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.

Prevalence of Self-reported Allergic Diseases and IgE Levels: A 2010 KNHANES Analysis.

PURPOSE: The prevalence of allergic diseases is known to be associated with both demographic and environmental factors. Herein, we aimed to determine significant factors associated with the prevalence of allergic diseases and with total immunoglobulin E (tIgE) and specific immunoglobulin E (sIgE) levels in Korea. METHODS: We analyzed unweighted data collected by the 2010 Korea National Health and Nutrition Examination Survey for 2,342 subjects who underwent serum tests for tIgE and sIgE to Dermatophagoides farinae, dog, and Blattella germanica, representing a sample of 16,003,645 citizens, by considering the sample weight and stratification. RESULTS: The overall prevalence of self-reported allergic diseases was 37.6%. The prevalence rates of allergic rhinitis and atopic dermatitis decreased with age, whereas the asthma prevalence was not affected by the age of the subjects. When analyzed according to the type of allergic diseases, the prevalence of self-reported allergic disease was significantly associated with various factors (e.g. age, occupation, living in urban areas, and depression). The tIgE level decreased with age, but later increased. Elevation of tIgE was significantly associated with male sex, type of occupation, obesity, and smoking status. However, the risk factors for the increased sIgE levels to each allergen were quite different. Sensitization to D. farinae was more likely in young subjects, whereas the prevalence of sensitization to B. germanica was significantly higher in subjects with male sex, residing in a house (houses), and with glucose intolerance. Finally, young age and the smoking status were significantly associated with sensitization to dog. CONCLUSIONS: Various demographic and environmental factors were significantly associated with the prevalence of self-reported allergic diseases and the levels of tIgE and sIgE to D. farinae, B. germanica, and dog in Korea.

Opportunistic diseases among HIV-infected patients: a multicenter-nationwide Korean HIV/AIDS cohort study, 2006 to 2013.

BACKGROUND/AIMS: The frequencies of opportunistic diseases (ODs) vary across countries based on genetic, environmental, and social differences. The Korean HIV/AIDS cohort study was initiated in 2006 to promote research on human immunodeficiency virus (HIV) infection in Korea, and to provide a logistical network to support multicenter projects on epidemiological, clinical, and laboratory aspects of HIV infection. This study evaluated the prevalence of ODs among HIV-infected patients in the era of highly active antiretroviral therapy, and the risk factors associated with ODs. METHODS: The study enrolled 1,086 HIV-infected patients from 19 hospitals. This study examined the baseline data of the HIV/AIDS Korean cohort study at the time of enrollment from December 2006 to July 2013. RESULTS: Candidiasis was the most prevalent opportunistic infection (n = 176, 16.2%), followed by Mycobacterium tuberculosis infection (n = 120, 10.9%), Pneumocystis jirovecii pneumonia (n = 121, 11.0%), cytomegalovirus infection (n = 52, 4.7%), and herpes zoster (n = 44, 4.0%). The prevalence rates of Kaposi's sarcoma (n = 8, 0.7%) and toxoplasmosis (n = 4, 0.4%) were very low compared with other countries. The risk factors for ODs were a low CD4 T cell count at the time of HIV diagnosis (odds ratio [OR], 1.01; p < 0.01), current smoking (OR, 2.27; p = 0.01), current alcohol use (OR, 2.57; p = 0.04), and a history of tuberculosis (OR, 5.23; p < 0.01). CONCLUSIONS: Using recent Korean nationwide data, this study demonstrated that an important predictor of ODs was a low CD4 T cell count at the time of HIV diagnosis. Tuberculosis remains one of the most important ODs in HIV-infected patients in Korea.

Anxiety and depressive symptoms among patients infected with human immunodeficiency virus in South Korea.

Patients infected with human immunodeficiency virus (HIV) may develop mental health problems such as anxiety and depression, which negatively impact of disease progression. We investigated factors associated with the prevalence of anxiety and depression symptoms among HIV-infected patients in Korea. A total of 840 HIV-infected patients who participated in the Korea HIV/AIDS Cohort Study from 2006 to 2012 were evaluated. Socio-demographic, epidemiologic, and clinical variables were obtained through standardized questionnaires. The State-Trait Anxiety Inventory and Beck Depression Inventory were used to assess the symptoms of anxiety and depression. Multiple logistic regression analyses were performed to identify factors associated with symptoms of anxiety and depression. The prevalence of anxiety and depressive symptoms among HIV-infected patients was 32% and 36%, respectively. Ex-smoker and persistent symptoms for more than one week within the past six months and diagnosis of HIV infection within one year were associated with increased anxiety symptoms (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.09-2.69; OR 1.52, 95% CI 1.09-2.11; OR 1.49, 95% CI 1.02-2.20) and current smoking and persistent symptoms were also associated with increased depressive symptoms (OR 2.10, 95% CI 1.31-3.30; OR 1.87, 95% CI 1.25-2.79). Marital status, current smoking, current drinking, and persistent symptoms were associated with both increased anxiety and depressive symptoms (OR 1.75, 95% CI 1.07-2.88; OR 1.66, 95% CI 1.06-2.61; OR 1.88, 95% CI 1.18-2.99). The prevalence of anxiety and depressive symptoms among HIV-infected patients is higher than those estimated for the general population. This study shows the necessity to evaluate symptoms of anxiety and depression and suggest psychological support for HIV-infected patients who smoke or have persistent symptoms or have sexual partner or drink.

Genome-wide association study of recalcitrant atopic dermatitis in Korean children.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous chronic inflammatory skin disease. Most AD during infancy resolves during childhood, but moderate-to-severe AD with allergic sensitization is more likely to persist into adulthood and more often occurs with other allergic diseases. OBJECTIVE: We sought to find susceptibility loci by performing the first genome-wide association study (GWAS) of AD in Korean children with recalcitrant AD, which was defined as moderate-to-severe AD with allergic sensitization. METHODS: Our study included 246 children with recalcitrant AD and 551 adult control subjects with a negative history of both allergic disease and allergic sensitization. DNA from these subjects was genotyped; sets of common single nucleotide polymorphisms (SNPs) were imputed and used in the GWAS after quality control checks. RESULTS: SNPs at a region on 13q21.31 were associated with recalcitrant AD at a genome-wide threshold of significance (P < 2.0 × 10(-8)). These associated SNPs are more than 1 Mb from the closest gene, protocadherin (PCDH)9. SNPs at 4 additional loci had P values of less than 1 × 10(-6), including SNPs at or near the neuroblastoma amplified sequence (NBAS; 2p24.3), thymus-expressed molecule involved in selection (THEMIS; 6q22.33), GATA3 (10p14), and S-phase cyclin A-associated protein in the ER (SCAPER; 15q24.3) genes. Further analysis of total serum IgE levels suggested 13q21.31 might be primarily an IgE locus, and analyses of published data demonstrated that SNPs at the 15q24.3 region are expression quantitative trait loci for 2 nearby genes, ISL2 and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), in immune cells. CONCLUSION: Our GWAS of recalcitrant AD identified new susceptibility regions containing genes involved in epithelial cell function and immune dysregulation, 2 key features of AD, and potentially extend our understanding of their role in pathogenesis.

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BACKGROUND: This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. METHODS/DESIGN: The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child's neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child's genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child's exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child's neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child's microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures. DISCUSSION: The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.

Establishment of a Korea HPV cohort study.

We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies.

Alveolar macrophages play a key role in cockroach-induced allergic inflammation via TNF-α pathway.

The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.

Endotoxin is not essential for the development of cockroach induced allergic airway inflammation.

PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be essential to the development of airway inflammation.

Sequence polymorphisms of Der f 1, Der p 1, Der f 2 and Der p 2 from Korean house dust mite isolates.

Amino acid sequence variations have possible influences on the allergenicity of allergens and may be important factors in allergen standardization. This study was undertaken to investigate the sequence polymorphisms of group 1 and 2 allergens from Korean isolates of the house dust mites Dermatophagoides farinae and D. pteronyssinus. cDNA sequences encoding group 1 and 2 allergens were amplified by RT-PCR and compared the deduced amino acid sequences. Der f 1.0101, which appeared in 64.0 % of the 50 sequences analyzed, was found to be predominant. Among the Der p 1 sequences, Der p 1.0102 and 1.0105 were predominant (58 %). Among the Der f 2 sequences, Der f 2.0102 (40.7 %) and a new variant with Gly at position 42 (27.8 %) were predominant. The deduced amino acid sequences of 60 Der p 2 clones were examined, and 28 variants with 1-5 amino acid substitutions were found. Interestingly, all of the Der p 2 sequences had Thr instead of Lys at position 49. Two variants (Leu40, Thr49, and Asn114 (26.6 %); Val40, Thr49, and Asn114 (20.0 %)) were found to be the most predominant forms of Der p 2. Der p 1 has a high rate of sporadic substitutions and the group 2 allergens show a more regular pattern with orderly associations of amino acid substitutions. Der f 1 and Der p 2 from Korean mite isolates have unique amino acid sequence polymorphisms. These findings provide important data for house dust mite allergen standardization.

Specific IgE measurement using AdvanSure® system: comparison of detection performance with ImmunoCAP® system in Korean allergy patients.

BACKGROUND: AdvanSure enzyme immunoassay (EIA) system is a recently developed multiple allergen screen test with specific immunoglobulin E (sIgE) detection assay, while ImmunoCAP fluorescent EIA (FEIA) has been widely used for sIgE detection. There has been no inter-assay comparison data for these two systems. We determined the detection performance of AdvanSure system compared to that of ImmunoCAP. METHODS: We performed an inter-method comparison using sera from 199 Korean allergy patients, including asthma (39.7%), allergic rhinitis (54.8%), atopic dermatitis (36.2%) and food allergies (21.6%). We compared the sIgE detection performance for nine major inhalant and four food allergens. RESULTS: 950 paired assay results were analyzed. Most allergen sIgE results showed above 0.5 intraclass correlation coefficient except Blattella germanica, alternaria and mugwort allergen. Intermethod comparison results showed multiple differences in a few allergens. The inter-method concordance was moderate to substantial for most allergens (κ=0.528-0.778, p<0.001), except for cat dander. CONCLUSION: AdvanSure system showed a good detection performance compared with ImmunoCAP in correlation and agreement in Korean allergy patients. However, in terms of differences in the methodologies used by these two systems, careful clinical correlation is needed for interpretation of AdvanSure EIA results.

Distinctive distribution of HPV16 E6 D25E and E7 N29S intratypic Asian variants in Korean commercial sex workers.

The distribution of HPV16 sequence variations differs geographically and specific HPV16 E6 and E7 variants might carry a high risk for development of invasive cervical cancer and cervical intraepithelial neoplasia in a given population. To investigate the genetic variation of HPV 16 E6 and E7 genes, genomic DNAs from 56 HPV16-infected commercial sex workers were extracted from their cervical swabs by using DNA isolation kit. The E6 and E7 coding region (34-880) with HPV16 E6/E7 specific PCR were amplified and analyzed by using the DNAstar software. At the nucleotide level, 26 variants of the HPV16 E6 and E7 genes were identified including 12 silent mutations. At the amino acid level, the isolates showed 14 variants including E6 Q14H, E6 D25E, E6 I27R, E6 H78Y, E6 L83V, and E7 N29S. The dominant HPV16 E6 and E7 variants were HPV16 E6 D25E (68%) and HPV16 E7 N29S (73%), respectively, which belong to Asian lineage. Although this study has some limitations such as a small sample size and not enough clinical data, these finding suggests that the distinctive distribution of HPV 16 As-variant E6 D25E and E7 N29S might be associated with geographical dependence rather than disease progression. Further study is needed to determine the clinical and biological effects of these variants.

An HIV type 1 subtype B founder effect in Korea: gp160 signature patterns infer circulation of CTL-escape strains at the population level.

HIV-1 subtype B predominates in the Republic of Korea. Phylogenetic analyses of sequences for complete nef genes and env gene fragments encoding the V3 loop have identified a major monophyletic Korean subclade that is distinct from Western subtype B sequences in the Los Alamos HIV Sequence Database. This was investigated further by sequence analysis of complete env genes recovered from the DNA of peripheral blood mononuclear cells for matched groups of Koreans, four patients per group, previously assigned as being infected with either Korean or Western strains. The phylogenetic classifications were confirmed and analysis of the translation products identified 32 amino acid signature pattern differences, dispersed throughout gp160, which differentiate the two subclades. Twenty-three of these positions map to epitopes recognized by HLA-I-restricted cytotoxic T-lymphocytes (CTL) as catalogued in the Los Alamos HIV Immunology Database. The remaining nine map at or close to sites predicted to be targets for immunoproteasomes that are involved in producing peptides that bind to MHC Class I. These results suggest that a founder effect in the Korean population is based on the spread of CTL-escape/host-adapted HIV-1 strains.

Genital human papillomavirus genotyping by HPV oligonucleotide microarray in Korean commercial sex workers.

Because of the diversity in human papillomavirus (HPV) distribution, according to the population and region, detailed investigations of HPV genotypes are important in designing more effective HPV vaccines for any given country. HPV DNA oligonucleotide microarray was used to investigate the distribution of HPV genotypes among commercial sex workers. The prevalence of HPV in Korean commercial sex workers was 47%, with HPV-16 and HPV-51 as the dominant genotypes. HPV subtypes in 148 commercial sex workers comprised 70 with one genotype, 42 with two genotypes, 17 with three genotypes, and 19 with four or more genotypes. HPV-40, the most dominant low-risk genotype, was not detected in single-infection commercial sex workers. All women with multiple infections of low-risk genotypes had the HPV-40 genotype. This molecular epidemiological study of genital HPV will be useful for the development of a favorable strategy to prevent the spread of this potentially serious infection.