America. We further investigated the duration for which the viral RNA and virus-specific antibodies were detectable after the symptom onset. After the day of symptom onset, Zika virus was detectable until 6 days in serum, 14 days in urine and saliva, and 58 days in semen. Immunoglobulin M against Zika virus was detected as early as 2 days after the symptom onset and was maintained at these levels until 41 days, whereas Immunoglobulin G was detectable from 8 days after the symptom onset and was maintained until 52 days. These findings would help diagnostic laboratories improve their testing programs for Zika virus infection.

Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016.

Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19-64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

First Imported Case of Zika Virus Infection into Korea.

Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

Nosocomial transmission of severe fever with thrombocytopenia syndrome in Korea.

Of the 27 healthcare workers (HCWs) who had contact with a fatally ill patient with severe thrombocytopenia syndrome in Korea (SFTS), 4 who were involved in cardiopulmonary resuscitation complained of fever and were diagnosed with SFTS via seroconversion. Exposure to respiratory secretions, blood, or gowns soiled by body fluids was significantly associated with infection of HCWs.

Measles Elimination Activities in the Western Pacific Region: Experience from the Republic of Korea.

We describe the global status of measles control and elimination, including surveillance and vaccination coverage data provided by the World Health Organization (WHO). Since 2000, two doses of measles vaccine (MCV2) became recommended globally and the achievement of high vaccination coverage has led to dramatic decrease in the measles incidence. Our finding indicates that, in the Western Pacific Region (WPR), substantial progress has been made to control measles transmission in some countries; however, the measles virus continues to circulate, causing outbreaks. The Republic of Korea (ROK) experienced a series of resurgence of measles due to the importation and healthcare-associated transmission in infants, however overall incidence and surveillance indicators met the WHO criteria for measles elimination. The ROK was verified to be measles-free along with Australia, Mongolia, and Macau, China in 2014. One of the effective elimination activities was the establishment of solid keep-up vaccination system in school settings. The lessons learnt from the measles elimination activities in Korea may contribute to enhancing the surveillance schemes and strengthening of vaccination programs in member countries and areas of WPR.

Maintaining polio-free certification in the World Health Organization Western Pacific Region for over a decade.

On 29 October 2000, the World Health Organization (WHO) Regional Commission for the Certification of Poliomyelitis Eradication in the Western Pacific certified the WHO Western Pacific Region as free of indigenous wild poliovirus. This status has been maintained to date: wild poliovirus importations into Singapore (in 2006) and Australia (in 2007) did not lead to secondary cases, and an outbreak in China (in 2011) was rapidly controlled. Circulation of vaccine derived polioviruses in Cambodia, China and the Philippines was quickly interrupted. A robust acute flaccid paralysis surveillance system, including a multitiered polio laboratory network, has been maintained, forming the platform for integrating measles, neonatal tetanus, and other vaccine-preventable disease surveillance and their respective control goals. While polio elimination remains one of the most important achievements in public health in the Western Pacific Region, extended delays in global eradication have, however, led to shifting and competing public health priorities among member states and partners and have made the region increasingly vulnerable.

Accuracy of diagnostic methods and surveillance sensitivity for human enterovirus, South Korea, 1999-2011.

The epidemiology of enteroviral infection in South Korea during 1999-2011 chronicles nationwide outbreaks and changing detection and subtyping methods used over the 13-year period. Of 14,657 patients whose samples were tested, 4,762 (32.5%) samples were positive for human enterovirus (human EV); as diagnostic methods improved, the rate of positive results increased. A seasonal trend of outbreaks was documented. Genotypes enterovirus 71, echovirus 30, coxsackievirus B5, enterovirus 6, and coxsackievirus B2 were the most common genotypes identified. Accurate test results correlated clinical syndromes to enterovirus genotypes: aseptic meningitis to echovirus 30, enterovirus 6, and coxsackievirus B5; hand, foot and mouth disease to coxsackievirus A16; and hand, foot and mouth disease with neurologic complications to enterovirus 71. There are currently no treatments specific to human EV infections; surveillance of enterovirus infections such as this study provides may assist with evaluating the need to research and develop treatments for infections caused by virulent human EV genotypes.

Effect of the interval between birth and second dose of hepatitis B vaccine on perinatal transmission of hepatitis B virus.

Preventing perinatal transmission is important for hepatitis B (HepB) elimination. We conducted a retrospective cohort study to assess the interval between HepB birth-dose (HepB-BD) to second-dose (HepB-SD) vaccination on perinatal transmission. Among 39,313 infants born to HepB s-antigen (HBsAg)-positive mothers from a Korean national database 38,411 (97.7%) had completed timely immunophylaxis with HepB-BD 41,572 (99.8%) with hepatitis B immune globulin, and 1027 (2.6%) were HBsAg-positive at ≥ 9 months. Maternal factors (i.e. HepB e-antigen status, age, or nationality) were associated with an increased risk of infection whereas short gestational length decreased it. The HepB-BD - HepB-SD interval (<8 vs. ≥8 weeks) did not alter the risk.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Multiplicative synergistic risk of hepatocellular carcinoma development among hepatitis B and C co-infected subjects in HBV endemic area: a community-based cohort study.

BACKGROUND: There has been limited study on the effect of infection with different hepatitis C virus (HCV) genotypes on the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) endemic regions of Asia. METHODS: Hazard ratios of HCC development were estimated for HBV and HCV co-infected subjects among a community-based prospective cohort. HCV genotype was determined in HCV RNA-positive samples. Incident HCC cases were identified through linkage to the cancer registry. RESULTS: HCC incidence was 79 per 100,000 person-years in the study population (50 incident cases among 6,694 individuals within 63,170 person-years with an average of 9.4 years of follow-up); seroprevalence of HBsAg and anti-HCV was 5.2% and 5.6%. Adjusted hazard ratios of HCC by HBsAg positivity and anti-HCV positivity were 13.3 (CI: 7.3-24.4) and 6.7 (CI: 3.6-12.6). HRs of HBV and HCV monoinfection, and HBV/HCV coinfection were 17.1 (CI: 8.4-34.8), 10.4 (CI: 4.9-22.1) and 115.0 (CI: 32.5-407.3). Multiplicative synergistic effect of HBV/HCV coinfection on HCC risk was also observed (synergy index: 4.5, CI: 1.3-15.5). Infection with HCV genotype 1 (HR: 29.7, CI: 13.6-46.8) and mixed infection with genotype 1 and 2 (HR: 68.7, CI: 16.4-288.4) significantly elevated HCC risk, much higher than HBV infection. CONCLUSIONS: The effect of differences in HCV genotype and the multiplicative synergistic effect of HBV/HCV coinfection on HCC risk shown in the present study underline the need for comprehensive identification of hepatitis infection status in order to prevent and control HCC in this HBV endemic area.

Progress and challenges for measles elimination by 2012 in the Western Pacific Region.

BACKGROUND: The 37 countries and areas of the World Health Organization (WHO) Western Pacific Region have targeted measles for elimination by 2012. METHODS: We reviewed routine and supplementary immunization coverage based on 2010 WHO/United Nation's Children's Fund (UNICEF) estimates and Joint Reporting Forms and epidemiologic and laboratory data submitted by the countries and areas. RESULTS: In 2009, 21 of 37 countries and areas had ≥90% coverage with a first dose of measles vaccine; 32 countries and areas provided 2 routine doses of measles vaccine with 94% weighted average coverage among those reporting. From 1996 to 2009, 235 million persons received measles vaccine during 94 immunization campaigns in 30 countries and areas. As of 2009, 2.8 suspected cases per 100,000 population were discarded as nonmeasles; however, only 43% of second level administrative units reported at least 1 discarded case per 100,000. Adequate specimen collection rate was 71%. Measles incidence was 34 per million population in 2009, a 58% decrease compared with 2008 and the lowest ever reported. As many as 25 countries and areas already may have eliminated measles. CONCLUSIONS: Achieving the 2012 measles elimination goal is feasible provided political and financial commitments are increased at every level to further improve routine and supplementary immunization activity (SIA) coverage and surveillance in every district.

Outbreak of measles in the Republic of Korea, 2007: importance of nosocomial transmission.

BACKGROUND: From 2002 through 2006, Republic of Korea conducted extensive measles elimination activities and declared elimination in 2006. An outbreak of measles involving 180 confirmed cases occurred during 2007. METHODS: An outbreak investigation was performed and enhanced surveillance was implemented. Detailed case investigations and laboratory testing included serologic and molecular diagnostic methods. Cases were classified according to World Health Organization and national guidelines. RESULTS: During 2007, 451 suspected cases were reported and 180 (40%) cases were confirmed as measles during epidemiologic weeks 14-42. Incidence during the outbreak was 3.7 cases per million persons, excluding imported cases. Most confirmed cases were reported from Seoul; 137 (76%) cases were among children <24 months old, 124 (69%) case patients had no history of measles vaccination, and 81 (45%) case patients resulted from nosocomial transmission in 6 hospitals. Community members, patients, and health care workers all contributed to measles virus transmission. Limited outbreak control measures were implemented; high population immunity likely accounted for the self-limited transmission during this outbreak. CONCLUSIONS: Limited outbreaks of measles, in which nosocomial transmission can play an important role, may occur after countries have declared elimination. Timely and opportunistic vaccination may help prevent such outbreaks; high-quality surveillance is critical for their detection.

Expansion of the global measles and rubella laboratory network 2005-09.

Enhancing measles surveillance with integration of epidemiologic and laboratory information is one of the key strategies for accelerated measles control and elimination. The World Health Organization (WHO) Global Measles and Rubella Laboratory Network (LabNet) has been developed since 2000 to currently include 690 laboratories serving 183 countries. The LabNet testing strategy follows well-validated, standardized procedures for confirming suspected cases and for monitoring measles and rubella virus transmission patterns. The strength of the LabNet is a strong quality assurance program that monitors the performance of all laboratories through annual proficiency testing and continuous assessment. In the 5-year period 2005-2009, the results of >1 million measles immunoglobulin M (IgM) tests have been reported by the LabNet and, in addition, sequence information on >7000 measles and 600 rubella viruses has been shared. Progress with the development of the LabNet during 2005-2009 is discussed.

Global distribution of measles genotypes and measles molecular epidemiology.

A critical component of laboratory surveillance for measles is the genetic characterization of circulating wild-type viruses. The World Health Organization (WHO) Measles and Rubella Laboratory Network (LabNet), provides for standardized testing in 183 countries and supports genetic characterization of currently circulating strains of measles viruses. The goal of this report is to describe the lessons learned from nearly 20 years of virologic surveillance for measles, to describe the global databases for measles sequences, and to provide regional updates about measles genotypes detected by recent surveillance activities. Virologic surveillance for measles is now well established in all of the WHO regions, and most countries have conducted at least some baseline surveillance. The WHO Global Genotype Database contains >7000 genotype reports, and the Measles Nucleotide Surveillance (MeaNS) contains >4000 entries. This sequence information has proven to be extremely useful for tracking global transmission patterns and for documenting the interruption of transmission in some countries. The future challenges will be to develop quality control programs for molecular methods and to continue to expand virologic surveillance activities in all regions.

Status of global virologic surveillance for rubella viruses.

The suspected measles case definition captures rubella cases. Therefore, measles surveillance will be improved in the course of the control and eventual elimination of rubella transmission. One aspect of rubella control, virologic surveillance, is reviewed here. A systematic nomenclature for rubella viruses (RVs) based on 13 genotypes has been established and is updated when warranted by increases in information about RVs. From 2005 through 2010, the genotypes of RVs most frequently reported were 1E, 1G, and 2B, and genotypes 1a, 1B, 1C, 1h, 1j, and 2C were less frequently reported. Virologic surveillance can support rubella control and elimination. Synopses of rubella virologic surveillance in various countries, regions, and globally are given, including characterization of viruses from imported cases in a country that has eliminated rubella and studies of endemic viruses circulating in countries without rubella control objectives. Current challenges are discussed.