| Hye-Jin Ahn | 37 Articles |
This study determined the recent status and trend of Pneumocystis jirovecii pneumonia (PcP) in the non-human immunodeficiency virus (HIV) (non-HIV-PcP) and HIV (HIV-PcP) infected populations using data from the Health Insurance Review & Assessment Service (HIRA) and the Korea Disease Control and Prevention Agency (KDCA). SaTScan and Joinpoint were used for statistical analyses. Non-HIV-PcP cases showed an upward trend during the study period from 2010 to 2021, with the largest number in 2021 (551 cases). The upward trend was similar until 2020 after adjusting for the population. Seoul had the highest number of cases (1,597) in the non-HIV-PcP group, which was the same after adjusting for the population (162 cases/1,000,000). It was followed by Jeju-do (89 cases/1,000,000). The most likely cluster (MLC) for the non-HIV-PCP group was Seoul (Relative Risk (RR)=4.59, Log Likelihood Ratio (LLR)=825.531), followed by Jeju-do (RR=1.59, LLR=5.431). An upward trend was observed among the non-HIV-PcP group in the Jeju-do/Jeollanam-do/Jeollabuk-do/Gyeongsangnam-do/Busan/Daejeon/Daegu/Ulsan joint cluster (29.02%, LLR=11.638, P<0.001) located in the southern part of Korea. Both women and men in the non-HIV groups showed an overall upward trend of PcP during the study period. Men in the 60-69 age group had the highest annual percentage change (APC 41.8) during 2014-2019. In contrast, the HIV groups showed a falling trend of PcP recently. Men in the 60-69 age group had the most decrease (APC -17.6) during 2018-2021. This study provides an analytic basis for health measures and a nationwide epidemiological surveillance system for the management of PcP.
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This study provides an overview of the current status of clonorchiasis and cholangiocarcinoma (CCA), and their relationship in Korea during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service of Korea. Cluster, trend, and correlation analyses were performed. Gyeongsangnam-do and Seoul had the highest average number of cases (1,026 and 4,208) and adjusted rate (306 and 424) for clonorchiasis and CCA, respectively. The most likely clusters (MLC) for clonorchiasis and CCA were Busan/Gyeongsangnam-do/Ulsan/Daegu/Gyeongsangbuk-do (Relative Risk; RR = 4.55, Likelihood Ratio; LLR = 9,131.115) joint cluster and Seoul (RR = 2.29, LLR = 7,602.472), respectively. The MLC for clonorchiasis was in the southeastern part of Korea, while that for CCA was in the southern part. Clonorchiasis showed a decreasing trend in the southeastern districts, while increased in the southwestern districts. Cities in the central region had a decreasing trend, while the western districts had an increasing trend. In most adults (30-59), infection rate of clonorchiasis showed a significant decrease until 2018, while thereafter increased, although not significant. CCA showed a sharply decreasing tendency. The incidence of clonorchiasis and CCA were positively correlated. In general, the correlation was weak (r = 0.39, P < 0.001), but it was strongly positive around the 4 river basins (r = 0.74, P < 0.001). This study might provide an analytic basis for developing an effective system against clonorchiasis and CCA.
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This study was done to provide an overview of the latest trichomoniasis status in Korea by finding disease clusters and analyzing temporal trends during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service (HIRA) of Korea. SaTScan and Joinpoint programs were used for statistical analyses. Gyeonggi-do had the highest average population and highest number of cases. The high incidence of T. vaginalis infections were observed among women aged 40-49 and 30-39 years (33,830/year and 33,179/year, respectively). Similarly, the 40-49 and 30-39 age group in men showed the highest average cases (1,319/year and 1,282/year, respectively). Jeollabuk-do was the most likely cluster, followed by Busan/Gyeongsangnam-do/Ulsan/Daegu and Jeju-do and Gwangju. Urban and rural differences were prominent. Trichomoniasis has decreased significantly in most clusters, except for Incheon. Trichomoniasis was decreasing in women recently after peaking around 2014. Men showed different trends according to age. Trichomoniasis was increasing in the 10-39 age groups, but decreasing in the 40-59 age groups. This study might provide an analytic basis for future health measures, policy-makers, and health authorities in developing effective system for prevention of trichomoniasis.
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This study was done to provide an analytical overview on the latest malaria infection clusters by evaluating temporal trends during 2010-2019 in Korea. Incheon was the most likely cluster (MLC) for all cases of malaria during the total period. MLCs for P. falciparum, vivax, malariae, ovale, and clinically diagnosed malaria without parasitological confirmation were Jeollanam-do, Incheon, Gangwon-do, Gyeongsangnam-do, and Jeollabuk-do, respectively. Malaria was decreasing in most significant clusters, but Gwangju showed an increase for all cases of malaria, P. vivax and clinically diagnosed cases. Malaria overall, P. falciparum and P. vivax seem to be under control thanks to aggressive health measures. This study might provide a sound scientific basis for future control measures against malaria in Korea.
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We find out the clusters with high toxoplasmosis risk to discuss the geographical pattern in Gyodong-myeon and Samsan-myeon of Ganghwa-gun, Cheorwon-gun, and Goseong-gun, Korea. Seroepidemiological data of toxoplasmosis surveyed using rapid diagnostic tests for the residents in the areas in 2019 were analyzed to detect clusters of the infection. The cluster was investigated using the SaTScan program which is based on Kulldorff’s scan statistic. The clusters were found with P-values in each region analyzed in the program, and the risk and patient incidence of specific areas can be examined by the values such as relative risk and log likelihood ratio. Jiseok-ri and Insa-ri were found to be a cluster in Gyodong-myeon and Seokmo-ri was the cluster in Samsan-myeon. Yangji-ri and Igil-ri were found to be a cluster in Cheorwon-gun and Madal-ri and Baebong-ri were the cluster in Goseong-gun. This findings can be used to monitor and prevent toxoplasmosis infections occurring in vulnerable areas.
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Toxoplasma gondii seroprevalence have been rapidly increasing in some parts of Korea. We analyzed prevalence of anti-Toxoplasma gondii antibodies, using a rapid diagnostic test (RDT), in the sera of 552 residents in Ganghwa-gun, 661 ones in Cheorwon-gun, and 305 ones in Goseong-gun, Korea in 2019. IgG/IgM RDT mounted with recombinant fragment of major surface antigen (SAG1), glutathione-S-transferase-linker-SAG1A, were applied to the sera. IgG seroprevalence was 28.1% in Ganghwa-gun, 19.5% in Cheorwon-gun and 35.7% in Goseong-gun. Odds ratios comparing Cheorwon vs Ganghwa was 0.63 (P=0.001) and Goesong versus Ganghwa was 1.47 (P=0.01) adjusting age and sex. Goseong had highest seroprevalence among the 3 counties both in crude rates and logistic regression. Although Cheorwon and Goseong are adjacent to the demilitarized zone (DMZ) in Korea, seroprevalence rate was much higher in Goseong. Further investigation on other DMZ-closed areas is necessary whether they have high prevalence rates compared to the other areas. T. gondii prevalence in Korea is still persists; proper health policy should be established.
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This study was performed to find out the clusters with high parasite infection risk to discuss the geographical pattern. Clusters were detected using SatScan software, which is a statistical spatial scan program using Kulldorff’s scan statistic. Information on the parasitic infection cases in Korea 2011-2019 were collected from the Korea Centers for Disease Control and Prevention. Clusters of Ascaris lumbricoides infection were detected in Jeollabuk-do, and T. trichiura in Ulsan, Busan, and Gyeongsangnam-do. C. sinensis clusters were detected in Ulsan, Daegu, Busan, Gyeongsangnam-do, and Gyeongsangbuk-do. Clusters of intestinal trematodes were detected in Ulsan, Busan, and Gyeongsangnam-do. P. westermani cluster was found in Jeollabuk-do. E. vermicularis clusters were distributed in Gangwon-do, Jeju-do, Daegu, Daejeon, and Gwangju. This clustering information can be referred for surveillance and control on the parasitic infection outbreak in the infection-prone areas.
The purpose of this study is to find out the clusters with high toxoplasmosis risk to discuss the geographical pattern in 2 islands of Gyodong-myeon and Samsan-myeon in Ganghwa-gun, Korea. Seroepidemiological data of toxoplasmosis surveyed using rapid diagnostic tests for the residents in 2 islands from 2010 to 2013 were analyzed to detect clusters of the infection. The cluster was investigated using the SatScan program which is based on Kulldorff’s scan statistic. The clusters were found with P-values in each region analyzed in the program, and the risk and patient incidence of specific areas can be examined by the values such as relative risk and log likelyhood ratio. Jiseok-ri was found to be a cluster in Gyodong-myeon and Ha-ri was the cluster in Samsan-myeon. This findings can be used to monitor and prevent toxoplasmosis infections occurring in vulnerable areas.
Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.
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Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and is endemic in many Latin American countries. Diagnosis is based on serologic testing and the WHO recommends two or more serological tests for confirmation. Acidic ribosomal P protein of T. cruzi showed strong reactivity against positive sera of patients, and we cloned the protein after fragmenting it to enhance its antigenicity and solubility. Twelve positive sera of Chagas disease patients were reacted with the fragmented ribosomal P protein using western blot. Detection rate and density for each fragment were determined. Fragments F1R1, F1R2, and F2R1 showed 100% rate of detection, and average density scoring of 2.00, 1.67, and 2.42 from a maximum of 3.0, respectively. Therefore, the F2R1 fragment of the ribosomal P protein of T. cruzi could be a promising antigen to use in the diagnosis of Chagas disease in endemic regions with high specificity and sensitivity.
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A rapid diagnostic test (RDT) kit was developed to detect non-structural protein 1 (NS1) of yellow fever virus (YFV) using monoclonal antibody. NS1 protein was purified from the cultured YFV and used to immunize mice. Monoclonal antibody to NS1 was selected and conjugated with colloidal gold to produce the YFV NS1 RDT kit. The YFV RDTs were evaluated for sensitivity and specificity using positive and negative samples of monkeys from Brazil and negative human blood samples from Korea. Among monoclonal antibodies, clones 3A11 and 3B7 proved most sensitive, and used for YFV RDT kit. Diagnostic accuracy of YFV RDT was fairly high; Sensitivity was 0.0% and specificity was 100% against Dengue viruses type 2 and 3, Zika, Chikungunya and Mayaro viruses. This YFV RDT kit could be employed as a test of choice for point-of-care diagnosis and large scale surveys of YFV infection under clinical or field conditions in endemic areas and on the globe.
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We developed a Rapid Diagnostic Test (RDT) kit for detecting IgG/IgM antibodies against Zika virus (ZIKV) using monoclonal antibodies to the envelope (E) and non-structural protein 1 (NS1) of ZIKV. These proteins were produced using baculovirus expression vector with Sf9 cells. Monoclonal antibodies J2G7 to NS1 and J5E1 to E protein were selected and conjugated with colloidal gold to produce the Zika IgG/IgM RDT kit (Zika RDT). Comparisons with ELISA, plaque reduction neutralization test (PRNT), and PCR were done to investigate the analytical sensitivity of Zika RDT, which resulted in 100% identical results. Sensitivity and specificity of Zika RDT in a field test was determined using positive and negative samples from Brazil and Korea. The diagnostic accuracy of Zika RDT was fairly high; sensitivity and specificity for IgG was 99.0 and 99.3%, respectively, while for IgM it was 96.7 and 98.7%, respectively. Cross reaction with dengue virus was evaluated using anti-Dengue Mixed Titer Performance Panel (PVD201), in which the Zika RDT showed cross-reactions with DENV in 16.7% and 5.6% in IgG and IgM, respectively. Cross reactions were not observed with West Nile, yellow fever, and hepatitis C virus infected sera. Zika RDT kit is very simple to use, rapid to assay, and very sensitive, and highly specific. Therefore, it would serve as a choice of method for point-of-care diagnosis and large scale surveys of ZIKV infection under clinical or field conditions worldwide in endemic areas.
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The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine (5 ?M) at 20 μM and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at 1-5 μM, but host cells were destroyed at 10-20 ?M. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.
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Seroprevalence of Toxoplasma gondii infection among the residents of Cheorwon-gun, Gangwon-do, Korea, which partly includes the demilitarized zone (DMZ), were surveyed for 4 years and evaluated by RDT using recombinant fragment of major surface antigen (SAG1A). Sera from 1336, 583, 526, and 583 adult residents were collected on a yearly basis from 2010 to 2013, respectively. The total positive seroprevalence was 19.3, 21.9, 23.4, and 26.8% from 2010 to 2013, respectively. The positive seroprevalence in men (23.6, 27.5, 29.5, 34.6%) was far higher than women (14.1, 18.3, 19.4, 21.4%), from 2010 to 2013, respectively. This high seroprevalence of toxoplasmosis in Cheorwon-gun may have been influenced in part by its geographical locality of the area as it includes the DMZ, where civilian access is strictly limited, thus creating a relatively isolated area that is a well-preserved habitat. Further research is necessary to study the epidemiology of toxoplasmosis in this area.
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ELISA has been used for the diagnosis of toxoplasmosis, but it is being gradually replaced by a rapid diagnostic test (RDT). We compared and analyzed ELISA and RDT results using the sera collected during 4 consecutive years from residents of Gyodong-do (Island), Incheon-city, Korea. Sera from 921, 993, 940, and 838 adult residents were collected on a yearly basis (2010-2013). ELISA was performed by using a crude extract of T. gondii RH strain antigen and IgG/IgM RDT mounted with recombinant fragment of major surface antigen (SAG1), GST-linker-SAG1A, were applied to the sera. Comparison between groups was analyzed by the Student’s t-test. The positive seroprevalence surged from 14.7% (135/921, 2010), 23.1% (231/993, 2011), 23.6% (222/940, 2012), and 32.1% (269/838, 2013) by ELISA. In contrast, RDT showed a more moderate increasing trend from 21.7% (200/921, 2010), 25.5% (253/993, 2011), 28.9% (272/940, 2012) and 33.1% (277/838, 2013). Discrepancies between ELISA and RDT were noted near the cut-off value. At the OD 0.15-0.24 range, RDT could detect 16.1% (169/1051) more positives, which suggests an early or acute toxoplasmosis, but at the OD 0.25-0.34 range, ELISA could detect 35.9% (92/256) more positives of possible chronic infections. Over the OD > 0.35 ELISA and RDT agreed in the majority of the cases. This surge in seroprevalence may be caused by the organic agriculture in addition to eating behavior or increase in pets among Koreans. These facts may be applied on a full-scale national survey using RDT to supplement ELISA to define the characteristics of the infection.
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Seroprevalence of Toxoplasma gondii infection among the residents of Seokmo-do (Island) in Ganghwa-gun, Incheon, Korea was surveyed for 4 years by a rapid diagnostic test (RDT) using recombinant fragment of major surface antigen (SAG1), GST-linker-SAG1A. Sera from 312, 343, 390, and 362 adult residents were collected on a yearly basis from 2010 to 2013, respectively. Total positive seroprevalence regardless of gender was 29.2, 35.3, 38.7, and 45.3% from 2010 to 2013, respectively. Positive seroprevalence in male adults was 43.9, 48.2, 45.4, and 55.3%, which was far higher than that of the corresponding female adults which was 20.7, 29.2, 33.9, and 38.9%, from 2010 to 2013, respectively. This high seroprevalence of toxoplasmosis in Seokmo-do may have been caused in part by peculiar changes in the toxoplasmic environment of the island as it is a relatively isolated area preserving its natural habitat while also being connected by a bridge to the mainland. Further study is necessary to find out symptomatic patients and to confirm the risk factors.
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Chikungunya virus (CHIKV), a tropical pathogen, has re-emerged and has massive outbreaks abruptly all over the world. Containing many dominant epitopes, the envelope E2 protein of CHIKV has been explored for the vaccination or diagnosis. In the present study, the antigenicity of a recombinant expressed intrinsically disorder domain (IUD) of E2 was tested for the detection of the antibody against CHIKV through western blot method. The gene of the IUD of E2 was inserted into 2 different vectors and expressed as recombinant GST-E2 and recombinant MBP-E2 fusion protein, respectively. Two kinds of fusion proteins were tested with 30 CHIKV patient sera and 30 normal sera, respectively. Both proteins were detected by 25 patients sera (83.3%) and 1 normal serum (3.3%). This test showed a relatively high sensitivity and very high specificity of the recombinant E2 proteins to be used as diagnostic antigens against CHIKV infection.
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Specific gene expressions of host cells by spontaneous STAT6 phosphorylation are major strategy for the survival of intracellular Toxoplasma gondii against parasiticidal events through STAT1 phosphorylation by infection provoked IFN-γ. We determined the effects of small molecules of tyrosine kinase inhibitors (TKIs) on the growth of T. gondii and on the relationship with STAT1 and STAT6 phosphorylation in ARPE-19 cells. We counted the number of T. gondii RH tachyzoites per parasitophorous vacuolar membrane (PVM) after treatment with TKIs at 12-hr intervals for 72 hr. The change of STAT6 phosphorylation was assessed via western blot and immunofluorescence assay. Among the tested TKIs, Afatinib (pan ErbB/EGFR inhibitor, 5 ?M) inhibited 98.0% of the growth of T. gondii, which was comparable to pyrimethamine (5 ?M) at 96.9% and followed by Erlotinib (ErbB1/EGFR inhibitor, 20 ?M) at 33.8% and Sunitinib (PDGFR or c-Kit inhibitor, 10 ?M) at 21.3%. In the early stage of the infection (2, 4, and 8 hr after T. gondii challenge), Afatinib inhibited the phosphorylation of STAT6 in western blot and immunofluorescence assay. Both JAK1 and JAK3, the upper hierarchical kinases of cytokine signaling, were strongly phosphorylated at 2 hr and then disappeared entirely after 4 hr. Some TKIs, especially the EGFR inhibitors, might play an important role in the inhibition of intracellular replication of T. gondii through the inhibition of the direct phosphorylation of STAT6 by T. gondii.
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Mouse models of chronic toxoplasmosis and atopic dermatitis (AD) were combined to clarify the effect of opportunistic Toxoplama gondii infection on the development of AD. AD was induced as a chronic contact hypersensitivity (CHS) with repeated challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) on the dorsal skin of mice. TNCB induced skin thickness increases in both normal and toxoplasmic mice. The changing patterns were different from the sigmoidal which saturated at 20 days in normal mice to the convex saturated at 12 days in toxoplasmic mice with the crossing at 18 days. Compared to normal mice, toxoplasmic mice presented CHS more severely in earlier times and then moderately in later times. These data suggest that host immune modification by T. gondii infection enhances CHS in early times of atopic stimulation but soothes the reaction of CHS in later times in mouse model.
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The seroepidemiological status of toxoplasmosis was surveyed among the residents of Cheorwon-gun, Gangwon-do by means of ELISA using a crude extract antigen of Citations Citations to this article as recorded by
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Seroepidemiological status of toxoplasmosis among the residents of Jeju island was surveyed and evaluated by ELISA with crude extract of Citations Citations to this article as recorded by
Dendritic cells have been known as a member of strong innate immune cells against infectious organelles. In this study, we evaluated the cytokine expression of splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming Me49 strain and demonstrated the distribution of lymphoid dendritic cells by fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI) and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS analysis showed that the number of CD8α+/CD11c+ splenic dendritic cells increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic dendritic cells showed early and rapid cytokine changes and may have important protective roles in early phases of murine toxoplasmosis. Citations Citations to this article as recorded by
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An ELISA was developed for the diagnosis of vivax malaria using multiple stage-specific recombinant antigens of Citations Citations to this article as recorded by
An ELISA was established to measure bovine IgG directed against the recombinant antigenic determinant of Nc-p43, a major surface antigen of Citations Citations to this article as recorded by
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